An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)
A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups.
A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
A hypnotic and sedative. Its use has been largely superseded by other drugs.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Derivatives of adipic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,6-carboxy terminated aliphatic structure.
Heparin derivatives. The term has also been used more loosely to include naturally occurring and synthetic highly-sulphated polysaccharides of similar structure. Heparinoid preparations have been used for a wide range of applications including as anticoagulants and anti-inflammatories and they have been claimed to have hypolipidemic properties. (From Martindale, The Extra Pharmacopoeia, 30th, p232)
A urine test for formiminoglutamic acid, an intermediate metabolite in L-histidine catabolism in the conversion of L-histidine to L-glutamic acid. It may be an indicator of vitamin B12 or folic acid deficiency or liver disease.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.
An enzyme that catalyzes the conversion of L-TYROSINE and 2-oxoglutarate to 4-hydroxyphenylpyruvate and L-GLUTAMATE. It is a pyridoxal-phosphate protein. L-PHENYLALANINE is hydroxylated to L-tyrosine. The mitochondrial enzyme may be identical with ASPARTATE AMINOTRANSFERASES (EC 2.6.1.1.). Deficiency of this enzyme may cause type II Tyrosinemia (see TYROSINEMIAS). EC 2.6.1.5.
Tetrahydrocortisone is a weak, endogenous glucocorticoid hormone, specifically a 3α,17,21-trihydroxy-5β-pregnane, that is synthesized in the adrenal gland from tetrahydrocortisol and further metabolized in the liver.
A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is a LIVER-specific enzyme that is the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.
A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression.
A very complex, but reproducible mixture of at least 177 C10 polychloro derivatives, having an approximate overall empirical formula of C10-H10-Cl8. It is used as an insecticide and may reasonably be anticipated to be a carcinogen: Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.
The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.
An antiepileptic agent related to the barbiturates; it is partly metabolized to PHENOBARBITAL in the body and owes some of its actions to this metabolite. Adverse effects are reported to be more frequent than with PHENOBARBITAL. (From Martindale, The Extra Pharmacopoeia, 30th ed, p309)
A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.
A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)
An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.
A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased.
An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.
Aminopyrine N-Demethylase is an enzyme, specifically a cytochrome P450 isoform, involved in the metabolism of drugs and xenobiotics, responsible for catalyzing the N-demethylation reaction.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.
A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Organic compounds with the general formula R-NCS.
Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
The rate dynamics in chemical or physical systems.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Drugs used to prevent SEIZURES or reduce their severity.
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.
A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.
A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine.
Elements of limited time intervals, contributing to particular results or situations.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.
A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.
An essential branched-chain amino acid important for hemoglobin formation.
Established cell cultures that have the potential to propagate indefinitely.
An anti-inflammatory 9-fluoro-glucocorticoid.
The measurement of an organ in volume, mass, or heaviness.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
Experimentally induced tumors of the LIVER.
Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
F344 rats are an inbred strain of albino laboratory rats (Rattus norvegicus) that have been widely used in biomedical research due to their consistent and reliable genetic background, which facilitates the study of disease mechanisms and therapeutic interventions.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
The complex processes of initiating CELL DIFFERENTIATION in the embryo. The precise regulation by cell interactions leads to diversity of cell types and specific pattern of organization (EMBRYOGENESIS).
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Initial drug treatment designed to bring about REMISSION INDUCTION. It is typically a short-term and high-dose drug treatment that is followed by CONSOLIDATION CHEMOTHERAPY and then MAINTENANCE CHEMOTHERAPY.
Therapeutic act or process that initiates a response to a complete or partial remission level.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A cell line derived from cultured tumor cells.
Inbred BALB/c mice are a strain of laboratory mice that have been selectively bred to be genetically identical to each other, making them useful for scientific research and experiments due to their consistent genetic background and predictable responses to various stimuli or treatments.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

An investigation into the binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to DNA in vitro. (1/8768)

After metabolic activation the carcinogen 15,16-dihydro-11-[3H]methylcyclopenta[a]phenanthren-17-one binds to DNA in vitro, and this binding is prevented by 7,8-benzoflavone. Radioactivity cannot be removed from the DNA with organic solvents or by chromatography on Sephadex G-50, even after heat denaturation of the DNA. Enzymatic hydrolysis yields radioactive fractions, which elute from a column of Sephadex LH-20 immediately after the natural nucleosides. At least two species of reactive metabolites are involved in this bending, those with a half-life of a few hr and others with greater stability. After extraction from the aqueous incubation mixture, they could be detected in discrete polar fractions from separations of the complex metabolite mixture by high-pressure liquid chromatography. Their ability to bind to DNA decreased with time at ambient temperature, and they were rapidly deactivated by acid. 7,8-Benzolflavone acted by suppressing the formation of polar metabolites derived from enzymatic oxidation of the aromatic double bonds. The inhibitor had no effect on the enzymes hydroxylating saturated carbon; hence it is unlikely that metabolism of the methyl group is important in conversion of this carcinogen to its proximate form, although the presence of the 11-methyl group is essential for carcinogenic activity in this series.  (+info)

The incorporation of 5-iodo-2'-deoxyuridine into the DNA of HeLa cells and the induction of alkaline phosphatase activity. (2/8768)

Inhibition of DNA synthesis during the period of exposure of HeLa cells to 5-iodo-2'-deoxyuridine (IUdR) inhibited the induction of alkaline phosphatase activity. This finding, taken together with previous findings that IUdR did not induce alkaline phosphatase activity in the presence of 2-fold molar excess thymidinemonstrated that IUdR incorporation into DNA is correlated with the increase in alkaline phosphatase activity. With the exception of an interim period described in the text, induction of alkaline phosphatase activity was linearly related to medium concentrations of IUdR of up to at least 3 muM. However, the extent of IUdR substitution in DNA did not appear to be related to the degree of enzyme induction. Alkaline phosphatase activity continued to increase at medium concentrations of IUdR from 1 to 3 muM, while little further substitution of DNA occurred.  (+info)

Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. (3/8768)

Shp-2 is an SH2 domain-containing protein tyrosine phosphatase. Although the mechanism remains to be defined, substantial experimental data suggest that Shp-2 is primarily a positive regulator in cell growth and development. We present evidence here that Shp-2, while acting to promote mitogenic signals, also functions as a negative effector in interferon (IFN)-induced growth-inhibitory and apoptotic pathways. Treatment of mouse fibroblast cells lacking a functional Shp-2 with IFN-alpha or IFN-gamma resulted in an augmented suppression of cell viability compared to that of wild-type cells. To dissect the molecular mechanism, we examined IFN-induced activation of signal transducers and activators of transcription (STATs) by electrophoretic mobility shift assay, using a specific DNA probe (hSIE). The amounts of STAT proteins bound to hSIE upon IFN-alpha or IFN-gamma stimulation were significantly increased in Shp-2(-/-) cells. Consistently, tyrosine phosphorylation levels of Stat1 upon IFN-gamma treatment and, to a lesser extent, upon IFN-alpha stimulation were markedly elevated in mutant cells. Furthermore, IFN-gamma induced a higher level of caspase 1 expression in Shp-2(-/-) cells than in wild-type cells. Reintroduction of wild-type Shp-2 protein reversed the hypersensitivity of Shp-2(-/-) fibroblasts to the cytotoxic effect of IFN-alpha and IFN-gamma. Excessive activation of STATs by IFNs was also diminished in mutant cells in which Shp-2 had been reintroduced. Together, these results establish that Shp-2 functions as a negative regulator of the Jak/STAT pathway. We propose that Shp-2 acts to promote cell growth and survival through two mechanisms, i.e., the stimulation of growth factor-initiated mitogenic pathways and the suppression of cytotoxic effect elicited by cytokines, such as IFNs.  (+info)

Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2. (4/8768)

The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.  (+info)

Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human malignant melanoma. (5/8768)

Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor aggressiveness. We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. Instead, IL-6 caused a marked induction of the cdk inhibitor p21WAF1/CIP1 in three different IL-6 sensitive cell lines, two of which also showed a marked accumulation of the cdk inhibitor p27Kip1. In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. In fact, of five IL-6 resistant cell lines, only two expressed detectable levels of p21WAF1/CIP1 mRNA and protein, while in three other lines, p21WAF1/CIP1 was undetectable. IL-6 dependent upregulation of p21WAF1/CIP1 was associated with binding of both STAT3 and STAT1 to the p21WAF1/CIP1 promoter. Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. In somatic cell hybrids of IL-6 sensitive and resistant cell lines, the resistant phenotype was dominant and IL-6 failed to induce p21WAF1/CIP1. Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event.  (+info)

Estrogen-dependent and independent activation of the P1 promoter of the p53 gene in transiently transfected breast cancer cells. (6/8768)

Loss of p53 function by mutational inactivation is the most common marker of the cancerous phenotype. Previous studies from our laboratory have demonstrated 17 beta estradiol (E2) induction of p53 protein expression in breast cancer cells. Although direct effects of E2 on the expression of p53 gene are not known, the steroid is a potent regulator of c-Myc transcription. In the present studies, we have examined the ability of E2 and antiestrogens to regulate the P1 promoter of the p53 gene which contains a c-Myc responsive element. Estrogen receptor (ER)-positive T47D and MCF-7 cells were transiently transfected with the P1CAT reporter plasmid and levels of CAT activity in response to serum, E2 and antiestrogens were monitored. Factors in serum were noted to be the dominant inducers of chloramphenicol acetyltransferase (CAT) expression in MCF-7 cells. The levels of CAT were drastically reduced when cells were maintained in serum free medium (SFM). However, a subtle ER-mediated induction of CAT expression was detectable when MCF-7 cells, cultured in SFM, were treated with E2. In serum-stimulated T47D cells, the CAT expression was minimal. The full ER antagonist, ICI 182 780 (ICI) had no effect. Treatment with E2 or 4-hydroxy tamoxifen (OHT) resulted in P1CAT induction; OHT was more effective than E2. Consistent with c-Myc regulation of the P1 promoter, E2 stimulated endogenous c-Myc in both cell lines. Two forms of c-Myc were expressed independent of E2 stimuli. The expression of a third more rapidly migrating form was E2-dependent and ER-mediated since it was blocked by the full ER antagonist, ICI, but not by the ER agonist/antagonist OHT. These data demonstrate both ER-mediated and ER-independent regulation of c-Myc and the P1 promoter of the p53 gene, and show differential effects of the two classes of antiestrogens in their ability to induce the P1 promoter of the p53 gene in breast cancer cells.  (+info)

Hyperoxia induces the neuronal differentiated phenotype of PC12 cells via a sustained activity of mitogen-activated protein kinase induced by Bcl-2. (7/8768)

We previously reported that rat pheochromocytoma PC12 cells express the neuronal differentiated phenotype under hyperoxia through the production of reactive oxygen species (ROS). In the present study, we found that in this phenotype, Bcl-2, an apoptosis inhibitor, affects mitogen-activated protein (MAP)-kinase activity, which is known as a key enzyme of the signal-transduction cascade for differentiation. When PC12 cells were cultured under hyperoxia, a rapid increase in MAP-kinase activity, including that of both p42 and p44, was observed. Although the activity level then decreased quickly, activity higher than the control level was observed for 48 h. PD98059, an inhibitor of MAP kinase, suppressed the hyperoxia-induced neurite extensions, suggesting the involvement of MAP-kinase activity in the mechanism of differentiation induced by ROS. An elevation of Bcl-2 expression was observed after culturing PC12 cells for 24 h under hyperoxia. This Bcl-2 elevation was not affected by treatment with PD98059, suggesting that it did not directly induce neurite extension under hyperoxia. However, the blockade of the Bcl-2 elevation by an antisense oligonucleotide inhibited the sustained MAP-kinase activity and neurite extensions under hyperoxia. Further, in PC12 cells highly expressing Bcl-2, the sustained MAP-kinase activity and neurite extensions under hyperoxia were enhanced. These results suggested that MAP kinase is activated through the production of ROS, and the subsequent elevation of Bcl-2 expression sustains the MAP-kinase activity, resulting in the induction of the neuronal-differentiation phenotype of PC12 cells under hyperoxia.  (+info)

In vivo modulation of alternative pathways of P-450-catalyzed cyclophosphamide metabolism: impact on pharmacokinetics and antitumor activity. (8/8768)

