Evaluación del lipidograma y ciertos factores de riesgo de ateroesclerosis en niños cuyos padres tuvieron arteriopatía coronaria de inicio temprano / Assessment of lipid profile and some risk factors of atherosclerosis in children whose parents had early onset coronary artery disease

Antecedentes/Objetivo. El objetivo de nuestro estudio fue analizar el lipidograma y ciertos factores de riesgo de ateroesclerosis, tales como las lipoproteínas de baja densidad oxidadas (ox-LDL, por su sigla en inglés) y las lipoproteínas de baja densidad pequeñas y densas (sdLDL, por su sigla en inglés) en los hijos de pacientes con cardiopatía coronaria (CC) prematura. Población y métodos. Hijos de padres con CC de inicio temprano emparejados con pares de su misma edad y mismo sexo. Se analizaron las concentraciones de lípidos, apolipoproteínas (ApoA, B, E), ox-LDL, sdLDL y lipoproteína (a) [Lp(a)] en los niños de estudio y de referencia. Los datos se evaluaron con el programa SPSS, junto con la prueba t de Student y la prueba U de Mann-Whitney. Resultados. Los niños del grupo de estudio (n: 43) tenían niveles más elevados de LDL, Lp(a) y ox-LDL y cocientes mayores de CT/HDL, ApoB/ApoA, LDL/HDL y ox-LDL/HDL (p < 0,05) que los del grupo de referencia. Conclusión. Con base en estos hallazgos, se sugiere que la dislipidemia y las concentraciones elevadas de LDL, Lp(a) y ox-LDL son frecuentes en los hijos de pacientes con CC de inicio temprano y representan gran parte de la predisposición familiar a tener CC

Background/Aim: The objective of our study was to analyze the lipid profile and some risk factors of atherosclerosis such as oxidized-low density lipoprotein (ox-LDL), small dense LDL (sd LDL) in the offspring of patients with premature coronary heart disease (CHD). Population and Methods: Children whose parents had early onset CHD were matched with age and sex pairs. Study and controls were analyzed for lipid levels, apolipoproteins (Apo- A,B,E), ox-LDL, sd LDL and lipoprotein (a) [Lp(a)]. The data were evaluated with SPSS using "Student tand Mann-Whitney U" tests. Results: Thestudy group children (n: 43) had higher LDL, Lp(a) and ox-LDL levels, ratios of TC/HDL, Apo-B/A, LDL/HDL and ox-LDL/HDL (p<0.05) than control group. Conclusion: These findings suggest that dyslipidemia and increased LDL, Lp(a) and ox-LDL levels are common in the offspring of patients with early onset CHD and account largely for their familial predisposition for CHD.

Assessment of lipid profile and some risk factors of atherosclerosis in children whose parents had early onset coronary artery disease. / Evaluación del lipidograma y ciertos factores de riesgo de ateroesclerosis en niños cuyos padres tuvieron arteriopatía coronaria de inicio temprano.

BACKGROUND/AIM: The objective of our study was to analyze the lipid profile and some risk factors of atherosclerosis such as oxidized-low density lipoprotein (ox-LDL), small dense LDL (sd LDL) in the offspring of patients with premature coronary heart disease (CHD). POPULATION AND METHODS: Children whose parents had early onset CHD were matched with age and sex pairs. Study and controls were analyzed for lipid levels, apolipoproteins (Apo- A,B,E), ox-LDL, sd LDL and lipoprotein (a) [Lp(a)]. The data were evaluated with SPSS using "Student t and Mann-Whitney U" tests. RESULTS: The study group children (n: 43) had higher LDL, Lp(a) and ox-LDL levels, ratios of TC/HDL, Apo-B/A, LDL/HDL and ox-LDL/HDL (p<0.05) than control group. CONCLUSION: These findings suggest that dyslipidemia and increased LDL, Lp(a) and ox-LDL levels are common in the offspring of patients with early onset CHD and account largely for their familial predisposition for CHD.

