Fatores associados à deficiência de vitamina D em mulheres gestantes e lactantes / Factores asociados a la deficiencia de vitamina D en mujeres embarazadas y lactantes / Factors associated with vitamin d deficiency in pregnant and lactatingwomen

Introdução: A deficiência de vitamina D durante a gestação e a lactação pode repercutir negativamente no desenvolvimento fetal e infantil, devido seu papel fundamental nos sistemas imunológico, cardíaco, ósseo, muscular e neural. Objetivo: Realizar uma revisão de literatura para integrar estudos que evidenciam a deficiência de vitamina D em gestantes e lactantes, e os fatores de risco associados a essa carência. Metodologia: Foi realizado um levantamento bibliográfico entre agosto e outubro de 2021, com atualização entre outubro e novembro de 2022 através de pesquisas às bases Pubmed e Scielo, bem como às listas de referências dos artigos selecionados. Foram empregados os descritores consumo alimentar, vitamina D, deficiência de vitamina D, gestantes e lactantes, usando-se o operador booleano AND para a associação entre eles. Como critérios de inclusão foram adotados o tipo de estudo (epidemiológicos, ensaios clínicos e revisões integrativa e sistemática), o idioma (espanhol, inglês e português) e o período de publicação (2010 a 2022). Resultados: Evidenciou-se que existem vários fatores de riscos para a inadequação do status de vitamina D em gestantes e lactantes como a baixa exposição da pele à luz solar e fatores relacionados (uso excessivo de protetor solar, menor tempo de atividades ao ar livre, clima, religião e hábitos culturais, maior escolaridade);a pigmentação mais escura da pele; o baixo consumo alimentar de vitamina D e variáveis associadas; a menor idade materna; o primeiro trimestre gestacional; a primiparidade e o excesso de tecido adiposo. Conclusões: Em gestantes e lactantes, a carência de vitamina D associa-se a distintos fatores, com destaque principalmente para a baixa exposição à luz solar, a pigmentação mais escura da pele e o excesso de tecido adiposo, sendo de extrema importância que sejam abordados com cautela, visando ações voltadas a variáveis modificáveis, de modo a auxiliar na redução da hipovitaminose D nestes grupos (AU).

Introduction: Vitamin D deficiency during pregnancy and breastfeeding can have a negative impact on fetal and infant development due to its fundamental role in the immune, cardiac, bone, muscular and neural systems. Objective: To conduct a literature review to integrate studies which show the Vitamin D deficiency in pregnant andlactating women, and the risk factors associated with this deficiency. Methodology: A bibliographic survey was carried out between August and October 2021, with an update between October and November 2022 through searches in the Pubmed and Scielo databases, as well as the reference lists of the selected articles. The descriptors food consumption, vitamin D, vitamin D deficiency, pregnant and lactating women were used, using the Boolean operator AND for the association between them. The type of study (epidemiological, clinical trials and integrative and systematic reviews), language (Spanish, English and Portuguese) and publication period (2010 to 2022) was adopted as inclusion criteria.Results:It was shown that there are several risk factors for inadequate vitamin D status in pregnant and lactating women, such as low skin exposure to sunlight and related factors (excessive use of sunscreen, less time spent outdoors, climate, religion and cultural habits, higher education); darker skin pigmentation; low dietary intake of vitamin D and associated variables; the lowest maternal age; the first gestational trimester; primiparity and excess adipose tissue.Conclusions: Vitamin D deficiency in pregnant and lactating women is associated with different factors, witha main emphasis on low exposure to sunlight, darker skin pigmentation and excess adipose tissue. Furthermore, it is extremely important that these factors are approached with caution, implementing actions aimed at modifiable variables in order to help reduce hypovitaminosis D in these groups (AU).

