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1.
Am J Physiol Endocrinol Metab ; 316(2): E305-E318, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30532989

RESUMO

Heat shock protein 72 (HSP72) is a major inducible molecule in the heat shock response that enhances intracellular stress tolerance. Decreased expression of HSP72 is observed in type 2 diabetes, which may contribute to the development of insulin resistance and chronic inflammation. We used HSP72 knockout (HSP72-KO) mice to investigate the impact of HSP72 on glucose metabolism and endoplasmic reticulum (ER) stress, particularly in the liver. Under a high-fat diet (HFD) condition, HSP72-KO mice showed glucose intolerance, insulin resistance, impaired insulin secretion, and enhanced hepatic gluconeogenic activity. Furthermore, activity of the c-Jun NH2-terminal kinase (JNK) was increased and insulin signaling suppressed in the liver. Liver-specific expression of HSP72 by lentivirus (lenti) in HFD-fed HSP72-KO mice ameliorated insulin resistance and hepatic gluconeogenic activity. Furthermore, increased adipocyte size and hepatic steatosis induced by the HFD were suppressed in HSP72-KO lenti-HSP72 mice. Increased JNK activity and ER stress upon HFD were suppressed in the liver as well as the white adipose tissue of HSP72-KO lenti-HSP72 mice. Thus, HSP72 KO caused a deterioration in glucose metabolism, hepatic gluconeogenic activity, and ß-cell function. Moreover, liver-specific recovery of HSP72 restored glucose homeostasis. Therefore, hepatic HSP72 may play a critical role in the pathogenesis of type 2 diabetes.


Assuntos
Tecido Adiposo Branco/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese/genética , Proteínas de Choque Térmico HSP72/genética , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Animais , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático/genética , Glucose/metabolismo , Resistência à Insulina/genética , Secreção de Insulina/genética , Camundongos , Camundongos Knockout , Transdução de Sinais
2.
Cardiovasc Diabetol ; 12: 160, 2013 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-24188631

RESUMO

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors modulate incretin hormones and exert anti-diabetic effects in type 2 diabetes mellitus. Treatment with angiotensin II type 1 receptor blockers (ARB) is a proven successful intervention for hypertension with type 2 diabetes. The present study investigated the combined effects of the DPP-4 inhibitor vildagliptin and the ARB valsartan in a mouse model of type 2 diabetes. METHODS: C57BL/6 J mice fed with high-fat diet (HFD) or db/db mice were treated with placebo, phloridzin (PHZ), vildagliptin alone (ViL), valsartan alone (VaL) or ViL with VaL (ViLVaL) for 8 weeks. RESULTS: Glucose metabolism was improved in response to PHZ, ViL and ViLVaL in both HFD and db/db mice. Upon glucose challenge, ViLVaL showed the greatest suppression of blood glucose excursions, with increased insulin secretion, in db/db mice. ViLVaL treatment also showed an improvement of insulin sensitivity in db/db mice. Serum inflammatory cytokines were significantly decreased, and adiponectin was highest, in the ViLVaL group. ViLVaL improved insulin signaling and attenuated stress signaling in liver with amelioration of hepatic steatosis due to activated fatty acid oxidation in db/db mice. Furthermore, immunohistochemical analysis of the pancreas revealed that the combination treatment resulted in an increased expression of insulin and PDX-1, and increased insulin content. CONCLUSIONS: The combination therapy of ViL and VaL improves both pancreatic beta-cell function and insulin sensitivity, with a reduction of the inflammatory and cell stress milieu in mouse models of T2DM. Our results suggest that this combination therapy exerts additive or even synergistic benefits to treat T2DM.


