38 resultados para 3-Hydroxysteroid Dehydrogenases -- genetics -- metabolism


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Dietary fat composition can interfere in the development of obesity due to the specific roles of some fatty acids that have different metabolic activities, which can alter both fat oxidation and deposition rates, resulting in changes in body weight and/or composition. High-fat diets in general are associated with hyperphagia, but the type of dietary fat seems to be more important since saturated fats are linked to a positive fat balance and omental adipose tissue accumulation when compared to other types of fat, while polyunsaturated fats, omega-3 and omega-6, seem to increase energy expenditure and decrease energy intake by specific mechanisms involving hormone-sensitive lipase, activation of peroxisome proliferator-activated receptor α (PPARα) and others. Saturated fat intake can also impair insulin sensitivity compared to omega-3 fat, which has the opposite effect due to alterations in cell membranes. Obesity is also associated with impaired mitochondrial function. Fat excess favors the production of malonyl-CoA, which reduces GLUT4 efficiency. The tricarboxylic acid cycle and beta-oxidation are temporarily uncoupled, forming metabolite byproducts that augment reactive oxygen species production. Exercise can restore mitochondrial function and insulin sensitivity, which may be crucial for a better prognosis in treating or preventing obesity.

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Our objective was to evaluate the concentrations of serum 25-hydroxyvitamin D [25(OH)D], serum calcium, serum phosphorus, alkaline phosphatase, and parathormone (PTH) in patients with polyarticular juvenile idiopathic arthritis (JIA) and to associate them with disease duration and activity, bone mineral density and use of medications. In a cross-sectional and controlled study, 30 patients with polyarticular JIA were evaluated and compared to 30 healthy individuals matched for age and gender. Clinical status, anthropometry, laboratory markers in both patients and controls, and bone mineral density, only in the patients, were measured. Of the 30 patients included in the study, 23 (76.7%) were female and 16 (53.3%) non-Caucasian; mean age was 14 years (range = 4 to 20 years). Mean disease duration was 5 years (range = 1 to 12 years). The mean concentrations of serum albumin-corrected calcium (9.04 ± 0.41 mg/dL) and alkaline phosphatase (153.3 ± 100.1 IU) were significantly lower in patients with JIA than in controls (P < 0.0001 and P = 0.001, respectively). No differences in 25(OH)D, PTH or serum phosphorus were observed between JIA and control subjects. Regarding 25(OH)D concentration, 8 patients (26.7%) and 5 controls (16.7%) had 25(OH)D concentrations compatible with deficiency (lower than 20 ng/mL) and 14 patients (46.7%) and 18 controls (60%) had concentrations compatible with insufficiency (20-32 ng/mL). These values were not associated with disease activity, use of medications or bone mineral density. We observed a high frequency of 25(OH)D insufficiency and deficiency in the study sample. The compromised bone metabolism emphasizes the importance of follow-up of JIA patients.

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Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

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Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.

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The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.

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Although the metabolism of early bovine embryos has not been fully elucidated, several publications have addressed this important issue to improve culture conditions for cattle reproductive biotechnologies, with the ultimate goal of producing in vitro embryos similar in quality to those developing in vivo. Here, we review general aspects of bovine embryo metabolism in vitro and in vivo, and discuss the use of metabolic analysis of embryos produced in vitro to assess viability and predict a viable pregnancy after transference to the female tract.

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We evaluated the effects of defatted amaranth (Amaranthus caudatus L.) snacks on plasma lipids in moderate hypercholesterolemic patients. Twenty-two subjects [30-65 years old), 11 males, with total cholesterol (TC) > 240 mg.dL-1, low-density cholesterol (LDL-c) 160-190 mg.dL-1 and plasma triglycerides (TG) < 400 mg.dL-1] were randomized in a double blind clinical trial to receive an amaranth snack (50 g/day) or equivalent corn snack (placebo) for 2 months. There were no differences between amaranth and placebo on TC and LDL-c, and TG respectively: -8.4 and -5.7% (p = 0.17); -12.3 and -9.7% (p = 0.41) and -0.6 and -7.3% (p = 0.47). However, amaranth snacks significantly reduced high-density cholesterol (HDL-c): -15.2 vs. -4% (p = 0.03). In conclusion, the intake of 50 g of extruded amaranth daily during 60 days did not significantly reduce LDL-c in moderate hypercholesterolemic subjects; furthermore there was a significant reduction in HDL-c. Studies with greater number of subjects and greater quantity of this food are necessary to test the effects of amaranth on lipid metabolism in humans.

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Abstract The present work aimed at studying the effect of different drying methods applied to tilapia byproducts (heads, viscera and carcasses) fed with flaxseed, verifying the contents of omega-3 fatty acids. Two diets were given to the tilapia: a control and a flaxseed formulation, over the course of 60 days. After this period, they were slaughtered and their byproducts (heads, viscera and carcasses) were collected. These fish parts were analyzed in natura, lyophilized and oven dried. Byproducts from tilapia fed with flaxseed presented docosapentaenoic, eicopentaenoic and docosahexanoic fatty acids as a result of the enzymatic metabolism of the fish. The byproducts from the oven drying process had lower levels of polyunsaturated fatty acids. In the multivariate analysis, the byproducts from fish fed with flaxseed had a greater composition of fatty acids. The addition of flaxseed in fish diets, as well as the utilization of their byproducts, may become a good business strategy. Additionally, the byproducts may be dried to facilitate transport and storage.