Kynurenine, Kynurenic Acid, Quinolinic Acid and Interleukin-6 Levels in the Serum of Patients with Autism Spectrum Disorder.

Background and Objectives: It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2-3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods: Forty-three ASD children aged 2-9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results: The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD (p < 0.05), there was no significant difference (p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters (p > 0.05). Conclusions: We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD.

Assessing the relationship between antipsychotic drug use and prolidase enzyme activity and oxidative stress in schizophrenia patients: a case-control study.

BACKGROUND: The relationship between proline, its association with oxidative stress, and its connection to schizophrenia is a subject that has not been sufficiently investigated. OBJECTIVE: The aim of this study is to evaluate the possible effects of atypical and combined (typical and atypical) antipsychotic use on serum prolidase enzyme activity (SPEA) and serum oxidative stress parameters, and to assess the relationship between SPEA and oxidative stress in patients with schizophrenia. METHODS: A total of 57 patients with schizophrenia, of which 34 were using atypical (AAPG) and 23 were using combined (typical and atypical) (CAPG) antipsychotic therapy, and 28 healthy volunteers (control group) were included in this case-control study. RESULTS: SPEA levels of AAPG and CAPG were significantly lower than that of control group ( P  = 0.003). The oxidative stress index (OSI) value of AAPG was significantly higher than the other two groups ( P  = 0.001). SPEA (<1860 U/l) and OSI (≥0.54) could discriminate schizophrenia patients with antipsychotic therapy from control groups ( P  = 0.001 and P  = 0.007, respectively). Lower SPEA levels were associated with antipsychotic use ( P  = 0.007). CONCLUSION: The SPEA values of patients with schizophrenia on antipsychotics were significantly lower compared to controls. OSI values were significantly higher in atypical antipsychotic recipients compared to those on combined antipsychotics and healthy controls.

A Preliminary Study on Investigation of Blood-Brain Barrier Damage Markers in Patients with Alcohol Use Disorder Before and After Therapy.

AIM: The use of alcohol affects the central nervous system and plays important roles in various neurological disorders through neurotoxicity resulting from blood-brain barrier (BBB) permeability. The BBB is regulated by tight junction proteins interacting closely with endothelial cells. This study evaluated the serum levels of proteins and spectrin degradation products associated with BBB damage in patients with alcohol use disorder. METHODS: This preliminary case-control study was conducted with 30 healthy volunteers and 26 alcohol use disorder patients. The serum levels of spectrin breakdown product 145 (SBDP145), spectrin breakdown product 150 (SBDP150), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), ubiquitin ligase cullin-3 (ULC), occludin and claudin were measured with enzyme-linked immunosorbent assay. RESULTS: There was no significant difference between the levels of SBDP145, SBDP150, UCHL1, ULC, occludin and claudin before and after treatment in patients with alcohol use disorder. SBDP150 levels were significantly lower in patients than controls (P < 0.001). The area under the curve was 0.841 (0.733-0.949) with the 95% confidence interval for SPDP150. CONCLUSION: A decrease of the serum SBDP150 levels appears to be associated with alcohol use disorder. Future studies might clarify whether diminished serum SBDP150 levels are associated with BBB damage in patients with alcohol use disorder.

Evaluation of Changes in Peripheric Biomarkers Related to Blood Brain Barrier Damage in Patients with Schizophrenia and Their Correlation with Symptoms.

