Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
R Soc Open Sci ; 11(1): 231893, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38204785

RESUMO

[This corrects the article DOI: 10.1098/rsos.180139.][This corrects the article DOI: 10.1098/rsos.180139.].

2.
Phys Rev E ; 104(4-2): 045001, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781439

RESUMO

A system of three-variable differential equations, which has a nonstationary trajectory transition through the control of a single rate parameter, is formulated. For the nondimensional system, the critical trajectory creeps before a transition in a long-lasting plateau region in which the velocity vector of the system hardly changes and then diverges positively or negatively in finite time. The mathematical model well represents the compressive viscoelasticity of a spring-damper structure simulated by the multibody dynamics analysis. In the simulation, the post-transition behaviors realize a tangent stiffness of the self-contacted structure that is polarized after transition. The mathematical model is reduced not only to concisely express the abnormal compression problem, but also to elucidate the intrinsic mechanism of creep-to-transition trajectories in a general system.

3.
R Soc Open Sci ; 8(10): 210768, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34703621

RESUMO

A very low-frequency mode supported within an auxetic structure is presented. We propose a constrained periodic framework with corner-to-corner and edge-to-edge sharing of tetrahedra and develop a kinematic model incorporating two types of linear springs to calculate the momentum term under infinitesimal transformations. The modal analysis shows that the microstructure with its two degrees of freedom has both low- and high-frequency modes under auxetic transformations. The low-frequency mode approaches zero frequency when the corresponding spring constant tends to zero. With regard to coupled eigenmodes, the stress-strain relationship of the uniaxial forced vibration covers a wide range. When excited, a very slow motion is clearly observed along with a structural expansion for almost zero values of the linear elastic modulus.

4.
R Soc Open Sci ; 5(6): 180139, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30110423

RESUMO

A specific periodic bar-and-joint framework with limited degrees of freedom is shown to have a transition mechanism when subjected to an external force. The static nonlinear elasticity of this framework under a uniaxial load is modelled with the two angular variables specifying the rotation and distortion of the linked square components. Numerically exploring the equilibrium paths then reveals a transition state of the structure at a critical value of the internal stiffness. A simplified formulation of the model with weak nonlinear terms yields an exact solution of its transition state. Load-displacement behaviour and stability for the two systems with or without approximation are analysed and compared.

5.
Diabetologia ; 56(5): 1088-97, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23412604

RESUMO

AIMS/HYPOTHESIS: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. METHODS: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. RESULTS: BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. CONCLUSIONS/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.


Assuntos
Citoesqueleto de Actina/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Neuropeptídeos/metabolismo , Via Secretória , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Hiperglicemia/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Masculino , Camundongos , Camundongos Knockout , Neuropeptídeos/antagonistas & inibidores , Neuropeptídeos/genética , Pâncreas/citologia , Pâncreas/metabolismo , Perfusão , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Ratos , Técnicas de Cultura de Tecidos , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/genética
6.
Anal Sci ; 17(8): 975-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11708103

RESUMO

A chemiluminescence method with potassium permanganate was developed for use as an indicator of organic pollutants in fresh water. This method could be applied to the determination of organic pollutants in seawater as well. However, the flow chemiluminescence method suffered from the interference of chloride ions at the same concentration of seawater because of the production of manganese dioxide in the oxidation of chloride ions with permanganate. The conditions (concentrations of potassium permanganate and sulfuric acid and sample volume, i.e. flow injection method) were chosen to minimize the interference of chloride ions. The chemiluminescence method shows a good correlation with the chemical oxygen demand method on fresh water added artificial sea salt and seawater samples. Natural seawater was analyzed by the chemiluminescence method. The results obtained were compared with those obtained by chemical oxygen demand under the alkaline condition and total organic carbon methods. The chemiluminescence method has higher sensitivity and reproducibility than the conventional chemical oxygen demand and total organic carbon methods.


Assuntos
Permanganato de Potássio/química , Água do Mar/análise , Poluentes Químicos da Água/análise , Cromatografia Líquida , Análise de Injeção de Fluxo , Indicadores e Reagentes , Medições Luminescentes
7.
J Org Chem ; 66(21): 7008-12, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11597221

RESUMO

Synthetic procedures for monoazathiacrown ethers were explored, and monoazatrithia-12-crown-4, monoazatetrathia-15-crown-5, and monoazapentathia-18-crown-6 were obtained in moderate yields by the reaction of bis(2-chloroethyl)amine with the appropriate dithiols in the presence of lithium hydroxide in THF. To evaluate metal-ion binding properties of the monoazathiacrown ethers by solvent extraction, lipophilic dodecyl and dodecanoyl groups were incorporated onto the monoazathiacrown ethers. The solvent extraction experiments suggested that monoazathiacrown ethers have Ag(+) and Hg(2+) selectivities and that the relative selectivity between Ag(+) and Hg(2+) depends on their nitrogen atom properties and numbers of sulfur atoms reflecting the respective affinities of nitrogen and sulfur atoms to Hg(2+) and Ag(+). An interesting ability to bind Mg(2+) was observed in the case of N-dodecyl monoazatrithia-12-crown-4.

