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Csanyi G Lepran I Flesch T Telegdy G Szabo G Mezei Z 《Pharmacological reports : PR》2007,59(4):447-455
It is not known whether the impairment of nitric oxide (NO)-dependent vasodilation of the aorta of diabetic rats is associated with any changes in the endothelial production of vasoactive prostanoids and endothelium-derived hyperpolarizing factor (EDHF). Therefore, we analyzed the contribution of NO, vasoactive prostanoids and EDHF to the decreased endothelium-dependent vasorelaxation in Sprague-Dawley rats at 4 and 8 weeks after diabetes mellitus induced by streptozotocin (STZ). The acetylcholine-induced (Ach) endothelium-dependent relaxation was significantly decreased in the thoracic aorta 8 weeks after the STZ-injection (Ach 10(-6) M: 73.1 +/- 7.4% and 56.7 +/- 7.9% for control and diabetic rats, respectively). The sodium nitroprusside-induced (NaNP) endothelium-independent vasodilation was also impaired in the diabetic rats (8 weeks after STZ) (NaNP 10(-8) M: 74.2 +/- 11.4% and 35.9 +/- 9.4% for control and diabetic rats, respectively). In contrast, the basal NO production, as assessed by the N omega-nitro-L-arginine methyl ester (L-NAME)-induced vasoconstriction was not modified in diabetes. Moreover, the amount of 6-keto-PGF(1 alpha) (stable metabolite of prostacyclin / prostaglandin I2 / PGI2 ), 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) and thromboxane B2 (TxB2 ) (stable metabolite of thromboxane A2 - TxA2) were significantly increased in the 8 weeks diabetic rat aorta. The EDHF-pathway did not change in the aortic endothelium during the development of STZ-induced diabetes. Our results indicate that STZ-induced diabetes mellitus did not modify the basal NO production, but induced the impairment of acetylcholine- and sodium nitroprusside-induced vasodilation in the thoracic aorta. In parallel with the impairment of NO-dependent vasodilation, the basal PGI2, 12-HHT and TxA2 synthesis were increased. The EDHF-pathway did not contribute to the endothelium-dependent relaxation either in control or diabetic aorta. The above alterations in the endothelial function may play an important role in the development of endothelial dysfunction and vascular complications of diabetes. 相似文献
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Toth T Deak L Fazakas F Zheng J Muszbek L Sziklai I 《International journal of molecular medicine》2007,20(4):545-550
The electromotility of cochlear outer hair cells (OHCs) is a major factor in cochlear amplification that enhances the sensitivity of hearing in humans. Prestin is associated with presumed conformational changes in an integral membrane protein. Prestin knockout (-/-) mice display loss of OHC electromotility and a 40- to 60-dB reduction in cochlear sensitivity in vivo. In the present study we described the results of a direct sequencing mutation in the pres gene that was found in genetic screening performed in 47 patients characterized by non-syndromic, mild-to-moderate hearing impairment (30-70 dB) and in 50 control subjects from Hungary, after exclusion of GJB (GJB2, GJB6) mutations in the background. Only one patient and his normal-hearing father showed a heterozygous missense mutation (R150Q/WT) in the 6th coding exon of the pres gene. None of the 50 control subjects with normal hearing carried this mutation. Electrophysiological studies on the R150Q (homozygous and heterozygous) prestin mutant transiently transfected into reporting cells demonstrated nonlinear capacitance functions (NLC) as a signature of OHC electromotility. The capacitance function in human kidney cell line TSA 201 was similar for wild-type prestin and the mutant. However, for the mutant the voltage where the maximal charge displacement occurred (V1/2) significantly shifted in the hyperpolarizing direction ( approximately 15 mV). This is the first genetic and electrophysiological analysis of a human mutation in a coding exon of the pres gene by 47 patients with non-syndromic, sensorineural, mild-to-moderate hearing impairment; although the pathogenic role of the R150Q mutation is not unambiguous. 相似文献
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Erika Marek Timea Dergez Gabor Rebek-Nagy Istvan Szilard Istvan Kiss Istvan Ember Peter Gocze Gibson D’Cruz 《Vaccine》2012
The alarming national data on the mortality and morbidity rates of cervical cancer as well as the results of a Hungarian survey demonstrating adolescents’ low level of understanding of human papillomavirus (HPV) infection and HPV vaccination encouraged the authors to conduct an educational intervention. The aim of this survey was to explore the impact of a brief, HPV-focused program on adolescents’ knowledge, beliefs and attitudes. 相似文献
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Agnes Petrohai Gergely Nagy Szilvia Bösze Ferenc Hudecz Emese Zsiros György Paragh Zoltán Nyárády Péter Németh Timea Berki 《Transplant international》2004,17(12):834-840
Abstract Autoimmune mechanisms play an important role in the pathogenesis of allograft vasculopathy following heart transplantation, but the autoantigens involved have been only sparsely studied. Citrate synthase (CS) enzyme is a conserved molecule, and, as an important mitochondrial autoantigen, it is protected by the "immunological homunculus". Tissue destruction and alteration of the immune regulatory mechanisms can induce pathological immune response against CS in other autoimmune diseases. In our present study we aimed to detect CS-specific autoantibodies in heart transplant patients, therefore, prospective, randomised clinical tests were conducted on 33 heart transplant patients and compared with 130 healthy blood donors. The level and isotype of CS antibodies were detected by simple binding indirect enzyme-linked immunosorbent assay (ELISA). The epitope specificities of the autoantibodies were measured on synthetic overlapping peptide sequences of CS enzyme by an indirect multi-pin ELISA method. Mainly IgM isotype CS autoantibodies were found in healthy controls, while IgG was found at higher levels and frequency (four-times higher) in heart transplant patients. Autoantibodies of IgG isotype recognise different epitopes than do autoantibodies of IgM isotype, even within the same group and individual. New epitope-specific IgG and IgM isotype autoantibodies appeared in heart transplant patients when compared with the controls. Our findings suggest a possible role of CS-specific autoantibodies in the pathomechanism of allograft vasculopathy. 相似文献
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Dome P Halmai Z Dobos J Lazary J Gonda X Kenessey I Sallai T Makkos Z Faludi G 《Journal of affective disorders》2012,136(3):1159-1163
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AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantit... 相似文献
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Csak T Folhoffer A Horvath A Halász J Diczházi C Schaff Z Szalay F 《World journal of gastroenterology : WJG》2006,12(9):1485-1487
A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome: photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma. 相似文献