神经激肽-2受体的过度表达与慢性胰腺炎的疼痛相关

目的:了解神经激肽-2受体(NK-2R)在正常胰腺和慢性胰腺炎组织中的表达, 探讨其表达与慢性胰腺炎疼痛发生的关系。方法:25个慢性胰腺炎标本取自慢性胰腺炎手术, 男性18例, 女性7例, 正常胰腺组织取自20个器官捐献者, 男性11例, 女性9例。应用实时定量逆转录聚合酶链反应技术, 检测正常胰腺和慢性胰腺炎组织NK-2R的mRNA水平, 应用Western blot技术检测NK-2R的蛋白水平, 应用免疫组织化学方法进行NK-2R的组织学定位。将NK-2R mRNA水平与疼痛的程度、发作频率和持续时间进行分析, 寻找其中的相关性。结果:与正常胰腺相比, 慢性胰腺炎组织中NK-2R mRNA和蛋白都过度表达, NK-2R mRNA水平与疼痛的程度(r=0.59, P＜0.01)、发作频率(r＝0.51, P＜0.05)和持续时间(r=0.53, P＜0.05)明显相关。免疫组化检查显示, NK-2R的表达主要位于胰腺腺泡、胰腺导管、神经纤维和炎性细胞。结论：慢性胰腺炎组织中NK-2R的mRNA和蛋白表达水平都明显上调, 扰乱了神经激肽的作用环节;NK-2R的过度表达与疼痛发生有关。     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.     

Circle of Willis atherosclerosis,Alzheimer’s disease and the Dean number

The important role of atherosclerosis in pathophysiology of Alzheimer’s Disease has become evident. Mechanisms such as hyperlipidemia, inflammation, abdominal obesity and insulin resistance are important yet they may not fully explain the specific involvement of the Circle of Willis in these pathologies. The Circle of Wills is a complex geometrical structure which has several areas with different curvature as well as various branching angles of vessels composing the circle. The hemodynamics in this region should take into account the Dean number which indicates the influence of curvature on the resistance to blood flow. Thus, areas with various curvature and angles may have different hemodynamics and there are certain areas in the Circle of Willis that are more likely to develop atherosclerotic changes. Therefore, this could suggest the novel pathophysiological pathway resulting from the geometric peculiarities of the Circle of Willis. One of the directions of future research is to examine whether specific areas of the Circle of Willis are more likely to develop atherosclerotic changes compared to other ones. Selective areas of the Circle of Willis affected by atherosclerotic changes could indicate the primary role of atherosclerosis promoting Alzheimer’s disease although other pathophysiological mechanisms suggesting the opposite direction should be also examined in prospective studies.     

新诊断2型糖尿病患者采取沙格列汀联合二甲双胍治疗的疗效及安全性分析

目的：探究新诊断2型糖尿病患者开展沙格列汀联合二甲双胍治疗的临床疗效及安全性,并为这类患者最优化诊疗服务积累循证经验。方法选取该院内分泌科2012年2月—2014年1月收治的94例新诊断2型糖尿病患者,利用随机数字表法进行分组,分别设为观察组和对照组,每组各47例。其中对照组给予阿卡波糖联合二甲双胍治疗方案,观察组给予沙格列汀联合二甲双胍治疗方案。记录二组患者治疗前后空腹血糖（FBG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素、胰岛素抵抗指数（HOM A －IR）、体重及体质指数,同时比较二组服药依从性情况及不良反应发生率。结果二组治疗前FBG、2hPG及HbA1 c值差异无统计学意义（P＞0．05）;治疗后,观察组FBG、2hPG及 HbA1 c值均低于对照组,差异有统计学意义（P＜0．05）。二组治疗前空腹胰岛素水平及 HOMA －IR值差异无统计学意义（P＞0．05）;治疗后,观察组空腹胰岛素水平高于对照组（P＜0．05）,HOMA －IR值低于对照组（P＜0．05）。二组治疗期间低血糖发生率差异无统计学意义（P＞0．05）;观察组 HbA1 c达标率高于对照组,差异有统计学意义（P＜0．05）。二组治疗前后体重及体重指数差异无统计学意义（P＞0．05）。观察组药物漏服率及错服率均低于对照组,差异有统计学意义（P＜0．05）。结论二甲双胍配伍沙格列汀治疗2型糖尿病患者的临床疗效优于二甲双胍配伍阿卡波糖方案,且安全性尚佳,值得在临床上进一步推广。     

Human splanchnic metabolism during diabetic ketoacidosis.

