1, 25-(OH)2-VitD3 attenuates renal tubulointerstitial fibrosis in diabetic kidney disease by inhibiting Snail1-SMAD3/SMAD4 complex formation / 细胞与分子免疫学杂志

Objective To investigate the effect of 1, 25-(OH)2-VitD3 (VitD3) on renal tubuleinterstitial fibrosis in diabetic kidney disease. Methods NRK-52E renal tubular epithelial cells were divided into control group (5.5 mmol/L glucose medium treatment), high glucose group (25 mmol/L glucose medium treatment) and high glucose with added VitD3 group (25 mmol/L glucose medium combined with 10-8 mmol/L VitD3). The mRNA and protein expression of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in NRK-52E cells were detected by real-time quantitative PCR and Western blot analysis respectively. The expression and localization of Snail1, SMAD3 and SMAD4 were detected by immunofluorescence cytochemical staining. The binding of Snail1 with SMAD3/SMAD4 complex to the promoter of Coxsackie-adenovirus receptor (CAR) was detected by chromatin immunoprecipitation. The interaction among Snail1, SMAD3/SMAD4 and E-cadherin were detected by luciferase assay. Small interfering RNA (siRNA) was used to inhibit the expression of Snail1 and SMAD4, and the expression of mRNA of E-cadherin was detected by real-time quantitative PCR. SD rats were randomly divided into control group, DKD group and VitD3-treated group. DKD model was established by injection of streptozotocin (STZ) in DKD group and VitD3-treated group. After DKD modeling, VitD3-treated group was given VitD3 (60 ng/kg) intragastric administration. Control group and DKD group were given normal saline intragastric administration. In the DKD group and VitD3-treated group, insulin (1-2 U/kg) was injected subcutaneously to control blood glucose for 8 weeks. The mRNA and protein levels of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in renal tissues were detected by real-time quantitative PCR and Western blot analysis respectively. Immunohistochemistry was used to detect the expression and localization of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in renal tissue. Results Compared with the control group, the mRNA and protein expressions of Snail1, SMAD3, SMAD4 and α-SMA in NRK-52E cells cultured with high glucose and in DKD renal tissues were up-regulated, while E-cadherin expression was down-regulated. After the intervention of VitD3, the expression levels of Snail1, SMAD3, SMAD4, α-SMA and E-cadherin in the DKD model improved to be close to those in the control group. Chromatin immunoprecipitation showed that Snail1 and SMAD3/SMAD4 bound to CAR promoter IV, while VitD3 prevented Snail1 and SMAD3/SMAD4 from binding to CAR promoter IV. Luciferase assay confirmed the interaction among Snail1, SMAD3/SMAD4 and E-cadherin. After the mRNA of Snail1 and SMAD4 was inhibited by siRNA, the expression of E-cadherin induced by high glucose was up-regulated. Conclusion VitD3 could inhibit the formation of Snail1-SMAD3/SMAD4 complex and alleviate the renal tubulointerstitial fibrosis in DKD.

Vitamin D supplementation during pregnancy to prevent vitamin D deficiency in newborns: a systematic review and meta-analysis / Suplementação de vitamina D durante a gravidez para a prevenção da deficiência de vitamina D em recém-nascidos: uma revisão sistemática e meta-análise

Abstract Objectives: to assess the effects of vitamin D supplementation during pregnancy on the outcomes of vitamin D concentration in newborns, length at birth, overall health (Apgar), birth weight and maternal vitamin D concentration after childbirth. Methods: this research was conducted in the electronic databases of MEDLINE, LILACS, EMBASE and Cochrane Library until December 2020, using the terms "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" and their synonyms. Randomized controlled trials were searched by evaluating the effects of maternal vitamin D supplementation in neonates. The data was analyzed on RevMan 5.4 software and the quality of evidence on GRADE. Results: the newborn's overall health condition was presented as Apgar, with a mean difference (MD) of 0.15 (CI95%=0.06-0.25; p=0.002; I2=0%, two studies, 648 participants, moderate quality evidence) at the first minute and 0.11 (CI95%=0.04-0.17; p=0.001; I2=0%, two studies, 648 participants, moderate quality evidence) at the fifth minute. Significant effects were also presented at the length at birth considering any supplemented dose (MD=0.19; CI95%=0.08-0.30; p=0.0010; I2=0%, 1452 participants, low quality evidence) and birth weight in doses higher than 4000IU/day (MD=257.05 (CI95%=137.81-376.29; p<0.0001; I2=14%, 176 participants, moderate quality evidence). Conclusion: vitamin D supplementation during pregnancy improves serum 25 (OH) D concentration and suggests positive effects on overall health condition, length at birth and birth weight. PROSPERO CRD42017073292.

