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1.
Benedita Sampaio-Maia Mónica Moreira-Rodrigues Paula Serr?o Manuel Pestana 《Nephrology, dialysis, transplantation》2006,21(2):314-323
BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria. 相似文献
2.
Spermidine/Spermine N-Acetyltransferase, a New Biochemical Marker for Epithelial Proliferation in Rat Bladder 总被引:4,自引:4,他引:0
Isao Matsui-Yuasa Shuzo Otani Yoshihisa Yano Nobuyasu Takada Masa-Aki Shibata Shoji Fukushima 《Cancer science》1992,83(10):1037-1040
We examined the activity of spermidine/spermine N 1 -acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N -butyl- N -(4–hydroxybutyI)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis. 相似文献
3.
Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dtsz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder. 相似文献
4.
Fa-Lin XU Chang-Lian ZHU Xiao-Yang WANG Department of Pediatrics the Third Affiliated Hospital of Zhengzhou University Zhengzhou China 《中国神经科学杂志》2006,(1)
Objective To study the developmental changes of glutamic acid decarboxylase-67 (GAD-67, a GABA synthetic enzyme) in normal and hypoxic ischemic (HI) brain. Methods C57/BL6 mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature (P21, P60) and immature (P5, P9) brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia (HI) insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that (15.6±7.0)% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain. 相似文献
5.
Previous work showed that GABAergic differentiation in developing chick retina depends on insulin and cell interactions. Here, we investigated whether it depended on cell signaling mediated by retina cognin, a 50 kDa cell recognition molecule. Cognin mediates cell adhesion in vitro and occurs on retinal neurons that become both GABAergic and cholinergic. We investigated two markers of GABAergic differentiation: glutamate decarboxylase (GAD) activity and high-affinity GABA uptake. Both increase during differentiation of retinal neurons in culture and can be easily measured. We blocked cognin-mediated cell signaling with cognin antibody and found a reduction of the developmental increase in GAD activity in cultures of retinal neurons from 7 and 11 day chick embryos. There was no reduction of high-affinity GABA uptake. This suggested that cognin-mediated signaling was necessary for the normal developmental increase in GAD but not for high-affinity GABA uptake. These results contrasted with our previous observations on cholinergic differentiation in cultured retinal neurons. We found that cognin antibody blocked the normal developmental increase in choline acetyltransferase (ChAT) only if the cells were exposed before embryonic day 7. Thus, while both GAD and ChAT activity appear to be controlled by cell signaling involving cognin, the periods of developmental sensitivity for the two differentiation markers are different. Antibodies to other adhesion molecules, Ng-CAM, and N-cadherin, did not similarly affect GAD activity. Antibodies to laminin at a 10-fold higher concentration inhibited GAD activity only in early embryonic retina. Tests for protein synthesis and “housekeeping” enzyme activity demonstrated that the cognin antibody effect was selective for neuronal differentiation pathways. Thus, GABAergic differentiation in developing retina is sensitive to cell signaling mediated in part by cognin. 相似文献
6.
The antitumorigenic effect of cryptoporic acid E (CPA-E), a dimeric drimane sesquiterpenoid isolated from the fungus Cryptoporus volvatus , on colon carcinogenesis was investigated. Female F344 rats given an intrarectal instillation of 2 mg of N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 were fed diet containing 0.2% CPA-E from week 3. Femal ICR mice given 15 weekly intraperitoneal injections of 10 mg of 1,2-dimethylhydrazine/kg body weight during weeks 1 to 15 were fed diet containing 0.06% CPA-E from week 1. The experiment was terminated at week 35 for rats and at week 25 for mice. The incidence and the number of tumors per animal were reduced in CPA-E-fed animals compared to the controls: 31% vs. 75% (P<0.05) and 0.4±0.2 (SEM) vs. 0.9 ± 0.2 (0.1> P >0.05) in rats, and 31% vs. 63% (0.1>P>0.05) and 0.4±0.2 vs. 2.4 ± 0.8 (P<0.05) in mice (16 animals in each group). Intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity was significantly lowered in CPA-E-fed animals compared to controls. This shows an antipromoting activity of CPA-E against colon carcinogenesis. Thus, it was concluded that CPA-E inhibits colon cancer development in both rats and mice treated with 2 different colon carcinogens. 相似文献
7.
目的:探讨肠嗜铬样细胞与大鼠实验性胃溃疡自愈的关系. 方法:通过制备大鼠乙酸性胃体溃疡模型,采用免疫组化、逆转录聚合酶链反应(RT-PCR)和放射免疫测定的方法,观察溃疡自愈过程中大鼠胃黏膜内ECL细胞形态、组氨酸脱羧酶(HDC)mRNA和组胺含量的变化. 结果:胃溃疡大鼠胃黏膜内HDC阳性细胞率和胞质平均灰度值在制模术后第1日即开始降低,术后第6日达到最低,随后开始回升,术后第12日基本正常. 胃黏膜内HDC mRNA表达在制模术后第1日开始降低,第3日最明显,第6日开始恢复,第9日后接近正常. 制模术后胃黏膜内组胺含量也出现下调,以术后第6日为最低. 结论:ECL细胞可通过减弱其合成组胺的功能,参与胃溃疡自愈的调节过程. 相似文献
8.
目的探讨谷氨酸脱羧酶抗体(GAD-Ab)检测在2型糖尿病患者早期诊断中的意义。方法比较2型糖尿病患者GAD-Ab阳性组12例与阴性组86例的临床特征、体重指数、C肽、糖化血红蛋白等指标。结果GAD-Ab阳性组发病年龄低于阴性组,空腹及餐后2 h C肽值较低,使用胰岛素者比例较高,酮症酸中毒发生率高。结论检测2型糖尿病患者的GAD-Ab可帮助临床上早期发现迟发自身免疫糖尿病病人,尽早采用胰岛素治疗,对保护残存的胰岛功能有重要意义。 相似文献
9.
目的建立测定谷氨酸脱羧酶(GAD)抗体的方法,以探讨该抗体对胰岛素依赖型糖尿病(IDDM)的预测、早期诊断及其发病机制研究的意义。方法用专用酶反应试管建立放射性同位素底物测定GAD活性的分析方法。结果底物浓度为4mmol/ml(37kBq)时,酶活性测定在一定浓度范围内剂量效应呈直线关系(r=0989)。结合免疫沉淀与酶活性分析,建立了免疫沉淀酶活性分析测定GAD抗体的方法,2份IDDM患者GAD抗体阳性血清与酶活性免疫沉淀指数存在剂量效应关系。用免疫沉淀酶法测定15例正常人及20例病程1年以内的IDDM患者血清,两组酶活性免疫沉淀指数分别为0193±0087和0381±0121,差异有显著性(P<001)。按照超过正常人组免疫沉淀指数x+2s为阳性区分,20例IDDM患者血清中GAD抗体阳性9例,占45%。结论该方法简单,能直接反映酶活性的改变,无需高纯度的GAD,特别适用于刚开始从事GAD抗体研究的实验室及阳性血清筛查。 相似文献
10.
Abstract We previously demonstrated that epidermal growth factor (EGF) induces a several-fold increase in ornithine decarboxylase (ODC) activity and the steady-state level of ODC mRNA in cultured SV40-transformed human keratinocytes (1). Pretreatment of cell cultures with ultraviolet B (UVB) radiation resulted in a reduction of EGF-induced ODC activity. To determine whether UVB inhibits the accumulation of ODC mRNA by EGF, cells were pretreated with 20 mJ/cm2 UVB or sham-irradiated and then incubated with 100 ng/ml EGF. Northern blot analysis revealed that UVB irradiation entirely blocked the EGF induction of ODC mRNA. Since the binding of EGF to its plasma membrane receptor is the first step in initiating a biological response, the effect of UVB on EGF binding was evaluated. UVB treatment of cultured keratinocytes resulted in an immediate and dose-dependent reduction of EGF binding. Scatchard analysis revealed thai the reduction of EGF binding was due to a 52% decrease in the number of available receptors, from 6.2 × 104/cell to 3.0 × 104/cell. However, UVB decreased the EGF-binding affinity very little (Kd = 0.60 nM in control and Kd=0.75 nM in UVB-treated Z114 cells). In addition, UVB did not alter the rate of EGF internalization. These data suggest that UVB blocks the signal transduction pathway of EGF that is involved in regulation of ODC gene expression. Immunoblot analysis of extracts from irradiated cells showed that UVB induced tyro-sine phosphorylation of EGFR and that the quantity of EGFR protein was unaffected by UVB treatment. Phosphorylation of EGFR may be responsible for decreased binding of EGF to its receptor. 相似文献