Organ crosstalk: the potent roles of inflammation and fibrotic changes in the course of organ interactions.

BACKGROUND: Organ crosstalk can be defined as the complex and mutual biological communication between distant organs mediated by signaling factors. Normally, crosstalk helps to coordinate and maintain homeostasis, but sudden or chronic dysfunction in any organ causes dysregulation in another organ. Many signal molecules, including cytokines and growth factors, are involved in the metabolic dysregulation, and excessive or inappropriate release of these molecules leads to organ dysfunction or disease (e.g., obesity, type 2 diabetes). AIM AND METHOD: The aim of this review is to reveal the impact of organ crosstalk on the pathogenesis of diseases associated with organ interactions and the role of inflammatory and fibrotic changes in the organ dysfunction. After searching in MEDLINE, PubMed and Google Scholar databases using 'organ crosstalk' as a keyword, studies related to organ crosstalk and organ interaction were compiled and examined. CONCLUSION: The organ crosstalk and the functional integration of organ systems are exceedingly complex processes. Organ crosstalk contributes to metabolic homeostasis and affects the inflammatory response, related pathways and fibrotic changes. As in the case of interactions between adipose tissue and intestine, stimulation of inflammatory mechanisms plays an active role in the development of diseases including insulin resistance, obesity, type 2 diabetes and hepatic steatosis. The increased level of knowledge about the 'crosstalk' between any organ and distant organs will facilitate the early diagnosis of the disease as well as the management of the treatment practices in the short- and long-term organ dysfunction.

Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin-induced renal fibrosis model.

AIM: Renal fibrosis is a common cause of renal dysfunction with chronic kidney diseases. This process is characterized by excessive production of extracellular matrix (ECM) or inhibition of ECM degradation. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases, which are widely presented in mammals, have very critical roles in ECM remodelling. We aimed to study the role of ADAMTS proteinases and some of the ECM markers in the pathogenesis of renal fibrosis and to investigate the effects of hypoxia on these biomarkers. METHODS: In addition to the control group, Adriamycin (ADR) treated rats were divided into four groups as ADR, sham and two hypoxia groups. Renal nephropathy was assessed biochemical assays, pathological and immunohistochemical staining methods. The expression of ADAMTSs and mRNA were determined using Western blotting and real-time PCR, respectively. RESULTS: Renal dysfuntion and tissue damage in favour of ECM accumulation and renal fibrosis were observed in the ADR group. This was approved by remarkable changes in the expression of ADAMTS such as increased ADAMTS-1, -12 and -15. In addition, it was found that hypoxia and duration of hypoxia enhanced markers of tubulointerstitial fibrosis in the rat kidney tissues. Also, expression differences especially in ADAMTS-1, -6 and -15 were observed in the hypoxia groups. The variable and different expression patterns of ADAMTS proteinases in the ADR-induced renal fibrosis suggest that ADAMTS family members are involved in the development and progression of fibrosis. CONCLUSION: The expression changes of ADAMTS proteinases in kidney and association with hypoxia have potential clues to contribute to the early diagnosis and treatment options of renal fibrosis.

Increased Exhaled 8-Isoprostane and Interleukin-6 in Patients with Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori (H. pylori) infection triggers both local inflammation, usually in gastric mucosa, and chronic systemic inflammation. It is assumed that this local and systemic inflammation is caused by extracellular products excreted by H. pylori. The aim of this study was to investigate the possible association between H. pylori infection and a local inflammatory response in the airway by using exhaled breath condensate technique. MATERIALS AND METHODS: This study includes 41 H. pylori seropositive patients who have gastric symptoms and 27 healthy control subjects. Pulmonary function tests (PFT), chest X ray, and physical examination were performed in all patients and interleukin-6 (IL-6), 8-isoprostane and nitrotyrosine levels were measured in exhaled breath condensate. RESULTS: Levels of IL-6 and 8-isoprostane in exhaled breath condensate (EBC) were significantly higher in H. pylori positive patients than control subjects (p < 0.05). Nitrotyrosine levels were also higher in H. pylori positive patients but the difference was not statistically significant. Both groups had similar leukocyte counts, C-reactive protein (CRP) levels and PFT parameters. CONCLUSION: H. pylori infection causes an asymptomatic airway inflammation which can be detected by exhaled breath condensate. The clinical importance of this inflammation remains unclear.

