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PURPOSE: Nitrite is a stable end-product of nitric oxide oxidation. The aim of the present study was to quantitatively analyze peri-implant sulcular fluid (PISF) nitrite levels in a longitudinal study design to evaluate the potential changes in nitric oxide metabolism in relation to the clinical status of the peri-implant site and the loading style of the dental implants. MATERIALS AND METHODS: A total of 34 implants, either early loaded (EL) or delayed loaded (DL), in 17 patients were followed up for a period of 18 months. Clinical parameters were recorded, PISF samples were obtained, and PISF nitrite levels were spectrophotometrically determined. Clinical measurements and nitrite analysis were repeated at 1, 3, 6, 9, 12, and 18 months. RESULTS: Despite the gradual decrease in clinical parameters, fluctuations in PISF total nitrite levels were observed during follow-up. The pattern of nitric oxide metabolism, as reflected by PISF nitrite levels, also demonstrated differences between EL and DL implants that diminished toward the end of the experimental period. DISCUSSION: Although the presence of clinical and subclinical gingival inflammation contributes to the PISF total nitrite levels, nitric oxide metabolism is also associated with healing and bone remodeling, and the pattern of loading seemed to have an impact on nitric oxide production at dental implant sites. CONCLUSION: Nitric oxide production at dental implant sites seems to be tightly regulated to enable the maintenance of peri-implant bone. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although it is well-described that proteoglycans (PGs) are among the major non-collagenous components of the matrix which are degraded during periodontal diseases, the relationship between PG metabolism and seventy of periodontal breakdown, the extent of degradation of PGs together with the resulting end-products, and the elimination pathways of these catabolic end-products is likely to need further clarification. OBJECTIVE: The main aim of the present study was to analyze the possible impact of severity of periodontal destruction on PG metabolism of gingiva and gingival crevicular fluid (GCF). MATERIAL AND METHODS: For this purpose, gingiva and GCF samples obtained from patients (n = 45) exhibiting sites (n = 57) with moderate periodontal breakdown (MP) or severe periodontal breakdown (SP) were analyzed for PG metabolism via spectrophotometric determination of uronic acid levels. Gingiva and GCF samples were obtained from the same sites in every patient to analyze the possible relationship between uronic acid content of gingival tissue and GCF. RESULTS: No significant differences were found in uronic acid levels between sites with MP and SP (p > 0.05). The uronic acid content of GCF and gingiva showed significant overlaps between MP and SP sites and uronic acid levels did not present any constant correlation with the clinical parameters (p > 0.05). In a similar manner, uronic acid content of GCF and gingival tissue was not correlated (p > 0.05). CONCLUSION: The lack of a significant correlation between the uronic acid content of gingival tissue and GCF may suggest that the passage of PG metabolites from gingiva to GCF is likely to be under the influence of multifactorial interactions rather than being linear. As a general measure of PG metabolism, uronic acid levels do not seem to be related with the severity of periodontal destruction and tend to act as different measures when compared to traditional clinical parameters. [ABSTRACT FROM AUTHOR]

Background Adrenaline tolerance improves survival in animal models of shock. The purpose of this study was to determine the effects of adrenaline tolerance on intestinal ischaemia–reperfusion in a mouse model. Methods Adrenaline tolerance was developed by injecting intravenous adrenaline, gradually increasing the dose to 2 mg/kg over 5 days. In experimental animals the superior mesenteric artery was clamped for 120 min and then released. Evans blue dye was given intravenously to all animals to quantify pulmonary microvascular injury. Some 60 min after clamp release, the animals were killed and the effects of reperfusion assessed on tissue samples. Results Evans blue dye concentrations were significantly higher in animals with intestinal ischaemia–reperfusion than in those having sham intestinal ischaemia–reperfusion or in adrenaline-tolerant mice having intestinal ischaemia–reperfusion or sham ischaemia–reperfusion (P<0·01). Malonyldialdehyde levels increased significantly in the lung in the intestinal ischaemia–reperfusion group compared with those in the sham ischaemia–reperfusion group (P<0·001 for liver, lung and small intestine), whereas there was no difference in adrenaline-tolerant animals. There was no significant change induced by adrenaline tolerance in myeloperoxidase levels in any organ. Conclusion Adrenaline tolerance reduced the lung permeability caused by intestinal ischaemia–reperfusion. Catecholamines may play a role in free radical generation induced by ischaemia–reperfusion. [ABSTRACT FROM AUTHOR]

Background/aim: Propolis is a bee product with antioxidative, antimutagenic, and other beneficial properties, and it is used as a natural drug. It is rich in polyphenolic compounds. Its composition varies depending on the particular geographical region. Oxidative stress is caused by an imbalanced free radical production and antioxidant system. The effects of flavonoids on the expression of DNA repair enzymes have been examined previously; however, no study has investigated the effects of propolis. This study investigated the effects of ethanolic extracts of Turkish propolis (EEP) on the expression of DNA repair enzymes., Materials and Methods: The effects of EEP and tertiary-butyl-hydroperoxide (t-BHP) on cell viability were determined using MTT DNA damage was determined using comet assay. mRNA expression of target enzymes was detected using RT-PCR., Results: According to the cytotoxicity analysis, after a recovery time of 4 h, appropriate damage agent t-BHP and optimum EEP concentrations were 300 µM and 200 µg/mL, respectively. 8-Oxoguanine-glycosylase (hOGG-1) and endonuclease-VIII-like-1 (NEIL-1) expressions increased in the positive control group (t-BHP alone) and the study group (t-BHP+EEP). Maximum increase in NEIL-I expression was at hour 12 in the positive control group and at hour 8 in the study group., Conclusion: EEP can be considered as a potential source of functional food and pharmaceutical agents.

