Significance of O6-methyl guanine methyltransferase promoter methylation in high grade glioma patients: optimal cutoff point, CpG locus, and genetic assay.

PURPOSE: To evaluate O6-methyl guanine methyltransferase (MGMT) promoter methylation status in high grade glioma patients and to identify the best cutoff point as well as the most predictive CpG loci for patients survival. METHOD: Consecutive high grade glioma patients treated with surgical gross total resection followed by concomitant radiochemotherapy and adjuvant chemotherapy were included in this retrospective observational study. Methylation status of MGMT promoter CpG island of resected tumor tissue were evaluated using next generation sequencing assay. The outcomes were grouped as CpG 70-78, CpG 79-83, CpG 84-87, CpG 70-87, and whole promoter. Quantitative analyses were dichotomized as methylated or unmethylated based on the cutoff points set to %10, and methylation was further graded as <%10 unmethylated, %10-30 low-methylated, and %30-100 high-methylated. RESULTS: Total of 95 patients with the mean age of 51.50 ± 12.36 years were included in the study. Overall survival (OS) and progression free survival (PFS) were 14.53 ± 1.92 (95% CI 10.77-18.30) and 10.90 ± 2.05 (95% CI 6.89-14.92) months, respectively. MGMT promoter was methylated in 38.2% of cases and high-methylated in 10.5% of cases. Methylation status of MGMT promoter was recognized as a very powerful predictor of OS and PFS. In particular, high-methylation of CpG 79-83 and CpG 84-87 islands at promoter region were strongly associated with better survival outcomes (p < 0.05). CONCLUSION: Our outcomes support the prognostic value of MGMT promoter methylation in patients with high grade glioma. Sequencing of whole promoter CpG islands demonstrated that methylation of particular CpG sites might predict clinical outcomes more precisely.

Anti-inflammatory and anti-oxidant role of ursolic acid in cerulein-induced acute pancreatitis in rats.

BACKGROUND: Ursolic acid (UA) is found in many plants, and has been reported to have anti-protease, antioxidant, anti-inflammatory, antimicrobial, nephroprotective, hepatoprotective, and cardioprotective effects. OBJECTIVE: The purpose of this study was to investigate the effects of ursolic acid in cerulein-induced acute pancreatitis (AP). MATERIALS AND METHODS: Thirty-two Wistar albino rats were randomly assigned to 4 equal groups: Sham, acute pancreatitis, treatment, and ursolic acid group. RESULTS: Serum amylase levels in the AP and treatment groups were significantly higher than in the others (p < 0.05). In addition, serum IL-1ß, IL-6, and TNF-α levels were significantly higher in the AP group in comparison with the treatment group. Although pancreatic tissue total oxidant activity in the AP and treatment groups was similar, pancreatic tissue total antioxidant capacity was significantly higher in the treatment group than in the AP group. CONCLUSIONS: Damage to the pancreas and remote organs in AP was observed to be reduced by UA. In addition, oxidative stress was observed to be decreased by the effect of UA.

ANTECEDENTES: El ácido ursólico se encuentra en numerosas plantas y se ha informado que tiene efectos antiproteasas, antioxidantes, antiinflamatorios, antimicrobianos, nefroprotectores, hepatoprotectores y cardioprotectores. OBJETIVO: Este estudio tuvo como objetivo investigar los efectos del ácido ursólico en la pancreatitis aguda inducida por ceruleína. MATERIAL Y MÉTODOS: Treinta y dos ratas albinas Wistar fueron asignadas aleatoriamente a cuatro grupos iguales: grupo simulado, grupo de pancreatitis aguda, grupo de tratamiento y grupo de ácido ursólico. RESULTADOS: Los niveles de amilasa sérica en los grupos de pancreatitis aguda y de tratamiento fueron significativamente más altos que en los otros grupos (p < 0.05). Además, los niveles séricos de IL-1ß, IL-6 y TNF-α fueron significativamente más altos en el grupo de pancreatitis aguda en comparación con el grupo de tratamiento. Aunque la actividad oxidante total del tejido pancreático en ambos grupos fue similar, la capacidad antioxidante total del tejido pancreático en el grupo de tratamiento fue significativamente mayor. CONCLUSIÓN: Se observó que el ácido ursólico reduce el daño al páncreas y órganos remotos en la pancreatitis aguda, al igual que el estrés oxidativo.

