Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity

Prostasin, a membrane-bound serine protease, is known to increase the activity of the epithelial sodium channel (ENaC). Gene expression of prostasin was shown to be regulated by aldosterone, which increases the rate of sodium reabsorption through ENaC. To clarify the physiological relationships among prostasin, aldosterone and ENaC, we developed a specific radioimmunoassay (RIA) for human prostasin. Prostasin levels in urine were determined in 26 normotensive and 121 hypertensive subjects. Aldosterone content in urine and plasma, urinary Na/K ratio and other clinical parameters were also measured. We observed a highly significant correlation between prostasin and aldosterone concentration in urine (correlation coefficient: 0.673, P<0.0001). A significant correlation was also found between urinary prostasin and plasma aldosterone concentration (correlation coefficient: 0.229, P<0.05). In addition, urinary prostasin excretion was inversely correlated with urinary Na/K ratio (correlation coefficient: -0.425, P<0.0001). In conclusion, we developed a prostasin-specific RIA and applied it to the clinical study. Our findings suggest that urinary prostasin level is strongly correlated with urinary or plasma aldosterone level and may serve as a surrogate marker for ENaC activation in hypertensive patients. However, it is not clear, at the present time, whether endogenous aldosterone regulates prostasin expression or vice versa

The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n=53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n=35, 5-ALA-SFC; n=18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141

Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity

Prostasin, a membrane-bound serine protease, is known to increase the activity of the epithelial sodium channel (ENaC). Gene expression of prostasin was shown to be regulated by aldosterone, which increases the rate of sodium reabsorption through ENaC. To clarify the physiological relationships among prostasin, aldosterone and ENaC, we developed a specific radioimmunoassay (RIA) for human prostasin. Prostasin levels in urine were determined in 26 normotensive and 121 hypertensive subjects. Aldosterone content in urine and plasma, urinary Na/K ratio and other clinical parameters were also measured. We observed a highly significant correlation between prostasin and aldosterone concentration in urine (correlation coefficient: 0.673, P<0.0001). A significant correlation was also found between urinary prostasin and plasma aldosterone concentration (correlation coefficient: 0.229, P<0.05). In addition, urinary prostasin excretion was inversely correlated with urinary Na/K ratio (correlation coefficient: -0.425, P<0.0001). In conclusion, we developed a prostasin-specific RIA and applied it to the clinical study. Our findings suggest that urinary prostasin level is strongly correlated with urinary or plasma aldosterone level and may serve as a surrogate marker for ENaC activation in hypertensive patients. However, it is not clear, at the present time, whether endogenous aldosterone regulates prostasin expression or vice versa