Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.
A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.
An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.
An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.
Pyrimidinones are heterocyclic organic compounds that consist of a pyrimidine ring fused with a ketone group, which have significant applications in medicinal chemistry due to their wide range of biological activities, including antibacterial, antiviral, and anticancer properties.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
A group of compounds that contain the structure SO2NH2.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
Peptides composed of between two and twelve amino acids.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.
An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.
A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
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.
Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
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.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
A proteinase inhibitor found in various BODILY SECRETIONS that coat mucosal surfaces such as SEMINAL PLASMA; CERVICAL MUCUS; and bronchial secretions. It plays a role in protecting epithelial tissues from LEUKOCYTE-derived serine proteases such as NEUTROPHIL ELASTASE.
Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
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 order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).
Established cell cultures that have the potential to propagate indefinitely.
Peptides and proteins found in BODILY SECRETIONS and BODY FLUIDS that are PROTEASE INHIBITORS. They play a role in INFLAMMATION, tissue repair and innate immunity (IMMUNITY, INNATE) by inhibiting endogenous proteinases such as those produced by LEUKOCYTES and exogenous proteases such as those produced by invading microorganisms.
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
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.
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.
2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.
A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
A prokaryotic ATP-dependent protease that plays a role in the degradation of many abnormal proteins. It is a tetramer of 87-kDa subunits, each of which contains a proteolytic site and a ATP-binding site.
A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Keto-pyrans.
An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.
A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
A cell line derived from cultured tumor cells.
Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. They are usually comprised of large multi-subunit assemblies. The domains can occur within a single peptide chain or on distinct subunits.
A low-molecular-weight protein (minimum molecular weight 8000) which has the ability to inhibit trypsin as well as chymotrypsin at independent binding sites. It is characterized by a high cystine content and the absence of glycine.
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.
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 rate dynamics in chemical or physical systems.
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.
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.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
An oligopeptide produced by various bacteria which acts as a protease inhibitor.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.

Issues in the treatment of active tuberculosis in human immunodeficiency virus-infected patients. (1/1724)

Most HIV-infected patients with tuberculosis can be treated satisfactorily with standard regimens with expectations of good results. Treatment of tuberculosis in these patients has been complicated by the introduction of HAART, which relies on drugs that interfere with the most potent class of antituberculous medications. Rifampin-free regimens or regimens that employ rifabutin may be acceptable strategies for patients who are receiving protease inhibitors, although these regimens have not been rigorously evaluated in patients with AIDS. At present, there is good reason to believe that a 6-month course of a rifabutin-containing regimen or a 9-12-month course of a regimen of streptomycin, isoniazid, and pyrazinamide should be adequate therapy for most patients with drug-susceptible disease. As the treatment of HIV infection with antiretroviral agents evolves, the treatment of tuberculosis in patients with AIDS is likely to evolve as well. This will require careful coordination of antituberculosis and antiretroviral therapies.  (+info)

Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells. (2/1724)

8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection.  (+info)

Metabolic characterization of a tripeptide human immunodeficiency virus type 1 protease inhibitor, KNI-272, in rat liver microsomes. (3/1724)

KNI-272 is a tripeptide protease inhibitor for treating human immunodeficiency virus type 1 (HIV-1). In in vitro stability studies using rat tissue homogenates, KNI-272 concentrations in the liver, kidney, and brain decreased significantly with time. Moreover, in tissue distribution studies, KNI-272 distributed highly to the liver, kidney, and small intestine in vivo. From these results and reported physiological parameters such as the tissue volume and tissue blood flow rate, we considered the liver to be the main organ which takes part in the metabolic elimination of KNI-272. Then the hepatic metabolism of KNI-272 was more thoroughly investigated by using rat liver microsomes. KNI-272 was metabolized in the rat liver microsomes, and five metabolites were found. The initial metabolic rate constant (kmetabolism) tended to decrease when the KNI-272 concentration in microsomal suspensions increased. The calculated Michaelis-Menten constant (K(m)) and the maximum velocity of KNI-272 metabolism (Vmax), after correction for the unbound drug concentration, were 1.12 +/- 0.09 micrograms/ml (1.68 +/- 0.13 microM) and 0.372 +/- 0.008 microgram/mg of protein/min (0.558 +/- 0.012 nmol/mg of protein per min), respectively. The metabolic clearance (CLint,metabo), calculated as Vmax/K(m), was 0.332 ml/mg of protein per min. Moreover, by using selective cytochrome P-450 inhibitors and recombinant human CYP3A4 fractions, KNI-272 was determined to be metabolized mainly by the CYP3A isoform. In addition, ketoconazole, a representative CYP3A inhibitor, inhibited KNI-272 metabolism competitively, and the inhibition constant (Ki) was 4.32 microM.  (+info)

Effects of human immunodeficiency virus type 1 resistance to protease inhibitors on reverse transcriptase processing, activity, and drug sensitivity. (4/1724)

Human immunodeficiency virus type 1 (HIV-1) variants resistant to protease inhibitors often display a reduced replicative capacity as a result of an impairment of protease function. Such fitness-impaired viruses display Gag precursor maturation defects. Here, we report that some protease inhibitor-resistant viruses also display abnormalities in the processing of reverse transcriptase (RT) by the protease. In three recombinant viruses carrying resistant protease sequences from patient plasma, we observed a marked decrease in the amount of mature RT subunits and of particle-associated RT activity compared to their parental pretherapy counterparts. We investigated the possibility that a decrease in the amount of particle-associated mature RT could affect the sensitivity of the corresponding virus to RT inhibitors. We observed a twofold increase of sensitivity to zidovudine (AZT) when a virus which carried AZT mutations was processed by a resistant protease. Interestingly, the presence of AZT-resistance mutations partially rescued the replication defect associated with the mutated protease. The interplay between resistance to protease inhibitors and to RT inhibitors described here may be relevant to the therapeutic control of HIV-1 infection.  (+info)

Molecular mechanisms of resistance: free energy calculations of mutation effects on inhibitor binding to HIV-1 protease. (5/1724)

The changes in the inhibitor binding constants due to the mutation of isoleucine to valine at position 84 of HIV-1 protease are calculated using molecular dynamics simulations. The calculations are done for three potent inhibitors--KNI-272, L-735,524 (indinavir or MK-639), and Ro 31-8959 (saquinavir). The calculations agree with the experimental data both in terms of an overall trend and in the magnitude of the resulting free energy change. HIV-1 protease is a homodimer, so each mutation causes two changes in the enzyme. The decrease in the binding free energy from each mutated side chain differs among the three inhibitors and correlates well with the size of the cavities induced in the protein interior near the mutated residue. The cavities are created as a result of a mutation to a smaller side chain, but the cavities are less than would be predicted from the wild-type structures, indicating that there is significant relaxation to partially fill the cavities.  (+info)

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. (6/1724)

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were +info)

Genotypic resistance and the treatment of HIV-1 infection in Espirito Santo, Brazil. (7/1724)

Before December 1997, in Espirito Santo, Brazil, combination antiretroviral therapy was used without routine virologic or immunologic monitoring. To examine consequences of therapy in this setting, clinical information, human immunodeficiency virus type 1 (HIV-1) RNA levels, CD4 cell counts, and protease and reverse transcriptase sequences were determined for consecutive HIV-1-infected outpatients. Of 48 treatment-naive individuals, 11 were started on therapy for HIV-related symptoms; however, 44 (92%) had an RNA level >20,000 copies/mL, a CD4 cell count <500/mm3, or symptoms. Eighteen (51%) of 35 patients on therapy had an RNA level >20,000 copies/mL. Nucleoside-resistance mutations were observed in 21 (68%) of 31 nucleoside-experienced subjects. Protease mutations necessary for high-level protease inhibitor (PI) resistance were present together with permissive mutations in 3 of 10 PI-experienced patients. Inability to identify high-risk individuals and to detect virologic failure may limit the effectiveness of antiretroviral drug programs and may promote the spread of drug resistance where virologic and immunologic monitoring are not available.  (+info)

Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. (8/1724)

The relative replicative fitness of human immunodeficiency virus type 1 (HIV-1) mutants selected by different protease inhibitors (PIs) in vivo was determined. Each mutant was compared to wild type (WT), NL4-3, in the absence of drugs by several methods, including clonal genotyping of cultures infected with two competing viral variants, kinetics of viral antigen production, and viral infectivity/virion particle ratios. A nelfinavir-selected protease D30N substitution substantially decreased replicative capacity relative to WT, while a saquinavir-selected L90M substitution moderately decreased fitness. The D30N mutant virus was also outcompeted by the L90M mutant in the absence of drugs. A major natural polymorphism of the HIV-1 protease, L63P, compensated well for the impairment of fitness caused by L90M but only slightly improved the fitness of D30N. Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and L10R/M46I/L63P/V82T/I84V were just as fit as WT. These results indicate that the mutations which are usually initially selected by nelfinavir and saquinavir, D30N and L90M, respectively, impair fitness. However, additional mutations may improve the replicative capacity of these and other drug-resistant mutants. Hypotheses based on the greater fitness impairment of the nelfinavir-selected D30N mutant are suggested to explain observations that prolonged responses to delayed salvage regimens, including alternate PIs, may be relatively common after nelfinavir failure.  (+info)

HIV Protease Inhibitors are a class of antiretroviral medications used in the treatment of HIV infection. They work by blocking the activity of the HIV protease enzyme, which is necessary for the virus to replicate and infect new cells. By inhibiting this enzyme, the medication prevents the virus from maturing and assembling into new infectious particles.

HIV protease inhibitors are often used in combination with other antiretroviral drugs as part of a highly active antiretroviral therapy (HAART) regimen. This approach has been shown to effectively suppress viral replication, reduce the amount of virus in the bloodstream (viral load), and improve the health and longevity of people living with HIV.

Examples of HIV protease inhibitors include saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, fosamprenavir, atazanavir, darunavir, and tipranavir. These medications are usually taken orally in the form of tablets or capsules, and may be prescribed alone or in combination with other antiretroviral drugs.

It is important to note that HIV protease inhibitors can have significant side effects, including gastrointestinal symptoms such as nausea, diarrhea, and abdominal pain, as well as metabolic changes such as increased cholesterol and triglyceride levels. Therefore, regular monitoring of liver function, lipid levels, and other health parameters is necessary to ensure safe and effective use of these medications.

