İbrahim Kaplan

BDNF and cortisol levels in children with or without post-traumatic stress disorder after sustaining sexual abuse

OBJECTIVE There are studies reporting that cortisol and brain-derived neurotropic factor (BDNF) play a role in the pathophysiology of post-traumatic stress disorder (PTSD). However, up-to-date no study evaluated the relationship between PTSD and the levels of cortisol and BDNF in children and adolescents who have sustained trauma. The aim of this study was to investigate whether BDNF, cortisol and adrenocorticotropine (ACTH) levels differ between individuals who developed PTSD or not following a sexual trauma. METHOD The study included 55 children aged between 6 and 17 years who sustained sexual assault (M/F: 13/42). The patients were divided into two groups, with or without PTSD based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Of the participants, 49% (n=27) were diagnosed with PTSD. Cortisol, ACTH, and BDNF levels were evaluated using the ELISA method. RESULTS There were no significant differences between patients with or without PTSD in terms of cortisol, ACTH, BDNF levels. There were no correlations between CAPS-CA scores and cortisol, ACTH, and BDNF levels in patients with or without PTSD. In patients with PTSD, decreased cortisol levels were found with increasing time after trauma, and no significant correlation was found with the cortisol levels in patients without PTSD. CONCLUSION Although no significant association was found between biochemical parameters and the presence or severity of PTSD; decreasing cortisol levels with increasing time after trauma in patients with PTSD suggest that cortisol might have played a role in the pathophysiology of this disorder.

Fibulin-3 as a Diagnostic Biomarker in Patients with Malignant Mesothelioma

BACKGROUND New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. MATERIALS AND METHODS This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. RESULTS Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). CONCLUSIONS We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

Identifying autonomic nervous system dysfunction in acute cerebrovascular attack by assessments of heart rate variability and catecholamine levels.

Objective: This study aimed to evaluate changes in the autonomic nervous system caused by cerebral lesions due to acute stroke. We assessed heart rate variability and catecholamine levels in lieu of stroke lesion localization. Materials and Methods: A total of 60 stroke patients and 31 healthy controls were enrolled in the study. Plasma epinephrine and norepinephrine levels were measured on the first, third, and seventh days following the stroke event. Heart rate variability was evaluated with time-domain and frequency-domain analyses via 24-hour Holter monitor recordings. Results: On the first and third day following the stroke, norepinephrine levels were significantly higher in all patient groups as compared to controls. Epinephrine levels on the first, third and seventh days after the stroke were significantly higher in patients with lesions in the right middle cerebral artery territory than controls. In frequency-domain analysis, patients with right middle cerebral artery territory lesions had greater low frequency and low frequency to high frequency ratio values than controls. Time-domain analysis revealed significant decreases in the standard deviation from the mean for 5-minute 288 R-R intervals in patients with lesions in the right middle cerebral artery and posterior cerebral artery territory when contrasted with controls. Patients with lesions in the right middle cerebral artery territory demonstrated the highest increase in the percentage of consecutive R-R intervals differing by more than 50 ms (pNN50) as compared to the control group. Conclusion: These findings indicate that autonomic dysfunction favoring an increase in sympathetic activity occurs in acute stroke patients.

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE.

Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

Diagnostic performance of increased prolidase activity in schizophrenia.

We investigated whether prolidase activity has a diagnostic test value in schizophrenia and assessed the relation between prolidase activity and sociodemographic-clinical characteristics of patients with schizophrenia. Fifty patients with schizophrenia (diagnosed as schizophrenia according to DSM-V criteria) and 50 healthy volunteers were included in this study. Case and control groups had a similar distribution in age, sex, body mass index (BMI), and smoking status. Serum prolidase activity was measured in both groups and was determined to be significantly higher in the patient group (509.706±41.918) compared to the control group (335.4±13.6; t=6.231; p=0.0001). A cut-off point of 392.65U/L prolidase was determined for diagnostic measures from the plotted ROC curve. The area under the ROC curve was 1.000, which was significant (p<0.0001). Higher values were assigned as the disease state. Both positive predictive value (PPV) and negative predictive value (NPV) were 100% at the cut-off point of 392.650U/L. The prolidase levels of the control group were all below the cut-off point. There were no statistically significant differences between the two groups with regard to age, gender, or BMI (p>0.05), and no correlation was found between mean prolidase activity and age of onset of the disease, family history, disease duration, number of hospitalizations, subtypes of schizophrenia, PANSS scores or sub-scores, CGI-S scores, S-A scale scores, and the antipsychotic treatment (p>0.05). The results of this study indicate that serum prolidase activity may be a useful diagnostic test for schizophrenia; however, further studies are needed to verify this.

Therapeutic effects of thymoquinone in a model of neuropathic pain.

