Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.

Heat stress, hydration and uric acid: a cross-sectional study in workers of three occupations in a hotspot of Mesoamerican nephropathy in Nicaragua.

OBJECTIVES: To study Mesoamerican nephropathy (MeN) and its risk factors in three hot occupations. DESIGN: Cross-sectional. SETTING: Chinandega and León municipalities, a MeN hotspot on the Nicaraguan Pacific coast, January-February 2013. PARTICIPANTS: 194 male workers aged 17-39 years: 86 sugarcane cutters, 56 construction workers, 52 small-scale farmers. OUTCOME MEASURES: (1) Differences between the three occupational groups in prevalences/levels of socioeconomic, occupational, lifestyle and health risk factors for chronic kidney disease (CKD) and in biomarkers of kidney function and hydration; (2) differences in prevalences/levels of CKD risk factors between workers with reduced estimated glomerular filtration rate (eGFRCKD-EPI <80 mL/min/1.73 m2) and workers with normal kidney function (eGFRCKD-EPI ≥80 mL/min/1.73 m2). RESULTS: Sugarcane cutters were more exposed to heat and consumed more fluid on workdays and had less obesity, lower blood sugar, lower blood pressure and a better lipid profile. Reduced eGFR occurred in 16%, 9% and 2% of sugarcane cutters, construction workers and farmers, respectively (trend cane > construction > farming, p=0.003). Significant trends (cane > construction > farming) were also observed for high serum urea nitrogen (blood urea nitrogen (BUN) >20 mg/dL), high serum creatinine (SCr >1.2 mg/dL), low urinary pH (≤5.5) and high BUN/SCr ratio (>20) but not for high urinary specific gravity (≥1.030). Sugarcane cutters also more often had proteinuria and blood and leucocytes in the urine. Workers with eGFR <80 mL/min/1.73 m2 reported a higher intake of water and lower intake of sugary beverages. Serum uric acid levels related strongly and inversely to eGFR levels (adj ß -10.4 mL/min/1.73 m2, 95% CI -12.2 to -8.5, p<0.001). No associations were observed for other metabolic risk factors, pesticides, non-steroidal anti-inflammatory drugs or alcohol. Among cane cutters, consumption of electrolyte hydration solution appeared preventive (adj ß 8.1 mL/min/1.73 m2, p=0.09). CONCLUSIONS: Heat stress, dehydration and kidney dysfunction were most common among sugarcane cutters. Kidney dysfunction also occurred to a lesser extent among construction workers, but hardly at all among small-scale farmers. High serum uric acid was associated with reduced kidney function.

Serum uric acid and hypertension in adults: a paradoxical relationship in type 1 diabetes.

Adults with type 1 diabetes have lower serum uric acid levels compared with nondiabetic adults. Little is known about the relationship between serum uric acid and blood pressure in type 1 diabetes and whether it differs from the positive relationship found in nondiabetic adults. The authors assessed the cross-sectional and longitudinal relationships over 6 years between serum uric acid and blood pressure in adults with (35±9 years [n=393]) and without (38±9 years [n=685]) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study. In nondiabetic adults, serum uric acid was associated with systolic blood pressure in multivariable models adjusted for cardiovascular risk factors. In adults with type 1 diabetes, a negative association was observed between serum uric acid and systolic blood pressure after multivariable adjustments. A positive association was observed between serum uric acid and systolic blood pressure in nondiabetic adults. In contrast, an inverse relationship was demonstrated after multivariable adjustments in type 1 diabetes.

High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase.

UNLABELLED: Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with a high-fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild-type or fructokinase knockout mice were fed a low-fat (11%), high-fat (36%), or high-fat (36%) and high-sucrose (30%) diet for 15 weeks. Both wild-type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence of hepatic inflammation on a high-fat diet compared to a low-fat diet. In contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis with low-grade inflammation and fibrosis, as noted by increased CD68, tumor necrosis factor alpha, monocyte chemoattractant protein-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. CONCLUSION: An additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high-fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis.

Hiperuricemia como factor de riesgo para el desarrollo de hipertensión, daño renal crónico y síndrome metabólico / Hyperuricemia as a risk factor for developing hypertension, chronic kidney damage and metabolic syndrome

Por mucho tiempo se ha descrito una asociación entre la hiperuricemia y el desarrollo de hipertensión arterial, enfermedades cardiovascular y renal, así como síndrome metabólico: sin embargo el mecanismo de año asociado a la hiperuricemia no ha sido aclarado totalmente, principalmente debido a la fala de un modelo experimental adecuado. actualmente existe un renovado interés por el posible papel patogénico del ácido úrico; estudios clínicos, epidemiológicos y expeirmentales sugieren que la hiperuricemia puede contribuir al desarrollo y permanencia de la hipertension arterial sistémica, las enfermedades cardiovasculares y renales, el síndrome metabólico y posiblemente la diabetes mellitus tipo 2.

Hiperuricemia como factor de riesgo para el desarrollo de hipertensión, daño renal crónico y síndrome metabólico / Hyperuricemia as a risk factor for developing hypertension, chronic kidney damage and metabolic syndrome

Por mucho tiempo se ha descrito una asociación entre la hiperuricemia y el desarrollo de hipertensión arterial, enfermedades cardiovascular y renal, así como síndrome metabólico: sin embargo el mecanismo de año asociado a la hiperuricemia no ha sido aclarado totalmente, principalmente debido a la fala de un modelo experimental adecuado. actualmente existe un renovado interés por el posible papel patogénico del ácido úrico; estudios clínicos, epidemiológicos y expeirmentales sugieren que la hiperuricemia puede contribuir al desarrollo y permanencia de la hipertension arterial sistémica, las enfermedades cardiovasculares y renales, el síndrome metabólico y posiblemente la diabetes mellitus tipo 2.(AU)