Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events.

Background: Recently, more clinical trials are being conducted in Africa and Asia, therefore, background morbidity in the respective populations is of interest. Between 2000 and 2007, the International AIDS Vaccine Initiative sponsored 19 Phase 1 or 2A preventive HIV vaccine trials in the US, Europe, Sub-Saharan Africa and India, enrolling 900 healthy HIV-1 uninfected volunteers.   Objective To assess background morbidity as reflected by unsolicited adverse events (AEs), unrelated to study vaccine, reported in clinical trials from four continents. Methods All but three clinical trials were double-blind, randomized, and placebo-controlled. Study procedures and data collection methods were standardized. The frequency and severity of AEs reported during the first year of the trials were analyzed. To avoid confounding by vaccine-related events, solicited reactogenicity and other AEs occurring within 28 d after any vaccination were excluded. Results In total, 2134 AEs were reported by 76% of all participants; 73% of all events were mild. The rate of AEs did not differ between placebo and vaccine recipients. Overall, the percentage of participants with any AE was higher in Africa (83%) compared with Europe (71%), US (74%) and India (65%), while the percentage of participants with AEs of moderate or greater severity was similar in all regions except India. In all regions, the most frequently reported AEs were infectious diseases, followed by gastrointestinal disorders. Conclusions Despite some regional differences, in these healthy participants selected for low risk of HIV infection, background morbidity posed no obstacle to clinical trial conduct and interpretation. Data from controlled clinical trials of preventive interventions can offer valuable insights into the health of the eligible population.

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours.

BACKGROUND Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. METHODS Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5-12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. RESULTS Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in Cmax and AUC0-t were dose proportional for the 6-12 mg/m2 doses. CONCLUSION The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10 mg/m2. The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. TRIAL REGISTRATION The study was registered with ClinicalTrials.gov as NCT01755390.

Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial.

In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥ 2 × 10(6) CD34(+) cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥ 5 × 10(6) CD34(+) cells/kg for non-Hodgkin's lymphoma or ≥ 6 × 10(6) CD34(+) cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with minimal toxicity, providing further data supporting the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma or myeloma.

Metabólitos secundários da família bromeliaceae

This review describes aspects of the Bromeliaceae family dealing the traditional applications, biological activities and distribution of secondary metabolites in distinct subfamilies. Some species are used with medicinal purposed in the treatment of respiratory, diabetes or inflammation diseases, and gastrointestinal disorders. Special emphasis on cycloartane triterpenoids and flavonoids, typical metabolites of this family, are presented. Bromeliaceae is unique amongst the monocotyledons in the frequency and variety of flavonoids with hydroxylation or methoxylation at the 6-position. Other compound classes as steroids, hidroxycinnamic acids, phenylpropane diglycerides, lignans, are presented.

Occurrence of Campylobacter jejuni and C. coli on broiler carcasses after chilling in southern Brazil

Campylobacter jejuniand C. colihave been associated with gastrointestinal disorders in human beings, due mainly to the consumption of chicken meat. Despite control measures for reducing contamination by these bacteria, the detection of Campylobacter in carcasses after chilling remains high.A total of 105 carcasses were assessed by the horizontal detection method in five federally inspected slaughterhouses in southern Brazil in 2012 and in the first three months of 2013. Campylobacterwas isolated in 37.1% of the carcasses, of which 97.5% contained C. jejuni and 2.5% were infected by C. coli. The rate of positive carcasses across the slaughterhouses ranged from 0 to 71.4%. Determining the occurrence of Campylobacteramong flocks is crucial for estimating the microbial load at specific points along the slaughtering process and for minimizing the risk of contamination of end products by Campylobacter.

From Escherichia coli heat-stable enterotoxin to mammalian endogenous guanylin hormones

The isolation of heat-stable enterotoxin (STa) from Escherichia coli and cholera toxin from Vibrio cholerae has increased our knowledge of specific mechanisms of action that could be used as pharmacological tools to understand the guanylyl cyclase-C and the adenylyl cyclase enzymatic systems. These discoveries have also been instrumental in increasing our understanding of the basic mechanisms that control the electrolyte and water balance in the gut, kidney, and urinary tracts under normal conditions and in disease. Herein, we review the evolution of genes of the guanylin family and STa genes from bacteria to fish and mammals. We also describe new developments and perspectives regarding these novel bacterial compounds and peptide hormones that act in electrolyte and water balance. The available data point toward new therapeutic perspectives for pathological features such as functional gastrointestinal disorders associated with constipation, colorectal cancer, cystic fibrosis, asthma, hypertension, gastrointestinal barrier function damage associated with enteropathy, enteric infection, malnutrition, satiety, food preferences, obesity, metabolic syndrome, and effects on behavior and brain disorders such as attention deficit, hyperactivity disorder, and schizophrenia.

