Comparison between ultrasonography and X-ray as evaluation methods of central venous catheter positioning and their complications in pediatrics.

PURPOSE: This study evaluates the capacity of ultrasonography as a diagnostic method to confirm the proper positioning of central venous catheter (CVC) when compared to the current gold standard, chest radiography (CR). METHODS: A prospective study was performed including children from 0 to 14 incomplete years, who underwent CVC placement between March and May 2018 at a teaching hospital in Brazil. A four-chamber view of the heart was performed with ultrasound during a rapid injection of saline solution to identify hyperechoic images and confirm the central position of the catheter. After that, a CR was performed. The diagnostic quality of ultrasound was evaluated based on accuracy, sensitivity, specificity, positive and negative predictive values. RESULTS: A total of 21 patients were analyzed. The mean age was 3.95 ± 4.01 years. The preferred puncture site was the right internal jugular vein (71.4%). Ultrasound accuracy to detect CVC positioning was 81%. Sensitivity, specificity and positive and negative predictive values were 33%, 100%, 100% and 79%, respectively. CONCLUSION: Ultrasound is a reliable method for detection of CVC positioning. Even so, with the four-chamber cardiac view, this method is unable to identify catheters inside heart chambers, therefore, needing to confirm the positioning with CR.

Compatibility study of paracetamol, chlorpheniramine maleate and phenylephrine hydrochloride in physical mixtures.

Paracetamol (PAR), phenylephrine hydrochloride (PHE) and chlorpheniramine maleate (CPM) are commonly used in clinical practice as antipyretic and analgesic drugs to ameliorate pain and fever in cold and flu conditions. The present work describes the use of thermal analysis for the characterization of the physicochemical compatibility between drugs and excipients during the development of solid dosage forms. Thermogravimetric analysis (TGA) and Differential Scanning Calorimetry (DSC) were used to study the thermal stability of the drug and of the physical mixture (drug/excipients) in solid binary mixtures (1:1). DSC thermograms demonstrated reproducible melting event of the prepared physical mixture. Starch, mannitol, lactose and magnesium stearate influence thermal parameters. Information recorded from the derivative thermogravimetric (DTG) and TGA curves demonstrated the decomposition of drugs in well-defined thermal events, translating the suitability of these techniques for the characterization of the drug/excipients interactions.

Solid dosage forms for active antiretroviral therapy (HAART): dissolution profile study of nevirapine by experimental factorial design.

Nevirapine is the first antiretroviral member of non-nucleoside reverse transcriptase inhibitor used in active antiretroviral therapy (HAART). The aim of this work was the evaluation of the dissolution profile of nevirapine tablets by means of the Disk Intrinsic Dissolution Rate (DIDR) using a 2(3) factorial design. This study used a triplicate in central point and was based on three independent variables: the rotational speed of the apparatus, the compression force of nevirapine disk, and the distance of the tank dissolution. The dependent variable was set as intrinsic dissolution speed (IDS). IDS was strongly dependent on the rotational speed, compression force, and distance of the apparatus, analyzed by Student's t test with 95% confidence, and confirmed by ANOVA. The rotational speed of nevirapine disks was the main factor contributing to the IDS, whereas the compression force and the distance of disks on the dissolution apparatus revealed no effects.

Hiatus hernia with gastric volvulus and duodenum component: a case report.

Gastric volvulus is a rare condition defined as an abnormal stomach rotation around its axis, which usually presents in children under a year or in adults in their fifth decade. Cases over 70-year-old are rare and only 30% of cases of this disease present with mesenteric-axial rotation of the stomach. In this article, we report a rare case of mesenteroaxial gastric volvulus associated with hiatal hernia, in an 88-year-old woman, who presented to the Emergency Department of our institution with bowel obstruction symptoms. The diagnosis could be difficult due to the rarity of the pathology, the patient's age outside the expected incidence age range and the less common mesenteroaxial presentation. This report highlights the importance of the differential diagnosis of gastric volvulus as a cause of intestinal obstruction.

Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions.

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.

Inflammation and structural changes of splenic lymphoid tissue in visceral leishmaniasis: a study on naturally infected dogs.