Resumo Objetivos: avaliar os efeitos da suplementação materna de vitamina D durante a gravidez nos desfechos concentração de vitamina D no recém-nascido, comprimento ao nascer, estado geral de saúde (Apgar), peso ao nascer e concentração de vitamina D materna após o nascimento. Métodos: a pesquisa foi conduzida nas bases de dados eletrônicas MEDLINE, LILACS, EMBASE e Cochrane Library até dezembro de 2020, utilizando os termos "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" e seus sinônimos. Pesquisou-se por ensaios clínicos randomizados avaliando os efeitos da suplementação materna de vitamina D no neonato. Os dados foram analisados pelo software RevMan 5.4 e a avaliação da qualidade das evidências pelo GRADE. Resultados: o estado geral de saúde do recém-nascido foi apresentado como Apgar, com uma diferença de média (DM) de 0,15 (IC95%=0,06-0,25; p=0,002; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para o teste no primeiro minuto e 0,11 (IC95%=0,04-0,17; p=0,001; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para quinto minuto. Efeitos significativos também foram apresentados para o comprimento ao nascer em qualquer dose suplementada (DM=0,19 (IC95%=0,08-0,30; p=0,0010; I2=0%, 1452 participantes, evidência de baixa qualidade) e peso ao nascer em doses maiores que 4000UI/dia (DM=257,05 (IC95%=137,81-376,29; p<0,0001; I2=14%, 176 participantes, evidência de qualidade moderada). Conclusão: a suplementação de vitamina D durante a gravidez melhora a concentração sérica de 25 (OH)D e sugere apresentar efeitos positivos no estado geral de saúde, comprimento ao nascer e peso ao nascer. PROSPERO CRD42017073292.

Does vitamin D play a role in the management of Covid-19 in Brazil?

ABSTRACT The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. Based on literature review, we highlight the findings regarding the protective role of vitamin D for infectious diseases of the respiratory system. However, randomized controlled trials are currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of high insolation. Authors recommend ecological, epidemiological and randomized controlled trials studies to verify this hypothesis.

Suplementação de vitamina D e seus análogos para tratamento de disfunção endotelial e doenças cardiovasculares / Supplementation with vitamin D and its analogs for treatment of endothelial dysfunction and cardiovascular disease

Resumo A vitamina D (1,25-dihidroxicolecalciferol) é um pró-hormônio que tem despertado a atenção de pesquisadores após estudos demonstrarem que seus efeitos não estão restritos ao metabolismo ósseo. Assim, a presente revisão sintetiza os achados mais recentes e discute a utilidade da prescrição de vitamina D e seus análogos no tratamento e prevenção de afecções cardiovasculares e disfunção endotelial. Este trabalho consiste em uma revisão narrativa da literatura feita a partir da seleção de artigos publicados no período de 2012 a 2019. Estudos demonstraram efeitos benéficos da vitamina D3 e seus análogos sobre a função endotelial; no entanto, tais resultados mostram-se controversos, visto que pesquisas com maior amostragem e duração não encontraram redução na morbimortalidade ou nos fatores de risco cardiovascular após o uso de tais substâncias. Frente ao estado atual da arte, não existe embasamento científico claro para suplementação de vitamina D ou seus análogos para tratamento de disfunção endotelial ou doenças cardiovasculares.

