实验性2型糖尿病大鼠模型的建立和评价(Ⅰ)——体重、血糖和肝糖原的变化

目的：用高脂饲料加小剂量STZ腹腔注射建立实验性2型糖尿病大鼠模型。方法：采用Wistar大鼠,分为正常对照组、高脂饲料组、小剂量STZ组（30 mg/kg）和高脂饲料加小剂量STZ（30 mg/kg）组,每10 d测定大鼠体重、空腹血糖和肝糖原等指标,连续50 d,对各组大鼠上述指标进行比较和评价。结果：①体重：高脂饲料组大鼠体重呈连续上升趋势,小剂量STZ组和高脂饲料加小剂量STZ组大鼠体重呈先降低再恢复的趋势;②空腹血糖：高脂饲料组大鼠空腹血糖轻微升高,小剂量STZ组大鼠空腹血糖呈上升的趋势,高脂饲料加小剂量STZ组大鼠空腹血糖呈明显上升趋势;③肝糖原：高脂饲料组大鼠肝糖原明显升高,小剂量STZ组、高脂饲料加小剂量STZ组大鼠肝糖原未见明显改变;结论：高脂饲料加小剂量STZ腹腔注射能成功诱导2型糖尿病大鼠模型,这种造模方法具有成模后血糖维持在较高水平、自身缓解较少、症状较轻和动物状态良好等优点。     

Inhibitory effect of ketamine on phosphorylation of the extracellular signal-regulated kinase1/2 following brain ischemia and reperfusion in rats with hyperglycemia

To determine if the inhibitory effects of ketamine on the extracellular signal-regulated kinase (ERK) 1/2 are involved in reduction of the hyperglycemia-exaggerated cerebral ischemic lesion, rats with normoglycemia, hyperglycemia, or hyperglycemia supplemented with ketamine were subjected to 15 min of forebrain ischemia, and then, reperfusion for 0.5, 1, and 3h. Phosphorylation of ERK1/2 in the brain tissues was assessed by immunohistochemistry and Western blot analysis. In rats with normoglycemia, we demonstrated a moderate increase of the ERK1/2 phosphorylation in the cingulum cortex and hippocampus CA3 following an ischemic intervention. It quickly dropped to control levels after reperfusion for 0.5h. In rats with hyperglycemia, however, the increase of the ERK1/2 phosphorylation in these areas was significantly higher in all animals reperfused. The neuronal death, detected by the TdT-mediated-dUTP nick end labeling assays, was found in the cingulum cortex (5.23+/-2.34, per high power feild) and hippocampus CA3 areas (6.29+/-3.68, per 1mm(2)) in hyperglycemic group after reperfusion for 3h. With ketamine treatment, the ERK1/2 phosphorylation in cingulum cortex and hippocampus CA1 and CA3 areas was found to be the same as that in normoglycemia rats. Our results suggest that hyperglycemia may increase the ischemic insult through modulation of the signal transduction pathways involving ERK1/2. The inhibitory effects of ketamine on the hyperglycemia-activated ERK1/2 phosphorylation are probably through inhibition of the N-methyl d-aspartate-mediated calcium influx, which subsequently reduce the hyperglycemia-exaggerated cerebral damage.     

Substantia nigra damage induced by ischemia in hyperglycemic rats

Summary Preischemic hyperglycemia induced by feeding or glucose infusion worsens the brain damage and the clinical outcome following ischemia of a given duration and density, and characteristically causes postischemic seizure activity. Light microscopy has previously showed that, in the rat, transient hyperglycemic ischemia induced by bilateral carotid occlusion in combination with arterial hypotension causes a uni- or bilateral lesion in the pars reticulata of the substantia nigra. Since this region has a central role in preventing seizure discharges the present study was carried out to determine the ultrastructural characteristics of this lesion. In rats with 10 min of transient hyperglycemic ischemia followed by recirculation for 1 to 18 h, the pars reticulata of the substantia nigra showed signs of status spongiosus, as well as extensive nerve cell alterations. These changes were observed after all recovery periods studied. The spongiotic appearance was mainly caused by swelling of dendrites and, to a lesser degree, by astrocytic swelling. The dendrites were expanded at all recovery times but the severity increased during the later periods of recirculation. These swollen dendrites contained severely expanded mitochondrias and endoplasmic reticulum. The cytoskeletal elements showed disordered lining of microtubules. Two major types of nerve cell alterations were present: a pale and a dark variety. The pale type was the most frequent cell alteration. It occurred in all experimental groups and at all time points. Redistribution of the nuclear chromatin and of cytoplasmic organelles as well as swelling of the same type as in the dendrites were the essential changes. The dark neurons were much fewer in number and occupied a peripheral position in the pars reticulata. Astrocytic foot processes appeared to be dilated around the dark neurons. Swelling of astrocyte processes was most pronounced in the 1 h recovery animals. Both types of neurons showed severe mitochondrial alterations of the type observed in dendrites. Occasionally, mitochondrial alterations were found in astrocytic processes as well. Blood vessel alterations were lacking. Previous studies have shown that in this model of ischemia the substantia nigra has a relatively well-preserved blood perfusion. In view of this the extensive histopathological lesions are surprising. We speculate that the lesions primarily involve excitotoxic damage to dendrites, with pronounced lactic acidosis playing a contributory role in causing axonal and glial pathology as well.Supported by grants from the Swedish Medical Research Council (project 12X-03020 and project 14X-263) and from the U.S. Public Health Service via the N.I.H. (grant No. 5 RO1 NS07838)     

