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71.
72.
高糖损伤兔主动脉内皮依赖性舒张反应(英文) 总被引:4,自引:2,他引:2
目的:研究高糖对兔胸主动脉内皮依赖性舒张反应(EDR)的影响及L-精氨酸、超氧化物歧化酶(SOD)和高糖撤除的作用。方法:以主动脉环EDR为检测指标。结果:高糖可使乙酰胆碱(ACh)诱导的EDR明显受损,高糖撤除24h后不能恢复ACh的舒血管作用,而甘露醇(19.5mmol·L~(-1))不影响血管环EDR。L-精氨酸1mmol·L~(-1)或SOD 150U·L~(-1)可取消高糖对EDR的损伤作用,高糖不影响硝普钠的舒血管作用。结论:高糖可损伤血管EDR,短时间高糖撤除不能逆转,其机制可能与自由基产生及L-精氨酸代谢改变有关。 相似文献
73.
Fraser TB Turner SW Wen C Li M Burrell LM Whitworth JA 《Clinical and experimental pharmacology & physiology》2000,27(11):866-870
1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality and electrolyte concentrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + OPC-21268 for 16 days. Systolic blood pressure (SBP), water intake, urine volume (UV), urine osmolality and electrolytes, food intake, bodyweight and plasma osmolality and electrolyte concentrations were measured. 3. In the acute study, direct mean arterial blood pressure did not change with OPC 21268 (122+/-2 and 120+/-3 mmHg at 0 and 240 min, respectively). 4. In the chronic study, OPC 21268 did not affect ACTH-induced rises in blood pressure (from 125+/-2 (control) to 145+/-5 mmHg (group 4) compared with 122+/-3 (control) to 149+/-5 mmHg (group2)). Water intake and UV increased (from 29+/-2 to 83+/-6 mL/day; and from 5+/-1 to 36+/-5 mL/day, respectively) and the change in bodyweight decreased from 0+/-2 to -107+/-7 g. 5. These results suggest that AVP (at the V1a receptor) does not play a significant role in the maintenance of ACTH-induced hypertension. 相似文献
74.
L-NNA对脑缺血再灌注后海马区细胞凋亡的影响 总被引:1,自引:1,他引:0
自从一氧化氮(Nitricoxide,NO)作为一种特殊的效应分子引起人们的关注以来,许多生物学效应被归因于NO的作用。在脑血管系统中,NO的生物学效应对调节脑血管功能有重要意义。已有文献报道细胞的NO依赖性死亡是通过细胞凋亡实现的。本文探讨一氧化氮合酶(Nitricoxidesynthase,NOS)抑制剂LNNA与海马区细胞凋亡的关系。1 材料与方法1.1 实验动物 ♂沙土鼠70~80g(约12wk龄)20只,随机分为两组,实验组及对照组各10只。19991030收稿,19991224修回山东省自然科学基金资助课题,NoY98C19048作… 相似文献
75.
Zhang Tieyuan Jin Zhezhu Jin Zhengnan Jin LimeiDepartment of Pharmacology Yanbian MedicaI CollegeResearch Institute of Biological Immunity Yanbian Medical CollegeDepartment of Pharmacology Jilin Health School 《延边医学院学报》1995,(1)
Preliminarystudyonanti-inflammationofdiclofenacarginineZhangTieyuan1,JinZhezhu,JinZhengnan,JinLimeiDepartmentofPharmacology,Y... 相似文献
76.
