DNA damage in children with scoliosis following X-ray exposure.

AIM: It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X-ray for diagnosis and follow-up. X-ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8-Hydroxydeoxyguanosine (8-OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G-Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. METHODS: A total of 31 children with adolescent idiopathic scoliosis and 21 age-matched healthy children were included in the study. Serum levels of 8-OHdG and p53 were measured with ELISA kits. SOD and G-Px activities were determined with spectrophotometric assays. RESULTS: Serum levels of 8-OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age-matched controls. There was no significant difference between the groups for G-Px activity. CONCLUSION: Our data show that X-ray exposure causes increased 8-OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X-ray mediated DNA damage.

DNA damage in children with scoliosis following X-ray exposure.

AIM: It has been suggested that cancer incidence is high in subjects with scoliosis who are relatively more often exposed to X--ray for diagnosis and follow--up. X--ray is a kind of ionizing radiation and leads to formation of oxygen free radicals which are capable of damage to DNA, thus altered gen expression and mutation. p53 tumor suppressor gene plays a crucial role in the damage response. It controls the checkpoint of cell cycle and redirects the cell metabolism to either repair of damaged DNA or apoptosis as response to DNA damage. The aim of the present study was to examine serum levels of 8--Hydroxydeoxyguanosine (8--OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide dismutase (SOD) and glutathione peroxidase (G--Px), as antioxidant activity, in children with scoliosis who had got whole spine radiograph two times during the last year. METHODS: A total of 31 children with adolescent idiopathic scoliosis and age--matched 21 healthy children were included in the study. Serum levels of 8--OHdG and p53 were measured with ELISA kits. SOD and G--Px activities were determined with spectrophotometric assays. RESULTS: Serum levels of 8--OHdG and p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was found to be lower (P<0.001) in the children with scoliosis as compared to age--matched controls. There was no significant difference between the groups for G--Px activity. CONCLUSION: Our data show that X--ray exposure causes increased 8--OHdG level, and decreased SOD activity, which both may reflect a tumor promoting condition. Increased p53 level may be interpreted as a compensatory effort of cell to X--ray mediated DNA damage.

Paraoxonase, oxidized low density lipoprotein, monocyte chemoattractant protein-1 and adhesion molecules are associated with macrovascular complications in patients with type 2 diabetes mellitus.

AIM: The aim of this paper was to evaluate the association between blood glucose, oxidative stress, inflammation, endothelial dysfunction and paraoxonase activity as contributors to the accelerated atherosclerosis seen in type 2 diabetic patients. METHODS: Plasma malondialdehyde (MDA), oxidized LDL (oxLDL), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1) levels and paraoxonase-1 (PON1) activity were measured in sixty type 2 diabetic patients, 30 of whom had macrovascular complications, and 30 controls. RESULTS: Diabetics with macrovascular complications had higher levels of MDA, oxLDL, MCP-1, ICAM-1, VCAM-1 than those without, and the difference was significant for all molecules except for ICAM-1. PON1 activity and ApoA1 levels of the controls were significantly higher than that of the patients, while PON1 activity and ApoA1 levels in the patients with macrovascular complications were significantly lower than that in patients without. Ambient plasma glucose concentration showed a significant positive association with plasma MDA, oxLDL, MCP-1, and VCAM, and a significant inverse association with PON1 and ApoA1 in diabetic patients. A significant positive correlation between oxLDL and MDA, a negative correlation between oxLDL and PON1; a significant inverse association between MDA and PON1; a positive correlation between MDA and MCP-1 and VCAM while a negative correlation between PON1 and MCP-1 and VCAM were detected in patients. CONCLUSION: Hyperglycemia might play a significant role in generating increased oxidative stress, and decreased PON1 activity, resulting in elevated oxLDL, MCP-1 and VCAM levels. This might be one of the causal pathogenic factors initiating accelerated atherosclerosis in patients with type 2 diabetes mellitus. The implication of these findings are unclear and therefore further studies are required.

Serum levels of fetuin A and 8-hydroxydeoxyguanosine in morbidly obese subjects.

Insulin resistance is one of the feature of obesity. Fetuin A is inhibitor of insulin receptor which belongs the family of receptor tyrosine kinase. It has been observed that fetuin-null mice are resistant to diet-induced obesity and they exhibit increased insulin sensitivity. Increased production of reactive oxygen species is suggested to be associated with insulin resistance. Attacks of reactive oxygen species to DNA results in base oxidation. Among the oxidized bases, 8-hydroxydeoxyguanosine is predominant lesion with pro-mutagenic potential. In the present study; measurement of serum levels of fetuin A and 8-hydroxydeoxyguanosine in obese subjects (n=46) and healthy controls (n=22), and examination of the relations between these parameters and insulin resistance have been purposed. Blood samples were taken form morbidly obese subjects after a 12 h fasting. Serum levels of fetuin A and 8-hydroxydeoxyguanosine were measured by ELISA. Statistical analysis was performed by Mann Whitney U test and correlations were examined by Spearman correlation coefficient. Serum levels of total cholesterol, HDL, LDL, VLDL, triglycerides, free T3, free T4, fasting glucose, c-peptide and %HbA1c in the obese group were found to be different from those in the control group. Serum level of fetuin A was found to be higher, 8-hydroxydeoxyguanosine level was found to be lower in the morbid obese group than those in the control group. Fetuin A was found to be positively correlated with HOMA-IR (r:0,40, P<0.05) and negatively correlated with 8-hydroxydeoxyguanosine (r:-0,52, P<0.01). No significant association was determined between body mass index and measured parameters. In conclusion, serum level of fetuin A is high in morbidly obese subjects and is negatively associated with 8-hydroxydeoxyguanosine level in peripheral circulation. Fetuin A may be a promising link between insulin resistance and obesity as well its comorbidities.

