Sleep apnea and occupational exposure to solvents.

Objectives: The possible effects of exposure to neurotoxic substances such as gasoline, diesel fuel, paint, varnish, and solvents on the pathogenesis of obstructive sleep apnea were examined.

Methods: Four hundred and forty-three persons with incident obstructive sleep apnea were recruited within the framework of a case-referent study. A reference population (N=397) was included as the first reference group.

Polyomavirus viruria in bone marrow transplant recipients: lack of correlation with clinical symptoms.

Background: Human polyomavirus (HPV) infection is controversially discussed as a factor influencing the outcome of bone marrow transplantation (BMT).

Patients And Methods: Here we report on 62 patients undergoing BMT with clinical signs of urocystitis, such as micro- or macrohematuria with more or less severe dysuria. These patients were tested for the presence of HPV in urine specimens (n = 80) by transmission electron microscopy (TEM).

Tissue distribution of imipenem in critically ill patients.

Background And Methods: Imipenem is a broad-spectrum antibiotic used mainly for serious infections in critically ill patients. Because the infection originates mostly from a certain tissue, we assessed tissue concentrations of imipenem using microdialysis in patients in intensive care with serious infections compared with healthy volunteers. Most patients were >60 years old and had renal failure; most patients also had impaired liver, heart, or lung function.

Bovine seminal ribonuclease inhibits in vivo growth of human neuroblastoma cells.

Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with specific antitumor activities. It is selectively toxic for neuroblastoma (NB) cells in vitro with no significant effects on the viability of normal human cells. We evaluated the antitumoral effects of BS-RNase on human NB xenografts from UKF-NB-3 cells in athymic (nude) mice.

Effects of barbiturates on the expression of the inducible nitric oxide synthase in vascular smooth muscle.

Certain cytokines stimulate the expression of the inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMCs) and in many other cell types. The large amounts of nitric oxide (NO) generated by iNOS in the vascular wall contribute to the unrelenting hypotension in septic shock. Because septic patients are often treated with barbiturates, we examined the effect of these anesthetic agents on the expression of iNOS in VSMCs.

Inhibition by antioxidants of nitric oxide synthase expression in murine macrophages: role of nuclear factor kappa B and interferon regulatory factor 1.

1. In view of the potential deleterious effects of high amounts of nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) in inflammation, the prevention of the expression of this enzyme represents an important therapeutic goal. In cytokine-stimulated cells, activation of nuclear factor kappa B (NF-kappa B) is crucial for the increase in iNOS gene expression.

Etomidate and thiopental inhibit the release of endothelium-derived hyperpolarizing factor in the human renal artery.

Background: Endothelium-derived hyperpolarizing factor is thought to be a cytochrome P450-derived arachidonic acid metabolite that hyperpolarizes vascular smooth muscle cells by opening Ca(2+)-activated K+ channels (K+Ca channels). In the rabbit carotid artery both volatile and intravenous anesthetics inhibit the acetylcholine-stimulated release of endothelium-derived hyperpolarizing factor. Because the release of this factor may help to maintain vascular tone in humans under conditions of a failing nitric oxide synthesis, e.

Antioxidants differentially affect nuclear factor kappa B-mediated nitric oxide synthase expression in vascular smooth muscle cells.

Increased 'oxidative stress' resulting in the activation of nuclear factor kappa B (NF-kappa B) is thought to play a crucial role in the cytokine-mediated expression of the inducible isoform of nitric oxide synthase (iNOS) in different cell types. Therefore, the effects of four different antioxidants, carbocromen, chrysin, 3,4-dichloroisocoumarin (DCI) and N-acetylserotonin (NAS), on iNOS expression were investigated in vascular smooth muscle cells (VSMC). All antioxidants strongly reduced the phorbol ester-stimulating superoxide anion formation in native VSMC.

S-nitrosation of serum albumin by dinitrosyl-iron complex.

The objective of this study was to identify a potential mechanism for S-nitrosation of proteins. Therefore, we assessed S-nitrosation of bovine serum albumin by dinitrosyl-iron-di-L-cysteine complex [(NO)2Fe(L-cysteine)2], a compound similar to naturally occurring iron-nitrosyls. Within 5-10 min, (NO)2Fe(L-cysteine)2 generated paramagnetic albumin-bound dinitrosyl-iron complex and S-nitrosoalbumin in a ratio of 4:1.

In vivo spin trapping of glyceryl trinitrate-derived nitric oxide in rabbit blood vessels and organs.

Background: The objectives of this study were (1) to assess glyceryl trinitrate (GTN)-derived nitric oxide (NO) formation in vascular tissues and organs of anesthetized rabbits in vivo, (2) to establish a correlation between tissue NO levels and a biological response, and (3) to verify biotransformation of GTN to NO by cytochrome P-450.

Methods And Results: NO was trapped in tissues in vivo as a stable paramagnetic mononitrosyl-iron-diethyldithiocarbamate complex [NOFe(DETC)2]. After removal of the tissues, NO was determined by cryogenic electron spin resonance spectroscopy.

