移植肾急性排斥血流灌注与生化指标变化关系的实验研究

目的探讨超谐波声学造影(UHCI)和声学密度定量(AD)技术,定量评价异体移植肾急性排斥(AR)反应时皮质血流灌注的价值;并研究各灌注参数与血肌酐(SCr)、24h内生肌酐清除值(CCr)变化的关系。方法建立犬异体移植肾急性排斥模型,分别于术后第1、3、5、7、9、11d(T1、T3、T5、T7、T9、T11)共6个时间点,采用UHCI和AD技术检查移植肾,测定肾皮质造影后峰值密度(PI)、曲线下面积(AUC)、降支减半时间(HT)及平均通过时间(MTT)等有关灌注参数;并同时抽血查SCr、CCr,将化验结果与肾皮质灌注参数作相关性分析。结果移植肾皮质造影后各灌注参数(PI、AUC、HT、MTT)与CCr均于T5时间点发生明显变化,与T1比较差异显著(P<0.05);而SCr于T7时间点发生明显变化(P<0.05)。从T1~T11,PI、AUC、HT、MTT与SCr成不同程度的负相关,与CCr成不同程度的正相关。结论UHCI是评价移植肾AR反应时皮质血流灌注的有效方法,结合AD分析所获得的血流灌注参数可提供有关AR存在及严重性的有价值信息,对肾移植术后AR的诊断有着广泛的应用前景。     

Dexamethasone suppression test and sleep deprivation in endogenous depression

The dexamethasone suppression test (DST) was carried out in 24 endogenously depressed and 15 non-endogenously depressed patients before and on the day after therapeutic sleep deprivation (SD) for one night. The diagnostic selectivity of DST results was not improved by combination with SD. The alteration of DST cortisol levels after SD, irrespective of the direction of change (so-called cortisol response) was significantly higher in endogenous depressives than in neurotic depressives. No unequivocal statement was possible on (a) the predictive value of DST data for the SD effect and (b) the relationship between neuroendocrine changes and the antidepressive effect of SD.     

CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> Regulatory T Cells Have Divergent Effects on Intestinal Inflammation in IL-10 Gene-Deficient Mice

The regulatory effect of murine CD4⁺CD25⁺ T-cells in vivo appears to be dependent on the secretion of IL-10. The lack of IL-10 in the IL-10 gene-deficient mouse has a profoundly negative effect on the mouse’s regulation of the response to intestinal bacteria, resulting in severe enterocolitis. We investigated the effect of neonatal injection with wild-type CD4⁺CD25⁺ T-cells on the intestinal immune response in IL-10 gene-deficient mice. At the time of analysis, 8–15 weeks later, all mice demonstrated an increased, antigen-stimulated systemic response. However, the intestinal response was divergent with about half of the mice developing an intestinal inflammation with a high injury score, the other half demonstrating a remarkable reduction in injury score with a marked decrease in intestinal IFNγ release. Our data demonstrate that CD4⁺CD25⁺ T-cells can be activated in IL-10 gene-deficient mice and that this stimulation under stringent conditions has the potential to reduce intestinal inflammation.     

Endogenous Pain Modulation Profiles Among Individuals With Chronic Pain: Relation to Opioid Use

It is generally assumed that individuals exhibiting high pain inhibition also tend to exhibit low pain facilitation, but little research has examined this association in individuals with pain. The aims of this cross-sectional study were 1) to examine the association between measures of conditioned pain modulation (CPM) and temporal summation (TS) in individuals with chronic pain, and 2) to examine whether this association was moderated by demographic (age, sex), psychological (depression, catastrophizing), or medication-related (opioid use) variables. Individuals (N= 190) with back or neck pain completed questionnaires and underwent a series of quantitative sensory testing procedures assessing CPM and TS. Results indicated that individuals with higher levels of CPM showed lower levels of TS, r = –.20, P < .01. Analyses, however, revealed that the magnitude of this association was substantially weaker among opioid users (r= –.08, NS) than nonusers (r= ?.34, P < .01). None of the demographic or psychological variables included in our study influenced the association between CPM and TS. The magnitude of CPM was lower for opioid users than nonusers, suggesting that opioid use might dampen the functioning of endogenous pain-inhibitory systems and possibly contribute to a discordance between measures of pain inhibition and pain facilitation.

Diurnal rhythm in endogenous glucose production is a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour?

