[Ibuprofen: Safety and Efficiency of Its Use in Wide Clinical Practice].

[Ibuprofen: safety and efficiency of its use in wide clinical practice].

Ter Arkh. 2013; 85(3): 118-24

The paper presents data on the pharmacokinetics of the nonsteroidal anti-inflammatory drug ibuprofen and a review of the evidence base that suggests its clinical efficacy and safety in different categories of patients and discusses new, potentially possible indications for the use of this drug. Ibuprofen has marked anti-inflammatory, analgesic, and antipyretic effects, which along with its good tolerability, predictability of side effects, and a low risk of complications, allows it to be widely use in clinical practice. There are various ibuprofen formulations on the drug market. There may be not only an oral formulation of ibuprofen, but its topical (gel), rectal (suppositories), and parenteral (solution for intravenous injection) ones. More than 40 years’ experience with ibuprofen used as an over-the-counter drug in wide clinical practice in approximately 80 countries worldwide serves as an illustrative example of the efficacy and safety of this agent. HubMed – drug

[First clinical experience with endothelin receptor antagonist bosentan used in patients with pulmonary hypertension: results of a one-year study].

Ter Arkh. 2013; 85(3): 38-43

To evaluate the efficiency and safety of long-term (12-month) treatment with the endothelin receptor antagonist bosentan (tracleer (Actelion, Switzerland)) in patients with pulmonary hypertension (PH).The prospective observational study enrolled 10 patients (8 with idiopathic PH and 2 with PH and systemic scleroderma). The patients’ mean age was 50.0 +/- 6.9 years; mean pulmonary artery pressure (mPAP) 65 +/- 12 mm Hg; cardiac output (CO) 3.4 +/- 0.8 l/min; 6-minute walk test (6’WT) distance, 318 +/- 94 m. Before and 3, 6, and 12 months after the treatment, the patients underwent Doppler echocardiography, arterial blood gas analysis, external respiratory function test, and dyspnea evaluation using the MRC scale and 6’WT. The initial dose of bosentan was 62.5 mg b.i.d., then 125 mg b.i.d. following 4 weeks.Bosentan treatment resulted in a reduction in pulmonary artery systolic pressure and mPAP (at 12 months: 76.8 +/- 11.5 and 58.8 +/- 11.4 mm Hg, respectively; p < 0.01) and an increase in CO (at 12 months: 4.2 +/- 1.2 l/min; p = 0.002). Six patients were observed to have a lower WHO classification functional class (FC). Lung diffusing capacity tended to improve (at 12 months, the increment was more than 6% of the reference value; p = 0.059). In the patients, dyspnea was relieved as shown by MRS scores from 3.1 +/- 0.7 (at baseline) to 2.1 +/- 0.6 (at 12 months); p = 0.002. The 6'WT distance increased up to 342 +/- 67 m (at 12 months); p = 0.005. The drug was well tolerated; only one patient had a transient increase in the activity of liver enzymes.The long-term bosentan treatment in patients with PH leads to improvements in pulmonary hemodynamics, WHO classification functional class, a reduction in dyspnea, and a rise in exercise tolerance. HubMed – drug

Optimization of a ligase detection reaction fluorescent microsphere assay for the characterization of resistance-mediating polymorphisms in African samples of Plasmodium falciparum.

J Clin Microbiol. 2013 May 29;
Leclair NP, Conrad MD, Baliraine FN, Nsanzabana C, Nsobya SL, Rosenthal PJ

Genetic polymorphisms in the malaria parasite Plasmodium falciparum mediate alterations in sensitivity to important antimalarial drugs. Surveillance for these polymorphisms is helpful in assessing the prevalence of drug resistance and designing strategies for malaria control. Multiple methods are available for the assessment of P. falciparum genetic polymorphisms, but these suffer from low throughput, technical limitations, and high cost. We have optimized and tested a multiplex ligase detection reaction fluorescent microsphere (LDR-FM) assay for the identification of important P. falciparum genetic polymorphisms. For 84 clinical samples from Kampala, Uganda, a region where transmission intensity and infection complexity are both high, DNA was extracted from dried blood spots, genes of interest were amplified, amplicons were subjected to multiplex ligase detection reactions to add bead-specific oligonucleotides and biotin, fragments were hybridized to magnetic beads, and polymorphism prevalences were assessed fluorometrically in a multiplex format. A total of 19 alleles from the pfcrt, pfmdr1, pfmrp1, pfdhfr, and pfdhps genes were analyzed by LDR-FM and restriction fragment length polymorphism (RFLP) analysis. Considering samples with results from both assays, concordance between the assays was good, with 78-100% of results identical at individual alleles, most non-concordant results differing only between a mixed and pure genotype call, and full disagreement at individual alleles in only 0-3% of results. We estimate the LDR-FM assay to offer much higher throughput and lower cost compared to RFLP. Our results suggest that the LDR-FM system offers an accurate high throughput means of classifying genetic polymorphisms in field samples of P. falciparum. HubMed – drug

An Engineered GluCl Channel for Sensitive, Consistent Neuronal Silencing by Ivermectin.

J Biol Chem. 2013 May 29;
Frazier SJ, Cohen BN, Lester HA

A modified invertebrate glutamate-gated Cl- channel (GluCl ??) was previously employed to allow pharmacologically induced silencing of electrical activity in CNS neurons upon exposure to the anthelmintic drug ivermectin (IVM). Usefulness of the previous receptor was limited by (1) the high concentration of IVM necessary to elicit a consistent silencing phenotype, raising concern about potential side effects, and (2) the variable extent of neuronal spike suppression, due to variations in the co-expression levels of the fluorescent protein-tagged ? and ? subunits. To address these issues, mutant receptors generated via rational protein engineering strategies were examined for improvement. Introduction of a gain-of-function mutation (L9’F) in the second transmembrane domain of the ? subunit appears to facilitate ? subunit incorporation and substantially increase heteromeric GluCl ?? sensitivity to IVM without increasing background conductance (see Frazier et al., JBC Submitted). Removal of an arginine-based endoplasmic reticulum retention motif (RSR mutated to AAA) from the intracellular loop of the ? subunit further promotes heteromeric expression at the plasma membrane possibly by preventing endoplasmic reticulum (ER)-associated degradation of the ? subunit rather than simply reducing ER retention. A monomeric XFP (mXFP) mutation that prevents fluorescent protein dimerization complements the mutant channel effects. Expression of the newly engineered GluCl opt ?-mXFP L9’F + opt ?-mXFP Y182F RSR_AAA receptor in dissociated neuronal cultures markedly increases conductance and reduces variability in spike suppression at 1 nM IVM. This receptor, named GluClv2.0, is an improved tool for IVM-induced silencing. HubMed – drug