Abstract Vitamin D (1,25-dihydroxycolecalciferol) is a prohormone that has attracted the interest of researchers since studies have shown that its effects are not restricted to bone metabolism. Thus, the present review summarizes the most recent findings and discusses the usefulness of prescribing vitamin D and its analogues for treatment and prevention of cardiovascular disorders and endothelial dysfunction. The paper constitutes a narrative review of the literature, selecting articles published from 2012 to 2019. Studies have shown that vitamin D3 and its analogues have beneficial effects on endothelial function, but these results are controversial, since research with larger samples and of longer duration found no reduction in morbidity and mortality or cardiovascular risk factors after use of these substances. Given the current state of the art, there is no clear scientific basis for supplementation with vitamin D or its analogues for treatment of endothelial dysfunction or cardiovascular disease.

The effect of vitamin D on cognitive functions in young female patients: a prospective controlled study using the Montreal Cognitive Assessment / O efeito da vitamina D nas funções cognitivas em pacientes jovens do sexo feminino: um estudo prospectivo controlado usando a avaliação cognitiva de Montreal

ABSTRACT Aim: Our aim was to determine whether there is a relationship between vitamin D [25(OH)D] and cognitive functioning in women with low 25(OH)D levels. Methods: Ninety female patients, 25-45 years of age, who attended our outpatient clinic and had 25(OH)D levels < 30 ng/mL, were included. The Montreal Cognitive Assessment (MoCA) scale was used to determine cognitive functioning; the scale is divided into seven subgroups. Patients were divided into three subgroups according to their 25(OH)D levels. After a three-month period of 25(OH) D replacement, the patients underwent a re-evaluation using the MoCA scale. Results: The total MoCA score before treatment was significantly different from the score after treatment (p < 0.05). Language and delayed recall functions were significantly different before and after treatment (p < 0.05). Conclusion: Vitamin D levels were related to cognitive functioning in our study group.

RESUMO Objetivo: Nosso objetivo foi determinar se existe uma relação entre a vitamina D [25(OH)D] e o funcionamento cognitivo em mulheres com baixos níveis de 25(OH)D. Métodos: Noventa pacientes do sexo feminino (25-45 anos de idade) que se apresentaram ao nosso ambulatório e tinham níveis de 25(OH)D <30 ng/mL foram incluídas. A escala de avaliação cognitiva de Montreal (MoCA) foi usada para determinar o funcionamento cognitivo; a escala é dividida em sete subgrupos. As pacientes foram divididas em três subgrupos de acordo com seus níveis de 25(OH)D. Após um período de três meses de reposição de 25(OH)D, as pacientes foram submetidas a uma reavaliação de acordo com a escala MoCA. Resultados: O escore total da MoCA antes do tratamento foi significativamente diferente do escore após o tratamento (p <0,05). As funções de idioma e recordação atrasada foram mais significativamente diferentes entre antes e depois do tratamento (p <0,05). Conclusão: O nível de vitamina D foi relacionado ao funcionamento cognitivo em nosso grupo de estudo.

The effect of vitamin D on sperm motility and the underlying mechanism / 亚洲男科学杂志(英文版)

Vitamin D deficiency is a common health issue around the world. We therefore evaluated the associations of semen quality with both serum and seminal plasma vitamin D levels and studied the mechanisms underlying these by incubating spermatozoa with 1,25(OH)2D In vitro. Two hundred and twenty-two men were included in our study. Vitamin D was detected using an electrochemiluminescence method. Spermatozoa used for In vitro experiments were isolated by density gradient centrifugation. Positive relationships of serum 25(OH)D with semen volume and seminal plasma fructose were identified. Seminal plasma 25(OH)D level showed no relationship with serum 25(OH)D level, while it was inversely associated with sperm concentration and positively correlated with semen volume and sperm kinetic values. In vitro, sperm kinetic parameters increased after incubation with 1,25(OH)2D, especially upon incubation for 30 min with it at a concentration of 0.1 nmol l-1. Under these incubation conditions, the upward migration of spermatozoa increased remarkably with increasing adenosine triphosphate (ATP) concentration. The concentration of cyclic adenosine monophosphate (cAMP) and the activity of protein kinase A (PKA) were both elevated, and the PKA inhibitor, N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89) reversed the increase of ATP production. The concentrations of cytoplasmic calcium ions and nicotinamide adenine dinucleotide (NADH) were both enhanced, while mitochondrial calcium uniporter (MCU) inhibitor, Ruthenium 360 (Ru360) did not reverse the increase of ATP production. Therefore, seminal plasma vitamin D may be involved in regulating sperm motility, and 1,25(OH)2D may enhance sperm motility by promoting the synthesis of ATP both through the cAMP/PKA pathway and the increase in intracellular calcium ions.

