Seasonal variation of vitamin D among healthy adult men in a subtropical region.

OBJECTIVE: To evaluate seasonal variation of 25(OH)vitamin D [25(OH)D3] levels, and factors associated with it, in healthy adult men, who exercised outdoors for 50 min., at least twice a week, from 10AM to 4PM, in a Brazilian semitropical region. METHODS: Blood samples were collected at the end of each season for 25(OH)D3, measured by liquid chromatography with tandem mass spectrometry. Ultraviolet irradiation was estimated by radiometer, calculating the daily photobiological response to vitamin D synthesis in human skin (D-VitD). The prevalence of 25(OH)D3 <20ng/mL changed with the seasons (p=0.000): 8.7% (n=6/69), 1.5% (n=1/66), 0 (n=0/64), and 21.7% (n=13/60), respectively, at the end of winter, spring, summer, and autumn. The prevalence, adjusted for multiple comparisons, was higher in winter than summer (p=0.026), and in autumn than spring (p=0.001) and summer (p=0.000). There were no associations of 25(OH) D3 levels with BMI (p=0.207), body fat (p=0.064), and phototype (p=0.485), in univariate analysis. It was associated with D-VitD in the 30 days before blood sampling (p=0.000), after adjustment to body fat. The prevalence of 25(OH)D3 <30ng/mL varied seasonally (p=0.000): 69.6% (n=48/69), 68.2% (n=45/66), 43.8% (n=28/64), and 88.4% (n=53/60), respectively, in winter, spring, summer, and autumn. CONCLUSIONS: In a Brazilian subtropical region, a seasonal variation in 25(OH)D3 was observed in healthy adult males, although they spent at least 50 min outdoors twice a week, wearing shorts and T-shirts. 25(OH)D3 <20ng/mL was 21.7% in autumn; D-vitD 30 days prior to blood sampling was the only factor independently associated with 25(OH)D3 levels.

Seasonal variation of vitamin D among healthy adult men in a subtropical region

SUMMARY OBJECTIVE: To evaluate seasonal variation of 25(OH)vitamin D [25(OH)D3] levels, and factors associated with it, in healthy adult men, who exercised outdoors for 50 min., at least twice a week, from 10AM to 4PM, in a Brazilian semitropical region. METHODS: Blood samples were collected at the end of each season for 25(OH)D3, measured by liquid chromatography with tandem mass spectrometry. Ultraviolet irradiation was estimated by radiometer, calculating the daily photobiological response to vitamin D synthesis in human skin (D-VitD). The prevalence of 25(OH)D3 <20ng/mL changed with the seasons (p=0.000): 8.7% (n=6/69), 1.5% (n=1/66), 0 (n=0/64), and 21.7% (n=13/60), respectively, at the end of winter, spring, summer, and autumn. The prevalence, adjusted for multiple comparisons, was higher in winter than summer (p=0.026), and in autumn than spring (p=0.001) and summer (p=0.000). There were no associations of 25(OH) D3 levels with BMI (p=0.207), body fat (p=0.064), and phototype (p=0.485), in univariate analysis. It was associated with D-VitD in the 30 days before blood sampling (p=0.000), after adjustment to body fat. The prevalence of 25(OH)D3 <30ng/mL varied seasonally (p=0.000): 69.6% (n=48/69), 68.2% (n=45/66), 43.8% (n=28/64), and 88.4% (n=53/60), respectively, in winter, spring, summer, and autumn. CONCLUSIONS: In a Brazilian subtropical region, a seasonal variation in 25(OH)D3 was observed in healthy adult males, although they spent at least 50 min outdoors twice a week, wearing shorts and T-shirts. 25(OH)D3 <20ng/mL was 21.7% in autumn; D-vitD 30 days prior to blood sampling was the only factor independently associated with 25(OH)D3 levels.