Introducción: La deficiencia de vitamina D durante el embarazo y la lactancia puede tener un impacto negativo en el desarrollo fetal e infantil, por su papel fundamental en los sistemas inmunológico, cardíaco, óseo, muscular y neural. Objetivo: Realizar una revisión bibliográfica para integrar estudios que evidencien la deficiencia de vitamina D en mujeres embarazadas y lactantes, y los factores de riesgo asociados. Metodología:Se realizó un levantamiento bibliográfico entre agosto y octubre de 2021, con actualizaciones entre octubre y noviembre de 2022 mediante búsquedas en las bases de datos Pubmed y Scielo, así como en las listas de referencias de los artículos seleccionados. Se utilizaron los descriptores consumo de alimentos, vitamina D, deficiencia de vitamina D, gestantes y lactantes, utilizándose el operador booleano AND para la asociación entre ellos. Se adoptaron como criterios de inclusión el tipo de estudio (epidemiológicos, clínicos, revisiones integradoras y sistemáticas), idioma (español, inglés y portugués) y período de publicación (2010 a 2022).Resultados: Existen varios factores de riesgo para un estado inadecuado de vitamina D en mujeres embarazadas y lactantes, como la baja exposición de la piel a la luz solar y factores relacionados (uso excesivo de protector solar, menor tiempo al aire libre, clima, religión y hábitos culturales, educación más alta); pigmentación de la piel más oscura; baja ingesta dietética de vitamina D y variables asociadas; la edad materna más baja; el primer trimestre gestacional; Primiparidad y exceso de tejido adiposo. Conclusiones:En mujeres embarazadas y lactantes, el déficit de vitamina D se asocia a diferentes factores, especialmente la baja exposición solar, la pigmentación de la piel más oscura y el exceso de tejido adiposo, y es de suma importancia abordarlos con precaución, apuntando a acciones dirigidas a variables modificables, con el fin de ayudar a reducir la hipovitaminosis D en estos grupos (AU).

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

ABSTRACT Objective: The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment. Subjects and methods: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure. Results: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively. Conclusion: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

A comparative study of cholecalciferol and vildagliptin on fasting blood glucose level of streptozotocin-nicotinamide-induced Type 2 diabetic albino rats

Background: The lack of vitamin D deficiency has been found to be closely associated with many health problems such as metabolic syndrome, cancer, cardiovascular disease, and type 2 diabetes. This interest has also arisen due to the identification that most cells, along with the pancreatic beta-cells, incorporate the vitamin D receptor. Aims and Objectives: In this study, we tested the potential anti-diabetic effect of cholecalciferol, one of the vitamin D analogs, alone or in combination with vildagliptin in type 2 diabetic rats. Materials and Methods: Type 2 diabetic model rats were induced by intraperitoneal injection of streptozotocin followed by nicotinamide. Rats were assigned into five groups each of six rats divided as follows: Normal (non-diabetic) control (Group A), untreated diabetic group receiving the vehicles only (Group B), cholecalciferol-treated group (Group C), vildagliptin-treated group (Group D), and group receiving a combination of cholecalciferol and vildagliptin (Group E). The treatment course lasted for 1 month. For the estimation of fasting blood sugar, the rats were kept deprived of food overnight and were allowed free access to water. Blood samples were collected from the tail of rat with the help of glucometer. Statistical analysis was performed using SPSS version 20 software. One-way ANOVA test was used to compare the effect of drugs on different group. Post hoc analysis was done using Turkeys HSD (honestly significant difference) test. Differences were considered significant at (P < 0.05). Results: Mean FBS value of vitamin D, vildagliptin, and their combination was 181.50 mg/dl, 95.0 mg/dl, and 84.83 mg/dl on day 28. It showed that the combination of both drugs acquired much closer value of FBS as compared to normal non-diabetic control group and thus achieved normal glucose level more effectively. Furthermore, coadministration showed greater fall in fasting blood glucose at the extent of 61.15% as compared to 56.45% by vildagliptin and 17% by cholecalciferol alone on day 28. Conclusion: Therefore, it may be suggested through this study that vitamin D has blood glucose lowering property and coadministration of vitamin D and vildagliptin potentiate the action of each other.

A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto’s Thyroiditis

Introduction : Several studies have reported a low Vitamin D status in Autoimmune Thyroid Diseases (AITD), indicating association between Vitamin D deficiency (<20 ng/ml) and thyroid autoimmunity. If supplementation of Vitamin D decreases anti-TPO antibody titres, in future it may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency (21-29 ng/ml) or deficiency. Objectives : Our study aims to assess any potential therapeutic role of Vitamin D in the management of HT. Study Design : It is a randomised, double blind, single centre, placebo-controlled study. Results : Significant negative correlation between Serum anti TPO Antibody and Vitamin D level; statistically significant reduction of anti TPO Antibody titre in intervention group compared to placebo group. Conclusions : Vitamin D can be a therapeutic option in Hashimoto's Thyroiditis.

Deficiency and Insufficiency of Vitamin D in Women of Childbearing Age: A Systematic Review and Meta-analysis / Deficiência e insuficiência de vitamina D em mulheres na idade reprodutiva: Uma revisão sistemática e meta-análise

Abstract Objective To estimate the prevalence of inadequate vitamin D level and its associated factors for women of childbearing age in Brazil. Methods A systematic reviewwas conducted (last updatedMay 2020).Meta-analyses were performed using the inverse-variance for fixed models with summary proportion calculation by Freeman-Tukey double arcsine. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. Results Our review identified 31 studies, comprising 4,006 participants. All the studies had at least one weakness, mainly due to the use of convenience sampling and small sample size. The overall prevalence of vitamin D deficiency, insufficiency, and both deficiency and insufficiency were 35% (confidence interval, 95%CI: 34-37%), 42% (95%CI: 41-44%), and 72% (95%CI: 71-74%), respectively. Conclusion Although the magnitude of the prevalence of inadequate levels of vitamin D is uncertain, the evidence suggests that presence of vitamin D deficiency or insufficiency in women of reproductive age can cause moderate to severe problems.

