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Comparison of capillary electrophoresis with HPLC for diagnosis of factitious hypoglycemia

CLINICAL CHEMISTRY 2000年第11期46卷 1773-1780页

作者： Paroni, R Comuzzi, B Arcelloni, C Brocco, S de Kreutzenberg, S Tiengo, A Ciucci, A Beck-Peccoz, P Genovese, S Hosp San Raffaele Lab Separat Techniques IRCCS I-20132 Milan Italy Azienda Osped Unit Metab Dis I-35100 Padua Italy Univ Padua I-35100 Padua Italy Ist Clin Humanitas Endocrinol & Diabet Unit I-20089 Milan Italy Osped Maggiore IRCCS Inst Endocrinol Sci I-20122 Milan Italy

Background: The diagnosis of "factitious hypoglycemia" is essentially based on the disclosure of hypoglycemic agents in blood or urine. The aim of this study was to evaluate the performance of capillary electrophoresis (CE) as a quantitative method for determination of chlorpropamide, tolbutamide, glipizide, gliclazide, and glibenclamide in serum. Methods: Serum samples (1 mt), with internal standard added, were purified by solid-phase extraction on OASIS(TM) HLB cartridges (Waters), dried under reduced pressure, and reconstituted with 30-60 muL, of acetonitrile: H2O. Analysis was carried out by micellar electrokinetic capillary chromatography in 5 mmol/L berate, 5 mmol/L phosphate, 75 mmol/L sodium cholate, pH 8.5, containing 25 mL/L methanol. Separation was accomplished in a 20 cm x 50 mum (i.d.) silica capillary at 25 degreesC and a constant voltage of +10 kV. Pharmacokinetics of gliclazide (80-mg tablet) in a diabetic patient were assayed by both HPLC and CE. Two hypoglycemic patients positive by HPLC analysis for unreported gliclazide and tolbutamide overdose were also screened by CE. Results: Separation of six drugs (including the internal standard) was accomplished in 5 min plus 5 min rinsing. The between-day CV of the ratio of the areas of the sulfonylurea drugs to internal standard was <1% (n = 10). Linearity (r(2) 0.998) and recovery (greater than or equal to 80%) were good for all sulfonylurea drugs tested. Pharmacokinetic curves for gliclazide by CE and HPLC were superimposable. CE analysis confirmed the HPLC diagnosis of surreptitious abuse of gliclazide and tolbutamide. Conclusion: CE is a useful tool in the clinical chemistry and toxicology laboratory for drug monitoring and pharmacokinetic investigations. (C) 2000 American Association for Clinical Chemistry.

关键词：色谱法高压液相糖尿病 2型/血液糖尿病 2型/药物疗法电泳毛细管格列齐特/副作用格列齐特/血液格列齐特/药代动力学低血糖症/血液低血糖症/化学诱导低血糖症/诊断降血糖药/副作用降血糖药/血液降血糖药/药代动力学结果可重复性磺酰脲化合物/副作用磺酰脲化合物/血液磺酰脲化合物/药代动力学甲苯磺丁脲/副作用甲苯磺丁脲/血液成年人女(雌)性人类中年人

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IMPROVED CARE OF PATIENTS WITH DIABETES THROUGH TELECOMMUNICATIONS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES 1992年第1期670卷 141-145页

作者： SHULTZ, EK BAUMAN, A HAYWARD, M HOLZMAN, R Program in Medical Information Science Dartmouth-Hitchcock Medical Center Hanover New Hampshire 03756

This project tested the importance of enhanced information transfer of home monitoring results to health care providers. The study tested whether computer-assisted communication of medical information between the chronic care patient and the physician can result in health care benefit. The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus. Patients connected a glucometer to an intelligent modem weekly for six to nine months. Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site. Data smoothing, trend analysis, and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit. The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period. A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group, but not in the control group.

