更新于：2024-05-01

Potassium Aggravated Myotonia

钾加重肌强直

更新于：2024-05-01

基本信息

别名

Acetazolamide responsive myotonia congenita、K+-aggravated myotonia、K-aggravated myotonia

+ [21]

简介

A group of autosomal dominant inherited non-dystrophic myotonias caused by mutations of the SCN4A gene, resulting in sodium muscle channelopathy. They are characterized by muscle stiffness, which worsens by ingestion of potassium-rich food. This group includes myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia.

关联

项与钾加重肌强直相关的临床试验

NCT06385756 / Not yet recruiting临床4期IIT

Effect of Amobarbital Sodium Combined With Low-dose Propofol on Hemodynamics During Induction and Perioperative Adverse Reactions in Gynecological Laparoscopic Surgery

At present, there are limited data on perioperative efficacy of barbiturates at home and abroad. The purpose of this clinical trial is to observe the effects of amobarbital sodium combined with low-dose propofol on hemodynamics during induction and perioperative adverse reactions in gynecological laparoscopic surgery patients, and to provide a more reasonable, safe and comfortable anesthesia program for female patients who undergoing laparoscopic surgery.
The main questions it aims to answer are:
whether the combination of the two results on more stable hemodynamics during induction in gynecological laparoscopic surgery patients;
whether the incidence of perioperative oxidative stress and inflammation and postoperative nausea and vomiting（ponv） improved after the use of the two combinations of anesthesia induction.
Participants will:
Induction of anesthesia with the experimental drug or placebo；
5 ml of venous blood was retained before, after, and 1 day after surgery for follow-up determination of serum associated factor levels；
To record their vital signs at any point during the anaesthetic process; Serum serological indexes related to oxidative stress and inflammation were determined. The agitation during the recovery period was recorded. The incidence and severity of ponv were recorded at 2h, 2-6h, and 6-24h postoperatively, and the use of palonosetron was also recorded.

开始日期2024-05-01

申办/合作机构

上海市同济医院

NCT01939561 / Completed临床3期

Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study

Myotonia is a functional limiting symptom where the muscle stiffens on action leading to arrest of movement. Pharmacological treatment may make the difference between a physically restricted and a normal life. Today, patients with myotonia are treated with Mexiletine a medications resulting in adverse events up to 40 % and which very expensive and difficult to obtain.
Our clinic has, forced by the above problems related to Mexiletine, treated a few patients with the drug Lamotrigine with pronounced positive effect in all. Lamotrigine belongs to the same category of drugs as Mexiletine but has fewer and milder side effects. Based on the similarities of the 2 drugs in pharmacological action and the positive experiences investigators are convinced that Lamotrigine will show a positive effect if evaluated in a broader scale. Due to the advantages of Lamotrigine compared to Mexiletine investigators find it of outmost importance for patients that this drug is assessed formally to establish Lamotrigine as a treatment choice for myotonia. Investigators believe that this will potentially make a huge difference in life quality for persons with myotonia. Investigators aim at investigating the efficacy and tolerability of Lamotrigine in the treatment of myotonia in a randomized doublet blinded placebo controlled crossover study.

开始日期2013-11-30

申办/合作机构

Rigshospitalet

EUCTR2013-003309-24-DK / Not yet recruitingN/A

Lamotrigine as treatment of Myotonia

开始日期2013-10-28

申办/合作机构-

100 项与钾加重肌强直相关的临床结果

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100 项与钾加重肌强直相关的转化医学

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0 项与钾加重肌强直相关的专利（医药）

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项与钾加重肌强直相关的文献（医药）

2024-02-20·EMBO molecular medicine

Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.

Article

作者: Sailan Wang ; Pernilla Nikamo ; Leena Laasonen ; Bjorn Gudbjornsson ; Leif Ejstrup ; Lars Iversen ; Ulla Lindqvist ; Jessica J Alm ; Jesper Eisfeldt ; Xiaowei Zheng ; Sergiu-Bogdan Catrina ; Fulya Taylan ; Raquel Vaz ; Mona Ståhle ; Isabel Tapia-Paez

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target.

