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Background: Systemic arterial hypertension is a risk factor for cardiac, renal, and metabolic dysfunction. The search for new strategies to prevent and treat cardiovascular diseases led to the synthesis of new N-acylhydrazones to produce antihypertensive effect. Adenosine receptors are an alternative target to reduce blood pressure because of their vasodilatory action and antioxidant properties, which may reduce oxidative stress characteristic of systemic arterial hypertension., Objective: To evaluate the antihypertensive profile of novel selenium-containing compounds designed to improve their interaction with adenosine receptors., Methods: Vascular reactivity was evaluated by recording the isometric tension of pre-contracted thoracic aorta of male Wistar rats after exposure to increasing concentrations of each derivative (0.1 to 100 μM). To investigate the antihypertensive effect in spontaneously hypertensive rats, systolic, diastolic, and mean arterial pressure and heart rate were determined after intravenous administration of 10 and 30 μmol/kg of the selected compound LASSBio-2062., Results: Compounds named LASSBio-2062, LASSBio-2063, LASSBio-2075, LASSBio-2076, LASSBio-2084, LASSBio-430, LASSBio-2092, and LASSBio-2093 promoted vasodilation with mean effective concentrations of 15.5 ± 6.5; 14.6 ± 2.9; 18.7 ± 9.6; 6.7 ± 4.1; > 100; 6.0 ± 3.6; 37.8 ± 11.8; and 15.9 ± 5.7 μM, respectively. LASSBio-2062 (30 μmol/kg) reduced mean arterial pressure in spontaneously hypertensive rats from 124.6 ± 8.6 to 72.0 ± 12.3 mmHg (p < 0.05). Activation of adenosine receptor subtype A3 and potassium channels seem to be involved in the antihypertensive effect of LASSBio-2062., Conclusions: The new agonist of adenosine receptor and activator of potassium channels is a potential therapeutic agent to treat systemic arterial hypertension.

Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-α, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.

Aim: Oral manifestations are common in HIV+ children, but the impact of these diseases on their daily life is unknown. So the aim of this study was to assess the impact of oral problems on the daily activities of HIV+ children., Methods: The Child-OIDP-B was used with 59 10-12 year-old HIV+ children, who were outpatients at two public hospitals for HIV treatment in Rio de Janeiro, Brazil. Caries, biofilm and gingival bleeding indexes were recorded. The Kruskall-Wallis and Mann-Whitney tests as well as the Spearman's correlation coefficient were used for analysis. Statistical evaluation: Replies were analysed using the Statgraphics ® Plus Version 5.0 statistics software system, in order to obtain comparative diagrams and graphs using the ANOVA multifactorial system., Results: The Child-OIDP-B scores ranged from 0 to 30, (mean=6.09) and 71.2% of the children were affected by oral problems. Association was found between oral impact and number of caries (p=0.009). Children receiving HAART therapy had a Child-OIDP-B score (4.87), much lower than those who were not (8.87) (p=0.038). The most reported oral impact of the disease was eating (55.6%), but oral wounds were the most prevalent type of lesions (76.3%). As regards the level of intensity of the impact, moderate severity was prevalent in all 59 children and 66.1% reported that oral impacts affected 1-4 daily activities, 50.8% of all children were not satisfied with their appearance and oral health; 23.7% perceived the impact of HIV-infection on general health., Conclusion: Most children suffered the impact of oral problems on their daily activities, mainly functional impacts.