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1.
Artigo em Chinês | MEDLINE | ID: mdl-29429181

RESUMO

Objective: To investigate the effect of melatonin on the expression of prestin protein in the inner ear of mice following a single dose radiation therapy, so as to provide the basis for the mechanism study of radiation induced inner ear injury and its prevention. Methods: Sixty 4-week-old male mice were randomly divided into six groups, including the control group (A group), 50 mg/kg MLT group (B group), 5 mg/kg MLT group (C group), 50 mg/kg MLT + radiotherapy group (D group), 5 mg/kg MLT+ radiotherapy group (E group), and 16 Gy radiotherapy group (F group). Each experimental group was randomly subdivided into two subgroups, which were killed to harvest the cochlea on the 3rd and 7th days following 16 Gy radiation. The specimens were used for immunostaining and Western blot to detect the expression of prestin protein. SPSS 19.0 software was used for statistical analysis. Results: Prestin protein mainly distributed in the lateral membrane above the outer hair cell nucleus. When compared with A, B and C group, the expression of prestin protein in the inner ear was significantly up-regulated in F group (P<0.05). However, D and E group reduced the abnormal expression of prestin following radiotherapy when compared with F group, the difference was statistically significant (P<0.05), and the effect of D group was more significant than E group (P<0.05). Conclusions: The prestin protein of cochlea is mainly distributed in the lateral membrane above the outer hair cell nucleus. Following the high-dose radiotherapy, the prestin expression is upregulated, and melatonin can control the abnormal expression of prestin protein induced by radiotherapy with dose dependent.


Assuntos
Orelha Interna/metabolismo , Orelha Interna/efeitos da radiação , Células Ciliadas Auditivas Externas/metabolismo , Melatonina/farmacologia , Proteínas Motores Moleculares/metabolismo , Animais , Cóclea/efeitos dos fármacos , Cóclea/efeitos da radiação , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/efeitos da radiação , Masculino , Camundongos , Distribuição Aleatória
2.
Bioorg Med Chem ; 6(7): 1077-87, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9730245

RESUMO

A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable inhibition of eosinophil adhesion to TNF- (tumor necrosis factor) alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.


Assuntos
Antialérgicos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Nitrilas/síntese química , Administração Oral , Animais , Antialérgicos/administração & dosagem , Antialérgicos/química , Antialérgicos/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Adesão Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Eosinófilos/fisiologia , Humanos , Masculino , Nitrilas/administração & dosagem , Nitrilas/química , Nitrilas/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/fisiologia
3.
Biochim Biophys Acta ; 1261(3): 381-93, 1995 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-7742367

RESUMO

In the mammalian calpain system, two isozymes, mu- and m-types, have been well-characterized, and are considered to be conserved in the avian system as well. Thus, chicken calpain, whose large subunit was cloned in 1984, has long been regarded as 'm-type', since chicken also possesses 'mu-type' activity, although its structure has not yet been elucidated. In this study, we identified three kinds of cDNAs encoding distinct chicken calpain large subunits. Two of the three were highly similar to the mammalian mu-type and p94, respectively. The third shows a much higher similarity to mammalian m-type than the first identified chicken calpain, indicating that this molecule, which has been considered as 'm-type', should be renamed. We, therefore, designated it 'mu/m-calpain', because its sequence and Ca(2+)-sensitivity lie between mu- and m-types. Northern blot analyses revealed that chicken mCL and muCL, as well as mu/mCL, show ubiquitous expression, while p94 was detected predominantly in skeletal muscle, as previously reported. Chicken skeletal muscle, therefore, expresses at least four types of calpain, three ubiquitous and one tissue-specific.


