Serum levels of 25-hydroxy vitamin D in psoriatic patients

Studies have shown a relationship between vitamin D and psoriasis. We compared serum levels of vitamin D of 20 psoriasis patients and 20 controls. The median vitamin D level was 22.80 +/- 4.60 ng/ml; the median in the cases was 23.55 +/- 7.6 ng/ml, and in controls 22.35 +/- 3.10 ng/ml (p = 0.73). Only 2 cases and 4 controls had sufficient levels of vitamin D, although without statistical significance between the groups (p = 0.608). Levels were lower in women with psoriasis compared with those in male patients (20.85 +/- 6.70 x 25.35 +/- 2.90 ng/ml, p = 0.03), a finding that was not observed among controls.

Associação entre concentração sérica de vitamina D e alterações da massa muscular esquelética em pacientes com doenças inflamatórias intestinais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência da vitamina D sérica na adiponectina, visfatina e resistina nas alterações histológicas no fígado de pacientes com doença hepática gordurosa não alcoólica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insuficiência de vitamina D em pacientes infectados pelo HIV tratados com terapia antirretroviral contendo tenofovir

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insuficiência de vitamina D em pacientes infectados pelo HIV tratados com terapia antirretroviral contendo tenofovir

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health

Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (acurrency sign20 ng/mL) were compared to those with levels > 20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 +/- 7.91 vs 22.54 +/- 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (acurrency sign20 ng/mL) were further compared to the 26 JoSLE patients with levels > 20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 +/- 4.35 vs 1.00 +/- 2.48, p = 0.018), lower C4 levels (12.79 +/- 6.78 vs 18.38 +/- 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 +/- 0.148 vs 0.880 +/- 0.127 g/cm2, p = 0.037) and whole body BMD (0.962 +/- 0.109 vs 1.027 +/- 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels. Lupus (2012) 21, 1335-1342.

The influence of breakfast and dairy products on dietary calcium and vitamin D intake in postpubertal adolescents and young adults

Background: Given the importance of both calcium and vitamin D for bone health and the high prevalence of vitamin D from around the world, the present study aimed to evaluate calcium and vitamin D intake in a group of healthy Brazilian adolescents and young adults and to examine the influence of breakfast and dairy products in the total intake of these nutrients. Methods: One hundred and sixty adolescents and young adults, aged 1620 years old, from a public school, participated in the present study. Three-day dietary records were used to assess calcium and vitamin D intakes. Serum 25(OH) D levels were measured using a radioimmunoassay kit. The results were expressed as the mean (SD). Results: Only 3.8% of the subjects met the daily adequate intake recommendation for calcium, and none for vitamin D [682.2 (132.2) mg day(-1) and 124.0 (28.0) IU day(-1), respectively]. 25(OH) D serum levels were insufficient in 51.5% and deficient in 9.7% of the individuals [72.5 (22.3) nmol L(-1)]. There was a significant positive correlation between dairy product intake with both calcium and vitamin D (r = 0.597 and r = 0.561, respectively; P = 0.000). Adolescents who ate breakfast had a significant higher mean calcium, vitamin D and dairy product intake than adolescents who did not report this meal. Conclusions: The majority of adolescents and young adults did not consume recommended intakes of calcium and vitamin D and also presented 25(OH) D insufficiency. The results indicate that a regular breakfast and the consumption of dairy products represent important strategies in improving calcium and vitamin D intake in the diet.

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P > 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P > 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

