Effect of Vitamin D3 to Platelet Activation Mediated by Tumor Cell Culture Medium / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of vitamin D3 to platelet activation by tumor cell culture medium.@*METHODS@#The peripheral blood platelets of BALB/c mice were isolated. The platelets were activated in 4T1 culture fluid for 24 h. The platelets were divided into 7 groups: control group, activation group, 1 nmol/L vitamin D3 group, 10 nmol/L vitamin D3 group, 50 nmol/L vitamin D3 group, 100 nmol/L vitamin D3 group, and positive drug (0.1 μmol/L eptifibatide) group. CCK-8 assay was used to detect the platelet proliferation at 24, 48 and 72 h. Flow cytometry was used to detect the expression of CD61 and CD62p and receptor for advanced glycation end products (RAGE) at 24, 48 and 72 h. ELISA was used to detect the level of platelet-endothelial cell adhesion molecule-1 (PECAM-1) at 24, 48 and 72 h.@*RESULTS@#The CD41@*CONCLUSION@#Vitamin D3 shows antiplatelet effect and can inhibit platelet proliferation and activation.

Effect of vitamin D3 supplementation on 25 OHD plasma levels in the presence of VDR gene polymorphisms / Efecto de la suplementación con vitamina D3 en los niveles plasmáticos de 25 OHD, en presencia de polimorfismos del gen VDR

The objective of this review was to investigate the effect of vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration in individuals with single-nucleotide polymorphisms in the vitamin D receptor gene. The research was conducted on 241 articles found in the PubMed, Scopus, Science Direct, and Cochrane Library databases between November and December 2018. After article screening, three randomized double-blind placebo-controlled clinical trials were identified as eligible for this review. Participants were Australian, Brazilian, and Chinese individuals, who ingested doses of vitamin D3 ranging from 2000 IU to a megadose of 200,000 IU. The presence of the BB/Bb genotype of the BsmI polymorphism and the FokI G allele caused an increase in the serum concentrations of vitamin D after supplementation. Nonetheless, the few studies on this subject are not unanimous in their results. It is possible that differences among populations, sample sizes, doses, and time of supplementation have an impact on data and outcomes.

El objetivo de esta revisión fue investigar el efecto de la suplementación con vitamina D3 sobre la concentración sérica de 25-hidroxivitamina D en individuos con los polimorfismos de un solo nucleótido en el gen del receptor de la vitamina D. La investigación se realizó en 241 artículos encontrados en las bases de datos PubMed, Scopus, Science Direct y Cochrane Library entre noviembre y diciembre de 2018. Después de la selección del artículo, se identificaron tres ensayos clínicos aleatorios, controlados con placebo, doble ciego, como elegibles para esta revisión. Los participantes fueron australianos, brasileños y chinos, quienes ingirieron dosis de vitamina D3 que iban desde las 2000 UI hasta una megadosis de 200,000 UI. La presencia del genotipo BB / Bb del polimorfismo BsmI y el alelo FokI G causó un aumento en las concentraciones séricas de vitamina D después de la suplementación. No obstante, los pocos estudios sobre este tema no son unánimes en sus resultados. Es posible que las diferencias entre poblaciones, tamaños de muestra, dosis y tiempo de suplementación tengan un impacto en los datos y resultados de la investigación.

De la osteología a la osteomiología: tres décadas de aportes originales continuos al análisis biomecánico osteomuscular / From osteology to osteo-myology: three decades of continuous, original contributions to musculoskeletal biomechanical analysis