Antecedentes/Objetivo. El objetivo de nuestro estudio fue analizar el lipidograma y ciertos factores de riesgo de ateroesclerosis, tales como las lipoproteínas de baja densidad oxidadas (ox-LDL, por su sigla en inglés) y las lipoproteínas de baja densidad pequeñas y densas (sdLDL, por su sigla en inglés) en los hijos de pacientes con cardiopatía coronaria (CC) prematura. Población y métodos. Hijos de padres con CC de inicio temprano emparejados con pares de su misma edad y mismo sexo. Se analizaron las concentraciones de lípidos, apolipoproteínas (ApoA, B, E), ox-LDL, sdLDL y lipoproteína (a) [Lp(a)] en los niños de estudio y de referencia. Los datos se evaluaron con el programa SPSS, junto con la prueba t de Student y la prueba U de Mann-Whitney. Resultados. Los niños del grupo de estudio (n: 43) tenían niveles más elevados de LDL, Lp(a) y ox-LDL y cocientes mayores de CT/HDL, ApoB/ApoA, LDL/HDL y ox-LDL/HDL (p < 0,05) que los del grupo de referencia. Conclusión. Con base en estos hallazgos, se sugiere que la dislipidemia y las concentraciones elevadas de LDL, Lp(a) y ox-LDL son frecuentes en los hijos de pacientes con CC de inicio temprano y representan gran parte de la predisposición familiar a tener CC

Cardiotrophin-1: A new predictor of atrial fibrillation relapses after successful cardioversion.

We aimed to investigate whether or not cardiotrophin-1 (CT-1) can be used as a predictor of sinus rhythm constancy in patients with atrial fibrillation (AF) converted to sinus rhythm. Thirty two patients with AF (48-78 years), without any structural heart disease were enrolled for the study. The control group consisted of 32, age and gender matched healthy persons. Measurements of CT-1 were made after transthoracic and transesophageal echocardiography prior to cardioversion (CV). Relapses of AF were investigated by monthly electrocardiograms (ECGs) and ambulatory ECGs at 1st, 3rd, and 6th month. At the end of 6th month, measurements of CT-1 were repeated. At the beginning patients with AF had increased CT-1 levels when compared to controls (0.94 ± 0.32 pg/mL vs. 0.30 ± 0.12 pg/mL, [p < 0.001]). At the end of follow-up of the 32 patients, 17 (53%) had AF relapse. Age, initial duration of AF, left ventricle diameters, ejection fraction, left atrium appendix flow rates were similar among patients with and without AF relapse. However, basal left atrium diameter (4.24 ± 0.14 cm vs. 4.04 ± 0.22 cm, p = 0.005), pulmonary artery pressure (32.82 ± 5 vs. 28.60 ± 6.23 mmHg, p = 0.004) and CT-1 values (1.08 ± 0.37 vs. 0.82 ± 0.16 pg/mL, p = 0.02) were significantly increased in patients with AF relapse. Furthermore, patients with relapsed AF had higher CT-1 levels at 6th month when compared to those in sinus rhythm (1.00 ± 0.40 vs. 0.71 ± 0.23 pg/mL). We conclude that post-CV, AF relapses are more frequent among patients with increased baseline CT-1 levels, and CT-1 may be a potential predictor of AF relapse.

Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats.

Doxorubicin (DOX) is known to increase in oxidative stress in several organs. Olive leaf extract (OLE) has potent antioxidant effects; therefore, we evaluated the ability of OLE to reduce DOX-induced toxicity in the heart, liver, and kidneys of rats. DOX (30mg/kg; i.p.) was administered to rats, which were sacrificed 4 days after DOX. The rats received OLE (6 and 12mL/L in drinking water) for 12 days. Serum cardiac troponin I (cTnI) levels, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, urea and creatinine levels, as well as prooxidant and antioxidant status in organs were measured. DOX was found to increase serum markers that indicate tissue injury, malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) levels, and to decrease glutathione (GSH) levels in organs. Histopathologic changes were also evaluated. OLE, especially OLE 1000, led to decreases in serum cTnI and urea levels, ALT and AST activities, and amelioration in histopathologic findings. Decreases in MDA, DC, and PC, and increases in GSH levels were observed in organs of DOX-treated rats due to OLE. We conclude that OLE treatment may be effective in decreasing DOX-induced cardiac, hepatic and renal oxidative stress and injury.

Effect of statins on endothelial function in patients with acute coronary syndrome: a prospective study using adhesion molecules and flow-mediated dilatation.

BACKGROUND: Accumulating evidence suggests that inflammatory mechanisms play a central role in the development, progression and outcome of atherosclerosis. Recent evidence suggests that statins improve anti-inflammatory, anti-thrombotic and endothelial functions, along with their lipid-decreasing effects. We examined the effect of statins on endothelial function using biochemical markers of endothelial dysfunction and brachial artery flow-mediated dilatation (FMD). METHODS: Thirty male patients presenting with acute coronary syndrome (ACS) and 26 age-matched healthy control subjects aged 40 - 60 years who were not on any medication were enrolled in the study. The patient group was started on atorvastatin (40 mg/day) without consideration of their low-density lipoprotein (LDL)-cholesterol levels. Endothelin, sICAM and E-selectin from stored serum samples were measured using commercially available enzyme-linked immunosorbant assays (ELISAs). Endothelial function was assessed using brachial artery FMD. RESULTS: Prior to statin treatment, E-selectin, sICAM and endothelin levels, endothelial dysfunction markers, were 99.74 ± 34.67 ng/mL, 568.8 ± 149.0 ng/mL and 0.62 ± 0.33 fmol/mL, respectively in the patient group. E-selectin and sICAM levels were significantly higher in the patients than in the control subjects (P < 0.001); however, endothelin levels were not significantly different between groups. Statin treatment significantly reduced E-selectin and sICAM levels (P < 0.001); however, the decrease in endothelin levels was not statistically significant. %FMD values were significantly increased after statin treatment (P = 0.005), and levels of C-reactive protein (CRP), an inflammation marker, were significantly reduced. CONCLUSION: Our results indicate that statins play an important role in treatment endothelial dysfunction by reducing adhesion of inflammatory cells.

The umbilical cord alpha-fetoprotein levels for predicting hyperbilirubinemia in term neonates.

OBJECTIVE: The aim of this study was to investigate the possible relationship between cord bloodalpha-fetoprotein (AFP) level and development of subsequent neonatal hyperbilirubinemia. STUDY DESIGN: The term newborns born between March 2005 and October 2005 were included in the study. Infants with Coombs-positive ABO and/or Rh incompatibility and/or hemolytic jaundice, asphyxia, congenital anomaly and signs of bleeding were excluded from the study. Cord blood AFP levels were measured in 504 full term newborns in this period. Infants were followed-up for possible neonatal hyperbilirubinemia. The capillary bilirubin level (CBL) was examined expeditiously in newborns developing jaundice and in other infants at the time discharge while the screening test was being performed. RESULTS: The mean umbilical cord AFP level was 49.1 ± 44.9 mg/L (range 1.1-396.2 mg/L), mean CBL was 5.8 ± 3.1 mg/dL (range 1-19.4 mg/dL), and the mean bilirubin detection time was 37 ± 23.2 hours (range 12-144 h) of age. Although a significant positive correlation was found between umbilical cord AFP and CBL levels, it was weak (r = 0.187, p < 0.001). Comparison of AFP levels in terms of bilirubin percentile values appropriate for postnatal age also showed a significant weak positive correlation (r = 0.113, p < 0.001). CONCLUSION: The umbilical cord AFP levels may not be used as a strong predictor for the determination of newborns at risk for hyperbilirubinemia.

Increased interleukin 1 and tumor necrosis factor alpha levels after thyroid surgery.

OBJECTIVE: The aim of this study was to consider levels of the proinflammatory cytokines IL-1 and TNFα after thyroid surgery. MATERIAL AND METHODS: A total of 200 patients who underwent total thyroidectomy enrolled in this study. Drain fluid samples were taken. IL-1 and TNFα results and their relationship with other factors were analyzed. RESULTS: There was a positive correlation between IL-1 and hyperthyroidism (rs=0.614, p<0.001), operative time (rs=0.770, p<0.001), and excised thyroid volume (rs=0.829, p<0.001). Moreover, there was a positive correlation between TNFα and hyperthyroidism (rs=0.430, p<0.001), operative time (rs=0.392, p<0.001), and excised thyroid volume (rs=0.398, p<0.001). CONCLUSION: The results of this study showed us that the parameters related to increased proinflammatory cytokine levels after thyroid surgery were hyperthyroidism, operative time, and excised thyroid volume, but this increase did not show us any clinical outcomes related to these parameters.

Evaluation of endocrine function in children admitted to pediatric intensive care unit.

BACKGROUND: Although studied widely in adulthood, little is known about endocrinological disorders during critical illnesses in childhood. The aims of this study were to define the endocrinological changes in patients admitted to pediatric intensive care unit (PICU) and to identify their effects on prognosis. METHODS: Forty patients with a mean age of 5.1 years admitted to PICU were enrolled in the study. Blood samples were taken at admission and at 24 and 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient's condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores. RESULTS: PRISM and PELOD scores were significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP-3 and IL-6 were not significantly different between the survivors and non-survivors. There was a negative correlation between baseline IGFBP-3 and PRISM scores. A positive correlation was seen between cortisol level at 24 h and PRISM score. On multivariate linear regression analysis, PRISM score was best explained by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL-6 at 24 h and PELOD scores. CONCLUSIONS: Although there was no difference between survivors and non-survivors regarding the studied endocrine parameters, there were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment scores, and, given that these scores correlated with mortality, these parameters might be useful as prognostic factors.

The effect of glutamine on oxidative damage in an experimental abdominal compartment syndrome model in rats.

BACKGROUND: The aim was to investigate whether or not glutamine, an antioxidant effective amino acid, improves the reperfusion-induced oxidative injury of abdominal hypertension. METHODS: Wistar Albino rats were used. Group 1: Abdominal compartment syndrome alone: With the rats under anesthesia, intraabdominal pressure was obtained. Three days later, the rats were sacrificed, and intestine, lung and liver samples were removed for determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels as oxidative injury parameters and of myeloperoxidase (MPO) activity as an inflammatory parameter. Trunk blood was analyzed for the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Group 2: Abdominal compartment syndrome and glutamine: intragastric glutamine was given for seven days before and three days following establishment of the abdominal compartment syndrome model. The same examination procedure was then performed. Group 3: Glutamine administration alone. Group 4: Control group. RESULTS: Intraabdominal pressure significantly increased the intestine, lung and liver MDA levels and MPO activities in comparison to the control group. Glutamine was associated with decreased MDA levels and MPO activities and increased GSH levels. CONCLUSION: Glutamine appears to have protective effects against reperfusion-induced oxidative damage via its anti-inflammatory and antioxidant effect.

Cholesteryl ester transfer protein Taq1B polymorphism in an angiographically assessed Turkish population: no effects on coronary artery disease risk.

BACKGROUND: Taq1B polymorphism of cholesteryl ester transfer protein (CETP) is believed to associate with high-density lipoprotein-cholesterol (HDL-C) levels and may alter the susceptibility to atherosclerosis. AIM OF THE STUDY: This study investigated the effects of Taq1B polymorphism on HDL-C and coronary artery disease (CAD) risk in angiographically defined CAD patients. METHODS: One hundred thirty-five CAD patients and 112 healthy controls were screened for the CETP Taq1B genotype and plasma lipids. RESULTS: The genotype frequency of CAD patients and controls were similar. The HDL-C levels of all genotypes in the CAD group were significantly lower than the corresponding controls. Smoking and plasma triglycerides were the predictors of the HDL-C level in B1B1 bearers, whereas the subjects with a polymorphic B2 allele were affected by smoking and sex. CONCLUSION: CETP Taq1B polymorphism neither plays a role in determining HDL-C levels nor is a useful predictor of the risk of CAD.

Heme oxygenase-1 prevents hyperthyroidism induced hepatic damage via an antioxidant and antiapoptotic pathway.

BACKGROUND: The exact pathogenesis of hepatic dysfunction in hyperthyroidism is still unknown. We aimed to investigate the pathogenesis of liver dysfunction caused by hyperthyroidism through inducing heme oxygenase-1 (HO-1) expression, which has antioxidant and anti-apoptotic properties. METHODS: Rats were divided into six groups: untreated (group 1), treated with zinc protoporphyrin (ZnPP) (group 2), treated with hemin (group 3), treated with tri-iodothyronine (T3) (group 4), treated with T3 and ZnPP (group 5), and treated with T3 and hemin (group 6). After 22 d, oxidative stress and antioxidant enzymes and the expression of HO-1, mitochondrial permeability transition, cytochrome c, Bax, Bcl-2, caspase-3, caspase-8, and caspase-3 activity, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were examined. RESULTS: Hyperthyroidism induced oxidative stress of liver tissue was ameliorated by HO-1 induction. Administration of hemin (HO-1 inducer) increased Bcl-2 expression. Decreased expression of cytochrome c was accompanied by a decrease in caspase-3, caspase-8, Bax expression, and caspase-3 activity. The apoptotic activity and oxidative damage were found to be increased by the administration of ZnPP (HO-1 inhibitor). Immunohistochemistry findings supported these results. CONCLUSION: HO-1 induction plays a protective role in the pathogenesis of the liver dysfunction in hyperthyroidism. This effect is dependent on modulation of the antiapoptotic and antioxidative pathways by HO-1 expression.

