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1.
Dis Esophagus ; 30(11): 1-8, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881900

RESUMO

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Transtornos da Motilidade Esofágica/diagnóstico , Esofagoscopia/efeitos adversos , Manometria/métodos , Complicações Pós-Operatórias/diagnóstico , Idoso , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Ressecção Endoscópica de Mucosa/métodos , Transtornos da Motilidade Esofágica/etiologia , Neoplasias Esofágicas/fisiopatologia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Esôfago/fisiopatologia , Esôfago/cirurgia , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Análise de Regressão
2.
Br J Cancer ; 111(12): 2229-34, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25255100

RESUMO

BACKGROUND: The most significant problem of intra-arterial chemotherapy for advanced paranasal sinus carcinomas and residual cancers supplied by internal carotid artery (ICA) and involving the skull base is the lack of salvage therapies. OBJECTIVE: The objective of the study was to evaluate the usefulness of intra-arterial chemotherapy including ICA infusion for treating advanced paranasal sinus carcinomas, which have invaded the skull base. METHODS: Forty-six patients with advanced paranasal sinus carcinomas supplied by ICA were treated by intra-arterial chemotherapy using CDDP and sodium thiosulphate (STS) as a neutraliser of CDDP toxicity. After evaluating CT angiography, 150 mg m(-2) of CDDP was superselectively administered weekly to each feeding artery including ICA four times. RESULTS: The 10-year overall survival rate and progression-free survival rate were 70.7 and 60.2%, respectively. Compared with control group without infusing ICA, recurrences at anterior skullbase or anterior ethomoid sinus were significantly diminished. Of 32 patients in which the orbital apex had been invaded, 29 patients were treated with successful preservation of orbital contents. The CT angiography could efficiently determine all feeding arteries supplying the cancers. Consequently, chemotherapy could be administered on schedule, and side effects were minimal and acceptable. CONCLUSIONS: This new method has promising applications in the treatment of advanced paranasal sinus carcinomas involving the skull base.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias dos Seios Paranasais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Carótida Interna , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade
5.
Mol Psychiatry ; 16(2): 202-15, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20038947

RESUMO

We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻7), SP4 (P=7.68 x 10⁻7) and GRM7 (P=1.11 x 10⁻6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.


Assuntos
Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Adolescente , Adulto , Idade de Início , Idoso , Europa (Continente) , Feminino , Perfilação da Expressão Gênica/métodos , Genótipo , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal , Receptores de Glutamato Metabotrópico/genética , Fator de Transcrição Sp4/genética , ATPases Vacuolares Próton-Translocadoras/genética , Adulto Jovem
6.
J Int Med Res ; 36(1): 137-46, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18230277

RESUMO

We investigated the effects of high-monounsaturated fatty acid (MUFA) versus high-carbohydrate enteral formula on post-prandial plasma glucose concentration and insulin response in Japanese patients with type 2 diabetes mellitus and healthy Japanese volunteers. Ten healthy volunteers aged 20.8 +/- 1.2 years and 12 diabetic patients with good glycaemic control (glycosylated haemoglobulin < 7%) aged 58.6 +/- 7.7 years were randomly assigned to take high-MUFA or high-carbohydrate formula after a 12-h overnight fast. The patients switched to the other formula after 7 days. Post-prandial plasma glucose and insulin response were significantly lower in all subjects after taking high-MUFA formula compared with high-carbohydrate formula. No differences were observed in free fatty acids, triglycerides and plasma glucagon between the two diet groups. In conclusion, a high-MUFA enteral formula suppresses post-prandial hyperglycaemia without exaggerated insulin secretion compared with a high-carbohydrate enteral diet in patients with type 2 diabetes and healthy subjects.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/dietoterapia , Carboidratos da Dieta/administração & dosagem , Nutrição Enteral/métodos , Ácidos Graxos Monoinsaturados/administração & dosagem , Insulina/metabolismo , Adulto , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Hemoglobinas Glicadas/análise , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
7.
Kyobu Geka ; 61(5): 388-91, 2008 May.
Artigo em Japonês | MEDLINE | ID: mdl-18464485

RESUMO

A 76-year-old female was admitted to the hospital with dyspnea and hypertention. She had the giant thyroid tumor which had been awared but not treated for 40 years. On a computed tomography (CT) scan and magnetic resonance imaging (MRI), the tumor was 14 x 10 cm and the tracheal stenosis was completely intrathoracic, which was 5 x 7 mm. Tracheal incubation was performed safety by using percutaneous cardiopulmonary support. A subtotal thyroidectomy was performed by midsternotomy with cervical incision. The weight of the resected specimen was 340 g and the pathological diagnosis was follicular thyroid carcinoma. The postoperative course was uneventful and the patient suffered no hoarseness and dyspnea.