The aim of this study was to identify splenic immuno-inflammatory patterns associated with natural infection by Leishmania chagasi. Spleen samples were obtained from 72 stray dogs from an endemic area of visceral leishmaniasis. The animals were grouped into four categories as follows: (i) potentially resistant to visceral leishmaniasis, with a positive leishmanin skin test result, and negative splenic culture for Leishmania parasites (ii) potentially susceptible to visceral leishmaniasis, with a negative leishmanin skin test and positive splenic culture for Leishmania (iii) infected with undefined susceptibility status, with a positive leishmanin skin test and positive splenic culture for Leishmania, and (iv) noninfected, with a negative leishmanin skin test, negative splenic culture for Leishmania, and negative serology for anti-Leishmania antibodies. Histopathological analyses showed that there was a higher frequency of perisplenitis (18/25, P < 0.0001), granuloma (7/25, P = 0.0102), structural disorganization (14/25, P < 0.0001), and atrophy of the lymphoid follicles (20/25, P = 0.0036) and of the marginal zone (15/25, P = 0.0025) in the potentially susceptible group than in the other groups. The data presented here show changes in the white pulp of the spleen that are associated with naturally acquired visceral leishmaniasis.

Associations among immunological, parasitological and clinical parameters in canine visceral leishmaniasis: Emaciation, spleen parasitism, specific antibodies and leishmanin skin test reaction.

Associations among parameters commonly used as markers of infection by Leishmania sp., or of susceptibility to visceral leishmaniasis, were investigated in 325 stray dogs from an area where this disease is endemic. Evidence of infection (presence of Leishmania in splenic cultures, positive leishmanin skin test (LST) or detection of anti-Leishmania antibody activity in the serum) was found in 57% of the animals. Both evidence of weight loss (chi(2)-test, P=0.0005) and presence of specific antibody activity in the serum (chi(2)-test, P<0.0001) were directly associated with positive splenic culture. The frequencies of animals with positive splenic culture were directly correlated with the intensities of antibody activity in the serum as measured by ELISA (relative risk of 3.4 for animals with moderate antibody levels and relative risk of 8.43 for animals with high-antibody levels). A negative association was observed between positive leishmanin skin test results and emaciation (chi(2), P=0.0089). Furthermore, animals with positive splenic cultures and negative leishmanin skin test results had higher levels of total serum IgG (Kruskal-Wallis test, P=0.001) and IgG2 (Kruskal-Wallis test, P=0.05) than animals with negative splenic cultures, and were more emaciated than animals with negative LST results and positive splenic cultures. The data presented herein suggest that associating these common parameters may improve their performance in predicting susceptibility to canine visceral leishmaniasis.

Anti-inflammatory activity of Vismia guianensis (Aubl.) Pers. extracts and antifungal activity against Sporothrix schenckii.

ETHNOPHARMACOLOGICAL RELEVANCE: Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. MATERIAL AND METHODS: The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). RESULTS: Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. CONCLUSION: The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis.

Desordens hematológicas em onças-pardas (Puma concolor; Linnaeus, 1771) infectadas por Citauxzoon felis / [Hematological disorders in Brown jaguars (Puma concolor; Linnaeus 1771) infected by Citauxzoon felis]

Este estudo objetivou descrever o aspecto hematológico de seis onças-pardas (Puma concolor) infectadas pelo Cytauxzoon felis. Os seis casos de infecção foram identificados durante o manejo sanitário de 11 animais de um centro de reabilitação de animais silvestres. Estruturas compatíveis com piroplasmídeos foram observadas durante a avaliação do esfregaço sanguíneo e confirmadas como Cytauxzoon felis pela técnica de PCR. A análise estatística demonstrou diferença significativa (P<0,05) no número absoluto dos linfócitos entre os grupos dos animais infectados e não infectados. Assim, expressivas alterações hematológicas e bioquímicas entre os grupos investigados alertam para a dificuldade de identificação de onças-pardas infectadas por C. felis, apoiada apenas em exames de rotina, bem como para o risco, sobretudo, da reintrodução desses animais na natureza.(AU)

This Cytauxzoon felis by the PCR technique. Statistical analysis showed a significant difference is study aimed to describe the hematological appearance of six puma (puma concolor) infected with cytauxzoon felis. The six cases of infection were identified during the sanitary management of 11 animals from a wild animal rehabilitation center. Piroplasmid compatible structures were observed during the blood smear evaluation and confirmed as (P<0.05) in the absolute number of lymphocytes between the groups of infected and uninfected animals. Thus expressive hematological and biochemical alterations between the groups investigated alert to the difficulty of identifying infected brown jaguars by C. felis, supported only by routine examinations, and the risk especially when aiming at the reintroduction of these animals in the wild.(AU)

Anti-CD4 treatment of NZB mice prevents the development of erythrocyte autoantibodies but hastens the appearance of anaemia.

