Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients.

OBJECTIVES: We examine how well ozone/oxygen gas therapy treats chronic hepatitis C patients with varying degrees of liver fibrosis. Also to study the effect of giving multiple anti-oxidants with the ozone/oxygen gas mixture, to see if this addition would have any additive or synergistic effect. METHODS: Two hundred and twenty three patients with chronic hepatitis C. Liver biopsies were carried out at after 12 weeks of administering an ozone/oxygen gas mixture. RESULTS: The mean stage of fibrosis decreased from 1.98 to 1.41 and the mean grade of inflammation decreased from 10.08 to 7.94, both with a p value less than 0.001. After 12 weeks of treatment, mean PCR values increased. No single significant complication was recorded in a total of >9,000 settings of ozone therapy. CONCLUSIONS: Ozone oxygen gas mixture is safe and effective in treatment of hepatic fibrosis due to chronic viral hepatitis C.

Protective effect of hot peppers against amyloid ß peptide and brain injury in AlCl3-induced Alzheimer's disease in rats.

Objectives: This study investigated the therapeutic effect of red hot pepper (Capsicum annuum) methanolic extract in induced Alzheimer's disease using AlCl3 in male rats. Materials and Methods: Rats were injected with AlCl3 intraperitoneally (IP) daily for two months. Starting from the 2nd month of AlCl3, rats received, in addition, IP treatments with Capsicum extract (25 and 50 mg/kg) or saline. Other groups received only saline or Capsicum extract at 50 mg/kg for two months. Brain levels of reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were determined. Additionally, paraoxonase-1 (PON-1) activity, interleukin-6 (IL-6), Aß-peptide, and acetylcholinesterase (AChE) concentrations in the brain were measured. Behavioral testing included wire-hanging tests for neuromuscular strength and memory tests such as Y-maze and Morris water maze. Histopathology of the brain was also done. Results: Compared with saline-treated rats, AlCl3 caused significant elevation of brain oxidative stress as GSH level and PON-1 activity were depleted along with MDA and NO level elevation in the brain. There were also significant increases in brain Aß-peptide, IL-6, and AChE levels. Behavioral testing indicated that AlCl3 decreased neuromuscular strength and impaired memory performance. Capsicum extract given to AlCl3-treated rats significantly alleviated oxidative stress and decreased Aß-peptide and IL-6 in the brain. It also improved grip strength and memory functioning and prevented neuronal degeneration in the cerebral cortex, hippocampus, and substantia nigra of AlCl3-treated rats. Conclusion: Short-term administration of ASA (50 mg/kg) has adverse effects on male reproductive function in mice. Co-administration of melatonin protects against ASA-induced impairment of male reproductive function by preventing the reduction in serum TAC and testosterone levels seen with ASA treatment alone.

The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome.

OBJECTIVES: Premature atherosclerosis and ischemic heart disease represent a major cause of comorbidities among children with Turner syndrome. The identification of non-traditional risk aspects is crucial for the early identification and management of such comorbidities through establishing effective preventive measures. The aim of the study is to explore the role of the deficiency of vitamin B12, folic acid and homocysteine in children with Turner syndrome. METHODS: The study included 78 children with Turner syndrome and 67 healthy age and sex matched children. Karyotype was implemented for all patients. The serum levels of vitamin B12, folic acid and serum homocysteine were assessed. The prevalence of the deficiency of vitamin B12 and folic acid was estimated to study its correlation to hyperhomocysteinemia in Turner syndrome children. RESULTS: The karyotype analysis showed 45,X (monosomy X) in the 78 patients. Vitamin B12 and folic acid were significantly decreased in children with Turner syndrome in 65-73% of the patients, respectively, while the serum level of homocysteine significantly increased to 48.7% compared to healthy controls. Homocysteine level negatively correlated with vitamin B12 and folic acid. The deficiency of vitamin B12 and folic acid increased the risk of hyperhomocysteinemia in children with Turner syndrome (OR 2.49 and 2.36, respectively). CONCLUSIONS: This report highlights that hyperhomocyste-inemia in children with Turner syndrome may be related to the deficiency vitamin B12 and folic acid.

Acidic Exo-Polysaccharide Obtained from Bacillus sp. NRC5 Attenuates Testosterone-DMBA-Induced Prostate Cancer in Rats via Inhibition of 5 α-Reductase and Na+/K+ ATPase Activity Mechanisms.

Bacillus sp. NRC5 is a new strain that grows in Egyptian beaches. This strain produces acidic exo-polysaccharide that have excellent antioxidant, anti-inflammatory and anti-tumor properties. The current study aimed to introduce a new natural product feasible for prostate cancer therapies. The anti-prostate cancer of acidic exo-polysaccharide produced from marine Bacillus sp. NRC5 (EBPS) was determined using 7,12-dimethylbenz-(a)-anthracene; DMBA-induced prostate cancer in male Sprague Dawley rats. Rats were subcutaneously injected with testosterone (3 mg/kg/day for 3 months) and a single dose of DMBA (65 mg/kg) for induction of prostate cancer. EBPS was administrated orally at dose 200 mg/kg/day for 3 months. To study protective effect of EBPS, animals received EBPS before cancer induction, meanwhile in therapeutic effect animals received EBPS after cancer induction. EBPS debug oxidative stress and inflammatory conditions associated with prostate cancer. EBPS either protective or therapeutic material considerably reduced cancer growth rate-limiting enzyme-i.e., 5-α-reductase (46.89 ± 1.72 and 44.86 ± 2.56 µg Eq/mL) and Na+/K+ ATPase (0.44 ± 0.03 and 0.42 ± 0.02 µg Eq/mL), compared to cancer control (69.68 ± 3.46 µg Eq/mL). In addition, both cancer biomarkers-i.e., prostate-specific antigen and carcinoembryonic antigen were significantly lowered as evidence of the ability of EBPS to protect and treat prostate cancer in chemically induced rats. EBPS showed protective and therapeutic efficacy on testosterone-DMBA-induced prostate cancer rats with a good safety margin. This study may go to clinical trials after a repeated study on another type of small experimental animal, their offspring, and one big experimental animal.

Inhibition of aluminum chloride-induced amyloid Aß peptide accumulation and brain neurodegeneration by Bougainvillea spectabilis flower decoction.

OBJECTIVES: To investigate the potential therapeutic effect of Bougainvillea spectabilis flower decoction on aluminum chloride (AlCl3)-induced neurotoxicity. MATERIALS AND METHODS: Rats received daily intraperitoneal injections of AlCl3 at 10 mg/kg for two months and were treated with B. spectabilis decoction at 50 or 100 mg/kg or saline during the 2nd month of the study. The control group received saline. Brain malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), acetylcholinesterase (AChE), amyloid Aß peptide, and interleukin-6 (IL-6) concentrations and paraoxonase-1 (PON-1) activity were determined and brain histology was done. Behavioral and neurological testing included Morris water maze (WMZ), Y maze, and wire hanging. RESULTS: Compared with saline controls, AlCl3 significantly increased brain MDA and NO along with decreased GSH and PON-1 activity. It also increased AChE, IL-6, and amyloid Aß concentrations. AlCl3 impaired motor strength and memory performance and caused brain neurodegeneration. B. spectabilis decoction given at 50 or 100 mg/kg protected against the biochemical and histopathological alterations evoked by AlCl3 by alleviating the increase in MDA and NO, and decrease in GSH and PON-1 activity. B. spectabilis decoction showed no significant effect on AChE but markedly decreased IL-6 and amyloid Aß in the brain of AlCl3-treated rats. It also restored memory performance and motor strength, and protected against AlCl3-induced neurodegeneration. CONCLUSION: These results suggest that B. spectabilis flower decoction might prove of value in the treatment of Alzheimer's disease.

Circulating glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase-L1 as markers of neuronal damage in children with epileptic seizures.

BACKGROUND: Epilepsy is a common neurological disease that has a negative impact on physical, social, and cognitive function. Seizure-induced neuronal injury is one of the suggested mechanisms of epilepsy complications. We aimed to evaluate the circulating level of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) as markers of neuronal damage in children with epilepsy and its relation to epilepsy characteristics. STUDY DESIGN: METHODS: This case control study included 30 children with epilepsy and 30 healthy children as a control group. Seizure severity was determined based on Chalfont score. Serum level of GFAP and UCH-L1were measured, and their associations with epilepsy characteristics were investigated. RESULTS: Circulating levels of GFAP and UCH-L1 were significantly higher in children with epilepsy than in controls (17.440 ± 6.74 and 5.700 ± 1.64 vs 7.06 ± 3.30 and 1.81 ± 0.23, respectively) especially in those with generalized and active seizures. GFAP and UCH-L1 were significantly correlated to the severity of seizures in the previous 6 months. Elevated GFAP level was a predictor for active seizures (OR 1.841, 95%CI 1.043-3.250, P = 0.035). CONCLUSION: Circulating GFAP and UCH-L1 expression is increased in children with epilepsy especially those with active seizures. SIGNIFICANCE: GFAP and UCH-L 1may serve as peripheral biomarkers for neuronal damage in children with epilepsy that can be used to monitor disease progression and severity for early identification of those with drug-resistant epilepsy and those who are in need for epilepsy surgery.

The effect of low dose amphetamine in rotenone-induced toxicity in a mice model of Parkinson's disease.

OBJECTIVES: The effects of low dose amphetamine on oxidative stress and rotenone-induced neurotoxicity and liver injury were examined in vivo in a mice model of Parkinson's disease. MATERIALS AND METHODS: Male mice were treated with rotenone (1.5 mg/kg, every other day for two weeks, subcutaneously). Mice received either the vehicle or amphetamine intraperitoneally at doses of 0.5, 1.0, or 2.0 mg/kg. Oxidative stress was assessed by measurement of the lipid peroxidation product malondialdehyde (MDA), nitric oxide (NO), total anti-oxidant capacity (TAC), and paraoxonase-1 (PON-1) activity in the brain and liver. In addition, brain concentrations of nuclear factor kappa B (NF-κB) and tyrosine hydroxylase were determined and histopathology and Bax/Bcl-2 immunohistochemistry were performed. RESULTS: The levels of lipid peroxidation and NO were increased and TAC and PON-1 were decreased significantly compared with vehicle-injected control mice. There were also significantly increased NF-κB and decreased tyrosine hydroxylase in the brain following rotenone administration. These changes were significantly attenuated by amphetamine. Rotenone caused neurodegenerative changes in the substantia nigra, cerebral cortex, and hippocampus. The liver showed degenerative changes in hepatocytes and infiltration of Kupffer cells. Bax/Bcl2 ratio was significantly increased in brain and liver tissues. Amphetamine prevented these histopathological changes and the increase in apoptosis evoked by rotenone. CONCLUSION: These results suggest that low dose amphetamine exerts anti-oxidant and anti-apoptotic effects, protects against rotenone-induced neurodegeneration, and could prevent neuronal cell degeneration in Parkinson's disease.

The role of KATP channel blockade and activation in the protection against neurodegeneration in the rotenone model of Parkinson's disease.

AIMS: Several studies suggested that ATP-sensitive potassium channels (KATP) are potential therapeutic targets for protection against various neurodegenerative disorders, yet, there is an ongoing controversy regarding their role in Parkinson's disease (PD). Thus, the aim of the current study is to investigate the protective effect of KATP blockade and activation in the mice rotenone model of PD. MAIN METHODS: PD has been induced by 9 subcutaneous injections of rotenone (1.5 mg/kg; 3 times/week) in adult male Swiss albino mice. For 3 consecutive weeks, parkinsonian mice were either untreated or treated with L-dopa (25 mg/kg), the KATP channel blocker glibenclamide (3 mg/kg) or the KATP channel opener nicorandil (6 mg/kg). KEY FINDINGS: Glibenclamide significantly improved motor performance in the wire hanging and stair tests and halted the decline in striatal dopamine content as well as dopaminergic neurons' density. In addition, it reduced the rotenone-induced apoptosis as portrayed in the immunohistopathological examination via increasing Bcl-2 and decreasing caspases-3, -8, -9 contents. Furthermore, through its anti-inflammatory potential, glibenclamide reduced tumor necrosis factor-alpha level. On the other hand, nicorandil failed to mitigate the rotenone-induced neurodegenerative consequences. SIGNIFICANCE: KATP channel blockade by glibenclamide has neuroprotective effect against rotenone-induced neurotoxicity, that was mediated by its anti-inflammatory effect along with hindering apoptosis through extrinsic and intrinsic pathways.

Correction to: Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures.

The original version of this article unfortunately contains an error in the Y axis units in Fig. 1b, c (the symbol µ is not clear: µmol/g.tissue). This has been corrected by publishing this erratum.

Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures.

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.

Acidic Exopolysaccharide Produced from Marine Bacillus amyloliquefaciens 3MS 2017 for the Protection and Treatment of Breast Cancer.

PURPOSE: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine Bacillus amyloliquefaciens 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms. METHODS: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA). B. amyloliquefaciens 3MS 2017 anti-breast-cancer property was evaluated by studying its effects on cancer-growth-rate-limiting enzymes (aromatase and Na+/K+ ATPase), sexual hormones (estrogen and progesterone), antioxidant and inflammatory biomarkers (cyclooxygenase-1; COX-1 and cyclooxygenase-2; COX-2). The incidence of breast cancer by DMBA was dependent on the level of carcinoembryonic antigen (CEA) and aromatase. RESULTS: 7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na+/K+ ATPase subunits levels and CEA close to the normal level. Besides, BAEPS modulated a sexual hormone, in comparison with the cancer control group (P ⩽ .05). B. amyloliquefaciens 3MS 2017 selectively inhibited COX-2 in parallel with promising antioxidant properties. The curative characters of BAEPS were more promising than the prophylactic. CONCLUSION: The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.

Bee venom attenuates neurodegeneration and motor impairment and modulates the response to L-dopa or rasagiline in a mice model of Parkinson's disease.

OBJECTIVES: This study aimed to investigate the effect of bee venom, a form of alternative therapy, on rotenone-induced Parkinson's disease (PD) in mice. Moreover, the possible modulation by bee venom of the effect of L-dopa/carbidopa or rasagiline was examined. MATERIALS AND METHODS: Rotenone (1.5 mg/kg, subcutaneously; SC) was administered every other day for two weeks and at the same time mice received the vehicle (DMSO, SC), bee venom (0.065, 0.13, and 0.26 mg/kg; intradermal; ID), L-dopa/carbidopa (25 mg/kg, intraperitoneal; IP), L-dopa/carbidopa+bee venom (0.13 mg/kg, ID), rasagiline (1 mg/kg, IP) or rasagiline+bee venom (0.13 mg/kg, ID). Then, wire hanging and staircase tests were performed and mice were euthanized and brains' striata separated. Oxidative stress biomarkers namely, malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), paraoxonase-1 (PON-1), and total antioxidant capacity (TAC) were measured. Additionally, butyrylcholinesterase (BuChE), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and dopamine (DA) were evaluated. Brain histopathological changes and caspase-3- expression were done. RESULTS: Bee venom significantly enhanced motor performance and inhibited rotenone-induced oxidative/nitrosative stress, observed as a reduction in both MDA and NO along with increasing GSH, PON-1, and TAC. Besides, bee venom decreased MCP-1, TNF-α, and caspase-3 expression together with an increase in BuChE activity and DA content. CONCLUSION: Bee venom alone or in combination with L-dopa/carbidopa or rasagiline alleviated neuronal degeneration compared with L-dopa/carbidopa or rasagiline treatment only. Bee venom via its antioxidant and cytokine reducing potentials might be of value either alone or as adjunctive therapy in the management of PD.

Differential expression of miRNAs regulating NF-κB and STAT3 crosstalk during colitis-associated tumorigenesis.

Inflammatory bowel disease (IBD) is mostly responsible for the development of colitis-associated colon cancer. Of the several signaling pathways involved in colonic inflammation, the activation and crosstalk between NF-κB and STAT3 serve as the pivotal regulatory hubs that regulate epithelial tumorigenesis by linking inflammation with cancer development. Understanding the molecular mechanisms regulating the crosstalk between NF-κB and STAT3 will help in targeting these signaling pathways and halt epithelial tumorigenesis. MicroRNAs (miRNAs) play important role in the regulation of NF-κB and STAT3 and function in a positive- or negative feedback loop to regulate the crosstalk of these transcription factor. In the present study we evaluated the aberrant expression of a selected panel of miRNAs (miR-181b, miR-31, miR-34a, miR-146b, miR-221, and miR-155) that regulate the crosstalk between NF-κB and STAT3 during colitis-associated tumorigenesis. We used the stepwise colorectal carcinogenesis murine model known as Azoxymethane (AOM)/Dextran sodium sulphate (DSS) to recapitulate the different stages of tumorigenesis. Our results revealed that the expression of the selected miRNAs changed dynamically in a stepwise pattern as colonic tissue transforms from normal to actively inflamed to neoplastic state, in accordance with the gradual activation of NF-κB and STAT3, suggesting that the aberrant expression of these miRNAs could function as the epigenetic switch between inflammation and colorectal tumorigenesis. We were able to elucidate the contribution of miRNAs in the NF-κB - STAT3 crosstalk during the stepwise development of colitis-associated carcinoma, and this could improve our understanding of the molecular pathology of colorectal tumorigenesis and even suggesting a therapeutic strategy by modulating the expression of these regulating miRNAs.

Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects.

Background Depression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms. Methods This research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. Results The sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues. Conclusions Geranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

Polyneuropathy Associated with Severe Iron Overload and Oxidative Stress in ß-Thalassemia Patients.