Aim: The use of endosseous dental implants (DI) has become a successful treatment alternative. However, providing periimplant tissue health and achieving a natural esthetic look are important topics in this treatment. The aim of the present study was to evaluate periodontal and esthetic parameters around DI and natural teeth (NT) and also to analyze myeloperoxidase (MPO) levels in gingival crevicular fluid (GCF) and peri-implant sulcus fluid (PISF)., Materials and Methods: Twenty DI supported fixed prosthesis and contralateral 20 NT were enrolled to the present study. Clinical periodontal parameters (probing depth, clinical attachment level, gingival bleeding time index and gingival index) were recorded and GCF/PISF samples were obtained from mesial (mesiobuccal and mesiolingual) and distal (distobuccal and distolingual) sites of DI and NT. MPO levels were spectrophotometrically determined. Additionally clinical photographs were obtained and esthetical evaluations were performed by using Jemt papilla index. The parameters belong to DI and NT were compared and correlations were evaluated using statistical analysis., Results: A total of 40 samples were evaluated. No statistically significant differences were detected between groups in all periodontal parameters and MPO levels from mesial and distal sites. Jemt papilla index scores were slightly higher in NT however, this difference was not statistically significant (p > 0.05). Total PES score were similiar in DI and NT groups. Significant correlations were detected between MPO and gingival index values as expected., Conclusion: These results suggest that DI and NT have similar inflammatory conditions and esthetics, representing DI as a predictable treatment option., Clinical Significance: Dental implants are satisfactory treatments, they provide patient esthetic natural looking, phonetic and masticatory functions.

Background: The goal of most acute therapies for spinal cord injury (SCI) in humans include attenuation of the early inflammatory response and may limit the extent of tissue injury and the consequent disability., Objective: The purpose of this study was to investigate the early effects of methothrexate (MTX) treatment on myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also compared with methylprednisolone sodium succinate (MPSS) treatment., Methods: Wistar rats were divided into seven groups: control; trauma alone (50 g/cm weight drop trauma); SCI + MPSS (30 mg/kg); SCI + low-dose (0.5 mg/kg) MTX (LDMTX); SCI + higher-dose (1 mg/kg) MTX (HDMTX); non-trauma + LDMTX; non-trauma + HDMTX., Results: Administration of MTX and MPSS treatments significantly decreased MPO activity (p < 0.05) and MDA level (p < 0.05) in the first 24 h. The MTX treatments, particularly HDMTX, were more effective than MPSS in reducing MPO activity, and MTX treatments were also more effective than MPSS in reducing MDA level (p < 0.05). The MTX treatment was more protective on large- and medium-diameter myelinated axons in minimizing ultrastructural changes in the spinal-cord-injured rats, but did not induce neurotoxicity in normal spinal cord., Conclusion: The results of this study indicate that MTX treatment has a beneficial effect by reducing early neutrophil infiltration and the associated lipid peroxidation, and has significantly protective effects on the injured spinal cord tissue in the first 24 h after SCI. Given the anti-inflammatory properties of MTX, a single dose of MTX a week is used for non-neoplastic disease in humans, and MTX may have a beneficial role in the immediate management of acute SCI.

Background: Cathepsin-K is an enzyme involved in bone metabolism which may make this feature important for both natural teeth and dental implants. The aims of the present study are to comparatively analyze the gingival crevicular fluid (GCF)/peri-implant sulcus fluid (PISF) cathepsin-K levels of natural teeth and dental implants, and to assess the potential relationship between this biochemical parameter and alveolar bone loss around natural teeth and dental implants., Methods: Probing depth, bleeding on probing, gingival index, and plaque index clinical parameters were assessed, and GCF/PISF samples were obtained from natural teeth/dental implants presenting with either clinical health, gingivitis/peri-implant mucositis, or chronic periodontitis/peri-implantitis. Cathepsin-K activity levels of 42 GCF samples and 54 PISF samples were determined, and marginal bone loss (MBL) measures were calculated from digitalized standardized intraoral periapical radiographs obtained from natural teeth and dental implants by using cemento-enamel junction and the actual distance between two consecutive threads of the dental implant as reference points for natural teeth and dental implants, respectively., Results: Comparing the natural teeth group with dental implant group with regard to MBL measure, cathepsin-K activity, and GCF/PISF volume revealed no significant differences. In both natural teeth and dental implant groups, despite higher MBL measures, cathepsin-K activity, and GCF/PISF volumes with the presence of inflammation, it was the presence of alveolar bone loss that lead to significantly higher values for these parameters., Conclusion: We suggest cathepsin-K as a biochemical parameter for monitoring periodontal/peri-implant alveolar bone loss.

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 μg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Paraoxonase 1 (PON1) is synthesized in the liver and secreted into the blood, where it is associated exclusively with HDL. In this study, rabbit liver PON1 enzyme was purified to homogeneity using a new purification approach, and the kinetic properties of the enzyme were investigated using phenyl acetate and homocysteine thiolactone as substrates. Rabbit liver PON1 was purified through the preparation of liver microsomal fraction, Sephacryl S300 HR gel filtration chromatography, DEAE Trisacryl M ion-exchange chromatography and hydroxyapatite chromatography steps. Using this method, rabbit liver PON1 was purified 576 times with a specific activity of 2726 U/mg protein. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed the obtained enzyme as a single protein band close to 40 kDa. The Km of the this enzyme was found as 0.55+/-0.024 mM for phenyl acetate and 17.31+/-1.2 mM for homocysteine thiolactone. In this study, a new approach was used to purify PON1 enzyme from rabbit liver and for the first time in the literature, its kinetics was studied with homocysteine thiolactone as substrate.