New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia as the result of production of autoantibodies to erythrocytes. We have recently shown that antibodies to CD4 prevent the development of erythrocyte autoantibodies in young mice (Coombs' negative). In spite of this inhibition of erythrocyte autoantibody production, the anti-CD4-treated mice show a precocious and severe anaemia. Balb/c mice treated with the same protocol do not develop anaemia. Our results suggest that erythropoiesis in NZB mice is particularly sensitive to depletion of CD4+ T cells.

Cohort study on canine emigration and Leishmania infection in an endemic area for American visceral leishmaniasis. Implications for the disease control.

American visceral leishmaniasis is a main public health matter in Brazil. Since dogs have been incriminated as the main urban reservoir of AVL agent Leishmania chagasi, a cohort study aimed at understanding the dynamics of the canine infection was carried out in Jequié--an endemic community in the Northeast of Brazil. The inhabited urban and periurban areas of Jequié were divided into 140 clusters of 0.25 km2. All 1681 dogs domiciled in 34 randomly selected clusters were screened for Leishmania antibodies in an enzyme-linked immunosorbent assay. After the seropositive dogs were painlessly eliminated, a cohort of 1286 seronegative dogs was followed up for 18 months, yielding a total of 1739.7 dog-years. The overall incidence of Leishmania infection, as assessed by the detection of Leishmania antibodies in blood samples collected every six months, was 6.55 cases/100 dog-years (95% confidence interval; CI 6.04-7.26). Two subsets of clusters, with 0.70 and 1.35 relative risks of infection, were identified. The annual emigration rate was 2.26 cases/100 dog-years (95% CI 1.86-2.66). The implications of these findings for the control of American visceral leishmaniasis are discussed.

Psychopharmacological effects of the essential oil fraction and of the hydrolate obtained from the seeds of Licaria puchury-major.

An essential oil fraction obtained from powdered seeds of Licaria puchury-major contained 51.3% of safrol, 3.3% of eugenol and 2.9% of methyleugenol, among other substances. Fifty to 800 mg/kg of this fraction reduced motor activity and anesthetized mice; it also protected the animals against transcorneal electroshock. A hydrolate obtained from the powder, contained 0.2 mg of essential oil fraction per ml: 0.1 and 0.2 ml/10 g of this hydrolate reduced motor activity and potentiated barbiturate sleeping time of mice; 2.5-10 ml/kg given to rats produced a drop in body temperature. The hydrolate, however, did not anesthetize and did not protect mice against convulsions induced by electrical shock. These amounts of the hydrolate corresponded to dosing the animals with 2-4 mg/kg of the essential oil (or 1-2 mg/kg of safrol), doses which were inactive per se. This suggested that the pharmacological activity of the hydrolate was not due to its essential oil content. Corroborating this possibility the hydrosoluble portion of the hydrolate mimicked all of its effects: reduced motor activity, potentiated barbiturate sleeping time of mice and decreased body temperature of rats. The hydrosoluble material, as the hydrolate, was also incapable of anesthetizing and protecting mice against electroshock induced convulsions.

Compatibility studies of nevirapine in physical mixtures with excipients for oral HAART.

Nevirapine is a hydrophobic non-nucleoside reverse transcriptase inhibitor, used in first line regimens of highly active antiretroviral therapy (HAART). The drug has more than one crystalline form, which may have implications for its behaviour during production and also for its in vivo performance. This study was aimed at exploring the suitability of thermoanalytical methods for the solid-state characterization of commercial crystalline forms of nevirapine. The drug powder was characterized by ultraviolet spectrophotometry, stereoscopy, scanning electron microscopy, wide-angle X-ray diffraction, measurements of density, flowability, solubility and intrinsic dissolution rate (IDR), differential scanning calorimetry, thermogravimetric analysis, and photostability measurements. The results showed that nevirapine has high stability and is not susceptible to degradation under light exposure. The drug showed compatibility with the excipients tested (lactose, microcrystalline cellulose, polyvinylpyrrolidone and polyvinyl acetate copolymer (PVP/PVA), and hydroxypropylmethylcellulose (HPMC)). Nevirapine has low solubility, an acid medium being the most appropriate medium for assessing the release of the drug from dosage forms. However, the data obtained from IDR testing indicate that dissolution is the critical factor for the bioavailability of this drug.

