Navegando por Palavras-chave "Receptor De Vitamina D"

Agora exibindo 1 - 2 de 2
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Avaliação da expressão do receptor de vitamina d (VDR) e das hidroxilases CYP27B1 e CYP24A1 e concentração sérica de 1,25-dihidroxivitamina D em pacientes litiásicos
    (Universidade Federal de São Paulo (UNIFESP), 2019-06-03) Melo, Thalita Lima [UNIFESP]; Heilberg, Ita Pfeferman [UNIFESP]; http://lattes.cnpq.br/5039409992847018; http://lattes.cnpq.br/0399585291142239; Universidade Federal de São Paulo (UNIFESP)
    Introduction: The pathophysiological mechanisms for hypercalciuria comprise increased intestinal calcium absorption, reduced renal tubular reabsorption and increased bone resorption, which are influenced by calciotropic hormones such as PTH, FGF-23, 25OHD and 1,25(OH)D. The 1,25(OH)D is synthesized from 25(OH)D by the enzyme CYP27B1 (1α-hydroxylase), exerts its biological functions through binding to the vitamin D receptor (VDR) and is degraded by the enzyme CYP24A1. The expression of VDR and levels of 1,25(OH)D exceed the values of controls in some but not all hypercalciuric stone formers. Objective: We aimed to evaluate the expression of VDR, CYP27B1 and CYP24A1, and the serum 1,25(OH)D levels in hypercalciuric stone formers (HSF) in comparison with normocalciuric stone formers (NSF) and healthy subjects as controls (HS). Methods: Twenty-four-hour urine collections, blood samples for determination of biochemical and hormonal parameters including Klotho and FGF-23 and a 3-day dietary record were obtained from 30 participants from each of the groups. All participants were paired by gender, age and body mass index. VDR, CYP27B1 and CYP24A1 expression were measured by flow cytometry. Results: HSF compared to NSF and HS presented significantly higher urinary volume (2021±101 vs 1547±101 and 1488±101 ml/24h, p=0.000, mean ± standard error) and higher urinary excretion of calcium (345±12 vs 166±12 and 149±12 mg/24h, p=0.000), sodium (215±12 vs 168±10 and 179±10 mEq/24h, p=0.006), magnesium (108.5±6.8 vs 72.8±6.6 and 82.1±6.7 mg/24h, p=0.001), oxalate (25.3±1.6 vs 21.0±1.6 and 19.7±1.5 mg/24h, p=0.03), uric acid (690±26 vs 572±26 and 556±26 mg/24h, p=0.000) and phosphorus (979±49 vs 791±48 and 702±49 mg/24h, p=0.000). Calcium intake was lower in HSF versus NSF and HS (442±41 vs 594±42 and 559±41mg, respectively, p=0.027) and salt (NaCl) intake was higher in HSF versus NSF and HS (12.6±0.6 vs 9.8±0.6 e 10.5±0.6 g/day, p=0.006). Protein intake, assessed by protein equivalent of nitrogen appearance (PNA), was lower in HSF and NSF versus HS (1.1±0.0 and 1.0±0.0 vs 1.4±0.0 g/kg/day, p=0.006) with no differences in estimated potential renal acid load (PRAL), phosphorus and potassium intake among groups. Ionized calcium was significantly lower in HSF than NSF (1.29±0.0 vs 1.31±0.0 mmol/L, p<0.01). Serum 1,25(OH)D was significantly higher, even within normal ranges, in HSF and NSF than HS (22.5±1.2; 22.2±1.2 vs 17.4±1.2 pg/ml, p=0.007, respectively) but serum 25(OH)D, PTH, α-Klotho and plasma FGF-23 did not differ among groups. The VDR expression was higher in HSF and NSF than HS (80.8±3.2; 78.7±3.3 vs 68.6±3.2%, p=0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43±0.25 and 0.56±0.10 than 0.34±0.06, p=0.00). Conclusions: Stone-formers, regardless of urinary calcium levels, had higher VDR expression and 1,25(OH)D levels compared to controls. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    O papel da vitamina D na fisiopatologia dos miomas uterinos: revisão sistemática em modelos animais, estudos in vitro e observações clínicas
    (Universidade Federal de São Paulo (UNIFESP), 2020-08-27) Barillari, Priscila Cristina Souza Giolo [UNIFESP]; Silva, Ivaldo Da [UNIFESP]; Universidade Federal de São Paulo
    Fibroids are benign tumors in women of reproductive age and although associated with hormonal, genetic and molecular factors, the exact factor leading to its development is unknown. About 50% of patients are asymptomatic, but the other 50% may have symptoms such as abnormal uterine bleeding, pelvic pressure or pain, compressive symptoms, causing significant morbidity and affecting their quality of life, as well as infertility. Treatment of this condition should be individualized depending on various factors such as number, size and location of the tumor. In most cases, the treatment is performed surgically, either by myomectomy or hysterectomy. Over the years, a search for less aggressive treatments in the medical area using medications that can prevent growth and problems caused by fibroids are on course. Within the pharmacological options there are several therapeutic classes of medications such as steroid synthesis inhibitors and steroid receptor modulators that control the symptoms and decrease the volume of the fibroid. However, surgical treatment remains the most effective and definitive treatment when pharmacological therapy is not sufficient to control symptoms. Several studies have now shown the role of vitamin D in the development of fibroids and studies are demonstrating the reduction in fibroid size when myomatous cells are brought into contact with high doses of vitamin D. The presence of vitamin D was able to prevent and decrease the proliferation of fibroids and their cells. The mechanisms by which vitamin D influences the development of fibroids are not yet fully known. This systematic review suggests that the hormone (1,25 (OH)2 D3) plays an important role in controlling cell growth, programmed cell death, damage to DNA, and low levels of vitamin D appears to be a critical factor for the etiopathogenesis of uterine fibroids. Currently, there are several attempts to create a drug that is safe, effective and inexpensive for the treatment and prevention of fibroids and the identification of modifiable risk factors, such as 1,25 (OH)2 D3 deficiency is promising. In addition, it is assumed that vitamin D can regulate the excess of specific proteins present in tumor cells, proteins that would be at high levels compared to uterine cells without fibroids. These proteins are known as metalloproteinases and are enzymes that degrade extracellular material, leading to tumor growth, when in excess.