Search

Prodrug Olmesartan Medoxomil (OM) is an angiotensin II receptor blocker (ARB) and a vitamin D Receptor (VDR) agonist. Reducing the inflammation and improving the immune system OM prevents organ damage. Angiotensin II receptor blockers (ARBs) can raise serum and tissue levels of the membrane-bound form of monocarboxypeptidase angiotensin converting enzyme 2 (ACE2). Increased ACE2 activity causes the balance in the RAAS to shift towards the positive ACE2-Ang-(1-7). Therefore It can be useful with anti-inflammatory, anti-fibrotic and anti-oxidative stress signals in the treatment of immune system diseases. OM is also known to have adverse effects, such as celiac-like enteropathy which was accepted by the FDA. The mechanism of OM's intestinal injury is thought to be the excessive consumption of the enzymes PDX1 and carboxymethylenebutenolidase, which are also responsible for the the digestion of gliadin during the hydrolysis of the drug. Cell-mediated immune response and genetic predisposition are the other factors. Our histopathological findings of olmesartan-induced celiac-like enteropathy in rat intestines were increased mononuclear cell infiltration and villous atrophy. In this study these various action mechanisms of OM and its possible immun system booster effects were discussed. The findings of our rat intestines after exposure to OM-Suspension supported and correlated clinical findings of OM. In conclusion, by making extensive evaluations, OM can be a promising in u nunomodulator agent in immune system diseases., Aliye Uster Foundation; Ege University Scientific Research Project Commission (BAP) , Izmir-Turkey [15-ECZ-014], The author acknowledges to Aliye Uster Foundation for funding of this study. This work was also supported by the Ege University Scientific Research Project Commission (BAP) , Izmir-Turkey, Grant Number 15-ECZ-014.

The main branch of vitamin D-3 metabolism involves several hydroxylation reactions to obtain mono-, di- and trihydroxylated metabolites, including the circulating and active forms-25(OH)D-3 and 1,25(OH)(2)D-3, respectively. However, most clinical trials strictly target the determination of 25(OH)D-3 to offer a view of the metabolic status of vitamin D-3. Due to the growing interest in expanding this restricted view, we have developed a method for measuring vitamin D-3 metabolism by determination of vitamin D-3, 25(OH)D-3, 24,25(OH)(2)D-3, 1,25(OH)(2)D-3 and 1,24,25(OH)(3)D-3 in human plasma. The method was based on SPE-LC-MS/MS with a large volume injection of human plasma (240 mu L). Detection of di- and trihydroxymetabolites, found at the picogram per milliliter level, was attained by the combined action of high preconcentration and clean-up effects. The method allows obtaining information about ratios such as the known vitamin D metabolite ratio (24,25(OH)(2)D-3/25(OH)D-3), which can provide complementary views of vitamin D-3 metabolic status. The method was applied to a cohort of obese patients and a reference cohort of healthy volunteers to find metabolic correlations between target analytes as well as differences as a function of vitamin D levels within and between cohorts.