Assuntos
Adenocarcinoma Folicular/complicações , Adenocarcinoma Folicular/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/cirurgia , Estenose Traqueal/etiologia , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Idoso , Ponte Cardiopulmonar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-28745833

RESUMO

BACKGROUND: Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. METHODS: Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. KEY RESULTS: Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. CONCLUSIONS & INFERENCES: Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.


Assuntos
Acalasia Esofágica/patologia , Mucosa Esofágica/patologia , Esfíncter Esofágico Inferior/patologia , Adulto , Atrofia , Endoscopia do Sistema Digestório , Acalasia Esofágica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Clin Oncol ; 17(10): 3216-20, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10506621

RESUMO

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neuroblastoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , DNA de Neoplasias/análise , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Prognóstico , Proto-Oncogene Mas , Sobreviventes , Vincristina/administração & dosagem
10.
Diabetes Care ; 16(5): 824-7, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8495625

RESUMO

OBJECTIVE: To investigate the social and economic backgrounds of youth-onset insulin-treated diabetes mellitus in Japan. RESEARCH DESIGN AND METHODS: We conducted a case-control study on 35 diabetic patients with age at onset of 19.5 +/- 5.1 yr and duration of diabetes 14.9 +/- 6.7 yr. Sex- and age-matched (within 5 yr) siblings were selected as control subjects. Thirty-five matched pairs were asked to complete a questionnaire, including employment status and educational achievement. RESULTS: Overall, diabetic patients were more likely to encounter job refusal in their lives than sibling control subjects (20 vs. 0%), and most patients (6/7) who had an experience of job refusal told job interviewers about their diabetes. Although the full-time employment rate and unemployment rate did not differ significantly between patients and control subjects, income levels were lower among patients than in the sibling (1600 vs. 2500 thousand yen). A multivariate analysis indicated that patients had lower incomes than control subjects after adjusting for the effect of physical disability. Educational achievements in the patients were similar to those in the siblings. CONCLUSIONS: These results suggested that diabetic patients had several social and economic problems in Japan. Further studies in more subjects are required to grasp the social and economic impact on diabetes precisely, and minimize the social handicaps on diabetic patients.


Assuntos
Diabetes Mellitus Tipo 1 , Fatores Socioeconômicos , Absenteísmo , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/reabilitação , Educação , Emprego , Feminino , Hemoglobinas Glicadas/análise , Humanos , Japão , Masculino , Análise Multivariada , Análise de Regressão , Inquéritos e Questionários
11.
Diabetes Care ; 22(6): 908-12, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10372240

