Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur J Pharmacol ; 863: 172695, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31560869

RESUMO

Pioglitazone (Pio), a peroxisome proliferators-activated receptor-γ (PPAR-γ) agonist, may protect against renal ischemia/reperfusion injury (IRI). Recent studies have shown that autophagy plays a protective role in IRI. We aimed to evaluate whether autophagy was involved in pioglitazone-induced protection during tubular cell hypoxia/reoxygenation (H/R). Normal rat kidney proximal tubular cells NRK-52E were subjected to H/R injury, and they were divided into 6 groups: control, control + Pio, H/R, H/R + Pio, H/R + MA, H/R + MA + Pio. Autophagy-related proteins were primarily assessed by Western blot and TUNEL was performed to assess cell apoptosis. Our results showed pioglitazone pretreatment had a cytoprotective effect against H/R injury. The H/R + Pio group had an increased ratio of LC3-II to LC3-I and increased Beclin-1, decreased p62. Pioglitazone also reduced apoptosis and enhanced cell survival while inducing autophagy. Correspondingly, autophagy inhibition with 3-MA alleviated this protective effect. Furthermore, pioglitazone-induced enhancement of autophagy could be related to increased AMP-activated protein kinase (AMPK) phosphorylation and decreased Mammalian target of rapamycin (mTOR) phosphorylation. Thus, pioglitazone pretreatment protects against H/R injury by enhancting autophagy through the AMPK-mTOR signaling pathway.

3.
Front Pharmacol ; 9: 851, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127742

RESUMO

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway.

4.
J Diabetes ; 10(2): 121-129, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28449408

RESUMO

BACKGROUND: The E23K variant of the potassium voltage-gated channel subfamily J member 11 (KCNJ11) gene has been reported to be associated with type 2 diabetes (T2D) in many populations. However, little is known about the role of E23K in the development of prediabetes in Chinese youth. METHODS: To investigate the role of E23K in the development of prediabetes, 279 subjects with prediabetes and 240 normal controls (mean [± SD] age 18.1 ± 3.2 and 17.8 ± 4.3 years, respectively) were recruited to the study. Height, weight, and hip and waist circumferences were measured by trained physicians. Genotyping of KCNJ11 polymorphisms and clinical laboratory tests to determine cholesterol, triglyceride (TG), blood glucose, and insulin levels were performed. RESULTS: The carrier rate of K23 allele-containing genotypes was higher for prediabetic than control subjects (P = 0.005). Logistic regression analyses revealed that higher body mass index percentiles (P = 0.013), lower insulin levels at 30 min during an oral glucose tolerance test (P = 0.001), a higher ratio of total cholesterol: high-density lipoprotein cholesterol (P = 0.001), and a K allele-containing genotype (P = 0.019) are independent risk factors for prediabetes in Chinese Han youth. Furthermore, K23 allele-containing genotypes were associated with impaired indices of insulin secretion and ß-cell function in female youth with prediabetes. These effects were not seen in male youth with prediabetes. CONCLUSIONS: The results confirm that the common E23K polymorphism of KCNJ11 carries a higher susceptibility to the development of prediabetes in the Chinese Han population. The results suggest that E23K may have a greater effect on the development of T2D in female Chinese youth.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Polimorfismo Genético , Canais de Potássio Corretores do Fluxo de Internalização/genética , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/genética , Adolescente , Biomarcadores/análise , Glicemia/análise , Estudos de Casos e Controles , China/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Hemoglobina A Glicada/análise , Humanos , Masculino , Prognóstico
5.
Oncotarget ; 8(67): 110774-110784, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29340015

RESUMO

Background: To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation and pain relief. Results: In phase I study, common apatinib-related AEs (arAEs) were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN). Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study, combination apatinib with RT cohorts, AEs events increased comparing with either apatinib alone or RT alone; at the same time, combination cohorts showed PSA declines of ≥50% in 12 patients, and stable disease in 6 patients. Combination cohorts had pain control significantly improved in both level and duration comparing with RT alone. Conclusions: In SBPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg daily in combining with RT synergized pain control, the overall AEs were manageable. Further studies are needed in large sample size future trials.

