Purpose: Atopic dermatitis (AD) is characterized by chronic inflammation, which frequently recurs, is exacerbated, and enters remission. A maintenance remission period is important for AD patients. We developed a formulation for use during AD remission, containing heparinoid and pseudo-ceramide that forms a lamellar structure. We evaluated the allergen permeability and examined the formulation's efficacy in maintaining remission in patients with AD. Materials and Methods: Seventeen AD patients applied a cream containing 0.3% heparinoid and pseudo-ceramide (test cream group, n = 10), or a general cream containing 0.3% heparinoid (control cream group, n = 7) to their arm for four weeks after inducing remission with the application of a steroid cream for two weeks. Results:The lamellar structure of the test cream was confirmed with small-and wide-angle x-ray scattering analysis and observation by transmission electron microscopy. The test cream inhibited the penetration of V8 protease significantly compared to the control cream in vitro. According to AD severity score by dermatologists, the effects remission maintenance of the test cream group were comparable to those of the control cream group. However, the test cream group had a significantly increased skin hydration value compared to the control cream group. A significant decrease in transepidermal water loss, an indicator of skin barrier function, was shown in the test cream group compared to the control cream group. Conclusion:The cream with lamellar structures containing heparinoid and pseudoceramides may inhibit allergen penetration. Moreover, skin properties improved during the remission period; thus, the formulation we developed was suitable for use during the AD remission period.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure. Methods: We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms. Results: The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small-and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the doubleblind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p \ 0.01) and significant decrease in transepidermal water loss (p \ 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group. Conclusion:The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. However, as most clinical trials were performed in type 2 DM, the effects of SGLT2 inhibitors in patients with type 1 DM still need further clarification. In this study, we evaluated the effects of long-term treatment with the SGLT2 inhibitor dapagliflozin on cardiac remodeling, myocardial function, and energy metabolism in rats with type 1 DM. Methods Male Wistar rats were divided into three groups: control (C, n=15); DM (n=15); and DM treated with dapagliflozin (DM+DAPA, n=15) for 30 weeks. DM was induced by streptozotocin; DAPA was added to the rat chow (5 mg/kg/day). Cardiac performance was evaluated by echocardiogram and myocardial function in isolated left ventricular (LV) papillary muscle preparations. Myocardial energy metabolism enzyme activities were evaluated by spectrophotometry. Statistical analyzes: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results DM+DAPA had lower glycemia than DM [C 112 (108–116); DM 531 (522–535)*; DM+DAPA 267 (179–339) mg/dL; p<0.05 vs C and DM+DAPA]. Echocardiogram showed that DM and DM+DAPA had left atrium and left ventricle dilatation with systolic and diastolic dysfunction; in DM+DAPA, the changes were attenuated in relation to DM. Developed tension and +dT/dt were higher in DM+DAPA than DM in basal condition. After inotropic stimulation with post-pause contraction, extracellular calcium concentration elevation, and isoproterenol addition to the nutrient solution, +dT/dt and –dT/dt were higher in DM+DAPA than DM. Hexokinase, phosphofructokinase, and pyruvate kinase activity was lower in DM than the C. Phosphofructokinase and pyruvate kinase activity was higher in DM+DAPA than DM. Conclusion Long-term dapagliflozin treatment attenuates cardiac remodeling and myocardial dysfunction and preserves hexokinase, phosphofructokinase and pyruvate kinase activity in rats with type 1 diabetes mellitus. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CNPq - National Council for Scientific and Technological Developmentdoctor

Introduction Exercise is an important therapeutic strategy for heart failure (HF). However, the myocardial effects of resistance exercise during HF are not completely understood. In this study, we investigated the influence of resistance exercise on cardiac remodeling and molecular myocardial changes of rats with myocardial infarction (MI)-induced HF. Methods Three months after MI induction or simulated surgery, Wistar rats were divided into three groups: Sham (n=14); MI (n=9); and MI subjected to resistance exercise (MI-R, n=13). Exercised rats trained 3 times a week during 12 weeks performing four climbs in a ladder with progressive loads. Cardiac structure and left ventricular function were assessed by echocardiogram. Myocyte diameters were measured in histological sections. Energy metabolism, lipid hydroperoxide, antioxidant enzymes activity, malondialdehyde, and protein carbonylation were evaluated by spectrophotometry. NADPH oxidase subunits (Nox2, Nox4, p22phox and p47phox) gene expression was assessed by RT-PCR. Statistical analysis: ANOVA and Tukey test or Dunn's test. Results Mortality did not differ between MI-R and MI groups. MI-R and MI presented dilated left atrium and left ventricle with systolic and diastolic dysfunction. Exercise improved maximum carrying load with no changes in cardiac structure or left ventricle function. Myocyte diameter was lower in MI than Sham and MI-R. Lactate dehydrogenase and creatine kinase activities were lower in MI than Sham. Activity of citrate synthase and catalase was lower in MI and MI-R than Sham. Lipid hydroperoxide concentration was lower in MI-R than MI. Nox2 and p22phox gene expression was higher in MI-R than Sham. Gene expression of Nox4 was higher in both infarcted groups and gene expression of p47phox was lower in MI than Sham. Conclusion Resistance exercise is safe and well tolerated by infarcted rats. Exercise increases maximum carrying load and reduces myocardial oxidative stress with no changes in cardiac structure or left ventricle function of infarcted rats. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CNPq - National Council for Scientific and Technological Development

Introduction Skeletal muscle energy metabolism is commonly altered in heart failure patients, with a metabolic shift from oxidative to glycolytic muscle fiber. These changes contribute to reduced functional capacity. Sodium glucose co-transporter type 2 (SGLT2) inhibitors improve cardiovascular outcomes in both diabetic and non-diabetic patients, as well as those with and without heart failure. However, the effects of SGLT2 inhibitors on skeletal muscle during heart failure have not been established. The aim of this study was to assess the metabolic effect of empagliflozin (EMPA) on skeletal muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction or simulated surgery, male Wistar rats were divided into four groups: Sham (n=10), Sham+Empa (n=12), MI (n=10), and MI+Empa (n=09). EMPA was added to rat chow (5 mg/kg/day). Rats were supplied with ad libitum water and chow for 12 weeks. Infarct size was measured by histological analysis. Metabolic enzyme activity in the soleus muscle was assessed by spectrophotometry. Statistical analysis: ANOVA and Tukey, and Student's t tests. Results Only rats with infarction size greater than 35% of total left ventricle area were included in this study. Infarction size did not differ between infarcted groups (MI 41.8±4.2; MI+Empa 40.7±5.7 of total left ventricle area). In the MI soleus muscle, metabolic enzyme activity of glucose-6-phosphate-dehydrogenase, citrate synthase and beta-hydroxy-acyl-dehydrogenase was higher than the Sham group. These changes were not observed in the MI+Empa group. MI+Empa had lower hexokinase, phosfructokinase, and pyruvate kinase activity (glycolytic metabolism enzymes), and lower citrate synthase and glucose-6-phosphate-dehydrogenase activity than MI. Conclusion Chronic treatment with SGLT2 inhibitor empagliflozin prevents metabolic abnormalities in skeletal muscle in infarcted rats. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): CAPES, CNPq, FAPESP