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1.
Eur Rev Med Pharmacol Sci ; 26(7): 2422-2430, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35442497

RESUMO

OBJECTIVE: Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC. PATIENTS AND METHODS: Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design. RESULTS: The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p < 0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL. CONCLUSIONS: Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.


Assuntos
Glicemia , Galinhas , Animais , Glicemia/análise , Glicemia/metabolismo , Galinhas/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Humanos , Insulina , Secreção de Insulina , Período Pós-Prandial/fisiologia , Água
2.
J Nutr Health Aging ; 22(3): 341-353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29484347

RESUMO

OBJECTIVES: This study aimed to examine the relationships among subjective well-being, food and health behaviors, socioeconomic factors, and geography in chronically ill older Japanese adults living alone. DESIGN: The design was a cross-sectional, multilevel survey. A questionnaire was distributed by post and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select a representative sample of older people living alone based on their proximity to a supermarket. Study recruitment was conducted with municipal assistance. MEASUREMENTS: To assess subjective well-being and food and health behaviors of respondents with disease, a logistic regression analysis was performed using stepwise variable analyses, adjusted for respondent age, socioeconomic status, and proximity to a supermarket. The dependent variable was good or poor subjective well-being. RESULTS: In total, 2,165 older people (744 men, 1,421 women) completed the questionnaire (63.5% response rate). Data from 737 men and 1,414 women were used in this study. Among people with a chronic disease, individuals with good subjective well-being had significantly higher rates than those with poor subjective well-being for satisfaction with meal quality and chewing ability, food diversity, food intake frequency, perception of shopping ease, having someone to help with food shopping, eating home-produced vegetables, preparing breakfast themselves, eating with other people, and high alcohol consumption. A stepwise logistic analysis showed that the factors strongly related to poor subjective well-being were shopping difficulty (men: odds ratio [OR] = 3.19, 95% confidence interval [CI], 1.94-5.23; P < 0.0001; women: OR = 2.20, 95% CI, 1.54-3.14; P < 0.0001), not having someone to help with food shopping (women: OR = 1.41, 95% CI, 1.01-1.97; P = 0.043), not preparing breakfast (women: OR = 2.36, 95% CI, 1.40-3.98; P = 0.001), and eating together less often (women: OR = 1.99, 95% CI, 1.32-3.00; P = 0.002). CONCLUSION: Subjective well-being of people with chronic diseases is associated with food intake and food behavior. The factors that affect poor subjective well-being in chronically ill older Japanese people living alone include food accessibility and social communication.


Assuntos
Doença Crônica/psicologia , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Qualidade de Vida/psicologia , Características de Residência/estatística & dados numéricos , Classe Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Demografia/estatística & dados numéricos , Dieta , Ingestão de Alimentos , Hipersensibilidade a Ovo , Feminino , Abastecimento de Alimentos , Fragilidade , Humanos , Renda , Japão/epidemiologia , Masculino , Refeições , Razão de Chances , Satisfação Pessoal , Estudos Prospectivos , Fatores Socioeconômicos , Inquéritos e Questionários , Verduras
3.
J Nutr Health Aging ; 21(5): 514-520, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28448081

RESUMO

OBJECTIVE: This study aimed to examine perceptions of shopping difficulty, and the relationships with satisfaction with state of health and meals, physical condition, food diversity and health behavior in older people living alone in Japan. DESIGN: A cross-sectional, multilevel survey was designed. The questionnaire was distributed by mail and self-completed by participants. SETTING: The sample was drawn from seven towns and cities across Japan. PARTICIPANTS: A geographic information system was used to select the sample of older people living alone, by proximity to a supermarket. In total, 2,346 older people (827 men and 1,519 women) completed the questionnaire. MEASUREMENTS: The dependent variable was whether shopping was easy or difficult. A logistic regression analysis was performed, adjusting for age, socioeconomic status and proximity of residence to a supermarket using stepwise variable analyses. RESULTS: The response rate was 67.8%. Overall, 14.5% of men and 21.7% of women considered shopping difficult. The stepwise logistic analysis showed that the factors most strongly related to shopping difficulty were a subjective feeling of poor health (men: OR = 3.01, women: OR = 2.16) and lack of satisfaction with meals (men: OR = 2.82, women: OR = 3.69). Other related physical condition and dietary factors were requiring nursing care (men: OR = 3.69, women: OR = 1.54), a high level of frailty, measured using the frailty index score (women: OR = 0.36) and low food diversity score (men: OR = 1.84, women: OR = 1.36). CONCLUSION: The study found that older people's assessment of their shopping difficulty was related to satisfaction aspects, including a subjective feeling of poor health, and lack of satisfaction with meals, as well as physical condition. These have a greater influence on shopping difficulty than income in both sexes, and proximity to a supermarket in women.


