Modeling cue-exposure therapy for alcohol use disorder in rhesus monkeys: Effects of putative cognitive enhancers.

BACKGROUND: Cue-exposure therapy (CET) is an effective approach for anxiety-related disorders, but its effectiveness for substance use disorders is less clear. One potential means of improving CET outcomes is to include a cognitive-enhancing pharmacotherapy. This study evaluated d-cycloserine (DCS) and RY-023, putative cognitive enhancers targeting glutamate and GABA systems, respectively, in a monkey model of CET for alcohol use disorder. METHODS: Male rhesus monkeys (n = 4) underwent multiple cycles of the CET procedure. During baseline (Phase 1), monkeys self-administered an ethanol solution under a fixed-ratio schedule and limited access conditions such that every 5th response in a 3-h session resulted in 30-s access to a drinking spout and a change in ethanol-paired cue lights from white to red. Behavior then was extinguished (Phase 2) by omitting the ethanol solution yet retaining the ethanol-paired stimulus lights. Monkeys also received injections of vehicle, DCS (3 mg/kg), a partial agonist at the glycine modulatory site on glutamatergic NMDA receptors, or the α5GABAA receptor-selective inverse agonist RY-023 (0.03 or 0.3 mg/kg). Once responding declined, monkeys underwent a cue reactivity test (Phase 3), and then returned to self-administration the following day to assess reacquisition (Phase 4). RESULTS: Through multiple cycles, self-administration remained stable. Compared to vehicle, DCS facilitated extinction of ethanol seeking (Phase 2) and delayed reacquisition of ethanol self-administration (Phase 4). In contrast, RY-023 facilitated extinction (Phase 2) and reduced cue reactivity (Phase 3). CONCLUSIONS: Adjunctive pharmacotherapy can improve CET outcomes, but the choice of pharmacotherapy should be dependent on the outcome of interest.

Prelacteal and early formula feeding increase risk of infant hospitalisation: a prospective cohort study.

OBJECTIVE: To ascertain the relationship between prelacteal feeding, early formula feeding and adverse health outcomes, especially hospitalisation during the first year of life. DESIGN: Multicentre prospective cohort study. SETTING: Six hospitals across three cities in Vietnam. PATIENTS: A total of 2030 pregnant women were recruited at 24-28 weeks of gestation and followed up at hospital discharge, 1, 3, 6 and 12 months post partum. MAIN OUTCOME MEASURES: Rates of infant hospitalisation, diarrhoea and lower respiratory tract infection during the first 12 months. RESULTS: For the final complete sample (n=1709, 84%), about one-quarter of the infants experienced diarrhoea (25.5%) or were admitted to hospital with at least one episode (24.8%), and almost half (47.6%) the cohort contracted lower respiratory tract infection by 12 months. The prevalence of prelacteal feeding was high (56.5%) while formula feeding was common (79.5%) before hospital discharge, both of which increased the risks of adverse health outcomes particularly hospitalisation by approximately 1.5-fold, with adjusted OR (95% CI) 1.43 (1.09 to 1.88) and 1.48 (1.07 to 2.05), respectively for these infants by 12 months, when compared with others who were exclusively breast fed. CONCLUSIONS: Prelacteal feeding and early formula feeding before hospital discharge are associated with higher risks of infection and hospital admission in Vietnamese infants. Support for exclusive breast feeding should be provided to mothers to avoid the adverse consequences of giving formula milk and prelateal foods.

A survey of irritable bowel syndrome in Vietnam using the Rome criteria.

Prevalence estimates for irritable bowel syndrome from surveys in Western countries are 4.4% to 22%, generally higher in women than men, and only a minority seek health care. There are few studies of bowel patterns in Asian countries. We conducted a survey of a nonpatient population in Ho Chi Minh City, Vietnam, to determine bowel patterns and the prevalence of bowel dysfunction. A forced-choice, self-report questionnaire was distributed to 738 predominantly health care workers, as well as patient relatives, at Cho Ray Hospital in Ho Chi Minh City and returned by 411 (response rate of 55.7%). Results were analyzed for men and women using Student's t-test for continuous variables and chi-square test for categorical variables. Subjects were 53.6% female, with a mean age of 27.7+/-6.9 years. Overall perception of health was excellent/very good in 13.6%, good in 54.2%, and fair/poor in 32.1% (males, 17.1%, 51.3%, and 31.5%, vs. females, 10.6%, 56.7%, and 32.7%; P=NS). The mean number of stools reported per week was 6.5 (males, 6.6, vs. females, 6.4; P=NS) and ranged between 3 and 21 stools per week in 95.5%. The frequency of irritable bowel syndrome symptoms (using Rome I criteria) was 7.2% (95% CI=4.8-10.1), with males at 4.8% (95% CI=2.2-8.9) vs. females at 9.2% (95% CI=5.7-13.9) (P=0.08). Of the subjects with irritable bowel syndrome symptoms, 6 of 29 (20.7%) had seen a physician for bowel symptoms. There were no gender differences in reported infrequent stool (12.0%), frequent stool (11.3%), hard stool (17.5%), loose stool (6.5%), straining (14.5%), incomplete emptying (16.2%), bloating (15.0%), urgency (10.0%), or mucus (2.7%). In conclusion, this survey of a nonpatient population in Vietnam showed that irritable bowel syndrome symptoms as defined by Rome criteria were common and that there were no significant differences between sexes in either stool frequency or prevalence of irritable bowel syndrome, unlike previous studies from the United States. The prevalence of irritable bowel syndrome in Vietnam in this study was in the lower range of reported data from Western countries, possibly in part related to the use of the Rome criteria. Only a minority of subjects with irritable bowel syndrome symptoms reported seeking health care for these symptoms.

Cell membrane array fabrication and assay technology.

BACKGROUND: Microarray technology has been used extensively over the past 10 years for assessing gene expression, and has facilitated precise genetic profiling of everything from tumors to small molecule drugs. By contrast, arraying cell membranes in a manner which preserves their ability to mediate biochemical processes has been considerably more difficult. RESULTS: In this article, we describe a novel technology for generating cell membrane microarrays for performing high throughput biology. Our robotically-arrayed supported membranes are physiologically fluid, a critical property which differentiates this technology from other previous membrane systems and makes it useful for studying cellular processes on an industrialized scale. Membrane array elements consist of a solid substrate, above which resides a fluid supported lipid bilayer containing biologically-active molecules of interest. Incorporation of transmembrane proteins into the arrayed membranes enables the study of ligand/receptor binding, as well as interactions with live intact cells. The fluidity of these molecules in the planar lipid bilayer facilitates dimerization and other higher order interactions necessary for biological signaling events. In order to demonstrate the utility of our fluid membrane array technology to ligand/receptor studies, we investigated the multivalent binding of the cholera toxin B-subunit (CTB) to the membrane ganglioside GM1. We have also displayed a number of bona fide drug targets, including bacterial endotoxin (also referred to as lipopolysaccharide (LPS)) and membrane proteins important in T cell activation. CONCLUSION: We have demonstrated the applicability of our fluid cell membrane array technology to both academic research applications and industrial drug discovery. Our technology facilitates the study of ligand/receptor interactions and cell-cell signaling, providing rich qualitative and quantitative information.