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Roncal-Jimenez C.A.,University of Colorado at Denver | Garcia-Trabanino R.,Scientific Board | Wesseling C.,Karolinska Institutet | Johnson R.J.,University of Colorado at Denver
Blood Purification | Year: 2016

Background: An epidemic of chronic kidney disease (CKD) of unknown cause has emerged along the Pacific Coast of Central America. The disease primarily affects men working manually outdoors, and the major group affected is sugarcane workers. The disease presents with an asymptomatic rise in serum creatinine that progresses to end-stage renal disease over several years. Renal biopsies show chronic tubulointerstitial disease. While the cause remains unknown, recent studies suggest that it is driven by recurrent dehydration in the hot climate. Potential mechanisms include the development of hyperosmolarity with the activation of the aldose reductase-fructokinase pathway in the proximal tubule leading to local injury and inflammation, and the possibility that renal injury may be the consequence of repeated uricosuria and urate crystal formation as a consequence of both increased generation and urinary concentration, similar to a chronic tumor lysis syndrome. The epidemic is postulated to be increasing due to the effects of global warming. Summary: An epidemic of CKD has led to the death of more than 20,000 lives in Central America. The cause is unknown, but appears to be due to recurrent dehydration. Potential mechanisms for injury are renal damage as a consequence of recurrent hyperosmolarity and/or injury to the tubules from repeated episodes of uricosuria. Key Messages: The epidemic of CKD in Mesoamerica may be due to chronic recurrent dehydration as a consequence of global warming and working conditions. This entity may be one of the first major diseases attributed to climate change and the greenhouse effect. © 2016 S. Karger AG, Basel.

Rezaeian A.,Scientific Board | Ghayour-Mobarhan M.,Biochemistry of Nutritional Research Center | Mazloum S.R.,Nursing and Midwifery School | Yavari M.,Educational Development Office | Jafari S.-A.,Mashhad University of Medical Sciences
Singapore Medical Journal | Year: 2014

INTRODUCTION Iron deficiency, associated with a decline in cognitive function, is the most common nutritional deficiency globally. The present study aimed to identify the impact of weekly iron supplements on the attention function of female students from a high school in North Khorasan Province, Iran.METHODS This was a blind, controlled, clinical trial study, involving 200 female students who were chosen using the stratified randomised sampling method. First, laboratory studies were performed to detect iron consumption limitations. Next, the 200 students were divided randomly and equally into case and control groups. The case group was treated with 50 mg of ferrous sulfate twice a week for 16 weeks. We compared both groups’ data on attention, iron status and erythrocyte indices. Questionnaires were used to collect demographic data, while clinical data was collected using complete blood count and Toulouse-Piéron tests. Data was analysed using descriptive statistics, as well as paired and independent t-tests.RESULTS The mean attention scores of the case and control groups were 104.8 ± 7.0 and 52.7 ± 9.6, respectively (p < 0.001). The mean haemoglobin levels of the two groups were 12.5 ± 0.9 and 11.2 ± 1.0, respectively (p < 0.001). Compared to the control group, the attention scores and haemoglobin concentrations of the case group were found to be improved by approximately 90% and 10%, respectively.CONCLUSION Oral iron supplements (50 mg twice a week for 16 weeks) were able to improve the attention span and haematologic indices of female high school students. © 2014, Singapore Medical Association. All rights reserved.

Loginov V.I.,Russian Academy of Medical Sciences | Dmitriev A.A.,RAS Engelhardt Institute of Molecular Biology | Senchenko V.N.,RAS Engelhardt Institute of Molecular Biology | Pronina I.V.,Russian Academy of Medical Sciences | And 12 more authors.
PLoS ONE | Year: 2015

The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression. © 2015 Loginov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Roncal-Jimenez C.,University of Colorado at Denver | Garcia-Trabanino R.,Scientific Board | Barregard L.,Sahlgrenska University Hospital | Lanaspa M.A.,University of Colorado at Denver | And 10 more authors.
American Journal of Kidney Diseases | Year: 2016

Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention. © 2016 National Kidney Foundation, Inc.

Garcia-Trabanino R.,Scientific Board | Jarquin E.,Agency for Agricultural Health and Development AGDYSA | Wesseling C.,Karolinska Institutet | Johnson R.J.,University of Colorado at Denver | And 9 more authors.
Environmental Research | Year: 2015

Background: An epidemic of progressive kidney failure afflicts sugarcane workers in Central America. Repeated high-intensity work in hot environments is a possible cause. Objectives: To assess heat stress, dehydration, biomarkers of renal function and their possible associations. A secondary aim was to evaluate the prevalence of pre-shift renal damage and possible causal factors. Methods: Sugarcane cutters (N=189, aged 18-49 years, 168 of them male) from three regions in El Salvador were examined before and after shift. Cross-shift changes in markers of dehydration and renal function were examined and associations with temperature, work time, region, and fluid intake were assessed. Pre-shift glomerular filtration rate was estimated (eGFR) from serum creatinine. Results: The mean work-time was 4 (1.4-11) hours. Mean workday temperature was 34-36. °C before noon, and 39-42. °C at noon. The mean liquid intake during work was 0.8. L per hour. There were statistically significant changes across shift. The mean urine specific gravity, urine osmolality and creatinine increased, and urinary pH decreased. Serum creatinine, uric acid and urea nitrogen increased, while chloride and potassium decreased. Pre-shift serum uric acid levels were remarkably high and pre-shift eGFR was reduced (<60. mL/min) in 23 male workers (14%). Conclusions: The high prevalence of reduced eGFR, and the cross-shift changes are consistent with recurrent dehydration from strenuous work in a hot and humid environment as an important causal factor. The pathophysiology may include decreased renal blood flow, high demands on tubular reabsorption, and increased levels of uric acid. © 2015 The Authors.

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