Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans

Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA_A receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA_A activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA_A activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI  ( F _3,9= 3.19, P = 0.039)  . In contrast to SICI, SAI was significantly reduced by lorazepam  ( F _3,9= 9.39, P = 0.0002)  . Our findings demonstrate that GABA_A activity enhancement determines a suppression of SAI and an increase of SICI.     

Gut–liver axis: The impact of gut microbiota on non alcoholic fatty liver disease

AimTo examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis.Data synthesisEmerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of gut–liver axis health. Disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster “bacterial translocation”, defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20–75%) of patients with chronic liver disease. In addition, evidence implicating the gut–liver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years.ConclusionsComplex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD.     

Evaluation of a commercial serological kit for detection of salivary immunoglobulin G to Helicobacter pylori: a multicentre study

OBJECTIVE: To evaluate the usefulness of a commercial serological enzyme immunoassay (EIA) for detecting salivary immunoglobulin (Ig) G to Helicobacter pylori. DESIGN: Prospective, multicentre study. SETTING: The study was conducted at 11 gastroenterology hospital centres throughout Italy. PARTICIPANTS AND INTERVENTIONS: Two hundred and thirteen dyspeptic patients underwent gastroscopy with antral biopsies. At each centre, two of the following three tests for H. pylori diagnosis were performed: urease quick test, histology, and 13C-urea breath test. Samples of unstimulated saliva and venous blood were collected from each patient. Salivary and serum H. pylori IgG were determined with the EIA Helori-test IgG (Eurospital, Trieste, Italy). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and accuracy of the salivary and serum EIAs. RESULTS: By using a receiver operating characteristic curve, salivary EIA yielded 81% (95% confidence interval 73-87%) sensitivity, 73% (62-83%) specificity, 84% (76-90%) positive predictive value, 69% (58-79%) negative predictive value, and 78% (72-84%) accuracy. At the cut-off suggested by the manufacturer, serum EIA had 90% (84-95%) sensitivity, 78% (67-86%) specificity, 88% (81-93%) positive predictive value, 82% (71-90%) negative predictive value, and 86% (81-91%) accuracy. CONCLUSION: In this large multicentre study, detection of salivary H. pylori IgG with a commercial serological EIA was a fairly accurate diagnostic method. Data confirm that saliva testing does not compare favourably with serology in the assessment of H. pylori status.     

Helicobacter pylori antigen stool test and 13C-urea breath test in patients after eradication treatments

OBJECTIVES: Current guidelines recommend either the urea breath test (UBT) or the Helicobacter pylori antigen stool test (HpSA) for monitoring H. pylori infection. The aim of this study was to evaluate the agreement between the two tests in patients after treatment. METHODS: After eradication treatments, patients were tested with both UBT and HpSA. Cut-off values (delta value over baseline at 30') for UBT were positive (> or = 5 per thousand), indeterminate (3.01-4.99 per thousand), and negative (< or = 3 per thousand). Cut-off values (absorbance at 450 nm) for HpSA test were positive (> or = 0.160), indeterminate (0.159-0.140), and negative (< 0.140). Patients with either discordant or indeterminate tests underwent repeat endoscopy with multiple gastric biopsies for rapid urease test (RUT), culture, histology, and immunohistochemistry to detect H. pylori and to assess the ratio between coccoid and bacillary forms. RESULTS: A total of 458 patients were studied. Of these, 422 (92.2%) had concordant tests, three (0.6%) indeterminate tests (one on UBT and two on HpSA), and 33 (7.2%) discordant tests. A total of 28 patients (25 with discordant and three with indeterminate tests) underwent endoscopy. The HpSA was inaccurate in 24 cases (18 false negative, four false positive, and two indeterminate results), whereas the UBT was inaccurate in four cases (two false positive, one false negative, and one indeterminate results). Biopsy-based tests showed no bacillary or coccoid forms in all five endoscoped patients who were negative on UBT and positive on HpSA, but in one in whom the ratio between coccoid and bacillary forms was 3:1 in the antrum and corpus. CONCLUSIONS: UBT and HpSA test give discordant or indeterminate results in nearly 8% of patients after treatment. The HpSA test is less accurate than the UBT. Coccoid forms do not cause false positive HpSA results.