Inhibition of Cu2+-induced LDL oxidation by nitric oxide: a study using donors with different half-time of NO release

The incubation of low density lipoproteins with Cu++ promotes oxidative modifications that make them atherogenic. Comparable alterations occur in vivo and are modulated by the generation of nitric oxide by endothelial cells or macrophages. Here we report that two donors (NOC-9 and NOC-18) with different half times of NO release (2.7 and >500 min, respectively) inhibit in vitro lipoprotein oxidation promoted by Cu++. Both donors increase the duration of the lag-phase and decrease the maximum rate of conjugated diene formation, prevent the loss of tryptophan in Apo B100, and decrease the formation of fluorescent adducts. The protective effect of NOC-9 was rapidly exhausted and its overall efficacy in preventing LDL oxidation was two orders of magnitude lower than that exhibited by NOC-18. These findings suggest that a continuous flux of NO generation, even at lower concentrations, is more efficient than considerably higher doses released as a burst in protecting both the lipid and the protein moiety of LDL from oxidation.     

Volcanogenic fluorine in rainwater around active degassing volcanoes: Mt. Etna and Stromboli Island,Italy

Many studies have assessed the strong influence of volcanic activity on the surrounding environment. This is particularly true for strong gas emitters such as Mt. Etna and Stromboli volcanoes. Among volcanic gases, fluorine compounds are potentially very harmful. Fluorine cycling through rainwater in the above volcanic areas was studied analysing more than 400 monthly bulk samples. Data indicate that only approximately 1% of fluorine emission through the plume is deposited on the two volcanic areas by meteoric precipitations. Although measured bulk rainwater fluorine fluxes are comparable to and sometimes higher than in heavily polluted areas, their influence on the surrounding vegetation is limited. Only annual crops, in fact, show some damage that could be an effect of fluorine deposition, indicating that long-living endemic plant species or varieties have developed some kind of resistance.     

Modulation of Aβ42 Aggregation Kinetics and Pathway by Low-Molecular-Weight Inhibitors

The aggregation of amyloid-β 42 (Aβ42) is directly related to the pathogenesis of Alzheimer's disease. Here, we have investigated the early stages of the aggregation process, during which most of the cytotoxic species are formed. Aβ42 aggregation kinetics, characterized by the quantification of Aβ42 monomer consumption, were tracked by real-time solution NMR spectroscopy (RT-NMR) allowing the impact that low-molecular-weight (LMW) inhibitors and modulators exert on the aggregation process to be analysed. Distinct differences in the Aβ42 kinetic profiles were apparent and were further investigated kinetically and structurally by using thioflavin T (ThT) and transmission electron microscopy (TEM), respectively. LMW inhibitors were shown to have a differential impact on early-state aggregation. Insight provided here could direct future therapeutic design based on kinetic profiling of the process of fibril formation.     

Hematologic, clinical, and cytogenetic analysis in 109 patients with primary myelodysplastic syndrome. Prognostic significance of morphology and chromosome findings

One hundred and nine patients with primary myelodysplastic syndrome (MDS) were classified according to the French-American-British (FAB) criteria: 27 refractory anemia (RA, 25%), 26 RA with ringed sideroblasts (RARS, 24%), 16 RA with excess of blasts (RAEB, 15%), 10 RAEB in transformation (RAEB-t, 9%), 25 chronic myelomonocytic leukemia (CMMoL, 23%), and five unclassifiable MDS (4%). Forty-three were women and 66 were men (sex ratio 2:3). Age ranged from 30-92 years (mean 69 years) with nine patients aged less than 50 years (8%). A cytogenetic result was obtained in all cases. At initial study, a chromosome defect was observed in 56% of patients. Rates of abnormality depended on FAB subtype: 52% in RA, 100% in RA 5q-, 50% in RARS, 56% in RAEB, 70% in RAEB-t and 44% in CMMoL. The most frequent single defects were del(5q), -7/del(7q), del(20q), Y loss, and +8. Except for the 5q- syndrome entity, specific chromosome defects were not associated with particular FAB subtypes. Bone marrow (BM) insufficiency (22%) and leukemic transformation (21%) were the most important causes of death. The rate of leukemic transformation increased with the number of dysplastic BM cell lineages and was also associated with karyotype complexity and the proportion of abnormal/normal metaphases. The longest median survivals were observed in RARS (142 months) and RA/RA5q- (91 months) types. Median survivals decreased with increasing Bournemouth score values. Patients with three abnormal cell lineages had a median survival shorter than those with one or two abnormal lineages. Similarly, patients with complex defects had shorter survival than those with single or double defects or a normal karyotype. There was no statistically significant difference between survival of NN (normal), AN (abnormal/normal), and AA patients or between survival of patients with del(5q), -7/del(7q), +8 or del(20q).     