RESUMO

OBJECTIVE: Troglitazone was recently reported to specifically promote the differentiation of pre-adipocytes into adipocytes in vitro in subcutaneous fat only, indicating a relation to insulin-resistance-improving action of troglitazone. To expand on this finding, we investigated at the clinical level how long-term administration of troglitazone influences the body fat distribution in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Troglitazone (400 mg/day) was administered for 6 months to 30 type 2 diabetic patients whose glycemic control was poor. A total of 18 patients received diet therapy alone (in the single-treatment group, BMI 26.0 +/- 4.6, HbA1c 8.2 +/- 1.7%), and 12 patients concomitantly received glibenclamide (1.25-7.5 mg/day) (in the concomitant sulfonylurea group, BMI 25.4 +/- 4.7, HbA1c 9.2 +/- 1.2%). BMI, HbA1c, serum lipid level, and body fat distribution, which were determined by computed tomography (CT) scan at the umbilical level, were measured and compared before and after troglitazone treatment. RESULTS: During the 6-month troglitazone treatment, HbA1c levels decreased and BMI increased in both groups. As for body fat distribution in the single-treatment group, visceral fat area (VFA) decreased (from 118.3 +/- 54.3 to 101.1 +/- 50.8 cm2; P < 0.001), and subcutaneous fat area (SFA) increased (from 189.7 +/- 93.3 to 221.6 +/- 101.6 cm2; P < 0.001), resulting in a decrease in visceral/subcutaneous (V/S) ratio (from 0.74 +/- 0.48 to 0.50 +/- 0.32; P < 0.001). In the concomitant sulfonylurea group, VFA was unchanged (from 108.1 +/- 53.5 to 112.5 +/- 59.9 cm2), while SFA increased (from 144.6 +/- 122.0 to 180.5 +/- 143.5 cm2; P < 0.01), thereby decreasing the V/S ratio (from 0.91 +/- 0.46 to 0.77 +/- 0.44; P < 0.01). The serum triglyceride level and the area under glucose curve during the 75-g oral glucose tolerance test decreased significantly in the single-treatment group. CONCLUSIONS: According to our data, troglitazone appears to promote fat accumulation in the subcutaneous adipose tissue rather than in the visceral adipose tissue in mildly obese Japanese people with type 2 diabetes. This shift of energy accumulation from the visceral to subcutaneous adipose tissue may greatly contribute to the troglitazone-mediated amelioration of insulin resistance.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Cromanos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Tiazóis/uso terapêutico , Tiazolidinedionas , Abdome , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/diagnóstico por imagem , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Quimioterapia Combinada , Feminino , Teste de Tolerância a Glucose , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pele , Tomografia Computadorizada por Raios X , Troglitazona , Vísceras
12.
Am J Clin Nutr ; 56(1 Suppl): 275S-276S, 1992 07.
Artigo em Inglês | MEDLINE | ID: mdl-1615900

RESUMO

Forty-five overweight patients (12 male, 33 female) were prescribed a very-low-calorie diet (VLCD) or a supplemental low-calorie diet (LCD), randomly, at an outpatient clinic. Twenty obese patients [31.6 +/- 13.1 y; body mass index (BMI) 32.9 +/- 6.1] were treated with a VLCD of 1757 kJ/d for 1-2 mo (five packages of Optifast 70/d; Sandoz Nutrition, Minneapolis). Another 25 patients (35.3 +/- 11.7 y; BMI 31.9 +/- 4.4) were treated by a supplemental LCD of 3515-5021 kJ/d for 1-2 months, which consisted of two to three packages of Optifast 70 and 2678-3682 kJ of conventional balanced meals. By the fourth week, the weight reduction obtained by the VLCD was significantly greater than that achieved by the supplemental LCD (P less than 0.01). At the eighth week, however, effect of the VLCD and the supplemental LCD in terms of weight reduction did not differ significantly. No serious side effects were observed in either treatment group. However, remarkable elevation of serum uric acid concentration was detected in seven patients on the VLCD. The treatment period of the VLCD is limited to less than or equal to 3 mo. On the other hand, obese patients can be treated with the supplemental LCD for greater than 3 mo. Therefore, the supplemental LCD is considered to be useful in the treatment of moderately obese Japanese patients on an outpatient basis.


Assuntos
Dieta Redutora , Ingestão de Energia , Obesidade/dietoterapia , Adulto , Dieta Redutora/efeitos adversos , Feminino , Humanos , Masculino , Redução de Peso
13.
Proc Biol Sci ; 268(1472): 1113-21, 2001 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-11375097

RESUMO

The over 700 species of Ficus are thought to have co-speciated with their obligate pollinators (family Agaonidae). Some of these wasp species pollinate figs actively, while others are passive pollinators. Based on direct observations of mode of pollination in 88 species, we show that mode of pollination can confidently be predicted from fig traits only (anther-to-ovule ratio) or from wasp traits only (presence of coxal combs). The presence of pollen pockets is not a predictor of mode of pollination. Data, direct and indirect, on 142 species, demonstrate numerous cases of the loss of active pollination and suggest one or few origins of active pollination. Hence, active pollination, an impressive example of the sophisticated traits that may result from mutualistic coevolution, depends on selective forces that can be overcome in some species, allowing reversions. Despite frequent loss, active pollination remains the predominant mode of pollination in Ficus.


