The impact of high-dose acetylcholine on bovine corneal epithelium.

Purpose: Ion channels are formed when acetylcholine (ACh) combines with specific receptors on the postsynaptic membrane. We are testing whether this occurs in vitro in corneal epithelial cells when exposed to ACh, using intracellular ascorbic acid (AA) as a tracer.

Methods: The corneal epithelium was separated from Bowman's membrane as an intact sheet with thermolysin (TL).

The role of bradykinin and the effect of the bradykinin receptor antagonist icatibant in porcine sepsis.

Bradykinin (BK) is regarded as an important mediator of edema, shock, and inflammation during sepsis. In this study, we evaluated the contribution of BK in porcine sepsis by blocking BK and by measuring the stable BK metabolite, BK1-5, using anesthetized pigs. The effect of BK alone, the efficacy of icatibant to block this effect, and the recovery of BK measured as plasma BK1-5 were first investigated.

Identification of a novel CYP2C19-mediated metabolic pathway of S-citalopram in vitro.

Systemic exposure of the antidepressant S-citalopram (escitalopram, SCIT) differs several-fold according to variable cytochrome P450 2C19 activity, demonstrating the importance of this enzyme for the metabolic clearance of SCIT in vivo. However, previous studies have indicated that the involvement of CYP2C19 in formation of the metabolite N-desmethyl S-citalopram (SDCIT) is limited. Therefore, the purpose of the present in vitro study was to investigate to what extent the CYP2C19-mediated clearance of SCIT was due to a metabolic pathway different from N-desmethylation and to identify the product(s) of this possible alternative metabolic reaction.

Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients.

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs.

Absolute ProGRP quantification in a clinical relevant concentration range using LC-MS/MS and a comprehensive internal standard.

The objective of this study was to develop a method using liquid chromatography with tandem mass spectrometric detection for the absolute quantification of the small cell lung cancer biomarker ProGRP in human serum, using its tryptic signature peptide NLLGLIEAK. The samples were precipitated for most of its proteins using acetonitrile prior to tryptic digestion. Further sample clean-up and enrichment was achieved by the use of an on-line restricted access media column, followed by separation on a BioBasic C8 column.