Association of sun exposure and seasonality with vitamin D levels in Brazilian children and adolescents.

OBJECTIVE: This study aimed to verify vitamin D concentration in children and adolescents during the seasons of the year and to compare vitamin D concentration between children engaged in outdoor activities and those engaged in indoor activities. METHODS: This is a cross-sectional study with a sample of 708 children and adolescents (aged 6-18 years), excluding 109 (16 were over 19 years old; 39 had a disease that required continuous treatment; 20 were on continuous medication; and 34 had no vitamin D data), ending with 599. The plasma concentration of 25-hydroxyvitamin D2 was measured with commercial kits following manufacturer instructions. RESULTS: Participants who engaged in outdoor activities, as well as those who had data collected during summer and spring, had higher levels of vitamin D. According to the Poisson regression, the proportion of participants with inadequate levels of vitamin D was greater in the participants whose vitamin D was measured during spring (PR 1.15, 95%CI 1.03-1.29) and winter (PR 1.18, 95%CI 1.05-1.32). Also, a greater proportion of inadequate vitamin D was observed for those engaged in indoor activities (PR 1.08, 95%CI 1.01-1.15). CONCLUSIONS: Participants who measured the vitamin during the summer and autumn had a lower prevalence of hypovitaminosis D. Even in regions with high solar incidence throughout the year, vitamin D levels can vary significantly during the period's seasons.

Association of sun exposure and seasonality with vitamin D levels in Brazilian children and adolescents / Associação da exposição solar e da sazonalidade com os níveis de vitamina D em crianças e adolescentes brasileiros

Abstract Objective: This study aimed to verify vitamin D concentration in children and adolescents during the seasons of the year and to compare vitamin D concentration between children engaged in outdoor activities and those engaged in indoor activities. Methods: This is a cross-sectional study with a sample of 708 children and adolescents (aged 6-18 years), excluding 109 (16 were over 19 years old; 39 had a disease that required continuous treatment; 20 were on continuous medication; and 34 had no vitamin D data), ending with 599. The plasma concentration of 25-hydroxyvitamin D2 was measured with commercial kits following manufacturer instructions. Results: Participants who engaged in outdoor activities, as well as those who had data collected during summer and spring, had higher levels of vitamin D. According to the Poisson regression, the proportion of participants with inadequate levels of vitamin D was greater in the participants whose vitamin D was measured during spring (PR 1.15, 95%CI 1.03-1.29) and winter (PR 1.18, 95%CI 1.05-1.32). Also, a greater proportion of inadequate vitamin D was observed for those engaged in indoor activities (PR 1.08, 95%CI 1.01-1.15). Conclusions: Participants who measured the vitamin during the summer and autumn had a lower prevalence of hypovitaminosis D. Even in regions with high solar incidence throughout the year, vitamin D levels can vary significantly during the period's seasons.

Resumo Objetivo: Verificar a concentração de vitamina D em crianças e adolescentes durante as estações do ano e comparar essa concentração entre crianças praticantes de atividades ao ar livre e aquelas praticantes de atividades em ambiente fechado. Métodos: Trata-se de estudo transversal com amostra de 708 crianças e adolescentes (seis a 18 anos), excluindo-se 109, pois 16 eram maiores de 19 anos; 39 tinham doença que exigia tratamento contínuo; 20 estavam em uso de medicação contínua; e 34 não tinham dados de vitamina D. Terminou-se, assim, com 599 pacientes. A concentração plasmática de 25-hidroxivitamina D2 foi medida com kits comerciais, seguindo as instruções do fabricante. Resultados: Os participantes que realizaram atividades ao ar livre, assim como aqueles que tiveram dados coletados durante o verão e a primavera, apresentaram níveis mais elevados de vitamina D. De acordo com a regressão de Poisson, a proporção de participantes com níveis inadequados de vitamina D foi maior naqueles cuja medição foi realizada durante a primavera (razão de prevalência — RP 1,15, intervalo de confiança — IC95% 1,03-1,29) e o inverno (RP 1,18, IC95% 1,05-1,32). Além disso, maior proporção de vitamina D inadequada foi observada para aqueles envolvidos em atividades internas (RP 1,08, IC95% 1,01-1,15). Conclusões: Participantes que mediram a vitamina durante o verão e o outono tiveram menor prevalência para hipovitaminose D. Mesmo em regiões com alta incidência solar ao longo do ano os níveis de vitamina D podem variar significativamente durante as estações.

Lifestyle and NR3C1 exon 1F gene methylation is associated with changes in glucose levels and insulin resistance.

