Search

Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α −308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the −308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α −308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes mellitus is a chronic disease characterized by an overproduction of reactive oxygen species, which perturbs zinc metabolism and promotes the onset of cardiovascular disease (CVD) in diabetic patients. Metallothioneins (MT) are cysteine-rich metal-binding proteins which, by means of their antioxidant and zinc-buffering properties, might prevent the development of diabetic cardiovascular complications. A recent investigation shows that a polymorphism (+647 A/C) in the human MT-1A gene, affects the intracellular zinc ion release (iZnR) from the proteins and is associated with longevity in Italian population. The aim of the present study is to assess the involvement of +647 A/C and +1245 A/G MT1A polymorphisms with the susceptibility to type 2 diabetes (DM2) and cardiovascular complications. The study included 694 old individuals: 242 old healthy controls, 217 DM2 patients without clinical evidence of CVD (DNC) and 235 diabetic patients with diagnosis of CVD (DCVD). +647 A/C MT1A polymorphism, but not the second SNP, was associated with DM2. C allele carriers were more prevalent in DNC and DCVD patients than in control group (OR=1.37, p =0.034; OR=1.54, p =0.002, respectively). C+ carriers was associated with higher glycemia and glycosylated hemoglobin in DCVD patients, but not in DNC or control subjects. No differences in plasma zinc, but a modulation of MT levels and iZnR in PBMCs were observed in DCVD cohort when related to +647 A/C MT1A polymorphism. In summary, this work provides novel evidence on the association of the +647 A/C MT1A polymorphism with DM2. Moreover, C+ carriers in DCVD patients presented a worse glycemic control, a reduced iZnR and a higher MT levels, suggesting a possible role of MT in diabetic cardiovascular complications. [Copyright &y& Elsevier]

Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-α) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-α production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the−308A/G locus for TNF-α seems to affect the clinical outcome of some infectious diseases. In fact, the−308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the−308G/A locus (PCR–RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A– (GG genotype) and data on IL-6, TNF-α, IL-10, NK cell cytotoxicity, zinc and metallothioneins (MTs) gene expression (RT–PCR) were stratified according to different TNF-α genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A– young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-α and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A– patients. However, the data reported are gender independent. Therefore, the−308A polymorphism at the locus of TNF-α may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the−308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases. [ABSTRACT FROM AUTHOR]

Results are presented from an X-ray survey of ∼50 square degrees of the high galactic latitude sky at sensitivities in the range 7·10 - 5·10 erg/cm sec (0·3-3·5 keV) carried out with the Imaging Proportional Counter (IPC) aboard the Einstein Observatory. The extragalactic sample consists of 48 sources which have been used to determine the number flux relation. The content of the sample is analyzed in terms of types of sources and is found to be significantly different from the content of similar samples selected at higher fluxes. [ABSTRACT FROM AUTHOR]

Methods are discussed for establishing the optical identification of X ray sources in the 'medium' and 'deep' X-ray surveys of the Einstein Observatory. Of the 63 X-ray sources with a statistical significance of ≥ 5σ in the medium survey (Maccacaro et al. 1981), optical identification work is summarized for 51, of which identifications have been made with 30 active galactic nuclei. The optical properties of some of these X-ray selected objects are briefly discussed. The Einstein deep survey of Pavo (Griffiths et al. 1981) is used to illustrate the problems and methods used for securing optical identifications for X-ray sources in the deep survey fields. Identifications have been made with 4 QSOs at the bright end of the optical candidate distribution (together with 3 G stars) and it is shown that a further ∼7 fainter objects are also likely to be QSOs. [ABSTRACT FROM AUTHOR]

Summary Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions.a2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Becausea 2 (-macroglobulin has a binding affinity ()(K)d() for) zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented a 2 (-macroglobulin in the) circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin anda 2 (-macroglobulin ()(r)(= 0.75,)(P)(< 0.01,)(r)(= 0.78,)(P)(< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2) production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase ina 2 (-macroglobulin,) which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. [ABSTRACT FROM AUTHOR]

We review the progress made at our laboratory over the past several years in developing grazing-incidence imaging X-ray optics. Mirrors, detection systems and dispersion techniques are discussed and experimental results are given. We discuss the application of two telescope systems to a number of experimental observations in X-ray astronomy. [ABSTRACT FROM AUTHOR]

Epidemiological studies have linked high consumption of meat with major age-related diseases including cardiovascular diseases. Abnormal postprandial increases in plasma lipids after a meat meal have been hypothesized among the pathogenetic mechanisms. However, it is still unknown if the postprandial serum derived after a normal meat meal is able to affect endothelial function, and if the type of meat and the age of the donors are critical factors. Here, we show the effects of postprandial sera derived from healthy adults and elderly volunteers who consumed meat meals on human coronary artery endothelial cell (HCAEC) oxidative stress, gene expression, DNA damage, and cellular senescence. We observed that a single exposure to postprandial serum induces a slight increase in ROS that is associated with modulation of gene expression pathways related to oxidative stress response and metabolism. The postprandial-induced increase in ROS is not associated with a measurable DNA oxidative damage. However, repeated exposure to postprandial serum induces an acceleration of cellular senescence. Taking into account the deleterious role of cellular senescence in age-related vascular diseases, the results suggest a new mechanism by which excessive meat consumption and time spent in postprandial state may affect health status during aging.