Molecular cloning and restriction endonuclease analysis of bovine adenovirus type 3

Bovine adenovirus type 3 (BAV3) is a medium size DNA virus that causes respiratory and gastrointestinal disorders in cattle. The viral genome consists of a 35,000 base pair, linear, double-stranded DNA molecule with inverted terminal repeats and a 55 kilodalton protein covalently linked to each of the 5' ends. In this study, the viral genome was cloned in the form of subgenomic restriction fragments. Five EcoRI internal fragments spanning 3.4 to 89.0 % and two Xb a I internal fragments spanning 35.7 to 82.9 % of the viral genome were cloned into the EcoRI and Xbal sites of the bacterial vector pUC19. To generate overlap between cloned fragments, ten Hi n dIll internal fragments spanning 3.9 to 84.9 and 85.5 to 96% and two BAV3 BamHI internal fragments spanning 59.8 to 84.9% of the viral genome were cloned into the HindllI and BamHI sites of pUC19. The HindlII cloning strategy also resulted in six recombinant plasmids carrying two or more Hi ndII I fragments. These fragments provided valuable information on the linear orientation of the cloned fragments within the viral genome. Cloning of the terminal fragments required the removal of the residual peptides that remain attached to the 5' ends of the genome. This was accomplished by alkaline hydrolysis of the DNA-peptide bond. BamH I restriction fragments of the peptide-free DNA were cloned into pUC19 and resulted in two plasmids carrying the BAV3 Bam HI terminal fragments spanning 0 to 53.9% and 84.9 to 100% of the viral genome.

Évaluation gastro-intestinale chez des chiens présentant un comportement de léchage excessif de surface

L’objectif de cette étude était de démontrer que le léchage excessif de surface (LES) chez le chien représente un signe clinique d’un trouble digestif sous-jacent plutôt qu’un trouble obsessionnel compulsif. Vingt chiens présentés pour LES (groupe L) ont été divisés en 2 sous-groupes de 10 chiens chacun : L0, sans, et LD, avec des signes cliniques digestifs concomitants. Dix chiens en santé ont été assignés à un groupe contrôle (groupe C). Une évaluation comportementale complète, un examen physique et neurologique ont été réalisés avant un bilan diagnostic gastro-intestinal (GI) complet (hématologie, biochimie, analyse urinaire, mesure des acides biliaires pré et post-prandiaux et de l’immunoréactivité spécifique de la lipase pancréatique canine, flottaison fécale au sulfate de zinc, culture de selles, échographie abdominale et endoscopie GI haute avec prise de biopsies). En fonction des résultats, un interniste recommandait un traitement approprié. Les chiens étaient suivis pendant 90 jours durant lesquels le comportement de léchage était enregistré. Des troubles GI ont été identifiés chez 14/20 chiens du groupe L. Ces troubles GI sous-jacents incluaient une infiltration éosinophilique du tractus GI, une infiltration lymphoplasmocytaire du tractus GI, un retard de vidange gastrique, un syndrome du côlon irritable, une pancréatite chronique, un corps étranger gastrique et une giardiose. Une amélioration >50% en fréquence ou en durée par rapport au comportement de léchage initial a été observée chez une majorité de chiens (56%). La moitié des chiens ont complètement cessé le LES. En dehors du LES, il n’y avait pas de différence significative de comportement (p.ex. anxiété), entre les chiens L et les chiens C. Les troubles GI doivent être considérés dans le diagnostic différentiel du LES chez le chien.

Circulation symbolique des désordres fonctionnels gastro-intestinaux : étude réalisée dans les familles québécoises francophones