Nelfinavir is a medication that belongs to a class of antiretroviral drugs called protease inhibitors. It is used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). Nelfinavir works by blocking the activity of HIV protease, an enzyme that is necessary for the replication of the virus. By inhibiting this enzyme, nelfinavir prevents the virus from multiplying and thus slows down the progression of the disease.

Here's a medical definition of Nelfinavir:

"Nelfinavir mesylate is a synthetic peptidomimetic inhibitor of the HIV-1 protease, an enzyme essential for the processing of viral gag and gag-pol polyproteins, reverse transcriptase, and integrase. Nelfinavir is used in combination with other antiretroviral agents for the treatment of HIV infection and AIDS."

It's important to note that nelfinavir is not a cure for HIV or AIDS, but it can help manage the disease by reducing the amount of virus in the body and improving the immune system function. As with any medication, nelfinavir has potential side effects and risks, so it should be taken under the guidance and supervision of a healthcare provider.

Ritonavir is an antiretroviral medication used in the treatment and prevention of HIV/AIDS. It is a protease inhibitor, which works by blocking the action of protease, an enzyme that the virus needs to multiply. By doing this, Ritonavir helps to reduce the amount of HIV in the body, keeping it at a low level and preventing the disease from progressing.

Ritonavir is often used in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART). It is also sometimes used at lower doses to boost the levels of other protease inhibitors in the body, a practice known as "pharmacologic boosting."

It's important to note that Ritonavir does not cure HIV/AIDS, but it can help people with HIV live longer, healthier lives. As with all medications, Ritonavir can have side effects, and it may interact with other drugs, so it's important to take it exactly as prescribed by a healthcare provider.

HIV Protease is a crucial enzyme that plays a significant role in the replication cycle of the Human Immunodeficiency Virus (HIV). It is responsible for cleaving or cutting specific long protein chains, produced during the translation of viral RNA, into smaller functional proteins. These proteins are essential for the formation of new virus particles.

The HIV Protease enzyme functions like a pair of molecular scissors, recognizing and cutting particular amino acid sequences in these polyprotein chains. By inhibiting this enzyme's activity with antiretroviral drugs known as protease inhibitors, the production of mature, infectious viral particles can be effectively prevented, which is a crucial component of highly active antiretroviral therapy (HAART) for managing HIV infection and reducing the risk of transmitting the virus to others.

Indinavir is an antiretroviral medication used in the treatment and management of HIV (Human Immunodeficiency Virus) infection. It belongs to a class of drugs known as protease inhibitors, which work by blocking the action of protease enzymes that are necessary for the HIV virus to replicate. By inhibiting this process, indinavir helps prevent the spread of HIV in the body and reduces the risk of developing AIDS (Acquired Immunodeficiency Syndrome).

Indinavir is often prescribed as part of a combination therapy regimen with other antiretroviral drugs. It is available in capsule form and is typically taken several times a day, usually on an empty stomach. As with all medications, indinavir can have side effects, which may include nausea, diarrhea, headache, and changes in liver function. Regular monitoring of blood tests is necessary to ensure that the drug is working effectively and not causing any harmful side effects.

It's important to note that while antiretroviral therapy can help manage HIV infection and improve quality of life, it does not cure the disease. Therefore, it is essential for individuals with HIV to continue taking their medications as prescribed and to follow up regularly with their healthcare provider.

Saquinavir is an antiretroviral medication used in the treatment and management of HIV (Human Immunodeficiency Virus) infection. It is a type of protease inhibitor, which works by blocking the action of protease, an enzyme that the virus needs to multiply. By inhibiting this enzyme, saquinavir helps prevent the virus from replicating and slows down the progression of HIV to AIDS (Acquired Immunodeficiency Syndrome).

Saquinavir is often used in combination with other antiretroviral drugs as part of a highly active antiretroviral therapy (HAART) regimen. It is important to note that saquinavir does not cure HIV or AIDS, but it can help reduce the amount of virus in the body and improve the immune system function, reducing the risk of opportunistic infections and other complications associated with HIV/AIDS.

As with any medication, saquinavir can have side effects, including gastrointestinal symptoms such as nausea, diarrhea, and abdominal pain, as well as headaches, rash, and elevated liver enzymes. It is essential to take saquinavir exactly as prescribed by a healthcare provider and to report any side effects or changes in health status promptly.

Lopinavir is an antiretroviral medication used in the treatment and management of HIV (Human Immunodeficiency Virus) infection. It is a protease inhibitor, which works by blocking the action of protease, an enzyme that the virus needs to multiply. Lopinavir is often prescribed in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART). The medication is available under the brand name Kaletra, which is a fixed-dose combination of lopinavir and ritonavir.

It's important to note that while lopinavir can help manage HIV infection and reduce the risk of transmission, it does not cure the disease. Regular adherence to the medication regimen is necessary to maintain its effectiveness and prevent the development of drug-resistant strains of the virus.

Pyrimidinones are a class of heterocyclic organic compounds that contain a pyrimidine ring fused with a ketone group. The basic structure of a pyrimidinone consists of two nitrogen atoms and four carbon atoms in a six-membered ring, with a carbonyl (C=O) group attached to one of the carbon atoms.

In a medical context, pyrimidinones are important because many naturally occurring and synthetic compounds that contain this structure have been found to have biological activity. For example, some pyrimidinones have antiviral, antibacterial, or anticancer properties, making them useful in the development of new drugs for various medical conditions.

One well-known drug that contains a pyrimidinone ring is the antiviral medication Ribavirin, which is used to treat hepatitis C and certain viral hemorrhagic fevers. Other pyrimidinones are being studied for their potential therapeutic benefits in areas such as cancer therapy, neuroprotection, and inflammation.

Protease inhibitors are a class of antiviral drugs that are used to treat infections caused by retroviruses, such as the human immunodeficiency virus (HIV), which is responsible for causing AIDS. These drugs work by blocking the activity of protease enzymes, which are necessary for the replication and multiplication of the virus within infected cells.

Protease enzymes play a crucial role in the life cycle of retroviruses by cleaving viral polyproteins into functional units that are required for the assembly of new viral particles. By inhibiting the activity of these enzymes, protease inhibitors prevent the virus from replicating and spreading to other cells, thereby slowing down the progression of the infection.

Protease inhibitors are often used in combination with other antiretroviral drugs as part of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS. Common examples of protease inhibitors include saquinavir, ritonavir, indinavir, and atazanavir. While these drugs have been successful in improving the outcomes of people living with HIV/AIDS, they can also cause side effects such as nausea, diarrhea, headaches, and lipodystrophy (changes in body fat distribution).

Carbamates are a group of organic compounds that contain the carbamate functional group, which is a carbon atom double-bonded to oxygen and single-bonded to a nitrogen atom (> N-C=O). In the context of pharmaceuticals and agriculture, carbamates are a class of drugs and pesticides that have carbamate as their core structure.

Carbamate insecticides work by inhibiting the enzyme acetylcholinesterase, which is responsible for breaking down the neurotransmitter acetylcholine in the synapses of the nervous system. When this enzyme is inhibited, acetylcholine accumulates in the synaptic cleft, leading to overstimulation of the nervous system and ultimately causing paralysis and death in insects.

Carbamate drugs are used for a variety of medical indications, including as anticonvulsants, muscle relaxants, and psychotropic medications. They work by modulating various neurotransmitter systems in the brain, such as GABA, glutamate, and dopamine. Carbamates can also be used as anti- parasitic agents, such as ivermectin, which is effective against a range of parasites including nematodes, arthropods, and some protozoa.

It's important to note that carbamate pesticides can be toxic to non-target organisms, including humans, if not used properly. Therefore, it's essential to follow all safety guidelines when handling or using these products.

HIV (Human Immunodeficiency Virus) infection is a viral illness that progressively attacks and weakens the immune system, making individuals more susceptible to other infections and diseases. The virus primarily infects CD4+ T cells, a type of white blood cell essential for fighting off infections. Over time, as the number of these immune cells declines, the body becomes increasingly vulnerable to opportunistic infections and cancers.

HIV infection has three stages:

1. Acute HIV infection: This is the initial stage that occurs within 2-4 weeks after exposure to the virus. During this period, individuals may experience flu-like symptoms such as fever, fatigue, rash, swollen glands, and muscle aches. The virus replicates rapidly, and the viral load in the body is very high.
2. Chronic HIV infection (Clinical latency): This stage follows the acute infection and can last several years if left untreated. Although individuals may not show any symptoms during this phase, the virus continues to replicate at low levels, and the immune system gradually weakens. The viral load remains relatively stable, but the number of CD4+ T cells declines over time.
3. AIDS (Acquired Immunodeficiency Syndrome): This is the most advanced stage of HIV infection, characterized by a severely damaged immune system and numerous opportunistic infections or cancers. At this stage, the CD4+ T cell count drops below 200 cells/mm3 of blood.

It's important to note that with proper antiretroviral therapy (ART), individuals with HIV infection can effectively manage the virus, maintain a healthy immune system, and significantly reduce the risk of transmission to others. Early diagnosis and treatment are crucial for improving long-term health outcomes and reducing the spread of HIV.

Sulfonamides are a group of synthetic antibacterial drugs that contain the sulfonamide group (SO2NH2) in their chemical structure. They are bacteriostatic agents, meaning they inhibit bacterial growth rather than killing them outright. Sulfonamides work by preventing the bacteria from synthesizing folic acid, which is essential for their survival.

The first sulfonamide drug was introduced in the 1930s and since then, many different sulfonamides have been developed with varying chemical structures and pharmacological properties. They are used to treat a wide range of bacterial infections, including urinary tract infections, respiratory tract infections, skin and soft tissue infections, and ear infections.

Some common sulfonamide drugs include sulfisoxazole, sulfamethoxazole, and trimethoprim-sulfamethoxazole (a combination of a sulfonamide and another antibiotic called trimethoprim). While sulfonamides are generally safe and effective when used as directed, they can cause side effects such as rash, nausea, and allergic reactions. It is important to follow the prescribing physician's instructions carefully and to report any unusual symptoms or side effects promptly.

Anti-HIV agents are a class of medications specifically designed to treat HIV (Human Immunodeficiency Virus) infection. These drugs work by interfering with various stages of the HIV replication cycle, preventing the virus from infecting and killing CD4+ T cells, which are crucial for maintaining a healthy immune system.

