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Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa department of Critical Care medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan department of Clinical toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural Institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

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Transporter-Mediated Organ Toxicity

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毒理学杂志 2005年第S1期 173-174页

作者： Hitoshi Endou,Yoshikatsu Kanai department of pharmacology and toxicology kyorin university school of medicine 6-20-2 shinkawa mitaka tokyo 181-8611 japan department of pharmacology and toxicology kyorin university school of medicine 6-20-2 shinkawa mitaka tokyo 181-8611 japan

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Transporter-Mediated Organ Toxicity

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毒理学杂志 2005年第A3期19卷 173-174页

作者： Hitoshi Endou Yoshikatsu Kanai department of pharmacology and toxicology Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka Tokyo 181-8611 Japan Department of Pharmacology and Toxicology Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka Tokyo 181-8611 Japan

The absorption, distribution and excretion of most of xenobiotics, drugs, environmental toxins and their metabolites are mediated by membrane transporters.

关键词：环境毒素调节机构输送机构分子水平

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Transporter-Mediated Organ Toxicity

Transporter-Mediated Organ Toxicity

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中国毒理学会第四届全国学术会议

作者： Hitoshi Endou Yoshikatsu Kanai department of pharmacology and toxicology kyorin university school of medicine 6-20-2 shinkawa mitaka tokyo 181-8611 japan department of pharmacology and toxicology kyorin university school of medicine 6-20-2 shinkawa mitaka tokyo 181-8611 japan

＜正＞The absorption, distribution and excretion of most of xenobiotics, drugs, environmental toxins and their metabolites are mediated by membrane transporters. Recent advances in the transporter research have made it possible to investigate the mechanisms of transport of those exogenous compounds and their transporter-mediated organ toxicity at the molecular level. Exogenous compounds including drugs and toxic substances occurring in the environment pass through the transporters with broad substrate selectivity, namely "multispecific" transporters, to enter the cells and exert their toxic effects. The remarkable examples of such transporter-mediated toxicity are l-methyl-4-phenyl-2,3-dihydropyridinium （MPP+）-neurotoxicity mediated by dopamine transporters, cephaloridine-nephrotoxicity and ochratoxin A-nephrotoxicity mediated by organic anion transporters and methylmercury-toxicity mediated by system L amino acid transporters （LATs）.

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Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity

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World Journal of Gastroenterology 2006年第7期12卷 1071-1077页

作者： Osamu Kanauchi Masanobu Fukuda Yoshiaki Matsumoto Shino Ishii Toyokazu Ozawa Makiko Shimizu Keiichi Mitsuyama Akira Andoh Kirin Brewery Co.Ltd. 10-1-2 Shinkawa Chuo-kuTokyo104-8288Japan College of Pharmacy Nihon University 7-7-1 Narashinodai FunabashiChiba 274-8555Japan department of Clinical pharmacology and toxicology Showa Pharmaceutical University3-3165Higashi-TamagawagakuenMachidaTokyo194-8543Japan Kurume university school of medicine 67 Asahi-machiKurumeFukuoka 830-0011Japan Shiga university of Medical Science TsukinowaSetaOtsuShiga520-2100Japan

AIM： To examine the effect of Eubacteriuro Iiroosuro （***） on colonic epithelial cell line in vitro, and to evaluate the effect of *** on experimental colitis.METHODS： *** was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the *** metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 （TLR4） was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized *** （n=7） or control diet （n=7）. Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.RESULTS： The *** produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 retool/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with *** significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.CONCLUSION： *** can ameliorate experimental colonic inflammation. In part, the metabolite of ***, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.

关键词： Intestinal Microflora, Butyrate, Eubacterium limosum Toll like receptor, IL-6

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c-Fos expression within the L_5 spinal cord dorsal horn after spinal nerve ligation in rats Is intraplantar administration of glutamate different from intrathecal administration?

