Tegaserod does not alter fasting or meal-induced biliary tract motility

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.     

72例鼻咽结核的临床分析

目的 探讨鼻咽结核的诊断与治疗。方法 对72例经活检病理证实的鼻咽结核进行回顾性分析。结果 72例患者中男性31例，女性41例，男女比例为1：1．32，平均年龄为30．7岁；鼻咽结核以局部症状为特征，颈淋巴结肿大发生率为79．2％（57／72）；鼻咽结核在临床上误诊率较高；抗结核治疗9～12个月治愈，随访1～5年，未见复发。结论 近年来鼻咽结核有增加的趋势，尤以原发性病例居多。鼻咽镜活检可确诊，规则抗结核治疗可治愈。     

Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans

The Caenorhabditis elegans defecation motor program (DMP) is a highly coordinated rhythmic behavior that requires two GABAergic neurons that synapse onto the enteric muscles. One class of DMP mutants, called anterior body wall muscle contraction and expulsion defective (aex) mutants, exhibits similar defects to those caused by the loss of these two neurons. Here, we demonstrate that aex-2 encodes a G-protein-coupled receptor (GPCR) and aex-4 encodes an exocytic SNAP25 homologue. We found that aex-2 functions in the nervous system and activates a G(s)alpha signaling pathway to regulate defecation. aex-4, on the other hand, functions in the intestinal epithelial cells. Furthermore, we show that aex-5, which encodes a pro-protein convertase, functions in the intestine to regulate the DMP and that its secretion from the intestine is impaired in aex-4 mutants. Activation of the G(s)alpha GPCR pathway in GABAergic neurons can suppress the defecation defect of the intestinal mutants aex-4 and aex-5. Lastly, we demonstrate that activation of GABAergic neurons using the light-gated cation channel channelrhodopsin-2 is sufficient to suppress the behavioral defects of aex-2, aex-4, and aex-5. These results genetically place intestinal genes aex-4 and aex-5 upstream of GABAergic GPCR signaling. We propose a model whereby the intestinal genes aex-4 and aex-5 control the DMP by regulating the secretion of a signal, which activates the neuronal receptor aex-2.     

Modulation of platelet and leucocyte function by a Chinese herbal formulation as compared with conventional antiplatelet agents

Platelet and leucocyte activity are important in the acute development of thrombosis and in the pathogenesis of ischaemic vascular disease. Dan Shen Di Wan (DS, Cardiotonic Pill or Dantonic(R) Pill) is one of the most commonly used Chinese herbal formulations for treating patients with atherosclerotic disease in China and several Asian countries. We studied the effect of DS on platelet and leucocyte function and compared the effects with conventional antiplatelet agents, cangrelor (ADP P2Y(12) receptor antagonist) and aspirin (acetyl salicylic acid, ASA). Measurements were made by platelet aggregation (%) and activation (CD62P %), platelet-monocyte conjugate formation (P/M, CD42a median fluorescence, mf), platelet-neutrophil conjugate formation (P/N, mf), and leucocyte activation (CD11b median fluorescence on monocytes and neutrophils, mf) in response to 3.3 micromol/L adenosine diphosphate (ADP), 1.0 micromol/L platelet activating factor (PAF), 5.0 micromol/L adrenaline and 0.5 microg/mL collagen. We also evaluated the effect of its main component, water soluble extract of salvia miltiorrhiza (SME) on intracellular calcium mobilization in platelets triggered by 10 micromol/L ADP, 10 micromol/L PAF, 2 microg/mL collagen and 15 micromol/L thrombin receptor activating peptide (TRAP). Overall DS showed inhibition of platelet aggregation, platelet activation, platelet-leucocyte conjugate formation and leucocyte activation in response to all the agonists apart from adrenaline (all p < 0.01). DS showed inhibition of platelet aggregation and leucocyte activation equivalent to cangrelor 100 nmol/L and ASA 100 micromol/L. SME dose-dependently inhibited intracellular calcium mobilization in platelets following stimulation with all the platelet agonists with maximum effective at 0.36 mg/mL (all p < 0.01). When used at 0.18 mg/mL its inhibitory effect was equivalent to cangrelor and ASA. We conclude that DS is a potential inhibitor of both platelet and leucocyte activation.     