Oxidative damage plays a role in neurodegenerative diseases. Levels of cerebrospinal fluid nitrite and nitrate levels (oxidation products that provide an indirect estimation of nitric oxide) were investigated in relation to clinical and laboratory features in subacute sclerosing panencephalitis (n = 47) and age-matched control (n = 43) groups. Significantly decreased levels of nitrite (median, 4.91 micromol/L) and nitrate (median, 6.14 micromol/L) were found in the patients. Nitrite and nitrate levels did not correlate with clinical or laboratory findings, except for presence of myoclonus. Cerebrospinal fluid nitrite levels of subacute sclerosing panencephalitis patients without myoclonic jerks were significantly higher than in those with myoclonus (median, 15.63 vs 4.34 micromol/L, respectively). The higher levels of nitrite in these patients can be explained by short disease duration and early stages of disease. Nitrate levels in subacute sclerosing panencephalitis patients with myoclonus (median, 9.26 micromol/L) were higher than in those without myoclonus (median, 4.25 micromol/L). Microbleeding resulting in conversion of nitrite to nitrate and increased production of superoxide can be suggested as possible mechanisms underlying these findings.

There is evidence demonstrating the protective effect of cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors against ischemic injury in certain tissues. In this study, sildenafil, a potent inhibitor of PDE5, was tested for its beneficial effects in the prevention of disrupted ileal contractility and damage to tissue caused by intestinal ischemia-reperfusion in rats. Male Sprague-Dawley rats were divided into four groups: sham-operated; sham-operated with sildenafil pretreatment; ischemia-reperfusion with vehicle pretreatment; and ischemia-reperfusion with sildenafil pretreatment. The superior mesenteric artery was occluded for 45 min to induce ischemia. The clamp was then removed for a 60 min period of reperfusion. Sildenafil (1 mg/kg, i.v.) or saline was administered prior to the surgical procedure in the ischemia-reperfusion and sham-operated groups. Isometric contractions of the ileal segments in response to acetylcholine or electrical field stimulation (120 V, 2 ms pulse for 5 s, 1-20 Hz) were recorded. Additionally, levels of thiobarbituric acid reactive substances and myeloperoxidase activity were measured in addition to a histopathological examination of the ileal tissue. The contractions induced by both acetylcholine and electrical field stimulations were markedly inhibited after ischemia-reperfusion. Sildenafil pretreatment (1 mg/kg, i.v.) abolished the inhibition of responses to acetylcholine. The increased levels of thiobarbituric acid reactive substances and myeloperoxidase activity caused by ischemia-reperfusion were reversed to control levels with sildenafil pretreatment. Intestinal ischemia-reperfusion caused severe ischemic injury in rat ileum, which was prevented by sildenafil. These results suggest that sildenafil pretreatment has a protective effect against ileal dysfunction and damage induced by intestinal ischemia-reperfusion in the rat.

Background: As well as gingival crevicular fluid (GCF), peri-implant sulcus fluid (PISF) may have a potential diagnostic value for the early identification of metabolic and destructive processes., Purpose: The aim of this study was to analyze the potential impact of inflammation and loading on PISF myeloperoxidase (MPO) levels, in comparison with GCF., Materials and Methods: A total of 220 sites, dental implant (immediately [IL] or delayed loaded [DL]), and natural tooth, either healthy/noninflamed or gingivitis/inflamed, were classified. Clinical parameters were recorded, and GCF/PISF samples were obtained. GCF/PISF MPO levels were spectrophotometrically determined., Results: Clinical parameters demonstrated increases with the presence of gingival/peri-implant inflammation. Total MPO levels were higher at inflamed tooth and implant sites compared to noninflamed/healthy sites (p < .05). Although they did not reach a significance level, inflamed IL sites had higher total MPO levels than inflamed DL sites (p = .401). Gingival index and total MPO levels exhibited significant correlations (p < .05)., Conclusion: Using implants and natural teeth in the same study design, the findings of the present study support the close relationship between MPO production and inflammation, and may speculate a potential for loading of dental implants, contributing to the MPO content of PISF.

Background: The present study was conducted to determine the possible effect of naproxen sodium on clinical status and the enzymatic profile of gingival crevicular fluid (GCF) when given as adjunct to periodontal treatment., Methods: A total of 34 subjects with chronic periodontitis were selected and divided into two groups to receive either naproxen sodium or placebo. At baseline, GCF samples were obtained and probing depths (PD), gingival index (GI), plaque index (PI), and gingival bleeding index (GBI) scores were recorded. In the non-steroidal anti-inflammatory drug (NSAID) group, patients were treated with a protocol consisting of baseline periodontal treatment (scaling, root planing) and naproxen sodium (275 mg) administration daily for 6 weeks. In the placebo group, patients received the same treatment except placebo was given instead of naproxen sodium. At the end of the experimental period, clinical recordings and GCF sampling were repeated. Myeloperoxidase (MPO) and elastase-like enzyme activity (ELA) levels were determined in GCF samples by a spectrophotometric method. GCF enzymatic content was calculated both as total enzyme activity and enzyme concentration., Results: All of the clinical parameters, except mean GBI, were significantly lower in the experimental group (P <0.05). At baseline and at the end of the experimental period, there were no significant differences between the NSAID and placebo groups regarding GCF MPO and ELA levels in either mode of data presentation (P <0.05). However, in the NSAID group, mean ELA concentration (P = 0.002) and mean total ELA (P = 0.003) presented significant decreases with treatment. Also, with treatment, a general reduction in MPO levels was seen; however, this difference was not significant. Although constant and stable correlations between GCF enzyme levels and clinical parameters could not be found, positive and strong correlations were observed between total enzyme activity and enzyme concentrations., Conclusion: Based on the positive clinical effect and the ELA profile of GCF, it can be suggested that NSAIDs given as an adjunct to baseline periodontal treatment could be beneficial in the outcome of treatment.