There are several classes of anti-HIV agents, including:

1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs): These drugs act as faulty building blocks that the virus incorporates into its genetic material, causing the replication process to halt. Examples include zidovudine (AZT), lamivudine (3TC), and tenofovir.
2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): These medications bind directly to the reverse transcriptase enzyme, altering its shape and preventing it from functioning properly. Examples include efavirenz, nevirapine, and rilpivirine.
3. Protease Inhibitors (PIs): These drugs target the protease enzyme, which is responsible for cleaving viral polyproteins into functional components. By inhibiting this enzyme, PIs prevent the formation of mature, infectious virus particles. Examples include atazanavir, darunavir, and lopinavir.
4. Integrase Strand Transfer Inhibitors (INSTIs): These medications block the integrase enzyme, which is responsible for inserting the viral genetic material into the host cell's DNA. By inhibiting this step, INSTIs prevent the virus from establishing a permanent infection within the host cell. Examples include raltegravir, dolutegravir, and bictegravir.
5. Fusion/Entry Inhibitors: These drugs target different steps of the viral entry process, preventing HIV from infecting CD4+ T cells. Examples include enfuvirtide (T-20), maraviroc, and ibalizumab.
6. Post-Attachment Inhibitors: This class of medications prevents the virus from attaching to the host cell's receptors, thereby inhibiting infection. Currently, there is only one approved post-attachment inhibitor, fostemsavir.

Combination therapy using multiple classes of antiretroviral drugs has been shown to effectively suppress viral replication and improve clinical outcomes in people living with HIV. Regular adherence to the prescribed treatment regimen is crucial for maintaining an undetectable viral load and reducing the risk of transmission.

Oligopeptides are defined in medicine and biochemistry as short chains of amino acids, typically containing fewer than 20 amino acid residues. These small peptides are important components in various biological processes, such as serving as signaling molecules, enzyme inhibitors, or structural elements in some proteins. They can be found naturally in foods and may also be synthesized for use in medical research and therapeutic applications.

Serine proteinase inhibitors, also known as serine protease inhibitors or serpins, are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins in a process called proteolysis. Serine proteinases are important in many biological processes such as blood coagulation, fibrinolysis, inflammation and cell death. The inhibition of these enzymes by serpin proteins is an essential regulatory mechanism to maintain the balance and prevent uncontrolled proteolytic activity that can lead to diseases.

Serpins work by forming a covalent complex with their target serine proteinases, irreversibly inactivating them. The active site of serpins contains a reactive center loop (RCL) that mimics the protease's target protein sequence and acts as a bait for the enzyme. When the protease cleaves the RCL, it gets trapped within the serpin structure, leading to its inactivation.

Serpin proteinase inhibitors play crucial roles in various physiological processes, including:

1. Blood coagulation and fibrinolysis regulation: Serpins such as antithrombin, heparin cofactor II, and protease nexin-2 control the activity of enzymes involved in blood clotting and dissolution to prevent excessive or insufficient clot formation.
2. Inflammation modulation: Serpins like α1-antitrypsin, α2-macroglobulin, and C1 inhibitor regulate the activity of proteases released during inflammation, protecting tissues from damage.
3. Cell death regulation: Some serpins, such as PI-9/SERPINB9, control apoptosis (programmed cell death) by inhibiting granzyme B, a protease involved in this process.
4. Embryonic development and tissue remodeling: Serpins like plasminogen activator inhibitor-1 (PAI-1) and PAI-2 regulate the activity of enzymes involved in extracellular matrix degradation during embryonic development and tissue remodeling.
5. Neuroprotection: Serpins such as neuroserpin protect neurons from damage by inhibiting proteases released during neuroinflammation or neurodegenerative diseases.

Dysregulation of serpins has been implicated in various pathological conditions, including thrombosis, emphysema, Alzheimer's disease, and cancer. Understanding the roles of serpins in these processes may provide insights into potential therapeutic strategies for treating these diseases.

I'm sorry for any confusion, but "Pyridines" is not a medical term. It is a chemical term that refers to a class of organic compounds with the chemical structure of a six-membered ring containing one nitrogen atom and five carbon atoms (heterocyclic aromatic compound).

In a biological or medical context, pyridine derivatives can be found in various natural and synthetic substances. For example, some medications contain pyridine rings as part of their chemical structure. However, "Pyridines" itself is not a medical term or condition.

HIV-1 (Human Immunodeficiency Virus type 1) is a species of the retrovirus genus that causes acquired immunodeficiency syndrome (AIDS). It is primarily transmitted through sexual contact, exposure to infected blood or blood products, and from mother to child during pregnancy, childbirth, or breastfeeding. HIV-1 infects vital cells in the human immune system, such as CD4+ T cells, macrophages, and dendritic cells, leading to a decline in their numbers and weakening of the immune response over time. This results in the individual becoming susceptible to various opportunistic infections and cancers that ultimately cause death if left untreated. HIV-1 is the most prevalent form of HIV worldwide and has been identified as the causative agent of the global AIDS pandemic.

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.

HIV (Human Immunodeficiency Virus) is a species of lentivirus (a subgroup of retrovirus) that causes HIV infection and over time, HIV infection can lead to AIDS (Acquired Immunodeficiency Syndrome). This virus attacks the immune system, specifically the CD4 cells, also known as T cells, which are a type of white blood cell that helps coordinate the body's immune response. As HIV destroys these cells, the body becomes more vulnerable to other infections and diseases. It is primarily spread through bodily fluids like blood, semen, vaginal fluids, and breast milk.

It's important to note that while there is no cure for HIV, with proper medical care, HIV can be controlled. Treatment for HIV is called antiretroviral therapy (ART). If taken as prescribed, this medicine reduces the amount of HIV in the body to a very low level, which keeps the immune system working and prevents illness. This treatment also greatly reduces the risk of transmission.

Organic Cation Transporter 1 (OCT1) is a protein that belongs to the solute carrier family 22 (SLC22A). It is primarily expressed in the liver and plays an essential role in the uptake and elimination of various organic cations, including many drugs, from the systemic circulation into hepatocytes. OCT1 also transports some endogenous substances such as neurotransmitters and hormones. Mutations or variants in the OCT1 gene can affect drug response and disposition, making it an important factor to consider in personalized medicine.

P-glycoprotein (P-gp) is a type of membrane transport protein that plays a crucial role in the efflux (extrusion) of various substrates, including drugs and toxins, out of cells. It is also known as multidrug resistance protein 1 (MDR1).

P-gp is encoded by the ABCB1 gene and is primarily located on the apical membrane of epithelial cells in several tissues, such as the intestine, liver, kidney, and blood-brain barrier. Its main function is to protect these organs from harmful substances by actively pumping them out of the cells and back into the lumen or bloodstream.

In the context of pharmacology, P-gp can contribute to multidrug resistance (MDR) in cancer cells. When overexpressed, P-gp can reduce the intracellular concentration of various anticancer drugs, making them less effective. This has led to extensive research on inhibitors of P-gp as potential adjuvants for cancer therapy.

In summary, P-glycoprotein is a vital efflux transporter that helps maintain homeostasis by removing potentially harmful substances from cells and can impact drug disposition and response in various tissues, including the intestine, liver, kidney, and blood-brain barrier.

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.

Antiretroviral Therapy, Highly Active (HAART) is a medical treatment regimen used to manage HIV infection. It involves the combination of three or more antiretroviral drugs from at least two different classes, aiming to maximally suppress viral replication and prevent the development of drug resistance. The goal of HAART is to reduce the amount of HIV in the body to undetectable levels, preserve immune function, and improve quality of life for people living with HIV. Commonly used antiretroviral classes include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and fusion inhibitors.

Serine endopeptidases are a type of enzymes that cleave peptide bonds within proteins (endopeptidases) and utilize serine as the nucleophilic amino acid in their active site for catalysis. These enzymes play crucial roles in various biological processes, including digestion, blood coagulation, and programmed cell death (apoptosis). Examples of serine endopeptidases include trypsin, chymotrypsin, thrombin, and elastase.

Peptide hydrolases, also known as proteases or peptidases, are a group of enzymes that catalyze the hydrolysis of peptide bonds in proteins and peptides. They play a crucial role in various biological processes such as protein degradation, digestion, cell signaling, and regulation of various physiological functions. Based on their catalytic mechanism and the specificity for the peptide bond, they are classified into several types, including serine proteases, cysteine proteases, aspartic proteases, and metalloproteases. These enzymes have important clinical applications in the diagnosis and treatment of various diseases, such as cancer, viral infections, and inflammatory disorders.

"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.

Drug resistance, viral, refers to the ability of a virus to continue replicating in the presence of antiviral drugs that are designed to inhibit or stop its growth. This occurs when the virus mutates and changes its genetic makeup in such a way that the drug can no longer effectively bind to and inhibit the function of its target protein, allowing the virus to continue infecting host cells and causing disease.

Viral drug resistance can develop due to several factors, including:

1. Mutations in the viral genome that alter the structure or function of the drug's target protein.
2. Changes in the expression levels or location of the drug's target protein within the virus-infected cell.
3. Activation of alternative pathways that allow the virus to replicate despite the presence of the drug.
4. Increased efflux of the drug from the virus-infected cell, reducing its intracellular concentration and effectiveness.

Viral drug resistance is a significant concern in the treatment of viral infections such as HIV, hepatitis B and C, herpes simplex virus, and influenza. It can lead to reduced treatment efficacy, increased risk of treatment failure, and the need for more toxic or expensive drugs. Therefore, it is essential to monitor viral drug resistance during treatment and adjust therapy accordingly to ensure optimal outcomes.

Secretory Leukocyte Protease Inhibitor (SLPI) is a protein that belongs to the family of serine protease inhibitors. It is primarily produced by the epithelial cells of various tissues, including the respiratory and gastrointestinal tracts, as well as the genital mucosa. SLPI functions as an important defense mechanism against inflammation and infection by inhibiting the activity of proteolytic enzymes released by neutrophils and other immune cells during the inflammatory response. These enzymes can cause tissue damage if they are not properly regulated, so SLPI plays a crucial role in maintaining the integrity and health of the epithelial barrier. In addition to its anti-inflammatory effects, SLPI has also been shown to have antimicrobial properties against a variety of pathogens, including bacteria, viruses, and fungi.

Adipocytes are specialized cells that comprise adipose tissue, also known as fat tissue. They are responsible for storing energy in the form of lipids, particularly triglycerides, and releasing energy when needed through a process called lipolysis. There are two main types of adipocytes: white adipocytes and brown adipocytes. White adipocytes primarily store energy, while brown adipocytes dissipate energy as heat through the action of uncoupling protein 1 (UCP1).

