Flávio Santos da Silva

Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats

Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young’s modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective effect of zinc under chronic diabetic conditions. Furthermore, these results indicate that zinc supplementation could act as a complementary therapy in chronic T1DM.

Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non‐molecular parameters in a chronic animal model of T1DM‐induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa‐B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p < 0.001) and trabecular bone area (BAr, p < 0.01), reduced trabecular separation (TbSp, p < 0.01) and increased Youngs modulus (p < 0.05). Moreover, molecular analyses indicated that the expression of OPG and OC was up‐regulated (p < 0.001 and p < 0.05, respectively). In summary, the up‐regulation of OPG and OC in the T1DMI group supports an anabolic effect of insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM‐induced bone loss via the effects on the bone formation.

Overview of ultrasound usage trends in orthopedic and sports physiotherapy.

BackgroundThe purpose of this study is to examine current beliefs about the use, the clinical importance, the theoretical fundamentals and the utilization criteria of therapeutic ultrasound (TUS) among physical therapists on the clinical practice in orthopedic and sports physiotherapy in Brazil.MethodsA brief survey was developed based on previous studies and was sent to 55 physical therapists with advanced competency in orthopedics and sports physiotherapy. The questions addressed general topics about the professional profile and ultrasound usage and dosage.ResultsOur data show the wide availability and frequent use of TUS in this sample of physical therapists. TUS is used in distinct musculoskeletal injuries and/or disorders in both acute and chronic conditions. Muscles, tendons and ligaments represented the major structures where TUS is used. Questions on the basic theory of TUS demonstrated a lack of knowledge of the ultrasound physiological effects as well as its interaction with biological tissues and TUS absolute contraindication.ConclusionA Brazilian profile about the US usage and dosage in orthopedic and sports physiotherapy is presented and highlights the need for a continuous upgrading process and further research into its effects.

Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats☆

BACKGROUND The aim was to investigate whether exercise training (ExT) would ameliorate expression of key genes for myocardial morphostructure and mitigate adverse left ventricular (LV) remodeling in experimental type 1 diabetes (T1D). METHODS AND RESULTS Male Wistar rats were divided into four groups: sedentary control (SC, n=9), trained control (TC, n=13), sedentary diabetic (SD, n=20), and trained diabetic (TD, n=17). T1D was induced by 40 mg/kg streptozotocin (single dose, i.v.). Training program consisted of 4-week treadmill running (60 min/day, 5 days/wk). Structure of the LV was evaluated using histomorphometric techniques. Gene expression changes of LV collagens I and III, metalloproteinases (MMPs) 2 and 9, and transforming growth factor-β1 were detected by reverse transcriptase quantitative polymerase chain reaction. Compared with SC, SD rats presented LV eccentric remodeling, myocyte hypertrophy, and fibrosis, whereas TD animals showed normal LV geometry and collagen content but thinner myocytes. Expression of collagens and type I/III collagen messenger RNA (mRNA) ratio were diminished in diabetic hearts compared with SC. MMP-2 gene was down-regulated in SD, whereas TD group showed decreased MMP-9 mRNA levels and MMP-2 expression comparable to that of SC rats. CONCLUSIONS Attenuation of MMP-2 down-regulation and reduction in MMP-9 mRNA expression may constitute an underlying mechanism by which ExT counteracts progression of adverse LV remodeling in T1D.

Efeito do ultrassom terapêutico sobre as propriedades mecânicas do gastrocnêmio em ratos

