Individual Assessment of Arteriosclerosis by Empiric Clinical Profiling

BACKGROUND: Arteriosclerosis is a common cause of chronic morbidity and mortality. Myocardial infarction, stroke or other cardiovascular events identify vulnerable patients who suffer from symptomatic arteriosclerosis. Biomarkers to identify vulnerable patients before cardiovascular events occur are warranted to improve care for affected individuals. We tested how accurately basic clinical data can describe and assess the activity of arteriosclerosis in the individual patient. METHODOLOGY/PRINCIPAL FINDINGS: 269 in-patients who were treated for various conditions at the department of general medicine of an academic tertiary care center were included in a cross-sectional study. Personal history and clinical examination were obtained. When paraclinical tests were performed, the results were added to the dataset. The numerical variables in the clinical examination were statistically compared between patients with proven symptomatic arteriosclerosis (n = 100) and patients who had never experienced cardiovascular events in the past (n = 110). 25 variables were different between these two patient groups and contributed to the disease activity score. The percentile distribution of these variables defined the empiric clinical profile. Anthropometric data, signs of arterial, cardiac and renal disease, systemic inflammation and health economics formed the major categories of the empiric clinical profile that described an individual patient's disease activity. The area under the curve of the receiver operating curve for symptomatic arteriosclerosis was 0.891 (95% CI 0.799-0.983) for the novel disease activity score compared to 0.684 (95% CI 0.600-0.769) for the 10-year risk calculated according to the Framingham score. In patients suffering from symptomatic arteriosclerosis, the disease activity score deteriorated more rapidly after two years of follow-up (from 1.25 to 1.48, P = 0.005) compared to age- and sex-matched individuals free of cardiovascular events (from 1.09 to 1.19, P = 0.125). CONCLUSIONS/SIGNIFICANCE: Empiric clinical profiling and the disease activity score that are based on accessible, available and affordable clinical data are valid markers for symptomatic arteriosclerosis

Elevated Non-Esterified Fatty Acid Concentrations during Bovine Oocyte Maturation Compromise Early Embryo Physiology

Elevated concentrations of serum non-esterified fatty acids (NEFA), associated with maternal disorders such as obesity and type II diabetes, alter the ovarian follicular micro-environment and have been associated with subfertility arising from reduced oocyte developmental competence. We have asked whether elevated NEFA concentrations during oocyte maturation affect the development and physiology of zygotes formed from such oocytes, using the cow as a model. The zygotes were grown to blastocysts, which were evaluated for their quality in terms of cell number, apoptosis, expression of key genes, amino acid turnover and oxidative metabolism. Oocyte maturation under elevated NEFA concentrations resulted in blastocysts with significantly lower cell number, increased apoptotic cell ratio and altered mRNA abundance of DNMT3A, IGF2R and SLC2A1. In addition, the blastocysts displayed reduced oxygen, pyruvate and glucose consumption, up-regulated lactate consumption and higher amino acid metabolism. These data indicate that exposure of maturing oocytes to elevated NEFA concentrations has a negative impact on fertility not only through a reduction in oocyte developmental capacity but through compromised early embryo quality, viability and metabolism

Molecular mechanisms of vaspin action: from adipose tissue to skin and bone, from blood vessels to the brain

Visceral adipose tissue derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that  were specifically expressed or overexpressed in the intra abdominal or visceral adipose tissue  (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral  obesity, insulin resistance, hyperinsulinemia and ‐glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type  2 diabetes.  The follow-up study reporting the cloning, expression and functional characterization of  vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs. This review will give an update on mechanistic and structural aspects of vaspin with a focus on its serpin function, the physiology and regulation of vaspin expression, and will summarize the latest on vaspin function in various tissues such as the different adipose tissue depots as well as the vasculature, skin, bone and the brain