Influência dos polimorfismos Taql e Bsml do gene do receptor de vitamina D no surgimento de infecção, tempo de internação e mortalidade em pacientes queimados

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Análise de pathway e network em tecido adiposo in vivo e o papel da vitamina D na adipogênese in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

Parenteral administration of vitamins A, D and E on the oxidative metabolism and function of polymorphonuclear leukocytes in swine

The weaning period of piglets is characterized by physiological alterations, such as decreased weight gain, increased reactive oxygen species (ROS) and increased serum cortisol levels with possible effects on the immune response. The effect of parenteral administration of vitamins A, D and E on production performance, oxidative metabolism, and the function of polymorphonuclear leukocytes (PMNLs) was assessed in piglets during the weaning period. The sample was comprised of 20 male piglets that were given an injectable ADE vitamin combination (135,000 IU vitamin A, 40,000 IU vitamin D and 40mg vitamin E/animal) at 20 and 40 days of age. Weight gain, concentration of reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and the microbicidal and phagocytic activity of PMNLs were assessed. No difference was observed in the average piglet weight during the study; however, a greater percentage of weight gain was observed after weaning in the treated group. The concentrations of GSH and SOD did not differ between groups, although lipid peroxidation was greater in the control group at 60 days of age. The investigated variables of oxidative metabolism were correlated as follows: -0.41 for GSH and MDA, -0.54 for GSH and SOD and 0.34 for MDA and SOD. The intensity of intracellular ROS production, the percentage of ROS-producing PMNLs and the intensity of phagocytosis by PMNLs did not differ between treatment groups. Administration of the injectable ADE combination improved the percentage of weight gain between 20 and 40 days of age, decreased oxidative stress at 60 days of age and did not influence the function of PMNLs in piglets.

Nutrient Intake of Women 3 Years After Roux-en-Y Gastric Bypass Surgery

Nutritional deficiencies, especially micronutrient deficiencies, can occur in obese individuals. Surgical treatment may aggravate or cause these deficiencies, depending on the type of procedure, food intake and the use of multivitamins, minerals or other supplements. The objective of the study was to evaluate the nutrient intake of women who had undergone Roux-en-Y gastric bypass (RYGB) surgery. A cross-sectional, controlled study was conducted among 44 women after RYGB (operated-group, OG; mean years post-operation = 3.4) and a control group of 38 healthy women (non-operated group, NOG) matched by age and economic condition. The women reported their dietary intake using a 4-day record. The Dietary Reference Intakes was used as a reference. The macronutrient contributions to dietary energy intake presented an acceptable distribution for proteins and carbohydrates. Lipid intake was high among women in the OG and the NOG (43.2 and 55.3 %, respectively). In the evaluation of micronutrients, a statistically significant difference was observed between the groups for iron, zinc and vitamins B1 and B12. Both groups were at high risk for inadequate calcium intake, and the OG was at risk for inadequate zinc, iron and vitamin B1 intake. The nutrient intake of women who had undergone RYGB is very similar to that of non-operated women, with the exception of a reduced intake of iron, zinc and vitamins B1 and B12, which may be due to the difficulty of consuming meat and a balanced diet. The findings of this study emphasize the importance of appropriate nutritional intervention and the regular use of multivitamin and mineral supplements for these patients.

Statistical Innovations Improve Prevalence Estimates of Nutrient Risk Populations: Applications in Sao Paulo, Brazil

The objective of this study was to estimate the prevalence of inadequate micronutrient intake and excess sodium intake among adults age 19 years and older in the city of Sao Paulo, Brazil. Twenty-four hour dietary recall and sociodemographic data were collected from each participant (n=1,663) in a cross-sectional study, Inquiry of Health of Sao Paulo, of a representative sample of the adult population of the city of Sao Paulo in 2003 (ISA-2003). The variability in intake was measured through two replications of the 24-hour recall in a subsample of this population in 2007 (ISA-2007). Usual intake was estimated by the PC-SIDE program (version 1.0, 2003, Department of Statistics, Iowa State University), which uses an approach developed by Iowa State University. The prevalence of nutrient inadequacy was calculated using the Estimated Average Requirement cut-point method for vitamins A and C, thiamin, riboflavin, niacin, copper, phosphorus, and selenium. For vitamin D, pantothenic acid, manganese, and sodium, the proportion of individuals with usual intake equal to or more than the Adequate Intake value was calculated. The percentage of individuals with intake equal to more than the Tolerable Upper Intake Level was calculated for sodium. The highest prevalence of inadequacy for males and females, respectively, occurred for vitamin A (67% and 58%), vitamin C (52% and 62%), thiamin (41% and 50%), and riboflavin (29% and 19%). The adjustment for the within-person variation presented lower prevalence of inadequacy due to removal of within-person variability. All adult residents of Sao Paulo had excess sodium intake, and the rates of nutrient inadequacy were high for certain key micronutrients. J Acad Nutr Diet. 2012;112:1614-1618.

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.

Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism

Objective: To confirm previous evidence suggesting an association between autism and low vitamin D serum levels. Methods: This preliminary exploratory study assessed the circulating levels of 25-hydroxyvitamin D (25-OHD) in pediatric patients with autism and in typically developing controls from Juiz de Fora, Brazil. Results: Serum levels of 25-OHD were lower in children with autism (26.48 ± 3.48 ng mL-1) when compared to typically developing subjects (40.52 ± 3.13 ng mL-1) (p < 0.001). Conclusion: Our findings attest to the importance of vitamin supplementation during pregnancy and in the treatment of children with autism, who tend to present low vitamin D consumption rates.

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.

