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Tyrosine Hydroxylase as a Target for Deltamethrin in the Nigrostriatal Dopaminergic Pathway

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Biomedical and Environmental Sciences 2006年第1期19卷 27-34页

作者： GONG-PING LIU QIANG MA NIAN SHI Department of toxicology MOE key Laboratory of Environmental and Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei China Receptor Biology Laboratory Toxicology and Molecular Biology Branch Health Effects Laboratory Division National Institute for Occupational Safety and Health Centers for Disease Control and Prevention Morgantown WV 26505 USA

Objective To study the effects of deltamethrin on tyrosine hydroxylase in nigrostriatum of male rats. Methods Sprague-Dawley rats were daily treated with deltamethrin at 6.25 or 12.5 mg/kg body weight by gavage for 10 days. Then HPLC-fluorescence detection was used to analyze the contents of dopamine （DA）, 3,4-dihydmxyphenylacetic acid （DOPAC） and homoranillic acid （HVA） in substantial nigra and striatum. The activities of tyrosine hydroxylase （TH） were also detected by HPLC-fluorescence detection. TH mRNA or TH protein levels were measured by RT-PCR and immunohistochemistry method. Results The content of DA in stfiatum was significantly decreased by the treatments, suggesting an inhibition of DA synthesis by deltamethrin. The contents of DA metabolites DOPAC and HVA increased, indicating increased dopamine turnover. Furthermore, deltamethrin significantly decreased the activity, as well as the mRNA and protein levels of TH. Conclusions These findings reveal a novel aspect of deltamethfin neurotoxicity and suggest tyrosine hydroxylase as a molecular target of deltamethin on dopamine metabolism in the nigrostriatal pathway.

关键词： Deltamethrin Nigrostriatum Dopamine Tyrosine hydroxylase Parkinson's disease

Biogenic Amines as Biomarkers for Neurotoxicity

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Biomedical and Environmental Sciences 1991年第Z1期 207-216页

作者： SYED F.ALI,LOUIS W.CHANG,WILLIAM SLIKKER,JR division of Reproductive and Developmental toxicology National Center for Toxicological Research Jefferson Department of Pharmacology and toxicology Department of Biochemistry and Molecular Biology division of Reproductive and Developmental toxicology National Center for Toxicological Research Jefferson division of Reproductive and Developmental toxicology National Center for Toxicological Research Jefferson Arkansas 72079-9502 Department of Pharmacology and toxicology Department of Biochemistry and Molecular Biology Department of Pharmacology University of Arkansas for medical Sciences Little Rock Arkansas 72205 Arkansas 72079-9502 Department of Pharmacology and toxicology Department of Pediatrics Universtiy of Arkansas for medical Sciences and Arkansas Children's Hospital Little Rock Arkansas 72205 Arkansas 72079-9502 Department of Pharmacology and toxicology Department of Pediatrics Universtiy of Arkansas for medical Sciences and Arkansas Children's Hospital Little Rock Arkansas 72205

There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers

关键词： MDMA Biogenic Amines as Biomarkers for Neurotoxicity oral DOPAC

Comprehensive Application of Graphene: Emphasis on Biomedical Concerns

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Nano-Micro Letters 2019年第1期11卷 101-131页

作者： S.Syama P.V.Mohanan toxicology division Biomedical Technology Wing Sree Chitra Tirunal Institute for Medical Sciences and Technology

Graphene, sp^2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional(2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a sca old for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications.

