Coronary heart disease and cerebrovascular disease mortality in young adults: recent trends in Europe.

Background: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). Design: We analyzed trends in CHD (X ICD codes: I20-I25) and CVD (X ICD codes: I60-I69) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. Methods: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). Results: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). Conclusions: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.

Mortality from cardiovascular and cerebrovascular diseases in Europe and other areas of the world: an update.

OBJECTIVE: To update trends in mortality from coronary heart diseases (CHD) and cerebrovascular diseases (CVD) over the period 1981-2004 in Europe, the USA, Latin America, Japan and other selected areas of the world. METHODS: Age-standardized mortality rates were derived from the World Health Organization database. Joinpoint analysis was used to identify significant changes in trends. RESULTS: In the European Union (27 countries), CHD mortality in men declined from 139/100,000 in 1985-1989 to 93/100,000 in 2000-2004 (-33%). In women, the fall was from 61/100,000 to 44/100,000 (-27%). In this area, a decline by over 30% was also registered in CVD mortality for both sexes. In the Russian Federation and other countries of the former Soviet Union, CHD rates in 2000-2004 were exceedingly high, around 380/100,000 men and 170/100,000 women in Russia, 430 for men and 240 for women in Ukraine, 420 and 200 in Belarus. For CVD, a similar situation was registered, with mortality rates of 226/100,000 for men and 159/100,000 for women in 2004 in the Russian Federation, and more than 24% increase since the late 1980s for men and 15% for women. CHD and CVD mortality continued to decline in most Latin American countries, Australia and other areas considered, including Asia (even if with marked differences). CONCLUSION: Although mortality from CHD and CVD continues to decline in several areas of the world including most countries of Europe and of the America providing data and Australia, unfavourable trends were still observed in the Russian Federation and other countries of the former Soviet Union, whose recent rates remain exceedingly high.

Trypanosoma cruzi: serum antibody reactivity to the parasite antigens in susceptible and resistant mice

The specific antibody responses were compared among susceptible (A/Sn), moderately susceptible (Balb/c) and resistant (C57 BL/lOJ) mice infected with Trypanosoma cruzi (Y strain). Sera obtained during the second week of infection recognized a surface trypomastigote antigen of apparent Mr 80 kDa while displaying complex reactivity to surface epimastigote antigens. Complex trypomastigote antigens recognition was detected around the middle of the third week of infection. No major differences were observed along the infection, among the three strains of mice, neither in the patterns of surface antigen recognition by sera, nor in the titres of antibodies against blood trypomastigotes (lytic antibodies), tissue culture trypomastigotes or epimastigotes. On immunoblot analysis, however, IgG of the resistant strain displayed the most complex array of specificities against both trypo and epimastigote antigens, followed by the susceptible strain. IgM antibodies exhibited a more restricted antigen reactivity, in the three mouse strains studied. Balb/c sera (IgG and IgM) showed the least complex patterns of reactivity to antigens in the range of 30 kDa to 80 kDa. The onset of reactivity in the serum to trypomastigote surface antigens was also dependent on the parasite load to which the experimental animal was subjected.

Immunoglobulin classes in aquatic mammals. Characterization by serologic cross-reactivity, molecular size and binding of human free secretory component.

On the basis of serologic cross-reactivity, three immunoglobulin classes homologous to human IgG, IgM and IgA were identified in two species of acquatic mammal representing the orders Cetacea (dolphin) and Pinnipedea (sea lion). Molecular size was estimated by sucrose density gradient ultracentrifugation and Sephadex G-200 chromatography, indicating a 7S IgG, 19S IgM and heterogeneous serum IgA. Human secretory component was readily bound to the IgM of both species and to an apparently lesser extent to the larger molecular size populations of IgA. No binding was observed with IgG. Several antisera specific for human γ-chains gave a single precipitin line with the sea lion IgG but when made to react with dolphin serum produced two lines, suggesting the presence of two different subclasses of IgG in this species.

Transmission blocking immunity as observed in a feeder system and serological reactivity to Pfs 48/45 and Pfs230 in field sera

Monoclonal antibodies (mAbs) and human sera from gametocyte carriers were applied in the bio-assay to test for their transmission-blocking capacity. Competition ELISA's have been developed for the detection of natural transmission blocking antibodies. Approximately 55 of the sera blocking in the bio-assay gave positive results in these competition ELISA's.

Emotional reactivity at 12 months in very preterm infants born at <29 weeks of gestation.