Objective: Cyclosporine A (CsA) with its immunosuppressive actions and methylprednisolone (MP) as a free radical scavenger were suggested together to alleviate neural tissue damage after an ischemic insult. The aim of this study was to investigate neuroprotective properties of CsA and MP in a global cerebral ischemia model., Methods: Twenty-eight male Sprague-Dawley rats were divided randomly into four separate groups: CsA, MP, sham and control. Global cerebral ischemia was performed with the four-vessel occlusion model. After 30 minutes of ischemia, reperfusion was started with concomitant intraventricular administration of saline, MP (20 mg/kg) and CsA (10 mg/kg) into the lateral ventricle. Lipid peroxidation levels were measured from all experimental groups. Rats subjected to global cerebral ischemia exhibited a significant increase in cerebral lipid peroxide levels 6 hours after the onset of reperfusion. Both CsA and MP treatment significantly attenuated the degree of lipid peroxidation in cerebral tissues (p<0.05). Histopathological examinations of the CA1 sector of the hippocampus verified the neuroprotective properties of MP and CsA., Conclusions: The results suggested the neuroprotective properties of both agents, emphasizing more potent protection against ischemia by CsA. It was proposed that CsA could have exerted this effect with the blockage of mitochondrial permeability transition (MPT) pores, which are also critical if the necrotic and apoptotic cascades of the cell are considered. MP is judged to be neuroprotective, particularly in terms of its effects on lipid peroxidation. In conclusion, CsA and MP are ascertained to be neuroprotective agents as long as they cross the blood-brain barrier.

Purpose: The aim of the present study was to analyze the possible impact of clinical status, presence and severity of inflammation, and loading on nitric oxide (NO) metabolism around mandibular dental implants., Materials and Methods: A total of 34 implants in 17 patients, loaded either early (EL) or after a delay (DL), were classified according to the presence and severity of clinical inflammation in the peri-implant sites. Clinical parameters were recorded, peri-implant sulcular fluid (PISF) samples were obtained, and PISF nitrite levels were spectrophotometrically determined. Clinical measurements and nitrite analysis were repeated at 1, 3, 6, and 9 months postloading at available sites., Results: Compared to noninflamed sites, inflamed sites demonstrated higher mean total nitrite levels (P = .032) that tended to increase with the severity of inflammation at both EL and DL implants. At noninflamed sites, EL implants provided significantly higher PISF volume than DL implants (P = .001). At noninflamed sites, EL implants revealed higher total nitrite levels; on the contrary, at inflamed sites, DL implants revealed higher total nitrite levels. In general, nitrite levels demonstrated a pattern of decrease followed by an increase during follow-up., Discussion: Increased NO production with the presence and the severity of inflammation supports the contribution of NO in the peri-implant inflammatory process. Loading is also likely to have an impact on NO metabolism, which suggests a role for NO in remodeling and adaptation of bone around dental implants., Conclusion: Besides the presence of inflammation, the severity of inflammation and loading also seem to have an impact on NO metabolism around dental implants.

We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 micromol/kg/d, intra peritoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.

Pertussis toxin (PT) and filamentous hemagglutinin (FHA) were purified from culture supernatant of Bordetella pertussis Saadet and Tohama strains, using CM-Sepharose CL-6B cation-exchange chromatography. By the rapid purification method described here, both proteins were separately eluted from the same column in pure forms. The PT and FHA in the extract of culture supernatant were bounded to CM-Sepharose CL-6B cation-exchange column in 50 mM phosphate buffer containing 2 M urea (Buffer A), pH 6.0. Then the PT was eluted from the column with Buffer A (pH 7.4) and after elution of the PT, the FHA was eluted with 0.5 M NaCl in 50 mM phosphate buffer. Pertussis toxin and filamentous haemagglutinin purified by this procedure were electrophoretically and immunologically identical to the reference preparations.

Background: Nitric oxide (NO) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in the last trimester of pregnancy caused intrauterine growth retardation and hind-limb disruptions in rats. In the present study, the effect of maternal NO inhibition with NG-nitro-l-arginine (l-NNA) on hypoxic newborn rats was investigated., Methods: Timed-pregnant rats were obtained on gestational day 17. Four groups of rats were used: control, hypoxic, l-NNA and l-NNA + hypoxic groups. In the last two groups, l-NNA (2 mg/kg bolus, i.p.) was administered to the mothers of pups antenatally on 3 consecutive days. Hypoxia was induced in newborn rats by breathing of a mixture of 8% oxygen and 92% nitrogen for 3 h. Pups were then allowed to inhale normal atmospheric air for 30 min. All newborn rats were decapitated on the first day of life after hypoxia and reoxygenation. Brain, heart, lung, liver, kidney and intestinal tissues were studied biochemically. Hypoxia-induced biochemical changes were determined by measuring lipid peroxidation. Histopathologic examination of lung tissue was performed., Results: Nitric oxide synthase inhibition in pregnancy did not cause fetal growth retardation. Hypoxia increased lipid peroxidation in all tissues except the heart; this increase was decreased by maternal l-NNA administration in brain, lung, liver and kidney tissues. However, lipid peroxidation was increased by NO synthase inhibition in the intestines. In the lungs, pulmonary hemorrhage was observed in the hypoxic group. Minimal pulmonary hemorrhage was detected in the l-NNA and l-NNA + hypoxic groups., Conclusions: These data suggest that antenatal administration of an NO synthase inhibitor acts as both a destructive and protective agent in hypoxic newborn rats.

