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71.
The ultrastructure of lipofuscin (age pigment) and dense bodies induced by intraventricular administration of leupeptin, a cysteine proteinase inhibitor, were investigated in the neurons of rat hippocampal dentate gyrus. Four-day treatment with leupeptin (0.5 mg/day) rapidly caused a considerable accumulation of intracytoplasmic dense bodies and swelling of neuronal processes. We demonstrated, as inner structures of the pigments, that pentalaminar structure with a thickness of 12–13 nm and finely granular matrix were exactly common to the leupeptin-induced dense bodies and lipofuscin granules. Furthermore, the transitional stages from lysosomes into the dense granules were observed in the neurons of the leupeptin-treated rats. On the other hand, some morphological differences between the leupeptin-induced dense bodies and lipofuscin granules have been shown: (1) distribution in different cell types, (2) intracytoplasmic location, (3) tendencies to associate with vacuoles, and (4) electron density. The present findings suggested that the decline of the lysosomal protein degradation could play a role in lipofuscinogenesis, especially in the genesis of their electron-dense portion, but some other mechanisms might participate in the formation and accumulation of lipofuscin with aging 相似文献
72.
A. Fjellestad-Paulsen L. d’Agay-Abensour P. Höglund J.-C. Rambaud 《European journal of clinical pharmacology》1996,50(6):491-495
Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor,
was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration.
Methods:
For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly,
in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of
isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and
aprotinin was administered enterally at the constant rate of 5 ml⋅min−1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement
of lipase, chymotrypsin and pH every 30 min for 5 h.
Results:
The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified.
After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg−1. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal
administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was
similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of
an enzyme inhibitor.
Received: 27 October 1995/Accepted in revised form: 26 February 1996 相似文献
73.
J. J. M. Askenasy MD. PhD. M. D. Yahr 《Journal of neural transmission (Vienna, Austria : 1996)》1988,72(1):67-76
Summary In the present study a single case observation of myoclonus during sleep-wave transition was monitored in a depressed patient treated with the monoamine oxidase inhibitor, phenelzine. The myoclonus had a rhythm of 1 c/second and lasted for two years, the duration of phenelzine treatment. Myoclonus appeared neither during wakefulness nor during sleep, but at wake-sleep-wake transitions. This switch myoclonus was associated with phasic muscle hyperactivity during REM sleep.Methysergide a 5-HT suppressor, decreased the switch myoclonus frequency and the REM muscle hyperactivity, indicating serotoninergic involvement in the mechanism of phenelzine induced myoclonus. 相似文献
74.
L. Laurian Z. Oberman E. Hoerer E. Graf 《Journal of neural transmission (Vienna, Austria : 1996)》1988,73(3):167-176
Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion. 相似文献
75.
孙长荣 《军事医学科学院院刊》1988,(4)
本文报告了我所自己合成的可逆性胆硷酯酶抑制剂——二甲氨基甲酸-3-叔丁基-4-〔2-(1-哌啶基)乙氧基〕苯酯(代号"8294")与生理对抗剂或胆硷酯酶重活化剂伍用,对不同神经性毒剂中毒的预防效价、安全系数、有效时间以及与催醒宁("705")比较等所进行的观察.结果显示,"8294"比"705"的毒性小,安全系数大,效价高,有效时间长. 相似文献
76.
型糖尿病常合并脂代谢紊乱,脂代谢紊乱加重胰岛素抵抗,同时也参与糖尿病并发症的发生、发展。新型降糖药钠-葡萄糖耦联转运体-2(SGLT-2)抑制剂通过抑制肾脏对葡萄糖的重吸收发挥降糖作用,进而调控机体糖、脂代谢,改善2型糖尿病患者血脂、异位脂肪沉积及胰岛素抵抗。本文对SGLT-2抑制剂改善2型糖尿病脂代谢的相关研究进展做一综述。 相似文献
77.
