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

effect of experimentally induced oxidative stress on rat lung and the possible protective role of pentoxifylline: a histological and biochemical study

Acute lung injury and its most severe form, the acute respiratory distress syndrome are frequent complications in critically ill patients and are responsible for significant morbidity and mortality. Skeletal muscle breakdown [rhabdomyolysis] causes biochemical, functional and histological changes of kidney. The effects of rhabdomyolysis are likely mediated by increased oxidative stress leading to renal tubular cytotoxicity. Oxidative stress has a close relation to acute respiratory distress syndrome. This work was carried out to demonstrate the effect of experimentally induced oxidative stress on the lung histologically and biochemically and to study the role of pentoxii'lline in ameliorating these effects. Seventy adult male albino rats were used and divided into three main groups; the control [Group I] consisted of 20 rats and each experimental group consisted of 25 rats. Group II injected by i.m. glycerol once to induce rhabdomyolysis and consequently oxidative stress and group III received pentoxifylline before i.m glycerol injection. Heparinized blood samples were taken for assessment of total creatine kinase, total glutathione peroxidase, thiobarbituric acid reactive substances, plasma antioxidants, PaO[2] and PaCO[2]. Bronchoalveolar lavage [BAL] was taken for cellular profile and lung specimens for histological study. All samples were taken 6 hours after glycerol injection. Experimental group II showed significant increase in creatine kinase, total glutathione peroxidase and thiobarbituric acid reactive substance [TBARS]. Arterial blood gases showed significant decrease in PaO[2] and PaCO[2]. In BAL there was a significant increase in neutrophils and a non significant increase in macrophages. The lung showed increase in the thickness of the interalveolar septa with cellular infiltration associated with alveolar damage and many collapsed alveoli. Ultrastructurally, pneumocytes type II showed degenerative changes in the form of cytoplasmic vacuolation and destruction of lamellar bodies and mitochondria but in group III, all changes showed improvement with presence of minimal affection. Induced oxidative stress could lead to acute lung injury with biochemical alterations of many parameters. Meanwhile, pentoxifylline showed ameliorative effect on all of these parameters

Vascular endothelial growth factor as an indicator of severity of diabetic retinopathy

To evaluate vascular endothelial growth factor [VEGF] as an indicator of severity in diabetic retinopathy. The study included 120 patients divided equally into 3 groups [proliferative diabetic retinopathy [PDR] group, non proliferative diabetic retinopathy [NPDR] group and non diabetics control group]. Vitreous and blood samples were collected from all patients. VEGF concentrations were determined using enzyme linked immuno-sorbent assay and correlated with retinopathy grading. Vitreous concentrations were statistically significant higher than serum concentrations in both retinopathy groups with strong positive correlation [r = 0.927 at p < 0.001 in PDR and r = 0.646 at p < 0.001 in NPDR]. Serum and vitreous VEGF concentrations in diabetics were statistically significant higher than control group [p<0.01]. Both increased with the progression of retinopathy. Very mild NPDR patients had the lowest vitreous concentration [mean = 20.33 ng / ml] but still higher than controls [mean = 4.53 ng / ml]. PDR patients with tractional detachment had the highest vitreous concentration [mean = 225.18 ng / ml]. VEGF concentrations were statistically significant higher in NPDR patients with maculopathy than NPDR patients without maculopathy. There is a strong direct positive correlation between VEGF concentrations and retinopathy grading

Assessment of stanniocalcin-1 mRNA as a molecular marker for micrometastases of breast cancer

Very few tumor molecular markers have been identified that are highly specific for breast cancer cells when applied to blood. Stanniocalcin [STC]-1 is a recently discovered human gene that has been implicated in cellular calcium homeostasis and is located on chromosome 8p in a region associated with amplification of breast cancer. We investigated STC-1 mRNA as a molecular marker for detecting occult breast cancer cells in blood. Using real time PCR detection assay to assess for STC-1 mRNA expression, we evaluated the blood of 25 breast cancer patients with different stages [I-IV] according to American Joint Committee on Cancer, 7 patients with benign breast lumps as fibroadenomas and fibrocystic swelling, and 8 healthy women as control subjects. In this study there was blood STC-1 gene expression of the malignant group; the mean value of the STC-1 positive blood specimen [copies number] was 8103.1+491.0, without blood expression in the other two groups. Also, the results of this work showed that, 19 [76%] patients of 25 patients of cancer breast had detectable STC-1 mRNA [copies] in their blood, without detectable expression in the other 6 [24%], p<0.001 with significant increase of STC-1 copy numbers with progression of AJCC stages, P<0.001. Finally in this study, the presence of STC-1 mRNA in the blood significantly correlated with primary tumor size [P<0.001], the involved lymph nodes characteristics [P<0.001], the presence of distant metastasis [P<0.001] and the overall AJCC stage [P<0.001]. STC-1 mRNA assay may be a useful and sensitive molecular marker for breast cancer cases with different stages without expression in the normal blood cells. Also, the presence of breast cancer associated STC-1 mRNA in the blood cells correlated significantly with the primary clinico-pathological determinants of disease outcome