Background/aims: The aim was to measure the deposition of collagens and proteoglycans and the underlying mechanism leading to lipid peroxidation due to oxidative stress in partially hepatectomized normal and cirrhotic rats., Methodology: Four groups of adult Wistar rats were used comprising normal livers, regenerated normal livers, cirrhotic livers, and regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Hydroxyproline, as a constituent of collagens, uronic acid, as a constituent of proteoglycans, and malondealdehyde, an end-product of lipid peroxides, were measured in normal and cirrhotic rats, and following partial hepatectomy., Results: Hydroxyproline, uronic acid and malondealdehyde levels were 234.2 +/- 41.2, 11.82 +/- 1.92, 46.3 +/- 5.8 and 211.8 +/- 43.6, 9.16 +/- 1.41, 48.5 +/- 7.5 for normal and regenerated normal livers respectively. The values after partial hepatectomy in cirrhotic and regenerated cirrhotic livers were 396.9 +/- 48.5, 17.96 +/- 1.62, 144.5 +/- 25.1 and 309.6 +/- 43.2, 13.35 +/- 1.72, 229.9 +/- 24.4, respectively. When the cirrhotic liver group was compared with the normal liver group, the levels of hydroxyproline, uronic acid and malondealdehyde were significantly higher (p < 0.001). Uronic acid levels of regenerated normal and regenerated cirrhotic livers and hydroxyproline level of regenerated cirrhotic liver were significantly less than those of their non-regenerated states (p < 0.01). Although the malondealdehyde levels of normal and regenerated normal livers did not differ significantly (p > 0.05), the malondealdehyde levels of regenerated cirrhotic liver was significantly higher than cirrhotic liver (p < 0.01). The histopathological examination with light microscopy did not reveal any obvious difference between the groups other than between normal and cirrhotic., Conclusions: Cirrhotic livers revealed a significantly higher amount of extracellular matrix constituents and lipid peroxidation than normal livers. Although partial hepatectomy in cirrhotic livers caused decreases in the tissue levels of collagens and proteoglycans, it did not actually lower the ongoing oxidative stress, known as physiological lipid peroxidation, in normal and cirrhotic livers following partial hepatectomy.

Aim: To determine the ultrastructural effects of sildenafil on the female genital organs., Methods: Twenty female cycling Wistar albino rats weighing 250+/-20 g were randomly divided into two groups of 10 each. Rats of one group were gavaged with 0.5 mg.kg(-1).d(-1) of sildenafil 3 days in a week for 4 weeks and the other served as the controls. After cessation of treatment animals were sacrificed by cervical dislocation under methoxyflurane anaesthesia. The clitoris, vagina, uterus and bartholin glands were taken at the estrous and were fixed with 10% formalin solution for light microscopy and 2.5% glutaraldehyde and osmic acid for electron microscopy., Results: Under the light microscope, the fibrocollageous tissue was found increased, the capillaries enlarged and the connecting tissue elements increased in the corpus cavernosum in the treated group. On electron microscopy, increased connective tissue, fibroblasts with notched nucleus, shorten immature collagen fibers without striation were seen. Abundant foldings and penetration with collagen bundles were observed in the basal membrane. Large connection complexes, especially gap junctions among the wide capillary endothelial cells were observed., Conclusion: There are evident histological changes due to sildenafil citrate in female rat corpus cavernosum. The clitoris and bartholin glands were the most effected organs. While the histopathological changes of clitoral tissue could be expected, an increase in the mass of bartholin gland was surprising.

Background/aims: We have previously shown that in the canine small bowel autotransplantation model, adding alpha - tocopherol to Euro Collins solution for perfusion enhanced the integrity of the small bowel mucosa for up to 12 hours in the posttransplantation period. The purpose of this study was to investigate the effects of verapamil and a tocopherol on reperfusion injury in the canine small bowel autotransplantation model., Methods: The study consisted of four groups of six animals each. In Group 1 (control group) grafts were perfused with Euro Collins solution while those of Group 2 were perfused with Euro Collins and alpha- tocopherol. Group 3 grafts were perfused with Euro Collins + verapamil and Group 4 with Euro Collins, alpha- tocopherol and verapamil. Autotransplantation model was used to avoid immunological injury. Graft function and mucosal integrity were assessed by the analysis of enzymatic activities (mucosal glutaminase, maltase and lactase) and histopathological examination. Malonyldialdehyde (per gram tissue) was used as an indicator of lipid peroxidation., Results: Glutaminase activity of Group 4 was found to be higher than that of the other groups at all time points (p<0.05). In the verapamil group (Group 3), the amount of lipid peroxidation showed the greatest decrease in comparison to other groups at the 12 hour time point (p<0.05). Maltase activity in Group 3 was significantly different at all time points (p<0.05). Lactase activity showed no significant difference between groups at each time point. The microscopic appearance of tissue injury shown by histopathological examination of tissue samples obtained at different time points was related to decrease in mucosal enzymatic activities., Conclusions: alpha- tocopherol is a promising agent for the prevention of tissue injury caused by free oxygen radicals during organ transplantation. Verapamil, as an antioxidant, also has preventive effects in organ preservation. Using verapamil together with alpha- tocopherol in the same preservation solution did not increase the preventive effect of alpha- tocopherol.