Assuntos
Atitude , Comportamento Alimentar , Abastecimento de Alimentos , Comportamentos Relacionados com a Saúde , Nível de Saúde , Satisfação Pessoal , Qualidade de Vida , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dieta , Feminino , Humanos , Renda , Japão , Modelos Logísticos , Masculino , Refeições , Razão de Chances , Percepção , Meio Social , Inquéritos e Questionários
4.
Eur Rev Med Pharmacol Sci ; 19(2): 334-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25683952

RESUMO

OBJECTIVE: The aim of the study was to investigate the effects of nicotine on learning and memory deficits induced by intracerebroventricular infusion of amyloid-ß peptide (Aß) in rats. MATERIALS AND METHODS: Neuronal dysfunction in rats was induced by an infusion of Aß(1-42) (20 µg/body, over 3 days) into right ventricle. Nicotine was administered intraperitoneally to the rats at 0.2 mg/kg, once a day for 9 weeks beginning 3 weeks after the Aß infusion. Learning and memory functions were examined by behavioral tests including Morris water maze task performed on days 87-90. As biochemical analyses, choline acetyltransferase (ChAT) activity and hemicholinium-3 (HC-3) binding were measured in brain tissues after the behavioral examination. RESULTS: The Aß infusion induced significant learning and memory deficits in rats, judging from the behavioral tests. Treatment of the rats with nicotine significantly improved the Aß-induced learning and memory deficits in water maze task. The Aß infusion also decreased significantly not only the level of ChAT activity in posterior cortex and striatum, but the HC-3 binding in anterior cortex, posterior cortex, and hippocampus. The nicotine treatment did not reverse the level of ChAT but significantly inhibited the decrease in HC-3 binding, indicating improvement of cholinergic function without affecting the number of ACh terminals. CONCLUSIONS: Nicotine ameliorated learning and memory deficits in the Aß(1-42)-induced animal model, which is mediated, at least in part, by enhancement of cholinergic neurotransmission. nAChR ligands including nicotine is thought to be useful as a treatment for Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Neurônios/efeitos dos fármacos , Nicotina/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Infusões Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Agonistas Nicotínicos/farmacologia , Ratos , Ratos Endogâmicos F344
5.
Kyobu Geka ; 64(7): 590-3, 2011 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-21766714

RESUMO

A 58-year-old woman was admitted to our institute. Aortitis syndrome was diagnosed when she was 39 years old. She developed intractable hypertension several years prior, and a computed tomography (CT) scan showed severe calcified stenosis of the descending aorta. The ankle brachial pressure index of the right leg was 0.70 and that of the left leg was 0.63. Plasma renin activity was 4.8 ng/ml/h. Ascending aorta-abdominal aorta bypass grafting was scheduled. The operation was successfully performed under partial cardiopulmonary bypass to control arterial blood pressure. An implanted graft was 14 mm in diameter. The postoperative ankle brachial pressure index of the right leg was 1.07 and that of the left leg was 1.03. Postoperative plasma renin activity was 0.2 ng/ml/h, and three-dimensional CT revealed that the implanted graft was patent. Postoperatively, hypertension was well controlled without medication.


Assuntos
Aorta Abdominal/cirurgia , Aorta/cirurgia , Hipertensão Renal/etiologia , Hipertensão Renal/cirurgia , Arterite de Takayasu/complicações , Prótese Vascular , Feminino , Humanos , Pessoa de Meia-Idade
6.
Gene Ther ; 18(3): 266-74, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20981113

