Association between elevated aminotransferase levels and the metabolic syndrome in Northern Turkey.

INTRODUCTION: Elevated aminotransferase levels(ATLs) are alert the physicians for liver-affecting disease and may reflect liver injury. We aimed to determine the prevalence of elevated ATLs and the association of elevated ATLs with the metabolic syndrome (MetS) in a northern province of Turkey. MATERIALS AND METHODS: Elevated ATLs were evaluated among 1,095 individuals of the Tokat Prevalence Study which have been described in detail elsewhere. 1,095 participants had been selected by a simple random sampling method among 530,000 inhabitants in 70 (12 urban and 58 rural) areas in the province of Tokat which is located in the Black Sea Region of Turkey. RESULTS: The prevalence of elevated serum ALT, AST, and ALT and/or AST were found as 11%, 7.2%, and 13.3%, respectively. Increased BMI, fatty liver, and MetS were higher in our general population with elevated ATLs. After exclusion of individuals with hepatitis B or hepatitis C infection, 132 individuals with elevated ATLs (91 male and 41 female) were evaluated. MetS was found in 59 participants and its prevalence was markedly higher in females with elevated ATLs (p < 0.0001). When the males with elevated ATLs were evaluated, the ALT levels of the persons who have no risk of MetS (p =0.007) and the persons who have one risk of MetS (p = 0.001) were lower than the persons with MetS. CONCLUSIONS: Elevated ATLs are common and it's an important cause is MetS in Northern Turkey.

Comparison of the effects of troxerutin and heparinoid on flap necrosis.

We aimed to assess the effects of local troxerutin and heparinoid (HEP) treatments in a model of flap necrosis. Three groups of Wistar albino rats, each comprising 10 animals were used. A cranially based 6x3-cm full-thickness random-pattern skin flap was raised and sutured to the same area in each model. The control group was treated daily with normal saline, the second with topical HEP and the third with topical troxerutin. The amount of flap necrosis was measured in all groups by the end of the seventh day. Flap tissues were excised for histological analysis and evaluation of the expression of vascular endothelial growth factor (VEGF) levels. Assessment of the blood levels of nitric oxide was also performed in each animal by cardiac puncture. The mean area of flap necrosis was 110.6mm(2) in the control, 39.44 mm(2) in the troxerutin and 47.11 mm(2) in the heparinoid-treated rats. The treatment arms exhibited significant reduction in areas of flap necrosis, compared with the control group (p<0.001), but it was similar among treatment groups (p=0.60). The rates of fibroblast proliferation were decreased in control group as compared to HEP and troxerutin arms (p<0.001). The mean level of collagen density, collagen organisation, granulation tissue and demarcation were similar in all rats. Measurement of VEGF expression did not show any significant difference between the groups (p=0.30). Nitric oxide levels were significantly higher in control rats, as compared to treatment groups (p<0.0001), but were similar in treatment arms (p=0.45). Our results suggest that troxerutin and HEP effectively reduce the flap necrosis and improve flap survival. The observed effects might be due to their anti-oedematogenic, radical-scavenging, antioxidant effects and supportive activities on capillary permeability and transudation.

Serum nitric oxide levels in patients with head and neck squamous cell carcinoma.

OBJECTIVES: We determined serum nitric oxide (NO) levels in patients with head and neck squamous cell carcinoma (SCC) and sought correlations with TNM staging, tumor localization, and tumor grade. PATIENTS AND METHODS: Serum samples were obtained from 36 patients (mean age 63 years; range 37 to 80 years) with head and neck SCC prior to treatment and from 20 healthy individuals (mean age 56 years; range 30 to 72 years) as controls. Tumor staging was based on the criteria of the American Joint Committee of Cancer staging system in 2002. Thirteen patients had stage I-II, and 23 patients had stage III-IV tumors and all had well- or moderately-differentiated SCC (grade 1-2). Serum NO levels were analyzed by a spectrophotometric method based on the determination of total nitrite levels in serum and compared between the patient and control groups. RESULTS: The mean serum NO levels were 20.08+/-1.40 micromol/l and 13.57+/-0.99 micromol/l in cancer patients and controls, respectively (p=0.001). There were no correlations between NO levels and age, sex, tumor stage, localization, and histological grade. CONCLUSION: These data suggest that head and neck SCC is associated with increased serum NO levels, which may play a role in tumor growth.

Iodopovidone pleurodesis does not effect thyroid function in normal adults.

