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Different Drugs (different + drug)
Selected AbstractsComparison of ciprofloxacin hydrochloride-loaded protein, lipid, and chitosan nanoparticles for drug deliveryJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2008Dharmendra Jain Abstract The aim of the present study was to develop single dose delivery systems based on nanotechnology for prolonged antibiotic release in a controlled manner. Five different drug,carrier ratios of ciprofloxacin hydrochloride-loaded nanoparticles of albumin, gelatin, chitosan (CS), and lipid [solid lipid nanoparticles (SLNs)] were prepared and characterized. Average particle size was found to be in the range of 73 ± 2 to 98 ± 44 nm for SLNs, 140 ± 7 to 175 ± 24 nm for albumin nanoparticles, 143 ± 18 to 184 ± 27 nm for gelatin nanoparticles, and 247 ± 48 to 322 ± 52 nm for CS nanoparticles. A drug-to-carrier ratio of 0.5:1 was preferred for CS nanoparticles having zeta potential of >20 mV and drug encapsulation of 35.01% ± 2.66%. Similarly, 0.6:1 ratio was preferred for albumin nanoparticles with zeta potential >16 mV and drug encapsulation 48.20% ± 3.01%. Zeta potentials of gelatin nanoparticles loaded with ciprofloxacin suggested that they were unstable and prone to flocculation. SLN with 0.25:1 drug carrier ratio showed 38.71% ± 2.38% drug entrapment and ,28 ± 1 mV surface charge. All the nanoparticles showed sustained drug release avoiding "burst effect" of the free drugs for up to 120 h for albumin nanoparticles, 96 h for CS and gelatin nanoparticles, and 80 h for SLNs. The drug release profiles followed Higuchi model. Results suggest that CS nanoparticles and SLNs can act as promising carriers for sustained ciprofloxacin release in infective conditions. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [source] Unified QSAR & network-based computational chemistry approach to antimicrobials.JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2010Abstract In the previous work, we reported a multitarget Quantitative Structure-Activity Relationship (mt-QSAR) model to predict drug activity against different fungal species. This mt-QSAR allowed us to construct a drug,drug multispecies Complex Network (msCN) to investigate drug,drug similarity (González-Díaz and Prado-Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species,species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt-QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug,drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug,drug msCN and species,species mdsCN with random networks. We also introduced here the inverse methodology to construct species,species msCN based on a mt-QSAR model. Last, we reported the first substructural analysis of drug,drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [source] Latest news and product developmentsPRESCRIBER, Issue 3 2008Article first published online: 26 FEB 200 Higher risk of CV events in aspirin resistance More than one in four patients may have aspirin resistance, a new metaanalysis shows, and they face a four-to sixfold increased risk of a major cardiovascular event or death compared with aspirin-sensitive patients taking low-dose aspirin (BMJ online: 17 Jan 2008; doi:10. 1136/bmj.39430.529549.BE). The analysis included 20 studies involving a total of 2930 patients with cardiovascular disease. Of these, 28 per cent were defined as having aspirin resistance (according to the various definitions in each study). Compared with aspirin-sensitive patients, the odds ratio of any cardiovascular event or acute coronary syndrome was about 4 and the odds ratio of death was 6. Aspirin-resistant patients did not benefit from other antiplatelet treatment. ADOPT: rosiglitazone fracture risk in women A new analysis of the ADOPT trial (N Engl J Med 2006;355: 2427-43) has found that the risk of fractures during treatment with rosiglitazone (Avandia) is approximately twice as high as with metformin or glibenclamide, but mainly in women (Diabetes Care online: 25 Jan 2008; doi: 10.2337/dc07-2270). The study found a significant difference in risk between the drugs only for women, with a cumulative incidence of 15.1 per cent with rosiglitazone, 7.3 per cent with metformin and 7.7 per cent with glibenclamide after five years. No risk factors were identified although the incidence of fractures was higher among postmenopausal than premenopausal women. New from NICE Infliximab for the treatment of adults with psoriasis. Technology Appraisal Guidance No. 134, Jan 2008 Infliximab (Remicade), a monoclonal antibody against TNF-alpha, should be an option for treating very severe plaque psoriasis in adults, NICE recommends. Using its fast-track single technology appraisal procedure, NICE concluded that infliximab should be considered when standard therapies,methotrexate or ciclosporin (Neoral), or PUVA , have failed or are unsuitable. The criteria for disease severity are defined by the Psoriasis Area Severity Index (PASI) score (,20) and the Dermatology Life Quality Index (DLQI) score (>18). Treatment response is also defined by these measures and infliximab should be continued for longer than 10 weeks only when predefined thresholds are met. Infliximab costs an average of £11 750 annually. In 2006, NICE recommended etanercept (Enbrel) and efalizumab (Raptiva) for patients with severe psoriasis (PASI ,10 and DLQI >10). Commons committee wants tougher targets Most GPs get full QOF points for medicines management even though there is inexplicably large variation in good prescribing practice between PCTs, the Public Accounts Select Committee points out in its latest report, Prescribing Costs in Primary