中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值在重症肺炎支原体肺炎中的诊断价值北大核心CSCD

目的研究中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)在重症肺炎支原体肺炎(MPP)中的诊断价值。方法回顾性分析2015年1月至2017年12月苏州大学附属儿童医院住院的616例MPP患儿(MPP组)的临床资料和实验室数据,选取同期100例健康体检儿童为健康对照组。采用t检验或秩和检验比较MPP组与健康对照组、重症MPP组与普通MPP组间的NLR及PLR的差异。筛选出影响重症MPP的危险因素,描绘受试者工作特征曲线(ROC)并寻找最佳截断点。结果1.MPP组患儿白细胞计数(WBC)、中性粒细胞数(N)、血小板计数(PLT)、NLR、PLR、免疫球蛋白(Ig)M的中位数及CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均高于健康对照组[8.36×10^(9)/L比7.49×10^(9)/L、4.41×10^(9)/L比3.11×10^(9)/L、340.92×10^(9)/L比234.00×10^(9)/L、1.70比0.91、112.99比70.34、1.33 g/L比1.29 g/L、20.95%比17.10%、11.25%比9.70%];淋巴细胞数(L)、IgA的中位数及CD3^(+)、CD3^(+)CD8^(+)、CD3^(-)CD_((16+56))^(+)百分比的中位数均低于健康对照组[2.64×10^(9)/L比3.37×10^(9)/L、0.86 g/L比1.30 g/L、64.55%比68.00%、23.65%比24.90%、10.50%比12.20%],差异均有统计学意义(Z=-3.074、-2.413、-2.972、-1.357、-1.863、-2.251、-4.282、-3.420、-2.221、-4.181、-2.784、-2.024、-2.791,均P<0.05)。2.重症MPP组患儿N、NLR、PLR、IgA、IgG、IgM的中位数及CD3^(+)、CD3^(+)CD8^(+)百分比均高于普通MPP组[5.18×10^(9)/L比3.52×10^(9)/L、2.39比1.03、149.32比94.23、1.29 g/L比0.71 g/L、9.63 g/L比8.19 g/L、1.40 g/L比1.29 g/L、(65.53±9.75)%比(62.81±9.89)%、(25.35±6.65)%比(23.38±6.91)%];L的中位数、CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均低于普通MPP组(2.02×10^(9)/L比3.25×10^(9)/L、17.40%比21.50%、9.00%比11.70%),差异均有统计学意义(Z/t=-7.807、-11.313、-10.452、-8.819、-6.162、-3.047、-3.128、-3.270、-9.402、-5.191、-5.214,均P<0.05)。3.通过单因素和多因素的Logistic回归分析发现,CD3^(-)CD_(19)^(+)是患儿发生重症MPP的保护因素;N、NLR、PLR是患重症MPP的危险因素(均P<0.05),且相对危险度由高到低依次为NLR>PLR>N。4.NLR、PLR诊断重症MPP的ROC曲线下面积(AUC)分别为:NLR(AUC=0.789,95%CI:0.754~0.823,P<0.001);PLR(AUC=0.767,95%CI:0.730~0.804,P<0.001)。当NLR的截断值为1.09时,敏感性为98.9%,特异性为70.6%;当PLR的截断值为97.47时,敏感性为88.5%,特异性为69.4%。结论NLR、PLR可作为发生重症MPP的独立影响因素,对诊断重症MPP有一定价值。     

儿童急性肺源性心脏病的发病机制

急性肺源性心脏病通常继发于严重肺部疾病或肺循环障碍所导致的肺动脉高压,以急性右心功能障碍、右心衰竭为主要特征。其中,低氧血症、高碳酸血症及正压通气均可导致肺动脉高压的发生。在危重患儿救治过程中,特别是呼吸支持过程中,应早期识别急性肺源性心脏病,考虑实施以右心功能监护和保护为核心的"肺保护"及"循环保护"。     

Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptor α-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation

AIM: To explore the effect of recombinant human interleukin-11 (rhIL-11) on the expressions of interleukin-11 receptor α-chain (IL-11Rα) and an additional signal transducer glycoprotein 130 (gp130) in intestinal epithelium cell line-6 (IEC-6) after neutron irradiation.METHODS: Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis.RESULTS: The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h (P ＜ 0.01), IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells (P ＜ 0.05). In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation (P ＜ 0.01) and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL-11Rα expression was higher than that of irradiated cells (P ＜ 0.05). When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein (P ＜ 0.05) in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells (P ＜ 0.05).CONCLUSION: rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.     

Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant/glucose-intolerant state in hamsters

Bromocriptine, a potent dopamine D2 receptor agonist, suppresses lipogenesis and improves glucose intolerance and insulin resistance. Recent evidence suggests that bromocriptine may produce these effects by altering central nervous system (CNS) regulation of metabolism. To determine whether or not the CNS plays a critical role in these bromocriptine-mediated effects on peripheral metabolism, we compared the metabolic responses to bromocriptine when administered peripherally versus centrally in naturally obese and glucose intolerant Syrian hamsters. Male hamsters (BW 194 +/- 5 g) were treated with bromocriptine or vehicle either intraperitoneally (i.p., 800 microgram/animal) or intracerebroventricularly (i.c.v., 1 microgram/animal) daily at 1 h after light onset for 14 days while held on 14-hour daily photoperiods. Glucose tolerance tests (GTTs, 3 g glucose/kg BW) were conducted after treatment. Compared to control animals, bromocriptine i.p. significantly reduced weight gain (11.7 vs. -2.4 g) and the areas under the glucose and insulin GTT curves by 29 and 48%, respectively. Similarly, compared with vehicle-treated controls, bromocriptine i.c.v. at 1 microgram/animal substantially reduced weight gain (8.7 vs. -6.3 g), the areas under the glucose and insulin GTT curves by 31 and 44% respectively, and the basal plasma insulin concentration by 41% (p < 0.05). Furthermore, both treatments significantly improved insulin-mediated suppression of hepatic glucose production during a hyperinsulinemic-euglycemic clamp. Thus, daily administration of bromocriptine at a very low dose i.c.v. replicates the metabolic effects of bromocriptine administered i.p. at a much higher dose. This finding demonstrates for the first time that the CNS is a critical target of bromocriptine's metabolic effects.     

不同日摄氟量对人体健康影响的研究

以日摄氟量作为评价环境氟对人体健康影响的指标,比单一用空气、饮水和食物等的含氟量进行分析要合理。日摄氟量的计算各家不一,我们是将各点大气、饮水、粮食、蔬菜的实测含氟量分别乘大气12m~3、饮水3L、粮食0.6kg、蔬菜0.5kg,其和即是。研究结果表明:(1)成人的尿氟与日摄量呈非常显著的正相关(r=0.8809,P<0.01)。(2)成人的牙齿,各调查点的斑釉率和斑釉指数均随日摄氟量的增加而上升,二者分别与日摄氟量呈高度显著和显著的正相关(r=0.9048,p<0.01;r=0.8154,p<0.05)。(3)成人的胫腓骨、尺挠骨和骨盆的X线改变,以骨质增生、骨质的密度、结构改变和骨周肌腱韧带附着处钙化为主要表现,其改变的总阳性率与日摄氟量有一定的关系。