Combined use of melatonin and terazosin restores bladder contractility in rabbits with partial outlet obstruction.

OBJECTIVES: To investigate the effects of terazosin and melatonin on isolated rabbit bladder strips after partial bladder outlet obstruction and determine responses to agonist-induced contractility and changes in oxidant-antioxidant system. METHODS: We created partial bladder outlet obstruction in 5 groups of rabbits, each containing 8. Rabbits with sham operation (group 1) received no drug treatment. Similarly, animals in group 2 underwent partial bladder outlet obstruction and received no drug treatment. Rabbits in groups 3 were administered 5 mg/day oral terazosin, and rabbits in group 4 received 10 mg/kg/day melatonin intraperitoneally. Animals in group 5 received both terazosin and melatonin. We removed their bladders and performed histopathological and biochemical measurements. We assessed tissue malondialdehyde and antioxidant enzyme activity levels and recorded in vitro contractility response to KCl in isolated organ baths. RESULTS: The thickness of muscularis propria was significantly increased in group 2 compared with all other groups. KCl-evoked contractions after partial outlet obstruction were significantly impaired in group 3 and 4 animals receiving terazosin and melatonin, respectively. However, combined use of melatonin and terazosin in group 5 showed contractility responses similar to sham-operated animals (P <0.05). Melatonin administration to groups 4 and 5 showed decreased levels of lipid peroxidation. Similarly, animals receiving melatonin and melatonin plus terazosin showed statistically significant increase in antioxidant enzyme activities. CONCLUSIONS: In the present study, we showed that oxidative stress induced by partial bladder outlet obstruction can be successfully antagonized by the potent antioxidant melatonin, and its combined use with an alpha-antagonist such as terazosin may restore in vitro contractility.

Antioxidant effect of zinc picolinate in patients with chronic obstructive pulmonary disease.

An imbalance between oxidative stress and antioxidant capacity is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, studies in regard to stable COPD patients and effect of zinc supplementation are lacking. We investigated the effects of zinc picolinate supplementation on the oxidant stress, and pulmonary function tests (PFTs) of patients with stable COPD. Thirty patients with COPD, and 15 healthy non-smokers who were matched for age and sex were included in the study. Their baseline spirometry, plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and zinc levels were measured. All parameters were repeated after 8 weeks of supplementation with 22 mg of zinc picolinate daily. The mean MDA levels in the COPD group at baseline were higher than controls (0.51+/-0.15 vs 0.39+/-0.15 nmol/mL, p=0.037), while SOD (0.16+/-0.022 vs 0.20+/-0.04 U/mL, p=0.000), CAT (14.79+/-3.03 vs 17.37+/-2.60k/mL, p=0.008) and zinc levels (77.33+/-4.29 vs 91.45+/-3.95 mg/dL, p=0.000) were lower in the patients compared to controls. Eight weeks of zinc supplementation produced significant increase in mean SOD (p=0.029) and zinc levels (p<0.001). However, no significant change in mean MDA, CAT levels and forced expiratory volume in one second (FEV1) (% predicted), and FEV1/FVC (%) parameters was observed after zinc supplementation. The Pearson's coefficients of correlation between MDA, SOD, CAT, Zn levels and spirometric measurements were not significant on either day 1 nor 8 weeks of zinc supplementation. In conclusion, the results indicate that zinc supplementation may have favorable effects on oxidant-antioxidant balance in patients with COPD. The lack of an effect on PFT may be due to the short duration of the supplementation. Longer duration of zinc supplementation may be necessary to see clinical benefit.

The value of serum tau protein for the diagnosis of intracranial injury in minor head trauma.

OBJECTIVE: Tau protein localizes in the axons of neuron cells, and it is released secondarily from the central nervous system because of hypoxia and trauma. In the present study, it was aimed to investigate the value of serum tau protein levels in diagnosing intracranial pathologies in minor head trauma. METHODS: Patients were categorized into 2 groups: those without intracranial lesions in head CTs (group 1) and those with lesions in head CTs (group 2). Serum tau protein levels were determined. RESULTS: Group 1 (n = 55) median serum tau protein level was 16.29 pg/mL (2.12-215.97 pg/mL) and group 2 (n = 33) median serum tau protein level was 18.39 pg/mL (2.19-714.47 pg/mL). Statistical analysis revealed no significant difference between the 2 groups for tau protein values, sex, age, mechanism of trauma, and Glasgow Coma Scale score. CONCLUSION: It is suggested that serum tau protein has limited value in minor head trauma.

Apo E gene polymorphism on development of diabetic nephropathy.

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.

Abnormal asymmetric dimethylarginine/nitric oxide balance in patients with documented coronary artery disease: relation to renal function and homocysteine.