The contribution of postnatal steroid administration to early brain damage in preterm babies with bronchopulmonary dysplasia

Background/aim: Postnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment. Materials and methods: In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group. Results: There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values. Conclusion: NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone.

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.

Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p < 0.01 for both measurements). Similarly, earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis.

BACKGROUND Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. MATERIAL AND METHODS Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. RESULTS In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). CONCLUSIONS When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties.

Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester (CAPE) on Hepatotoxicity and Pancreatic Injury Caused by Dichlorvos in Rats.

The present study was aimed to the investigate the protective effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity and pancreatic injury caused by acute dichlorvos (D) intoxication in rats. Forty-eight Wistar rats were randomly divided into seven groups each containing seven rats except control groups. The groups included control, D, CAPE, IL, D + CAPE, D + IL, and D + CAPE + IL. Total antioxidant status and total oxidative stress levels were measured by automated colorimetric assay. Tissues were evaluated using hematoxylin and eosin (H&E) staining. Tissues were analyzed with hematoxylin and eosin by using standard protocols. Also, Bcl-2, Bax and caspase-3 were evaluated by immunohistochemical method in liver tissue. Total oxidant status in control, CAPE, and IL groups were significantly lower, and total antioxidant status in the D + CAPE, D + IL, and D + IL + CAPE groups were significantly higher compared to the D group. CAPE and IL treatment decreased the apoptotic and mitotic cell count in liver tissue. Parenchymal necrosis caused by dichlorvos is observed in pancreas tissues of rats. Mild congestion and edema formation occurred in pancreas tissues following D + CAPE and D + IL therapies. These results indicate that CAPE and IL have the potential to decrease oxidative stress and hepatic and pancreatic injuries caused by acute dichlorvos intoxication. These drugs can be considered as a new method for supportive and protective therapy against pesticide intoxication.

The effects of roflumilast on the pancreas and remote organs in a cerulein-induced experimental acute pancreatitis model in rats.

PURPOSE: Systemic damage in acute pancreatitis (AP) can be characterized by oxidative stress and the release of pro-inflammatory cytokines. Roflumilast has been shown to be a potent anti-inflammatory and antioxidant agent. In the present study, we aimed to investigate the effect of roflumilast in cerulein-induced AP. METHODS: Thirty-two male rats were divided into four groups: group 1 (sham), group 2 (Roflumilast), group 3 (AP), and group 4 (AP + Roflumilast). AP was induced by injecting 4 × 75 µg/kg of body weight at an interval of 1 h. Rats were killed after 12 h following the last cerulein administration. AP was confirmed by measuring the serum amylase level and inflammatory features. RESULTS: Morphological changes were observed in the pancreas. Amylase levels were higher in the AP and AP + Roflumilast groups than the sham and Roflumilast groups. The serum levels of TNF-α, IL-1ß, and IL-6 increased in the AP group, whereas they decreased in the Roflumilast group. The total oxidant activity (TOA) was higher and the total antioxidant capacity (TAC) was lower in the AP group. The administration of roflumilast decreased the TOA and increased the TAC in comparison with the AP group (p < 0.05 for both). CONCLUSIONS: Roflumilast significantly decreases oxidative stress and inflammatory mediators in the plasma, pancreas, and lung in cerulein-induced AP rats.

Urinary kidney injury molecules in children with febrile seizures.

OBJECTIVE: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. METHODS: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. RESULTS: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively; p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16, p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16, p < 0.001). CONCLUSION: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.

The Levels of Cortisol, Oxidative Stress, and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study.

