Interaction between intestinal dendritic cells and bacteria translocated from the gut in rats with cirrhosis.

Unlabelled: Cirrhosis with ascites is associated with a high rate of gut bacterial translocation (GBT) and spontaneous bacterial infections of enteric origin. We addressed the activation state and role of intestinal dendritic cells (DCs) in experimental ascitic cirrhosis and their relationship with GBT. Cirrhosis with ascites was CCl(4) induced in rats.

Selectivity of action of pregabalin on Ca(2+) channels but not on fusion pore, exocytotic machinery, or mitochondria in chromaffin cells of the adrenal gland.

The present study was planned to investigate the action of pregabalin on voltage-dependent Ca(2+) channels (VDCCs) and novel targets (fusion pore formed between the secretory vesicle and the plasma membrane, exocytotic machinery, and mitochondria) that would further explain its inhibitory action on neurotransmitter release. Electrophysiological recordings in the perforated-patch configuration of the patch-clamp technique revealed that pregabalin inhibits by 33.4 ± 2.

Insulin resistance in patients with cirrhosis and portal hypertension.

Insulin resistance (IR) is involved in the pathogenesis of endothelial dysfunction and is also present in patients with cirrhosis. Intrahepatic endothelial dysfunction plays a major role, increasing hepatic vascular resistance and promoting portal hypertension (PH). In addition, β-adrenergic agonists and insulin share several intracellular signaling pathways.

Native α6β4* nicotinic receptors control exocytosis in human chromaffin cells of the adrenal gland.

In the present study, we have electrophysiologically characterized native nicotinic acetylcholine receptors (nAChRs) in human chromaffin cells of the adrenal gland as well as their contribution to the exocytotic process. α-Conotoxin AuIB blocked by 14 ± 1% the acetylcholine (ACh)-induced nicotinic current. α-Conotoxin MII (α-Ctx MII) exhibited an almost full blockade of the nicotinic current at nanomolar concentrations (IC(50)=21.

Pharmacological characterization of native α7 nicotinic ACh receptors and their contribution to depolarization-elicited exocytosis in human chromaffin cells.

Background And Purpose: Expression of α7 nicotinic acetylcholine receptors (nAChRs) and their role in exocytosis have not yet been examined in human chromaffin cells.

Experimental Approach: To characterize these receptors and investigate their function, patch-clamp experiments were performed in human chromaffin cells from organ donors.

Key Results: The nicotinic current provoked by 300µM ACh in voltage-clamped cells was blocked by the nicotinic receptor antagonists α-bungarotoxin (α-Bgtx; 1µM; 6 ± 1.

Loss of surface antigens is a conserved feature of apoptotic lymphocytes from several mammalian species.

Human lymphocytes lose the expression of lineage antigens (LAgs) along apoptosis. Our aim was to extent our previous studies of LAg loss to rodent species, quantifying LAg expression on apoptotic murine lymphocytes using flow cytometry to measure alterations in cell permeability, phosphatidylserine exposure and caspase activation of CD3, CD5, CD4, CD8, CD19 and CD28 LAgs in highly purified lymphocyte populations. We found loss of expression by apoptotic cells of all LAgs studied in the three species analyzed except for CD3 antigen in mouse.

Past, present and future of human chromaffin cells: role in physiology and therapeutics.

Chromaffin cells are neuroendocrine cells mainly found in the medulla of the adrenal gland. Most existing knowledge of these cells has been the outcome of extensive research performed in animals, mainly in the cow, cat, mouse and rat. However, some insight into the physiology of this neuroendocrine cell in humans has been gained.

Critical role of the liver in the induction of systemic inflammation in rats with preascitic cirrhosis.

Unlabelled: Systemic activation of the inflammatory immune system contributes to the progression of cirrhosis with ascites. Immune cells become activated after interacting at the mesenteric lymph nodes (MLNs) with bacteria translocated from the gut, and thereafter reach the bloodstream through recirculation. It is unknown whether systemic activation of the immune system is present in pre-ascitic cirrhosis, in which gut bacterial translocation has not been described.

Different roles attributed to Cav1 channel subtypes in spontaneous action potential firing and fine tuning of exocytosis in mouse chromaffin cells.

This study examines the Cav1 isoforms expressed in mouse chromaffin cells and compares their biophysical properties and roles played in cell excitability and exocytosis. Using immunocytochemical and electrophysiological techniques in mice lacking the Cav1.3α1 subunit (Cav1.