Care. The Committee wants to see tougher QOF targets among several initiatives to reduce prescribing costs. Although most publicity centred on its endorsement of the National Audit Office claim that GPs could save £200 million by prescribing lower-cost drugs, the report contains some more far-reaching proposals. GPs should prescribe generic alternatives within a therapeutic category, so when a brand is not available generically, eg Lipitor, a different drug that is, eg simvastatin, should be used when clinically appropriate. Further, this form of substitution should be rewarded via QOF targets. There should be greater uniformity in the appearance, labelling and packaging of generic and branded equivalents. The Department of Health should consider raising awareness of the value of medicines by printing the cost on packaging, and to reduce the £100 million wasted annually in dumped medicines, it should investigate which drugs aren't used and why patients won't take them. Strategic health authorities should work with the National Prescribing Centre to develop more prescribing indicators with which to measure PCT performance and support PCTs to promulgate best practice. They should also collaborate on promoting joint primary-secondary care formularies and increase the consistency of prescribing, not only between hospital specialists and GPs but also between PCTs. To monitor the influence of the pharmaceutical industry, PCTs should keep a record of gifts and hospitality and publish a register. Questions to ask about mental health treatment The Department of Health has published a booklet designed to raise awareness of medicines management issues affecting people using mental health services and their carers, and professionals in the health and social services. Although one aim of Medicines Management: Everybody's Business is to empower people with mental health problems to ask about their medication, its formal style is better suited to staff who need to improve their person-centred approach to care. It covers what information people should expect and what questions to ask when drug treatment is being considered, what to expect at review and issues to consider when contemplating stopping treatment. Copies can be downloaded at www.dh.gov.uk. Consider statins for all patients with diabetes Treatment with a statin should be considered for all patients with diabetes unless their risk is low, say the authors of a new study (Lancet 2008;371:117-25). Their meta-analysis of 14 randomised trials involving 18 686 people with diabetes and an average follow-up of 4.3 years found that statins reduced vascular events and vascular mortality as much as in nondiabetic populations. The overall benefit was 42 fewer major events per 1000 people treated for five years. This was independent of a history of vascular disease or other baseline characteristics. No evidence for OTC cough medicines There is no evidence that over-the-counter cough medicines for adults and children are effective in relieving acute cough, a new Cochrane review has concluded (Cochrane Database of Systematic Reviews 2008, Issue 1). The review of 17 randomised trials involving 2876 adults and eight involving 616 children reported conflicting findings of uncertain clinical relevance. The trials were heterogeneous and of low quality. Copyright © 2008 Wiley Interface Ltd [source] Are we becoming more alike?DRUG AND ALCOHOL REVIEW, Issue 5 20082004 national household surveys, Comparison of substance use in Australia, the United States as seen in the 199 Abstract Introduction. This paper reports the results of the 1995, 1998, 2001 and 2004 Australian and US household surveys, with emphasis on changes since 2001. Design and Methods. The US survey data were recalculated to match age groups in the Australian data. Statistically significant changes are reported. Differences in prevalence of use by gender within age group were tested for significance. Results. The past-year use of ,any illicit drug', cannabis, cocaine, tranquillisers and injecting drugs decreased between 2001 and 2004 in Australia, but remained stable for all these drugs except ecstasy between 2002 and 2004 in the United States. The use of hallucinogens decreased in both countries. Alcohol and use of many illicit drugs by teenage girls in both countries increased to rates similar to or higher than boys, and teens in both countries reported binge and heavy drinking in the past month. Australians in their 20s had the highest rates of use, but in the United States, past-year use of many drugs was highest among teenagers. Discussion. More treatment services are needed, particularly for people dependent upon non-opiate drugs. The changes in acceptability of use of different drugs and their perceived availability are related to changes in prevalence rates. Even with the similarities in levels of use, there are differences in patterns of use and preferences for certain drugs in each country, and geographic proximity to drug sources is a factor. [source] Outcome predictors, efficacy and safety of Botox and Dysport in the long-term treatment of hemifacial spasmEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009A. R. Bentivoglio Background and purpose:, To review the clinical characteristics and the long-term outcome of patients with hemifacial spasm (HFS) who received botulinum neurotoxin (BoNT) over the past 10 years. Results:, A total of 108 patients received 665 treatments. Mean latency of clinical effect was 5.4 ± 5.3 days for Botox and 4.9 ± 4.6 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher after the injection of Dysport than Botox: 105.9 ± 54.2 and 85.4 ± 41.6 days respectively (P < 0.01). The percentage of treatment failures was 6.5% for Botox and 4.6% for Dysport (P > 0.05). The doses of Botox significantly increased over time (, = 0.35, P < 0. 