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1.
Nat Genet ; 6(1): 14-8, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8136826

RESUMO

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7-23 in normal individuals. In patients one allele was expanded to between 49-75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.


Assuntos
Cromossomos Humanos Par 12 , Doenças do Sistema Nervoso/genética , Sequências Repetitivas de Ácido Nucleico , Alelos , Sequência de Aminoácidos , Atrofia , Sequência de Bases , Encéfalo/patologia , Ataxia Cerebelar/genética , Primers do DNA/genética , Feminino , Globo Pálido/patologia , Humanos , Masculino , Dados de Sequência Molecular , Doenças do Sistema Nervoso/patologia , Oligodesoxirribonucleotídeos/genética , Linhagem
2.
Eur Rev Med Pharmacol Sci ; 27(18): 8829-8841, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37782192

RESUMO

OBJECTIVE: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study. SUBJECTS AND METHODS: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food. RESULTS: We found a 0.60 Spearman's correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson's correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values. CONCLUSIONS: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake.


Assuntos
Ingestão de Líquidos , Alimentos , Estudos Transversais , Bebidas , Inquéritos e Questionários , Etanol , Reprodutibilidade dos Testes , Dieta
3.
Eur Rev Med Pharmacol Sci ; 26(23): 8700-8712, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36524489

RESUMO

OBJECTIVE: This study aimed to examine the effects of quercetin glycoside-containing beverages on cognitive function and cerebral blood flow (CBF) in adult men and women aged between 60 and 75 years. PATIENTS AND METHODS: Eighty healthy men and women with no cognitive impairment and aware of ageing-related forgetfulness underwent a placebo-controlled, randomized, double-blind, and parallel-group trial. They regularly consumed 500 mL of beverage containing 110 mg of quercetin glycoside as isoquercitrin for 40 weeks. Cognitive function assessment by Cognitrax was the endpoint of the study. The participants were assessed for CBF, health-related quality of life, as well as physical, biological, and hematological parameters, and lateral index. RESULTS: Cognitrax demonstrated that the reaction time significantly improved in the quercetin glycoside intake group. The CBF measurement suggested that quercetin glycoside intake could likely suppress the decrease in cerebral blood volume, CBF, and cerebral activity owing to stress alleviation and inhibition of the accumulation of amyloid ß (Aß), a waste product in the brain, although there were no significant differences between the groups. CONCLUSIONS: Quercetin glycoside intake as a beverage could improve reaction time and may potentially inhibit the decrease in CBF and suppress Aß accumulation.


Assuntos
Cognição , Quercetina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Método Duplo-Cego , Glicosídeos/farmacologia , Qualidade de Vida , Quercetina/farmacologia
4.
Eur Rev Med Pharmacol Sci ; 26(8): 2765-2774, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35503621

RESUMO

OBJECTIVE: We aimed to classify Japanese adults without diabetes into different categories based on the oral glucose tolerance test (OGTT) and characterize their insulin sensitivity and insulin secretion. PATIENTS AND METHODS: The OGTT was performed on 1,085 Japanese individuals without diabetes (aged 20-64 years); blood glucose and insulin levels were measured at 0, 30-, 60-, 90-, and 120-min. Fasting blood chemistry, hematology, and urine were analyzed. The participants were classified into four categories based on the following: (A) 30 min post-load plasma glucose levels < 157 mg/dL and/or (B) 120 min post-load plasma glucose levels < 126 mg/dL and Matsuda index > 4.97. Category 1 satisfied both conditions, category 2 satisfied condition A but not B, category 3 satisfied condition B but not A, and category 4 satisfied neither condition. RESULTS: Overall, 46%, 21%, 13%, and 20% of the participants were classified into categories 1, 2, 3, and 4, respectively. Compared with category 1, the characteristics of the other categories were: 2, low insulin sensitivity and high blood glucose levels during the later period; 3, low insulin secretion and a rapid increase in blood glucose levels; and 4, combined characteristics of categories 2 and 3. Most blood test values besides glucose metabolism in category 4 were also worse than those in category 1. Categories 1 and 2 had a high proportion of females, whereas categories 3 and 4 had a low proportion. CONCLUSIONS: Japanese adults without diabetes are classified into four categories with different insulin sensitivities and insulin secretion using OGTT results. Each category has different characteristics of age and sex distribution and clinical values besides glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Resistência à Insulina , Adulto , Glicemia/metabolismo , Diabetes Mellitus/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina , Japão
5.
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
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.
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
8.
Eur Rev Med Pharmacol Sci ; 25(21): 6623-6632, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34787866

