A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)
A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)
An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.
A uricosuric and muscle relaxant. Zoxazolamine acts centrally as a muscle relaxant, but the mechanism of its action is not understood.
An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.
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.
Salts and esters of hippuric acid.
A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)
A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis.
Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3.
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
The pharmacological result, either desirable or undesirable, of drugs interacting with components of the diet. (From Stedman, 25th ed)
A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.
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.

Post-translational inhibition of cytochrome P-450 2E1 expression by chlomethiazole in Fao hepatoma cells. (1/78)

Chlomethiazole (CMZ) is a sedative and anticonvulsant drug that has been shown to be an efficient transcriptional inhibitor of expression of rat hepatic ethanol-inducible cytochrome P-450 2E1 (CYP2E1). Recent results have shown that human CYP2E1 expression in vivo is almost completely inhibited in control subjects and in alcoholic patients treated with CMZ. In the present investigation, we evaluated the mode of action of CMZ on CYP2E1 expression in Fao rat hepatoma cells. Transcriptional activity of the CYP2E1 gene was monitored using reverse transcription-polymerase chain reaction-based quantification of CYP2E1 heterologous nuclear RNA (hnRNA) against a mimic DNA standard, mRNA was detected by Northern blotting, enzyme protein was detected by Western blotting, and CYP2E1-dependent catalytic activity was detected by assay of chlorzoxazone-6-hydroxylation. Six hours after CMZ treatment, the levels of both CYP2E1 protein and catalytic activity were concomitantly reduced at an IC50 value of about 5 microM. Ethanol treatment of the cells caused a 2-fold induction of CYP2E1 protein levels, which was inhibited by CMZ. Change of medium unexpectedly caused an increase in CYP2E1 gene transcription 4 h later, as monitored by quantitative determination of CYP2E1 hnRNA. However, CMZ failed to influence the expression of CYP2E1 hnRNA or mRNA both constitutively and after medium change, indicating no effect on gene transcription or mRNA synthesis/stability. Cycloheximide treatment of the cells did not abolish the inhibitory action of CMZ, further indicating an action at the post-translational level; in addition, CMZ inhibited CYP2E1 expression in V79 cells with stably expressed CYP2E1 under the control of the SV40 promoter. The data indicate that the CYP2E1 gene is transcriptionally activated in response to medium change and that CMZ, apart from a transcriptional inhibitor of CYP2E1 expression, acts in addition as an efficient high-affinity post-translational inhibitor of CYP2E1, probably due to an allosteric destabilization of the enzyme. This indicates a very rapid and effective CMZ-mediated inhibition of CYP2E1 in vivo.  (+info)

Toxicokinetic interactions between orally ingested chlorzoxazone and inhaled acetone or toluene in male volunteers. (2/78)

The aim of this study was to examine if the drug chlorzoxazone has any influence on the toxicokinetics of acetone and toluene. Chlorzoxazone is mainly metabolized by the same enzyme (Cytochrome P450 2E1) as ethanol and many other organic solvents. Ten male volunteers were exposed to solvent vapor (2 h, 50 watt) in an exposure chamber. Each subject was exposed to acetone only (250 ppm), acetone + chlorzoxazone, toluene (50 ppm) only, toluene + chlorzoxazone, and chlorzoxazone only. Chlorzoxazone (500 mg) was taken as two tablets 1 h prior to solvent exposure. Samples of blood, urine and exhaled air were collected before, during and until 20 h post exposure. The samples were analyzed by head-space gas chromatography (acetone and toluene) and high-performance liquid chromatography (chlorzoxazone, 6-hydroxychlorzoxazone and hippuric acid). The time-concentration curves of acetone and toluene in blood were fitted to one- and four-compartment toxicokinetic models, respectively. Intake of chlorzoxazone was associated with slight but significant increases in the area under the blood concentration-time curve (AUC) and steady state concentration of acetone in blood, along with non significant tendencies to an increased half time in blood and an increased AUC in urine. Except for a delayed excretion of hippuric acid in urine, no effects on the toluene toxicokinetics were seen after chlorzoxazone treatment. Small increases in chlorzoxazone plasma levels were seen after exposure compared to chlorzoxazone alone. These interactions, although statistically significant, seem to be small compared to the interindividual variability on metabolism and toxicokinetics.  (+info)

Genetic and dietary predictors of CYP2E1 activity: a phenotyping study in Hawaii Japanese using chlorzoxazone. (3/78)