OBJECTIVE: To examine family-based transmission of the number of 5' flanking arginine vasopressin V1a receptor (AVPR1A) microsatellites, which include [(GATA)(14)] and complex [(CT)(4)-TT-(CT)(8)-(GT)(24)] repeats, in probands with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP). Preferential transmission of the number of AVPR1A microsatellite repeats to hypersexual and uninhibited people-seeking probands was hypothesized, based on reports from preclinical work in the literature. METHODS: Probands were 83 participants in an ongoing controlled study of PEA-BP. The PEA-BP phenotype was defined by DSM-IV mania with at least one of the cardinal symptoms of mania (elation and/or grandiosity) to avoid diagnosing mania only by symptoms that overlapped with those for attention-deficit hyperactivity disorder (ADHD). Comprehensive assessment of the probands included separate Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) interviews of parents about their children and of children about themselves. Hypersexuality and uninhibited people-seeking were assessed from the corresponding WASH-U-KSADS items. Microsatellite genotyping of the AVPR1A repeats was conducted using fluorescently labeled primers and detected by laser-induced fluorescence. Alleles were determined with the assistance of semi-automated allele-calling software. There were 32 complete, biological trios (28 informative families) for the GATA repeat and 34 complete, biological trios (30 informative families) for the complex repeat. Data were analyzed using case-control and family-based association methods. RESULTS: Preferential transmission of AVPR1A GATA or complex repeats was not significant for hypersexuality or uninhibited people-seeking, using the transmission disequilibrium test. Similarly, case-control analyses found no significant associations between hypersexuality or uninhibited people-seeking and the number of AVPR1A GATA or complex repeats. For p < 0.05, there was about 80% power to detect odds ratios of 5.0 and 4.0 (in the family-based analyses) and 3.5 and 2.6 (in the case-control analyses), for allele frequencies of 0.1 and 0.5, respectively. CONCLUSION: Preferential transmission of AVPR1A to hypersexual or uninhibited people-seeking probands was not supported. 相似文献
77.
Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium 总被引:8,自引:0,他引:8 下载免费PDF全文
Zhao M Yang M Li XM Jiang P Baranov E Li S Xu M Penman S Hoffman RM 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(3):755-760
Here we report a genetically modified bacteria strain, Salmonella typhimurium A1, selected for anticancer activity in vivo. The strain grows in tumor xenografts. In sharp contrast, normal tissue is cleared of these bacteria even in immunodeficient athymic mice. S. typhimurium A1 is auxotrophic (Leu/Arg-dependent) but apparently receives sufficient support from the neoplastic tissue to grow locally. Whether additional genetic lesions are present is not known. In in vitro infection, the GFP-expressing bacteria grew in the cytoplasm of PC-3 human prostate cancer cells and caused nuclear destruction. These effects were visualized in cells labeled with GFP in the nucleus and red fluorescent protein in the cytoplasm. In vivo, the bacteria caused tumor inhibition and regression of xenografts visualized by whole-body imaging. The bacteria, introduced i.v. or intratumorally, invaded and replicated intracellularly in PC-3 prostate cancer cells labeled with red fluorescent protein grafted into nude mice. By day 15, S. typhimurium A1 was undetectable in the liver, lung, spleen, and kidney, but it continued to proliferate in the PC-3 tumor, which stopped growing. When the bacteria were injected intratumorally, the tumor completely regressed by day 20. There were no obvious adverse effects on the host when the bacteria were injected by either route. The S. typhimurium A1 strain grew throughout the tumor, including viable malignant tissue. This result is in marked contrast to bacteria previously tried for cancer therapy that were confined to necrotic areas of the tumor, which may account, in part, for the strain's unique antitumor efficacy. 相似文献
78.
In this Mini-Review we present a new hypothesis in support of the neurodegenerative theory as a mechanism for the pathogenesis of multiple sclerosis (MS). The pathogenesis of MS results from changes in two distinct CNS compartments. These are the "myelin" and "nonmyelin" compartments. The myelin compartment is where primary demyelination, amidst attempts at remyelination, is superseded in the CNS by ongoing disease. Recent evidence obtained via magnetic resonance imaging and spectroscopy techniques supports the view that the normal-appearing white matter (NAWM) in the MS brain is altered. Several biochemical changes in NAWM have been determined. These include the cationicity of myelin basic protein (MBP) as a result of the action of peptidyl argininedeiminase (PAD) activity converting arginyl residues to citrulline. The accompanying loss of positive charge makes myelin susceptible to vesiculation and MBP more susceptible to proteolytic activity. An increase of MBP autocatalysis in the MS brain might also contribute to the generation of immunodominant epitopes. Accompanying the destruction of myelin in the myelin compartment is the activation of astrocytes and microglia. These contribute to the inflammatory response and T-cell activation leading to autoimmunity. The complex environment that exists in the demyelinating brain also affects the "nonmyelin" compartment. The inappropriate up-regulation of molecules, including those of the Jagged-1-Notch-1 signal transduction pathway, affects oligodendrocyte precursor cell (OPC) differentiation. Other effectors of oligodendrocyte maturation include stathmin, a microtubule-destabilizing protein, which prevents healing in the demyelinating brain. The hypothesis we present suggests a therapeutic strategy that should 1) target the effectors within the myelin compartment and 2) enable resident OPC maturation in the nonmyelin compartment, allowing for effective repair of myelin loss. The net effect of this new therapeutic strategy is the modification of the disease environment and the stimulation of healing and repair. 相似文献
79.