A simple computer program for insulin dose adjustment in diabetic patients

A program is described for the adjustment of insulin dose in diabetic patients. The program is written in BASIC and runs on a Casio FX-770P portable computer. On the basis of the maximum daily dose variation allowed, seven twice-daily glucose determinations and the previous insulin dose, the program generated 'cautious' and 'normal' insulin dose adjustment for 66 patients which correlated well with the judgements made by four expert diabetologists.     

Mathematical modelling and nonlinear dynamics of a class of homokinetic systemsModele mathematique et la dynamique non-lineaire d'une classe de systemes homocinetiques

This paper deals with the analysis of the dynamics of a particular transmission system constituted by two sliding and rotating elements connected by a constant velocity joint. In particular, a mathematical model is here proposed for the simulation of the system and the dynamics of the system itself is studied, in detail, on the basis of the said model.     

Un problema di approssimazione connesso con la sintesi di filtri digitali non ricorsivi

In this paper we present a synthesis algorithm for non-recursive digital filters. By the well-known «frequency sampling method», the approximation problem can be related to a convex optimization problem. Finally, we exhibit a synthesis procedure based on the classical simplex algorithm.     

Different mechanisms are progressively recruited to promote Cu(II) reduction by isolated human low-density lipoprotein undergoing oxidation

The kinetics of Cu(II) reduction and its relationship to the process of low density lipoprotein (LDL) oxidation were investigated in isolated human LDL incubated with CuSO4 by using the Cu(I) chelator and indicator dye bathocuproine disulfonate (BC). The inclusion of BC in the incubation medium containing isolated LDL and different concentrations of CuSO4 revealed a biphasic kinetics of Cu(II) reduction consisting of an early phase followed by a plateau phase and a subsequent extensive reduction phase. The amount of Cu(I) formed during the early phase, as well as the rate of its generation, were strictly dependent on both the level of Cu(II) available (saturation was observed at 20 and 50 microM CuSO4) and the concentration of alpha-tocopherol within native LDL particles. Artificial enrichment of LDL with different concentrations of alpha-tocopherol led to a parallel increase of both the amount of Cu(II) reduced and the rate of reduction. The late phase of Cu(II) reduction was strictly related to the availability of copper but was largely independent from alpha-tocopherol. Neither the amount of Cu(I) generated nor the rate of generation were saturated at concentrations of copper up to 100 microM. Comparable results were obtained by adding BC at different time-points to the LDL-copper mixture, in order to measure at the same time-points both the true rate of Cu(II) reduction and the generation of TBARS during the dynamic process of LDL oxidation. The rate of Cu(II) reduction was already high during the lag-phase of the LDL oxidation profile and progressively decreased as alpha-tocopherol concentration decreased. The subsequent increase in the rate of Cu(II) reduction paralleled the formation of TBARS during the extensive LDL oxidation phase. These results suggest that different mechanisms of Cu(II) reduction, namely alpha-tocopherol-dependent and independent (likely lipid peroxide-dependent), are progressively recruited during copper-promoted LDL oxidation.