Role of endoscopy in primary prophylaxis for esophageal variceal bleeding.

Cirrhosis is the leading cause of portal hypertension in the Western world. From a clinical standpoint, the most significant consequence of portal hypertension is the development of esophageal varices. Despite the many advances in the management of variceal bleeding, it remains a life-threatening complication of portal hypertension.

The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis.

Background: An inflammatory immune system response ensues in the liver and in the systemic circulation in cirrhosis, where it contributes to hepatic fibrosis and peripheral vasodilation. Modulation of the inflammatory response without increasing susceptibility to infection is a therapeutic target in cirrhosis. AM3 is a low-toxicity biological response modifier with regulatory effects on innate and adaptative immunity, and the ability to normalise the production of tumour necrosis factor alpha (TNFalpha).

Endoscopic follow-up of gastric ulcer in a population at intermediate risk for gastric cancer.

Objectives: Primary: to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer. Secondary: to assess correlation between endoscopic findings and pathology diagnosis.

Patients And Methods: a prospective analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real (Spain) over three years.

[Liver diseases].

In Digestive Disease Week 2008, interesting advances in the treatment of hepatitis C were presented, especially related to the promising increase in the therapeutic efficacy of the combination of conventional treatment with the protease inhibitor, telaprevir. Also revealed was the influence of viral replication of hepatitis B virus in the development of complications, including hepatocarcinoma. In this sense, drugs such as entecavir and tenofovir seem to provide sustained inhibition of viral replication without the development of resistance.

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre randomised controlled trial.

Background And Aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes

Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4-6 weeks on medical therapy.

Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.

Background & Aims: Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension.

Methods: Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial.

Portal hypertension-related complications after acute portal vein thrombosis: impact of early anticoagulation.

Background & Aims: Acute portal vein thrombosis (APVT) is a rare disorder that causes chronic portal hypertension if recanalization is not obtained. However, response to anticoagulation and long-term prognosis of APVT are not well-defined.

Methods: Thirty-eight patients diagnosed with APVT between 1995 and 2003 from 5 Spanish referral hospitals, in whom cirrhosis and malignancy were specifically excluded, were included in this retrospective study.

Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis.

Background: Combining endoscopic therapy and beta-blockers may improve outcomes in patients with cirrhosis and bleeding esophageal varices.

Purpose: To assess whether a combination of endoscopic and drug therapy prevents overall and variceal rebleeding and improves survival better than either therapy alone.

Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and conference proceedings through 30 December 2007.

Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells.

In this study, we explored the pharmacological and biophysical properties of voltage-activated Ca2+ channels in human chromaffin cells using the perforated-patch configuration of the patch-clamp technique. According to their pharmacological sensitivity to Ca2+ channel blockers, cells could be sorted into two groups of similar size showing the predominance of either N- or P/Q-type Ca2+ channels. R-type Ca2+ channels, blocked by 77% with 20 muM Cd2+ and not affected by 50 muM Ni2+, were detected for the first time in human chromaffin cells.

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial.

Unlabelled: A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg).

Preventing first variceal hemorrhage in cirrhosis.

Variceal bleeding is still a life-threatening complication of portal hypertension responsible for an appreciable rate of morbidity and mortality. The most appropriate treatment approach, whether drugs (nonselective beta-blockers) or endoscopic (variceal band ligation) therapy, to prevent the initial bleed, or primary prophylaxis, is an issue of controversy. Meta-analysis of randomized controlled trials indicates that banding seems to be somehow slightly more effective than beta-blockers at preventing a first bleeding episode, but this does not translate to improved survival.

Key role of the nicotinic receptor in neurotransmitter exocytosis in human chromaffin cells.

The whole-cell secretory response evoked by acetylcholine (ACh) in human chromaffin cells was examined using a new protocol based on quickly switching from the voltage-clamp to the current-clamp (CC) configuration of the patch-clamp technique. Our experiments revealed that Ca(2+) entry through the nicotinic receptor at hyperpolarized membrane potentials contributed as much to the exocytosis (100.4 +/- 27.

[Hepatitis C virus in populations at risk for infection. Venezuela].

Objective: The aim of this study was to establish the prevalence of hepatitis C virus infection in different populations at risk for infection.

Methods: This was a descriptive, transversal study whose variables were evaluated by Pearson s correlation analysis. Different populations were selected: 100 drug users, 47 sex workers, and 50 hemodialysis patients for a total of 197 individuals.