Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

Aims/hypothesis A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin may be involved in the regulation of insulin secretion in vivo and in vitro. Methods The effect of adiponectin on insulin secretion was measured in vitro and in vivo, along with the effects of adiponectin on ATP generation, membrane potentials, Ca²⁺ currents, cytosolic calcium concentration and state of 5′-AMP-activated protein kinase (AMPK). In addition, insulin granule transport was measured by membrane capacitance and total internal reflection fluorescence (TIRF) analysis. Results Adiponectin significantly stimulated insulin secretion from pancreatic islets to approximately 2.3-fold the baseline value in the presence of a glucose concentration of 5.6 mmol/l. Although adiponectin had no effect on ATP generation, membrane potentials, Ca²⁺ currents, cytosolic calcium concentrations or activation status of AMPK, it caused a significant increase of membrane capacitance to approximately 2.3-fold the baseline value. TIRF analysis revealed that adiponectin induced a significant increase in the number of fusion events in mouse pancreatic beta cells under 5.6 mmol/l glucose loading, without affecting the status of previously docked granules. Moreover, intravenous injection of adiponectin significantly increased insulin secretion to approximately 1.6-fold of baseline in C57BL/6 mice. Conclusions/interpretation The above results indicate that adiponectin induces insulin secretion in vitro and in vivo. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. M. Okamoto and M. Ohara-Imaizumi contributed equally to this study.     

托伐普坦联合尿毒清颗粒治疗肾病综合征的临床效果

目的观察托伐普坦联合尿毒清颗粒治疗肾病综合征患者的临床效果。方法选择2017年8月-2018年12月四川省资阳市第一人民医院肾病内科诊治肾病综合征患者90例作为研究对象,依据随机数字表法将患者分为对照组(n=45)和观察组(n=45),入院后根据诊疗规范进行治疗,对照组给予托伐普坦,观察组在对照组基础上给予尿毒清颗粒,治疗1个月后,比较2组治疗前后的血肌酐、尿素氮、尿量、血红蛋白、血清白蛋白、钾离子和钙离子水平,记录不良反应发生情况。结果治疗1个月后,2组血肌酐与尿素氮水平均降低,且观察组降低幅度大于对照组(t/P=3.999/0.000、2.316/0.023);2组的尿量、血红蛋白和血清白蛋白均上升,且观察组上升幅度大于对照组(t/P=-11.320/0.000、-4.606/0.000、-3.068/0.003),2组治疗前后的钾、钙离子浓度均未发生明显变化(P>0.05);不良反应发生率比较差异亦无统计学意义(P>0.05)。结论使用托伐普坦联合尿毒清颗粒治疗肾病综合征患者,可以改善患者的肾功能,改善尿量和营养状态,稳定体内电解质水平,安全性良好。     

九味镇心颗粒联合米氮平治疗对功能性消化不良合并抑郁患者的疗效及安全性分析

目的 探讨九味镇心颗粒联合米氮平治疗功能性消化不良合并抑郁患者的临床疗效及安全性。方法 收集2017年7月～2018年12月于台州市第二人民医院精神科就诊的112例功能性消化不良合并抑郁患者作为观察对象,随机分为对照组和观察组,每组56例。对照组予米氮平治疗,观察组予九味镇心颗粒联合米氮平治疗。采用汉密尔顿抑郁量表17项目(HAMD)进行抑郁临床疗效评价。8周疗程结束后,比较两组的临床疗效、HAMD评分、消化不良症状积分及不良反应。结果 8周疗程结束后,临床疗效显示,观察组治疗总有效率高于对照组(91.1%vs 76.8%,P0.05)。治疗前,对照组和观察组患者HAMD评分比较无统计学差异[(26.5±4.7)分vs (27.3±4.2)分,P0.05)]。治疗后,与对照组比较,观察组患者HAMD评分降低(10.9±2.4分vs 15.8±3.1分),消化不良症状程度积分和频次积分降低[(1.14±0.41)分vs (1.92±0.60)分,(1.02±0.39)分vs (1.83±0.55)分],差异有统计学意义(P均0.05)]。治疗过程中,两组患者均未出现严重不良反应病例。对照组和观察组患者不良反应发生率比较,无统计学差异(21.4%vs 28.6%,P0.05)。结论 九味镇心颗粒联合米氮平是功能性消化不良合并抑郁患者的有效治疗方案,抑郁治疗有效率高,能够明显改善消化不良症状,且药物安全性好。     

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.During vertebrate evolution, the female reproductive pattern underwent a remarkable transition from spawning of large number of eggs in primitive species under favorable conditions to more tightly controlled ovarian cycles in higher vertebrates, such that only a limited number (rodents) or a single (human and nonhuman primates) egg is released per cycle (1, 2). Coincident with this event, the single pituitary gonadotropic hormone that exists in primitive vertebrates has given rise to two gonadotropins, FSH and luteinizing hormone (LH), which coordinate gametogenesis and steroidogenesis (3–7). FSH and LH are heterodimeric glycoproteins that contain a common α-subunit and a hormone-specific β-subunit (3). Although synthesized in the same cell, the gonadotrope, FSH is mostly constitutively released in many species, whereas LH is stored in dense core granules (DCGs) and secreted in pulses via the regulated pathway in response to gonadotropin-releasing hormone (GnRH) (8, 9). Although this pattern is evolutionarily conserved, how distinct modes of gonadotropin secretion affect ovarian development and target cell responses remain unclear. Although models in which variations in secretion of gonadotropins have been achieved in vivo (10) and in vitro, including basolateral and apically polarized secretion (11), the in vivo consequences of altered mode of gonadotropin trafficking and release (constitutive vs. regulated) from pituitary are untested. We sought to identify why the two gonadotropins, LH and FSH, expressed in the same pituitary cell have evolved to exit via different routes to regulate ovarian physiology.     

