OBJECTIVES: I. Determine whether diverse mutations of the vasopressin-neurophysin II (AVP-NPII) gene cause autosomal dominant familial neurohypophyseal diabetes insipidus by directing the production of an abnormal preprohormone.
II. Determine whether the AVP-NPII gene-directed preprohormone accumulates and destroys magnocellular neurons because it cannot be folded and processed efficiently.

开始日期1995-12-01

申办/合作机构

Shanghai Municipal Water Res Dev & Uti Nat Eng Center Co. Ltd

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100 项与氯磺丙脲相关的临床结果

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100 项与氯磺丙脲相关的转化医学

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100 项与氯磺丙脲相关的专利（医药）

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1,506

项与氯磺丙脲相关的文献（医药）

2024-11-01·DRUG METABOLISM AND DISPOSITION

Effects of Compound Probiotics on Pharmacokinetics of Cytochrome 450 Probe Drugs in Rats

Article

作者: Zhu, Peng ; Wu, Tianyuan ; Li, Xiong ; Zhang, Wei ; Xiao, Yayi ; Zhou, Jian ; Li, Qing ; Yang, Xuechun ; Guo, Fugang ; Zhou, Rong ; Liu, Yujie ; Shu, Yan ; Yin, Jianhui ; Chen, Zhi ; Xiong, Yalan ; Yang, Haijun ; Zhou, Honghao ; Zhang, Yanjuan ; Liao, Shang ; Xiong, Yanling

Compound probiotics have been widely used and commonly coadministered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (P450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin, and chlorzoxazone. Male Wistar rats were administered drinking water containing VSL#3 or not for 14 days and then intragastrically administered a P450 probe cocktail; this was done to investigate the host P450's metabolic phenotype. Stool, liver/jejunum, and serum samples were collected for 16S ribosomal RNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both α and β diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1417 and 4004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of P450 genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum-conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and intestinal structure in rats, which could be reasons for pharmacokinetic changes. SIGNIFICANCE STATEMENT: This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of cytochrome P450 probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the present study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, combined here with the bile acid profile and histopathological analysis.

2024-09-20·JOURNAL OF ORGANIC CHEMISTRY

Metal-Free Synthesis of Pharmaceutically Relevant Sulfonylureas via Direct Reaction of Sulfonamides with Amides

Article

作者: Banerjee, Biplab ; Mondal, Sahil ; Dash, Rageshree ; Sati, Rakhi ; Hashim, Muhammed ; Nishad, Chandra Shekhar

A metal-free process has been developed for the sustainable synthesis of medicinally important sulfonylureas in one pot via the direct reaction of sulfonamides with amides in green solvent (DMC). The reaction proceeded efficiently at room temperature, and the products were obtained in good to excellent yields. The use of readily accessible, inexpensive, and environmentally benign starting materials and reagents, metal-free mild reaction conditions, wide substrate scope, tolerance to air and moisture, operational simplicity, and good atom economy are the salient features of this reaction protocol. Gram-scale synthesis of antidiabetic drugs tolbutamide and chlorpropamide in excellent yields further revealed the practical utility of this procedure. Additionally, the synthetic value of this straightforward method is showcased by the late-stage modification of drug molecules, including drug-drug conjugation with good yields. Preliminary mechanistic studies indicated the in situ generation of an isocyanate intermediate, which further reacts with sulfonamide to form sulfonylurea. As compared to other related methods reported for sulfonylurea synthesis, the current method obviates the requirement of traditional multistep protocols involving isolation of hazardous isocyanates and avoids the use of toxic phosgene.

2024-09-04·Horticulture Research

Dynamic temporal transcriptome analysis reveals grape VlMYB59-VlCKX4 regulatory module controls fruit set

Article

作者: Yang, Yingjun ; Yang, Shengdi ; Yu, Yihe ; Li, Xufei ; Zhao, Xiaochun ; Yue, Yihan ; Shi, Qiaofang

Abstract:

Fruit set is a key stage in determining yield potential and guaranteeing quality formation and regulation. N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) has been widely applied in grape production, the most iconic of which is the promotion of grape fruit set. However, current studies still lack the molecular mechanism of CPPU-induced grape fruit set. Here, the dynamic, high-resolution stage-specific transcriptome profiles were generated based on two different treatments and five developmental periods during fruit set in ‘Kyoho’ grape (Vitis vinifera L. × V. labrusca L.). Pairwise comparison and functional category analysis showed that phytohormone action cytokinin was significantly enriched during the CPPU-induced grape fruit set, but not the natural one. Value differentially expressed gene (VDEG) was a newly proposed analysis strategy for mining genes related to the grape fruit set. Notably, the cytokinin metabolic process was significantly enriched among up-regulated VDEGs. Of importance, a key VDEG VlCKX4 related to the cytokinin metabolic process was identified as related to the grape fruit set. Overexpression of VlCKX4 gene promoted the Arabidopsis plants that produce more and heavier siliques. The transcription factor VlMYB59 directly bound to the promoter of VlCKX4 and activated its expression. Moreover, overexpression of VlMYB59 gene also promoted the Arabidopsis fruit set. Overall, VlMYB59 responded to CPPU treatment and directly activated the expression of VlCKX4, thus promoting the fruit set. A regulatory pathway of the VlMYB59-VlCKX4 module in the fruit set was uncovered, which provides important insights into the molecular mechanisms of the fruit set and good genetic resources for high fruit set rate breeding.