8.
J Electrocardiol ; 34(3): 243-50, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11455515

RESUMO

This article investigates the development of cardiovascular autonomic dysfunction caused by diabetes mellitus. We performed power spectral analysis of heart rate variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of the rats was measured continuously for 24 hours with an implanted telemetric transmitter, and power spectral analysis of heart rate variability was performed on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a tendency toward a decrease in plasma insulin concentration without hyperglycemia. At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm of the blood pressure. By the power spectral analysis of heart rate variability, it became apparent that the circadian rhythm of the low frequency/high frequency ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian rhythms of the high-frequency power level and low frequency/high frequency ratio were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic nervous system in WBN/Kob rats is progressively damaged from the prediabetic to diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized by the appearance of sympathetic overactivity that precedes the impairment of parasympathetic activity.


Assuntos
Ritmo Circadiano/fisiologia , Neuropatias Diabéticas/diagnóstico , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Processamento de Sinais Assistido por Computador , Animais , Neuropatias Diabéticas/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos , Ratos Wistar
9.
J Org Chem ; 66(5): 1533-7, 2001 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-11262094

RESUMO

Spirobenzopyran derivatives carrying an oxymethylcrown ether moiety were synthesized, and their photochromism was studied in the presence of various metal ions in acetonitrile. The metal ion complexing ability of the crown ether moiety in crowned spirobenzopyrans affects both thermal isomerization and photoisomerization of their spirobenzopyran moiety to a great extent. When the interaction of the crown ether moiety with a metal ion was strong enough to cause thermal isomerization of the spirobenzopyran moiety to its corresponding merocyanine form and to suppress UV-induced isomerization to the merocyanine form, a negative photochromism appears. On the other hand, a relatively weak interaction of the crown ether moiety with a metal ion affords a positive photochromism. This phenomenon enables us to switch the photochromic behavior between positive and negative photochromisms.

10.
Am J Vet Res ; 62(1): 37-42, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11197557

RESUMO

OBJECTIVE: To determine characteristics of power spectral analysis of heart rate variability (HRV) during a 24-hour period in dogs and to evaluate the effects of vagal and sympathetic tone on HRV ANIMALS: 16 healthy adult Beagles. PROCEDURE: Power spectral analysis of HRV was conducted, using 24-hour ambulatory ECG recordings. Circadian rhythms were evaluated in terms of absolute units of low-frequency (LF) and high-frequency (HF) powers, their ratio (LF:HF), and their adjusted (normalized) units (LF[norm] and HF[norm]). Three or 4 dogs were used for simultaneous measurement of heart rate and respiratory waveform as well as to evaluate treatment (propranolol, atropine, or both) administered to cause blockade of the autonomic nervous system. RESULTS: Values for LF and HF powers, LF:HF, LF(norm), and HF(norm) had obvious rhythmicity in clinically normal dogs. The HF power of HRV in dogs was extremely high, compared with that of other species, and HF peaks corresponded to peaks obtained from respiratory waveforms. Blockade of the autonomic nervous system documented that HRV in dogs was mostly attributable to vagal activity. CONCLUSION AND CLINICAL RELEVANCE: We determined characteristics of power spectral analysis of HRV in dogs, including circadian rhythm of the autonomic nervous system. Power spectral analysis of HRV may provide a useful noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs.


Assuntos
Ritmo Circadiano/fisiologia , Cães/fisiologia , Frequência Cardíaca/fisiologia , Animais , Eletrocardiografia Ambulatorial/veterinária , Feminino , Masculino , Valores de Referência
11.
Clin Chim Acta ; 304(1-2): 153-8, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11165212

RESUMO

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.