脑梗死并发高血糖临床研究

目的:探讨并发高血糖对脑梗死的临床影响。方法:对136例脑梗死的临床资料进行回顾性分析。结果:脑梗死并发高血糖28例(20.6％),高血糖组与正常血糖组比较,高血糖组临床神经功能缺损程度重,治愈率低。结论:血糖升高与脑梗死临床病情密切相关。检测血糖可作为观察脑梗死病情及判定预后的一项客观指标。     

老年Ⅱ型糖尿病患者血清C反应蛋白与血糖相关性分析

目的 :考察老年Ⅱ型糖尿病 (NIDDM)患者血清C 反应蛋白水平及其与血糖水平的相关性。方法 :选取老年NIDDM患者 183例 ,其中病史 5年以上血糖控制良好、无并发症且无感染性疾病者 97例 ;初次确诊、血糖控制不良者 86例 ,其中无感染性疾病者 5 0例 ,有急性腹泻或尿路感染者 36例。未患NIDDM者 70人作为对照组 ,其中 35人为健康体检者 ,另 35人为有发热性疾病、有症状的感染或慢性感染性疾病患者。测定空腹血糖和C 反应蛋白浓度。结果 :老年NID DM患者血清C 反应蛋白水平显著升高 ,结论 :高血糖可能是血清C 反应蛋白水平增高的相关因素。     

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was triciribine 20 mg/m² per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m² per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m² until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed The maximum dose was 40 mg/m². Two patients died, one each at the 35 and 40 mg/m² levels, respectively, 3 months and 6 weeks after their last course, one without interveing disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of 35 mg/m² has unacceptable toxic effects.This work was performed under National Cancer Institute contract 1-CM-57739     

Decrease of some metabolic and physiologic effects of diazoxide by propranolol in rat

Summary Diazoxide significantly decreased the blood pressure and relaxed the uterine muscle in anaesthetized normotensive rats. A marked elevation of blood glucose followed the intravenous injection of diazoxide. The hyperglycemic and the uterine relaxing response could be significantly decreased by injection of propranolol prior to diazoxide. The hypotensive effect was not diminished by propranolol, however. In liver and uterus the content of cAMP was increased following diazoxide treatment in vivo. The rise in cAMP could be completely inhibited by propranolol, indicating a -receptor stimulation being the cause of the cAMP elevation.     

A study on the glycemic,lipid and blood pressure control among the type 2 diabetes patients of north Kerala,India

AimThe aim of the study was to detect the level of comprehensive diabetes control among the diabetic patients of Kerala, India.MethodsPatients (1200) were randomly selected from a diabetes care center. Their blood sugar, biochemical and anthropometric measurements were done and statistically analyzed.ResultsOnly 28.3% had their HbA1c at or below 7% and 45% above 9%. One-third of the female and one-fifth of the male patients had coronary artery disease. The prevalence of hypertension was almost equal in both sexes. However, there was a statistically significant higher systolic blood pressure (mean 162.12 mmHg vs 147.49 mmHg, p = 0.01044) among females. The total cholesterol was above 200 mg/dl in 42.1% of males and 45.61% of females. The triglyceride was >150 mg/dl in 38.6% males and 50.88% females. Low high density lipoprotein (HDL) cholesterol levels were found in 20.07% of males and 41.12% of females (p = 0.0445). The mean low density lipoprotein (LDL) was 121.75 (± 32.29)ConclusionThe mean blood sugar values are found to be high, which will lead to a predictable increase in vascular disease, which in turn will affect the quality of health and productivity of the individual and the economic growth of the society as a whole. Studies suggest that therapeutic interventions to improve glycemic control may reduce the risk of cardiovascular disease and microvascular disease.This study shows that the level of diabetes control in Kerala is unsatisfactory. We need more medications, better strategies and more emphasis on glycemic management than we are currently able to apply.