Background The goal of our study was to determine the therapeutic effects of thymoquinone in a dose-dependent manner in a model of neuropathic pain following an experimentally applied spinal cord injury (SCI). Methods Fifty female adult Wistar albino rats weighing between 220 and 260 g were included in the study and were divided into 5 groups as follows: Group S (sham), Group C (control), Group T100 (100 mg/kg thymoquinone), Group T200 (200 mg/kg thymoquinone), and Group T400 (400 mg/kg thymoquinone). To begin the experiment, SCI was applied to all groups (with the exception of the sham group) following a mechanical and heat–cold test. Two weeks later, the mechanical and heat–cold tests were repeated, and a single normal saline dose was given to the sham and control groups, whereas 3 varying doses of thymoquinone were given to the other groups. The mechanical and heat–cold tests were repeated at 30, 60, 120, and 180 minutes after receiving thymoquinone. Finally, the animals were put to death via the removal of intracardiac blood. The levels of nitric oxide, total oxidant status, total antioxidant status, paraoxonase, malondialdehyde, tumor necrosis factor-α, and interleukin-1β were determined in all of the blood samples. Results The withdrawal threshold and withdrawal latency values recorded from the mechanical and heat–cold allodynia measurements for all 3 thymoquinone groups were higher than that of the control group at all time points (ie, 30, 60, 120, and 180 minutes). There were no differences in these results between the 3 thymoquinone groups. The paraoxonase and total antioxidant status serum levels of all 3 thymoquinone groups were higher than those of the control group, whereas total oxidant status, nitric oxide, malondialdehyde, interleuken-1β, and tumor necrosis factor-α levels were lower in the 3 thymoquinone groups than in the control group. Conclusions Thymoquinone is beneficial for decreasing experimental neuropathic pain following SCI. However, increasing the dose does not change the effect.

Oxidative Stress and DNA Damage in Untreated First-Episode Psychosis in Adolescents.

Objective: Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents. Methods: This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM-IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined using the ELISA method and commercial ELISA kits. Results: The mean age was 14.5 ± 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 ± 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05). Conclusions: This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia.

Examining the levels of BDNF and cortisol in children and adolescent victims of sexual abuse—a preliminary study

BACKGROUND Previous reports have suggested the biological and psychological effects of trauma induced by cortisol and brain-derived neurotrophic factor (BDNF). The present study compared the levels of BDNF, cortisol, and adrenocorticotropic hormone (ACTH) in children and adolescent victims of sexual abuse to those without a trauma history. METHODS The study was conducted in the Department of Child Psychiatry at Dicle University. The study included 44 children (M/F: 12/32) aged between 8 and 17years who experienced sexual abuse with 42 age-and gender-matched children who did not have a history of trauma. Cortisol, ACTH, and BDNF levels were measured using ELISA. RESULTS Cortisol levels were higher and BDNF levels were significantly lower in the victims of sexual abuse compared to the control group. The mean time that elapsed from the initial sexual abuse occurrence until the date of examination was 22.7±21.7months. The evaluation of the relationship between this time span and cortisol levels revealed that cortisol levels decreased with increasing time after trauma. Cortisol and BDNF levels were lower in the victims who experienced multiple sexual assaults. CONCLUSIONS The results of the present study suggest that cortisol and BDNF could be biological molecular mediators of the effects of trauma on biological and psychological systems. This is the first report on the effects of cortisol and BDNF induced trauma in child and adolescent victims of sexual abuse.

Cortisol and Brain-Derived Neurotrophic Factor Levels Prior to Treatment in Children With Obsessive-Compulsive Disorder.

OBJECTIVE In this study, we investigated serum brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels between children with obsessive-compulsive disorder (OCD) prior to treatment and healthy controls. In addition, the study aimed to assess any correlations between OCD symptom severity and BDNF, ACTH, and cortisol levels. METHODS Twenty-nine children, aged from 7 to 17 years (male/female: 21/8) and diagnosed with OCD according to DSM-IV prior to treatment, were compared with 25 healthy control subjects (male/female: 16/9). The study was conducted between December 2012 and December 2013. The Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL), Childrens Yale-Brown Obsessive Compulsive Scale, and Childrens Depression Inventory (CDI) were administered to the children. BDNF, ACTH, and cortisol levels were detected using a prepared kit with the enzyme-linked immunosorbent assay method. RESULTS BDNF, ACTH, and cortisol levels in the OCD group were significantly higher when compared with the control group (P = .02, P = .03, and P = .046, respectively). No association was detected between the severity and duration of OCD symptoms and BDNF, ACTH, and cortisol levels. CDI scores in both groups were similar. The mean (SD) duration of OCD symptoms was 17.9 (18.5) months. CONCLUSIONS Our findings suggest that BDNF levels adaptively increase as a result of the damaging effects of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity on brain tissue in the early stages of OCD. HPA axis abnormalities and BDNF may play a role in the pathogenesis of the disease.