2024-02-09·Current problems in cardiology

Severe Pulmonary Hypertension in Pulmonary Alveolar Microlithiasis: A Comprehensive Literature Review.

Review

作者: Guillermo Cueto-Robledo ; Maria-Del-Carmen Cantero-Ceballos ; Leslie-Marisol Gonzalez-Hermosillo ; Dulce-Iliana Navarro-Vergara ; Marisol Garcia-Cesar ; Maria-Berenice Torres-Rojas ; Lizbeth Hernandez-Villa ; Brenda-Guadalupe Serrato ; Ana Alfaro-Cruz

This review focuses on Pulmonary Alveolar Microlithiasis (PAM), an autosomal recessive genetic disorder characterized by calcium crystal deposits (microliths) resulting from loss of function of the SLC34A2 gene. PAM is a rare disease with approximately 1100 reported cases globally. The historical context of its discovery and the genetic, epidemiological, and pathophysiological aspects are discussed. PAM falls under interstitial lung diseases and is associated with pulmonary hypertension (PH), primarily categorized as Group 3 PH. The clinical manifestations, diagnostic approaches, and challenging aspects of treatment are explored. A clinical case of PAM with severe pulmonary hypertension is presented, emphasizing the importance of comprehensive evaluation and the potential benefits of phosphodiesterase-5 inhibitors (PDE5i) therapy. Despite limited therapeutic options and challenging diagnosis, this review sheds light on recent developments and emerging treatments for PAM and associated pulmonary hypertension.

2024-01-23·Melanoma research

Pregnancy-associated melanoma: characteristics and outcomes from 2002 to 2020.

Article

作者: Tara M Davidson ; Tina J Hieken ; Amy E Glasgow ; Elizabeth B Habermann ; Yiyi Yan

Melanoma diagnosed within 1 year of pregnancy is defined as pregnancy-associated melanoma (PAM). No robust data on how pregnancy influences melanoma nor guidelines for PAM management exist. With IRB approval, female patients with a pathology-confirmed melanoma diagnosis within 1 year of pregnancy treated at our institution from 2000 to 2020 were identified. Controls from the cancer registry were matched 1 : 4 when available on decade of age, year of surgery (±5), and stage. We identified 83 PAM patients with median follow-up of 86 months. Mean age at diagnosis was 31 years. 80% AJCC V8 stage I, 2.4% stage II, 13% stage III, 4.8% stage IV. Mean Breslow thickness was 0.79 mm and 3.6% exhibited ulceration. The mean mitotic rate was 0.76/mm2. In terms of PAM management, 98.6% of ESD patients and 86.7% of LSD patients received standard-of-care therapy per NCCN guidelines for their disease stage. No clinically significant delays in treatment were noted. Time to treatment from diagnosis to systemic therapy for LSD patients was an average of 46 days (95% CI: 34-59 days). Comparing the 83 PAM patients to 309 controls matched on age, stage, and year of diagnosis, similar 5-year overall survival (97% vs. 97%, P = 0.95) or recurrence-free survival (96% vs. 96%, P = 0.86) was observed. The outcomes of PAM following SOC treatment at a highly specialized center for melanoma care were comparable to non-PAM when matched by clinical-pathologic features. Specialty center care is encouraged for women with PAM.