Resumo Objetivo Estimar a prevalência de níveis inadequados de vitamina D e seus fatores associados para mulheres em idade fértil no Brasil. Métodos Uma revisão sistemática foi realizada (última atualização em maio de 2020). As meta-análises foram realizadas usando o inverso da variância para o modelo fixo com cálculo de proporção sumarizada por transformação arco-seno duplo de Freeman-Tukey. A qualidade metodológica e de reporte foi avaliada usando a ferramenta do Joanna Briggs Institute para estudos de prevalência. Resultados Nossa revisão identificou 31 estudos, compreendendo 4.006 participantes. Todos os estudos apresentaram pelo menos uma limitação, principalmente devido ao uso de amostra de conveniência e tamanho amostral pequeno. As prevalências gerais de deficiência, insuficiência e deficiência de vitamina D foram 35% (intervalo de confiança, IC 95%: 34-37%), 42% (IC 95%: 41-44%) e 72% (IC 95%: 71-74%), respectivamente. Conclusão Embora a magnitude da prevalência de níveis inadequados de vitamina D seja incerta, a evidência sugere que presença de deficiência ou insuficiência de vitamina D em mulheres em idade reprodutiva pode causar problemas moderados a graves.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets

Justification: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. Objectives: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. Process: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. Recommendations: The group reiterates the serum 25- hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study

Abstract Objective To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes. Methods Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed. Results Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported. Conclusion Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies. Registry of Clinical Trials (www.ctri.nic.in) under number REF/2021/03/041415 N.

Vitamin D concentrations and their relationship with iron parameters in patients with chronic kidney disease / Concentrações de vitamina D e sua relação com parâmetros de ferro em pacientes com doença renal crônica

ABSTRACT Objective To investigate the relationship between calcidiol (25(OH)D3) concentrations and iron parameters in patients with chronic kidney disease. Methods This is a cross-sectional, descriptive, and quantitative study. The sample consisted of 86 adult patients of both sexes undergoing dialysis. 25(OH)D3 concentrations were determined by chemiluminescence; food consumption was assessed using 24-hour recalls, and the serum levels of hemoglobin, iron, ferritin, and transferrin saturation were assessed. Data analysis was performed using the program Stata, with a significance level of p<0.05. Results The results pointed to 25(OH)D3 concentrations compatible with sufficiency, iron levels consistent with normality, and ferritin and transferrin saturation above the reference values. The consumption of carbohydrates and lipids was higher in females. There was no relationship between the adequacy of 25(OH)D3 and the presence of anemia and iron parameters. Conclusion Considering that the mean serum levels of iron and 25(OH)D3 were adequate, it is suggested that resistance to erythropoietin and the inflammatory process may have contributed to the percentage of anemic individuals found in the study.

RESUMO Objetivo Investigar a relação entre as concentrações de calcidiol (25(OH)D3) e os parâmetros de ferro em pacientes com doença renal crônica. Métodos É um estudo transversal, descritivo e quantitativo. A amostra foi composta por 86 pacientes, adultos, de ambos os sexos, em terapia dialítica. As concentrações de 25(OH)D3 foram determinadas pelo método de quimioluminescência; o consumo alimentar foi avaliado pela aplicação de Recordatórios de 24 horas e foram avaliados os níveis séricos de hemoglobina, ferro, ferritina e saturação de transferrina. A análise dos dados foi realizada no programa Stata, com nível de significância p<0.05. Resultados Os resultados apontaram para concentrações de 25(OH)D3 compatíveis com suficiência, níveis de ferro compatíveis com a normalidade e ferritina e saturação de transferrina superiores à referência. O consumo de carboidratos e lipídios foi superior no sexo feminino. Não foi verificada relação entre a adequação de 25(OH)D3 e a presença de anemia e parâmetros de ferro. Conclusão Tendo em vista que os níveis médios séricos de ferro e 25(OH)D3 estavam adequados, sugere-se que a resistência à eritropoietina e o processo inflamatório podem ter contribuído para o percentual de anêmicos constatado no estudo.