关键词：算法血糖自我监测计算机通信网络/组织和管理费用效益分析糖尿病 1型/血液糖尿病 1型/并发症糖尿病 1型/药物疗法诊断计算机辅助家庭护理(非专业) 高血糖症/血液低血糖症/血液胰岛素/治疗应用病案微型计算机卫生保健质量女(雌)性人类男(雄)性

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Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: Blood genomic fingerprints of disease

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ANNALS OF NEUROLOGY 2001年第6期50卷 699-707页

作者： Tang, Y Lu, AG Aronow, BJ Sharp, FR Univ Cincinnati Vontz Ctr Mol Studies Dept Neurol Cincinnati OH 45267 USA Univ Cincinnati Program Neurosci Cincinnati OH 45267 USA Univ Cincinnati Childrens Hosp Res Fdn Div Mol Dev Biol & Informat Cincinnati OH 45267 USA

Using microarray technology, we investigated whether the gene expression profile in white blood cells could be used as a fingerprint of different disease states. Adult rats were subjected to ischemic strokes, hemorrhagic strokes, sham surgeries, kainate-induced seizures, hypoxia, or insulin-induced hypoglycemia, and compared with controls. The white blood cell RNA expression patterns were assessed 24 hours later using oligonucleotide microarrays. Results showed that many genes were upregulated or downregulated at least twofold in white blood cells after each experimental condition. Blood genomic response patterns were different for each condition. These results demonstrate the potential of blood gene expression profiling for diagnostic, mechanistic, and therapeutic assessment of a wide variety of disease states.

关键词：缺氧/血液缺氧/遗传学缺氧/代谢脑出血/血液脑出血/化学诱导脑出血/代谢兴奋性氨基酸激动剂基因表达谱遗传标记葡萄糖/药理学低血糖症/血液低血糖症/遗传学低血糖症/代谢胰岛素/药理学红藻氨酸白细胞/药物作用白细胞/生理学寡核苷酸序列分析大鼠 Sprague-Dawley 逆转录聚合酶链反应发作/血液发作/化学诱导发作/遗传学发作/代谢动物人类男(雄)性大鼠

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EFFECT OF PROPRANOLOL ON SOME ADRENALINE-INDUCED AND INSULIN-INDUCED METABOLIC CHANGES IN MAN

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ACTA DIABETOLOGICA LATINA 1975年第1期12卷 41-51页

作者： MASSARA, F CAMANNI, F MOLINATTI, G UNIV TURIN IST FARMACOL & TERAPIA SPERIMENTALE CORSO POLONIA 14 10126 TURIN ITALY UNIV TURIN CATTEDRA ENDOCRINOL CORSO POLONIA 14 10126 TURIN ITALY

The effect of propranolol on adrenaline- and insulin-induced changes in blood glucose pyruvate, lactate, phosphorus and potassium were examined in 29 apparently healthy volunteers. A slight, but significant reduction in adrenaline-induced hyperglycaemia was noted, along with suppression of both the increase in pyruvate and lactate and the decrease in phosphorus and potassium attributable to this catecholamine. There was no significant change in the blood glucose curve after insulin whereas insulin-induced increases in pyruvate and lactate were reduced by 44%±17.7 (mean±SEM) and 78%±5.4 respectively, and the fall in phosphorus by 48%±3.1; the decrease in potassium, however, was not significantly modified. These findings suggest that changes in plasma pyruvate, lactate and inorganic phosphates induced by insulin, and regarded as espressions of its peripheral metabolism, are greatly dependent on the β-adrenergic effect of the endogenous catecholamines released during the time when blood glucose values are low.