In addition to their role in energy metabolism, adipocytes also secrete various hormones and signaling molecules that contribute to whole-body homeostasis. These include leptin, adiponectin, resistin, and inflammatory cytokines. Dysregulation of adipocyte function has been implicated in the development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease.

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.

Glucose Transporter Type 4 (GLUT4) is a type of glucose transporter protein that plays a crucial role in regulating insulin-mediated glucose uptake into cells, particularly in muscle and fat tissues. GLUT4 is primarily located in intracellular vesicles within these cell types and moves to the plasma membrane upon stimulation by insulin or muscle contraction, facilitating the influx of glucose into the cell. Dysfunction in GLUT4 regulation has been implicated in various metabolic disorders, including type 2 diabetes and insulin resistance.

Endopeptidases are a type of enzyme that breaks down proteins by cleaving peptide bonds inside the polypeptide chain. They are also known as proteinases or endoproteinases. These enzymes work within the interior of the protein molecule, cutting it at specific points along its length, as opposed to exopeptidases, which remove individual amino acids from the ends of the protein chain.

Endopeptidases play a crucial role in various biological processes, such as digestion, blood coagulation, and programmed cell death (apoptosis). They are classified based on their catalytic mechanism and the structure of their active site. Some examples of endopeptidase families include serine proteases, cysteine proteases, aspartic proteases, and metalloproteases.

It is important to note that while endopeptidases are essential for normal physiological functions, they can also contribute to disease processes when their activity is unregulated or misdirected. For instance, excessive endopeptidase activity has been implicated in the pathogenesis of neurodegenerative disorders, cancer, and inflammatory conditions.

Pepstatins are a group of naturally occurring cyclic peptides that inhibit aspartic proteases, a type of enzyme that breaks down proteins. They are isolated from various actinomycete species of Streptomyces and Actinosynnema. Pepstatins are often used in laboratory research to study the function of aspartic proteases and as tools to probe the mechanism of action of these enzymes. In addition, pepstatins have been explored for their potential therapeutic use in various diseases, including cancer, viral infections, and cardiovascular disease. However, they have not yet been approved for clinical use.

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.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

High-performance liquid chromatography (HPLC) is a type of chromatography that separates and analyzes compounds based on their interactions with a stationary phase and a mobile phase under high pressure. The mobile phase, which can be a gas or liquid, carries the sample mixture through a column containing the stationary phase.

In HPLC, the mobile phase is a liquid, and it is pumped through the column at high pressures (up to several hundred atmospheres) to achieve faster separation times and better resolution than other types of liquid chromatography. The stationary phase can be a solid or a liquid supported on a solid, and it interacts differently with each component in the sample mixture, causing them to separate as they travel through the column.

HPLC is widely used in analytical chemistry, pharmaceuticals, biotechnology, and other fields to separate, identify, and quantify compounds present in complex mixtures. It can be used to analyze a wide range of substances, including drugs, hormones, vitamins, pigments, flavors, and pollutants. HPLC is also used in the preparation of pure samples for further study or use.

HIV seropositivity is a term used to describe a positive result on an HIV antibody test. This means that the individual has developed antibodies against the Human Immunodeficiency Virus (HIV), indicating that they have been infected with the virus. However, it's important to note that this does not necessarily mean that the person has AIDS, as there can be a long period between HIV infection and the development of AIDS.

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.

Secretory proteinase inhibitory proteins (SPIPs) are a group of proteins that function to regulate the activity of proteinases, which are enzymes that break down other proteins. SPIPs are produced by various cell types and secreted into extracellular spaces, where they help maintain the balance between protein degradation and synthesis.

Proteinases play crucial roles in many physiological processes, including tissue remodeling, wound healing, and immune defense. However, uncontrolled or excessive proteinase activity can lead to tissue damage and disease. SPIPs help prevent this by inhibiting the activity of specific proteinases, thereby protecting tissues from unwanted proteolysis.

Examples of SPIPs include:

1. Alpha-1 antitrypsin (AAT): A serine proteinase inhibitor that primarily inhibits neutrophil elastase and protects lung tissue from damage during inflammation.
2. Secretory leukocyte protease inhibitor (SLPI): A serine proteinase inhibitor that inhibits several proteinases, including elastase, cathepsin G, and trypsin. SLPI is produced by epithelial cells and has anti-inflammatory properties.
3. Elafin: A serine proteinase inhibitor mainly expressed in the skin and mucous membranes that inhibits neutrophil elastase, proteinase 3, and trypsin.
4. Tissue inhibitors of metalloproteinases (TIMPs): A family of proteins that inhibit matrix metalloproteinases (MMPs), which are involved in extracellular matrix remodeling.
5. Cystatins: A group of proteins that inhibit cysteine proteinases, which play a role in various physiological and pathological processes, including inflammation, immune response, and cancer.

Dysregulation of SPIPs has been implicated in several diseases, such as emphysema, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and cancer.

Trypsin inhibitors are substances that inhibit the activity of trypsin, an enzyme that helps digest proteins in the small intestine. Trypsin inhibitors can be found in various foods such as soybeans, corn, and raw egg whites. In the case of soybeans, trypsin inhibitors are denatured and inactivated during cooking and processing.

In a medical context, trypsin inhibitors may be used therapeutically to regulate excessive trypsin activity in certain conditions such as pancreatitis, where there is inflammation of the pancreas leading to the release of activated digestive enzymes, including trypsin, into the pancreas and surrounding tissues. By inhibiting trypsin activity, these inhibitors can help reduce tissue damage and inflammation.

SERPINs are an acronym for "serine protease inhibitors." They are a group of proteins that inhibit serine proteases, which are enzymes that cut other proteins. SERPINs are found in various tissues and body fluids, including blood, and play important roles in regulating biological processes such as inflammation, blood clotting, and cell death. They do this by forming covalent complexes with their target proteases, thereby preventing them from carrying out their proteolytic activities. Mutations in SERPIN genes have been associated with several genetic disorders, including emphysema, cirrhosis, and dementia.

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).

Cysteine proteases are a type of enzymes that cleave peptide bonds in proteins, and they require a cysteine residue in their active site to do so. These enzymes play important roles in various biological processes, including protein degradation, cell signaling, and inflammation. They can be found in various tissues and organisms, including humans, where they are involved in many physiological and pathological conditions.

Cysteine proteases are characterized by a conserved catalytic mechanism that involves a nucleophilic attack on the peptide bond carbonyl carbon by the thiolate anion of the cysteine residue, resulting in the formation of an acyl-enzyme intermediate. This intermediate is then hydrolyzed to release the cleaved protein fragments.

Some examples of cysteine proteases include cathepsins, caspases, and calpains, which are involved in various cellular processes such as apoptosis, autophagy, and signal transduction. Dysregulation of these enzymes has been implicated in several diseases, including cancer, neurodegenerative disorders, and infectious diseases. Therefore, cysteine proteases have emerged as important therapeutic targets for the development of new drugs to treat these conditions.

Multidrug Resistance-Associated Proteins (MRPs) are a subfamily of ATP-binding cassette (ABC) transporter proteins that play a crucial role in the efflux of various substrates, including drugs and organic anions, out of cells. They are located in the plasma membrane of many cell types, including epithelial cells in the liver, intestine, kidney, and blood-brain barrier.

MRPs are known to transport a wide range of molecules, such as glutathione conjugates, bilirubin, bile acids, and various clinical drugs. One of the most well-known MRPs is MRP1 (ABCC1), which was initially identified in drug-resistant tumor cells. MRP1 can confer resistance to chemotherapeutic agents by actively pumping them out of cancer cells, thereby reducing their intracellular concentration and effectiveness.

The activity of MRPs can have significant implications for the pharmacokinetics and pharmacodynamics of drugs, as they can affect drug absorption, distribution, metabolism, and excretion (ADME). Understanding the function and regulation of MRPs is essential for developing strategies to overcome multidrug resistance in cancer therapy and optimizing drug dosing regimens in various clinical settings.

Deoxyglucose is a glucose molecule that has had one oxygen atom removed, resulting in the absence of a hydroxyl group (-OH) at the 2' position of the carbon chain. It is used in research and medical settings as a metabolic tracer to study glucose uptake and metabolism in cells and organisms.

Deoxyglucose can be taken up by cells through glucose transporters, but it cannot be further metabolized by glycolysis or other glucose-utilizing pathways. This leads to the accumulation of deoxyglucose within the cell, which can interfere with normal cellular processes and cause toxicity in high concentrations.

In medical research, deoxyglucose is sometimes labeled with radioactive isotopes such as carbon-14 or fluorine-18 to create radiolabeled deoxyglucose (FDG), which can be used in positron emission tomography (PET) scans to visualize and measure glucose uptake in tissues. This technique is commonly used in cancer imaging, as tumors often have increased glucose metabolism compared to normal tissue.

Caspases are a family of protease enzymes that play essential roles in programmed cell death, also known as apoptosis. These enzymes are produced as inactive precursors and are activated when cells receive signals to undergo apoptosis. Once activated, caspases cleave specific protein substrates, leading to the characteristic morphological changes and DNA fragmentation associated with apoptotic cell death. Caspases also play roles in other cellular processes, including inflammation and differentiation. There are two types of caspases: initiator caspases (caspase-2, -8, -9, and -10) and effector caspases (caspase-3, -6, and -7). Initiator caspases are activated in response to various apoptotic signals and then activate the effector caspases, which carry out the proteolytic cleavage of cellular proteins. Dysregulation of caspase activity has been implicated in a variety of diseases, including neurodegenerative disorders, ischemic injury, and cancer.

Cysteine endopeptidases are a type of enzymes that cleave peptide bonds within proteins. They are also known as cysteine proteases or cysteine proteinases. These enzymes contain a catalytic triad consisting of three amino acids: cysteine, histidine, and aspartate. The thiol group (-SH) of the cysteine residue acts as a nucleophile and attacks the carbonyl carbon of the peptide bond, leading to its cleavage.

Cysteine endopeptidases play important roles in various biological processes, including protein degradation, cell signaling, and inflammation. They are involved in many physiological and pathological conditions, such as apoptosis, immune response, and cancer. Some examples of cysteine endopeptidases include cathepsins, caspases, and calpains.