Concanavalin A inhibits pathophysiological effects of anti-ganglioside GQ1b antibodies at the mouse neuromuscular synapse 总被引:1,自引:0,他引:1
Bullens RW Halstead SK O'Hanlon GM Veitch J Molenaar PC Willison HJ Plomp JJ 《Muscle & nerve》2005,31(6):751-760
Anti-GQ1b antibodies are present in the Miller Fisher syndrome (MFS), a monophasic neuropathy characterized by ataxia, areflexia, ophthalmoplegia, and sometimes cranial muscle weakness. We have previously shown, at the mouse neuromuscular junction (NMJ) ex vivo, that anti-GQ1b antibodies, through complement classic pathway activation, block synaptic transmission in a way that resembles the effect of the pore-forming alpha-latrotoxin (alphaLTx). In order to clarify the mechanism of these alphaLTx-like effects, including possible involvement of the alternative and mannose-binding protein complement pathways, we studied the effects of concanavalin A (ConA), a lectin known to block the action of alphaLTx, immunoglobulins, and early complement components. With electrophysiological, immunohistological, and bioassay experiments, we showed that the alphaLTx-like effects of anti-GQ1b antibody and complement were inhibited by pre- and coincubation with ConA. However, ConA was not able to inhibit evolution of alphaLTx-like effects when coincubated upon addition of complement at NMJs that had already bound anti-GQ1b antibody. Our data suggest that the mannose-binding protein pathway is not involved in the alphaLTx-like effect and that the inhibiting effect of ConA principally arises through interference with presynaptic binding of anti-GQ1b antibody. In control experiments, ConA prevented the neuroexocytotic effects of alphaLTx, indicating that alphaLTx receptors were inhibited under these conditions. We conclude that, although the physiological effects at the NMJ of anti-GQ1b antibody and alphaLTx are very similar, the activity of anti-GQ1b antibody is not mediated through activation of alphaLTx receptors, but rather is caused by direct presynaptic membrane damage through classic complement pathway activation. 相似文献
80.
Oral arginine reduces gut mucosal injury caused by lipopolysaccharide endotoxemia in rat 总被引:2,自引:0,他引:2
Sukhotnik I Mogilner J Krausz MM Lurie M Hirsh M Coran AG Shiloni E 《The Journal of surgical research》2004,122(2):256-262
BACKGROUND: The objective of this study was to evaluate the effects of lipopolysaccharide (LPS) endotoxemia and enteral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis in rat. METHODS: Male Sprague-Dawley rats, weighing 250-280 g, were divided into three experimental groups: control rats, LPS rats treated with lipopolysaccharide given ip at a dose of 10 mg/kg every 24 h (two injections), and LPS-ARG rats treated with enteral arginine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined on day 3 following the first LPS injection. RESULTS: LPS rats demonstrated a significant decrease in bowel weight in duodenum, mucosal weight in duodenum, jejunum, and ileum, mucosal DNA and protein in jejunum and ileum, and villus height in jejunum and ileum compared to control animals. LPS rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in jejunum and ileum compared to control rats. LPS-ARG animals demonstrated greater duodenal bowel weight, duodenal and ileal mucosal weight, ileal mucosal DNA and protein, ileal villus height, and jejunal and ileal cell proliferation index compared to LPS animals. CONCLUSIONS: LPS endotoxemia impairs the integrity of the gastrointestinal mucosa in rat. Decreased cell proliferation and increased apoptosis may be considered the main mechanisms responsible for the decreased cell mass. Enteral arginine administration decreases the mucosal injury caused by lipopolysaccharide. 相似文献