Assuntos
Rosales , Vespas , Animais , Feminino , Pólen
14.
Int J Oncol ; 14(4): 673-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10087313

RESUMO

The efficacy of granisetron hydrochloride 20 microg/kg and 40 microg/kg were compared using a cross-over method to determine the optimal dose in children with solid tumors receiving high-dose chemotherapy. Granisetron controlled the onset of vomiting in 17 of 23 patients (73.9%) who were given 40 microg/kg of granisetron, while 8 of 21 patients (38.1%) were free of vomiting in the 20 microg/kg group. The average frequency of vomiting was 7.22 times in the 20 microg/kg dose versus 4.44 times in the 40 microg/kg dose. No safety problems were associated with either dose. The 40 microg/kg dose of granisetron appears to be more optimal.


Assuntos
Antieméticos/uso terapêutico , Granisetron/uso terapêutico , Vômito/tratamento farmacológico , Adolescente , Antieméticos/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Estudos Cross-Over , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Granisetron/efeitos adversos , Humanos , Lactente , Masculino , Neoplasias/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Vômito/induzido quimicamente
15.
Metabolism ; 48(9): 1089-95, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10484046

RESUMO

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to lard on the development of hypertension and insulin resistance in Dahl salt-sensitive (Dahl-S) rats fed a high-sucrose diet (HSD), a model of salt-sensitive hypertension. After 16 weeks of treatment, the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test significantly increased in the HSD-EPA-E group compared with the HSD-water or -lard control group. The GIR was approximately three times higher in the HSD-EPA-E group versus the HSD-water or -lard control group, and it was about 70% of the rate in the calorically deprived control group fed a low-fat-high-fiber diet (LF-HFD). In addition, EPA-E significantly suppressed the elevation of plasma glucose and insulin levels after oral glucose loading. These results indicate that EPA-E prevents the development of insulin resistance in Dahl-S rats fed a HSD. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase in C18:2, C20:5, and C22:5 components in the HSD-EPA-E group and, conversely, a significant decrease in C16:0, C20:4, and C22:6. The present results indicate that the beneficial effect of EPA-E on insulin resistance in Dahl-S rats fed a HSD is likely dependent on the modification of phospholipid components in the skeletal muscle membrane. These findings suggest that EPA-E might prevent the development of insulin resistance in dietary obesity. In addition, the HSD-EPA-E group showed a significant increase in the level of uncoupling protein (UCP) in brown adipose tissue as compared with the HSD-water or -lard control group. However, EPA-E had no effect on the development of hypertension and obesity in Dahl-S rats fed the HSD.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Hipertensão/metabolismo , Resistência à Insulina , Animais , Glicemia/análise , Pressão Sanguínea , Peso Corporal , Proteínas de Transporte/metabolismo , Catecolaminas/urina , Diabetes Mellitus Tipo 2/metabolismo , Dieta com Restrição de Gorduras , Gorduras na Dieta/metabolismo , Ingestão de Alimentos , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/análise , Insulina/sangue , Canais Iônicos , Lipídeos/análise , Masculino , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais , Ratos , Ratos Endogâmicos Dahl , Sacarose/farmacologia , Proteína Desacopladora 1
16.
Metabolism ; 50(4): 414-7, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11288035

