Endothelium-derived endothelin-1

One year after the revelation by Dr. Furchgott in 1980 that the endothelium was obligatory for acetylcholine to relax isolated arteries, it was clearly shown that the endothelium could also promote contraction. In 1988, Dr. Yanagisawa’s group identified endothelin-1 (ET-1) as the first endothelium-derived contracting factor. The circulating levels of this short (21-amino acid) peptide were quickly determined in humans, and it was reported that, in most cardiovascular diseases, circulating levels of ET-1 were increased, and ET-1 was then tagged as “a bad guy.” The discovery of two receptor subtypes in 1990, ET(A) and ET(B), permitted optimization of the first dual ET-1 receptor antagonist in 1993 by Dr. Clozel’s team, who entered clinical development with bosentan, which was offered to patients with pulmonary arterial hypertension in 2001. The revelation of Dr. Furchgott opened a Pandora’s box with ET-1 as one of the actors. In this brief review, we will discuss the physiological and pathophysiological role of endothelium-derived ET-1 focusing on the regulation of the vascular tone, and as much as possible in humans. The coronary bed will be used as a running example in this review because it is the most susceptible to endothelial dysfunction, but references to the cerebral and renal circulation will also be made. Many of the cardiovascular complications associated with aging and cardiovascular risk factors are initially attributable, at least in part, to endothelial dysfunction, particularly dysregulation of the vascular function associated with an imbalance in the close interdependence of nitric oxide and ET-1

Correlation Between Proinflammatory Serum Markers: High Sensitivity C-Reactive Protein, Interleukin-6 with Disability Score in Acute Ischemic Stroke

Stroke being the third leading cause of death and foremost cause of disability, if potential diagnostic utility of blood borne protein biomarkers in predicting acute stroke is established, it would be a substantial adjunct to computerized tomography and magnetic resonance imaging which have their own limitations. This study was done to correlate serum Interleukin 6, high sensitivity C reactive protein at the time of admission with neurological worsening assessed by NIHSS at the time of admission and 7 days after admission. 46 Patients admitted in neurology department SAIMS, Indore with first ever ischemic stroke within 72 h of onset were included in the study. All patients with history of stroke of more than 72 h onset, Infection & peripartum stroke were excluded from the study. Disability scoring was done by NIHSS and their serum samples assayed for hsCRP, IL6 by commercially available quantitative sandwich enzyme-linked immunoadsorbent assay kits. Serum samples of 50 control cases which included healthy volunteers and staff from SAIMS were also analyzed for hsCRP, IL6 for comparative study. A significant correlation was observed between NIHSS scoring and serum hsCRP and IL6 at the time of admission. Patients with initial high serum IL6 and hsCRP also showed significant clinical deterioration as assessed by NIHSS scoring 7 days after admission. Elevated hsCRP and IL6 within 72 h of admission strongly correlated with functional disability in study population in India and may serve as useful adjunct to CT Scan in emergency setting