INTRODUÇÃO: Hipovitaminose D é bem documentada em pacientes portadores de doença renal crônica (DRC). Espera-se níveis inferiores em habitantes de regiões não tropicais em relação aos habitantes de regiões tropicais, pela inferição de uma maior exposição solar e maior produção de vitamina D. OBJETIVO: Analisar os níveis séricos de vitamina D, como 25-hidroxivitamina D - 25(OH)D, de 125 pacientes brasileiros portadores de DRC em fase pré-dialítica. MÉTODOS: Foram estudados 125 pacientes (57,4 ± 16,2 anos, 78 brancos e 55,2% homens), com creatinina de 2,67 ± 1,73 mg/dL e o clearance estimado 43,7 ± 34,5 mL/min. O índice de massa corporal era de 27,4 ± 4,7 kg/m² e a circunferência abdominal de 95,0 ± 14,0 cm. O cálcio era de 9,3 ± 0,6 mg/dL, o paratormônio intacto (PTHi) 212,6 ± 221,2 pg/mL e a albumina sérica 4,2 ± 0,6 g/dL. A média de 25(OH)D era de 23,9 ± 10,7 ng/mL. RESULTADOS: Dos 125 pacientes, 92 (72,6%) apresentavam níveis de 25(OH)D < 30 ng/mL, sendo que 65 (52%) apresentavam insuficiência (15-29 ng/mL); 27 (21,5%) apresentavam deficiência (5-14 ng/mL) e apenas um paciente apresentava deficiência severa < 5 ng/mL. Não foram observadas diferenças entre os níveis de 25(OH)D nos pacientes estratificados quanto ao estágio de DRC. Os níveis de 25(OH)D foram maiores nos homens (38,1 ± 20,6 versus 22,4 ± 9,7 ng/ml; p < 0,0001), havendo também uma correlação inversa entre os níveis de 25(OH)D e de PTHi, proteinúria e circunferência abdominal, e uma correlação positiva entre 25(OH)D e cálcio total e albumina sérica. Na análise multivariada, encontrou-se apenas correlação inversa entre 25(OH)D e circunferência abdominal e PTHi. CONCLUSÃO: A despeito de a população do Brasil estar em um clima tropical, a maioria dos pacientes analisados apresentou níveis séricos subótimos de vitamina D, podendo este achado estar relacionado ao desenvolvimento de hiperparatireoidismo.

Progenitori endoteliali nei pazienti con Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) in fase uremica: effetti del trattamento con vitamina D.

L'insufficienza renale cronica (CKD) è associata ad un rischio cardiovascolare più elevato rispetto alla popolazione generale: fattori come uremia, stress ossidativo, età dialitica, infiammazione, alterazioni del metabolismo minerale e presenza di calcificazioni vascolari incidono fortemente sulla morbosità e mortalità per cause cardiovascolari nel paziente uremico. Diversi studi hanno verificato il coinvolgimento dei progenitori endoteliali (EPC) nella malattia aterosclerotica ed è stato dimostrato che esprimono osteocalcina, marcatore di calcificazione. Inoltre, nella CKD è presente una disfunzione in numero e funzionalità delle EPC. Attualmente, il ruolo delle EPC nella formazione delle calcificazioni vascolari nei pazienti in dialisi non è stato ancora chiarito. Lo scopo della tesi è quello di studiare le EPC prelevate da pazienti con CKD, al fine di determinarne numero e fenotipo. È stato anche valutato l'effetto del trattamento in vitro e in vivo con calcitriolo e paracalcitolo sulle EPC, dato il deficit di vitamina D dei pazienti con CKD: il trattamento con vitamina D sembra avere effetti positivi sul sistema cardiovascolare. Sono stati valutati: numero di EPC circolanti e la relativa espressione di osteocalcina e del recettore della vitamina D; morfologia e fenotipo EPC in vitro; effetti di calcitriolo e paracalcitolo sull’espressione di osteocalcina e sui depositi di calcio. I risultati dello studio suggeriscono che il trattamento con vitamina D abbia un effetto positivo sulle EPC, aumentando il numero di EPC circolanti e normalizzandone la morfologia. Sia calcitriolo che paracalcitolo sono in grado di ridurre notevolmente l’espressione di OC, mentre solo il paracalcitolo ha un effetto significativo sulla riduzione dei depositi di calcio in coltura. In conclusione, il trattamento con vitamina D sembra ridurre il potenziale calcifico delle EPC nell’uremia, aprendo nuove strade per la gestione del rischio cardiovascolare nei pazienti affetti da CKD.

The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients

Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients.

Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation

In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species-dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D.

Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

BACKGROUND: Surfactant protein D (SP-D) deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D) has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. METHODS: SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. MAIN RESULTS: After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. CONCLUSION: Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are characterized by decreased SP-D levels in the lung.

Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study.

BACKGROUND Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity. METHODS A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups--severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml)--were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed. RESULTS About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer. CONCLUSIONS Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

BACKGROUND Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation. RESULTS A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year. CONCLUSIONS This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.