Selective inhibition by barbiturates of the synthesis of endothelium-derived hyperpolarizing factor in the rabbit carotid artery.

1. Several lines of evidence suggest that both volatile and intravenous anaesthetics may interfere with the synthesis and release of endothelium-derived vasoactive factors. We have investigated the effects of three different barbiturates on the release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in phenylephrine (1 microM)-preconstricted, endothelium-intact ring segments of the rabbit carotid artery.

Characterization of the stable L-arginine-derived relaxing factor released from cytokine-stimulated vascular smooth muscle cells as an NG-hydroxyl-L-arginine-nitric oxide adduct.

The nature of an L-arginine-derived relaxing factor released from vascular smooth muscle cells cultured on microcarrier beads and stimulated for 20 h with interleukin 1 beta was investigated. Unlike the unstable relaxation elicited by authentic nitric oxide (NO) in a cascade superfusion bioassay system, the effluate from vascular smooth muscle cells induced a stable relaxation that was susceptible to inhibition by oxyhemoglobin. Three putative endogenous NO carriers mimicked this stable relaxing effect: S-nitroso-L-cysteine, low molecular weight dinitrosyl-iron complexes (DNICs), and the adduct of NG-hydroxy-L-arginine (HOArg) with NO.

Inhibition of arginase by NG-hydroxy-L-arginine in alveolar macrophages: implications for the utilization of L-arginine for nitric oxide synthesis.

The hypothesis was investigated that the nitric oxide (NO) synthase intermediate, NG-hydroxy-L-arginine (HOArg), is an arginase inhibitor in rabbit or rat alveolar macrophages. Exogenously applied HOArg strongly inhibited the arginase activity present in these cells (IC50 > or = 15 microM), and attenuated L-[3H]arginine transport (IC50 > or = 500 microM) in rabbit alveolar macrophages. Moreover, up to 37 microM HOArg were detected in the conditioned medium, but not in the lysate, of rat alveolar macrophages exposed to bacterial lipopolysaccharide for 18 h.

Display of the characteristics of endothelium-derived hyperpolarizing factor by a cytochrome P450-derived arachidonic acid metabolite in the coronary microcirculation.

1. In addition to nitric oxide (NO) and prostacyclin (PGI2) an endothelium-derived factor, which hyperpolarizes vascular smooth muscle cells via activation of K+ channels, contributes to the dilator effect of bradykinin in different vascular beds. Since this so-called endothelium-derived hyperpolarizing factor (EDHF) also seems to play an important role in the coronary circulation, we investigated its nature and mechanism of action in the rat isolated perfused heart (Langendorff preparation).

Characterization of endothelium-derived hyperpolarizing factor as a cytochrome P450-derived arachidonic acid metabolite in mammals.

1. In addition to nitric oxide (NO) and prostacyclin (PGI2) an as yet unidentified endothelium-derived hyperpolarizing factor (EDHF) contributes to the dilator effect of bradykinin in different vascular beds. We have investigated the nature and mechanism of action of this factor in freshly isolated bovine and porcine coronary artery segments which were preconstricted with the thromboxane mimetic U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha, 10-30 nM).

Subcellular localization and characterization of neuronal nitric oxide synthase.

In contrast to the predominantly particulate, Ca2+/calmodulin-dependent nitric oxide (NO) synthase in endothelial cells, the corresponding neuronal isoenzyme is considered to be mainly soluble, presumably owing to the lack of a posttranslational myristoylation. However, preliminary findings from this and other laboratories suggest that a substantial portion of the neuronal NO synthase activity may in fact be membrane bound. We have therefore investigated the distribution of this enzyme among subcellular fractions of the rat and rabbit cerebellum in more detail.

Release of nitric oxide by angiotensin-(1-7) from porcine coronary endothelium: implications for a novel angiotensin receptor.

The angiotensin I (AI) metabolite, A(1-7), elicited a concentration-dependent dilator response (ED50 > or = 2 microM) in porcine coronary artery rings which was markedly attenuated by the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, and abolished after removal of the endothelium. This effect of the heptapeptide was not mimicked by AII, AIII or A(3-8) at comparable concentrations. The A(1-7)-induced relaxation was not affected by AT1 or AT2 receptor blockade or cyclo-oxygenase inhibition, but was attenuated by the B2 receptor antagonist, Hoe 140, and augmented by the angiotensin-converting enzyme (ACE) inhibitor, quinaprilat.

Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart.

We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (> or = 10 nmol/l) this plateau phase was lower than the initial CPP level.

Effect of free fatty acids on the binding kinetics at the benzodiazepine binding site of glycated human serum albumin.

The effect of free fatty acids (FFA) and non-enzymatic glycation on the binding kinetics of dansylsarcosine (DS) to human serum albumin (HSA) was studied using the stopped-flow technique. The influence of FFA on the binding parameters of 25% glycated HSA depended on the type of fatty acid. The addition of stearic, oleic and linoleic acids in a concentration of 0.