Assuntos
Adamantano/análogos & derivados , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Nitrilas/farmacologia , Pirrolidinas/farmacologia , Tetrazóis/farmacologia , Valina/análogos & derivados , Adamantano/farmacologia , Adamantano/uso terapêutico , Adiponectina/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Glicemia/metabolismo , Citocinas/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Modelos Animais de Doenças , Quimioterapia Combinada , Fígado Gorduroso , Proteínas de Homeodomínio/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , Inflamação , Resistência à Insulina , Secreção de Insulina , Camundongos , Camundongos Endogâmicos C57BL , Nitrilas/uso terapêutico , Florizina/farmacologia , Pirrolidinas/uso terapêutico , Tetrazóis/uso terapêutico , Transativadores/efeitos dos fármacos , Transativadores/metabolismo , Valina/farmacologia , Valina/uso terapêutico , Valsartana , Vildagliptina
3.
Endocr J ; 60(10): 1207-14, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23912974

RESUMO

To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 µg/mL at baseline to 9.6±5.5 µg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).


Assuntos
Glicemia/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Pirazinas/uso terapêutico , Triazóis/uso terapêutico , Idoso , Povo Asiático , Glicemia/metabolismo , Automonitorização da Glicemia , Índice de Massa Corporal , Desoxiglucose/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Fosfato de Sitagliptina , Triazóis/efeitos adversos
4.
Intern Med ; 60(9): 1433-1442, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952814

RESUMO

The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became evident. Weekly administration of a glucagon-like peptide (GLP)-1 receptor agonist (RA) dramatically improved his glucose control. Levels of GLP-1 or gastric inhibitory polypeptide (GIP) were low at the baseline in the duodenum and serum of the patient. After 11 months of GLP-1RA treatment, his HbA1c worsened again, and intensive insulin therapy was necessary to control his glucose levels. Our report may explain the significance of residual incretin for maintaining the pancreatic ß-cell function.


Assuntos
Diabetes Mellitus Tipo 2 , Incretinas , Adulto , Glicemia , Polipeptídeo Inibidor Gástrico , Glucose , Homeostase , Humanos , Insulina , Masculino , Adulto Jovem
5.
Endocr Connect ; 10(5): 521-533, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33883285

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

6.
Endocr J ; 57(3): 229-36, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20032567

RESUMO

Ectopic adrenocorticotropic hormone (ACTH) production by the pancreatic neuroendocrine tumor (p-NET) is relatively rare, and patients with this tumor show poor prognosis. In this study, we present the case of a 64-year-old woman who presented with ectopic ACTH syndrome due to p-NET with multiple liver metastases. Computed tomography revealed that she had multiple masses in the liver and a solid mass in the head of the pancreas. Endocrinological examinations revealed markedly elevated plasma ACTH (735.0 pg/mL) and cortisol (34.7 microg/dL) levels associated with hypokalemia (2.7 mEq/L), diabetes and typical Cushingoid features. Histological examinations by needle biopsy of liver tumors in S5 and S8 indicated metastatic ACTH-producing NET, which was also confirmed by venous sampling. The metastatic live tumor was somatostatin receptor (SSTR)-2a- and SSTR-5-positive as revealed by immunohistochemical staining, and reverse transcription polymerase chain reaction revealed divergent expression patterns of SSTRs, pro-opiomelanocortin, and gastrin mRNA. To avoid complications of hypercortisolemia, metyrapone was first administered to reduce the cortisol levels. After near-normalization of cortisol levels, transarterial chemoembolization and somatostatin analogue treatment were performed. The combination of these treatments effectively decreased ACTH and cortisol levels and also ameliorated hyperglycemia. We have achieved controlled hormone secretion and prevented tumor growth in this patient for more than 20 months, suggesting that highly individualized treatment for NET should be undertaken because of its divergent and heterogeneous characteristics.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Hormônios Ectópicos/sangue , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Quimioembolização Terapêutica , Feminino , Humanos , Hidrocortisona/sangue , Achados Incidentais , Neoplasias Hepáticas/terapia , Metirapona/uso terapêutico , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Neoplasias Pancreáticas/terapia , Receptores de Somatostatina/metabolismo , Tomografia Computadorizada por Raios X
7.
Int J Oncol ; 34(3): 847-52, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19212690

