Discriminative value of pulse wave velocity for arterial stiffness and cardiac injury in prediabetic patients.

Background: Prediabetes (PD) is defined as impaired fasting glucose and/or impaired glucose tolerance (IGT) and may be associated with high risk of cardiovascular injury. It is recommended that PD patients be screened for signs of arterial stiffness and cardiovascular injury to reinforce therapeutic strategies. Objectives: To identify pulse wave velocity values discriminative for arterial stiffness and cardiovascular injury in PD patients. Methods: A cross-sectional study was conducted with PD (N=43) and normoglycemic (N=37) patients who underwent clinical evaluation, arterial stiffness assessment by carotid-femoral pulse wave velocity (cfPWV) using SphygmoCor, laboratory blood analysis, investigation of morphological and functional cardiac variables by transthoracic echocardiogram, and assessment of carotid intima-media-thickness (CIMT) by carotid ultrasonography. A statistical analysis was performed using SPSS software and values of p<0.05 were considered significant. Results: A cfPWV cut-off value of 6.9 m/s was identified for IGT (Sensitivity [SE]: 74% and Specificity [SP]: 51%). Comparison of general data and risk factors between subsets with values above and below this cutoff value revealed higher rates of fasting glucose (p=0.02), obesity (p=0.03), dyslipidemia (p=0.004), early signs of left ventricle (p=0.017) and right ventricle (p=0.03) impaired diastolic function, and elevated CIMT in subjects with cfPWV ≥ 6.9m/s (p=0.04). Conclusions: In PD patients, a cfPWV cutoff of 6.9 m/s was considered a discriminative value for arterial stiffness. These findings highlight the value of early investigation of cardiovascular injury and aggressive therapy strategies with good control of risk factors in PD.

Contexto: O pré-diabetes (PD) é definido como glicemia de jejum alterada e/ou tolerância à glicose alterada (TGA) e pode estar associado a alto risco de lesão cardiovascular. Recomenda-se discriminar quais pacientes com PD podem apresentar sinais de rigidez arterial e lesão cardiovascular para reforçar as estratégias terapêuticas. Objetivos: Identificar os valores discriminativos da velocidade de onda de pulso determinantes de rigidez arterial e lesão cardiovascular em pacientes com PD. Métodos: Estudo transversal em pacientes com PD (N=43) e normoglicêmicos (N=37) submetidos a avaliação clínica, avaliação da rigidez arterial pela velocidade da onda de pulso carótido-femoral (cfPWV) utilizando SphygmoCor, análise laboratorial de sangue, investigação de alterações morfológicas e variáveis cardíacas funcionais por ecocardiograma transtorácico e avaliação da espessura íntima-média carotídea (EIMC) pela ultrassonografia da carótida. A análise estatística foi realizada no software SPSS, e valores de p<0,05 foram considerados significativos. Resultados: Foi identificado um valor de corte cfPWV de 6,9 m/s para TGA (sensibilidade 74% e especificidade 51%). A comparação dos dados e fatores de risco entre valores acima e abaixo do valor de corte estabelecido revelou glicemia de jejum elevada (p=0,02), obesidade (p=0,03), dislipidemia (p=0,004), sinais precoces de função diastólica prejudicada do ventrículo esquerdo (p=0,017) e ventrículo direito (p=0,03) e maior EIMC em cfPWV ≥6,9m/s (p=0,04). Conclusões: Em pacientes com PD, o cfPWV de 6,9 m/s foi considerado um valor discriminativo de rigidez arterial. Esses achados reforçam que a investigação precoce da lesão cardiovascular e uma estratégia com terapia agressiva são valiosas no controle dos fatores de risco na PD.

Comparison of two different biomaterials in the bone regeneration (15, 30 and 60 days) of critical defects in rats.