Técnicas de citologia aspirativa, biópsia e citobloco de medula óssea para identificação e determinação de intensidade parasitária na leishmaniose visceral canina / Techniques of aspiration cytology, biopsy and cell block of the bone marrow for the identification and determination of parasite intensity in Canine Visceral Leishmaniasis

O objetivo com este estudo foi comparar as técnicas de citologia aspirativa, biópsia e citobloco para identificação e quantificação parasitológica de Leishmania (Leishmania) infantum chagasi em medula óssea de cães. Amostras de tecido medular de 26 animais, em diferentes estágios clínico-laboratoriais da doença, foram estudadas obedecendo-se os mesmos critérios de investigação nas técnicas de citologia aspirativa, biópsia e citobloco. O menor número de campos para a confirmação parasitológica foi constatado no esfregaço direto obtido por citologia aspirativa. O estágio clínico-laboratorial não influenciou no número de campos necessários para a primeira visualização do agente em nenhuma das técnicas (p>0,05), e menor intensidade parasitária foi observada nas lâminas de citobloco. As técnicas de citologia aspirativa e biópsia concordaram na estimativa do coeficiente de infectividade no tecido estudado (p<0,05). Apesar de a técnica de citobloco permitir a concentração de células e o melhor reaproveitamento de amostras, não demonstrou ser um método adequado para rápida identificação e quantificação parasitológica na leishmaniose visceral canina. Considerando-se suas vantagens, a citologia aspirativa foi o melhor método para detecção microscópica do parasito e determinação do nível de intensidade parasitária no tecido estudado.(AU)

The aim of the present study was to compare the aspiration cytology, biopsy and cell block techniques for identification and parasitological quantification of Leishmania (Leishmania) infantum chagasi in dog bone marrow. Bone marrow tissue samples from 26 animals, in different clinical-laboratory stages of the disease, were studied according to the same criteria of investigation in the aspiration cytology, biopsy and cell block techniques. The lowest number of fields for the parasitological confirmation was found in the direct smear obtained by aspiration cytology. The clinical-laboratory stage did not influence the number of fields required for the first visualization of the agent in any of the techniques (p> 0.05) and less parasitic intensity was observed in the cell block slides. The aspiration cytology and biopsy techniques agreed on the estimation of infectivity coefficient in the tissue studied (p< 0.05). Although the cell block technique allows the concentration of cells and better reutilization of samples, it has not been shown to be an adequate method for rapid identification and parasitological quantification in canine visceral leishmaniasis. Considering its advantages, aspiration cytology was the best method for microscopic detection of the parasite and determination of the level of parasite intensity in the tissue studied.(AU)

Indicadores biológicos séricos em veado-campeiro ( Ozotoceros bezoarticus bezoarticus, Linnaeus 1758) de vida livre do Pantanal Sul-Mato-Grossense / Serum biological indicators in free-living pampas deer (Ozotoceros bezoarticus bezoarticus, Linnaeus 1758) of the Pantanal Sul-Mato-Grossense

O objetivo com este estudo foi estabelecer os intervalos de referência de diferentes analitos séricos em Ozotoceros bezoarticus bezoarticus de vida livre. Foram coletadas amostras de sangue de 54 fêmeas e 14 machos adultos, capturados no Pantanal de Mato Grosso do Sul. A determinação das concentrações de cálcio total, albumina, colesterol total, creatinina, glicose, fósforo, proteína total, triglicerídeos e ureia séricas e a atividade das enzimas alanina aminotransferase, aspartato aminotransferase, creatina quinase fração MB e fosfatase alcalina foi realizada em equipamento automático. Valores de globulinas, cálcio total e proporções (razões) entre analitos foram realizados por meio de cálculo matemático. Esta é a primeira descrição do intervalo de referência de parâmetros bioquímicos séricos em veado-campeiro de vida livre do Pantanal de Mato Grosso do Sul. O tamanho da amostra e a distribuição dos dados indicam que os valores médios obtidos são representativos e podem ser usados para a monitorização da saúde, do estado nutricional e do diagnóstico de enfermidades nesse estrato populacional.(AU)

