Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia.

OBJECTIVES: The heterogeneity of schizophrenia mainly results from variations in clinical expressions of the disease, such as age at onset, gender differences in onset of illness, symptoms and response to antipsychotic treatment. Enhanced sensitisation of dopamine pathways in males, having consistently an earlier onset, might be implicated as disease modifiers for schizophrenia in males. METHODS: In this study, we performed a case (n = 87)-control (n = 100) association study between the DBH5'-ins/del and DBH-444g/a polymorphisms of the DBH gene and also compared the level of psychotic symptoms between patients with different DBH genotypes/haplotypes with respect to antipsychotic therapeutic response and gender difference. RESULTS: No significant differences between allele and genotype and haplotype frequencies at either groups (p < 0.05). When the age is considered in patient group, a significant difference was observed between patients with ID genotype and with II genotype (p = 0.018). Patients with ID genotype have been diagnosed as schizophrenics in early ages when compared to II genotype carriers. We also found a significant difference between II and ID genotype (p = 0.007) when the gender had taken into account, showing that the ID genotype carriers had an early onset to schizophrenia. CONCLUSIONS: This association was more significant in male schizophrenia patients than females. Thus, this finding may constitute a novel biological support for the prior finding that onset of schizophrenia varies with gender. The results also showed that critical genetic vulnerability may be associated with the presence or absence of the ID genotype of DBH5'-ins/del.

Determination of pain intensity risk factors among school children with nonspecific low back pain.

BACKGROUND: Low back pain (LBP) is a common disease among people under the age of 20. To the best of our knowledge few studies have been carried out on LBP among school children in Turkey, and none of them studied the correlation between pain intensity and related variables with LBP. MATERIAL/METHODS: This cross-sectional study was carried out to investigate the risk factors and their correlations with pain intensity among 222 school children (106 girls and 116 boys) aged 10-18 years in the city of Denizli. A self-reported questionnaire was used to collect the data. The regression tree method (RTM) was used to determine the risk factors by using the STATISTICA program package. Pain intensity was the outcome variable, and 8 independent variables (body mass index (BMI), sex, regular exercise habit, studying posture, transportation to/from school, duration of studying, bag handling, and type of bed) were used to detect their effect on pain intensity. RESULTS: The results showed that pain intensity is significantly affected by 4 independent variables: duration of studying, type of bed, transportation to/from school, and BMI. The overall mean and standard deviation of pain intensity was 2.58 ± 0.86 (minimum=1, maximum=5). CONCLUSIONS: Results from the literature, as well as our study, show that taking parents' and teachers' concerns seriously is of vital importance. Our results indicate that parents and teachers should be informed about duration of studying, type of bed, transportation and obesity as risk factors predicting NLBP in school children.

Arginase, NOS activities, and clinical features in fibromyalgia patients.

OBJECTIVES: Fibromyalgia (FM) is a form of nonarticular rheumatism characterized by chronic widespread musculoskeletal aching and tender points. The aim of the present study was to investigate the effect of arginase and nitric oxide synthase (NOS) enzyme activities in FM with respect to their importance in pathogenesis, and the relationship with FM-related clinical parameters. METHODS: After obtaining informed consent, 25 female FM patients were compared with 23 healthy female controls. NOS and arginase enzyme activities were measured spectrophometrically in sera. Tender points were examined using the protocol described by Wolfe et al. The health status of patients was assessed by Fibromyalgia Impact Questionnaire. Musculoskeletal pain was scored according to visual analog scale. Health Assessment Questionnaire, Beck depression and Beck anxiety scales, and dyspnea scores were administered to analyze functional, psychiatric, and respiratory status of the patients. RESULTS: We found that NOS activity was significantly higher whereas arginase activity was lower in patients with FM. In the correlation analysis, NOS levels showed statistically significant positive correlation with chest pain and dyspnea parameters. NOS enzyme activities were higher in subjects with positive history of migraine, pain, and morning stiffness. On the other hand, arginase levels were lower in subjects with positive history of irritable bowel syndrome and morning stiffness. CONCLUSION: Animal experiments have suggested that nitric oxide (NO) is an important transmitter in pain pathways. It can also stimulate cyclooxygenase activity. We observed increased NOS activity and reduced arginase activity in FM patients, which may be due to increased cyclooxygenase enzyme activity and oxidant/antioxidant imbalance. In conclusion, we think that future studies concerning clinical control of pain with selective NOS inhibitors are needed in order to determine new therapeutic approaches and the exact pathophysiologic mechanisms in FM patients.

