Reactions of bovine liver catalase with superoxide radicals and hydrogen peroxide

The oxidized intermediates generated upon exposure of bovine liver catalase to hydrogen peroxide (H2O2) and superoxide radical (O2-) fluxes were examined with UV-visible spectrophotometry. H2O2 and O2- were generated by means of glucose/glucose oxidase and xanthine/xanthine oxidase systems. Serial overlay of absorption spectra in the Soret (350-450 nm) and visible (450-700 nm) regions showed that three oxidized intermediates, namely Compounds I, II and III, can be observed upon exposure of catalase to enzymatically generated H2O2 and O2-. Compound I is formed during the reaction of native enzyme with H2O2 and disappears in two ways: (i) via the catalytic reaction with H2O2 to restore native catalase and (ii) via the reaction with O2- to form Compound II. At low H2O2 concentrations (< 4.8 x 10(-9) M H2O2), Compound II reverts towards the native state mainly in a direct one-step reaction, whereas at higher H2O2 concentrations the pathway of Compound II back to the native enzyme involves Compound III. Formation of the latter from Compound II and H2O2 is irreversible and the rate constant of this reaction is 6.1 +/- 0.2 x 10(4) M-1 s-1. The formation of Compound III through the direct reaction of O2- with native enzyme has also been observed. Depending on the experimental conditions, the inactivation of catalase by O2- can be due to accumulation of Compound II ("slow" inhibition) or to the formation of Compound III ("rapid" inhibition) part of which leads to a dead end product. Formation of Compound III and of this dead end product are responsible for the irreversible inactivation in presence of an excess of H2O2.     

Reduced epicardial coronary vasodilator capacity in patients with left ventricular hypertrophy

BACKGROUND: Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. METHODS AND RESULTS: Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 micrograms intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2 +/- 2.2 mm) than in control subjects (8.6 +/- 1.5 mm; P < .001); after 100 micrograms intracoronary nitroglycerin, it increased to 12.9 +/- 2.2 mm (6 +/- 5%) in those with LV hypertrophy and to 10.3 +/- 1.5 mm (21 +/- 8%; P < .001) in control subjects. An inverse relation between baseline circumferential length and its percent increase after nitroglycerin was found (r = -.71, P < .001). CONCLUSIONS: Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries.     

Human herpesvirus-8: detection of novel herpesvirus-like DNA sequences in Kaposi's sarcoma and other lesions

Kaposi's sarcoma (KS) is a malignancy suspected of having an infectious etiology. Unique viral DNA sequences were recognized in KS lesions, using a novel technique that identifies small differences between two complex genomes. The virus had homology with the herpesvirus family, especially Epstein Barr virus (EBV), yet it was distinct from the known herpesviridae, and was appropriately named human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus (KSHV). HHV-8 DNA sequences were present in AIDS-associated KS, classic KS, African endemic KS, Mediterranean KS, iatrogenic KS, and KS in homosexual men without HIV infection. HHV-8 DNA sequences were also present in peripheral blood mononuclear cells (PBMC) of KS+ patients; body-cavity-based lymphomas in HIV positive patients without KS; and in tissue from a number of malignant and non-malignant lesions in patients without HIV infection. The role of HHV-8 in KS and other malignancies is not known. Viruses are notoriously trophic for lesional tissue. Therefore, in order to determine the role of HHV-8 in KS pathogenesis, HHV-8 needs to be isolated and shown to induce immortalization in a suitable system. Regardless of its role in KS, another human herpesvirus has been discovered, and the extent of its pathogenicity needs to be uncovered.     

Microprocessor-based portable system for heart condition diagnosis

Early diagnosis of heart disease is typically based on a cassette recording of the electrocardiogram (ECG) signal which is then studied and analysed using a microcomputer. The system is bulky, unreliable and prone to mechanical failure. This paper presents the design and implementation of a compact microprocessor-based portable system used for heart condition diagnosis over a long period. The system reads, stores and analyses the ECG signals repetitively in real time for a specified period. The diagnostic data and samples of ECG signals are stored throughout the test period. The system hardware and software design are oriented towards a single-chip microcomputer-based system, hence minimizing size. The operating algorithm is based on a logical approach to ECG signal diagnosis and hence requires little memory.     

A wide range kinetic modeling study of the pyrolysis and combustion of naphthenes

The aim of this paper is to analyze and discuss the kinetics of the pyrolysis and combustion of naphthenes. The primary propagation reactions of cyclohexane and methylcyclohexane are presented to extend the validity of a semi-detailed kinetic model for the pyrolysis and oxidation of hydrocarbons. Naphthenes are relevant species as reference components in liquid fuels and surrogate blends. A lumped approach is used to reduce the complexity of the overall scheme in terms of species and reactions. Particular attention is devoted to the role of the isomerization or internal abstraction of H atoms in competition with β−decomposition ones. Primary oxidation and decomposition reactions of the cyclohexyl radical are discussed to explain and justify this lumping procedure. The modeling predictions are compared with different sets of measurements. The validation of the low temperature oxidation mechanism of cyclohexane is based on the ignition delay times obtained both in the rapid compression machine at Lille and in closed vessels. Jet-stirred reactors at different pressures and stoichiometric ratios also confirm the reliability of the overall mechanism of oxidation. The comparisons between the model’s predictions and the measurements relating to the pyrolysis and oxidation of methylcyclohexane in the Princeton turbulent flow reactor further support this extension of the kinetic scheme to naphthenes. Finally, the agreement with the oxidation experiments using mixtures of toluene + methylcyclohexane is a primary and simple example of the model’s ability to deal with the combustion of real fuels or surrogate blends.     

The partitioning of phosphoramide mustard and its aziridinium ions among alkylation and P-N bond hydrolysis reactions

NMR (1H and 31P) and HPLC techniques were used to study the partitioning of phosphoramide mustard (PM) and its aziridinium ions among alkylation and P-N bond hydrolysis reactions as a function of the concentration and strength of added nucleophiles at 37 degrees C and pH 7.4. With water as the nucleophile, bisalkylation accounted for only 10-13% of the product distribution given by PM. The remainder of the products resulted from P-N bond hydrolysis reactions. With 50 mM thiosulfate or 55-110 mM glutathione (GSH), bisalkylation by a strong nucleophile increased to 55-76%. The rest of the PM was lost to either HOH alkylation or P-N bond hydrolysis reactions. Strong experimental and theoretical evidence was obtained to support the hypothesis that the P-N bond scission observed at neutral pH does not occur in the parent PM to produce nornitrogen mustard; rather it is an aziridinium ion derived from PM which undergoes P-N bond hydrolysis to give chloroethylaziridine. In every buffer studied (bis-Tris, lutidine, triethanolamine, and Tris), the decomposition of PM (with and without GSH) gave rise to 31P NMR signals which could not be attributed to products of HOH or GSH alkylation or P-N bond hydrolysis. The intensities of these unidentified signals were dependent on the concentration of buffer.