The widely used anticancer prodrug cyclophosphamide (CPA) is activated in liver by a 4-hydroxylation reaction primarily catalyzed by cytochrome P-4502B and P-4502C enzymes. An alternative metabolic pathway involves CPA N-dechloroethylation to yield chloroacetaldehyde (CA), a P-4503A-catalyzed deactivation/neurotoxication reaction. The in vivo modulation of these alternative, competing pathways of P-450 metabolism was investigated in pharmacokinetic studies carried out in the rat model. Peak plasma concentrations (Cmax) for 4-OH-CPA and CA were increased by 3- to 4-fold, and apparent plasma half-lives of both metabolites were correspondingly shortened in rats pretreated with phenobarbital (PB), an inducer of P-4502B and P-4503A enzymes. However, PB had no net impact on the extent of drug activation or its partitioning between these alternative metabolic pathways, as judged from AUC values (area-under-the-plasma concentration x time curve) for 4-OH-CPA and CA. The P-4503A inhibitor troleandomycin (TAO) decreased plasma Cmax and AUC of CA (80-85% decrease) without changing the Cmax or AUC of 4-OH-CPA in uninduced rats. In PB-induced rats, TAO decreased AUCCA by 73%, whereas it increased AUC4-OH-CPA by 93%. TAO thus selectively suppresses CPA N-dechloroethylation, thereby increasing the availability of drug for P-450 activation via 4-hydroxylation. By contrast, dexamethasone, a P-4503A inducer and antiemetic widely used in patients with cancer, stimulated large, undesirable increases in the Cmax and AUC of CA (8- and 4-fold, respectively) while reducing the AUC of the 4-hydroxylation pathway by approximately 60%. Tumor excision/in vitro colony formation and tumor growth delay assays using an in vivo 9L gliosarcoma solid tumor model revealed that TAO suppression of CPA N-dechloroethylation could be achieved without compromising the antitumor effect of CPA. The combination of PB with TAO did not, however, enhance the antitumor activity of CPA, despite the approximately 2-fold increase in AUC4-OH-CPA, suggesting that other PB-inducible activities, such as aldehyde dehydrogenase, may counter this increase through enhanced deactivation of the 4-hydroxy metabolite. Together, these studies demonstrate that the P-4503A inhibitor TAO can be used to effectively modulate CPA metabolism and pharmacokinetics in vivo in a manner that decreases the formation of toxic metabolites that do not contribute to antitumor activity.  (+info)

Enzyme induction is a process by which the activity or expression of an enzyme is increased in response to some stimulus, such as a drug, hormone, or other environmental factor. This can occur through several mechanisms, including increasing the transcription of the enzyme's gene, stabilizing the mRNA that encodes the enzyme, or increasing the translation of the mRNA into protein.

In some cases, enzyme induction can be a beneficial process, such as when it helps the body to metabolize and clear drugs more quickly. However, in other cases, enzyme induction can have negative consequences, such as when it leads to the increased metabolism of important endogenous compounds or the activation of harmful procarcinogens.

Enzyme induction is an important concept in pharmacology and toxicology, as it can affect the efficacy and safety of drugs and other xenobiotics. It is also relevant to the study of drug interactions, as the induction of one enzyme by a drug can lead to altered metabolism and effects of another drug that is metabolized by the same enzyme.

Antipyrine is a chemical compound that was commonly used as a fever reducer and pain reliever in the past. It is a type of phenylpyrazole antipyretic and analgesic. However, due to its potential for causing liver damage and other side effects, it has largely been replaced by other medications and is not widely used in modern medicine.

The medical definition of Antipyrine refers to this specific chemical compound with the formula C11H13N3O2, and not to any broader category of drugs or substances. It is a white crystalline powder that is soluble in alcohol, chloroform, and ether, but insoluble in water.

Antipyrine was first synthesized in 1883 and was widely used as a fever reducer and pain reliever until the mid-20th century. However, its use declined due to concerns about its safety profile, including the potential for liver damage, skin reactions, and other side effects.

Today, Antipyrine is still used in some medical applications, such as in the measurement of earwax conductivity as a way to assess hearing function. It may also be used in some topical creams and ointments for pain relief. However, its use as a systemic medication is generally not recommended due to its potential for causing harm.

Glucaric acid, also known as saccharic acid, is not a medication or a medical treatment. It is an organic compound that occurs naturally in various fruits and vegetables, such as oranges, apples, and corn. Glucaric acid is a type of dicarboxylic acid, which means it contains two carboxyl groups.

In the human body, glucaric acid is produced as a byproduct of glucose metabolism and can be found in small amounts in urine. It is also produced synthetically for industrial uses, such as in the production of cleaning products, textiles, and plastics.

There has been some research on the potential health benefits of glucaric acid, including its role in detoxification and cancer prevention. However, more studies are needed to confirm these effects and establish recommended intake levels or dosages. Therefore, it is not currently considered a medical treatment for any specific condition.

Phenobarbital is a barbiturate medication that is primarily used for the treatment of seizures and convulsions. It works by suppressing the abnormal electrical activity in the brain that leads to seizures. In addition to its anticonvulsant properties, phenobarbital also has sedative and hypnotic effects, which can be useful for treating anxiety, insomnia, and agitation.

Phenobarbital is available in various forms, including tablets, capsules, and elixirs, and it is typically taken orally. The medication works by binding to specific receptors in the brain called gamma-aminobutyric acid (GABA) receptors, which help to regulate nerve impulses in the brain. By increasing the activity of GABA, phenobarbital can help to reduce excessive neural activity and prevent seizures.

While phenobarbital is an effective medication for treating seizures and other conditions, it can also be habit-forming and carries a risk of dependence and addiction. Long-term use of the medication can lead to tolerance, meaning that higher doses may be needed to achieve the same effects. Abruptly stopping the medication can also lead to withdrawal symptoms, such as anxiety, restlessness, and seizures.

Like all medications, phenobarbital can have side effects, including dizziness, drowsiness, and impaired coordination. It can also interact with other medications, such as certain antidepressants and sedatives, so it is important to inform your healthcare provider of all medications you are taking before starting phenobarbital.

In summary, phenobarbital is a barbiturate medication used primarily for the treatment of seizures and convulsions. It works by binding to GABA receptors in the brain and increasing their activity, which helps to reduce excessive neural activity and prevent seizures. While phenobarbital can be effective, it carries a risk of dependence and addiction and can have side effects and drug interactions.

Glutethimide is a sedative-hypnotic drug that was previously used for the treatment of insomnia and anxiety disorders. It belongs to the class of drugs known as non-barbiturate hypnotics. Glutethimide works by depressing the central nervous system (CNS), producing a calming effect on the brain.

Due to its potential for abuse, addiction, and its narrow therapeutic index, glutethimide is no longer commonly used in clinical practice. It has been replaced by safer and more effective sleep aids with fewer side effects and lower potential for misuse.

It's important to note that the use of glutethimide should be under the strict supervision of a healthcare professional, and it should only be taken as prescribed. Misuse or overuse of this medication can lead to serious health consequences, including respiratory depression, coma, and even death.

The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:

1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.

Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.

Adipates are a group of chemical compounds that are esters of adipic acid. Adipic acid is a dicarboxylic acid with the formula (CH₂)₄(COOH)₂. Adipates are commonly used as plasticizers in the manufacture of polyvinyl chloride (PVC) products, such as pipes, cables, and flooring. They can also be found in cosmetics, personal care products, and some food additives.

Adipates are generally considered to be safe for use in consumer products, but like all chemicals, they should be used with caution and in accordance with recommended guidelines. Some adipates have been shown to have potential health effects, such as endocrine disruption and reproductive toxicity, at high levels of exposure. Therefore, it is important to follow proper handling and disposal procedures to minimize exposure.

Heparinoids are a group of substances that have similar properties to heparin, a highly sulfated glycosaminoglycan found in mast cells and basophils. Heparin is a powerful anticoagulant that works by accelerating the action of an enzyme called antithrombin III, which inhibits the formation of blood clots.

Heparinoids are often used as alternative anticoagulants to heparin in clinical settings. They have similar mechanisms of action and can also inhibit the coagulation cascade, preventing the formation of blood clots. However, heparinoids have a lower anticoagulant activity than heparin and may have different side effect profiles.

Examples of heparinoids include low molecular weight heparins (LMWHs), fondaparinux, and danaparoid. LMWHs are derived from standard heparin by chemical or enzymatic depolymerization and have a lower molecular weight than heparin. They have a more predictable anticoagulant response and longer half-life than standard heparin, making them useful for outpatient treatment of deep vein thrombosis and pulmonary embolism.

Fondaparinux is a synthetic pentasaccharide that selectively binds to antithrombin III and enhances its inhibitory activity against factor Xa, a key enzyme in the coagulation cascade. It has a long half-life and predictable pharmacokinetics, making it useful for the prevention and treatment of venous thromboembolism.

Danaparoid is a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate derived from pig intestinal mucosa. It has a lower anticoagulant activity than heparin but a longer half-life and less frequent dosing requirements. Danaparoid is used for the prevention and treatment of venous thromboembolism, as well as for the management of heparin-induced thrombocytopenia (HIT), a rare but serious complication of heparin therapy.

The FIGLU (Formiminoglutamic acid excretion) test is not a medical definition itself, but it is a test used to help diagnose Phenylketonuria (PKU), an inherited disorder of amino acid metabolism.

In PKU, the body cannot break down the amino acid phenylalanine properly due to a deficiency in the enzyme phenylalanine hydroxylase. As a result, phenylalanine and its toxic byproducts accumulate in the body, which can cause brain damage and intellectual disability if left untreated.

The FIGLU test measures the amount of formiminoglutamic acid (FIGLU) in the urine after a patient is given a load of histidine, another amino acid. In people with PKU, the accumulation of phenylalanine inhibits the conversion of histidine to glutamic acid, leading to an increase in FIGLU excretion in the urine. Therefore, a positive FIGLU test can indicate the presence of PKU. However, it is not a definitive diagnostic test and should be confirmed with other tests such as plasma amino acid analysis and/or genetic testing.

Microsomes, liver refers to a subcellular fraction of liver cells (hepatocytes) that are obtained during tissue homogenization and subsequent centrifugation. These microsomal fractions are rich in membranous structures known as the endoplasmic reticulum (ER), particularly the rough ER. They are involved in various important cellular processes, most notably the metabolism of xenobiotics (foreign substances) including drugs, toxins, and carcinogens.

The liver microsomes contain a variety of enzymes, such as cytochrome P450 monooxygenases, that are crucial for phase I drug metabolism. These enzymes help in the oxidation, reduction, or hydrolysis of xenobiotics, making them more water-soluble and facilitating their excretion from the body. Additionally, liver microsomes also host other enzymes involved in phase II conjugation reactions, where the metabolites from phase I are further modified by adding polar molecules like glucuronic acid, sulfate, or acetyl groups.

In summary, liver microsomes are a subcellular fraction of liver cells that play a significant role in the metabolism and detoxification of xenobiotics, contributing to the overall protection and maintenance of cellular homeostasis within the body.

The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.

The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.

The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.

There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:

1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.

Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.

Carbamazepine is an anticonvulsant medication that is primarily used to treat seizure disorders (epilepsy) and neuropathic pain. It works by decreasing the abnormal electrical activity in the brain, which helps to reduce the frequency and severity of seizures. Carbamazepine may also be used off-label for other conditions such as bipolar disorder and trigeminal neuralgia.

The medication is available in various forms, including tablets, extended-release tablets, chewable tablets, and suspension. It is usually taken two to four times a day with food to reduce stomach upset. Common side effects of carbamazepine include dizziness, drowsiness, headache, nausea, vomiting, and unsteady gait.

It is important to note that carbamazepine can interact with other medications, including some antidepressants, antipsychotics, and birth control pills, so it is essential to inform your healthcare provider of all the medications you are taking before starting carbamazepine. Additionally, carbamazepine levels in the blood may need to be monitored regularly to ensure that the medication is working effectively and not causing toxicity.

Tyrosine transaminase, also known as tyrosine aminotransferase or TAT, is an enzyme that plays a crucial role in the metabolism of the amino acid tyrosine. This enzyme catalyzes the transfer of an amino group from tyrosine to a ketoacid, such as alpha-ketoglutarate, resulting in the formation of a new amino acid, glutamate, and a ketone derivative of tyrosine.

Tyrosine transaminase is primarily found in the liver and its activity can be used as a biomarker for liver function. Increased levels of this enzyme in the blood may indicate liver damage or disease, such as hepatitis or cirrhosis. Therefore, measuring tyrosine transaminase activity is often part of routine liver function tests.

