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[PMID]:26375719
[Au] Autor:Ozolins TR; Weston AD; Perretta A; Thomson JJ; Brown NA
[Ad] Endereço:Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen's University, Botterell Hall, Kingston, ON K7L 3N6, Canada. Electronic address: ozolinst@queensu.ca.
[Ti] Título:Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels.
[So] Source:Toxicol Appl Pharmacol;289(1):89-97, 2015 Nov 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40-100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome.
[Mh] Termos MeSH primário: Dimetadiona/toxicidade
Embrião de Mamíferos/efeitos dos fármacos
Desenvolvimento Embrionário/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/toxicidade
Dimetadiona/sangue
Relação Dose-Resposta a Droga
Técnicas de Cultura Embrionária
Feminino
Idade Gestacional
Gravidez
Ratos
Ratos Sprague-Dawley
Trimetadiona/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); ALU9NPM703 (Dimethadione); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:151031
[Lr] Data última revisão:
151031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150917
[St] Status:MEDLINE


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[PMID]:26233654
[Au] Autor:Ashizawa N; Hamano K; Noda A
[Ad] Endereço:Division of Gastroenterology, Japan Community Healthcare Organization Tamatsukuri Hospital, Tamayu-cho, Yumachi 1-2, Matsue, 699-0293, Japan. ashizawa.n@smn.enjoy.ne.jp.
[Ti] Título:Effectiveness of oral litholysis therapy for improving glucose intolerance and malnutrition in patients with poor results following endoscopic therapy and extracorporeal shock wave lithotripsy for calcified pancreatic stones.
[So] Source:Clin J Gastroenterol;8(5):294-9, 2015 Oct.
[Is] ISSN:1865-7265
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We report a case of pancreatolithiasis in which glucose intolerance and malnutrition were significantly improved after starting oral litholysis therapy (OLT) with use of trimethadione. A 43-year-old female with multiple calcified stones in the main and peripheral pancreatic ducts had experienced recurrent and severe attacks of pain for 7 years (from 21 to28 years of age). Impaired glucose tolerance was first noted at the age of 32 years. We started OLT after interventional endoscopic therapy combined with extracorporeal shock wave lithotripsy failed because of kink and stenosis of the main pancreatic duct (MPD). Over the next 9 years, a significant decrease in total pancreatic calcified stone volume was shown by computer analysis of follow-up computed tomography images. Larger stones completely disappeared without attacks of pain. In addition, both glucose intolerance and insulin secretion were significantly ameliorated, followed by improvement of malnutrition. OLT may induce intraductal decompression by dissolving stones in the peripheral ducts as well as the MPD, with resulting preservation of endocrine function and improvement of malnutrition. Since the present results were obtained in a single case, further clinical trials are necessary to evaluate the value of performing OLT under various conditions to eliminate stones.
[Mh] Termos MeSH primário: Cálculos/complicações
Cálculos/tratamento farmacológico
Intolerância à Glucose/terapia
Desnutrição/terapia
Pancreatite/complicações
Pancreatite/tratamento farmacológico
Trimetadiona/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Colangiopancreatografia Retrógrada Endoscópica
Feminino
Intolerância à Glucose/etiologia
Seres Humanos
Insulina/sangue
Litotripsia
Desnutrição/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151113
[Lr] Data última revisão:
151113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150803
[St] Status:MEDLINE
[do] DOI:10.1007/s12328-015-0591-x


