Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

Prognostic value of TNF alpha mRNA and VEGF mRNA expression in patients with chronic hepatitis C geno-type-4, with and without cirrhosis and hepatocellular carcinoma to predict disease outcome

The study aimed to clarify whether vascular endothelial growth factor mRNA [VEGF mRNA] and TNF alpha mRNA in the HCC tissues on top of HCV with and without cirrhosis obtained from specimens after curative hepatic resection has a prognostic value and recurrence predictive value compared to other tumor criteria. A total of 160 patients were studied. The preoperative laboratory, radiological and staging to patients was done. Using in situ hybridization technique, VEGF mRNA and TNF alpha mRNA were determined in liver tissues of, 10 controls, 50 with HCC, 50 with HCV without cirrhosis and 50 HCV with cirrhosis. The results showed that in HCC cases there was positive correlation between increasing age, loss of weight, INR and AFP but not in other cases of CHC with or without cirrhosis. AFP, vascular invasion, encapsulation, tumor size and grade and platelet count were related to patients outcome and recurrence of tumor after follow up of most cases for 3 years. The expression of VEGF in liver tissues was proportional to progress of viral hepatitis to cirrhosis with more expression in cases progressed to malignant changes. More expression of VEGF in HCC was more evident with intense expression in cases with Vascular and capsular invasion and higher level of AFP. Expression of TNF alpha mRNA and VEGF mRNA shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positive with cases developed HCC

Hepatoprotective effects of rolipram on experimental murine model of immune-mediated fulminant hepatitis

Autoimmune fulminant hepatic failure has a specific clinical and social importance. However, it still lacks its effective and targeting medication. Herein, we investigated the influence of rolipram, a selective PDE-IV inhibitor, on D-galactosamine/lipopolysaccharide [DGalN/ LPS]-induced immune-mediated and dose-dependent fulminant hepatitis and acute lethality in mice; in which tumor necrosis factor-alpha [TNF-alpha] plays a pivotal role. Two complementary sets of experiments were conducted in this work. Firstly, we assessed the distinct hepatoprotective effects of rolipram on this model. After an intraperitoneal [i.p.] injection of a single sub-lethal dose of D-GalN/LPS [0.2 mg/g + 5 microg/g] into mice a serious destructive hepatic injury was developed over a period of 4 days, and it was associated with abundant increases in the serum levels of liver enzymes [AST and ALT] and the concentrations of TNF-alpha in serum and hepatic tissues, as well as an over-production of vascular cellular adhesion mlocule-1 [VCAM-1] on liver tissues. Additionally, the histopathological findings showed the features of severely injured liver. Interestingly, treatment with rolipram [3 mg/kg, i.p.; at days +0, +1, +2, and +3] remarkably reversed all the aforementioned biochemical, immunological, and histopathological hallmarks of D-GalN/ LPS-induced hepatitis. Secondly, the prophylactic administration of rolipram [10 mg/kg, i.p.; at -24, -12, and -1 h] efficiently prevented the severe acute deaths and massive systemic TNF-alpha production that induced by a lethal dose of D-GalN/LPS [0.6 mg/g + 15 microg/g; i.p.] over 24-h period. The results reveal that rolipram; via, at least in part, inhibition of TNF-alpha production and VCAM-1 over-expression, has obvious hepatoprotective effects on D-GalN/LPS-induced lethal destructive hepatitis in mice. In addition, the beneficial role of rolipram in suppressing the progression of human hepatitis in which TNF-alpha is markedly involved could be considered

Assessment of fatigue in chronic hepatitis C Egyptian patients: relation to TNF-alpha, Leptin, IL-i and IL-6

