Relationship of Oxidant and Antioxidant Markers to Asthma Severity in Egyptian Asthmatic Children

BACKGROUND: Asthma is a chronic airway disease which is characterized by oxidant antioxidant imbalance with the generation of oxidative stress related mediators.AIM: The study aimed to evaluate the role of asymmetric dimethylarginine, and malondialdehyde as oxidant markers and serum paraoxonase activity as an antioxidant marker in asthma, and to determine their relationship to the asthma severity and lung function among asthmatic children in Egypt.PATIENTS AND METHODS: This case control study was conducted on sixty patients with asthma compared with sixty apparently healthy children of matched age and sex.RESULTS: Serum concentrations of oxidant markers as asymmetric dimethylarginine and malondialdehyde were significantly increased in asthmatic patients while anti-oxidant marker as paraoxonase activity was significantly decreased compared to healthy controls (P < 0.05). ANOVA test revealed highly significant elevation of the serum concentrations of oxidant markers while anti-oxidant marker was significantly decreased in severe asthmatic patients (P < 0.001) compared to the patients with moderate and mild asthma respectively. Serum malondialdehyde concentration was a strong predictor of asthma severity by multiple regression analysis (P < 0.05).CONCLUSION: The study revealed an imbalance between oxidative and antioxidant defence systems in asthmatic children. Serum concentration of malondialdehyde was the most predictive biomarker having a significant association with asthma severity

Serum Asymmetric Dimethylarginine, and Adiponectin as Predictors of Atherosclerotic Risk among Obese Egyptian Children

BACKGROUND: Obesity is associated with an increased risk of developing hyperinsulinemia, dyslipidemia, hypertension, premature atherosclerosis, and coronary artery disease in the future.AIM: This study is designed to assess the relationship between serum adiponectin, asymmetric dimethylarginine (ADMA), and lipid profile among Egyptian overweight and obese children.METHODS: This cross sectional case control study included 40 selected pre-pubertal overweight and obese children, 24 girls (60%) and 16 boys (40%) aged between 5 to 13 years (8.85 ± 2.7 years), from new cases attending the National nutrition institute clinic during 2013. Forty apparently healthy children of matched age and sex were recruited as a control group.RESULTS: Obese group showed highly significant higher levels of serum ADMA, triglycerides, and total cholesterol compared with healthy controls (P <0.000 in all). However, serum adiponectin levels were highly significant lower in obese children compared to healthy controls (P < 0.000). Serum ADMA showed significant positive correlations with height, serum total cholesterol and serum triglycerides levels and significant negative correlation with the body mass index and weight for age z score.  Serum adiponectin showed significant negative correlations with BMI, weight, and weight for age z score and significant positive correlation with serum triglycerides. By linear regression analysis; serum adiponectin, and serum triglycerides levels were significant predictors of high serum ADMA level (p =0.045 and 0.015 respectively). BMI, weight, height and serum triglycerides were significant predictors of low serum adiponectin levels (p = 0.005, 0.022, 0.026 and 0.015 respectively).CONCLUSIONS: Our results revealed that ADMA, Adiponectin and lipid profile can be considered as predictive biomarkers in prediction and prevention of atherosclerotic risk in the future among overweight and obese Egyptian children

ROLE OF APELIN/MONOCYTE CHEMOATTRACTANT PROTEIN-1, INFLAMMATORY, APOPTOTIC MARKERS IN THE REGULATION OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Objective: The objective of this study is to investigate blood nuclear factor κB (NF-κB), apelin, Lipid peroxide product ; thiobarbituric acid (TBA) malonaldehyde (MDA), monocyte chemoattractant protein-1 (MCP-1), B-cell lymphoma 2 (Bcl2), and paraoxonase (PON1) levels in patients with non -alcoholic fatty liver disease (NAFLD) in a trail to correlate the significance of these biomarkers in the diagnosis and initiation of NAFLD patients.Methods: A total of 32 patients with NAFLD and 45 healthy controls were enrolled in the study. Apelin levels were measured along with, NF-κB, MCP1, MDA, Bcl2, and PON1 were detected.Results: Significant increase in serum NF-κB, MDA, MCP1, and apelin levels in NAFLD patients with percentages increase 1031.23, 293.02, 165.93, and 120 %, respectively, while significant reduction in PON1 and BCl2 with percentages decrease 54.58 and 79.03 %, respectively, were detected as compared to controls. A significant correlation was found between serum concentration of the measured biomarkers with the incidence of NAFLD.Conclusions: It could be concluded that the patients with NAFLD have significantly increased circulating apelin, NF-κB, and MDA levels as compared to healthy control subjects while significant reduction in BCl2 and PON1 levels were recorded. Besides, the NAFLD status is tightly attributed to the existence of insulin resistance and oxidative stress