6.
Curr Stem Cell Res Ther ; 12(3): 183-187, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27781940

RESUMO

Acute renal failure (ARF) is a syndrome of abrupt decline in renal function induced by a number of different insults. In clinic, the common etiology for ARF is ischemia-reperfusion injury (IRI). The pathophysiological process of renal IRI is complex, there is no good treatment. Stem cell therapy is a new and promising treatment for renal IRI. Mesenchymal stem cells (MSCs) have the ability to differentiate into tissues of mesodermal lineages. MSCs are under intensive study as potential therapeutic strategy for renal IRI. MSCs have been investigated with immunomodulatory, anti-inflammatory and tissue repair properties which could attenuate ischemic injury and accelerate the regeneration process in the condition of renal IRI. Moreover, the MSCs have the ability to migrate to the injury sites and to stimulate repair by paracrine mechanisms rather by differentiating into the injured cells. Here we review the latest information on MSCs, their biological characteristics, including their therapeutic perspectives, and envisage their putative role in renal ischaemic conditioning.


Assuntos
Lesão Renal Aguda/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Traumatismo por Reperfusão/terapia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Movimento Celular , Citocinas/metabolismo , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Células-Tronco Mesenquimais/metabolismo , Comunicação Parácrina , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
7.
PLoS One ; 11(12): e0166606, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27935952

RESUMO

BACKGROUND: To study the feasibility of down stage the borderline resectable pancreatic cancer (BRPC) to resectable disease, we reported our institutional results using an intensity-modulated radiation therapy (IMRT) simultaneous integrated boost (SIB) dose escalation approach to improve R0 resectability. METHODS: We reviewed our past 7 years of experience of using neoadjuvant induction chemotherapy with Gemcitabine followed by concurrent chemoradiaiton for BRPC. During the concurrent, chemo was 5-FU and radiation were IMRT with SIB technique to target the key areas with dose escalation to 5600 in 28 fractions. The key areas were defined by PET positive area. This was followed by restaging imaging to rule out distant metastases before resection. RESULTS: 25 finished dose escalation protocol. 2 of the 25 cases developed distant metastases, 23 (92%) patients without distant metastases underwent pancreatectomy. Among the those received pancreatectomy, 22 (95%) achieved negative margin (R0). The gastrointestinal toxicity > grade 2 was 8% and there was no grade 4 toxicity. CONCLUSION: Neoadjuvant Gemcitabine-based induction chemotherapy followed by 5-FU-based IMRT-SIB is a feasible option in improving the likelihood of R0 resection rate in BRPC without compromising the organs at risk for toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/terapia , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Colite/etiologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Estudos de Viabilidade , Neutropenia Febril/etiologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pâncreas/efeitos dos fármacos , Pâncreas/efeitos da radiação , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Trombocitopenia/etiologia , Resultado do Tratamento
8.
Zhonghua Zhong Liu Za Zhi ; 37(7): 517-20, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26463328

RESUMO

OBJECTIVE: To explore the expression of cancerous inhibitor of phosphatase 2A (CIP2A) protein in small cell lung cancer and their relationship with clinicpathological features and prognosis. METHODS: A total of 112 cases of surgical specimens or bronchoscopic biopsies of small cell lung cancer were collected. There were specimens of 94 cases of SCLC tissues and 40 cases of paracancerous lung tissues. Quantitative RT-PCR and immunohistochemistry analysis were performed to determine the CIP2A expression in SCLC tissues. Kaplan-Meier curves were used to estimate the association between CIP2A expression and clinicopathological characteristics and prognosis of the patients. RESULTS: The expression of CIP2A in SCLC tissue was 7.605 ± 1.893, significantly higher than that in the paracancerous tissues (1.041 ± 0.786) (P < 0.01). The positive rate of CIP2A expression in cancer tissues was 82.8%, significantly higher than that in the paracancerous tissues (13.3%) (P < 0.01). The median disease-free survival was 9.88 months in the CIP2A-high expressing patients, significantly shorter than the 20.92 months in CIP2A-low expressing patients (P < 0.001). CIP2A expression was significantly correlated with the tumor stage, chemotherapeutic sensitivity, and survival (P < 0.05 for all). CONCLUSIONS: CIP2A expression is associated with the pathogenesis of SCLC, and may become a potential prognostic indicator of SCLC.