关键词： Graphene Biomedical Bioprinting Toxicity Photothermal therapy

Drug therapy for Parkinson's disease: An update

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World Journal of Pharmacology 2015年第1期4卷 117-143页

作者： Omar ME Abdel-Salam Department of toxicology and Narcotics Medical DivisionNational Research Centre

Parkinson's disease(PD) is the most common neurodegenerative movement disorder, affecting about 1% of the population above the age of 65. PD is characterized by a selective degeneration of the dopaminergic neurons of the substantia nigra pars compacta. This results in a marked loss of striatal dopamine and the development of the characteristic features of the disease, i.e., bradykinesia, rest tremor, rigidity, gait abnormalities and postural instability. Other types of neurons/neurotransmitters are also involved in PD, including cholinergic, serotonergic, glutamatergic, adenosine, and GABAergic neurotransmission which might have relevance to the motor, non-motor, neuro-psychiatric and cognitive disturbances that occur in the course of the disease. The treatment of PD relies on replacement therapy with levodopa(L-dopa), the precursor of dopamine, in combination with a peripheral decarboxylase inhibitor(carbidopa or benserazide). The effect of L-dopa, however, declines over time together with the development of motor complications especially dyskinesia in a significant proportion of patients within 5 years of therapy. Other drugs include dopaminereceptor-agonists, catechol-O-methyltransferase inhibitors, monoamine oxidase type B(MAO-B) inhibitors, anticholinergics and adjuvant therapy with the antiviral drug and the N-methyl-D-aspartate glutamate receptor antagonist amantadine. Although, these medications can result in substantial improvements in parkinsonian symptoms, especially during the early stages of the disease, they are often not successful in advanced disease. Moreover, dopaminergic cell death continues over time, emphasizing the need for neuroprotective or neuroregenerative therapies. In recent years, research has focused on non-dopaminergic approach such as the use of A2 A receptor antagonists: istradefylline and preladenant or the calcium channel antagonist isradipine. Safinamide is a selective and reversible inhibitor of MAO-B, a glutamate receptor inhibi

关键词： Parkinson disease Levodopa Dopaminergic drugs Neuroprotective agents Non-dopaminergic drugs Mitochondrial enhancers

Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

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World Journal of Gastroenterology 2008年第1期14卷 38-45页

作者： Yvonne Meier Tina Zodan Carmen Lang Roland Zimmermann Gerd A Kullak-Ublick Peter J Meier Bruno Stieger Christiane Pauli-Magnus division of Clinical Pharmacology and toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Department of Gynecology and Obstetrics University Hospital Zurich Zurich Switzerland division of Clinical Pharmacology and toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Clinical Trial Unit University Hospital Basel Basel Switzerland

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

关键词： Cholestasis of pregnancy Contraceptive-induced cholestasis Bile salt export pump Multidrugresistance associated protein 2 Pharmacogenetics

Highlights and new Editorial Advisory Board members of the Journal of Environmental Sciences

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Journal of Environmental Sciences 2016年第9期28卷 1-6页

作者： Qingcai Feng Suqin Liu Zhengang Mao Jian Xu Zixuan Wang X.Chris Le Research Center for Eco-Environmental Sciences Chinese Academy of Sciences division of Analytical and Environmental toxicology Department of Laboratory Medicine and PathologyUniversity of Alberta

The Journal of Environmental Sciences（JES）is honored to welcome Professors/Drs William ***,Jiuhui Qu,Susan ***,Jerald ***,Hongxiao Tang,Shu Tao,and Hugh *** to serve on the Editorial Advisory Board（EAB）.Their tremendous experience in scientific publications,leading expertise in topic areas pertinent to JES,diverse international networks/perspectives,and exemplary dedication to scientific excellence will guide and help the continuing healthy growth of JES.

关键词： honored welcome publications expertise Richardson continuing diverse excellence tremendous disinfection

Pathology of atherosclerotic coronary artery disease in the young Indian population

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Forensic Sciences Research 2019年第3期4卷 241-246页

作者： Pradeep Vaideeswar Shashank Tyagi Saranya Singaravel Department of Pathology(Cardiovascular&Thoracic division) Seth GS Medical College&KEM HospitalMumbaiIndia Department of Forensic Medicine&toxicology Seth GS Medical College&KEM HospitalMumbaiIndia