Objective: The aim of the study was to evaluate the levels of peripheric biomarkers that have been associated with blood brain barrier (BBB) damage in healthy controls and two groups of patients with schizophrenia, those who received typical-atypical antipsychotics and those who received only atypical antipsychotics. Additionally, we sought relationships between these biomarkers and schizophrenia symptoms. Methods: This study was conducted with the inclusion of 41 healthy volunteers and 75 patients with schizophrenia. The biomarkers measured to evaluate BBB injury were as follows: spectrin breakdown product 145 (SBDP145), spectrin breakdown product 150 (SBDP150), ubiquitin carboxy terminal hydrolase L1 (UCHL1), ubiquitin ligase cullin-3 (cullin), occludin and claudin, which were measured via ELISA. Symptoms of patients with schizophrenia were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, the Clinical Global Impression Scale (CGI), and the general assessment of functionality (GAF). Results: Compared to controls, SBDP145 (p = 0.022) and cullin (p = 0.046) levels were significantly higher in patients with schizophrenia receiving atypical antipsychotic treatment. SBDP150 levels were lower in the combination treatment group compared to the control group (p = 0.022). Claudin (p = 0.804), occludin (p = 0.058) and UCHL1 (p = 0.715) levels were similar among groups. In recipients of combination treatment, SBDP145 levels were found to be positively correlated with SAPS-total (r = 0.440, p = 0.036) and SAPS-delusions (r = 0.494, p = 0.017) scores. Conclusion: The relationships demonstrated in this study indicate that more comprehensive research is needed to understand whether BBB defects contribute to clinical characteristics in patients with schizophrenia.

End-To-End Computerized Diagnosis of Spondylolisthesis Using Only Lumbar X-rays.

Lumbar spondylolisthesis (LS) is the anterior shift of one of the lower vertebrae about the subjacent vertebrae. There are several symptoms to define LS, and these symptoms are not detected in the early stages of LS. This leads to disease progress further without being identified. Thus, advanced treatment mechanisms are required to implement for diagnosing LS, which is crucial in terms of early diagnosis, rehabilitation, and treatment planning. Herein, a transfer learning-based CNN model is developed that uses only lumbar X-rays. The model was trained with 1922 images, and 187 images were used for validation. Later, the model was tested with 598 images. During training, the model extracts the region of interests (ROIs) via Yolov3, and then the ROIs are split into training and validation sets. Later, the ROIs are fed into the fine-tuned MobileNet CNN to accomplish the training. However, during testing, the images enter the model, and then they are classified as spondylolisthesis or normal. The end-to-end transfer learning-based CNN model reached the test accuracy of 99%, whereas the test sensitivity was 98% and the test specificity 99%. The performance results are encouraging and state that the model can be used in outpatient clinics where any experts are not present.

In Silico Prediction of the Effects of Nonsynonymous Single Nucleotide Polymorphisms in the Human Catechol-O-Methyltransferase (COMT) Gene.

Catechol-O-methyltransferase (COMT) enzyme performs transfer of methyl group to endogenous and exogenous catechol substrates. The COMT enzyme draws interest because of its association with psychiatric, neurological and cardiovascular diseases, and several cancers. Moreover, many prescribed drugs, supplements, and their metabolites are used as substrates of COMT enzyme. The human COMT gene has 226 nonsynonymous single nucleotide polymorphisms (nsSNPs) according to public databases. Uncovering of the molecular impacts of nsSNPs on COMT enzyme function and structure may provide standpoint on how COMT nsSNPs affect enzyme activity and contribute to disease development. Therefore, we aimed in this study to predict possible structural and functional damaging effects of all knowns nsSNPs in COMT gene by applying various bioinformatics tools. Two hundred and twenty-six nsSNPs were obtained from Ensembl, HGMD, ClinVar, and dbSNP databases. Twenty-eight nsSNPs were found to be high-risk changes for protein structure. Some of them were detected in extremely conserved sequences have functional and structural properties. Besides, high-risk nsSNPs were also uncovered to change properties of native COMT protein. Our findings demonstrated the significance of COMT high-risk nsSNPs on protein structure and function. We expect that our results will be helpful in future studies concerning experimental evaluation of the COMT gene polymorphisms and/or the association between COMT polymorphisms and disease development.

Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin-Proteosome System in Autism Spectrum Disorder?

