Deniz Erbas

The effects of exercise and exercise-related changes in blood nitric oxide level on migraine headache

Objective: To observe the effects of moderate aerobic exercise on migraine headache, to assess exercise-related changes in blood nitric oxide (NO) levels, and to examine the impact of such changes on migraine attacks. Design: Controlled clinical trial. Setting: School of Physical Therapy and Rehabilitation. Subjects: Forty women with general migraine attending the Neurology Department of the Faculty of Medicine Faculty of Dokuz Eylül University. Intervention: Patients were assigned alternately into two groups: exercise group undertaking 1 hour aerobic exercise three times weekly, and a control group. Main outcome measures: Patients were assessed before and after treatment using three clinical scales – visual analogue scale for headache, Pain Disability Index and Quality of Life Scale – and chemiluminescence analysis for plasma nitric oxide. Results: After the eight-week therapy period, patient complaints concerning the intensity, frequency and duration of pain had decreased significantly in both groups; however, visual analogue scale scoring showed better pain relief in the exercised group than in the controls (from 8.8 ± 1.7 to 4.0 ± 1.4 and from 8.5 ± 0.8 to 7.0 ± 0.9 respectively). Quality of life measures also revealed better migraine relief in the exercised women than in those who received medical treatment only. Blood NO rose significantly from pre to post-therapy in the exercised group, but the change was not significant in the control group. Conclusion: The study showed that regular long-term aerobic exercise reduced migraine pain severity, frequency and duration possibly due to increased nitric oxide production.

Airway Inflammation in Premenstrual Asthma

Premenstrual asthma (PMA) is a clinical picture with worsening of asthmatic symptoms and pulmonary functions in the late luteal phase of the menstrual cycle. The aim of this study was to evaluate the inflammatory changes in asthmatic women who complain of PMA. Forty asthmatic women attending our outpatient clinic were questioned about worsening of their asthma before menstruation. Eleven women (aged 17–40) who complained of PMA participated in the study. Subjects were asked to record peak expiratory flow rates, symptom scores, and β-agonist use daily. After the first menses on the seventh day of their cycle, and before the onset of the next menstruation, on the 26±3rd day of the cycle, patients were evaluated with pulmonary function tests, methacholine challenge test, and fractionated exhaled nitric oxide (FeNO) levels. Eosinophils in peripheral blood and induced sputum were also evaluated. When comparing the two groups of results, the significant changes were in FeNO levels, day-time symptom scores, and eosinophils in induced sputum (29.25 ppb/9.16 ppb p<0.05, 1/0.45 p = 0.05, %6.63/%4.09 p<0.01, respectively, before and after menstruation). These results show that PMA is not only a clinical picture with a decrease in airway calibre that can be related to the regulation of 2 receptors, but also a complex state with worsening of airway inflammation.

Cerebrospinal fluid and serum vascular endothelial growth factor and nitric oxide levels in newborns with hypoxic ischemic encephalopathy

Excitatory amino acids, cytokines and nitric oxide (NO) have been studied in the etiology and pathogenesis of hypoxic ischemic encephalopathy (HIE) of the newborn. Vascular endothelial growth factor (VEGF) is a known mediator of angiogenesis and has been shown to induce vascular proliferation and permeability via NO-mediated mechanism during hypoxia. The objective of this study was to investigate the cerebrospinal fluid and serum VEGF and NO levels in different stages of HIE and the correlation between the two mediators. Cerebrospinal fluid (CSF) and serum samples of 19 newborns with HIE and 13 controls were obtained within the first 24 h of life and kept at -70 degrees C until the time of measurement. NO levels were determined by Sievers NOA by chemiluminescence method and VEGF levels were measured by the enzyme-linked immunosorbent assay double sandwich method. The NO levels in CSF were higher than the control and mild HIE group in newborns with moderate to severe HIE, and VEGF levels in CSF were higher in the mild HIE group compared to controls but similar in the moderate to severe HIE group compared to mild HIE and control patients. There was no difference between groups with regard to serum NO or VEGF levels, and no correlation was observed between NO and VEGF levels both in CSF and serum samples. Depending on the severity of the hypoxic insult the stimulus for NO production by VEGF may have variable effects on endothelial cells which may give rise to the current results.

