Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation.

BACKGROUND: Gastric nitric oxide (NO) production in response to Helicobacter pylori via inducible nitric oxide synthase (iNOS) is suggested as a biomarker of inflammation and cytotoxicity. The aim of this study was to investigate relationships between gastric [NO], immunological biomarkers and histopathology. MATERIALS AND METHODS: Esophagogastroduodenoscopy was done in 96 dyspepsia patients. Luminal [NO] was measured by chemiluminescence. Biopsies were taken from gastric antrum and corpus for culture and histopathology. H. pylori IgG was detected by immunoblot assay. Biobanked plasma from 76 dyspepsia patients (11 H. pylori positives) was analyzed for 39 cytokines by multiplexed ELISA. RESULTS: H. pylori-positive patients had higher [NO] (336 ± 26 ppb, mean ± 95% CI, n = 77) than H. pylori-negative patients (128 ± 47 ppb, n = 19) (P < 0.0001). Histopathological changes were found in 99% of H. pylori-positive and 37% of H. pylori-negative patients. Histopathological concordance was 78-100% between corpus and antrum. Correlations were found between gastric [NO] and severity of acute, but not chronic, inflammation. Plasma IL-8 (increased in H. pylori positives) had greatest difference between positive and negative groups, with eotaxin, MIP-1ß, MCP-4, VEGF-A, and VEGF-C also higher (P < 0.004 to P < 0.032). Diagnostic odds ratios using 75% cut-off concentration were 7.53 for IL-8, 1.15 for CRP, and 2.88 for gastric NO. CONCLUSIONS: Of the parameters tested, increased gastric [NO] and circulating IL-8 align most consistently and selectively in H. pylori-infected patients. Severity of mucosal inflammatory changes is proportional to luminal [NO], which might be tied to IL-8 production. It is proposed that IL-8 be further investigated as a blood biomarker of treatment outcomes.

Utility of animal gastrointestinal motility and transit models in functional gastrointestinal disorders.

Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human like scintigraphy, breath test and wireless motility capsule may directly translate to the clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human.

Exploring Electronic Communication Modes Between Iraqi Faculty and Students of Pharmacy Schools Using the Technology Acceptance Model.

Objective. To explore for the first time the extent to which Iraqi pharmacy students and faculty use Facebook and university email for academic communications, and to examine factors influencing utilization within the framework of the Technology Acceptance Model (TAM). Methods. An electronic survey was administered to convenience samples of students and faculty of six Iraqi public schools and colleges of pharmacy in 2015. Results. Responses included 489 student and 128 faculty usable surveys. Both students and faculty use Facebook more than university email for academic communications. Less than a third of the faculty used university email. Students used Facebook for academic purposes twice as much as faculty. Conclusion. Absence of university email in Iraqi schools and colleges of pharmacy makes Facebook essential for faculty-student communications. The majority (71.1% to 82%) of respondents perceived that Facebook was easy to use. Three TAM variables (intention to use, attitude toward use and perceived usefulness) had significant positive associations with actual use of both Facebook messaging and university email.

Quantitative real time PCR analysis of apoptotic gene expression in chronic lymphocytic leukemia patients and their relationships with chemosensitivity

Background: Apoptosis-related gene expression such as BCL2, and p53 has been suggested in predicting the patient response to chemo- or radiotherapy, as well as patient's survival. Methods: The aim of this study was to determine changes in BCL2 and p53 apoptosis related gene expressions in chronic lymphocytic leukemia (CLL) patients in response to different chemotherapy regimens and number of treatment courses. The study was conducted on 55 CLL patients (44 CLL and 11 CLL/SLL; small lymphocytic lymphoma) and 40 healthy individuals as control, over three-months period. The RNA was extracted by exploitation total RNA extraction kit, treated with DNAse, then cDNA was synthesized and qRT-PCR used to analyze antiapoptotic BCL2 and tumor suppresser p53 gene expressions. Results: CLL/SLL showed higher BCL2 and p53 gene expression than CLL. The patients with CLL showed three-fold increase in BCL2 gene expression compared to healthy controls (p < 0.05), and 50% decrease in p53 gene expressions (p < 0.05). BCL2 gene expression was higher, particularly, for those who were treated with higher range of treatment courses and combination of fludarabine, cyclophosphamide and rituximab (FCR) regimen. P53 gene expression reciprocally related with BCL2 and vice versa. Conclusions: In contrary to BCL2, p53 gene was extremely expressed in patients treated with chemotherapy agents, particularly after 24­30 months disease duration; suggesting a late expression of p53 during advanced stages of the disease. A proportional change in BCL2 and p53 gene expression was reported with different treatment regimens; Chlorambucil (Clb) decreased and FCR regimen increased BCL2 gene expression. Higher p53 gene expression reported with the Chlorambucil + (Chlorambucil + Prednisolone) regimen (AU)

Drugs acting at the GABAA receptor attenuate ethanol-induced gastric mucosal damage in vitro.

1. Benzodiazepines (BZ) have been reported to protect against ethanol-induced gastric damage in rats in both in vivo and in vitro models. However, the effects of some drugs in the new in vitro model do not agree with results reported previously in in vivo studies. 2. Therefore, the aim of the present study was to modify the new in vitro model to a model that more closely resembles the in vivo model and, using the new in vitro model, to reassess the gastroprotective effects of some BZ and to assess the effects of some new compounds. 3. The rat stomach was isolated from the whole animal and kept in aerated Krebs' solution at 37 degrees C in an organ bath. Gastric mucosal damage was induced by instillation of 1 mL of 100% ethanol into the stomach. Drugs or their vehicle were administered inside the bath 15 min before ethanol instillation into the stomach. One hour after the instillation of ethanol, the stomach was removed from the organ bath, opened along the greater curvature and then examined for gastric mucosal damage. 4. The results indicate that, compared with vehicle pretreatment, ethanol-induced gastric mucosal damage was significantly reduced in a dose-dependent manner by pretreatment with clonazepam, a drug that acts as an agonist at central BZ sites of the GABAA receptor, and Ro 15-4513, a partial inverse agonist at BZ sites of the GABAA receptor. Flumazenil (an antagonist of central BZ sites of the GABAA receptor) did not affect gastric mucosal lesions provoked by ethanol. However, flumazenil significantly reversed the mucosal protective effects of clonazepam and Ro 15-4513. 5. CGS 9896 (a partial agonist at BZ sites of the GABAA receptor, with anxiolytic and anticonvulsant but no sedative effects) did not offer any protection against ethanol-induced gastric mucosal damage. Ro 5-3663, an atypical BZ that binds to the picrotoxin site of the GABAA receptor and reported to be a potent convulsant and only a weak antagonist of GABA, did not show any protection against the development of lesions. 6. The results suggest local gastric mediation of the effects of ethanol, as well as the gastric protective effects of BZ, through an action at local central-type BZ sites of the GABAA receptor located in the rat stomach.