Fatigue is a common symptom in chronic hepatitis C [CHC]; but it is not well understood and remains poorly investigated. One of the major obstacles to research is the highly non specific nature of fatigue. In 1994; the fatigue impact scale [FIS] was developed to improve our understanding of the effect of fatigue on quality of life. Recent attention has focused on the role of leptin and energy expenditure in chronic hepatitis C [CHC]. The importance of leptin in the regulation of energy balance, body composition and food intake has been demonstrated in both animal and human studies. 4herations in immune activation and cytokine release have been implicated in the occurrence of fatigue in CHC patients. The purpose of this study is to analyze fatigue in chronic hepatitis C Egyptian patients and to determine its relationship with the degree of underlying hepatitis, resting energy expenditure [PEE], circulating leptin and tumor necrosis factor-a [TNF-alpha], IL-1, and IL-6. Ninety patients were included in the study [61 males, 29 females], who were referred to the department of Tropical Medicine Al Hussein and Bab-Al-Sharyia University Hospitals during the period from March 2004 to March 2006. They were divided into two groups. Group I: 65 patients with chronic hepatitis C. Group II: 25 healthy persons, tested negative for hepatitis C [Control group]. All were submitted to history and clinical examination, liver function tests, HCV [Ab and PCR], the modified fatigue impact scale, resting energy expenditure, tumour necrosis factor [TNF-alpha], serum leptin. IL-alpha, and IL-6. FIS and REE, serum leptin, TNF-, IL-alpha and IL-6 were significantly elevated among HCV patients in comparison to controls. Fatigue didn't correlate with the degree of underlying hepatitis. Fatigue impact scale is a beneficial tool for subjective valuation of fatigue. Fatigue is present in CHC patients but it is not related to the degree of hepatitis. TNF-alpha, IL-1 and IL-6 may contribute partially to the occurrence of fatigue in these patients

Serum OX40 ligand: a potential marker of atopic dermatitis disease severity in children

OX40 ligand [OX40L] and OX40 are members of the tumor necrosis factor [TNF] and TNF receptor [TNFR] super families respectively. Recent studies have indicated the critical involvement of OX40/OX40L nteraction in the pathogenesis of atopic dermatitis. To our knowledge, no data could be cited in literature concerning OX40L levels in serum or in other biological fluids of atopic dermatitis children. This study was done to explore the expression of OX40L in the serum of atopic dermatitis children with respect to disease activity and severity. This follow-up, case-control longitudinal study was conducted on 64 children as a stratified non-random sample; 34 with atopic dermatitis and 30 healthy children. Serum concentrations of OX40L were measured by and wich enzyme immunoassay. The severity of atopic dermatitis was assessed according to the Leicester Sign Score [LSS], Simple Scoring System [SSS], Scoring Atopic Dermatitis [SCORAD] index, and Objective SCORAD. Serum OX40L levels [pg/ml] in atopic dermatitis patients were significantly elevated as compared to controls [176.6 +/- 45.9] whether during flare [1007 +/- 241.5] or quiescence [699 +/- 198.5]. There were significant positive correlations between serum OX40L levels and each of the LSS, SSS and SCORAD indices of atopic dermatitis disease severity, while it was insignificant regarding the objective SCORAD. However, when atopic dermatitis children were classified according to the objective SCORAD index of severity into mild, moderate and severe, it was found that the mean serum level in the severe group was significantly higher than the corresponding values of the mild or the moderate group. OX40L levels did not correlate with serum total IgE or absolute eosinophils count. Serum total LDH levels correlated positively with each of the serum OX40L levels and the LSS and SCORAD indices of severity. Serum OX40L level is an objective reliable marker of atopic dermatitis severity in children. It may be useful for follow up and may help to improve research and management of this disease. Blockade of interactions between OX40 on Th2 cells and OX40L on activated dendritic cells using an OX40L-specific monoclonal antibody could represent a novel strategy for the treatment of atopic dermatitis

