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Increased acoplasmic transport of H3-dopamine in nigro-neostriatal neurons after reserpine 总被引:1,自引:0,他引:1
Recent evidence suggests that dopamine can undergo axoplasmic transport in nigro-neostriatal neurons by binding to amine storage granules. In the present experiments it was demonstrated that reserpine pretreatment (10 mg/kg) 24 hours before stereotaxic injections of 3H-DOPA or 3H-dopamine into the substantia nigra increases the amount of 3H-dopamine transported to the neostriatum by about 300 percent. The activity recovered from the substantia nigra was significantly reduced by reserpine pretreatment however. Stereotaxic injection of 14C-leucine into the substantia nigra indicated that neither fast nor slow axoplasmic transport of protein was influenced by reserpine pretreatment in these same neurons. The increased transport of dopamine appears therefore to be due to a relatively selective action of reserpine. The results suggest that reserpine either (i) increases the binding of dopamine to newly synthesized amine storage granules, (ii) increases the number of newly synthesized amine storage granules, or (iii) accelerates the rate of transport of amine storage granules. In addition, the results support the view that reserpine can increase the membrane permeability of adrenergic neurons to the outward movement of catecholamines. 相似文献
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During the last decade, there has been a dramatic resurgence of necrotizing fasciitis caused by group A streptococcal disease with mortality rates from 43 to 58 percent. The objective of this study was to review recent clinical experience regarding the diagnosis and management of streptococcal necrotizing fasciitis, including the use of high-dose intravenous immunoglobulin. From April of 1995 to December of 1997, 20 consecutive adult patients meeting clinical and/or histopathologic criteria for streptococcal necrotizing fasciitis were identified in the Toronto area. Of those, 16 (80 percent) were treated with > or = 1 mg/kg of intravenous immunoglobulin. Fourteen men and 6 women ranging in age from 33 to 89 were identified (median age 55.5 years). Sixteen patients (80 percent) with necrotizing fasciitis survived. Ten patients had necrotizing fasciitis alone, none of whom died. Eight patients were identified with myonecrosis and necrotizing fasciitis, three of whom died. The case fatality rate of all patients who received intravenous immunoglobulin was 19 percent (3 of 16) and was not statistically significantly different (p = 1.0) from the case fatality rate of 25 percent (1 of 4) in those patients who did not receive intravenous immunoglobulin. A total of seven patients (35 percent) were diagnosed as having a cause for their signs and symptoms other than necrotizing fasciitis when they initially presented to a physician; one of these patients died. There was no correlation with the M type or the streptococcal pyrogenic exotoxin genotype and outcome. 相似文献
45.
Atlantic salmon embryos and alevins Salmo salar that had been exposed to isosorbide dinitrate (ISDN) for 4 weeks, on transfer to fresh water, showed an increase in heart rate. Unexposed embryos and alevins showed a decrease in heart rate following transfer to 100 μmol l−1 ISDN for 4 h. This is in contrast to adult rainbow trout and higher vertebrates where tachycardia occurred in response to nitric oxide (NO) donors. The decreased heart rate in response to ISDN was inhibited by 2 mg 1−1 methylene blue, indicating that NO activates cardiovascular events via guanylyl cyclase and cyclic guanidine monophosphate. Heart rate of rainbow trout alevins Oncorhynchus mykiss exposed to 100 μmol l−1 aminoguanidine responded with a slowly developed but significant bradycardia over 10 min as did those reared in aminoguanidine for 4 weeks then transferred to fresh water. A potentiated increase in heart rate on exposure to the NO donor sodium nitroprusside (SNP), occurred within 1 min in salmon alevins reared in l -nitro-arginine methyl ester ( l -NAME) for 4 weeks, indicating up-regulation of NO receptors. The evidence for down-regulation of SNP-reared alevins exposed to l -NAME was less well defined. The results suggest that both salmonid embryos and alevins have a functional l -arginine-NO pathway and that NO has a physiological role in control of cardiovascular events. 相似文献
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Hong Qing Yanyan Zhang Yulin Deng P.L. McGeer 《Biochemical and biophysical research communications》2009,390(4):1229-540
Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are the leading cause of genetically inherited Parkinson’s disease (PD) and its more severe variant diffuse Lewy body disease (DLB). Pathological mutations in Lrrk2 are autosomal dominant, suggesting a gain of function. Mutations in α-synuclein also produce autosomal dominant disease. Here we report an interaction between Lrrk2 and α-synuclein in a series of diffuse Lewy body (DLB) cases and in an oxidative stress cell based assay. All five cases of DLB, but none of five controls, showed co-immunoprecipitation of Lrrk2 and α-synuclein in soluble brain extracts. Colocalization was also found in pathological deposits in DLB postmortem brains by double immunostaining. In HEK cells transfected simultaneously with plasmids expressing Lrrk2 and α-synuclein, co-immunoprecipitation of Lrrk2 and α-synuclein was detected when they were exposed to oxidative stress by H2O2. Taken together, these results suggest the possibility that in PD and related synucleinopathies, oxidative stress upregulates α-syn and Lrrk2 expression, paving the way for pathological interactions. New therapeutic approaches to PD and the synucleinopathies may result from limiting the interaction between Lrrk2 and α-synuclein. 相似文献
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Mark AJ Roberts Elias August Abdullah Hamadeh Philip K Maini Patrick E McSharry Judith P Armitage Antonis Papachristodoulou 《BMC systems biology》2009,3(1):105-14
Background
Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models. 相似文献50.
Agron Plevneshi Tomislav Svoboda Irene Armstrong Gregory J. Tyrrell Anna Miranda Karen Green Donald Low Allison McGeer for the Toronto Invasive Bacterial Diseases Network 《PloS one》2009,4(9)