En consonancia con la orientación tradicional de nuestras investigaciones, la Osteología está incorporando progresivamente el análisis estructural-biomecánico óseo y las interacciones músculo-esqueléticas. En este artículo se sintetizan los aportes originales del CEMFoC a la Osteología moderna en el terreno biomecánico en forma didáctica, para que el lector aprecie sus posibles aplicaciones clínicas. Los hallazgos aportaron evidencias sucesivas en apoyo de dos proposiciones fundamentales: a) los huesos deben interpretarse como estructuras resistivas, biológicamente servocontroladas ("Los huesos tienden siempre a mantener un factor de seguridad que permite al cuerpo trabajar normalmente sin fracturarse" ­ Paradigma de Utah) y b) los huesos interactúan con su entorno mecánico, determinado principalmente por las contracciones musculares, en forma subordinada al entorno metabólico ("Los huesos son lo que los músculos quieren que sean, siempre que las hormonas lo permitan"). Los avances producidos se refieren, tanto cronológica como didácticamente, al conocimiento osteológico en general y al desarrollo de recursos novedosos para el diagnóstico no invasivo de fragilidad ósea, para distinguir entre osteopenias y osteoporosis, y para discriminar entre sus etiologías 'mecánica' y 'sistémica'. Finalmente, el nuevo conocimiento se integra en la proposición de un algoritmo diagnóstico para osteopenias y osteoporosis. El espíritu general de la presentación destaca que la evaluación osteomuscular dinámicamente integrada genera un nuevo espacio de análisis personalizado de los pacientes para la atención de cualquier osteopatía fragilizante con criterio biomecánico. (AU)

In consonance with the traditional spirit of our studies, skeletal research is being progressively focused on the structural-biomechanical analysis of bone and the muscle-bone interactions. In this article, the CEMFoC's members summarize their original findings in bone biomechanics and their potential clinical applications. These findings provided evidence supporting two fundamental hypotheses, namely, A. bones constitute resistive structures, which are biologically servo-controlled ('Bones tend to maintain a safety factor which allows the body to function normally avoiding fractures' ­ the 'Utah paradigm'), and B. the interactions of bones with their mechanical environment mainly are determined by the contraction of local muscles - 'bone-muscle units'), and are subordinated to the control of the metabolic environment ('Bones are what muscles wish them to be, provided that hormones allow for it'). The achievements in the field are presented in a chronological and didactical sequence concerning the general knowledge in Osteology and the development of novel resources for non-invasive diagnosis of bone fragility, aiming to distinguish between osteopenias and osteoporosis and the 'mechanical' and 'metabolic' etiology of these conditions. Finally, the integrated new knowledge is presented as supporting for a proposed diagnostic algorithm for osteopenias and osteoporosis. In general terms, the article highlights the dynamic evaluation of the musculoskeletal system as a whole, opening a new diagnostic field for a personalized evaluation of the patients affected by a boneweakening disease, based on functional and biomechanical criteria. (AU)

Efeito da suplementação de colecalciferol nos RNA mensageiros urinários associados ao podócito em pacientes com doença renal crônica / Effect of cholecalciferol supplementation on urine podocyte-associated messenger RNAs in patients with chronic kidney disease

RESUMO Introdução: A vitamina D reduz a albuminúria em pacientes com doença renal crônica (DRC), mas o seu efeito sobre os podócitos glomerulares ainda não é claro. Objetivos: Avaliar se a suplementação de colecalciferol reduz os RNAm urinários associados ao podócito em pacientes com DRC. Métodos: Vinte e sete pacientes com DRC estágios 2 a 4 e níveis sub-ótimos de 25-hidroxi-vitamina D [25(OH)D] sérica foram tratados com colecalciferol por seis meses. Foram medidos antes e após a intervenção a 25(OH)D sérica e o RNAm urinário da nefrina, podocina, podocalixina, receptor transitório potencial do canal de cátions, subfamília C, membro 6 (TRPC6), fator A de crescimento do endotélio vascular (VEGF-A) e fator de crescimento transformador beta (TGF-β1). Resultados: A TFGe reduziu em média 4,71 mL/min/1,73 m2 (p = 0,010 vs. basal), sendo 28 ± 16 mL/min/1,73 m2 aos seis meses. Os RNAm dos produtos do podócito na urina não tiveram alteração significativa após o tratamento. Entretanto, pacientes que atingiram níveis de 25(OH)D ≥ 20 ng/mL aos 6 meses tiveram tendência de redução do RNAm da nefrina e da podocina na urina; nos pacientes em que a 25(OH)D permaneceu < 20 ng/mL houve aumento significativo da podocalixina, e tendência de maior expressão do RNAm da nefrina e da podocina. Conclusão: A reposição de colecalciferol por seis meses não teve efeito sobre os RNAm associados ao podócito nestes pacientes com DRC avançada. O efeito protetor da vitamina D ou seus análogos sobre o podócito glomerular deve ser investigado em estágios mais precoces da DRC e com maior tempo de tratamento.