关键词：血糖肾上腺素/药理学低血糖症/血液胰岛素/药理学乳酸盐类/血液磷/血液钾/血液普萘洛尔/药理学丙酮酸盐类/血液成年人女(雌)性人类男(雄)性

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Chlorpropamide toxicity with survival despite 27-day hypoglycemia

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JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY 1999年第7期37卷 869-871页

作者： Ciechanowski, K Borowiak, KS Potocka, BA Nowacka, M Dutkiewicz, G Pomeranian Med Univ Dept Forens Med PL-70111 Szczecin Poland

Case Report: In the past 5 years at our institution, 12 cases involving the ingestion of chlorpropamide 3-15 g were fatal. We report a 23-year-old woman with an estimated ingestion of chlorpropamide 5-10 g. Initial cardiovascular collapse, attributed to the blockade of potassium channel transport, responded to intensive support including 3 days of cardiac pacing. Urinary excretion of chlorpropamide and hypoglycemia persisted until day 27. The toxic mechanisms and high risk of chlorpropamide are summarized. A fatal therapeutic dose ratio as low as 4:1 has made this antidiabetic agent obsolete.

关键词：氯磺丙脲/中毒氯磺丙脲/尿心电描记术低血糖症/血液低血糖症/化学诱导降血糖药/中毒降血糖药/尿呼吸人工休克/化学诱导休克/病理生理学自杀未遂成年人女(雌)性人类

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Pancreatic β-cell K_ATP channel activity and membrane-binding studies with nateglinide:: A comparison with sulfonylureas and repaglinide

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第2期293卷 444-452页

作者： Hu, SL Wang, SY Fanelli, B Bell, PA Dunning, BE Geisse, S Schmitz, R Boettcher, BR Novartis Inst Biomed Res Metab & Cardiovasc Dis Dept Summit NJ 07901 USA Novartis Pharma Res Core Technol Area Basel Switzerland

Nateglinide (A-4166) is an amino acid derivative with insulinotrophic action in clinical development for treatment of type 2 diabetes. The aim of this study was to determine whether nateglinide's interaction at the K-ATP channel/sulfonylurea receptor underlies its more rapid onset and shorter duration of action in animal models. Binding studies were carried out with membranes prepared from RIN-m5F cells and HEK-293 cells expressing recombinant human sulfonylurea receptor 1 (SUR1). The relative order for displacement of [H-3]glibenclamide in competitive binding experiments with RIN-m5F cell membranes was glibenclamide > glimepiride > repaglinide > glipizide > nateglinide > L-nateglinide > tolbutamide. The results with HEK-293/recombinant human SUR1 cells were similar with the exception that glipizide was more potent than repaglinide. Neither nateglinide nor repaglinide had any effect on the dissociation kinetics for [H-3]glibenclamide, consistent with both compounds competitively binding to the glibenclamide-binding site on SUR1. Finally, the inability to measure [H-3]nateglinide binding suggests that nateglinide dissociates rapidly from SUR1. Direct interaction of nateglinide with K-ATP channels in rat pancreatic beta-cells was investigated with the patch-clamp method. The relative potency for inhibition of the K-ATP channel was repaglinide. glibenclamide. nateglinide. Kinetics of the inhibitory effect on K-ATP current showed that the onset of inhibition by nateglinide was comparable to glibenclamide but more rapid than that of repaglinide. The time for reversal of channel inhibition by nateglinide was also faster than with glibenclamide and repaglinide. These results suggest that the unique characteristics of nateglinide are largely the result of its interaction at the K-ATP channel.

关键词： ATP结合匣式转运子结合竞争性/药物作用氨甲酸酯类/药代动力学氨甲酸酯类/药理学细胞膜/药物作用细胞膜/代谢细胞分离细胞培养的环己烷类/药理学葡萄糖/代谢格列本脲/药理学糖基转移酶类低血糖症/血液低血糖症/化学诱导降血糖药/药理学胰岛素/代谢胰岛/代谢 KATP通道动力学膜蛋白质类膜片钳术苯丙氨酸/类似物和衍生物苯丙氨酸/药理学哌啶类/药代动力学哌啶类/药理学钾通道阻滞剂钾通道/药物作用钾通道内向整流大鼠 Sprague-Dawley 阻遏蛋白质类/生物合成阻遏蛋白质类/遗传学酿酒酵母蛋白质类磺酰脲化合物/药代动力学磺酰脲化合物/药理学动物人类男(雄)性大鼠