Iodopovidone is an effective, safe, cheap, and easily available agent for pleurodesis. On the other hand, topical applications of iodopovidone may cause thyroid dysfunction. The purpose of this retrospective study was to determine the effects of intrapleural administration of iodopovidone on thyroid function. Twelve patients have undergone iodopovidone pleurodesis so far. A mixture of 20 ml 10% iodopovidone and 80 ml 0.9% saline solution was administered into the pleural cavity through the chest tube. Thyroid hormone (TSH, TT4, TT3, FT4, FT3) levels were routinely measured just before pleurodesis, and at the 24th and 72nd h of pleurodesis. No statistically significant alteration in thyroid function was determined (P>0.05). We did not observe any signs or symptoms of hyper- or hypothyroidism in any patient. Nine patients had a complete response to pleurodesis (75%). One patient who had undergone iodopovidone pleurodesis suffered from a moderate degree of transient chest pain. In conclusion, iodopovidone pleurodesis is safe and does not cause any thyroid dysfunction in normal adults.

The effects of chronic exposure to ethanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney.

The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Rats in E, CS and CS+E groups were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys were removed to determine the activity of xanthine oxidase (XO), myeloperoxidase (MPO) and the levels of nitric oxide (NO). Histopathological and immunohistochemical analysis were performed in kidney tissues. The activity of XO/g protein were 2.8 +/- 0.3, 5.2 +/- 0.3, 3.2 +/- 0.1, and 7.4 +/- 0.7 U for C, E, CS and CS+E groups, respectively. In groups E, and CS+E, the XO values were significantly higher than in group C (P < 0.05). The increase in XO activity of CS was not significantly different from group C (P > 0.05). There was a significant increase in XO activity of group CS+E as compared to CS and E groups (P < 0.05), and also a significant difference in XO activity between E and CS was observed (P < 0.05). The activity of MPO/g protein were 13.5 +/- 0.6, 16.2 +/- 1.1, 14.7 +/- 1.1, 23.8 +/- 0.9 U for C, E, CS, and CS+E groups, respectively. While MPO activity of kidneys from group CS+E were significantly higher as compared to C, CS, and E groups (P < 0.05), there was no significant difference among the groups of C, CS, E (P > 0.05). The levels of NO/g wet tissue were 347.7 +/- 8.5, 261.1 +/- 4.8, 329.8 +/- 5.6, and 254.2 +/- 3.8 nmol for C, E, CS, and CS+E groups, respectively. In groups of E and CS+E, the NO values were significantly lower than that of group C animals (P < 0.05). Although we detected lower NO levels in the E and CS+E groups than in CS group (P < 0.05), a significant difference in NO levels between CS+E and E groups was not observed. In the histopathological analysis of the kidney slices, severe degenerations in kidney tissues of group CS, E, CS+E were observed. Generally, the histological changes in kidney of CS+E and E groups were more severe than those observed in CS alone. While we observed a strong immunoreactivity for anti-nitrotyrosine antibody in kidneys of group CS+E, examination of sections from rat kidneys in group E revealed moderate staining. On the other hand, group CS had very little immunostaining. There was no immunostaining in group C. We concluded that chronic ethanol administration and cigarette smoke exposure may cause oxidative and nitrosative stress which lead to rat kidney damage.

Levels of iron, zinc, and copper in aqueous humor, lens, and serum in nondiabetic and diabetic patients: their relation to cataract.

The purpose of this study was to investigate iron (Fe), zinc (Zn), and copper (Cu) levels of aqueous humor, lens, and serum in nondiabetics and diabetics and to determine the effects of diabetes on Fe, Zn, and Cu contents in the lens. Fe, Zn, and Cu contents of aqueous humor, lens, and serum samples of 19 patients (9 nondiabetic patients with a mean age of 62.3 +/- 5.4 yr, and 10 diabetic patients with a mean age of 59.5 +/- 5.9 yr) were analyzed by atomic absorption spectrometry using a prospective study design. The lens levels of Cu in diabetic patients were significantly higher compared with nondiabetic patients (p = 0.02); however; there was no difference in the other elements (Zn, Fe; p = 0.28, p = 0.74, respectively). The levels of Fe, Zn, and Cu in the aqueous humor and serum of diabetic patients were not found to be statistically significant when compared to nondiabetics (p = 0.46, p = 0.11, p = 0.18, and p = 0.22, p = 0.43, p = 0.72, respectively). These results demonstrate that increased Cu content of the lens presumably has a greater association with the development of lens opacification in diabetics than Zn and Fe content.

The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester.

The aim of this experimental study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on cisplatin-induced hepatotoxicity through adenosine deaminase (AD), xanthine oxidase (XO), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) and nitric oxide (NO) levels in liver tissue of rats. Wistar albino rats were divided into three groups: control group (n = 6), cisplatin group (n = 9) and CAPE + cisplatin group (n = 8). All the chemicals used were applied intraperitoneally. Spectrophotometric methods were used to determine the activities of the above-mentioned enzymes in the liver tissue. NO level and XO activity were found to be increased in the cisplatin group compared to the control group. NO level was found to be decreased in the cisplatin + CAPE group in comparison with the cisplatin group. There was no significant change in the activity of XO between the cisplatin and cisplatin + CAPE groups. The activity of SOD was lower in the cisplatin group than both the control and cisplatin + CAPE groups. There was no significant change in the activity of CAT between the control and cisplatin groups. CAT activity was increased in the cisplatin + CAPE group compared to the cisplatin group. The AD activity and MDA level remained unchanged in all groups. The results obtained suggested that CAPE significantly attenuated the hepatotoxicity as an indirect target of cisplatin in an animal model of cisplatin-induced nephrotoxicity.