Assuntos
Autoantígenos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pulmão/metabolismo , Neoplasias Pulmonares/mortalidade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Pequenas Células do Pulmão/mortalidade
9.
Asian Pac J Trop Med ; 8(8): 643-50, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26321518

RESUMO

OBJECTIVE: To explore the correlation between tumor-associated macrophages and the proliferation and invasion of type I endometrial carcinoma. METHODS: Immunohistochemistry was used to investigate the infiltration of macrophages in normal and different types of hyperplastic endometrial lesions. The proliferation and invasion ability of type I endometrial carcinoma cell line RL95-2 influenced by mononuclear macrophage cell line THP-1 (constructed M2 type macrophages) was detected by CCK8 and transwell technologies respectively. Transwell was used to evaluate the recruiting ability of RL95-2 on THP-1 cells. Otherwise, the western blot was also used to detect the expression of CyclinD1 and MMP-2 in RL95-2 with the influence of THP-1. RESULTS: Immunohistochemistry result showed a positive correlation between the number of infiltrating macrophages and the progression of endometrial hyperplasia. THP-1 recruited by RL95-2 could promote its proliferation and invasion and enhance the expression of the CyclinD1 and MMP-2 protein in a time dependent manner (P < 0.05). CONCLUSIONS: Increase of the number of infiltrating macrophages and its contribution to the tumor inflammatory microenvironment may result in the development of the type I endometrial carcinoma.

10.
Biochem Biophys Res Commun ; 458(2): 321-7, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25656571

RESUMO

Single nucleotide polymorphism (SNP) rs11671784 is in the loop of pre-miR-27a and the G/A variation can significantly decrease mature miR-27a expression. This study explored the role of miR-27a in chemo-sensitivity of bladder cancer and how rs11671784 G/A variation affects the sensitivity. Blood and tumor samples from 89 bladder cancer cases were analyzed. In-vitro study was performed to explore the mechanism of chemo-sensitivity and the downstream target of miR-27a by using bladder cancer cell lines. This study identified a causative relationship between rs11671784 G/A variation, lowered miR-27a expression, increased RUNX-1 expression and following weakened chemo-sensitivity. rs11671784 G allele has significantly stronger effect over A allele in promoting chemo-sensitivity in bladder cancer. miR-27a mediates chemotherapy at least partially through reducing P-gp expression and increasing apoptosis. In addition, RUNX-1 is a novel direct target of miR-27a, which is involved in its regulation of chemo-sensitivity in bladder cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Resistencia a Medicamentos Antineoplásicos/genética , Marcação de Genes/métodos , MicroRNAs/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Marcadores Genéticos/genética , Variação Genética/genética , Humanos , Paclitaxel/administração & dosagem , Polimorfismo de Nucleotídeo Único/genética , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
11.
Int J Clin Exp Med ; 8(10): 17902-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770384

RESUMO

The present study was designed to investigate the effects of sitagliptin on metabolic parameters as well as the expression levels of retinol-binding protein 4 (RBP4) and glucose transporter type 4 (GLUT4) in a rat model of type 2 diabetes mellitus. A rat model of type 2 diabetes mellitus was established by a combination of a high-fat diet and intraperitoneal injection of low-dose streptozotocin. Rats were divided into three groups: normal control group, diabetes group, and diabetes + sitagliptin group. Body weight, glycemic parameters, lipid profiles, fasting insulin (FINS) and serum RBP4 levels were assessed at baseline and after 6 weeks of therapy. Western blotting was used to detect the tissue RBP4 and GLUT4 expression levels. After treatment for 6 weeks, the diabetes + sitagliptin group displayed significantly improve levels of blood sugar, blood grease, and insulin sensitizing functions (P < 0.05) than the diabetes group. Sitagliptin markedly down regulated RBP4 expression levels and up-regulated GLUT4 expression levels in adipose tissue and skeletal muscle. The results indicate that sitagliptin can modulate the RBP4-GLUT4 system in adipose tissue and skeletal muscle. Modulation of the RBP4-GLUT4 system may be one of the mechanisms by which sitagliptin ameliorates the symptoms of type 2 diabetes mellitus.