Cytochrome P4502E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. An RsaI polymorphism is present in the 5'-flanking region of the CYP2E1 gene, which could possibly affect its transcription. However, the relationship between genotype and the phenotypic catalytic activity of the enzyme has not been defined. Also, the effects in humans of specific dietary factors, other than ethanol, which have been shown in animal and in vitro studies to modulate CYP2E1 activity, are unknown. Accordingly, the CYP2E1-mediated metabolism of chlorzoxazone to its 6-hydroxy metabolite was investigated in 50 healthy Japanese of both sexes in Hawaii. The oral clearance of the in vivo probe, the trait measure of CYP2E1 activity, was smaller than that reported in European-Americans. Significantly, after adjustment for age and sex, the oral clearance of chlorzoxazone decreased with the number of variant c2 alleles, and its mean in the c2/c2 genotype (147 ml/min) was statistically lower (P < or = 0.05) than that for either the homozygous wild-type (238 ml/min) or the heterozygote (201 ml/min) genotypes. Stepwise multiple regression analysis indicated that body weight was a major contributor to the interindividual variability in the oral clearance of chlorzoxazone, accounting for 43% of the variance. Consumption of lettuce, broccoli, and black tea explained additional components of the variability (7, 5, and 6%, respectively), as did medication use (3%), age (4%), and CYP2E1 genotype (5%). Overall, 73% of the variance could be accounted for by these variables. Body weight, lettuce, and use of medications were associated with increased CYP2E1 activity, and the other covariates were associated with reduced enzyme function. Because of the role that CYP2E1 plays in procarcinogen activation, especially of N-nitrosamines involved in lung cancer, the identified factors may account in part for observed differences in individual susceptibility to disease and may also have implications for cancer prevention.  (+info)

Effect of the acute-phase response on the pharmacokinetics of chlorzoxazone and cytochrome P-450 2E1 in vitro activity in rats. (4/78)

The acute-phase response is known to produce alterations in hepatic cytochrome P-450 (CYP) expression. Lipopolysaccharide (LPS), a well known inducer of acute-phase response decreases hepatic CYP2E1 in vitro activity in rats. This study was designed to determine if LPS administration produced alterations in the pharmacokinetics of chlorzoxazone (CZN), a marker for CYP2E1 expression. Sprague-Dawley rats were administered a single i.p. injection of LPS (5 mg/kg) or saline control approximately 24 h before a single i.v. bolus dose of CZN (15 mg/kg). Serial blood samples were collected over a 120-min period to quantitate CZN plasma concentrations and protein binding. In addition, livers were removed and processed for evaluating in vitro CYP2E1 protein concentrations and activity. Systemic clearance decreased by 35% in LPS-treated rats, whereas half-life and steady-state volume of distribution increased by 167 and 66%, respectively. The plasma free-fraction of CZN increased 2-fold after LPS treatment. The CZN intrinsic clearance decreased in LPS rats by 71% compared with control values. The CYP2E1 liver microsomal activity decreased between 55 and 75% along with a 41% decrease in CYP2E1 protein concentration. The CZN intrinsic clearance was significantly correlated with both the CZN and p-nitrophenol liver microsomal activity (r = 0.97 and r = 0.91, respectively). This study demonstrated that LPS administration produced expected reductions in the in vivo intrinsic clearance of CZN, and these changes were highly correlated with in vitro activity studies. In addition, LPS produced significant increases in the steady-state volume of distribution of CZN secondary to reductions in its plasma protein binding.  (+info)

Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. (5/78)

Disulfiram (DSF) is a mechanism-based inhibitor of cytochrome P-450 2E1 (CYP2E1), resulting in loss of CYP2E1 protein and activity, which may be useful in preventing CYP2E1-mediated xenobiotic toxicity. The duration of inhibition after a single DSF dose is, however, unknown. The purpose of this investigation was to determine this duration, and CYP2E1 formation and degradation rates, in humans. Oral chlorzoxazone (CLZ) was used as the selective in vivo probe for CYP2E1. Healthy subjects received CLZ to determine baseline CYP2E1 activity (CLZ plasma clearance and 6-hydroxychlorzoxazone fractional metabolic clearance). One week later, DSF (500 mg orally) was administered at bedtime, and CLZ administered the following morning and 3, 6, 8, 10, and 13 days after DSF. A terminal DSF metabolite, 2-thiothiazolidine-4 carboxylic acid, was also measured in each 24-h urine sample. The mean CLZ clearance and 6-hydroxychlorzoxazone fractional metabolic clearance on the first day declined to 10.2 and 5.5% of baseline values, indicating rapid and profound CYP2E1 inhibition. CYP2E1 activity returned to half that of control on day 3, and to baseline values on day 8. Assuming zero-order synthesis and first-order degradation, the in vivo CYP2E1 synthesis rate and degradation half-life was estimated to be 11 +/- 5 nmol/h and 50 +/- 19 h, respectively. Significant amounts of 2-thiothiazolidine-4 carboxylic acid were present only on day 1, suggesting that the return of in vivo CYP2E1 activity was not caused by inhibitor washout, but by enzyme resynthesis. Results regarding CYP2E1 disposition may be useful for modeling the effects of CYP2E1 inducers and inhibitors. For prevention of CYP2E1-mediated bioactivation, depending on protoxicant disposition, a second DSF dose might be necessary to completely prevent toxicity.  (+info)

Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. (6/78)

Different roles of individual forms of human cytochrome P-450 (CYP) in the oxidation of 7-ethoxycoumarin and chlorzoxazone were investigated in liver microsomes of different human samples, and the microsomal activities thus obtained were predicted with kinetic parameters obtained from cDNA-derived recombinant CYP enzymes in microsomes of Trichoplusia ni cells. Of 14 forms of recombinant CYP examined, CYP1A1 had the highest activities (V(max)/K(m) ratio) in catalyzing 7-ethoxycoumarin O-deethylation followed by CYP1A2, 2E1, 2A6, and 2B6, although CYP1A1 has been shown to be an extrahepatic enzyme. With these kinetic parameters (excluding CYP1A1) we found that CYP1A2 and 2E1 were the major enzymes catalyzing 7-ethoxycoumarin; the contributions of these two forms were dependent on the contents of these CYPs in liver microsomes of different humans. Similarly, chlorzoxazone 6-hydroxylation activities of liver microsomes were predicted with kinetic parameters of recombinant human CYP enzymes and it was found that CYP3A4 as well as CYP1A2 and 2E1 were involved in chlorzoxazone hydroxylation, depending on the contents of these CYP forms in the livers. Recombinant CYP2A6 and 2B6 and CYP2D6 had considerable roles (V(max)/K(m) ratio) for 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxylation, respectively; however, these CYP forms had relatively minor roles in the reactions, probably due to low expression in human livers. These results support the view that the roles of individual CYP enzymes in the oxidation of xenobiotic chemicals in human liver microsomes could be predicted by kinetic parameters of individual CYP enzymes and by the levels of each of the CYP enzymes in liver microsomes of human samples.  (+info)

Stimulation of Cl(-) secretion by chlorzoxazone. (7/78)

We previously demonstrated that 1-ethyl-2-benzimidazolone (1-EBIO) directly activates basolateral membrane calcium-activated K(+) channels (K(Ca)), thereby stimulating Cl(-) secretion across several epithelia. In our pursuit to identify potent modulators of Cl(-) secretion that may be useful to overcome the Cl(-) secretory defect in cystic fibrosis (CF), we have identified chlorzoxazone [5-chloro-2(3H)-benzoxazolone], a clinically used centrally acting muscle relaxant, as a stimulator of Cl(-) secretion in several epithelial cell types, including T84, Calu-3, and human bronchial epithelium. The Cl(-) secretory response induced by chlorzoxazone was blocked by charybdotoxin (CTX), a known blocker of K(Ca). In nystatin-permeabilized monolayers, chlorzoxazone stimulated a basolateral membrane I(K), which was inhibited by CTX and also stimulated an apical I(Cl) that was inhibited by glibenclamide, indicating that the G(Cl) responsible for this I(Cl) may be cystic fibrosis transmembrane conductance regulator (CFTR). In membrane vesicles prepared from T84 cells, chlorzoxazone stimulated (86)Rb(+) uptake in a CTX-sensitive manner. In excised, inside-out patches, chlorzoxazone activated an inwardly-rectifying K(+) channel, which was inhibited by CTX. 6-Hydroxychlorzoxazone, the major metabolite of chlorzoxazone, did not activate K(Ca), whereas zoxazolamine (2-amino-5-chlorzoxazole) showed a similar response profile as chlorzoxazone. In normal human nasal epithelium, chlorzoxazone elicited hyperpolarization of the potential difference that was similar in magnitude to isoproterenol. However, in the nasal epithelium of CF patients with the DeltaF508 mutation of CFTR, there was no detectable Cl(-) secretory response to chlorzoxazone. These studies demonstrate that chlorzoxazone stimulates transepithelial Cl(-) secretion in normal airway epithelium in vitro and in vivo, and suggest that stimulation requires functional CFTR in the epithelia.  (+info)

