Rats with high or low sociability are differently affected by chronic variable stress

Depression is strongly related to social behavior. We have previously shown that social behavior of rats is individually stable. The purpose of the present study was to compare the sensitivity of animals with different sociability to chronic variable stress (CVS). Four social interaction tests were performed with 60 single-housed male Sprague-Dawley rats. Twenty rats with the lowest and 20 with the highest average social activity time were selected as low sociability (LS) and high sociability (HS) rats, respectively. Both groups were further divided into control and stress groups with equal average body weight. The CVS procedure lasted for 3 weeks. The stressors applied were cold water and wet bedding, imitation of injection, stroboscopic light, movement restriction in a small cage, tail pinch with a clothespin, and strong illumination during the predicted dark phase. In HS-rats, but not in LS-rats, CVS reduced sucrose intake compared with baseline after 3 weeks, suggesting that HS-rats are more vulnerable to anhedonia elicited by CVS. LS-animals were more anxious in the social interaction and open field tests, but stress eliminated differences with HS-animals in the social interaction test and increased their activity in the forced swimming test. In LS-rats stress increased ex vivo dopamine levels and reduced 5-HT levels in the frontal cortex, suggesting that the increased behavioral activity after stress may be related to increased impulsivity. This study thus revealed that animals with high sociability trait are more vulnerable to anhedonia elicited by chronic stress in conditions of single housing.     

恶性肿瘤患者化疗相关贫血的治疗

目的本课题研究我科恶性肿瘤患者化疗后贫血的发生状况及药物干预治疗。方法选择我科2008年1月～2010年7月收治的化疗前血红蛋白正常的肿瘤患者82例,统计化疗后贫血的发生率,贫血的程度,含铂与非含铂方案对贫血的影响,对发生贫血的患者分为两组,单药组单用促红细胞生成素10000U,皮下注射,每周3次,连续8周治疗36例;联合组给予促红细胞生成素10000U,皮下注射,每周3次,和蔗糖铁0.2g,静脉滴注,每周2次,连续8周治疗37例,观察治疗前后血红蛋白的变化及不良反应。结果 82例恶性肿瘤患者化疗后贫血的发生率为85.37%,其中轻度贫血37例（45.12%）,中度贫血22例（26.83%）,重度贫血9例（10.98%）,极重度贫血2例（2.44%）,无贫血12例（14.63%）。单药组治疗后血红蛋白平均升高（20.1±3.3）g/L,联合组治疗后血红蛋白平均升高（22.1±3.5）g/L,两组比较差异有统计学意义。化疗后贫血发生以轻到中度为主（71.95%）,含铂方案贫血发生率90.63%,非含铂方案贫血发生率66.67%,两组比较差异有统计学意义。未见促红细胞生成素和蔗糖铁的明显不良作用。结论恶性肿瘤患者化疗后贫血的发生率高,含铂方案的化疗导致贫血的发生率更高。促红细胞生成素、蔗糖铁能纠正恶性肿瘤患者化疗所致的贫血,两者联合使用疗效更佳。     

促红细胞生成素联合蔗糖铁治疗血液透析患者肾性贫血的疗效观察

目的:探讨促红组胞生成素(EPO)联合蔗糖铁治疗血液透析患者肾性贫血的临床疗效。方法:本样本回顾分析我科2009年1～12月门诊及住院收治的80例慢性肾衰竭(CRF)行透析的肾性贫血患者,运用EPO联合蔗糖铁治疗贫血的临床资料。结果:观察组总有效率明显高于对照组,差异有统计学意义,两组患者治疗后均明显高于治疗前,差异有统计学意义(P<0.05)。治疗后RBC、HCT、Hb观察组均高于对照组但差异,无统计学意义(P>0.05)。观察组未发生不良反应;对照组有2例发生短暂性的腹痛、1例肌肉疼痛,未停药而自行缓解。两组不良反应比较差异无统计学意义(P>0.05)。两组血肝肾功能指标均无明显变化。结论:蔗糖铁联合EPO是治疗缺铁性血液透析患者肾性贫血的有效方法,可较好地改善血透患者的贫血状况,无明显不良反应,值得临床进一步推广使用。     