RESUMO

OBJECTIVE: We previously established a descriptive dietary record method that accurately quantifies habitual water intake from food and beverages, to ascertain the relationship between water intake and health. Here, we verified the validity of a selective recall method, which is easy for users to answer and analyze. PATIENTS AND METHODS: Japanese men and women aged 20-44 years (n = 16) and 45-64 years (n = 16) participated over three working days and one non-working day. The day following each of the surveyed days, participants collected their first morning urine for urinalysis and completed a selective recall and descriptive dietary record questionnaire. RESULTS: The two methods of determining water intake were positively correlated (r = 0.94, p < 0.0001). Water intake volumes from non-alcoholic beverages (r = 0.94, p < 0.0001), alcoholic beverages (r = 1.00, p < 0.0001), and food (r = 0.72, p < 0.0001), calculated using the two methods, exhibited strong correlation. No correlation was observed between urinalysis parameters and total water intake. A significant, negative correlation was observed between urine osmolarity and total water intake in men (r = -0.55, p = 0.0011) and women (r = -0.51, p = 0.0032) aged 20-44 years. CONCLUSIONS: Selective recall is a valid method for assessing water intake from food and beverages.


Assuntos
Ingestão de Líquidos , Rememoração Mental , Inquéritos e Questionários , Adulto , Bebidas , Registros de Dieta , Feminino , Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estado de Hidratação do Organismo , Reprodutibilidade dos Testes , Urinálise , Adulto Jovem
9.
Xenobiotica ; 39(3): 227-35, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19280521

RESUMO

Rapid prediction of hepatic clearance for drug candidates plays an important role for decision-making in the early drug-discovery stage. Although knowledge of protein binding in both plasma and microsomal components is needed in the prediction of metabolic clearance from metabolic stability studies, the capacity of protein binding assays are generally lower than those of metabolic stability assays. However, many in silico prediction methods for protein binding are now available and software packages such as ACDLabs, ADMET Predictor and SimCYP incorporate various aspects of in silico predictions relevant to estimating binding and clearance. This has facilitated the use of various estimated or measured physicochemical parameters, relevant to binding, to predict clearance. In this study, prediction of protein binding for 33 drugs was evaluated using various combinations of estimated physicochemical properties. Subsequently, the most accurate estimated protein binding values were used to predict hepatic clearance using the SimCYP software. For the drugs used herein, SimCYP provided the most accurate prediction for protein binding in both plasma and microsomes using physiochemical properties estimated with the ACDLabs software. In conclusion, the use of in silico methods as an integrated part of predicting hepatic clearance in early drug-discovery stage is recommended.


Assuntos
Descoberta de Drogas/métodos , Fígado/metabolismo , Preparações Farmacêuticas/metabolismo , Software , Fenômenos Químicos/efeitos dos fármacos , Humanos , Taxa de Depuração Metabólica/efeitos dos fármacos , Microssomos/metabolismo , Preparações Farmacêuticas/sangue , Ligação Proteica/efeitos dos fármacos
10.
Aging Ment Health ; 13(4): 563-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19629781

RESUMO

The mechanism underlying delusion in Alzheimer's disease patients has not been fully clarified; however, the occurrence of delusion is a critical issue for dementia patients and their caregivers. In Japan, delusion of theft is the most frequent delusion in AD patients. We examined the risk factors for delusion of theft in AD patients showing mild dementia. Fifty-six AD patients were administered HDS-R, MMSE and COGNISTAT, including the 'speech sample', to assess their neuropsychological and social cognitive functions. The age, years of education, presence of cohabiting family members and premorbid personality traits were obtained from family members. About 25.0% of AD patients showed delusion of theft (D-group), and 75% did not (non-D-group). About 33.3% of female patients and 5.9% of male patients were included in the D-group (p < 0.05). About 13.6% of patients who were cohabiting with family members and 66.7% of patients who were living alone were included in the D-group (p < 0.05). About 35.1% of patients who had a neurotic personality and 5.3% of patients who did not were included in the D-group (p < 0.05). There were no significant differences in scores on HDS-R, MMSE and COGNISTAT sub-scales, except for 'speech sample', between the two groups. In the 'speech sample', 38.7% of patients who understood a relationship between two boys and 12.0% of patients who did not were included in the D-group (p < 0.05). These results indicated that delusion of theft in AD patients was related to female gender, absence of cohabiting family members, neurotic personality and retained social cognitive function.