AIMS: the present study aimed to investigate how glucose and insulin levels may be associated with changes in NR3C1 gene methylation levels in adults. MAIN METHODS: 375 volunteers users of the Brazilian Public Unified Health System (SUS) were recruited to assess socioeconomic status, lifestyle, anthropometric data, blood glucose and serum cortisol levels, insulin resistance, and NR3C1 gene methylation assessment. Factors associated with glucose levels and insulin resistance were investigated using multivariate analysis GLzM at 5% significance (p<0.05). KEY FINDINGS: our results verified that glucose levels and insulin resistance were directly related to NR3C1 gene methylation and age, while not being overweight and obese and no tobacco consumption were indirectly related to glucose levels and insulin resistance. SIGNIFICANCE: habits and lifestyle may influence NR3C1 gene regulation, revealing the complexity of environmental impacts on NR3C1 methylation. Furthermore, associated risk factors must be taken into account in epigenetic studies as they directly interfere with blood glucose levels and insulin resistance.

Laser Therapy as a Preventive Approach for Oral Mucositis in Cancer Patients Undergoing Chemotherapy: The Potential Role of Superoxide Dismutase.

PURPOSE: Oral mucositis is a painful condition that occurs in patients who undergo chemotherapy. Due to the worsening of oral mucositis, the patient may progress to a worse clinical condition and interrupt antineoplastic treatment. There is little literature on low-power laser therapy in chemotherapy for other solid tumors. The purpose of this study was to investigate whether low-level laser therapy (LLLT) applied before chemotherapy could prevent oral mucositis in patients with solid tumors. METHODS: Laser therapy was applied at a frequency of 630nm, with a dose of 2J / cm2, for the prevention of oral mucositis induced by chemotherapy specifically for non-hematological tumors. Epidemiological data, total neutrophils, general side effects, development of oral mucositis and degree, and the performance of low-power laser therapy to prevent oral mucositis were collected. The involvement of oxidative stress was evaluated by the enzyme superoxide dismutase (SOD) through blood samples, before and after chemotherapy treatments. RESULTS: LLLT in the proposed protocol is efficient in reducing the development of oral mucositis (only at grade I/II) in patients under chemotherapy and able to reduce the severity of oral mucosal lesions, in patients who developed mucositis after the use of the laser for prevention. All individuals who underwent LLLT protocol did not show a significant reduction of SOD activity after the last chemotherapy cycle. CONCLUSIONS: The prophylactic laser therapy protocol proposed by the study, defined at a frequency of 630nm, a dose of 2J / cm2, demonstrated the ability to decrease the occurrence of oral mucositis in patients undergoing chemotherapy protocols to solid tumors. This effect could be related to preserved SOD activity, as it was observed that oral mucositis is related to leukopenia and reduced SOD activity and LLLT protocol prevented the decrease of SOD activity.

Acute hypotensive effect of diminazene aceturate in spontaneously hypertensive rats: role of NO and Mas receptor.

Diminazene aceturate (DIZE) has been described as an angiotensin-converting enzyme 2 (ACE2) activator. We aimed to investigate DIZE effects on blood pressure (BP) of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. BP was recorded in awake and unrestrained rats 24 hours after femoral artery catheterization. DIZE (15 mg/kg, s.c.) produced a fast BP decrease only in SHR (P < .01). Pre-treatment with L-NAME (10 mg/kg, iv) did not change the hypotensive effect on systolic BP whereas mitigated the DIZE effect on diastolic BP (∆ Emax: -31 ± 5 DIZE vs -15 ± 1 mm Hg DIZE + L-NAME, P < .05). BP changes after DIZE remained unchanged after the treatment of rats with A-779 (50 ug/kg, iv), a Mas receptor blocker. Vasodilatation curves to DIZE (10-9 to 10-4  mol/L) in mesenteric arteries confirmed the NO-mediation on DIZE effects in SHR, as L-NAME (300 µmol/L) reduced the vascular sensitivity (∆EC50: -5.12 ± 0.09 CONTROL vs -4.66 ± 0.08 L-NAME, P < .05) and the magnitude of DIZE effect (area under the curve (AUC), 357.5 ± 8.2 DIZE vs 424.7 ± 11.6 L-NAME; P < .001), whereas A-779 (1 µmol/L) enhanced DIZE response (AUC, 357.5 ± 8.2 DIZE vs 309.8 ± 14.7 A-779, P < .05). Our findings indicate that DIZE acutely reduces the BP in SHR possibly by a mechanism other than Mas receptor activation. This effect seems to be mediated, at least partially, by NO.