It is important to note that these enzymes require a reducing environment to maintain the reduced state of their active site cysteine residue. Therefore, they are sensitive to oxidizing agents and inhibitors that target the thiol group. Understanding the structure and function of cysteine endopeptidases is crucial for developing therapeutic strategies that target these enzymes in various diseases.

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.

Cysteine proteinase inhibitors are a type of molecule that bind to and inhibit the activity of cysteine proteases, which are enzymes that cleave proteins at specific sites containing the amino acid cysteine. These inhibitors play important roles in regulating various biological processes, including inflammation, immune response, and programmed cell death (apoptosis). They can also have potential therapeutic applications in diseases where excessive protease activity contributes to pathology, such as cancer, arthritis, and neurodegenerative disorders. Examples of cysteine proteinase inhibitors include cystatins, kininogens, and serpins.

Reverse Transcriptase Inhibitors (RTIs) are a class of antiretroviral drugs that are primarily used in the treatment and management of HIV (Human Immunodeficiency Virus) infection. They work by inhibiting the reverse transcriptase enzyme, which is essential for the replication of HIV.

HIV is a retrovirus, meaning it has an RNA genome and uses a unique enzyme called reverse transcriptase to convert its RNA into DNA. This process is necessary for the virus to integrate into the host cell's genome and replicate. Reverse Transcriptase Inhibitors interfere with this process by binding to the reverse transcriptase enzyme, preventing it from converting the viral RNA into DNA.

RTIs can be further divided into two categories: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). NRTIs are analogs of the building blocks of DNA, which get incorporated into the growing DNA chain during replication, causing termination of the chain. NNRTIs bind directly to the reverse transcriptase enzyme, causing a conformational change that prevents it from functioning.

By inhibiting the reverse transcriptase enzyme, RTIs can prevent the virus from replicating and reduce the viral load in an infected individual, thereby slowing down the progression of HIV infection and AIDS (Acquired Immunodeficiency Syndrome).

The term "Area Under Curve" (AUC) is commonly used in the medical field, particularly in the analysis of diagnostic tests or pharmacokinetic studies. The AUC refers to the mathematical calculation of the area between a curve and the x-axis in a graph, typically representing a concentration-time profile.

In the context of diagnostic tests, the AUC is used to evaluate the performance of a test by measuring the entire two-dimensional area underneath the receiver operating characteristic (ROC) curve, which plots the true positive rate (sensitivity) against the false positive rate (1-specificity) at various threshold settings. The AUC ranges from 0 to 1, where a higher AUC indicates better test performance:

* An AUC of 0.5 suggests that the test is no better than chance.
* An AUC between 0.7 and 0.8 implies moderate accuracy.
* An AUC between 0.8 and 0.9 indicates high accuracy.
* An AUC greater than 0.9 signifies very high accuracy.

In pharmacokinetic studies, the AUC is used to assess drug exposure over time by calculating the area under a plasma concentration-time curve (AUC(0-t) or AUC(0-\∞)) following drug administration. This value can help determine dosing regimens and evaluate potential drug interactions:

* AUC(0-t): Represents the area under the plasma concentration-time curve from time zero to the last measurable concentration (t).
* AUC(0-\∞): Refers to the area under the plasma concentration-time curve from time zero to infinity, which estimates total drug exposure.

Molecular structure, in the context of biochemistry and molecular biology, refers to the arrangement and organization of atoms and chemical bonds within a molecule. It describes the three-dimensional layout of the constituent elements, including their spatial relationships, bond lengths, and angles. Understanding molecular structure is crucial for elucidating the functions and reactivities of biological macromolecules such as proteins, nucleic acids, lipids, and carbohydrates. Various experimental techniques, like X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM), are employed to determine molecular structures at atomic resolution, providing valuable insights into their biological roles and potential therapeutic targets.

Protease nexins are a group of proteins that regulate the activity of proteases, which are enzymes that break down other proteins. Proteases play important roles in various biological processes, including blood clotting, immune response, and cell death. However, uncontrolled or excessive protease activity can lead to harmful effects, such as tissue damage and disease progression.

Protease nexins function by forming stable complexes with specific proteases, thereby inhibiting their activity. These complexes also serve as a reservoir of inactive proteases that can be rapidly activated when needed. Protease nexins are involved in various physiological and pathological processes, such as inflammation, neurodegeneration, and cancer.

One well-known example of a protease nexin is the tissue plasminogen activator (tPA) - neuroserpin complex. Neuroserpin is a serine protease inhibitor that forms a complex with tPA, an enzyme that plays a critical role in breaking down blood clots. By forming this complex, neuroserpin regulates the activity of tPA and prevents excessive fibrinolysis, which can lead to bleeding disorders. Mutations in the gene encoding neuroserpin have been associated with familial dementia with Lewy bodies, a form of neurodegenerative disorder.

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.

Protein-kinase B, also known as AKT, is a group of intracellular proteins that play a crucial role in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. The AKT family includes three isoforms: AKT1, AKT2, and AKT3, which are encoded by the genes PKBalpha, PKBbeta, and PKBgamma, respectively.

Proto-oncogene proteins c-AKT refer to the normal, non-mutated forms of these proteins that are involved in the regulation of cell growth and survival under physiological conditions. However, when these genes are mutated or overexpressed, they can become oncogenes, leading to uncontrolled cell growth and cancer development.

Activation of c-AKT occurs through a signaling cascade that begins with the binding of extracellular ligands such as insulin-like growth factor 1 (IGF-1) or epidermal growth factor (EGF) to their respective receptors on the cell surface. This triggers a series of phosphorylation events that ultimately lead to the activation of c-AKT, which then phosphorylates downstream targets involved in various cellular processes.

In summary, proto-oncogene proteins c-AKT are normal intracellular proteins that play essential roles in regulating cell growth and survival under physiological conditions. However, their dysregulation can contribute to cancer development and progression.

Alpha 1-antitrypsin (AAT, or α1-antiproteinase, A1AP) is a protein that is primarily produced by the liver and released into the bloodstream. It belongs to a group of proteins called serine protease inhibitors, which help regulate inflammation and protect tissues from damage caused by enzymes involved in the immune response.

Alpha 1-antitrypsin is particularly important for protecting the lungs from damage caused by neutrophil elastase, an enzyme released by white blood cells called neutrophils during inflammation. In the lungs, AAT binds to and inhibits neutrophil elastase, preventing it from degrading the extracellular matrix and damaging lung tissue.

Deficiency in alpha 1-antitrypsin can lead to chronic obstructive pulmonary disease (COPD) and liver disease. The most common cause of AAT deficiency is a genetic mutation that results in abnormal folding and accumulation of the protein within liver cells, leading to reduced levels of functional AAT in the bloodstream. This condition is called alpha 1-antitrypsin deficiency (AATD) and can be inherited in an autosomal codominant manner. Individuals with severe AATD may require augmentation therapy with intravenous infusions of purified human AAT to help prevent lung damage.

Aspartic acid endopeptidases are a type of enzyme that cleave peptide bonds within proteins. They are also known as aspartyl proteases or aspartic proteinases. These enzymes contain two catalytic aspartic acid residues in their active site, which work together to hydrolyze the peptide bond.

Aspartic acid endopeptidases play important roles in various biological processes, including protein degradation, processing, and activation. They are found in many organisms, including viruses, bacteria, fungi, plants, and animals. Some well-known examples of aspartic acid endopeptidases include pepsin, cathepsin D, and HIV protease.

Pepsin is a digestive enzyme found in the stomach that helps break down proteins in food. Cathepsin D is a lysosomal enzyme that plays a role in protein turnover and degradation within cells. HIV protease is an essential enzyme for the replication of the human immunodeficiency virus (HIV), which causes AIDS. Inhibitors of HIV protease are used as antiretroviral drugs to treat HIV infection.

Biological transport refers to the movement of molecules, ions, or solutes across biological membranes or through cells in living organisms. This process is essential for maintaining homeostasis, regulating cellular functions, and enabling communication between cells. There are two main types of biological transport: passive transport and active transport.

Passive transport does not require the input of energy and includes:

1. Diffusion: The random movement of molecules from an area of high concentration to an area of low concentration until equilibrium is reached.
2. Osmosis: The diffusion of solvent molecules (usually water) across a semi-permeable membrane from an area of lower solute concentration to an area of higher solute concentration.
3. Facilitated diffusion: The assisted passage of polar or charged substances through protein channels or carriers in the cell membrane, which increases the rate of diffusion without consuming energy.

Active transport requires the input of energy (in the form of ATP) and includes:

1. Primary active transport: The direct use of ATP to move molecules against their concentration gradient, often driven by specific transport proteins called pumps.
2. Secondary active transport: The coupling of the movement of one substance down its electrochemical gradient with the uphill transport of another substance, mediated by a shared transport protein. This process is also known as co-transport or counter-transport.

Aprotinin is a medication that belongs to a class of drugs called serine protease inhibitors. It works by inhibiting the activity of certain enzymes in the body that can cause tissue damage and bleeding. Aprotinin is used in medical procedures such as heart bypass surgery to reduce blood loss and the need for blood transfusions. It is administered intravenously and its use is typically stopped a few days after the surgical procedure.

Aprotinin was first approved for use in the United States in 1993, but its use has been restricted or withdrawn in many countries due to concerns about its safety. In 2006, a study found an increased risk of kidney damage and death associated with the use of aprotinin during heart bypass surgery, leading to its withdrawal from the market in Europe and Canada. However, it is still available for use in the United States under a restricted access program.

It's important to note that the use of aprotinin should be carefully considered and discussed with the healthcare provider, taking into account the potential benefits and risks of the medication.

Insulin resistance is a condition in which the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. In response to this decreased sensitivity, the pancreas produces more insulin to help glucose enter the cells. However, over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to high levels of glucose in the blood and potentially resulting in type 2 diabetes, prediabetes, or other health issues such as metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease. Insulin resistance is often associated with obesity, physical inactivity, and genetic factors.

I'm sorry for any confusion, but "Protease La" doesn't seem to be a standard term in medicine or biochemistry. It's possible that there might be a misunderstanding or a typo in the term. Proteases are enzymes that break down proteins into smaller peptides or individual amino acids. If you have more context or if you meant a different term, please provide additional information so I can give a more accurate response.

Lipodystrophy is a medical condition characterized by abnormal distribution or absence of fat (adipose tissue) in the body. It can lead to metabolic complications such as insulin resistance, diabetes mellitus, high levels of fats in the blood (dyslipidemia), and liver disease. There are different types of lipodystrophy, including congenital generalized lipodystrophy, acquired generalized lipodystrophy, and partial lipodystrophy, which can affect different parts of the body and have varying symptoms and causes.

Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.

Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.

Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.

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.

Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).

Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.

Substrate specificity can be categorized as:

1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.

Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.

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.

I believe there might be a misunderstanding in your question. "Pyrones" is not a medical term, but rather a chemical term used to describe a class of organic compounds known as lactones with a characteristic eight-membered ring. These compounds are found in various natural sources such as plants and fungi, and some have been studied for their potential biological activities.

However, if you meant "pyrexia" instead of "pyrones," then I can provide the medical definition:

Pyrexia is a term used to describe an abnormally elevated body temperature, also known as fever. In adults, a core body temperature of 100.4°F (38°C) or higher is generally considered indicative of pyrexia. Fever is often a response to an infection or inflammation in the body and can be part of the immune system's effort to combat pathogens.

Tosyllysine Chloromethyl Ketone (TLCK) is not a medical term, but a chemical compound used in biochemical research. It is often used as an irreversible inhibitor of serine proteases, a type of enzyme that cuts other proteins. TLCK modifies the active site of these enzymes, rendering them inactive. This property makes it useful in studying the role of specific proteases in various biological processes.

Gabexate is a medicinal drug that belongs to the class of agents known as serine protease inhibitors. It is used in the treatment and prevention of inflammation and damage to tissues caused by various surgical procedures, pancreatitis, and other conditions associated with the activation of proteolytic enzymes.

Gabexate works by inhibiting the activity of certain enzymes such as trypsin, chymotrypsin, and thrombin, which play a key role in the inflammatory response and blood clotting cascade. By doing so, it helps to reduce the release of inflammatory mediators, prevent further tissue damage, and promote healing.

Gabexate is available in various forms, including injectable solutions and enteric-coated tablets, and its use is typically reserved for clinical settings under the supervision of a healthcare professional. As with any medication, it should be used only under the direction of a qualified medical practitioner, and its potential benefits and risks should be carefully weighed against those of other available treatment options.

"Drug design" is the process of creating and developing a new medication or therapeutic agent to treat or prevent a specific disease or condition. It involves identifying potential targets within the body, such as proteins or enzymes that are involved in the disease process, and then designing small molecules or biologics that can interact with these targets to produce a desired effect.

The drug design process typically involves several stages, including:

1. Target identification: Researchers identify a specific molecular target that is involved in the disease process.
2. Lead identification: Using computational methods and high-throughput screening techniques, researchers identify small molecules or biologics that can interact with the target.
3. Lead optimization: Researchers modify the chemical structure of the lead compound to improve its ability to interact with the target, as well as its safety and pharmacokinetic properties.
4. Preclinical testing: The optimized lead compound is tested in vitro (in a test tube or petri dish) and in vivo (in animals) to evaluate its safety and efficacy.
5. Clinical trials: If the preclinical testing is successful, the drug moves on to clinical trials in humans to further evaluate its safety and efficacy.

The ultimate goal of drug design is to create a new medication that is safe, effective, and can be used to improve the lives of patients with a specific disease or condition.

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.

ATP-dependent proteases are a type of protein complex that play a crucial role in maintaining cellular homeostasis by breaking down damaged or misfolded proteins. They use the energy from ATP (adenosine triphosphate) hydrolysis to unfold and degrade these proteins into smaller peptides or individual amino acids, which can then be recycled or disposed of by the cell.

These proteases are essential for a variety of cellular processes, including protein quality control, regulation of cell signaling pathways, and clearance of damaged organelles. They are also involved in various cellular responses to stress, such as the unfolded protein response (UPR) and autophagy.

There are several different types of ATP-dependent proteases, including the 26S proteasome, which is responsible for degrading most intracellular proteins, and the Clp/Hsp100 family of proteases, which are involved in protein folding and disaggregation. Dysregulation of ATP-dependent proteases has been implicated in various diseases, including neurodegenerative disorders, cancer, and infectious diseases.

The Trypsin Inhibitor, Bowman-Birk Soybean is a type of protease inhibitor that is found in soybeans. It is named after its discoverer, Henry B. Bowman, and the location where it was first discovered, the Birk farm in Ohio. This protein inhibits the activity of trypsin, an enzyme that helps digest proteins in the body.

The Bowman-Birk Trypsin Inhibitor (BBTI) is a small protein with a molecular weight of approximately 8000 Da and consists of two inhibitory domains, each containing a reactive site for trypsin. This dual inhibitory property allows BBTI to inhibit both trypsin and chymotrypsin, another proteolytic enzyme.

BBTI has been studied extensively due to its potential health benefits. It has been shown to have anti-cancer properties, as it can inhibit the growth of cancer cells and induce apoptosis (programmed cell death). Additionally, BBTI may also have anti-inflammatory effects and has been shown to protect against oxidative stress.

However, it is important to note that excessive consumption of BBTI may interfere with protein digestion and absorption in the body, as it inhibits trypsin activity. Therefore, soybeans and soybean-derived products should be consumed in moderation as part of a balanced diet.

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.

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.

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.

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.

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.

Insulin is a hormone produced by the beta cells of the pancreatic islets, primarily in response to elevated levels of glucose in the circulating blood. It plays a crucial role in regulating blood glucose levels and facilitating the uptake and utilization of glucose by peripheral tissues, such as muscle and adipose tissue, for energy production and storage. Insulin also inhibits glucose production in the liver and promotes the storage of excess glucose as glycogen or triglycerides.

Deficiency in insulin secretion or action leads to impaired glucose regulation and can result in conditions such as diabetes mellitus, characterized by chronic hyperglycemia and associated complications. Exogenous insulin is used as a replacement therapy in individuals with diabetes to help manage their blood glucose levels and prevent long-term complications.

Antipain is a naturally occurring organic compound that is found in various types of streptomyces bacteria. It is classified as a protease inhibitor, which means that it works by blocking the action of certain enzymes called proteases, which are involved in breaking down proteins in the body. Antipain has been shown to have anti-inflammatory and analgesic (pain-relieving) effects, and it is sometimes used in research to study the role of proteases in various biological processes. It is not approved for use as a medication in humans.

Cathepsins are a type of proteolytic enzymes, which are found in lysosomes and are responsible for breaking down proteins inside the cell. They are classified as papain-like cysteine proteases and play important roles in various physiological processes, including tissue remodeling, antigen presentation, and apoptosis (programmed cell death). There are several different types of cathepsins, including cathepsin B, C, D, F, H, K, L, S, V, and X/Z, each with distinct substrate specificities and functions.

Dysregulation of cathepsins has been implicated in various pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders. For example, overexpression or hyperactivation of certain cathepsins has been shown to contribute to tumor invasion and metastasis, while their inhibition has been explored as a potential therapeutic strategy in cancer treatment. Similarly, abnormal levels of cathepsins have been linked to the progression of neurodegenerative diseases like Alzheimer's and Parkinson's, making them attractive targets for drug development.