Preventive effects of cannabis on neurotoxic and hepatotoxic activities of malathion in rat

Objective: To investigate the effect of Cannabis sativa extract on the development of neuro- and hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ-Tetrahydrocannabinol content of the extract (20%) was quantified using gas chromatography–mass spectrometry. The doses of cannabis extract were expressed as Δ -tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion (150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract (10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide and paraoxonase-1 (PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase (BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased (P<0.05) and GSH significantly decreased with respect to control levels (P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1% (P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg. Conclusions: Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p < 0.05). A statistically significant higher mean level serum neopterin concentration (p < 0.05) was found in JIA patients (20.43 ± 8.73 nmol/L) than in controls (6.88 ± 2.87 nmol/L) (p < 0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-a, IL-6, MCP-1, and JADAS-27 (p < 0.05). No correlation was found between serum neopterin and CRP (p > 0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05).CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients

Neuroprotection by misoprostol against rotenone-induced neurotoxicity in rat brain

Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods: Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000 μ g/kg. Rats were evaluated for brain lipid peroxidation (malondialdehyde: MDA), reduced glutathione (GSH), nitric oxide (NO) levels, and paraoxonase-1 (PON-1) activity. The concentrations of the anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase (iNOS) in the cerebral cortex and striatum were also performed. Results: Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation (MDA) by 61% (P<0.05) accompanied by an increase in NO by 73.1% (P<0.05) and a decrease in GSH concentration by 29.4% (P<0.05). In addition, brain PON-1 activity significantly decreased by 63.0% (P<0.05) and striatal Bcl-2 significantly decreased by 27.9% (P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation. Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum. Treatment with misoprostol at doses of 100 and 1 000 μ g/kg resulted in decreased brain MDA (by 16.5%-23.0%) (P<0.05) and NO levels (by 37.1%-40.7%) (P<0.05) and increased GSH concentrations (by 18.8%-30.1%) (P<0.05). PON-1 activity was significantly increased by 80.0%-114.8% (P<0.05) by misoprostol at 100 and 1 000 μ g/kg, respectively. In addition, misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats. Conclusions: These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study

OBJECTIVE:the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia.METHODS:the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls.RESULTS:mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes.CONCLUSION:children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research

Diagnostic utility of biomarkers in diagnosis of early stages of neonatal sepsis in neonatal intensive care unit in Egypt

Background: Neonatal sepsis is considered one of the major causes of morbidity and mortality in NICUs. To avoid unnecessary treatment of non-infected neonates, emergence of multidrug resistance organisms, prolonged hospitalization and a considerable economic burden, particularly in developing countries with poorly-equipped NICUs, an early, sensitive and specific laboratory test would be helpful to guide clinicians in neonatal units to decide whether or not to start antibiotics. Objective: C-reactive protein (CRP), tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1 (IL-1) were measured in an attempt to identify a set of tests which can confirm or refute the diagnosis of neonatal sepsis at an early stage before administration of antibiotics. Methods: Assessment of serum levels of CRP, TNF-α, IL-6 and IL-1 was done using quantitative enzyme immunoassay sandwich technique in 116 neonates (36 newborns with clinically suspected sepsis, 48 newborns with culture-proven sepsis and 32 infection-free neonates). Results: The cutoff levels for CRP at >12 mg/l had a sensitivity of 91% and specificity of 100%, for TNF-α at >113.2 ng/ml had a sensitivity of 83% and specificity of 100%, for IL-6 at >16.8 pg/ml had a sensitivity of 100% and specificity of 47%, and for IL-1 at >15 pg/ml had a sensitivity of 100% and specificity of 47% for the diagnosis of infection before antibiotics. Conclusion: The area under ROC curve (AUC) of TNF and CRP in the diagnosis of sepsis was superior to determinations of IL-1 and IL-6. From our data analysis and based on our financial backgrounds, we can conclude that abnormal of CRP levels together with immature-to-total neutrophil ratio above 0.2 with or without elevated IL-1, IL-6 or TNF can be used as early markers of sepsis in neonates