Monocytes chemoattractant protein-1 [MCP-1] and other proinflamatory cytokines in children with autism

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication, speech, repetitive behaviors, and social withdrawal. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. Cytokines are protein or peptide that include, interleukines, interferons, tumor necrosis factor and others. Cytokines can influence physiological functions such as sleep and food intake; they also interact with a number of neurotransmitters in the brain. Cytokines, and the immune system together, may play a very important role in the development of autism and there is now some evidence that autism may be accompanied by abnormalities in the inflammatory response system [IRS]. Products of the IRS, such as proinflammatory cytokines, may induce some of the behavioral symptoms of autism, such as social withdrawal, resistance to novelty and sleep disturbances. Thus, a potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from children with autism compared with age-matched control children. Was to evaluate, if autism is accompanied by an activation of the inflammatory response system, and to investigate whether immunemediated mechanisms are involved in the pathogenesis of autism or not through evaluation of the plasma levels of the proinflammatory cytokines as interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] in children with autism, and compare them with the age-matched healthy control children. This study was carried out in the Psychiatry Unit, Department of Pediatrics, Tanta University Hospital. Thirty children with prior diagnosis of autism[24 males, 6 females] were included in the study, their age range was[3-9 years]with the mean age of 5 +/- 1.8 years. Diagnosis of autism was based on the criteria for the diagnosis of autism that are set out in the Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR [Fourth Edition, Text Revision]. The intial Childhood Autism Rating Scale [CARS] score for these children was >/= 30, as children with a CARS score >/= 30 were considered to have autism. Intial CARS score range for children with autism was [31-60]. The control group consisted of thirty healthy children [10 females, 20 males]. Their age range was [2-10 years] and the mean age was 5.31 +/- 2.4 years. Plasma levels of the proinflammatory cytokines as interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] were evaluated for children with autism, and the control children. The mean plasma levels of the proinflammtory cytokines, interleukin-6 [IL-6], interleukin-1 beta [IL-1 beta], tumor necrosis factor [TNF]-alpha and monocyte chemoattractant protein -1[MCP-1] in children with autism, were significantly higher than the mean plasma levels of these proinflammatory cytokines in the control children [P<0.01]. In conclusion, Increased levels of plasma proinflammatory cytokines in children with autism, support the hypothesis that an abnormal immune response could be another component of this multifactorial disorder. These findings serve as further evidence that inflammation may be an important part of the pathogenesis of autism and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of autism

Antioxidant enzymes and ceruloplasmin plasma levels in children with autism

Autism is a behaviorally defined neuron-developmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders as autism. Levels of the major antioxidant serum proteins, namely Glutathione peroxidase, Superoxide Dismutase and ceruloplasmin, are decreased in children with autism. The aim of this study: was to evaluate the plasma levels of the major antioxidant enzymes include. Superoxide Dismutase [SOD], Glutathione Peroxidase [GSH-Px] and Ceruloplasmin in children with autism, compare them with normal control children and to correlate between the plasma levels of these major antioxidant and the severity of autism .This study was carried out in The Psychiatry Unit, Department of Pediatrics, Tanta University Hospital. Thirty children with prior diagnosis of autism[24 males, 6 females] were included in the study, their age range was[3-9 years] with the mean age was [5 +/- 1.8 years]. The intial Childhood Autism Rating Scale [CARS] score for these children was >/= 30. Children with a CARS score >/= 30 were considered to have autism. Intial CARS score range for chidren with autism was [31-60]. The control group consisted of thirty healthy children [10 females, 20 males]. Their age range was [2-10 years] and the mean age was 5.3 +/- 2.4 years. The plasma levels of the major antioxidant, Glutathione Peroxidase, Superoxide Dismutase and Ceruloplasmin In children with autism, were significantly lower than the plasma levels of these antioxidants in the control children [P<0.01]. Also there was a significant inverse correlation between the plasma levels of this major antioxidant and the severity of autism according to CARS score. These data revealed that, antioxidants defense mechanisms might be impaired in children with autism, understanding these basic pathologic processes may yield novel target for the development of more effective treatment for autism

Plasma carnitine in children with idiopathic epilepsy treated with old and new antiepileptic drugs

Prolonged antiepileptic drugs treatment can result in secondary carnitine deficiency. Clinical studies indicate a decrease in free and total carnitine in children treated with old-generation antiepileptic drugs [especially valproate]. Some studies on valproic acid [VPA]-induced hepatotoxicity showed decreased free serum carnitine, but some did not. A number of studies on the effect of VPA and/or other antiepileptic drugs on carnitine concentrations yielded contradictory results. The effect of new antiepileptic drugs as oxcarbazepine and lamotrigine on carnitine metabolism has not been reported previously. The aim of this study was performed to evaluate the plasma carnitine level in children with idiopathic epilepsy treated with old antiepileptic drugs [valproic acid and carbamazepine] and new antiepileptic drugs [lamotrigine and oxcarbazepine]. This study was carried out in Tanta University Hospital Pediatric Department, Neurology Unit. Fifty children with newly diagnosed idiopathic epilepsy were selected from those attending the pediatric neurology out-patient clinic. Thirty four [34] males and sixteen [16] females were enrolled in the study with the age range was 1-12 years with the mean age was [6.8 +/- 3 years]. Patients were grouped according to their antiepileptic treatment into: Group 1, twenty patients received valproic acid as monotherapy without any antiepileptic drugs treatment before. Group 2 ten patients received valproic acid as polytherapy after three months treatment with carbamazepine. Group 3, ten patients received lamotrigine as monotherapy, and group 4, ten patients received oxcarbazepine as monotherapy. Twenty healthy children served as control group with the age range was, 2-12 years with the mean age was [8 +/- 2 years]. Estimation of the plasma carnitine levels were done for all the studied groups. Group 1 and group 2 epileptic children, treated with valproic acid monotherapy and polytherapy had significantly lower plasma carnitine levels than the control group [P<0.05]. There was significant correlation between the age and the plasma carnitine in group 1 and group 2 epileptic children, the younger the age the more reduction in the plasma carnitine level Patients treated with valproic acid polytherapy had significantly lower plasma carnitine than patients treated with valproic acid monotherapy [P<0.05] .There was no significant difference between the plasma carnitine in children with epilepsy treated with oxcarbazepine and lamotrigine and the control group [P>0.05]. In conclusion, 1-Carnitine deficiency is not uncommon among children with epilepsy and is mainly linked to valproate therapy. 2-valproate may induce carnitine deficiency, but most cases are asymptomatic. 3-In contrast new-generation antiepileptic drugs probably do not cause carnitine deficiency. 4-These findings suggest a need to monitor serum carnitine levels in children treated with any of these drugs

Cardiac troponin T as a diagnostic marker of hypoxic myocardial injury in sick full-term and preterm neonates

Perinatal asphyxia is associated with cardiac dysfunction; this may be secondary to myocardial ischemia. Also, in preterm infants with respiratory distress syndrome, cardiac function is negatively influenced by the severity of lung disease. Cardiac troponin T [cTnT] is the ideal marker used in the detection of myocardial injury. The aim of the present work was to provide evidence of the usefulness of cTnT in the diagnosis of myocardial injury in neonates after intrauterine hypoxia or with respiratory distress syndrome. Forty five neonates were enrolled in the study and were divided into three groups: group I, fifteen full-term neonates with perinatal asphyxia; group II, fifteen preterm neonates with respiratory distress syndrome; and control group, fifteen healthy full term neonates. Arterial blood gases were measured for sick neonates; serum cTnT was assayed and echocardiography was performed for all neonates. Serum cTnT levels were significantly higher in sick neonates [groups I and II] than the control group [P<0.001]. There was significant correlation between cTnT levels and arterial blood gases [pH, PO[2], PCO[2], HCO[3]] and also with echocardiographic parameters of ventricular function [FS% and EF%] [P<0.01]. cTnT is a useful diagnostic marker used for assessment of post hypoxic myocardial injury in fullterm neonates with perinatal asphyxia or preterm neonates with respiratory distress syndrome

Prognostic value of serum S100 protein level in newborn infants with hypoxic ischemic encephalopathy

Hypoxic ischemic encephalopathy [HIE] is the most common cause of neurologic disease during neonatel period and is associated with high mortality and morbidity rate including cerebral palsy, mental retardation and seizures. S100 beta[2] is normally present in serum in very low concentrations, but found in high concentrations in the brain both in glial cells and in neurons. Serum S100 protein peaked in the first day after birth in asphyxiated newborn infants. The aim of this study was to clarify the prognostic value of serum S100 protein level as a marker of cerebral injury in newborn infants with birth asphyxia [HIE]. 20 newborns with HIE were investigated successively in the first 3 days after birth in comparison with 20 healthy newborn infants as a control group. S100 protein levels were detected by a monoclonal two-site immuno-luminometric assay. Follow up of the cases for 6 months after discharge from incubators was done to detect cases that developed cerebral palsy. We found significant increase in serum S100 protein level in newborn infants with birth asphyxia as compared to control group, also we found significant positive correlation between day 1 S100 protein levels and severity of HIE and positive correlation between day 1 S100 protein levels and future development of cerebral palsy. Early determination of serum S100 protein in first day after birth in newborn infants with hypoxic ischemic encephalopathy may be used as a good marker for assessment of severity of HIE and extent of brain damage and to predict the possibility of future development of cerebral palsy in newborn infants with HIE