ABSTRACT Introduction: Vitamin D reduces albuminuria in patients with chronic kidney disease (CKD) but its effects on glomerular podocytes are not entirely understood. Objective: To evaluate if cholecalciferol supplementation reduces the levels of podocyte-associated urine mRNAs in patients with CKD. Methods: A total of 27 patients with stages 2 to 4 CKD and suboptimal serum vitamin D [25(OH)D] levels were treated with cholecalciferol for 6 months. Serum 25(OH)D level, estimated glomerular filtration rate (eGFR), proteinuria, and urine mRNA of nephrin, podocin, podocalyxin, transient receptor potential cation channel 6, vascular endothelial growth factor A, and transforming growth factor beta were assessed before and after intervention. Results: eGFR declined at an average rate of -4.71 mL/min/1.73 m2 (p = 0.010 vs. baseline), being 28 ± 16 mL/min/1.73 m2 at six months. No changes in proteinuria or mineral and bone metabolism parameters were observed after cholecalciferol supplementation. Urinary podocyte-associated mRNAs did not change significantly after treatment. However, patients who achieved 25(OH)D level > 20 ng/mL at six months showed a trend of reduction of urinary nephrin and podocin mRNA levels; in patients with 25(OH)D that remained < 20 ng/mL there was a significant increase in urinary podocalyxin, and a trend of higher expression of urinary nephrin and podocin mRNA. Conclusion: Six months of cholecalciferol supplementation had no effect on urine podocyte-associated mRNA profile of patients with advanced CKD. The protective effect of vitamin D or its analogues on the glomerular podocyte should be investigated in early stages of CKD with a longer treatment period.

O papel da vitamina D na força muscular em idosos / The role of vitamin D in muscle strength among the elderly

A hipovitaminose D é uma condição frequente em idosos e está associada ao risco aumentado de fratura. A deficiência de vitamina D é comum entre indivíduos idosos em localidades de grandes latitudes e muito comum entre os institucionalizados. Atualmente há também evidências de que a baixa concentração vitamina D é associada com vários distúrbios de origem não musculo-esquelética, tais como doenças cardiovasculares, inflamação, doenças infecciosas, entre outras. Além disso, estudos clínicos em idosos têm demonstrado que os baixos níveis séricos de vitamina D correlacionam-se com força muscular reduzida em membros inferiores e pior desempenho físico. No entanto, os níveis necessários para manter a função muscular adequada e força ainda não foram estabelecidos. Objetivo: Avaliar as evidências recentes dos efeitos da vitamina D na força muscular de indivíduos idosos. Métodos: Realizou-se levantamento dos estudos publicados no período de 2010 a 2014 nas bases Pubmed, Medline e Scopus, usando os termos "cholecalciferol", "muscle strength" e "elderly". Resultados: Sete estudos foram selecionados. Os resultados obtidos sugeriram influência positiva da vitamina D na força muscular de idosos. Conclusão: Esta revisão demonstrou que, apesar da ação da vitamina D no sistema musculoesquelético ainda parecer incerto, houve uma tendência de maior benefício com a suplementação de vitamina D em doses maiores. Entretanto, estudos adicionais são necessários para definição do melhor perfil terapêutico