Tetrahydrocortisone is a physiological inactive end product of cortisol metabolism. It's a type of steroid hormone that is produced by the adrenal gland and plays a role in the response to stress, the regulation of metabolism, and the immune system.

Tetrahydrocortisone is formed when cortisol, also known as hydrocortisone, is metabolized in the liver by the enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD). This reaction converts cortisol to tetrahydrocortisone, which is then conjugated with glucuronic acid and excreted in the urine.

Tetrahydrocortisone has no known biological activity, and its measurement in the body is primarily used as a marker for cortisol metabolism. Abnormal levels of tetrahydrocortisone may indicate disorders of cortisol metabolism or adrenal gland function.

Tryptophan oxygenase, also known as tryptophan 2,3-dioxygenase (TDO) or tryptophan pyrrolase, is an enzyme that catalyzes the breakdown of the essential amino acid tryptophan. This enzyme requires molecular oxygen and plays a crucial role in regulating tryptophan levels within the body.

The reaction catalyzed by tryptophan oxygenase involves the oxidation of the indole ring of tryptophan, leading to the formation of N-formylkynurenine. This metabolite is further broken down through several enzymatic steps to produce other biologically active compounds, such as kynurenine and niacin (vitamin B3).

Tryptophan oxygenase activity is primarily found in the liver and is induced by various factors, including corticosteroids, cytokines, and tryptophan itself. The regulation of this enzyme has implications for several physiological processes, such as immune response, neurotransmitter synthesis, and energy metabolism. Dysregulation of tryptophan oxygenase activity can contribute to the development of various pathological conditions, including neurological disorders and cancer.

Barbital is a type of barbiturate drug that was commonly used as a sedative and sleep aid in the past. Its chemical name is sodium 5,5-diethylbarbituric acid, and it is also known by its brand name, Veronal. Barbital has a long duration of action, typically lasting between 6 to 10 hours, and was used for the treatment of insomnia, anxiety, and seizure disorders.

Barbital works by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits the activity of nerve cells in the brain. This results in a sedative effect, reducing anxiety and promoting sleep. However, barbital also has a high potential for abuse and dependence, and its use has declined significantly due to the development of safer and more effective alternative medications.

It is important to note that barbital is a controlled substance, and its possession and use are regulated by law in many countries. It should only be used under the supervision of a licensed healthcare professional, and its use should be avoided in individuals with a history of addiction or substance abuse.

Toxaphene is not typically defined in a medical context as it is not a medication or a condition. However, it is a chemical compound that has been used as a pesticide and has been banned in many countries due to its toxicity and environmental persistence.

Medically, toxaphene exposure can lead to various health issues, including skin and eye irritation, respiratory problems, neurological symptoms, and potential cancer risk. Therefore, it is sometimes mentioned in medical literature in the context of occupational or environmental health.

Xenobiotics are substances that are foreign to a living organism and usually originate outside of the body. This term is often used in the context of pharmacology and toxicology to refer to drugs, chemicals, or other agents that are not naturally produced by or expected to be found within the body.

When xenobiotics enter the body, they undergo a series of biotransformation processes, which involve metabolic reactions that convert them into forms that can be more easily excreted from the body. These processes are primarily carried out by enzymes in the liver and other organs.

It's worth noting that some xenobiotics can have beneficial effects on the body when used as medications or therapeutic agents, while others can be harmful or toxic. Therefore, understanding how the body metabolizes and eliminates xenobiotics is important for developing safe and effective drugs, as well as for assessing the potential health risks associated with exposure to environmental chemicals and pollutants.

In the context of pharmacology, "half-life" refers to the time it takes for the concentration or amount of a drug in the body to be reduced by half during its elimination phase. This is typically influenced by factors such as metabolism and excretion rates of the drug. It's a key factor in determining dosage intervals and therapeutic effectiveness of medications, as well as potential side effects or toxicity risks.

Primidone is an anticonvulsant medication primarily used in the treatment of seizure disorders. It is a barbiturate derivative that has sedative and muscle relaxant properties. Primidone is metabolized in the body into two other anticonvulsants, phenobarbital and phenylethylmalonamide (PEMA). Together, these active metabolites help to reduce the frequency and severity of seizures.

Primidone is used primarily for generalized tonic-clonic seizures and complex partial seizures. It may also be considered for use in absence seizures, although other medications are typically preferred for this type of seizure. The medication works by decreasing abnormal electrical activity in the brain, which helps to prevent or reduce the occurrence of seizures.

Like all anticonvulsant medications, primidone carries a risk of side effects, including dizziness, drowsiness, and unsteady gait. It may also cause rash, nausea, vomiting, and loss of appetite in some individuals. In rare cases, primidone can cause more serious side effects such as blood disorders, liver damage, or suicidal thoughts.

It is important for patients taking primidone to be closely monitored by their healthcare provider to ensure that the medication is working effectively and to monitor for any potential side effects. Dosages of primidone may need to be adjusted over time based on the patient's response to treatment and any adverse reactions that occur.

Beta-Naphthoflavone is a type of compound known as an aromatic hydrocarbon receptor (AHR) agonist. It is often used in research to study the effects of AHR activation on various biological processes, including the regulation of gene expression and the development of certain diseases such as cancer.

In the medical field, beta-Naphthoflavone may be used in experimental settings to investigate its potential as a therapeutic agent or as a tool for understanding the mechanisms underlying AHR-mediated diseases. However, it is not currently approved for use as a medication in humans.

Gamma-glutamyltransferase (GGT), also known as gamma-glutamyl transpeptidase, is an enzyme found in many tissues, including the liver, bile ducts, and pancreas. GGT is involved in the metabolism of certain amino acids and plays a role in the detoxification of various substances in the body.

GGT is often measured as a part of a panel of tests used to evaluate liver function. Elevated levels of GGT in the blood may indicate liver disease or injury, bile duct obstruction, or alcohol consumption. However, it's important to note that several other factors can also affect GGT levels, so abnormal results should be interpreted in conjunction with other clinical findings and diagnostic tests.

17-Hydroxycorticosteroids are a class of steroid hormones that are produced in the adrenal gland. They are formed from the metabolism of cortisol, which is a hormone that helps regulate metabolism, immune response, and stress response. 17-Hydroxycorticosteroids include compounds such as cortisone and corticosterone.

These hormones have various functions in the body, including:

* Regulation of carbohydrate, fat, and protein metabolism
* Suppression of the immune system
* Modulation of the stress response
* Influence on blood pressure and electrolyte balance

Abnormal levels of 17-hydroxycorticosteroids can indicate problems with the adrenal gland or pituitary gland, which regulates adrenal function. They are often measured in urine or blood tests to help diagnose conditions such as Cushing's syndrome (overproduction of cortisol) and Addison's disease (underproduction of cortisol).

Phenytoin is an anticonvulsant drug, primarily used in the treatment of seizures and prevention of seizure recurrence. It works by reducing the spread of seizure activity in the brain and stabilizing the electrical activity of neurons. Phenytoin is also known to have anti-arrhythmic properties and is occasionally used in the management of certain cardiac arrhythmias.

The drug is available in various forms, including immediate-release tablets, extended-release capsules, and a liquid formulation. Common side effects of phenytoin include dizziness, drowsiness, headache, nausea, vomiting, and unsteady gait. Regular monitoring of blood levels is necessary to ensure that the drug remains within the therapeutic range, as both low and high levels can lead to adverse effects.

It's important to note that phenytoin has several potential drug-drug interactions, particularly with other anticonvulsant medications, certain antibiotics, and oral contraceptives. Therefore, it is crucial to inform healthcare providers about all the medications being taken to minimize the risk of interactions and optimize treatment outcomes.

Dactinomycin is an antineoplastic antibiotic, which means it is used to treat cancer. It is specifically used to treat certain types of testicular cancer, Wilms' tumor (a type of kidney cancer that occurs in children), and some gestational trophoblastic tumors (a type of tumor that can develop in the uterus after pregnancy). Dactinomycin works by interfering with the DNA in cancer cells, which prevents them from dividing and growing. It is often used in combination with other chemotherapy drugs as part of a treatment regimen.

Dactinomycin is administered intravenously (through an IV) and its use is usually limited to hospitals or specialized cancer treatment centers due to the need for careful monitoring during administration. Common side effects include nausea, vomiting, and hair loss. More serious side effects can include bone marrow suppression, which can lead to an increased risk of infection, and tissue damage at the site where the drug is injected. Dactinomycin can also cause severe allergic reactions in some people.

It's important to note that dactinomycin should only be used under the supervision of a qualified healthcare professional, as its use requires careful monitoring and management of potential side effects.

Cytochrome P-450 CYP2B1 is a specific isoform of the cytochrome P-450 enzyme system, which is involved in the metabolism of drugs and other xenobiotics in the liver. This particular isoenzyme is primarily found in rats and is responsible for the metabolism of a variety of substrates, including certain drugs, steroids, and environmental toxins.

The cytochrome P-450 system is a group of enzymes located in the endoplasmic reticulum of cells, particularly in the liver. These enzymes play a crucial role in the metabolism of various substances, including drugs, hormones, and toxins. They work by catalyzing oxidation-reduction reactions that convert lipophilic compounds into more hydrophilic ones, which can then be excreted from the body.

CYP2B1 is one of many isoforms of cytochrome P-450, and it has a preference for certain types of substrates. It is involved in the metabolism of drugs such as cyclophosphamide, ifosfamide, and methadone, as well as steroids like progesterone and environmental toxins like pentachlorophenol.

It's important to note that while CYP2B1 is an essential enzyme in rats, its human counterpart, CYP2B6, plays a similar role in drug metabolism in humans. Understanding the function and regulation of these enzymes can help in predicting drug interactions, designing new drugs, and tailoring therapies to individual patients based on their genetic makeup.

A drug interaction is the effect of combining two or more drugs, or a drug and another substance (such as food or alcohol), which can alter the effectiveness or side effects of one or both of the substances. These interactions can be categorized as follows:

1. Pharmacodynamic interactions: These occur when two or more drugs act on the same target organ or receptor, leading to an additive, synergistic, or antagonistic effect. For example, taking a sedative and an antihistamine together can result in increased drowsiness due to their combined depressant effects on the central nervous system.
2. Pharmacokinetic interactions: These occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. For example, taking certain antibiotics with grapefruit juice can increase the concentration of the antibiotic in the bloodstream, leading to potential toxicity.
3. Food-drug interactions: Some drugs may interact with specific foods, affecting their absorption, metabolism, or excretion. An example is the interaction between warfarin (a blood thinner) and green leafy vegetables, which can increase the risk of bleeding due to enhanced vitamin K absorption from the vegetables.
4. Drug-herb interactions: Some herbal supplements may interact with medications, leading to altered drug levels or increased side effects. For instance, St. John's Wort can decrease the effectiveness of certain antidepressants and oral contraceptives by inducing their metabolism.
5. Drug-alcohol interactions: Alcohol can interact with various medications, causing additive sedative effects, impaired judgment, or increased risk of liver damage. For example, combining alcohol with benzodiazepines or opioids can lead to dangerous levels of sedation and respiratory depression.

It is essential for healthcare providers and patients to be aware of potential drug interactions to minimize adverse effects and optimize treatment outcomes.

Cycloheximide is an antibiotic that is primarily used in laboratory settings to inhibit protein synthesis in eukaryotic cells. It is derived from the actinobacteria species Streptomyces griseus. In medical terms, it is not used as a therapeutic drug in humans due to its significant side effects, including liver toxicity and potential neurotoxicity. However, it remains a valuable tool in research for studying protein function and cellular processes.

The antibiotic works by binding to the 60S subunit of the ribosome, thereby preventing the transfer RNA (tRNA) from delivering amino acids to the growing polypeptide chain during translation. This inhibition of protein synthesis can be lethal to cells, making cycloheximide a useful tool in studying cellular responses to protein depletion or misregulation.

In summary, while cycloheximide has significant research applications due to its ability to inhibit protein synthesis in eukaryotic cells, it is not used as a therapeutic drug in humans because of its toxic side effects.

Aniline hydroxylase is an enzyme that is involved in the metabolism of aromatic compounds, including aniline and other related substances. The enzyme catalyzes the addition of a hydroxyl group (-OH) to the aromatic ring of these compounds, which helps to make them more water-soluble and facilitates their excretion from the body.

Aniline hydroxylase is found in various tissues throughout the body, including the liver, lung, and kidney. It is a member of the cytochrome P450 family of enzymes, which are known for their role in drug metabolism and other xenobiotic-metabolizing reactions.