Pharmacological activation of cloned intermediate- and small-conductance Ca(2+)-activated K(+) channels. (8/78)

We previously characterized 1-ethyl-2-benzimidazolinone (1-EBIO), as well as the clinically useful benzoxazoles, chlorzoxazone (CZ), and zoxazolamine (ZOX), as pharmacological activators of the intermediate-conductance Ca(2+)-activated K(+) channel, hIK1. The mechanism of activation of hIK1, as well as the highly homologous small-conductance, Ca(2+)-dependent K(+) channel, rSK2, was determined following heterologous expression in Xenopus oocytes using two-electrode voltage clamp (TEVC) and excised, inside-out patch-clamp techniques. 1-EBIO, CZ, and ZOX activated both hIK1 and rSK2 in TEVC and excised inside-out patch-clamp experiments. In excised, inside-out patches, 1-EBIO and CZ induced a concentration-dependent activation of hIK1, with half-maximal (K(1/2)) values of 84 microM and 98 microM, respectively. Similarly, CZ activated rSK2 with a K(1/2) of 87 microM. In the absence of CZ, the Ca(2+)-dependent activation of hIK1 was best fit with a K(1/2) of 700 nM and a Hill coefficient (n) of 2.0. rSK2 was activated by Ca(2+) with a K(1/2) of 700 nM and an n of 2.5. Addition of CZ had no effect on either the K(1/2) or n for Ca(2+)-dependent activation of either hIK1 or rSK2. Rather, CZ increased channel activity at all Ca(2+) concentrations (V(max)). Event-duration analysis revealed hIK1 was minimally described by two open and three closed times. Activation by 1-EBIO had no effect on tau(o1), tau(o2), or tau(c1), whereas tau(c2) and tau(c3) were reduced from 9.0 and 92.6 ms to 5.0 and 44.1 ms, respectively. In conclusion, we define 1-EBIO, CZ, and ZOX as the first known activators of hIK1 and rSK2. Openers of IK and SK channels may be therapeutically beneficial in cystic fibrosis and vascular diseases.  (+info)

Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. Blood levels of chlorzoxazone can be detected in people during the first 30 minutes and peak levels may be reached, in the majority of the subjects, in about 1 to 2 hours after oral administration of chlorzoxazone. Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide. Less than one percent of a dose of chlorzoxazone is excreted unchanged in the urine in 24 hours.. ...
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The 6-hydroxylation of chlorzoxazone (CLZ) is currently being used in both in vivo and in vitro studies to quantify cytochrome P450 2E1 (CYP2E1) activity in humans. Comparatively little is known with regard to the biotransformation of this drug in other species. The NADPH-dependent biotransformation …
Chlorzoxazone, a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Chlorzoxazone is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis. Chlorzoxazone is also a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles ...
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Syrosingopine (O-carbethoxysyringoyl methylreserpate; SU-3118), a drug derived from reserpine* which was originally developed by Ciba (now Novartis) for the treatment of hypertension in 1958, in combination with the widely used diabetes drug metformin, an oral antidiabetic of the biguanide class, killed tumor cells in blood samples from leukemia patients, while it did not damage blood cells in samples from healthy patients. The combination also reduced or eliminated tumors in mice with malignant liver cancer. [1]. The benefit of the drug combination was discovered by researchers from the University of Basels Biozentrum two years ago. In a follow-up study, supported by the Swiss National Science Foundation, the Louis-Jeantet Foundation, the European Research Council (MERiC), and the Canton of Basel and recently published in Cell Reports, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.[2][3] ...
CINCINNATI (WKRC) - November is epilepsy awareness month and a local woman who struggled with seizures for years said a drug cocktail and an amazing treatment team has given her back part of her life.She was just 16 when she was diagnosed and since then wa
The primary purpose of this study is to establish a validated drug cocktail, containing up to 7 probes, for assessing the activity of six drug metabolizing enzymes (CYP 1A2, 2C8, 2C9, 2C19, 2D6, 3A4/5) and the OATP1B1 transporter. In Part 1, the study will determine if there are pharmacokinetic interactions among the probe drugs by comparing the pharmacokinetics of the probe drugs when administered alone and in combination (i.e., as a cocktail). In Part 2, the study will evaluate the quantitative performance of the cocktail by examining the effect of select inhibitors on the pharmacokinetics of respective probe drugs when the probe drugs are administered alone versus when administered in the cocktail.. This study aims to establish a standard probe cocktail that can be used for drug-drug interaction studies, with the intention that any subset of the 7-drug cocktail could be selected for study with a drug in development.. In addition, this study will provide a proof-of-principle evaluation of ...
Lorzone is a skeletal muscle relaxant used to relieve discomfort caused by acute painful muscle or bone conditions. This drug acts on the spinal cord and subcortical areas of the...
1M8D: Conformational Changes in Nitric Oxide Synthases Induced by Chlorzoxazone and Nitroindazoles: Crystallographic and Computational Analyses of Inhibitor Potency
Mus-Lax information about active ingredients, pharmaceutical forms and doses by King Pharmaceuticals, Mus-Lax indications, usages and related health products lists
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Glioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient
A cocktail of four chemotherapy drugs improves average survival by more than 60% in people with pancreatic cancer, French researchers reported Wednesday. The drugs had a variety of side effects, but
This open-label single-arm study will evaluate the effect of RO5185426 [RG7204; PLEXXIKON: PLX4032] on the pharmacokinetics of five CYP450 substrates (c
When a person has a disease or an injury, the bone marrow (the spongy tissue within bone) mobilises different types of stem cells to help repair and regenerate tissue.. The new research, involving scientists from Beaumont Health in the U.S, suggests it may be possible to boost the bodys ability to repair itself and speed repair, by using new drug combinations to put the bone marrow into a state of red alert and send specific kinds of stem cells into action.. In the new study, funded by Wellcome, the researchers used drugs to trigger the bone marrow of healthy rats to release mesenchymal stem cells, a type of adult stem cell that can turn into bone, and help repair bone fractures.. Professor Sara Rankin, corresponding author of the study from the National Heart and Lung Institute at Imperial College London, said: The body repairs itself all the time. We know that when bones break they will heal, and this requires the activation of stem cells in the bone. However, when the damage is severe, ...
Many health insurance plans pay for aid-in-dying drugs, but some dont, and the medications arent covered by federal programs such as Medicare or Catholic-run health care systems. That can create a barrier for terminally ill patients who want to use the law.
A combination of cocaine and PMA, the amphetamine drug known as Dr Death, claimed the life of a fifth Dubliner in a two-month period last year.
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A simplified, rapid, selective HPLC method for determining five cytochrome P450 (CYP) probe drugs in single run is described. The five specific probe substrates of caffeine, chlorzoxazone, tolbutamide, metoprolol and midazolam, together with the internal standard diazepam, were...