001) whilst Dysport dose remained unchanged (, = 0.16, n.s.). The duration of clinical benefit slightly increased with Botox (, = 0.12; P < 0.01), but remained constant for Dysport. Side effects occurred in 17.4% of treatments: 16.7% of patients who had received Botox, and in 19.7% who had received Dysport (P > 0.05). The most common side effects were palpebral ptosis and lacrimation; ptosis and lagophtalmos was more common in Dysport treatments (P < 0.005). Conclusions:, Both brands are effective and safe in treating HFS; efficacy is long-lasting. The differences in outcome and side effects confirm that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs. [source] Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populationsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2003Jue Quin Yang Abstract Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants. The frequency of these alleles in different ethnic populations is extremely variable. In this study, we compared the frequencies of CYP2C9 allelic variants among 394 Chinese living in Shanghai to 151 French Caucasians living in Paris. The allelic frequencies of CYP2C9 variants of the Chinese and the French subjects were 0.963, 0.001, 0.036 and 0.77, 0.15, 0.08 for CYP2C9*1, CYP2C9*2, CYP2C9*3, respectively. Chinese CYP2C9*3 allelic frequency was twice as lower as the French subjects, but three times higher than Korean (0.036 vs. 0.011). The CYP2C9*2 allele could be detected in only one Chinese subject, whereas it represented the major allelic variant in French Caucasians. The low frequency of the CYP2C9*2 and CYP2C9*3 allelic variants in Chinese subjects does not justify their detection in clinical practice, unlike French Caucasians. [source] Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regressionHAEMOPHILIA, Issue 2 2009M. J. TREUR Summary., The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 ,g kg,1 rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg,1 aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h. [source] Efficacy and toxicity of orally administered anticoccidial drugs for innovative treatments of Polysporoplasma sparis (Sitja-Bobadilla and Alvarez-Pellitero 1985) infection in Sparus aurata L.JOURNAL OF APPLIED ICHTHYOLOGY, Issue 5 2004F. Athanassopoulou Summary The purpose of this study was to test experimentally different drugs and therapeutic schemes in order to find a efficient commercial treatment for fish infected with myxosporeans. Two series of land-based experiments and one experimental cage trial were performed for this purpose. In the first land-based experiment, 10 and 30 g Sparus aurata naturally infected in the kidneys with Polysporoplasma sparis were used. Initially, six different doses of Fumagillin, two doses of Toltrazuril, and one dose of Amprolium, ESB3 and Salinomycin were tested. In the second land-based experiment, 25 and 50 g fish infected with the same parasite were treated with Origanum essential oils, Toltrazuril with propylene glycol, Amprolium, and a combination of Salinomycin 12% + Amprolium (SA). In the field trials, 15 and 155 g S. aurata infected with the same parasite were treated with SA, Origanum essential oils and Fumagillin. In all trials the drugs were incorporated in food and administered according to the selected schemes, while their efficacy was evaluated in terms of mortality (acceptable level <2%), pathology and prevalence rate of P. sparis. According to our results the SA combination proved to be the most effective treatment against P. sparis infection in S. aurata: (i) the therapeutic scheme and commercial product used was not toxic and (ii) a significant reduction in percentage of prevalence was observed. [source] Prescribed medications and pharmacy interventions for acute respiratory tract infections in Swiss primary careJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2009K. E. Hersberger PhD Summary Background and objectives:, Symptomatic medications are often not considered in clinical studies assessing interventions to reduce prescribing of antibiotics for acute respiratory tract infections (ARTI). Our study objectives were to examine prescribing patterns of antibiotics and symptomatic medications for ARTI in Swiss primary care and to monitor pharmacists' interventions during the prescription-dispensing process. Methods:, Medical records of 695 patients participating in a clinical trial which was designed to reduce use of antibiotics for ARTI in primary care, were linked to their prescriptions. Matching of prescribed and dispensed medications enabled the assessment of interventions by community pharmacists. Results:, On average, 2·4 different drugs were prescribed per patient (in total 142 antibiotics, 1599 symptomatic medications, and 56 non-ARTI-medication). Most patients (80%) were treated only with symptomatic medications. Most frequently prescribed symptomatic ARTI-medications were nasal decongestants (39%), cough suppressants (36%), and mucolytics (31%). Patients with prescribed antibiotics received significantly fewer symptomatic medications (odds ratio, 0·24; 95% confidence interval 0·16,0·37). Over 20% of prescriptions prompted at least one intervention by a pharmacist in the dispensing process. A discrepancy between prescribed and dispensed medications was seen in 19% of patients. Conclusions:, Prescription rates of antibiotics for ARTI in this trial were low and patients were treated mainly with non-antibiotic symptomatic medications. Efforts to reduce