RESUMO

Monotherapy with sulfonylurea may result in the exhaustion of pancreatic beta-cell function, fat accumulation, and dyslipidemia. We examined the possibility of dose reduction by administering sulfonylurea together with troglitazone, and investigated changes in insulin secretion and fat deposition. Seventy-eight patients with type 2 diabetes adequately controlled with glibenclamide were randomly allocated to a troglitazone (400 mg/d)-added group (n = 40) or a control group without placebo (n = 38) and monitored for 24 weeks. The daily dose of glibenclamide was adjusted to maintain stable HbA(1c) levels. Fat accumulation to the liver and thigh muscle were measured in mean Hounsfield units determined on computed tomography (CT) scan. Visceral fat accumulation (V), subcutaneous fat accumulation (S), and the V/S ratio were also determined by CT scan. The daily dose of glibenclamide and serum fasting insulin level in the troglitazone-added group significantly decreased (from 4.05 +/- 2.50 mg/d to 1.84 +/- 1.65 mg/d and from 8.47 +/- 4.62 microU/mL to 6.49 +/- 3.28 microU/mL, respectively) during the observation period compared with the control group (P < .01 and P < .01, respectively). Serum triglyceride and homeostasis model insulin resistance index (HOMA-R) in the troglitazone-added group decreased significantly in comparison to the control group (P < .05 and P < .01, respectively). The mean Hounsfield units of liver significantly decreased in the control group compared with the troglitazone-added group (P < .05). Visceral fat area and the V/S ratio significantly increased in the control group compared with the troglitazone-added group (P < .01 and P < .01, respectively). Glibenclamide monotherapy resulted in fat accumulation accompanied by dyslipidemia. An alternate conclusion is that troglitazone reversed type 2 diabetes (not sulfonylurea)-associated fat accumulation. The addition of troglitazone decreased daily doses of glibenclamide, preserved fasting insulin secretion, improved fat accumulation in liver, and prevented dyslipidemia.


Assuntos
Cromanos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus/prevenção & controle , Fígado Gorduroso/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade , Compostos de Sulfonilureia/efeitos adversos , Tiazóis/uso terapêutico , Tiazolidinedionas , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/crescimento & desenvolvimento , Idoso , Diabetes Mellitus/sangue , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Fígado Gorduroso/sangue , Fígado Gorduroso/induzido quimicamente , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Compostos de Sulfonilureia/uso terapêutico , Troglitazona
17.
Metabolism ; 46(12): 1458-64, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9439543

RESUMO

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to the effects of lard, olive oil, safflower oil, or distilled water as the control on the development of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) with obesity. After 17 or 18 weeks of treatment, the glucose infusion rate (GIR) in the euglycemic insulin-glucose clamp test only showed a significant increase in EPA-E-treated rats compared with control rats given distilled water alone as the vehicle. The GIR in EPA-E-treated animals was approximately three times greater than in the controls. This is the first report to display the influence of various fatty acids on the development of insulin resistance in OLETF rats. We demonstrated that EPA-E prevents the onset of insulin resistance, whereas olive oil and safflower oil have no effect and lard exacerbates insulin resistance. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase of the C18:2, C20:5, and C22:5 components in EPA-E-treated rats and, conversely, a significant decrease in C20:4. In addition, EPA-E-treated rats showed a significant increase in GLUT4 mRNA in skeletal muscle when compared with control rats. Our results indicate that the beneficial effect of EPA-E on insulin resistance in OLETF rats is likely to be dependent on modification of the phospholipid components of the skeletal muscle membrane. These findings suggest that dietary fatty acids may play a key role in the development of insulin resistance in patients with NIDDM.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Ácido Eicosapentaenoico/análogos & derivados , Resistência à Insulina/fisiologia , Proteínas Musculares , Inibidores da Agregação Plaquetária/farmacologia , Animais , Glicemia/análise , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Gorduras na Dieta/farmacologia , Modelos Animais de Doenças , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/análise , Ácidos Graxos/sangue , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4 , Insulina/sangue , Lipídeos/análise , Lipídeos/sangue , Fígado/química , Masculino , Proteínas de Transporte de Monossacarídeos/análise , Proteínas de Transporte de Monossacarídeos/genética , Músculo Esquelético/química , Azeite de Oliva , Pâncreas/patologia , Óleos de Plantas/farmacologia , RNA Mensageiro/análise , Ratos , Óleo de Cártamo/farmacologia , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/fisiologia
18.
Pancreas ; 7(5): 569-77, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1513804

