Does ß-Glucan can have protective role against oxidative stress in experimental sepsis model in rats?

BACKGROUND: Very high mortality rate in sepsis may be related to oxidative stress. This study was conducted on the rats to investigate the presence of oxidative stress and also the potential protective effects of the ß-glucan in the intra-abdominal sepsis model formed by cecal ligation-perforation (CLP). METHODS: In this study, 30 Male rats were equally divided into three groups as 'Sham', 'Sepsis' and 'ß-Glucan'. Only laparotomy was performed in the Sham group, and sepsis was induced by CLP in Sepsis and ß-Glucan groups. Following CLP, a single dose of 4 mg ß-glucan/kg was also intraperitoneally administered to the ß-Glucan group. Blood and tissue (liver, lung and kidney) samples were taken from Sepsis and ß-Glucan groups after sepsis development determined at the end of the 48th hour, also from the Sham group. The levels of myeloperoxidase (MPO) and advanced oxidation protein products (AOPP) were determined in plasma samples, and the malondialdehyde (MDA) was measured in plasma and tissues. RESULTS: MPO and AOPP were higher in both the Sepsis and ß-Glucan groups; however, plasma and tissue MDA levels were higher only in the Sepsis group than the Sham group (p<0.05). However, when compared to the Sepsis group, all parameters measured, except kidney MDA, were significantly lower in the ß-Glucan group (p<0.05). CONCLUSION: To our knowledge, this is the first study to investigate the AOPP levels in the CLP sepsis model, ROS produced by the reaction of MPO derived from neutrophils may form oxidative damage to the proteins, compared to the lipids, and ß-glucan may be used as an alternative agent for sepsis treatment.

Treatment of male hypogonadism partially reverses oxidative stress in patients with hypogonadism.

There are some studies regarding the presence/absence of oxidative stress in patients with hypogonadism with limited number of parameters. We aimed to investigate the effects of male hypogonadism and its treatment on oxidative stress parameters. Thirteen male patients with hypogonadotropic hypogonadism and 20 healthy subjects were involved in the study. Patients with hypogonadism were evaluated before and after six months of therapy. Markers indicating lipid and protein oxidation, total oxidant status (TOS) and total anti-oxidant capacity (TAC) were evaluated. Control subjects had significantly higher serum testosterone levels in comparison to hypogonadal patients before the treatment period. After the treatment of hypogonadism serum testosterone levels increased significantly. Myeloperoxidase (MPO) activity, levels of advanced oxidation protein products (AOPP), total lipid hydroperoxide and protein carbonyl compounds (PCC) were similar between the control subjects and the patient group before treatment. Pyrrolized protein and TOS were significantly lower and thiol levels and TAC were significantly higher in the control subjects than in patients with hypogonadism. Treatment of hypogonadism resulted in a significant decrease in AOPP levels while a significant increase was determined in TAC. No significant change was found in MPO activity. In conclusion, patients with hypogonadism have an increased status of oxidative stress which is at least partially improved after appropriate therapy.

Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren.

AIM: we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6-15 years and to investigate the relationship between their nutritional habits and oxalate excretion. MATERIALS AND METHODS: Random urine specimens from 953 healthy children aged 6-15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10-12 years, n = 335), and Group III (13-15 years, n = 265). RESULTS: The 95th percentile of the oxalate to creatinine ratio for subjects aged 6-9, 10-12, and 13-15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate. CONCLUSIONS: These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate.

A novel approach in psoriasis: first usage of known protein oxidation markers to prove oxidative stress.