目的 探讨环氧酶-2抑制剂对关节炎大鼠小肠黏膜的影响。方法 将32只雄性SD大鼠随机分为空白对照组、造模对照组、空白给药组和造模给药组,造模对照组、造模给药组给予弗氏完全佐剂右后足跖注射,空白对照组、空白给药组注射等量生理盐水。1周后造模给药组、空白给药组给予选择性环氧酶-2抑制剂塞来昔布(溶于1%甲基纤维素)灌胃28 d,空白对照组、造模对照组给予等量溶剂。处死大鼠后观察小肠黏膜大体损伤、病理评分,酶联免疫吸附试验检测末段小肠前列腺素浓度。结果 造模对照组与造模给药组模型复制第7天的足周径比较,差异无统计学意义(P>0.05),但两组分别与空白对照组和空白给药组比较,差异有统计学意义(P <0.05),空白对照组与空白给药组比较,差异无统计学意义(P>0.05)。空白对照组与造模对照组小肠黏膜损伤面积比较,差异有统计学意义(P <0.05),空白给药组与空白对照组比较,差异有统计学意义(P <0.05)。造模对照组、空白给药组和造模给药组组间小肠黏膜病理评分比较,差异无统计学意义(P>0.05),且空白对照组与其他3组比较,差异有统计学意义(P &... 相似文献
78.
Although treatment of one unusually aggressive case of postmenopausal endometriosis with an aromatase inhibitor has been strikingly successful, large clinical trials are required to establish whether aromatase inhibitors will have a significant role in the medical management of endometriosis. Introduction of aromatase inhibitors into the treatment of endometriosis underscores the importance of basic research leading to the development of novel strategies in reproductive disorders. It was shown earlier that aromatase activity was not detectable in normal endometrium. Aromatase, however, is expressed inappropriately in endometriosis and stimulated by prostaglandin E2. Aromatase activity gives rise to local biosynthesis of oestrogen, which, in turn, stimulates prostaglandin E2 production, thus establishing a positive feedback cycle. This favours accumulation of oestrogen and prostaglandins in endometriosis, which is an inflammatory disorder dependent on oestrogen for growth. 相似文献
79.
目的:观察米氮平对神经性厌食症的疗效。方法:42例符合CCMD-3神经性厌食症患者被随机分成2组,分别给予米氮平和5-羟色胺再摄取抑制剂(SSRIs)治疗12周,而后随访12周。比较患者治疗前后的体重变化、汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评分及药物不良反应。结果:共38例患者完成治疗全过程,其中米氮平组20例,SSRIs组18例。在治疗6周时,米氮平组的体重增加大于SSRIs组,差异有显著性(P〈0.01);治疗12周时,两组体重增加值差异没有显著性。治疗后两组HAMD和HAMA评分均明显减低(P〈0.01),但两组间差异无显著性(P〉0.05)。两组均未出现严重的药物不良反应,主要不良反应SSRIs组为胃肠道不适,米氮平有嗜睡、体重增加等。结论:米氮平能明显提高神经性厌食症患者的食欲和体重,改善焦虑抑郁情绪,依从性好,起效时间早于SSRIs,值得在临床上选用。 相似文献
80.
Inhibition of HIV-1 by modification of a host membrane protease 总被引:3,自引:0,他引:3
Bristow Cindy L.; Fiscus Susan A.; Flood Patrick M.; Arnold Roland R. 《International immunology》1995,7(2):239-249
While it is clear that CD4 Is the receptor for the gp120 envelopeprotein of HIV-1, substantial evidence suggests that other hostcell proteins are required for successful membrane fusion. Studieswere initiated to examine the potential for a protein receptorwhich has an elastase-like character to participate in fusionof HIV-1 with permissive host cells. A synthetic elastase inhibitorwas shown to significantly reduce HIV-1 infectivity when presentduring, but not after, the initial contact between virus andcells. A human T cell elastase-like membrane component was purifiedand shown to be lipid-associated. By competitive Inhibition,the purified protein was shown to bind gp160 within the HIV-1fusion domain. The binding parameters of whole T cell membraneextract, with a hydrophobic pentapeptide representative of thefusion domain, suggested an elastase-like protein is the single,secondary T cell receptor for HIV-1 (K = 1x103 M–1). Thepentapeptide interacted with porcine and human (epithelial andpolymorphonuclear leukocyte), but not murine, elastase isoforms,suggesting its participation In the permissiveness of host cellsto infection. 相似文献