PURPOSE: To evaluate and compare two types of different scaffolds in critical bone defects in rats. METHODS: Seventy male Wistar rats (280 ± 20 grams) divided into three groups: control group (CG), untreated animals; biomaterial group 1 (BG1), animals that received the scaffold implanted hydroxyapatite (HA)/poly(lactic-co-glycolic) acid (PLGA); and biomaterial group 2 (BG2), animals that received the scaffolds HA/PLGA/Bleed. The critical bone defect was induced in the medial region of the skull calotte with the aid of an 8-mm-diameter trephine drill. The biomaterial was implanted in the form of 1.5 mm thick scaffolds, and samples were collected after 15, 30 and 60 days. Non-parametric Mann-Whitney test was used, with the significance level of 5% (p ≤ 0.05). RESULTS: Histology revealed morphological and structural differences of the neoformed tissue between the experimental groups. Collagen-1 (Col-1) findings are consistent with the histological ones, in which BG2 presented the highest amount of fibers in its tissue matrix in all evaluated periods. In contrast, the results of receptor activator of nuclear factor kappa-Β ligand (Rank-L) immunoexpression were higher in BG2 in the periods of 30 and 60 days, indicating an increase of the degradation of the biomaterial and the remodeling activity of the bone. CONCLUSIONS: The properties of the HA/PLGA/Bleed scaffold were superior when compared to the scaffold composed only by HA/PLGA.

Biphasic Dose/Response of Photobiomodulation Therapy on Culture of Human Fibroblasts.

Objective: The objective of this study was to evaluate the effects of application of different fluences and energies of laser in the 24-, 48-, and 72-h periods in fibroblasts originating from human skin (HFF-1). Methods: The cell used as a template for cell proliferation was HFF-1. For the photobiomodulation (PBM) application, a 660 nm laser with a power of 40 mW and energies of 0.84, 1.40, 5.88, and 6.72 J was used. Five experimental groups were studied: one control group (CG) with simulated PBM and four groups that received PBM in different doses. The changes observed after laser irradiation were evaluated by cell viability (trypan blue) and proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] tests. Intergroup comparisons were performed using two-way analysis of variance and the Tukey post hoc test (software GraphPad Prism 7.0). Results: In the trypan blue test, the total number of cells was significantly different between the irradiated groups and the CG at all times studied. The total number of cells increased in laser group (LG)1 (0.84 J) and LG2 (1.40 J) and decreased in LG4 (6.72 J). The mitochondrial activity increased significantly in LG1 and LG2 at 48 and 72 h and decreased in LG3 (5.88 J) and LG4 (6.72 J) compared with CG. Conclusions: The results indicate that the lower doses (0.45 and 0.75 J/cm2) of PBM induce the highest mitochondrial activity and cellular viability.

Evaluation of Cardiac Autonomic Modulation Using Symbolic Dynamics After Cardiac Transplantation.

OBJECTIVE: To characterize the behavior of cardiac autonomic modulation in individuals with different times after orthotopic heart transplantation (HTx) using symbolic dynamics analysis. METHODS: Sixty patients were evaluated after HTx. We recorded their instantaneous R-R intervals (RRi) by cardiac monitor Polar® RS800CX™ (Polar Electro Oy, Kempele, Finland) for 10 minutes. The same sequence of RRi with 256 consecutive beats was used to perform spectral analysis and symbolic dynamics analysis. We used hierarchical clustering to form groups. One-way analysis of variance (ANOVA) (with Holm-Sidak method) or one-way Kruskal-Wallis test (with Dunn´s post-hoc test) was used to analyze the difference between groups. Linear correlation analysis between variables was performed using Pearson's or Spearman's tests. P-value < 0.05 was considered statistically significant. RESULTS: The 0V% index increased, the 2UV% index and the normalized complexity index decreased with an increase of HTx postoperative time. There were a negative correlation between complexity indexes and 0V% and a positive correlation between complexity indexes and 2UV%. CONCLUSION: Symbolic dynamics indexes were able to show a specific cardiac autonomic modulation pattern for HTx recipients with different postoperative times.