INTRODUCAO: Apesar de algumas controversias quanto a sua utilizacao, o ultrassom terapeutico (UST) e um recurso comumente aplicado na reabilitacao desportiva para aceleracao do reparo tecidual de lesoes musculares. Sabe-se que lesoes musculares influenciam negativamente as propriedades mecânicas da musculatura estriada esqueletica e algumas evidencias demonstram que o UST poderia ter efeitos beneficos sobre o reparo muscular e, consequentemente, sobre suas propriedades mecânicas.OBJETIVO: Analisar o efeito do UST no reparo tecidual por meio das propriedades mecânicas musculares de ratos apos trauma por criolesao.METODOS: Foram utilizados no estudo 30 ratos da linhagem Wistar, os quais foram divididos em tres grupos: grupo controle intacto (GC), grupo lesionado sem tratamento (GL), e grupo lesionado e estimulado com UST (frequencia de 1 MHz; intensidade de 0,5 W/cm2; ciclo de trabalho de 50%; por quatro minutos diarios), durante sete dias consecutivos (GLUST). As propriedades mecânicas obtidas atraves de ensaio mecânico de tracao foram avaliadas em uma maquina universal de ensaios.RESULTADOS: Foram analisados estatisticamente, com nivel de significância de 95% (P<0,05). Apos sete sessoes de tratamento, houve melhora estatisticamente significativa nas propriedades mecânicas de carga no limite de proporcionalidade, carga no limite maximo e resiliencia para o GLUST em relacao ao GL (p<0,05).CONCLUSAO: O UST foi eficaz no processo de reparo tecidual, conferindo ao tecido muscular maior resistencia a tracao e absorcao de energia.Introduction: Despite controversial, ultrasonic therapy (UST) is commonly applied in sports rehabilitation practice to accelerate tissue repair after muscle damage. Muscle injuries have a negative influence on the mechanical properties of skeletal striated muscles and some scientific evidence shows that UST could have a positive effects on tissue repair and, therefore, on its mechanical properties. Objective: To analyze the effect of UST on muscle repair by evaluation of the mechanical properties of rat muscles after cryolesion. Methods: We used 30 adult Wistar rats which were divided into three groups: CG (control group), IG (injured group) and IGUST (injured plus UST) (frequency of 1 MHz; intensity of 0.5 W/cm2; pulsed to 50%; four minutes daily) for seven consecutive days. The mechanical properties obtained through mechanical tests were evaluated in a universal testing machine. Results: Data were statistically analyzed with a significance level of 95% (p<0.05). After seven treatment sessions, we found significant improvement in the mechanical properties of load at the proportionality limit, load at maximum limit and resilience in IGUST compared to IG (p<0.05). Conclusion: The UST was effective in the tissue repair process, giving higher tensile strength and energy absorption to the muscle tissue.

Efecto del ultrasounido terapéutico sobre las propiedades mecánicas del gastrocnemio en ratones

INTRODUCAO: Apesar de algumas controversias quanto a sua utilizacao, o ultrassom terapeutico (UST) e um recurso comumente aplicado na reabilitacao desportiva para aceleracao do reparo tecidual de lesoes musculares. Sabe-se que lesoes musculares influenciam negativamente as propriedades mecânicas da musculatura estriada esqueletica e algumas evidencias demonstram que o UST poderia ter efeitos beneficos sobre o reparo muscular e, consequentemente, sobre suas propriedades mecânicas.OBJETIVO: Analisar o efeito do UST no reparo tecidual por meio das propriedades mecânicas musculares de ratos apos trauma por criolesao.METODOS: Foram utilizados no estudo 30 ratos da linhagem Wistar, os quais foram divididos em tres grupos: grupo controle intacto (GC), grupo lesionado sem tratamento (GL), e grupo lesionado e estimulado com UST (frequencia de 1 MHz; intensidade de 0,5 W/cm2; ciclo de trabalho de 50%; por quatro minutos diarios), durante sete dias consecutivos (GLUST). As propriedades mecânicas obtidas atraves de ensaio mecânico de tracao foram avaliadas em uma maquina universal de ensaios.RESULTADOS: Foram analisados estatisticamente, com nivel de significância de 95% (P<0,05). Apos sete sessoes de tratamento, houve melhora estatisticamente significativa nas propriedades mecânicas de carga no limite de proporcionalidade, carga no limite maximo e resiliencia para o GLUST em relacao ao GL (p<0,05).CONCLUSAO: O UST foi eficaz no processo de reparo tecidual, conferindo ao tecido muscular maior resistencia a tracao e absorcao de energia.Introduction: Despite controversial, ultrasonic therapy (UST) is commonly applied in sports rehabilitation practice to accelerate tissue repair after muscle damage. Muscle injuries have a negative influence on the mechanical properties of skeletal striated muscles and some scientific evidence shows that UST could have a positive effects on tissue repair and, therefore, on its mechanical properties. Objective: To analyze the effect of UST on muscle repair by evaluation of the mechanical properties of rat muscles after cryolesion. Methods: We used 30 adult Wistar rats which were divided into three groups: CG (control group), IG (injured group) and IGUST (injured plus UST) (frequency of 1 MHz; intensity of 0.5 W/cm2; pulsed to 50%; four minutes daily) for seven consecutive days. The mechanical properties obtained through mechanical tests were evaluated in a universal testing machine. Results: Data were statistically analyzed with a significance level of 95% (p<0.05). After seven treatment sessions, we found significant improvement in the mechanical properties of load at the proportionality limit, load at maximum limit and resilience in IGUST compared to IG (p<0.05). Conclusion: The UST was effective in the tissue repair process, giving higher tensile strength and energy absorption to the muscle tissue.