Vitamin D deficiency is a common condition among the elderly and it is associated with an increased risk of fractures. The condition is common among elderly at higher latitude locations and very common among the institutionalized. Currently there is also evidence that low levels of vitamin D are associated with multiple disorders such as cardiovascular diseases, inflammation, and infectious diseases, among other things. In addition, clinical studies on the elderly have shown that the low vitamin D levels correlate with reduced muscle strength in the lower limbs and poor physical performance. However, suitable levels for maintaining proper muscle function and strength have not yet been established. Objective: To verify recent evidence of the effects of vitamin D on muscle strength in the elderly. Method: A survey of studies published between 2010 and 2014 in Pubmed, Medline, and Scopus using the terms "cholecalciferol", "muscle strength," and "elderly." Results: Seven studies were selected. The results suggest a positive influence of vitamin D on muscle strength in the elderly. Conclusion: This review showed that despite the action of vitamin D on the musculoskeletal system, there is still uncertainty; there tended to be a greater benefit with vitamin D supplementation at higher doses. However, additional studies are needed to define the best therapeutic profile

Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats

ABSTRACT The use of natural substances and micronutritional approaches has been suggested as a therapeutic alternative to benefit the bone healing associated with no side effects. Nevertheless, the influence of micronutritional interventions with therapeutic proprieties on the bone repair has yet to be intensely evaluated, and no evidence is available exploring the impact of micronutrient supplementation on the peri-implant bone healing. Objective This study investigated the effect of micronutrients supplementation on the bone repair around implants. Material and Methods One screw-shaped titanium implant was inserted in each tibia of each rat, which were assigned to: daily administration, for 30 d, of the placebo solution (Placebo group-n:18) or micronutrients supplementation (Micronutrients group-n:18), based on calcium, magnesium, zinc, and vitamin D3 intake. After, the animals were sacrificed. One of the implants was removed by applying a counter-torque force to evaluate the force to rupture the bone-implant interface. The other implant was evaluated by microcomputed tomography (CT) examination to determine the bone-to-implant contact (BIC) and the bone volume (BV/TV). Results No statistically significant differences were observed between the groups for both counter-torque values and microCT parameters (p>0.05). Conclusion Within the limits of this study, micronutrients supplementation did not provide additional benefits to the bone healing around dental implants.

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

effects of cholecalciferol treatment on mineral metabolism and inflammation markers in Turkish hemodialysis patients

To evaluate the effects of 25-hydroxycholecalciferol [25- [OH] D] on bone mineral metabolism and inflammation parameters in hemodialysis patients. The study was carried out at Hitit University Corum Education and Research Hospital, Corum, Turkey between July and September 2012. All of the 36 patients that underwent treatment in our hemodialysis unit were included in this study. Four patients were excluded from the study due to other complications. Of the remaining 32 patients, 28 patients [mean age; 52 +/- 18 years; 15 males and 13 females] with a 25-[OH] vitamin D level of <30 ng/mL were included in the study. Four of the 32 remaining patients were excluded as their 25-[OH] vitamin D levels was >30 ng/ml. Patients with a 25-[OH] D level of <30 ng/mL were treated with 20,000 IU oral cholecalciferol once a week for 12 weeks. The level of vitamin D, mineral metabolism markers, and C-reactive protein [CRP] were evaluated. After the treatment, the 25-[OH] D levels increased to >30 ng/mL in all patients [12.5 +/- 7.1 ng/mL versus 59.9 +/- 15.5 ng/mL; p<0.001]. While there was a significant, but not life-threatening, increase in calcium levels [7.9 [7.26 to 8.32] mg/dL versus 8.48 [7.55 to 9.25] mg/dL, p<0.001], a statistically significant decrease was observed in CRP levels [9.34 +/- 4.4mg/L versus 4.4 +/- 1.6mg/L; p<0.001]. Alkaline phosphatase, phosphorus, and parathyroid hormone levels did not change. Vitamin D deficiency is a common problem in HD patients. Short-term weekly cholecalciferol treatment is safe and effective in this patient group, and cholecalciferol treatment had a positive effect on inflammatory markers

[Effects of co-administration of soy extract and vitamin D3 on serum calcium level and thyroid function in mice]