Discriminative value of pulse wave velocity for arterial stiffness and cardiac injury in prediabetic patients / Valor discriminativo da velocidade da onda de pulso para rigidez arterial e lesão cardíaca em pacientes pré-diabéticos

Abstract Background Prediabetes (PD) is defined as impaired fasting glucose and/or impaired glucose tolerance (IGT) and may be associated with high risk of cardiovascular injury. It is recommended that PD patients be screened for signs of arterial stiffness and cardiovascular injury to reinforce therapeutic strategies. Objectives To identify pulse wave velocity values discriminative for arterial stiffness and cardiovascular injury in PD patients. Methods A cross-sectional study was conducted with PD (N=43) and normoglycemic (N=37) patients who underwent clinical evaluation, arterial stiffness assessment by carotid-femoral pulse wave velocity (cfPWV) using SphygmoCor, laboratory blood analysis, investigation of morphological and functional cardiac variables by transthoracic echocardiogram, and assessment of carotid intima-media-thickness (CIMT) by carotid ultrasonography. A statistical analysis was performed using SPSS software and values of p<0.05 were considered significant. Results A cfPWV cut-off value of 6.9 m/s was identified for IGT (Sensitivity [SE]: 74% and Specificity [SP]: 51%). Comparison of general data and risk factors between subsets with values above and below this cutoff value revealed higher rates of fasting glucose (p=0.02), obesity (p=0.03), dyslipidemia (p=0.004), early signs of left ventricle (p=0.017) and right ventricle (p=0.03) impaired diastolic function, and elevated CIMT in subjects with cfPWV ≥ 6.9m/s (p=0.04). Conclusions In PD patients, a cfPWV cutoff of 6.9 m/s was considered a discriminative value for arterial stiffness. These findings highlight the value of early investigation of cardiovascular injury and aggressive therapy strategies with good control of risk factors in PD.

Resumo Contexto O pré-diabetes (PD) é definido como glicemia de jejum alterada e/ou tolerância à glicose alterada (TGA) e pode estar associado a alto risco de lesão cardiovascular. Recomenda-se discriminar quais pacientes com PD podem apresentar sinais de rigidez arterial e lesão cardiovascular para reforçar as estratégias terapêuticas. Objetivos Identificar os valores discriminativos da velocidade de onda de pulso determinantes de rigidez arterial e lesão cardiovascular em pacientes com PD. Métodos Estudo transversal em pacientes com PD (N=43) e normoglicêmicos (N=37) submetidos a avaliação clínica, avaliação da rigidez arterial pela velocidade da onda de pulso carótido-femoral (cfPWV) utilizando SphygmoCor, análise laboratorial de sangue, investigação de alterações morfológicas e variáveis cardíacas funcionais por ecocardiograma transtorácico e avaliação da espessura íntima-média carotídea (EIMC) pela ultrassonografia da carótida. A análise estatística foi realizada no software SPSS, e valores de p<0,05 foram considerados significativos. Resultados Foi identificado um valor de corte cfPWV de 6,9 m/s para TGA (sensibilidade 74% e especificidade 51%). A comparação dos dados e fatores de risco entre valores acima e abaixo do valor de corte estabelecido revelou glicemia de jejum elevada (p=0,02), obesidade (p=0,03), dislipidemia (p=0,004), sinais precoces de função diastólica prejudicada do ventrículo esquerdo (p=0,017) e ventrículo direito (p=0,03) e maior EIMC em cfPWV ≥6,9m/s (p=0,04). Conclusões Em pacientes com PD, o cfPWV de 6,9 m/s foi considerado um valor discriminativo de rigidez arterial. Esses achados reforçam que a investigação precoce da lesão cardiovascular e uma estratégia com terapia agressiva são valiosas no controle dos fatores de risco na PD.

Comparison of two different biomaterials in the bone regeneration (15, 30 and 60 days) of critical defects in rats

ABSTRACT Purpose To evaluate and compare two types of different scaffolds in critical bone defects in rats. Methods Seventy male Wistar rats (280 ± 20 grams) divided into three groups: control group (CG), untreated animals; biomaterial group 1 (BG1), animals that received the scaffold implanted hydroxyapatite (HA)/poly(lactic-co-glycolic) acid (PLGA); and biomaterial group 2 (BG2), animals that received the scaffolds HA/PLGA/Bleed. The critical bone defect was induced in the medial region of the skull calotte with the aid of an 8-mm-diameter trephine drill. The biomaterial was implanted in the form of 1.5 mm thick scaffolds, and samples were collected after 15, 30 and 60 days. Non-parametric Mann-Whitney test was used, with the significance level of 5% (p ≤ 0.05). Results Histology revealed morphological and structural differences of the neoformed tissue between the experimental groups. Collagen-1 (Col-1) findings are consistent with the histological ones, in which BG2 presented the highest amount of fibers in its tissue matrix in all evaluated periods. In contrast, the results of receptor activator of nuclear factor kappa-Β ligand (Rank-L) immunoexpression were higher in BG2 in the periods of 30 and 60 days, indicating an increase of the degradation of the biomaterial and the remodeling activity of the bone. Conclusions The properties of the HA/PLGA/Bleed scaffold were superior when compared to the scaffold composed only by HA/PLGA.