12.
Zhongguo Fei Ai Za Zhi ; 17(11): 769-77, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25404266

RESUMO

BACKGROUND AND OBJECTIVE: Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 15% of all histological types consist of small cell lung cancer (SCLC). Chemotherapy is one of the major treatment method. Though the current first-line standard chemotherapy regimen for SCLC is active in most SCLC cases, however the disease recurs shortly after the first successful treatment with multi-drug resistance (MDR) phenotype. Our previously study showed that SPHK1 was associated with MDR in SCLC. The aim of this study is to investigate the role of sphingosine kinase 1 (SPHK1) showed in small cell lung multi-drug resistance. METHODS: Firstly, the analysis of QRT-PCR and Western blot were used to study differential expression of SPHK1 from mRNA and protein levels in both the H69 and H69AR cell lines. Then, Downregulation of SPHK1 by transfection with siRNA in H69AR. Moreover, the sensitivities of cells to chemotherapy drugs such as ADM, DDP, VP-16 were detected by CCK8 assay. The change of cell cycle and apoptosis rate were detected by flow cytometry. Meanwhile, expression of SPHK1 in clinical specimens were detected by QT-PCR and immunohistochemistry. Relation of SPHK1 expression with clinicopathological features and prognosis of patients was studied. RESULTS: The expression of SPHK1 was significantly decreased in H69AR cells that in the H69 cells. The sensitivities of H69AR cells to chemotherapy drugs were increased when up-regulated the expression of SPHK1, enforced SPHK1 expression increased cell apoptosis and the cell cycle arrest in G0/G1 phase in H69AR cells, the expression of SPHK1 was not associated with gender, age, but significantly correlated with clinical stage, chemosensitivity and overall survival (P<0.05). CONCLUSIONS: Our results suggest that SPHK1 is involved in the regulation of small cell lung cancer multi-drug resistance, SPHK1 may be as potentialtarget gene to evaluate the chemosensitivity and clinical prognostic for SCLC.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/enzimologia , Resultado do Tratamento
13.
Am J Nephrol ; 40(3): 215-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25322693

RESUMO

BACKGROUND: MicroRNAs (miR) have come into focus as powerful regulators of gene expression and potential diagnostic tools during renal ischemia reperfusion injury (IRI). The aim of this study was to investigate the molecular regulation and function of miR-21, and to analyze the relationship between caspases and miR-21 expression levels in an experimental model of renal IRI. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. The male BALB/c mice were randomly assigned to the following groups: pre-miR-21 + IRI group, antagomiR-21 + IRI group, PBS + IRI group, pre-miR-21 + sham operation group, antagomiR-21 + sham operation group, PBS + sham operation group. The pre-miR-21 or antagomiR-21 was administered intraperitoneally (200 ng/kg weight) 24 and 6 h before induction of ischemia. Renal function, histological damage, renal cell apoptosis proteins were evaluated at 24 h after reperfusion. RESULTS: Mice upregulated miR-21 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores and a decrease in programmed cell death 4 (PDCD4) mRNA and active caspase-3, caspase-8 proteins expressions. CONCLUSIONS: miR-21 is endowed with anti-apoptotic properties by suppressing the expression of PDCD4 gene and active caspase 3/8 fragments in the condition of renal IRI. miR-21 exerts significant functional protection in our renal murine model of IRI.


Assuntos
Caspases/metabolismo , Isquemia/metabolismo , Rim/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Caspase 8/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Interleucina-18/sangue , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Ligação a RNA/metabolismo , Distribuição Aleatória , Transdução de Sinais , Regulação para Cima
14.
Endocrine ; 45(3): 409-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23918212

RESUMO

Fenofibrate is a peroxisome proliferator-activated receptor-α that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of vaspin, an adipocytokine that has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly increased serum vaspin levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on vaspin mRNA and protein expressions in obese rats. Fenofibrate greatly increased vaspin mRNA and protein levels in visceral adipose tissue consisting of retroperitoneal, mesenteric, and periepididymal adipose tissue but not in the subcutaneous adipose tissue, which correlated with increased serum vaspin levels and increased insulin sensitivity in obese rats. Consistent with a direct effect on vaspin expression, fenofibrate treatment significantly increased the mRNA and protein expression levels of vaspin in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate upregulates vaspin expression in dyslipidemic human subjects and suggest that upregulation of vaspin expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.