La présente étude en anthropologie médicale propose d’examiner la dimension socioculturelle des désordres fonctionnels gastro-intestinaux (DFGI) en considérant l’expérience de six familles québécoises francophones où un pré-adolescent souffre de symptômes associés à un DFGI. Le regard anthropologique qui nous a permis d’appréhender ces expériences de douleur s’appuie principalement sur les travaux issus de la psychiatrie transculturelle, de même que sur les influences de l’anthropologie du corps et de la phénoménologie. À travers ce regard, la somatisation est considérée comme une forme de communication de la douleur, modulée de manière importante par le contexte socioculturel et représentative d’une certaine souffrance sociale. Ce langage ponctué d’idiomes de détresse et de métaphores permet aux individus d’exprimer leur souffrance et de mobiliser un soutien social efficace pour la prendre en charge. Dès lors, le corps doit être perçu comme un corps vécu; comme un lieu de marquage du social, mais également comme un instrument de positionnement social et une frontière où des mouvements d’appartenance et de divergence sont exprimés. Par l’exploration, dans chacune de ces familles, des différentes manières de décrire les symptômes, de les interpréter et d’y réagir, nous avons procédé à la reconstruction d’histoires particulières pour voir comment ces symptômes venaient s’inscrire dans la biographie individuelle et familiale. À travers l’analyse de la construction du sens de la douleur et des pratiques adoptées pour la contrôler, la douleur abdominale nous est apparue comme intimement liée à l’expérience sociale et la médicalisation comme une base pour une meilleure appréhension de cette douleur. Par ses maux de ventre, l’enfant exprime ses limites corporelles et sociales. À l’intérieur de la famille, l’expression de cette limite peut être parfois dérangeante, confrontante, et même entraîner des rapports conflictuels. C’est ainsi qu’est « négociée » une approche appropriée à la douleur qui redéfinit les rôles de chacun par rapport à cette dernière. Le ventre devient le médiateur qui permet le compromis nécessaire au « vivre ensemble » ou au « vivre dans le monde ». À l’issue de ii cette négociation qui implique la participation du médecin traitant, les rapports sont parfois reconstruits et la relation au monde et aux autres peut devenir différente.

Prevalencia de enfermedad celiaca en Latinoamérica: revisión sistemática de la literatura y meta-análisis

Introducción: La enfermedad celiaca (EC) es una enfermedad autoinmune (EA) intestinal desencadenada por la ingesta de gluten. Por la falta de información de la presencia de EC en Latinoamérica (LA), nosotros investigamos la prevalencia de la enfermedad en esta región utilizando una revisión sistemática de la literatura y un meta-análisis. Métodos y resultados: Este trabajo fue realizado en dos fases: La primera, fue un estudio de corte transversal de 300 individuos Colombianos. La segunda, fue una revisión sistemática y una meta-regresión siguiendo las guías PRSIMA. Nuestros resultados ponen de manifiesto una falta de anti-transglutaminasa tisular (tTG) e IgA anti-endomisio (EMA) en la población Colombiana. En la revisión sistemática, 72 artículos cumplían con los criterios de selección, la prevalencia estimada de EC en LA fue de 0,46% a 0,64%, mientras que la prevalencia en familiares de primer grado fue de 5,5 a 5,6%, y en los pacientes con diabetes mellitus tipo 1 fue de 4,6% a 8,7% Conclusión: Nuestro estudio muestra que la prevalencia de EC en pacientes sanos de LA es similar a la notificada en la población europea.

Prebiotics as gut microflora management tools

Functional foods is an often-used term applied to dietary ingredients that serve to improve consumer health. Over the last few decades, these foods have gained in popularity with sales continuing to increase rapidly. Recent scientific, and some lay, reports have shown the popularity of both probiotics and prebiotics. These serve to elicit changes in the gut microbiota composition that increase populations of purported beneficial gut bacterial genera, for example, lactobacilli or bifidobacteria. Probiotics use live microbial feed additions, whereas prebiotics target indigenous flora components. As gastrointestinal disorders are prevalent in terms of human health, both probiotics and prebiotics serve an important role in the prophylactic management of various acute and chronic gut derived conditions. Examples include protection from gastroenteritis and some inflammatory conditions.

Probiotics and prebiotics

The human large intestine is an intensively colonised area containing bacteria that are health promoting, as well as pathogenic - This has led to functional food developments that fortify the former at the expense of the latter - Probiotics have a long history of use in humans as live microbial feed additions - In contrast, a prebiotic is a non digestible food ingredient that beneficially affects the host by targeting indigenous components thought to be positive - Dietary carbohydrates, such as fibres are candidate prebiotics but most promise has been realised with oligosaccharides - As prebiotics exploit non-viable food ingredients, their applicability in diets is wide ranging - As gastrointestinal disorders are prevalent in terms of human health, both probiotics and prebiotics serve an important role in the prophylactic management of various acute and chronic gut derived conditions - Examples include protection from gastroenteritis and some inflammatory conditions.

Antidiarrhoeal effects of Mikania glomerata Spreng. (Asteraceae) leaf extract in mice

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genotoxicity testing of Ambelania occidentalis (Apocynaceae) leaf extract in vivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)