possible protective effect of exroxisome proliferator-activated receptors-gamma [PPAR-gamma]-agonist in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Focal cerebral ischemia [st, oke] is a leading cause of death and disability among adult population. Many pathological events including inflammation and oxidative stress during the acute period contribute to the secondary neuronal death. Peroxisome prohferator-activated receptors [PPARs] are ligand-activated transcription factors known to upstream to many inflammatory and antioxidant genes. The present study was carried out to evaluate the physiological role of PPAR-gamma and possible neuroprotective effects of its agonist, rosiglitazone, in experimentally induced focal cerebral ischemia in rats. The current study was conducted on 30 male albino rats [180-220 gm], they were divided into 3 groups: Group 1: included 10 normal healthy control rats that were sham operated. Group 2: included 10 rats that were subjected to middle cerebral artery occlusion [MCAO] induced focal cerebral ischemia for 2 h followed by reperfusion for 22 h. Group 3: included 10 rats that were pretreated with rosiglitazone 3mg/kg body weight orally for 7 days followed by MCAO induced focal cerebral ischemia. The following parameters were assessed in all rats of the studied groups: Serum levels of both tumor necrosis-alpha [TNF-alpha] and interleukin-6 [IL-6] and cerebral cortex tissue levels of glutathione reductase [GR], reduced glutathi one [GSH] and glutathi one peroxidase [GPx] The present study revealed that the induced focal cerebral ischemia in rats of group2 was associated with a statistical sign ifi cant increase in serum levels of both TNF-alpha and IL-6 as compared to normal controls. Pretreatment of rats with rosiglitazone in group3 resulted in a statistical significant reduction of the TNF-alpha and IL-6 levels as compared to group2 [This reflects that the ischemic neuronal injury is associated with massive inflammatory processes that lead to brain damage]. And treatment with rosiglitazone could have an anti-inflammatory neuroprotective role. Considering the brain tissue levels of GR, GSH and GPx, which are tissue oxidant defense mechanisms, the present study showed that focal cerebral ischemia in rats of group2 led to a statistical signfi cant reduction in their levels as compared to control group indicating that cerebral ischemia and reperfusion are responsible for oxidative stress by generation of free radicals which culminate to serious damaging effect and overproduction of free radicals takes the upper hand and predominates the detoxication and scavenging capacity of cellular antioxidant enzymes. Treatment of rats with rosiglitazone before induction of focal cerebral ischemia led to a statistical significant increase in the brain tissue levels of defense antioxidant enzymes as GR and GPx as well as GSH assuming its potential neuroprotective role which could be due to its ability to increase the natural defense mechanisms in case of ischemic oxidative stress. PPAR-gamma agonist [rosiglitzone] could be the drug of use in stroke therapy due to its potential to influence multiple molecular mechanisms by its ability to minimize both the inflammation and oxidative stress and at the same time promotes the antioxidant defense mechanisms and protein chaperones

Basic fibrolast growth factor and vascular endothelial growth factor levels as pulmonary biomarkers of chronic obstructive pulmonary disease

There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease [COPD]. The aim of this study is evaluating circulating basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF] levels to determine the value of these growth factors as biomarkers of COPD and as indicators of severity of COPD in patients with chronic obstructive pulmonary disease in comparison to the inflammatory cytokines, C-reactive protein [CRP], tumor necrosis factor- alpha [TNF- alpha and interleukin-6 [IL-6]. Also, to determine if there is a correlation between circulating levels of VEGF and bFGF and pulmonary function [FEV1]. The study included 86 patients with chronic obstructive pulmonary disease [COPD], Besides 20 healthy, age matched males with normal pulmonary function were included as controls. The patients were divided into 5 stages according to lung function measured by spirometer [FEV1% predicted]. All patients were subjected to determination of FEV1 and determination of circulating bFGF, VEGF. TNF- alpha CRP and IL-6. The results showed that the concentration of circulating bFGF, VEGF, TNF- alpha, CRP and IL-6 were significantly higher in patients with CORD in comparison to the control group and their levels increased according to the stage of disease. There was a negative correlation between the blood levels of VEGF and bFGF with FEV1 in the different stages of COPD [p<0.05]. Also, there was a strong positive correlation between VEGF and bFGF [p<0.05]. In conclusion, bFGF and VEGF could play an important role in the pathogenesis of COPD and could be considered as a reliable and early biomarker in the diagnosis of COPD