Atherosclerotic coronary artery disease (CAD) is of great concern in young adults because of its potential to cause great *** arena of cardiology has gained importance in South Asian countries,particularly India due to increased prevalence that is related to traditional risk factors,altered life styles and inherent risk *** this study,we sought to evaluate,at autopsy,the pathology of atherosclerotic CAD in young patients with ischemic heart disease (IHD).A 10-year retrospective autopsy-based study was carried out in a large tertiary-care centre and patients aged ≤45 years with IHD were *** of 545 autopsied cases of IHD,95 patients (17.4%) were *** these 95 patients,84 (88.4%) had IHD related to atherosclerotic CAD;the youngest patient was 18years *** there was sole involvement of left anterior descending artery and the presence of fibrous *** of the plaque morphology,the commonest complication was thrombosis produced by plaque erosion seen in 36.9% of *** coronary insufficiency was noted in 52 patients (61.9%),while healed infarctions were surprisingly noted in 28 patients (33.3%).Screening for IHD in the young population may help to improve prognosis by detecting subclinical disease,although more studies are necessary to establish reference limits for this young *** research must also focus on treatment concerns that are specific to young patients.

关键词： Forensic sciences forensic pathology ischemic heart disease coronary atherosclerosis young adults sudden cardiac death

Editorial: Effect of root anatomy and apoplastic barrier development on cadmium uptake in rice

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Journal of Environmental Sciences 2019年第5期31卷 361-363页

作者： Karen S.Hoy Jagdeesh S.Uppal X.Chris Le Department of Chemistry University of Alberta division of Analytical and Environmental toxicology Department of Laboratory Medicine and Pathology Faculty of Medicine and Dentistry University of Alberta

Cadmium (Cd) is a toxic metal with high mobility from soil and known translocation into plants (Song et al., 2015).Because the main source of human exposure to Cd is from food consumption, there has been increased res... 详细信息

关键词： Metal contamination Cadmium uptake and translocation Rice cultivar and roots Arsenic,lead,manganese,zinc Water and soil Apoplastic barrier

Global output of research on epidermal parasitic skin diseases from 1967 to 2017

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Infectious Diseases of Poverty 2018年第1期7卷 730-739页

作者： Waleed M.Sweileh Department of Physiology Pharmacology/ToxicologyDivision of Biomedical SciencesCollege of Medicine and Health SciencesAn-Najah National UniversityNablusPalestine

Background:Epidermal parasitic skin diseases(EPSD)occur in most countries and cause a considerable health and economic burden,particularly in the tropics and *** aim of this study was to assess and analyse peerreviewed literature on EPSD in *** results of this study serve as an indicator of the extent the scientific community,health authorities,and international health agencies interact with EPSD as a health problem that is commonly associated with poverty and poor ***:A bibliometric analysis methodology was *** Scopus database was used to retrieve documents about EPSD for the study period(1967-2017).The study focused on scabies,tungiasis,pediculosis,hookwormrelated cutaneous larva migrans(HrCLM),myiasis,and cutaneous *** that specifically and explicitly discuss EPSD in animals,aquatic organisms,and birds were ***:In total,4186 documents were retrieved.A fluctuated growth of publications on EPSD in the past five decades was *** retrieved documents received 43301 citations,an average of 10.3 citations per article and an h-index of *** keywords“scabies”and was the most commonly encountered keyword followed by the keywords“head lice”and“pediculosis”.The most active journal involved in publishing articles on EPSD was the International Journal of Dermatology(164;3.9%).Researchers from 93 different countries published the retrieved *** USA led with 735(17.6%)documents,followed by the UK(274;6.5%),and Germany(259;6.2%).In terms of institutions,the Charite-Universitätsmedizin Berlin in Germany was the most active in this field with 78(1.9%)publications,followed by the Universidade Federal do Cearáin Brazil with 52(1.2%)***:Research on scabies and pediculosis dominated the field of EPSD research to the expense of tungiasis,HrCLM,myiasis,and cutaneous *** was an underrepresentation of literature from the tropics and subtropics despite EPSD being com

关键词： Epidermal parasitic skin diseases Bibliometric analysis Keyword mapping Scopus