The association of mast cell density with myometrial invasion in endometrial carcinoma: a preliminary report.

It is known that cancer is not a single transformational event. It is rather a multistage process involving complex interactions with the surrounding cellular microenvironment. Mast cells accumulate at sites of tumor growth in response to numerous chemoattractants. Our aim was to investigate the relationship between mast cell density (MCD) and myometrial invasion in endometrial carcinomas. Immunohistochemistry was performed on 35 unselected consecutive hysterectomy specimens from patients with endometrial adenocarcinoma. C-kit-positive mast cell assessment was performed in the myometrium adjacent to tumor tissue. A mean number of or=16 mast cells was regarded as high mast cell density (H-MCD). A significant correlation (p=0.018, Pearson Chi-Square test) between H-MCD and the presence of myometrial invasion was demonstrated in endometrial carcinomas. H-MCD was found in 54% of all cases, and 94% of H-MCD cases had myometrial invasion, suggesting a role of mast cells or an interaction with tumor. Therapeutic modalities orientated to these cells or their microenvironment as a new target for adjuvant treatment might determine the prognosis in endometrial carcinomas.

Assessment of symptom severity and functional status in patients with carpal tunnel syndrome: reliability and functionality of the Turkish version of the Boston Questionnaire.

OBJECTIVES: The aim of this study was to develop a Turkish version of the Boston Questionnaire and assess its reliability and validity. METHODS: Sixty-seven patients with idiopathic carpal tunnel syndrome were included in the study. The Turkish version of Boston Questionnaire was obtained after translation process, and was then administered to subjects twice within seven days. Reliability was assessed by internal consistency (Cronbach's alpha and item-total correlation), and reproducibility. Validity was examined by correlating the Boston Questionnaire scores to general health status (Short Form-36), pain severity (Visual Analogue Scale) and pinch and grip strength measures. RESULTS: Reliability of the Turkish version was very good, with high internal consistency (Cronbach's alpha 0.82 for symptom severity scale, and 0.88 for functional status scale), and reproducibility (Pearson correlation coefficient 0.60 for symptom severity scale, and 0.77 for functional status scale). The Boston Questionnaire scores were correlated with Visual Analogue Scale, physical functioning, physical role, bodily pain and emotional role subscales of Short Form-36, pinch and grip strength scores to obtain coefficients for external construct validity. CONCLUSION: Adaptation of the Boston Questionnaire for use in Turkey was successful. Our results seem to support previous finding of the English version, indicating that it is valid and reliable.

Effects of trapidil on renal ischemia-reperfusion injury.

There is increasing evidence to suggest that reactive oxygen and nitrogen species play a role in the pathogenesis of renal ischemia-reperfusion (I/R) injury. This study was designed to determine the possible protective effects of trapidil treatment against oxidative and nitrosative tissue injury of kidney induced by I/R. A renal I/R injury was induced by a left renal pedicle occlusion by ischemia for 45 minutes, followed by 1 hour of reperfusion with contralateral nephrectomy in I/R and I/R + trapidil groups. Trapidil (8 mg/kg intravenously) was administrated immediately before reperfusion phase. At the end of the reperfusion period, rats were killed. Then, renal tissue samples were taken for biochemical analysis and histopathological evaluation, and blood samples were obtained to determinate serum urea, aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha) levels. Ischemia-reperfusion injury caused significant increases in myeloperoxidase activity and malondialdehyde and 3-nitrotyrosine levels in renal tissue and elevated serum urea, AST, and TNF-alpha levels. In addition, severe deterioration of renal morphology was seen in the I/R group. Trapidil treatment significantly reduced in biochemical parameters, as well as serum urea, AST, and TNF-alpha levels. Furthermore, renal tissue injury was markedly attenuated with trapidil treatment. These data suggest that reactive oxygen species and reactive nitrogen species play a causal role in I/R-induced renal tissue, and trapidil has a renoprotective effect against oxidative and nitrosative kidney damage.

Lack of association with TNF-alpha-308 promoter polymorphism in patients with vitiligo.