Aims/hypothesis An increase in endogenous glucose production (EGP) is a major contributor to fasting morning hyperglycaemia in type 2 diabetes. This increase is dissipated with fasting, later in the day. To understand its origin, EGP, gluconeogenesis and hormones that regulate metabolism were measured over 24 h. We hypothesised that EGP, and therefore glycaemia, would demonstrate a centrally mediated circadian rhythm in type 2 diabetes.Subjects and methods Seven subjects with type 2 diabetes and six age- and BMI-matched control subjects, fasting after breakfast (08.00 h), underwent a further 24-h fast, with the infusion of [U-¹³C]glucose and [3-¹⁴C]lactate, starting at 14.00 h. The MCR and production of total and gluconeogenic glucose were determined from the tracer concentrations using compartmental analysis.Results MCR was near constant: 1.73±0.10 in control and 1.40±0.14 ml kg⁻¹ min⁻¹ in diabetic subjects (p=0.04). EGP in diabetes rose gradually overnight from 8.2±0.7 to 11.3±0.5 μmol kg⁻¹ min⁻¹ at 06.00 h (p<0.05). Glucose utilisation lagged EGP, rising from 8.5±0.6 to 10.5±0.4 μmol kg⁻¹ min⁻¹ (p<0.05), inducing a fall in glycaemia from a peak of 8.0±0.5 mmol/l to 6.3±0.4 mmol/l (p<0.05). Cortisol and melatonin showed diurnal variations, whereas insulin, glucagon and leptin did not. Melatonin was most closely related to EGP, but its secretion was attenuated in diabetes (p<0.05).Conclusions/interpretation In type 2 diabetes, EGP and gluconeogenesis display diurnal rhythms that drive the fasting hyperglycaemia and are absent in healthy control subjects. The rise in EGP may be related to a deficit in suprachiasmatic nucleus activity in diabetes, or result from non-linear behaviour plus a transition from a normal steady state to a limit cycle pattern in diabetes, or both.     

中国人内源性高甘油三酯血症与载脂蛋白A5基因-1131T>C多态性、S19W多态性的相关性

目的探讨中国人内源性高甘油三酯血症患者载脂蛋白A5基因的-1131T〉C多态性及S19W多态性与血脂水平的关系。方法用聚合酶链反应-限制性片断长度多态性分析，对182名内源性高甘油三酯血症患者和200名血脂正常者的载脂蛋白A5基因启动子上游-1131T〉C单核苷酸多态性、编码区的S19W（c．56C〉G）多态性、空腹血脂及载脂蛋白水平进行分析。结果患者的体质指数、血清总甘油三酯和总胆固醇水平较对照组显著升高，高密度脂蛋白胆固醇水平则显著降低。-1131T／C单核苷酸多态性位点T和C等位基因频率在病例组和对照组分别为52．7％、47．3％和67.0％、33．0％。等位基因频率和基因型频率分布符合Hardy-Weinberg平衡定律。T/C基因多态性等位基因T和C频率在两组问的差异有显著性（P〈0．05）；S19W多态性与内源性高甘油三酯血症发病风险未见明显相关性。结论载脂蛋白A5基因-1131C等位基因与血清甘油三酯的升高相关。     

内源分泌型晚期糖化终末产物受体与2型糖尿病颈动脉内膜中层厚度相关

测定78例2型糖尿病患者颈动脉内膜中层厚度(CIMT).CIMT正常组血浆内源分泌型晚期糖化终末产物受体(esRAGE)高于CIMT增厚组[(0.257 3±0.1656对0.155 4±0.0701)峭/L,P<0.01].esRAGE与CIMT负相关r=-0.247,P<0.05).Logistic回归分析显示CIMT与esRAGE和高密度脂蛋白胆固醇负相关,与年龄正相关.

Abstract：

The carotid initima-media thickness(CIMT)in 78 cases of type 2 diabetic patients was measured.The level of plasma endogenous secretion receptor for advanced glycation end-products(esRAGE)in patients with normal CIMT was higher than those with chickened CIMT[(0.257 3±0.165 6 vs 0.155 4±0.0701)μg/L,P<0.01].esRAGE was negatively associated with CIMT(r=-0.247,P<0.05).Logistic regression analysis showed that CIMT was negatively associated with esRAGE and hish density lipoprotein cholesterol,but was positively associated with age.     

Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation

BACKGROUND: Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. METHODS: Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. RESULTS: The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. CONCLUSIONS: This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are discussed together with previous findings suggesting a putative linkage between brain ethanol metabolism and the endogenous opioid system to explain some of the neuroendocrine effects of ethanol.     

对几种内生肌酐清除率估计公式实用性的探讨

目的通过对血肌酐计算法计算的内生肌酐清除率（ECcr）与标准24h留尿法计算的内生肌酐清除率（MCcr）的统计分析,明确计算ECcr的几种公式的临床实用价值.方法对378例受检者的血肌酐水平用酶法进行检测,ECcr分别用Crockfrat-Count、Schwartz及修正的Counahan-Barrau公式算得;MCcr用全国临床检验操作规程要求的校正公式计算.结果 378例受检者的ECcr与相应的MCcr之间有较好的相关关系,相关系数r在0.67和0.68之间;依MCcr大小分组后,当MCcr值离正常参考范围越远,各ECcr与相应的MCcr的相关性越差.结论由于ECcr在估计MCcr时存在较大偏差,因此临床了解肾小球滤过率（GFR）仍需MCcr.