Tipranavir is a nonpeptidic HIV-1 protease inhibitor and reached the market in 2005. Unlike other HIV protease inhibitors on ... HIV protease inhibitors fit the active site of the HIV aspartic protease and were rationally designed utilizing knowledge of ... In 2009, ten protease inhibitors have reached the market for treatment against HIV but one protease inhibitor, amprenavir, was ... All the FDA approved protease inhibitors are listed below. All the HIV protease inhibitors on the market contain a central core ...
HIV protease inhibitors; the antidepressant nefazodone; the cardiovascular drug gemfibrozil; the immunosuppressant ciclosporin ... This discovery encouraged scientists worldwide to find an effective inhibitor of this enzyme. By 1976, Akira Endo had isolated ... August 2015). "HMG-CoA Reductase Inhibitors Bind to PPARα to Upregulate Neurotrophin Expression in the Brain and Improve Memory ... Tobert JA (July 2003). "Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors". Nature Reviews. Drug Discovery ...
This effect is also used in HIV therapy, where ritonavir is used in combination with another protease inhibitor to similarly ... Hull MW, Montaner JS (April 2011). "Ritonavir-boosted protease inhibitors in HIV therapy". Annals of Medicine. 43 (5): 375-388 ... Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is ... April 2018). "Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis". ...
Protease inhibitors, including ritonavir, effectively block HIV-1 protease, a crucial enzyme in the reproductive cycle of HIV-1 ... CYP2D6 inhibitors, CYP3A4 inhibitors, Hepatotoxins, HIV protease inhibitors, Isopropyl compounds, Pregnane X receptor agonists ... Ritonavir is a protease inhibitor and is used with other protease inhibitors. It may also be used in combination with other ... February 1998). "Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical ...
Protease inhibitors introduced, allowing HAART therapy against HIV; drastically reduces AIDS mortality. NASA's spacecraft ... Public education about safe sex curbed the spread of the HIV virus in developed countries. Generation X young people often ...
... (DMP-450) is an antiviral drug which was developed as a treatment for HIV/AIDS. It acts as an HIV protease inhibitor ... Li P, Wang S, Wang H, Yan H (2019). "2-Symmetric HIV-1 Protease Inhibitors and Docking Study". Biological & Pharmaceutical ... "The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues". Bioorganic & ... polarization effects of the HIV-1 protease on selected high affinity inhibitors". Journal of Medicinal Chemistry. 47 (27): 6673 ...
CYP3A4 inhibitors, GSK plc brands, HIV protease inhibitors, Prodrugs, Sulfonamides, Tetrahydrofurans). ... Amprenavir is a HIV protease inhibitor. "Telzir Product information". Health Canada. 25 April 2012. Archived from the original ... It is a prodrug of the protease inhibitor and antiretroviral drug amprenavir. It is marketed by ViiV Healthcare as the calcium ... Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT (September 2010). "Amprenavir complexes with HIV-1 protease and its drug ...
With its integral role in HIV replication, HIV protease has been a prime target for drug therapy. HIV protease inhibitors work ... A02.001 Proteopedia HIV-1_protease - the HIV-1 protease structure in interactive 3D. Proteopedia Flaps_Morph_for_HIV_Protease ... Several protease inhibitors have been licensed for HIV therapy. There are ten HIV-1 PR inhibitors that are currently approved ... Without effective HIV protease, HIV virions remain uninfectious. Mature HIV protease exists as a 22 kDa homodimer, with each ...
... and protease inhibitors (HIV treatment). Testosterone can also alter the effects of other drugs: Increases the blood thinning ... A potential solution is to start taking a 5α-reductase inhibitor after these desired aspects of masculinization have been well- ... Enzyme inhibitors - May cause increased levels of testosterone: Nefazodone, fluoxetine, paroxetine (antidepressants), ... Irwig MS (November 2021). "Is there a role for 5α-reductase inhibitors in transgender individuals?". Andrology. 9 (6): 1729- ...
"Computing Clinically Relevant Binding Free Energies of HIV-1 Protease Inhibitors". Journal of Chemical Theory and Computation. ... Understanding the Role of Potassium as a Clay Swelling Inhibitor". J. Am. Chem. Soc. 117 (50): 12608-12617. doi:10.1021/ ... "Rule based design of clay-swelling inhibitors". Energy & Environmental Science. 4 (11): 4572-4586. doi:10.1039/c1ee01280k. ...
Annaert P, Ye ZW, Stieger B, Augustijns P (March 2010). "Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1" ( ... Since tyrosine kinase inhibitors (TKIs) are metabolized in the liver, interaction of TKIs with OATP1B1 and OATP1B3 can be ... Khurana V, Minocha M, Pal D, Mitra AK (May 2014). "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug ... Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, ...
Drugs developed include amprenavir, an HIV protease inhibitor; telaprevir, a protease inhibitor for treatment of hepatitis C; ... Agenerase (amprenavir), an HIV protease inhibitor, was co-developed by Vertex and GlaxoSmithKline for the treatment of HIV/AIDS ... Vertex also developed Telaprevir, a protease inhibitor for treatment of hepatitis C. Telaprevir works by disabling a protein ... Scientists at Vertex first published the crystal structure for the protease of the hepatitis C virus in 1996. As part of the ...
"HIV protease inhibitors: a review of molecular selectivity and toxicity". HIV/AIDS. 7: 95-104. doi:10.2147/HIV.S79956. PMC ... It is of the protease inhibitor (PI) class and works by blocking HIV protease. Atazanavir was approved for medical use in the ... CYP3A4 inhibitors, HIV protease inhibitors, 2-Pyridyl compounds, Wikipedia medicine articles ready to translate, World Health ... Graziani AL (17 June 2014). "HIV protease inhibitors". UpToDate. Bold G, Fässler A, Capraro HG, Cozens R, Klimkait T, Lazdins J ...
... and protease inhibitors used to treat retroviral infections such as HIV. A common example of an irreversible inhibitor that is ... Wlodawer A, Vondrasek J (1998). "Inhibitors of HIV-1 protease: a major success of structure-assisted drug design". Annual ... A mixed inhibitor binds to an allosteric site and the binding of the substrate and the inhibitor affect each other. The ... Other enzyme inhibitors are poisons. For example, the poison cyanide is an irreversible enzyme inhibitor that combines with the ...
... is a protease inhibitor: it inhibits HIV-1 and HIV-2 proteases. HIV protease is an aspartate protease which splits ... All protease inhibitors bind to the protease, the precise mode of binding determines how the molecule inhibits the protease. ... CYP3A4 inhibitors, Decahydroisoquinolines, Hepatotoxins, HIV protease inhibitors, Hoffmann-La Roche brands, Pfizer brands, ... July 2005). "HIV-1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in ...
"Marijuana does not appear to alter viral loads of HIV patients taking protease inhibitors". University of California, San ... did not negatively interact with the protease inhibitors and actually did facilitate, increase caloric intake as well as weight ... Rathbun began working with the Shanti Project, a support group for people with HIV/AIDS. According to Peron: Those first 500 ... For the study, see: "Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection: A Randomized, Placebo-Controlled ...
"Parallel Screening and Activity Profiling with HIV Protease Inhibitor Pharmacophore Models". J. Chem. Inf. Model. 47 (2): 563- ... Other applications include the discovery of new Myeloperoxidase ligands, HIV reverse transcriptase inhibitors, applications in ... the development of models to predict HIV Protease activity, Cytochrome P450 activity prediction , and simulation models for the ... 3-dicarboxylic acid inhibitors of bacterial MurD and MurE ligases by structure-based virtual screening approach". Bioorganic & ...
The molecule ritonavir, marketed as Norvir, was developed as a protease inhibitor and used to target HIV infection. However, it ... "How an inhibitor of the HIV-I protease modulates proteasome activity". The Journal of Biological Chemistry. 274 (50): 35734-40 ... Inhibitors also show positive effects in rodent models of asthma. Labeling and inhibition of the proteasome is also of interest ... The inner two rings are made of seven β subunits that contain three to seven protease active sites. These sites are located on ...
... is an analog of the already approved HIV protease inhibitor, saquinavir. HIV protease inhibitor drugs not only work ... Adding a nitrate ester functional group to HIV protease inhibitors has been found to curb these negative effects as well as ... OX1001 is a nitrate ester analog of the approved HIV protease inhibitor, saquinavir. This modification increases the anti- ... "The new and less toxic protease inhibitor saquinavir-NO maintains anti-HIV-1 properties in vitro indistinguishable from those ...
Description of the now leading HIV protease inhibitor Prezista: TMC114, a novel human immunodeficiency virus type 1 protease ... a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor Active against Protease Inhibitor-Resistant Viruses, Including a ... Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. Development of drug Discovery method for SARS ... First paper on the discovery of the anti-HIV activity of a new class of inhibitors that laid the foundation for the anti-HIV ...
In 2010, he studied age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. Results of this study ... this includes early studies of HIV protease inhibitors, and the use of accelerator mass spectrometry to determine drug ... "Age-Related Changes in Plasma Concentrations of the HIV Protease Inhibitor Lopinavir". AIDS Research and Human Retroviruses. 26 ... American College of Clinical Pharmacology Protease Inhibitors in AIDS Therapy (2001) ISBN 9780824704612 HIV Drug Interaction ...
The HIV protease inhibitor Tipranavir is marketed for the treatment of AIDS. The first enantioselective medicinal chemistry ... 1998). "Tipranavir (PNU-140690): A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy- ... 1991). "Inhibitors of Cholesterol Biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(lH-pyrrol-l-yl)ethyl]-2H-pyran-2-one Inhibitors ...
Tenofovir also interacts with HIV-1 protease inhibitors such as atazanavir, by decreasing atazanavir concentrations while ... Tenofovir interacts with didanosine and HIV-1 protease inhibitors. Tenofovir increases didanosine concentrations and can result ... Tenofovir disoproxil is used for HIV-1 infection and chronic hepatitis B treatment. For HIV-1 infection, tenofovir is indicated ... HIV) therapy, in HIV-infected adults". Antimicrobial Agents and Chemotherapy. 42 (9): 2380-4. doi:10.1128/aac.42.9.2380. PMC ...
Special inhibitors of a virus-associated target (e.g. HIV protease inhibitors, RNAi) Vaccines, but vaccines require ...
At lowered levels, protease inhibitors may not be effective in people taking both drugs, which means the virus that causes HIV/ ... One group of drugs that efavirenz affects is protease inhibitors, which are used for HIV/AIDS. Efavirenz will lower the blood ... Similar to the effect seen with protease inhibitors, efavirenz lowers the blood levels of antifungal drugs like voriconazole, ... Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which ...
February 2001). "Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study ... lipodystrophy seems to be mainly due to HIV-1 protease inhibitors. Interference with lipid metabolism is postulated as ... HIV-associated lipodystrophy is a condition characterized by loss of subcutaneous fat associated with infection with HIV.: 497 ... 2006). "HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy". ...
The protease inhibitor darunavir for HIV treatment also contains a carbamate functional group. Ephedroxane also fits the mould ... Other carbamate based acetylcholinesterase inhibitors are known with even higher toxicity to humans, and some such as T-1123 ... While the carbamate acetylcholinesterase inhibitors are commonly referred to as "carbamate insecticides" due to their generally ... Colović, MB; Krstić, DZ; Lazarević-Pašti, TD; Bondžić, AM; Vasić, VM (2013). "Acetylcholinesterase inhibitors: pharmacology and ...
The first HIV protease inhibitor approved by the FDA was saquinavir, which was designed to target wild-type HIV-1 protease. ... However, this inhibitor is no longer effective due to resistance-causing mutations on the HIV-1 protease structure. The HIV ... It is of the protease inhibitor (PI) class and works by blocking HIV protease. Developed by pharmaceutical company Tibotec, ... It was developed to increase interactions with HIV-1 protease and to be more resistant against HIV-1 protease mutations. With a ...