Vitiligo is an acquired depigmentary disorder of the skin, characterized by incomplete penetrance, multiple susceptibility loci and genetic heterogeneity. An immunologic hypothesis is currently advanced as a possible pathogenesis of vitiligo. The cytokines have an important role in pathogenesis of autoimmunity in which tumor necrosis factor-alpha (TNF-alpha), a paracrine inhibitor of melanocytes, is especially important. Several single-nucleotide polymorphisms (SNP) have been identified in the human TNF gene promoter. The polymorphism at position -308 (TNF-308), which involves substituting G for A and designing the AA genotype, leads to a higher rate of TNF gene transcription than the wild-type GG genotype in in vitro expression studies. It has also been linked to increased susceptibility to several chronic metabolic, degenerative, inflammatory and autoimmune diseases. Therefore, we investigated the TNF-alpha-308 SNP in patients with vitiligo. We examined 61 patients with vitiligo. Healthy age-, ethnically- and sex-matched individuals (n = 123) served as controls. Polymerase chain reaction amplification was used for analysis of the polymorphism at position -308 in promoter of TNF-alpha gene. We found that the distribution of TNF-alpha genotypes in vitiligo patients did not differ from that in control subjects (P > 0.05). Moreover, there was no association between TNF-alpha genotypes and types of vitiligo. In conclusion, we suggest that TNF-alpha-308 SNP is not a genetic risk factor for vitiligo susceptibility.

Hearing loss in patients undergoing coronary artery bypass grafting with or without extracorporeal circulation.

BACKGROUND: Our aim was to investigate the differences in postoperative hearing thresholds in patients undergoing coronary artery bypass grafting with (Group I, n=20) or without (Group II, n=17) extracorporeal circulation. MATERIAL/METHODS: 37 patients undergoing coronary artery bypass grafting with or without extracorporeal circulation were prospectively evaluated in terms of hearing threshold changes with the intention of documenting hearing losses postoperatively. The t-test for two independent variables was used for statistical analysis. RESULTS: Hearing threshold changes were detected in 9 Group I patients (45%) and 3 Group II patients (17.65%). The difference between the two groups was statistically significant (p=0.0426). CONCLUSIONS: Postoperative hearing threshold changes, not necessarily revealed by clinical examinations, are encountered after coronary artery bypass grafting operations. Extracorporeal circulation usage seems to bring an additional risk in terms of hearing loss.

Angiographic and clinical outcome following paclitaxel-eluting stent (taxus) implantation: a single center experience.

Coronary stents dramatically improve acute outcomes of percutaneous coronary interventions but also induce abundant intraluminal neointimal growth. Drug-eluting stents reduce intimal hyperplasia, the main cause of in-stent restenosis. The safety and beneficial effects of paclitaxel-eluting stents (Taxus) in patients treated in daily practice remains to be defined. The aim of this study was to report the late outcomes of Taxus implantation in patients with coronary artery disease. The study population consisted of 151 patients (202 stents) who had undergone coronary Taxus stent implantation between March 2003 and May 2005. Patients were eligible for enrollment if there was symptomatic coronary artery disease or positive functional testing, and angiographic evidence of single or multivessel disease with a target lesion stenosis of 70% in a 2.0 mm vessel. The control coronary angiographies were performed after stent deployment at 12 +/- 2.8 months, and approximately 2 years of follow-up was completed. The polymer-based paclitaxel-eluting stent has been shown to be effective in reducing restenosis. Patients were followed-up for 16.7 +/- 7.4 months. All patients survived after stent implantation, but 2 (1.3%) patients experienced acute myocardial infarction after 3 and 9 months following angioplasty. Recurrent angina pectoris was observed in 3 patients. Angiographic evidence of restenosis was observed in these 5 patients. Three patients underwent angioplasty because of re- stenosis, and coronary artery bypass grafting was conducted in the other 2 patients. The results indicate that Taxus stents can be implanted with a very high success rate and have encouraging long-term angiographic and clinical results.

Determination of risk factors for hypertension through the classification tree method.

Most current statistical strategies for determining risk factors for hypertension (HT) among certain populations have proved inconclusive. In this study, the classification tree method, which is more practical and easy to understand than other statistical methods, was used to determine the risk for HT among outpatients in a clinic in Denizli province, western Turkey, between January 2002 and July 2004. The effects of 14 risk factors (body mass index, waist-to-hip ratio, age, serum total cholesterol, serum triglycerides, sex, HT in first-degree relatives, diabetes mellitus, smoking, stress factors, alcohol consumption, dyslipidemia in first-degree relatives, dyslipidemia [previously diagnosed], and saturated fat consumption) on HT were evaluated in this population. In all, 1761 adults at the outpatient clinic were recruited for lipid and HT measurements. The classification tree method revealed 7 main risk factors (body mass index, waist-to-hip ratio, sex, serum triglycerides, serum total cholesterol, HT in first-degree relatives, and saturated fat consumption) for HT. The findings of the present study suggest that the classification tree is a valuable statistical method for evaluating multiple risk factors for HT.