The effects of vitamin D3 supplementation on clinical remission in patients with Crohn′s disease treated with infliximab / 中华消化杂志

Objective:To retrospectively analyze the effects of vitamin D3 supplementation on clinical remission of patients with Crohn′s disease (CD) in the treatment of infliximab (IFX).Methods:From January 2014 to January 2020, 73 patients with initial moderate to severe CD (50 patients with vitamin D deficiency (the level of serum 25-hydroxyvitamin D (25(OH)D)<50 nmol/L)) receiving IFX treatment at Department of Gastroenterology were screened from the clinical database of the Second Affiliated Hospital of Wenzhou Medical University. Harvey-Bradshaw index (HBI) was applied to evaluate the disease activity of CD patients. All the patients underwent IFX treatment (5 mg/kg) for at least 54 weeks. According to whether vitamin D3 (125 U/d) was supplemented during IFX treatment, the patients were divided into supplemented group ( n=37) and non-supplemented group ( n=36). In supplemented group, the level of 25(OH) D of patients at the 54th week was compared with that before IFX treatment. At the 54th week, the clinical remission rate and decline range of HBI were compared between supplemented group and non-supplemented group. And the influencing factors of clinical remission rate were analyzed in CD patients. Paired t test, independent sample t test, chi-square test and multivariable logistic regression were used for statistical analysis. Results:In supplemented group, the level of serum 25(OH)D at the 54th week was higher than that before IFX treatment ((50.83±15.45) nmol/L vs. (37.68±16.75) nmol/L), and the difference was statistically significant ( t=-4.55, P<0.001). At the 54th week, the clinical remission rate of supplemented group was higher than that of non-supplemented group (83.8%, 31/37 vs. 61.1%, 22/36), the decline range of HBI was larger than that of non-supplemented group (7.41±3.00 vs. 6.28±2.75), and the differences were statistically significant ( χ2=4.71, t=2.41; P=0.030 and 0.023). The results of multivariable logistic regression analysis showed that vitamin D3 supplementation was an independent factor affecting the clinical remission rate in CD patients ( n=73) and the patients with vitamin D deficiency ( n=50) ( b= -1.67 and -1.92 , P=0.015 and 0.019). Conclusions:Vitamin D3 supplementation can significantly improve the clinical remission rate in CD patients with IFX treatment, especially in CD patients with vitamin D deficiency.

A preliminary study on the improved efficacy of mesalazine combined with vitamin D 3 in ulcerative colitis / 中华内科杂志

Objective:To analyze the influence of vitamin D 3 supplementation on the clinical efficacy of mesalazine in patients with ulcerative colitis (UC). Methods:From January 2015 to December 2020, patients with mild-to-moderate active UC were retrospectively and continuously enrolled, who accepted mesalazine treatment for at least 12 months at the Second Affiliated Hospital of Wenzhou Medical University. According to simultaneous supplement of vitamin D 3 (125 IU/d), the patients were divided into study group and control group. Demographic and disease characteristics, serum 25-hydroxyvitamin D[25(OH)D] levels and other information were collected through retrieving hospital database. Student′s t-test, Mann-Whitney U test and Chi-square test were applied for comparison of disease characteristics. The changes of modified Mayo scores[ΔMayo] and 25(OH)D[Δ25(OH)D] were compared before and after treatment by paired t-test, Wilcoxon signed rank test and Chi-square test. Multiple linear regression model was used to analyze the independent factors affecting ΔMayo and Δ25(OH)D, and variables with P-values less than 0.20 in the univariate analysis were allowed for further multivariate analysis. Results:A total of 74 UC patients (44 males, 30 females), with median age (range) 39.5 (20-76) years old, were analyzed and respectively assigned into study group ( n=36) and control group ( n=38). In study group, the average level of serum 25(OH)D was significantly increased at month 12 compared with that at baseline [(22.87±7.30) μg/L vs. (18.15±7.48) μg/L, P<0.001]. However, no significant elevation of serum 25(OH)D was found in control group [(19.17±8.49) μg/L vs. (19.82±9.47) μg/L, P=0.466]. Furthermore, there was a significant decrease of modified Mayo score [-3(-4.75, -1.25) vs.-2(-3.25, 0), P=0.034] and a higher clinical remission rate (55.6% vs. 28.9%, P=0.020) at month 12 in study group than those in control group. In addition, according to the baseline level of serum 25(OH)D before mesalazine treatment, 74 UC patients were divided into vitamin D deficiency group ( n=38, serum 25(OH)D<20 μg/L) and non-deficiency group ( n=36, serum 25(OH)D≥20 μg/L). At month 12 in vitamin D deficiency group, patients with vitamin D3 supplementation had a greater decline in modified Mayo score [-4(-5.75, -2) vs.-2(-4, 0), P=0.048] and a higher clinical remission rate (60.0% vs. 22.2%, P=0.019) compared with those without. Conclusions:In patients with mild-to-moderate active UC receiving mesalazine treatment, vitamin D3 supplementation may improve the clinical efficacy, especially in patients with vitamin D deficiency.