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Neural Regeneration Research 2010年第6期5卷 450-455页

作者： Youhong Jin Hongshui Zhu Zhihua Li Dongfang Li Jianhua Hu Motohide TakemuraO Norifumi YoneharaO department of Anatomy Affiliated Stomatological Hospital of Nanchang University Nanchang 330006 Jiangxi ProvinceChina department of Oral Anatomy and Neurobiology Osaka University Graduate School of Dentistry Suita 565-0871 Japan Divisions of pharmacology Ohu University School of Pharmaceutical Science Koriyama Fukushima 963-8611 Japan

BACKGROUND： Injection of glutamate （Glu） in normal animals can cause neuronal c-Fos expression; however, whether Glu can induce spinal neuronal c-Fos expression in pain models is unclear. OBJECTIVE： To examine the effects of intraplantar and intrathecal injection of Glu on c-Fos expression in the L5 spinal cord dorsal horn Ⅰ/Ⅱ and Ⅲ/Ⅳ layers after spinal nerve ligation, and to study the effects of the N-methyI-D-aspartic acid （NMDA） receptor antagonist, D-2-amino-5-phosphonopentanoate （D-AP5）, and a selective group I mGluR antagonist, 7-hydroyiminocyclo propan[a]chromen-lacarboxylic acid ethyl ester （cpccoEt）. DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the department of pharmacology, Oral Anatomy, and Neurobiology, Osaka university Graduate school of Dentistry, from December 2005 to December 2006. MATERIALS： Glu （5 μmol）, D-AP5 （50 nmot） and cpccoEt （250 nmol） were provided by Wako Pure Chemical Industries, Osaka, japan, and diluted in saline （50 μL）. The pH of all solutions was adjusted to 7.4. METHODS： Twelve rats were randomly divided into sham operation （n = 6） and spinal nerve ligation （SNL; n = 6） groups for behavioral assessments of neuropathic pain after ligation surgery of the left L5-6 nerve segment. Another 60 rats were randomly divided into sham operation, SNL, saline-intraplantar, saline-intrathecal, Glu-intraplantar, Glu-intrathecal, D-AP5-intrathecal, Glu-D-AP5-intrathecal, cpccoEt-intrathecal, and Glu-cpccoEt-intrathecal groups, with 6 rats in each group. All groups except sham operation group received a similar SNL. On day 14, rats received a 50-μL injection of saline, Glu, D-AP5, and/or cpccoEt into the left intraplantar or intrathecal L5-4 segments. MAIN OUTCOME MEASURES： The number of c-Fos positive neurons in both Ⅰ/Ⅱ and Ⅲ/Ⅳ spinal layers at L6 was observed using immunohistochemistry 2 hours after administration. RESULTS：（1） SNL increased the level of c-Fos expression in two sides of the spinal cord, parti

关键词： spinal cord nerve ligation glutamate c-Fos metabotropic glutamate receptors intrathecal administration intraplantar administration

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BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2490-2503页

作者： Xiu-Xiu Liu Xing-Hui Chen Zhi-Wei Zheng Qin Jiang Chen Li Lin Yang Xiang Chen Xing-Feng Mao Hao-Yang Yuan Li-Li Feng Quan Jiang Wei-Xing Shi Takuya Sasaki Kohji Fukunaga Zhong Chen Feng Han Ying-Mei Lu Key Laboratory of Cardiovascular&Cerebrovascular medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical University211166 NanjingChina department of Physiology School of Basic Medical SciencesNanjing Medical University211166 NanjingChina Institute of pharmacology and toxicology College of Pharmaceutical SciencesZhejiang University310058 HangzhouChina department of Pharmaceutical and Administrative Sciences Loma Linda University School of PharmacyLoma LindaCA 92350USA department of Basic Sciences Loma Linda University School of MedicineLoma LindaCA 92350USA department of pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai 980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical University210029 NanjingChina Gusu school Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical University215002 SuzhouChina

Cerebellar ataxias are characterized by a progressive decline in motor coordination,but the specific output circuits and underlying pathological mechanism remain poorly *** cell-type-specific manipulations,we discovered a novel GABAergic Purkinje cell(PC)circuit in the cerebellar IV/V lobe that projected to CaMKIIα+neurons in the fastigial nucleus(FN),which regulated sensorimotor ***,transcriptomics profiling analysis revealed various cerebellar neuronal identities,and we validated that biorientation defective 1(BOD1)played an important role in the circuit of IV/V lobe to ***1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs,accompany with ataxia ***,BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+neurons in the FN and ameliorated ataxia behaviors in L7-Cre;BOD1f/f ***,these findings further suggest that specific regulation of the cerebellar IV/V lobePCs→FNCaMKIIα+circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

关键词： fastigial reversed Together

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Histamine modulation of acute nociception involves regulation of Nav1.8 in primary afferent neurons in mice

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中国药理学与毒理学杂志 2012年第3期 432-433页

