Influence of hydroxyurea on tubular phosphate handling in sickle cell nephropathy.

OBJECTIVE: This study aims to evaluate the markers of tubular phosphate handling in adults with sickle cell anemia (SCA) and the influence of hydroxyurea (HU), the degree of anemia and Hb F concentration on these markers. METHODS: Eighty-eight steady state SCA patients in outpatient follow-up in Fortaleza, Ceara, Brazil and 31 healthy individuals were included in this study. Vitamin D (25OHD) was measured by enzyme-bound fluorescence assay, intact parathyroid hormone (iPTH) by electrochemiluminescence, and serum and urinary phosphate and creatinine by colorimetric methods. Details of Hb F and HU use were obtained from clinical records. Tubular reabsorption of phosphate (TRP) and maximum tubular reabsorption of phosphate (MTRP) were calculated. SCA patients were stratified according to the use of HU, degree of anemia and percentage of Hb F. The significance level was set for p-values <0.05. RESULTS: Compared to controls the 25OHD level (25 ± 11 vs. 30 ± 9 pg/mL) was lower in SCA, while serum phosphate and MTRP were higher (3.86 ± 0.94 vs. 3.46 ± 0.72 and 3.6 ± 1.21 vs. 3.21 ± 0.53, respectively). There was no significant difference in iPTH, TRP and phosphaturia. Serum phosphate showed correlation with TRP (r = 0.32; p-value = 0.008) and MTRP (r = 0.9; p-value <0.001) in SCA. Patients taking HU, especially those with Hb F >10 % presented reduced serum phosphate levels, and TRP and MTRP rates. Those with mild anemia presented reduced serum phosphate levels and MTRP rates. CONCLUSION: Serum phosphate levels and renal phosphate reabsorption rate were increased in SCA. HU use, high Hb F concentration and total Hb were associated with better control of tubular phosphate handling markers.

Experimental Bothropsatrox Envenomation: Blood Plasma Proteome Effects after Local Tissue Damage and Perspectives on Thromboinflammation.

The clinical manifestations of Bothrops atrox envenoming involve local and systemic changes, among which edema requires substantial attention due to its ability to progress to compartmental syndromes and sometimes cause tissue loss and amputations. However, the impact of edema on the poisoned body's system has not been explored. Thus, the present study aimed to explore the systemic pathological and inflammatory events that are altered by intraplantar injection of B. atrox venom in a mouse model through hematologic, lipidic, and shotgun proteomics analysis. Plasma samples collected showed a greater abundance of proteins related to complement, coagulation, lipid system, platelet and neutrophil degranulation, and pathways related to cell death and ischemic tolerance. Interestingly, some proteins, in particular, Prdx2 (peroxiredoxin 2), Hba (hemoglobin subunit alpha), and F9 (Factor IX), increased according to the amount of venom injected. Our findings support that B. atrox venom activates multiple blood systems that are involved in thromboinflammation, an observation that may have implications for the pathophysiological progression of envenomations. Furthermore, we report for the first time a potential role of Prdx2, Hba, and F9 as potential markers of the severity of edema/inflammation in mice caused by B. atrox.

Interleukin-18 promoter -137 G/C polymorphism (rs187238) is associated with biochemical markers of renal function and cardiovascular disease in type 2 diabetes patients.

BACKGROUND: Interleukin-18 (IL-18), a proinflammatory and proatherogenic cytokine, has been associated with type 2 diabetes, metabolic syndrome, stroke and coronary artery disease. Some studies have indicated that the IL-18 promoter -137 G/C polymorphism seems to be associated with changes in the IL-18 expression and may contribute to the development of cardiovascular disease (CVD). The aim of this study was to evaluate the association between -137 G/C polymorphism and the levels of IL-18, biochemical markers for cardiovascular disorders, anthropometric profile and cardiovascular disease in Brazilian patients with type 2 diabetes (T2DM). DESIGN & METHODS: Study subjects comprised 125 T2DM patients undergoing follow-up at a reference endocrinology service in northeastern Brazil. The -137G/C polymorphism in the IL-18 gene and serum IL-18 levels were determined by using allele-specific polymerase chain reaction (PCR) and enzyme-linked immune assay (ELISA), respectively. The anthropometric parameters were assessed using a Body Composition Monitor with Scale, and the laboratory data were measured using an automatic analyzer as well as spectrophotometric analysis. RESULTS: The genotype distribution of IL-18 -137 G/C genetic polymorphism was significantly different among T2DM patients with and without CVD. The results show an association between the CC genotype of -137G/C polymorphism and CVD in T2DM patients (p < 0.001). Serum levels of IL-18 were significantly higher in CC carriers (843.1 pg/mL) compared with GG or GC carriers (303.6 pg/mL and 292.0 pg/mL, respectively). In addition, the present study showed that carriers of the CC genotype also had significantly higher concentrations of creatinine and albuminuria than carriers of the GG or GC genotypes (p < 0.05 in both). CONCLUSION: These results suggest that Brazilian T2DM patients with the CC genotype seem to show a predisposition to CVD, as well as an elevation in markers of renal function.

Comparison of early cardiovascular risk among Brazilian and African university students.

Cardiovascular diseases are among the main causes of mortality worldwide, and dyslipidemia is a principal factor risk. Hence the study of biochemical markers is necessary for early diagnosis. OBJECTIVES: Evaluate biomarkers to diagnose the risks of cardiovascular diseases in healthy Brazilian and African young adults. DESIGN & METHODS: Weight, height, waist circumference, percentage of body fat and systemic blood pressure were measured; and fasting blood samples were taken for biochemical analysis. Triglycerides, total cholesterol, HDL-c, and apolipoproteins A-I and B were measured on automated equipment using commercially available kits, in addition to the tests of antioxidant capacity of HDL and the enzymatic activity of Paraoxonase 1. RESULTS: After statistical analysis, it was found that BMI, WC, fat (%), triglycerides, ApoB/ApoA-I ratio and Vmax were higher in Brazilians, while HDL-c, ApoA-I, Lag Time, Vmax and PON1 activity were higher in Africans. In Brazilians, the ApoB/ApoA-I ratio was related to obesity factors and lipid profile, but in Africans it was related only to lipids. The antioxidant capacity of HDL and PON1 activity was better in Africans. Through independence testing, we observed an association with moderate risk of myocardial infarction with gender in Africans. In the binary logistic regression analysis, it was found that men in general - and particularly African men - have higher risk of myocardial infarction than women; Odds Ratio 2144 (CI95%: 1343-3424) and 2281 (CI95%: 1082-4811), respectively. CONCLUSIONS: The anthropometric and biochemical parameters of Brazilians, especially men, predispose them to greater risks of cardiovascular diseases.