Brief communication: omega-3 essential fatty acid supplementation and erythrocyte oxidant/antioxidant status in rats.

Fish oil contains large amounts of essential omega-3 fatty acids, such as eicosapentaenoic and docosahexaneoic acids, which are building structures of cell membranes. The goal of this study was to elucidate the effects of dietary omega-3 fatty acid supplementation on the oxidant/antioxidant status of erythrocytes in rats. The malondialdehyde (MDA) and nitric oxide (NO) levels and the catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) activities were assayed in erythrocytes of male Wistar albino rats after 30 days of dietary supplementation with fish oil (0.4 g/kg/day). Erythrocyte CAT activity in the treated group was increased in comparison with the control group. Erythrocyte MDA and NO levels were lower in the treated group than the controls. Erythrocyte GSH-Px and SOD activities did not differ significantly in the 2 groups. Negative correlations were found between SOD and CAT activities, and between SOD and GSH-Px activities in the treated group. In conclusion, omega-3 fatty acid supplementation helps to prevent lipid peroxidation and to safeguard erythrocytes from oxidative injury. Dietary supplementation with omega-3 fatty acids might possibly protect tissues from oxygen free radical injury in the various diseases in which the oxidant/antioxidant defense mechanisms are disturbed.

The effect of pinealectomy and zinc deficiency on nitric oxide levels in rats with induced Toxoplasma gondii infection.

PRINCIPLES: This study aims at investigating how zinc deficiency and pinealectomy affect nitric oxide levels in rats infected by Toxoplasma gondii. METHODS: The study was conducted on a total of 50 adult, male rats of Spraque-Dawley species. The study groups were as follows: General, intact control group (Group I, n = 10), infected control group (Group II, n = 10), infected and zinc-deficient group (Group III, n = 10), infected and pinealectomized group (Group IV, n = 10), infected, zinc-deficient and pinealectomized group (Group V, n = 10). After the experiment the rats were decapitated and levels of zinc, melatonin and total nitrite were identified in the blood samples collected. RESULTS: The total nitrite levels in groups IV and V were more than those in all other groups (p <0.01). The total nitrite levels in Group II were also higher than those in Groups I and III (p <0.01). Plasma zinc levels in the zinc-deficient group and zinc-deficient and pinealectomized group were lower than those in all other groups, while melatonin levels were lower in infected pinealectomized group (Group IV) and infected, zinc-deficient and pinealectomized group (Group V) than all others (p <0.01). CONCLUSIONS: The present study shows that plasma nitric oxide levels increase during Toxoplasma gondii infection, but this increase becomes more apparent in the presence of melatonin deficiency and is inhibited by zinc deficiency.

Comparison of serum nitric oxide, malondialdehyde levels, and antioxidant enzyme activities in Behçet's disease with and without ocular disease.

OBJECTIVE: The pathogenesis of Behçet's disease (BD) may be related to excessive production of reactive oxygen species, activated neutrophils, and T lymphocytes. The goal of this prospective study was to investigate whether there is any relationship among the oxidant/antioxidant system and nitric oxide (NO) and malondialdehyde (MDA) levels in patients with BD and its subtypes: complete Behçet's disease (CBD) and incomplete Behçet's disease (ICBD), with or without ocular disease. METHODS: Thirty-two patients and 26 age- and sex-matched healthy control subjects were evaluated for NO and MDA levels and antioxidant enzyme activities. The patients with BD were divided into two subgroups: those with and without ocular disease. Twelve patients with CBD and 4 patients with ICBD had ocular disease. The serum NO level was determined by Griess reaction. The MDA level was detected by thiobarbituric acid reaction. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum were analyzed with spectrophotometric methods. RESULTS: Increased MDA levels but decreased GSH-Px activities in plasma were observed in BD patients with all subtypes, as compared with controls. Concerning the presence of ocular disease and the subtype (CBD or ICBD) compared with each other, there were no significant differences in MDA or NO serum levels and SOD or GSH-Px enzyme activities. CONCLUSIONS: Serum NO levels and SOD enzyme activities were not significantly changed in patients with BD and its subtypes; however, a remarkable decrease of GSH-Px enzyme activity and increase of MDA levels were found.

Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats.