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[PMID]:24846538
[Au] Autor:Pastore V; Wasowski C; Higgs J; Mangialavori IC; Bruno-Blanch LE; Marder M
[Ad] Endereço:Instituto de Química y Fisicoquímica Biológicas "Prof. Alejandro C. Paladini", Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 (C1113AAD), Buenos Aires, Argentina. Electronic address: vpastore@qb.ffyb.uba.ar.
[Ti] Título:A synthetic bioisoster of trimethadione and phenytoin elicits anticonvulsant effect, protects the brain oxidative damage produced by seizures and exerts antidepressant action in mice.
[So] Source:Eur Neuropsychopharmacol;24(8):1405-14, 2014 Aug.
[Is] ISSN:1873-7862
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Epilepsy is recognized as one of the most common and serious neurological disorder affecting 1-2% of the world׳s population. The present study demonstrates that systemic administration of 3-butyl-5,5-dimethyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (DIOXIDE), a synthetic compound bioisoster of trimethadione and phenytoin (classical anticonvulsants), elicits a dose dependent anticonvulsant response in mice submitted to the subcutaneous pentylenetetrazole seizure test (scPTZ). Among various factors supposed to play role in epilepsy, oxidative stress and reactive species have strongly emerged. The protection exerted by DIOXIDE over the extent of brain oxidative damage produced by PTZ was determined, by measuring the levels of lipid peroxidation and reduced glutathione and the activity of Na(+)/K(+)-ATPase. Psychiatric disorders represent frequent comorbidities in persons with epilepsy. In this report, the potential anxiolytic and antidepressant activities of DIOXIDE were evaluated in several widely used models for assessing anxiolytic and antidepressant activities in rodents. Although DIOXIDE did not evidence anxiolytic activity at the doses tested, it revealed a significant antidepressant-like effect. Preliminary studies of its mechanism of action, by means of its capacity to act via the GABAA receptor (using the [(3)H]flunitrazepam binding assay in vitro and the picrotoxin test in vivo) and the Na(+) channel (using the alkaloid veratrine, a voltage-Na(+) channel agonist) demonstrated that the anticonvulsant effect is not likely related to the GABAergic pathway and the antidepressant-like effect could be due to its Na(+) channel blocking properties. The results for DIOXIDE suggested it as a new anticonvulsant-antioxidant and antidepressant compound that deserves further development.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Antidepressivos/uso terapêutico
Lesões Encefálicas/prevenção & controle
Fenitoína/uso terapêutico
Convulsões/tratamento farmacológico
Convulsões/patologia
Trimetadiona/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Lesões Encefálicas/metabolismo
Modelos Animais de Doenças
Flunitrazepam/farmacocinética
Glutationa/metabolismo
Elevação dos Membros Posteriores/psicologia
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Atividade Motora/efeitos dos fármacos
Pentilenotetrazol/toxicidade
Fenitoína/química
Convulsões/induzido quimicamente
ATPase Trocadora de Sódio-Potássio/metabolismo
Fatores de Tempo
Trimetadiona/química
Veratrina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Antidepressive Agents); 6158TKW0C5 (Phenytoin); 620X0222FQ (Flunitrazepam); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); ERQ7M6C50B (Veratrine); GAN16C9B8O (Glutathione); R7GV3H6FQ4 (Trimethadione); WM5Z385K7T (Pentylenetetrazole)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:140801
[Lr] Data última revisão:
140801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140522
[St] Status:MEDLINE


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[PMID]:23321016
[Au] Autor:Pastore V; Sabatier L; Enrique A; Marder M; Bruno-Blanch LE
[Ad] Endereço:Química Medicinal, Departamento de Ciencias Biológicas, UNLP, calle 47 y 115, B1900BJW La Plata, Argentina. vpastore@qb.ffyb.uba.ar
[Ti] Título:Synthesis and anticonvulsant activity of bioisosteres of trimethadione, N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides from α-hydroxyamides.
[So] Source:Bioorg Med Chem;21(4):841-6, 2013 Feb 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The synthesis and anticonvulsant activity of novel heterocycles N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, bioisosteres of trimethadione (TMD, oxazolidine-2,4-dione) and phenytoin (PHE), are described. TMD is an anticonvulsant drug widely used against absences seizures in the early 80's and PHE is an antiepileptic drug with a wide spectrum activity. The intermediates of synthesis of N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, α-hydroxyamides, were obtained using microwave assisted synthesis. Anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetrazole seizures test (scPTZ). These new compounds showed a wide spectrum activity and were no neurotoxic in the RotoRod test. α-Hydroxyamides and N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides were 3-4700 times more potent than valproic acid in the MES test. Quantification of anticonvulsant protection was calculated (ED(50)) for the most active candidates; α-hydroxyamides 3a-c and 3e, and N-derivative-oxathiazolidine-4-one-2,2-dioxides 5a-c with ED(50) values of 9.1, 53.9, 44.6, 25.2, 15.1, 91.1 and 0.06mg/kg, respectively, in the MES test.
[Mh] Termos MeSH primário: Amidas/química
Anticonvulsivantes/síntese química
Tiazolidinas/química
Trimetadiona/química
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/química
Anticonvulsivantes/toxicidade
Comportamento Animal/efeitos dos fármacos
Masculino
Camundongos
Micro-Ondas
Fenitoína/química
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Relação Estrutura-Atividade
Trimetadiona/síntese química
Trimetadiona/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amides); 0 (Anticonvulsants); 0 (Thiazolidines); 6158TKW0C5 (Phenytoin); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:1308
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130117
[St] Status:MEDLINE