The Thyroid gland with two symmetrical lobes has an important role in metabolism of the body and regulating of calcium. Any factor making structural and hormonal changes in this gland can produce metabolic disorders. To investigate the functional changes of the thyroid gland following coadministration of soy extract and Vitamin D3, 42 mature female mice in 7 groups were studied for 35 days. Two doses of soy extract [5 and 10 g/kgBW/day]; two doses of Vitamin D3 [100 and 200 micro g/kgBW/day]; and, a combination of both soy extract and Vitamin D3 with two doses were fed to each mouse by gavage. At the end of the feeding trial, following anesthetizing by diethyl ether, mice were bled. Serum levels of calcium were determined by method Colorimetry, and serum concentrations of T3, T4, TSH were determined by method Radio Immuno Assay. Data was statistically analyzed by the one way ANOVA test and significant differences were observed between groups [p<0.001]. Results showed the occurrence of a dose-dependent hypothyroidism in mice receiving only soy extract. In mice receiving only vitamin D3, significant and dose dependent increases of calcium levels, significant and dose-dependent decreases of TSH levels and, insignificant decreases in serum concentrations of T3 and T4 were observed. Finally, groups receiving a combination of high doses of soy extract and Vitamin D3, showed hypothyroidism. In conclusion, this study suggests that co-administration of soy extract and Vitamin D3, only in low doses, can balance the effects of individual use of these components on thyroid function and calcium homeostasis

A new role for vitamin D: cholecalciferol promotes dermal wound strength and re-epithelization.

Vitamin D endocrine system is a potent regulator of cell growth and maturation. Vitamin D3 modulates growth kinetics of many cells and produces divergent actions. Keeping this in view, cholecalciferol is evaluated for its actions on dermal wound healing in Wistar rats. Intraperitonial cholecalciferol at 5, 10, 15 IU/g body weight doses produces increases in wound breaking strength and promotes epithelization significantly. Results suggest that there is some biological role for vitamin D endocrine system, ir wound repair. A clear understanding of this role of vitamin D3 may define new avenues in wound medication.

Effect of vitamin D supplementation in lactating rats on the neonatal growth.

In lactating rats consuming a commercial diet adequate in calcium, phosphorus and vitamin D, the effect of supplementation of 3000 IU and 7,500 IU of vitamin D3 on the lactational performance of the dams and soft tissue and skeletal growth in the pups has been investigated. On 28th day of age, the pups in the supplemented groups were significantly heavier than in the control group. Study of the indices of cellular growth in the liver and gastrocnemius muscle revealed that the increase in the soft tissue weight was due to a significant increase in protein, RNA and DNA contents (cellular hyperplasia) without any change in protein/DNA ratio (cell size). In the tibia, compared to controls, the dry bone weight and ash weight were more in the supplemented groups, but ash weight/dry bone weight ratio was not altered. The improvement in the neonatal growth was most probably due to the greater milk yield observed in the dams in supplemented groups and not due to any anabolic effect in the pups since direct administration of 500 IU or 1,000 IU of vitamin D3 in 10 day old pups did not increase their body weight.

Endocrine regulation of calcium and phosphate in rat eye lens and its significance in cataract formation.

Parathyroid hormone (PTH), calcitonin (CT)and calciferol (Vit. D3) operate synchronously to maintain a balance between calcium and phosphate levels in serum. An aberration of specific steps in the homeostatic process results in hypo/hyper phosphatemia. These aberrations may eventually lead to several diseased states. PTH and Vit. D3 induced hypercalcemia can, however, be significantly inhibited by calcitonin (CT). These findings have been correlated with the levels of calcium and phosphate obtained from human senile cataractous lenses of cortical and nuclear types. The comparison of the results indicate that amongst these three hormones PTH is most vulnerable in leading towards conditions for possible cataract formation in rat lens.

Efecto de l,25-dihidroxicolecalciferol sobre insulina en niños con insuficiencia renal crónica / Effect of 1-25 dihidroxycholecalciferol on insulin in children with chronic kidney failure

La insuficiencia renal crónica (IRC) es una entidad que independientemente de su génesis, condiciona una serie de alteraciones bioquímicas que dan por resultado un proceso patológico generalizado. Se conocen algunas medidas terapéuticas que se han utilizado para mejorar la homeostasis y condiciones generales del niño con IRC