RESUMO
BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
Assuntos
Acetofenonas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Sequestradores de Radicais Livres/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Estreptozocina , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catalase/sangue , Colágeno , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Glutationa Peroxidase/sangue , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Masculino , NADPH Oxidases/metabolismo , Ratos Wistar , Superóxido Dismutase/sangueRESUMO
PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM). METHODS: Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney. RESULTS: Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
Assuntos
Acetofenonas/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Catalase/metabolismo , Colágeno Tipo III/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Glutationa Peroxidase/metabolismo , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Ratos Endogâmicos SHR , Estreptozocina , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
This study investigated the response of human alveolar bone-derived cells to a novel poly(vinylidene fluoride-trifluoroethylene)/barium titanate (P(VDF-TrFE)/BT) membrane. Osteoblastic cells were cultured in osteogenic conditions either on P(VDF-TrFE)/BT or polytetrafluoroethylene (PTFE) for up to 14 days. At 7 and 14 days, the mRNA expression of Runt-related transcription factor 2 (RUNX2), Type I collagen (COL I), Osteopontin (OPN), Alkaline phosphatase (ALP), Bone sialoprotein (BSP), and Osteocalcin (OC), key markers of the osteoblastic phenotype, and of Bcl2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2), and Survivin (SUR), associated with the control of the apoptotic cell death, was assayed by real-time PCR. In situ ALP activity was qualitatively evaluated by means of Fast red staining. Surface characterization was also qualitatively and quantitatively assayed in terms of topography, roughness, and wettability. Cells grown on P(VDF-TrFE)/BT exhibited a significantly higher mRNA expression for all markers compared to the ones on PTFE, except for Bcl-2, which was not detected for both groups. Additionally, Fast red staining was noticeably stronger in cultures on P(VDF-TrFE)/BT at 7 and 14 days. At micron- and submicron scale, SEM images and roughness analysis revealed that PTFE and P(VDF-TrFE)/BT exhibited a smooth topography and a similar roughness, respectively. PTFE membrane displayed higher contact angles compared with P(VDF-TrFE)/BT, as indicated by wettability assay. The novel P(VDF-TrFE)/BT membrane supports the acquisition of the osteoblastic phenotype in vitro, while up-regulating the expression of apoptotic markers. Further in vivo experiments should be carried out to confirm the capacity of P(VDF-TrFE)/BT membrane in promoting bone formation in guided bone regeneration.
Assuntos
Compostos de Bário/química , Osso e Ossos/efeitos dos fármacos , Membranas Artificiais , Polivinil/química , Titânio/química , Alvéolo Dental/citologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Compostos de Bário/farmacologia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Regeneração Óssea/fisiologia , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/efeitos dos fármacos , Regeneração Tecidual Guiada , Humanos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Polivinil/farmacologia , Titânio/farmacologiaRESUMO
The aim of this paper is to compare the fluoride-releasing and mechanical properties of an experimental luting glass ionomer cement, which has a modified composition and a commercial luting cement. The experimental powder was obtained by sol-gel process and then, it was used to prepare the experimental cements. The properties of cement pastes, such as setting time and working time, microhardness and diametral tensile strength were determined. Fluoride release from GICs was evaluated at time intervals of 1, 7, 14, 21 and 28 days in deionized water. Atomic force microscopy (AFM) analyses showed that the surface of the experimental cements is more homogeneous than commercial GICs. The mechanical properties and the measure of liberation of fluoride of the two cements were influenced by ratio powder:liquid and chemical composition of the precursor powders. Experimental cements released less fluoride than commercial cements. However, this liberation was more constant during the analyzed period. Thus, the results obtained in this study indicated that the composition of the experimental powder modified by the niobium can lead the formation of the polysalt matrix with good mechanical properties. In other words, we can say that experimental powder offered considerable promise for exploitation in dental field.
