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

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

Free radical metabolism in human erythrocytes.

As the red cell emerges from the bone marrow, it loses its nucleus, ribosomes, and mitochondria and therefore all capacity for protein synthesis. However, because of the high O(2) tension in arterial blood and heme Fe content, reactive oxygen species (ROS) are continuously produced within red cells. Erythrocytes transport large amount of oxygen over their lifespan resulting in oxidative stress. Various factors can lead to the generation of oxidizing radicals such as O(2)(-), H(2)O(2), HO in erythrocytes. Evidence indicates that many physiological and pathological conditions such as aging, inflammation, eryptosis develop through ROS action. As such, red cells have potent antioxidant protection consisting of enzymatic and nonenzymatic pathways that modify highly ROS into substantially less reactive intermediates. The object of this review is to shed light on the role of ROS both at physiological and pathological levels and the structural requirements of antioxidants for appreciable radical-scavenging activity. Obviously, much is still to be discovered before we clearly understand mechanisms of free radical systems in erythrocytes. Ongoing trends in the field are recognition of undetermined oxidant/antioxidant interactions and elucidation of important signaling networks in radical metabolism.

The potential inflammatory role of arginase and iNOS in children with chronic adenotonsillar hypertrophy.

OBJECTIVE: Nitric oxide (NO) induced tissue damage has been implicated in the pathogenesis of several diseases. Although recurrent/chronic tonsillitis and hypertrophy are still the most frequent surgical procedures carried out on children in order to cure these pathologies, etiopathogenetic mechanisms underlying these entities are still unknown. We aimed to investigate the potential inflammatory role of NO regulatory enzymes, arginase and inducible nitric oxide synthase (iNOS), in children with adenotonsillar hypertrophy. MATERIALS AND METHODS: The study consisted of 22 children with chronic adenotonsillar hypertrophy and 30 control subjects with similar age and sex. All the patients and/or their parents had complaints of snoring, mouth breathing and pausing of breathe during sleep at least 6 months. All patients underwent an adenotonsillectomy operation under general anesthesia with curettage and cold dissection methods. Venous blood samples were taken pre-operatively and 4 weeks post-operatively. iNOS activity was based on the diazotization of sulfanilic acid by nitric oxide at acid pH and subsequent coupling to N-(1-naphthtyl)-ethylenediamine. Arginase activity was measured by the spectrophotometric method. RESULTS: The mean pre-operative and post-operative arginase activities in patient group were 4283.7 +/- 1823.7 and 2754.5 +/- 889.3 IU/L, respectively. In the control group, mean arginase activity was 2254.7 +/- 903 IU/L. When pre-, post-operative and control arginase values were compared with each other, the mean activity in pre-operative activity was significantly different from the post-operative and control values (p < 0.001). In the patient group, the mean levels of pre- and post-operative iNOS were 2.84 +/- 1.16 and 1.99 +/- 0.78 IU/ml, respectively. The difference was statistically significant (p = 0.007). Similarly, post-operative and control values were not significantly different (p > 0.05). CONCLUSION: The results of the present study supports that L-arginine:NO pathway may be key the participant in the pathogenesis of chronic adenotonsillar disease; arginase and iNOS activities are altered in children with adenotonsillar hypertrophy and this alteration improves after tonsillectomy.

Short term effects of L-carnitine on serum lipids in STZ-induced diabetic rats.

The aim of this study was to evaluate the effects of L-carnitine supplementation on serum triglyceride and total cholesterol levels in streptozotocin (STZ)-induced diabetic rats. Thirty-two male Wistar rats were divided into diabetic and diabetic-L-carnitine-supplemented groups. Diabetes was induced by injection of a single dose of streptozotocin (40 mg/kg, intraperitoneally) in citrate buffer. L-Carnitine was supplemented by IM injection of 100 mg/kg per day for 10 days. Serum glucose, triglyceride and total cholesterol levels were determined at days 0, 5 and 10. Rats receiving L-carnitine had lower triglyceride levels at both days 5 and 10 (P < 0.05). Total cholesterol levels in the carnitine-supplemented group were lower, but statistical significance was achieved only at day 10 (P < 0.05). These results suggest that L-carnitine exhibits hypotriglyceridemic and hypocholesterolemic effects in streptozotocin-induced diabetic rats. Clinical trials of L-carnitine supplementation on patients with diabetes induced hyperlipidemia must be further evaluated.

Malondialdehyde and antioxidant enzymes in children with obstructive adenotonsillar hypertrophy.

OBJECTIVE: Free radical induced tissue damage has been implicated in the pathogenesis of several diseases. We aimed to investigate the role of free radicals and scavenging enzymes in children with obstructive adenotonsillar hypertrophy. MATERIALS AND METHODS: The study consisted of 29 children with obstructive adenotonsillar hypertrophy and 51 control subjects with similar age and sex. All the patients and/or their parents had complaints of snoring, mouth breathing, and pausing of breath during sleep for at least 6 months. All patients underwent an adenotonsillectomy operation under general anesthesia with curettage and cold dissection methods. Venous blood was taken preoperatively and 4 weeks postoperatively. After collection of blood samples into citrate (3.5 mg/ml blood) containing glass tubes, erythrocyte sediments were prepared for the analyses. Then malondialdehyde (MDA) level, and superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities were measured. RESULTS: The levels of MDA and activities of SOD and GSHPx were significantly higher in the pre-tonsillectomy period than in the post-tonsillectomy period. However, CAT activity was not different in pre- and postoperative period. CONCLUSION: Our study supports the notion that oxidant and antioxidant defense mechanisms are altered in children with obstructive adenotonsillar hypertrophy, and this alteration improves after tonsillectomy.