Efficacy of fluticasone propionate cream alone or in combination with calcipotriol ointment in the treatment of mild to moderate plaque psoriasis: a randomized self-controlled study / 中华皮肤科杂志

Objective:To evaluate short-term efficacy and safety of fluticasone propionate 0.05% cream alone or in combination with calcipotriol 0.005% ointment in the treatment of mild to moderate plaque psoriasis.Methods:From October 2020 to January 2021, a randomized, open-labeled, self-controlled clinical trial was conducted among 30 patients with mild to moderate plaque psoriasis in Beijing Friendship Hospital. Skin lesions on the extremity of one side were topically treated with calcipotriol 0.005% ointment in the morning and fluticasone propionate 0.05% cream in the evening (combination group) , and lesions on the contralateral extremity were topically treated with fluticasone propionate 0.05% cream twice a day (fluticasone propionate group) . The treatment lasted 4 weeks. Before and 1, 2, 4 weeks after the start of treatment, the patients were followed up, clinical indices including static physician′s global assessment (sPGA) and psoriasis area and severity index (PASI) were evaluated, and adverse events were recorded. Efficacy and safety were evaluated by using repeated measures analysis of variance, multivariate analysis of variance, Mann-Whitney rank sum test and two-independent-sample t test. Results:Before the treatment, there was no significant difference in sPGA or PASI score between the combination group and fluticasone propionate group (both P > 0.05) . After 1-week treatment, the fluticasone propionate group showed significantly decreased sPGA (1.10 ± 0.31 points) and PASI scores (1.05 ± 0.51 points) compared with the combination group (1.73 ± 0.45 points, 1.38 ± 0.69 points, F= 40.74, 4.38, respectively, both P < 0.05) ; after 2- and 4-week treatment, the combination group showed significantly decreased sPGA (0.83 ± 0.46 points, 0.23 ± 0.43 points, respectively) and PASI scores (0.53 ± 0.47 points, 0.23 ± 0.50 points, respectively) compared with the fluticasone propionate group (sPGA: 1.03 ± 0.18 points, 0.97 ± 0.32 points, F= 4.88, 56.14, respectively, both P < 0.05; PASI: 1.03 ± 0.51 points, 0.92 ± 0.54 points, F= 15.20, 26.36, respectively, both P < 0.05) . After 1-week treatment, the infiltration/hypertrophy severity score was significantly lower in the fluticasone propionate group than in the combination group ( U= 165.00, P < 0.05) ; after 2- and 4-week treatment, the erythema and scaling severity scores were significantly lower in the combination group than in the fluticasone propionate group (erythema: U= 540.00, 765.00, respectively, both P < 0.05; scaling: U= 825.00, 795.00, respectively, both P < 0.05) . Conclusion:Fluticasone propionate 0.05% cream alone exhibited a rapid onset of efficacy in the treatment of psoriasis, while fluticasone propionate 0.05% cream combined with calcipotriol 0.005% ointment was more effective after 2- and 4-week treatment, and both regimens showed a favorable safety profile.

Vitamin D3 Attenuates Type 3 Diabetic-Associated Cognitive Deficits in Rats through Regulating Neurotrophins and Enhancing Cholinergic Transmission Pathway

Objective: To examine the protective effect of Vitamin D3 against Type 3 diabetes-induced cognitive dysfunction in rats. Materials and Methods: Type 3 diabetes was induced by a high-fat diet plus streptozotocin in rats. Rats were divided into seven groups: negative control, positive control, Vitamin D3 groups (100, 500 and 1000 IU/kg/day), Vitamin D3 plus rivastigmine, and rivastigmine monotherapy. A radial arm maze test was used to assess cognitive function. Levels of acetylcholinesterase (AChE), dopamine (DA), nerve growth factor, neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus were estimated by the enzyme-linked immunosorbent assay kits. Results: Chronic treatment with Vitamin D3 significantly (P < 0.05) and dose dependently alleviated cognitive deficits, with enhancing cholinergic transmission pathway activity through attenuated hippocampal AChE and increased DA level (P < 0.001). Moreover, Vitamin D3 significantly increased (P < 0.001) neurotrophin levels as an underlying mechanism for the resulted improvement. Conclusion: Vitamin D3 plus rivastigmine (combined group) is better than Vitamin D (100 and 500 mg/kg/day) for improvement of AChE, DA, NT-3, and GDNF levels. Vitamin D (500 and 1000 IU/kg/day) was effective as a combined group in terms of the behavioral test.