Cord blood cardiac troponin T and nonprotein-bound iron levels in newborns of mild pre-eclamptic mothers.

BACKGROUND: In hypoxic newborns, cardiac troponin T (cTnT) was shown to be an indicator of cardiac damage and increased levels of nonprotein-bound iron (NPBI), an indicator of increased free radical production and perinatal brain damage. OBJECTIVE: The aim of this study was to determine cord blood cTnT and NPBI levels in neonates of mild pre-eclamptic mothers. METHODS: The study included 50 babies of mild pre-eclamptic mothers and 50 babies of healthy mothers. cTnT and NPBI levels were measured in cord blood. RESULTS: The mean gestational age in the pre-eclamptic and healthy groups were 36.1 +/- 3.5 and 38.1 +/- 1.9 weeks, mean birth weights were 2,456 +/- 945 and 3,059 +/- 493 g. Cord blood median cTnT level was significantly higher in the pre-eclamptic group (0.024 vs. 0.015 ng/ml). Serum cTnT in the 95th percentile was 0.047 ng/ml in the healthy group. cTnT levels of preterm babies in the pre-eclamptic group was found to be significantly higher compared to term babies in the control group (0.038 vs. 0.013 ng/ml). It could not be demonstrated whether there is a statistically significant relation between cTnT levels and respiratory distress, gestation, type of delivery, sex and birth weight. The median NPBI level was higher in the control group (3.26 vs. 1.86 micromol/l). CONCLUSIONS: Increased levels of cTnT may be a biochemical marker of cardiac involvement in babies of mild pre-eclamptic mothers. In this study, no correlation was found between cTnT levels and NPBI levels.

Association of cholesteryl ester transfer protein -629C > A polymorphism with high-density lipoprotein cholesterol levels in coronary artery disease patients.

In Turkish population, plasma HDL-C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) -629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL-C level. In the present study, the frequency of -629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL-C was evaluated in a Turkish population. For this aim CETP -629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls. There was no statistical significance in the distribution of genotypes between patients and controls. Although A allele carriers with CAD had significantly lower HDL-C levels than controls, plasma lipid levels showed no difference according to the genotypes. Adjustment by a logistic regression model predicting CAD status through HDL-C and including some risk factors as covariate indicated that the HDL-C doesn't have a significant association with CAD risk in CA and AA genotype carriers. Smoking, gender and hypertension were the common predictors for the HDL-C levels in CA and AA carriers. Although HDL-C appeared to be the only significant predictor of CAD in our study groups, the contribution of CETP -629C > A polymorphism to the alterations in HDL-C level appears to be weak to mention a protective effect of this polymorphism for CAD. In conclusion, the findings of the present study indicate that the CETP -629C > A polymorphism is not among the determinants of the coronary artery disease in Turks.

The impact of age, vitamin D(3) level, and incidental parathyroidectomy on postoperative hypocalcemia after total or near total thyroidectomy.

BACKGROUND: Hypocalcemia caused by transient or definitive hypoparathyroidism is the most frequent complication after thyroidectomy. We aimed to compare the impact of incidental parathyroidectomy and serum vitamin D(3) level on postoperative hypocalcemia after total thyroidectomy (TT) or near total thyroidectomy (NTT). PATIENTS: Two hundred consecutive patients with nontoxic multinodular goiter treated by TT and NTT were included prospectively in the present study. Group 1 (n = 49) consisted of patients with a postoperative serum calcium level < or =8 mg/dL, and group 2 (n = 151) had a postoperative serum calcium level greater than 8 mg/dL. Patients were evaluated according to age, preoperative serum 25-hydroxy vitamin D (25-OHD) levels, postoperative serum calcium levels, incidental parathyroidectomy, and the type of thyroidectomy. RESULTS: Patients in group 1 (n = 49) were hypocalcemic, whereas patients in group 2 (n = 151) were normocalcemic. Preoperative serum 25-OHD levels in group 1 were significantly lower than in group 2 (P < .001). The incidence of hypoparathyroidism was significantly higher following TT (13.5%) than following NTT (2.5%) (P < .05). The risk for postoperative hypocalcemia was increased 25-fold for patients older than 50 years, 28-fold for patients with a preoperative serum 25-OHD level less than 15 ng/mL, and 71-fold for patients who underwent TT. Incidental parathyroidectomy did not have an impact on postoperative hypocalcemia. The highest risk of postoperative hypocalcemia was found in the patients with all of the above variables. CONCLUSIONS: Age, preoperative low serum 25-OHD, and TT are significantly associated with postoperative hypocalcemia. Patients with advanced age and low preoperative serum 25-OHD levels should be placed on calcium or vitamin D supplementation after TT to avoid postoperative hypocalcemia and decrease hospital stay.

Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients.

OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM = IGT +/- hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%)--without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7-18.0) vs. 7.0 (2.3-18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3-7.0) vs. 2.5 (0.7-7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.

Oxidative DNA damage is significantly correlated with flow-mediated dilation in patients with coronary artery disease.

BACKGROUND: Oxidative DNA damage was increased in patients with coronary artery disease (CAD) and correlated with the severity of the disease. Endothelial dysfunction plays a major role in atherosclerotic process. The aim of this study was to explore a relation between oxidative DNA damage and endothelial function in patients with CAD. METHODS: Forty patients with CAD and 20 age- and sex-matched healthy controls were included. Endothelial function was assessed by brachial artery ultrasonography. The DNA damage was determined by comet method. RESULTS: The DNA damage scores after incubation with repair enzymes were found significantly higher in the patients with CAD (P = 0.04). There was a significant negative correlation between oxidized DNA damage scores and flow-mediated dilation (FMD) measures in the patients with CAD (r = -0.41; P = 0.009). Oxidized DNA damage scores were significantly and independently associated with FMD (standardized beta = -0.455; P = 0.009) when adjusted by age, sex, smoking status, blood pressure, and cholesterol levels. CONCLUSIONS: The DNA damage scores were significantly inversely correlated with FMD measures. To our knowledge, this is the first study showing the presence of a relation between DNA damage scores and FMD.

Oxidative damage in an experimentally induced gastric and gastroduodenal reflux model.

The exact pathophysiologic mechanisms of esophageal cell damage and carcinogenesis by gastroesophageal reflux are not clearly understood. The aim of this study was to evaluate the damage to the esophageal epithelium that occurs after acid reflex and mixed acid and bile reflux by assessing histopathology, reactive oxygen species, and DNA damage. Eighty 10-week-old male Sprague-Dawley rats were divided into two groups, an acid reflux group and a mixed (acid/bile) reflux group. Acid reflux was achieved by esophagogastroplasty in which mixed reflux was encouraged via esophagoduodenal anastomosis. Each group contained a control subgroup that underwent sham laparotomy alone. The rats were killed 3, 6, 9, and 12 months after surgery. Malondialdehyde, protein carbonyl content, and DNA damage were determined in lymphocytes. Histopathologic analysis was performed according to the histologic activity index. Inflammation, ulcer, and regeneration in both reflux groups were significantly increased in the esophagus at 3, 6, 9, and 12 months compared with the control group. Mucosal damage was greater in the mixed reflux group compared with the gastric reflux group. Malondialdehyde and carbonyl content in the serum, and DNA damage in lymphocytes, were significantly increased in both reflux groups. At 9 and 12 months, oxidative damage was increased in the mixed reflux group compared with the acid reflux group. Oxygen-derived free radicals seem to be one of the important mediators in the evaluation and generation of reflux esophagitis. The impact of oxygen free radicals, as demonstrated in this study, can be evaluated by assessing the damage that they incur to lipid membranes, serum proteins, and circulating lymphocyte DNA. Serum malondialdehyde and carbonyl content as well as lymphocyte DNA damage were significantly increased in the setting of acid and mixed acid/bile reflux in these rodent models. Further, these serum and lymphocytic changes were associated with esophageal ulceration, inflammation, and regeneration. Evaluation of such markers as serum malondialdehyde and carbonyl content as well as evaluation of lymphocyte DNA might prove to be useful investigations in patients with precancerous and cancerous conditions in addition to conventional methods of diagnosis. Further studies, both animal and human are warranted.

Increased plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in patients with angiographically defined coronary artery disease.