项与钾加重肌强直相关的新闻（医药）

2023-11-05

·生物探索

Cell Discovery | 人类卵子非整倍体高发生率的潜在机理

非整倍体严重损害女性生育能力，增加出生缺陷的发生率。即使是来自年轻女性的人类卵子的非整倍体率也明显高于其他哺乳动物。然而，人类卵子非整倍体高发生率的内在遗传因素在很大程度上仍然未知。2023年10月24日，复旦大学王磊、武田宇及桑庆共同通讯在Cell Discovery（IF=34）在线发表题为“Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes”的研究论文，该研究发现人类TUBB8 在小鼠卵母细胞中的异位表达通过引起着丝点微管(K-MT)附着缺陷增加了非整倍体的发生率。在表达TUBB8的小鼠卵母细胞中，拉伸的二价体受到的张力较小，导致在I中期后期，AURKB/C对HEC1的持续磷酸化状态损害了已建立的正确的K-MT附着。该研究发现，没有C端尾的TUBB8异位表达通过减少错误的K-MT附着而降低了非整倍体率。重要的是，在复发性流产患者中发现了TUBB8 C端尾部的变异。小鼠卵母细胞中TUBB8变体的异位表达也会损害K-MT附着并增加非整倍体率。总之，该研究为人类卵子非整倍体的生理机制以及反复流产的病理生理机制提供了新的认识。人类卵子经常含有不正确数量的染色体，这种情况被称为非整倍体，它是女性不育/生育能力低下、反复流产和出生缺陷的主要原因之一。20 ~ 32岁女性非整倍体卵的发生率为20% ~ 30%，高于许多其他生殖年龄物种，如小鼠(1% ~ 4%)、猪(3% ~ 10%)、牛(5.8% ~ 7.1%)、马(~15.6%)和恒河猴(7.1% ~ 18.4%)。虽然在人类卵子中观察到高频率的非整倍体，但在生理条件下导致人类卵子高频率非整倍体的具体遗传因素和确切机制仍有待阐明。人类卵子的非整倍性是由减数分裂I中染色体分离错误引起的。研究表明，瞬态三极纺锤体诱导的三向分裂可能导致后期染色体分离容易出错。人类卵母细胞中缺乏KIFC1被认为是其不稳定和多纺锤极的原因，导致非整倍性增加。此外，短暂的不稳定多极纺锤体会导致人类卵母细胞中异常的着丝点微管(K-MT)附着，从而导致染色体误分离。成对的着丝点由来自相对纺锤极的微管连接，以确保准确的染色体分离。稳定的着丝点微管(也称为k-纤维)是正确的K-MT附着所必需的。TUBB8的异位表达增加了小鼠卵母细胞非整倍体的发生率（图源自Cell Discovery ）微管通常由保守的α和β-微管蛋白异二聚体组成。人β-微管蛋白由9个同型组成，包括TUBB1、TUBB2A、TUBB2B、TUBB3、TUBB4A、TUBB4B、TUBB5、TUBB6和TUBB8。除TUBB8外，在小鼠卵母细胞中也检测到8种。之前证明了TUBB8在人类卵母细胞纺锤体中是唯一表达的，纺锤体由含有显性β-微管蛋白同型编码的TUBB821的异源二聚体聚合而成。而小鼠卵母细胞纺锤体主要由β-微管蛋白同型组成，如TUBB3、TUBB4B、TUBB5和TUBB6。此外，之前的研究表明，TUBB8变异患者表现出由广泛的纺锤体缺陷引起的卵母细胞减数分裂停滞、早期胚胎发育停滞或非整倍体。该研究证明了灵长类特异性TUBB8的异位表达诱导小鼠卵母细胞非整倍体的升级，并进一步阐明了TUBB8诱导非整倍体的机制。此外，研究发现TUBB8 C端尾部的变异更容易产生非整倍体卵子，并与复发性流产有关。这些结果为人类卵子高频率非整倍体的生理和病理生理机制提供了新的认识。文章来源“iNature”责编|探索君排版|探索君参考文献：Dong, J., Jin, L., Bao, S. et al. Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes. Cell Discov 9, 105 (2023). https://doi.org/10.1038/s41421-023-00599-zEnd往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~