antibiotic prescribing may induce higher rates of use of medications for intensive symptomatic treatment. Considerable differences between prescribed and dispensed medications were noted. [source] Possible Role of Pseudoephedrine and Other Over-the-Counter Cold Medications in the Deaths of Very Young ChildrenJOURNAL OF FORENSIC SCIENCES, Issue 2 2007William E. Wingert Ph.D. ABSTRACT: The Philadelphia Medical Examiners Office has reported a series of 15 deaths between February 1999 and June 2005 of infants and toddlers 16 months and younger in which drugs commonly found in over-the-counter (OTC) cold medications were present. A total of 10 different drugs were detected: pseudoephedrine, dextromethorphan, acetaminophen, brompheniramine, carbinoxamine, chlorpheniramine, ethanol, doxylamine and the anticonvulsants, phenobarbital, and phenytoin. The drugs were confirmed and quantified by gas chromatography (GC)-mass spectrometry, with the exception of ethanol, which was analyzed by headspace GC and of phenobarbital and phenytoin that were quantified by GC with a nitrogen phosphorus detector. The most predominant drug was pseudoephedrine, which was found in all of the cases (blood concentration, n=14, range=0.10,17.0 mg/L, mean=3.34 mg/L) and was the sole drug detected in three cases. Acetaminophen was detected in blood from each of the five cases with sufficient sample. Other drugs (with frequency of detection) were dextromethorphan (five cases), carbinoxamine (four cases), chlorpheniramine (two cases) and brompheniramine, doxylamine, and ethanol (one case each). In the majority of the cases, toxicity from drugs found in easily available OTC medications was listed either as the direct cause of death or as a contributory factor. The manner of death was determined to be natural in only two of the cases. This postmortem study supports previous evidence that the administration of OTC cold medications to infants may, under some circumstances, be an unsafe practice and in some cases may even be fatal. The treating physicians and the general public need to be made more aware of the dangers of using OTC cold medications to treat very young children so that these types of tragedies might be avoided. [source] Polymeric enhancers of mucosal epithelia permeability: Synthesis, transepithelial penetration-enhancing properties, mechanism of action, safety issuesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2008Giacomo Di Colo Abstract Transmucosal drug administration across nasal, buccal, and ocular mucosae is noninvasive, eliminates hepatic first-pass metabolism and harsh environmental conditions, allows rapid onset, and further, mucosal surfaces are readily accessible. Generally, however, hydrophilic drugs, such as peptides and proteins, are poorly permeable across the epithelium, which results in insufficient bioavailability. Therefore, reversible modifications of epithelial barrier structure by permeation enhancers are required. Low molecular weight enhancers generally have physicochemical characteristics favoring their own absorption, whereas polymeric enhancers are not absorbed, and this minimizes the risk of systemic toxicity. The above considerations have warranted the present survey of the studies on polymeric transmucosal penetration-enhancers that have appeared in the literature during the last decade. Studies on intestinal permeation enhancers are also reviewed as they give information on the mechanism of action and safety of polymers. The synthesis and characterization of polymers, their effectiveness in enhancing the absorption of different drugs across different epithelium types, their mechanism of action and structure-efficacy relationship, and the relevant safety issues are reviewed. The active polymers are classified into: polycations (chitosan and its quaternary ammonium derivatives, poly- L -arginine (poly- L -Arg), aminated gelatin), polyanions (N-carboxymethyl chitosan, poly(acrylic acid)), and thiolated polymers (carboxymethyl cellulose-cysteine, polycarbophil (PCP)-cysteine, chitosan-thiobutylamidine, chitosan-thioglycolic acid, chitosan-glutathione conjugates). © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 1652,1680, 2008 [source] Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin testJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2008Lucielli Savegnago This study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe)2) in the formalin test. Mice were pre-treated with (PhSe)2 by the oral route (0.1,100 mg kg,1), 30 min before formalin injection. To address some of the mechanisms by which (PhSe)2 inhibits formalin-induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe)2 was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe)2 (10 mg kg,1, p.o.) was prevented by intrathecal injection of K+ channel blockers such as apamin and charybdotoxin (small- and large-conductance Ca2+ -activated K+ channel inhibitors, respectively) and tetraethylammonium (TEA, a non-selective voltage-dependent K+ channel inhibitor), but not glib-enclamide (an ATP-sensitive K+ channel inhibitor). The antinociceptive action caused by (PhSe)2 (10 mg kg,1, p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (N, -nitro- l -arginine, L-NOARG) and the soluble guanylate cyclase inhibitors 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca2+ and K+ channel pathways in the antinociceptive effect caused by (PhSe)2. [source] In-vitro permeation of drugs into porcine hair follicles: is it quantitatively equivalent to permeation into human hair follicles?