BACKGROUND: As an endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA) is reported to be associated with coronary artery disease (CAD). METHODS: We measured plasma levels of ADMA, nitrate + nitrite (NOx), total homocysteine (tHCY), and renal function in 106 people with angiographic evidence of coronary artery disease (CAD), including 46 with single vessel disease and 60 with double/triple vessel disease, and in 70 age-matched individuals without any angiography evidence of CAD. Also the levels of these parameters were evaluated according to their history of MI. Plasma tHcy and ADMA were measured by HPLC and the levels of NOx using the Griess reaction. RESULTS: Levels of ADMA, ACE and tHcy levels were significantly higher and NO level was significantly lower in CAD patients compared with controls but there were no significant differences among patients with or without history of MI and between patients with single compared to those with double/triple vessel disease. Additionally a negative correlation was found between ADMA-NOx (r = -0.396, p = 0.001) and between tHcy-NOx (r = -0.262, p = 0.027). In the entire study group, ADMA level was significantly higher in patients with creatinine clearance (CrCl) < 91 mL/min than in patients with CrCl > or = 91 mL/min (0.60 +/- 0.23 micromoles/L versus 0.49 +/- 0.25 micromoles/L, p = 0.05). CONCLUSIONS: We suggest that there is an abnormal plasma ADMA-to-NO balance in patients with documented CAD and that this may be due at least in part to an associated reduction in renal function.

Acute effect of standard heparin versus low molecular weight heparin on oxidative stress and inflammation in hemodialysis patients.

OBJECTIVE: Atherosclerotic cardiovascular diseases caused by traditional and non-traditional risk factors are the most common cause of morbidity and mortality in hemodialysis patients. Recently, much interest has been focused on non-traditional factors, such as oxidative stress, inflammation, and endothelial dysfunction. Hemodialysis patients are not only exposed to oxidative stress but also to inflammation. Although anticoagulants are the most frequently used drugs in hemodialysis patients, their effect upon oxidative stress and inflammation in dialysis patients are still unknown. METHODS: Thirty-three hemodialysis patients were randomized into three groups. Group 1 received standard heparin while group 2 received low molecular weight heparin during the dialysis therapy. Group 3 (control group) did not receive any anticoagulant agent. Investigators were blinded to the therapy. Serum concentrations of oxidative stress and inflammation markers, including C-reactive protein, tumor necrosis factor alpha, superoxide dismutase, and malondialdehyde, were measured before and after dialysis session. RESULTS: The oxidative stress and inflammation markers were significantly increased in groups 1 and 3 (p < 0.05 for each) compared to their baseline values. In contrast, baseline and end-treatment values of the oxidative stress and inflammation markers were comparable in the group 2 (p > 0.05). CONCLUSION: These findings indicate that the type of anticoagulants may take a role in the acute effect of hemodialysis upon oxidative stress and inflammation markers. A comparison of the groups revealed that low molecular weight heparin decreased the oxidative stress and inflammation, whereas standard heparin increased the oxidative stress and inflammation. Low molecular weight heparin appears to have an additive benefit for hemodialysis patients.

Glycaemic control, markers of endothelial cell activation and oxidative stress in children with type 1 diabetes mellitus.

BACKGROUND: The aim of this study was to compare the effect of glycaemic control on oxidative stress and biochemical markers of endothelial activation in type 1 diabetic children. METHODS: Serum total cholesterol, HDL cholesterol, VLDL cholesterol, apolipoprotein A1, apolipoprotein B, HbA(1c), MDA, VEGF, NO, ICAM levels were assessed in 100 children with type 1 DM aged 2-17 years. Study cases were evaluated in three groups in view of their mean HbA(1c) values, as metabolically well-controlled (HbA(1c)< or =8%) and poorly controlled (HbA(1c)>8%) patients with DM and 40 healthy children were included as normal controls. RESULTS: Levels of MDA, NO, VEGF, ICAM, apolipoprotein A1 and apolipoprotein B in metabolically poorly controlled diabetic patients were significantly higher than control group (P<0.05). In correlation analysis of HbA(1c) to VEGF, no significant correlations were detected in metabolically well-controlled DM, but there were significant correlations between HbA(1c) and NO, MDA, ICAM levels. In correlation analysis of HbA(1c) to VEGF, NO, MDA and ICAM levels, significant correlations were detected in poorly controlled diabetics (P<0.05). CONCLUSIONS: In the present study, increased levels of MDA, NO, ICAM-1 and VEGF levels showed that especially metabolically poorly controlled DM children are at high risk of atherosclerosis and vascular complications of DM and that there is a significant relationship between HbA(1c) and oxidative stress. It may be appropriate to evaluate levels of VEGF and sICAM-1 as well as markers of oxidative stress in addition to routine laboratory assessments in evaluation of type 1 DM pediatric patients.

The relationship between ACE insertion/deletion polymorphism and coronary artery disease with or without myocardial infarction.

