报告1例多系统萎缩(multiple system atrophy,MSA)伴抗利尿激素分泌不当综合征(syndrome of inap‐propriate antidiuretic hormone secretion,SIADHS)患者。患者为54岁男性,因反复晕厥、发热就诊。查体示平卧位转直立位3 min时血压下...报告1例多系统萎缩(multiple system atrophy,MSA)伴抗利尿激素分泌不当综合征(syndrome of inap‐propriate antidiuretic hormone secretion,SIADHS)患者。患者为54岁男性,因反复晕厥、发热就诊。查体示平卧位转直立位3 min时血压下降超过20 mmHg/10 mmHg,面部表情少,构音欠清,双侧咽反射消失,四肢肌张力增高,双上肢肌张力齿轮样增高,双上肢轮替试验笨拙,双手握拳试验笨拙,双足拍地运动笨拙,双上肢意向性震颤,双侧掌颌反射(+),双侧Babinski征(+)。胸部CT示肺部感染,血、尿炎性指标升高,血钠及血浆渗透压降低、尿钠升高,经抗感染治疗,肺部及泌尿系感染好转后体温未恢复正常。颅脑MRI示脑干、小脑萎缩。诊断MSA合并SIADHS、中枢性高热,予物理降温、降低环境温度、限水补钠后体温及血钠逐渐恢复正常。MSA合并SIADHS、中枢性高热临床罕见,本文分析该病例的诊治过程及复习相关文献,以提高临床医师对MSA非运动症状的认识,减少误诊、漏诊。展开更多
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under...Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.展开更多
基金funded by the National Natural Science Foundation of China,No.81971891(to KX),81571939(to KX),81772134(to KX),81772024(to JY),and 81860781(to FXL)the Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金the Natural Science Foundation of Hunan Province of China,No.2017JJ2339(to JY)the Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)
文摘Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.