Efecto sinérgico de un bifosfonato con vitamina D / Synergic effect of a biphosphonate with vitamin D

Introducción: Los bifosfonatos son considerados como un grupo de fármacos de gran utilidad en el tratamiento de enfermedades del tejido óseo ya que promueven su resorción. Han sido la primera línea para el tratamiento de la osteoporosis, enfermedad de Paget, mieloma múltiple e hipercalcemia maligna. Por su parte, la vitamina D es un nutriente esencial cuya función principal es la homeostasis de calcio (Ca+2) y fosfato (P4 3-). Objetivo: Describir los aspectos moleculares y farmacológicos de la acción de un bifosfonato (alendronato sódico) y la vitamina D, por los cuales potencian mutuamente sus efectos en enfermedades óseas. Métodos: Fueron seleccionadas las referencias más actualizadas que abordaran aspectos relevantes acerca del alendronato y la vitamina D. Se consultaron las bases de datos de PubMed, Uniprot y Protein Databank. Conclusiones: El sinergismo entre alendronarto y vitamina D generan efectos benéficos en el tejido óseo. Sin embargo, existen efectos colaterales que pueden afectar a otros tejidos, por lo que su uso debe ser controlado(AU)

Introduction: Biphosphonates are considered to be a group of very useful drugs used to treat osseous tissue conditions, since they foster resorption. They are first line in the treatment of osteoporosis, Paget's disease, multiple myeloma and malignant hypercalcemia. Vitamin D, on the other hand, is an essential nutrient whose main function is calcium (Ca+2) and phosphate (P4 3-) homeostasis. Objective: Describe the molecular and pharmacological aspects of the action of a biphosphonate (alendronate sodium) and vitamin D on osseous diseases. Methods: A selection was made of the most updated references about relevant aspects of alendronate and vitamin D. The databases consulted were Pubmed, Uniprot and Protein Databank. Conclusions: The synergy between alendronate and vitamin D generates beneficial effects on osseous tissue. However, their use should be controlled, since side-effects may affect other tissues(AU)

Critical analysis on the use of cholecalciferol as a COVID-19 intervention: a narrative review

ABSTRACT BACKGROUND: The World Health Organization has declared that a pandemic situation exists in relation to the disease caused by the new coronavirus, COVID-19. So far, the absence of a vaccine against the new coronavirus has led people worldwide to seek various therapeutic alternatives, including use of cholecalciferol. DESIGN AND SETTING: Narrative review developed by a research group at a public university in Recife (PE), Brazil. METHODS: We searched the literature on the use of cholecalciferol for prevention or treatment of COVID-19, using the MEDLINE and LILACS databases, with the keywords "vitamin D", "cholecalciferol", "SARS-CoV-2", "COVID-19" and "coronavirus", from January 1, 2020, to June 10, 2020. Narrative reviews, cohort studies and ecological studies were selected. RESULTS: We retrieved 32 references, of which 8 were considered eligible for intensive review and critical analysis. These comprised five narrative reviews, two observational studies and one protocol proposal. Most of the studies selected reported positive effects from use of vitamin D for prevention or treatment of COVID-19. However, there was little quantitative data to assess the real impact of using this vitamin as an intervention against this disease. CONCLUSIONS: Current studies on vitamin D used for purposes other than bone health promotion cannot be taken as support to justify its use in a disease as recent as COVID-19. Studies of greater robustness, with higher levels of clinical evidence, need to be conducted. Rational use of this vitamin needs to be ensured, thereby minimizing the impacts on the patient and the public healthcare system.

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.

Hypovitaminosis D and Calcium Intake in Adult Population / Hipovitaminosis D y la ingesta de calcio en población adulta / Hipovitaminose de ingestão de cálcio em população adulta

Abstract: Background: Daily dietary calcium intake below the requirements has been related to low levels of vitamin D (Vit-D) and osteoarticular diseases. Objective: To determine the prevalence of Vit-D deficiency in the general population living in Bogotá, its relationship to dietary calcium intake, and the influence of socio-demographic factors and sunlight exposure. Materials and methods: In a pro-spective cohort of the general population (randomly selected), excluding individuals with conditions affecting calcium absorption or adequate Vit-D action, the prevalence of hypovitaminosis D (95 % ci) and regular consumption of calcium (RCI, mg/day) is measured according to socio-demographic, anthropometric, biochemical, and sunlight exposure variables. A multiple regression model is implemented (no intercept) to predict Vit-D concentration based on the factors described. Results: Ninety-seven patients are included, 61 % of which are women, with a median age of 23 years, a weight of 65 kg (IQR: 55.2-70.5), a height of 165 cm ± 8.9, and BMI of 22.8 kg/m2 (IQR: 21.2-25.2). The RCI was 393.7 mg/day, less than the benchmark for Colombian adults (p < 0.001); serum calcium concentration was 9.7 mg/dL. The mean Vit-D concentration (95 % ci) was 23.7 ng/mL (22.6-24.7); hypovitaminosis D was identified in 87 % of the sample (80.6-94.7 %), 24.7 % were classified as poor (15.6-33.8 %) and 62.9% as insufficient (52.8-73%). Vit-D concentration was predicted in a quadratic function by the interaction between sex, sunlight exposure, and RCI (R2 > 90 %). Conclusion: The suspected high prevalence of Vit-D deficiency is confirmed in the general Colombian adult population as a result of low dietary calcium intake, demographic factors, and sunlight exposure.

