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1.
Actual. osteol ; 16(2): [95]-[103], mayo.-ago. 2020. ilus, graf, tab
Article in English | LILACS | ID: biblio-1129692

ABSTRACT

Introduction. Diabetes is a chronic disease associated with important comorbidities. Type 2 diabetes (T2DM) is associated with a three times increased risk of hip fracture but reports describing potential associations with vertebral fractures (VF) are contradictory. Our objective was to evaluate the factors involved in the prevalent VF in women with and without T2DM. Materials and methods. A cross-sectional design was used and the relationship between morphometric VF and T2DM in adult women was evaluated. The cases were adult women with morphometric VF and the controls were adult women without VF. Thoracic and spinal radiographs in lateral and antero-posterior projections were obtained. Bone mineral density (BMD) values of the lumbar spine (L-BMD) were measured by DXA. Results. A greater number of women with T2DM were found in the VF group (61% vs 31.5%). Non-T2DM women with VF were significantly older and with lower L-BMD than non-T2DM without VF. We observed a negative correlation between age and L-BMD (r=-0.463) in non-T2DM women, but not in the T2DM with FV group. T2DM was a risk factor for prevalent VF with OR of 3.540 (IC95% 1.750-7.160). Conclusion. Our study showed a higher prevalence of T2DM in the VF group. T2DM women with VF were younger and had higher L-BMD than non-T2DM women, L-BMD did not correlate with age and VF were not distributed according to BMD-L and age. (AU)


Introducción. La diabetes es una enfermedad crónica asociada con comorbilidades importantes. La diabetes tipo 2 (DM2) se asocia con un riesgo tres veces mayor de fractura de cadera pero la asociación con fracturas vertebrales (FV) es contradictoria. Nuestro objetivo fue evaluar los factores involucrados en las FV prevalentes en mujeres adultas con y sin DM2. Materiales y métodos. Se realizó un diseño transversal y se evaluó la relación entre FV morfométrica y DM2 en mujeres adultas. Los casos fueron mujeres adultas con FV morfométricas y los controles fueron mujeres adultas sin FV. Se obtuvieron radiografías torácicas y espinales en proyecciones lateral y anteroposterior. Los valores de densidad mineral ósea (DMO) de la columna lumbar (DMO-L) se midieron por DXA. Resultados. Se observó un mayor número de mujeres con DM2 en el grupo de FV (61% frente a 31.5%). Las mujeres sin DM2 con FV eran significativamente mayores y con una DMO-L más baja que las mujeres sin DM2 sin FV. Observamos una correlación negativa entre la edad y la DMO-L (r= -0.463) en mujeres sin DM2 y FV, pero no en DM2 con FV. La DM2 fue un factor de riesgo para FV prevalente con un OR 3.540 (IC95% 1.750-7.160). Conclusión. Nuestro estudio demostró una mayor prevalencia de DM2 en el grupo de FV. Las mujeres con DM2 y FV eran más jóvenes y tenían mayor DMO-L que las mujeres sin DM2, la DMO-L no correlacionó con la edad y las FV no se distribuyeron de acuerdo a la DMO-L y edad. (AU)


Subject(s)
Humans , Female , Adult , Young Adult , Spinal Fractures/microbiology , Diabetes Mellitus, Type 2/complications , Osteoporosis/complications , Vitamin D/blood , Absorptiometry, Photon , Bone Density , Cross-Sectional Studies , Risk Factors , Spinal Fractures/chemically induced , Spinal Fractures/diagnostic imaging , Age Factors , Thiazolidinediones/therapeutic use , PPAR gamma/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Rosiglitazone/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Pioglitazone/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use
2.
Rev. costarric. cardiol ; 19(1/2): 13-17, ene.-dic. 2017. tab
Article in Spanish | LILACS | ID: biblio-900881