INTRODUCTION: The mechanism of ubiquitination-related abnormalities causing neural development problems is still unclear. We examined the association between autism and serum transactive response DNA-binding protein-43 (TDP-43) and ubiquitin c-terminal hydrolase-L1 (UCH-L1) levels, both of which are members of the ubiquitin-proteosome system. METHODS: We measured serum levels of TDP-43 and UCH-L1 in 24 children with autism and 24 healthy children. Childhood Autism Rating Scale (CARS) was used to assess symptom severity at admission. RESULTS: The mean serum TDP-43 and UCH-L1 levels in children with autism spectrum disorder (ASD) were found to decrease compared to healthy controls (p<0.001, 506.21±780.97 ng/L and 1245.80±996.76 ng/L, respectively; 3.08±5.44 ng/mL and 8.64±6.67 ng/mL, respectively). A positive correlation between serum TDP-43 levels and UCH-L1 levels was found in the ASD group (r=0.947, n=24, p<0.001). The CARS score of children with ASD was 48.91 points (standard deviation [SD]: 5.82). CONCLUSION: Low serum levels of UCH-L1 and TDP-43 may reflect disturbed ubiquitination in autism.

Melatonin Supplementation Ameliorates Energy Charge and Oxidative Stress Induced by Acute Exercise in Rat Heart Tissue.

BACKGROUND: Regular physical exercises may help people to be more resistant to everyday problems; however, how acute and intense exercises affect the heart tissues functioning with maximum capacity and how melatonin changes the effect of acute and intense exercises are still not obvious. We aimed to comprehend whether melatonin intravenous injection supports the oxidative/antioxidative conditions and energy charge in heart tissues of rats exposed to acute swimming exercise. METHODS: Thirty Wistar-albino male rats were categorized into 3 groups with equal number of subjects. Control group performed no application, and acute intensive swimming exercise group were subjected to acute intensive swimming exercise for 30 minutes, and melatonin group were applied 25 mg/kg single dose melatonin administration prior to 30 minutes acute intensive swimming exercise. The levels of malondialdehyde (MDA), and superoxide dismutase, catalase and glutathione peroxidase activities were measured by spectrophotometric method; and the levels of 3-nitrotyrosine (3-NT) and energy charge were determined by a high performance liquid chromatography. RESULTS: Tissue MDA and 3-NT levels of the acute intensive exercise group were found to be higher than the control group. It was also found that the melatonin administration increased the energy charge and antioxidant activities, while decreased tissue MDA and 3-NT levels in heart tissues. Our results provide evidence for melatonin that can exert potent protective effects on oxidative stress and energy charge for heart tissues in acute swimming exercise. CONCLUSIONS: These findings suggest that the direct beneficial effects of melatonin could be potentially applied on prevention of oxidative stress and energy deficit.

A Preliminary Study on Investigation of Serum α-Synuclein and Tau Protein Levels in Children with Attention Deficit Hyperactivity Disorder.

Neurodegenerative molecules play an important role in maintaining a supply for synaptic vesicles; and they are also likely to help regulate the dopamine release which is the primary mechanism of action in pharmacological treatments for attention deficit hyperactivity disorder (ADHD). It is suggested that there could be interactions between α-synuclein and tau in cytoskeletal disorganization and synaptic dystrophy. Therefore, we aim to determine the serum levels of neurodegenerative molecules such as α-synuclein and tau in children with ADHD. The study group consisted of 25 children, aged 6-10, diagnosed with ADHD according to DSM-IV criteria and who appeared at Dicle University, Faculty of Medicine, and Department of Child Psychiatry in Diyarbakir, Turkey. 25 children, having no psychiatric disorders and medical illnesses, were selected as healthy control group. Serum α-synuclein and tau concentrations were determined by Enzyme-Linked Immuno Sorbent Assay. The α-synuclein levels of ADHD were not significantly different than those of controls. The tau levels of ADHD were found to be statistically significantly higher than those of controls. Moreover, α-synuclein levels showed a statistically significantly positive correlation with tau levels in children with ADHD. The results of our preliminary study can suggest that ADHD might possibly share a common disease mechanism with other diseases in terms of tau pathology. Increased serum tau level may be an indication of disturbance of microtubule transportation in the brains of children with ADHD.