Effect of therapeutic ultrasound on mecnanical properties of gastrocnemius in rats

INTRODUCAO: Apesar de algumas controversias quanto a sua utilizacao, o ultrassom terapeutico (UST) e um recurso comumente aplicado na reabilitacao desportiva para aceleracao do reparo tecidual de lesoes musculares. Sabe-se que lesoes musculares influenciam negativamente as propriedades mecânicas da musculatura estriada esqueletica e algumas evidencias demonstram que o UST poderia ter efeitos beneficos sobre o reparo muscular e, consequentemente, sobre suas propriedades mecânicas.OBJETIVO: Analisar o efeito do UST no reparo tecidual por meio das propriedades mecânicas musculares de ratos apos trauma por criolesao.METODOS: Foram utilizados no estudo 30 ratos da linhagem Wistar, os quais foram divididos em tres grupos: grupo controle intacto (GC), grupo lesionado sem tratamento (GL), e grupo lesionado e estimulado com UST (frequencia de 1 MHz; intensidade de 0,5 W/cm2; ciclo de trabalho de 50%; por quatro minutos diarios), durante sete dias consecutivos (GLUST). As propriedades mecânicas obtidas atraves de ensaio mecânico de tracao foram avaliadas em uma maquina universal de ensaios.RESULTADOS: Foram analisados estatisticamente, com nivel de significância de 95% (P<0,05). Apos sete sessoes de tratamento, houve melhora estatisticamente significativa nas propriedades mecânicas de carga no limite de proporcionalidade, carga no limite maximo e resiliencia para o GLUST em relacao ao GL (p<0,05).CONCLUSAO: O UST foi eficaz no processo de reparo tecidual, conferindo ao tecido muscular maior resistencia a tracao e absorcao de energia.Introduction: Despite controversial, ultrasonic therapy (UST) is commonly applied in sports rehabilitation practice to accelerate tissue repair after muscle damage. Muscle injuries have a negative influence on the mechanical properties of skeletal striated muscles and some scientific evidence shows that UST could have a positive effects on tissue repair and, therefore, on its mechanical properties. Objective: To analyze the effect of UST on muscle repair by evaluation of the mechanical properties of rat muscles after cryolesion. Methods: We used 30 adult Wistar rats which were divided into three groups: CG (control group), IG (injured group) and IGUST (injured plus UST) (frequency of 1 MHz; intensity of 0.5 W/cm2; pulsed to 50%; four minutes daily) for seven consecutive days. The mechanical properties obtained through mechanical tests were evaluated in a universal testing machine. Results: Data were statistically analyzed with a significance level of 95% (p<0.05). After seven treatment sessions, we found significant improvement in the mechanical properties of load at the proportionality limit, load at maximum limit and resilience in IGUST compared to IG (p<0.05). Conclusion: The UST was effective in the tissue repair process, giving higher tensile strength and energy absorption to the muscle tissue.