ABSTRACT

Resumen La Diabetes Mellitus tipo 2 (DM-2) es un equivalente de riesgo cardiovascular. Existe una gran variedad de fármacos para el control de la glicemia en los pacientes con DM-2, los cuales tienen diferencias en su perfil cardiovascular, unos han demostrado un beneficio en la reducción de riesgo de eventos cardiovasculares, otros tienen un efecto neutro, y en el caso de otros fármacos como las sulfonilureas y las tiazolinedionas existe dudas sobre su seguridad cardiovascular. Sien do DM-2 un equivalente de riesgo coronario, es fundamental tomar en cuenta el perfil de riesgo cardiovascular de estos medicamentos a la hora de iniciar alguna de estas drogas y no solo su eficacia para controlar los niveles de glicemia. El objetivo de esta revisión es comentar sobre los estudios más recientes que evalúan el riesgo cardiovascular con el uso de los distintos antidiabéticos orales.


Abstract Cardiovascular Safety of Oral Antidiabetics Diabetes Mellitus type 2 (DM-2) is an equivalent of cardiovascular risk. There is a wide variety of drugs for the glycemic control in patients with DM-2, which have differences in their cardiovascular profile, some have shown a benefit in reducing the risk of cardiovascular events, others have a neutral effect, and in the case of other drugs such as sulfonylurea and thiazolidinedione, there are doubts about their cardiovascular safety. Being DM-2 an equivalent of coronary risk, it is essential to consider the cardiovascular risk profile of these medicines when starting any of these drugs and not only their effectiveness in controlling glycaemia levels. The objective of this review is to comment on the most recent studies evaluating cardiovascular risk with the use of different oral antidiabetics.


Subject(s)
Humans , Blood Glucose , Glyburide/therapeutic use , Thiazolidinediones/therapeutic use , Diabetes Complications , Diabetes Mellitus, Type 2/drug therapy , Rosiglitazone/therapeutic use , Pioglitazone/therapeutic use , Glipizide/therapeutic use , Hypoglycemic Agents , Metformin/therapeutic use
5.
Arq. bras. endocrinol. metab ; 58(6): 630-639, 08/2014. tab, graf
Article in English | LILACS | ID: lil-721394

ABSTRACT

Objective: We sought to test the effect of different dosages of pioglitazone (PIO) on the glomerular expression of podocalyxin and urinary sediment podocalyxin excretion and to explore the potential renoprotective mechanism. Materials and methods: Type 1 diabetes induced with streptozotocin (65 mg/kg) in 36 male Sprague-Dawley rats were randomly allocated to be treated with vehicle or 10, 20, 30 mg/kg/d PIO respectively for 8 weeks. Eight rats were enrolled in the normal control group. Results: At 8th week, rats were sacrificed for the observation of kidney injury through electron microscope. Glomerular podocalyxin production including mRNA and protein were determined by RT-PCR and immunohistochemistry respectively. Levels of urinary albumin excretion and urinary sediment podocalyxin, kidney injury index were all significantly increased, whereas expression of glomerular podocalyxin protein and mRNA were decreased significantly in diabetic rats compared to normal control. Dosages-dependent analysis revealed that protective effect of PIO ameliorated the physiopathological changes and reached a peak at dosage of 20 mg/kg/d. Conclusion: PIO could alleviate diabetic kidney injury in a dose-dependent pattern and the role may be associated with restraining urinary sediment podocalyxin excretion and preserving the glomerular podocalyxin expression. .


Objetivo: Buscamos testar os efeitos de diferentes doses de pioglitazona (PIO) sobre a expressão glomerular de podocalixina e sobre a excreção de podocalixina em células do sedimento urinário, além de explorar o potencial mecanismo de proteção renal. Materiais e métodos: O diabetes tipo 1 foi induzido em 36 ratos Sprague-Dawley machos com estreptozotocina (65 mg/kg). Os animais foram tratados apenas com o veículo, ou com 10, 20, 30 mg/kg/d de PIO por 8 semanas. Oito ratos foram colocados no grupo controle. Resultados: Na oitava semana, os ratos foram sacrificados para se observar a lesão renal em microscopia eletrônica. A produção de podocalixina glomerular, incluindo mRNA e proteína, foi determinada por RT-PCR e imuno-histoquímica, respectivamente. Os níveis urinários de albumina e podocalixina nas células do sedimento urinário e o índice de lesão renal estavam todos significativamente aumentados, enquanto a expressão glomerular da proteína podocalixina e do mRNA estava significativamente diminuída em ratos diabéticos comparados com o controle normal. A análise dos efeitos dose-dependentes revelou que o efeito protetor da PIO melhorou as mudanças fisiopatológicas e atingiu um pico na dose de 20 mg/kg/dia. Conclusão: A PIO pode melhorar a injúria renal de forma dose-dependente e este papel pode estar associado com a prevenção da excreção de podocalixina nas células do sedimento urinário e com a preservação da expressão glomerular de podocalixina. .