项与氯磺丙脲相关的新闻（医药）

2024-02-08

·梅斯医学

医生怒斥杨波头孢配酒死不了的言论

2月4日下午，脱口秀演员杨波在其个人微博发文称，“这是一条定时微博，你们看到的时候我应该已经往生了，第一我心理承受能力不好；第二我确实做了错事，这是我的报应。”目前，该微博已删。随后他回应轻生称“大家别担心了，我没事儿，我发现头孢喝酒根本死不了，除了胃有点不舒服，一点事没有”。当天下午，记者从有关方面获悉，杨波确实有轻生行为，现在已经获救，目前处于平安状态。2月4日下午，400多万粉丝网红医生发文怒斥：请不要误导别人，不能宣传吃药喝酒没事，真的会带来悲剧，幸存者偏差的个例不能代表所有人都这么幸运。网友也纷纷表示，请不要这样误导人了。 “头孢就酒，说走就走”，真不是一句玩笑话，头孢与酒引起的双硫仑反应不容小觑。什么是双硫仑反应？吃药后喝酒引起的反应称之为双硫仑样反应。正常情况下，酒精进入人体后，约有10%左右会随着呼吸、尿液及汗液等以原形排出；其余则需要在各种酶的不断催化下逐步代谢，最终变成水和二氧化碳排出体外。如果乙醇在代谢过程中遇到阻碍，即乙醛脱氢酶的活性受到抑制，不能由乙醛代谢成乙酸，就会导致乙醛在体内蓄积。当血液中乙醛浓度升高5~10倍，就会出现乙醛蓄积综合征，即双硫仑样反应。严重的双硫仑样反应会致人死亡，虽然到不了“说走就走”的程度，但还是有“走”的可能。双硫仑是一种戒酒药物，又名戒酒硫。它在与乙醇联用时可不可逆的抑制肝脏中的乙醛脱氢酶，阻止乙醛的代谢，积累的高血清乙醛水平会引起令人不愉快的组胺样反应，称为双硫仑样反应。所以服用该药后即使饮用少量的酒，身体也会产生严重不适，而达到戒酒的目的。发生双硫仑反应，轻则头晕头痛、面部潮红、恶心呕吐，严重的还会出现血压降低、呼吸困难、心脏衰竭、肝功能衰竭、过敏性休克甚至死亡等症状。头孢类药物与双硫仑有什么关系？某些头孢类药物的分子结构上含有的甲硫四氮唑基团，与双硫仑的结构类似，对乙醛脱氢酶活性也有抑制作用。故当头孢类药物遇上乙醇就会出现与双硫仑样反应类似的表现，最终博得了“说走就走”的威名。其中，以头孢哌酮致双硫仑样反应的报告最多，此外常见的还有头孢美唑、头孢甲肟、头孢替安、拉氧头孢等。目前一些不含上述结构的药物，如头孢呋辛，也同样可能引起双硫仑样反应。其他还有如甲硝唑、甲苯磺丁脲、氯磺丙脲等药物。除头孢外还有很多药物也不能和酒同服1、对乙酰氨基酚片研究表明，饮酒有增加对乙酰氨基酚肝毒性的可能。2、降压药过量饮酒具有扩张血管、抑制交感神经及血管运动中枢、减弱心肌收缩力的作用。如果酒后服用降血压药，将使小血管更为扩张，血容量进一步减少，血压骤降，容易出现体位性低血压或晕厥。3、阿司匹林阿司匹林和酒精之间存在药代动力学的相互作用及一定药效学相互作用。任何浓度酒精的摄入都会增加对消化道的刺激，易引起胃黏膜病变或使溃疡复发，增加与阿司匹林相关的上消化道出血风险。4、镇静催眠药镇静催眠类药物与酒精合用后，对中枢的抑制程度与药物的种类、用药量、饮酒量有关，表现为嗜睡加重，反应灵敏度降低，注意力分散，协调能力差，严重的甚至可导致死亡。5、抗癫痫药酒精可影响某些抗癫痫药物的代谢，从而影响疗效。另外，饮酒本身也可能造成癫痫发作。因此，癫痫病人不适合饮酒。6.降糖药服用磺酰脲类药物期间饮酒，可发生严重低血糖或不可逆的神经系统病变。因为酒精可以阻碍甘油、乳酸和某些氨基酸转变为糖的过程而使血糖降低，还可引起“双硫仑样反应”。撰文 | Anna.An编辑 | Swagpp● 热议！北京协和医学院博士退学，近万名网友直呼太可惜、不理解！超50%博士会退学，博士为何难毕业？导师岗位是时候要规范了● 震撼！为了春节不值班，医生花2000，把班卖给博士师妹，自己倒贴1600！JAMA:值班让医生变胖！替人值班会成为医生新副业吗？● 要重视!欠薪8个月，601名员工，总额超4500万！山东某院长表示“自今日起绝食，以减少愧疚之心……”解决好问题，让医护过个好年版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」立刻下载梅斯医学APP！

AHA会议

2010-07-29

·Medical Design and Outsourcing

Giant EagleÃ‚® Expands Free Prescription Program To Include Free Diabetes Medicines in Western Pennsylvania

PITTSBURGH, July 29 /PRNewswire/ — With diabetes affecting the lives of hundreds of thousands of people throughout Pennsylvania and Ohio, Giant Eagle®, Inc. has announced that it will begin offering five commonly prescribed medications for the treatment of type 2 diabetes at no cost to medical prescription holders. (Logo: ) (Logo: ) The program, which begins July 29, includes the medications Glimepiride, Glipizide, Glyburide, Metformin and Chlorpropamide which were previously available on the supermarket retailer’s $4 prescription program. The free diabetes medication program was piloted in Columbus and Toledo, Ohio in April and to date has provided nearly $190,000 in customer savings on diabetes medications. Diabetes has become a leading cause of death in the United States, with more than 90 percent of the 24 million Americans diagnosed with type 2 diabetes. As a result, Giant Eagle has jo ‘/>”/> SOURCE

100 项与氯磺丙脲相关的药物交易

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