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For someone with liver disease, a cocktail is normally a forbidden luxury. But in some cases, it may be just what the doctor ordered. Two recently approved medications are now being combined with traditional treatments to form a powerful new drug cocktail, improving the outcomes among patients with this challenging disease ...
Had it been any other person then perhaps we would have greeted this news with a bagful of salt. But with Dr Y K Hamied, it is a different story altogether - in September 2000, at a meeting of European Commission, he shocked the world of big pharma and global policy-makers by announcing that he was ready to provide a three drug cocktail of anti-HIV drugs at just $1 a day. The cocktail (combinations of reverse transcriptase inhibitors like Lamivudine, Stavudine/Zidovudin and protease inhibitors like Ritonavir, Indinavir) - then the only combination available for slowing the progress of HIV/AIDS - used to sell at $12000 for a year. Even though big pharma companies actually called him a thief and pirate; policymakers, particularly African leaders rolled out red carpet for him. Dr Hamied kept his word - under special licensing, first Cipla and then a number of Indian companies were able to provide the live-saving drugs at a fraction of a price being charged by multinationals. A New York Times report ...
According to the World Center for EFT, taking drug cocktails can be seriously catastrophic. Whilst even the most pro-tablets advocate would probably admit taking cocktails is not a good idea and can have problems, there have been a surprisingly low number of studies conducted to determine the effects of mixing certain drugs. They report that taking 3 drugs requires seven separate tests to determine the safety, 4 drugs requires 25 tests, 5 drugs needs 121 tests, and ten drugs amounts to 362,881 separate tests. As such, taking a combination of tablets has the potential to wreak havoc in ways that we do not yet know - and yet, there is no warning on the box telling us not to ingest multiple tablets, nor do our doctors tell us not to. In fact, the contrary is true, with doctors often willingly putting their patients on multiple tablets and effectively playing roulette with the life and wellbeing of their patients. ...
Nearly 20 years ago I was coming off of a drug holiday and starting a new cocktail. 9/11 had just passed and I had exhausted what drug cocktails there were at the time for me. My CD4 count was ...
Poliovirus. Typhoid fever. Yellow fever. Measles.. When was the last time you worried about contracting any of these diseases? Well, for the most part, you never will, and thats thanks in part to vaccine research with nonhuman primates (NHPs). Being up to 98% genetically similar to people, primates are uniquely capable of revealing how many diseases work in the human body. Due to their similarities to humans, monkeys are irreplaceable for vaccine development because they alone mirror the entire biological process of infections in people. These days, scientists are studying NHPs to develop new vaccines for everything from cancer to Zika to HIV.. An HIV Vaccine. HIV is a virus that attacks the bodys immune system, specifically T cells. There is currently no cure, but HIV can be managed through the use of antiretroviral therapy (ART).. Those who are infected can expect to live normal lifespans if they receive one of the various ART drug cocktails, which have proven to be effective for so ...
Are we talking about PREDISOLONE? i cannot take any non steroidal anti inflammatories and so regularly rely on Predisolone to help the pain and inconvenience of gout in my hands and systemic osteoarthritis, all related to and worsening thanks to Stage 4 CKD. I am lucky in that this particular drug, mixed in with the 5 or 6 other meds Im prescribed each day only seems to have beneficial effects, but my nephrologist and brilliant GP tinker with my drug cocktail all the time as there are many substitutes for almost everything in their pharmacopeia these days, so Id ask to try something different if you cant cope with the side effects ...
PUBLICATIONS Peer-reviewed Articles 21. Cao, Z., Chen, F., Bao, N., He, H., Xu, P., Jana, S., Jung, S., Lian, H., Lu, C. Droplet Sorting Based on the Number of Encapsulated Particles Using a Solenoid Valve. Lab on a Chip, accepted 20. K.C. R., Xu P.*, Multicompartment Intracellular Self-expanding Nanogel for Targeted Delivery of Drug Cocktail. Advanced Materials, (2012) [1] 19. K.C. R., Thapa B., Xu P.*, pH and redox dual responsive nanoparticle for nuclear targeted drug delivery. Molecular Pharmaceutics, (2012) 9 (9), 2719-2729. [2] 18. K.C. R., Thapa B., Xu P.*, Design of serum compatible tetrary complexes for gene delivery. Macromol. Biosci. (2012), 12, 637-646. (Cover page) [3] ...
A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimers disease, and brain injuries. A team... Read more ...
The outrage began when the police investigation revealed that Rebecca was given the diagnoses of ADHD and bipolar disorder by Dr Kayoko Kifuji, at the Tufts-New England Medical Center, when she was only 2 and half-years-old and placed on a 3-drug cocktail of Clonidine, a drug approved to treat adults with high blood pressure, Depakote an antiseizure drug approved to treat adults with epilepsy, and Seroquel, approved to treat adults with schizophrenia or the mania of bipolar disorder ...