Oxidative stress may play a pivotal role in the pathogenesis of psoriasis, an inflammatory/hyperproliferative skin disease characterized by the cutaneous accumulation of neutrophils releasing reactive oxygen species, as revealed in a number of studies. This study was performed to demonstrate the presence of oxidative stress in psoriasis, as measured by protein oxidation markers. Twenty-nine psoriasis patients were selected based on disease severity assessment using body surface area as well as the psoriasis area severity index (PASI), and were grouped as mild (PASI ≤ 10) and moderate-to-severe (PASI > 10). The measured parameters in psoriatic patients and fourteen healthy volunteers were as follows: erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (CRP), myeloperoxidase (MPO) activity, neopterin, total lipid hydroperoxides (LHP), pyrrolized protein (PP), protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP), thiol levels, along with complete blood count. Except lower thiols, all parameters were found to be higher in total patients as well as in subgroups, compared to controls. There was no significant difference among the subgroups. In conclusion, protein oxidation in psoriatics, not only in moderate-to-severe, but also in mild patients, may be explained by the findings of inflammation, phagocytic cell oxidation, and MPO-hypochlorous acid-oxidation reactions; as reflected by increased total/differential leucocytes counts, CRP, ESR as well as MPO, neopterin, AOPP, PCC, PP, LHP, and decreased thiol levels. Demonstrating the AOPP and PP formation for the first time, oxidants from active neutrophils/monocytes may play an important role in the pathogenesis of psoriasis, leading to oxidative stress, especially by protein oxidation.

The effects of electroconvulsive therapy on GABAergic function in major depressive patients.

OBJECTIVES: It has been proposed that major depression is associated with a dysfunction of the gamma-aminobutyric acid (GABA) system. This study was planned to investigate whether there are any alterations in GABAergic activities in major depressive patients and, if there are, whether electroconvulsive therapy (ECT) has any effect on these changes. METHODS: Twenty-five depressed inpatients who responded to a course of ECT and 23 healthy subjects were included in the study. Serum GABA levels were measured 2 days before and 10 minutes after the first ECT and 3 days after the last ECT, and a baclofen challenge test was performed 2 days before the first ECT and 3 days after the last ECT in the patients. The same tests were carried out only once in the control group. RESULTS: Depressive patients had lower serum GABA levels compared with healthy individuals, and ECT caused a significant increase in these levels. The acute effect of the one-ECT procedure was a huge increase in the baseline GABA levels. Although there was no difference in the maximum alteration in growth hormone with baclofen between the patients and controls before the therapeutic ECT course, it became significantly higher in the depressive patients than in the controls after the treatment. CONCLUSIONS: The findings of this study support the GABA deficit hypothesis of major depression because major depressive patients have lower levels of serum GABA that are increased by a completed ECT course. ECT seems to increase brain GABA levels as well as GABAB activity, and these effects may contribute to its mechanism of therapeutic effect.

Is there an oxidative stress in children with Helicobacter pylori infection?

OBJECTIVE: To investigate the status of oxidative stress in children with Helicobacter pylori (HP) infection and their relationship with inflammatory parameters. METHODS: At the Pediatric Gastroenterology Department of Erciyes University, Kayseri, Turkey, between January 2004 to August 2005, 39 children undergoing upper gastrointestinal endoscopy were investigated for malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in gastric tissue and erythrocytes, and presence of HP infection by means of histology. RESULTS: There is an increase of the oxidative stress parameter, MDA, in gastric tissue, but not in erythrocytes in HP (+) patients. The antioxidant enzyme, SOD, levels both in gastric tissue and erythrocytes were not different between HP (+) and HP (-) patients. In 8 HP infected children after treatment with an anti-HP regimen, no change was observed except for tissue SOD activity, which is increased after therapy. No correlation was observed between histological findings and tissue, and erythrocyte MDA levels and SOD activities. CONCLUSION: Oxidative stress has some role in tissue damage in HP infection in children.

Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns.