Plasma reactive oxygen species activity and antioxidant potential levels in rosacea patients: correlation with seropositivity to Helicobacter pylori.

BACKGROUND: Recent studies have suggested that there might be an etiologic role for Helicobacter pylori (HP) in rosacea. HP is a Gram-negative bacterium that colonizes the gastric mucosa, increases the generation of reactive oxygen species (ROS), and decreases plasma antioxidants such as ascorbic acid. AIM: To investigate plasma ROS activities and antioxidant status, and their relationship with HP infection, in rosacea patients. METHODS: Twenty-nine rosacea patients and 20 age- and sex-matched healthy controls were examined for specific immunoglobulin G (IgG) and IgM against HP, plasma malondialdehyde (MDA), and antioxidant potential (AOP) levels. RESULTS: Compared with controls, the seropositivity of HP for IgM was significantly higher (P = 0.03) and the seropositivity of HP for IgG was significantly lower (P = 0.0001) in patients with rosacea. Plasma MDA levels were higher (P = 0.0001) and AOP levels were lower (P = 0.019) in patients than in controls, regardless of the severity of the disease. Plasma MDA and AOP levels were not affected by the seropositivity of HP for IgM and/or IgG in either group. CONCLUSION: Our results suggest that rosacea is an oxidative stress condition, as reflected by the increased ROS activity and decreased AOP, regardless of HP infection.

The effect of ethylenediaminetetraacetic acid on calcific degeneration in bovine pericardium.

Calcification is the most frequent cause of the clinical failure of bovine pericardium bioprosthetic valves, preventing their widespread application for surgical treatment. The aim of this study was to minimize calcific degeneration in bovine pericardium by using a chelating agent, ethylenediaminetetraacetic acid (EDTA). Freshly excised bovine pericardium was dissected free from adhering fat tissue and cut into 1-cm(2) pieces that were rinsed in phosphate-buffered saline solution (PBS) and transferred into 4 degrees C PBS containing 1% glutaraldehyde (GA) for initial fixation, then allocated into two groups. Group I received the same treatment in a fresh solution for 5 more days. Group II underwent an additional fixation step in PBS solution (pH 7.4, 37 degrees C) containing 11% EDTA for a period of 48 h (30 ml/g tissue) and was then transferred into freshly prepared PBS + 1% GA solution at 37 degrees C for another 3 days. To investigate the calcification rate, pericardial patches were inserted into the dorsal pouches of 25 male Wistar rats for 21 days. Calcium levels were measured with an atomic absorption spectrophotometer and examined histo-pathologically. The calcium content of EDTA-treated pericardium (Group II), 21 +/- 3.8 microg/mg, was significantly lower than that of Group I, 43.3 +/- 9.2 microg/mg. Assessment of the degree of calcification in the histological sections generally agreed well with the results of the chemical analyses. Calcium deposition in Group I samples were found to be solid mineral depositions, whereas in the Group II pericardial samples, only smaller traces of calcium were found. Calcific degeneration in bovine pericardium can be reduced by using chelates such as EDTA.

Oxidant / antioxidant status in patients with psoriasis.

Psoriasis is a common, chronic inflammatory skin disease with unknown etiology. Recently it has been suggested that increased ROS production and deficient function of antioxidant systems activities may be involved in the pathogenesis of the disease. Although there are several studies investigating oxidant/antioxidant systems in psoriatic patients, the data obtained from these studies is not concordant. In this study, superoxide dismutase (SOD) enzyme activity, and malondialdehyde (MDA) and antioxidant potential (AOP) levels in thirty-five patients with psoriasis were investigated and compared with those of twenty-four control subjects. Clinical severity of the disease was determined according to the Psoriasis Area and Severity Index (PASI) scores in the patients. Plasma SOD activity and MDA levels were significantly higher (p=0.012 and p=0.005 respectively), whereas AOP levels were lower, in patients than controls (p=0.001). There was no correlation between PASI scores and plasma SOD, MDA, and AOP levels. Our findings may provide some evidence for a potential role of increased ROS production and decreased antioxidant activity in psoriasis.

The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde levels in rabbit hepatic tissues.

Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has not been cleared yet. Therefore, investigation of antioxidant status of hepatic tissues exposed to cyclosporine A (CsA) and of free radical involvement in the CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days. Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected intramuscularly. After 10th day, animals were killed, and livers were prepared for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and, increased CAT activities and MDA levels were detected in hepatic tissues of rabbits treated with CsA as compared with controls. In the CsA plus vitamin group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged and MDA levels lower than the CsA group. In the vitamin-treated group, all of the enzyme activities were higher than the controls but MDA levels were unchanged. Correlation analysis revealed some significant differences between the groups. Results suggest that cyclosporine impairs the antioxidant defense system and thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has been established that this process can be prevented by antioxidant vitamin supplementation.