RESUMO

Prostaglandin E2 (PGE2) can stimulate tumor progression by both direct and indirect mechanisms. However, its influence on cell proliferation is still unclear. The present study characterized expression of subtypes of PGE2 receptors in oral squamous cell carcinomas, while also investigating the effects of EP3 and EP4 selective antagonists on oral carcinoma cell lines. EP1, EP2, EP3 and EP4 receptor mRNAs were detected in 4, 5, 10 and 10 of 11 surgical specimens respectively. Application of an EP3 antagonist (ONO-AE3-240) strongly inhibited cell growth in COX-2 and PGE2 high expression cells (Ca9-22) but not in COX-2 and PGE2 low expression cells (HSC4). The antagonist also reduced the production of endogenous PGE2 and induced G0/G1 phase cell arrest. Addition of exogenous PGE2 only partly abrogated the growth inhibition, indicating that the anti-proliferative effect via EP3 receptor signaling was not only due to PGE2-dependent but also PGE2-independent mechanisms. In contrast, an EP4 antagonist (ONO-AE3-208) did not inhibit growth in either of the cancer cell lines. In summary, PGE2 receptor EP3 signaling probably contributes to development of oral carcinomas and use of EP3 antagonist may be a new therapeutic strategy for head and neck cancer.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Receptores de Prostaglandina E/biossíntese , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Dinoprostona/farmacologia , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E Subtipo EP3 , Receptores de Prostaglandina E Subtipo EP4
8.
J Clin Med ; 8(5)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091693

RESUMO

Because the renin-angiotensin-aldosterone system influences glucose homeostasis, the mineralocorticoid receptor (MR) signal in pancreatic islets may regulate insulin response upon glucose load. Glucagon-like peptide-1 (GLP-1) production is stimulated by interleukin-6 (IL-6) in pancreatic α-cells. To determine how glucose homeostasis is regulated by interactions of MR, IL-6 and GLP-1 in islets, we performed glucose tolerance and histological analysis of islets in primary aldosteronism (PA) model rodents and conducted in vitro experiments using α-cell lines. We measured active GLP-1 concentration in primary aldosteronism (PA) patients before and after the administration of MR antagonist eplerenone. In PA model rodents, aldosterone decreased insulin-secretion and the islet/pancreas area ratio and eplerenone added on aldosterone (E+A) restored those with induction of IL-6 in α-cells. In α-cells treated with E+A, IL-6 and GLP-1 concentrations were increased, and anti-apoptotic signals were enhanced. The E+A-treatment also significantly increased MR and IL-6 mRNA and these upregulations were blunted by MR silencing using small interfering RNA (siRNA). Transcriptional activation of the IL-6 gene promoter by E+A-treatment required an intact MR binding element in the promoter. Active GLP-1 concentration was significantly increased in PA patients after eplerenone treatment. MR signal in α-cells may stimulate IL-6 production and increase GLP-1 secretion, thus protecting pancreatic ß-cells and improving glucose homeostasis.

9.
Oncol Rep ; 19(3): 645-50, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18288396

RESUMO

The purpose of this study was to determine the expression of cyclooxygenase-2 (COX-2) in normal epithelium, dysplasia and squamous cell carcinoma of the hypopharynx and to investigate associations with clinicopathological factors and survival. Seventy-five patients with hypopharyngeal squamous cell carcinomas (HPSCC) who underwent surgical treatment at the Department of Otolaryngology, Osaka Medical Center for Cancer and Cardiovascular Diseases, were investigated. COX-2 expression was determined by immunohistochemistry and 97.3% (73/75) of samples displayed immunostaining in tumor cells. COX-2 staining was localized mainly in the cytoplasm (73/75) and was rare in stromal cells (2/75). Over half of the areas of dysplastic cells adjacent to carcinomas also showed COX-2 staining (41/70, 58.6%). There were no significant correlations between the COX-2 expression and tumor size, location and tumor growth type, T- and N-stage, tumor recurrence, lymph node metastasis and survival in this study. COX-2 expression thus does not appear to have a prognostic significance for hypopharyngeal SCC although there was a tendency for higher values in T3/T4 than T1/T2 cases. Furthermore, COX-2 was found to be more strongly expressed in poorly-differentiated than in moderately/well-differentiated carcinomas. In this study group, COX-2 was up-regulated not only in SCCs but also in the dysplastic lesions of the hypopharynx, suggesting that COX-2 inhibition may be a useful chemopreventive strategy.


