Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery.

BACKGROUND: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. MATERIALS AND METHODS: Investigated population consisted of 71 patients aged 43⁻76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for ⁻108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR⁻RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. RESULTS: Significant correlations between diabetes mellitus and paraoxonase activity (R = ⁻0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = ⁻0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. CONCLUSIONS: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

Dynamic changes of paraoxonase 1 activity towards paroxon and phenyl acetate during coronary artery surgery.

BACKGROUND: Serum paraoxonase 1 (PON1), an enzyme associated with high - density lipoproteins (HDL) particles, inhibits the oxidation of serum lipoproteins and cell membranes. PON1 activity is lower in patients with atherosclerosis and in inflammatory diseases. The systemic inflammatory response provoked during cardiopulmonary bypass grafting may contribute to the development of postoperative complications. The aim of the present study was to estimate the dynamic changes in paraoxonase 1 (PON1) activity towards paraoxon and phenyl acetate during and after coronary artery surgery. METHODS: Twenty six patients with coronary heart disease undergoing coronary artery bypass grafting (CABG) were enrolled into the study. Venous blood samples were obtained preoperatively, after aortic clumping, after the end of operation, at 6, 18, 30 and 48 h after operation. Paraoxonase activity was measured spectrophotometrically in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0 mM CaCl2. Arylesterase activity was measured in 20 mM TrisCl buffer (pH 8.0) containing 1 mM phenyl acetate and 1 mM CaCl2. RESULTS: PON1 activity toward paraoxon and phenyl acetate significantly decreased after aorta cross clumping and increased directly after operation. PON1 activity towards paraoxon in preoperative period and PON1 activity towards phenyl acetate in seventh stage of experiment tended to inversely correlate with the occurrence of postoperative complications. CONCLUSION: The paraoxonase 1 plasma activity is markedly reduced during CABG surgery.

Prognostic value of paraoxonase 1 in patients undergoing coronary artery bypass grafting surgery.

BACKGROUND: The aim of this study was to evaluate whether -108C/T polymorphism of the paraoxonase 1 (PON1) gene and the plasma enzyme activity are risk factors for adverse cardiac events after coronary artery bypass grafting (CABG). MATERIAL AND METHODS: Seventy-one patients with coronary heart disease (CHD) undergoing CABG were enrolled in the study. Genomic DNA was extracted from the venous blood using the Gen Elute™ Blood Genomic DNA kit (Sigma) according to the manufacturer's instructions. PON1 activity was measured in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0mM CaCl2. RESULTS: The mean PON1 activity toward paraoxon and toward phenyl acetate was equal (166.5 ± 86.9 U/ml and 96.0 ± 47.2 U/ml, respectively) in patients with CHD. The -108C/T polymorphism of PON1 gene was tested. In CABG patients, PON1 activities in dependence on genotypes were significantly different and equalled 266.2 ± 117.9 U/ml for CC, 178.8 ± 64.7 U/ml for CT, and 98.9 ± 59.2 U/ml for TT genotype. Patients with PON1 activity lower than 193.5 U/ml exhibited significantly increased risk of a serious cardiac event in comparison with patients with PON1 activity higher or equal to this value (p=0.03). Additionally, TT genotype was significantly associated with shorter time of event-free survival in comparison with CT and CC genotypes (p=0.009). CONCLUSIONS: The PON1 polymorphism and enzyme plasma activity are associated with CHD occurrence. High PON1 activity connected with the presence of CC and CT genotypes decreases the recurrence of symptoms of coronary heart disease and improve prognosis after CABG.

Apoptosis of lymphocytes and sialic acid plasma level in patients undergoing cardiac surgery.

Increasing evidence shows that extensive tissue trauma and surgical stress are related to physical alterations of cells and cell death. It was previously reported that total sialic acid (SA) plasma concentration is elevated in patients undergoing coronary artery surgery. Shedding or secreting of SA from the cell membrane surface or releasing intracellular SA may induce apoptosis. It is possible that the terminal SA residues of carbohydrate moieties facilitate recognition and removal of apoptotic cells by phagocytes. The aim of the present study was to estimate the dynamic changes in rate ofapoptosis oflymphocytes and total sialic acid plasma level during coronary artery surgery. In 17 patients undergoing coronary artery bypass grafting surgery plasma total SA concentration was measured and the percentage of apoptotic lymphocytes was determined before operation, after aorta clumping, after the end of operation and at 6, 18, 30 and 48 h after operation. Plasma total SA concentration decreases after aortic clumping and then increases gradually during a 48 hr observation period. The percentage of apoptotic cells increases during and after surgery with the exception of a sample taken at 18 hours after operation. The findings indicate the bimodal character of apoptosis and dynamic increase in total SA plasma level, which may be considered a result of mechanical damage taken place during operation or inflammatory response to surgical trauma.

p53 protein accumulation in colorectal cancer tissue has prognostic value only in left-sided colon tumours.

UNLABELLED: The aim of this paper is to describe the prospective 10-year follow-up study of prognostic value of p53 protein accumulation in cancer cells in relation to the localisation of tumour in colorectum. METHODS: The p53 protein accumulation has been assessed immunohistochemically in tumour tissue samples obtained from 80 selected sporadic colorectal cancer patients. RESULTS: p53 protein accumulation was detected more often in rectum than in colon tumours. Lower survival rates were observed in patients with p53 protein accumulation in cancer cells independent of primary tumour site. Significantly lower cumulative survival rate was detected in the group of patients with left-sided colon cancer. The p53 protein accumulation was an independent prognostic factor in the left-sided colon tumours. CONCLUSIONS: The right-sided colon tumours may be developed in p53-independent manner and p53 protein accumulation in cancer cells has prognostic value only in the left-sided colorectal tumours.

Sialosyl-Tn expression in normal and pathological conditions of human endometrium. An immunohistochemical study.

To assess the clinico-prognostic relevance of the cell surface carbohydrate glycoprotein in normal and pathological conditions of human endometrium, Sialosyl-Tn (STn) antigen was immunohistochemically studied in normal (n = 10), hyperplastic (n = 18), and neoplastic (n = 60) endometrial lesions. There was no STn antigen reactivity in the proliferative endometrial slides, while weak staining was observed in all secretory endometria. STn expression was noted in 8/18 (44%) hyperplastic endometrial cases and in 40/60 (67%) endometrial carcinomas. Positive staining was observed throughout the cytoplasm of the glandular cancer cells, at the cell membranes, and in an intraluminar mucus. This antigen was mostly expressed heterogeneously as far as the distribution of positive cells is concerned. There was a statistically significant association between STn expression and the histological grading of cancer (p = 0.019). Advanced clinical stage (III-IV; p = 0.014) and infiltration of the myometrial wall (more than 1/2 of the myometrial wall; p = 0.004), but no STn immunoreactivity, were reported to be independent prognostic variables during follow-up. Our study shows that a) STn is not constantly expressed during the menstrual cycle, and is increased at the secretory phase of the cycle; b) Sialosyl-Tn reactivity decreases with the degree of tumor differentiation, but there was no relationship with other clinicopathological variables of cancer; c) this cell surface carbohydrate glycoprotein does not appear to predict the outcome of endometrial cancer patients.