Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study).

BACKGROUND: Short-term therapies for eradicating Helicobacter pylori in selected patients might offer advantages in terms of costs, compliance, and adverse effects in contrast to standard 1-week triple therapy. METHODS: To determine eradication success and influencing factors in a new short-term quadruple therapy, a total of 243 patients positive for H pylori were randomly assigned to 1 of 3 regimens according to age, smoking status, and diagnosis: a 5-day treatment with 3 antibiotics (amoxicillin, 1 g twice daily [bid]; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid) and lansoprazole (30 mg bid [L5; reference treatment]) or ranitidine hydrochloride (300 mg bid [R5]), or the same 3-day antibiotic-lansoprazole combination (L3) with a 2-day pretreatment with lansoprazole. RESULTS: A total of 234 patients completed the study. On an intention-to-treat basis, overall eradication of H pylori was confirmed in 86.4%: 89.2% in the L5 group vs 81.2% in the L3 group vs 88.8% in the R5 group; differences were not significant. Multiple logistic regression analysis showed that younger age (<55 years; P =.03), history of peptic ulcer disease (P =.04), smoking (P =.03), metronidazole resistance (P =.003), low ranitidine trough serum concentrations (P =.005), cytotoxin-associated gene A-negative strains in peptic ulcer disease (P =.04), and outer inflammatory protein A-positive strains (P =.02) were associated with eradication failure. CONCLUSIONS: This new quadruple H pylori eradication regimen is efficacious, safe, well tolerated, and cost saving, and may be a treatment option for patients older than 55 years with no history of peptic ulcer disease. Furthermore, strains that are sensitive to all antibiotics, cytotoxin-associated gene A-positive, and outer inflammatory protein A-negative could be suitable for short-term quadruple therapy. Patients with an unfavorable combination of characteristics should be treated for a minimum of 7 days.

Microarray analysis of genes expressed in the frontal cortex of rats chronically treated with morphine and after naloxone precipitated withdrawal.

Opioid dependence may be associated with adaptive changes in gene expression in the brain. In the present study we used DNA microarrays (U34A; Affymetrix) to analyze the expression of about 8000 genes in the frontal cortex of rats chronically treated with morphine and in rats after naloxone precipitated withdrawal. Chronic treatment for 10 days with ascending doses of morphine (10-50 mg/kg twice daily) resulted in a more than twofold induction of 14 genes after the last injection of morphine. The majority of these genes code for heat shock proteins (hsp70, hsp 27, hsp 40, hsp105, GRP78, etc.). The expression of the heat shock genes in the morphine-treated animals was reversed by naloxone (10 mg/kg). The opioid antagonist, in turn, precipitated withdrawal and increased the expression of a set of genes which are predominantly transcription factors (krox20, CREM, NGFI-B, IkappaB, etc). Only a few genes remained increased after naloxone application. Such persistently changed genes code for arc, a cytoskeleton-associated protein which is induced by synaptic activity, ania-3, a splice variant of the Homer 1 protein which is critically involved in activity-dependent alterations of synaptic function and rPer2, a protein regulating circadian rhythms. For selected genes the changes in gene expression were confirmed by real time PCR and by in situ hybridization. These findings indicate that the persistent changes in long-lasting plasticity during opiate dependence do not primarily depend on the increased expression levels of genes encoding for neurotransmitter, receptor and/or ion channel proteins, but rather on altered pattern of synaptic connectivity.

Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.

BACKGROUND: Previously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers. METHODS: In a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codeine phosphate plus 50 mg diclofenac sodium or codeine phosphate plus placebo. Over a 36 hour period serum concentrations of codeine and its metabolites as well as urinary excretion were analysed using LC-mass spectrometry. Side effects were recorded and analgesic efficacy was determined using the cold pressor test (0-6 h). RESULTS: A single dose of diclofenac did not alter the formation of codeine-6-glucuronide in healthy volunteers. Metabolic clearance of codeine to morphine was not affected by diclofenac. In terms of side effects, both treatments were well tolerated. Diclofenac did not significantly influence the analgesic effects of codeine in the cold pressor test. CONCLUSIONS: In contrast to recent in vitro data, a single oral dose of diclofenac did not alter the glucuronidation of codeine in healthy volunteers.

Gene expression profile after intense second messenger activation in cortical primary neurones.

Numerous stimuli induce immediate early gene (IEG) expression in neurones, but a comprehensive overview of the late-response genes is lacking. Therefore we aimed to identify changes in the neuronal gene expression profile following intense stimulation. Forskolin and 12-O-tetradecanoylphorbol-13-acetate (TPA), direct activators of intracellular second messengers, were applied to primary cultured cortical neurones. The gene expression profiles were analyzed on Affymetrix DNA chips which cover around 8000 rat genes. Out of these, 95 genes (1.2%) were increased at least three-fold, and 43 genes (0.5%) were at least three-fold decreased. The gene chip results were verified by testing 15 of the altered genes by quantitative real-time PCR. The majority of the up-regulated genes were transcription factors, neurotrophic factors or (putative) neuropeptides. Furthermore, there were marked changes in intracellular signal processing enzymes and in postsynaptic structural proteins (e.g. vesl, arc, narp), which have been implicated in synaptic plasticity. Notably, classical players in neurotransmission or plasticity such as glutamate and GABA receptors or voltage-gated ion channels were not increased. It is likely that the increased production of components of intracellular signalling and of postsynaptic proteins is involved in neuronal plasticity.