N-acetyltransferase 2 gene polymorphism and presbycusis.

OBJECTIVES/HYPOTHESIS: The enzyme of N-acetyltransferase (NAT) is involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species (ROS). The excessive amount of ROS generation occurs in the ageing inner ear. The exact etiopathogenesis of presbycusis is not known, but it is generally accepted that it is the result of series of insults, such as physiologic age-related degeneration, noise exposure, medical disorders and their treatment, as well as hereditary susceptibility. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of NAT2 genotypes may be associated with the risk of presbycusis. STUDY DESIGN: Hospital-based, case-control study. METHODS: We examined 68 adults with presbycusis and 98 healthy controls. DNA was extracted from whole blood, and the polymorphisms of NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. RESULTS: Gene polymorphisms at NAT2*5A, NAT2*7A/B, and NAT2*14A in subjects with presbycusis were not significantly different from in the controls (P > .05). However, in NAT2*6A, the risk of presbycusis was 15.2-fold more in individuals with mutant allele than subjects with wild genotype (P = .013). Individuals with NAT2*6A heterozygote allele had a 0.34-fold less risk in the development of presbycusis than subjects with mutant allele (P = .032) CONCLUSION: We demonstrated a significant association between the NAT2*6A polymorphism and age-related hearing loss in this population. However, the sample size was relatively small, and further studies need to investigate the exact role of NAT2 gene polymorphism in the etiopathogenesis of the presbycusis.

Inspiratory and expiratory HRCT findings in Behçet's disease and correlation with pulmonary function tests.

PURPOSE: The purpose of our study was to describe the pulmonary parenchymal changes of Behçet's disease using high-resolution computed tomography and to correlate them with pulmonary function tests. MATERIALS AND METHODS: Thirty-four patients with Behçet's disease (18 men, 16 women), 3 of whom were symptomatic, were included as the study group. Four of 34 patients were smokers. Twenty asymptomatic volunteers (12 men, 8 women), 4 of whom were smokers, constituted the control group. The pulmonary function tests and high-resolution computed tomography were performed for both groups. RESULTS: Inspiratory high-resolution computed tomography findings were abnormal in nine patients (26.5%) of the study group. In eight patients, there were multiple abnormalities, whereas one patient had only one abnormality. Pleural thickening and irregularities, major fissure thickening, emphysematous changes, bronchiectasis, parenchymal bands, and irregular densities, and parenchymal nodules were the encountered abnormalities. Inspiratory high-resolution computed tomography scans were normal in the control group. On expiratory scans, there was statistically significant difference between study group and control group when air trapping, especially grades 3 and 4, was compared (P<0.01). Pulmonary function tests of both the study and the control groups were in normal ranges, and there was no statistically significant difference between the two groups according to pulmonary function tests (P>0.05). DISCUSSION AND CONCLUSION: High-resolution computed tomography is sensitive in the demonstration of pulmonary changes in patients with Behçet's disease. End-expiratory high-resolution computed tomography examination is very useful and necessary to show the presence of air trapping, thus the presence of small airway disease, even if the patient is asymptomatic or has normal pulmonary function tests.

Apolipoprotein E polymorphism in diabetic and non-diabetic patients: does it really contribute to atherosclerosis?

OBJECTIVE: The exact mechanism of the increased cardiovascular morbidity and mortality in type-2 diabetes is still undefined. The aim of our study was to assess the impact of apolipoprotein E (apo E) polymorphism and other factors on atherosclerotic vascular disease in type-2 diabetic patients. We also examined the association between apo E polymorphism and lipid profile in diabetic patients. METHODS AND RESULTS: We assessed the apo E polymorphism in 295 atherosclerotic patients (124 of them had diabetes (according to WHO criteria) and 171 of them had coronary artery narrowing > 50). The detection of apo E polymorphism was made by Real-Time PCR using a Light-Cycler (Roche diagnostics, GmbH, Mannheim, Germany). Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)], apolipoprotein A (Apo A) and apolipoprotein B (Apo B) levels were determined by biochemical analyser. Genotypic distribution of apo E polymorphism did not differ between diabetic and non-diabetic atherosclerotic patients. The distributions of apo E2/2, E2/3, E2/4, E3/3, E3/4 and E4/4 genotypes in diabetic and non-diabetic atherosclerotic patients were 7.3%: 8.2%, 15.3%: 15.8%, 4.0%: 5.3%, 50.8%: 56.7%, 16.9%: 11.1% and 5.6%: 2.9%, respectively. Participants were grouped as apo E2 (E2/2 or E2/3), apo E3 (E3/3), or apo E4 (E4/4 or E4/3). The distributions of apo E2, E3 and E4 alleles were 23.5%, 52.9%, 23.5%, for diabetic patients, and 25.3%, 59.9%, 14.8% for non-diabetic patients, respectively. The apolipoprotein E genotype was not associated with the lipid levels in diabetic patients. CONCLUSIONS: Our findings imply that apo E polymorphism is not related to the development of atherosclerosis in patients with type-2 diabetes.