Assuntos
Calpaína/química , Isoenzimas/química , Músculos/enzimologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Calpaína/genética , Galinhas , DNA Complementar/química , Isoenzimas/genética , Dados de Sequência Molecular , RNA Mensageiro/análise
4.
Pediatrics ; 73(4): 489-92, 1984 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6424086

RESUMO

Two brothers with hyperdibasicaminoaciduria and postprandial hyperammonemia showed characteristics of lysinuric protein intolerance. Intravenous alanine load produced hyperammonemia that was aborted by oral supplementation with arginine in one brother but not in the other, although both patients had almost the same intestinal malabsorption of arginine. This occurrence suggests that even a small amount of arginine, when absorbed into the blood, can normalize the affected ammonia metabolism of lysinuric protein intolerance. Two patients with cystinuria developed marked hyperammonemia when they received an intravenous alanine load after a 19-hour fast. As both patients displayed a reduced plasma concentration of arginine and ornithine at this time, the hyperammonemia was assumed to arise from the low plasma amino acid level. It seems likely that a decrease in plasma levels of urea cycle substrate causes a failure of the tissue urea cycle metabolism. Thus the impaired ammonia metabolism in lysinuric protein intolerance would be attributed to the low plasma arginine and ornithine levels.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Amônia/sangue , Lisina/urina , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/genética , Amônia/metabolismo , Arginina/sangue , Criança , Cistinúria/etiologia , Humanos , Masculino , Ornitina/sangue
5.
Tohoku J Exp Med ; 142(1): 15-24, 1984 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6719441

RESUMO

In two sibling patients with lysinuric protein intolerance (LPI), the therapeutic effect of oral supplement of arginine and citrulline on postprandial hyperammonemia was investigated. Intravenous load of L-alanine (6.6 mmol/kg of body weight), and oral load of L-arginine (0.8 mmol/kg of body weight) or of L-citrulline (1.0 mmol/kg of body weight) during intravenous load of L-alanine were performed to study the preventive effect of arginine or citrulline supplement on hyperammonemia induced by intravenous amino nitrogen load. In the older sibling, the hyperammonemia induced by the intravenous amino nitrogen load was completely prevented by the oral supplement of citrulline, but not completely prevented in the younger sibling. On the other hand, the hyperammonemia was prevented by the oral supplement of arginine only in the younger sibling, but not in the older sibling. In the light of these results, the younger patient received an oral administration of L-arginine and the older patient L-citrulline for the treatment of postprandial hyperammonemia. Two-year observation of each patient revealed that postprandial hyperammonemia and aversion to protein-rich food completely disappeared and that a marked increase of body weight and height was obtained. Furthermore, there was no side effect with these amino acids supplements. The present study suggests that an oral supplement of arginine or citrulline is effective for preventing postprandial hyperammonemia in this disorder.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Diamino Aminoácidos/metabolismo , Arginina/administração & dosagem , Citrulina/administração & dosagem , Administração Oral , Adolescente , Diamino Aminoácidos/urina , Criança , Humanos , Masculino
6.
Arzneimittelforschung ; 32(5): 542-7, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-6809015

RESUMO

The antianginal efficacy of niludipine (Bay a 7167), a new calcium antagonistic drug, was investigated in 51 patients with ischemic heart disease. 16 patients were diagnosed as effort angina and 31 patients had both angina at rest and on effort. Six anginal patients had myocardial infarction. One patient was diagnosed as a variant form of angina and 3 others as unstable angina. 11 patients had essential hypertension. 49 completed the study and 2 dropped out. Niludipine (60 mg to 80 mg every 24 h) significantly reduced the mean weekly rate of angina attacks from 6.5 to 2.2 (p less than 0.001). Marked reductions of nitroglycerin requirement were also noted (p less than 0.001). In 71% of the patients complete control of anginal attacks was achieved, and in over 77% the frequency of angina was reduced by at least 50%. Niludipine was at 93.8% effective in patients with ischemic heart disease. It decreased significantly both systolic and diastolic blood pressure in angina patients with essential hypertension, but there were no significant changes of blood pressure in normotensive anginal patients. The agent was tolerated very well and there were no side effects. These findings suggest that niludipine is a highly effective drug for the treatment of both ischemic heart disease and essential hypertension.


Assuntos
Doença das Coronárias/tratamento farmacológico , Nifedipino/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Angina Pectoris/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/análogos & derivados , Nitroglicerina/uso terapêutico
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