High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

Maternal serum endoglin as an early marker of pre-eclampsia in high-risk patients

Tarek M Elhawary,1 Aml S El-Bendary,2 Hala Demerdash31Department of Obstetrics and Gynecology and Department of Clinical Pathology, 2Faculty of Medicine, Tanta University, Tanta, 3Alexandria Main University Hospital, Alexandria, EgyptBackground: Pre-eclampsia is a potentially serious condition that still accounts for significant morbidity and mortality for the affected mother and neonate. Although the pathogenesis is not fully understood, it is now widely accepted that vascular endothelial dysfunction is the most important and principal event in the pathophysiology of the disease. The aims of our study were to compare serum soluble endoglin levels at week 13 in normotensive pregnant women and in high-risk women, to determine whether the maternal plasma soluble endoglin concentration at 26 weeks is increased in pregnancies that subsequently develop pre-eclampsia, and to identify if soluble endoglin measurement improves the results of screening for pre-eclampsia.Methods: This work was conducted in 60 healthy pregnant controls and 110 pregnant women at high risk for pre-eclampsia. Gestational age was confirmed by date of last menstrual period and first trimester ultrasound. The time of onset of pre-eclampsia was defined as the time of first elevated blood pressure or urinary protein measurement leading to the diagnosis. Blood samples were collected for measurement of soluble endoglin and other routine laboratory tests, including measurement of urinary proteins. Serum soluble endoglin was estimated by sandwich enzyme-linked immunosorbent assay.Results: There was a highly significant increase in serum soluble endoglin in high-risk women compared with controls at week 13 (P < 0.001). Further determination of soluble endoglin revealed a more significant increase in women who developed early-onset pre-eclampsia compared with those who developed late-onset pre-eclampsia. Moreover, a significant positive correlation was found between soluble endoglin and both diastolic blood pressure and total urinary protein, ie, severity of pre-eclampsia.Conclusion: Estimation of serum soluble endoglin at gestational week 13 could be used as a sensitive screening test for women at high risk of developing pre-eclampsia prior to onset of its clinical manifestations, which could potentially improve the outcome of pregnancy.Keywords: pregnancy, pre-eclampsia, high risk, gestational age, endogli

Enzymatic biomarkers as indicators of dietary cadmium in gypsy moth caterpillars

Heavy metals damage the structure, chemistry, and function of cells, including enzyme systems inside them. Variation in the profile of biochemical biomarkers in prevalent species should be used for assessing environmental contamination. The present study pays attention to the phosphatases present in the midgut of gypsy moth fourth instar caterpillars, which had been exposed to short- and long-term cadmium intake at 10 and 30 μg Cd/g dry food. Chronic cadmium ingestion significantly inhibited the activity of all examined phosphatases, while only the activity of lysosomal phosphatase was acutely decreased. Total acid phosphatase activity recovered from both long-term cadmium treatments within 3 days. The low index of phenotypic plasticity was connected to high variability of plasticity. Dependence of phosphatase isoforms on genotype and duration of cadmium treatment was determined. We concluded that, with further investigations, profiling of total acid phosphatase activity, as well as the lysosomal fraction can be used as a biomarker for acute sublethal metal toxicity.Serbian Ministry of Education, Science and Technological Development [173027