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Various Drugs (various + drug)
Selected AbstractsManagement of Low Compliant Bladder in Spinal Cord Injured PatientsLUTS, Issue 2 2010Won Hee PARK Low bladder compliance means an abnormal volume and pressure relationship, and an incremental rise in bladder pressure during the bladder filling. It is well known that at the time bladder capacity decreases, intravesical pressure increases, and the risk of upper deterioration increases. Hypocompliance is usually thought to be the range from 1.0 to 20.0 mL/cmH2O. Though the exact cause of hypocompliance is not known, it may be caused by changes in the elastic and viscoelastic properties of the bladder, changes in detrusor muscle tone, or combinations of the two. Management aims at increasing bladder capacity with low intravesical pressure. The main is a medical therapy with antimuscarinics combined with clean intermittent catheterization. The results are sometimes unsatisfactory. Various drugs or agents through the mouth or the bladder, including oxybutynin, new antimuscarinics, capsaicin and resiniferatoxin were tried. Among them botulinum toxin-A is promising. Some patients eventually required surgical intervention in spite of the aggressive medical therapy. Finally most patients undergo the surgical treatment including autoaugmentation, diversion, and augmentation cystoplasty. Among them augmentation cystoplasty still seems the only clearly verified treatment method. [source] Therapeutics for alcoholism: what's the future?DRUG AND ALCOHOL REVIEW, Issue 1 2007ANDREW J. LAWRENCE Abstract As with other addictions, human alcoholism is characterised as a chronically relapsing condition. Consequently, the therapeutic goal is the development of clinically effective, safe drugs that promote high adherence rates and prevent relapse. These products can then be used in conjunction with psychosocial approaches. In this review, preclinical studies are highlighted that indicate the mechanism of action of currently used anti-craving medications or demonstrate the potential of novel pharmacological agents for the treatment of alcohol use disorders. While current pharmacological strategies are far from ideal, there are a number of candidate molecules that may ultimately be developed into therapeutic agents. In addition, prescribing clinicians should also consider strategies such as combinations of various drugs to aid in the regulation of aberrant alcohol consumption. [source] Drug classification: science, politics, both or neither?ADDICTION, Issue 7 2010Harold Kalant ABSTRACT Governments currently classify illicit drugs for various purposes: to guide courts in the sentencing of convicted violators of drug control laws, to prioritize targets of prevention measures and to educate the public about relative risks of the various drugs. It has been proposed that classification should be conducted by scientists and drug experts rather than by politicians, so that it will reflect only accurate factual knowledge of drug effects and risks rather than political biases. Although this is an appealing goal, it is inherently impossible because rank-ordering of the drugs inevitably requires value judgements concerning the different types of harm. Such judgements, even by scientists, depend upon subjective personal criteria and not only upon scientific facts. Moreover, classification that is meant to guide the legal system in controlling dangerous drug use can function only if it is in harmony with the values and sentiments of the public. In some respects, politicians may be better attuned to public attitudes and wishes, and to what policies the public will support, than are scientific experts. The problems inherent in such drug classification are illustrated by the examples of cannabis and of salvinorin A. They raise the question as to whether the classification process really serves any socially beneficial purpose. [source] PRECLINICAL STUDY: Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in miceADDICTION BIOLOGY, Issue 3 2009Emilie Belkaï ABSTRACT The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. [source] Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver,HEPATOLOGY, Issue 4 2009Anne T. Nies An important function of hepatocytes is the biotransformation and elimination of various drugs, many of which are organic cations and are taken up by organic cation transporters (OCTs) of the solute carrier family 22 (SLC22). Because interindividual variability of OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic and nongenetic factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver. OCT1 and OCT3 expression (messenger RNA [mRNA], protein) was analyzed in liver tissue samples from 150 Caucasian subjects. Hepatic OCTs were localized by way of immunofluorescence microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and genome-wide single-nucleotide polymorphism microarray technology served to genotype 92 variants in the SLC22A1-A3/OCT1-3 gene cluster. Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells. OCT1 mRNA and protein expression varied 113- and 83-fold, respectively; OCT3 mRNA expression varied 27-fold. OCT1 transcript levels were on average 15-fold higher compared with OCT3. We localized the OCT3 protein to the basolateral hepatocyte membrane and identified metformin as an OCT3 substrate. OCT1 and OCT3 expression are independent of age and sex but were significantly reduced in liver donors diagnosed as cholestatic (P , 0.01). Several haplotypes for OCT1 and OCT3 were identified. Multivariate analysis adjusted for multiple testing showed that only the OCT1-Arg61Cys variant (rs12208357) strongly correlated with decreased OCT1 protein expression (P < 0.0001), and four variants in OCT3 (rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P = 0.03). Conclusion: We identified cholestasis and genetic variants as critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression. This indicates consequences for hepatic elimination of and response to OCT substrates such as metformin. (HEPATOLOGY 2009.) [source] Nicolau Syndrome: three cases and reviewINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2006Kelli Luton MD Nicolau Syndrome, also known as livedo-like dermatitis (LLD) or embolia cutis medicamentosa (ECM), is an infrequent complication following intramuscular and intra-articular injection of various drugs. This rare entity is characterized by severe pain and erythematous-ecchymotic reticular lesions at the injection site, which in many cases lead to necrotic ulcers and scarring. We report three cases of Nicolau Syndrome following injection of diclofenac, penicillin G, and cyanocobalamin. [source] Development of an Antibody Hapten-Chip System for Detecting the Residues of Multiple Antibiotic Drugs,JOURNAL OF FORENSIC SCIENCES, Issue 4 2009Ailiang Chen M.Sc. Abstract:, The abuse of antibiotic drugs during animal production remains a worldwide problem and the subsequent detection of the residues of various drugs present at low concentrations in complex biological matrices poses significant analytical challenges. The present study outlines a practical biochip assay system to identify antibiotic residues in different animal tissue extracts. The system uses a simple but efficient multiresidue sample extraction procedure to isolate the antibiotic residues which were then identified directly using high-affinity monoclonal antibodies presented in a competitive immunoassay with conjugated antibiotic hapten-chips. The hapten-chip can analyze six samples each for eight antibiotics on a single chip within 3 h. The analytical results with both artificial positive standard samples and the incurred samples show that the antibody hapten-chip system has a comparable accuracy and a similar sensitivity to a standard ultra performance liquid chromatography,mass spectrometry (MS)/MS assay. In conclusion, an effective analytical screening system based on antibody hapten-chip was developed for detecting multiple antibiotic residues from multiple samples. [source] Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?JOURNAL OF INTERNAL MEDICINE, Issue 3 2006C. SÖDERBERG-NAUCLÉR Abstract. Human cytomegalovirus (HCMV) is a herpes virus that infects and is carried by 70,100% of the world's population. During its evolution, this virus has developed mechanisms that allow it to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen, as it appeared to cause only rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted for survival in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients and in patients undergoing immunosuppressive therapy following organ or bone marrow transplantation. HCMV-mediated disease in such patients has highlighted the possible role of this virus in the development of other diseases, in particular inflammatory diseases such as vascular diseases, autoimmune diseases and, more recently, with certain forms of cancers. Current research is focused on determining whether HCMV plays a causative role in these diseases or is merely an epiphenomenon of inflammation. Inflammation plays a central role in the pathogenesis of HCMV. This virus has developed a number of mechanisms that enable it to hide from the cells of the immune system and, at the same time, reactivation of a latent infection requires immune activation. Numerous products of the HCMV genome are devoted to control central functions of the innate and adaptive immune responses. By influencing the regulation of various cellular processes including the cell cycle, apoptosis and migration as well as tumour invasiveness and angiogenesis, HCMV may participate in disease development. Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases. [source] Validated assay for quantification of oxcarbazepine and its active dihydro metabolite 10-hydroxycarbazepine in plasma by atmospheric pressure chemical ionization liquid chromatography/mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2002Hans H. Maurer Abstract Oxcarbazepine (OX), a new antiepileptic, may lead to unwanted side-effects or even life-threatening intoxications after overdose. Therefore, a validated liquid chromatographic/mass spectrometric (LC/MS) assay was developed for the quantification of OX and its pharmacologically active dihydro metabolite (dihydrooxcarbazepine, DOX, often named 10-hydroxycarbazepine). OX and DOX were extracted from plasma by the authors' standard liquid/liquid extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. The compounds were quantified in the selected-ion monitoring mode using atmospheric pressure chemical ionization electrospray LC/MS. The assay was fully validated. It was found to be selective. The calibration curves were linear from 0.1 to 50 mg l,1 for OX and