Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients

BACKGROUND: Peritoneal dialysis (PD) patients have a high risk of cardiovascular mortality, which is not completely explained by conventional risk factors. Other factors related to chronic renal failure and/or dialysis treatment might lead to endothelial dysfunction, which is associated with an adverse cardiovascular outcome. One such factor is hyperhomocysteinaemia, which has a high prevalence in PD patients. METHODS: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated, and endothelium-independent, glyceryl trinitrate-induced, vasodilatation of the brachial artery in 29 PD patients and 29 control subjects. RESULTS: Endothelium-dependent vasodilatation was markedly reduced in the PD group: 5.7 +/- 1.0% vs 10.4 +/- 1.3% in the control group (P = 0.004). Endothelium-independent vasodilatation was not impaired. Plasma total homocysteine was elevated in the PD patients (45.2 +/- 6.2 micromol/l), but was not related to endothelium-dependent vasodilatation. CONCLUSION: Chronic peritoneal dialysis patients have impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.     

Acquired carnitine abnormalities in critically ill children

In order to characterize the role of carnitine during metabolic stress, we prospectively determined carnitine profiles in plasma and urine on admission, days 2, 5, 10 and 15, among 28 critically ill children free of any known conditions associated with secondary carnitine deficiency. More than 25% of plasma and 50% of urinary carnitine measurements were abnormal; 96% (27/28) of patients displayed on at least one occasion an abnormal [< -2 SD or > +2 SD] carnitine value in plasma. Three children had extremely low [< 10 micromol/l] free carnitine (FC) levels in plasma. Plasma esterified and FC levels on admission were not related to the risk of mortality [PRISM score], to muscle lysis [CK values], and to the caloric intake. Levels of FC and esterified carnitine in plasma were unrelated to those measured in urine. Conclusion: Abnormal plasma and urine carnitine measurements are frequently found in critically ill children; the biological significance of these perturbations remains unclear. Caution must be exercised before concluding that an abnormal carnitine value is indicative of an underlying hereditary metabolic disorder in this population.     

Polymeric materials

Summary The Polymer Section of the Santa Barbara Workshop on Modeling of Materials is briefly reviewed. Motivation and need for modeling in polymer-based materials are outlined and the recommendations resulting from the workshop reported.     

Modal convection and its effect on the stability of EDM wires

Recently, it has been shown that EDM wires undergo thermal buckling at low axial transport speeds and a series of transport instabilities at high axial transport speeds. Hence, only intermediate speeds ensure the straight wire configuration, which is needed for high-accuracy cutting. These conclusions are based on the assumption that the convective heat transfer coefficient remains piecewise constant along the length of the wire. However, a recent study on convection from a vibrating, flexible body shows that the convection coefficient becomes modal. The present study re-examines the wire stability problem with this modal effect in mind. It is shown that at low axial transport speeds, the straight wire configuration may be stable. Its stability hinges on vibration—large amplitude motion implies increased convection and increased stability from thermal buckling. At high transport speeds, the system still undergoes the reported transport instabilities. This work shows that the well-defined intermediate speed range is not so well-defined in the presence of wire vibrations.     

Gonadotrophin heterogeneity and biopotency: implications for assisted reproduction

The extensive heterogeneity of the gonadotrophin hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH), is due primarily to the heterogeneous nature of their carbohydrate side-chains, in particular sialic acid residues. In this review, we discuss the role of carbohydrate chains in receptor binding and activation, biological activity, and metabolic half-life. The synthesis and secretion of the various glycoforms of both FSH and LH appear to be under endocrine control with gonadotrophin-releasing hormone (GnRH), oestradiol and testosterone playing important roles. Evidence for different glycoforms having variable biopotency or different encoded functions is increasing, and the production and secretion of more or less acidic gonadotrophin species in different physiological states may represent an important mechanism whereby the pituitary regulates gonadal cell and organ function. This has potential importance for the development of new pharmaceutical reagents and new therapeutic regimens in assisted reproduction. It is envisaged that the use of existing and new forms of FSH/LH will allow patients to be treated in a more controlled and physiological manner, with treatment regimens individualized to the needs of the patient.     

