Persistent efficacy of topical eprinomectin against nematode parasites in cattle

Six studies were conducted to evaluate the persistent efficacy of eprinomectin pour-on against experimental challenges with infective nematode larvae in calves. In each study, calves were randomly assigned to one untreated group and up to four test groups, which were treated with eprinomectin at 500 μg/kg body weight at weekly intervals before single bolus challenge. The calves were necropsied approximately 4 weeks after challenge infection for nematode recovery. Eprinomectin pour-on provided ≥90% efficacy against challenge with Haemonchus placei, Trichostrongylus axei and T. colubriformis at 21 days after treatment and against Cooperia oncophora, C. punctata, C. surnabada, Dictyocaulus viviparus, Nematodirus helvetianus, Oesophagostomum radiatum and Ostertagia ostertagi at 28 days after treatment. Received: 14 April 2000 / Accepted: 18 May 2000     

Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice

We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.     

Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls (n=15), non-CAPD uremic patients (n=17), uremic patients on CAPD (n=27) and non-renal patients with inguinal hernia (n=12). To study myofibroblastic conversion of mesothelial cells, -smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and -SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.Manuel López-Cabrera and Rafael Selgas contributed equally to the article.     

Prime number variant of concealed trigeminy

A 53-year-old man with myocardial infarction was found to have frequent premature ventricular beats. The predominant pattern was classical concealed trigeminy; i.e., the number of conducted sinus beats, S, between extrasystoles satisfied the equation S = 3n + 2, where "n" is zero or any positive integer. Two other transient patterns also occurred. The first one was characterized by exceptional values of S, which satisfied the equation S = 3n + 3. In the second transient pattern, all values of S fitted the classical equation, but there were singularly absent values; i.e., the "n" in the equation was exclusively an odd number, giving rise to only prime numbers of interectopic conducted sinus beats. It is proposed in this last form that there are two sites of fixed block proximal to a variable distal block in a re-entry loop responsible for the ventricular extrasystoles.     

Surgical treatment of portal hypertension in schistosomiasis

Patients with mansonic schistosomiasis and portal hypertension are usually young, with good liver functional reserve, huge splenomegaly, and hypersplenism detectable only by alterations seen in laboratory tests. Patients who are not operated on do not develop portosystemic encephalopathy (PSE). Angiographic alterations are characteristic and totally different from those observed in patients with liver atrophy or cirrhosis. Digestive tract hemorrhage is the most severe complication. The patient with schistosomiasis is, therefore, a good model for the study of the consequences caused by the surgical treatment of portal hypertension. The evaluation, however, of results published in the literature regarding schistosomiasis is practically impossible. In a review of 130 publications referring to 4,516 surgically treated patients, the absence of prospective or retrospective studies with adequate controls was observed, and only 3.2% of the patients were followed for 5 years. According to available data, a total of 29 different surgical techniques has been employed, 81.6% of which are represented by simple splenectomy, esophagogastric devascularization (EGDS), and splenorenal shunt (SRS). Splenectomy was the surgical procedure showing the highest rate of recurrent hemorrhage (54.3%), and the portocaval shunt had the highest PSE incidence (60%). Portosystemic encephalopathy incidence after SRS was 29%. Thus, in view of a lack of objective information, in 1977 our group started a prospective, randomized study comparing the results of the surgical procedures most widely used in our country: selective portal decompression (SPD), EGDS, and SRS. The randomization was interrupted after 94 patients had been operated on (32 SRS, 30 SPD, and 32 EGDS) because of a highly significant PSE incidence in the SRS group. Preliminary results as of January, 1984, refer to an average follow-up period of 53 months (minimum 29, maximum 77 months). In the SRS group, the late mortality rate was 18.7%, and the incidence of PSE was 31.2%. Among the patients included in this group, 18.7% had arterial hypertension. In the SPD group, late mortality occurred in 10% of the cases, and PSE in 13.3%, while a mild hyperbilirubinemia was seen in 43.3% of patients. Recurrent hemorrhage and ascites had an approximately similar incidence in the 3 groups.

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Resumen Los pacientes con esquistosomiasis mansónica e hipertensión portal generalmente son jóvenes con buena reserva funcional hepática, enorme esplenomegalia e hipersplenismo detectable solamente por las pruebas de laboratorio. Los pacientes nó operados no desarrollan encefalopatia portosistémica (EPS). Los cambios angiográficos son característicos y totalmente diferentes de los que se presentan en pacientes con cirrosis y atrofia hepática. La complicación más grave es la hemorragia digestiva. Por consiguiente, el paciente con esquistosomiasis es un buen modelo para el estudio de las consecuencias que se derivan del tratamiento quirúrgico de la hipertensión portal. Sinembargo, la evaluación de los resultados en la esquistosomiasis que han sido publicados en la literatura es prácticamente imposible. En una revisión de 130 publicaciones relativas a 4516 pacientes operados, se pudo comprobar ausencia de estudios prospectivos o retrospectivos con controles adecuados, y apenas el 3.2% de los casos fué seguido por 5 años. De acuerdo con los datos disponibles, se empleó un total de 29 técnicas quirúrgicas diferentes, 81.6% de los cuales estuvo representado por simple esplenectomía, devascularización esofagogástrica (DEG) y shunt espleno-renal (SER). La esplenectomía fué el procedimiento quirúrgico que tuvo la más alta incidencia de hemorragia recurrente (54.3%) y el shunt portacava la más alta incidencia de EPS (60%). La incidencia de EPS después de SER fué de 29%.Por consiguiente, en vista de la ausencia de información objetiva, nuestro grupo inición en 1977 un estudio prospectivo y aleatorizado para comparar los resultados de los procedimientos quirúrgicos mayormente utilizados en nuestro país: descompresión portal selectiva (DPS), DEG y SER. La aleatorización fué interrumpida después de haber operado los primeros 94 pacientes (32 SER, 30 DPS y 32 DEG) debido a una muy significativa incidencia de la EPS en el grupo con SER. Los resultados preliminares (enero de 1984) se refieren a un período promedio de seguimiento de 53 meses (mínimo 29, máximo 77 meses). En el grupo de SER la mortalidad tardía fué de 18.7% y la incidencia de EPS fué de 31.2%.El 18.7% de los pacientes incluidos en este grupo exhibió hipertensión arterial. En el grupo de DPS la mortalidad tardía fué de 10% y la incidencia de EPS de 13.3%; se observó hiperbilirrubinemia leve en 43.3% de los pacientes. La incidencia de hemorragia recurrente y de ascitis fué aproximadamente igual en los tres grupos.

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Résumé Les malades qui accusent une hypertension portale d'origine bilharzienne sont généralement jeunes. Leurs fonctions hépatiques sont bonnes mais ils présentent une splénomégalie très importante et une hypersplénisme qui se manifeste seulement par des altérations des tests biologiques. Lorsqu'ils ne sont pas opérés ils ne présentent pas de manifestations d'encéphalopathie. Les caractères angiographiques sont très particuliers et totalement différents de ceux qui sont observés chez les sujets dont le foie est atrophié ou cirrhotique. L'hémorragie digestive représente la complication la plus sévère. Le malade atteint de bilharziose hépatique est par conséquent un bon modèle d'étude des conséquences provoquées par le traitement chirurgical de l'hypertension portale. Cependant les résultats du traitement publiés dans la littérature sont ininterprétables. Dans une revue de 130 publications concernant 4516 opérations, l'absence d'études prospectives ou rétrospectives bénéficiant d'un contrôle de qualité a été constatée, 3,2% seulement des malades ayant été suivis pendant 5 ans. En tenant compte des données disponibles 29 techniques chirurgicales ont été employées, 81,6% desquelles sont repésentées par les opérations suivantes: splénectomie, devascularisation et anastomose spléno-rénale. La splénectomie a été suivie du taux le plus élevé de récidive hémorragique (54,3%) et l'anastomose portocave du taux le plus important d'encéphalopathie (60%), l'anastomose spléno-rénale n'étant suivie d'encéphalopathie que dans 29% des cas. En raison du défaut d'information objective notre équipe a entrepris en 1977 une étude prospective faite selon la méthode du choix au hasard des 3 techniques chirurgicales les plus employées au Brésil: l'anastomose spléno-rénale, la décompression portale sélective et la dévascularisation. L'étude fut interrompue alors que 94 malades avaient été opérés (32 anastomose spléno-rénales, 30 décompressions portales sélectives et 32 dévascularisations oesophagogastriques) en raison du taux particulièrement élevé de l'encéphalopathie postopératoire. Les résultats de cette étude menée jusqu'en janvier 1984 répondent à une période postopératoire moyenne de 53 mois (minimum 29, maximum 77 mois). Dans le groupe traité par anastomose spléno-rénale le taux de la mortalité tardive fut de 18,7% et celui de l'encéphalopathie de 31,2%. Parmi les malades de ce groupe, 18,7% présentaient une hypertension artérielle. Dans le groupe traité par décompression portale selective le taux de la mortalité tardive fut de 10%, celui de l'encéphalopathie de 13,3%, cependant qu'une hyperbilirubinémie fut constatée chez 43,3% de ces opères. La récidive hémorragique et l'ascite atteignent un taux très voisin pour les trois opérations.

     

Prospective adverse event risk evaluation in clinical trials

Health Care Management Science - Proactive and objective regulatory risk management of ongoing clinical trials is limited, especially when it involves the safety of the trial. We seek to...     

Genetic association of the PERIOD3 (PER3) Clock gene with extreme obesity

BackgroundObesity has reached epidemic proportions worldwide, affecting life quality and span. Susceptibility to obesity is partly mediated by genetic differences. Indeed, several genes from the clock gene family have already been shown to be intimately associated with obesity in diverse ethnic groups. In the present study, an association between BMI and the rs707467, rs228697 and rs228729 PER3 (Period Circadian Clock 3) polymorphisms in subjects with class II (BMI ≥ 35.0–39.9 kg/m²) and class III obesity (>40 kg/m², extreme obesity) were carried out using TaqMan real-time PCR. Overall, 259 Brazilian adults were genotyped, of whom 122 had class II or III obesity (BMI ≥ 35.0 kg/m²) and 137 were controls having normal weight (BMI > 18.5 and <24.9 kg/m²).ResultsPER3 tag SNP (rs228729) shows a significant association with extreme obesity (1000 permutation p = 0.03 and p = 0.04), for genotype and allele frequency respectively) and a haplotype among the three assessed SNPs (alleles G/T/A, rs228697, rs228729, and rs707467, respectively, 1000 permutation p = 0.03) was significantly more prevalent in the group with obesity.ConclusionThis exploratory association study suggests that PER3 rs228729 may be associated with extreme obesity in Brazilian adults, however, replication is needed.     

What Are the Maternal Factors that Potentially Intervenes in the Nutritional Composition of Human Milk?

Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women. Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance. Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components. Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.