Resumen: El consumo diario de calcio en la dieta por debajo de los requerimientos se ha relacionado con bajos niveles de Vitamina D (Vit-D) y con enfermedades osteoarticulares. Objetivo: Determinar la prevalencia de la deficiencia de Vit-D en la población general que vive en Bogotá, su relación con la ingesta de calcio en la dieta y la influencia de factores sociodemográficos y de la exposición a la luz solar. Materiales y métodos: En una cohorte prospectiva seleccionada aleatoriamente de la población general, excluyendo individuos con condiciones que afectaran la absorción de calcio o la acción de la Vit-D, se midió la prevalencia de hipovitaminosis D (IC 95 %) y el consumo habitual de calcio (CHC, mg/día), según variables sociodemográficas, antropométricas, bioquímicas y de exposición solar; se implementó un modelo de regresión múltiple (sin el intercepto) para predecir la concentración de Vit-D en función de los factores descritos. Resultados: Se incluyeron 97 pacientes, edad mediana 23 años, 61 % mujeres; con peso mediano 65 kg (RIC; 55,2-70,5), estatura 165 cm ± 8,9 e IMC 22,8 kg/m2 (RIC; 21,2-25,2). El CHC fue 393,7 mg/día, menor que el recomendado para adultos colombianos (p < 0,001); la concentración de calcio sérico fue 9,7 mg/dL. La concentración media (IC 95 %) de Vit-D fue 23,7 ng/mL (22,6-24,7), se identificó hipovitaminosis D en 87% (80,6-94,7%); 24,7% se clasificaron como deficientes (15,6-33,8 %) y 62,9 % como insuficientes (52,8-73 %). La concentración de Vit-D se logró predecir, en función cuadrática, por la interacción entre el sexo, la exposición solar y el CHC (R2 > 90 %). Conclusiones: Teniendo en cuenta los resultados obtenidos, se confirma la sospecha de alta prevalencia de hipovitaminosis D en población general colombiana adulta, relacionada con un bajo consumo de calcio en la dieta habitual, factores demográficos y de exposición solar.

Resumo: Introdução: O consumo diário de cálcio na dieta abaixo dos requerimentos necessários tem sido relacionado com baixos níveis de vitamina D (Vit-D) e com doenças osteoarticulares. Objetivo: Determinar a prevalência da deficiência de Vit-D na população geral que vive em Bogotá, Colômbia, sua relação com a ingestão de cálcio na dieta, a influência de fatores sociodemográficos e a exposição à luz solar. Materiais e métodos: em uma coorte prospectiva selecionada aleatoriamente da população geral, excluindo indivíduos com condições que afetassem a absorção de cálcio ou a ação de Vit-D, foi medida a prevalência de hipovitaminose D (IC 95 %) e o consumo habitual de cálcio (CHC, mg/dia), segundo variáveis sociodemográficas, antropométricas, bioquímicas e exposição solar; foi implementado um modelo de regressão múltipla (sem o intercepto) para predizer a concentração de Vit-D em função dos fatores descritos. Resultados: Foram incluídos 97 pacientes, com idade média 23 anos, 61 % mulheres; com peso médio de 65 kg (RIC; 55,2-70,5), estatura 165 cm ± 8,9 e IMC 22,8 kg/ m2 (RIC; 21,2-25,2). O CHC foi 393,7 mg/dia, menor do que o recomendado para adultos colombianos (p < 0,001); a concentração sérica de cálcio foi 9,7 mg/dL. A concentração média (IC 95 %) de Vit-D foi 23,7 ng/mL (22,6-24,7), foi identificada hipovitaminose D em 87 % (80,6-94,7 %), foram classificados deficientes 24,7% (15,6-33,8%) e insuficientes 62,9% (52,8-73%). A concentração de Vit-D foi possível predizer, em função quadrática, pela interação entre sexo, exposição solar e CHC (R2 > 90%). Conclusões: A partir dos resultados obtidos, é confirmada a suspeita de alta prevalência de hipovita-minose D em população geral colombiana adulta, relacionada com um baixo consumo de cálcio na dieta habitual, fatores demográficos e exposição solar.