It's important to note that exposure to aniline and its derivatives can be harmful and may cause various health effects, including damage to the liver and other organs. Therefore, it is essential to handle these substances with care and follow appropriate safety precautions.

Aminopyrine N-demethylase is an enzyme that plays a role in the metabolism of drugs and other xenobiotics. It is primarily found in the liver and is responsible for catalyzing the N-demethylation of aminopyrine, a compound with analgesic and anti-inflammatory properties.

The enzyme works by transferring a methyl group from the aminopyrine molecule to a cofactor called NADPH, resulting in the formation of formaldehyde and dimethylaniline as products. This reaction is an important step in the biotransformation of many drugs and other foreign substances, allowing them to be more easily excreted from the body.

Aminopyrine N-demethylase is classified as a cytochrome P450 enzyme, which is a group of heme-containing proteins that are involved in oxidative metabolism. The activity of this enzyme can be influenced by various factors, including genetic polymorphisms, age, sex, and exposure to certain drugs or chemicals.

In addition to its role in drug metabolism, aminopyrine N-demethylase has also been used as a marker of liver function and as a tool for studying the regulation of cytochrome P450 enzymes.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Metabolic detoxification, in the context of drugs, refers to the series of biochemical processes that the body undergoes to transform drugs or other xenobiotics into water-soluble compounds so they can be excreted. This process typically involves two phases:

1. Phase I Detoxification: In this phase, enzymes such as cytochrome P450 oxidases introduce functional groups into the drug molecule, making it more polar and reactive. This can result in the formation of metabolites that are less active than the parent compound or, in some cases, more toxic.

2. Phase II Detoxification: In this phase, enzymes such as glutathione S-transferases, UDP-glucuronosyltransferases, and sulfotransferases conjugate these polar and reactive metabolites with endogenous molecules like glutathione, glucuronic acid, or sulfate. This further increases the water solubility of the compound, allowing it to be excreted by the kidneys or bile.

It's important to note that while these processes are essential for eliminating drugs and other harmful substances from the body, they can also produce reactive metabolites that may cause damage to cells and tissues if not properly regulated. Therefore, maintaining a balance in the activity of these detoxification enzymes is crucial for overall health and well-being.

Rifampin is an antibiotic medication that belongs to the class of drugs known as rifamycins. It works by inhibiting bacterial DNA-dependent RNA polymerase, thereby preventing bacterial growth and multiplication. Rifampin is used to treat a variety of infections caused by bacteria, including tuberculosis, Haemophilus influenzae, Neisseria meningitidis, and Legionella pneumophila. It is also used to prevent meningococcal disease in people who have been exposed to the bacteria.

Rifampin is available in various forms, including tablets, capsules, and injectable solutions. The medication is usually taken two to four times a day, depending on the type and severity of the infection being treated. Rifampin may be given alone or in combination with other antibiotics.

It is important to note that rifampin can interact with several other medications, including oral contraceptives, anticoagulants, and anti-seizure drugs, among others. Therefore, it is essential to inform your healthcare provider about all the medications you are taking before starting treatment with rifampin.

Rifampin may cause side effects such as nausea, vomiting, diarrhea, dizziness, headache, and changes in the color of urine, tears, sweat, and saliva to a reddish-orange color. These side effects are usually mild and go away on their own. However, if they persist or become bothersome, it is important to consult your healthcare provider.

In summary, rifampin is an antibiotic medication used to treat various bacterial infections and prevent meningococcal disease. It works by inhibiting bacterial DNA-dependent RNA polymerase, preventing bacterial growth and multiplication. Rifampin may interact with several other medications, and it can cause side effects such as nausea, vomiting, diarrhea, dizziness, headache, and changes in the color of body fluids.

Biotransformation is the metabolic modification of a chemical compound, typically a xenobiotic (a foreign chemical substance found within an living organism), by a biological system. This process often involves enzymatic conversion of the parent compound to one or more metabolites, which may be more or less active, toxic, or mutagenic than the original substance.

In the context of pharmacology and toxicology, biotransformation is an important aspect of drug metabolism and elimination from the body. The liver is the primary site of biotransformation, but other organs such as the kidneys, lungs, and gastrointestinal tract can also play a role.

Biotransformation can occur in two phases: phase I reactions involve functionalization of the parent compound through oxidation, reduction, or hydrolysis, while phase II reactions involve conjugation of the metabolite with endogenous molecules such as glucuronic acid, sulfate, or acetate to increase its water solubility and facilitate excretion.

Isothiocyanates are organic compounds that contain a functional group made up of a carbon atom, a nitrogen atom, and a sulfur atom, with the formula RN=C=S (where R can be an alkyl or aryl group). They are commonly found in cruciferous vegetables such as broccoli, brussels sprouts, and wasabi. Isothiocyanates have been studied for their potential health benefits, including their anticancer and anti-inflammatory properties. However, they can also be toxic in high concentrations.

Polychlorinated biphenyls (PCBs) are a group of man-made organic chemicals consisting of 209 individual compounds, known as congeners. The congeners are formed by the combination of two benzene rings with varying numbers and positions of chlorine atoms.

PCBs were widely used in electrical equipment, such as transformers and capacitors, due to their non-flammability, chemical stability, and insulating properties. They were also used in other applications, including coolants and lubricants, plasticizers, pigments, and copy oils. Although PCBs were banned in many countries in the 1970s and 1980s due to their toxicity and environmental persistence, they still pose significant health and environmental concerns because of their continued presence in the environment and in products manufactured before the ban.

PCBs are known to have various adverse health effects on humans and animals, including cancer, immune system suppression, reproductive and developmental toxicity, and endocrine disruption. They can also cause neurological damage and learning and memory impairment in both human and animal populations. PCBs are highly persistent in the environment and can accumulate in the food chain, leading to higher concentrations in animals at the top of the food chain, including humans.

Oxygenases are a class of enzymes that catalyze the incorporation of molecular oxygen (O2) into their substrates. They play crucial roles in various biological processes, including the biosynthesis of many natural products, as well as the detoxification and degradation of xenobiotics (foreign substances).

There are two main types of oxygenases: monooxygenases and dioxygenases. Monooxygenases introduce one atom of molecular oxygen into a substrate while reducing the other to water. An example of this type of enzyme is cytochrome P450, which is involved in drug metabolism and steroid hormone synthesis. Dioxygenases, on the other hand, incorporate both atoms of molecular oxygen into their substrates, often leading to the formation of new carbon-carbon bonds or the cleavage of existing ones.

It's important to note that while oxygenases are essential for many life-sustaining processes, they can also contribute to the production of harmful reactive oxygen species (ROS) during normal cellular metabolism. An imbalance in ROS levels can lead to oxidative stress and damage to cells and tissues, which has been linked to various diseases such as cancer, neurodegeneration, and cardiovascular disease.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Anticonvulsants are a class of drugs used primarily to treat seizure disorders, also known as epilepsy. These medications work by reducing the abnormal electrical activity in the brain that leads to seizures. In addition to their use in treating epilepsy, anticonvulsants are sometimes also prescribed for other conditions, such as neuropathic pain, bipolar disorder, and migraine headaches.

Anticonvulsants can work in different ways to reduce seizure activity. Some medications, such as phenytoin and carbamazepine, work by blocking sodium channels in the brain, which helps to stabilize nerve cell membranes and prevent excessive electrical activity. Other medications, such as valproic acid and gabapentin, increase the levels of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain, which has a calming effect on nerve cells and helps to reduce seizure activity.

While anticonvulsants are generally effective at reducing seizure frequency and severity, they can also have side effects, such as dizziness, drowsiness, and gastrointestinal symptoms. In some cases, these side effects may be managed by adjusting the dosage or switching to a different medication. It is important for individuals taking anticonvulsants to work closely with their healthcare provider to monitor their response to the medication and make any necessary adjustments.

Hydrocortisone is a synthetic glucocorticoid, which is a class of steroid hormones. It is identical to the naturally occurring cortisol, a hormone produced by the adrenal gland that helps regulate metabolism and helps your body respond to stress. Hydrocortisone has anti-inflammatory effects and is used to treat various inflammatory conditions such as allergies, skin disorders, and autoimmune diseases. It works by suppressing the immune system's response to reduce swelling, redness, itching, and other symptoms caused by inflammation.

Hydrocortisone is available in different forms, including oral tablets, topical creams, lotions, gels, and ointments, as well as injectable solutions. The specific use and dosage depend on the condition being treated and the individual patient's medical history and current health status.

As with any medication, hydrocortisone can have side effects, especially when used in high doses or for extended periods. Common side effects include increased appetite, weight gain, mood changes, insomnia, and skin thinning. Long-term use of hydrocortisone may also increase the risk of developing osteoporosis, diabetes, cataracts, and other health problems. Therefore, it is essential to follow your healthcare provider's instructions carefully when using this medication.

Cytochrome P-450 CYP3A is a subfamily of the cytochrome P-450 enzyme superfamily, which are primarily involved in drug metabolism in the human body. These enzymes are found predominantly in the liver, but also in other tissues such as the small intestine, kidneys, and brain.

CYP3A enzymes are responsible for metabolizing a wide variety of drugs, including many statins, benzodiazepines, antidepressants, and opioids. They can also metabolize endogenous compounds such as steroids and bile acids. The activity of CYP3A enzymes can be influenced by various factors, including genetic polymorphisms, age, sex, pregnancy, and the presence of other drugs or diseases.

The name "cytochrome P-450" refers to the fact that these enzymes contain a heme group that absorbs light at a wavelength of 450 nanometers when it is complexed with carbon monoxide. The term "CYP3A" denotes the specific subfamily of cytochrome P-450 enzymes that share a high degree of sequence similarity and function.

Mixed Function Oxygenases (MFOs) are a type of enzyme that catalyze the addition of one atom each from molecular oxygen (O2) to a substrate, while reducing the other oxygen atom to water. These enzymes play a crucial role in the metabolism of various endogenous and exogenous compounds, including drugs, carcinogens, and environmental pollutants.

MFOs are primarily located in the endoplasmic reticulum of cells and consist of two subunits: a flavoprotein component that contains FAD or FMN as a cofactor, and an iron-containing heme protein. The most well-known example of MFO is cytochrome P450, which is involved in the oxidation of xenobiotics and endogenous compounds such as steroids, fatty acids, and vitamins.

MFOs can catalyze a variety of reactions, including hydroxylation, epoxidation, dealkylation, and deamination, among others. These reactions often lead to the activation or detoxification of xenobiotics, making MFOs an important component of the body's defense system against foreign substances. However, in some cases, these reactions can also produce reactive intermediates that may cause toxicity or contribute to the development of diseases such as cancer.

Aryl hydrocarbon hydroxylases (AHH) are a group of enzymes that play a crucial role in the metabolism of various aromatic and heterocyclic compounds, including potentially harmful substances such as polycyclic aromatic hydrocarbons (PAHs) and dioxins. These enzymes are primarily located in the endoplasmic reticulum of cells, particularly in the liver, but can also be found in other tissues.

The AHH enzymes catalyze the addition of a hydroxyl group (-OH) to the aromatic ring structure of these compounds, which is the first step in their biotransformation and eventual elimination from the body. This process can sometimes lead to the formation of metabolites that are more reactive and potentially toxic than the original compound. Therefore, the overall impact of AHH enzymes on human health is complex and depends on various factors, including the specific compounds being metabolized and individual genetic differences in enzyme activity.

Ornithine decarboxylase (ODC) is a medical/biochemical term that refers to an enzyme (EC 4.1.1.17) involved in the metabolism of amino acids, particularly ornithine. This enzyme catalyzes the decarboxylation of ornithine to form putrescine, which is a precursor for the synthesis of polyamines, such as spermidine and spermine. Polyamines play crucial roles in various cellular processes, including cell growth, differentiation, and gene expression.

Ornithine decarboxylase is a rate-limiting enzyme in polyamine biosynthesis, meaning that its activity regulates the overall production of these molecules. The regulation of ODC activity is tightly controlled at multiple levels, including transcription, translation, and post-translational modifications. Dysregulation of ODC activity has been implicated in several pathological conditions, such as cancer, neurodegenerative disorders, and inflammatory diseases.

Inhibitors of ornithine decarboxylase have been explored as potential therapeutic agents for various diseases, including cancer, due to their ability to suppress polyamine synthesis and cell proliferation. However, the use of ODC inhibitors in clinical settings has faced challenges related to toxicity and limited efficacy.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

"Inbred strains of rats" are genetically identical rodents that have been produced through many generations of brother-sister mating. This results in a high degree of homozygosity, where the genes at any particular locus in the genome are identical in all members of the strain.