Background/aims: To date direct toxic effects of free oxygen radicals in vivo on pancreatic parenchyma have not been studied thoroughly. We aimed to study: 1) the detailed histopathological changes induced by free oxygen radicals in pancreas; and 2) the preventive effect of intraductal catalase in H2O2-induced acute pancreatitis., Methodology: Wistar Albine rats were randomized into six groups. 1) First experiment: Bile-pancreatic duct was cannulated close to the liver and perfused through the duodenum with (i) normal saline solution, (ii) iron sulfate (FeSO4), (iii) hydrogen peroxide (H2O2), (iv) hydrogen peroxide and iron sulfate simultaneously. 2) Second experiment: Bile pancreatic duct was perfused either with H2O2 or H2O2 + catalase. Serum amylase and pancreas malondialdehyde levels were measured in both experiments after 3 hours of perfusion period. Tissue samples were obtained for histopathological examinations., Results: 1) First experiment: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4 induced acute edematous pancreatitis with focal parenchymal necrosis. At the ultrastructural level, intracytoplasmic formation of vacuoles. fusion of the vacuoles and zymogen granules, and autophagosomes containing cellular organelles were found. Serum amylase and pancreas malondialdehyde levels, and morphological score were significantly higher in these groups than control group (p < 0.001). 2) Second experiment: Catalase perfusion simultaneously with H2O2 decreased the serum amylase and pancreas malondialdehyde levels, and morphological score significantly (p < 0.001) and prevented the desquamation of the columnar epithelium and development of gross edema but not parenchymal necrosis., Conclusions: Intraductal perfusion of FeSO4 or H2O2 or H2O2 + FeSO4-induced acute pancreatitis with marked light and electronmicroscopic changes. Intraductal perfusion of catalase and H2O2 simultaneously did not prevent or lessen the parenchymal necrosis. These findings have suggested that another mechanism of injury may also play a role in parenchymal injury in oxygen radical-induced acute pancreatitis.

Introduction: An experimental study was planned to evaluate and compare the effects of orchidopexy and orchidectomy on ipsilateral and contralateral testes in rats subjected to ipsilateral abdominal testis and vas deferens obstruction., Materials and Methods: Four groups of 12 rats each were established. Sham operation, intra-abdominal testis with vas deferens obstruction and orchidopexy or orchidectomy for prior intra-abdominal testis with vas deferens obstruction were performed in groups 1, 2, 3 and 4, respectively. While testes were maintained for 8 weeks in the same position in groups 1 and 2, orchidopexy or orchidectomy was performed in groups 3 and 4 after the first 4 weeks, and the remaining testes were harvested after an additional 4 weeks. Lactic acid hypoxanthine contents were determined and the groups were compared with the paired t test., Results: Maintaining intra-abdominal testis with vas deferens obstruction for 8 weeks and orchidopexy yielded the highest lactate values. However lactate levels in contralateral testes did not increase. On the other hand, hypoxanthine levels revealed the highest values after the initial 4 weeks. The 8-week study period resulted in increases of ipsilateral and contralateral testicular hypoxanthine levels. Orchidopexy caused a decrease in ipsilateral testicular values and ameliorated the increase in hypoxanthine levels in contralateral testes., Conclusions: Replacing an intra-abdominal testis with its vas deferens ligated into the scrotum ameliorates the oxidative stress in both ipsilateral and contralateral testes. Since orchidectomy does not result in better contralateral testicular values, orchidopexy should be preferred when treating an undescended testis with vasal obstruction., (Copyright 2003 S. Karger AG, Basel)

Background: Propofol can scavenge free radicals because it has a chemical structure similar to antioxidants., Methods: We examined if free radical scavenging occurs with propofol during CABG operations. We studied 24 patients undergoing CABG surgery for triple vessel disease, randomized into two groups. After induction of anaesthesia with fentanyl 10 micrograms kg-1 and midazolam 0.1 mg kg-1, patients in the fentanyl group (n = 14) received fentanyl infusion 10-30 micrograms kg-1 h-1 and patients in the propofol group (n = 10) received propofol infusion 3-6 mg kg-1 h-1 for maintenance of anaesthesia. Atrial tissue biopsies were taken during cannulation for bypass, 45 min after cross-clamp insertion, 5 min after unclamping, and in the decannulation period. Lipid peroxidation was assessed by measurement of thiobarbituric acid reactive substances (TBARS) in the atrial tissue samples., Results: Lipid peroxidation in the propofol group was less than in the fentanyl group (P < 0.05) in all sampling periods. Lipid peroxidation in the fentanyl group increased significantly during cardiopulmonary bypass (CPB) (P < 0.05), but no increase was found in the propofol group (P > 0.05)., Conclusion: In clinical doses, propofol strongly attenuates lipid peroxidation during CABG surgery.

Background/aims: We have previously shown that alpha tocopherol is a potent antioxidant which prevents reperfusion injury in a kidney and small bowel autotransplant model. In this study, the effect of systemic alpha tocopherol and verapamil on small bowel and hepatic functions following mesenteric ischemi-reperfusion was evaluated., Methods: Fourty male Wistar Albino rats (weight, 250-300 g) all subjected to an ischemia-reperfusion experiment were divided into four groups of 10 as follows: Group 1: (SHAM), Group 2, given prophylactic and systemic alpha tocopherol, Group 3: given verapamil and Group 4: given (both verapamil and alpha tocopherol)., Results: Glutaminase activities 120 minutes after reperfusion were found to be significant in liver tissues (p=0.004). The highest to the lowest glutaminase activities in liver tissue at 120 minutes after reperfusion were in Group 1, Group 3, Group 2 and Group 4 respectively. Significant differences in MDA levels were found in the small bowel at 30 minutes and 120 minutes time points (p<0.05). There were statistically significant higher glutaminase levels at 30 minutes and 120 minutes of reperfusion in the small bowel, especially in Group 4 (p=0.005)., Conclusion: Both small bowel and liver injuries reperfusion, can be decreased by prophylactic use of alpha tocopherol and verapamil. Glutaminase activity in liver tissue can also be affected by small bowel ischemia-reperfusion.