This study aimed to investigate the effect of allopurinol in the management of cerebral hypoxia-ischemia by monitoring nitric oxide levels of serum and cerebrospinal fluid. Sixty asphyxiated infants were divided randomly into two groups. Group I infants (n = 30) received allopurinol (40 mg/kg/day, 3 days) within 2 hours after birth. Group II infants (n = 30) received a placebo. Twenty healthy neonates served as control subjects. Cerebrospinal fluid and serum nitric oxide levels were measured within 0-24 hours and 72-96 hours after birth. Both serum and cerebrospinal fluid concentrations of nitric oxide were higher in severely asphyxiated infants (40.86 +/- 8.97, 17.3 +/- 3.63 micromol/L, respectively) but lower in mildly asphyxiated infants (25.85 +/- 3.57, 5.70 +/- 2.56 micromol/L, respectively) than in moderately asphyxiated infants (35.86 +/- 5.38, 11.06 +/- 3.37 micromol/L, respectively) within the first 0-24 hours after birth. Serum nitric oxide levels in control subjects were lower than those of moderately and severely asphyxiated infants. Serum nitric oxide levels of Group I infants within 72-96 hours after birth decreased significantly from their corresponding levels within 0-24 hours after birth. The asphyxiated newborns treated with allopurinol had better neurologic and neurodevelopmental outcome at 12 or more months of age.

Adenosine deaminase enzyme levels, their relation with disease activity, and the effect of colchicine on adenosine deaminase levels in patients with Behçet's disease.

Behçet's disease (BD) is a systemic vasculitis. Although its clinical characteristics are well defined, the etiology and immune pathogenesis are not clear yet. Neutrophilic vasculitis, which is a consequence of immunological events, is suggested as the underlying pathophysiological mechanism. Adenosine deaminase (ADA) is a non-specific marker of T-lymphocyte activation. A total of 75 patients with BD (45 women and 30 men) and 25 age-matched and gender-matched healthy control volunteers (13 women and 12 men) were included in this study. BD patients were divided into three groups according to their clinical findings: inactive BD patients (group 1, n=25); active BD patients under colchicine treatment (group 2, n=25); and active BD patients without colchicine treatment (group 3, n=25). Plasma ADA (p-ADA) levels of all BD patients and the control group were measured and compared. The relationship between p-ADA levels and disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels was evaluated and correlated. Patients with BD had significantly higher p-ADA levels (20.6+/-6.3 U/l) than control subjects (12.8+/-1.8 U/l; P<0.001). The p-ADA levels of patients with active BD were significantly (for each, P<0.05) higher than those of inactive BD patients or controls. On the other hand, the difference was not significant (P>0.05) between active patients with or without colchicine use. In addition, there were significantly positive correlations between p-ADA, ESR and CRP levels in patients with BD (for each, P<0.05). However, disease duration or haemoglobin levels were not relevant. ADA level may be a valuable and supportive indicator of disease activity and is not affected by colchicine therapy in BD.

Protective effect of beta-glucan on lung injury after cecal ligation and puncture in rats.

OBJECTIVE: Understanding the biological mediators involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations targeting treatment based on these mediators. This study investigated whether macrophage activator beta-glucan has a protective effect on acute lung injury in an experimental model of sepsis. DESIGN AND SETTING: Experimental study in an experimental research center. MATERIALS: 30 rats randomized into three groups (sham, sepsis, and beta-glucan). INTERVENTIONS: Cecal ligation and puncture were performed in the beta-glucan and sepsis groups. The beta-glucan group was given a single intraperitoneal dose of beta-glucan (4 mg/kg) following cecal ligation. MEASUREMENTS AND RESULTS: Rats treated with beta-glucan had fewer circulating neutrophils, more blood monocytes, and higher serum interleukin 6 levels than septic animals. The percentages of neutrophils and lymphocytes from the bronchoalveolar lavage fluid and the myeloperoxidase activity measured in the lung tissue were lower in the beta-glucan group than in the sepsis group. Less alveolar hemorrhage and neutrophil infiltration were observed in lungs from animals in the beta-glucan group in the septic groups. CONCLUSIONS: In this rat model of intra-abdominal sepsis beta-glucan treatment partially protected against secondary lung injury, decreased lung hemorrhages, and lung neutrophilia. These results suggest that beta-glucan protects against sepsis-associated lung damage.

Lipid peroxidation and erythrocyte antioxidant enzymes in patients with Behçet's disease.