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2008Yakov Frum It is already well-established that the general permeability properties of porcine skin are close to those of human skin. However, very little is known with respect to drug absorption into hair follicles and the similarities if any between the two types of tissue. The aim of this study was to use the skin sandwich system to quantify follicular drug absorption into porcine hair follicles. To our knowledge, this is the first time that the skin sandwich has been extended to porcine tissue. For this purpose, seven different drugs , estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine , exhibiting a wide range of log octanol-water partition coefficients (log Ko/w), but comparable molecular weights, were chosen as candidate solutes. The results showed a parabolic profile with maximal follicular contribution occurring at intermediate log Ko/w values. Linear regression analysis indicated that the follicular contributions in porcine skin correlated well with previously published follicular contributions in human skin (r2 = 0.87). The novelty of this research is that we show that porcine tissue is a good surrogate for modelling human skin permeability within the specific context of quantifying drug absorption into hair follicles. [source] Performance of electrospun nanofibers for SPE of drugs from aqueous solutionsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 18 2008Xue-jun Kang Abstract A novel extraction technique was reported. The solid phase material, nanofiber, was prepared by electrospinning using polystyrene. Twenty different drugs (10 ,g/L in water) were extracted using 1 mg of nanofibers within 5 min. The analytes can be desorpted from the fibers with 50 ,L of the methanol and then monitored by LC coupled to a UV detector. Packed-fiber SPE (PFSPE) provide high recoveries (>50%) for some relatively non-polar drugs (log P >1.5) (n -octanol-to-water partition ratio), and relatively low recoveries (9.9,39.8%) for the drugs within the log P window below 1. Experimental optimization of the technique has been carried out using seven representative drugs, edaravone, cinchonine, quinine, voriconazole, chlordiazepoxide, verapamil, and rutonding. Except for edaravone, the maximum yields of seven drugs (0.2 ,g/L) from water samples were approximately 100%, and were 33.7,88.2% from human plasma. The advantageous aspect of the technique encompasses high throughput, high sensitivity, simplicity, low cost, and green chemistry. [source] Chloroquine resistance in the malarial parasite, Plasmodium falciparumMEDICINAL RESEARCH REVIEWS, Issue 5 2002Lyann M.B. Ursos Abstract Malarial parasites remain a health problem of staggering proportions. Worldwide, they infect about 500 million, incapacitate tens of millions, and kill approximately 2.5 million (mostly children) annually. Four species infect humans, but most deaths are caused by one particular species, Plasmodium falciparum. The rising number of malarial deaths is due in part to increased drug resistance in P. falciparum. There are many varieties of antimalarial drug resistance, and there may very well be several molecular level contributions to each variety. This is because there are a number of different drugs with different mechanisms of action in use, and more than one molecular event may sometimes be relevant for resistance to any one class of drugs. Thus, "multidrug" resistance in a clinical setting likely entails complex combinations of overlapping resistance pathways, each specific for one class of drug, that then add together to confer the particular multidrug resistance phenotype. Nonetheless, rapid progress has been made in recent years in elucidating mechanisms of resistance to specific classes of antimalarial drugs. As one example, resistance to the antimalarial drug chloroquine, which has been the mainstay therapy for decades, is becoming well understood. This article focuses on recent advances in determining the molecular mechanism of chloroquine resistance, with particular attention to the biochemistry and biophysics of the P. falciparum digestive vacuole, wherein changes in pH have recently been found to be associated with chloroquine resistance. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 5, 465,491, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10016 [source] Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factorsMOLECULAR MICROBIOLOGY, Issue 4 2002Maria A. Schumacher Summary The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or activators. Some of these transcription factors are also multidrug-binding proteins, frequently recognizing the same array of drugs that are effluxed by the transporters that they regulate. How a single protein can recognize such chemically disparate compounds is an intriguing question from a structural standpoint and an important question in future drug development endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding regulatory proteins are more tractable systems for structural analyses. Here, we describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial transcription regulators that are also multidrug-binding proteins. Although our understanding of multidrug binding and transcriptional regulation by MarR is in its initial stages, the structure of a BmrR,TPP+,DNA complex has revealed important insights into the novel transcription activation mechanism of the MerR family, and the structures of a QacR,DNA complex and QacR bound to six different drugs have revealed not only the mechanism of induction of this repressor but has afforded the first view of any MDR protein bound to multiple drugs. [source] Neuroprotection trials in Parkinson's disease: Systematic review,,MOVEMENT DISORDERS, Issue 5 2009Robert G. Hart MD Abstract Treatments