Assuntos
Dislipidemias/metabolismo , Fenofibrato/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Obesidade Abdominal/metabolismo , Serpinas/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Tiazolidinedionas/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Animais , Modelos Animais de Doenças , Dislipidemias/tratamento farmacológico , Fenofibrato/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Resistência à Insulina/fisiologia , Masculino , Camundongos , Obesidade Abdominal/tratamento farmacológico , Pioglitazona , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Serpinas/sangue , Gordura Subcutânea Abdominal/efeitos dos fármacos , Tiazolidinedionas/administração & dosagem , Resultado do Tratamento , Regulação para Cima
15.
Vasc Health Risk Manag ; 9: 429-33, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24023518

RESUMO

Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk- benefit analysis to determine what role pioglitazone should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed. This review provides a comprehensive overview of the present literature. Clinical data currently available indicate that pioglitazone is an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse cardiovascular risk.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Tiazolidinedionas/administração & dosagem , Administração Oral , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Hipoglicemiantes/efeitos adversos , Seleção de Pacientes , Pioglitazona , Medição de Risco , Fatores de Risco , Tiazolidinedionas/efeitos adversos , Resultado do Tratamento
16.
J Surg Res ; 184(2): 1092-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23545406

RESUMO

BACKGROUND: In our previous study, we showed that pioglitazone exerts protective effects on renal ischemia-reperfusion injury (IRI) in mice by abrogating renal cell apoptosis. Oxidative stress due to excessive production of reactive oxygen species and subsequent lipid peroxidation plays a critical role in renal IRI. The purpose of the current study is to demonstrate the effect of pioglitazone on renal IRI by modulation of oxidative stress. MATERIALS AND METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Thirty healthy male Balb/c mice were randomly assigned to one of the following groups: phosphate buffer solution (PBS) + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests and kidney antioxidant activities were determined 24 h after reperfusion. RESULTS: Pretreatment with pioglitazone produced reduction in serum levels of blood urea nitrogen and creatinine caused by IRI. Pretreatment with pioglitazone before IRI resulted in a higher level of kidney enzymatic activities of superoxide dismutase, glutathione, catalase, and total antioxidant capacity than in the PBS-pretreated IRI group. CONCLUSIONS: Our results indicate that pioglitazone can provide protection for kidneys against IRI by enhancing antioxidant capacity. Therefore, pioglitazone could be a potential therapeutic approach to prevent renal IRI relevant to various clinical conditions.


Assuntos
Antioxidantes/uso terapêutico , Rim/irrigação sanguínea , Rim/patologia , Traumatismo por Reperfusão/prevenção & controle , Tiazolidinedionas/uso terapêutico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Pioglitazona , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Tiazolidinedionas/farmacologia
17.
J Clin Endocrinol Metab ; 97(11): 3835-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22918873

RESUMO

CONTEXT: We report on a case of adrenal angiomyolipoma. OBJECTIVE: The aim was to present a case report and review of the literature about adrenal angiomyolipoma. DESIGN: The case report includes a history of patient data and literature review. SETTING: The patient was offered adrenalectomy with adrenal gland neoplasms and gave consent. The tumor was completely removed. PATIENT: We present the case of a 55-yr-old patient with a 15 × 16-cm adrenal angiomyolipoma. INTERVENTION: We performed adrenalectomy with adrenal gland neoplasms. RESULTS: The histopathological features confirmed the diagnosis of adrenal angiomyolipoma. The patient made an uneventful recovery and was normal at the 6-month follow-up. CONCLUSIONS: Angiomyolipomas are rare mesenchymal tumors derived from perivascular epithelioid cells. These are commonly found in the kidney. Angiomyolipoma arising in the adrenal is a very rare entity. We present a case of adrenal angiomyolipoma. In our case, the tumor size was (15 × 16 cm), the largest being reported.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Angiomiolipoma/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Adrenalectomia , Angiomiolipoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
18.
J Surg Res ; 178(1): 460-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22507688

RESUMO

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a complex pathophysiologic process involving cell apoptosis and oxidant damages that leads to acute renal failure in both native kidneys and renal allografts. Pioglitazone is a novel class of oral antidiabetic agents currently used to treat type 2 diabetes mellitus. Pioglitazone exerts protective effects on acute myocardial ischemia and acute cerebral ischemia. The aim of this study was to investigate the possible beneficial effects of pioglitazone on renal IRI in mice. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Fifty-five healthy male Balb/c mice were randomly assigned to one of the following groups: PBS + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests, histopathologic examination, renal cell Bcl-2, and Bax expression were determined 24 h after reperfusion. Animals' survival was examined 7 days after operation. RESULTS: Animals pretreated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine caused by IRI, lower histopathologic scores, and improved survival rates following IRI. Renal cell apoptosis induced by IRI was abrogated in kidneys of mice pretreated by pioglitazone, with an increase in Bcl-2 expression and a decrease in Bax expression. Furthermore, pioglitazone pretreatment protected against lethal renal IRI. CONCLUSIONS: Peroxisome proliferator-activated receptor activation by pioglitazone exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis. Thus, pioglitazone could be a novel therapeutic tool in renal IRI.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Tiazolidinedionas/farmacologia , Lesão Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pioglitazona , Distribuição Aleatória , Traumatismo por Reperfusão/patologia
19.
Chin Med J (Engl) ; 124(11): 1616-22, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21740765