What they found was no intact HIV. They did find HIV remnants, which are essentially fragmentary fossils of HIV, but not intact HIV capable of infecting. Even though this is pretty thorough, it is still sampling, so they had to use a mathematical model to predict the probability of cure, which they estimate at greater than 99%. Whether or not this cure is permanent remains to be seen, as both patients will have to be followed, but these results are extremely encouraging.. What does this mean for HIV treatment going forward? Not much directly, as even the less aggressive treatment is still high risk and will only be used in extreme cases, such as life-threatening blood cancer. For most patients with HIV, standard anti-retroviral drug cocktail is still the standard of care. But these cases are an important proof of concept that has implications for future research.. One big lesson is that the CCR5 HIV resistant variant is an effective treatment for those already infected with HIV. So the next ...
A lot has changed for me. I cant seem to keep my mind off the backward way we bring babies into the world in this country. Viewing birth through a medical lens is so unnecessary. Unless there truly are problems that require a doctors intervention, why are we so set on having surgeons deliver our babies and care for us prenataly? Midwives are the shit and should be our first thought when were pregnant. We are taught that labor is the worst thing ever to happen and that it should be feared and medicated away. We are led to believe that screaming in terror and agony are par for the course, that laying down on our backs is how babies come out easiest and that doctors and nurses know best when it comes to our own bodies. Im here to tell you that giving birth without a drug cocktail was significantly less painful and frightening that it was with drugs. I was so present this time, so much more in control. Fear is unnecessary if you trust your body and your care team, and when your care team ...
[ATTACH]When Oliver Sacks got stoned on Artane as a young doctor, he had an animated conversation with a philosophical spider who sounded like Bertrand Russell. A drug cocktail containing LSD...
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Objective: This dissertation aims to evaluate factors impacting drug disposition and clinical outcomes.; Methods: Pharmacokinetic studies were conducted for gemcitabine in urothelial cancer, paclitaxel in breast cancer and capecitabine in colorectal caner among patients stratified into young and elderly groups. Cocktail consisting of chlorzoxazone (CYP2E1), caffeine (CYP1A2), dapsone (CYP3A4), mephenytoin (CYP2C19) and debrisoquine (CYP2D6) were administrated to OLTx patients to evaluate enzyme activity relating to recipients age and post-operative duration. To assess renal P-gp activity in cystic fibrosis (CF) patients, disposition of fexofenadine was evaluated and P-gp efflux activity in peripheral T cells was measured by flow cytometry. To assess interactions between tenofovir and ritonavir, renal function of HIV-infected patients were evaluated and tenofovir disposition was compared relating to regiments administrated. Kidney cell lines, MDCKII and HEK293, were treated with tenofovir alone ...
Marchand, Loïc Le, Grant R. Wilkinson, and Lynne R. Wilkens. Genetic and Dietary Predictors of CYP2E1 Activity: A Phenotyping Study in Hawaii Japanese Using Chlorzoxazone. Cancer Epidemiology and Prevention Biomarkers 8.6 (1999): 495-500. Web. 04 Aug. 2020. ...
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It was a big day for investors watching the race to create the next generation of hepatitis C drug cocktails. Most of the major players released data for the European Association for the Study of the Liver conference today.. In the segment below, health-care analyst David Williamson explains why small-cap Achillion has an uphill battle in front of it while attempting to dethrone big pharma and big biotech Goliaths. Watch and find out how Achillion disappointed investors today, but its real test is still ahead.. ...
Facebook today detailed what it claims is the first single AI model capable of predicting the effects of drug combinations, dosages, timing, and other types of interventions like gene deletion. Developed in collaboration with Helmholtz Zentrum München, Facebook says the model could accelerate the process of identifying combinations of medications and other treatments that might lead to better outcomes for diseases.. Discovering ways to repurpose existing drugs has proven to be a powerful tool to treat diseases including cancer. In recent years, doctors have seen success with drug cocktails to combat malignant conditions and continue to explore personalized treatments for patients. But finding an effective combination of existing drugs at the right dose is extremely challenging, in part because there are nearly infinite possibilities. Researchers would have to try from 5,000 to 19 billion solutions to find the optimal regimen given a pool of 100 drugs.. Facebooks open source model - ...
3) The hospital at which Sidney was born sucks. I am going to refrain from naming names (partly out of my gentlemanly nature, mostly because I dont want a letter from their lawyers), but that does not mean I am going to water this down. From the moment My Wife was admitted at 8pm on January 19 to the moment we were discharged with Sidney at 3pm on January 22, the parade of incompetence would make for a Comedy of Errors but for the facts that: (a) none of it involved mistaking twins for each other (the Lit majors should at least be chuckling); and (b) THIS IS MY SON, WHAT ARE YOU IDIOTS DOING. Keeping this brief, but accurate, the following happened: (a) the anesthesiologist needed 3 tries to get the epidural into My Wife ... 3 painful tries; (b) while we are on the epidural, they gave her the wrong dosage and drug cocktail on the epidural. Yeah, this one is a biggie, and they explained it several hours later as a labeling mistake (were following up on this one because I am a pissed off Dad ...