Inbred strains of rats are widely used in biomedical research because they provide a consistent and reproducible genetic background for studying various biological phenomena, including the effects of drugs, environmental factors, and genetic mutations on health and disease. Additionally, inbred strains can be used to create genetically modified models of human diseases by introducing specific mutations into their genomes.

Some commonly used inbred strains of rats include the Wistar Kyoto (WKY), Sprague-Dawley (SD), and Fischer 344 (F344) rat strains. Each strain has its own unique genetic characteristics, making them suitable for different types of research.

Cytochrome P-450 CYP1A1 is an enzyme that is part of the cytochrome P450 family, which are a group of enzymes involved in the metabolism of drugs and other xenobiotics (foreign substances) in the body. Specifically, CYP1A1 is found primarily in the liver and lungs and plays a role in the metabolism of polycyclic aromatic hydrocarbons (PAHs), which are chemicals found in tobacco smoke and are produced by the burning of fossil fuels and other organic materials.

CYP1A1 also has the ability to activate certain procarcinogens, which are substances that can be converted into cancer-causing agents (carcinogens) within the body. Therefore, variations in the CYP1A1 gene may influence an individual's susceptibility to cancer and other diseases.

The term "P-450" refers to the fact that these enzymes absorb light at a wavelength of 450 nanometers when they are combined with carbon monoxide, giving them a characteristic pink color. The "CYP" stands for "cytochrome P," and the number and letter designations (e.g., 1A1) indicate the specific enzyme within the family.

Hepatocytes are the predominant type of cells in the liver, accounting for about 80% of its cytoplasmic mass. They play a key role in protein synthesis, protein storage, transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, detoxification, modification, and excretion of exogenous and endogenous substances, initiation of formation and secretion of bile, and enzyme production. Hepatocytes are essential for the maintenance of homeostasis in the body.

Metabolic clearance rate is a term used in pharmacology to describe the volume of blood or plasma from which a drug is completely removed per unit time by metabolic processes. It is a measure of the body's ability to eliminate a particular substance and is usually expressed in units of volume (e.g., milliliters or liters) per time (e.g., minutes, hours, or days).

The metabolic clearance rate can be calculated by dividing the total amount of drug eliminated by the plasma concentration of the drug and the time over which it was eliminated. It provides important information about the pharmacokinetics of a drug, including its rate of elimination and the potential for drug-drug interactions that may affect metabolism.

It is worth noting that there are different types of clearance rates, such as renal clearance rate (which refers to the removal of a drug by the kidneys) or hepatic clearance rate (which refers to the removal of a drug by the liver). Metabolic clearance rate specifically refers to the elimination of a drug through metabolic processes, which can occur in various organs throughout the body.

Glucuronosyltransferase (UDP-glucuronosyltransferase) is an enzyme belonging to the family of glycosyltransferases. It plays a crucial role in the process of biotransformation and detoxification of various endogenous and exogenous substances, including drugs, hormones, and environmental toxins, in the liver and other organs.

The enzyme functions by transferring a glucuronic acid moiety from a donor molecule, uridine diphosphate glucuronic acid (UDP-GlcUA), to an acceptor molecule, which can be a variety of hydrophobic compounds. This reaction results in the formation of a more water-soluble glucuronide conjugate, facilitating the excretion of the substrate through urine or bile.

There are multiple isoforms of glucuronosyltransferase, classified into two main families: UGT1 and UGT2. These isoforms exhibit different substrate specificities and tissue distributions, allowing for a wide range of compounds to be metabolized through the glucuronidation pathway.

In summary, Glucuronosyltransferase is an essential enzyme in the detoxification process, facilitating the elimination of various substances from the body by conjugating them with a glucuronic acid moiety.

Leucine is an essential amino acid, meaning it cannot be produced by the human body and must be obtained through the diet. It is one of the three branched-chain amino acids (BCAAs), along with isoleucine and valine. Leucine is critical for protein synthesis and muscle growth, and it helps to regulate blood sugar levels, promote wound healing, and produce growth hormones.

Leucine is found in various food sources such as meat, dairy products, eggs, and certain plant-based proteins like soy and beans. It is also available as a dietary supplement for those looking to increase their intake for athletic performance or muscle recovery purposes. However, it's important to consult with a healthcare professional before starting any new supplement regimen.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Dexamethasone is a type of corticosteroid medication, which is a synthetic version of a natural hormone produced by the adrenal glands. It is often used to reduce inflammation and suppress the immune system in a variety of medical conditions, including allergies, asthma, rheumatoid arthritis, and certain skin conditions.

Dexamethasone works by binding to specific receptors in cells, which triggers a range of anti-inflammatory effects. These include reducing the production of chemicals that cause inflammation, suppressing the activity of immune cells, and stabilizing cell membranes.

In addition to its anti-inflammatory effects, dexamethasone can also be used to treat other medical conditions, such as certain types of cancer, brain swelling, and adrenal insufficiency. It is available in a variety of forms, including tablets, liquids, creams, and injectable solutions.

Like all medications, dexamethasone can have side effects, particularly if used for long periods of time or at high doses. These may include mood changes, increased appetite, weight gain, acne, thinning skin, easy bruising, and an increased risk of infections. It is important to follow the instructions of a healthcare provider when taking dexamethasone to minimize the risk of side effects.

Organ size refers to the volume or physical measurement of an organ in the body of an individual. It can be described in terms of length, width, and height or by using specialized techniques such as imaging studies (like CT scans or MRIs) to determine the volume. The size of an organ can vary depending on factors such as age, sex, body size, and overall health status. Changes in organ size may indicate various medical conditions, including growths, inflammation, or atrophy.

Anticarcinogenic agents are substances that prevent, inhibit or reduce the development of cancer. They can be natural or synthetic compounds that interfere with the process of carcinogenesis at various stages, such as initiation, promotion, and progression. Anticarcinogenic agents may work by preventing DNA damage, promoting DNA repair, reducing inflammation, inhibiting cell proliferation, inducing apoptosis (programmed cell death), or modulating immune responses.

Examples of anticarcinogenic agents include chemopreventive agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and retinoids; phytochemicals found in fruits, vegetables, and other plant-based foods; and medications used to treat cancer, such as chemotherapy, radiation therapy, and targeted therapies.

It is important to note that while some anticarcinogenic agents have been shown to be effective in preventing or reducing the risk of certain types of cancer, they may also have potential side effects and risks. Therefore, it is essential to consult with a healthcare professional before using any anticarcinogenic agent for cancer prevention or treatment purposes.

Experimental liver neoplasms refer to abnormal growths or tumors in the liver that are intentionally created or manipulated in a laboratory setting for the purpose of studying their development, progression, and potential treatment options. These experimental models can be established using various methods such as chemical induction, genetic modification, or transplantation of cancerous cells or tissues. The goal of this research is to advance our understanding of liver cancer biology and develop novel therapies for liver neoplasms in humans. It's important to note that these experiments are conducted under strict ethical guidelines and regulations to minimize harm and ensure the humane treatment of animals involved in such studies.

Carboxy-lyases are a class of enzymes that catalyze the removal of a carboxyl group from a substrate, often releasing carbon dioxide in the process. These enzymes play important roles in various metabolic pathways, such as the biosynthesis and degradation of amino acids, sugars, and other organic compounds.

Carboxy-lyases are classified under EC number 4.2 in the Enzyme Commission (EC) system. They can be further divided into several subclasses based on their specific mechanisms and substrates. For example, some carboxy-lyases require a cofactor such as biotin or thiamine pyrophosphate to facilitate the decarboxylation reaction, while others do not.

Examples of carboxy-lyases include:

1. Pyruvate decarboxylase: This enzyme catalyzes the conversion of pyruvate to acetaldehyde and carbon dioxide during fermentation in yeast and other organisms.
2. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO): This enzyme is essential for photosynthesis in plants and some bacteria, as it catalyzes the fixation of carbon dioxide into an organic molecule during the Calvin cycle.
3. Phosphoenolpyruvate carboxylase: Found in plants, algae, and some bacteria, this enzyme plays a role in anaplerotic reactions that replenish intermediates in the citric acid cycle. It catalyzes the conversion of phosphoenolpyruvate to oxaloacetate and inorganic phosphate.
4. Aspartate transcarbamylase: This enzyme is involved in the biosynthesis of pyrimidines, a class of nucleotides. It catalyzes the transfer of a carboxyl group from carbamoyl aspartate to carbamoyl phosphate, forming cytidine triphosphate (CTP) and fumarate.
5. Urocanase: Found in animals, this enzyme is involved in histidine catabolism. It catalyzes the conversion of urocanate to formiminoglutamate and ammonia.

Glutathione transferases (GSTs) are a group of enzymes involved in the detoxification of xenobiotics and endogenous compounds. They facilitate the conjugation of these compounds with glutathione, a tripeptide consisting of cysteine, glutamic acid, and glycine, which results in more water-soluble products that can be easily excreted from the body.

GSTs play a crucial role in protecting cells against oxidative stress and chemical injury by neutralizing reactive electrophilic species and peroxides. They are found in various tissues, including the liver, kidneys, lungs, and intestines, and are classified into several families based on their structure and function.

Abnormalities in GST activity have been associated with increased susceptibility to certain diseases, such as cancer, neurological disorders, and respiratory diseases. Therefore, GSTs have become a subject of interest in toxicology, pharmacology, and clinical research.

F344 is a strain code used to designate an outbred stock of rats that has been inbreeded for over 100 generations. The F344 rats, also known as Fischer 344 rats, were originally developed at the National Institutes of Health (NIH) and are now widely used in biomedical research due to their consistent and reliable genetic background.

Inbred strains, like the F344, are created by mating genetically identical individuals (siblings or parents and offspring) for many generations until a state of complete homozygosity is reached, meaning that all members of the strain have identical genomes. This genetic uniformity makes inbred strains ideal for use in studies where consistent and reproducible results are important.

F344 rats are known for their longevity, with a median lifespan of around 27-31 months, making them useful for aging research. They also have a relatively low incidence of spontaneous tumors compared to other rat strains. However, they may be more susceptible to certain types of cancer and other diseases due to their inbred status.

It's important to note that while F344 rats are often used as a standard laboratory rat strain, there can still be some genetic variation between individual animals within the same strain, particularly if they come from different suppliers or breeding colonies. Therefore, it's always important to consider the source and history of any animal model when designing experiments and interpreting results.

A cell-free system is a biochemical environment in which biological reactions can occur outside of an intact living cell. These systems are often used to study specific cellular processes or pathways, as they allow researchers to control and manipulate the conditions in which the reactions take place. In a cell-free system, the necessary enzymes, substrates, and cofactors for a particular reaction are provided in a test tube or other container, rather than within a whole cell.

Cell-free systems can be derived from various sources, including bacteria, yeast, and mammalian cells. They can be used to study a wide range of cellular processes, such as transcription, translation, protein folding, and metabolism. For example, a cell-free system might be used to express and purify a specific protein, or to investigate the regulation of a particular metabolic pathway.

One advantage of using cell-free systems is that they can provide valuable insights into the mechanisms of cellular processes without the need for time-consuming and resource-intensive cell culture or genetic manipulation. Additionally, because cell-free systems are not constrained by the limitations of a whole cell, they offer greater flexibility in terms of reaction conditions and the ability to study complex or transient interactions between biological molecules.

Overall, cell-free systems are an important tool in molecular biology and biochemistry, providing researchers with a versatile and powerful means of investigating the fundamental processes that underlie life at the cellular level.

Oxidoreductases are a class of enzymes that catalyze oxidation-reduction reactions, which involve the transfer of electrons from one molecule (the reductant) to another (the oxidant). These enzymes play a crucial role in various biological processes, including energy production, metabolism, and detoxification.

The oxidoreductase-catalyzed reaction typically involves the donation of electrons from a reducing agent (donor) to an oxidizing agent (acceptor), often through the transfer of hydrogen atoms or hydride ions. The enzyme itself does not undergo any permanent chemical change during this process, but rather acts as a catalyst to lower the activation energy required for the reaction to occur.

Oxidoreductases are classified and named based on the type of electron donor or acceptor involved in the reaction. For example, oxidoreductases that act on the CH-OH group of donors are called dehydrogenases, while those that act on the aldehyde or ketone groups are called oxidases. Other examples include reductases, peroxidases, and catalases.

Understanding the function and regulation of oxidoreductases is important for understanding various physiological processes and developing therapeutic strategies for diseases associated with impaired redox homeostasis, such as cancer, neurodegenerative disorders, and cardiovascular disease.