Decreased Expression of α-Synuclein, Nogo-A and UCH-L1 in Patients with Schizophrenia: A Preliminary Serum Study.

OBJECTIVE: α-synuclein, Nogo-A and Ubiquitin C-terminal hydrolase L1 (UCH-L1) have neuromodulatory roles for human brain. Therefore, abnormalities of these molecules are associated with neuropsychiatric disorders. Although some serum studies in the other disorders have been made, serum study of α-synuclein, Nogo-A and UCH-L1 is not present in patients with schizophrenia and healthy controls. Therefore, our aim was to compare serum levels of α-synuclein, Nogo-A and UCH-L1 of the patients with schizophrenia and healthy controls. METHODS: Forty-four patients with schizophrenia who is followed by psychotic disorders unit, and 40 healthy control were included in this study. Socio-demographic form and Positive and Negative Syndrome Scale (PANSS) was applied to patients, and sociodemographic form was applied to control group. Fasting bloods were collected and the serum levels of α-synuclein, Nogo-A and UCH-L1 were measured by ELISA method. RESULTS: Serum α-synuclein [patient: 12.73 (5.18-31.84) ng/mL; control: 41.77 (15.12-66.98) ng/mL], Nogo-A [patient: 33.58 (3.09-77.26) ng/mL; control: 286.05 (136.56-346.82) ng/mL] and UCH-L1 [patient: 5.26 (1.64-10.87) ng/mL; control: 20.48 (11.01-20.81) ng/mL] levels of the patients with schizophrenia were significianly lower than healthy controls (p<0.001). CONCLUSION: Our study results added new evidence for explaining the etiopathogenesis of schizophrenia on the basis of neurochemical markers.

Total Tau and Phosphorylated Tau Protein Serum Levels in Patients with Schizophrenia Compared with Controls.

Tau protein is located in the axons of neurons and in Alzheimer Disease, is abnormally phosphorylated and aggregates into paired helical filaments (neurofibrillary tangles) reflecting the degree of neurofibrillary pathology and neurodegeneration. Although tau and phosphorylated tau (p-Tau) pathology is a hallmark for dementia, few studies were performed in patients of schizophrenia. This preliminary serum study was designed to compare serum total tau and p-Tau levels of schizophrenia patients with healthy controls. The study was included 42 patients diagnosed with schizophrenia and 42 healthy control subjects. Sociodemographic form was applied to both groups and PANSS was applied to patient group. Serum total tau and p-Tau levels were measured by ELISA method. Total tau and p-Tau levels of patients were significantly lower than healthy controls. There was a positive correlation between amount of past electroconvulsive therapies and total tau level. However total tau and p-Tau levels were positively correlated. Our study results showed that serum total tau and p-Tau levels of patients with schizophrenia were significantly lower than healthy controls.

How Trace Element Levels of Public Drinking Water Affect Body Composition in Turkey.

Since waterborne minerals appear in ionic form and are readily absorbed by the gastrointestinal tract, drinking water could be a crucial source of mineral intake. However, no comprehensive research has yet determined how trace elements in drinking water relate to body composition. We aimed to assess the relationship between clinically important trace elements in public drinking water and body composition in average, overweight and obese individuals in Turkey. The study's population consisted of 423 participants: 143 overweight, 138 obese and 142 healthy control individuals, grouped according to clinical cutoff points of body mass index (BMI). We measured levels of lithium (Li), nickel (Ni), lead (Pb), silicon (Si), tin (Sn), strontium (Sr), boron (B), aluminium (Al), barium (Ba) and rubidium (Rb) in samples from wells of municipal water by using inductively coupled plasma mass spectrometry. We gauged all the participants' body composition measurements with a BC-418 body composition analyser. In all the participants, body weight values showed significant positive correlations with Ni levels in drinking water, as did BMI values with Al levels and percentage of obesity with Ni, Si and B levels. In particular, Ni levels showed significant positive correlations with the basal metabolic rate, activity calories, and total activity of participants. Giving findings showing correlations between obesity-related parameters and Al, Si, B and Ni content in drinking water, we hope that these associations will be clarified with further studies including cellular, experimental and clinical studies. Hence, medical practitioners must be aware of trace element levels in drinking water for overweight and obese patients.