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Secondary adrenal failure in a young woman presenting as hypoglycaemic coma

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ANNALS OF CLINICAL BIOCHEMISTRY 1999年第1期36卷 114-115页

作者： Al-Jubouri, MA Whiston Hosp Dept Chem Pathol Prescot L35 5DR Merseyside England

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新生儿感染并发低血糖及其血浆胰岛素水平的探讨

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中华儿科杂志 1985年第5期23卷 277-279+318-319页

作者：魏克伦王开荣张家骧吴荫云傅爱莲中国医科大学附属第三医院儿科

通过对101例患各种感染性疾病新生儿的血糖检测,发现其低血糖的并发率较高(21/101,20.8%)。观察组(低血糖)中12例存活者入院时血糖均值与恢复期比较,差异非常显著(t=10.612,P0.05),但也说明血糖改变与感染及其严重程度有关。血浆胰岛素... 详细信息

通过对101例患各种感染性疾病新生儿的血糖检测,发现其低血糖的并发率较高(21/101,20.8%)。观察组(低血糖)中12例存活者入院时血糖均值与恢复期比较,差异非常显著(t=10.612,P<0.01);存活者与死亡者入院时血糖均值差异虽不显著(t=2.079,P>0.05),但也说明血糖改变与感染及其严重程度有关。血浆胰岛素检测结果显示,观察组与对照组 (血糖正常) 差异不显著。本文提出新生儿生后3天内也应以40 mg/dl作为低血糖诊断界限值,且血糖在20 mg/dl以下者提示病情危重。

关键词：低血糖症/血液细菌感染/并发症胰岛素/血液

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Lipoic acid acutely induces hypoglycemia in fasting nondiabetic and diabetic rats

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METABOLISM-CLINICAL AND EXPERIMENTAL 1999年第4期48卷 504-510页

作者： Khamaisi, M Rudich, A Potashnik, R Tritschler, HJ Gutman, A Bashan, N Ben Gurion Univ Negev Fac Hlth Sci Dept Clin Biochem Beer Sheva Israel Soroka Med Ctr Fac Hlth Sci Dept Clin Biochem IL-84101 Beer Sheva Israel Asta Med Frankfurt Germany Hadassah Med Ctr Dept Clin Biochem IL-91120 Jerusalem Israel

Lipoic acid (LA) is a unique antioxidant that increases peripheral glucose utilization in diabetic patients. This study was conducted to investigate whether the inhibition of glucose production could be an additional mechanism for the action of LA. Intravenous (IV) LA injection (100 or 60 mg/kg body weight) to fasting nondiabetic or streptozotocin (STZ)-induced diabetic rats caused a rapid reduction in blood glucose with no effect on circulating insulin levels. In vivo conversion of fructose to glucose was not inhibited by LA, whereas the gluconeogenesis flux from alanine was completely prevented. Reduced liver pyruvate carboxylase (PC) activity in vivo is suggested by the finding that LA induced a decrease in liver coenzyme A (CoA) content (44% and 28% reduction in nondiabetic and diabetic rats, respectively, compared with vehicle-treated animals) and liver acetyl CoA content (80% and 67% reduction in nondiabetic and diabetic rats, respectively). A reduction in plasma free carnitine (42% and 22% in nondiabetic and diabetic rats, respectively) was observed in LA-treated animals, and acylcarnitine revels were increased twofold. This could be attributed to elevated levels of C16 and C18 acylcarnitine, without a detectable accumulation of lipoylcarnitine, Under such conditions, a significant increase in the plasma free fatty acid (FFA) concentration (204% in nondiabetic and 151% in diabetic animals) with no elevation in beta-hydroxybutyrate levels was noted. In conclusion, this study suggests that short-term administration of LA at high dosage to normal and diabetic rats causes an inhibition of gluconeogenesis secondary to an interference with hepatic fatty acid oxidation, This may render LA an antihyperglycemic agent for the treatment of diabetic subjects, who display glucose overproduction as a major metabolic abnormality, Copyright (C) 1999 by W.B. Saunders Company.