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[PMID]:23017458
[Au] Autor:Qin W; Hu ZY; Tong JW; Meng J; You XF; Zhang JP
[Ad] Endereço:Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. yd06413qw@126.com
[Ti] Título:[Toxic effects of trimethadione on zebrafish early development].
[So] Source:Yi Chuan;34(9):1165-73, 2012 Sep.
[Is] ISSN:0253-9772
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To further understand the neural toxicity and teratogenicity of antiepileptic drugs in clinic, we established a zebrafish model for antiepileptic toxicity using trimethadione as a probe drug. The results indicated that embryonic malformation occurred under trimethadione treatment in a concentration-dependent manner. The defects included growth retardation, small head, eyes and acoustic capsule, deficient semicircular canals and otolith, and abnormal cardiovascular system. The number of hair cells in neuromast ML2 was obviously reduced in the treated larvae. Whole mount in situ hybridization indicated that the gene expression patterns of brain marker genes, such as zic1 and xb51, and autophagic gene atg5 was changed significantly. The result of RT-PCR showed that the expressions of hearing genes val and hmx2 were also changed in the trimethadione-treated embryos. All these findings suggest that brain tissue and the neural sensors for body balance and hearing are the main targets of trimethadione toxicity, and that zebrafish is able to mimic mammal responses to the teratogenicity and the neural toxicity of trimethadione in the embryonic and larva development.
[Mh] Termos MeSH primário: Desenvolvimento Embrionário/efeitos dos fármacos
Teratogênios/toxicidade
Trimetadiona/toxicidade
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/induzido quimicamente
Animais
Desenvolvimento Embrionário/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Teratogens); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:1212
[Cu] Atualização por classe:161020
[Lr] Data última revisão:
161020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120929
[St] Status:MEDLINE


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[PMID]:21638752
[Au] Autor:Weston AD; Brown NA; Ozolins TR
[Ad] Endereço:Department of Developmental and Reprodutive Toxicology, Pfizer Global Research and Development, Groton, Connecticut, USA.
[Ti] Título:Co-variation in frequency and severity of cardiovascular and skeletal defects in Sprague-Dawley rats after maternal administration of dimethadione, the N-demethylated metabolite of trimethadione.
[So] Source:Birth Defects Res B Dev Reprod Toxicol;92(3):206-15, 2011 Jun.
[Is] ISSN:1542-9741
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The anticonvulsant trimethadione is a potent inducer of ventricular septation defects, both clinically and in rodents. Teratogenicity requires its N-demethylation to dimethadione, the proximate teratogen. It was previously demonstrated trimethadione only induced membranous ventricular septation defects in rat (Fleeman et al., 2004), and our present goal is to determine whether direct administration of dimethadione increases the incidence and severity of septation defects. METHODS: Pregnant Sprague-Dawley rats were divided into five groups and administered either distilled water (control) or four different regimens of dimethadione. The core treatment was 300 mg/kg dimethadione b.i.d. on gestation day 9, 10 with additional groups given one additional dose of dimethadione 12 hr earlier, 12 hr later or two additional doses 12 hr earlier and later. Caesarian sections occurred on gestation day 21 and fetuses were examined for standard developmental toxicity endpoints. RESULTS: The broadest dosing regimen yielded the highest incidence and the most severe heart and axioskeletal findings with a decrease in mean fetal body weight. The overall incidence of ventricular septation defects was 74%, of which 68% were membranous and 9% muscular. Outflow tract anomalies (17%) were also observed, as were malformations of the axioskeleton (97%), but not of the long bones, and of particular interest was the high incidence of sternoschesis. CONCLUSIONS: Unlike trimethadione, dimethadione induces more serious muscular septation defects that are believed to be more clinically relevant. This, when taken together with the high incidence of total septation anomalies suggests dimethadione is useful for the study of chemically induced ventricular septation defects.
[Mh] Termos MeSH primário: Osso e Ossos/anormalidades
Osso e Ossos/efeitos dos fármacos
Anormalidades Cardiovasculares/induzido quimicamente
Dimetadiona/toxicidade
Exposição Materna
Trimetadiona/análogos & derivados
Trimetadiona/toxicidade
[Mh] Termos MeSH secundário: Animais
Anormalidades Cardiovasculares/patologia
Cesárea
Dimetadiona/administração & dosagem
Feminino
Coração/efeitos dos fármacos
Gravidez
Efeitos Tardios da Exposição Pré-Natal/patologia
Ratos
Ratos Sprague-Dawley
Trimetadiona/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
ALU9NPM703 (Dimethadione); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:1201
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110604
[St] Status:MEDLINE
[do] DOI:10.1002/bdrb.20302


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[PMID]:21237239
[Au] Autor:Weigt S; Huebler N; Strecker R; Braunbeck T; Broschard TH
[Ad] Endereço:Institute of Toxicology, Merck KGaA, 64293 Darmstadt, Germany. stefan.weigt@merck.de
[Ti] Título:Zebrafish (Danio rerio) embryos as a model for testing proteratogens.
[So] Source:Toxicology;281(1-3):25-36, 2011 Mar 15.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Zebrafish embryos have been shown to be a useful model for the detection of direct acting teratogens. This communication presents a protocol for a 3-day in vitro zebrafish embryo teratogenicity assay and describes results obtained for 10 proteratogens: 2-acetylaminofluorene, benzo[a]pyrene, aflatoxin B(1), carbamazepine, phenytoin, trimethadione, cyclophosphamide, ifosfamide, tegafur and thio-TEPA. The selection of the test substances accounts for differences in structure, origin, metabolism and water solubility. Apart from 2-acetylaminofluorene, which mainly produces lethal effects, all proteratogens tested were teratogenic in zebrafish embryos exposed for 3 days. The test substances and/or the substance class produced characteristic patterns of fingerprint endpoints. Several substances produced effects that could be identified already at 1 dpf (days post fertilization), whereas the effects of others could only be identified unambiguously after hatching at ≥ 3 dpf. The LC50 and EC50 values were used to calculate the teratogenicity index (TI) for the different substances, and the EC20 values were related to human plasma concentrations. Results lead to the conclusion that zebrafish embryos are able to activate proteratogenic substances without addition of an exogenous metabolic activation system. Moreover, the teratogenic effects were observed at concentrations relevant to human exposure data. Along with other findings, our results indicate that zebrafish embryos are a useful alternative method for traditional teratogenicity testing with mammalian species.
[Mh] Termos MeSH primário: Testes de Mutagenicidade/métodos
Teratogênios/toxicidade
Peixe-Zebra
[Mh] Termos MeSH secundário: 2-Acetilaminofluoreno/toxicidade
Aflatoxina B1/toxicidade
Animais
Carbamazepina/toxicidade
Cinarizina/toxicidade
Ciclofosfamida/toxicidade
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Ifosfamida/toxicidade
Óvulo/efeitos dos fármacos
Piracetam/toxicidade
Tegafur/toxicidade
Tiotepa/toxicidade
Trimetadiona/toxicidade
Peixe-Zebra/embriologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Teratogens); 0 (phezam); 1548R74NSZ (Tegafur); 33CM23913M (Carbamazepine); 3DI2E1X18L (Cinnarizine); 8N3DW7272P (Cyclophosphamide); 905Z5W3GKH (Thiotepa); 9M98QLJ2DL (2-Acetylaminofluorene); 9N2N2Y55MH (Aflatoxin B1); R7GV3H6FQ4 (Trimethadione); UM20QQM95Y (Ifosfamide); ZH516LNZ10 (Piracetam)
[Em] Mês de entrada:1103
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110118
[St] Status:MEDLINE
[do] DOI:10.1016/j.tox.2011.01.004


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[PMID]:18248662
[Au] Autor:Evason K; Collins JJ; Huang C; Hughes S; Kornfeld K
[Ad] Endereço:Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8103, St. Louis, MO 63110, USA.
[Ti] Título:Valproic acid extends Caenorhabditis elegans lifespan.
[So] Source:Aging Cell;7(3):305-17, 2008 Jun.
[Is] ISSN:1474-9726
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging. Caenorhabditis elegans is a valuable model for studies of animal aging, and the analysis of drugs that extend the lifespan of this animal can elucidate mechanisms of aging and might lead to treatments for age-related disease. By testing drugs that are Food and Drug Administration approved for human use, we discovered that the mood stabilizer and anticonvulsant valproic acid (VA) extended C. elegans lifespan. VA also delayed age-related declines of body movement, indicating that VA delays aging. Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans. A structure-activity analysis demonstrated that the related compound valpromide also extends lifespan. Valproic acid treatment may modulate the insulin/IGF-1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF-16 nuclear localization. To investigate the mechanism of action of VA in delaying aging, we analyzed the effects of combining VA with other compounds that extend the lifespan of C. elegans. Combined treatment of animals with VA and the heterocyclic anticonvulsant trimethadione caused a lifespan extension that was significantly greater than treatment with either of these drugs alone. These data suggest that the mechanism of action of VA is distinct from that of trimethadione, and demonstrate that lifespan-extending drugs can be combined to produce additive effects.
[Mh] Termos MeSH primário: Caenorhabditis elegans/efeitos dos fármacos
Longevidade/efeitos dos fármacos
Ácido Valproico/farmacologia
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/crescimento & desenvolvimento
Caenorhabditis elegans/fisiologia
Relação Dose-Resposta a Droga
Etossuximida/farmacologia
Longevidade/fisiologia
Modelos Animais
Fatores de Tempo
Trimetadiona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
5SEH9X1D1D (Ethosuximide); 614OI1Z5WI (Valproic Acid); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:0810
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:080206
[St] Status:MEDLINE
[do] DOI:10.1111/j.1474-9726.2008.00375.x