Suplementação com Vitamina D atenua a resposta inflamatória aguda / Vitamin D supplementation attenuates acute inflammatory response

Este estudo avaliou os efeitos da suplementação diária de vitamina D na resposta inflamatória aguda em modelo experimental por diferentes agentes flogísticos: carragenina, prostaglandina e dextrana. Os animais (ratos) receberam por via oral (gavagem), dose única de vitamina D ou suplementação diária durante 7, 15 ou 30 dias antes da indução do edema de pata. A suplementação com vitamina D por 15 e 30 dias reduziu significativamente o processo inflamatório induzido por carragenina, o que poderia ser explicado, pelo menos parcialmente, pela redução dos níveis de fator de necrose tumoral α (TNFα). Os resultados indicam que a suplementação de vitamina D pode ser um útil adjuvante terapêutico para o controle do processo inflamatório agudo.

This study evaluated the effects of daily vitamin D supplementation on the acute inflammatory response in experimental model by different phlogistic agents: carrageenan, prostaglandin and dextran. Animals (rats) orally received (gavage) a single dose of vitamin D or daily supplementation for 7, 15 or 30 days prior to paw edema induced. Vitamin D supplementation for 15 and 30 days significantly reduced the carrageenan-induced inflammatory process, which could be at least partially explained by the reduction of tumor necrosis factor α levels (TNFα). Results indicate that vitamin D supplementation may be a useful therapeutic adjuvant for controlling the acute inflammatory process.

Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months.MATERIALS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6–12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections).RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D.CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

Clinical characteristics and genetic analysis of two cases of pseudohypoparathyroidism type Ⅰa with early-onset skin nodules as the diagnostic clue / 中华皮肤科杂志

Clinical features of and genetic mutations in two cases of pseudohypoparathyroidism type Ⅰ a(PHP Ⅰ a) with early-onset skin nodules were analyzed.Both of the two patients were males,and their ages at onset were 2 and 3 months respectively.They both presented with early-onset skin nodules as the main clinical manifestation,and were clinically characterized by a round face,short neck and early obesity.Histopathological examination of skin lesions showed subcutaneous ectopic osteogenesis in both patients.The first patient had low blood calcium,high blood phosphorus,high parathyroid hormone (PTH),and gene sequencing showed a heterozygous mutation c.399delT causing a T base deletion at position 399 in exon 5 of the GNAS gene.The second patient had normal blood calcium and phosphorus levels as well as normal PTH levels at early stage,and gene sequencing showed a heterozygous mutation c.939delT causing a T base deletion at position 939 in exon 9 of the GNAS gene.The blood PTH level was found to increase in the second patient after 1-year follow-up.Both the patients were confirmedly diagnosed with PHP Ⅰa.After treatment with vitamin D3,no new skin nodules occurred,and the blood calcium and phosphorus levels returned to normal.

Increased Left Atrial Volume and Its Relationship to Vitamin D in Primary Care

The study is based on the fact that left atrial (LA) volume measurement is a marker of the presence of diastolic dysfunction and that Vitamin D deficiency may be associated with ventricular remodeling, worsening of left ventricular (LV) diastolic and systolic function, and activation of the renin-angiotensin-aldosterone system. Objective: To evaluate whether LAV changes are related to vitamin D deficiency. Method: A cross-sectional, population-based, unicentric study in which 640 patients over 45 years of age enrolled in the Niterói's Médico de Família program, RJ, were evaluated. Patients were submitted to tissue Doppler echocardiography to evaluate the parameters of diastolic and systolic function and vitamin D dosage. The presence or absence of hypovitaminosis D associated with structural and functional cardiac changes was compared between each group. A p < 0.05 value was considered as an indicator of statistical significance. Results: Of the 640 individuals analyzed, hypovitaminosis D was confirmed in 39.2% of the patients, of whom 34.8% had diastolic dysfunction. The most relevant echocardiographic parameters that were statistically significant were non-indexed AEDs and LAV, E'/A' and E wave deceleration time, which were associated with the presence of hypovitaminosis D (P < 0.01). Conclusion: The study of the association of hypovitaminosis D and the appearance of structural and functional cardiac abnormalities may contribute to the discussion of the adoption of one more criterion to select individuals at risk of developing clinical cardiac insufficiency in primary care since, with the use of echocardiography, the subclinical condition of cardiac involvement, with prognostic and treatment implications for the referred patients with hypovitaminosis D, can be identified early