Pro-inflammatory cytokines, oxidative stress and intelligent quotient [IQ] in malnourished pediatric patients

Protein energy malnutrition [PEM] is one of the most common health problems among children of developing countries. Children with PEM lose their resistance to infection because of a disordered immune system. Protein energy malnutrition produces changes in inflammation related proteins characteristic off a low grade systemic inflammatory response and, thus, can serve as an inflammatory stimulus. Antioxidant status of PEM patients is significantly reduced. An increasing body of evidence indicates a link between malnutrition and poor cognitive ability in children [in particularly in early onset malnutrition]. This study included 28 children having malnutrition [17 patients had marasmus [loss of subcutaneous fat over the thigh or over the abdomen or loss the buccal bad of fat] and 11 patients had kwashiorkor[presented by generalized edema, sparse easily detachable hair, flag sign, cracky paint dermatosis and apathy], 15 males 13 females, their ages ranged from 4 months to 24 months, admitted to Gastroenterology Unit, Assuit University Children Hospital from April 2007 to December 2007 as well as 15 apparently healthy children of matchable ageand sex. All patients subjected to full history, complete clinical examination and the following investigations: serum levels of TNF-alpha, lL-6, nitric oxide [NO], lipid peroxide and zinc as well as Intelligent Quotient [IQ] were done. Serum levels TNF-alpha, lL-6, NO were significantly higher in patients with kwashiorkor and in patients with marasmus than in controls as well as higher in patient with kwashiorkor than in patients with marasmus. Serum levels of peroxide, was only significantly higher in patients with kwashiorkor and in patients with marasmus than in control. Also serum zinc level and I.Q were significantly lower in patients with kwashiorkor and in patients with marasmus than in controls as well as in patients with kwashiothor than in patients with marasmus. There are negative correlations between serum levels of TNF-alpha, lL-6 and lipid peroxide with I.Q in patients with marasums and patients with kwashiorkor. Also there is a positive correlation between serum level of zinc with IQ in patients with marasmus and in patients with kwashiorkor. in conclusion, oxidative stress imbalance and zinc deficiency in children with PEM play an important role in their neurocognitive development

Cytokines and growth factors in Duchene muscular dystrophy patients

Dystrophin deficiency associated with Duchene muscular dystrophy [DMD] results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of cytokine and growth factors. Most of the current researches test for such cytokines and growth factors in tissue biopsies, which is an invasive technique. Of the present study is to investigate whether cytokines and growth factors, as indicators of inflammatory response, can be detected in blood of DMD patients as non-invasive technique. Accordingly the cytokine tumor necrosis factor alpha [TNF TNF-alpha], as well as the growth factors basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF] were measured in blood of 24 boys with DMD diagnosed clinically and at the molecular level versus 20 age matching healthy boys. Showed a significant increases in TNF-alpha [30.2 +/- 9.5 vs. 3.6 +/- 0.9 pg/ml] and bFGF [21.7 +/- 10.3 vs. 4.75 +/- 2.2 pg/ml.], while VEGF was significantly decreased [190 +/- 115 vs. 210 +/- 142 pg/ml] in blood of DMD patients compared to controls. Results provide further proof that inflammatory response is associated with DMD pathogenesis and favours the use of biomarkers in blood of such patients as a non invasive technique

The Association of the Activation-Inducible Tumor Necrosis Factor Receptor and Ligand with Lumbar Disc Herniation