RESUMO OBJETIVOS: Avaliar a sazonalidade da 25(OH)vitamina D3 [25(OH)D3] e fatores associados em homens adultos saudáveis, que se exercitavam ao ar livre pelo menos 50 min duas vezes por semana, das 10 às 16h, em uma região subtropical. MÉTODOS: Sangue foi colhido no fim das estações para medir 25(OH)D3, por cromatografia líquida em tandem com espectroscopia de massas. A radiação ultravioleta foi estimada por radiômetro, calculando diariamente a resposta fotobiológica para sintetizar vitamina D na pele humana (D-VitD). RESULTADOS: A prevalência de 25(OH)D3 <20ng/mL foi sazonal (p=0.000): 8.7% (n=6/69), 1.5% (n=1/66), 0% (n= 0/64), e 21.7% (n=13/60), respectivamente, no final do inverno, primavera, verão e outono. A prevalência, ajustada para comparações múltiplas, foi maior no inverno do que no verão (p=0.026) e no outono do que na primavera (p=0.001) e verão (p=0.000). A 25(OH)D3 não se associou com o índice de massa corporal (p=0.207), gordura corporal (p=0.064) ou fototipo (p=0.485), na análise univariada. Associou-se à D-VitD nos 30 dias antes da coleta de sangue (p=0.000), ajustada para gordura corporal. Houve sazonalidade na prevalência de 25(OH)D3 <30ng/mL (p=0.000): 69.6% (n=48/69), 68.2% (n=45/66), 43.8% (n=28/64), e 88.4% (n=53/60), respectivamente, no inverno, primavera, verão e outono. CONCLUSÕES: Em uma região subtropical, houve sazonalidade na 25(OH)D3 em homens adultos, saudáveis, embora se exercitassem ao ar livre pelo menos 50 minutos duas vezes por semana, usando shorts e camiseta. 25(OH)D3 <20ng/mL foi 21.7% no outono e a D-vitD 30 dias antes da coleta do sangue foi o único fator associado de modo independente à 25(OH)D3.

Estrogen-dependent effects on behavior, lipid-profile, and glycemic index of ovariectomized rats subjected to chronic restraint stress.

Stress has been shown to negatively affect the immune system, alter the body's metabolism, and play a strong role in the development of mood disorders. These effects are mainly driven through the release of hormones from the hypothalamic-pituitary-adrenal axis (HPA). Additionally, women are more likely to be affected by stress due to the estrogen fluctuation associated with their menstrual cycle. This study aims to evaluate the effect of chronic restraint stress, applied for 30 days, and estrogen replacement on behavior, glucose level, and the lipid profile of ovariectomized rats. Our results suggest that stress increases sweet food consumption in OVX females treated with estradiol (E2), but reduces consumption in animals not treated. Furthermore, stress increases locomotor activity and anxiety as assessed by the Open Field test and in the Elevated Plus Maze. Similarly, our results suggest that E2 increases anxiety in female rats under the same behavioral tests. In addition, stress reduces glucose and TC levels. Moreover, stress increase TG levels in the presence of E2 and decrease in its absence, as well as the estradiol increase TG levels in stressed groups and reduced in non-stressed groups. Our data suggest an important interaction between stress and estrogen, showing that hormonal status can induce changes in the animal's response to stress.

Sensitive HPLC-PDA determination of tamoxifen and its metabolites N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in human plasma.

A highly sensitive HPLC-UV method for the simultaneous determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in human plasma samples was developed and validated. The method employs a two step liquid-liquid extraction and a reversed phase separation on a Hypersil Gold(®) C18 column (150mm×4.6mm, 5µm) with isocratic elution. Mobile phase was a mixture of triethylammonium phosphate buffer 5mM pH 3.3 and acetonitrile (57:43, v/v). Total analytical run time was 16min. Precision assays showed CV % lower than 10.53% and accuracy in the range of 93.0-104.2%. The lower limits of quantification (0.75-8.5ngml(-1)) are adequate to measure clinically relevant concentrations in plasma samples. The method was successfully applied to 110 clinical plasma samples. Median plasma levels and interquartile range were: tamoxifen 55.77ngml(-1) (38.42-83.69ngml(-1)), N-desmethyltamoxifen 124.83ngml(-1) (86.81-204.80ngml(-1)), 4-hydroxytamoxifen 1.09ngml(-1) (0.76-1.53ngml(-1)) and endoxifen 6.18ngml(-1) (4.17-8.22ngml(-1)). The procedure has adequate analytical performance and can be employed in therapeutic drug monitoring of tamoxifen or pharmacokinetics studies.

Endoxifen levels and its association with CYP2D6 genotype and phenotype: evaluation of a southern Brazilian population under tamoxifen pharmacotherapy.