Single and combined effect of bisphenol A with high sucrose diet on the diabetic and renal tubular dysfunction phenotypes in Drosophila melanogaster

In the present study, effect of exposure of bisphenol A (BPA) and combined exposure of BPA + HSD has been investigated on the glucose homeostasis and associated renal complications in Drosophila. Exposure of 1.0 mM BPA alone induced type 2 diabetes like condition (T2D) in adult male D. melanogaster via oxidative stress. Elevated TGF-β signaling was evident by increased expression of baboon (babo) in BPA exposed organism that stimulated the modulation of extracellular matrix (ECM) component collagen IV resulting in the fibrosis of the Malpighian tubules (MTs). Combined exposure of BPA + HSD (high sucrose diet) resulted in the increased magnitude of T2D and MTs dysfunction parameters. Taken together, the study illustrates that BPA has diabetogenic potential in exposed Drosophila that caused adverse effects on their MTs and combined exposure with BPA and HSD could aggravate the renal tubular dysfunction. The study further suggests the use of Drosophila model to study the environmental chemicals induced diabetes mediated renal dysfunction.     

Stabilization and formulation of a recombinant Human Cytomegalovirus vector for use as a candidate HIV-1 vaccine

Live attenuated viral vaccine/vector candidates are inherently unstable and infectivity titer losses can readily occur without defining appropriate formulations, storage conditions and clinical handling practices. During initial process development of a candidate vaccine against HIV-1 using a recombinant Human Cytomegalovirus vector (rHCMV-1), large vector titer losses were observed after storage at 4 °C and after undergoing freeze-thaw. Thus, the goal of this work was to develop candidate frozen liquid formulations of rHCMV-1 with improved freeze-thaw and short-term liquid stability for potential use in early clinical trials. To this end, a virus stability screening protocol was developed including use of a rapid, in vitro cell-based immunofluorescence focus assay to quantitate viral titers. A library of ∼50 pharmaceutical excipients (from various known classes of additives) were evaluated for their effect on vector stability after freeze-thaw cycling or incubation at 4 °C for several days. Certain additives including sugars and polymers (e.g., trehalose, sucrose, sorbitol, hydrolyzed gelatin, dextran 40) as well as removal of NaCl (lower ionic strength) protected rHCMV-1 against freeze-thaw mediated losses in viral titers. Optimized solution conditions (e.g., solution pH, buffers and sugar type) slowed the rate of rHCMV-1 titer losses in the liquid state at 4 °C. After evaluating various excipient combinations, three new candidate formulations were designed and rHCMV-1 stability was benchmarked against both the currently-used and a previously reported formulation. The new candidate formulations were significantly more stable in terms of reducing rHCMV-1 titer losses after 5 freeze-thaw cycles or incubation at 4 °C for 30 days. This case study highlights the utility of semi-empirical design of frozen liquid formulations of a live viral vaccine candidate, where protection against infectivity titer losses due to freeze-thaw and short-term liquid storage are sufficient to enable more rapid initiation of early clinical trials.     

多糖铁复合物口服与蔗糖铁注射治疗肾性贫血的疗效及不良反应对比

目的对比多糖铁复合物口服与蔗糖铁注射治疗肾性贫血的疗效及不良反应。方法收集2015年10月～2016年11月治疗的60例肾性贫血患者的一般资料,设为对照组(30例)、观察组(30例),对照组以多糖铁复合物口服,观察组以蔗糖铁注射,比较两组治疗效果。结果两组相关指标较治疗前有改善,且观察组Hb[(110.29±13.78)g/L]、SF[(509.43±84.17)μg/L]、Hct ([46.32±8.75)%]、TS[(45.27±4.73)%]水平较对照组高,生活质量中GH[(72.09±3.17)分]、PF[(73.43±3.59)分]、RP[(72.88±3.39)分]、SF[(73.81±3.48)分]指标较对照组高(P0.05);观察组不良反应率较对照组低(P0.05)。结论以蔗糖铁注射治疗能快速提高肾性贫血者临床指标,改善生活质量,且不良反应少。     