Assuntos
Xantina Desidrogenase/genética , Xantinas/urina , Sequência de Bases , Primers do DNA , DNA Complementar , Humanos , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Valores de Referência , Xantina Desidrogenase/metabolismo
12.
J Clin Pathol ; 53(11): 854-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11127269

RESUMO

BACKGROUND: During medical checkups of two unrelated female outpatients during their annual health examination and one male inpatient suffering from cardiac failure the glycated haemoglobin (HbA1C) concentrations measured by high performance liquid chromatography (HPLC) were low, in spite of normal fasting plasma glucose concentrations. However, HbA1C concentrations measured by latex immunoagglutination and fructosamine concentrations were within the normal range. METHOD: Investigations were performed to elucidate the reasons for these discrepancies. RESULTS: Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, were found. The HPLC chromatogram showed an additional peak near HbA1a + b, which resulted in falsely low HbA1C concentrations. Isoelectric focusing analysis of the patients' haemoglobin disclosed abnormal haemoglobins, which migrated faster than normal HbA1 in the two female patients and slower in the male patient. The cDNA sequence and amino acid analyses of the haemoglobin alpha-chains and beta-chains indicated the presence of the haemoglobin variant beta 120 Lys-->Gln in the two female patients and beta 80 Asn-->Lys in the male patient; that is, Hb Takamatsu and Hb G-Szuhu. CONCLUSIONS: These cases show how these silent haemoglobin variants can result in falsely low HbA1C concentration readings when using HPLC.


Assuntos
Hemoglobinas Glicadas/análise , Hemoglobinas Anormais/análise , Idoso , Cromatografia Líquida de Alta Pressão , Reações Falso-Negativas , Feminino , Humanos , Focalização Isoelétrica , Pessoa de Meia-Idade
13.
Toxicology ; 151(1-3): 91-101, 2000 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-11074304

RESUMO

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In order to elucidate a possible mechanism for its development and to account for this species difference, we determined the plasma level of growth hormone (GH) in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-dependent increase in their GH level; and, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These results were supported by evidence from immunohistochemical and morphometric analysis of the pituitary gland. In addition, dienogest and medroxyprogesterone acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mammary epithelial cells incubated under the same conditions. In conclusion, dienogest with progestational activity caused proliferation of the mammary gland in beagle dogs by increasing the secretion of GH, as do other progestational compounds. This change may be partially dependent on the direct effect of the drug.


Assuntos
Antagonistas de Hormônios/farmacologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Nandrolona/análogos & derivados , Animais , Células Cultivadas , Cães , Epitélio/efeitos dos fármacos , Epitélio/crescimento & desenvolvimento , Feminino , Antagonistas de Hormônios/farmacocinética , Hormônio do Crescimento Humano/sangue , Humanos , Imuno-Histoquímica , Macaca mulatta , Glândulas Mamárias Animais/efeitos dos fármacos , Acetato de Medroxiprogesterona/farmacologia , Nandrolona/farmacocinética , Nandrolona/farmacologia , Congêneres da Progesterona/farmacologia , Ratos , Estimulação Química
14.
No To Shinkei ; 52(7): 625-8, 2000 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-10934724

RESUMO

We report a rare case of intrasellar epidermoid cyst. A 61-year-old man presented with complaints of the disturbance of consciousness and general fatigability. His laboratory data showed panhypopituitarism and MRI revealed the cystic tumor located at the intrasellar region. Tumor was removed by transsphenoidal approach and histological examination of the surgical specimen showed that the cyst wall was composed of the stratified squamous epithelium with keratohyaline granules.


Assuntos
Encefalopatias/patologia , Cisto Epidérmico/patologia , Sela Túrcica , Encefalopatias/cirurgia , Cisto Epidérmico/cirurgia , Humanos , Hipopituitarismo/complicações , Masculino , Pessoa de Meia-Idade
15.
J Diabetes Complications ; 14(1): 60-2, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10925068

RESUMO

We present a case of a 31-year-old Type 1 diabetic woman who self-administered 2400 units of insulin mixture (70% NPH human insulin and 30% Regular human insulin) as a suicidal attempt. The subsequent hypoglycemia was prolonged probably due to delayed absorption of the subcutaneous insulin, but it was not very difficult to control despite the administration of large amounts of insulin. Although the estimated serum insulin level was not well correlated with the severity of hypoglycemia, the hypoglycemia subsided when the serum insulin level returned to the physiological level. Therefore, the study of insulin pharmacokinetics after insulin overdose may be useful to know the necessary duration of exogenous glucose administration required to manage the medical emergency of severe insulin intoxication in future cases.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Hipoglicemia/induzido quimicamente , Insulina/sangue , Insulina/intoxicação , Tentativa de Suicídio , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Feminino , Glucose/administração & dosagem , Glucose/uso terapêutico , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Insulina/farmacocinética , Fatores de Tempo
16.
Metabolism ; 49(7): 912-9, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10910004

RESUMO

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.