Use of vitamin D and infection in patients with chronic kidney disease / Uso de la vitamina D e infección en pacientes con enfermedad renal crónica / Uso da vitamina D e infecção em pacientes com doença renal crônica

ABSTRACT Objective: To evaluate the effectiveness of vitamin D supplementation as protection factor against infection of patients with chronic kidney disease on conservative treatment. Method: Retrospective cohort study carried out between 2013 and 2016 in the Conservative Treatment Outpatient Clinics (Ambulatório de Tratamento Conservador) of the Hypertension and Kidney Hospital (Hospital do Rim e Hipertensão) of the Universidade Federal de São Paulo. Data on sociodemographic factors, comorbidity, infection episodes and use or nonuse of vitamin D supplementation for at least 6 months were collected from medical records. The primary outcomes considered in both groups were: presence or absence of infection anywhere on the body (bloodstream, urinary, respiratory and surgical sites). Results: A total of 263 patients were included and those who received (n=43) vitamin D had 59% less chance of developing infections (OR=0.41; 95%CI; 0.15-0.99), when compared to those who did not receive. Conclusion: Vitamin D supplementation was a protective factor against infections of all causes.

RESUMEN Objetivo: evaluar la efectividad de la suplementación de vitamina D en pacientes con enfermedad renal crónica en tratamiento conservador como factor de protección contra infecciones. Método: Estudio de Cohorte retrospectiva realizado entre 2013 y 2016 en el Ambulatorio de Tratamiento Conservador del Hospital do Rim e Hipertensão da Universidade Federal São Paulo. Se recogieron de los prontuarios los datos sociodemográficos, de comorbilidad, episodios de infección, en uso o no de suplementación de vitamina D por lo menos 6 meses. Los resultados primarios considerados en los dos grupos fueron: la presencia o no de infección en cualquier sitio: urinario, respiratorio, corriente sanguínea y sitio quirúrgico. Resultados: Se incluyeron 263 pacientes y los que recibieron (n = 43) vitamina D tenían un 59% menos de posibilidades de desarrollar infección (OR = 0,41, IC95% 0,15-0,99), en comparación con los que no recibieron. Conclusión: La suplementación de vitamina D fue factor de protección contra infecciones de todas las causas.

RESUMO Objetivo: avaliar a efetividade da suplementação de vitamina D em pacientes com doença renal crônica em tratamento conservador como fator de proteção contra infecções. Método: Estudo de Coorte retrospectiva realizado entre 2013 e 2016 no Ambulatório de Tratamento Conservador do Hospital do Rim e Hipertensão da Universidade Federal de São Paulo. Foram coletados dos prontuários os dados sociodemográficos, de comorbidade, episódios de infecção, em uso ou não de suplementação de vitamina D por no mínimo 6 meses. Os desfechos primários considerados nos dois grupos foram: a presença ou não de infecção em qualquer sítio: urinário, respiratório, corrente sanguínea e sítio cirúrgico. Resultados: Foram incluídos 263 pacientes e os que receberam (n=43) vitamina D tiveram 59% menos chance de desenvolver infecção (OR=0,41; IC95% 0,15-0,99), quando comparados aos que não receberam. Conclusão: A suplementação de vitamina D foi fator de proteção contra infecções de todas as causas.