We have investigated the effect of caffeic acid phenethyl ester (CAPE) on cisplatin-induced nephrotoxicity in rats. Administration of a single dose of cisplatin resulted in the elevation of blood urea nitrogen and creatinine in serum, as well as nitric oxide in kidney tissue of rats. Cisplatin also caused reduction of catalase (P < 0.0001), superoxide dismutase (P = 0.149) and glutathrone peroxidase (P < 0.0001) activities in kidney tissue. Although cisplatin caused elevation in malondialdehyde levels and myeloperoxidase activities in kidney tissue, they were not statistically significant. Caffeic acid phenethyl ester was found to be protective against cisplatin-induced antioxidant enzyme reductions. Treatment with free-radical scavenger CAPE attenuated the increase in plasma blood urea nitrogen and kidney nitric oxide levels, and showed histopathological protection against cisplatin-induced acute renal failure. Extensive epithelial cell vacuolization, swelling, desquamation and necrosis were observed in the kidney of the cisplatin-treated rat. There were also larger tubular lumens in cisplatin-treated rats than those of the control and the CAPE groups. Caffeic acid phenethyl ester caused a marked reduction in the extent of tubular damage. It is concluded that administration of cisplatin imposes an oxidative stress to renal tissue and CAPE confers protection against the oxidative damage associated with cisplatin. This mechanism may be attributed to its free-oxygen-radical scavenging activity.

Melatonin protects against myocardial doxorubicin toxicity in rats: role of physiological concentrations.

Doxorubicin (Dox) is a widely used antineoplastic drug. Oxygen radical-induced injury of membrane lipids is considered to be the most important factor responsible for the development of Dox-induced cardiotoxicity. The pineal secretory product, melatonin, is known to be a potent free radical scavenger and its pharmacological concentrations have been shown to reduce Dox-induced cardiac damage. However, the physiological role of melatonin in the prevention of this damage is unknown. We investigated physiological and pharmacological effects of melatonin on Dox-induced changes in the levels of malondialdehyde (MDA), a lipid peroxidation product, and morphological changes in heart. Rats were pinealectomized (Px) or sham-operated (control) 2 months before the studies. Melatonin was administered [4 mg/kg, intraperitoneally (i.p.)] 1 hr before or 24 hr after the administration of a single dose of Dox (20 mg/kg, i.p.) and continued for 2 days. The levels of MDA Dox was found to be significantly higher in the Px rats (55.9 +/- 0.6 nmol/g tissue) than intact control animals (42.6 +/- 0.4). Dox administration to Px and non-Px rats significantly increased the MDA levels. Pre- and post-treatment with melatonin in both Px and intact rats significantly reduced MDA levels. Morphological changes parallelled the MDA alterations. These findings strongly suggest that both physiological and pharmacological concentrations of melatonin are important in protecting the heart from Dox-induced damage in rats. It would seem valuable to test melatonin in clinical trials for prevention of possible heart damage associated with Dox.

Degradation of vincristine by myeloperoxidase and hypochlorous acid in children with acute lymphoblastic leukemia.

Vincristine (VCR) is an effective drug against acute lymphoblastic leukemia (ALL), many solid tumors, but not acute myeloid leukemia. It has been hypothesized that resistance of myeloblasts to VCR is related to myeloperoxidase (MPO) and production of hypochlorous acid (HOCl). We investigated the relationship between VCR degradation and MPO expression and serum HOCl concentrations in pediatric patients with ALL, lymphoma and solid tumors. We studied the sera from 43 children, of which 23 were newly diagnosed and as yet untreated cancer patients, 10 on chemotherapy and 10 healthy control subjects. Patients' sera were incubated with VCR alone or in the presence of taurine (T) or acetaminophen (APAP) and post-incubation VCR and HOCL concentrations were measured. Significant correlations between serum MPO expression, HOCl concentrations and VCR degradation were seen. In the chemotherapy group, MPO-positive patients produced high levels of HOCl and reciprocally low post-incubation VCR levels. HOCl and VCR concentrations in this group were significantly different than other groups studied. Both APAP and T inhibited VCR degradation in the sera of the chemotherapy group but not to the same degree. The effects seen here were consistent for both ALL and the lymphoma/solid tumor cases. Our results indicate that HOCl can increase VCR degradation in vitro in the serum and this effect is significantly more pronounced in pediatric patients undergoing chemotherapy.

Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism.

BACKGROUND: There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. METHODS: We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n=27) compared to age- and sex-matched normal controls (n=30). RESULTS: In the autistic group, increased RBC NO levels (p<0.0001) and plasma GSH-Px activity (p<0.0001) and unchanged plasma TBARS levels and SOD activity were detected. CONCLUSIONS: These findings indicate a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.

Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury.

Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side-effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham-operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP-induced renal injury.