Assuntos
Transtornos da Coagulação Sanguínea/prevenção & controle , Diabetes Mellitus/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Inibidores da Agregação Plaquetária/uso terapêutico , Animais , Ácido Eicosapentaenoico/uso terapêutico , Fibrinólise/efeitos dos fármacos , Teste de Tolerância a Glucose , Insulina/sangue , Resistência à Insulina , Masculino , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar
17.
J Org Chem ; 65(14): 4342-4347, 2000 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-10891136

RESUMO

Spirobenzothiapyrans bearing monoaza-12-crown-4, -15-crown-5, -18-crown-6, and oligooxyethylene moieties were synthesized, and their photochromism was examined in the presence of cations in acetonitrile. The cation complexation by their crown ether moieties cannot induce thermal isomerization to their corresponding colored merocyanine form, unlike the corresponding spirobenzopyran derivatives. The UV-light-induced isomerization was, however, facilitated by the cation complexation of the crown ether moieties and the affinity of the merocyanine thiophenolate anion to metal ions, especially in the presence of Li(+) and Ag(+). The presence of Ag(+) brought about the most remarkable effect in the facilitation of photoisomerization of the spirobenzothiapyrans and the thermal stability of the colored merocyanine form mainly due to the powerful interaction of the thiophenolate anion with the soft metal ion.

18.
Thromb Res ; 98(6): 507-16, 2000 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10899350

RESUMO

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Coagulação Sanguínea/fisiologia , Modelos Animais de Doenças , Fatores Etários , Animais , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/fisiopatologia , Fatores de Coagulação Sanguínea/metabolismo , Glicemia/metabolismo , Plaquetas/química , Diabetes Mellitus Experimental/sangue , Feminino , Fibrinólise/fisiologia , Fibrinolíticos/metabolismo , Teste de Tolerância a Glucose , Insulina/sangue , Lipídeos/análise , Lipídeos/sangue , Masculino , Agregação Plaquetária/fisiologia , Ratos , Ratos Endogâmicos
19.
J Vet Med Sci ; 62(5): 491-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10852397

RESUMO

We previously reported that D0870 induced QT prolongation and sudden death due to torsades de pointes (TdP) in dogs and that catecholamines played an important part in the development of the sudden death. In the present study, we analyzed in detail the ambulatory electrocardiographic recordings obtained from the just-mentioned study to elucidate the mechanism of the onset of TdPs and conducted an in vitro study using isolated canine Purkinje fibers to assess the effect of D0870 on repolarization. The hearts with TdPs observed before the sudden death showed a higher sinus rate for 5 and 10 sec before the onset, a shorter coupling interval, and a higher ventricular tachycardia rate compared with those having the non-sustained TdPs. These findings suggest that D0870-induced fatal TdPs may be provoked by a triggered activity developed from delayed after depolarizations. In contrast, as the pause-dependent, non-sustained TdPs in bradycardia showed a typical "short-long-short" sequence, they may be developed from early afterdepolarization . Moreover, the results of the in vitro study supported our contention that D0870 induced QT prolongation in a reverse use-dependent manner in vivo and suggested that it may inhibit not only rapidly activating delayed rectifier potassium current (Ik(r)) but also L-type Ca current (I(ca-L)).


Assuntos
Antifúngicos/toxicidade , Cães/fisiologia , Torsades de Pointes/veterinária , Triazóis/toxicidade , Potenciais de Ação/efeitos dos fármacos , Animais , Estimulação Elétrica , Eletrocardiografia Ambulatorial/veterinária , Feminino , Masculino , Ramos Subendocárdicos/efeitos dos fármacos , Torsades de Pointes/induzido quimicamente
20.
J Electrocardiol ; 33(2): 181-8, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10819411

RESUMO

We previously reported the occurrence of QT prolongation and sudden death owing to torsades de pointes (TdP) in dogs treated with D0870, an antifungal agent. In the present study, we evaluated the influences of epinephrine and isoproterenol on the onset of TdP each time D0870 was given to 6 anesthetized open-chest dogs at a dosage of 20 mg/kg, 5 times every 40 minutes, by the simultaneous measurements of surface electrocardiogram and epicardial monophasic action potential (MAP). D0870 alone induced noticeable prolongation of the QT interval and action potential duration (APD), but neither ventricular premature contraction (VPC) nor sudden death. In contrast, the additional administration of the catecholamines induced a greater shortening of APD during the later phase of repolarization than during its earlier one and VPCs in all dogs tested, and sudden deaths owing to TdPs in 4 of the 6 dogs treated with D0870. These results suggest that D0870 alone does not induce TdP but that catecholamines play an important part in the development of sudden death induced by D0870 in dogs.


Assuntos
Antifúngicos/toxicidade , Catecolaminas/toxicidade , Morte Súbita Cardíaca , Triazóis/toxicidade , Potenciais de Ação , Animais , Cães , Eletrocardiografia , Epinefrina/toxicidade , Ventrículos do Coração/fisiopatologia , Isoproterenol/toxicidade , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...