Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

Avaliação hematológica de cães naturalmente infectados por Leishmania (Leishmania) chagasi submetidos a tratamento com antimoniato de meglumina

The present research was carried out aiming to assess the hematological response of dogs with visceral leishmaniasis submitted to treatment. For this, seven animals naturally infected by Leishmania sp. were submitted to a treatment with 75 mg/kg meglumine antimoniate subcutaneously, 12-12h/3 weeks. In all animals, a complete blood count and bone marrow aspiration biopsy were carried out for a descriptive evaluation at up to seven moments: before the treatment, 30, 60, 90, 120, 150 and 180 days after the start of the treatment. Before the beginning of the experiment hematological alterations were observed in four of the seven dogs (57.1%), among them, nonregenerative anemia, lymphopenia, lymphocytosis and monocytosis. During the course of the experiment the occurrence of leukocytoses, such as left shift neutrophilia and eosinophilia, were observed in some of the animals. Before the beginning of the treatment (M1), the occurrence of erythrocytic hypoplasia was detected by bone marrow cytology in two of the dogs (28.6%). This was reversed through an increase in the amount of erythroid progenitor cells after the administration of meglumine antimoniate. Thus, it can be concluded that the treatment led to normalization of the hematological alterations and recovery of the bone marrow.

Tratamento hepatoprotetor favorece a resposta leucocitária de ratos wistar intoxicados por CCL4

The aims of this investigation was to evaluate the effect of hepatoprotective treatments with a compound prepared by the association of N-Acetyl DL-Methionine (5%) + Choline chloride (2%) + Caffeine (1%) + Thiamine hydrochloride (1%) + Nicotinamida (0,5%)+ Pyridoxine hydrochloride (0.04%), administered through intramuscular (IM) route, at doses of 0.2, 0.6 and 1.0 mL/kg of BW, through the study of leukocytes responses in rats submitted to acute intoxication with CCl4. 147 females were randomized into 21 groups, performing five different treatments, which were evaluated seven animals in four periods: two, four, six and eight days after CCl4-induced intoxication. In this study, it was observed absolute eosinophilia and monocytosis in animals untreated and treated with the lowest dose of 0.2 mL. These responses were significantly better in animals treated with 0.6 and 1.0 mL/ kg BW. The untreated animals showed thrombocytopenia, when compared to treated animals. Absolute neutropenia and lymphocytosis was observed in all rats intoxicated with CCl4, there is no difference among treatments. The analysis of white blood cells demonstrated that the hepatoprotective treatments favored the leukocyte response, by act beneficially on the population of these cells, supporting the hypothesis that these events may reduce the deleterious effects in liver tissue after intoxication by CCl4.

Leucometric analysis of 1-day-old chicks inoculated with Salmonella Typhimurium or Lactobacilli

Salmonella infection is responsible for major economic losses in poultry industry. Consequently, the development of new methods for fighting such disease is desirable, such as the use of acid-lactic bacteria. However, reference values of chicks in such conditions are dissimilar to those of other species. Leucometry reference values for chicks have not been reported. The aim of this article was to evaluate and determine the leucometric values of chicks inoculated with Salmonella Typhimurium or treated with Lactobacilli probiotics. In this study, 144 1-day-old birds were divided in three groups of 48 animals each (non-treated group, Salmonella Typhimurium (ST)-inoculated group, and Lactobacilli inoculated group). A total of four blood collections were made with the first one performed 3 h after inoculation with ST or treatment with Lactobacilli. Subsequent samples were obtained every 48 h for 7 days. Leucometric evaluation was performed immediately after each collection. All birds presented an initial decrease pattern in general leukocyte values, and the chicks inoculated with ST revealed lymphomonoheteropaenic leukopaenia, eosinophilia and basophilia in conjunction with convalescence after 96 h of inoculation. The animals inoculated with Lactobacilli revealed leucocytosis with monocytosis, lymphocytosis and marked eosinopaenia. We conclude that there is no efficient bone marrow response in 1-day-old chicks challenged with Salmonella Typhimurium; additionally, an immunostimulatory effect in 1-day-old chicks treated with Lactobacilli-modulated probiotics could be stated. © 2011 Springer-Verlag London Limited.

Resposta imune na medula óssea e perfil hematológico de cães com Leishmaniose visceral

Pós-graduação em Medicina Veterinária - FCAV

Inflamação por Aeromonas hydrophila inativada e tioglicolato em Piaractus mesopotamicus suplemnetados com vitamina C, e ou sua associação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo clínico e etiológico da diarréia em potros

Pós-graduação em Medicina Veterinária - FMVZ

Alterações hematológicas em cães e gatos sob estresse

The leukocyte count interpretation on the blood helps on understanding about the possible dysfunction showed by the animal. In general, an abnormal leukogram allows the identification of pathological process. A lot of events lead to an increase in the number of neutrophils, among then, inflammatory process, infection and stress. Dependent on the stress mediator that the animal is submited, the leukocyte alteration will be different. Is important to know how the stress acts on the animal organism, changing the hematological parameters, in order to avoid mistakes on diseases‟ diagnosis. It‟s known that after a stress situation, it‟s expected that stress leukogram appears on the hemogram of the animal. However there are different kinds of stress with different responses. It‟s believed that when the animal is under an acute stress situation, a clinical picture of physiologic leukocytosis occurs which is mediated by the epinephrine. This is characterized by neutrophilia, lymphocytosis, monocytosis and eosinofilia. The physiologic leukocytosis is a transient alteration in the leukogram that occurs within minutes of the stimulus and due to fleeting effect of catecolamines it resolves within 20 to 30 minutes. However, if the animal is under chronicle stress, as solitude, it „s expected to find the stress leukogram on the leukogram, that can be noted especially in dogs. The stress leukogram is characterized by leukocytosis, neutrophilia, lymphopenia, monocytosis and eosinopenia. This kind of stress is induced by the glucocorticoids. It´s important to understand that stress leukogram takes time to occur. The variation on time depends on the animal species, although, in general, the glucocorticoides have a peak effects among 4 to 8 hours, which can last from 24 hours to 2 or 3 days

Prostaglandina E2 em cães portadores de linfoma multicêntrico submetidos ao protocolo quimioterápico de Madison-Wisconsin associado ou não a um inibidor de COX-2

Pós-graduação em Medicina Veterinária - FCAV

Spleenic Lymphoma and Hemoperitoneum in Jersey Bull: Clinical and Pathological Aspects

Lymphoma is the most prevalent neoplasia in dairy cattle. The etiology can be viral in animals affected by bovine leukemia virus (BLV) or be classified as primary. Lymphoma can affect several organs and according to the system involved, the clinical signs could manifest themselves in different ways. These tumors can be classified through macroscopic characteristics, histology and immunostaining. This classification can be used to predict prognosis and response to therapy. The aim of this case report was to immunostain and classify the tumor, for which anti-CD4, anti-CD8, anti-CD79 and anti-CD3 markers were used in addition to histopathological findings, in order to classify the tumor. The tumor was positive only for anti-CD3 marker, indicating that it is a tumor of young cells and, in association with histopathology and hematological data, it can be concluded that spleen neoplasia is lymphocytic lymphoma originated from a lymphocytic leukemia.

Estudo do efeito modulador do macrolídeo tilosina na reação inflamatória aguda de tilápias do Nilo (Oreochromis niloticus), vacinadas e desafiadas com Streptococcus agalactiae

Pós-graduação em Medicina Veterinária - FCAV