to slow the progression are a major unmet need in Parkinson's disease. Detailed assessment of randomized trials testing putative neuroprotective drugs was undertaken to inform the design, reporting, and interpretation of future studies. This study is a systematic review of trials testing neuroprotective drugs. Data were extracted independently by two coauthors. Fifteen completed, published trials involving 4,087 participants tested 13 different drugs in 18 double-blind comparisons with placebo. Seven comparisons involving 2,000 subjects assessed MAO-B inhibitors. The primary outcome was change in the Unified Parkinson's Disease Rating Scale score in eight trials and time to need for dopaminergic therapy in seven. Mean participant age was 62 years, 35% were women, the interval from diagnosis to entry averaged 11 months, and the number of participants averaged 272 (largest = 806). Follow-up averaged <16 months in all but two trials. Detailed randomization methods and success of double-blinding were reported in 20% and 13%, respectively. Based on the investigators' conclusions, six trials were interpreted as consistent with a neuroprotective effect, three as negative, and five as either confounded or not meeting criteria for futility. Neuroprotection trials have involved relatively uniform groups of participants early in the clinical disease course, with outcomes weighted heavily toward motor deterioration. Future trials should include participants with wider ranges of disease stages and assess broader neurological outcomes. © 2008 Movement Disorder Society [source] Number III Mucous membrane pemphigoidORAL DISEASES, Issue 4 2005J Bagan Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory,especially immunosuppressive,therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice. [source] The pattern of intravenous drug administration during the transfer of critically ill children by a specialist transport teamPEDIATRIC ANESTHESIA, Issue 10 2006AGNI S. SAHA MD Summary Background:, There are few published data on the patterns of intravenous drug administration by specialist pediatric intensive care unit (PICU) transport teams during the transfer of critically ill children between hospitals. Methods:, A retrospective review of retrieval documentation was undertaken for all patients transported by the Royal Manchester Children's Hospital PICU transport team over a period of 1 year. Results:, A total of 257 patients were transported during the study period, 82 patients (32%) were excluded owing to incomplete or absent documentation, leaving a sample of 175 available for analysis. Intravenous drugs were administered to 168 of these patients (96%). In total, 38 different drugs were administered. The four most commonly administered drugs were midazolam (130 patients), morphine (129 patients), atracurium (108 patients), and heparin (53 patients). Ten drugs accounted for 90% of all prescription episodes (total number of infusions and bolus doses administered), whilst 16 drugs were prescribed only once. The mean number of drugs administered per patient was 3.25 with a mean of 1.96 drug infusions and 1.29 bolus drugs administered per patient. Conclusions:, A relatively small number of drugs are used frequently during the retrieval of critically ill children, but the total range of drugs that are used is large. This has implications for the rational carriage of drugs by PICU transport teams, the potential for drug errors and also for the development of advanced nurse practitioners whose prescribing-like activities may depend on the development of Patient Group Directions. [source] Aerosol therapy in cystic fibrosis: Weighing the evidencePEDIATRIC PULMONOLOGY, Issue S9 2008Felix Ratjen MD Abstract Aggressive treatment of CF lung disease has markedly increased survival of CF patients and intense research efforts over the last decades have led to new treatment strategies, many of which target the lower airways directly via aerosol. The addition of any new therapy not only needs to be assessed in view of its individual efficacy, but also in context with other established therapies. This review will summarize the current evidence on aerosol therapy in CF focussing on therapies that hydrate airways, mucolytic therapy with dornase alfa and inhaled antibiotics. The different therapeutic regimens will be critically assessed in context to address the question of whether these different drugs can be used interchangeably or should be used in combination in CF lung disease. Pediatr Pulmonol. 2008; 43:S3,S4. © 2008 Wiley-Liss, Inc. [source] Integrating nine prescription opioid analgesics and/or four signal detection systems to summarize statewide prescription drug abuse in the United States in 2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 9 2009Michael F. Schneider MS Abstract Purpose Integrate statewide rankings of abuse across different drugs and/or signal detection systems to summarize prescription drug abuse in each state in 2007. Methods Four signal detection systems (Opioid Treatment Programs, Key Informants, Drug Diversion, and Poison Centers) that covered heterogeneous populations collected data on the abuse of nine opioids: hydrocodone, immediate-release oxycodone, tramadol, extended-release [ER] oxycodone, fentanyl, morphine, methadone, hydromorphone, and buprenorphine). We introduce here linearized maps which integrate nine drugs within each system; four systems for each drug; or all drugs and systems. Results When rankings were integrated across drugs, Rhode Island, New Hampshire, Maine, West Virginia, and Michigan were in the highest tertile of abuse in three systems. When rankings were integrated across signal detection systems, there was a geographic clustering of states with the highest rates for ER oxycodone (in Tennessee, Mississippi, Kentucky, Ohio, Indiana, Michigan, and in Massachusetts, New Hampshire, Maine, and Vermont) and methadone (Massachusetts, Rhode Island, New Hampshire, Maine, Vermont, Connecticut, and New Jersey). When rankings were integrated across both drugs and signal detection systems, states with 3-digit ZIP codes below 269 (i.e., from Massachusetts to West Virginia): Massachusetts, New Hampshire, Maine, Vermont, Washington DC, Virginia, and West Virginia were in the highest tertile and only Delaware was in the lowest tertile. Conclusions We have presented methods to integrate data on prescription opioid abuse collected by signal detection systems covering different populations. Linearized maps are effective graphical summaries that depict differences in the level of prescription opioid abuse at the state level. Copyright © 2009 John Wiley & Sons, Ltd. [source] High-throughput analysis in drug discovery: application of liquid chromatography/ion-trap mass spectrometry for simultaneous cassette analysis of ,-1a antagonists and their metabolites in mouse plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 8 2001Zongwei Cai The application of liquid chromatography/ion-trap mass spectrometry for simultaneous quantification of multiple drugs and detection of their metabolites for in vitro experiments was reported recently. In the current study, the use of these techniques was extended to in vivo pharmacokinetic (PK) studies of ,-1a antagonists. In combination with limited time-point PK, greatly increased throughput was demonstrated for the in vivo screening and investigation of in vivo,in vitro correlation. In addition to quantitative analyses, the technique allowed simultaneous detection of major in vivo metabolites without having to reanalyze the plasma samples. The drugs were individually dosed in mice intravenously via tail vein injection and the blood samples were collected 5,min and 2,h after dosing. After the plasma samples for the different drugs had been prepared separately, they were pooled for cassette analysis. The concentrations of five test compounds in the plasma samples at 2,h ranged from 36,1062,ng/mL, whereas their 5-min plasma levels were similar. From the same cassette analysis, major metabolites in the samples were also detected simultaneously through the interpretation of full-scan mass spectra. The metabolite identification confirmed the results from a previous report that the major sites of metabolism are hydroxylation of the phenyl ring not bearing the alkylsulfonamide substitutent, piperidine N-dealkylation, and N-demethylation of the alkylsulfonamide group. Copyright © 2001 John Wiley & Sons, Ltd. [source] Influence of topical antifungal drugs on ciliary beat frequency of human nasal mucosa,THE LARYNGOSCOPE, Issue 7 2010An In Vitro Study Abstract Objectives/Hypothesis: Topical antifungal treatment is a subject of discussion in the treatment of chronic rhinosinusitis. The aim of this research was to study the effects of antifungal drugs on ciliary beat frequency (CBF) of human nasal mucosa under in vitro conditions. Study Design: Case series of in vitro experiments and in vitro study of cultured ciliated cells of human nasal mucosa. Methods: Human nasal mucosa was acquired during routine endoscopic sinus surgery. Cells were cultivated on object slides and exposed to different antifungal drugs in a newly developed test system. This system allowed continuous and reproducible exposure to different drugs at constant temperature, pH value, and osmolarity. The drugs were amphotericin B in two different concentrations and itraconazole. Results: Rinsing with higher concentrations of amphotericin B led to an immediate decrease of CBF, with a total stop after 15 minutes. A different result was seen in the group with lower concentrations; CBF decreased again quickly after rinsing with the test drug, but all of them recovered after rinsing with neutral solution. When using itraconazole a decline in CBF was observed again; one half of the samples returned to activity. Conclusions: Our in vitro results demonstrate a dose-dependent effect of the antifungal drugs amphotericin B and itraconazole on ciliary beat frequency of human nose epithelium. Laryngoscope, 2010 [source] Quantitative separation of oxytocin, norfloxacin and diclofenac sodium in milk samples using capillary electrophoresisBIOMEDICAL CHROMATOGRAPHY, Issue 9 2009Amber R. Solangi Abstract A simple, sensitive and rapid method has been developed for simultaneous separation and quantification of three different drugs: oxytocin (OT), norfloxacin (NOR) and diclofenac (DIC) sodium in milk samples using capillary electrophoresis (CE) with UV detection at 220 nm. Factors affecting the separation were pH, concentration of buffer and applied voltage. Separation was obtained in less than 9 min with sodium tetraborate buffer of pH 10.0 and applied voltage 30 kV. The separation was carried out from uncoated fused silica capillary with effective length of 50 cm with 75 µm i.d. The carrier electrolyte gave reproducible separation with calibration plots linear over 0.15,4.0 µg/mL for OT, 5,1000 µg/mL for NOR and 3,125 µg/mL for DIC. The lower limits of detection (LOD) were found to be 50 ng/mL for OT, and 1 µg/mL for NOR and DIC. The method was validated for the analysis of drugs in milk samples and pharmaceutical preparations with recovery of drugs within the range 96,100% with RSD 0.9,2.8%. Copyright © 2009 John Wiley & Sons, Ltd. [source] Efficacy of levetiracetam in pharmacoresistant