Objective: Melatonin (5-methoxy-N-acetyltrypamine), a chemical naturally produced in the pineal gland, has been suggested to be a free radical scavenger and an antioxidant. In the present study, the effect of melatonin on cold-induced brain edema was evaluated by determination of cerebral water content, blood-brain barrier permeability, and areas of infarct; the effects were also studied histopathologically., Methods: Brain edema was produced in rats by creating a lesion via cortical freezing. Animals were separated into four groups: sham-operated (craniectomy only); control (cold injury); sham-vehicle (cold injury plus saline); and melatonin treatment (cold injury plus melatonin). Melatonin was administered (50 mg/kg intraperitoneally) 15 minutes after the cold injury was induced. Twenty-four hours later, tissue samples from the core, from the periphery of the cold-injured hemisphere, and from the contralateral hemisphere symmetrical to the cold injury were obtained., Results: Melatonin treatment reduced edema (mean +/- standard deviation; 86.22 +/- 1.54% in the control group versus 80.78 +/- 2.76% in the melatonin treatment group, P < 0.001) and blood-brain barrier permeability (45.34 +/- 2.75% in the control group versus 38.26 +/- 3.40% in the melatonin treatment group, P < 0.001) at the periphery of cold injury. Area of infarct reduced from 5.84 +/- 0.58% in the control group to 3.30 +/- 0.89% in the melatonin treatment group (P < 0.001). The effect of melatonin was also confirmed histopathologically., Conclusion: Melatonin was found to be neuroprotective in instances of cold-induced brain edema. Thus, melatonin may be a valuable therapeutic agent in the treatment of cerebral edema.

Objective: Myeloperoxidase (MPO) exists in neutrophils and has an important bactericidal role. During phagocytosis, MPO catalyzes a peroxidative reaction using chloride ion and hydrogen peroxide (H2O2) as substrate. The aim of the present study was to investigate whether 5-fluorouracil (5-FU), a chemotherapeutic agent, has a direct inhibitory effect on MPO and to evaluate some properties of this inhibition., Methods: The inhibitory effect of 5-FU on MPO was studied in rat tissue, human leukocytes, and leukocytes from cancer patients under 5-FU therapy. MPO was solubilized in a detergent-containing buffer. MPO activity was measured spectrophotometrically through the oxidation of a synthetic substrate tetramethyl benzidine in the presence of H2O2., Results: 5-FU inhibited tissue-associated MPO activity in a dose-dependent but not time-dependent manner with an IC50 value of 0.6 mg/ml. 5-FU also inhibited MPO activity in isolated human leukocytes in a dose-dependent manner, and the IC50 value was 0.75 mg/ml. Using this 5-FU concentration, the inhibitory effect was monitored at different substrate concentrations. Leukocyte MPO activities of patients receiving 5-FU therapy were compared before treatment and after the first, second, and third administration cycles. 5-FU treatment resulted in a significant decrease in leukocyte MPO activity, and repeated 5-FU treatment caused additional decrease., Conclusion: Our data showed that 5-FU directly inhibited the MPO activity of human leukocytes in vitro and in vivo. We concluded that, the patients treated with 5-FU should be intensively followed for the risk of infections.

Background: Elevated C-reactive protein (CRP) has been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that CRP may be involved in initiation process of coagulation; however, the role of CRP level in the formation of left ventricular (LV) thrombus has not been studied., Hypothesis: This study investigated whether CRP is a risk factor for LV thrombus in patients with AMI., Methods: Clinical, echocardiographic, and biochemical data were analyzed in 141 consecutive patients (aged 57 +/- 13 years; 33 women) with first anterior AMI. Two-dimensional and Doppler echocardiographic examinations were performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained every day during hospitalization. Serum CRP concentrations were measured by an ultrasensitive immunonephelometry method., Results: Left ventricular thrombus was detected in 33 (23.4%) patients. Univariate analysis showed that patients with LV thrombus had a higher peak creatine kinase (CK) level (2,879 +/- 742 vs. 1,693 +/- 1,210 I/U, p = 0.001), higher peak CRP level (14.9 +/- 7.1 vs. 9.2 +/- 6.8 mg/dl, p = 0.001), higher wall motion score index (1.8 +/- 0.2 vs. 1.5 +/- 0.3, p = 0.002), higher apical wall motion score index (2.35 +/- 0.72 vs. 2.07 +/- 0.70, p = 0.001), larger end-diastolic volume (145.2 +/- 43.7 vs. 116.5 +/- 44.2 ml, p = 0.002), larger end-systolic volume (85.4 +/- 37.2 vs. 62.9 +/- 31.6 ml, p = 0.003), and lower ejection fraction (42.1 +/- 12 vs. 47.3 +/- 13, p = 0.04). In multivariate analyses, only peak CK level (p = 0.0001), LV apical wall motion score index (p = 0.001), and CRP levels (p = 0.001) were independent predictors of LV thrombus formation., Conclusions: These results suggest that CRP is a risk factor for LV thrombus in patients with AMI.

The levels of lipid peroxidation in sera of asymmetric small-for-gestational-age (SGA) babies at the second hour of life were investigated. Lipid peroxidation levels, measured as malondialdehyde (MDA), were 3.3 +/- 1.1 and 3.9 +/- 1.2 mmol/L in SGA and appropriate-for-gestational age (AGA) groups, respectively. The difference was not significant (p>0.05). This result may indicate that free radical scavengers are sufficient in SGA babies.

Intense exercise accompanied by a manifold increase in oxygen utilization over resting conditions has been shown to elevate the probability of the appearance of free radicals. One of the effects of free radicals appears to be the peroxidation of cell membrane lipids resulting in malondialdehyde formation, which is detrimental to cell function. A common method for the measurement of malondialdehyde involves a reaction with thiobarbituric acid. The aim of this study was to evaluate the influence of exercise on concentrations of thiobarbituric acid-reactive substances (TBARS) in the gastrocnemius and soleus muscles of rats. Thirty male rats were used in this study. Soleus and gastrocnemius muscle biopsies were performed and TBARS levels were studied in these two muscles. The rats were randomly assigned to three groups of ten each. Group A was the control group and did not perform exercise. In group B, gastrocnemius and soleus muscle biopsies were performed immediately after exercise, and in group C muscle biopsies were performed on the 2nd postexercise day. The exercise resulted in a significant increase in TBARS in the gastrocnemius muscle. In the soleus, TBARS also increased, but this was not statistically significant. In conclusion, exercise-induced free radical changes may depend on the muscle type studied.