Prevention of doxorubicin-induced cardiotoxicity by melatonin

Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents. Cardiotoxicity made by these agents develops as a complication of the cancer chemotherapy. Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. We decided to evaluate the tissue-protective effect of melatonin against myocardial toxic effects of doxorubicin in six groups of rats. Rats were given doxorubicin (Dx) (45 mg/kg dose) and melatonin (MEL) (10 mg/kg), first doxorubicin and then melatonin (DM), first melatonin and then doxorubicin (MD). The degree of cardiac muscle cell alterations were examined either histologically (mean total score technique) or biochemically. In doxorubicin-treated group, malondialdehyde (MDA) levels of the heart tissue were significantly increased, glutathione (GSH) levels were decreased compared to the control rats. In the group in which first doxorubicin and then melatonin was given, MDA levels were significantly decreased and glutathione (GSH) levels were increased compared to the doxorubicin-treated group. During ultrastructural analysis, in doxorubicin-treated group, cellular edema, mitochondrial deformation, decreased glycogen stores, and disordered myofibrillary structure were observed. In contrast, in first doxorubicin and then melatonin-treated group, normal cellular structure was observed. But, first melatonin and then doxorubicin-treated group was not significantly preserved from the doxorubicin-induced changes. By preventing lipid peroxidation and myocardial lesions, melatonin may be highly effective in protecting against doxorubicin-induced cardiotoxicity.

Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to 14-year-old children with seasonal allergic rhinitis.

BACKGROUND Cysteinyl leukotrienes have been found to exert potent inflammatory effects in the upper airways and play a fundamental role in the pathogenesis of allergic rhinitis. Previous studies have reported increased levels of exhaled nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms. OBJECTIVE To investigate the role of treatment with montelukast on symptoms, eNO levels, and peripheral eosinophil counts of children with seasonal allergic rhinitis during pollen season. METHODS A randomized, double-blind, parallel-group study performed between April and June 2005 in 57 children aged 7 to 14 years with seasonal allergic rhinitis was performed. The study comprised a 1-week screening period, a 1-week run-in period, and a 2-week treatment period with once daily montelukast, 5 mg, or matching placebo. RESULTS No significant difference at baseline was found in symptom scores, eNO levels, and blood eosinophil counts between the treatment and placebo groups. After 2 weeks of montelukast treatment, improvements from the baseline in the daytime nasal, composite, and daytime eye symptoms scores were significantly greater in the montelukast group compared with the placebo group (P < .001, P < .001, and P < .01, respectively). A significant decrease was also found in eosinophil counts (P < .001) in the montelukast group compared with the placebo group after treatment. Montelukast treatment did not produce a significant effect on eNO levels compared with placebo (P = .96). CONCLUSION Montelukast treatment provided significant improvement in symptoms and peripheral eosinophil counts of school-age children with seasonal allergic rhinitis; however, it did not show a significant effect on eNO levels.

The seroprevalence of Helicobacter pylori and nitric oxide in acne rosacea

Background Acne rosacea is a dermatosis with unknown etiology. Some studies have reported a high prevalence of Helicobacter pylori infection in acne rosacea. Other studies have reported a decrease in the severity of the lesions of acne rosacea after eradication of H. pylori. H. pylori is a Gram‐negative bacterium which colonizes the gastric mucosa and increases the synthesis of oxygen radicals, such as superoxide and proinflammatory cytokines. These cytokines have been demonstrated to stimulate the synthesis of the inflammatory species nitric oxide (NO). In this study, we examined the role of NO in the possible effect of H. pylori in acne rosacea.

The serum nitric oxide levels in patients with Duchenne muscular dystrophy

Nitric oxide is formed in skeletal muscle by the neuronal type nitric oxide synthase and the signalling function of dystrophin and related compounds are in part mediated by nitric oxide. Duchenne muscular dystrophy, mdx mice and patients with Becker dystrophy demonstrated neuronal type nitric oxide synthase deficiency in muscle biopsy specimens. We have intended to find out whether the plasma nitric oxide levels show any abnormality in patients with Duchenne muscular dystrophy. Serum NO levels of Duchenne patients (4.191+/-2.82 micromol/l) were significantly lower than those of the control (39.53+/-19.43 micromol/l) and cerebral palsy (77.84+/-21.70 micromol/l) groups.

Nitric oxide in Henoch-Schönlein purpura.

Objective : To assess the value of nitric oxide (NO) production on the disease activity in children with Henoch-Schönlein purpura (HSP) by measuring serum nitrate levels and urinary nitrate excretion as an indicator for NO production. Methods : The study group consisted of 25 patients and 20 healthy children. We measured serum nitrate, urinary excretion of nitrate, and CRP levels in the acute phase and after remission. Results : Serum nitrate levels in the acute phase of the disease were found to be increased compared to the remission phase (28.67 - 10.3 mmol/l, 14.16 - 2.02 mmol/l) (p<0.001) and the control group (13.15 - 2.28 mmol/l) (p<0.001). Urinary nitrate excretion in the acute phase of the patients (15.32 - 9 mmol/mg) was increased compared to that in the remission phase (8.26 - 4.3 mmol/mg) (p=0.016) and in the control group (7.24 - 4.9 mmol/mg) (p<0.01). Conclusion : Serum NO and urinary nitrate excretion were found to be elevated in patients with HSP and this increase was associated with activation of the disease rather than its severity. These findings suggest a role for NO in the pathogenesis of HSP, but nitric oxide in HSP should be further studied in order to elucidate the pathophysiology of the disease

Taurine and calcium interaction in protection of myocardium exposed to ischemic reperfusion injury

We aimed to investigate the cardio-protective role of taurine with low calcium level against reperfusion damage by adding taurine to extracellular fluid. Guinea-pig hearts were mounted on Langendorf perfusion apparatus and different compositions of perfusion solutions were prepared for each experimental group. After 20 min of normothermic ischemia the hearts were reperfused. Pre-ischemic, post-ischemic and post-reperfusion percentage changes of heart rate and contractile force were compared. Post-reperfusion tissue weight, malondialdehyde (MDA) and prostaglandin E-like activity (PGE-like activity) were assessed. Taurine-added low-calcium perfusion solution significantly decreased the postischemic myocardial injury.

Impact of Stress, Gender and Menstrual Cycle on Immune System: Possible Role of Nitric Oxide

Stress is a factor found to be involved in the etiology of many diseases. Gender and menstrual cycle phases are other factors affecting the predisposition of individuals for certain diseases. Results from animal and human studies suggest that the distribution of immune system cells may change at different phases of the menstrual cycle. Acute mental stress in humans alters immune variables, too. The increase in the number of natural killer (NK) cells is the most consistent finding among the immune variables, though there are controversies for the other lymphocyte groups. Nitric oxide (NO) as an immune mediator has an unsettled role whether it causes the redistribution of the immune cells, or is an end product of lymphocyte activation. This study was planned to investigate the effect of mental stress on lymphocyte subtypes and the role of NO, for men and women at different phases of the cycle. For this purpose, healthy men (n = 10) and women (n = 10), during the follicular and luteal phases underwent Stroop colour-word interference and cold pressor tests. The immune system responses before and after the tests were determined by cell counts with the flowcytometer. Menstrual cycle phase was ascertained by plasma estrogen and progesterone measurements. Stress response was evaluated by blood pressure (BP) and heart rate (HR) measurements throughout the tests and plasma cortisol and urinary metanephrine and vanillylmandelic acid (VMA) measurements before and after the tests. Plasma and urinary NO determinations were performed before and after the test was completed. All the results were analysed with the appropriate statistical methods. The luteal phase differed from the other groups due to the presence of suppressed immune response to acute stress, including decreased CD4/CD8 ratio and NK cell percentage. On the other hand, acute stress caused a shift from cellular to humoral immunity in men. As indicated by these results, individual reaction towards stress is affected by gender and menstrual cycle phase. NO appears to be a possible effector molecule for these differences.