The comparison of the efficacy of scoring systems in organophosphate poisoning.

The purpose of this study was to evaluate the impact of the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems for organophosphate poisoning (OPP) in an intensive care unit (ICU). The following data were collected on all consecutive patients who were admitted to the ICU between June 1999 and December 2004. Demographic data, GCS, APACHE II and SAPS II scoring systems were recorded. Predicted mortality was calculated using original regression formulas. Standardized mortality ratio (SMR) was computed with 95% confidence intervals (CI). The sensitivity and specificity for each scoring system were evaluated by calculating the Area Under the Receiver Operating Characteristic Curves. The actual mortality in OPP was 21.9%. Predicted mortality by all systems was not significantly different from actual mortality [SMR and 95% CI for GCS: 1.00 (0.65 1.35), APACHE II: 0.87 (0.54-1.03), SAPS II: 1.40 (0.98-1.82)]. The area under the ROC curve for APACHE II is largest, but there is no statistically significant difference when compared with SAPS II and GCS (GCS 0.900 +/- 0.059, APACHE II 0.929 +/- 0.045 and SAPS II 0.891 +/- 0.057). In our ICU group of patients, in predicting the mortality rates in OPP, the three scoring systems, which are GCS, APACHE II and SAPS II, had similar impacts; however, GCS system has superiority over the other systems in being easy to perform, and not requiring complex physiologic parameters and laboratory methods.

Determination of osteoporosis risk factors using a multiple logistic regression model in postmenopausal Turkish women.

OBJECTIVE: To determine the risk factors of osteoporosis using a multiple binary logistic regression method and to assess the risk variables for osteoporosis, which is a major and growing health problem in many countries. METHODS: We presented a case-control study, consisting of 126 postmenopausal healthy women as control group and 225 postmenopausal osteoporotic women as the case group. The study was carried out in the Department of Physical Medicine and Rehabilitation, Dicle University, Diyarbakir, Turkey between 1999-2002. The data from the 351 participants were collected using a standard questionnaire that contains 43 variables. A multiple logistic regression model was then used to evaluate the data and to find the best regression model. RESULTS: We classified 80.1% (281/351) of the participants using the regression model. Furthermore, the specificity value of the model was 67% (84/126) of the control group while the sensitivity value was 88% (197/225) of the case group. We found the distribution of residual values standardized for final model to be exponential using the Kolmogorow-Smirnow test (p=0.193). The receiver operating characteristic curve was found successful to predict patients with risk for osteoporosis. This study suggests that low levels of dietary calcium intake, physical activity, education, and longer duration of menopause are independent predictors of the risk of low bone density in our population. CONCLUSION: Adequate dietary calcium intake in combination with maintaining a daily physical activity, increasing educational level, decreasing birth rate, and duration of breast-feeding may contribute to healthy bones and play a role in practical prevention of osteoporosis in Southeast Anatolia. In addition, the findings of the present study indicate that the use of multivariate statistical method as a multiple logistic regression in osteoporosis, which maybe influenced by many variables, is better than univariate statistical evaluation.

