赛庚啶对大鼠胰岛B细胞内分泌功能的影响

目的　探讨赛庚啶对大鼠胰岛Ｂ细胞内分泌功能的影响。方法　应用放射免疫分析、生化分析法和电子显微镜研究赛庚啶（Ｃｙｐｒｏｈｅｐｔａｄｉｎｅ,Ｃｙｐ）对大鼠胰岛Ｂ 细胞内分泌功能的影响。结果　Ｃｙｐ ２．３ｍ ｇ／（ｋｇ·ｄ）,灌胃给药,连续用药 １０ｄ 可引起大鼠血清胰岛素含量降低（Ｐ＜ ０．０１）,而血糖水平则无显著改变。Ｃｙｐ ４．６ｍ ｇ／（ｋｇ·ｄ）,不但引起血清胰岛素含量显著降低,而且使血糖水平显著升高（Ｐ＜ ０．０１）。电镜观察,大鼠胰岛Ｂ 细胞超微结构亦呈退行性改变。结论　Ｃｙｐ 连续用药可抑制大鼠胰岛Ｂ 细胞的内分泌功能。     

Contribution of cholinergic and gabaergic functions to memory processes in BALB/cANnCrlBR mice

Several lines of evidence indicate that glucose influences on memory depend on interactions between glucose, glucoregulation and hippocampal cholinergic function. We previously demonstrated that glucose and scopolamine differentially affected memory consolidation for an operant bar pressing task in two closely-related BALB/c mouse strains. Whereas glucose normally improves memory in several animal strains, memory consolidation was not effected by systemic glucose injections in BALB/cANnCrlBR mice. Moreover, these mice were relatively insensitive to the normally observed amnestic effects of scopolamine. We therefore sought to determine whether cholinergic mechanisms in the dorsal hippocampus were involved in such atypical drug effects on memory processing in that strain of mice. In Experiment 1, we examined whether post-training oxotremorine would also atypically influence memory consolidation for an appetitively reinforced operant bar pressing task following microinjection in the dorsal hippocampus. In Experiment 2, we examined the effects of intrahippocampal GABAA drugs on memory consolidation. The non-selective muscarinic agonist, oxotremorine, dose-dependently impaired memory and the GABAA antagonist, bicuculline, improved retention in BALB/cANnCrlBR mice. It was concluded that GABA-mediated influences on hippocampal pyramidal output in BALB/cANnCrlBR mice and other strains are similar; but the amnestic effects of oxotremorine from the dorsal hippocampus were opposite to facilitating effects normally observed in other animal strains. Results are discussed relative to possible altered septo-hippocampal cholinergic neurotransmission in BALB/cANnCrlBR mice.     

Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors

Summary In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.Presented at the symposium "New Approaches in the Therapy of Breast Cancer", Georgetown University Medical Center, Washington DC, October 1994, generously supported by an education grant from Bristol-Myers Squibb.     

Comparison of in situ hybridization and immunocytochemistry for the detection of residual beta cells in the pancreas of streptozotocin-treated diabetic rats

The relative efficacy of immunocytochemistry versus in situ hybridization in identifying residual beta cells was studied in rats with streptozotocin-induced diabetes. Consecutive sections of pancreas of streptozotocin-treated diabetic rats and control animals were alternately subjected to in situ hybridization (synthetic oligonucleotides complementary to rat preproinsulin mRNA) and immunocytochemistry (monoclonal antibodies to insulin). The results obtained with both methods were quantitated with the use of computer-assisted image analysis, and the ratio of cells positive by immunocytochemistry to those positive by in situ hybridization was determined. Under normoglycaemic conditions the values obtained by immunocytochemistry correlated well with those obtained by in situ hybridization (immuno/in situ > 95%). In the streptozotocin diabetic animals, however, immunocytochemistry resulted in a distinct underestimation of the number of residual beta cells (immuno/in situ < 80%). This difference was even more striking in small islet cell clusters (<100 m) immuno/in situ 20%). These results suggest that in situ hybridization for prohormone mRNA is the method of choice for the identification of residual or regenerating beta cells with very low insulin content. Caution should be used when interpreting quantitative data in diabetic conditions that are based exclusively on immunocytochemical detection methods.     

Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Devices for the treatment of diabetes: today

Although single or multiple daily subcutaneous injections of insulin with syringes are the mainstay of insulin delivery techniques for the treatment of diabetes mellitus, several other methods are now available. The present paper will review the main problems occurring with the classical subcutaneous insulin therapy and the possible solutions given by the use of new devices, including more particularly insulin jet injectors, pens, and portable pumps. This review has to be considered as an introduction to the presentations of this symposium devoted to implantable pumps, glucose sensors, and artificial pancreas, respectively.     

Effects of prostacyclin analogue,OP-2507, on function and metabolism in the ischemic working rat heart

We examined the effects of a new stable prostacyclin analogue, OP-2507, on myocardial function and metabolism in the ischemic working rat heart preparation. The hearts were perfused with Krebs-Henseleit bicarbonate (KHB) buffer, and whole heart ischemia was induced by one-way aortic valve for 15min follows by reperfusion for 30min. In the treated hearts, OP-2507, 20ng·ml^–1, was administered to KHB buffer from the beginning to the end of experiment. During ischemia, coronary flow in the OP-2507 group increased significantly more than that in the control group. The mechanical performance of both groups was impaired after ischemia. However, the recovery of coronary flow, cardiac output, peak systolic pressure and LV dP/dT_max was significantly higher in the treated group than in the control group. The incidence of ventricular fibrillation during reperfusion was 100% and 25% in the control and the OP-2507 groups, respectively. Myocardial ATP content was significantly higher in the treated hearts than that in the control hearts. These results indicate that this stable prostacyclin analogue is beneficial in myocardial ischemia, even without its well known action of preventing platelet aggregation.(Oguchi T, Kashimoto S, Nakamura T, et al.: Effects of prostacyclin analogue, OP-2507, on function and metabolism in the ischemic working rat heart. J Anesth 6: 446–454, 1992)     

胰岛素基础--大剂量方案治疗青春期1型糖尿病儿童的疗效观察

目的：观察胰岛素基础—大剂量注射方案治疗青春期1型糖尿病儿童的临床疗效。方法：采用胰岛素基础—大剂量治疗方案4次／d(睡前注射中效，三餐前注射短效)治疗4例青春期糖尿病患儿6月。结果：4例患儿慢性高血糖症得以控制，空腹及餐后血糖水平接近正常，糖化血红蛋白(HbA1α)基本恢复正常，酮症酸中毒发生减少。结论：胰岛素基础—大剂量方案治疗能够控制青春期糖尿病血糖水平。     

GAD-Ab、ICA和IAA联合检测对成人隐匿性自身免疫性糖尿病的诊断价值（附138例分析）

目的 评价血清谷氨酸脱羧酶抗体(GAD—Ab)、胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA)联合测定对成人隐匿性自身免疫性糖尿病(LADA)的诊断价值。方法 利用ELISA法测定138例临床诊断为2型糖尿病患者及46例健康者的血清GAD—Ab、ICA和IAA，并比较抗体阳性和阴性患者的临床特征。结果 临床诊断为2型糖尿病患者GAD-Ab和ICA的阳性率分别为20．3％和11．6％，与对照组比较差异有显著性(X^2=8．528，P=0．003；X^2=5．841，P=0．016)；IAA的阳性率8．0％。与对照组比较无显著性差异(X^2=1．902，P=0．168)。抗体阳性患者血清C肽水平较低。结论 胰岛自身抗体联合检测可提高LADA患者的检出率；LADA患者胰岛储备功能较差。     

针灸对胰岛素抵抗影响研究的概况

本文系统回顾了近年来胰岛素抵抗的针灸治疗的研究概况。发现针灸在调节高血压、糖尿病、中风、肥胖症等的胰岛素抵抗方面有显著的疗效．对于胰岛素抵抗可致的各方面的病理生理改变均有不同程度改善。