We investigated the oxidative modifications of lipids, proteins and DNA, three potential molecular targets of oxidative stress, in 30 patients with angiographically defined coronary artery disease (CAD) and 30 healthy control subjects. In addition, we examined relationships between these oxidative modifications and the severity of vascular lesions in patients with CAD. Malondialdehyde (MDA) and protein carbonyl (PC) levels, as well as ferric reducing antioxidant power (FRAP), were measured in the plasma. DNA damage was evaluated as single strand breaks (SSBs), formamidopyrimidine glycosylase (Fpg) and endonuclease III (E-III)-sensitive sites by the comet assay in DNA isolated from lymphocytes. MDA and PC levels increased, but FRAP values decreased, in patients as compared to controls. However, these values did not vary with the number of affected coronary vessels and were not correlated with Duke score, a parameter of the severity of vascular lesions in patients with CAD. We also found that lymphocyte DNA damage (SSBs, Fpg and E-III sites) were increased in patients. Although there were no significant differences in SSBs values in patients grouped according to affected vessel number, Fpg and E-III sites increased. We also detected significant correlations between Duke scores and SSBs and Fpg sites. Serum cholesterol, triglyceride and LDL-cholesterol levels were found to increase, but HDL-cholesterol levels decreased in CAD patients, but these lipids were not correlated with Duke scores. The results of this study reinforce the presence of increased combined oxidative modifications in lipid, protein and DNA in patients with CAD. However, lymphocyte DNA damage seems to be a more reliable assay than MDA and PC determinations to detect the severity of vascular lesions in patients.

Molecular correlates of temporomandibular joint disease.

OBJECTIVE: The relation between disease severity and the known mediators of pain, inflammation, and tissue damage-prostaglandin E 2 (PGE 2 ), leukotriene B 4 (LTB 4 ), malondialdehyde (MDA), nitric oxide (NO), and myeloperoxidase (MPO)-was examined in the synovial fluid of patients with internal derangement (ID) of the temporomandibular joint (TMJ). STUDY DESIGN: Thirty-two patients with ID were classified according to Wilkes by clinical and radiological examinations, and TMJ synovial fluid samples were obtained by arthrocentesis. PGE 2 and LTB 4 levels were measured by ELISA kits, MDA levels were determined by a fluorometric method, myeloperoxidase activity was determined by an end-point method, and NO levels were measured by Griess reaction. RESULTS: The earliest significant increase was observed in NO levels (stage II) and this elevation persisted in the subsequent stages. The first significant elevation in PGE 2 and LTB 4 levels and MPO activity were observed in stage III. Both PGE 2 and LTB 4 levels were increased in stage III and were correlated with each at this stage and in the subsequent stage. Significant increases in MDA levels were observed only in stage IV. At stage IV there was correlation between MDA and PGE 2 , MDA and LTB 4 , and MDA and MPO. The relation between PGE 2 and MDA was the most powerful one. CONCLUSION: Results of this cross-sectional study point out the relation between disease severity and levels of some molecular mediators in synovial fluid of TMJ. Longitudinal studies are needed to explore the role of these molecular mediators in the progression of ID.

Age-related increases in plasma malondialdehyde and protein carbonyl levels and lymphocyte DNA damage in elderly subjects.

OBJECTIVES: Increased oxidative stress has been hypothesized to play an important role in the aging process. A role for oxidative damage in normal aging is supported by studies in experimental animals, but there is limited evidence in humans. To investigate the relationship between the oxidative stress and aging in humans, we determined lipid and protein oxidation in plasma as well as DNA damage in lymphocytes in young and elderly subjects. DESIGN AND METHODS: 55 healthy subjects were divided into young (21-40 years) and elderly (61-85 years) groups. Plasma malondialdehyde (MDA), protein carbonyl (PC) levels, and grade of DNA damage in lymphocytes using comet assay as well as total ferric reducing antioxidant power (FRAP) in plasma were determined in young and elderly subjects. RESULTS: Plasma MDA and PC levels were found to be increased in plasma of elderly subjects as compared to young subjects. Increases in endogenous and H2O2-induced DNA damage were also observed in lymphocytes of elderly subjects. In addition, we detected a significant decrease in FRAP values in elderly subjects. Plasma MDA, PC levels and endogenous and H2O2-induced DNA damage were positively correlated with aging, but negatively with FRAP values. CONCLUSION: We evaluated MDA, PC levels and lymphocyte DNA damage altogether in both young and elderly subjects for the first time. The results of this study strongly support the presence of increased oxidative stress in elderly subjects.