RESUMO

The development of ocular, renal, and neural lesions was examined in male diabetic WBN/Kob rats with endoexocrine pancreatic insufficiency. As for the ocular lesions, around 15 months of age, opacity of the lens began to appear. Opacity was first observed in the periphery of the lens, and then increased rapidly in severity, extending concentrically and centripetally, until total cataracts developed. The incidence of cataracts in male rats was gradually increased and reached almost 100% at 24 months of age. As for renal lesions, the 24-h urinary total protein began to increase at about 13 months of age and reached 50-300 mg/24 h at 13-28 month of age, which was significantly higher than in age-matched male Wistar rats (15-25 mg/24 h). Electrophoretic analysis revealed that the urinary protein was almost all albumin. Morphologically, an increased GBM thickness and glomeruli with segmental or global enlargement of mesangial areas were observed. As for neural lesions, a reduction in motor nerve conduction velocity was demonstrated electrophysiologically, and a marked decrease in density and diameter of myelinated fibers in the sciatic nerves were observed morphometrically. In conclusion, the WBN/Kob rat strain with slowly developing but severe lesions associated with pancreatopathy presents a suitable model for human diabetic complications.


Assuntos
Diabetes Mellitus Experimental/complicações , Albuminúria/urina , Animais , Membrana Basal/patologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Retinopatia Diabética/patologia , Retinopatia Diabética/fisiopatologia , Feminino , Glomérulos Renais/patologia , Masculino , Fibras Nervosas Mielinizadas/patologia , Condução Nervosa , Proteinúria/urina , Ratos , Ratos Endogâmicos
19.
Pancreas ; 5(4): 452-9, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1696384

RESUMO

A spontaneously developed endocrine-exocrine pancreatic dysfunction was observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. Nonobese male WBN/Kob rats developed glycosuria and hyperglycemia at around 9 months of age. Cumulative incidence of diabetes in male rats was 43% (33 of 76) at 12 months of age and reached 90% at the age of 21 months. In contrast, female rats did not become diabetic. Urinary excretion of amylase in WBN/Kob rats was significantly increased in comparison with control Wistar rats. Moreover, the exocrine pancreatic function test was impaired in WBN/Kob rats. Pathological examination of pancreata revealed infiltration of inflammatory cells, hemorrhage, deposition of hemosiderin, and fibrinous exudation around pancreatic ducts and blood vessels at 3 months of age. A gradual increase of fibrous tissue into the exocrine tissue and islets was observed with advancing age. The extremely enlarged interlobular lymph nodes were also observed. At the age of 12 months, the fibrous tissue replaced extensive areas of the pancreas and involved islets. The amylase content of pancreata in WBN/Kob rats was markedly decreased in comparison with that in Wistar rats at 12 months of age. Islets composed of few endocrine cells were detected. Immunohistochemical staining for insulin and glucagon showed a decreased number of not only B cells but also A cells. Moreover, both the pancreatic insulin and glucagon contents were markedly decreased in WBN/Kob rats in comparison with Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Diabetes Mellitus Experimental/complicações , Ilhotas Pancreáticas/fisiopatologia , Pâncreas/fisiopatologia , Pancreatopatias/etiologia , Amilases/metabolismo , Amilases/urina , Animais , Autoanticorpos/análise , Feminino , Fibrose , Imunofluorescência , Teste de Tolerância a Glucose , Imuno-Histoquímica , Insulina/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Pâncreas/imunologia , Pâncreas/patologia , Pancreatopatias/patologia , Pancreatopatias/fisiopatologia , Ratos , Ratos Endogâmicos
20.
Oncol Rep ; 3(3): 519-25, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-21594404

RESUMO

Sixteen consecutive stem cell transplantations (SCT) were performed after myeloablative chemotherapy in patients with high-risk solid tumors of childhood. Seven patients received autologous bone marrow transplantation (ABMT), seven received peripheral blood stem cell transplantation (PBSCT) and two received ABMT + PBSCT. The progression-free survival was similar in three types of transplants (57% ABMT, 43% PBSCT vs. 50% ABMT + PBSCT). The rate of relapse in site of distant organs was also similar (57% ABMT, 57% PBSCT vs. 50% ABMT + PBSCT). There was no statistically significant difference in the hematopoietic recovery time between each group. PBSCT group had a significantly fewer days of food intolerance and a lower morbidity than ABMT group. The disease-free survival was 71% for neuroblastoma, 50% for small round cell tumors and 25% for rhabdomyosarcoma. Post-SCT therapy for possible reinfused tumor cells should be mandatory to decrease the frequency of relapse.

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