No abstract

Numerous publications have described measurements of breath isoprene in humans, and there has been a hope that breath isoprene analyses could be a noninvasive diagnostic tool to assess blood cholesterol levels or cholesterol synthesis rate. However, significant analytic problems in breath isoprene analysis and variability in isoprene levels with age, exercise, diet, etc., have limited the usefulness of these measurements. Here, we have applied proton transfer reaction-mass spectrometry to this problem, allowing on-line detection of breath isoprene. We show that breath isoprene concentration increases within a few seconds after exercise is started as a result of a rapid increase in heart rate and then reaches a lower steady state when breath rate stabilizes. Additional experiments demonstrated that increases in heart rate associated with standing after reclining or sleeping are associated with increased breath isoprene concentrations. An isoprene gas-exchange model was developed and shows excellent fit to breath isoprene levels measured during exercise. In a preliminary experiment, we demonstrated that atorvastatin therapy leads to a decrease in serum cholesterol and low-density-lipoprotein levels and a parallel decrease in breath isoprene levels. This work suggests that there is constant endogenous production of isoprene during the day and night and reaffirms the possibility that breath isoprene can be a noninvasive marker of cholesterologenesis if care is taken to measure breath isoprene under standard conditions at constant heart rate.

No abstract

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. iNOS-derived NO plays an important role in numerous physiological and pathophysiological conditions, e.g. blood pressure regulation, inflammation, infection, and the onset and progression of malignant diseases. iNOS has been conjectured both as a marker and a therapeutic target in these situations. iNOS is a mediator of unspecific host defence, central in the clearance of bacterial, viral, fungal and parasitic infections. However, excess production of NO appears to be linked to tissue damage and organ dysfunction, e.g. the hypotensive and vasoplegic state characteristic for septic shock. However, the use of iNOS-inhibitors in septic patients should be performed carefully with regard to the essential functions and properties of NO in blood pressure/blood flow regulation. Considering iNOS-derived NO as a multifactorial transmitter of tumorigenesis and tumor progression, it is tempting to speculate on therapeutical interference with iNOS activity, especially in tumors where metastatic activity, host denfence mechanisms and the level of differentiation seem to be correlated to iNOS expression. It is the aim of this review to provide basic insights into the NOS family of enzymes as well as their regulation. In the second part of the review, we will point out the pivotal roles NOS play in inflammation and neoplastic diseases.