In spite of unknown etiology, it is now accepted that reactive oxygen species (ROS) produced by neutrophils may be related to the pathogenesis of Behçet's Disease (BD). The objective was to investigate whether increased production of ROS may affect erythrocyte oxidant/antioxidant system in patients with BD. The levels of malondialdehyde (MDA), one of the end products of lipid peroxidation, in plasma and erythrocyte, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), antioxidant enzymes, in erythrocyte, also C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in 22 patients in active stage of the disease and also in 30 healthy controls. Increased CRP, ESR, and MDA levels in plasma and erythrocyte and increased SOD but decreased GSH-Px activities in erythrocytes were observed in the patients, when compared to the controls. In addition, significantly positive correlations between plasma and erythrocyte MDA levels, and erythrocyte MDA-CRP, MDA-ESR, MDA-SOD, SOD-ESR and SOD-CRP levels, but negative correlation between plasma MDA and erythrocyte GSH-Px, were found in BD patients. It may be suggested that increased production of ROS in BD, as reflected by higher plasma and erythrocyte MDA levels, may impair erythrocyte membrane integrity and also may lead to the alterations in the erythrocyte antioxidant defense system, as reflected by higher SOD and lower GSH-Px activities in erythrocytes.

Antioxidant potential of propylthiouracil in patients with psoriasis.

OBJECTIVE: There is growing evidence supporting the reactive oxygen species (ROS) in the pathogenesis of psoriasis. Propylthiouracil(PTU), an antithyroid drug, has been shown to have beneficial effects on psoriasis. The aim of this study was to investigate both disturbances in oxidant/antioxidant system in psoriasis and whether PTU, shown to have immunomodulatory effects and antioxidant potential, has effects on oxidant/antioxidant system and clinical improvement in psoriatics. DESIGN AND METHODS: Malondialdehyde (MDA), end product of lipid peroxidation, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and antioxidant enzymes were measured in plasma, erythrocytes and skin biopsies of psoriatics who were resistant to conventional therapy before and after 8 weeks of oral treatment with PTU (300 mg/day) or PTU/thyroxine (25 microg/day- to prevent possible hypothyroidism). The same parameters were also studied in healthy controls. Psoriasis Area and Severity Index (PASI) scores were used to evaluate the severity of the disease, and routine analyses and thyroid function tests were measured during the study. RESULTS: Increased baseline MDA in all samples were found to be lower. In addition baseline SOD and GSH-Px in skin and erythrocytes were also lower. The increased plasma SOD levels in skin and erythrocytes of the study groups was found to be higher and lower,respectively in all patients after the treatment. No tissue parameters or erythrocyte GSH-Px were different from control levels at the end of the study. Significant clinical improvement and decreased PASI scores were observed in all patients. Post treatment TSH levels were higher in all patients, but these levels were within the reference range and none had clinical hypothyroidism. CONCLUSION: These findings may provide some evidence for a potential role of increased lipid peroxidation and decreased antioxidant activity in psoriasis. PTU may be considered as treatment model in psoriasis, in particular for resistant cases, because of its antioxidant potential, and also antiproliferative and immunomodulatory effects.

Monoamine oxidase-B activity in alcohol withdrawal of smokers: is there any relationship with aggressiveness?

There is a considerable inconsistency in terms of the association between alcoholism and alterations in monoamine oxidase (MAO) activity. The main objectives of this study were to investigate the changes in platelet MAO-B activity throughout the alcohol withdrawal period and whether or not MAO-B activity differed between patients with high- and low-aggression tendency. We assayed platelet MAO-B levels spectrophotometrically in 22 male inpatients with alcohol dependence in their first and fourth weeks of withdrawal and in 20 healthy controls. Patients were divided into two high- and low-aggression subgroups according to scores obtained in a Brown-Goodwin Assessment for Life History of Aggression. Our data revealed that the significantly lower platelet MAO-B activity observed during the first week of alcohol withdrawal in patients, compared to controls, did not continue in the fourth week, and that there was no relationship between aggressiveness and MAO activity. These results suggest that low platelet MAO activity may be a state marker of alcohol withdrawal period or a result of high alcohol consumption rather than a trait marker of alcoholism.