The objective of the present study is to establish the reference intervals of different serum analytes in free - living Ozotoceros bezoarticus bezoarticus. Blood samples were drawn from the 54 females and 14 males, adults, captured in the Pantanal of Mato Grosso do Sul. A determination of total calcium, albumin, total cholesterol, creatinine, glucose, phosphorus, total protein, triglycerides, and serum urea concentrations and an activity of the enzymes alanine aminotransferase, aspartate aminotransferase, creatine kinase MB fraction and alkaline phosphatase were performed in automated equipment. Values of globulins, total calcium and proportions among analytes were performed by means of mathematical calculations. This is a first description of the reference parameters for serum biochemistry of free - living pampas deer in the Pantanal of Mato Grosso do Sul. Sample size and distribution of data indicate that the mean values obtained are representative and can be used for a health monitoring, nutritional status, and diagnosis of diseases in this population stratum.(AU)

Ceratoconjuntivite nodular em um caso de leishmaniose visceral canina: relato de caso / Nodular keratoconjunctivitis in a case of canine visceral leishmaniasis: case report

Relata-se um caso de leishmaniose visceral canina com ceratoconjuntivite nodular como queixa exclusiva do proprietário. O diagnóstico se deu pela observação de formas amastigotas de Leishmania sp. no exame parasitológico direto de citologia aspirativa conjuntival. Lesões oculares raramente são queixas principais únicas de cães com leishmaniose, como o caso em questão, o que demonstra a variabilidade de apresentação clínica da doença e a importância da realização de testes laboratoriais diagnósticos para leishmaniose como triagem para pacientes de áreas endêmicas.(AU)

We describe a case of canine visceral leishmaniasis with nodular keratoconjunctivits as the owner's only complaint. Diagnosis was made by the observation of Leishmania sp. amastigotes in parasitological examination from conjunctival aspirative cytology. Eye lesions are rarely the only complaint of dogs suspected of leishmaniasis, as the case reported, demonstrating the variability of clinical presentation of the disease and the importance of performing screening diagnostic laboratorial tests for leishmaniasis in endemic areas.(AU)

Partial hepatectomy in a calf with an omphalocele: case report / Hepatectomia parcial em bezerra portadora de onfalocele: relato de caso

An omphalocele is a defect in the closure of the abdominal wall during the embryonic stage, preventing the return of some abdominal organs to the cavity. In stillborn animals, the involvement of the liver in the omphalocele has been reported. The aim of the present study is to report the success of a partial liver resection in a female bovine at two days of age which presented an omphalocele at birth. Surgical intervention was indicated to reduce and suture the abdominal wall. During the surgical procedure, the presence of hard, reddish tissue was noted inside the sac covered by the amniotic membrane, with characteristics consistent with hepatic parenchyma. Due to the impossibility of reducing the contents added to the suggestion of tissue infection, we elected to perform a partial resection. The histopathological examination confirmed that the resected tissue was of the hepatic parenchyma. Antibiotic and systemic anti-inflammatory therapies were performed post-surgery. Fifteen days after surgery, infection was detected at the surgical site in addition to abdominal wound dehiscence; surgical reintervention was performed. On physical examination, carried out 4 months after the second operation, the heifer presented normal development for the species. In conclusion, omphalocele may contain liver. Ectopic liver is an extremely rare condition. Surgical treatment in the presented case focused on umbilicus with exploration of the abdominal cavity appeared to be sufficient.(AU)