Influence of CPAP treatment on airway and systemic inflammation in OSAS patients.

AIM: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent respiratory disorders in the upper airways during sleep. Although continuous positive airway pressure (CPAP) has been accepted to be the most effective treatment for OSAS, its role on inflammation remains debatable. In this study, our aim was to examine the influence of 3 months of CPAP treatment on tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), 8-isoprostane, and peroxynitrite levels in exhaled breathing condensates (EBC) and serum. METHODS: Thirty-five patients who were newly diagnosed as moderate or severe OSAS with full night polysomnography and used CPAP therapy regularly for 3 months were included in the study. Polysomnography, spirometric tests, fasting blood samples, and EBC were ascertained on entry into the study and after 3 months of treatment. All patients were assessed monthly for treatment adherence and side effects. RESULTS: We found that all polysomnographic parameters were normalized after CPAP therapy in the control polysomnogram. Also, all markers in EBC and nitrotyrosine and 8-isoprostane levels in serum were decreased significantly with CPAP treatment. Sedimentation rate, C-reactive protein, IL-6, and TNF-α remained unchanged in serum after treatment. We found that baseline nitrotyrosine levels were significantly correlated with apnea-hypopnea index, oxygen desaturation index, and percent time in SpO2 < 90 % (p < 0.01). CONCLUSIONS: CPAP therapy has primarily a relevant impact on airways, and nitrotyrosine levels correlated well with severity of OSAS. This treatment decreases both inflammation and oxidative stress levels in airways in OSAS patients. Also, this treatment helps to decrease systemic oxidative stress levels in serum.

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

PURPOSE: To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients. METHODS: Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis. RESULTS: PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group. CONCLUSION: In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal damage in a rat model of gastric injury.

The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.

In vivo and in vitro antineoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.

Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at µM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.

Lymphocyte subpopulations in Sheehan's syndrome.

The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

Inter-organ Crosstalk and the Effect on the Aging Process in Obesity.

Aging is characterized by progressive regression in tissue and organ functions and an increased risk of disease and death. Aging is also accompanied by chronic low-grade inflammation. Both obesity and aging are associated with the development of metabolic diseases, leading to an increase in the senescent cell burden in multiple organs. Chronic low-grade inflammation of adipose tissue is one of the mechanisms implicated in the progression of these diseases. As a real endocrine organ, adipose tissue secretes many mediators and hormones (adipokines) to maintain metabolic homeostasis, and their dysfunction has been causally linked to a wide range of metabolic diseases. Dysfunctional adipose tissue participates in interorgan communication both by producing new signaling mediators and by transforming or disrupting signal mediators, reaching from other organs. In addition to obesity and similar metabolic diseases, this situation causes dysfunction in more organs in the aging process, and the complexity of the problem causes challenges in the diagnosis and treatment processes. This review aims to highlight recent developments and current information supporting the relationship between obesity and adipose tissue dysfunction with aging and the role of homeostatic and physio-pathological processes that mediate interorgan communication in aging progress. More understanding clearly of interorgan communication in the process of obesity and aging will facilitate the early diagnosis as well as the management of treatment practices in short- and long-term organ dysfunction.

The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity.

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.

Uric acid and pentraxin-3 levels are independently associated with coronary artery disease risk in patients with stage 2 and 3 kidney disease.

BACKGROUND AND OBJECTIVES: Cardiovascular disease is prevalent in chronic kidney disease (CKD). Uric acid is increased in subjects with CKD and has been linked with cardiovascular mortality in this population. However, no study has evaluated the relationship of uric acid with angiographically proven coronary artery disease (CAD) in this population. We therefore investigated the link between serum uric acid (SUA) levels and (i) extent of CAD assessed by the Gensini score and (ii) inflammatory parameters, including C-reactive protein (CRP) and pentraxin-3, in patients with mild-to-moderate CKD. MATERIAL AND METHODS: In an unselected population of 130 patients with estimated glomerular filtration rate (eGFR) between 90 and 30 ml/min/1.73 m(2), we measured SUA, serum pentraxin-3, CRP, urinary protein-to-creatinine ratio, lipid parameters and the severity of CAD as assessed by coronary angiography and quantified by the Gensini lesion severity score. RESULTS: The mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively. The Gensini scores significantly correlated in univariate analysis with gender (R = -0.379, p = 0.02), uric acid (R = 0.42, p = 0.001), pentraxin-3 (R = 0.54, p = 0.001), CRP (R = 0.29, p = 0.006) levels, eGFR (R = -0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with smoking status, diabetes mellitus, and lipid parameters. After adjustments for traditional cardiovascular risk factors, only uric acid (R = 0.21, p = 0.02) and pentraxin-3 (R = 0.28, p = 0.01) remained significant predictors of the Gensini score. CONCLUSIONS: SUA and pentraxin-3 levels are independent determinants of severity of CAD in patients with mild-to-moderate CKD. We recommend a clinical trial to determine whether lowering uric acid could prevent progression of CAD in patients with CKD.