Splanchnic exchange rates of glucose, acetoacetate, beta-hydroxybutyrate, lactate, pyruvate, glycerol, alanine, glutamine, glutamate, free fatty acids, and triglycerides were measured in eight patients during moderate to severe diabetic ketoacidosis. Their arterial glucose concentration was 20.68 (9.80-52.79) mumole/liter and tic glucose release was 0.77 (0.09-2.44) mmole/min. Gluconeogenesis accounted for about one-half of net splanchnic glucose release, assuming quantitative conversion of net splanchnic extracted lactate, pyruvate, glycerol, alanine, and alpha-ketoglutarate equivalents to glucose. Net splanchnic free fatty acid extraction was 0.24 (0.09-0.52) mmole/min. There was a positive correlation between free fatty acid uptake and ketone-body release. Net splanchnic acetoacetate release was 0.50 (0.05-0.92) mmole/min and beta-hydroxybutyrate release was 0.35 (-0.16 to 0.84) mmole/min. Total ketone-body release was 0.84 (0.37-1.61) mmole/min. The wide ranges of net splanchnic glucose and ketone-body production rates show the heterogeneous characteristics of the diabetic patient in ketoacidosis. It is concluded that the hyperglycemia and hyperketonemia of diabetic ketoacidosis is due to the lack of reciprocity among rates of hepatic glycogenlysis, gluconeogenesis, and ketogenesis resulting in inappropriate net splanchnic release of glucose and ketone bodies.     

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome; 16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block.

Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.

In contrast to findings in patients manifesting only typical exertional angina, the hemodynamic findings during spasm were those of a hypodynamic state. Left ventricular systolic pressure decreased from 138.9 ± 6.0 (mean ± standard error of the mean) to 113.2 ± 6.2 mm Hg; left ventricular end-diastolic pressure did not change significantly. Myocardial lactate extraction during spasm was invariably markedly reduced: −53.19 percent ± 15.44 (P < 0.001). However, the effect of coronary sinus pacing on myocardial lactate extraction was not significantly abnormal: +15.74 percent ± 6.66.

The respective roles of medical and surgical intervention are uncertain. Only 3 patients had a completely satisfactory pharmacologic response to nitrates alone or in combination with propranolol, and the condition of 5 others was partially improved; the remaining 21 patients were judged intractable to medical management. Coronary bypass surgery was performed as the ultimate recourse in 18 patients. However, short-term results reveal that only nine (50 percent) showed improvement, four (22 percent) had myocardial infarction during or after surgery and four (22 percent) died.

These studies confirm that coronary arterial spasm is a definite pathogenetic factor in a variety of acute myocardial ischemic syndromes. The incidence and full clinical significance of this functional disorder remain to be determined.     

Plasma cyclic adenosine 3'5'-monophosphate (AMP) levels in acute myocardial infarction

Plasma cyclic adenosine 3′5′-monophosphate (AMP) levels were measured in 44 patients with acute myocardial infarction, 33 patients with other cardiac and noncardiac diseases and 20 normal volunteers. The normal range of cyclic AMP was 4 to 16 picomoles/ml. The 35 surviving patients with acute myocardial infarction tended to have a slightly increased level of plasma cyclic AMP during the first 24 hours with a subsequent return to normal; the 9 nonsurvivors had abnormally high levels of cyclic AMP. An inverse correlation was found between cyclic AMP levels and stroke work index, and plasma cyclic AMP levels were of equal or better prognostic value than stroke work index. Plasma cyclic AMP levels were in the normal range in patients without acute myocardial infarction. Thus, very high levels of plasma cyclic AMP, found in patients with fatal myocardial infarction, appear to have clinical significance.