Study on oxidative stress and inflammatory/antioxidant substance levels in autism spectrum disorder.

BACKGROUND: The etiology of autism spectrum disorder (ASD) includes oxidative stress and brain inflammation. We investigated the relationship among oxidative stress markers, in vivo inflammatory substances, and antioxidants that can be easily measured in the clinic and compared them between children with ASD and those with typical development (TD). METHODS: Sixty-one children with TD and 199 with untreated ASD were investigated. They were Japanese children aged 2-15 years and were divided into those aged <7 and ≥7 years. Serum levels of reactive oxygen metabolites (ROMs), high-sensitivity C-reactive protein (hsCRP), prolactin (PRL), albumin (Alb), total bilirubin (T-Bil), and uric acid (UA) were measured. These measurements were compared between TD and ASD, and the relationship between oxidative stress and relevant laboratory parameters was analyzed. RESULTS: The hsCRP and PRL levels were significantly higher in patients with ASD than in those with TD. Among those aged <7 years, hsCRP and PRL were significantly higher in those with ASD than in those with TD. Among those aged ≥7 years, ROMs, hsCRP, and PRL were significantly higher in those with ASD than in those with TD. In ASD, ROMs were significantly correlated with hsCRP, Alb, T-Bil, and PRL. In contrast, no significant correlations were found in the TD group except for the relationship between ROMs and hsCRP in those aged <7 years. CONCLUSION: The results suggest that serum levels of in vivo inflammatory substances, stress-related substances, and antioxidants are altered in ASD under oxidative stress.

Three cases in which drug-induced hyponatremia was improved by replacing carbamazepine with lacosamide.

Carbamazepine often causes drug-induced hyponatremia. Hyponatremia due to carbamazepine may be improved by changing to the same mechanism of action, lacosamide.

Evaluation of the efficacy of drug treatment based on measurement of the oxidative stress, using reactive oxygen metabolites and biological antioxidant potential, in children with autism spectrum disorder and attention deficit hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, mainly characterized by impairment of social communication and restricted interests. ASD is frequently accompanied by attention deficit hyperactivity disorder (ADHD), which is characterized by carelessness, hyperactivity and impulsivity (ASD/ADHD). It has been suggested that ASD and ADHD are associated with oxidative stress, that is, that patients with ASD/ADHD are in a state of increased oxidative stress. There are currenr tly no objective or biological test criteria for evaluating the efficacy of drug therapy in these patients. The purpose of this study was to evaluate whether oxidative stress markers [serum reactive oxygen metabolites (d-ROMs) levels and biological antioxidant potential (BAP)] can be used as objective indicators for evaluating the efficacy of drug treatment in ASD/ADHD patients. METHODS: The subjects of this study subjects were 50 Japanese patients with ASD/ADHD aged 4 to 14 years old. Serum samples were obtained from the patients to measure the serum levels of d-ROMs and the serum BAP. The study subjects were divided into two age groups: preschool children (4 to 6 years old) and school-age children (7 to 14 years old), and the serum levels of d-ROMs, serum BAP, serum BAP/d-ROMs ratio (hereinafter, the prefix serum will be dropped), and scores on the Parent-interview ASD Rating Scales-Text Revision (PARS-TR) and ADHD Rating Scale (ADHD-RS) were determined before and after drug therapy and compared between the two groups. In addition, changes in the d-ROMs, BAP and BAP/d-ROMs ratio and changes in the scores on the PARS-TR and ADHD-RS after treatment were also analyzed. RESULTS: Significant decrease of the d-ROMs, BAP, and scores on the PARS-TR and ADHD-RS, with a significant increase of the BAP/d-ROMs ratio, was observed after treatment. In addition, a significant correlation was observed between the changes in the d-ROMs and changes in the scores on the PARS-TR and ADHD-RS after treatment in the school-age ASD/ADHD children. CONCLUSION: Our results suggest the possibility that the serum level of d-ROMs may be useful as an objective assessment marker to supplement the subjective assessment of the effects of drug treatment in school-age children with ASD/ADHD.

Assessment of oxidative stress in autism spectrum disorder using reactive oxygen metabolites and biological antioxidant potential.

There are several studies on oxidative stress of Autism Spectrum Disorder (ASD), but in these cases there is no study to measure oxidative stress and antioxidant capacity at the same time or studies considering childhood development. Therefore, this study comprehensively assessed the level of oxidative stress in ASD children by simultaneously measuring reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The subjects were Japanese, 77 typical development (TD) children, 98 ASD children, samples were plasma. The subjects were divided into age groups: toddlers/preschool age (2-6 years) and school age (7-15 years), to compare the relationships among the d-ROMs levels and BAP/d-ROMs ratios. Furthermore, the correlations between the Parent-interview ASD Rating Scales (PARS) scores and the measured values were analyzed. The levels of d-ROMs were significantly higher in the ASD (7-15 years) than in TD (7-15 years). The PARS scores were significantly higher in the ASD and were significantly correlated with d-ROMs levels. These results suggested that d-ROMs and BAP/d-ROMs ratios could be objective, measured indicators that could be used in clinical practice to assess stress in ASD children.

Evaluation of oxidative stress and antioxidant capacity in healthy children.

BACKGROUND: Measurement of the levels of the derivatives of reactive oxygen metabolites (d-ROMs) and of the biological antioxidant potential (BAP) enables simultaneous assessment of oxidation degree and antioxidant capacity, using the same sample and testing equipment. At present, reference values of healthy adults are clarified, but the reference value of healthy children is unknown. This study was undertaken to clarify the age-related changes and the reference values of d-ROMs and BAP in healthy children. METHODS: The study population consisted of 77 children, ranging in age from 2 to 15 years, in normal mental and physical health as examined by a pediatrician, and seven healthy adult volunteers. Serum samples were obtained from the subjects for assay. Using these samples, d-ROMs and BAP values were measured, and the relationship with age was analyzed. RESULTS: The d-ROMs level decreased as the age increased, while the BAP showed no correlation with the age. The d-ROMs level was significantly higher in 2-6 years group than in 7-11 years group, 12-15 years group, or healthy adults group. The BAP/d-ROMs ratio, an index of antioxidant capacity, increased significantly with higher age. CONCLUSION: This study was carried out for the first time in healthy children in oxidative stress assessment using d-ROMs and BAP. In the infancy 2-6 years, the d-ROMs value was significantly higher and the BAP/d-ROMs ratio was significantly lower. From this, it was suggested that age should be considered when performing oxidative stress assessment using d-ROMs and BAP in children.

Impact of Oxidative Stress and Newer Antiepileptic Drugs on the Albumin and Cortisol Value in Severe Motor and Intellectual Disabilities With Epilepsy.

BACKGROUND: Epilepsy is a common complication in patients with severe motor and intellectual disabilities (SMID). There are no reports as yet of the effects of these medications in vivo other than their epileptic efficacy. The purpose of this study was to clarify the effects of the newer antiepileptic drugs (AEDs) on the blood biochemical parameters and oxidative stress in SMID with epilepsy by comparing the therapeutic effects between a group of patients receiving lamotrigine (LTG) and levetiracetam (LEV) in addition to the conventional AEDs (newer AED group) and a group receiving conventional AEDs alone (old AED group). METHODS: The study population consisted of 44 SMID patients with epilepsy, of which 23 were allocated to the newer AED group and 21 were allocated to the old AED group. In the newer AED group, measurements of the reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP) and serum albumin were carried out at the following two time points: 1 week before and 1 year after the start of administration of the newer AEDs. In the old AED group, measurements of the same variables were performed at two time points 1 year apart. RESULTS: A significant decrease of the d-ROM levels and a significant increase of the BAP were noted in the newer AED group. A significant elevation of the serum albumin was also evident. In the old AED group, a significant increase of the d-ROMs levels was noted at the second measurement. Cortisol levels which have been described to be related to the albumin, revealed a significant decrease of the serum cortisol in relation to elevation of serum albumin in the newer AED group. CONCLUSIONS: The present study results suggest that the addition of newer AEDs reduces the oxidative stress load and improves the antioxidant potential of the body. Furthermore, the present data also demonstrate that the newer AEDs have indirect impact on biological parameters.

A study of oxidative stress and the newer antiepileptic drugs in epilepsy associated with severe motor and intellectual disabilities.

BACKGROUND: Patients with severe motor and intellectual disabilities (SMID) are those who have both severe intellectual disabilities and severe physical disabilities. Intractable epilepsy is often associated with SMID. The purpose of this study was to elucidate the relationship between epilepsy associated with SMID and oxidative stress, and to clarify the safety and efficacy of the newer antiepileptic drugs (newer AEDs), lamotrigine and levetiracetam. METHODS: This study was conducted in 27 SMID patients with epilepsy who were treated with the newer AEDs. The patient characteristics and the safety and efficacy of the newer AEDs were investigated. The reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP) levels were measured as indicators of the degree of oxidative stress. The relationship between the investigation results (the patient characteristics, and the safety and efficacy of the newer AEDs) and the results of measurements of the d-ROMs/BAP were analyzed. RESULTS: All the patients who discontinued the newer AEDs had abnormal plasma d-ROM levels. In addition, all the patients who developed adverse events also had abnormal d-ROM levels. Furthermore, there was a trend toward a lower response rate in patients with higher plasma d-ROM levels. CONCLUSION: The results of this study suggested that d-ROM levels are useful for predicting the safety and efficacy of the newer AEDs (lamotrigine, levetiracetam) in SMID patients with intractable epilepsy. Therefore, d-ROMs could be important biomarkers for determining the safety and efficacy of drug therapy in SMID patients with epilepsy.

Oxidative Stress Measurement and Prediction of Epileptic Seizure in Children and Adults With Severe Motor and Intellectual Disabilities.

BACKGROUND: The medical care of severe motor and intellectual disabilities (SMID) depends on the empirical medical care. Epileptic seizure specific to SMID is difficult to suppress using anti-epileptic drugs, and its tendency to persist for long periods poses an issue. The present study was undertaken to evaluate the relationship between epileptic seizure in cases with SMID and oxidative stress in the living body by examining endogenous antioxidants, the degree of oxidation (reactive oxygen metabolites (d-ROMs)), and the biological antioxidant potential (BAP) as indicators. METHODS: Target patients were 43 SMID epilepsy patients. Blood was sampled before breakfast and medication. As for the specimen, d-ROMs and BAP were measured using the free radical analyzer. RESULTS: The present study did not reveal any correlation between endogenous antioxidants (albumin) and the frequency of epileptic seizures. On the other hand, d-ROMs were correlated with the frequency of epileptic seizure. In particular, strong correlations between the frequency of epileptic seizures and the d-ROMs/BAP ratio as well as the BAP/d-ROMs ratio were noted. CONCLUSIONS: These results indicate that the use of d-ROMs and BAP as biomarkers can provide a tool for predicting the prognosis of epileptic seizures in patients with SMID.