The potential pathophysiological role of altered lipid metabolism and electronegative low-density lipoprotein (LDL) in non-alcoholic fatty liver disease and cardiovascular diseases.

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a range of conditions caused by a build-up of fat in the liver. It is usually seen in people who are overweight or obese. Increasingly common around the world, this disease is the most common chronic liver disease in the United States, affecting about a quarter of the population. Recently, the designation of NAFLD as 'metabolic dysfunction-associated fatty liver disease' (MAFLD) has been a subject of current debate. In this context, 'insulin resistance' is the underlying common and basic pathophysiological mechanism of metabolic dysfunction due to its association with obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome, dyslipidemia and NAFLD. All these pathological conditions are among the metabolic risk factors for cardiovascular diseases, too. Also, due to the bidirectional causality between NAFLD and cardiovascular diseases, a liver-heart axis is suggested. Therefore, various factors such as insulin resistance as well as systemic inflammation, cytokines, oxidative stress, adipokines, hepatokines, genes and intestinal microbiota have been identified as possible pathogenic factors that play a role in the explanation of the complex NAFLD and cardiovascular risk relationship. Recent data and cumulative evidence show that electronegative low-density lipoprotein [LDL (-)/L5] cholesterol is a promising biomarker for complex organ interactions and diseases associated with liver-heart axis. In this mini review, we focus not only on recent data on NAFLD mechanisms, but also on the potential of the lipid mediator LDL (-)/L5 as a diagnostic and therapeutic target for liver-heart line diseases.

Association of serum fetuin-A with valvular calcium concentration in rheumatic mitral valve disease.

BACKGROUND AND AIM OF THE STUDY: Fetuin-A is an acute-phase glycoprotein that inhibits ectopic calcification. The study aim was to assess serum fetuin-A levels in patients with rheumatic mitral valve disease (RMVD), and to evaluate the association of fetuin-A with the extent of mitral valve calcification, determined either echocardiographically or by the measurement of calcium and phosphorus concentrations in the resected valve tissues. METHODS: The study group comprised 21 patients (14 females, seven males; mean age 48 +/- 12.4 years) with RMVD, who were scheduled for mitral valve replacement surgery, while 30 age- and gender-matched healthy subjects (17 females, 13 males; mean age 43.6 +/- 11.1 years) served as a control group. Baseline serum fetuin-A levels were measured using ELISA, and high-sensitivity C-reactive protein (hs-CRP) levels using immunonepholometry. A Wilkins score was calculated using transesophageal echocardiography, and the resected valve tissues were analyzed for concentrations of calcium and phosphorus. RESULTS: Serum fetuin-A levels were lower and hs-CRP levels higher in the study group than in controls (300.4 +/- 92.5 microg/ml versus 352.6 +/- 55.3 microg/ml, p = 0.028; and 1.9 +/- 1.2 mg/dl versus 0.3 +/- 0.2 mg/dl, p < 0.0001, respectively). An inverse correlation was found between serum fetuin-A and hs-CRP levels (r = -0.690, p = 0.001). A significant association of either serum fetuin-A or hs-CRP was also found to occur with calcium concentration in the mitral valve tissue (r = -0.684, p = 0.001, and r = 0.510, p = 0.018, respectively), but not with the Wilkins calcium score. Serum fetuin-A and phosphorus concentrations in the MV tissue were independent predictors of calcium concentration in the MV tissue. CONCLUSION: Serum fetuin-A, which is significantly decreased in patients with RMVD, is an independent predictor of calcium concentration in the mitral valve tissue.

