Prostacyclin (PGI2) plays a critical role in nephrogenesis and renal physiology. However, our understanding of how prostacyclin release in the kidney is regulated remains poorly defined. We studied expression of prostacyclin synthase (PGIS) in developing and adult human kidneys, and also in selected pediatric renal diseases. We also examined PGI2 formation in human mesangial cells in vitro. We ...

The detection and quantification of potential genotoxic impurities (PGIs) play an important role in the pharmaceutical industry. The industry needs highly selective and sensitive analytical methods for trace level quantification of these PGIs in drug substances. A sensitive and stability indicating LC-MS/MS method was developed for the simultaneous detection and quantification of (S)-4-(4-amino...

The development of cyclooxygenase-2 (COX-2) selective inhibitors prompted studies aimed at treating chronic inflammatory diseases and cancer by using this new generation of drugs.Yet, several recent reports pointed out that long-term treatment of patients with COX-2 selective inhibitors (especially rofecoxib) caused severe cardiovascular complicances. The aim of this study was to ascertain whet...

Prostacyclin synthase (PGIS) is the final committed enzyme in the metabolic pathway of prostacyclin production. The therapeutic option of intravenous prostacyclin infusion in patients with pulmonary arterial hypertension is limited by the short half-life of the drug and life-threatening catheter-related complications. To develop a better delivery system for prostacyclin, we examined the feasibi...

Background: Impurity profiling is now receiving critical attention from regulatory authorities. For trace level quantification of potential genotoxic impurities (PGIs), conventional analytical techniques like high-performance liquid chromatography (HPLC) and gas chromatography (GC) are inadequate; consequently, there is a great need to apply hyphenated analytical techniques to develop sensitive...

BACKGROUND We tested the hypothesis that combined cyclooxygenase-1 (COX-1) and prostacyclin synthase (PGIS) gene transfer selectively augments prostacyclin production without a concurrent overproduction of other prostanoids. METHODS AND RESULTS ECV304 cells were transfected with bicistronic pCOX-1/PGIS versus pCOX-1 or pPGIS, and prostanoids were analyzed. Contrary to the high prostaglandin E...

Prostacyclin synthase (PGIS) is a cytochrome P450 (P450) enzyme that catalyzes production of prostacyclin from prostaglandin H(2). PGIS is unusual in that it catalyzes an isomerization rather than a monooxygenation, which is typical of P450 enzymes. To understand the structural basis for prostacyclin biosynthesis in greater detail, we have determined the crystal structures of ligand-free, inhib...

Prostaglandins (PGs) are critical regulators of a number of reproductive processes. To date, the presence and regulation of PGS in the rat endometrium have not yet been described. The objective of the present study was to investigate the expression of PGD synthase (PGDS) and prostacyclin synthase (PGIS) in the endometrium. Endometrial proteins and tissues were collected from cyclic non-pregnant...

Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk. We hypothesized that genetic variation altering the function of these enzymes would modify risk of colorectal polyps. In a Minnesota-based case-control study of adenomatous (n = 517) or hyperplastic (n = 192) polyps ...

This paper was accepted for publication in July 2005 This paper critically reviews and analyses participatory GIS (PGIS) and participatory mapping applications within participatory spatial planning for community-based natural resource management in developing countries. There is an often implicit assumption that PGIS use is effective, in that it meets content needs, satisfies underlying local s...