Exercise alters myostatin protein expression in sedentary and exercised streptozotocin-diabetic rats.

OBJECTIVE: The aim of this study was to analyze the effect of exercise on the pattern of muscle myostatin (MSTN) protein expression in two important metabolic disorders, i.e., obesity and diabetes mellitus. MATERIALS AND METHODS: MSTN, is a negative regulator of skeletal muscle mass. We evaluated the effect of exercise on MSTN protein expression in diabetes mellitus and high fat diet-induced obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia in both diabetic and obese animals. RESULTS: The expression of precursor and processed protein forms of MSTN and the weight of gastrocnemius muscle did not vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius muscle weight in sedentary animals. However, gastrocnemius muscle weight increased in diabetic exercised animals. Both the precursor and processed forms of muscle MSTN protein were significantly higher in sedentary diabetic rats than in control rats. The precursor form was significantly lower in diabetic exercised animals than in diabetic sedentary animals. However, the processed form did not change. CONCLUSION: These results demonstrate that exercise can modulate the muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be involved in energy homeostasis.

Metabolic and pancreatic effects of bone marrow mesenchymal stem cells transplantation in mice fed high-fat diet.

The purpose of this study was to investigate the effects of multiple infusions of allogeneic MSCs on glucose homeostasis and morphometry of pancreatic islets in high- fat diet (HFD) fed mice. Swiss mice were fed standard diet (C group) or HFD (HFD group). After 8 weeks, animals of HFD group received sterile phosphate-buffered saline infusions (HFD-PBS) or four infusions of MSCs one week apart (HFD-MSCs). Fasting glycemia (FG) was determined weekly and glucose (GTT) and insulin (ITT) tolerance tests were performed 4, 8, 12, and 16 weeks after the infusions of MSCs. The MSCs transplanted mice were classified as responder (FG < 180 mg/dL, 72.2% of transplanted mice) or non-responder (FG > 180mg/dL, 28.8%) Seven weeks after MSCs infusions, FG decreased in HFD-MSCs responder mice compared with the HFD-PBS group. Sixteen weeks post MSCs infusions, GTT and ITT areas under the curve (AUC) decreased in HFD-MSCs responder mice compared to HFD-PBS group. Serum insulin concentration was higher in HFD-PBS group than in control animals and was not different compared with the other groups. The relative volume of α-cells was significantly smaller in HFD-PBS group than in C group and significantly higher in HFD-MSCs-NR than in HFD-PBS and HFD-MSCs-R groups. Cell apoptosis in the islets was higher in HFD-PBS group than in C group, and lower in HFD-MSCs responder mice than in HFD-PBS group and non-responder animals. The results demonstrate the ability of multiple infusions of MSCs to promote prolonged decrease in hyperglycemia and apoptosis in pancreatic islets and increase in insulin sensitivity in HFD fed mice.

Evaluation of cardiac autonomic modulation using symbolic dynamics after cardiac transplantation

Abstract Objective: To characterize the behavior of cardiac autonomic modulation in individuals with different times after orthotopic heart transplantation (HTx) using symbolic dynamics analysis. Methods: Sixty patients were evaluated after HTx. We recorded their instantaneous R-R intervals (RRi) by cardiac monitor Polar® RS800CX™ (Polar Electro Oy, Kempele, Finland) for 10 minutes. The same sequence of RRi with 256 consecutive beats was used to perform spectral analysis and symbolic dynamics analysis. We used hierarchical clustering to form groups. One-way analysis of variance (ANOVA) (with Holm-Sidak method) or one-way Kruskal-Wallis test (with Dunn´s post-hoc test) was used to analyze the difference between groups. Linear correlation analysis between variables was performed using Pearson's or Spearman's tests. P-value < 0.05 was considered statistically significant. Results: The 0V% index increased, the 2UV% index and the normalized complexity index decreased with an increase of HTx postoperative time. There were a negative correlation between complexity indexes and 0V% and a positive correlation between complexity indexes and 2UV%. Conclusion: Symbolic dynamics indexes were able to show a specific cardiac autonomic modulation pattern for HTx recipients with different postoperative times.