Molecular basis and species specificity of high affinity binding of vasoactive intestinal polypeptide by the rat secretin receptor

The affinity and specificity of the binding interaction between ligands and their receptors are key for appropriate hormonal regulation of target tissues. However, it is now apparent that vasoactive intestinal polypeptide (VIP) binds to the rat secretin receptor with similar affinity to that for its natural ligand, secretin (Holtmann et al., 1995). In this report, we establish that this is not a characteristic of the human secretin receptor, and use rat-human secretin receptor chimeras, site mutants and truncated receptor constructs to establish the molecular basis for this unusual binding interaction. Of note, isolated N-terminal domains of the rat secretin and the VIP receptors are capable of high affinity binding of VIP. In the recently recognized secretin family of receptors, this domain has six conserved cysteine residues and disulfide bonds that are likely important to achieve the complex conformation critical for this binding. A single acidic residue (Asp98) present in the rat secretin receptor appears to be critical, because a site-mutant changing this to the polar, but uncharged residue present in that position in the human receptor (Asn) eliminates the high affinity binding of VIP. Of interest, a previously identified critical basic residue in VIP (Lys15) provides a candidate for charge-pairing with this residue, potentially aligning the peptide ligand in a nonproductive orientation within this receptor.     

Regional 5-hydroxyindoleacetic acid production in humans

Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain.     

Verminderung des Gehaltes von Blei und anderen Elementen in Wein mit Hilfe von Pectins?ure

Zusammenfassung Der Bleigehalt von Wein kann durch Zusatz von Pectinsäure (PS) vermindert werden. Die Wirksamkeit der Bleiverminderung durch PS hängt von der Qualitätsstufe des Weines ab. In Auslesewein (Wein A) senkten 6250 mg PS/1 den Bleigehalt in 24 h von 0,88 mg/l auf 0,28 mg/l und in Spätlese (Wein B) von 0,83 mg/l auf 0,06 mg/1. Unter den gleichen Bedingungen nahm in Wein A der Gehalt an Fe, Zn und Cu von 8,85 mg/l auf 7,05 mg/1, von 4,75 mg/l auf 1,25 mg/l and von 0,67 mg/l auf 0.57 mg/l ab; bei Wein B reduzierte sich der Gehalt von Fe, Zn und Cu von 6,70 mg/l auf 5,41 mg/1, von 1,17 mg/l auf 0,28 mg/l und von 0,46 mg/l auf 0,28 mg/1. Durch Filtration des Weines wurde PS nahezu quantitativ entfernt. Eine geschmackliche Beeinträchtigung des Weines durch PS ist bei 750 mg and 1500 mg PS/1 nicht feststellbar, jedoch bei 6 250 mg PS/1 nicht auszuschließen. Aufgrund ihrer hohen Bindungsaffinität zu Blei scheint PS geeignet, Blei auch aus anderen flüssi-gen Lebensmitteln zu entfernen.

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Reduction of lead content and of other metals in wine by means of pectic acid

Summary A procedure for reducing the Pb content in wines containing high levels of Pb is described. The reduction of Pb by means of pectic acid (PA) depends on the quality grade of the wine. In Auslese (wine A) 6250 mg PA/l diminished Pb content in 24 h from 0.88 mg/l to 0.28 mg/1; in Spatlese (wine B) from 0.83 mg/l to 0.06 mg/1. Under the same conditions the content of Fe, Zn, Cu decreased in wine A from 8.85 mg/l to 7.05 mg/1, from 4.75 mg/l to 1.25 mg/1, from 0.67 mg/l to 0.57 mg/l and in wine B from 6.70 mg/l to 5.41 mg/1, from 1.17 mg/l to 0.28 mg, 0.46 mg/l to 0.28 mg/l, respectively. PA is removed almost quantitatively by filtration. Sensory properties of treated wines were unchanged with concentrations of PA of 750 mg and 1500 mg/l. A slight effect on taste at 6250 mg PA/l wine cannot be excluded. On account of its high affinity to Pb, PA will probably remove Pb from other liquid foods as well.

     

Superconductivity and magnetic interactions in Yb1.2−x Eu x Mo6S8 pseudoternary compounds

The superconducting and magnetic properties of the Yb_1.2–x Eu _x Mo₆S₈ series of compounds have been investigated by means of ac magnetic susceptibility, electrical resistivity, and upper critical magnetic fieldH _c2 measurements. The superconducting transition temperature at ambient pressure is depressed by Eu additions, until superconductivity disappears completely atx0.7. For Eu concentrationsx<0.45,H _c2 is enhanced at low temperatures and exceeds the values for pure Yb_1.2Mo₆S₈. The temperature dependence ofH _c2 for the various Yb_1.2–x Eu _x Mo₆S₈ compounds is analyzed using a multiple pair-breaking theory that includes the compensation of the applied magnetic field by the negative exchange field produced by antiferromagnetic interactions between the conduction electron spins and the Eu²⁺ spins (Jaccarino-Peter effect). Hydrostatic pressure was found to induce superconductivity in all Eu-rich compositions that were not superconducting at ambient pressure.