An Isolated Perfused Rat Kidney Model for the Evaluation of the Effect of Glucose on Renal Tubular Epithelial Morphology

An isolated perfused kidney model was used to evaluate the effect of hyperglycemia on renal tubular epithelial cell morphology. Ten Sprague–Dawley rat kidneys were perfused with Krebs–Henseleit buffer containing 70 mmol/L of glucose (five for 1 h and five for 2 h). Two control groups consisted of 10 kidneys perfused with Krebs–Henseleit buffer without hyperglycemia (five for 1 h and five for 2 h), and 10 nonperfused contralateral kidneys placed in the same environment for the same duration. The hyperglycemia group had significantly increased renal tubular vacuolization (p < 0.001) compared to both control groups at 1 and 2 h. The isolated perfused kidney model recapitulates the renal tubular vacuolization phenotype found in hyperglycemia and may be a potential tool for the investigation into causal factors in renal histology. The full pattern of the Armanni–Ebstein phenomenon was not, however, reproduced, suggesting that this change requires more time or involves more complex factors.     

Septic Ketoacidosis—A Potentially Lethal Entity with Renal Tubular Epithelial Vacuolization

Fatal ketoacidosis due to diabetes mellitus, alcoholism, and starvation may produce characteristic basal vacuolization of renal tubular epithelial cells (RTEC). Septic ketoacidosis has recently been recognized clinically as a distinct condition in which septicemia can lead to elevation of ketones and various anions unrelated to diabetes mellitus, alcoholism, or caloric deprivation. We report four lethal cases with significantly elevated vitreous ketones secondary to sepsis and/or severe localized infection in individuals with no history of diabetes mellitus, alcoholism, or starvation. Three of four cases exhibited typical basal vacuolization of RTEC. We suggest that septic ketoacidosis is an appropriate cause of death in the forensic setting where sepsis or severe localized infection is found with significant ketoacidosis (β‐hydroxybutyrate > 5 mmol/L)—in the absence of diabetes mellitus, alcoholism, starvation, or other states associated with accelerated ketogenesis. The finding of basal vacuolization of RTEC in such cases provides morphological support for the underlying metabolic derangement.     

Vitreous Fluid and/or Urine Glucose Concentrations in 1335 Civil Aviation Accident Pilot Fatalities*

Abstract: During aviation accident investigations, vitreous fluid and urine samples from pilot fatalities are analyzed for glucose and blood for hemoglobin A_1c (HbA_1c) to monitor diabetic pilots and to discover other pilots with undiagnosed/unreported diabetes. The prevalence of elevated glucose concentrations in fatally injured pilots was evaluated by searching the Civil Aerospace Medical Institute’s Toxicology Database for the period 1998–2005. Out of 1335 pilots involving 363 vitreous fluid, 365 urine, and 607 vitreous fluid and urine analyses, 43 pilots had elevated glucose in vitreous fluid (>125 mg/dL) and/or in urine (>100 mg/dL). Of the 20 pilots whose blood samples were analyzed, nine had >6% HbA_1c—four were known diabetics, and five were unknown diabetics. Urinary glucose levels were elevated in all 13 known hyperglycemic pilots. A considerable number of pilots (30 of 43) had elevated glucose and HbA_1c (5 of 20), suggesting undiagnosed/unreported diabetic conditions.     

Fatal Diabetic Ketoacidosis and Antipsychotic Medication

Hyperglycemia and new onset diabetes have been described with certain antipsychotic medications and some of the initial presentations are fatal diabetic ketoacidosis (DKA). We report 17 deaths due to DKA in psychiatric patients treated with second generation antipsychotic medications. Death certificates and toxicology data were searched for DKA and hyperglycemia. We reviewed the medical examiner records which included the autopsy, toxicology, police, and medical examiner investigators' reports. The decedents ranged in age from 32 to 57 years (average 48 years). There were 15 men and two women. The immediate cause of death was DKA in all. The psychiatric disorders included: 10 schizophrenia, three bipolar/schizophrenia, two bipolar, and two major depression. The most frequent atypical antipsychotic medications found were quetiapine and olanzapine followed by risperidone. In 16 deaths, we considered the medication as primary or contributory to the cause of death.     