In this study we aimed to investigate serum cortisol, oxidative stress, and DNA damage in children who are sexual abuse victims. The study included 38 children who sustained child sexual abuse and 38 age- and gender-matched children who did not have a history of trauma. Cortisol levels reflecting the status of the hypothalamic-pituitary-adrenal axis, anti-oxidant enzymes glutathione peroxidase, superoxide dismutase, natural anti-oxidant coenzyme Q, and 8-hydroxy-2-deoxyguanosine as the indicator of DNA damage were analyzed in serum samples using the enzyme linked immunosorbent assay method. Cortisol levels were significantly higher in the child sexual abuse group compared to the control group. There were no significant differences between the groups in terms of oxidative stress and DNA damage. Cortisol and 8-hydroxy-2-deoxyguanosine levels decreased as the time elapsed since the sexual abuse increased. Coenzyme Q level was lower in victims who sustained multiple assaults than in the victims of a single assault. Cortisol and superoxide dismutase levels were lower in the victims of familial sexual abuse. Decreases in cortisol and 8-hydroxy-2-deoxyguanosine levels as time elapsed may be an adaptation to the toxic effects of high cortisol levels over a prolonged period of time. Child sexual abuse did not result in oxidative stress and DNA damage; however, some features of sexual abuse raised the level of oxidative stress.

Lower Brain-Derived Neurotropic Factor Levels in Untreated Adolescents With First-Episode Psychosis.

OBJECTIVE: Brain-derived neurotropic factor (BDNF) is known to play a role in the pathogenesis of schizophrenia. However, the relationship between early onset schizophrenia and BDNF has not been extensively studied. The aim of the study was to compare the levels of BDNF between adolescent patients with first-episode psychosis (FEP) and the healthy control subjects. METHOD: The study was conducted in the Department of Child Psychiatry at Dicle University. A total of 26 adolescent patients aged between 11 and 17 years who had not received previous therapy and whose conditions were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and 26 age- and sex-matched healthy adolescent control subjects were included. Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and the Positive and Negative Symptom Scale were conducted with all participants. The clinical global impression was used to evaluate disease severity. The BDNF levels were measured in the serum by enzyme-linked immunosorbent assay method. RESULTS: The mean (SD) age was 14.6 (1.6) years in both FEP group (male/female, 11/15) and the control group (P > 0.05). The FEP group had significantly lower serum BDNF levels (2.0 ± 1.9 ng/mL) compared with the control group (3.4 ± 3.0 ng/mL, P = 0.03). There was no significant relationship between BDNF concentration and the Positive and Negative Symptom Scale (positive and negative scores) scores (r = -0.14, P = 0.74 and r = 0.49, P = 0.22, respectively). There was no significant relationship between the duration of untreated psychosis and serum BDNF levels (r = -0.22, P = 0.32). CONCLUSIONS: High incidence of schizophrenia in patients with FEP suggests a relationship between BDNF levels and the pathogenesis of schizophrenia. We suggest that BDNF may be a useful neurobiological marker 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.

The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson's disease.

The role of carcinoembryonic antigen (CEA) in Parkinson's disease (PD) has not been previously investigated. The aim of the present study was to evaluate the serum level of carcinoembryonic antigen, high-sensitivity C-reactive protein (hs-CRP), and Neutrophil/lymphocyte ratio (NLR) among patients with Parkinson's disease and to examine the relationship between these inflammatory markers. The cross-sectional design includes 51 patients with Parkinson's disease and 50 age- and sex-matched healthy controls. We investigated the differences in hs-CRP, CEA, and NLR levels between these two groups. CEA was significantly higher in PD patients relative to the control group (mean 2.40 ± 1.51 vs. 1.72 ± 0.87 (ng/mL), respectively; p = 0.015). Mean NLR was significantly higher in PD patients relative to the control group (mean 3.1 ± 1.3 vs. 2.1 ± 0.32, respectively; p < 0.001). Serum level of hs-CRP was higher in PD patients than in control group (mean 1.04 ± 0.62 and 0.54 ± 0.31, respectively; p < 0.01). Correlation analysis revealed significant correlation between hs-CRP, CEA, and Neutrophil/lymphocyte ratio (p < 0.05). This study demonstrates for the first time the association between CEA, hs-CRP, NLR, and PD. We found CEA, hs-CRP, and NLR levels to be significantly higher in the PD patients than in the normal controls.