Exercise alters myostatin protein expression in sedentary and exercised streptozotocin-diabetic rats

Objective The aim of this study was to analyze the effect of exercise on the pattern of muscle myostatin (MSTN) protein expression in two important metabolic disorders, i.e., obesity and diabetes mellitus. Materials and methods MSTN, is a negative regulator of skeletal muscle mass. We evaluated the effect of exercise on MSTN protein expression in diabetes mellitus and high fat diet-induced obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia in both diabetic and obese animals. Results The expression of precursor and processed protein forms of MSTN and the weight of gastrocnemius muscle did not vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius muscle weight in sedentary animals. However, gastrocnemius muscle weight increased in diabetic exercised animals. Both the precursor and processed forms of muscle MSTN protein were significantly higher in sedentary diabetic rats than in control rats. The precursor form was significantly lower in diabetic exercised animals than in diabetic sedentary animals. However, the processed form did not change. Conclusion These results demonstrate that exercise can modulate the muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be involved in energy homeostasis. .

[Prevalence of diabetes and impaired glucose tolerance in the urban population of 30 to 79 years of the city of São Carlos, São Paulo]. / Prevalência de diabetes melito e tolerância à glicose diminuída na população urbana de 30 a 79 anos da cidade de São Carlos, São Paulo.

OBJECTIVE: To assess the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the urban population aged 30-79 years of the city of São Carlos, São Paulo, Brazil. METHODS: It was performed a population survey, from August 2007 to June 2008. Non diabetic individuals, excluding pregnant women, and those with fasting capillary glycemia

Prevalência de diabetes melito e tolerância à glicose diminuída na população urbana de 30 a 79 anos da cidade de São Carlos, São Paulo / Prevalence of diabetes and impaired glucose tolerance in the urban population of 30 to 79 years of the city of São Carlos, São Paulo

OBJETIVO: Estimar a prevalência de diabetes melito (DM) e tolerância à glicose diminuída (TGD) na população urbana de 30 a 79 anos da cidade de São Carlos, São Paulo. MÉTODOS: Foi realizado estudo de base populacional entre agosto de 2007 e junho de 2008. Todos os indivíduos, exceto mulheres grávidas, não diabéticos e aqueles com glicemia capilar em jejum < 199 mg/dl foram submetidos a teste oral de tolerância à glicose e classificados em diabéticos, com TGD ou com tolerância normal à glicose. RESULTADOS: Participaram da pesquisa 1.116 voluntários. As prevalências gerais de DM e TGD foram 13,5 por cento e 5 por cento, respectivamente. Houve associação entre DM e TGD e as variáveis "idade", "escolaridade", "índice de massa corpórea" e "circunferência abdominal". Não houve associação entre DM ou TGD e as variáveis "gênero", "cor da pele" e "rendimento mensal". CONCLUSÕES: Houve aumento na prevalência de DM em comparação a estudos anteriores no Brasil e na região. Embora tenha havido avanços no diagnóstico, o tratamento do DM requer otimização.

OBJECTIVE: To assess the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the urban population aged 30-79 years of the city of São Carlos, São Paulo, Brazil. METHODS: It was performed a population survey, from August 2007 to June 2008. Non diabetic individuals, excluding pregnant women, and those with fasting capillary glycemia < 199 mg/dl were administered oral glucose tolerance test and classified as diabetic, with IGT or with normal glucose tolerance. RESULTS: The number of individuals who participated in the study was 1,116. The overall rates of DM and IGT were 13.5 percent and 5 percent, respectively. DM and IGT were associated with age, education, body mass index and waist. They were not associated with gender, race or income. CONCLUSIONS: The prevalence of DM has increased when compared with previous studies in Brazil and in the state. Improvement in the diagnosis has occurred, however, treatment requires optimization.