continuous spikes and waves during slow sleepACTA NEUROLOGICA SCANDINAVICA, Issue 3 2004G. Capovilla Objective , To evaluate the efficacy of levetiracetam (LEV) in continuous spikes and waves during slow sleep (CSWS). Despite first description dates back to 1971, no agreement exists about CSWS treatment. The condition is rare and controlled clinical trials are very difficult to perform, so the reports about efficacy of different drugs are anecdotal. Patients and methods , We introduced LEV in three children affected by symptomatic focal epilepsy and pharmacoresistant CSWS and evaluated clinical, neuropsychological and electroencephalographic outcome. Results , Two cases responded completely, one case showed only a mild reduction of spikes and waves during slow sleep. Conclusion , Even if our report is anecdotal, LEV expands the spectrum of antiepileptic drugs that can be used for the treatment of CSWS. LEV efficacy should be confirmed in larger series. [source] Tapetoretinal degenerations: Experiences, experiments and expectationsACTA OPHTHALMOLOGICA, Issue 3 2000Berndt Ehinger ABSTRACT. Tapetoretinal degenerations are a common cause for vision problems, but have until recently not been amenable to rational treatment. With rapidly increasing insights into basic neurobiology and pathobiology this has now begun to change. From having been a relatively small group of largely unknown yet fairly prevalent disorders, they are rapidly forming a large set of well defined diseases, and it is easy to predict that our knowledge about them will continue to increase for many years to come. Vitamin A (15 ,000 IU daily) is currently the only rational treatment available. However, in experimental animals, therapy strategies are now actively being developed along several different lines. Apoptotic photoreceptor cell death can be delayed with different drugs, and at least one of them, diltiazem, is approved for human use in cardiovascular diseases. It remains to be seen if it has any clinically significant effect in human tapetoretinal degenerations. Other strategies aim at counteracting the production of harmful protein variants, acting either on DNA or mRNA levels. Transgenes can also be used to induce the production of important but missing metabolic components. Finally, cells or retina sheets can be transplanted, either to replace failing cells or as a source for missing trophic factors. Neither of these strategies has yet been transferred to humans, but trials are under way. With the high increase in the flow of new information on tapetoretinal disorders, much more precise diagnoses and much improved treatments are soon to be expected, augmenting considerably the possibilities for ophthalmologists to help patients with such diseases. It is not likely that there will be a single treatment for all the many varieties. Instead, we are most likely going to see pharmacological treatments for some of them, DNA transfers for some, and transplantations for others. [source] Drug prescribing by Italian family paediatricians: an exception?ACTA PAEDIATRICA, Issue 5 2010A Clavenna Abstract Aims:, To identify which drugs are considered ,essential' by Italian family paediatricians based on their prescriptions. Methods:, Prescriptions reimbursed by the National Health System, involving 923 177 children < 14 years old, and dispensed during 2005 by the retail pharmacies of 15 local health units (LHUs) in the Lombardy Region, were analysed. The percentage of family paediatricians prescribing each single drug was calculated. A percentage ,75% was considered as a high degree of agreement. Results:, In all, 746 different drugs were prescribed to 486 405 children (52.7%). The median number of drugs prescribed by each paediatrician was 60 (interquartile range 51,71). A total of 22 drugs were prescribed by at least 75% of paediatricians and six were prescribed by all the paediatricians. In all, 95% of the paediatricians prescribed four or more cephalosporins and 92% prescribed four inhaled steroids. Only eight of the 22 most frequent drugs are included in the World Health Organization Essential Medicines for children list. Conclusion:, Despite the huge number of drugs prescribed, only for 22 there was a concordance between family paediatricians. Initiatives to evaluate and promote a more rational use of drugs in Italian children are necessary. [source] Sedoanalgesia in paediatric intensive care: a survey of 19 Italian unitsACTA PAEDIATRICA, Issue 5 2010F Benini Abstract Aim:, To analyse the methods used to manage and monitor sedoanalgesia at Italian paediatric intensive care units (ICUs). Methods:, Data were collected by administering a questionnaire that aimed to investigate whether ICUs adopted a validated protocol to manage sedoanalgesia. Results:, The results revealed that a majority of the ICUs adopt a protocol for dealing with sedation and analgesia, but this protocol is implemented with difficulty or not at all in routine clinical practice. The most often used pharmacological combination, is midazolam and fentanyl. Several weaknesses remain in terms of the methods used to assess sedoanalgesia, which are generally not standardized, but rather based on recording the patient's physiological parameters. Conclusion:, Sedation and analgesia are priority issues in the management of critically ill children. None of the numerous drugs available is ideal and the protocols currently used in clinical practice involve the combined use of different drugs. There is currently no shared and validated approach as to which is the most effective and safest sedoanalgesic regimen in critically ill children. [source] | |||||||||||||||||||||||||