2型糖尿病患者常见体质与IL 6、IL 10、IL 10R1基因多态性的相关性研究

目的 研究2型糖尿病人群常见体质类型阴虚质、痰湿质与白细胞介素 6（interleukin 6, IL 6）、白细胞介素 10（interleukin 10,IL 10）、白细胞介素 10受体1（interleukin 10 receptor 1,IL 10R1） 基因多态性的相关性,筛选2型糖尿病常见中医体质的部分易感基因,为2型糖尿病的早期防治提供一定的依据。方法 收集2型糖尿病患者共395例,进行基因检测,应用聚合酶链反应 限制性片段长度多态性（PCR RFLP）技术检测IL 6的rs1800796位点、IL 10的rs1800871位点、IL 10R1的rs2228055位点,进行基因分型。参照中华中医药学会《中医体质分类与判定》进行中医体质辨识。对2型糖尿病常见体质类型阴虚质、痰湿质与IL 6、IL 10、IL 10R1基因多态性的相关性进行统计分析。结果 痰湿质组IL 10 rs1800871 CT基因型比例明显低于非痰湿质CT基因型比例（30.4% vs 45.9%,χ2=6.137,P=0.013）。以IL 10 rs1800871 CC为参照,IL 10 rs1800871 CT为2型糖尿病阴虚质的主要危险因素（P=0.019,OR=2.593,95% CI为1.710～5.746）;以IL 10 rs1800871 CT为参照,IL 10 rs1800871 TT为2型糖尿病痰湿质的主要危险因素（P=0.025,OR=1.809,95% CI为1.076～3.041）。结论 IL 10 rs1800871位点CT基因型是2型糖尿病阴虚质患者的危险因素,IL 10 rs1800871位点TT基因型是2型糖尿病痰湿质患者的危险因素,IL 10基因多态性可能是2型糖尿病阴虚质、痰湿质的分子遗传学基础之一。     

益气养阴活血法对糖尿病合并脑缺血大鼠海马脑源性神经营养因子表达及空间学习记忆的影响

目的 观察益气养阴活血法对糖尿病合并脑缺血大鼠空间学习记忆能力及脑源性神经营养因子（brain derived neurotrophic factor, BDNF）表达的影响,并运用工具药（BDNF的Trk受体抑制剂）证实BDNF通路在其中的作用。方法 将大鼠分为假手术组、模型对照组（糖尿病合并脑缺血伴气阴两虚、瘀血阻络证）、益气养阴活血组、益气养阴活血+K252a组、益气活血组,每组20只,选用具有益气养阴活血作用的人参、川芎、玉竹、黄精组合,运用免疫组织化学法和Morris水迷宫实验观察益气养阴活血药对糖尿病合并脑缺血模型大鼠空间学习记忆的作用及对BDNF表达的影响。结果 与模型对照组比较,益气养阴活血药物和益气活血药物均可以明显增加糖尿病合并脑缺血大鼠海马齿状回BDNF的表达（P<0.01）,益气养阴活血药物显著缩短模型大鼠找到水下平台的潜伏期（P<0.01）,益气养阴活血药物和益气活血药物均显著延长大鼠在原水下平台的停留时间（P<0.05,或P<0.01）,其中益气养阴活血药物效果优于益气活血药物（P<0.05）。侧脑室注射K252a可以阻断益气养阴活血药物促进模型大鼠的空间记忆能力的恢复（P<0.01）。结论 益气养阴活血药物可能通过促进模型大鼠海马齿状回BDNF的表达而改善空间记忆功能。     

非胰岛素依赖性糖尿病针刺辨治探要

非胰岛素依赖性糖悄病的病理改变是当液代谢失调，而脾胃功能失常是重要的致病因素，肾气不足亦不可忽视。辩证分为胃肠实热、脾虚湿阻、肾气不足和肝郁气滞甲型，主要治疗方法有清泻胃肠实热、平调脾胃功能、补益肾气、通调水道、疏肝理气等。     

针刺对2型糖尿病大鼠脂肪组织INSR基因表达的影响

目的探讨针刺对2型糖尿病(type 2 diabetes mellitus,T2DM)机体脂肪组织胰岛素受体(insulinreceptor,INSR)基因表达的影响。方法给食源性肥胖大鼠腹腔注射小剂量链脲佐菌素复制T2DM模型,随机分为针刺组、优降糖组和模型组,设正常对照组。处理4周后,采用罗氏活力型血糖仪测空腹血糖(fast-ing blood sugar,FBS),采用放射免疫法检测空腹胰岛素(fastinginsulin,FINS),采用原位杂交检测脂肪细胞INSRmRNA表达,计算胰岛素敏感性指数(insulin sensitivity index,ISI)和稳态模型评估胰岛素抵抗(homeostasis model assessment of insulin resistance,Homa-IR)指数。结果与正常组比较,模型组FBS、FINS、ISI、Homa-IR水平显著上升(P<0.01),INSR基因水平表达显著降低(P<0.01);与模型组比较,治疗后优降糖组和针刺组FBS、FINS、ISI、Homa-IR显著下降(P<0.05,或P<0.01),INSR基因表达显著升高(P<0.01)。...