Atopic dermatitis and vitamin D: facts and controversies / Dermatite atopica e vitamina D: fatos e controversias

Patients with atopic dermatitis have genetically determined risk factors that affect the barrier function of the skin and immune responses that interact with environmental factors. Clinically, this results in an intensely pruriginous and inflamed skin that allows the penetration of irritants and allergens and predisposes patients to colonization and infection by microorganisms. Among the various etiological factors responsible for the increased prevalence of atopic diseases over the past few decades, the role of vitamin D has been emphasized. As the pathogenesis of AD involves a complex interplay of epidermal barrier dysfunction and dysregulated immune response, and vitamin D is involved in both processes, it is reasonable to expect that vitamin D's status could be associated with atopic dermatitis' risk or severity. Such association is suggested by epidemiological and experimental data. In this review, we will discuss the evidence for and against this controversial relationship, emphasizing the possible etiopathogenic mechanisms involved.

Pacientes com dermatite atópica têm fatores de risco geneticamente determinados que afetam a função de barreira da pele e as respostas imunes, as quais interagem com fatores ambientais. Clinicamente, isso resulta em uma pele intensamente pruriginosa, inflamada, que permite a penetração de irritantes e alérgenos e predispõe os pacientes à colonização e à infecção por micro-organismos. Dentre os diversos fatores etiológicos responsáveis pelo aumento da prevalência de doenças atópicas nas últimas décadas, o papel da vitamina D tem ganhado destaque. Uma vez que a patogênese da dermatite envolve uma interação complexa da disfunção da barreira epidérmica e desregulação da resposta imune - e a vitamina D está envolvida em ambos os processos-, é razoável esperar que a vitamina D esteja associada ao risco ou à gravidade da dermatite atópica. Tal associação é sugerida por dados epidemiológicos e experimentais. Nessa revisão, serão abordadas as evidências favoráveis e contrárias a essa polêmica relação, enfatizando os possíveis mecanismos etiopatogênicos envolvidos.

Vitamin D enhances IL-1 beta secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis [MTB], the bacterium responsible for tuberculosis [TB], has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages [hMDMs] from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100 nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin [IL]-1 beta and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-alpha [tumor necrosis factor-alpha] and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth

Can vitamin D suppress endothelial cells apoptosis in multiple sclerosis patients?

Multiple sclerosis [MS] is an autoimmune disease of central nerves system, in which neurological disabilities occur in young adults. Despite increasing number of studies on MS, some aspects of this disorder are still unclear. In the previous studies, it has been proven that there is direct relation between MS incidence and vitamin D deficiency. Thereby, strong evidence in MS pathogenesis suggests that endothelial cells [EC] could be harmed in MS. In addition, functional changes in EC and macrovascular injuries lead blood-brain barrier disruption in MS. Current study is the first investigation to elucidate positive influences of vitamin D against EC apoptosis in MS. Human umbilical vein endothelial cells [HUVECs] were cultured and then treated with sera from patients with active MS [in relapse] and sera from healthy volunteer participants as control group [each group n=15]. 3-[4,5-dimethylthiazol-2-yl]-5- [3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt [MTS] assay for cell surveillance and cell-death detection kit for evaluating apoptosis were used in this study. There was a significant decrease in apoptosis rate by the serum of patients, just when 1,25[OH][2]D[3] applied before treating HUVECs with sera from active MS [in relapse]. Furthermore, the cells surveillance increased markedly with the presence of 1,25[OH][2]D[3] in culture, too. With regard to increment in EC apoptosis rate, which treated by the sera from MS patients and decrement in apoptosis rate by the presence of vitamin D in culture media, it could be proposed that vitamin D pre-treatment can be used for MS patients, due to its beneficial effects on protecting EC apoptosis

Vitamina D y cáncer: acción antineoplásica de la 1α, 25(OH)2 -vitamina D3 / Vitamin D and cancer: antineoplastic effects of 1α,25(OH)2-vitamin D3

La forma hormonalmente activa de la vitamina D, 1α,25(OH)2-vitamina D3 (1α,25(OH)2D3), además de desempeñar un rol crucial en el mantenimiento de la homeostasis de calcio en el cuerpo, también regula el crecimiento y la diferenciación de diferentes tipos celulares, incluyendo células cancerosas. Actualmente hay numerosos estudios que investigan los efectos de la hormona en estas células, debido al interés en el uso terapéutico del 1α,25(OH)2D3 y de análogos con menor actividad calcémica para el tratamiento o prevención del cáncer. En este trabajo de revisión se describe el sistema endocrino de la vitamina D, su mecanismo de acción, su acción antineoplásica y se provee información sobre los últimos avances en el estudio de nuevos análogos de la hormona con menos actividad calcémica para el tratamiento del cáncer.

