Anti-Fas Induces Hepatic Chemokines and Promotes Inflammation by an NF-κB-independent, Caspase-3-dependent Pathway

Agonistic antibodies against the Fas receptor, when administered to mice in vivo, cause significant apoptosis in the liver. In this study we show that anti-Fas antibody not only causes apoptosis of liver cells but also provokes hepatic inflammation. Two hours after injection of anti-Fas, when mice displayed evidence of caspase-3 activation and apoptosis, we found significant hepatic induction of the CXC chemokines macrophage inflammatory protein-2 and KC. Coincident with the chemokine induction was infiltration of the hepatic parenchyma by neutrophils. Neutralization experiments identified that chemokines were the cause of Fas-induced hepatic inflammation, with KC having the predominant effect. Chemokine induction in the livers of anti-Fas-treated mice was not associated with activation of NF-kappa B. Instead, it coincided with nuclear translocation of activator protein-1 (AP-1). AP-1 activation in liver was detected 1-2 h after anti-Fas treatment, suggesting a connection to the onset of apoptosis. When apoptosis was prevented by pretreating mice with a caspase-3 inhibitor, AP-1 activation and hepatic chemokine production were both significantly reduced. Hepatic inflammation was also reduced by 70%. Taken together, these findings indicate that Fas ligation can induce inflammation in the liver in vivo. Inflammation does not arise from Fas-mediated signaling through NF-kappa B; rather, it represents an indirect effect, requiring activation of caspase-3 and nuclear translocation of AP-1

European Society of Cardiology: Cardiovascular Disease Statistics 2019

Aims The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets. Methods and results In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% [interquartile range (IQR) 22.5–23.1%] vs. 15.7% (IQR 14.5–21.1%)}, diabetes [7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%)], and among males smoking [43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%)] although among females smoking was less common in middle-income countries [8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%)]. There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income [7160 (IQR 5655–8115)] compared with high-income [2235 (IQR 1896–3602)] countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures. Conclusion A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest

Chemical and Elemental Composition of Ammi visnaga L. and Calendula officinalis L. from Meknes, Morocco

The powders of Ammi visnaga L. and Calendula officinalis L. plants collected from Meknes region were subjected to three types of analysis, including FTIR analysis, CHNS/O analysis, and ICP-AES analysis with the aim of comparing and giving an insight into the nutritional value, medicinal properties, and potential applications in different fields. The results of the FTIR analysis showed absorbance bands in the same wavelengths, but with different peaks, indicating the presence of long-chain linear aliphatic compounds, lipids, amides, aromatic compounds, and other functional groups in both plants. The CHNS/O analysis revealed high levels of carbon and oxygen, followed by hydrogen, nitrogen, and sulfur for both plants, with no significant differences in the values. The ICP analysis detected 16 minerals, including calcium, potassium, phosphorus, and magnesium in Ammi visnaga, and low levels of sodium in comparison to Calendula officinalis. Calendula officinalis accumulated more aluminum and lead than Ammi visnaga, indicating higher tolerance to contaminations. Zinc, iron, manganese, and copper were important micronutrients present in both plants. The findings of this study suggest that both plants have significant amounts of phytochemical compounds and minerals, which could be beneficial for their potential use in the pharmaceutical, nutraceutical, and cosmetic industries

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence