Imunofenótipos de linfócitos T no sangue e no liquor de cães com leishmaniose visceral: correlação com as lesões encefálicas

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

A doença de Parkinson no doente idoso

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Organização nuclear do sistema serotonérgico no encéfalo de morcegos Artibeus planirostris

Serotonin or 5-hydroxytryptamine (5-HT) is a substance found in many tissues of the body, including the nervous system acting as a neurotransmitter. Within the neuro-axis, the location of the majority of the 5-HT neurons is superimposed with raphe nuclei of the brain stem, in the median line or its vicinity, so that neuronal 5-HT can be considered a marker of the raphe nuclei. Serotonergic neurons are projected to almost all areas of the brain. Studies show the participation of serotonin in regulating the temperature, feeding behavior, sexual behavior, biological rhythms, sleep, locomotor function, learning, among others. The anatomy of these groups has been revised in many species, including mouse, rabbit, cat and primates, but never before in a bat species from South America. This study aimed to characterize the serotonergic clusters in the brain of the bat Artibeus planirostris through immunohistochemistry for serotonin. Seven adult bat males of Artibeus planirostris species (Microchiroptera, Mammalia) were used in this study. The animals were anesthetized, transcardially perfused and their brains were removed. Coronal sections of the frozen brain of bats were obtained in sliding microtome and subjected to immunohistochemistry for 5-HT. Delimit the caudal linear (CLi), dorsal (DR), median (MnR), paramedian (PMnR), pontine (PNR), magnus (MgR), pallidus (RPA) and obscurus (ROb) raphe nucleus, in addition to the groups B9 and rostral and caudal ventrolateral (RVL/CVL). The serotonergic groups of this kind of cheiroptera present morphology and cytoarchitecture relatively similar to that described in rodents and primates, confirming the phylogenetic stability of these cell clusters.

Síndrome de Sjögren Primário

A Síndrome de Sjögren (SS) é uma das três patologias autoimunes mais frequentes na população mundial, ainda assim frequentemente infradiagnosticada. Esta síndrome é uma doença autoimune crónica que afeta as glândulas exócrinas, particularmente as glândulas salivares e lacrimais. A SS primária (SSp) afeta especificamente as glândulas exócrinas, enquanto que a SS secundária (SSs) aparece associada a outras patologias autoimunes sistémicas. A SS é caracterizada, histopatologicamente, por um infiltrado inflamatório linfocitário que interfere com a função glandular normal. Afeta 0,5% da população mundial, sendo claramente mais predominante em mulheres (9:1 versus homens), principalmente por volta dos 50 anos (após a menopausa), ainda que também possa aparecer depois da menarca (entre os 20 e os 30 anos). Considera se que a etiologia da SS é multifatorial. Fatores genéticos, ambientais, hormonais e virais estão implicados na sua etiopatogénese. É muito importante o papel dos Médicos Dentistas no diagnóstico da SSp, uma vez que na maior parte dos casos são eles quem detetam os primeiros sintomas, mais propriamente a boca seca. Diversos testes auxiliares são utilizados para o diagnóstico desta doença, tais como: o teste de Schimer, o teste de Rosa Bengala, a Sialometria, a Sialografia, a Biópsia das glândulas salivares, entre outros. A SSp, regra geral, tem um curso não doloroso, sendo a boca seca e a secura ocular as suas duas características clínicas mais salientes. A maior parte das manifestações orais que se apresentam nestes pacientes são resultado de hipofunção das glândulas salivares (da boca seca), tais como: a cárie dentária, a doença periodontal, as infeções fúngicas, entre outras. Esta doença também se pode associar a problemas a nível sistémico, que podem ser subdivididos em não viscerais (pele, artralgia, mialgia) e viscerais (pulmão, coração, rim, sistema gastrointestinal, sistema endócrino e sistema nervoso central e periférico). O tratamento é empírico, sintomático e direcionado a tratar as complicações da doença mais inicial, que consiste em limitar os danos da xerostomia e da queratoconjuntivite. A prevenção dos sintomas a nível oral e ocular é fundamental em pacientes com SSp, para assim terem maior qualidade de vida.

Inibição de linhagens do complexo Fusarium Graminearum por compostos naturais e sintéticos