Elevated levels of tissue plasminogen activator and E-selectin in male children with autism spectrum disorder.

Although the etiopathology of autism spectrum disorder (ASD) is not clear, immune dysfunction has been proposed as a mechanism for the pathophysiology of ASD. The purpose of this study is to examine serum levels of tissue plasminogen activator (t-PA) and some adhesion molecules in children with ASD that have not been investigated previously in detail. The study group included 35 male children aged from 2 to 9 diagnosed with ASD according to DSM-V criteria. Soluble platelet endothelial adhesion molecule-1 (sPECAM-1), P-selectin, E-selectin, and t-PA in the serum were determined with enzyme-linked immunosorbent assay. Autism behavior check list (ABC) is used for the assessment of ASD severity. The levels of t-PA (P = 0.025) and E-selectin (P = 0.007) was detected significantly higher in children with ASD than control group. Serum levels of sPECAM-1 showed statistically significant negative correlation with sensory, body and object-use, language, social, and self-help and total scores in the patient group (r = -0.349, P = 0.04; r = -0.411, P = 0.01; r = -0.412, P = 0.01; r = -0.417, P = 0.01, and r = -0.531, P < 0.01, respectively). Serum levels of P-selectin levels showed statistically significant negative correlation with ABC total score in the patient group (r = -0.378, P = 0.03). It may be suggested that t-PA, E-selectin, P-selectin, and sPECAM-1 a crucial role in inflammatory conditions in children with ASD. Autism Res 2016, 9: 1241-1247. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Serum levels of glial fibrillary acidic protein and Nogo-A in children with autism spectrum disorders.

CONTEXT: Improved biomarkers would facilitate the diagnosis and treatment of autism spectrum disorders (ASD). OBJECTIVE: Our objective was to examine the levels of Nogo-A and glial fibrillary acidic protein (GFAP) in children with ASD. MATERIALS AND METHODS: Serum concentrations of GFAP and Nogo-A were determined by enzyme-linked immunosorbent assay. RESULTS: In this preliminary study, we found that serum Nogo-A was not found significantly different between groups, while serum levels of GFAP were significantly lower in ASD than controls. DISCUSSION AND CONCLUSIONS: It will be of great interest to determine other potential causes of elevated serum levels of GFAP, and whether this elevation has any phenotypic effect.

Low Serum Level α-Synuclein and Tau Protein in Autism Spectrum Disorder Compared to Controls.

α-Synuclein (α-syn) and tau proteins are thought to be related with the synaptic loss and cell death underlying several important neurodegenerative diseases. The aim of our study was to investigate serum α-syn and tau levels in autism. Serum levels of α-syn and tau were measured, and autism spectrum disorder (ASD) severity was assessed at admission using the Childhood Autism Rating Scale (CARS) total score. The mean CARS score of the autism group on admission was 47.91 points (SD: 5.97). The results indicated that the mean serum α-syn and serum tau levels were significantly (p < 0.001) lower in children with ASD as compared with normal cases (33.01 ± 20.78 and 55.19 ± 15.34 ng/mL and 241.23 ± 290.5 and 509.78 ± 269.25 ng/mL, respectively). There was a significant positive correlation between serum α-syn levels and serum levels of tau identified by Pearson correlation analysis (r = 0.922, n = 28, p < 0.001). Synaptic abnormality in autism may result from microglial activity. Furthermore, α-syn and tau aggregation may lead to synaptic dysfunction, and this may contribute to either neuronal or synaptic dysfunction or neurodegeneration. Our preliminary study suggests that low levels of serum α-syn and tau may be implicated in the relationship between synaptic activity and autism.