Assuntos
Doença de Alzheimer/psicologia , Delusões/epidemiologia , Demência/psicologia , Roubo , Doença de Alzheimer/complicações , Cognição , Delusões/etiologia , Delusões/psicologia , Demência/complicações , Escolaridade , Feminino , Humanos , Japão/epidemiologia , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Sexuais
11.
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
12.
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
13.
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
14.
Plant Signal Behav ; 13(8): e1473668, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30060711

RESUMO

Pod setting rate in soybean is an important trait that determines pod number, which is highly correlated with seed yield. Using two soybean cultivars with different pod setting rates, we examined the relationship between plant growth regulation by gibberellin (GA) and pod setting rate. Plant growth rate (PGR) after flowering was significantly higher in 'Fukuyutaka' (low pod setting rate) than in 'Kariyutaka' (high pod setting rate); this difference was caused by increasing of GA biosynthesis-related genes expression. Additionally, pod setting rate in 'Fukuyutaka' was lower than that in 'Kariyutaka'. Furthermore, when 'Kariyutaka' was treated with GA after flowering, the PGR increased and pod setting rate decreased. These results suggest that pod setting rate in soybean is regulated by vegetative growth after flowering through GA biosynthesis.


Assuntos
Giberelinas/biossíntese , Giberelinas/metabolismo , Glycine max/metabolismo , Reguladores de Crescimento de Plantas/biossíntese , Reguladores de Crescimento de Plantas/metabolismo
15.
J Clin Invest ; 75(6): 1869-79, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2989335

RESUMO

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.


Assuntos
Diabetes Insípido/induzido quimicamente , Túbulos Renais Coletores/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Lítio/toxicidade , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Inibidores de Adenilil Ciclases , Animais , Arginina Vasopressina/antagonistas & inibidores , AMP Cíclico/metabolismo , Diabetes Insípido/patologia , Capacidade de Concentração Renal/efeitos dos fármacos , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Lítio/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Ratos Mutantes , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
16.
J Clin Invest ; 76(2): 474-81, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2993360

RESUMO

Observations in vivo suggest that catecholamines modulate reabsorptive functions of proximal tubules by acting on beta-adrenoceptors. However, beta-catecholamine binding sites or beta-adrenoceptor-sensitive adenylate cyclase (AdC) has not been found in segments of proximal tubules of rat, rabbit, or mouse kidney. In the present study, we investigated the responsiveness of AdC to catecholamines, [8-Arg]vasopressin (AVP), and to parathyroid hormone (PTH) in proximal convoluted tubules (PCT), proximal straight tubules (PST), and in late distal convoluted tubules (LDCT) microdissected from canine kidney. Isoproterenol (ISO) caused a marked and dose-dependent stimulation of AdC in PST (maximum: delta + 850%; half maximum stimulation at 10(-7) M ISO), but ISO had no effect on AdC in PCT. The AdC in both PCT and PST was markedly stimulated by PTH; AVP stimulated the AdC in LDCT but not in PST or in PCT. The stimulatory effect of 10(-5) M ISO in PST (delta + 725%) was significantly greater than in LDCT (delta + 307%); norepinephrine and epinephrine had stimulatory effects in PST similar to ISO. The stimulation of AdC in PST by ISO was blocked by propranolol and by beta 2-blocker ICI-118551. On the other hand, alpha-blocker phentolamine and beta 1-blocker metoprolol did not abolish the stimulation of AdC in PST by ISO. The accumulation of cAMP in intact PCT and PST incubated in vitro was stimulated by PTH both in PST and in PCT, but ISO elevated cAMP (delta + 683%) only in PST. Our results show that proximal tubules of canine nephron, PST but not PCT, contain beta-adrenoceptors of beta 2 subtype coupled to AdC. These observations provide direct evidence that the effects of catecholamines, either released from renal nerve endings or arriving from blood supply, can act directly on beta 2-adrenoceptors located in proximal tubules, and also suggest that at least some of the catecholamine effects in proximal tubules are mediated via cAMP generation.