Trace element levels in ischemia-reperfusion injury after left colonic anastomosis in rats and effects of papaverine and pentoxiphylline on vascular endothelial growth factor in anastomosis healing.

BACKGROUND AND STUDY AIMS: Due to their high morbidity and mortality, anastomotic leakage and disruption are still serious problems in colonic surgery. Bowel clamps applied during anastomosis in order to prevent abdominal contamination with colonic contents, may cause microcirculation and perfusion problems and subsequent ischemia-reperfusion injury. Papaverine, a myorelaxant and vasodilatator, and pentoxiphylline, a hemorrheologic agent are used for microcirculation disorders and vascular endothelial growth factor (VEGF) is a stimulator of angiogenesis. With this experimental study, we aimed to measure trace element [copper (Cu) and zinc (Zn)] levels in ischemia-reperfusion injury due to clamps after left colonic anastomosis in rats and show the effects of papaverine and pentoxiphylline on VEGF that stimulates angiogenesis in anastomotic healing. MATERIALS AND METHODS: 50 female Wistar albino rats were randomized in 5 groups (n: 10). Laparotomy in group 1, left colonic transsection and anastomosis in group 2, and clamp application 1 cm proximal and distal to the anastomosis (for about 20 minutes long) during left colonic transsection and anastomosis in groups 3, 4 and 5 were performed. Additionally, after the operations, pentoxiphylline (Group 4) and papaverin (Group 5) were injected intraperitoneally. On the 10th postoperative day, plasma trace element and plasma VEGF levels were measured. RESULTS: In this study, VEGF levels in group 1 were significantly low and this was explained as being exposed to hypoxic damage less than the other groups. In group 3, VEGF levels were significantly higher showing that the hypoxic stimulus continued without any treatment and in Group 4, significantly lower than Group 3 related to the inhibition of pentoxiphylline. Lower VEGF levels in Group 1 were thought to be related to lower VEGF induction due to less hypoxic effect. Zinc, an important trace element of the antioxidant system showed significantly higher levels in Group 4 with pentoxiphylline treatment, and this was thought to be related to the antioxidant characteristics of pentoxiphylline. CONCLUSIONS: During surgical procedures, care should be taken not to cause ischemia to the intestinal tissues, and trace elements that are important in ischemia reperfusion injury should be replaced appropriately. Although the antioxidant effect of pentoxiphylline in ischemia reperfusion injury may be benefical in treatment, its inhibition of VEGF is a disadvantage in wound healing.

Energy-absorbing car seat designs for reducing whiplash.

OBJECTIVES: This study presents an investigation of anti-whiplash features that can be implemented in a car seat to reduce whiplash injuries in the case of a rear impact. The main emphasis is on achieving a seat design with good energy absorption properties. METHODS: A biofidelic 50th percentile male multi-body human model for rear impact is developed to evaluate the performance of car seat design concepts. The model is validated using the responses of 7 volunteers from the Japanese Automobile Research Institute (JARI) sled tests, which were performed at an impact speed of 8 kph with a rigid seat and without head restraint and seatbelt. A generic multi-body car seat model is also developed to implement various seatback and recliner properties, anti-whiplash devices, and head restraints. Using the same driving posture and the rigid seat in the JARI sled tests as the basic configuration, several anti-whiplash seats are designed to allow different types of motion for the seatback and seat-pan. RESULTS: The anti-whiplash car seat design concepts limit neck internal motion successfully until the head-to-head restraint contact occurs and they exhibit low NIC(max) values (7 m(2)/s(2) on average). They are also effective in reducing neck compression forces and T1 forward accelerations. In principle, these car seat design concepts employ controlled recliner rotation and seat-pan displacement to limit the formation of S-shape. This is accomplished by using anti-whiplash devices that absorb the crash energy in such a way that an optimum protection is provided at different severities. CONCLUSIONS: The results indicate that the energy absorbing car seat design concepts all demonstrate good whiplash-reducing performances at the IIWPG standard pulse. Especially in higher severity rear impacts, two of the car seat design concepts reduce the ramping of the occupant considerably.

Prognostic significances of oxidative DNA damage evaluated by 8-hydroxy-deoxyguanosine and antioxidant enzymes in patients undergoing resection of gastric and colon carcinoma.

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. In order to determine whether the degree of oxidative DNA damage and antioxidant enzyme activities in plasma obtained from patients with gastric and colon cancer who undergo resection can be used as a useful prognostic predictor, plasma level of 8-hydroxydeoxyguanosine (8-OHdG), activities of glutathione peroxidase (G-Px) and superoxide dismutase (SOD) were examined. 19 patients with gastric cancer and 26 patients with colon cancer who were undergoing resection of tumor were included by the study. Venous blood samples were taken just before the surgery. Plasma level of 8-OHdG was determined with ELISA, SOD and G-Px activities in plasma were measured by spectrophotometric kits. 8-OHdG level and activity of G-Px were found to be decreased, SOD activity was found to be increased in both gastric and colon cancer groups as compared to control group. Alpha fetoprotein was found to be correlated with G-Px in the gastric cancer group and correlated with 8-OHdG in the colon cancer group. SOD activity was correlated with CA-15-3 in the gastric cancer group. Low plasma level of 8-OHdG and altered antioxidant activity may implicate the deficient repair of oxidative DNA damage in patients with gastric and colon cancer. Those measured parameters were not found to be related with histopathological data but correlated with some tumor markers.