DOX. Limits of quantification were 0.1 mg l,1 for OX and DOX. The absolute recoveries were between 60 and 86%. The accuracy and precision data were within the required limits. The analytes in frozen plasma samples were stable for at least 1 month. The method was successfully applied to several authentic plasma samples from patients treated or intoxicated with OX. The measured therapeutic plasma levels ranged from 1 to 2 mg l,1 for OX and from 10 to 40 mg l,1 for DOX. The validated LC/MS assay proved to be appropriate for quantification of OX and DOX in plasma for clinical toxicology and therapeutic drug monitoring purposes. The assay is part of a general analysis procedure for the isolation, separation and quantification of various drugs and for their full-scan screening and identification. Copyright © 2002 John Wiley & Sons, Ltd. [source] Deep percutaneous penetration into muscles and jointsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Christine M. Lee Abstract The transdermal absorption of drugs and its subsequent deep tissue delivery is a complex process, with many factors influencing the penetration mechanisms. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the treatment of joint and muscle diseases. However, the dangers associated with oral medications highlight the need for alternative methods of targeting and retaining drugs; one such means is through topical delivery. The drug's lipophilicity, permeability, and fraction unbound found in the viable skin are some physiochemical factors influencing the delivery mechanism after transdermal absorption. These and other variables play a role in determining whether the drug reaches the deep tissues via direct penetration or from systemic redistribution. Pharmacokinetic models have been developed to help elucidate the penetration routes and efficacy for various drugs. While there are still uncertainties regarding the deep tissue penetration kinetics, improvements to current research methodologies may bring about a greater understanding of percutaneous absorption into the deep muscle and joints. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1405,1413, 2006 [source] Paramedical treatment in primary dystonia: A systematic review,MOVEMENT DISORDERS, Issue 15 2009Cathérine C.S. Delnooz MD Abstract Dystonia is a disabling movement disorder with a significant impact on quality of life. The current therapeutic armamentarium includes various drugs, botulinum toxin injections, and occasionally (neuro)surgery. In addition, many patients are referred for paramedical (including allied health care) interventions. An enormous variation in the paramedical treatment is provided, largely because evidence-based, accepted treatment regimes are not available. We have conducted a systematic review of studies that explored the effect of various paramedical interventions in primary dystonia. Only studies that have used clinical outcome measures were included. There were no class A1 or A2 studies and therefore, level 1 or 2 practice recommendations for a specific intervention could not be deducted. Many papers were case reports, mostly with a very limited number of patients and a clear publication bias for beneficial effects of a particular paramedical intervention. Some potentially interesting interventions come from class B studies, which include physical therapy in addition to botulinum toxin injections (BoNT-A) in cervical dystonia; sensorimotor training and transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech therapy added to BoNT-A injections in laryngeal dystonia. Good quality clinical studies are therefore warranted, which should have the aim to be generally applicable. A design in which the paramedical intervention is added to a current gold standard, for example, BoNT-A injections in cervical dystonia, is recommended. © 2009 Movement Disorder Society [source] Clinical Experience with Molecular Adsorbent Recirculating System (MARS) in Patients with Drug-induced Liver FailureARTIFICIAL ORGANS, Issue 5 2004Xin-min Zhou Abstract:, The molecular adsorbent recirculating system (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in a group of fourteen patients with drug-induced liver failure. Fourteen patients, aged 22,83 years, with acute or subacute liver failure [mean Child,Turcotte,Pugh (CTP) score 11 (range 8,15)] due to the intake of various drugs (diet pill overdose,2; Chinese traditional medicine (CTM),4; antibiotic, paracetamol, tuberculostatic, or vasodilator abuse,8) were treated with one to seven sessions of MARS. Beneficial effects such as the improvement of encephalopathy and prothrombin activity, as well as a reduction of bilirubin and ammonia were recorded during MARS treatments. Thirteen out of fourteen patients survived the hospitalization (93%), and two of the discharged patients died during the follow-up of 6,12 months. The overall survival rate was about 79%. MARS therapy can contribute to the improved treatment of drug-induced liver failure patients. [source] The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body modelBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2004Eyal Sobol Abstract Rationale. In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t1/2). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation: C=Ae,,t+Be,,t, where A and B are concentration unit-coefficients and , and , are exponential coefficients. The relationships between t1/2 and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t1/2. Methods. In the current paper new equations have been developed that describe the relationships between the terminal t1/2 (or t1/2,) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). Results. A critical value (CV) equals to the quotient of (1,ln2) and (1,,/,) (CV=(1,ln2)/(1,,/,)=0.307/(1,,/,)) has been derived and was compared with the fraction (f1) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f1=A/,/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1,ln2) and infinity. As long as f1 Differential inhibitory effects of drugs acting at the noradrenaline and 5-hydroxytryptamine transporters in rat and human neocortical synaptosomes,BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2009M Mantovani Background and purpose:, Although the amino acid sequences of rat and human 5-hydroxytryptamine (5-HT) and noradrenaline (NA) transporters (i.e. SERT and NET) are highly homologous, species differences exist in the inhibitory effects of drugs acting at these transporters. Therefore, comparison of the potencies of drugs acting at SERT and NET in native human and rat neocortex may serve to more accurately predict their clinical profile. Experimental approach:, Synaptosomes prepared from fresh human and rat neocortical tissues were used for [3H]-5-HT and [3H]-NA saturation and competition uptake experiments. The drugs tested included NA reuptake inhibitors (desipramine, atomoxetine and (S,S)-reboxetine), 5-HT reuptake blockers (citalopram, fluoxetine and fluvoxamine) and dual 5-HT/NA reuptake inhibitors (duloxetine and milnacipran). Key results:, In saturation experiments on synaptosomal [3H]-5-HT and [3H]-NA uptake, the dissociation constants did not indicate species differences although a smaller density of both SERT and NET was observed in human tissues. In competition experiments with the various drugs, marked species differences in their potencies were observed, especially at SERT. The rank order of selectivity ratios (SERT/NET) in human neocortex was as follows: citalopram , duloxetine = fluvoxamine , fluoxetine > milnacipran > desipramine = atomoxetine > (S,S)-reboxetine. Significant species differences in these ratios were observed for duloxetine, atomoxetine and desipramine. Conclusions and implications:, This study provides the first compilation of drug potency at native human neocortical SERT and NET. The significant species differences (viz., human vs. rat) in drug potency suggest that the general use of rodent data should be limited to predict clinical efficacy or profile. [source] Off-Target Decoding of a Multitarget Kinase Inhibitor by Chemical ProteomicsCHEMBIOCHEM, Issue 7 2009Enrico Missner Abstract Unbiased: Chemical proteomics was used to profile compound interactions in an unbiased fashion. We present here the application of different compound-immobilization routes for decoding nonprotein kinase off-targets of the multitarget kinase inhibitor C1, which interacts with distinct compound moieties. Since the approval of the first selective tyrosine kinase inhibitor, imatinib, various drugs have been developed to target protein kinases. However, due to a high degree of structural conservation of the ATP binding site, off-target effects have been reported for several drugs. Here, we report on off-target decoding for a multitarget protein kinase inhibitor by chemical proteomics, by focusing on interactions with nonprotein kinases. We tested two different routes for the immobilization of the inhibitor on a carrier matrix, and thus identified off-targets that interact with distinct compound moieties. Besides several of the kinases known to bind to the compound, the pyridoxal kinase (PDXK), which has been described to interact with the CDK inhibitor (R)-roscovitine, was captured. The PDXK,inhibitor interaction was shown to occur at the substrate binding site rather than at the ATP binding site. In addition, carbonic anhydrase 2 (CA2) binding was demonstrated, and the determination of the IC50 revealed an enzyme inhibition in the submicromolar range. The data demonstrate that different compound immobilization routes for chemical proteomics approaches are a valuable method to improve the knowledge about the off-target profile of a compound. [source] Opioid-induced pruritus: an updateCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2010A. Reich Summary Pruritus is an unpleasant sensation leading to scratching. It can be a feature of numerous skin or systemic diseases, and may also be a side-effect of various drugs. Opioids are one of the best-known medicines evoking pruritus. The pathogenesis of opioid-induced pruritus is still not fully known, but two different mechanisms have been proposed: peripheral and central. Several treatment options have been tested for opioid-induced pruritus, but none has been completely satisfactory. Opioid antagonists seem to be the most potent antipruritic drugs, but they also decrease analgesia, which limits their usage. Many other treatments have been tried, but to date, the data are conflicting or only limited studies have been performed to confirm their efficacy. Further studies are still needed to better elucidate the mechanism of opioid-induced pruritus and to develop more effective treatment options. [source]
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