RESUMO
Immunocompromised patients are at risk of chronic hepatitis E (HEV) infection. Recurrent T cell and borderline rejections in a pediatric patient with high HEV copy numbers led us to study HEV infection within renal transplants. To investigate the frequency of renal HEV infection in transplanted patients, 15 samples from patients with contemporaneous diagnoses of HEV infection were identified at our center. Ten samples had sufficient residual paraffin tissue for immunofluorescence (IF) and RNA-fluorescence-in-situ-hybridization (RNA-FISH). The biopsy of the pediatric index patient was additionally sufficient for tissue polymerase chain reaction and electron microscopy. HEV RNA was detected in paraffin tissue of the index patient by tissue polymerase chain reaction. Subsequently, HEV infection was localized in tubular epithelial cells by IF, RNA-FISH, and electron microscopy. One additional biopsy from an adult was positive for HEV by RNA-FISH and IF. Focal IF positivity for HEV peptide was observed in 7 additional allografts. Ribavirin therapy was not successful in the pediatric index patient; after relapse, ribavirin is still administered. In the second patient, successful elimination of HEV was achieved after short-course ribavirin therapy. HEV infection is an important differential diagnosis for T cell rejection within transplanted kidneys. Immunostaining of HEV peptide does not necessarily prove acute infection. RNA-FISH seems to be a reliable method to localize HEV.
Assuntos
Vírus da Hepatite E , Hepatite E , Adulto , Humanos , Criança , Hepatite E/diagnóstico , Hepatite E/epidemiologia , Hepatite E/etiologia , Vírus da Hepatite E/genética , Ribavirina/efeitos adversos , Antivirais/uso terapêutico , Parafina/uso terapêutico , RNA Viral/genética , RNA Viral/análise , Rim , PeptídeosRESUMO
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with episodic, recurrent, and painful neuropathies affecting the nerves of the brachial plexus. In this study, we report on a family of Lebanese descent with HNA onset in early childhood. The affected family members presented with platelet dysfunction. Platelet aggregation was reduced after stimulation with the agonists ADP and epinephrine in all affected family members. Flow cytometric analyses revealed impaired platelet δ-secretion. The index patient and one brother suffered from kidney cysts. Molecular genetic analysis revealed a heterozygous duplication of exon 2 within the septin 9 (SEPT9) gene in all the affected family members. Such a young child with HNA (aged 2 years) caused by SEPT9 duplication has not been described so far.
Assuntos
Neurite do Plexo Braquial/genética , Septinas/genética , Adolescente , Criança , Pré-Escolar , Éxons/genética , Feminino , Citometria de Fluxo , Duplicação Gênica/genética , Heterozigoto , Humanos , Masculino , Mutação/genética , Agregação Plaquetária/genética , Agregação Plaquetária/fisiologiaRESUMO
Fluorescently labeled histamine H(2) receptor antagonists were synthesized starting from N-cyano-N'-[3-(3-piperidin-1-ylmethylphenoxy)propyl]guanidines with an additional N"-omega-aminoalkyl substituent (chain lengths 2-8 methylene groups) or from 3-(3-piperidin-1-ylmethylphenoxy)propylamine. The primary amino group was derivatized with various fluorophores (fluorescein, acridine, dansyl, nitrobenzoxadiazole (NBD), indolo[2,3-a]quinolizine). On the isolated spontaneously beating guinea pig right atrium most of the fluorescent probes were only weakly active, however, the NBD-labeled substances proved to be potent histamine H(2) receptor antagonists achieving pA(2) values in the range of 7.5-8.0, comparable to the activity of famotidine.
Assuntos
Antagonistas dos Receptores H2 da Histamina/síntese química , Animais , Corantes Fluorescentes , Guanidinas/síntese química , Guanidinas/farmacologia , Cobaias , Átrios do Coração/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/farmacologia , Técnicas In Vitro , Propilaminas/síntese química , Propilaminas/farmacologia , Análise Espectral , Relação Estrutura-AtividadeRESUMO
Fluorescently labeled histamine H(1) receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of omega-aminoalkyl chains (2-8 methylene groups in length) followed by derivatization of the terminal NH(2) group with various fluorophores (fluorescein, naphthofluorescein, rhodamine, tetramethylrhodamine, BODIPY, dansyl, and nitrobenzoxadiazole (NBD)). On the isolated guinea pig ileum and in a Ca(2+) assay on U373MG human glioblastoma cells the highest H(1) antagonistic activities were found in 5- and 6-carboxyfluorescein labeled compounds with hexa- and octamethylene spacers and in an analogous NBD-aminohexanoyl derivative (pA(2) or pK(B) values in the range: 8.3-9.0; compared to 9.3-9.4 for mepyramine).