To evaluate the possible effect of sampling technique and sequential sampling on gingival crevicular fluid (GCF) volume and myeloperoxidase (MPO) activity, 14 patients presenting at least two symmetrical maxillary sites with mild/moderate periodontitis were selected. Two sites in each individual were sequentially sampled using either the deep-intracrevicular or orifice technique. Spectrophotometrically determined MPO levels were presented either as total MPO activity or MPO concentration. Although the clinical periodontal status of the 20 sampling sites were similar, the deep-intracrevicular technique regularly provided larger GCF volumes. With both techniques, the last samples contained the highest GCF volume. During sequential orifice sampling, GCF volume was relatively more stable. In general, a depletion of MPO activity was observed with sequential sampling performed with either of the techniques. Depletion of MPO did not replenish to baseline levels at the end of the 10-min sequential sampling. Although MPO activity showed a general reduction during sequential orifice sampling with both modes of data presentation, total MPO activity and MPO concentration did not match with the deep-intracrevicular technique. Due to the potential of affecting GCF volume/composition, the selection of sampling technique seems to be a critical methodological decision in GCF-profile studies, primarily during sequential sampling. In GCF-profile studies, mode of data presentation should also be considered.

Background: In order to determine whether angiotensin-converting enzyme inhibitors (ACEI s) attenuate ischemia-reperfusion injury, we investigated and compared the effects of lisinopril via different routes of administration in an isolated guinea pig heart model of ischaemia reperfusion., Methods: The effect of lisinopril cardioplegia, oral pretreatment with lisinopril and lisinopril enriched reperfusion solution on myocardium after a normothermic global ischemia of 90 minutes and 30 minutes of reperfusion in the modified Langendorff model was randomly studied in 4 groups (n=8 in each). In all groups, cardioplegic arrest was achieved by administering St. Thomas Hospital Cardioplegic Solution (STHCS). The first group was utilized as the control. In the second group, hearts were arrested with lisinopril (1 micromol/L) enriched STHCS. In the third group, animals were pretreated with oral lisinopril (0.2 mg/kg/twice a day) for ten days. In the last group hearts were again pretreated with oral lisinopril (like in Group 3) and the heart were reperfused with lisinopril enriched (1 micromol/L) Krebs-Henseleit solution during the reperfusion period., Results: Contractility, which was expressed as contractile force (g contractility/g heart weight), was preserved better in the study groups. In the last group, the hearts had the best left ventricular contractile function, where contractile force was 58.4%+/-4.82% of the preischaemic values. In Group I, Group II and Group III they achieved 29.5%+/-5.6%, 41.9%+/-4.9%, and 55.3%+/-5.8% of their preischaemic contractile force values respectively. Creatine kinase leakage was significantly lower and also post- ischaemic coronary flows were significantly higher in the 4th group. Coronary flow after reperfusion increased from 48.0+/-6.2 to 68.0+/-4.51 ml/min.g.heart, in Group IV (p<0.05)., Conclusions: Myocardial MDA and GSH contents showed that there was a correlation between the depletion of myocardial GSH content and increased lipid peroxidation. The myocardial GSH content indicates that the best results were obtained in the last group as compared to the other groups. These preliminary results showed that oral preconditioning improved postischaemic myocardial function and decreased myocardial injury. Because the best results were achieved in the last group, it can be suggested that lisinopril may also play a protective role against reperfusion injury.

It is well known that the incidence of left ventricular (LV) thrombosis is high in patients with acute myocardial infarction (AMI). Due to the high degree of structural homology with plasminogen, lipoprotein(a) may produce thrombogenic effects by modulating the fibrinolytic system. However, the role of Lp(a) level in the formation of LV thrombus has not been studied. This study sought to determine whether Lp(a) is a risk factor for LV thrombus in patients with AMI. We have analyzed clinical, echocardiographic and biochemical data in 102 consecutive patients (aged 58+/-12 years, 92 men / 10 women) with first anterior AMI. Two-dimensional examination was performed on days 1, 3, 7, 15, and 30. Blood samples were obtained within 12 h after the onset of symptoms and before beginning the therapy. Plasma levels of fibrinogen and Lp(a) were measured using enzyme-linked immunosorbent assay and immunonephelometric methods, respectively. LV thrombus was detected in 20 (20.3%) patients. No significant difference was found for admission Lp(a) levels between patients with or without thrombus (30.5+/-17.2 vs 32.3+/-22.4 mg/dl, p = 0.7). Univariate analysis showed that patients with LV thrombus had a higher wall motion score index (1.8+/-0.3 vs 1.4+/-0.3, p = 0.002), a higher peak creatine kinase level (2945+/-898 vs 1805+/-1336, I / U p = 0.004), a larger end-diastolic volume (139.7+/-38.6 vs 114.1+/-41.8 ml, p = 0.04), a larger end-systolic volume (83.1+/-34.3 vs 59.2+/-30.6 ml, p = 0.02 ), and a lower ejection fraction (38+/-12 vs 47+/-11, p = 0.04). In multivariate analyses, only peak creatine kinase level (p = 0.04) and LV wall motion score index (p = 0.002) were independent predictors of left ventricular thrombus formation. These results suggest that Lp (a) is not a risk factor for LV thrombus in patients with AMI. Our data demonstrate that the best predictors of LV thrombus formation after AMI are a high peak creatine kinase level and a high LV wall motion score index.