To investigate the frequency of peripheral neuropathy in patients with ß-thalassemia, and to assess its relation to iron overload and oxidative stress. Sixty ß-thalassemia patients with mean age of 19 ± 4.9 years were recruited. Serum ferritin was quantitatively assessed by enzyme-linked immunoassay and biomarkers of oxidative stress were estimated calorimetrically. Electrophysiological studies using NEMUS 2, Galileu Software were carried out. The patients were separated into two groups: those with abnormal nerve conduction studies (NCS) {Group A; N = 38} and those with normal NCS {Group B; N = 22}. Thirty-eight (63.3%) patients had axonal motor neuropathy as evidenced by abnormal NCS (group A), they showed higher mean serum ferritin (p < 0.01), higher mean malondialdehyde (MDA) (p < 0.01), and lower mean nitrous oxide, total antioxidant capacity, paraoxonase-1 (PON1) (p < 0.01) compared to group B. Bivariate analysis of NCS data demonstrated that abnormal NCS were more frequent in splenectomized patients (p = 0.002), and poorly-chelated patients with serum ferritin ≥ 2000 ng/ml (p = 0.001). Significant variables associated with abnormal motor NCS were entered in stepwise regression analysis and only elevated serum ferritin (p = 0.01) was independently associated with abnormal motor NCS (p = 0.02; 95% CI 1.433-51.791). None of the studied patients had sensory neuropathy or myopathy. Peripheral motor neuropathy may occur in ß-thalassemia patients at a high frequency, regardless of their age and gender. Severe iron overload may contribute to the pathogenesis of neuropathy. Other factors including chelation therapy, splenectomy, and oxidative stress might have an enhancing effect that couldn't be proved in this study.

[Omega-6/omega-3 ratio and cognition in children with epilepsy]. / Cociente omega-6/omega-3 y cognición en niños con epilepsia.

INTRODUCTION: Cognitive impairment is a common consequence of epilepsy in children. This study aimed to assess the ratio of omega-6 to omega-3 fatty acid levels and its impact on cognitive function in children with idiopathic epilepsy. PATIENTS AND METHODS: We performed a case-control study in 30 children with idiopathic epilepsy and 20 healthy children. We measured levels of alpha-linolenic acid (omega-3) and linoleic acid (omega-6) by means of gas-liquid chromatography. We assessed cognitive function with the Arabic version of the fourth edition of the Stanford-Binet test and the P300 component of event-related potentials. All children had an intelligent quotient greater than 70. RESULTS: Children with epilepsy had lower levels of omega-3 and higher levels of omega-6 fatty acids and an abnormal omega-6/omega-3 ratio compared to non-epileptic children. We found a significant positive correlation of serum omega-3 levels and a significant negative correlation of serum omega-6 levels with cognitive function scores and P300 latency in children with epilepsy. CONCLUSION: Children with epilepsy have abnormal ratios of omega-6 to omega-3 fatty acid serum levels, which is associated with impaired cognitive function in these children.

Oxidative stress contribution to attention deficit hyperactivity disorder in children with epilepsy.

Children with epilepsy have a high incidence of attention deficit hyperactivity disorder (ADHD). Oxidation stress and disturbed neurotransmitters are suggested mechanisms; however, their role is not fully explored. This study evaluates the association between circulating malondialdehyde as an oxidation stress marker, apelin neuropeptide, and ADHD in children with epilepsy. Fifty children with epilepsy of unknown etiology, of which 25 have ADHD, as well as 35 healthy children were included. Serum levels of malondialdehyde and apelin were estimated. We investigated the association between seizure severity, response to medications, malondialdehyde, apelin levels, and ADHD in children with epilepsy. Serum malondialdehyde and apelin levels were higher in children with epilepsy, especially those with ADHD. Malondialdehyde and apelin levels have significant positive correlation with the Chalfont Seizure Severity Score. Regression analysis showed that elevated malondialdehyde is an independent risk factor for ADHD in children with epilepsy (OR: 1.401, 95%CI: 1.056-1.859, p= 0.02). No significant association was found between malondialdehyde and apelin levels and the type of epilepsy or ADHD. Longer duration of epilepsy, increased seizure severity, and uncontrolled seizures are associated with increased oxidation stress, which further increased susceptibility for ADHD. In spite of elevated apelin in children with ADHD, the elevation did not increase the risk of ADHD in children with epilepsy.

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy.

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6 months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point > 191.38 ng/ml and > 151.2 ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.