RESUMO
We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin-angiotensin and kallikrein-kinin systems.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anticonvulsivantes/farmacologia , Carbamazepina/farmacologia , Epilepsia do Lobo Temporal/fisiopatologia , Peptidil Dipeptidase A/fisiologia , Alelos , Animais , Lobectomia Temporal Anterior , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Genótipo , Humanos , Mutação INDEL , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/patologiaRESUMO
CONTEXT: A definite cause of sarcoidosis has not been identified, however past research suggests that environmental factors may be triggers of the granulomatous response in genetically susceptible individuals. CASE PRESENTATION: A 22-year-old male non-smoker, presented with progressive exertional dyspnea and cough of 3 months duration. One year before, when he started working in tunnel excavation, he had a normal chest radiograph. Chest imaging revealed bilateral nodules and masses of peribronchovascular distribution plus mediastinal lymphadenomegaly. Histologic lymph node analysis revealed non-caseating confluent granulomas. Sarcoidosis was diagnosed. The patient was treated with corticosteroids and advised to change jobs. Complete remission of the disease was achieved and persisted for at least one year without steroid treatment. DISCUSSION: Sarcoidosis is believed to have environmental triggers. The timing of the onset of sarcoidosis in this patient following intensive exposure to tunnel dust suggests an environmental contribution. The recognition that sarcoidosis may have occupational triggers have medical, employment, and legal implications.
Assuntos
Mediastino/patologia , Exposição Ocupacional , Sarcoidose Pulmonar , Corticosteroides/uso terapêutico , Humanos , Linfonodos/patologia , Masculino , Radiografia , Sarcoidose Pulmonar/induzido quimicamente , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/tratamento farmacológico , Adulto JovemRESUMO
In this study we used proteomics approaches to obtain the protein profile of human epileptic hippocampi (N=6) and control hippocampi obtained from autopsy (N=6). We used two-dimensional gel electrophoresis (2-D) coupled to HPLC and Mass spectroscopy (MALDI-TOF) to identify proteins differentially expressed. Nine proteins were differentially expressed comparing the hippocampus of patients with the hippocampus of control. Proteins that were increased in the hippocampus of patients with TLE were: isoform 1 of serum albumin, HSP 70, dihydropyrimidinase-related protein 2, isoform 1 of myelin basic protein, proton ATPase catalytic subunit A, and dihydrolipoyllysine-residue acethyltransferase component of pyruvate dehydrogenase complex. The expression of isoform 3 of spectrin alpha chain (fodrin) was down-regulated while the proteins glutathione S-transferase P and the DJ-1 (PARK7) were detected only in the hippocampus of patients with TLE. Taken together, our results provide evidence supporting a direct link between metabolic disturb and oxidative damage related to pathophysiology of TLE. Besides, indicates biomarkers for further investigations as therapies targeted to epilepsy.
No presente estudo empregou-se o método de proteômica para obter a expressão diferencial de proteínas em hipocampo de pacientes com epilepsia do lobo temporal (ELT) (N=6) comparado a hipocampos controle obtidos por meio de autópsia (N=6). O estudo foi feito por meio de eletroforese bidimensional, acoplada a HPLC e espectroscopia de massa. As proteínas que tiveram expressão aumentada no hipocampo de pacientes com ELT foram: isoforma-1 da soroalbumina, HSP70, diidropirimidinase-2, isoforma-1 da proteína básica da mielina, subunidade catalítica A da próton ATPase, glutationa S-transferase P, proteína DJ-1 (PARK7), e resíduo diidropolilisina do componente acetil-transferase do complexo da piruvato desidrogenase. A expressão da isoforma-3 da cadeia alfa da espectrina (fodrina) foi menor no hipocampo de pacientes com epilepsia do lobo temporal e as proteínas glutationa S-transferase P e PARK7 foram detectadas somente no tecido epiléptico. Assim, nossos resultados trazem evidencias sobre a direta relação entre distúrbio metabólico e dano oxidativo na patofisiologia da ELT. Além disto, o estudo indica biomarcadores para futuras investigações como alvos terapêuticos para epilepsia.
Assuntos
Humanos , Biomarcadores , Epilepsia do Lobo Temporal , HipocampoRESUMO
INTRODUCTION: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition "marginal," nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. MATERIALS AND METHODS: After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. RESULTS: The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440-1454 dynes/sec/cm(5); LC was in the range of 26-90 mL/cmH(2)O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. CONCLUSIONS: The ex vivo evaluation model can improve oxygenation capacity of "marginal" lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list.
Assuntos
Transplante de Pulmão/fisiologia , Pulmão/irrigação sanguínea , Seleção de Pacientes , Idoso , Gasometria , Cadáver , Causas de Morte , Feminino , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Complacência Pulmonar , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Perfusão/métodos , Respiração com Pressão Positiva , Recusa em Tratar/estatística & dados numéricos , Doadores de Tecidos , Resistência VascularRESUMO
The hantavirus pulmonary syndrome was first recognized in cases that occurred in the U.S. in 1993, which served as an alert not only for American physicians but also for physicians in other countries for the identification of the disease. In the city of São Paulo, Brazil, 3 cases of the syndrome were recorded in 1993. The patients were young brothers residing in the Mata Atlântica (Atlantic Forest) region submitted to recent deforestation. Two of the patients died of acute respiratory insufficiency and the third recovered without sequelae. In the surviving patient the diagnosis was established by a laboratory criterion based on the detection of specific IgM and IgG class antibodies by indirect immunofluorescence. In the two patients who died, the diagnosis was confirmed by laboratory tests using immunoperoxidase technique for hantavirus in tissue, in histological lung and heart sections in one case, and by clinical and epidemiological data in the other.