Phytochemical analysis and biological activities of three wild Mesembryanthemum species growing in heterogeneous habitats

The objective of this study was to analyze the phytochemicals and to determine the antioxidant, antibacterial and allelopathic potential of three wild Mesembryanthemum species (M. crystallinum L., M. forsskaolii Hochst. Ex Boiss and M. nodiflorum L.). The phytochemical composition of the methanolic extract of studied species revealed the considerable quantities that might be responsible for their powerful antioxidant activity. The IC50 values were 386.51, 592.97, and 752.23µg/ml for M. nodiflorum, M. crystallinum and M. forsskaolii extracts respectively. The antibacterial activity index was calculated for each extract in comparison with the standard antibiotics. M. nodiflorum showed higher potency than ampicillin and penicillin G against against Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis. The allelopathic potential showed that the studied Mesembryanthemum species expressed a significant phytotoxic activity against Chenopodium murale weed in a dose dependent manner. M. nodiflorum sample showed the most phytotoxic effect among the studied species

Switching to different generic medicines: A checklist for safety issues

Конкуренцията между предлаганите на пазара генерични лекарствени продукти води до по-ниски цени и намалени разходи за здравеопазване. Въвеждането на нов генеричен продукт обаче би могло да доведе до проблеми с прилагането му в клиничната практика. Ние изготвихме контролна карта със списък въпроси, с помощта на която да се изследват различията между продуктите. Нашата цел с този списък е да установим свойства на алтернативните генерични лекарства, които биха могли да са проблематични при клинична употреба. Навременното предсказване на евентуални проблеми подпомага внимателния подбор и обуславя въвеждането на подходящото генерично лекарство в клиничната практика. В настоящата статия разглеждаме различните позиции в нашата карта и споменаваме за някои от проблемите, които сме срещали през последните няколко години. Вярваме, че с използването на контролната карта болничните фармацевти ще могат по-добре да правят оптималния избор на генерично лекарство, съответстващо на конкретните изисквания на дадена болница.

Antipsychotic-Induced Movement Disorders in Long-Stay Psychiatric Patients and 45 Tag SNPs in 7 Candidate Genes: A Prospective Study

Objective: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1). Methods: Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. Results: Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, r

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate—a validated assay for the clinic

The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5–1,500 ng/mL for oseltamivir and 20–1,500 ng/mL for the oseltamivircarboxylate metabolite. As a proof of concept, oseltamivir and oseltamivircarboxylate levels were determined in DBS obtained from healthy volunteers who received a single oral dose of Tamiflu®

Likelihood of mechanistic roles for dopaminergic, serotonergic and glutamatergic receptors in tardive dyskinesia:A comparison of genetic variants in two independent patient populations

Objectives: An established theory for the pathogenesis of tardive dyskinesia is disturbed dopaminergic receptor sensitivity and/or dopaminergic intracellular signaling. We examined associations between genetic variants of neurotransmitter receptors and tardive dyskinesia. Methods: We assessed tardive dyskinesia in Caucasian psychiatric inpatients from Siberia (N = 431) and a long-stay population from the Netherlands (N = 168). These patients were genotyped for 43 tag single nucleotide polymorphisms in five neurotransmitter receptor genes, and the results for the two populations were compared. Results: Several significant associations with tardive dyskinesia were identified, but only GRIN2A (rs1345423) was found in both patient populations. This lack of agreement was probably due to the small effect size of the associations, the multiple testing and the small sample size of the Dutch patient population. After reviewing the literature, we propose that the constitutive stimulatory activity of serotonergic type 2 receptors may be relevant. Conclusions: Inactivity of the serotonergic, type 2C receptor or blockade of these receptors by atypical antipsychotic drugs may decrease the vulnerability to develop tardive dyskinesia