The present study evaluated the socio-emotional development of very preterm born infants at 12 months corrected age. Forty-one infants born very preterm (<29 weeks of gestation) were compared to 22 infants born full term on a standardized behavioral assessment and a parental temperament questionnaire, both measuring emotional reactivity to joy, anger and fear, as well as sustained attention. The behavioral assessment showed that very preterm infants exhibited as much joy as full term infants during a joy-eliciting episode. However, they expressed a significantly higher reactivity in anger-eliciting situations and a reduced reactivity toward fear-eliciting situations. For all three emotion-eliciting situations, the preterm infants reacted with a higher level of motor activity. The preterm infants also exhibited a distinct attention pattern with a significantly higher initial attention level which declined rapidly throughout the episode. The questionnaire did not show any group differences. The clinical relevance of these results in terms of preliminary hallmarks of later behavioral difficulties such attention deficit/hyperactivity disorder are discussed as well as the inconsistencies observed between the questionnaire and the behavioral assessment.

Portal veins of mice infected with Schistosoma mansoni exhibit an increased reactivity to 5-hydroxytryptamine

In chronic severe infection with Schistosoma mansoni, portal hypertension and related vascular alterations usually develop as a consequence of granulomatous response to eggs. In order to investigate a putative direct effect of worms on the reactivity of their host portal vein, mice infected only with male worms were used in the present study. An higher reactivity to 5-hydroxytryptamine (5-HT) characterized by an increase in the maximal contraction and sensitivity was observed in portal vein from infected mice compared to healthy mice. Blockade of NO-synthase with l-NAME induced a small increase in 5-HT potency in portal vein from non-infected mice without changing the amplitude of the contractions, whereas it did not alter the reactivity of veins from infected mice. The present results show that unisexual infection of mice with male S. mansoni increased the reactivity of the portal vein to 5-HT which seems to be partially related to an alteration in the nitric oxide release by endothelium.

Nanoparticle reactivity toward dithiothreitol

Hazard determination of nanoparticles (NP) is challenging and should be based on a predictive and pragmatic tier approach. The biological effects of NP appear to be related not only to surface/size but also to their ability to generate free radicals/oxidants. We propose that the measurement of this property by acellular assays could be helpful for NP toxicity screening. This study investigated the effect of dispersing conditions on the oxidative capacity of a small selection of carbonaceous NP toward dithiothreitol (DTT). Increasing surfactant concentration decreased the DTT reactivity on these studied particles. Afterward, a panel of NP were studied under constant conditions. Classification of the NP panel based on their DTT reactivity was found to be dependent on the metric used (mass or surface) but not on the surfactant type. The DTT assay may be useful for an initial evaluation of the hazardousness of manufactured or unintentionally produced NP. However, the predictive potential of such a test towards biological effects still needs to be evaluated. [Authors]

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline.

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.

Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen

Human cancer vaccines are often prepared with altered "analog" or "heteroclitic" antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity

Serological cross-reactivity between different Chlamydia-like organisms.

The serological cross-reactivity between different recently described Chlamydia-related organisms was determined. Mouse sera exhibited a strong reactivity against autologous antigen and closely related heterologous antigen but no cross-reactivity with distantly related species. These results are important to better interpret serological studies and assess the pathogenic role of these obligate intracellular bacteria.

Connexin 37 limits thrombus propensity by downregulating platelet reactivity.

Background- Formation of platelet plug initiates hemostasis after vascular injury and triggers thrombosis in ischemic disease. However, the mechanisms leading to the formation of a stable thrombus are poorly understood. Connexins comprise a family of proteins that form gap junctions enabling intercellular coordination of tissue activity, a process termed gap junctional intercellular communication. Methods and Results- In the present study, we show that megakaryocytes and platelets express connexin 37 (Cx37). Deletion of the Cx37 gene in mice shortens bleeding time and increases thrombus propensity. Aggregation is increased in murine Cx37(-/-) platelets or in murine Cx37(+/+) and human platelets treated with gap junction blockers. Intracellular microinjection of neurobiotin, a Cx37-permeant tracer, revealed gap junctional intercellular communication in platelet aggregates, which was impaired in Cx37(-/-) platelets and in human platelets exposed to gap junction blockers. Finally, healthy subjects homozygous for Cx37-1019C, a prognostic marker for atherosclerosis, display increased platelet responses compared with subjects carrying the Cx37-1019T allele. Expression of these polymorphic channels in communication-deficient cells revealed a decreased permeability of Cx37-1019C channels for neurobiotin. Conclusions- We propose that the establishment of gap junctional communication between Cx37-expressing platelets provides a mechanism to limit thrombus propensity. To our knowledge, these data provide the first evidence incriminating gap junctions in the pathogenesis of thrombosis.