The hormonal form of vitamin D, 1α,25(OH)2-vitamin D3 (1α,25(OH)2D3), in addition of playing a central role in the control of calcium homeostasis in the body, regulates the growth and differentiation of different cell types, including cancer cells. At present several epidemiologic and clinical studies investigate the effect of the hormone in these cells due to the interest in the therapeutic use of 1α,25(OH)2D3 and analogues with less calcemic activity for prevention or treatment of cancer. This review describes vitamin D endocrine system, its mechanism of action, its antineoplastic activity and provides information about the latest advances in the study of new hormone analogues with less calcemic activity for cancer treatment.

Pauta de vitamina D / Guidelines on vitmanin D

La revisión de la recomendación actual sobre la indicación de vitamina D en los lactantes ha sido realizada por un grupo técnico interdisciplinario integrado por el Comité de Nutrición de la SUP y el Programa Nacional de Salud de la Niñez del MSP. Esta revisión fue motivada por los cambios recientes en las recomendaciones nutricionales realizadas en otros países, como es el caso de EEUU. Uruguay presenta características diferentes en cuanto a ubicación geográfica, tipo de alimentación y disponibilidad de alimentos fortificados con vitamina D. Estos factores fueron analizados para adaptar las recomendaciones y elaborar el presente documento consensuado sobre la suplementación de vitamina D para los niños

Influência da vitamina D na atividade osteoclástica em um modelo de cultura de órgãos ósseos / Influence of vitamin D on osteoclastic activity in a bone organ culture model

INTRODUÇÃO: A remodelação óssea é regulada por várias citocinas e hormônios, como a vitamina D3. Essa vitamina, em particular, regula positiva e negativamente a expressão do ligante do receptor ativador do fator nuclear kappa-B (RANKL) e da osteoprotegerina (OPG), respectivamente, e é usada como um indutor da formação de osteoclastos in vitro. OBJETIVO: Estudar o efeito da vitamina D (VitD) sobre a atividade osteoclástica em cultura de calvárias. MATERIAL E MÉTODO: Fragmentos de calvária de camundongos foram cultivados com meio básico (controle) ou com meio contendo VitD (10 nM: baixa dose; 100 nM: alta dose). Após os intervalos de 24, 48 e 72 horas, o meio de cultura foi coletado para dosagem de cálcio e os fragmentos foram fixados para análise em microscopia confocal. RESULTADOS: Observou-se que a adição de VitD nas duas dosagens promoveu aumento nos níveis de cálcio no meio, porém só foram encontradas diferenças estatisticamente significativas entre alta e baixa dose no intervalo de 24 horas. Na microscopia, foram observadas áreas de desmineralização mais amplas nos fragmentos de calvária cultivados com altas doses de VitD. CONCLUSÃO: A VitD promove aumento da atividade osteoclástica in vitro, de modo concentração-efeito.

INTRODUCTION: Bone remodeling is controlled by various cytokines and hormones, such as vitamin D3, which regulates receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression levels positively and negatively. It is also used as an inducer of osteoclast formation in vitro. OBJECTIVE: To evaluate the effect of vitamin D (VitD) on osteoclastic activity in cultured calvariae. MATERIAL AND METHOD: Fragments of mice calvaria were cultured in basic medium (control) or VitD-containing medium (10 nM: low dose; 100 nM: high dose). After intervals of 24, 48 and 72 hours, the culture medium was collected for calcium measurement and the fragments were fixed for confocal microscopy. RESULTS: It was observed that the addition of vitamin D in both concentrations promoted an increase of calcium levels in the medium. Nonetheless, statistically significant differences between high and low doses were detected only in the 24-hour interval. In the microscopic analysis, areas of demineralization were more extensive among calvariae cultured with high doses of VitD. CONCLUSION: VitD increases osteoclastic activity in vitro in a dose-dependent effect.