金银花配方颗粒评价性抽验结果分析与建议

目的：通过开展金银花配方颗粒评价性抽验,比较分析不同厂家金银花配方颗粒的质量情况,并提出监管建议。方法：收集各企业金银花配方颗粒质量标准,依据企业标准进行法定检验。结果：共抽验117批金银花配方颗粒,涉及9家生产企业。按各自企业标准进行检验,总体合格率为100%。但是各企业之间金银花配方颗粒含量差异较大且每克颗粒相当的药材（饮片）量不同,转移率不同。结论：通过本次抽验发现金银花配方颗粒的整体质量较高,但是不同厂家之间所用原料药材及生产工艺存在一定差异,导致最终产品质量参差不齐。因此,有必要规范中药配方颗粒生产工艺,尽快统一标准,加强监管。     

妇康宁颗粒的药效学研究

目的研究妇康宁颗粒剂的药效学。方法采用小鼠扭体法和热板法考察妇康宁颗粒的镇痛作用,采用小鼠耳肿胀法和大鼠纸片包埋法考察妇康宁颗粒的抗炎作用,采用小鼠凝血时间、出血时间试验考察妇康宁颗粒的止血作用,采用小鼠碳廓清试验考察妇康宁颗粒调节免疫作用。结果妇康宁颗粒对化学、物理刺激引发的疼痛具有良好的抑制作用。妇康宁颗粒剂对急性渗出性炎症和慢性增殖性炎症具有一定的抑制作用,具有剂量相关性。妇康宁颗粒剂具有一定的凝血和止血作用。妇康宁颗粒可以促进小鼠免疫器官的发育,增加小鼠单位时间清除血液异物的速度。结论妇康宁颗粒具有抗炎、止血、调节免疫作用,为临床应用提供了科学的依据。     

超滤工艺在清肺止咳颗粒中的应用

目的：考察3种不同孔径的陶瓷膜对清肺止咳颗粒醇提液中黄芩苷含量、总固体量的影响,以及对制剂稳定性的影响。方法：以黄芩苷转移率、除杂率为指标,采用单因素试验法优选陶瓷膜种类。按照《原料药与药物制剂稳定性试验指导原则》进行考察。结果：3种陶瓷膜对清肺止咳颗粒醇提液的过滤存在差异,采用0.02μm陶瓷膜进行超滤,其黄芩苷转移率、除杂率均优于其他两种。制剂中黄芩苷含量变化不大。结论：采用0.02μm陶瓷膜超滤工艺可以纯化提取液,提高了有效成分的转移率,适用于大生产的使用。     

山银花、金银花中绿原酸和总黄酮含量及抗氧化活性测定

目的对3个不同产地山银花和金银花中绿原酸、总黄酮含量及抗氧化活性进行分析,并比较之间的差异。方法对绿原酸提取条件进行优化,最佳提取条件为65℃下60%乙醇溶液按料液比1∶20超声提取30 min;总黄酮最佳提取条件为65℃下用60%甲醇溶液按料液比1∶10超声提取30 min。分别采用高效液相色谱法和紫外分光光度法对样品的绿原酸和总黄酮进行含量测定,并用DPPH自由基清除率来检测山银花、金银花的抗氧化活性。结果建立了良好的绿原酸和总黄酮含量分析方法,绿原酸在0.119～1.190 mg/m L内线性关系良好,r2为0.999 2(n=6);总黄酮在8.48～50.88μg/m L内线性关系良好,r2为0.999 5(n=6)。湖南产地山银花绿原酸量、总黄酮量及自由基清除率分别为3.99%、13.43%、62.41%。重庆产地山银花绿原酸量、总黄酮量及自由基清除率分别为3.29%、10.08%、51.48%。广西产地金银花绿原酸量、总黄酮量、自由基清除率分别为2.55%、7.10%、39.51%。结论提出了结合化学成分分析和抗氧化性活性来比较不同产地山银花和金银花之间区别的分析方法,从"谱-效"结合思路,为山银花和金银花质量控制及鉴别提供一种新的模式。     

无糖型半夏泻心颗粒制备工艺的研究

目的：优选无糖型半夏泻心颗粒最佳制备工艺。方法以黄芩苷、小檗碱含量和出膏率为指标,应用L 9(34)正交设计和多指标综合评分法优选无糖型半夏泻心颗粒最佳水提取工艺;以成型性、制粒情况为指标,考察辅料、矫味剂的种类和配比。结果最佳提取工艺为黄连用70%乙醇提取后,药渣与处方中其他6味药混合,提取3次,第一次加9倍量水,煎煮1 h,第二次加8倍量水,煎煮1 h,第三次加6倍量水,煎煮0.5 h;最佳的辅料种类和比例为浸膏粉∶糊精∶可溶性淀粉∶甜味素=1∶0.6∶0.2∶0.015,85%乙醇为润湿剂。结论该工艺合理可行,适宜做无糖型半夏泻心颗粒的制备工艺。