Alkaline phosphatase (ALP) is an enzyme found in various body tissues, including the liver, bile ducts, digestive system, bones, and kidneys. It plays a role in breaking down proteins and minerals, such as phosphate, in the body.

The medical definition of alkaline phosphatase refers to its function as a hydrolase enzyme that removes phosphate groups from molecules at an alkaline pH level. In clinical settings, ALP is often measured through blood tests as a biomarker for various health conditions.

Elevated levels of ALP in the blood may indicate liver or bone diseases, such as hepatitis, cirrhosis, bone fractures, or cancer. Therefore, physicians may order an alkaline phosphatase test to help diagnose and monitor these conditions. However, it is essential to interpret ALP results in conjunction with other diagnostic tests and clinical findings for accurate diagnosis and treatment.

Embryonic induction is a process that occurs during the development of a multicellular organism, where one group of cells in the embryo signals and influences the developmental fate of another group of cells. This interaction leads to the formation of specific structures or organs in the developing embryo. The signaling cells that initiate the process are called organizers, and they release signaling molecules known as morphogens that bind to receptors on the target cells and trigger a cascade of intracellular signals that ultimately lead to changes in gene expression and cell fate. Embryonic induction is a crucial step in the development of complex organisms and plays a key role in establishing the body plan and organizing the different tissues and organs in the developing embryo.

Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.

In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.

Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Apoptosis is a programmed and controlled cell death process that occurs in multicellular organisms. It is a natural process that helps maintain tissue homeostasis by eliminating damaged, infected, or unwanted cells. During apoptosis, the cell undergoes a series of morphological changes, including cell shrinkage, chromatin condensation, and fragmentation into membrane-bound vesicles called apoptotic bodies. These bodies are then recognized and engulfed by neighboring cells or phagocytic cells, preventing an inflammatory response. Apoptosis is regulated by a complex network of intracellular signaling pathways that involve proteins such as caspases, Bcl-2 family members, and inhibitors of apoptosis (IAPs).

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.

During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.

Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

Induction chemotherapy is a type of cancer treatment that involves the use of cytotoxic drugs to reduce the size of tumors prior to administering other forms of therapy, such as radiation therapy or surgery. The goal of induction chemotherapy is to eliminate as many cancer cells as possible and shrink the tumor to improve the chances of a successful outcome with subsequent treatments.

This approach is often used in the treatment of certain types of cancer, including lymphoma, leukemia, and testicular cancer, among others. The specific drugs used and the duration of treatment may vary depending on the type and stage of cancer being treated.

It's important to note that induction chemotherapy is a complex medical procedure that should be administered under the close supervision of an experienced oncologist. Patients undergoing this treatment may experience side effects, such as nausea, vomiting, fatigue, and hair loss, among others. However, these side effects can often be managed with supportive care and medications.

Remission induction is a treatment approach in medicine, particularly in the field of oncology and hematology. It refers to the initial phase of therapy aimed at reducing or eliminating the signs and symptoms of active disease, such as cancer or autoimmune disorders. The primary goal of remission induction is to achieve a complete response (disappearance of all detectable signs of the disease) or a partial response (a decrease in the measurable extent of the disease). This phase of treatment is often intensive and may involve the use of multiple drugs or therapies, including chemotherapy, immunotherapy, or targeted therapy. After remission induction, patients may receive additional treatments to maintain the remission and prevent relapse, known as consolidation or maintenance therapy.

'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.

The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.

It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

A cell line that is derived from tumor cells and has been adapted to grow in culture. These cell lines are often used in research to study the characteristics of cancer cells, including their growth patterns, genetic changes, and responses to various treatments. They can be established from many different types of tumors, such as carcinomas, sarcomas, and leukemias. Once established, these cell lines can be grown and maintained indefinitely in the laboratory, allowing researchers to conduct experiments and studies that would not be feasible using primary tumor cells. It is important to note that tumor cell lines may not always accurately represent the behavior of the original tumor, as they can undergo genetic changes during their time in culture.

BALB/c is an inbred strain of laboratory mouse that is widely used in biomedical research. The strain was developed at the Institute of Cancer Research in London by Henry Baldwin and his colleagues in the 1920s, and it has since become one of the most commonly used inbred strains in the world.

BALB/c mice are characterized by their black coat color, which is determined by a recessive allele at the tyrosinase locus. They are also known for their docile and friendly temperament, making them easy to handle and work with in the laboratory.

One of the key features of BALB/c mice that makes them useful for research is their susceptibility to certain types of tumors and immune responses. For example, they are highly susceptible to developing mammary tumors, which can be induced by chemical carcinogens or viral infection. They also have a strong Th2-biased immune response, which makes them useful models for studying allergic diseases and asthma.

BALB/c mice are also commonly used in studies of genetics, neuroscience, behavior, and infectious diseases. Because they are an inbred strain, they have a uniform genetic background, which makes it easier to control for genetic factors in experiments. Additionally, because they have been bred in the laboratory for many generations, they are highly standardized and reproducible, making them ideal subjects for scientific research.

Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.

The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.

Up-regulation is a term used in molecular biology and medicine to describe an increase in the expression or activity of a gene, protein, or receptor in response to a stimulus. This can occur through various mechanisms such as increased transcription, translation, or reduced degradation of the molecule. Up-regulation can have important functional consequences, for example, enhancing the sensitivity or response of a cell to a hormone, neurotransmitter, or drug. It is a normal physiological process that can also be induced by disease or pharmacological interventions.

Western blotting is a laboratory technique used in molecular biology to detect and quantify specific proteins in a mixture of many different proteins. This technique is commonly used to confirm the expression of a protein of interest, determine its size, and investigate its post-translational modifications. The name "Western" blotting distinguishes this technique from Southern blotting (for DNA) and Northern blotting (for RNA).

The Western blotting procedure involves several steps:

1. Protein extraction: The sample containing the proteins of interest is first extracted, often by breaking open cells or tissues and using a buffer to extract the proteins.
2. Separation of proteins by electrophoresis: The extracted proteins are then separated based on their size by loading them onto a polyacrylamide gel and running an electric current through the gel (a process called sodium dodecyl sulfate-polyacrylamide gel electrophoresis or SDS-PAGE). This separates the proteins according to their molecular weight, with smaller proteins migrating faster than larger ones.
3. Transfer of proteins to a membrane: After separation, the proteins are transferred from the gel onto a nitrocellulose or polyvinylidene fluoride (PVDF) membrane using an electric current in a process called blotting. This creates a replica of the protein pattern on the gel but now immobilized on the membrane for further analysis.
4. Blocking: The membrane is then blocked with a blocking agent, such as non-fat dry milk or bovine serum albumin (BSA), to prevent non-specific binding of antibodies in subsequent steps.
5. Primary antibody incubation: A primary antibody that specifically recognizes the protein of interest is added and allowed to bind to its target protein on the membrane. This step may be performed at room temperature or 4°C overnight, depending on the antibody's properties.
6. Washing: The membrane is washed with a buffer to remove unbound primary antibodies.
7. Secondary antibody incubation: A secondary antibody that recognizes the primary antibody (often coupled to an enzyme or fluorophore) is added and allowed to bind to the primary antibody. This step may involve using a horseradish peroxidase (HRP)-conjugated or alkaline phosphatase (AP)-conjugated secondary antibody, depending on the detection method used later.
8. Washing: The membrane is washed again to remove unbound secondary antibodies.
9. Detection: A detection reagent is added to visualize the protein of interest by detecting the signal generated from the enzyme-conjugated or fluorophore-conjugated secondary antibody. This can be done using chemiluminescent, colorimetric, or fluorescent methods.
10. Analysis: The resulting image is analyzed to determine the presence and quantity of the protein of interest in the sample.

Western blotting is a powerful technique for identifying and quantifying specific proteins within complex mixtures. It can be used to study protein expression, post-translational modifications, protein-protein interactions, and more. However, it requires careful optimization and validation to ensure accurate and reproducible results.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.

Transcriptional activation is the process by which a cell increases the rate of transcription of specific genes from DNA to RNA. This process is tightly regulated and plays a crucial role in various biological processes, including development, differentiation, and response to environmental stimuli.

Transcriptional activation occurs when transcription factors (proteins that bind to specific DNA sequences) interact with the promoter region of a gene and recruit co-activator proteins. These co-activators help to remodel the chromatin structure around the gene, making it more accessible for the transcription machinery to bind and initiate transcription.

