Prevention of Travelers' Diarrhea by Nonantibiotic Drugs

Travelers have resorted to a variety of drugs for prevention of diarrhea. No beneficial prophylactic effect has been confirmed for halogenated hydroxyquinolines, lactobacilli, antimotility drugs, ethacridine, and various other agents. In contrast, bismuth subsalicyate (BSS) in liquid form reduced the incidence of diarrhea in students from the United States living in Mexico and in tablet form in volunteers challenged by enterotoxigenic Escherichia coli. In tourists visiting various developing countries, a randomized, double-blind study was conducted in which 390 persons received a total of 2.1 or 1.05 g of BSS daily or placebo in tablet form in two doses. BSS reduced the incidence of diarrhea by 41% in the high-dose group and by 35% in the low-dose group without causing important adverse reaction

Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, self-administration sessions were preceded by a taste cue that signaled delayed drug availability. Assessments of hedonic responses indicated that this delay cue became aversive during training. Both the self-administration behavior and the immediate cue were subsequently extinguished in the absence of cocaine. After extinction of self-administration behavior, the presentation of the aversive delay cue reinstated drug seeking. In vivo electrophysiology and voltammetry recordings in the nucleus accumbens measured the neural responses to both the delay and immediate drug cues after extinction. Interestingly, the presentation of the delay cue simultaneously decreased dopamine signaling and increased excitatory encoding of the immediate cue. Most importantly, the delay cue selectively enhanced the baseline activity of neurons that would later encode drug seeking. Together these observations reveal how cocaine cues can modulate not only affective state, but also the neurochemical and downstream neurophysiological environment of striatal circuits in a manner that promotes drug seeking

Five year outcomes in a cohort study of physicians treated for substance use disorders in the United States

Objective To evaluate the effectiveness of US state physician health programmes in treating physicians with substance use disorders

Development of a new travellers' diarrhoea clinical severity classification and its utility in confirming rifamycin-SV efficacy

BACKGROUND travellers' diarrhoea (TD) is frequently reported with incidence up to 40% in high-risk destinations. Previous studies showed that the number of loose stools alone is inadequate to holistically predict the severity of TD. To improve the prediction of prognosis and to optimize treatments, a simple risk-based clinical severity classification has been developed. METHODS pooled baseline data of signs and symptoms and number of loose stools from 1098 subjects enrolled in two double-blind Phase 3 trials of rifamycin-SV were analyzed with correlation, multiple correspondence analyses, prognostic factor criteria, and Contal and O'Quigley method to generate a TD severity classification (mild, moderate and severe). The relative importance of this classification on resolution of TD was assessed by Cox proportional model hazard model on the time to last unformed stool (TLUS). RESULTS the analysis showed that TLUS were longer for the severe [hazard ratio (HR) 0.24; P < 0.001; n = 173] and moderate (HR 0.54; P = 0.0272; n = 912) vs mild. Additionally, when the treatment assigned in the studies was investigated in the severity classification, the results yielded that rifamycin-SV significantly shortened TLUS vs placebo for all subjects (HR 1.9; P = 0.0006), severe (HR 5.9; P = 0.0232) and moderate (HR 1.7; P = 0.0078) groups and was as equally efficacious as ciprofloxacin for all subjects, moderate and severe groups (HRs: 0.962, 0.9, 1.2; all P = NS, respectively). When reassessed by this classification, rifamycin-SV showed consistent efficacy with the Phase 3 studies. CONCLUSIONS this newly developed TD clinical severity classification demonstrated strong prognostic value and clinical utility by combining patients' multiple signs and symptoms of enteric infection and number of loose stools to provide a holistic assessment of TD. By expanding on the current classification by incorporating patient reported outcomes in addition to TLUS, a classification like the one developed, may help optimize patient selection for future clinical studies

Markers of Inflammation in Bacterial Diarrhea among Travelers, with a Focus on Enteroaggregative Escherichia coli Pathogenicity