Quando produtos alimentícios e especiarias são contaminados por micotoxinas é quase impossível detoxificar utilizando processos usuais da indústria de alimentos ou durante o preparo doméstico. Por isso, controlar o crescimento do fungo e a produção de toxinas é uma demanda para garantir a segurança alimentar. Os agrotóxicos são rotineiramente utilizados como estratégia para proteger as plantas de doenças provocadas pela contaminação fúngica. No entanto, eles estão associados a efeitos adversos ao sistema nervoso central e periférico, têm ação imunodepressora e são cancerígenos. Em virtude disso, o objetivo deste trabalho foi estudar a inibição do desenvolvimento, do potencial toxigênico e da expressão gênica de linhagens do Complexo Fusarium graminearum por compostos naturais comparativamente aos fungicidas azoxistrobina e trifloxistrobina. Do farelo de arroz, foram extraídos o γ-orizanol e os ácidos fenólicos (EFF). Das sementes de nim foram extraídos os ácidos fenólicos (EFN), totalizando três extratos naturais. A capacidade antioxidante dos extratos foi verificada pelo consumo do radical livre DPPH• , capacidade de captura do radical ABTS●+, redução do ferro e inibição da oxidação enzimática. Os mecanismos de inibição de três linhagens de F. graminearum foram avaliados através da determinação de compostos estruturais (glicosamina e ergosterol) e da atividade de enzimas do metabolismo primário (α- amilase e proteases). Foram determinadas as micotoxinas de Fusarium: deoxinivalenol (DON), 15 acetildeoxinivalenol (15AcDON), 3 acetildeoxinivalenol (3AcDON), nivalenol (NIV) e zearalenona (ZEA). A expressão dos genes Tri1 e Tri5 foi determinada a fim de verificar se ocorria modificação da expressão gênica nas linhagens do Complexo F. graminearum ocasionada pela presença dos antifúngicos. O EFF apresenta atividade antioxidante destacada em relação aos demais extratos naturais para inibir a iniciação do processo, a propagação do radical livre e a catálise enzimática. A presença dos compostos naturais mostrou efeito promissor como antifúngico para as linhagens, sendo que a concentração necessária para inibir 50% do crescimento radial das colônias (MIC50) foi 0,9 g/kg para γ-orizanol; 0,032 g/kg para EFF e 0,037 g/kg para EFN, portanto, os extratos fenólicos são mais eficazes para inibição de F. graminearum do que o γ-orizanol. Os extratos naturais afetaram as atividades das enzimas α-amilase e proteases. Também ocorreu a redução da formação de componentes estruturais (glicosamina e ergosterol). Os extratos naturais se destacaram pela capacidade de inibição de micotoxinas produzidas pela biomassa fúngica, com destaque para o EFN sobre a produção de DON, 15AcDON, 3AcDON e ZEA. Sendo assim, é possível dizer que há uma relação direta entre a atividade antioxidante na inibição do fungo e na manifestação do seu potencial toxigênico. Além disso, esse estudo contribuiu com a elucidação do mecanismo de ação dos antifúngicos naturais estudados. Ocorre modificação na expressão gênica quando a linhagem é submetida ao tratamento com antifúngico, havendo uma relação direta entre a expressão do gene Tri5 e a produção de DON.

Scaffold piezoelettrici in PVDF/PCL per la rigenerazione del tessuto nervoso periferico

Le lesioni del sistema nervoso periferico, causate da eventi traumatici o da patologie degenerative, costituiscono un danno che può portare alla perdita di specifiche funzionalità motorie o sensoriali. In questi casi, la terapia chirurgica è necessaria per riparare la perdita di continuità assonale. Il gold standard operatorio attuale è costituito dal trapianto nella sede lesionata di un nervo da donatore o dallo stesso soggetto affetto dal danno. Recentemente, un approccio basato su tecniche di ingegneria dei tessuti propone l’impianto di biomateriali modellati come condotti che favoriscano la rigenerazione assonale. Ne è un esempio chiaro un recente lavoro di ricerca, nel quale Cheng et al. propongono una strategia basata sull’impiego di scaffold piezoelettrici prodotti attraverso una tecnica di "casting annealing displacement " che utilizza Polivinilidenfluoruro (PVDF) e Policaprolattone (PCL). Confrontando in vitro scaffold in PCL, in PVDF e PCL/PVDF, in particolare analizzandone le proprietà piezoelettriche e quelle meccaniche, si rilevano i vantaggi della copolimerizzazione. Questi risultati di interesse vengono inoltre confermati dai risultati funzionali ottenuti con l’impianto in vivo in topi con una lesione di 15 mm al nervo sciatico.

Neural Mechanisms And Delayed Gastric Emptying Of Liquid Induced Through Acute Myocardial Infarction In Rats.

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos.

Edema pulmonar neurogênico: relato de dois casos

Neurogenic pulmonary edema is a rare and serious complication in patients with head injury. It also may develop after a variety of cerebral insults such as subarachnoid hemorrhage, brain tumors and after epileptic seizures. Thirty six patients with severe head injury and four patients with cerebrovascular insults treated in Intensive Care Unit of HC-UNICAMP from January to September 1995 were evaluated. In this period there were two patients with neurogenic pulmonary edema, one with head injury and other with intracerebral hemorrhage. Diagnosis was made by rapid onset of pulmonary edema, severe hypoxemia, decrease of pulmonary complacence and diffuse pulmonary infiltrations, without previous history of tracheal aspiration or any other risk factor for developement of adult respiratory distress syndrom. In the first case, with severe head trauma, neurogenic pulmonary edema was diagnosed at admission one hour after trauma, associated with severe systemic inflammatory reaction, and good outcome in three days. The second case, with hemorragic vascular insult, developed neurogenic pulmonary edema the fourth day after drenage of intracerebral hematom and died.