Subject(s)
Animals , Male , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Podocytes/pathology , Sialoglycoproteins/metabolism , Thiazolidinediones/therapeutic use , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Diabetes Mellitus, Experimental/pathology , Immunohistochemistry , Kidney Glomerulus/drug effects , Kidney Glomerulus/injuries , Kidney Glomerulus/ultrastructure , Microscopy, Electron , Random Allocation , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , RNA, Messenger/isolation & purification , Sialoglycoproteins/genetics , Sialoglycoproteins/urine , Triglycerides/blood
6.
J. bras. med ; 102(3)jul. 2014.
Article in Portuguese | LILACS | ID: lil-719968

ABSTRACT

O diabetes mellitus tipo 2 (DM2) apresenta alta prevalência, com aumento inclusive em crianças e adolescentes. A importância de um estrito controle glicêmico pode ser comprovada com a redução das complicações crônicas microvasculares. Já em relação à redução da doença macrovascular, principal causa de mortalidade nestes pacientes, são fundamentais o controle da glicemia, bem como de outros fatores de risco cardiovasculares, tais como hipertensão arterial, dislipidemia, peso, e a manutenção de hábitos saudáveis de vida. Temos vários medicamentos para o tratamento do DM2, sendo que a metformina é ainda a droga de primeira escolha, devido ao seu baixo custo e eficácia comprovada...


Type 2 diabetes mellitus (DM2) is highly prevalent and is increasing even in children and adolescents. The importance of strict glycemic control can be proven to reduce chronic microvascular complications. Regarding the reduction of macrovascular disease, the leading cause of mortality in these patients, it is essential tight glycemic control, as well as other cardiovascular risk factors, such as arterial hypertension, dyslipidemia, weight control, and maintaining healthy lifestyles. We have a lot of drugs for the treatment of DM2, and metformin is still the drug of first choice due to its low cost and proven effectiveness...


Subject(s)
Humans , Male , Female , /drug therapy , Metformin/therapeutic use , Administration, Oral , alpha-Glucosidases , Sulfonylurea Compounds/therapeutic use , Glycemic Index , Hypoglycemic Agents/administration & dosage , Incretins/therapeutic use , Glucagon-Like Peptide 1/agonists , Thiazolidinediones/therapeutic use
7.
Article in English | WPRIM | ID: wpr-35684

ABSTRACT

It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had > or = 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.


Subject(s)
Aged , Asian Continental Ancestry Group , Case-Control Studies , Cohort Studies , Diabetes Mellitus, Type 2/complications , Female , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Prevalence , Republic of Korea , Retrospective Studies , Risk Factors , Tertiary Care Centers , Thiazolidinediones/therapeutic use , Urinary Bladder Neoplasms/complications
8.
Article in English | WPRIM | ID: wpr-109967

ABSTRACT

OBJECTIVE: The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. MATERIALS AND METHODS: We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. RESULTS: One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 +/- 1.4 at 3 weeks to 0.9 +/- 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n = 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. CONCLUSION: A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.


Subject(s)
Animals , Bleomycin , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Observer Variation , Pulmonary Fibrosis/chemically induced , Thiazolidinediones/therapeutic use , X-Ray Microtomography
9.
Yonsei Medical Journal ; : 99-106, 2014.
Article in English | WPRIM | ID: wpr-86935

ABSTRACT

PURPOSE: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-gamma agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. RESULTS: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. CONCLUSION: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.