Assuntos
Cimentos Dentários/química , Cimentos de Ionômeros de Vidro/química , Força Compressiva , Odontologia/métodos , Desenho de Equipamento , Dureza , Teste de Materiais , Microscopia de Força Atômica/métodos , Nióbio/química , Pós , Estresse Mecânico , Temperatura , Resistência à Tração , Fatores de Tempo , Difração de Raios XRESUMO
UNLABELLED: We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. CONCLUSION: Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.
Assuntos
Diabetes Mellitus Experimental/terapia , Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Remodelação Ventricular/fisiologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Terapia por Exercício , Coração/fisiopatologia , Masculino , Ratos , Ratos WistarRESUMO
The aim of this work was to evaluate the biocompatibility of poly(vinylidene fluoride-trifluoroethylene)/barium titanate (P(VDF-TrFE)/BT) membrane to be used in guided tissue regeneration (GTR). Fibroblasts from human periodontal ligament (hPDLF) and keratinocytes (SCC9) were plated on P(VDF-TrFE)/BT and polytetrafluorethylene membranes at a cell density of 20,000 cells well(-1) and cultured for up to 21 days. Cell morphology, adhesion and proliferation were evaluated in hPDLF and keratinocytes, while total protein content and alkaline phosphatase (ALP) activity were assayed only for hPDLF. Using a higher cell density, real-time polymerase chain reaction (PCR) was performed to assess the expression of typical genes of hPDLF, such as periostin, PDLs17, S100A4 and fibromodulin, and key phenotypic markers of keratinocytes, including involucrin, keratins 1, 10 and 14. Expression of the apoptotic genes bax, bcl-2 and survivin was evaluated for both cultures. hPDLF adhered and spread more on P(VDF-TrFE)/BT, whereas keratinocytes showed a round shape on both membranes. hPDLF adhesion was greater on P(VDF-TrFE)/BT at 2 and 4h, while keratinocyte adhesion was similar for both membranes. Whereas proliferation was significantly higher for hPDLF on P(VDF-TrFE)/BT at days 1 and 7, no signs of keratinocyte proliferation could be noticed for both membranes. Total protein content was greater on P(VDF-TrFE)/BT at 7, 14 and 21 days, and higher levels of ALP activity were observed on P(VDF-TrFE)/BT at 21 days. Real-time PCR revealed higher expression of phenotypic markers of hPDLF and keratinocytes as well as greater expression of apoptotic genes in cultures grown on P(VDF-TrFE)/BT. These results indicate that, by favoring hPDLF adhesion, spreading, proliferation and typical mRNA expression, P(VDF-TrFE)/BT membrane should be considered an advantageous alternative for GTR.
Assuntos
Compostos de Bário/química , Materiais Biocompatíveis/química , Fibroblastos/fisiologia , Regeneração Tecidual Guiada Periodontal/métodos , Hidrocarbonetos Fluorados/química , Queratinócitos/fisiologia , Ligamento Periodontal/fisiologia , Polivinil/química , Titânio/química , Células Cultivadas , Fibroblastos/citologia , Humanos , Queratinócitos/citologia , Teste de Materiais , Ligamento Periodontal/citologiaRESUMO
INTRODUCTION: Over recent years it has become possible to retrain motor activity among patients with partial spinal cord injury, especially for walking. AIM. To assess the impact of gait training on a treadmill with body weight support, regarding temporospatial parameters and quality of life. PATIENTS AND METHODS: Twelve patients of both sexes were evaluated. They had been diagnosed with partial spinal cord injury of traumatic origin at least 12 months earlier. They were able to walk and their motor function below the level of the injury was partially preserved and classified as level C or D. After the initial evaluation, the participants were trained on a treadmill with body weight support, with two sessions per week lasting 30 minutes each, over a four-month period, thus totaling 30 sessions. The patients' temporospatial gait parameters and quality of life were analyzed before and after the training. RESULTS: There were improvements in all the temporospatial parameters evaluated (p < 0.0001), but no changes in quality of life were seen (p > 0.05). CONCLUSION: Treadmill training with body weight support among patients with spinal cord injury was effective in improving the temporospatial gait parameters, but without changing their quality of life.