PURPOSE: Herniated nucleus pulposus fragments are recognized by the immune system as a foreign-body, which results in an autoimmune reaction. Human activation-inducible tumor necrosis factor receptor (AITR) and its ligand, AITRL, are important costimulatory molecules in the pathogenesis of autoimmune diseases. Despite the importance of these costimulatory molecules in autoimmune disease, their role in the autoimmune reaction to herniated disc fragments has yet to be explored. The purpose of the present study is to investigate whether the overexpression of AITR and AITRL might be associated with lumbar disc herniation. MATERIALS AND METHODS: The study population consisted of 20 symptomatic lumbar disc herniation patients. Ten macroscopically normal control discs were obtained from patients with spinal fractures managed with anterior procedures that involved a discectomy. Peripheral blood samples from both the study patients and controls were collected. The expression levels of AITR and AITRL were investigated by flow cytometric analysis, confocal laser scanning microscopy, immunohistochemistry and by reverse transcriptase-polymerase chain reaction (RT-PCR). The soluble AITR and AITRL serum levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Flow cytometric analysis revealed significantly higher levels of both AITR and AITRL in the lumbar disc herniation patients than in the controls. The AITRL expression levels were also increased in patients with lumbar disc herniation, shown by using confocal laser scanning microscopy, immunohisto-chemistry, and RT-PCR. Finally, soluble AITR and AITRL were elevated in the patients with lumbar disc herniations. CONCLUSION: The AITR and AITRL are increased in both the herniated disc tissue and the peripheral blood of patients with lumbar disc herniation.

Do desipramine and fluoxetine ameliorate the extent of colonic damage induced by acetic acid in rats?

The present study was aimed to compare the anti-inflammatory and antioxidant effects of two antidepressant drugs; desipramine and fluoxetine, administered in two different doses, on experimentally induced colitis in rats. Two doses for each drug [10, 20 mg/kg/d] were injected intraperitoneally in forty eight adult male albino rats for 2 weeks after induction of colitis by intra-colonic administration of 2ml 3% acetic acid. Several parameters including, macroscopic [ulcer score index], microscopic [histological] and biochemical such as myeloperoxidase [MPO], reduced glutathione [GSH], tumor necrosis factor alpha [TNF-alpha] and interleukin-1 Beta [IL-1beta] were measured using standard assay procedures. The study demonstrated that both desipramine and fluoxetine significantly attenuated the extent and the severity of the macroscopic and microscopic histological signs of cell damage. Both drugs significantly reduced tissue MPO activity in a dose dependent manner. Both desipramine and fluoxetine at either dose increased significantly the GSH in colonic tissue. On the contrary, both desipramine and fluoxetine significantly reduced TNF-alpha and IL-beta in a dose dependent manner. However, desipramine at the dose of 20 mg/kg produced more decrease in the level of TNF-alpha compared to the effect of the smaller dose, and on the contrary, fluoxetine at the dose of 10 mg/kg showed more decrease in the level of IL-beta compared to the effect of the larger dose. The available data indicate that both desipramine and fluoxetine have anti-inflammatory and antioxidants effects in experimentally induced colitis in rats opening the avenue to their possible protective role in patients with inflammatory bowel disease

Evaluation of hyperbilirubinemia in acute inflammation of appendix: a prospective study of 45 cases.

BACKGROUND: Hyperbilirubinemia is the result of imbalance between production and excretion of bilirubin by the liver. It may be because of hepatocellular, cholestatic or haemolytic diseases. Liver receives blood mainly through portal venous system, which receives blood from abdominal organs. Portal blood carries nutrients and other substances absorbed from gut including bacteria and its product (toxins). In small percentage, even in normal healthy people, bacteria are found in portal blood. It is commonly cleared by detoxification and immunological action of reticuloendothelial (RES) system of liver that act as first line defence in clearing toxic substances, bacteria and it's products. But when bacterial load overwhelms the Kuffer cell function, may cause dysfunction or damage to the hepatocytes (liver parenchyma). It reflects, rise in serum bilirubin (SB) alone or in combination with liver enzymes depending upon the type, severity and site of lesion. Recently, another substance known as Cytokines e.g. IL-6, Tumour necrosis factor (TNF), have also been labelled to be responsible for depressed excretory function of liver and may lead to increase in SB level without rise in liver enzymes. AIM: To evaluate hyperbilirubinemia associated in acute inflammation of appendix (acute appendicitis and its complication). MATERIAL AND METHODS: This is a prospective study conducted at NGMC Teaching hospital Nepalgunj, Nepal during Oct.2004-Oct.2005. 45 Consecutive cases of acute appendicitis admitted in surgical unit III, were recruited for this study. Clinically suspected cases were subjected to investigations to confirm the diagnosis. Investigations included total leucocytes count, differential leucocytes count, urine analysis and ultrasound. These cases were also subjected to routine liver function tests. Subsequently these cases were operated and clinical diagnosis was confirmed per-operatively and post operatively by histopathological examination of the specimen. Their clinical and investigative data were compiled and analyzed and following observations were obtained. Routine liver function test results were compared with laboratory reference values given in Table- 1, 2 and 3. INCLUSION CRITERIA: Case with acute appendicitis and its complication with test negative for HBSAg and no past history of jaundice. EXCLUSION CRITERIA: Case with acute appendicitis and its complication with test positive for HBSAg and /or past history of jaundice. RESULTS: Total number cases were 45. Of 45, 25 were males and 20 were females. Their age ranged from 11 years to 60 years. The average was 27.2 years. Duration of symptoms ranged from 5 hours to maximum 9 days. Among 45 cases diagnosed as acute appendicitis clinically (preoperatively), per operatively, 36 cases had inflamed appendix, 3 cases had gangrene, 5 cases had perforation with peritonitis (4 localized and 1 generalized peritonitis) and only a single case was noted to be of normal appendix (Table 4). Liver function tests (LFT) analysis revealed following results, Among 45 cases, SB was raised in 39 cases where as 6 cases had normal SB level. The raised SB ranged from 1.2 mg/dL to 8.4 mg/dL. The average level of SB was 2.38 mg/dL. All the cases had indirect fraction of SB above 15%. (Table 4). The rise in SB was without concomitant much rise in liver enzymes. CONCLUSION: Following conclusion can be drawn from the present study. Firstly, There was Hyperbilirubinemia in 86.6% of the patients of acute inflammation of appendix (i.e. acute appendicitis and its complications). Secondly, Raised SB ranged from 1.2mg/dL - 8.4 mg/dL. Thirdly, The rise in SB was mixed in type (both indirect and direct). Finally, The hyperbilirubinemia was intra hepatic cholestatic in type due either to abnormality in permeability of hepatocyte or ductular membrane enzyme inhibition as the liver enzymes were not much elevated.

Detection of DNA damage in nonalcoholic steatohepatitis; and its correlation with serum imbalance of adiponectin/tumor necrosis factor-alpha