Subject(s)
Animals , Bronchopulmonary Dysplasia/drug therapy , Female , Hypertension, Pulmonary/drug therapy , Immunohistochemistry , Lung/drug effects , PPAR gamma/agonists , Rats , Rats, Sprague-Dawley , Thiazolidinediones/therapeutic use , Vasodilator Agents/therapeutic use
10.
Braz. j. med. biol. res ; 46(6): 528-532, 02/jul. 2013. tab
Article in English | LILACS | ID: lil-679209

ABSTRACT

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Aryldialkylphosphatase/blood , /drug therapy , Hypoglycemic Agents/therapeutic use , Metabolome/drug effects , Thiazolidinediones/therapeutic use , Biomarkers , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Drug Therapy, Combination , /metabolism , Homocysteine/blood , Insulin/therapeutic use , Malondialdehyde/blood , Metformin/therapeutic use , Sulfonylurea Compounds/therapeutic use , Triglycerides/blood
11.
Yonsei Medical Journal ; : 1127-1136, 2013.
Article in English | WPRIM | ID: wpr-198364

ABSTRACT

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.


Subject(s)
Adiponectin/metabolism , Adiposity/drug effects , Animals , Cell Proliferation/drug effects , Diabetes Mellitus, Type 2/diet therapy , Eating/drug effects , Glucose Intolerance/diet therapy , Insulin Resistance , Insulin-Secreting Cells/drug effects , Male , Piperidines/adverse effects , Pyrazoles/adverse effects , Rats , Rats, Inbred OLETF , Receptor, Cannabinoid, CB1/physiology , Thiazolidinediones/therapeutic use
13.
J. bras. med ; 99(2): 32-38, jun.-set. 2011. tab
Article in Portuguese | LILACS | ID: lil-616480

ABSTRACT

O diabetes mellitus tipo 2 (DM2) está alcançando proporções epidêmicas, e embora as mudanças no estilo de vida possam manter o controle glicêmico, o curso da doença, em longo prazo, requer algum tipo de intervenção farmacológica. É bem conhecido que os indivíduos que se mantêm mal controlados apresentam mais complicações macro e microvasculares e a redução da hemoglobina glicada (HbA1c) diminui significativamente o risco de desenvolvimento de complicações microvasculares em pacientes com DM2. Atualmente há seis classes de antidiabéticos orais: sulfonilureias, meglitinidas, biguanidas, tiazolidinedionas (TZDs), inibidores da alfa-glicosidase e os incretinomiméticos. As sulfonilureias e as meglitinidas estimulam a secreção de insulina; a metformina age principalmente suprimindo a produção hepática de glicose; as tiazolidinedionas melhoram a resistência periférica à insulina e os inibidores da alfa-glicosidase retardam a degredação e a digestão dos carboidratos complexos no intestino. Uma nova opção terapêutica para o DM2 são as drogas incretinomiméticas. Dentre elas temos os análogos de GLP-1 (exenatida e liraglutida) e os inibidores da DPP-IV. Ambos estimulam a secreção de insulina, suprimem a secreção de glucagon e desaceleram o esvaziamento gástrico; a redução de peso é característica dos análogos. O bom controle glicêmico em longo prazo e a prevenção do DM2 requerem uma abordagem agressiva e abrangente. No entanto, uma vez instalada a doença, além das modificações do estilo de vida, o tratamento farmacológico deve ser iniciado e cuidadosamente monitorado, com o uso de drogas que agem nos diversos mecanismos fisiopatológicos conhecidos. Novos estudos serão sempre necessários para se obter mais informações a respeito do diabetes e, assim, aprimorar o desenvolvimento de novas drogas.


The type 2 diabetes has reached epidemic proportions in the worldwide and lifestyle modification provide insufficient glucose control over the long-term course of the disease, the vast majority of patients require some type of pharmacological intervention. Several studies have shown that individuals who remain poorly controlled have more macro and microvascular complications and the decrease in glycated hemoglobin (HbA1c) significantly reduces the risk of developing microvascular complications in type 2 diabetes. At the moment, there are six classes of oral antidiabetics drugs: sulfonylureas, meglitinides, biguanides (metformin), thiazolidinediones (pioglitazone), alpha-glucosidase inhibitors (acarbose) and incretin-mimetics drugs. The sulfonylureas and meglitinide acting insulin secretion; metformin acts primarily by suppressing hepatic glucose production; thiazolidinediones improve insulin resistance; and alpha-glucosidade inhibitors retard the degradation and digestion of complex carbohydrates in the intestine and incretin-mimetics drugs that stimulate insulin secretion, suppress glucagon secretion, slows gastric emptying and weight loss (it is characteristic of the GLP-1 analogues). The good longterm glycemic control and prevention of type 2 diabetes requires an aggressive and comprehensive approach. However, once installed the disease, in addition to lifestyle modifications, pharmacotherapy should be initiated and carefully monitored using drugs that act on different pathophysiologicals mechanisms. New studies are always necessary to obtain more information about diabetes and thus improve the development of new drugs.


Subject(s)
Humans , Male , Female , Biguanides/therapeutic use , Sulfonylurea Compounds/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors , /prevention & control , /drug therapy , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Life Style , Thiazolidinediones/therapeutic use , alpha-Glucosidases/antagonists & inhibitors , Blood Glucose/analysis , Blood Glucose
14.
Braz. j. med. biol. res ; 44(7): 652-659, July 2011. ilus, tab
Article in English | LILACS | ID: lil-595696

ABSTRACT

Silybin, a natural antioxidant, has been traditionally used against a variety of liver ailments. To investigate its effect and the underlying mechanisms of action on non-alcoholic fatty liver in rats, we used 60 4-6-week-old male Sprague-Dawley rats to establish fatty liver models by feeding a high-fat diet for 6 weeks. Hepatic enzyme, serum lipid levels, oxidative production, mitochondrial membrane fluidity, homeostasis model assessment-insulin resistance index (HOMA-IR), gene and protein expression of adiponectin, and resistin were evaluated by biochemical, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Compared with the model group, silybin treatment (26.25 mg·kg-1·day-1, started at the beginning of the protocol) significantly protected against high-fat-induced fatty liver by stabilizing mitochondrial membrane fluidity, reducing serum content of alanine aminotransferase (ALT) from 450 to 304 U/L, decreasing hepatic malondialdehyde (MDA) from 1.24 to 0.93 nmol/mg protein, but increasing superoxide dismutase (SOD) and glutathione (GSH) levels from 8.03 to 9.31 U/mg protein and from 3.65 to 4.52 nmol/mg protein, respectively. Moreover, silybin enhanced the gene and protein expression of adiponectin from 215.95 to 552.40, but inhibited that of resistin from 0.118 to 0.018. Compared to rosiglitazone (0.5 mg·kg-1·day-1, started at the beginning of the protocol), silybin was effective in stabilizing mitochondrial membrane fluidity, reducing SOD as well as ALT, and regulating gene and protein expression of adiponectin (P < 0.05). These results suggest that mitochondrial membrane stabilization, oxidative stress inhibition, as well as improved insulin resistance, may be the essential mechanisms for the hepatoprotective effect of silybin on non-alcoholic fatty liver disease in rats. Silybin was more effective than rosiglitazone in terms of maintaining mitochondrial membrane fluidity and reducing oxidative stress.


Subject(s)
Animals , Male , Rats , Antioxidants/therapeutic use , Fatty Liver/drug therapy , Hypoglycemic Agents/therapeutic use , Oxidative Stress/drug effects , Silymarin/therapeutic use , Thiazolidinediones/therapeutic use , Antioxidants/administration & dosage , Dietary Fats , Disease Models, Animal , Drug Evaluation, Preclinical , Fatty Liver/chemically induced , Fatty Liver/prevention & control , Homeostasis , Hypoglycemic Agents/administration & dosage , Insulin Resistance/physiology , Lipid Peroxidation/drug effects , Lipids/blood , Liver/drug effects , Random Allocation , Rats, Sprague-Dawley , Silymarin/administration & dosage , Thiazolidinediones/administration & dosage
15.
Article in English | WPRIM | ID: wpr-210394

ABSTRACT

A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-alpha , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.


Subject(s)
Animals , Atherosclerosis/drug therapy , Cell Adhesion/drug effects , Cell Line , Cell Movement/drug effects , Chemokine CCL2/metabolism , Dinoprostone/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Leukotriene B4/metabolism , Macrophages/cytology , Male , Mice , Monocytes/cytology , Random Allocation , Receptors, LDL/deficiency , Thiazolidinediones/therapeutic use , Tumor Necrosis Factor-alpha/pharmacology
16.
J. bras. med ; 98(5): 23-30, out.-dez. 2010. ilus
Article in Portuguese | LILACS | ID: lil-575355

ABSTRACT

A Federação Internacional de Diabetes (/DF) publicou novos dados indicando a enormidade da epidemia mundial da doença. Esses dados demonstram que o diabetes afeta atualmente 246 milhões de pessoas em todo o mundo, sendo que 46% destes com idades entre 40 e 59 anos. Dados atuais predizem que, se nada for feito, o número total de portadores de diabetes ultrapassará 380 milhões de pessoas em 20 anos. O estilo de vida moderno trouxe inúmeras mudanças de hábito e comportamento, como menor tempo dedicado à prática de atividades físicas regulares, um cotidiano mais estressante, além da maior oferta de alimentos industrializados, ricos em carboidratos simples e gorduras, pobres em fibras, minerais e vitaminas. Atualmente dedica-se mais tempo a atividades em frente às telas de computadores e a jogos de videogame e programas de televisão. Como consequência, tem-se observado maior incidência de doenças metabólicas, tais como obesidade, diabetes mellitus tipo 2 (DM 2), hipertensão arterial sistêmica (HAS), dislipidemia e, portanto, doenças cardiovasculares (DCVs), gerando a necessidade crescente de pesquisas em busca de novas opções terapêuticas para estas doenças. O presente trabalho visa fazer uma breve revisão sobre os avanços terapêuticos do diabetes mellitus tipo 2.


The International Diabetes Federation (/DF) has published new data indicating the enormity of the diabetes epidemic in the globe. That data show that the disease now affects a staggering 246 million people worldwide, with 46% of a11 those affected in the 40-59 age group. The new data predict that the total number of people living with diabetes will skyrocket to 380 million within twenty years if nothing is done. The modern life style has brought many changes such as more variety of food rich in sugar, fat and poor in fiber, vitamins and minerals, less time to practice a regular physical activity and a more stressful lifestyle. Nowadays, people spend more time in front of their computers, playing video games and watching programs of TV. As a consequence, many metabolic diseases have been increasing such as obesity, type I1 diabetes mellitus, high blood pressure, hyperlipidemia and cardiovascular diseases, leading the growing necessity of researches for new therapeutic options to these diseases. This article is a short review of type II diabetes mellitus's new treatment.


Subject(s)
Humans , Male , Female , /complications , /epidemiology , /etiology , /physiopathology , /therapy , Biguanides/therapeutic use , Diabetes Complications/classification , Sulfonylurea Compounds/therapeutic use , Incretins/therapeutic use , Insulin/therapeutic use , Diabetic Nephropathies/physiopathology , Diabetic Neuropathies/physiopathology , Obesity/complications , Diabetic Retinopathy/physiopathology , Thiazolidinediones/therapeutic use
17.
Article in Korean | WPRIM | ID: wpr-121792

ABSTRACT

Thiazolidinediones (TZD), which are widely used as insulin sensitizers, and fibrates, which are lipid-lowering drugs, are used in the treatment of dyslipidemia that commonly accompanies diabetes. Several reports suggest elevated levels of high-density lipoprotein (HDL) cholesterol, but the paradoxical reduction of HDL cholesterol level during single or combined TZD and fibrate therapies has been occasionally reported. Herein, we report a case of paradoxical decrease in HDL cholesterol and apolipoprotein A-1 levels during rosiglitazone and fenofibrate treatment for the first time in Korea. The patient was a 56-yr-old man presenting with type 2 diabetes mellitus and dyslipidemia. His HDL cholesterol and apolipoprotein A-1 levels returned to normal after the cessation of fenofibrate therapy. Since diabetes is an established risk factor of cardiovascular diseases, low HDL cholesterol can be a key cause of concern for patients with diabetes. Therefore, HDL cholesterol level should be determined before and after starting TZD and/or fibrate therapy in diabetic patients.


Subject(s)
Apolipoprotein A-I/metabolism , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/complications , Dyslipidemias/complications , Fenofibrate/therapeutic use , Humans , Hypolipidemic Agents/therapeutic use , Male , Middle Aged , Thiazolidinediones/therapeutic use
18.
Femina ; 37(5): 255-260, maio 2009.
Article in Portuguese | LILACS | ID: lil-539342

ABSTRACT

A síndrome dos ovários policísticos (SOP) é uma das mais comuns endocrinopatias que acometem mulheres em idade reprodutiva, com prevalência de 4 a 12 % em diferentes populações. Mudança nos hábitos de vida são estratégias iniciais no tratamento de mulheres obesas com SOP, melhorando sensibilidade à insulina, hiperandrogenismo, fatores de riscos metabólicos, ciclos menstruais e ovulação, e reduzindo tanto o número de folículos ovarianos retidos como o volume ovariano, regulando a fertilidade e a capacidade reprodutiva. Uma dieta pobre em gorduras saturadas e rica em fibras, com alimentos de baixo índice glicêmico de carboidratos, é geralmente adequada para mulheres com SOP. Os agentes sensibilizadores da insulina também fazem parte do manejo dessas pacientes. Avaliação do uso de metformina e citrato de clomifeno mostrou que as taxas de ovulação foram efetivas tanto com o uso isolado da metformina quanto em associação ao citrato de clomifeno, porém, quanto ao número de gestações, foi obtido melhor resultado com a associação de ambos os medicamentos. As glitazonas também têm sido utilizadas nas desordens metabólicas na SOP. A administração de rosiglitazona 4 mg/dia ou de pioglitazona 30 mg/dia a mulheres obesas e não obesas com SOP levou a uma melhoria da resistência a insulina, diminuição da produção androgênica ovariana, restauração da ovulação espontânea.


Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases affecting women in reproductive age with prevalence estimated at 4 a 12 % in different populations. Lifestyle changes are the first strategy for the treatment of obese women with PCOS, improving insulin sensitivity, hyperandrogenaemia, metabolic risk factors, menstrual cycles and ovulation, reducing the number of un-ruptured follicles, the ovarian volume, regulating fertility and reproduction capacity. A low-liped diet, rich in fibers and with food of low carbohydrate rate is usually adequate for women with PCOS. Insulin-sensitizing agents also play a role on the management of these patients. Evaluation of the use of metformin and citrate of clomiphen demonstrated that ovulatin were effective not only with metformin alone, but also in association with citrate of clomiphene; however, concerning the number of pregnancies, better results were achieved in the association of both drugs. Glitazones have been also used in metabolic disorders of PCOS. The administration of rosigliatazone 4 mg/day or pioglitazone 30 mg/day in obese and non-obese women led to an improvement in insulin resistance, reduction of ovarian androgen production and recuperation of spontaneous ovulation.


Subject(s)
Female , Insulin Resistance , Metformin/therapeutic use , Overweight , Obesity/drug therapy , Obesity/therapy , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/therapy , Thiazolidinediones/therapeutic use , Exercise , Life Style
19.
Article in English | WPRIM | ID: wpr-150687

ABSTRACT

BACKGROUND/AIMS: Thiazolidinediones reduce urinary albumin excretion and may prevent the development of renal injury. We evaluated the long-term effects of rosiglitazone on the progression of renal dysfunction in patients with type 2 diabetes mellitus. METHODS: We enrolled patients with type 2 diabetes mellitus who initially had normal or mildly impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of 60-120 mL/min per 1.73 m2, and normoalbuminuria. Patients were divided into two groups according to their use of rosiglitazone during 3 years of follow-up: those treated with rosiglitazone (rosiglitazone group, n=52) and those treated without rosiglitazone (control group, n=85). Progression of renal dysfunction was defined as a decrease in eGFR of > or =9 mL/min per 1.73 m2 after 3 years. RESULTS: A greater difference was observed in the decrease in eGFR between the rosiglitazone and control groups after 3 years (3.8+/-9.9 vs. 12.6+/-10.5 mL/min per 1.73 m2, p<0.001). Seventeen of 52 (32.7%) patients in the rosiglitazone group and 53 of 85 (62.3%) patients in the control group showed progression of renal dysfunction (p=0.001). The progressors had a longer duration of diabetes (6.7+/-5.9 vs. 3.9+/-4.1 years, p=0.002), higher HbA1c levels (7.4+/-1.8 vs. 6.8+/-1.3%, p=0.023), and less frequent use of rosiglitazone (24.2 vs. 52.2%, p<0.001) compared to non-progressors. Multiple logistic regression analysis revealed that the use of rosiglitazone was a significant and independent predictor of the progression of renal dysfunction. CONCLUSIONS: This study suggests that rosiglitazone theatment slows the progressive deterioration of renal function in patients with type 2 diabetes.


Subject(s)
Adult , Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/prevention & control , Female , Glomerular Filtration Rate , Humans , Hypoglycemic Agents/therapeutic use , Kidney/physiopathology , Male , Middle Aged , Retrospective Studies , Thiazolidinediones/therapeutic use
20.
Femina ; 36(12): 731-735, dez. 2008.
Article in Portuguese | LILACS | ID: lil-511411

ABSTRACT

A síndrome dos ovários policísticos é a mais comum afecção endócrina na idade reprodutiva, acometendo 5 a 10 porcento das mulheres. Caracteriza-se por anovulação crônica, anormalidades menstruais e hiperandrogenismo laboratorial e ou clínico. O principal distúrbio na fisiopatologia ainda é desconhecido, mas há importantes evidências de que a resistência insulínica, hiperandrogenismo e alterações na liberação pulsátil das gonadotrofinas estejam envolvidos. Além das gonodatrofinas, fatores de crescimento e outros peptídeos participam da regulação do desenvolvimento folicular ovariano e da esteroidogênese e podem ter participação na SOP. Além disso, sabe-se que muitas mulheres com esta síndrome têm resistência insulínica, que pode ser corrigida pelos agentes sensibilizadores do receptor de insulina. Nesta revisão, analisou-se a ação da tiazolidinediona rosiglitazona em amenizar a sintomatologia na SOP, corrigindo a hiperinsulinemia. Sugere-se, então, que a rosiglitazona é alternativa para a correção da resistência insulínica em mulheres com a síndrome dos ovários policísticos.


The polycystic ovary syndrome is the most common endocrine-gynecological disorder of premenopausal women, affecting 5 - 10 percent of this population. It is characterized by chronic anovulation, menstrual disturbance and laboratorial and or clinic hyperandrogenism. The primary pathophysiological defect is unknown, but important characteristics include insulin resistance, androgen excess and abnormal gonadotropin dynamics. Growth factors, such as IGF-I, and other peptides have also been shown to play an important role in the regulation of ovarian follicular maturation and steroidogenesis. These factors might have important role in PCOS. Furthermore, some patients with PCOS may have insulin resistance and the insulin-sensitizing drugs may correct this condition. In this review, we analyzed the action of the thiazolidinedione rosiglitazone on decreasing SOP symptoms and regulating hyperinsulism. Our review suggests that rosiglitazone is an alternative to ameliorate insulin resistance in women with polycystic ovary syndrome.


Subject(s)
Female , Hyperinsulinism/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin Antagonists , Insulin Resistance , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/therapy , Thiazolidinediones/therapeutic use
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