Assuntos
Carcinoma de Células Escamosas/patologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Hipofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/enzimologia , Feminino , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/enzimologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
PLoS One ; 13(1): e0191553, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29364977

RESUMO

MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs have recently been implicated in glucose metabolism, but the roles of miRNAs in insulin-resistant conditions, such as obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222, the expression of which was increased in the livers of high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin, indicating that miR-222 negatively regulates insulin signaling. As per in silico analysis, miR-222 potentially binds to the 3' untranslated region (3' UTR) of the IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct interaction between miR-222 and the 3' UTR of IRS-1 via luciferase assays. Our findings suggest that up-regulation of miR-222 followed by reduction in IRS-1 expression may be a viable mechanism of insulin resistance in the liver.


Assuntos
Proteínas Substratos do Receptor de Insulina/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Animais , Gluconeogênese/genética , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
11.
Auris Nasus Larynx ; 43(3): 292-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26498699

RESUMO

OBJECTIVE: Intranasal corticosteroid sprays (INCSs) are commonly used for therapy of allergic rhinitis (AR). Adherence to regular use of INCSs is influenced by patient perception and preferences of products. The study objective was to compare perceived sensory attributes of fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal spray (MFNS) in AR patients. METHODS: In a multicenter, randomized, crossover, prospective study, 40 seasonal AR patients were administered both FFNS and MFNS for 2 weeks each in a crossover fashion, for a total of 4 weeks. Patients completed questionnaires for each product regarding perceived sensory attributes at the end of each two-week period of product administration. RESULTS: FFNS was significantly preferred over MFNS. Significantly, fewer subjects perceived a bitter taste (p=0.01), medication running down their throat (p=0.033), and medication running out of their nose (p=0.002) with FFNS. MFNS was more frequently reported to induce nasal irritation (p=0.012), sneezing (p=0.017), and rhinorrhea (p=0.007) compared to FFNS. Interestingly, these findings were markedly observed in females. Medicine dripping out of the nose and nasal shooting were the most common problems reported for MFNS with a higher proportion of subjects who felt moderate-to-severe discomfort. Overall, 52.5% of patients expressed a preference for FFNS compared with 22.5% for MFNS. CONCLUSION: Several perceived sensory attributes of FFNS were rated significantly superior to MFNS. FFNS may contribute to enhanced treatment outcomes in AR patients due to improved treatment adherence.


Assuntos
Androstadienos/uso terapêutico , Antialérgicos/uso terapêutico , Furoato de Mometasona/uso terapêutico , Preferência do Paciente , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Fatores Sexuais , Espirro , Inquéritos e Questionários , Paladar
12.
Sci Rep ; 6: 35690, 2016 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-27759092

RESUMO

Activation of heat shock response (HSR) improves accumulated visceral adiposity and metabolic abnormalities in type 2 diabetes. To identify the optimal intervention strategy of the activation of the HSR provided by mild electrical stimulation (MES) with heat shock (HS) in type 2 diabetes. This study was a prospective, frequency-escalating, randomized, open-label, triple-arm trial in Japan. A total of 60 obese type 2 diabetes patients were randomized into three groups receiving two, four, or seven treatments per week for 12 weeks. No adverse events were identified. MES + HS treatment (when all three groups were combined), significantly improved visceral adiposity, glycemic control, insulin resistance, systemic inflammation, renal function, hepatic steatosis and lipid profile compared to baseline. The reduction in HbA1c was significantly greater among those treated four times per week (-0.36%) or seven times per week (-0.65%) than among those treated two times per week (-0.10%). The relative HbA1c levels in seven times per week group was significantly decreased when adjusted by two times per week group (-0.55%. p = 0.001). This research provides the positive impact of MES + HS to treat obese patients with type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Terapia por Estimulação Elétrica/métodos , Resposta ao Choque Térmico , Obesidade/complicações , Obesidade/terapia , Idoso , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Hemoglobinas Glicadas/análise , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sujeitos da Pesquisa , Resultado do Tratamento
13.
Regul Pept ; 127(1-3): 233-8, 2005 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-15680492