关键词： 3-羟基丁酸/血液丙氨酸/血液血糖/代谢肉碱/血液糖尿病实验性/血液禁食/血液脂肪酸类非酯化/血液胰高血糖素/药理学糖原异生/药物作用低血糖症/血液低血糖症/化学诱导肝/酶学肝/代谢丙酮酸/血液大鼠 Sprague-Dawley 硫辛酸/药理学动物男(雄)性大鼠

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Increased responses of glucagon and glucose production to hypoglycemia with intraperitoneal versus subcutaneous insulin treatment

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METABOLISM-CLINICAL AND EXPERIMENTAL 2000年第8期49卷 984-989页

作者： Wan, CKN Giacca, A Matsuhisa, M El-Bahrani, B Lam, L Rodgers, C Shi, ZQ Univ Toronto Dept Physiol Toronto ON Canada Univ Toronto Fac Phys & Hlth Educ Toronto ON Canada Osaka Univ Sch Med Dept Med 1 Osaka 553 Japan

The study aim was to investigate the effect of the route of insulin treatment on the glucagon and glucose production (GP) responses to hypoglycemia in the diabetic rat. Experiments were performed in 4 groups of rats: (1) streptozotocin (STZ)-induced diabetic, untreated (D, n = 7), (2) diabetic treated with subcutaneous insulin (DSC, n = 8), (3) diabetic treated with intraperitoneal insulin (DIP, n = 6), and (4) normal control (N, n = 10). Slow-release insulin implants were used in DSC and DIP rats for 10 to 14 days (3 U/d). A hyperinsulinemic (120 pmol . kg(-1) . min(-1) insulin)-hypoglycemic (glycemia = 2.5 +/- 0.1 mmol/L) clamp following an isoglycemic basal period was performed in 5-hour fasted rats. Basal plasma glucose was normalized in both DSC and DIP rats;however, in DSC but not DIP rats, glucose normalization required peripheral hyperinsulinemia. Tracer-determined GP, which was elevated in D rats, was completely normalized in DIP but only partially corrected in DSC rats. Basal glucagon levels were similar in all groups. During hypoglycemia, GP was suppressed in D rats (Delta, -28.9 +/- 5.0 mu mol . kg(-1) . min(-1)), moderately increased in DSC rats (Delta, 6.1 +/- 5.6, P < .01 v D), but markedly increased in DIP and N rats (Delta, 34.5 +/- 4.5 for DIP and 16.8 +/- 2.8 for N;P < .01 v D, P < .05 for DIP v DSC or N). Plasma glucagon increased 6-fold in N (945 +/- 129 pg/mL), only doubled in D (424 +/- 54), and tripled in DSC (588 +/- 83), but increased 5-fold in DIP rats (1,031 +/- 75, P < .05 v D and DSC). We conclude that in STZ-diabetic rats, (1) intraperitoneal but not subcutaneous insulin treatment normalizes basal GP and (2) intraperitoneal insulin treatment as compared with subcutaneous treatment alleviates peripheral hyperinsulinemia and results in increased glucagon and GP responses to hypoglycemia. Copyright (C) 2000 by W.B. Saunders Company.

关键词：血糖/生物合成血糖/药物作用迟效制剂糖尿病实验性/血液肾上腺素/血液胰高血糖素/生物合成胰高血糖素/血液葡萄糖/投药和剂量低血糖症/血液低血糖症/代谢降血糖药/投药和剂量降血糖药/血液注射腹腔内注射皮下胰岛素/投药和剂量胰岛素/血液去甲肾上腺素/血液大鼠 Sprague-Dawley 动物男(雄)性大鼠

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