RESUMO

BACKGROUND: Intensive blood glucose control is proven to be associated with the diabetic microvascular and macrovascular complications, which could affect quality of life (QOL). This study was performed to determine the effects of intensive glucose control therapy on QOL of elderly patients with type 2 diabetes in Anhui Province. METHODS: Ninety-seven elderly patients with type 2 diabetes in Anhui were randomly assigned to standard treatment group and intensive therapy group. All patients were followed up for five years on average. Correlated information has been collected during the regular follow-up. RESULTS: Patients with microvascular complications reported significantly lower European Quality of Life-5 Dimensions (EQ-5D) scores and had more problems with usual activities, pain and anxiety than those without complications (P < 0.05). Patients having experienced hypoglycemic episodes had significantly more problems with anxiety than those without hypoglycemic episodes (P < 0.05). No significant difference was detected in all dimensions in quality of life, as well as in Visual Analog Scale score between two groups (P > 0.05). There was no significant difference in quality of life at the fifth year compared with that of the first year in both groups. Women had more feelings of pain and anxiety than men (P < 0.05) and longer disease course was associated with increased levels of pain and anxiety (P < 0.05), as well as with lower QOL. In addition, patients with higher body mass index (BMI) had more problems with daily activities than patients with lower BMI (P < 0.05). CONCLUSIONS: Anxiety is common in elderly diabetic patients and they experienced frequent hypoglycemic episodes. Diabetic vascular complications significantly affect QOL of the patients. Intensive glucose control has no significant effect on QOL of the diabetic patients. Female, older age, long disease course, less education and high BMI are all factors caused reduced QOL and patients with these factors should be given more psychological support. Frequent mild hypoglycemic episodes do not cause impaired function of the central nervous system.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Qualidade de Vida , Idoso , Glicemia/metabolismo , Jejum/sangue , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Pathol ; 225(2): 265-75, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21630270

RESUMO

Renal ischaemia-reperfusion injury (IRI) is consecutive to tissue oxidative damage and cell apoptosis that lead to acute renal failure (ARF) in renal allografts. The aim of this study was to investigate the beneficial effects of a pretreatment by clopidogrel on renal IRI in mice. IRI was induced by bilateral renal ischaemia for 45 min followed by reperfusion. Sixty-two healthy male BALB/c mice were randomly assigned to one of the following groups: PBS + ischaemia-reperfusion (IR); clopidogrel + IR; PBS + sham IR; clopidogrel + sham IR. Clopidogrel (25 mg/kg) or PBS was administered per os to the animals via a gastric cannula 24 h before operation. All mice were given a single dose of clopidogrel or PBS. Renal function histological damage, renal cell apoptosis, renal antioxidant activities, and CD41 expression were determined 24 h after reperfusion. The survival rates were evaluated over 7 days. Animals pretreated with clopidogrel had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores, and improved survival rates following IR. Renal cell apoptosis induced by IR was decreased in kidneys of mice pretreated by clopidogrel, with an increase in Bcl-2 and Bcl-xL expression and a decrease in caspase-3, caspase-8, and Bax expression. Renal reduced glutathione, superoxide dismutase, and catalase activities were unmodified by the pretreatment with clopidogrel. However, clopidogrel resulted in an increased total antioxidant capacity of the kidney. Furthermore, pretreatment by clopidogrel decreased the number of CD41-positive cells. Thus, clopidogrel exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis as a consequence of improved renal antioxidant capacity and could be tried as a novel therapeutic tool in renal IRI.


Assuntos
Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Ticlopidina/análogos & derivados , Animais , Clopidogrel , Modelos Animais de Doenças , Imunofluorescência , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ticlopidina/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA