Posttraumatic Stress Disorder in individuals with diagnosis of Autistic Spectrum Disorders

Although children and adolescents with developmental disabilities are said to have higher risks of abuse than those without, trauma and Posttraumatic Stress Disorder (PTSD) are little examined in those diagnosed with Autistic Spectrum Disorders (ASDs). Our study aims to assess trauma types, prevalence, risk factors and symptoms; and PTSD in individuals with diagnosis of ASD. Participants were 69 children and adolescents (53 males, 16 females) who were consecutively followed-up at our clinic and met DSM-IV criteria for ASD. Assessment was done using semi-structured interview forms. 18 had trauma history and 12 were diagnosed with PTSD. Witnessing or being a victim of accidents/disasters/violence was the most common type of trauma. Interestingly, the rate of sexual and/or physical abuse was less than in the general population. Trauma history and PTSD rates were higher in girls than boys. Deterioration in social and communicative abilities, increase in stereotypes, aggression, distractibility, sleep disorders, agitation, hyperactivity, self-injury, and loss of self-care skills were the most common symptoms detected following trauma. These results underscore the importance of detailed assessment of behavioral and emotional problems in this group by ruling out any trauma history at periods which might otherwise be misdiagnosed as an exacerbation of symptoms of ASD.     

The ultrastructural and biochemical evidences of the beneficial effects of chronic caffeic acid phenethyl ester and melatonin administration on brain and cerebellum of aged rats

Nervous system is highly vulnerable to the deleterious effects of age‐related oxidative stress. A large body of researches has consistently confirmed the implication of free radicals both in normal cerebral ageing and ageing‐related pathologies. In the present study, in addition to the light and electron microscopic pictures of brain and cerebellum of young, old and antioxidant administered old Sprague–Dawley rats, pro‐oxidant status was evaluated in terms of measurements of total glutathione, lipid peroxidation (malondialdehyde) and activities of superoxide dismutase, catalase and glutathione peroxidase. Taking the results together, we suggest that supplemental administration of caffeic acid phenethyl ester and melatonin is beneficial in delaying age‐related cellular damage in nervous system.     

Effects of Subchronic Parathion Exposure on Cyclosporine Pharmacokinetics in Rats

Parathion undergoes enzymatic oxidation by hepatic cytochrome P-450 (CYP450) enzymes to the active metabolite paraoxon. Consequently, alterations in CYP450- dependent oxidation may affect the pharmacokinetics and pharmacodynamics of drugs that are metabolized in the liver. The CYP3A family is known to be responsible for the majority of cyclosporine metabolism. The aim of the present study was to assess the disposition kinetics of cyclosporine during subchronic parathion exposure. Male Wistar rats were administered either water or two different doses of parathion (1/100 LD50, 1/25 LD50; LD50 = 14 mg/kg) by gavage for 6 wk. Subsequently, rats in each experimental group received a single oral dose of cyclosporine (10 mg/kg), and serial blood samples were drawn from the carotid artery over a period of 48 h. Pharmacokinetic analysis showed that parathion increased the blood cyclosporine concentration twofold as evidenced by AUC (area under the curve), half life (t _½) and peak plasma concentration (C _max). This may be due to inhibition of cyclosporine metabolism, an interaction that may be of clinical relevance in immunosuppression therapy.     

Protective role of alpha-tocopherol and caffeic acid phenethyl ester on ischemia-reperfusion injury via nitric oxide and myeloperoxidase in rat kidneys

BACKGROUND: The aim of this study was to determine the acute effects of antioxidant caffeic acid phenethyl ester (CAPE) and alpha-tocopherol (vitamin E) on nitric oxide (NO) production, neutrophil infiltration, and antioxidant enzyme activities on an in vivo model of renal ischemia-reperfusion injury. METHODS: Rats were divided into five equal groups each consisting six rats: sham operation, ischemia, ischemia-reperfusion (I/R), I/R plus CAPE, and I/R plus vitamin E groups. CAPE or vitamin E was administered intraperitoneally before reperfusion. After experimental procedure, rats were sacrificed and both ipsilateral and contralateral kidneys were removed and prepared for NO concentrations, myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) activities. RESULTS: Acute administration of vitamin E decreased NO concentrations in both ipsilateral and contralateral renal tissues compared to I/R group. SOD activity was increased in I/R and I/R + CAPE groups compared to sham operation group. The most prominent results were encountered in MPO activities, which did not change in contralateral kidneys in both ischemia and I/R groups. There was a significant decrease in ipsilateral MPO activity in ischemia group and a significant increase in I/R group compared to sham operation group. Pretreatment with intraperitoneal CAPE significantly diminished the tissue MPO activity indicating the prevention of the neutrophil sequestration into the kidney. CONCLUSION: There is a role for CAPE in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration.     

Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats

AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg·d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis,apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8,0.74±0.02 μmol/g, and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.     

The Role of Rac1 on Carbachol‐induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin‐induced Diabetic Rats

This study was designed to determine the role of the small GTPase Rac1 on carbachol‐induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)‐induced diabetic rat model, three study groups were composed of control, diabetic and insulin‐treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8–12 weeks after STZ injection. Carbachol (CCh) (10^?9–10^?4 M) concentration–response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes‐related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose‐dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh‐induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin‐treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh‐induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes‐related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity.     

Etiology and outcome of acute kidney injury in children

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1–24 days), and 67.4% were children aged?>1 month (median 2.99 years, range 1 month–18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged?>1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged?>1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p?<?0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation [relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88–61.42], hypervolemia (RR 12.90, 95% CI 1.97–84.37), CHD (RR 9.85, 95% CI 2.08–46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90–20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95–19.29), hypoxia (RR 5.35, 95% CI 2.26–12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04–11.78) in children? aged >1 month.     

Effect of early corticosteroid therapy on development of Henoch-Schönlein nephritis

BACKGROUND: Henoch-Sch?nlein purpura (HSP) is a systemic, small vessel vasculitis, which is very common among pediatric population. Findings of previous reports addressing the preventive effect of corticosteroid treatment in HSP nephritis have been inconsistent. The aim of this study was to determine whether corticosteroid therapy was effective in preventing Henoch-Sch?nlein nephritis. METHODS: The medical records of 216 children with HSP, seen in 2 tertiary care pediatric nephrology centers, were reviewed retrospectively. The effect of corticosteroid therapy on preventing nephritis was assessed in 157 patients who had no evidence of nephritis at the initial urinalysis. The treatment group (n=61) had received oral corticosteroids for gastrointestinal symptoms and/or arthritis. The dosage of prednisone was 1 mg/kg per day for 1-2 weeks, with weaning over a week. We compared the rate of renal involvement during follow-up between the groups who were treated with corticosteroids and not. RESULTS: Nephritis developed in 17 of the 61 (27.8%) corticosteroid-treated patients and 18 of the 96 (18.7%) untreated patients during follow-up. CONCLUSION: There was no evidence that corticosteroids reduced the risk of renal involvement in HSP, and these results do not support the use of corticosteroids in early HSP to prevent renal injury.