RESUMO

We had previously reported that transduction of the channelrhodopsin-2 (ChR2) gene into retinal ganglion cells restores visual function in genetically blind, dystrophic Royal College of Surgeons (RCS) rats. In this study, we attempted to reveal the safety and influence of exogenous ChR2 gene expression. Adeno-associated virus (AAV) type 2 encoding ChR2 fused to Venus (rAAV-ChR2V) was administered by intra-vitreous injection to dystrophic RCS rats. However, rAAV-ChR2 gene expression was detected in non-target organs (intestine, lung and heart) in some cases. ChR2 function, monitored by recording visually evoked potentials, was stable across the observation period (64 weeks). No change in retinal histology and no inflammatory marker of leucocyte adhesion in the retinal vasculature were observed. Although antibodies to rAAV (0.01-12.21 µg ml(-1)) and ChR2 (0-4.77 µg ml(-1)) were detected, their levels were too low for rejection. T-lymphocyte analysis revealed recognition by T cells and a transient inflammation-like immune reaction only until 1 month after the rAAV-ChR2V injection. In conclusion, ChR2, which originates from Chlamydomonas reinhardtii, can be expressed without immunologically harmful reactions in vivo. These findings will help studies of ChR2 gene transfer to restore vision in progressed retinitis pigmentosa.


Assuntos
Dependovirus/imunologia , Potenciais Evocados Visuais/fisiologia , Terapia Genética/métodos , Retinose Pigmentar/terapia , Rodopsina/imunologia , Animais , Anticorpos Antivirais/sangue , Primers do DNA/genética , Dependovirus/genética , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Microscopia de Fluorescência , Ratos , Retinose Pigmentar/genética , Rodopsina/genética , Rodopsina/metabolismo , Linfócitos T/imunologia , Transdução Genética
7.
Xenobiotica ; 38(12): 1471-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18949658

RESUMO

1. The distribution of an anti-cancer agent carboplatin to brains was investigated in combination with hyperbaric oxygenation treatment in rats. 2. After intravenous administration of carboplatin (30 mg kg(-1)) to male Wistar rats, elimination curves of plasma drug concentrations plotted against a time of 45 min were not different with or without hyperbaric oxygenation (at 0.20-0.25 MPa for last 20 min) treatments. 3. Carboplatin concentrations of livers, lungs and kidneys in each group were similar at the endpoint of hyperbaric oxygenation treatment. 4. Under these atmosphere conditions (at 0.10 MPa), carboplatin concentration was at an undetectable level in rat brains (<0.1 microg g(-1) tissue, n = 6). On the contrary, carboplatin was detected in all brains tested at the levels of 0.5 +/- 0.3 microg g(-1) tissue (mean and standard deviation (SD), n = 6), 0.8 +/- 0.5 microg g(-1) tissue, and 0.4 +/- 0.2 microg g(-1) tissue in combination with hyperbaric oxygenation at 0.20, 0.22, and 0.25 MPa, respectively, at the endpoint of hyperbaric oxygenation treatment. 5. The results suggest that carboplatin could be uptaken into rat brains at the detectable levels by the aid of hyperbaric oxygenation, consistently with the reported findings of enhanced transendothelial permeability and improved clinical efficacy of carboplatin combined hyperbaric oxygenation therapy.


Assuntos
Antineoplásicos/farmacocinética , Encéfalo/metabolismo , Carboplatina/farmacocinética , Oxigenoterapia Hiperbárica , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Masculino , Ratos , Ratos Wistar
8.
Xenobiotica ; 38(10): 1298-304, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18798124

RESUMO

1. The objective was to investigate the transport of an anticancer agent carboplatin across the blood-brain barrier in combination with hyperbaric oxygenation treatment. An in vitro well-validated model of bovine brain capillary endothelial cells was used. 2. A transendothelial transport of doxorubicin, a known P-glycoprotein substrate, was enhanced 1.5-fold by verapamil for 2-h incubation at 37 degrees C. A transendothelial permeability coefficient of carboplatin (1.29 x 10(-3)cm min-1) was also increased 1.8-fold by verapamil. 3. Under the hyperbaric oxygenation conditions (at 0.2 MPa for the first 10 min), the transendothelial transport for 2 h of doxorubicin and carboplatin were increased 1.3- to 1.8-fold by hyperbaric oxygenation, like the suppressive effects of verapamil on P-gp function, without increase of the transport of lucifer yellow, a non P-glycoprotein substrate. 4. Combination of hyperbaric oxygenation treatment and verapamil could not further increase the permeability coefficients of these drugs that were already enhanced by either treatment, implying the P-glycoprotein-mediated carboplatin efflux transport similarly as doxorubicin. 5. Together with our reported high efficacy of carboplatin combined with hyperbaric oxygenation therapy on brain tumours, the present results suggest that carboplatin could be transported by P-glycoprotein, but that this efflux mechanism would be reduced by the hyperbaric oxygenation with the consequences of clinical efficacy.