Lipid disorders among Black Africans non-users of lipid-lowering medication.

OBJECTIVE: Angola is a sub-Saharan African country where the population has scarce access to lipidlowering medication. We sought to determine the frequency of lipid disorders among Angolan nonusers of lipid-lowering medication. MATERIAL AND METHODS: A cross-sectional descriptive study was carried out in a sample of 604 workers from the public sector. Blood pressure and anthropometric data were measured along with biochemical parameters including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). LDL-C to HDL-C ratio (LDL-C/HDL-C) was obtained from LDL-C and HDL-C levels. RESULTS: High frequencies of elevated blood pressure (44.8%), metabolic syndrome (20.2%), increased TC (39.2%) and increased LDL-C (19.3%) were found. Low HDL-C was more frequent in women (62.4% vs. 36.1%, p < 0.001). Isolated hypercholesterolemia was more frequent in men (9.6% vs. 2.5%, p < 0.001). Among men TC, TG, LDL-C and LDL-C/HDL-C ratio were higher and HDL-C was lower in obese than in low-weight and normal-weight participants. Among women TC, TG, LDL-C and LDL-C/HDL-C ratio were higher in obese than in normal-weight participants. Significant linear trend of increasing TC and LDL-C levels as age increased was detected for both genders (p for trend < 0.05). CONCLUSION: The results of our study showed a high frequency of lipid disorders in Angolan non-users of lipid-lowering medication.

Lipid disorders among Black Africans non-users of lipid-lowering medication

ABSTRACT Objective: Angola is a sub-Saharan African country where the population has scarce access to lipidlowering medication. We sought to determine the frequency of lipid disorders among Angolan nonusers of lipid-lowering medication. Material and methods: A cross-sectional descriptive study was carried out in a sample of 604 workers from the public sector. Blood pressure and anthropometric data were measured along with biochemical parameters including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). LDL-C to HDL-C ratio (LDL-C/HDL-C) was obtained from LDL-C and HDL-C levels. Results: High frequencies of elevated blood pressure (44.8%), metabolic syndrome (20.2%), increased TC (39.2%) and increased LDL-C (19.3%) were found. Low HDL-C was more frequent in women (62.4% vs. 36.1%, p < 0.001). Isolated hypercholesterolemia was more frequent in men (9.6% vs. 2.5%, p < 0.001). Among men TC, TG, LDL-C and LDL-C/HDL-C ratio were higher and HDL-C was lower in obese than in low-weight and normal-weight participants. Among women TC, TG, LDL-C and LDL-C/HDL-C ratio were higher in obese than in normal-weight participants. Significant linear trend of increasing TC and LDL-C levels as age increased was detected for both genders (p for trend < 0.05). Conclusion: The results of our study showed a high frequency of lipid disorders in Angolan non-users of lipid-lowering medication.

The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats.

Diminazene aceturate (DIZE) has been reported to enhance the catalytic efficiency of ACE-2 and presumably increases angiotensin 1-7 generation, interfering with cardiac remodeling after myocardial infarction (MI). Our aim was to investigate the chronic effects of DIZE on cardiac dysfunction post-MI. Male Wistar rats underwent myocardial infarction (MI) or SHAM surgery (SO) and were divided into groups treated with DIZE 15 mg/kg/day, s.c. or vehicle (Control). After 4 weeks, the hemodynamic variables were recorded by cardiac catheterism. Hearts were then arrested to obtain the left ventricular (LV) pressure-volume curves in situ. Cardiomyocyte hypertrophy and collagen content were determined by histology. DIZE prevented LV end-diastolic pressure increases in MI rats (MI: 26 ± 3.3 vs. MI-DIZE: 15 ± 1.6 mmHg, P < 0.001) without a significant effect on LV systolic pressure (LVSP). Moreover, DIZE improved LV contractility (+dP/dt, MI: 3014 ± 161 vs. MI-DIZE: 3884 ± 104 mmHg/s, P < 0.001) and relaxation (-dP/dt, MI: -2333 ± 91 vs. MI-DIZE: -2798 ± 120 mmHg/s, P < 0.05). Right ventricular SP was increased in the MI compared to that in the SO group (40 ± 0.6 vs. 30 ± 1.2 mmHg; P < 0.01), and DIZE partially prevented this augmentation. LV stiffness was reduced in MI-DIZE compared with that in MI (0.64 ± 0.01 vs. 0.78 ± 0.02 mmHg/mL; P < 0.01). DIZE treatment reduced the interstitial collagen content by 18% in the surviving LV myocardium. Cardiomyocyte hypertrophy remained unaffected by DIZE treatment. Our findings show that chronic DIZE treatment post-MI attenuates the morphofunctional changes induced by MI in rats. The effects on LV -dP/dt, chamber stiffness and collagen content suggest this drug can be used as a therapeutic agent to reduce interstitial fibrosis and diastolic dysfunction after MI.