Researchers have developed a capsule that can deliver a weeks worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule of dosing required for the drug cocktails used to fight the virus, the researchers say. The new capsule is designed so that patients can take it just once a week, and the drug will release gradually throughout the week. This type of delivery system could not only improve patients adherence to their treatment schedule but also be used by people at risk of HIV exposure to help prevent them from becoming infected, the researchers say. One of the main barriers to treating and preventing HIV is adherence, says Giovanni Traverso, a Research Affiliate at MITs Koch Institute for Integrative Cancer Research and a Gastroenterologist and Biomedical Engineer at Brigham and Womens Hospital. The ability to make doses less frequent stands to improve adherence and make a significant impact at the patient level. We are all ...
How fatal is Ebola?. One of the problems with treating the virus is that in its earliest stages it mimics a number of other diseases endemic to Africa. Usually within eight to 10 days of infection, according to the CDC, patients experience a fever, a headache, and muscle fatigue. Some people get better, but most-up to 90 percent-get worse. In a victims last days, he or she will begin to hemorrhage blood, internally and externally, as the disease lays waste to internal organs. There are no drugs approved for treating Ebola. For the infected, the only hope is that the virus will pass. According to the CDC, the only treatments available fall under the category of supportive therapy-providing patients with water, maintaining blood pressure, and treating for complicating infections-with the hope that a patients immune system can fight off the virus. Lab researchers have had some luck using drug cocktails to block the disease in animals shortly after exposure, but they havent yet tested these ...
Changes in body fat became a signature struggle among the HIV population during the early years of the modern era of antiretroviral (ARV) treatment, which began in 1996 with the introduction of the first of the triple combination drug cocktails.
Doctors are worried about a type of malaria spreading in South East Asia that is not responding to usual treatments. Doctors can still treat infected patients with stronger drug cocktails. But they worry that it is just a matter of time before those medicines also become ineffective.
Combining oxycodone and Xanax or other benzodiazepines is dangerous and can be deadly. Learn more about why you should avoid this lethal drug cocktail.
The paper by Ribba et al. (2012) [1, BIOMD0000000521] exemplifies a remarkable example of a model developed in close collaboration between modellers and clinicians for which the data has been collected for over 10 years. At the time of publication, it was the first model that successfully described the time course of tumour growth inhibition for patients with low-grade gliomas (LGG) as consequence of chemotherapy and radiotherapy. The model is based on the observation that after a termination of PCV chemotherapy, LGGs often continue to shrink in volume for an extended period of time, ranging from months to years. The hypothesis explaining this phenomenon assumes a certain delay in the action of chemotherapy on non proliferating cells. This is in line with the known cell-cycle non-specific mechanism of action of the PCV regimen related agent. PCV stands for a drug cocktail, i.e. a mixture of three chemotherapeutic components: ...
Lets just say Im a bit anxious about todays chemotherapy infusion. This will be the first infusion of cycle 2. I go in three week cycles; 1 chemo 1 week, 1 chemo the next week, and then the third week off. During each cycle, the first chemo of each cycle is a two drug cocktail - Gemcitabin (aka Gemzar - an antimetabolite) & Carboplatin (aka Paraplatin - an alkylating agent). AND the first chemo of the first cycle was hell, putting it mildly. So you can see where the anxiety is coming from ...
The day when ovarian cancer can be treated with a single, painless pill instead of a toxic drug cocktail is the ultimate goal of pioneering research by professor Preethi Gunaratne. Her work in ovarian cancer gained exceptional notice and momentum this year with a series of high-profile research grants.
SINCE THE DISCOVERY of protease inhibitors, commonly known as antiretroviral drug cocktails, in 1995, much has changed for the nearly 850,000 Americans living with HIV/AIDS. A diagnosis no longer brings the spectre of rapid wasting, debilitation, and death. But complacency can be disastrous when combatting an infectious disease as cunning and persistent as AIDS. Prevention efforts remain as important as medical treatments, say Emory researchers who are joining forces to fight the epidemic on all fronts.. There s a misperception that inhibitors are a cure: If I pop these pills, I ll have the disease under control. . . . I won t have to wear condoms anymore, says Lawrence Bryant (above), a senior research coordinator for the behavioral science core of Emory s Center for AIDS Research (CFAR). The younger generation hasn t experienced AIDS the way the older generation has losing close friends every other day, seeing the disease manifest itself in its entirety. There s not the same urgency to be safe ...
I have to say-- this is probably something your state doesnt want to be known for. Last post, I discussed how EU pharmaceutical companies are refusing to allow their drugs to be used in executions.More recently, was the botched execution of Oklahoma prisoner, Clayton Lockett.Whats interesting is that in Oklahoma, the drug cocktail was kept…
A local attorney tells WPBF 25 News that he is seeing a disturbing trend; a sharp spike in the number of cases involving a dangerous drug cocktail and DUIs.
Even though effective drug cocktails have improved the outlook for many patients with HIV, disease progression, including the time from AIDS onset to death, varies widely from patient to patient. Now, a study led by the University of North Carolina at Chapel Hill School of Medicine provides new evidence that psychological factors play a role…
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