Genetic polymorphism of N-acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to investigate whether polymorphism of N-acetyltransferase 2 (NAT2) genotypes are associated with the risk of laryngeal squamous cell carcinoma (SCC). METHODS: The study group consisted of 45 white patients with laryngeal SCC (42 men, with a mean age of 54 years [range, 37-70 years] and three women, with a mean age of 47 years [range, 32-55 years]) and 104 control subjects (68 men and 36 women; mean age, 50 years; range, 28-73 years). All of the patients were primarily treated with surgical intervention. Blood samples (5 mL) were obtained before surgery or from the patients under follow-up to 5 years after surgery (mean follow-up, 27 months; range, 6-48 months). DNA was extracted from the lymphocytes by high pure template preparation kit. NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were detected by use of LightCycler-NAT2 mutation detection kit by real-time polymerase chain reaction with Light Cycler instruments. The association between NAT2 polymorphisms and laryngeal SCC was prospectively modeled through multivariate logistic regression analysis. RESULTS: We found that the risk of laryngeal SCC was 7.3-fold higher in individuals with NAT2*5 mutant allele, 3.8-fold higher in subjects with NAT2*6 heterozygote allele, and 38.3-fold higher in NAT2*6 mutant allele. We also found that individuals with NAT2*7 heterozygote allele had a 0.2-fold less risk for the development of laryngeal SCC (p = .018). CONCLUSION: In this population, patients with NAT2*5 mutant and *6 heterozygous and mutant genotypes had a significantly higher risk for development of laryngeal SCC.

Effects of trapidil after crush injury in peripheral nerve.

In this study, we evaluated the effects of trapidil on crush injury by monitoring nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels and by transmission electron microscopy in the rat sciatic nerve. The sciatic nerve was compressed for 20 sec by using a jewelers forceps. Trapidil treatment groups were administrated a single dose of trapidil (8 mg/kg) intraperitoneally just after the injury. The crush and crush + trapidil treatment groups were evaluated on the 2nd, 7th, 15th, 30th and 45th days of the post-crush period. On the 7th and 15th days, damage in thin and thick myelinated axons, endoneural edema and mitochondrial swelling were less severe in the trapidil group histopathologically. These findings supported the idea that trapidil prevented cell damage and edema at the injury site. Day/group interaction with regard to serum nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels did not show significant changes.

Protective effect of trapidil against oxidative organ damage in burn injury.

Animal models of thermal injury indicate reactive oxygen species and inflammatory cytokines as causative agents in tissue injury on various organs distant from the original wound. Trapidil has various properties, such as inhibition of platelet aggregation and lipid peroxidation as well as reduction of the inflammatory response to injury. This study was designed to determine the possible protective effect of trapidil treatment against oxidative organ damage in lung, intestine and kidney induced by cutaneous thermal injury. Thirty Wistar rats were randomly divided into five groups. Sham group (n=6) was exposed to 21 degrees C water while burn-3 h group (n=6) and burn+trap-3h group (n=6), burn-24 h (n=6) and burn+trap-24 h groups were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In both burn+trap-3 h and burn-trap-24 h group, 8 mg/kg trapidil was given intravenously immediately after thermal injury. Three and 24 h later, tissue samples were taken for biochemical analysis from lung, intestine and kidney and blood samples were obtained to determinate serum TNF-alpha levels. Cutaneous thermal injury caused a significant increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) and 3-nitrotyrozine (3-NT) levels in all tissues and elevated serum TNF-alpha levels at post-burn 3 and 24 h. Trapidil treatment significantly reduced in biochemical parameters, as well as serum TNF-alpha levels. These data suggest that trapidil has a protective effect against oxidative organ damage in burn injury.

Glutathione S-transferase M1, T1, P1 genotypes and risk for development of colorectal cancer.

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06-2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10-2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24-4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15-3.00; OR = 1.70, 95% CI: 1.02-2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02-7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.

Effects of apolipoprotein E genotypes on the development of exfoliation syndrome.

Apolipoprotein E (apo E) is directly involved in the amyloid deposition and fibril formation and is present in many cerebral and systemic amyloidoses immunologically. It is encoded by a polymorphic gene and it has three common alleles-epsilon2, epsilon3, and epsilon4. Exfoliation syndrome (XFS) is characterized by the deposition throughout the body of focal fibrillogranular aggregates in which there have been some reports of amyloid or amyloid-like features. We evaluated the possible association between apo E polymorphism and the occurrence of XFS. Using High Pure PCR Template Preparation Kits, genomic DNAs were extracted from whole blood and apo E polymorphisms were determined by using Lightcycler-Apo E Mutation Detection Kits in 76 patients with XFS and 74 controls. The E2/E2, E2/E3 and E2/E4 genotypes (OR 29.9, 95% CI 3.1-293.7; OR 56.1, 95% CI 12.5-252.7; OR 43.9, 95% CI 7.4-257.6, respectively) and the in2 allele are found to have an increased risk of developing XFS (p=0.0001); whereas the in3 allele was found to be protective (p=0.0001). Apo E polymorphism and the presence of in2 allele are seem to be significantly associated with the development of XFS.