Early sex differences in central arterial wave reflection are mediated by different timing of forward and reflected pressure waves.

Non-invasive assessment of central arterial pulse wave augmentation has been proved to be useful in predicting cardiovascular adverse events. Previous studies have shown that pre-pubescent girls had greater central augmentation pressure compared with height-matched boys. This study sought to investigate which factors contribute to the body height-independent sexual differences in central arterial wave reflection observed in childhood. This cross-sectional study involved 819 children and adolescents (6-18 years of age) of both sexes. Phenotypes of central haemodynamic were obtained by radial applanation tonometry. Heart rate corrected augmentation index (Aix@75) was greater in girls compared with boys (2.9 ± 10.7 vs -1.7 ± 12.9%, P < .001) as well as the central augmented pressure (cAP; 1.3 ± 3.3 vs 0.1 ± 3.8 mm Hg, P < .001), even adjusting for age, heart rate and body height. Left ventricular ejection duration (ED) was longer (320 ± 26 vs 314 ± 24 ms, P = .004) and time to inflection point (Tr) was shorter in girls (139 ± 14 vs 141 ± 21 ms, P = .014). The reduction of Aix@75 with increasing body height was steeper in boys (-0.499 ± 0.030 vs -0.428 ± 0.036%/cm, P < .001) as well as the reduction of cAP with increasing body height (-0.108 ± 0.010 vs -0.066 ± 0.013 mm Hg/cm, P < .001). Body height-independent sexual differences observed in the pulse wave reflection indices from early adolescence were mediated by different timing of forward and reflected pressure waves.

Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat.

BACKGROUND: Symptoms and signs of myocardial ischemia in the absence of obstructive coronary disease are common in hypertensive patients. This can be explained by CMD due to adverse remodeling of coronary arterioles which have also been reported in the SHR. OBJECTIVE: The aim of this study was to compare the effects of ramipril, perindopril, candesartan, atenolol, amlodipine, indapamide, and HMR1766 on CMD in the SHR. METHODS: Eight groups of 24-wk-old SHR were treated for 8 wk. BP was measured invasively at the end of the treatment. After sacrifice, hearts were mounted on a Langendorff apparatus for the measurement of hyperemic CF. Hearts were then processed for histomorphometric analysis. RESULTS: All compounds, except HMR1766, induced a significant reduction in BP. Perindopril and candesartan increased hyperemic CF, whereas the other compounds had no significant effect. Perindopril, ramipril, atenolol, indapamide, and HMR1766 induced significant reverse arteriolar remodeling, whereas candesartan and amlodipine did not. CONCLUSIONS: The effect of antihypertensive treatment on CMD is not exclusively dependent on BP reduction. Compounds with comparable antihypertensive efficacy may exert different effects on CF and induce different degrees of reverse arteriolar remodeling.

Influence of ovariectomy on cardiac oxidative stress in a renovascular hypertension model.

The aim of this study was to evaluate the potential influence of endogenous ovarian hormones on cardiac oxidative stress in renovascular hypertension. Female Wistar rats (N = 10 per group) were divided among 4 groups: (i) normotensive control; (ii) hypertensive control; (iii) normotensive ovariectomized; and (iv) hypertensive ovariectomized rats. To induce hypertension, 2-kidney 1-clip (2K1C) Goldblatt's method was followed. Blood pressure (BP) was enhanced (25%) in 2K1C and it was not further altered in hypertensive ovariectomized animals. Lipid peroxidation (measured by thiobarbituric acid reactive substances; TBARS) increased in heart homogenates after ovariectomy (253%) and was additionally augmented when associated with hypertension (by 28%). Superoxide dismutase and catalase activities were similar in both hypertensive groups. Hypertension enhanced glutathione peroxidase activity (75%), but the association with ovariectomy prevented this change. Total radical trapping antioxidant potential (TRAP) decreased in hypertensive rats (34%) and was recovered when associated with ovariectomy. However, this adaptation seems not to be sufficient to avoid the increased oxidative damage in ovariectomized hypertensive animals. These results suggest a protective role for physiological ovarian hormones in the cardiac oxidative stress induced by 2K1C hypertension.