The effect of inhibitors of receptor internalization on the desensitization and resensitization of three Gs-coupled receptor responses

1. Many G protein-coupled receptors (GPCRs) are known to internalize following agonist exposure, however the relative importance of this mechanism for the desensitization and resensitization of different GPCRs is unclear. In the present study, we have pretreated NG108-15 cells with hypertonic sucrose or concanavalin A (con A), to investigate the effects of these inhibitors of internalization on the agonist-induced desensitization and subsequent resensitization of three G_s-coupled receptor responses.
2. Incubation of cells with sucrose or con A did not affect subsequent acute agonist stimulation of the A_2A adenosine receptor or the agonist-induced desensitization of this receptor response. However, the resensitization of the A_2A adenosine receptor response following agonist removal was abolished in the presence of sucrose or con A.
3. Sucrose or con A treatment affected neither the desensitization nor resensitization of IP-prostanoid receptor responsiveness. On the other hand con A but not sucrose reduced the agonist-induced desensitization of secretin receptor responsiveness. However, secretin receptor responsiveness did not resensitize within the time period studied whether or not inhibitors of internalization were present.
4. These results indicate that receptor internalization appears to subserve different functions for different GPCRs.

     

基于差示浓度法的远志及其炮制品中三种成分的分析

[目的] 采用差示浓度法分析远志及其炮制品中远志（口山）酮Ⅲ（PXⅢ）、3,6''-二芥子酰基蔗糖（DISS）、甘草酸（GA）的含量,以GA为标志物区分制远志与生远志、蜜远志。[方法] 采用超高效液相色谱法（UPLC）,以甲醇-0.1%甲酸水为流动相,梯度洗脱,流速0.3 mL/min;柱温60℃;检测波长320、237 nm;进样量2 μL;测定高浓度供试品溶液中低含量成分（GA）,测定低浓度供试品溶液中高含量成分（PXⅢ、DISS）。[结果] 差示浓度法能够分析远志及其炮制品中含量悬殊的PXⅢ、DISS和GA的含量。[结论] 该方法灵敏度高、准确性好,以GA为标志物能够区分制远志与生远志、蜜远志。     

微型pH电极直接测试人牙菌斑pH的应用研究

目的：进一步探讨微型ｐＨ电极在原位检测人牙菌斑ｐＨ的可行性，了解漱糖后对菌斑ｐＨ的影响。方法：采用微型蜂式ｐＨ指示电极直接测试人牙邻面菌斑ｐＨ变化。结果：微型ｐＨ电极与玻璃ｐＨ大电极所测结果基本一致；漱糖后菌斑ｐＨ呈下降趋势，２０ｍｉｎ时达到最低点；无龋组与龋敏感组之间的ｐＨ改变无显著性差异。结论：微型ｐＨ电极适用于在原位直接测试菌斑ｐＨ；漱糖后菌斑ｐＨ发生改变，但龋坏与否的个体之间未见明显不同     

Box-Behnken响应面法优选海马益智方提取工艺

目的：利用Box-Behnken响应面法优选海马益智方提取工艺。方法：以远志酮Ⅲ和3,6'-二芥子酰基蔗糖含量及复方浸膏得率为评价指标,采用多指标综合评分法,以加水量、提取时间、提取次数作为考察因素,在单因素试验基础上运用Box-Behnken响应面法对海马益智方的提取工艺进行优化,并进行验证试验。结果：优选得出的最佳提取工艺为：加水量10倍,提取时间1.5 h,提取次数2次。验证试验中预测综合评分为98.66,而实际综合评分均值为97.34,与预测值间的差异较小。结论：优选的海马益智方提取工艺稳定可行、重现性良好,可为海马益智方的研究开发提供参考依据及技术支持。