RESUMO

FTY720 has been originally developed as a new immunosuppressive agent, which prolongs graft survival in organ transplantation. Adrenomedullin (AM) participates in the regulation of sodium homeostasis and has renoprotective effects. The possible involvement of renal AM in the pathophysiology of glomerulonephritis (GN) and the effect of FTY720 has been evaluated in rats. HgCl2 (1 mg/kg body weight) was inoculated subcutaneously 3 times/week for a total of 2 weeks. FTY720 (3 or 10 mg/kg) was inoculated subcutaneously daily. The proteinuria, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum total cholesterol levels were increased and serum albumin level was reduced in rats with HgCl2-induced GN compared with controls. FTY720 reduced proteinuria (3 mg/kg: -25%; 10 mg/kg: -41%), urinary NAG excretion (-11%; -52%) and total cholesterol level (-21%; -55%) in a dose-dependent manner. Renal AM level and its mRNA expression were increased in rats with GN compared with controls (Peptide Cortex: +69%; Medulla: +82%; mRNA Cortex: +25%). Interestingly, FTY720 additionally increased these levels (Peptide Cortex: +38%; Medulla: +39%; mRNA Cortex: +20%). Renal AM levels correlated with urinary NAG excretion and creatinine clearance. These results suggest that FTY720 suppresses the renal damage in rats with GN and renal AM may participate in the pathophysiology of GN and the renoprotective effects of FTY720.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/imunologia , Imunossupressores/uso terapêutico , Peptídeos/metabolismo , Propilenoglicóis/uso terapêutico , Proteinúria/tratamento farmacológico , Adrenomedulina , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Análise Química do Sangue , Cloridrato de Fingolimode , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/fisiopatologia , Humanos , Imunossupressores/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Cloreto de Mercúrio , Propilenoglicóis/metabolismo , Radioimunoensaio , Distribuição Aleatória , Ratos , Esfingosina/análogos & derivados , Estatística como Assunto , Urina/química
14.
J Atheroscler Thromb ; 12(3): 149-53, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16020915

RESUMO

We reported previously that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (RIs) suppressed in vitro oxidized-low density lipoprotein-induced macrophage growth. To elucidate whether HMG-CoA RIs have anti-atherogenic effects separate from their cholesterol-lowering effect, total plasma levels of cholesterol in patients with type 2 diabetes mellitus (type 2 DM) and hypercholesterolemia were reduced to normal by one-year treatment with HMG-CoA RIs and intimal-medial thickness (IMT) of the common carotid arteries (CCA) was measured. Patients with type 2 DM and hypercholesterolemia received either pravastatin (n = 15) or simvastatin (n = 15), while another group of type 2 DM patients with normocholesterolemia did not receive these agents. IMT of the CCA was measured using Powervision SSA-370A, probe 7.5 Mhz. The mean IMT and the rate of increase of IMT were relatively elevated in the order of the simvastatin-treatment group, pravastatin-treatment group, and control group. Our results suggested that HMG-CoA RIs might have anti-atherogenic effects in addition to their cholesterol-lowering effect.


Assuntos
Artéria Carótida Primitiva/efeitos dos fármacos , Diabetes Mellitus Tipo 2/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/patologia , Pravastatina/farmacologia , Sinvastatina/farmacologia , Túnica Íntima/efeitos dos fármacos , Túnica Média/efeitos dos fármacos , Idoso , Artéria Carótida Primitiva/patologia , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Pravastatina/administração & dosagem , Sinvastatina/administração & dosagem , Túnica Íntima/patologia , Túnica Média/patologia
15.
PLoS One ; 10(7): e0130760, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26176947