... including HIV protease inhibitors and GS-7340, in vitro". Antimicrobial Agents and Chemotherapy. 56 (10): 5409-13. doi:10.1128/ ... Additionally, in existence are a fixed-dose combination of cobicistat and protease inhibitor darunavir (darunavir/cobicistat; ... Highleyman, L. Elvitegravir "Quad" Single-tablet Regimen Shows Continued HIV Suppression at 48 Weeks. HIV and Hepatitis.com R ... an HIV integrase inhibitor. By combining cobicistat with elvitegravir, higher concentrations of the latter are achieved in the ...
Structure-activity studies on renin inhibitors proved to be of great value for developing HIV protease inhibitors. ... CYP3A4 inhibitors, HIV protease inhibitors, Sulfonamides, Tetrahydrofurans, 1992 in science, All stub articles, Antiinfective ... Amprenavir (original brand name Agenerase, GlaxoSmithKline) is a protease inhibitor used to treat HIV infection. It was ... Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT (September 2010). "Amprenavir complexes with HIV-1 protease and its drug ...
Tipranavir is a nonpeptidic HIV-1 protease inhibitor and reached the market in 2005. Unlike other HIV protease inhibitors on ... HIV protease inhibitors fit the active site of the HIV aspartic protease and were rationally designed utilizing knowledge of ... In 2009, ten protease inhibitors have reached the market for treatment against HIV but one protease inhibitor, amprenavir, was ... All the FDA approved protease inhibitors are listed below. All the HIV protease inhibitors on the market contain a central core ...
HIV-1 PROTEASESULFATE ION[1-BENZYL-3-(8-SEC-BUTYL-7,10-DIOXO-2-OXA-6,9-DIAZA-BICYCLO[11.2.2] HEPTADECA-1(16),13(17),14-TRIEN-11 ... 1MTR: HIV-1 PROTEASE COMPLEXED WITH A CYCLIC PHE-ILE-VAL PEPTIDOMIMETIC INHIBITOR. ...
HIV disease is caused by infection with HIV-1 or HIV-2, which are retroviruses in the Retrovir... ... HIV) is a blood-borne virus typically transmitted via sexual intercourse, shared intravenous drug paraphernalia, and mother-to- ... HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother. 2010 Oct. 54(10):4253-61. [QxMD ... Integrase inhibitor that is used in combination with an HIV protease inhibitor (ie, atazanavir, lopinavir, darunavir, ...
Lipodystrophy in patients with HIV-1 infection: effect of stopping protease inhibitors on TNF-receptor levels, insulin ... Its possible that the dysregulation which might lead to lipodystrophy could be due to HIV or HIV therapy or both. Its also ... are reversed by stopping protease inhibitors (PIs).. Methods:. Ten patients with lipodystrophy were studied while on PIs and 3 ... In addition, 10 HIV subjects on PIs without lipo-dystrophy were also studied. All patients were assessed by CT scans and bio- ...
... are potent and specific inhibitors of HIV-1 protease, one of the major enzymes encoded by the retrovirus. These protease ... 1996) Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent HIV protease inhibitor. Drug Metab Dispos 24:307-314. ... 1996) Disposition of indinavir, a potent HIV-1 protease inhibitor, after an oral dose in humans. Drug Metab Dispos 24:1389-1394 ... Inhibition of Methadone and BuprenorphineN-Dealkylations by Three HIV-1 Protease Inhibitors. Christelle Iribarne, François ...
... were similar among people with HIV-1 newly treated with an integrase inhibitor- or protease inhibitor-based regimen. ... HIV)-1 taking integrase inhibitor (INI)- or protease inhibitor (PI)-based regimens. This study evaluated the prevalence, ... were similar among people with HIV-1 newly treated with an integrase inhibitor- or protease inhibitor-based regimen. ... Data are scarce regarding the incidence of neuropsychiatric events in people with HIV-1 taking integrase inhibitor- or protease ...
Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke. Posted at 00:00h in by AIGHD ... INTEREST (HIV) Conference. Vacancies. ANBI. Diversity, Equity & Inclusion. Privacy Statement. Cookie Policy. Portal ...
Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East ... Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East ... Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East ... Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East ...
... boosted protease inhibitor (PI) combinations, according to preliminary data from a clinical trial and a warning issued to ... The hepatitis C protease inhibitor Victrelis (boceprevir) has some significant drug-drug interactions with common Norvir ( ... "Merck does not recommend the coadministration of Victrelis and ritonavir-boosted HIV protease inhibitors," the letter states. ... The hepatitis C protease inhibitor Victrelis (boceprevir) has some significant drug-drug interactions with common Norvir ( ...
... as second-line and third-line regimens in pregnant women living with HIV (WLHIV). US, European, and UK guidelines include PI- ... The World Health Organization recommends protease inhibitor (PI)-based antiretroviral therapy (ART) ... Antiretroviral therapy, HIV, Meta-analysis, Perinatal outcome, Preterm birth, Protease inhibitor, Small for gestational age, ... Adverse perinatal outcomes associated with protease inhibitor-based antiretroviral therapy in pregnant women living with HIV: A ...
Transplantation. lymphocyte count number continued to be below preoperative level for 12 months posttransplant and WBC matters were considerably lower for three years after transplant weighed against pretransplant level. Cytomegalovirus an infection and infection happened in 28% and 36% of sufferers, respectively. Eleven percent of sufferers created donor-specific antibodies and 7% of sufferers experienced antibody-mediated rejection. Bottom line A single dosage of 30 mg alemtuzumab induction with steroid-free maintenance immunosuppression attained excellent mid-term individual and graft success for pancreas transplantation with appropriate complication price. 0.0003)= 0.09)= 0.12)= 0.002)2 yrMuthusamy= Astragaloside A 0.017)= 0.6)2 yrFarney et al.= 0.29)Median 2 yr Open up in another screen SPK, simultaneous kidney-pancreas transplantation; PAK, pancreas after kidney transplantation; PTA, pancreas transplant by itself; CMV, cytomegalovirus; Tac, tacrolimus; MMF, mycophenolate mofetil; Pred, ...
We thus suggest that suramin is really a guaranteeing scaffold that to develop a fresh type H3FL of healing inhibitor to take ... We hence sought to recognize a little molecule inhibitor of TIMP-3 endocytosis which could serve as a business lead compound ...
Protease inhibitors are in the category of antiretroviral drugs and are currently in use to treat HIV/AIDS and hepatitis C ... Side Effects of HIV Protease Inhibitors. The following list shows side effects that may occur when taking protease inhibitors ... What Do Protease Inhibitors Do?. In short, protease inhibitors block the action of protease which results in viruses that no ... HIV Protease Inhibitors. In todays world of HIV medications, you will hear reference to cART which stands for combination ...
HIV Protease Inhibitor In Breast Cancer. Category: Actin. A recently available meta-analysis of 147 randomized tests of ... The xanthine oxidase inhibitors allopurinol and febuxostat have already been used for this function widely. The xanthine ... The xanthine oxidase inhibitors allopurinol and febuxostat have already been used for this function widely ... oxidase inhibitors allopurinol and febuxostat have already been used for this function widely. Allopurinol continues to be used ...
HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic ... Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. ... Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 ( ... Patients should be informed that VIRACEPT is not a cure for HIV infection and that they may continue to acquire illnesses ...
HIV Protease Inhibitor In Breast Cancer. Month: December 2022. A recently available meta-analysis of 147 randomized tests of ...
HIV-1 Gag, Gag inhibitors, protease, protease inhibitors, drug resistance mutations, drug design ... HIV protease inhibitors against the viral protease are often hampered by drug resistance mutations in protease and in the viral ... Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs ... Reviewing HIV-1 Gag Mutations in Protease Inhibitors Resistance: Insights for Possible Novel Gag Inhibitor Designs ...
Protease Inhibitors. Class Summary. Protease inhibitors inhibit HIV protease, which is required for HIV replication and the ... HIV/AIDS and the Sexual Assault Survivor, 2008. HIV/AIDS & Victim Services, 2001. HIV/AIDS Legislation, 1999. Available at http ... protease inhibitor [PI] or a nonnucleoside reverse transcriptase inhibitor [NNRTI]) for high-risk incidents. [53, 18] ... Nucleoside Reverse Transcriptase Inhibitors. Class Summary. NRTIs are nucleoside or nucleotide reverse transcriptase inhibitor ...
7.2 HIV-1 Protease Inhibitors 7.3 Drugs Affecting Renal Function 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing ... 7.2 HIV-1 Protease Inhibitors. VIREAD decreases the AUC and Cmin of atazanavir [See Clinical Pharmacology (12.3)]. When ... HIV-1 protease inhibitors: Coadministration decreases atazanavir concentrations and increases tenofovir concentrations. When ... containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or a HIV-1 protease inhibitor ...
Development and Structural Modification of HIV protease inhibitors © 2023. All Rights Reserved. ... test can be performed to differentiate between coagulation element deficiencies or the presence of heparin or an inhibitor ...
Protease Inhibitors. Subject HIV infections. Subject HIV (Viruses). Subject AIDS (Disease). Subject Proteolytic enzymes. ... Studies directed towards the synthesis of chromone carbaldehyde-derived HIV-1 protease inhibitors. Creator Molefe, Duduzile ... Studies directed towards the synthesis of chromone carbaldehyde-derived HIV-1 protease inhibitors. ... Interactive docking of the chromone-containing ligands into the HIV -1 protease receptor site, using the Ligandfit module, has ...
The interaction between HIV-1 protease and inhibitors has been studied with optical biosensor technology. Optimized ... Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology. 01 January ... Several of the inhibitors had very high association rates, and estimation of kinetic constants was therefore performed with a ... Of the clinical inhibitors studied, saquinavir had the highest affinity for the enzyme, a result of the lowest dissociation ...
Simvastatin (Zocor) Use in HIV Patients on Protease Inhibitors (PIs) vs Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs ... simvastatin should never be given concurrently with any protease inhibitor.. *Use of simvastatin with protease inhibitors ... Prescribing of contraindicated protease inhibitor and statin combinations among HIV-infected persons. J Acquir Immune Defic ... Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS ...
... inhibitor of HIV replication in vitro and represents a new class of de novo designed non-peptidyl inhibitors of HIV-1 protease. ... OBJECTIVE: Currently the most potent inhibitors of HIV protease are peptidyl in nature. Our objective was to use the ... RESULTS: XM323, a representative of a new class of non-peptidyl inhibitors, was identified as a potent inhibitor of HIV-1 and ... crystallographic structural information of HIV-1 protease to design and synthesize novel non-peptidyl inhibitors of the enzyme ...
What is the protease inhibitor-based regimen of antiretroviral therapy (ART) for HIV infection? ... What are acceptable protease inhibitor-based regimens of antiretroviral therapy (ART) for HIV infection? ... What are the alternative protease inhibitor-based regimens of antiretroviral therapy (ART) for HIV infection? ... a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacologic enhancer (ie, ...
The results presented here show a potential anti-HIV-1 activity of A. catechu mediated by the inhibition of the functions of ... tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors* Substances * Antiviral Agents * HIV Protease ... Extracts from Acacia catechu suppress HIV-1 replication by inhibiting the activities of the viral protease and Tat Virol J. ... The active n-butanol fraction was evaluated for its inhibition against HIV-1 reverse transcriptase, integrase, protease, pro- ...
Fármacos Anti-HIV; Inibidores da Protease de HIV; HIV-1; Humanos; Inibidores da Protease de HIV/química; Protease de HIV/ ... Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. Discovery of Novel HIV Protease Inhibitors ... Inibidores da Protease de HIV / Fármacos Anti-HIV Limite: Humanos Idioma: Inglês Ano de publicação: 2022 Tipo de documento: ... Inibidores da Protease de HIV / Fármacos Anti-HIV Limite: Humanos Idioma: Inglês Ano de publicação: 2022 Tipo de documento: ...
Background Examination of sponsor cell-based inhibitors of HIV-1 transcription could be. Posted on December 13, 2018. by ... Background Examination of sponsor cell-based inhibitors of HIV-1 transcription could be very important to attenuating viral ... The inhibitors of Tat/TAR axis consist of TAR RNA decoys [15,16], little molecule inhibitors and ribozyme [17-24]. Additional ... The nascent transcripts from HIV-1 Longer Terminal Do it again (LTR) include a exclusive structured RNA domains inside the 5′- ...

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