The intestinal inflammatory response of traveler's diarrhea acquired in Goa, India, and Guadalajara, Mexico, was studied. Fecal lactoferrin was found in stool samples in which enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli, or Salmonella or Shigella species were isolated, with Shigella-positive cases showing the highest level. Samples from cases of Shigella-associated diarrhea had the highest concentrations of fecal cytokines. Travelers to India who had EAEC-associated diarrhea showed elevated levels of interleukin (IL)-8 (median, 341.15 pg/mL) and IL-1β (median, 749.90 pg/mL). Although 15 travelers to Mexico who had EAEC-associated diarrhea had a median concentration of 0 pg/mL for both IL-8 and IL-1β, 2 had high levels of IL-8 (1853 and 11,786 pg/mL), and 5 showed elevated levels of IL-1β (1-1240 pg/mL). Samples from patients in India who had pathogen-negative diarrhea or from patients in Mexico who had asymptomatic EAEC infection were negative for cytokines. Bacterial pathogens causing traveler's diarrhea commonly produce intestinal inflammation, although a subset of patients with EAEC-associated diarrhea fail to develop an inflammatory respons

Mesozoic-Cenozoic evolution of the Xining-Minhe and Dangchang basins, northeastern Tibetan Plateau: Magnetostratigraphic and biostratigraphic results

Accurate stratigraphic ages are crucial to understanding the deformation history of the Tibetan Plateau prior to and during the Indo-Asian collision. Efforts to quantify Mesozoic-Cenozoic ages are hindered by limited fossils and a paucity of volcanic horizons and regionally correlative strata. Magnetostratigraphic and biostratigraphic results from the Xining-Minhe-Longzhong basin complex and Dangchang basin provide an improved chronology of nonmarine basin development over a large region of the northeastern Tibetan Plateau (34–37°N, 101–105°E). Analyses of 171 magnetostratigraphic levels and 24 palynological assemblages (\u3e120 species) indicate Late Jurassic-Early Cretaceous to mid-Tertiary deposition. Although magnetic polarity zonation is incomplete, independent palynological age control partially restricts possible correlations to the Geomagnetic Polarity Timescale. The sediment accumulation record, basin provenance, structural geology, and published thermochronological data support a history of Jurassic exhumation, Late Jurassic-Early Cretaceous fault-related basin initiation, and Cretaceous-Paleogene reduced accumulation. These patterns, which are compatible with Late Jurassic-Early Cretaceous extension and Cretaceous-Paleogene postrift thermal subsidence, were disrupted at about 40–30 Ma, when shortening related to the Indo-Asian collision induced localized range uplift, vertical axis rotation, and amplified subsidence

Travelers' Diarrhea in West Africa and Mexico: Fecal Transport Systems and Liquid Bismuth Subsalicylate for Self-Therapy

The goals of this study were threefold: to compare the etiology of travelers' diarrhea in West Africa and Mexico, to evaluate two fecal transport systems for the recovery of enteropathogens, and to verify the efficacy of liquid bismuth subsalicylate (BSS) in different locations and under different entrance criteria for disease severity. The study populations consisted of 133 European tourists in West Africa and 112 American students in Mexico who had suffered from travelers' diarrhea. In 60% and 38% of the stool samples at the two study sites, similar proportions of enteropathogens were detected. A two-vial system consisting of Enteric Plus medium and polyvinyl alcohol fixative was slightly superior for identifying enteric pathogens than was a three-vial system with buffered glycerol saline, Cary-Blair medium with campylobacter antibodies, and polyvinyl alcohol fixative. In a parallel, double-blind, randomized trial, BSS significantly shortened disease duration at both study site

Improved Detection of Enterotoxigenic Escherichia coli among Patients with Travelers' Diarrhea, by Use of the Polymerase Chain Reaction Technique

This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be ∼100-1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P < .0001

The ovarian follicle of ruminants: The path from conceptus to adult

This review resulted from an international workshop and presents a consensus view of critical advances over the past decade in our understanding of follicle function in ruminants. The major concepts covered include: (1) the value of major genes; (2) the dynamics of fetal ovarian development and its sensitivity to nutritional and environmental influences; (3) the concept of an ovarian follicle reserve, aligned with the rise of anti-Müllerian hormone as a controller of ovarian processes; (4) renewed recognition of the diverse and important roles of theca cells; (5) the importance of follicular fluid as a microenvironment that determines oocyte quality; (6) the \u27adipokinome\u27 as a key concept linking metabolic inputs with follicle development; and (7) the contribution of follicle development to the success of conception. These concepts are important because, in sheep and cattle, ovulation rate is tightly regulated and, as the primary determinant of litter size, it is a major component of reproductive efficiency and therefore productivity. Nowadays, reproductive efficiency is also a target for improving the \u27methane efficiency\u27 of livestock enterprises, increasing the need to understand the processes of ovarian development and folliculogenesis, while avoiding detrimental trade-offs as greater performance is sought