Prostaglandin D2 is synthesized by hematopoietic-type PGD-synthase (H-PGDS) in mast cells and is released in large quantities during allergic and asthmatic anaphylaxis. PGD2 is also produced in the brain by lipocalin-PGD-synthase also known as β-trace. In the brain, PGD2 produces normal physiological sleep and lowering of body temperature. Further pharmacological actions include inhibition of platelet aggregation and relaxation of vascular smooth muscle. tetranor-PGDM is a major metabolite of PGD2 that is detectable in human and mouse urine. The levels of tetranor-PGDM and 2,3-dinor-11β-PGF2α , a related PGD2 metabolite, in human urine were found to be 1.5 ± 0.3 and 0.6 ± ng mg creatinine, respectively. tetranor-PGDM was detected in murine urine at a level of 8.1 ± 1.3 ng mg creatinine.
Paromomycin (Sulfate Salt) is an aminoglycoside that is active against Gram-negative and many Gram-positive bacteria as well as some protozoa and cestodes. Paromomycin in combination with sodium stibogluconate has proven to be effective in African and Indian VL (visceral leishmaniasis) and improves survival in African VL[3]. PS (Paromomycin Sulfate) is effective for elimination of B. coli without hematological side effects[4]. The activity of phosphoglucose isomerase was slightly inhibited by 10(-3) M paromomycin sulfate while those of hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase were not inhibited[5]. In addition, with regard to correlation of endotoxemia with renal impairment, endogenous creatinine clearance and p-aminohippurate clearance were significantly improved (P less than 0.02) in those patients whose endotoxemia disappeared on paromomycin sulfate administration. Paromomycin sulfate seems to be effective in the prevention of endotoxemia and the associated renal impairment in cirrhosis in man[6]. Significantly higher frequencies of resistance to paromomycin, kanamycin, neomycin and tobramycin were observed in S. aureus isolates from PS (paromomycin supplemented) birds. Paromomycin supplementation resulted in resistance to aminoglycosides in bacteria of PS turkeys. Co-selection for resistance to other antimicrobial agents was observed in E. coli isolates[7].
Indoxyl sulfate-d5 is intended for use as an internal standard for the quantification of indoxyl sulfate by GC- or LC-MS. Indoxyl sulfate is a uremic toxin and a metabolite of tryptophan. It is formed via sulfation of indole, an intermediate generated from tryptophan by intestinal bacteria, by the sulfotransferase (SULT) isoform 1A1 variant 2 (SULT1A1*2) in the liver. Indoxyl sulfate activates the aryl hydrocarbon receptor (AhR) in HepG2 40 6 hepatoma cells (EC50 = 12.1 nM in a reporter assay). It also inhibits the organic anion transporter (OAT) isoforms OAT1 and OAT3 (Kis = 34.2 and 74.4 µM, respectively for the rat transporters) in S2 proximal tubule cells. Indoxyl sulfate (0.2 and 1 mM) increases superoxide anion and nitric oxide levels in isolated human mononuclear blood cells. It increases serum creatinine and blood urea nitrogen (BUN) levels in the 5 6 nephrectomized rat model of chronic renal failure when administered at a dose of 50 mg kg.