A onfalocele é um defeito no fechamento da parede abdominal durante a fase embrionária, não permitindo o retorno de alguns órgãos abdominais à cavidade. O envolvimento do fígado em onfalocele tem sido relatado, porém em animais natimortos. Com o presente estudo, objetiva-se relatar uma ressecção parcial do fígado realizada com sucesso em uma fêmea bovina com dois dias de idade apresentando onfalocele ao nascimento. Foi indicada a intervenção cirúrgica para a redução e rafia da parede abdominal. Durante o procedimento cirúrgico, notou-se, no interior do saco recoberto pela membrana amniótica, a presença de tecido firme, de coloração avermelhada, com características compatíveis com parênquima hepático. Devido à impossibilidade de redução do conteúdo e sugestão de infecção do tecido encontrado, optou-se pela ressecção parcial dele. O exame histopatológico confirmou tratar-se de parênquima hepático o tecido resseccionado. No pós-cirúrgico, realizaram-se terapias antibiótica e antiinflamatória sistêmicas. Após 15 dias do procedimento cirúrgico, foi detectada infecção do sítio operatório e deiscência da sutura abdominal, sendo realizada reintervenção cirúrgica. No exame físico, realizado no animal após quatro meses da segunda intervenção cirúrgica, constatou-se desenvolvimento normal para a espécie. Conclui-se que o fígado pode ser conteúdo da onfalolocele, sendo uma condição extremamente rara. O tratamento cirúrgico no caso apresentado, com exploração da cicatriz umbilical e da cavidade abdominal, foi suficiente.(AU)

Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism.

The brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that BDNF levels in autistic children (n = 146) were significantly higher (t = 6.82; P < 0.0001) than in control children (n = 50) and were positively correlated with platelet serotonin distribution (r = 0.22; P = 0.004). Heritability of BDNF was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six single nucleotide polymorphisms (SNPs) [0.004 (Z((1df)) = 2.85) < P < 0.039 (Z((1df)) = 2.06)] and multiple haplotypes [5 × 10(-4) (χ((3df)) = 17.77) < P < 0.042 (χ((9df)) = 17.450)] in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however, reflect a trend toward association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase in BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/tyrosine kinase B (TrkB) signaling contribute to an increased vulnerability to autism.

The subclinical form of experimental visceral leishmaniasis in dogs.

Pathological aspects of a subclinical form of experimental canine leishmaniasis is reported here for the first time. Fifteen mongrel dogs were used in the present study. Eight dogs were infected and seven were used as control. Four of the control dogs were inoculated with spleen cells from non-infected hamsters. The eight mongrel dogs inoculated intravenously with amastigotes forms of Leishmania chagasi evolved for periods as long as 25 months without any clinical characteristic sign of classical Visceral Leishmaniasis (VL). Most of the laboratory test results were compatible to those of the seven control animals but culture of bone marrow aspirated material and serologic testing (IIF) demonstrated or provided evidence that the animals were infected. The most important and predominant histopathological lesion in infected animals were epithelioid granulomas presented in the liver, spleen, adrenal gland and lung of some animals. Channels containing erythrocytes in some granulomas of the liver suggest that these granulomas are formed inside sinusoidal capillaries. Despite the animals were proved to be infected and presented characteristic histologic lesions, they did not present external signs of disease. The granulomatous aspect of the lesions indicates a good immunologic reactivity and suggest that a host-parasite equilibrium does exist in the dog experimental model.

Role of the central nervous system in the adult respiratory distress syndrome.

The CNS might play an important pathophysiologic role in the induction of the adult respiratory distress syndrome (ARDS). Post-traumatic development of cerebral microthromboses seems to be a major feature. To test this hypothesis, we subjected Wistar rats with postburn ARDS to the following microneurosurgical procedures in an attempt to morphologically detect modifications in the evolving pattern: a) anterior (AH) or posterior (PH) hypothalamus nuclei stereotaxic electrolytic lesion; b) intracerebroventricular microinjections of phenoxybenzamine (PB)-50, micrograms propranolol-0.5 micrograms, cocaine-5 micrograms, epinephrine-0.5 micrograms, carbachol(CA)-5 micrograms, pirilamine-20 micrograms, cimetidine-30 micrograms, lidocaine-20 micrograms, atropine (AT)-40 micrograms; c) intra-AH microinjections of CA-10 micrograms, AT-20 micrograms; and d) intra-PH microinjections of PB-10 micrograms, norepinephrine-0.05 microgram. The results showed that the alpha-adrenergic components of PH induce a potentiation in ARDS whereas the cholinergic components of AH seem to attenuate this syndrome. This work suggests that a damaged CNS may suffer cybernetic derangements as to induce it to generate inappropriate adaptative responses that can result in the development of ARDS.