Ventricular-arterial coupling in a rat model of reduced arterial compliance provoked by hypervitaminosis D and nicotine

The vitamin D(3) and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group (n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 +/- 6 vs. 116 +/- 13 mmHg, P < 0.01) and pulse (42 +/- 10 vs. 26 +/- 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 +/- 0.08 vs. 0.21 +/- 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 +/- 2.5 vs. 5.1 +/- 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group (P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 +/- 0.06 vs. 0.52 +/- 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 +/- 3.1 vs. 8.4 +/- 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.

[Hypercalcemia in sarcoidosis--case report, prevalence, pathophysiology and therapeutic options]

Hypercalcemia is a highly prevalent complication of sarcoidosis. A medical history of a patient with sarcoidosis is shown as case report. Depending on the population studied about 2-63% of sarcoidosis patients show hypercalcemia. The major difference in the prevalence of hypercalcemia may be in part due to the undulating course of subacute sarcoidosis, so hypercalcemia may be missed when serum calcium is not frequently measured. Hypercalciuria appears to be twice as prevalent then hypercalcemia and should be looked for in every sarcoidosis patient. Hypercalcemia in sarcoidosis is due to the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages. 1,25-dihydroxyvitamin D3 leads to an increased absorption of calcium in the intestine and to an increased resorption of calcium in the bone. Immunoregulatory properties have been ascribed to 1,25-dihydroxyvitamin D3. It is an important inhibitor of interleukin-2 and of interferon-gamma-synthesis, two cytokines that are important in granuloma formation in sarcoidosis. It is thought that 1,25-dihydroxyvitamin D3 counterregulates uncontrolled granuloma formation. Treatment of hypercalcemia depends on the serum level of hypercalcemia and its persistence. Generally sarcoidotic patients should be advised to avoid sun exposition to reduce vitamin D3 synthesis in the skin, to omit fish oils that are rich of vitamin D and to produce more than two liters urine a day by adapting fluid intake. Although severe hypercalcemia seems to be rare, glucocorticosteroid treatment should be started if corrected total calcium level rises beyond 3 mmol/l. If hypercalcemia is symptomatic, treatment should be started even at lower levels. Glucocorticosteroids act by inhibition of the overly 1alpha-hydroxylase activity of macrophages. Alternatively, treatment with chloroquine or ketoconazole can be established. If isolated hypercalciuria without hypercalcemia is present with evidence for recurrent nephrolithiasis, patients can be treated with a thiazide diuretic.

[Osteoporosis diet]

Bone requires a wide variety of nutrients to develop normally and to maintain itself after growth. Most important--in the sense that bony abnormalities are associated with their deficiencies--are protein, calcium, phosphorus, vitamin D, C and K, zinc, manganese and copper. The nutrients most likely to be deficient in citizens of industrialized countries are calcium and vitamin D. In this review of the current literature about nutritional aspects of osteoporosis, we have focused on factors influencing calcium requirement: the principal interacting nutrients are sodium, protein, caffeine, fiber, oxalate, phytate, and the acid/alkaline ash character of the overall diet. Fiber and caffeine decrease calcium absorption from the gut and typically exert relatively minor effects, while sodium, protein and the acid/alkaline balance of the diet increase urinary excretion of calcium and are of much greater significance for the calcium homeostasis. Alkali buffers, whether vegetables or fruits reverse this urinary calcium loss. As long as accompanied by adequate calcium intake, protein-rich diet is not deleterious to bone: a calcium-to-protein ratio of 20:1 (mg calcium/g protein) is recommended. Whether a nutrition-based therapeutic approach to osteoporosis is feasible in the near future is yet unclear: at least there are some recent promising data from in-vitro as well as from rat studies showing that extracts taken from various vegetables, mainly from the onion family inhibit bone resorption in a dose-dependent manner.

ROLE OF VITAMIN-D3 AND RETINOIC ACID IN A HUMAN THP-1 MACROPHAGE MODEL OF MYCOBACTERIUM TUBERCULOSIS INFECTION

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited thesubsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb infected THPs that fused with adjacent cells to formmultinucleate giant cells (MNGCs). Typically MNGCs occurred over 30 days of in vitro culture and contained non-replicating persisting Mtb for as long as 60 days in culture. We propose that the RAVD mediated inhibition of replicating Mtb leading to persistence of non-replicating Mtb within THPs may provide a novel human macrophage model simulating formation of MNGCs in humanlungs.

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.

Baseline hypovitaminosis D is not associated with poor clinical outcomes in osteoarticular infections

OBJECTIVES Although vitamin D is recognized as an important factor in bone health, its role in osteoarticular infections is unclear. We hypothesized that low vitamin D (25-hydroxycholecalciferol) levels are associated with a lower likelihood of treatment success in osteoarticular infections. METHODS This was a retrospective cohort study of patients with orthopedic infections who had a 25-hydroxycholecalciferol level drawn when their infection was diagnosed. Outcomes were determined at early (3-6 months) and late (≥6 months) follow-up after completing intravenous antibiotics. RESULTS We included 223 patients seen during an 11-month period with osteoarticular infections and baseline 25-hydroxycholecalciferol levels. During the initial inpatient management of the infection, hypovitaminosis D was identified and treated. The mean 25-hydroxycholecalciferol level was 23±14ng/ml; 167 (75%) patients had levels <30ng/ml. Overall, infection treatment success was 91% (159/174) at early follow-up and 88% (145/164) at late follow-up. 25-Hydroxycholecalciferol baseline levels were similar in those with and without successful clinical outcomes, both at early (25±15 vs. 21±9ng/ml; p=0.3) and late follow-up (25±15 vs. 23±16ng/ml; p=0.6). CONCLUSIONS To our knowledge this is the first report on hypovitaminosis D and its impact on outcomes of osteoarticular infections. Hypovitaminosis D was frequent in this cohort. With vitamin D repletion, there was no difference in treatment success whether patients had baseline hypovitaminosis or not.