Assuntos
Antineoplásicos/farmacocinética , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar/fisiologia , Carboplatina/administração & dosagem , Carboplatina/farmacocinética , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Oxigenoterapia Hiperbárica , Animais , Antineoplásicos/administração & dosagem , Bovinos , Células Cultivadas , Ratos
9.
Aust Vet J ; 84(1-2): 36-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16498832

RESUMO

A 4-year-old Beagle dog was presented for investigation of a left pelvic limb gait abnormality. Neurolocalisation indicated a lumbar (L2 to L5) spinal cord lesion. On magnetic resonance imaging (MRI), an intramedullary mass was demonstrated at L3. The mass was partially removed under general anaesthesia and a diagnosis of ependymoma was made on histological examination. The dog was treated with postoperative orthovoltage x-ray radiation (total dose; 44 Gy given in 11 fractions over a 4 week period) combined with low dose carboplatin (25 mg/m2). The dog was alive 16 months after surgery without further neurological deficits. No further tumour growth was detected on subsequent MRI evaluations.


Assuntos
Doenças do Cão/radioterapia , Doenças do Cão/cirurgia , Ependimoma/veterinária , Neoplasias da Medula Espinal/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Ependimoma/diagnóstico , Ependimoma/radioterapia , Ependimoma/cirurgia , Vértebras Lombares , Imageamento por Ressonância Magnética/veterinária , Masculino , Recidiva Local de Neoplasia/veterinária , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/cirurgia , Resultado do Tratamento
10.
Kyobu Geka ; 59(2): 137-40, 2006 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-16482908

RESUMO

A 79-year-old man with repeated and massive hemoptysis due to bronchiectasis was admitted to our department for surgery. The patient had undergone left upper lobectomy for pulmonary tuberculosis, and descending aortic replacement for Stanford type B aortic dissection. The patient underwent occlusion of the left main bronchus by suturing through median sternotomy. The reasons we did not choose completion pneumonectomy were advanced age, poor physical condition immediately after hemorrhagic shock, and the difficulty of performing pneumonectomy due to previous surgery and anastomotic aneurysm of descending aorta. The postoperative course was uneventful and the patient left the hospital on the 16th postoperative day. The patient did not develop pneumonia or empyema thereafter, but died suddenly of unknown etiology 1.5 years postoperatively. Lung exclusion by suturing a bronchus is thought to be a useful alternative for repeated and massive hemoptysis without pneumonia in a case of difficult lung resection.


Assuntos
Hemoptise/cirurgia , Técnicas de Sutura , Idoso , Brônquios/cirurgia , Artérias Brônquicas , Bronquiectasia/complicações , Embolização Terapêutica , Hemoptise/etiologia , Humanos , Masculino , Pneumonectomia , Recidiva , Esterno/cirurgia
11.
Mycoses ; 46(3-4): 145-8, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12870205

RESUMO

We report a case of subcutaneous phaeohyphomycosis by Exophiala jeanselmei that appeared on the extensor surface of the left lower leg of a 34-year-old woman with systemic lupus erythematosus (SLE). The superficial symptoms were a subcutaneous nodule 2.5 x 2 cm in size discharging a serous exudate from its center. Histopathological examination revealed granulomatous changes including large numbers of neutrophils in the dermis and the subcutaneous tissues. In addition, periodic acid-Schiff-positive fungal elements consisting of many yeast-like cells and chains of cells with hyphae were seen. The statistics on E. jeanselmei infections in Japan indicated that 54 cases (24 in men and 30 in women) had been reported, of which 50 (21 in men and 29 in women) were phaeohyphomycosis, and about half had underlying diseases; and the sites of the lesions were mainly on the extremities.


Assuntos
Dermatomicoses/diagnóstico , Dermatomicoses/microbiologia , Exophiala/isolamento & purificação , Lúpus Eritematoso Sistêmico/complicações , Adulto , Dermatomicoses/cirurgia , Feminino , Humanos
12.
Environ Health Perspect ; 109(12): 1265-70, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11748034