The relationship between obstructive sleep apnea syndrome and obesity: A new perspective on the pathogenesis in terms of organ crosstalk.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a common disorder that has a major impact on public health. The connection between OSAS and obesity is very complex and likely represents an interaction between biological and lifestyle factors. Oxidative stress, inflammation and metabolic dysregulation are both actors involved in the pathogenesis of OSAS and obesity. Also, the current evidence suggests that gut microbiota plays a significant role in the emergence and progression of some metabolic disorders. When the relationship between OSAS and obesity is evaluated extensively, it is understood that they show mutual causality with each other, and that metabolic challenges such as impaired microbiota affect this bidirectional organ interaction, and by ensuing organ injury. OBJECTIVES: The aim of this study is to investigate the association between OSAS and obesity, and the effect of "organ crosstalk" on the pathogenesis of the relationship and to contribute to the diagnosis and treatment options in the light of current data. DATA SOURCE: We performed an electronic database search including PubMed, EMBASE and Web of Science. We used the following search terms: OSAS, obesity, inflammation, metabolic dysregulation and gut microbiota. CONCLUSION: Obesity and OSAS adversely affect many organs and systems. Besides the factors affecting the diagnosis of the OSAS-obesity relationship, mutual organ interactions among the respiratory system, adipose tissue and intestines should not be ignored for prevention and treatment of OSAS and obesity. Comprehensive clinical trials addressing the efficacy and efficiency of current or potential treatments on therapeutic applications in the OSAS-obesity relationship are needed.

Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment.

BACKGROUND: There has been much evidence in recent years that free oxygen radicals and nitric oxide (NO) may play an important role in the pathophysiology of neuropsychiatric disorders. In this study, we aimed to investigate whether NO, xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) levels are associated with major depression (MD) and to evaluate the impact of antidepressant treatments on NO, SOD, ADA and XO levels in MD. METHODS: Thirty-six patients who were diagnosed as MD according to DSM-IV criteria and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured by spectrophotometric methods both in patients and controls. Patients were treated with antidepressant drugs for 8 weeks. All patients were assessed by Hamilton Depression Rating Scale (HDRS) both before and after antidepressant treatment. RESULTS: ADA and XO levels of the patients were significantly higher than the controls. SOD level of the patients was significantly lower than the controls. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between HDRS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased, whereas NO and, XO levels decreased significantly. CONCLUSIONS: ADA, XO, and SOD activity may have a pathophysiological role in MD and may predict prognosis of MD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment.

Examination of lung toxicity, oxidant/antioxidant status and effect of erdosteine in rats kept in coal mine ambience.

Occupational exposure to coal dust causes pneumoconiosis and other diseases. Reactive oxygen species (ROS) have been implicated in the pathogenesis of coal dust-induced lung toxicity. In this experimental study, we investigated the oxidant/antioxidant status, nitric oxide (NO) and hydroxyproline (HP) levels in lungs and blood of rats exposed to coal dust in mine ambience. In addition, we also investigated the attenuating effects of erdosteine. At the end of the experiment processes, tissue levels of HP, malondialdehyde (MDA) and NO, as well as the activities of superoxide dismutase, glutathione peroxidase, catalase, xanthine oxidase (XO), myeloperoxidase (MPO) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated in the lung tissues, plasma samples or erythrocytes of rats. Exposure to coal dust resulted in a significant increase in the oxidant parameters (MDA, NO levels, and XO activity) and HP levels, as compared to the controls. A decrease in activities of antioxidant enzymes, and an increase in MPO activity were found in the study group, compared to the controls. Increased NO levels of lung were found in the study groups, that were significantly reduced by erdosteine. Our studies provide evidence that supports the hypothesis for ROS mediated coal workers' pneumoconiosis. Erdosteine may be beneficial in the coal dust-induced lung toxicity via antioxidant and free radical scavenger properties.

The role of electronegative low-density lipoprotein in cardiovascular diseases and its therapeutic implications.

Cardiovascular disease (CVD) is a health problem of great concern to both the public and medical authorities. Low-density lipoprotein (LDL) has been reported to play an important role in both the development and progression of CVD, but studies are underway to determine how LDL exerts its effects. In recent years, it has been found that LDL has several subfractions, each of which affects endothelial function differently; L5, the most electronegative fraction, has been shown to be unique in that it induces an atherogenic response. This review examines the current knowledge concerning the relationships between L5 and CVD and highlights the role of L5 in the pathophysiology of CVD, especially with regards to atherosclerosis.

Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes.

Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.