NASH is a potentially serious condition, since as many as 25% of patients with NASH may progress to cirrhosis and experience complications of portal hypertension, liver failure, and hepatocellular carcinoma. The aim of the present work is to study DNA damage in patients with NASH and correlate this damage with serum levels of adiponectin and TNF-alpha in those patients to evaluate their role in the pathogenesis of the disease. The study was carried out on 20 patients with NASH [8 males and 12 females] and 10 healthy age and sex matched individuals as a control group. Detection of DNA damage in liver tissues was performed by gel electrophoresis. Serum levels of adiponectin and TNF-alpha were estimated in all patients and control group. There was a statistically significant increase in DNA damage in NASH patients than control subjects, detected by the intensity of the damaged DNA bands expressed by maximum optical density [max. OD], where it was 36.57 +/- 18.60 in NASH group and 0.088 +/- 0.02 in control subjects [p<0.001]. The intensity of the damage and fragmentation of DNA was not the same in all patients with NASH. More damage was detected in subgroup A, the max. OD in this group was 66.834 +/- 7.21. There was significant decrease in serum adiponectin level and significant increase in serum TNF- a level in NASH patients than control subjects [5.69 +/- 1.49 micro g/ml versus 13.67 +/- 1.6 micro g/ml and 9.12 +/- 3.1 pico g/ml versus 2.7 +/- 1.4 pg/ml respectively]. TNF- a serum level in NASH patients had significant positive correlation with DNA damage in those patients [r = 0.46, p <0.001], while serum adiponectin level had negative correlation with DNA damage in NASH [r = - 0.63, p 0.001]. DNA damage occurs in NASH patients as a result of increased oxidative stress and altered cytokine metabolism in the form of increased TNF- alpha and decreased adiponectin levels. Measures to prevent oxidative stress or inhibit TNF-alpha or increase adiponectin may improve NASH

Tumour necrosis factor alpha [TNF-Alpha] levels in toxoplasma gondii infected cases with or without repeated abortions

The aim of this study was to evaluate the tumor necrosis factor alpha [TNF-alpha] as one of cytokines produced in chronic toxoplasmosis in seropositive cases with anti-toxoplasma specific antibodies who have repeated abortions and in cases with normal delivery outcomes, compared to sero negative cases. TNF-alpha was found to be higher in seropositive cases with repeated abortion than in scronegative cases with repeated abortions and seronegative cases with normal delivery outcome

Serum terminal complement complex as a prognostic predictor in children with congestive heart failure

The activation of the complement system in pediatric patients with congestive heart failure [CHF] still remains unclear. The objective of this study was to measure the serum levels of terminal complement complex [C5b-9] to determine its predictive value for the prognosis in children with CHF, and to correlate these levels with clinical and echocardiographic assessment of heart failure. Forty cardiac patients with CHF, with a mean age of 5.2 years, were enrolled in the study. According to Ross classification of CHF, they were classified as: Ross class II [12 patients], class III [13 patients], and class IV [15 patients]. Twenty healthy children served as a control group. Serum C5b-9 was assessed with Enzyme lmmunoassay and serum tumor necrosis factor- alpha [TNF- alpha] was measured using ELISA kits. Echocardiographic assessment of left ventricular systolic and diastolic functions was performed. Clinical outcomes were determined at follow-up period of 6months [death or major adverse cardiac events]. The results showed that serum C5b-9 [and also serum TNF- alpha] were significantly higher in patients with CHF as compared to controls [P<0.001] and increased with the severity of the disease, with the highest levels in Ross class IV children and in patients with adverse clinical outcomes by 6 months [P<0.001]. there were significant positive correlations between Ross class of CHF and serum c5b-9 levels, and significant negative correlations between echocardiographic parameters of ventricular function and C5b-9 levels [P<0.001]. Serum C5b-9 [the terminal complement complex] is significantly elevated in children with CHF, increasing with the severity of the disease, and it is a prognostic predictor of adverse clinical outcome. Complement may be a novel target for therapeutic intervention with specific complement inhibitors in patients with CHF

relationship of IL-6 and TNF alpha in serum and gingival cervicular fluid of Egyptian pregnant women with periodontitis to preterm labor