RESUMO

Spot urine samples were collected from the inhabitants of two rural communities in northwestern Bangladesh. We compared arsenic levels in the urine samples ([As](u); n = 346) with those in water from tube wells ([As](tw); range < 1-535 microg/L; n = 86) on an individual basis. The small variation of [As](u) within subjects and highly positive correlation with [As](tw) indicate that [As](u) is a useful indicator of exposure. Analyses of [As](u) showed that creatinine correction was necessary, that [As](u) only reflected recent exposure, and that there were substantial interindividual differences for a given [As](tw) level. To evaluate the toxic effects of arsenic exposure, we constructed a system for rating skin manifestations, which revealed distinct sex-related differences. Comparison of males and females in the same households confirmed that skin manifestations were more severe in the males, and in the males of one community a dose-response relationship between [As](u) and the degree of skin manifestation was evident. The results of this study indicate that [As](u) in spot urine samples can be used as an exposure indicator for As. They suggest that there might be sex-related, and perhaps community-related, differences in the relationship between [As](u) and skin manifestations, although several confounding factors, including sunlight exposure and smoking habits, might contribute to the observed sex difference. The existence of such differences should be further confirmed and examined in other populations to identify the subpopulations sensitive to chronic arsenic toxicity.


Assuntos
Arsênio/efeitos adversos , Dermatopatias/induzido quimicamente , Abastecimento de Água , Adulto , Arsênio/urina , Bangladesh , Fatores de Confusão Epidemiológicos , Relação Dose-Resposta a Droga , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Melanose/etiologia , População Rural , Fatores Sexuais
13.
Brain Res ; 912(2): 128-36, 2001 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-11532428

RESUMO

The behavioral, neurochemical and histological changes of rats subjected to 3 days treatment with intracerebroventricular infusion of beta-amyloid peptides(Abeta)(1-42) were investigated 20 days and 80 days after the surgery. Abeta(1-42) produced a dose-dependent and a time-dependent impairment in the spontaneous alternation performance in the Y-maze (spatial working memory), place navigation task in a water maze (spatial reference memory) and passive avoidance retention (non-spatial long-term memory) at doses of 10 and 20 microg/rat. The learning impairments were more severe at 80 days than 20 days after infusion of Abeta(1-42). At 25 days after the infusion, a significant decrease in hemicholinium-3 (HC-3) binding was observed only in the hippocampus, although choline acetyltransferase (ChAT) activity was unchanged in the brain regions tested as compared with the vehicle (Abeta(40-1)) treatment. In contrast, the reduction in ChAT activity 85 days after Abeta(1-42) infusion was significant in hippocampus and striatum. HC-3 binding was also significantly decreased in the posterior cortex, hippocampus and striatum. In the histological analysis, brain atrophy was observed inasmuch as ventricular enlargement and neuronal damage in the CA1 area of the hippocampus were seen 85 days after Abeta(1-42) infusion. These results suggest that the rats subjected to intracerebroventricular infusion of Abeta(1-42) suffered from progressive brain dysfunction, and could be useful as an animal model for evaluating the developmental processes at the early and/or middle stage of Alzheimer's-type dementia.


Assuntos
Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/farmacologia , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Degeneração Neural/induzido quimicamente , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Colina O-Acetiltransferase/metabolismo , Colinérgicos/farmacocinética , Relação Dose-Resposta a Droga , Hemicolínio 3/farmacocinética , Hipocampo/enzimologia , Hipocampo/patologia , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/enzimologia , Transtornos da Memória/patologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Neocórtex/efeitos dos fármacos , Neocórtex/enzimologia , Neocórtex/patologia , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Neostriado/patologia , Degeneração Neural/enzimologia , Degeneração Neural/patologia , Neurônios/enzimologia , Neurônios/patologia , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Ratos , Ratos Endogâmicos F344 , Percepção Espacial/fisiologia
14.
Jpn J Cancer Res ; 92(5): 524-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11376561

RESUMO

To examine the role of cytochrome P450 2A6 (CYP2A6) in the cellular sensitivity to an anti-tumor prodrug, tegafur (FT), a CYP2A6 cDNA construct was transfected into cells of a colon cancer cell line, DLD-1. CYP2A6-expressing cells (DLD-1 / CYP2A6 cells) more efficiently catalyzed the conversion of FT to 5-fluorouracil (5-FU) (2.6-fold) and the 7-hydroxylation of coumarin (7.9-fold) than cells transfected with a null construct (DLD-1 / null cells). These results indicated that the expressed CYP2A6 was functionally active. The extent of growth inhibition of the DLD-1 / CYP2A6 cells by FT was greater than that of DLD-1 / null cells; the difference between the DLD-1 / CYP2A6 and DLD-1 / null cells was statistically significant at the concentrations of 250, 500 and 1000 mM. 5-FU, an active metabolite of FT, inhibited the growth of both types of cells to the same extent. Thus, intracellular expression of CYP2A6 can sensitize cells to FT.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Hidrocarboneto de Aril Hidroxilases , Neoplasias do Colo/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Expressão Gênica , Oxigenases de Função Mista/genética , Tegafur/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Cumarínicos/metabolismo , Citocromo P-450 CYP2A6 , Fluoruracila/metabolismo , Humanos , Hidroxilação , Microssomos/metabolismo , Tegafur/metabolismo , Tegafur/farmacologia , Transfecção , Células Tumorais Cultivadas
15.
Biol Pharm Bull ; 24(12): 1427-30, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11767116