RESUMO

The purpose of this study was to develop quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the analysis of proteins involved in metastasis of breast cancer for diagnosis and determining disease prognosis, as well as to further our understand of metastatic mechanisms. We have previously demonstrated that the protein type XIV collagen may be specifically expressed in metastatic tissues by two dimensional LC-MS/MS. In this study, we developed quantitative LC-MS/MS methods for type XIV collagen. Type XIV collagen was quantified by analyzing 2 peptides generated by digesting type XIV collagen using stable isotope-labeled peptides. The individual concentrations were equivalent between 2 different peptides of type XIV collagen by evaluation of imprecise transitions and using the best transition for the peptide concentration. The results indicated that type XIV collagen is highly expressed in metastatic tissues of patients with massive lymph node involvement compared to non-metastatic tissues. These findings were validated by quantitative real-time RT-PCR. Further studies on type XIV collagen are desired to verify its role as a prognostic factor and diagnosis marker for metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cromatografia Líquida/métodos , Proteínas de Neoplasias/metabolismo , Espectrometria de Massas em Tandem/métodos , Sequência de Aminoácidos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Cromatografia Líquida/normas , Colágeno/química , Colágeno/genética , Colágeno/metabolismo , Glicoproteínas/química , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Metástase Linfática , Dados de Sequência Molecular , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Peptídeos/química , Peptídeos/metabolismo , Prognóstico , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/normas
16.
Diabetes Res Clin Pract ; 110(1): e5-e8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26293448

RESUMO

An association between remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and insulin or dipeptidyl peptidase-4 (DPP4) inhibitor therapy were previously reported. We encountered four cases of RS3PE syndrome with type 2 diabetes mellitus or impaired glucose tolerance (IGT) without insulin or DPP4 inhibitor medication.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Edema/diagnóstico , Intolerância à Glucose/diagnóstico , Sinovite/diagnóstico , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/complicações , Feminino , Intolerância à Glucose/complicações , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Síndrome , Sinovite/complicações
17.
Eur J Pharmacol ; 489(1-2): 127-33, 2004 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-15063164

RESUMO

We studied the effects of mycophenolate mofetil, a specific inhibitor of inosine monophosphate dehydrogenase, on the mercuric chloride induced autoimmune glomerulonephritis in Brown Norway rats and also on the renal contents of adrenomedullin. In the rats with autoimmune glomerulonephritis, plasma and renal tissue adrenomedullin levels were increased significantly. Coadministration of mycophenolate mofetil resulted in prevention of autoimmune glomerulonephritis and also in maintaining of plasma and renal tissue adrenomedullin levels at control levels. Adrenomedullin mRNA expressions in the renal cortex were also higher in the rats with autoimmune glomerulonephritis. Significant positive correlations were found between renal cortical adrenomedullin levels and urinary Na+ and N-acetyl-beta-D-glucosaminidase excretion. A significant negative correlation between renal cortical adrenomedullin levels and creatinine clearance was also found. These results suggest that mycophenolate mofetil suppresses the renal damage in rats with autoimmune glomerulonephritis and renal adrenomedullin may participate in the pathophysiology of autoimmune glomerulonephritis.


Assuntos
Glomerulonefrite Membranoproliferativa/prevenção & controle , Imunossupressores/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacologia , Peptídeos/metabolismo , Adrenomedulina , Animais , Northern Blotting , Glomerulonefrite Membranoproliferativa/patologia , IMP Desidrogenase/antagonistas & inibidores , Imunossupressores/uso terapêutico , Masculino , Cloreto de Mercúrio/farmacologia , Ácido Micofenólico/uso terapêutico , Proteinúria/tratamento farmacológico , Purinas/metabolismo , Radioimunoensaio , Ratos , Ratos Endogâmicos BN
18.
Auris Nasus Larynx ; 29(3): 301-3, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12167456

RESUMO

Thermal burns of the larynx after swallowing hot beverages are extremely rare among adults. Most reported cases have occurred among young children. We report the case of a male adult who, upon swallowing hot milk from a bottle, experienced a burn of the larynx affecting the epiglottis and surrounding supraglottic structures. Since dyspnea usually occurs within hours of a burn of the larynx, the importance of airway management in this case is emphasized.