Transcriptional activation can be regulated at multiple levels, including the availability and activity of transcription factors, the modification of histone proteins, and the recruitment of co-activators or co-repressors. Dysregulation of transcriptional activation has been implicated in various diseases, including cancer and genetic disorders.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Enzyme inhibition can refer to the inhibition of the expression of the enzyme by another molecule interference at the enzyme- ... Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an ... If the molecule induces enzymes that are responsible for its own metabolism, this is called auto-induction (or auto-inhibition ... the French molecular biologists François Jacob and Jacques Monod became the first to explain enzyme induction, in the context ...
Possible role of enzyme induction". Gastroenterology. 75 (3): 492-496. doi:10.1016/0016-5085(78)90856-9. PMID 680506. Neil ...
Migraine therapy by enzyme induction with proxibarbital]". Therapie der Gegenwart (in German). 115 (12): 2088-103. PMID 14412. ...
Brodie MJ, Mintzer S, Pack AM, Gidal BE, Vecht CJ, Schmidt D (January 2013). "Enzyme induction with antiepileptic drugs: cause ... Phenobarbital is a cytochrome P450 hepatic enzyme inducer. It binds transcription factor receptors that activate cytochrome ...
... levels can also be regulated by changing the rate of enzyme degradation.: 30.1.1 The opposite of enzyme induction is ... Alternatively, the enzyme can be sequestered near its substrate to activate the enzyme. For example, the enzyme can be soluble ... a low constant activity provided by one enzyme but an inducible high activity from a second enzyme. Enzymes determine what ... If an enzyme produces too much of one substance in the organism, that substance may act as an inhibitor for the enzyme at the ...
Safe S, Kohli J, Crawford A (April 1978). "FireMaster BP-6: Fractionation, Metabolic and Enzyme Induction Studies". ...
Conney, AH; Gilman, AG (1963). "Puromycin inhibition of enzyme induction by 3-methylcholanthrene and phenobarbital". The ... Cyclic AMP is formed from ATP by the enzymes adenylyl cyclase. In 1970 Martin Rodbell found that hormones did not directly ... Gilman, AG; Conney, AH (1963). "The induction of aminoazo dye N-demethylase in nonhepatic tissues by 3-methylcholanthrene". ... was a responsible for activating enzymes in the cell, and that cyclic AMP is produced only when hormones (the first messengers ...
Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells". Neurosci. Lett. 314 (1-2): 45-8. doi:10.1016/ ... This enzyme is a member of the cytochrome P450 (CYP) superfamily of enzymes. Like many other CYP enzymes that act on ... This enzyme has also been found at low quantities in the retina, where it performs the same function to a lesser degree. ... The ability for inhibition by various xenobiotics makes this enzyme a prime candidate for drug therapy for AD or other brain ...
Other early effects noted were peripheral neuropathy and liver enzyme induction. The ascertainment of other, possibly severe ...
The induction of xylanase enzymes varies between strains; in group D1 strains (49, H17c, 12) xylanase expression appears to be ... Most isolates are amylolytic and are able to degrade xylan by producing xylanolytic and esterase enzymes. ... enzymes. Several carbohydrate binding modules (CBM) have also been identified that are predicted to bind glycogen (CBM family ...
production of extracellular cellulolytic enzymes by cellulose induction. Antonie van Leeuwenhoek 87, (4) (05): 301-10 Saettler ... One enzyme, endopolygalacturonase, is a highly specialized cell wall-degrading enzyme which is critical for the growth of the ... In order to more easily ramify throughout the host tissue, the hyphae release enzymes which break down host-specific proteins. ... C. lindemuthianum releases large amounts of this enzyme, which not only weakens the cell wall by removing the polygalacturonan ...
Gaal AB, Neujahr HY (1981). "Induction of phenol-metabolizing enzymes in Trichosporon cutaneum". Arch. Microbiol. 130 (1): 54- ... This enzyme is also called maleolylacetate reductase. This enzyme participates in 3 metabolic pathways: gamma- ... NADH-dependent enzymes, Enzymes of unknown structure, All stub articles, EC 1.3 stubs). ... This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-CH group of donor with NAD+ or NADP+ ...
Phase II and I enzymes PXR carries out induction. Expression of PXR is mainly evident in the liver, testis, human embryonic ... Induction of PB in xenobiotic-metabolizes of cytochromes CYP2b undergoes a transcriptional process, thus raising mRNA levels. ... Research conducted in 1998 said that PXR was responsible for the induction of CYP3A and differences in the species in the ... This was explained by the induction of the CYP3A relationships obtained from the steroid structure-activity evaluation results ...
Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O (November 2020). "Inhibition and induction of CYP enzymes in humans: an update ... Altered Metabolism Some medications can either inhibit or induce key drug metabolizing enzymes or drug transporters, which when ...
1995). "Induction of ubiquitin-conjugating enzymes during terminal erythroid differentiation". Proc. Natl. Acad. Sci. U.S.A. 92 ... Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes ... Ubiquitin-conjugating enzyme E2 H is a protein that in humans is encoded by the UBE2H gene. The modification of proteins with ... This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein sequence is 100% identical to the ...
This procedure of enhancing the activity of the enzyme is known as enzyme induction. The evidence shows that there is in fact ... That same bovine enzyme has more than 70% homology with human placental enzyme. However, the human liver enzyme and the ... Due to the location of the enzyme, and the protein layout of the enzyme, the enzyme is in solution with a smaller amount of ... The optimal pH for the activity of the E. coli enzyme is 8.0 while the bovine enzyme optimum pH is slightly higher at 8.5. ...
... "c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction". Oncogene. 21 (34): ... "NF-kappa B p65 antagonizes IL-4 induction by c-maf in minimal change nephrotic syndrome". Journal of Immunology. 172 (1): 688- ...
"An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements ... "c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction". Oncogene. 21 (34): ... Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes. ... proteins negatively regulate antioxidant response element-mediated expression and antioxidant induction of the NAD(P)H:Quinone ...
Hence, there is no response to treatment with phenobarbital, which causes CYP450 enzyme induction. Most patients (type IA) have ...
Decker K, Bleeg H (1965). "Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans". ... This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as ... The systematic name of this enzyme class is (S)-6-hydroxynicotine:oxygen oxidoreductase. Other names in common use include L-6- ... In enzymology, a (S)-6-hydroxynicotine oxidase (EC 1.5.3.5) is an enzyme that catalyzes the chemical reaction (S)-6- ...
Decker K, Bleeg H (1965). "Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans". ... This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as ... As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 2BVF, 2BVG, and 2BVH. ... The systematic name of this enzyme class is (R)-6-hydroxynicotine:oxygen oxidoreductase. Other names in common use include D-6- ...
They were used to study drug metabolism and toxicity, including phase I and phase II enzyme metabolism, induction, and ... inhibition and induction of CYP enzymes in HepaRG cells". Toxicology in Vitro. 23 (4): 748-753. doi:10.1016/j.tiv.2009.03.008. ... The high reproducibility of the drug-induced metabolic enzyme levels between batches enables routine high-throughput analysis ... Anthérieu, Sébastien; Rogue, Alexandra; Fromenty, Bernard; Guillouzo, André; Robin, Marie‐Anne (June 2011). "Induction of ...
Nguyen Van Thoai Thome-Beau F, Olomucki A (1966). "[Induction and specificity of enzymes of the new catabolic arginine pathway ... Portal: Biology v t e (EC 3.5.3, Manganese enzymes, Enzymes of unknown structure, All stub articles, EC 3.5 stubs). ... This enzyme participates in urea cycle and metabolism of amino groups. It employs one cofactor, manganese. Mora J, Tarrab R, ... This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically ...
Finally, no inhibition or induction of cytochrome P450 enzymes was observed. Following a 100 mg dose of eluxadoline, the Cmax ...
Decker K, Bleeg H (1965). "Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans". ... Metal enzymes, Flavoproteins, Enzymes of unknown structure, All stub articles, Oxidoreductase stubs). ... This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with other ... In enzymology, a nicotine dehydrogenase (EC 1.5.99.4) is an enzyme that catalyzes the chemical reaction (S)-nicotine + acceptor ...
The function of the enzymes can either be stimulated (enzyme induction) or inhibited (enzyme inhibition). If a specific drug, ... An example of this is shown in the following table for the CYP1A2 enzyme, which is the most common enzyme found in the human ... The table shows the substrates (drugs metabolized by this enzyme) and the inductors and inhibitors of its activity: Enzyme ... If drug A is metabolized by a cytochrome P450 enzyme and drug B induces or increases the enzyme's activity, then blood plasma ...
This enzyme induction can be initiated by many natural or synthetic compounds, e.g., carcinogenic polycyclic hydrocarbons such ... Surprisingly, enzyme induction, several developmental effects and aversion to novel foods occur at similar dose levels in ... Therefore it has been suggested that dioxin effects be divided to type I effects (enzyme induction etc.) and type II effects ( ... Some of these low-dose effects can in fact be interpreted as protective rather than toxic (enzyme induction, aversion to novel ...
Estetrol shows minimal to no inhibition or induction of cytochrome P450 enzymes. In addition, estetrol undergoes minimal phase ... In addition, estetrol showed no affinity (>10 μM) for a set of 124 receptors and enzymes, with the sole exception of very weak ... Furthermore, estetrol showed no inhibition of the major cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 at ... and ethinylestradiol moderately inhibited the enzyme (by 45%). These findings suggest that estetrol has a low potential for ...
... shows potent induction potential of cytochrome P450 enzymes similarly to enzalutamide. It is a strong inducer of ... This change is considered to be likely due to CYP3A4 auto-induction. Approximately 65% of apalutamide is excreted in urine (1.2 ... A major active metabolite, N-desmethylapalutamide, is formed by these enzymes, with similar contribution of each of these ... elevated liver enzymes and hepatotoxicity have not been reported with apalutamide. Case reports of rare interstitial lung ...
The first is a side effect of the adaptive response in which the induction of metabolizing enzymes results in the production of ... The adaptive response is manifested as the induction of xenobiotic metabolizing enzymes. Evidence of this response was first ... Xenobiotic metabolizing enzymes help with the metabolic process by transforming and the excretion of chemicals. The most potent ... It was originally thought to function primarily as a sensor of xenobiotic chemicals and also as the regulator of enzymes such ...
Enzyme inhibition can refer to the inhibition of the expression of the enzyme by another molecule interference at the enzyme- ... Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an ... If the molecule induces enzymes that are responsible for its own metabolism, this is called auto-induction (or auto-inhibition ... the French molecular biologists François Jacob and Jacques Monod became the first to explain enzyme induction, in the context ...
Minimal Artificial Enzymes: Expanding the Application of Backdoor Induction through new Substrates and new Asymmetric ... These minimal artificial enzymes could find applications in asymmetric synthesis of drugs or drug intermediates produced by ... A beta-turn structure is proposed as key feature of chiral catalysts that resemble artificial enzymes with a minimal but ... The chirality is transmitted by backdoor induction via hydrogen bonding of distant pendant amino acids that represent the ...
Further studies of the induction of the liver microsomal drug-hydroxylating enzyme system by pretreatment of rats with various ... ENZYME-MEMBRANE RELATIONSHIP IN PHENOBARBITAL INDUCTION OF SYNTHESIS OF DRUG-METABOLIZING ENZYME SYSTEM AND PROLIFERATION OF ... FURTHER STUDIES ON THE INDUCTION OF THE DRUG-HYDROXYLATING ENZYME SYSTEM OF LIVER MICROSOMES Sten Orrenius Sten Orrenius ... Sten Orrenius; FURTHER STUDIES ON THE INDUCTION OF THE DRUG-HYDROXYLATING ENZYME SYSTEM OF LIVER MICROSOMES . J Cell Biol 1 ...
If induction of CYP3A4 enzymes is observed, the sponsor should also evaluate the induction potential of CYP2C enzymes (CYP2C8, ... Drug-Drug InteractionsEnzyme InductionEnzyme InhibitionMetabolite IdentificationReaction Phenotyping. Genomics & NGS ... Select 5 concentrations for cytotoxicity, 7 for mRNA induction,and 3 for enzyme activity induction ... Regulatory considerations for enzyme induction studies. These studies are recommended by both FDA and EMA drug-drug interaction ...
Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific ... "Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific ... Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific ... "Impact of adolescent nicotine exposure on adenylyl cyclase-mediated cell signaling: enzyme induction, neurotransmitter-specific ...
Click for meanings of enzyme induction, including synonyms, antonyms. ... enzyme induction meaning in Marathi मराठी is a translation of enzyme induction in Marathi मराठी dictionary. ... Marathi मराठी enzyme induction translation enzyme induction meaning enzyme induction definition enzyme induction antonym enzyme ... enzyme induction phrases with enzyme induction synonyms enzyme induction antonyms enzyme induction pronunciations. ...
Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as ... Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as ... Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as ... Indeed, monitoring of enzyme induction has led to the recognition or isolation of novel, potent chemopreventive agents such as ...
OCCUPATIONAL EXPOSURE TO HALOTHANE RESULTS IN ENZYME INDUCTION IN ANESTHETISTS P. Duvaldestin, M.D.; P. Duvaldestin, M.D. ... P. Duvaldestin, R. I. Mazze, Y. Nivoche, J. M. Desmonts; OCCUPATIONAL EXPOSURE TO HALOTHANE RESULTS IN ENZYME INDUCTION IN ... Occupational Exposure to Halothane Results in Enzyme Induction in Anesthetists Anesthesiology (January 1981) ...
Enzyme induction. As mentioned above, heme-oxygenase-one (HO-1) is the inducible form of the first enzyme involved in the ... The first enzyme in the catabolic cascade leading to bilirubin is heme oxygenase. A constitutive form and an inducible form are ... Induction of early meconium evacuation: is it effective in reducing the level of neonatal hyperbilirubinemia?. Am J Perinatol. ... This enzyme is activated by physiologic stressors, such as hypothermia, acidosis, hypoxia, and infection (odds ratio 20.6 in ...
... and induction of oxidative enzymes polyphenol oxidase (PPO) and peroxidase (POD) in sunflower plants through seed immersion in ... Induction of defensive enzymes in sunflower plants treated with agrochemicals against Macrophomina phaseolina ... Induction of défense enzymes in Trichoderma harzianum treated groundnut plants against Macrophomina phaseolina. Journal of ... This study was carried out for the estimation of polyphenols (TP) and induction of oxidative enzymes polyphenol oxidase (PPO) ...