Circulating Thrombopoietin and Interleukin-11 in Thrombocytopenic Neonates with Sepsis

Thrombocytopenia is a commonly encountered hematological complication in neonates with sepsis. Thrombopoietin [TPO] is the major regulator of the platelet production in neonates. It is unique among the haematopoietic cytokines for maintenance of the most primitive haematopoietic stem cells. Interleukin-11[lL-11] stimulates megakaryorytopoiesis and platelet production. The aim of this study was to determine the variation in the TPQ and IL-11 levels and/or if they would correlate with platelet count or not in infected neonates with sepsis. Thirty five neonates with sepsis admitted to the Intensive Care Unit, Pediatric Department, Tanta University Hospital, were enrolled in this study. Twenty healthy neonates sewed as a control group. All these neonates were subjected to the following: Complete blood count [CBC], blood culture, C-reactive protein [CRP], chest X-ray, coagulation studies including prothrombin time, partial thromboplastin time, fibrinogen and D-dimer. Plasma TPO and IL-11 levels were performed using Enzyme-Linked lmmunosorbent Assay[ELISA], The results showed that sick neonates with sepsis had significantly higher plasma levels of both TPO and IL-11 [P<0. 05]. Also, there was significant inverse correlations between the platelet count and TPO and IL-11 levels [r=-0.917 and-0.908 respectively, P value<0.01]. TPO and IL-11 are significantly increased in neonatal sepsis with thrombocytopenia and they are being explored as potential therapeutic agents in these patients

Neonatal cerebrospinal fluid plasminogen and plasminogen activator inhibitor-1 assay as predictors of post hemorrhagic hydrocephalus

Massive intraventricular hemorrhage [IVH] in neonates is followed by progressive ventricular dilatation in 55-80% of cases if the infant survives. The initial mechanism of post hemorrhagic hydrocephalus [PHH] is thought to be obstruction by multiple small blood clots of the channels of the cerebrospinal fluid [CSF] to areas of absorption. Plasminogen activator inhibitor-1 [PAI-1] is the principal regulator of fibrinolysis in blood and one of the most highly controlled of the fibrinolytic components. The aim of this study is to measure plasminogen and plasminogen activator inhibitor-1 levels in the CSF of the neonates after IVH to assess endogenous fibrinolytic activity and to predict the development of post hemorrhagic hydrocephalus. Fifteen full term and preterm neonates with IVH were enrolled in the study. Ten neonates without IVH were used as a control group. Cranial ultrasound was performed at age of 2 weeks and 2 months. Plasma and CSF plasminogen and PAI-1 levels were assessed for these neonates. The results revealed that CSF PAI-1 was significantly higher in infants with IVH than in the controls [P<0.001]. There was no significant difference in the CSF and plasma plasminogen between infants with IVH and controls [p>0.05]. CSF PAI-1 was significantly higher in infants with PHH than in infants with post hemorrhagic ventricular dilatation [p<0.05], with a sensitivity [100%] and specificity [100%]. CSF PAI-1 is a very sensitive and specific parameter than CSF plasminogen for prediction of PHH in neonates with IVH, and this might be useful to evaluate the specific therapeutic programs of these neonates

Relationship of Monocyte chemoattractant protein-1 with diabetic nephropathy in children with type-1 diabetes: effect of high dose vitamin E therapy

Monocyte chemoattractant protein-1 [MCP-1] is a specific chemokine that activates monocytes from the circulation to the inflammatory sites. In diabetic nephropathy, similar to other glomerulonephropathies, infiltration and activation of monocytes / macrophages in the glomeruli have been implicated in the development of glomerular injury. The aim of this study was to examine a possible relationship of the MCP-1 with the development of diabetic nephropathy in children with type-1 diabetes before and after treatment with high dose of vitamin E for eight weeks. This study was carried out on thirty diabetic children, group 1; fifteen children with type 1 diabetes mellitus with persistent microalbuminuria, and group 2; fifteen children without microalbuminuria. Fifteen healthy children served as control group. Albumin excretion rate [AER] and glycosylated hemoglobin [HbA[1C]] were measured, also plasma MCP-1 levels were measured by ELISA before and after treatment with vitamin E for eight weeks. The results proved that plasma levels of MCP-1 were significantly higher in children with diabetic nephropathy than diabetic children without nephropathy and the control group [P<0.05]. There was strong positive correlation between HbA[1C] level and AER and MCP-1 [P<0.0001]. After treatment with vitamin E, there was a significant decrease in the MCP-1 plasma levels in diabetic children with nephropathy. This study suggests that facilitated MCP-1 production by the mesangial cells in diabetic children contributes to the initiation and progression of diabetic nephropathy. High-dose vitamin E supplementation may provide an additional benefit, as adjuvant therapy to insulin treatment, in reducing the risks for the development of diabetic nephropathy