Assuntos
Queimaduras/diagnóstico , Epiglote/lesões , Laringe/lesões , Faringe/lesões , Animais , Queimaduras/complicações , Queimaduras/terapia , Dispneia/etiologia , Calefação , Humanos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Leite
19.
Nihon Jibiinkoka Gakkai Kaiho ; 106(6): 700-4, 2003 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-12872725

RESUMO

Subjects were 51 patients undergoing folded pharyngeal flap surgery for velopharyngeal incompetence at the Department of Otolaryngology of Kagawa Medical University between August 1985 and July 2001. Causal diseases were cleft palate in 27 (53%), submucous cleft palate in 8 (16%), and congenital velopharyngeal incompetence in 16 (31%). In history, 31% with congenital velopharyngeal incompetence, 25% with submucous cleft palate, and 11% with cleft palate had congenital abnormalities. In addition, 56% with congenital velopharyngeal incompetence, 38% with submucous cleft palate, and 15% with cleft palate had mental retardation, indicating that it occurred with high frequency in patients with congenital velopharyngeal incompetence. The postoperative improvement of nasality was investigated in 48 patients whose progress could be observed for more than 1 year. Of 39 preoperatively diagnosed with advanced velopharyngeal dysfunction, 34 (87%) showed improved nasality. Of 9 with preoperatively slight deficiency, 8 (89%) improved nasality. The blowing test showed no difference in results between patients who had advanced and slight deficiency. Articulation on speech level improved to be normal in 78% of patients with slight deficiency, but only in 46% of those with advanced deficiency. Improvement of articulation on a speech level was high (86%) in patients with submucous cleft palate, but low in patients with congenital velopharyngeal incompetence who had mental retardation. Further study is required to detail postoperative prognosis factors.


Assuntos
Faringe/cirurgia , Retalhos Cirúrgicos , Insuficiência Velofaríngea/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Fissura Palatina/complicações , Fissura Palatina/cirurgia , Humanos , Deficiência Intelectual/complicações , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Distúrbios da Fala/complicações , Distúrbios da Fala/cirurgia , Insuficiência Velofaríngea/complicações
20.
Auris Nasus Larynx ; 41(3): 264-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24182690

RESUMO

OBJECTIVE: Silver-containing carboxymethylcellulose fiber dressing (Aquacel®-Ag) has been used to treat burns and ulcers with a large amount of exudate. The aim of this investigation was to confirm whether Aquacel®-Ag has beneficial effects when it is used as nasal packing. METHODS: We included 44 patients who underwent bilateral endoscopic sinus surgery due to chronic rhino-sinusitis. Beschitin-F® or Aquacel®-Ag was packed postoperatively into the bilateral middle meatus. Patient's comfort was recorded using a VAS, as well as wound healing, postoperative bleeding and local infection. Postoperative-specific organisms were also evaluated from the removed packing materials located in the middle meatus when they were removed on the 4th day after surgery. RESULTS: The scores for nasal obstruction and pain were not statistically different in each group. Postoperative bacteriologic studies indicated marked differences. Coagulase-negative staphylococci were predominant and potential pathogens were recovered in a few cases in the Aquacel®-Ag group. In contrast, potential pathogens, including Streptococcus pneumonia, Haemophilus influenza, and Gram-negative rods, were predominant in the Beschitin-F® group. CONCLUSION: The results indicate that Aquacel®-Ag might contribute to hemostasis, wound healing, and patient comfort after endonasal surgery, similar to Beschitin-F®. Additionally, it may have advantages concerning the prevention of postoperative infection.


Assuntos
Carboximetilcelulose Sódica/uso terapêutico , Seios Paranasais/cirurgia , Cuidados Pós-Operatórios/métodos , Hemorragia Pós-Operatória/prevenção & controle , Rinite/cirurgia , Compostos de Prata/uso terapêutico , Sinusite/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Bandagens , Doença Crônica , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Método Simples-Cego , Resultado do Tratamento , Cicatrização
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