临床1期临床结果

2022-12-19

·药研网

肺癌及卵巢癌潜力靶点：NaPi2b（SLC34A2）

12月14日，欧盟委员会（EC）将Mersana的NaPi2b ADC药物upifitamab rilsodotin（UpRi）指定为治疗卵巢癌的孤儿药。NaPi2b靶点在肺癌及卵巢癌中发挥了重要作用。01NaPi2b/SLC34A22b型钠依赖性磷酸盐转运体（NaPi-IIb）是一种多通道的膜蛋白，由690个氨基酸组成，是溶质载体SLC34家族的成员，该家族由NaPi-IIa（SLC34A1）、NaPi-IIb（SLC34A2）和NaPi-IIc（SLC34A3）构成。其中NaPi-IIb蛋白通过钠离子共转运介导无机磷酸盐进入上皮细胞，负责维持全身的磷酸盐平衡。跨上皮磷酸盐转运NaPi-IIb包含两个保守序列的倒置重复单元，由一个大的细胞外环连接，两个末端都位于细胞膜内。人类NaPi-IIb蛋白二级拓扑结构的预测模型[1]NaPi-IIb是由基因SLC34A2编码而来，SLC34A2的cDNA于1999年首次从人类小肠和肺部cDNA文库中分离并克隆出来，虽然SLC34A2在人类的各种组织中都有表达，但在肺、小肠和肾脏中的表达量最高。在肺部，SLC34A2只在II型肺泡上皮细胞（ATII细胞）的顶端膜上表达，并在胎儿肺部发育和胚胎发育过程中起着关键作用。ATII细胞作为多功能的干细胞，在经历了外源性或内源性的因素后，可能转化为NSCLC.最近的研究发现SLC34A2的表达在NSCLC的手术样本和正常组织之间有明显的差异，并且SLC34A2在肺腺癌细胞系A549中下调，上调SLC34A2的表达可以明显抑制A549的细胞活力和体外侵袭。这些结果表明，SLC34A2可能在NSCLC的发展中发挥重要作用。除肺癌外，SLC34A2主要影响的另一疾病就是卵巢癌，其在大部分上皮性卵巢癌中过表达。此外，SLC34A2的异常表达还与肺泡微石症（PAM）、低磷血症、不孕症、睾丸微石症（TM）和其他恶性肿瘤（包括甲状腺癌、乳腺癌等）有关。02在研药物目前在研的NaPi2b靶向药以Mersana为主，且均为ADC药物。Mersana是一家专研ADC药物的公司，手握下一代ADC技术平台，与GSK、杨森、武田等药企均有合作。XMT-1536（UpRi）UpRi一种靶向NaPi2b的同类首创Dolaflexin ADC，具有高 DAR 和可控旁观者效应。Dolaflexin平台是为克服传统ADC的低DAR而设计，它采用Mersana专有的Fleximer聚合物，一种可生物降解、高度生物相容的水溶性聚合物，能够携带多种药物分子。药物分子通过一个优化的、可裂解的连接物连接到Fleximer支架上，然后再通过一个不可裂解的连接物与抗体结合。Fleximer极大地改善了药物的可溶性、药代动力学和免疫原性，并大大增加了每个ADC所携带的药物分子数量（DAR 10-12）。UpRi针对高级别浆液性卵巢癌患者的1/1b期研究中，NaPi2b阳性卵巢癌患者ORR为34%。最常报道的治疗相关不良事件是低级别的，包括疲劳、恶心等。除Mersana外，Zymworks在12月的公司文件中介绍了其临床前NaPiZb ADC药物。参考：https://doi.org/10.1186/s12929-015-0158-7https://doi.org/10.1016/j.bbrep.2021.101104往期推荐重磅！Moderna/默沙东癌症疫苗IIb期达主要终点PROTAC全球布局一览最新：42家已获批新冠病毒抗原检测试剂盒点击下方“药研网”，关注更多精彩内容

孤儿药抗体药物偶联物临床2期临床1期