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81.
MASASHI YOSHIDA GO WAKABAYASHI HIDEKI ISHIKAWA YOSHIHIDE OTANI MOTOHIDE SHIMAZU TETSURO KUBOTA KOICHIRO KUMAI IWAO KUROSE SOICHIRO MIURA HIROMASA ISHII MASAKI KITAJIMA 《Journal of gastroenterology and hepatology》1998,13(1):104-108
The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury. 相似文献
82.
Wilkinson Karen F. Rush Bob D. Sharma Satish K. Evans David B. Ruwart Mary J. Friis Janice M. Bohanon Michael J. Tomich Paul K. 《Pharmaceutical research》1993,10(4):562-566
We showed previously that a commercially available synthetic tetradecapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, produces authentic angiotensin I (Ang I) upon incubation with the HIV-1 protease (S. K. Sharma et al., Anal. Biochem. 198:363, 1991). Therefore, we developed an Ang-I based activity assay for HIV protease inhibitors based on the technology developed earlier (M. J. Ruwart et al., Pharm. Res. 7:407, 1990; S. K. Sharma et al., Anal. Biochem. 186:24, 1990) for tracking renin inhibitors in rat sera. Ditekiren was either extracted from sera with ethyl acetate or assayed after the interfering substances in sera were precipitated with acetonitrile. Purified recombinant HIV-1 protease was added to extracted rat serum and the enzymatic reaction was initiated in the presence of the tetradecapeptide substrate. The inhibition of Ang I production was measured by a commercially available RIA kit. The cleanup methodology also enabled a commercially available Proteinase Scintillation Proximity Assay (SPA, Amersham) to quantify ditekiren in rat serum through the addition of recombinant HIV-1 protease and cleavage of substrate from SPA beads. Results were confirmed by HPLC or by the renin assay for ditekiren, which inhibits both aspartyl proteases. These technologies should prove useful for assessing serum levels of HIV protease inhibitors in rat. 相似文献
83.
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
84.
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
85.
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
86.
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
87.
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
88.
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
89.
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
90.
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