BACKGROUND: An association between CYP2D6 variation and clinical outcomes among women with breast cancer treated with tamoxifen (TAM) has been demonstrated, such that the presence of 2 functional CYP2D6 alleles was associated with better clinical outcomes. This association is mainly due to the CYP2D6-mediated hydroxylation of N-desmethyltamoxifen (NDT) to yield endoxifen (EDF), which because of its high antiestrogenic potency, is mainly responsible for the therapeutic efficacy of TAM. The aim of this study was to evaluate the relation of CYP2D6 genotyping and phenotyping with EDF levels and [NDT]/[EDF] metabolic ratio in breast cancer patients from South of Brazil under TAM therapy. METHODS: Trough blood samples were collected from 97 patients. CYP2D6 genotyping was performed with a luminex assay and calculation of genotypic activity scores. Tamoxifen and metabolites EDF, NDT, and 4-hydroxy-TAM were measured in plasma by high performance liquid chromatography with photo diode array detector. CYP2D6 phenotyping was performed by the determination of dextromethorphan (DMT) and dextrorphan (DTF) by high-performance liquid chromatography with fluorescence detection at plasma collected 3 hours after oral administration of 33 mg of DMF. Phenotypes were given according to [DMT]/[DTF] metabolic ratio. RESULTS: CYP2D6 genotyping indicated a prevalence of 4.1% poor metabolizer, 4.1% intermediate metabolizer, 49.5% extensive metabolizer slow activity, 39.2% extensive metabolizer fast activity, and 3.1% ultrarapid metabolizer. Genotype (genotypic activity scores) was significantly correlated with phenotype ([DMT]/[DTF]), with a moderate association (rs = -0.463; P < 0.001). Median plasma concentrations (nanograms per milliliter; N = 97) were TAM 57.17; 4-hydroxy-TAM 1.01; EDF 6.21; NDT 125.50. EDF levels were lower in poor metabolizers than that in extensive metabolizers (P < 0.05). Phenotype showed stronger, but still moderate, association with EDF and [NDT]/[EDF] than genotype (r = -0.507, r = 0.625, P < 0.001 versus r = 0.356, r = 0.516, P < 0.01). Phenotype accounted for 26% of the variability in EDF levels and 38% of [NDT]/[EDF], whereas genotype accounted for 12% and 27%, respectively. CONCLUSIONS: CYP2D6 genotyping and/or phenotyping could not fully predict EDF concentrations. Monitoring EDF itself could be considered during TAM therapy.

Pharmacological evaluation of Copaifera multijuga oil in rats.

CONTEXT: Copaiba oil is an oleoresin made up of resin acids and volatile compounds, and it is obtained by tapping the trunks of trees that are members of the Copaifera L. (Leguminoseae) genus and are found in tropical parts of Latin America. OBJECTIVE: This study analyzed the chemical composition of Copaifera multijuga Hayne oil and conducted preclinical trials to investigate anti-inflammatory effects and any action it may have on the central nervous system (CNS) of rats. MATERIALS AND METHODS: The chemical analysis was carried out using gas chromatography with mass spectroscopy. Anti-inflammatory activity was measured by leucocytes mobilization, by chemotaxis assay in Boyden's chamber, and by pleurisy model in rats. CNS effect was determined by plus maze and open-field assays. The statistical test applied was analysis of variance (ANOVA) followed by Tukey's test or ANOVA followed by Duncan's test. RESULTS: The oil was composed of sesquiterpenes with the predominance of ß-caryophyllene (36.0%), followed by α-copaene (18.8%), ß-bisabolene (8.5%), and α-trans-bergamotene (7.0%). Data demonstrated that at 100 and 200 mg/kg doses and at a concentration of 200 µl/ml copaiba essential oil presented anti-inflammatory effects both in vivo and in vitro based on reduced leukocyte migration to the rats' pleural cavity and to the chemotactic agent lipopolysaccharide solution, respectively. During the experiments investigating CNS effects, locomotive and exploratory activities were reduced and the animals' anxiety increased at 100 and 200 mg/kg. CONCLUSION: The results obtained suggest that copaiba oil has an interesting anti-inflammatory effect and important effect on the CNS.

Oxidative stress and DNA damage in older adults that do exercises regularly.

OBJECTIVES: Free radicals may damage lipids, proteins and DNA, which may lead to critical diseases in the aging. This work evaluated levels of malondialdehyde (MDA), glutathione peroxidase (GPx) and DNA damage by comet assay (SCGE) in older adults that do exercises regularly. DESIGN AND METHODS: 110 females, aged 66.3+/-8 years were divided into sedentary (n=54), walking (n=36) and muscle building (n=20) groups. Levels of MDA, GPx and SCGE were measured in venous blood before and after exercise. RESULTS: MDA levels were higher (P<0.005) and GPx levels were lower (P<0.005) in active groups than in sedentary group. SCGE index after physical activity was greater than at baseline (muscle building: P=0.004; walking: P=0.002). CONCLUSIONS: Exercise reduces the diseases risk, but may promote the production of free radicals. It remains unclear whether cell adaptations responsible for health benefits are associated with such events. However we may suggest the existence of a different biochemical pattern for older adults that do exercise regularly.