Assuntos
Adenilil Ciclases/metabolismo , Isoproterenol/farmacologia , Túbulos Renais Proximais/metabolismo , Néfrons/enzimologia , Receptores Adrenérgicos beta/metabolismo , Animais , AMP Cíclico/metabolismo , Cães , Metoprolol/farmacologia , Néfrons/efeitos dos fármacos , Norepinefrina/farmacologia , Propanolaminas/farmacologia , Propranolol/farmacologia
17.
J Nutr Health Aging ; 21(10): 1095-1101, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29188866

RESUMO

OBJECTIVE: The objective of this study was to identify lifestyle and nutritional factors associated with low BMI in Japanese older adults, with a focus on alcohol energy intake. DESIGN: Cross-sectional study. PARTICIPANTS: Data from 1,093 respondents (711 men and 382 women) to the National Health and Nutrition Survey aged 65 years and older were included in this study. MEASUREMENTS: Data were analyzed for associations between BMI and lifestyle, energy, and nutrient intake. Alcohol energy intake was calculated from total energy and participants were categorized into BMI quartiles. Energy-adjusted nutrient intakes were calculated as residuals from a regression model, with BMI as the independent variable and lifestyle factors and nutrient intake as dependent variables. Between-BMI quartile differences were assessed for each sex using multivariate logistic regression analysis. In addition, the nutrient intakes of men consuming more than 280 kcal and less than 280 kcal of alcohol energy per day were compared. RESULTS: Men and women in the lowest BMI quartile had lower total energy intake but higher alcohol energy intake than men in the other BMI quartiles. In multivariate logistic regression analysis, the lowest BMI quartile was associated with total energy (OR: 0.81, p = 0.0310) and alcohol energy intake (OR: 1.22, p = 0.0472) in men. In men, protein, carbohydrate, fat, calcium, iron, and vitamin intakes were less in those that consumed ≥ 280 kcal than in those that consumed < 280 kcal of alcohol per day. CONCLUSION: Our results demonstrate an association between alcohol energy intake and low BMI in older Japanese individuals.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Índice de Massa Corporal , Ingestão de Energia/fisiologia , Estado Nutricional/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , História do Século XXI , Humanos , Japão , Masculino , Inquéritos Nutricionais
18.
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
19.
J Nutr Health Aging ; 21(6): 662-672, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28537330

RESUMO

OBJECTIVE: This study aimed to examine the relationships between eating together and subjective health, frailty, food behaviors, food accessibility, food production, meal preparation, alcohol intake, socioeconomic factors and geography among older Japanese people who live alone. DESIGN: A cross-sectional, multilevel survey was designed. The 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 who lived alone based on their proximity to a supermarket. Recruitment for the study was conducted with municipal assistance. MEASUREMENTS: A logistic regression analysis was performed that adjusted for the respondent's age, socioeconomic status and proximity to a supermarket using stepwise variable analyses. The dependent variable was whether the respondent ate together more or less than once a month. RESULTS: In total, 2,196 older people (752 men and 1,444 women) completed the questionnaire (63.5% response rate). It was found that 47.1% of men and 23.9% of women ate together less than once a month. Those who ate together less than once a month had a significantly lower rate of subjective health, food diversity and food intake frequency than those who ate together more often. A stepwise logistic analysis showed that the factors most strongly related to eating together less than once a month were not having any food shopping assistance (men: OR = 3.06, women: OR = 2.71), not receiving any food from neighbors or relatives (men: OR = 1.74, women: OR = 1.82), daily alcohol intake (women: OR = 1.83), frailty (men: OR = 0.48) and income (men: OR = 2.16, women: OR = 1.32). CONCLUSION: Eating together is associated with subjective health and food intake. Factors that affect how often older Japanese people who live alone eat together include food accessibility, daily alcohol intake, frailty and a low income.


Assuntos
Consumo de Bebidas Alcoólicas , Ingestão de Energia , Comportamento Alimentar , Abastecimento de Alimentos , Idoso Fragilizado , Meio Social , Isolamento Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Demografia , Ingestão de Alimentos , Feminino , Nível de Saúde , Humanos , Renda , Japão , Modelos Logísticos , Masculino , Características de Residência , Classe Social , Inquéritos e Questionários
20.
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
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