作者：于捷 Hiroshi Ohtsu department of pharmacology Key Laboratory of Medical Neurobiology of the Ministry of Health of ChinaCollege of Pharmaceutical SciencesSchool of MedicineZhejiang University department of Engineering School of MedicineTohoku UniversityAoba-kuSendai 980-8775Japan

OBJECTIVE To explore the role of histamine in acute pain *** We studied the sensitivity to acute pain in histidine decarboxylase knockout mice(HDC-/-),wild-type mice treated with α-fluoromethylhistidine(α-FMH),a specific HDC inhibitor,and mice feed a low-histamine ***,Western blotting and Electrophysiology studies were taken to explore the involvement of sodium channel 1.8(Nav 1.8) in the pathological *** Behavioral tests revealed that HDC-/-mice had lower nociceptive thresholds for acute thermal(hot-plate),mechanical(tail-pressure) and chemical(acetic acid and formalin) stimulation than the *** low-histamine diet elevated the sensitivity to all these noxious stimuli in the wild-type,and to heat and formalin stimuli in the HDC-/-mice.α-FMH treatment also augmented acute thermal nociception in the *** and Western blotting studies showed that both HDC knockout and α-FMH treatment increased the expression of Nav1.8 in nociceptive primary afferent *** higher Nav1.8 current density in nociception-related small DRG neurons of HDC-/-mice verified this ***,the current required to evoke action potentials was significantly lower,and the firing rate in response to suprathreshold stimulation was higher in neurons from HDC-/-*** hyperexcitability of DRG neurons in HDC-/-mice was diminished by a Nav1.8 inhibitor,but not *** Our results indicate that histamine participates in acute pain modulation,which may be related to the regulation of Nav1.8 in,as well as the excitability of,nociceptive primary afferent neurons.

关键词： HDC FMH Histamine modulation of acute nociception involves regulation of Nav1.8 in primary afferent neurons in mice

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Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels

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Research 2023年第4期2023卷 739-753页

作者： Chu Tong Peng-Xiang Min Qian Zhang Ru-Xin Gu Yao-Hai Wen Yi Shi Yu-Huan Bao Xiang Chen Yi-Xuan Zhang Xing-Feng Mao Hao-Yang Yuan Xiu-Xiu Liu Takuya Sasaki Li Zhang Feng Han Ying-Mei Lu department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China department of Geriatrics Nanjing Brain Hospital Affiliated to Nanjing Medical UniversityNanjing210029China Institute of pharmacology and toxicology College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Gusu school Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou215002China department of pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like ***,the molecular mechanisms underlying this disturbance remain ***,we showed that cyclin-dependent kinase 5(Cdk5)was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing *** levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor ***,Cdk5 deficiency in cholinergic neurons triggered paw tremors,abnormal motor coordination,and motor balance deficits in *** symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+channels(BK channels).Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient ***,CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of *** of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f ***,these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuronmediated motor function,providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

关键词： Cdk5 Neuron CDK5

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A review on the pharmacological and toxicological aspects of Datura stramonium L.

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Journal of Integrative medicine 2013年第2期11卷 73-79页

作者： Bhakta Prasad Gaire Lalita Subedi department of Herbal pharmacology College of Oriental Medicine Kyung Hee University department of Pharmaceutical Sciences School of Health and Allied Sciences Pokhara University

Datura stramonium L., a wild-growing plant of the Solanaceae family, is widely distributed and easily accessible. It contains a variety of toxic tropane alkaloids such as atropine, hyoscamine, and scopolamine. In Eastern medicine, especially in Ayurvedic medicine, D. stramonium has been used for curing various human ailments, including ulcers, wounds, inflammation, rheumatism and gout, sciatica, bruises and swellings, fever, asthma and bronchitis, and toothache. A few previous studies have reported on the pharmacological effects of D. stramonium; however, complete information regarding the pharmacology, toxicity, ethnobotany and phytochemistry remains unclear. Ethnomedicinally, the frequent recreational abuse of D. stramonium has resulted in toxic syndromes. D. stramonium, in the form of paste or solution to relieve the local pain, may not have a deleterious effect; however, oral and systemic administration may lead to severe anticholinergic symptoms. For this reason, it is very important for individuals, mainly young people, to be aware of the toxic nature and potential risks associated with the use of this plant. This comprehensive review of D. stramonium includes information on botany, phytochemistry, pharmacology, toxicology and ethnomedicinal uses.

关键词： Datura stramonium pharmacologic actions medicine, traditional phytotherapy drug toxicity review

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