A pilot study of topiramate in children with Lennox-Gastaut syndrome

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.

Ressonância magnética e características clínicas em adultos com doenças desmielinizantes monofásicas: encefalomielite aguda disseminada ou uma variante da esclerose múltipla?

Acute disseminated encephalomyelitis (ADEM) is a widespread monophasic inflamatory disease affecting the central nervous system, that usually follows an infection or vaccination. In this study, we present an analysis of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and clinical aspects in four patients with clinical diagnosis of ADEM. The presence of MRI demyelinating lesions was crucial, but not in itself sufficient for definitive diagnosis. Clinical and MRI follow up, in order to exclude new lesions and to reevaluate the former ones, as well as CSF, were important for the differential diagnosis with other demyelinating diseases, particularly multiple sclerosis. In addition, we have shown that early treatment with methylprednisolone after the initial symptoms was effective for improving clinical manifestations as well as for reducing MRI lesions.

Pilocytic astrocytoma following radiotherapy for craniopharyngioma: case report

Administration of fractionated doses of irradiation is part of the adjutant therapy for CNS tumours such as craniopharyngiomas and pituitary adenomas. It can maximise cure rates or expand symptom-free period. Among the adverse effects of radiotherapy, the induction of a new tumour within the irradiated field has been frequently described. The precise clinical features that correlate irradiation and oncogenesis are not completely defined, but some authors have suggested that tumors are radiation induced when they are histologically different from the treated ones, arise in greater frequency in irradiated patients than among normal population and tend to occur in younger people with an unusual aggressiveness. In this article, we report a case of a papillary astrocytoma arising in a rather unusual latency period following radiotherapy for craniopharyngioma.

Whipple's disease with neurological manifestions: case report

Whipple's disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 yeards old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.

Plasticidade neural: relações com o comportamento e abordagens experimentais

Behavioral adaptiveness to different situations as well as behavioral individuality result from the interrelations between environmental sitmuli and the responses of an organism.These kind of interrelationships also shape the neural circuits as well as characterize the plasticity and the neural individuality of the organism. Studies on neural plasticity may analyze changes in neural circuitry after environmental manipulations or changes in behavior after lesions in the nervous system. Issues on neural plasticity and recovery of function refer both to physiology and behavior as well as to the subjacent mechanisms related to morphology, biochemistry and genetics. They may be approached at the systemic, behavioral, cellular and molecular levels. This work intends to characterize these kinds of studies pointing to their relations with the analyis of behavior and learning.The analysis of how the environmental-organismic interrelationships affect the neural substrates of behavior is pointed as a very stimulating area for investigation.

Influência da idade no comportamento da frequência cardíaca na transição repouso-exercício: uma análise por deltas e regressão linear

BACKGROUND: Changes in heart rate during rest-exercise transition can be characterized by the application of mathematical calculations, such as deltas 0-10 and 0-30 seconds to infer on the parasympathetic nervous system and linear regression and delta applied to data range from 60 to 240 seconds to infer on the sympathetic nervous system. The objective of this study was to test the hypothesis that young and middle-aged subjects have different heart rate responses in exercise of moderate and intense intensity, with different mathematical calculations. METHODS: Seven middle-aged men and ten young men apparently healthy were subject to constant load tests (intense and moderate) in cycle ergometer. The heart rate data were submitted to analysis of deltas (0-10, 0-30 and 60-240 seconds) and simple linear regression (60-240 seconds). The parameters obtained from simple linear regression analysis were: intercept and slope angle. We used the Shapiro-Wilk test to check the distribution of data and the t test for unpaired comparisons between groups. The level of statistical significance was 5%. RESULTS: The value of the intercept and delta 0-10 seconds was lower in middle age in two loads tested and the inclination angle was lower in moderate exercise in middle age. CONCLUSION: The young subjects present greater magnitude of vagal withdrawal in the initial stage of the HR response during constant load exercise and higher speed of adjustment of sympathetic response in moderate exercise.

Phenotypic variability in a family with x-linked adrenoleukodystrophy caused by the p.Trp132Ter mutation

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease with clinical heterogeneity varying from presymptomatic individuals to rapidly progressive cerebral ALD forms. This disease is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues. Affected individuals can be classified in different clinical settings, according to phenotypic expression and age at onset of initial symptoms. Molecular defects in X-ALD individuals usually result from ABCD1 gene mutations. In the present report we describe clinical data and the ABCD1 gene study in two boys affected with the childhood cerebral form that presented with different symptomatic manifestations at diagnosis. In addition, their maternal grandfather had been diagnosed with Addison's disease indicating phenotypic variation for X-ALD within this family. The mutation p.Trp132Ter was identified in both male patients; additionally, three females, out of eleven family members, were found to be heterozygous after screening for this mutation. In the present report, the molecular analysis was especially important since one of the heterozygous females was in first stages of pregnancy. Therefore, depending on the fetus outcome, if male and p.Trp132Ter carrier, storage of the umbilical cord blood should be recommended as hematopoietic stem cell transplantation could be considered as an option for treatment in the future.