Furazolidone, Co-amoxiclav, Colloidal Bismuth Subcitrate, and Esomeprazole for Patients Who Failed to Eradicate Helicobacter pylori with Triple Therapy

There is increasing evidence of Helicobacter pylori (H. pylori) resistance to the classical triple therapy consisting of a proton-pump inhibitor and clarithromycin with either amoxicillin or metronidazole. This study is aimed at establishing the efficacy and safety of a 14-day regimen to eradicate H. pylori in patients who have failed with the classical triple therapy given for 14 days. One hundred seventy-six patients diagnosed to have H. pylori infection were given triple therapy for 14 days. Fifty-two patients who failed to respond as evident from positive 14C-urea breath test (UBT) done 4–6 weeks after the completion of triple therapy were offered a combination regimen comprised of furazolidone 200 mg b.i.d, co-amoxiclav 1 g b.i.d., colloidal bismuth subcitrate 240 mg b.i.d., and esomeprazole 40 mg b.i.d. for 14 days. The mean age of these patients was 41 ± 13 years (range 20–67). Thirty-four were males. To document eradication of H. pylori, UBT was repeated 4 weeks after the completion of treatment. On an intention-to-treat analysis, the eradication rate was 81% (42 out of 52) whereas on per-protocol basis, the eradication rate was 82.4% (42 out of 51). In conclusion, this new regimen represents a suitable second-line therapy. This study was conducted under ClinicalTrials.gov number NCT00520949.     

Clinical trials update from the European Society of Cardiology Meeting 2009: AAA,RELY, PROTECT,ACTIVE‐I,European CRT survey,German pre‐SCD II registry,and MADIT‐CRT

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the European Society of Cardiology held in Barcelona in 2009. The AAA study does not support the routine use of aspirin for the prevention of vascular events in patients with asymptomatic atherosclerosis. RELY suggests that dabigatran may be more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Rolofylline was not superior to placebo in improving outcomes in patients with acute heart failure enrolled in the PROTECT study, but dyspnoea was improved. Data from ACTIVE‐I suggest that irbesartan does not provide additional therapeutic benefit in patients with atrial fibrillation who are well controlled on current therapy. The European cardiac resynchronization therapy (CRT) survey provides interesting epidemiological data on current CRT device usage. The German pre‐SCD II registry identified a low prevalence of patients with a reduced ejection fraction following myocardial infarction. Implantation of CRT‐D rather than an implantable cardioverter defibrillator in patients with mild heart failure and QRS ≥130 ms reduced the risk of hospitalization for heart failure in MADIT‐CRT; mortality was similarly low with each device.     

μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve

Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing α-subunit (Na(V)1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, Na(V)1.1, 1.2, 1.3, 1.6, and 1.7, are exquisitely sensitive to tetrodotoxin (TTX), and a functional differentiation of these presents a serious challenge. Here, we examined a panel of 11 μ-conopeptides for their ability to block rodent Na(V)1.1 through 1.8 expressed in Xenopus oocytes. Although none blocked Na(V)1.8, a TTX-resistant isoform, the resulting "activity matrix" revealed that the panel could readily discriminate between the members of all pair-wise combinations of the tested isoforms. To examine the identities of endogenous VGSCs, a subset of the panel was tested on A- and C-compound action potentials recorded from isolated preparations of rat sciatic nerve. The results show that the major subtypes in the corresponding A- and C-fibers were Na(V)1.6 and 1.7, respectively. Ruled out as major players in both fiber types were Na(V)1.1, 1.2, and 1.3. These results are consistent with immunohistochemical findings of others. To our awareness this is the first report describing a qualitative pharmacological survey of TTX-sensitive Na(V)1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of μ-conopeptides should be useful in identifying the functional contributions of Na(V)1 isoforms in other preparations.     

Characterization of the IVS-II-821 (A>C) (HBB: c.316-30A>C) Mutation in a β-Thalassemia Phenotype in Iran

β-Thalassemia (β-thal) is the most frequently observed hereditary blood disorder that results from genetic defects causing deficient synthesis of hemoglobin (Hb) polypeptide chains. Detecting thalassemia mutations are necessary for prenatal diagnosis (PND) programs leading a better quality of life for the patients, as well as a reduction in the cost of their medical care. There are more than 900 different genomic mutations of the β-globin gene described in the human hemoglobin variant (HbVar) database. In this study, we identified a mid-intronic mutation at IVS-II-821 (A>C) (HBB: c.316-30A>C) position in the HBB gene of an Iranian proband and two of her siblings that was associated with β-thal clinical features. Direct DNA sequence analysis was performed by mutation scanning of the β-globin gene. Based on the observed β-thal phenotype and bioinformatics analysis results, we concluded that this β-globin gene mutation was associated with a mild phenotype of β-thal through activating potential splice sites by creating exonic splicing enhancers (ESEs), exon-identity element (EIE) and exonic splicing regulatory sequences (ESRs) sites.     

The effect of Crocus sativus extract on human lymphocytes' cytokines and T helper 2/T helper 1 balance

The effects of macerated extracts of Crocus sativus (Family Iridaceae) (saffron) on cell viability and cytokine release of stimulated peripheral blood mononuclear cells by phytohemagglutinin (PHA) and nonstimulated cells were examined. The effects of three concentrations of macerated extract, dexamethasone, and saline on cell viability and production of cytokines, including interleukin (IL)-4, IL-10, and interferon-γ (IFN-γ) were evaluated. In cells stimulated with PHA, different concentrations of the extract significantly inhibited cell viability of lymphocytes (P<.001 for all concentrations). High concentrations of the extract (500 μg/mL) also inhibited secretion of IFN-γ in stimulated cells and IL-10 secretion in both stimulated and nonstimulated cells (P<.05 for all cases). The effects of high and low concentrations of the extract (500 and 50 μg/mL, respectively) on IL-4 secretion were lower than that of dexamethasone (P<.05 to P<.001). The extract showed a stimulatory effect on IFN-γ and IL-4 secretion in nonstimulated cells. The ratios of IFN-γ to IL-4 in the presence of all concentrations of saffron on stimulated cells were significantly higher than for the control group (P<.05 to P<.01). These results indicated that the extract of saffron leads to increased ratio of IFN-γ to IL-4.