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[PMID]:17291698
[Au] Autor:Shen H; Zhang B; Shin JH; Lei D; Du Y; Gao X; Wang Q; Ohlemiller KK; Piccirillo J; Bao J
[Ad] Endereço:Department of Otolaryngology, Center for Aging, Washington University, 4560 Clayton Avenue, St. Louis, MO 63110, USA.
[Ti] Título:Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss.
[So] Source:Hear Res;226(1-2):52-60, 2007 Apr.
[Is] ISSN:0378-5955
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cochlear noise injury is the second most frequent cause of sensorineural hearing loss, after aging. Because calcium dysregulation is a widely recognized contributor to noise injury, we examined the potential of calcium channel blockers to reduce noise-induced hearing loss (NIHL) in mice. We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. Young C57BL/6 mice of either gender were divided into three groups: a 'prevention' group receiving the blocker via drinking water before noise exposure; a 'treatment' group receiving the blocker via drinking water after noise exposure; and controls receiving noise alone. Trimethadione significantly reduced NIHL when applied before noise exposure, as determined by auditory brainstem recording. Both ethosuximide and trimethadione were effective in reducing NIHL when applied after noise exposure. Results were influenced by gender, with males generally receiving greater benefit than females. Quantitation of hair cell and neuronal density suggested that preservation of outer hair cells could account for the observed protection. Immunocytochemistry and RT-PCR suggested that this protection involves direct action of T-type blockers on alpha1 subunits comprising one or more Ca(v)3 calcium channel types in the cochlea. Our findings provide a basis for clinical studies testing T-type calcium blockers both to prevent and treat NIHL.
[Mh] Termos MeSH primário: Bloqueadores dos Canais de Cálcio/farmacologia
Etossuximida/farmacologia
Perda Auditiva Provocada por Ruído/tratamento farmacológico
Perda Auditiva Provocada por Ruído/prevenção & controle
Trimetadiona/farmacologia
[Mh] Termos MeSH secundário: Animais
Limiar Auditivo/efeitos dos fármacos
Sequência de Bases
Bloqueadores dos Canais de Cálcio/uso terapêutico
Canais de Cálcio Tipo T/efeitos dos fármacos
Canais de Cálcio Tipo T/genética
Canais de Cálcio Tipo T/metabolismo
Cóclea/efeitos dos fármacos
Cóclea/metabolismo
Cóclea/patologia
Primers do DNA/genética
Etossuximida/uso terapêutico
Feminino
Perda Auditiva Provocada por Ruído/genética
Perda Auditiva Provocada por Ruído/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Caracteres Sexuais
Trimetadiona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Calcium Channel Blockers); 0 (Calcium Channels, T-Type); 0 (DNA Primers); 5SEH9X1D1D (Ethosuximide); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:0705
[Cu] Atualização por classe:170219
[Lr] Data última revisão:
170219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:070213
[St] Status:MEDLINE


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[PMID]:16911703
[Au] Autor:Hashimoto A; Moritani I; Shimizu A; Shiraki K
[Ad] Endereço:Department of Internal Medicine, Saiseikai Matsusaka General Hospital, Matsusaka, Mie, Japan.
[Ti] Título:Education and imaging. Hepatobiliary and pancreatic: oral therapy for pancreatic duct stones.
[So] Source:J Gastroenterol Hepatol;21(9):1496, 2006 Sep.
[Is] ISSN:0815-9319
[Cp] País de publicação:Australia
[La] Idioma:eng
[Mh] Termos MeSH primário: Cálculos/tratamento farmacológico
Cálculos/patologia
Pâncreas/patologia
Ductos Pancreáticos/patologia
Trimetadiona/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Anticonvulsivantes/uso terapêutico
Cálculos/diagnóstico por imagem
Seres Humanos
Masculino
Pâncreas/diagnóstico por imagem
Ductos Pancreáticos/diagnóstico por imagem
Radiografia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); R7GV3H6FQ4 (Trimethadione)
[Em] Mês de entrada:0705
[Cu] Atualização por classe:161124
[Lr] Data última revisão:
161124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:060817
[St] Status:MEDLINE



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