OBJECTIVES: Presence of the D allele or homozygosity for the deletion (D) allele of the angiotensicen-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The D allele is associated with higher levels of circulating ACE and therefore may predispose one to cardiovascular damage. DESIGN AND METHODS: The study presented here was performed to investigate the association between the ACE genotype and ACE levels. The study group was comprised of 118 angiographically verified CAD patients. 65 patients were MI (+) and 53 patients were MI (-) in this group. A total of 70 healthy individuals were taken as controls. Genomic DNA of 188 subjects was extracted from whole blood. The polymerase chain reaction was used for ACE genotyping, and ACE levels were measured by ELISA. RESULTS: The D allele was found to be significantly more frequent in patients with MI (+) compared with controls (P = 0.024). ACE levels were significantly higher in both MI (-) and MI (+) groups with CAD patients than in controls (P < 0.005). Plasma ACE level was higher in all three groups in the DD genotype compared to II genotype. In groups I and III, this was statistically significant (P < 0.0001, P < 0.01). CONCLUSIONS: It was shown that the I/D polymorphism in the gene for ACE is a genetic risk factor for CAD patients who have a history of MI. ACE insertion/deletion gene polymorphism is also associated with plasma ACE levels in CAD patients with a history of MI.

Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis. The aim of this study is to investigate serum hyaluronic acid (HA), TNF-alpha, IL-8 levels in patients with non-alcoholic steatohepatitis and to assess their potential value as a noninvasive marker for the severity of histopathology. METHODOLOGY: Twenty-eight patients with biopsy-proven NASH, 14 patients with cirrhosis and 15 healthy controls were studied. Histopathological findings were graded and staged. HA, IL-8, TNF-levels were determined using by ELISA test RESULTS: Serum HA levels in patients with NASH were significantly higher than in the healthy control group (P < 0.05). However, the levels in patients with cirrhosis were markedly higher than in patients with NASH and healthy controls (P < 0.001). Serum TNF-alpha levels were significantly higher in patients with NASH and cirrhosis than in healthy controls (P < 0.05). Serum IL-8 levels in patients with NASH (P < 0.001) and cirrhosis (P < 0.05) were significantly higher than in the healthy control group. There was no correlation between serum HA and IL-8, TNF-alpha, ALT and AST levels. Serum HA level in patients with NASH was 187.26 +/- 139.21 and 143.49 +/- 93.14 in stage in stage 2-3 and in stage 0-1, respectively, but the difference was not significant (P > 0.05). CONCLUSIONS: In conclusion, serum HA, IL-8 and TNF-alpha levels increased in patients with NASH. Their relation with the severity of histopathology is not significant. Serum HA levels may be a useful marker to monitor the conversion from fibrosis to cirrhosis. Further studies are needed on this topic.

The effect of an angiotensin converting enzyme inhibitor on intestinal wound healing.

BACKGROUND: Dehiscence of intestinal anastomosis is associated with high mortality and morbidity rates. Angiotensin II is a potent agent in the acceleration of wound repair. Angiotensin converting enzyme (ACE) inhibitors have antifibrogenic effects. AIM: This study was performed to investigate the effect of ACE inhibitors on healing of intestinal anastomosis. MATERIALS AND METHODS: Forty-five male Wistar albino rats were divided into three groups. Ileum was divided above 10 cm from ileocecal valve after laparotomy and a single-layer ileoileal anastomosis was performed. While no treatment was given to rats in group 1, Lisinopril (an ACE inhibitor) was given to rats in group 2 and group 3 for post-operative 7 days in drinking water at 50 and 5 mg/l concentrations, respectively. Estimated amounts of supplied lisinopril were 6.5 and 0.65 mg/kg/day in groups. On post-operative 8th day, relaparotomy was performed and anastomosis-bursting pressures were measured. Then blood and tissue samples were taken for serum transforming growth factor beta-1 and tissue hydroxyproline measurements and histopathological examinations. RESULTS: High dose of lisinopril impaired the all parameters of anastomotic wound healing including bursting pressure, tissue hydoxyproline level, collagen deposition and epithelization (P < 0.001, group 2 versus groups 1 and 3). But low dose of lisinopril had no effect on those parameters (P > 0.05, group 1 versus group 3). CONCLUSION: It was concluded that lisinopril has impaired intestinal wound healing in a dose dependent manner and low doses of lisinopril can be safely used on patients with intestinal anastomosis.

Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats.

In the present study, protective effects of caffeic acid phenethyl ester (CAPE) have been evaluated on carbon tetrachloride (CCl4)-induced hepatotoxicity in rat. Twenty-four male Wistar rats were divided in three groups. Group I was used as control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and CAPE for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and conjugated bilirubin levels and hepatic malondialdehyde (MDA) contents were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All biochemical parameters in serum and the hepatic MDA content were significantly higher in animals treated with CCl4 than in the controls. Rats treated with CCl4 and CAPE showed a significant reduction in biochemical parameters in serum and hepatic MDA content. Livers of rats treated with CCl4 showed classic histology of cirrhosis, whereas the histopathological changes were reduced after administration of CCl4 and CAPE. A normal lobular appearance was observed in livers in this group except for fatty degeneration. The results of our study indicate that CAPE treatment prevents CCl4-induced liver damage in rats.