Calpain translocation and activation as pharmacological targets during myocardial ischemia/reperfusion.

Calpains contribute to reperfusion-induced myocardial cell death. However, it remains controversial whether its activation occurs during ischemia or reperfusion. We investigated the regulation and time-course of calpain activation secondary to transient ischemia and the efficacy of its inhibition at reperfusion as a therapeutic strategy to limit infarct size. In isolated rat hearts (Sprague-Dawley), ischemia induced a time-dependent translocation of m-calpain to the membrane that was not associated with calpain activation as assessed by proteolysis of its substrate alpha-fodrin. Translocation of calpain was dependent on Ca(2+) entry through reverse mode Na(+)/Ca(2+)-exchange and was independent of acidosis. Calpain activation occurred during reperfusion, but only after intracellular pH (pHi) normalization, and was not prevented by inhibiting its translocation during ischemia with methyl-beta-cyclodextrin. The intravenous infusion of MDL-28170 in an in vivo rat model with transient coronary occlusion during the first minutes of reperfusion resulted in a reduction of infarct size (43.9+/-3.9% vs. 60.2+/-4.7, P=0.046, n=18) and alpha-fodrin degradation. These results suggest that (1) Ca(2+)-induced calpain translocation to the membrane during ischemia is independent of its activation, (2) intracellular acidosis inhibits calpain activation during ischemia and pHi normalization allows activation upon reperfusion, and (3) calpain inhibition at the time of reperfusion appears as a potentially useful strategy to limit infarct size.

Mineralocorticoid receptor blockade improves vasomotor dysfunction and vascular oxidative stress early after myocardial infarction.

Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholine-induced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium-independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin-converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22(phox) were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability.

Effects of inducible nitric oxide synthase inhibition on the rat tail vascular bed reactivity three days after myocardium infarction.

The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascular beds from Wistar rats 3 days after coronary artery ligation (CAL) and sham-operated animals (SHAM). Rats were treated with the iNOS inhibitor S-methylisothiourea sulfate (SMT), 5 mg Kg day, i.p. or placebo. Concentration of plasma nitrite/nitrate (NOx) and the expression of iNOS mRNA in tail arteries were evaluated. The CAL group showed increased maximal vasoconstrictor response to phenylephrine (SHAM= 241 +/- 8; CAL= 288 +/- 13 mm Hg, P < 0.05) and SMT treatment normalized this effect (CAL-SMT = 253 +/- 7 mm Hg, P < 0.05). The sensitivity to acetylcholine was reduced in the CAL group, but SMT treatment did not alter this response. The plasma NOx and iNOS mRNA expression in tail arteries were increased in CAL rats. SMT treatment reduced the plasma NOx in the CAL group and the arterial expression of iNOS mRNA in SHAM and CAL group. In conclusion, iNOS inhibition prevented the increased phenylephrine reactivity in rat caudal vascular beds 3 days after myocardial infarction.

Differences in tail vascular bed reactivity in rats with and without heart failure following myocardial infarction.

Myocardial infarction (MI) was induced in rats by coronary ligation to compare changes in vascular reactivity from animals that developed heart failure (InfHF) with those that did not (Inf). Infarct size was similar in both groups. In vitro preparations of tail vascular bed were used to investigate the vascular responses to acetylcholine, sodium nitroprusside, and phenylephrine. Acetylcholine-induced relaxation was impaired in the Inf group (53 +/- 2%, n = 6) when compared with Sham (80 +/- 2%, n = 6, P < 0.05). The maximal response (E(max)) to phenylephrine increased in the Inf group (423 +/- 10 mm Hg, n = 9, P < 0.01) and decreased in InfHF (279 +/- 10 mm Hg, n = 7, P < 0.05) when compared with Sham (319 +/- 11 mm Hg, n = 8). Regardless of endothelial integrity, E(max) to phenylephrine increased in the Inf, nitro-l-arginine methyl ester, and indomethacin groups. An increased release of a prostanoid vasodilator was detected in the Inf group. Differently, the InfHF group presented a reduction of the E(max) to phenylephrine and an increment of nitric oxide release. This study demonstrates that MI without heart failure impairs endothelium-dependent relaxation and increases the reactivity to phenylephrine. This increase seems to involve a muscular component. The endothelium participates with an increased release of a vasodilator prostanoid, possibly to compensate the increased smooth muscle response. When heart failure follows MI, the reactivity to phenylephrine decreases, possibly due to an increased nitric oxide release.