In vivo assessment of a single adenine mutation in 5'UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study.

OBJECTIVE: Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 'A', adenine insertion variant in 5'UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. RESULTS: The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 'A' insertion variant in 5'UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted 'A' allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

BACKGROUND: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of ß-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect. AIM: This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG. METHODOLOGY: Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay. RESULTS: Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The allele frequencies between AF+ and AF- group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene. CONCLUSION: The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation.

Does sleep quality affects the immediate clinical outcome in patients undergoing coronary artery bypass grafting: A clinico-biochemical correlation.

OBJECTIVE: Poor sleep quality is emerging as high prevalence among the patients suffering from cardiometabolic disturbances. The vascular polypeptide endothelin 1 (ET-1) is involved in many of the health disorders. However, its potential involvement in patients having poor sleep quality along with cardiovascular problem is limited. The present study was formulated to conduct a prospective analysis of the relationship between ET-1 and in hospital outcome in sleep disorder patients undergoing routine coronary artery bypass grafting (CABG). METHODS: A total of 156 patients were enrolled and divided into two groups based on the Pittsburg Sleep Quality Index (PSQI) of ≤5 (Group I, n = 101) or >5 (Group II, n = 55). Blood sample was collected before anesthesia induction (ET-1a) and at 48 h (ET-1b) to analyze the plasma ET-1 and blood sugar level. The patients were monitored for any intraoperative adverse events and postoperative complications during their hospital stay. RESULTS: Both groups were comparable in relation to age, sex, incidence of smoking and alcohol consumption. The distribution of comorbid conditions was also similar in both groups. The ET-1 level was higher in Group II than Group I before anesthesia induction as well as 48 h postoperatively (4.5 ± 1.75 vs. 10.61 ± 9.3, P = 0.001; 2.08 ± 1.3 vs. 8.3 ± 9.86, P = 0.0001, respectively). The Group II patients had a longer duration of mechanical ventilation (14.6 ± 12.05 vs. 10.1 ± 8.19, P = 0.001), Intensive Care Unit stay (2.08 ± 0.95 vs. 2.7 ± 1.45, P = 0016) and hospital stay (5.98 ± 1.73 vs. 7.8 ± 3.66, P = 0.0001, respectively). The high number of patients from Group II required inotrope and intra-aortic balloon pump support while compared with Group I (P ≤ 0.05 in each). The overall postoperative complication rate was significantly higher among patients with PSQI of >5 (Group II) except the rate of infection and neurological complications which was similar among both group of patients. The postoperative in hospital mortality was nil in Group I and 3.6% in Group II (P = 0.05). There was a strong relationship between PSQI and ET-1 at both the time points. CONCLUSION: Poor sleep quality associated with a higher incidence of adverse perioperative events in patients undergoing elective CABG. There exists a potential link between poor sleep quality and ET-1 in these groups of patients.

Bioimaging of peroxynitrite in MCF-7 cells by a new fluorescent probe rhodamine B phenyl hydrazide.

Peroxynitrite is a potent oxidizing and nitrating agent which has detrimental effects on cells by altering the structure and function of biomolecules present within. A fluorescent probe rhodamine B phenyl hydrazide (RBPH) has been proposed for peroxynitrite (ONOO(-)) imaging in MCF-7 cells based on its oxidation property, which converts RBPH to pink colored and highly fluorescent rhodamine B. The fluorescence emission intensity of the rhodamine B produced in the above process is linearly related to the concentration of peroxynitrite. The method obeys Beer's law in the concentration range 2-20 nM and the detection limit has been found to be 1.4 nM. The possible reaction mechanism of peroxynitrite with RBPH to produce rhodamine B has been discussed with spectroscopic evidence. The Probe is selective to the peroxynitrite in the pH range 6-8 which is near physiological pH. Fluorescence microscopic studies suggest that the probe is cell permeable and hence peroxynitrite was imaged in MCF-7 cells.