Expression of interleukin[il]-18and il-6 in gastric cancer :diagnostic and prognostic role

Gastric cancer is the second most common cancer worldwide. The purpose of this study was to compare the recently identified interleukin [IL]-18, as well as IL-6 values in patients with gastric ulcer and gastric cancer to assess their diagnostic and prognostic values in patients with gastric cancer. The study comprised 40 patients attended for diagnostic upper gastrointestinal [GIT] endoscopy; 14 with histopathologically proven gastric cancer [Group I], 16 patients with gastric ulcer [Group II] and 10 patients with normal upper GIT endoscopy who served as controls [Group III]. All involved individuals were subjected to clinical examination, liver and renal function tests, complete blood picture, ESR, C-reactive protein, plain chest X-ray, abdominal ultrasound, urease test and gram staining of mucosal biopsies for Helicobacter pylori detection. Additionally chest,abdominal CT and bone scanning for group I gastric cancer were done to detect any metastasis. IL-18 and IL-6 gastric muscosal mRNA expression was assessed by quantitative real time-PCR [QRT-PCR] and their serum levels were estimated by ELISA. Gastric mucosal mRNA expression in parallel to serum values of IL-18 and IL-6 showed significant highly in-creased values in gastric cancer group compared to gastric ulcer and control groups [P<0.001] with elevated values in gastric ulcer group than those in controls. In gastric ulcer group, a positive relation was found between the studied cytokines and the histologically graded precancerous gastric lesions; gastric glandular atrophy grade was correlated with ser-um IL-18 [r=0.77; P < 0.001], gastric mRNA expression of IL-18 [ r= 0.603;P < 0.01] and IL-6 [r = 0.457;P <0.05], also intestinal metaplasia was positively related to IL-18 serum [t=-2.977; P < 0.01] and gastric mRNA expression [t =-2.365; P < 0.05] values. Higher cytokine values were related to H pylori infection in gastric ulcer [P < 0.01] not in gastric cancer group. In gastric cancer group a significant positive correlation was found between the cellular differentiation grade and IL-18 serum [r = 0.712; P <0.01] and gastric mRNA expression [ r = 0.658;P < 0.01] values, while IL-6 serum [r = 0.817; P <0.01] and gastric mRNA expression [r=0.844; P <0.01] values were positively correlated with the gastric cancer stage. Also patients with distant metastasis showed significantly higher IL-6 serum[t=-6.218 ; p < 0.001] and gastric mRNA expression [t = -2.47; P < 0.01]values compared to those without metastasis

In conclusion: IL-18 as a recently identified cytokine as well as IL-6 suggested to be vitally involved in gastric cancer pathogenesis. Serum IL-18 and IL-6 may be useful diagnostic markers for patients with gastriccancer. IL-18 may be used as a predictive marker of tumor grade and serum IL-6 could be used as a tumor marker for advanced gastric cancerstage and metastasis

Prediction of infants who may develop bronchopulmonary dysplasia in preterm babies with respiratory distress syndrome

The objective of this study was to test the neonatal polymorphism of TNF alpha to measure the day one levels of sL-selectin, sE-selectin and sICAM-1 in sera of neonate and placenta growth factor in cord blood, for the prediction of development of bronchopulmonary dysplasia [BPD]. The study design was a cross sectional one. Forty preterm neonates with respiratory distress and 10 normal full term neonates were enrolled. The neonates were divided into 2 subgroups; 15 who developed bronchopulmonary dysplasia and 25 without. Sampling was done and diagnostic evaluation of all parameters was accomplished. The results proved that infants. None of the infants with BPD carried the AA TNF- alpha -238 genotype, compared with 3 infants without BPD, and only 1 infant with BPD carried the GA TNF- alpha -238 genotype, compared with 7 infants without BPD. Higher sE-selectin has a diagnostic ability [sensitivity 73%, specificity 76%] higher PLGF has a sensitivity of 67% and specificity 68%. Combination of both, improved specificity to 80%. If we add to them, cases which have absence of GA TNF- alpha -238 genotype, we have got a very high sensitivity [93%] but with lower specificity. Combined all data supported a specificity 80% with a sensitivity of 86%. What had been found in this study might clarify the role of adhesion molecules, P1GF and TNF polymorphism as biological marker to determine which premature infants with RDS are at risk for development of BPD and to permit early intervention and might provide a new therapeutic target to prevent BPD