Urinary early kidney injury molecules in children with beta-thalassemia major.

BACKGROUND: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-ß-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in children with ß-thalassemia major (ß-TM). MATERIALS AND METHODS: Totally, 52 patients (29 boys, 23 girls) with ß-TM and 29 healthy controls (3-17 years) were included. Various demographic characteristics and blood transfusions/year, disease duration, and chelation therapy were recorded. Serum urea, creatinine, electrolytes, and ferritin and urinary creatinine, protein, calcium, phosphorus, sodium, potassium, and uric acid in first morning urine samples were measured and estimated glomerular filtration rate (eGFR) was calculated. Routine serum and urinary biochemical variables, urinary NAG to Creatinine (U(NAG/Cr)), U(NGAL/Cr), U(KIM-1/Cr), and U(L-FABP/Cr) ratios were determined. RESULTS: Patients had similar mean serum urea, creatinine and eGFR levels compared with controls (p > 0.05 for all). The mean urinary protein to creatinine (U(Protein/Cr)) ratio was significantly higher in patients compared to the healthy subjects (0.13 ± 0.09 mg/mg and 0.07 ± 0.04 mg/mg, respectively; p < 0.001). Significantly increased U(NAG/Cr) (0.48 ± 0.58 vs. 0.23 ± 0.16, p = 0.026) and U(NGAL/Cr) (22.1 ± 18.5 vs. 11.5 ± 6.17, p = 0.01) ratios were found in ß-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or U(KIM-1/Cr) and U(L-FABP/Cr) ratios between patients and controls (p > 0.05). Significant correlations were found between urinary biomarkers and urinary electrolytes (p < 0.05). CONCLUSIONS: Our results suggest that urinary NAG and NGAL may be considered to be reliable markers to monitor renal injury in ß-TM patients.

Serum levels of carcinoembryonic antigen (CEA) in patients with bipolar disorder.

OBJECTIVE: Carcinoembryonic antigen (CEA) is an oncofetal glycoprotein that is widely used as a tumour marker in adenocarcinomas. However, several non-neoplastic conditions, including acute and chronic inflammation and other inflammation-related conditions, are characterised by increased CEA concentrations. Bipolar disorder (BD) ranks seventh among the worldwide burden of non-fatal diseases. Inflammatory biomarkers have been considered as one of the main key pillars of a multifactorial approach for prediction of BD in an at-risk population. BP is accompanied by activation of inflammatory, cell-mediated and negative immunoregulatory cytokines. METHODS: We measured the levels of CEA in serum samples from 44 individuals with euthymic BP out-patients and 45 healthy controls. Patients were diagnosed according to the DSM-IV criteria. CEA was measured by an electrochemiluminescence immunoassay. RESULTS: The mean serum CEA concentration was 2.36±1.52 and 1.77±0.98 µg/l in patients and controls, respectively. CEA levels were significantly increased in euthymic BP patients when compared with controls (p=0.031). CONCLUSIONS: This study suggests that CEA is increased in BD and supports a role for immune activation in the core pathological mechanisms of BP. CEA levels may be a secondary marker for diagnosing BP.

Serum total oxidant and antioxidant status in earthquake survivors with post-traumatic stress disorder.

OBJECTIVE: Oxidative stress has been shown to play an important role in the pathogenesis of post-traumatic stress disorder (PTSD). Although there are some studies on oxidative stress and PTSD, there is no report available on the serum total oxidant and antioxidant status in earthquake survivors with PTSD. Therefore, this study aimed to investigate the serum total oxidant and antioxidant status in earthquake survivors with chronic PTSD. MATERIAL AND METHODS: The study group included 45 earthquake survivors with PTSD and 40 earthquake survivors without PTSD. The oxidative status was determined using the total antioxidant status and total oxidant status (TOS) measurements and by calculating the oxidative stress index (OSI). RESULTS: There were no statistically significant differences in the total antioxidant status, TOS, or OSI when comparing individuals with and without PTSD (all, p>0.05). There were no correlations between Clinician-Administered PTSD Scale scores and oxidant and antioxidant stress markers (all, p>0.05). CONCLUSIONS: Our results suggest that the total oxidant and antioxidant status may not affect earthquake survivors with PTSD. This is the first study to evaluate the oxidative status in earthquake survivors with PTSD. Further studies are necessary to confirm these findings.

Increased fibrinogen, D-dimer and galectin-3 levels in patients with migraine.

There are limited studies evaluating the fibrinogen levels in patients with migraine. It remains unknown whether the levels of the haematological marker of thromboembolism, D-dimer, and the levels of galectin-3, which plays an important role in inflammation as a proinflammatory mediator, change during the attacks in patients with migraine. The present study aims to compare galectin-3, fibrinogen and D-dimer levels in patients with migraine during the attacks and interictal periods, and to compare galectin-3, fibrinogen and D-dimer levels between patients with migraine and healthy controls to investigate the role of these parameters in the pathogenesis of migraine. Fifty-nine patients with migraine and 30 age-gender matched healthy control subjects were enrolled in the study. Blood galectin-3, fibrinogen and D-dimer levels were measured in patients with migraine. Patients with migraine had higher levels of galectin-3, fibrinogen and D-dimer compared to the healthy controls (p < 0.05). No statistically significant difference was found between galectin-3 and fibrinogen levels during the attacks and interictal period in the migraine group (p > 0.05). Migraine patients had higher D-dimer levels during the attacks compared to the patients in the interictal period in the migraine group (p = 0.05). In conclusion, we found increased levels of fibrinogen, D-dimer and galectin-3 in patients with migraine compared to the healthy control group. Furthermore, we showed increased galectin-3 levels in patients with migraine, and higher D-dimer levels during migraine attacks compared to the interictal periods for the first time. These findings may be associated with the hypercoagulability and neurogenic inflammation during migraine headaches.

The effects of pomegranate and carvacrol on methotrexate-induced bone marrow toxicity in rats.

PURPOSE: The aim of this study was to evaluate the effects of pomegranate (PMG) extract and carvacrol (CARV) on methotrexate (MTX)-induced oxidative stress and bone marrow toxicity. METHODS: Wistar albino rats (32 rats) were divided into four groups (n=8): Group 1 was control; Group 2 was given a single intraperitoneal injection of methotrexate (20 mg/kg); Group 3 was treated with carvacrol (73 mg/kg i.p.) one day before MTX (20 mg/kg i.p.) injection; and, Group 4 received a single dose of MTX (20 mg/kg i.p) while PMG was administered orally for seven days at 225 mg/kg. After animals were euthanized, blood samples were taken to evaluate hematological parameters and oxidative stress. In addition, the femur was cropped and bone marrow was extracted for examination. RESULTS: White blood cell count, hemoglobin, hematocrit and platelet count were found to be decreased in the MTX group, but these changes were prevented in the groups that received CARV and PMG. Furthermore, decreased bone marrow cellularity was found in the groups treated with MTX, whereas the PMG and CARV groups had cellularity similar to controls. Strikingly, oxidative stress increased in the MTX group, but was ultimately decreased in the rats that received the antioxidants PMG and CARV. CONCLUSION: Carvacrol and PMG were found to be protective against methotrexate-induced oxidative bone marrow damage. Use of these antioxidants, in combination with chemotherapeutics, may help to reduce some adverse effects of methotrexate.

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 AND 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.