Pleurotus sajar-caju secretes the major lignin modifying enzymes Laccase (Lac) and Manganese peroxidase (MnP) with low levels ... Induction of lignolytic enzymes by P. sajar-caju was tested in different farm agro wastes viz., sugarcane, banana, millets, ... Induction of lignolytic enzyme activities in different agro residues by the white rot fungi, Pleurotus sajar-caju. ... Thiribhuvanamala G, Kalaiselvi G, Parthasarathy S, Anusha B. Induction of lignolytic enzyme activities in different agro ...
Hepatic microsomal enzyme induction,. *Increased serum levels of liver-related enzymes indicative of possible hepatocellular ... The health implications of enzyme induction include the occurrence of disease secondary to increased metabolism of endogenous ... Exposure to PCBs can increase serum levels of hepatic enzymes and can induce microsomal enzyme function. ... an effect that is believed to be secondary to the induction of hepatic microsomal enzymes. Total bilirubin levels exhibit a ...
Enzyme Induction * Gluconeogenesis / drug effects * Liver / cytology* * Liver / metabolism * Rats * Tyrosine Transaminase / ... There was a marked induction of tyrosine aminotransferase (TAT) by dexamethasone, which was maintained for up to 72 hr ...
IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role ... IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the ... Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is ... In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), ...
N2 - The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. While this ... AB - The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. While this ... The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. While this group ... abstract = "The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. ...
Comparative study of combined co-enzyme Q10 and Clomiphene Citrate vs Clomiphene Citrate alone for ovulation induction in ... 2023). Comparative study of combined co-enzyme Q10 and Clomiphene Citrate vs Clomiphene Citrate alone for ovulation induction ... In group-A (CoQ10 plus Clomiphene citrate), successful ovulation induction was noted in 16 (23.5%) patients, showing that with ... the addition of CoQ10, the chances of ovulation induction increased.. Keywords: Co-enzyme Q10, Clomiphene Citrate, Ovulation ...
Dive into the research topics of Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: Effects on enzyme induction ... Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: Effects on enzyme induction and immunotoxicity. ...
Microsomal Enzyme Induction Preclinical studies have shown sertraline hydrochloride to induce hepatic microsomal enzymes. In ... Hepatobiliary disorders - elevated liver enzymes Immune system disorders - anaphylaxis Metabolism and nutrition disorders - ... clinical studies, sertraline hydrochloride was shown to induce hepatic enzymes minimally as determined by a small (5%) but ...
Enzyme induction Oxcarbazepine and its pharmacologically active metabolite (the monohydroxy derivative, MHD) are weak inducers ... The occurrence of liver tumours was most likely a consequence of the induction of hepatic microsomal enzymes; an inductive ... Enzyme inhibition Oxcarbazepine and MHD inhibit CYP2C19. Therefore, interactions could arise when co-administering high doses ... When initiating treatment with Trileptal or changing the dose, it may take 2 to 3 weeks to reach the new level of induction. ...
To cite: Boominathan, p63/p73 enhances the endothelial cell surface expression of ADP/AMP catabolic enzymes via induction of ... p63/p73 enhances the endothelial cell surface expression of ADP/AMP catabolic enzymes via induction of its target miRNA, 27/ ... p63/p73 enhances the endothelial cell surface expression of ADP/AMP catabolic enzymes via induction of its target miRNA, 27/ ...
Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase. GISAAA 31(6),8,1966. ... Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases. TOVEFN (1),29,1994. ... Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases. TOVEFN (1),29,1994. ... Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation ...
... the induction of Escherichia colis lac operon in response to a switch from glucose to lactose. How gene regulatory pathways ... Novick, A. & Weiner, M. Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566 (1957). ... A first attempt to measure the distribution of lac induction lag times in single cells was made by Boulineau et al.10, and a ... Tracking single-cell dynamics of lac operon induction. a Dynamics of growth and gene expression in lineages of single cells in ...
Hempel E, Böhm W, Carol W, Klinger G. [Enzyme induction by drugs and hormonal contraception]. Zentralbl Gynakol 1973;95:1451-7. ... A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion ... However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.. ... However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.. ...
Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 ... Am J Respir Cell Mol.... 2001. ...
Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 ... Am J Respir Cell Mol.... 2001. ...
These studies critically evaluated and characterized the principal enzymes responsible for drug metabolism. *Thesis: The Role ... In vitro tissue culture (induction, CaCo2) and in vivo animal models. Laboratory information management systems and GLP quality ... In vitro experiments included protocol development and analytical methodology for metabolic stability; P450 enzyme inhibition, ... induction, and identification; protein binding; blood to plasma partitioning *In vivo studies included oral and systemic ...
... sprout extract protected the liver from various types of xenobiotic substances through induction of detoxification enzymes and ... Pharmacological Actions : Hepatoprotective, Phase I Detoxification Enzyme Inducer, Phase II Detoxification Enzyme Inducer ... Pharmacological Actions : Hepatoprotective, Phase I Detoxification Enzyme Inducer, Phase II Detoxification Enzyme Inducer ... Pharmacological Actions : Antioxidants, Phase I Detoxification Enzyme Inducer, Phase II Detoxification Enzyme Inducer ...
  • Enzyme inhibition can refer to the inhibition of the expression of the enzyme by another molecule interference at the enzyme-level, basically with how the enzyme works. (wikipedia.org)
  • If the molecule induces enzymes that are responsible for its own metabolism, this is called auto-induction (or auto-inhibition if there is inhibition). (wikipedia.org)
  • Two aspects have been particularly taken into account: the changes or absence of changes in plasma/serum concentrations of concomitant drugs and the direct or indirect evidence of induction, inhibition or lack of effect on the six major human hepatic CYP isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), as well as on other CYP isozymes or enzyme systems. (nih.gov)
  • Events in the cellular transformation involved inhibition of normal differentiation, and induction of ornithine- decarboxylase, the rate limiting enzyme. (cdc.gov)
  • It induces enzymes such as CYP3A4 and inhibits enzymes such as CYP2C19 and those of the beta-oxidation pathway. (nih.gov)
  • The Induction of Two Similar Enzymes by One Inducer. (nih.gov)
  • Marshall Nirenberg argues that genetic information does not appear to be shared, but rather serves as an inducer for two similar enzymes in different metabolic pathways. (nih.gov)
  • Meanwhile, we also found that NBIF could up-regulate the expression of PPARα and PPARγ in hepatic cells, suggesting that the induction of UGT1A1 by NBIF was mainly mediated by PPARs. (frontiersin.org)
  • Brian Lake obtained a BSc in Biochemistry from the University of Surrey and then under the guidance of Professor D.V. Parke obtained a PhD in the field of induction of hepatic and extrahepatic xenobiotic metabolising enzymes. (thebts.org)
  • FireMaster BP-6: fractionation, metabolic and enzyme induction studies. (nih.gov)
  • UDP-glucuronosyltransferase 1A1 (UGT1A1) is an essential enzyme in mammals that is responsible for detoxification and metabolic clearance of the endogenous toxin bilirubin and a variety of xenobiotics, including some crucial therapeutic drugs. (frontiersin.org)
  • Lamotrigine appears to be a weak inducer of UGTs, whereas induction of CYP3A4 seems improbable as the compound does not change the concentrations of oral contraceptives or the urinary excretion of 6beta-hydroxycortisol. (nih.gov)
  • This study aims to find efficacious UGT1A1 inducer(s) from natural flavonoids, and to reveal the mechanism involved in up-regulating of this key conjugative enzyme by the flavonoid(s) with strong UGT1A1 induction activity. (frontiersin.org)
  • Stability of the microsomal monooxygenases during incubations for the liver microsomal assay with S-9 fractions of mouse liver under various inductions. (unibo.it)
  • Initiation of the induction of liver enzymes used for preparation S9 used in this study was 2 September 2019. (europa.eu)
  • 1999. Effect of carcinogen dose fractionation, diet and source of F344 rat on the induction of colonic aberrant crypts by 2-amino-3-methylimidazo[4,5-f]quinoline. . (oregonstate.edu)
  • Phase II detoxification enzymes are known to play essential roles in the detoxification and elimination of activated carcinogens during tumor initiation, while apoptosis is one of the most important chemopreventive targets for inhibiting tumor promotion in cancer. (kist.re.kr)
  • These data suggest that AHE and AHB act as bifunctional inducers and that their chemopreventive effects result from the biphasic induction of phase II detoxification enzymes and apoptosis. (kist.re.kr)
  • Another potential adverse effect associated with persistent induction of biotransformation enzymes, like UDP-glucuronyl transferases (UGTs) by PHAHs, is a long-term enhanced elimination of several important endogenous ligands such as vitamin A and thyroid hormones. (iwc.int)
  • Our results indicate that pharmacologically increased cellular concentrations of antioxidative enzymes might not necessarily exert radiomitigating short-term effects in IR-exposed PBMC. (uni-muenchen.de)
  • Up-regulation of phase 2 enzymes, including the glutathione transferases, can protect cells against carcinogens and has been documented to prevent carcinogen-induced tumors in a variety of animal models (7, 8). (brocon.co)
  • Proceedings: Study of enzyme induction in epileptic children. (bmj.com)
  • Thus, aberrant upregulation of the glycolytic enzyme PFKFB3 in neurons may contribute to CLN7 pathogenesis and targeting PFKFB3 could alleviate this and other lysosomal storage diseases. (nature.com)
  • Here, using the Cln7 ∆ex2 mouse model of CLN7 disease, we found an aberrant upregulation of pro-glycolytic enzyme PFKFB3 in neurons that may contribute to CLN7 pathogenesis. (nature.com)
  • We observed increased cellular levels of the antioxidative enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (quinone1) and mitochondrial superoxide dismutase 2 by immunoblotting. (uni-muenchen.de)
  • However, the increase of antioxidative enzymes could also be a result of a defensive cellular mechanism towards elevated ROS levels. (uni-muenchen.de)
  • Wistar rats: induction with 3-methylcholanthrene, corresponding control receiving corn oil), and four guinea pigs were treated with phenobarbital. (europa.eu)
  • The activity of the phase II enzyme UDP-glucuronosyltransferase towards linalool was enhanced by induction with phenobarbital in microsomes of both Wistar rats and guinea pigs. (europa.eu)
  • Induction with 3-methylcholanthrene in Wistar rats did not result in an enhancement of activity. (europa.eu)
  • These observations suggest that the biotin administration ameliorates abnormal glucose metabolism in diabetic patients, presumably by enhancing the activity of the biotin-dependent enzyme, pyruvate carboxylase, with a subsequent promotion of glucose utilization for the entry into the tricarboxylic acid cycle. (researchgate.net)
  • This induction is accompanied by, but not because of, increased intracellular glutathione synthesis. (brocon.co)
  • Cruciferae are known to contain high levels of the isothiocyanate sulforaphane, the most potent monofunctional phase 2 enzyme-inducing agent thus far identified (11). (brocon.co)
  • Among all the tested flavonoids, neobavaisoflavone (NBIF) displayed the most potent UGT1A1 induction activity, while its inductive effects were confirmed by both western blot and glucuronidation activity assays. (frontiersin.org)
  • The most common molecular genetic change in prostate cancer involves silencing of expression of GSTP13, a critical enzyme of carcinogen defense, through methylation of deoxycytidine residues in "CG islands" in the 5 regulatory region of the GSTP1 gene (4, 5). (brocon.co)
  • Quinone reductase enzymatic activity, a surrogate of global phase 2 enzyme activity, was assayed by the menadione-coupled reduction of tetrazolium dye. (brocon.co)
  • Sulforaphane and broccoli sprout extract potently induce quinone reductase activity in cultured prostate cells, and this induction appears to be mediated by increased transcription of the NQO-1 gene. (brocon.co)
  • Sulforaphane induces phase 2 enzyme expression and activity significantly in human prostatic cells. (brocon.co)
  • Phase 2-inducing agents have been reported to increase phase 2 enzyme activity through increased transcription at phase 2 enzyme gene loci (12). (brocon.co)
  • The study was designed to investigate the substrate specifities of the isofunctional Phase II enzyme UDP-glucuronosyltransferase (UDPGT) and to determine possible differences in the regulation. (europa.eu)
  • Our objective is to investigate the possible induction of manic symptoms by clarithromycin through two case reports and a review of the literature. (isciii.es)
  • In vivo genetic approach reveals elevated mitochondrial reactive oxygen species (mROS) in Cln7 ∆ex2 neurons that mediates glycolytic enzyme PFKFB3 activation and contributes to CLN7 pathogenesis. (nature.com)
  • Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. (oregonstate.edu)
  • Sulforaphane is known to bolster the defenses of cells against carcinogens through up-regulation of enzymes of carcinogen defense (phase 2 enzymes). (brocon.co)
  • We tested whether sulforaphane may act in prostatic cells by increasing phase 2 enzyme expression. (brocon.co)
  • In this study, the substrate specifities of the isofunctional Phase II enzyme UDP-glucuronosyltransferase (UDPGT) and possible differences in the regulation were investigated. (europa.eu)
  • Additional information on its enzyme inducing or inhibiting properties would be necessary, as data so far collected on its effect on the pharmacokinetics of other drugs are conflicting. (nih.gov)
  • Fulminant hepatitis might be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be increased as a consequence of the enzyme-inducing effect of rifampin and, possibly, other drugs administered for general anesthesia. (nih.gov)
  • The antipyrine kinetics results indicate that permethrin is capable or producing a dose-dependent marked enzyme-inducing effect. (unileon.es)
  • Being exemplified by the prediction of enzyme induction-associated drug-drug interaction, a method for predicting effect of small molecule drugs on pharmacokinetics of other or its own molecules was also developed. (nii.ac.jp)
  • Study of Enzyme Induction by Anesthetic Amounts Found in Ambient Air. (cdc.gov)
  • Sulforaphane also induces expression of -glutamylcysteine synthetase light subunit but not the heavy subunit, and this induction is associated with moderate increases in intracellular glutathione levels. (brocon.co)
  • The best medium for enzyme production was Mandels medium A with initial pH 5.3, supplemented with 0.3% mutan and 0.05% peptone and inoculated with 20% of the 72-h mycelium as inoculum. (scielo.br)
  • We also found that the AHE and AHB induced apoptosis, as evidenced by phosphatidylserine externalization, an increase in the sub-G0/G1 content, chromatin condensation, poly(ADP-ribose) polymerase cleavage, and p53 induction. (kist.re.kr)
  • Enzyme induction is a process in which a molecule (e.g. a drug) induces (i.e. initiates or enhances) the expression of an enzyme. (wikipedia.org)