A vitamina D,em doses elevadas,diminui quedas em idosos

Doses de 700 UI a 1.000 UI por dia de vitamina D (seja na forma de calcitriol ou colecalciferol) impedem uma queda adicional para cada 11 pacientes idosos que as tomam regularmente. Fórmulas com doses menores não são eficazes. Considerando seu baixo custo, disponibilidade adequada e poucos efeitos colaterais, a vitamina D (com ou sem cálcio) deve ser um suplemento regular em pacientes com mais de 65 anos de idade, uma vez que aproximadamente um em cada três idosos sofre quedas a cada ano.Nível de evidência: 1a = revisão sistemática de ensaios clínicos aleatórios controlados com metanálise.

Effect of menopause and renal function on vitamin D status in Iranian women

The effects of menopause and renal function on serum parameters of the vitamin D-endocrine system were studied in a cross-sectional sample of 676 healthy women aged 20-74 years in Shiraz. Low serum 25-hydroxyvitamin D [25-OHD] was found in 52.9% of the women. Serum parathyroid hormone [PTH] increased significantly over the age span in premenopausal women [r= 0.13, P= 0.02]. In premenopausal and postmenopausal women, serum levels of 25-OHD, phosphorus and calcium were stable across the age span. There was no significant correlation between creatinine clearance or serum PTH [r= -0.016, P= 0.66] and 25-OHD [r= 0.012, P= 0.74]. The high prevalence of vitamin D deficiency warrants consideration of dietary supplementation

Differential Effect of Vitamin K and Vitamin D Supplementation on Bone Mass in Young Rats Fed Normal or Low Calcium Diet

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25microgram/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.

La vitamina D induce la proliferación de células en cultivo del endometrio de rata / Vitamin D induces proliferation in rat endometrium cultured cells

Objetivo. Estudiar el efecto de 1,25-dihydroxycholecalciferol D(1,25-(OH)2D3 sobre la proliferación y muerte de las células de endometrio de la rata en cultivo. Material y métodos. Se usó la línea celular de endometrio de rata Rentro 1. El medio de incubación se suplementó con 1 por ciento de suero bovino fetal inactivado y previamente tratado con carbón para eliminar las hormonas esteroides. Las monocapas de células fueron mantenidas en presencia o ausencia de 1,25-(OH)2D3 o 17ß-estradiol o del vehículo. Posteriormente se evaluó la proliferación celular mediante conteo en un hemocitómetro, utilizando azul tripano 0.4 por ciento y se analizó la fase de síntesis de ADN por citofluorometría fe flujo. La muerte celular fue determinada por el análisis de la integridad del ADN genómico en geles de agarosa y tinción con bromuro de etidio. Resultados. Las células en presencia de 1 por ciento de suero bovina fetal sin hormonas esteroides en el medio de cultivo, estimuló su crecimiento de las mismas. Por otro lado, las células Rentro 1 no respondieron a la estimulación con 17ß-estradiol y sí al 1,25-(OH)2D3, lo que confirmó la ausencia del receptor de estrógenos en estas células y demostró la capacidad de esta línea celular para responder al 1,25-(OH)2D3. Por último, se encontró que a diferencia de otros tipos celulares, las células Rentro 1 no sufrieron daño a nivel del ADN (apoptosis) con el 1,25-(OH)2D3. Conclusiones. 1) El 1,25-(OH)2D3 promovió la proliferación de las células Rentro 1 de manera independiente de la dosis e independiente de la presencia del estímulo estrogénico; 2) el incremento en el número de células estuvo en relación con la activación de la fase de síntesis de ADN del ciclo celular; 3) la presencia de esta hormona en el cultivo celular no indujo la muerte celular no indujo la muerte celular por apoptosis