RESUMO

By sequencing genomic DNA from 73 established cell lines derived from Japanese individuals, we detected 9 single nucleotide polymorphisms (SNPs) in the CYP2C8 gene. Of them, 3 exonic SNPs resulted in amino acid alterations (g416a, R139K; a1196g, K399R; c1210g, P404A). The first two alterations were detected concurrently in one cell line and thought to be the same as CYP2C8*3. To examine the effects of these amino acid alterations on CYP2C8 function, wild-type and four types of variant CYP2C8 cDNA constructs (R139K, K399R, R139K/K399R and P404A) were transfected into Hep G2 cells and their paclitaxel 6a-hydroxylase activities were determined in vitro. Km values were not significantly different from that of the wild-type in any of the variants studied. The variant R139K/K399R showed reduced values for Vmax and clearance (Vmax/Km) similar to those of its single variant, R139K. The variant P404A also showed a significantly lowered clearance due to reduced level of protein expression. These results suggest that not only the double variant (R139K/K399R, CYP2C8*3) but also our novel variant P404A in the CYP2C8 gene are less efficient in paclitaxel metabolism.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Sistema Enzimático do Citocromo P-450/genética , Paclitaxel/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Esteroide 16-alfa-Hidroxilase , Esteroide Hidroxilases/genética , Substituição de Aminoácidos/genética , Antineoplásicos Fitogênicos/metabolismo , Linhagem Celular , Citocromo P-450 CYP2C8 , Sistema Enzimático do Citocromo P-450/metabolismo , Ativação Enzimática , Humanos , Esteroide Hidroxilases/metabolismo , Transfecção , Células Tumorais Cultivadas
16.
J Urol ; 164(5): 1686-90, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11025748

RESUMO

PURPOSE: We evaluated biofeedback training for incontinence due to detrusor overactivity in children. MATERIALS AND METHODS: Included in our study were 22 boys and 17 girls with a mean age of 11.2 years. We noted nighttime incontinence in 3 patients, nighttime incontinence and daytime urinary symptoms in 26, and daytime incontinence in 10. All patients had detrusor overactivity and incontinence refractory to conventional treatment, including bladder training, tricyclic antidepressants, anticholinergics, desmopressin and/or conditioning therapy. Urodynamic study was performed using an 8Fr double lumen transurethral catheter for cystometry, a double balloon transrectal catheter for rectal pressure and external anal sphincter pressure measurement, and surface electrodes for sphincter electromyography. During biofeedback training patients were instructed to contract the anal sphincter without raising abdominal pressure to inhibit overactive bladder contractions. Biofeedback training was repeated monthly until cystometry revealed a stable bladder or lower urinary tract symptoms improved considerably. RESULTS: Four patients were lost to followup. Of the remaining 35 children urinary symptoms were cured in 23 and improved in 4. Urodynamic studies after 6 months of biofeedback training in 33 cases showed that bladder overactivity disappeared in 10 and improved in 18. Bladder capacity at the initial desire to void and maximum cystometric capacity increased significantly (p = 0.0115 and <0.0001, respectively). Detrusor-sphincter dyssynergia in 2 patients before biofeedback training resolved in each after therapy. CONCLUSIONS: Biofeedback training for detrusor overactivity is effective even in pediatric cases refractory to conventional treatment.


Assuntos
Biorretroalimentação Psicológica , Bexiga Urinária/fisiopatologia , Incontinência Urinária/terapia , Criança , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular , Resultado do Tratamento , Incontinência Urinária/fisiopatologia , Urodinâmica
17.
Biochem Biophys Res Commun ; 274(2): 445-54, 2000 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-10913358

RESUMO

APP is a precursor of beta amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders.


Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Apoptose/genética , Neurônios/metabolismo , Doença de Alzheimer/genética , Clorometilcetonas de Aminoácidos/farmacologia , Substituição de Aminoácidos , Precursor de Proteína beta-Amiloide/farmacologia , Animais , Apolipoproteína E2 , Apolipoproteína E4 , Apolipoproteínas E/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Inibidores de Cisteína Proteinase/farmacologia , Relação Dose-Resposta a Droga , Ecdisona/antagonistas & inibidores , Ecdisona/farmacologia , Estradiol/farmacologia , Expressão Gênica/efeitos dos fármacos , Células Híbridas , Camundongos , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Oligopeptídeos/farmacologia , Toxina Pertussis , Ratos , Receptores de Esteroides/biossíntese , Proteínas Recombinantes/biossíntese , Transfecção , Fatores de Virulência de Bordetella/farmacologia
18.
Eur J Biochem ; 267(13): 4075-80, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10866809

RESUMO

A cDNA clone, 1.8 kb long, was isolated from a venom gland cDNA library of Agkistrodon blomhoffi that encodes a large plurifunctional precursor composed of 263 amino-acid residues. Nucleotide sequence analysis of this clone revealed that sequences which code for blomhotin and a novel peptide Leu3-blomhotin are located in the N-terminal region of the precursor polypeptide, followed by four tandemly aligned sequences which code for three types of bradykinin-potentiating peptide. In the C-terminal region, the sequence for the C-type natriuretic peptide was located along with a preceding processing signal. The deduced amino-acid sequences for the four bradykinin-potentiating peptides coincided exactly with previously known sequences for potentiator B, potentiator C and potentiator E. The actual Leu3-blomhotin peptide was subsequently isolated from the venom of A. blomhoffi and characterized. Leu3-blomhotin possesses contractile activity in isolated rat stomach fundus smooth muscle in the same manner as blomhotin. Furthermore, it was shown that blomhotin and Leu3-blomhotin retained activity to inhibit the angiotensin-converting enzyme.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Venenos de Crotalídeos/química , Peptídeo Natriurético Tipo C/genética , Peptídeos/isolamento & purificação , Precursores de Proteínas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar/química , DNA Complementar/isolamento & purificação , Dados de Sequência Molecular , Peptídeo Natriurético Tipo C/química , Precursores de Proteínas/química , Coelhos
19.
Neurourol Urodyn ; 19(3): 241-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10797581

RESUMO

The aim of this study was to investigate urodynamic findings and the outcome of surgical incision in patients with nighttime wetting due to urethral obstruction. A total of 239 patients with nighttime wetting (157 males and 82 females; mean age, 8.7; range, 4-18 years) was studied. One hundred and ten patients had monosymptomatic enuresis alone and 129 both nighttime wetting and daytime symptoms, that is, the majority was not simple bedwetters, but had signs of bladder overactivity. All patients were first treated with bladder training and fluid intake after dinner was restricted. The non-responders were then treated with tricyclic antidepressants, anticholinergics, or intra-nasal desmopressin and conditioning therapy. Ninety-seven patients who did not respond to these conventional treatments were investigated by voiding cystourethrography, bougie à boule, and urodynamic study. Urethral obstruction was noted in 34 patients (14.2%); posterior urethral valves in three males, ring stricture of the bulbar urethra in 26 males and distal urethral stenosis in five females. Detrusor instability was noted in 30 (94%) of 32 patients. Three patients had <15 mL/s of maximum flow rate and none had post-void residual urine. Pressure at maximum flow (PQ(max)) was 106.5 +/- 26.3 cm H(2)O in pressure/flow study. After surgery, nighttime wetting was cured in 25 patients (73.5%), improved in four (11.8%). Detrusor instability disappeared in six of 16 patients studied (37.5%) and improved in 8 (50%), and PQ(max) decreased significantly after operation (P = 0. 0034). In conclusion, most of the patients with urethral obstruction have detrusor instability and high pressure voiding, and these conditions improved after operation.


Assuntos
Enurese/fisiopatologia , Enurese/cirurgia , Obstrução Uretral/fisiopatologia , Obstrução Uretral/cirurgia , Urodinâmica , Adolescente , Criança , Pré-Escolar , Enurese/etiologia , Feminino , Humanos , Masculino , Resultado do Tratamento , Obstrução Uretral/complicações
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