Recent studies have suggested that periodontal disease is a risk factor for preterm labor [PL]. Our objective was to determine if maternal periodontitis could be a risk factor for PL through assessing and correlating the levels of IL-6 and TNF alpha in both serum and gingival crevicular fluid [GCF] from pregnant women in between [20-31] weeks of gestation with and without periodontitis and also to determine if periodontal treatment may have an effect on the level of IL-6 and TNF in GCF and serum to reduce the risk of PL.200 pregnant women with periodontal disease aged 25-35 were enrolled while receiving prenatal care in Antenatal Clinic of Maternal and Child Care of Tanta Hospitals. Women were assigned to control group [n= 40] which are free from any periodontal disease. Study grqup [n= 160] with attachment >6mm, this group included group A [treated group] [n=80] which received periodontal treatment [phase I therapy]. Group B [untreated group] [n=80] which did not receive any periodontal treatment. The level of IL-6 and TNF alpha in both local [GCF] and systemic [serum] was determined by ELISA. Of the 200 women enrolled, 134 were excluded from the analysis for different reasons. The incidence of PL in the treated group was 30% [6/15] but in the untreated group was 80% [18/23], and in the control group was 0%. Multivariate analysis showed that the effect of time changes was strong for plaque index [PI] by IL-6 and lastly GI [1, 0.759, and 0.604] respectively. Periodontal disease appears to be an independent risk factor for PL. Periodontal therapy significantly reduces the level of IL-6, TNF alpha in both GCF and serum which in turn reduce the rate of PL in this population of women with periodontal disease

TNF-alpha in NIDDM, obese and non obese persons

Adipocytes are producing a variety of molecules that are capable of Junctioning in both a paracrine and autocrine fashion, tumor necrosis factor alpha is one of these molecules that has been shown to be elevated in obese and diabetic patients a finding which was correlated to insulin resistance, lipid abnormalities and certain types of obesity. the present study was conducted on 46 persons; 26 diabetics, 10 obese non diabetic and 10 non obese non diabetic persons. All of them were subjected to the following investigations: weight, height, BMI, W/H ratio, fat%, lipid profile, HBAlc and TNF alpha determination. It was found that there is a significant elevation of [LDL, TG, cholesterol VLDL, fasting blood glucose, HBAlc and TNF alpha] in diabetic group as compared to control non obese group. The same situation applies to the difference between diabetic group and obese non-diabetic group when comparing [TG, cholesterol, VLDL, fasting blood glucose, HBAlc and TNF alpha]. Comparing obese and non obese normal persons, it was found TNFalpha was insignificantly elevated. Correlating TNF alpha with different other parameters showed the following findings; in group 1 there was a positive correlation with BMI and fat% while there was no significant correlation with W/H ratio, in groups 2 and 3 there was no significant correlation between TNFalpha and any of the different parameters, interestingly, making this correlation in the whole sample [26 diabetic patients, 10 non obese normal persons and 10 obese non diabetic persons] it was found that TNF alpha is significantly correlated to W/H ratio, LDL, cholesterol VLDL, fasting blood glucose and HBAlc our results show that TNF alpha is significantly elevated in diabetic group more than other group and is related to fat% and BMI, this confirms the results of the previous studies and stresses its importance in the pathogenesis of insulin resistance and hyperglycemia and may be vascular remodeling in addition to other factors

role of interleukin-1 receptor antagonist in the pathogenesis of arthritis

The objectives from this study was to compare serum levels of interleukin-1 receptor antagonist [IL-1Ra] with synovial fluid levels in patients with rheumatoid arthritis [RA] and osteoarthritis [OA], and to correlate the level of the naturally occurring IL-1 inhibitor with indices of disease activity and severity in RA patients. A correlation was also done between IL-1Ra and tumor necrosis factor alpha [TNF-alpha] with knee radiographs in OA patients as a parameter of disease severity. IL-1Ra and TNF-alpha were assessed by Enzyme Linked Immunosorbent Assay [ELISA] in serum and synovial fluids in 20 female patients with RA, 20 female patients with OA and in the serum of 15 controls. We found that IL-1Ra and TNF-alpha concentrations were increased in both RA and OA sera compared with the control group. Although there was no significant difference between the concentration of serum IL-1Ra in RA patients when compared to those with OA, we observed that its mean level were higher in patients with RA. Moreover, IL-1Ra levels were correlated significantly with the levels of ESR, CRP as well as all the clinical parameters of disease activity measured in RA patients. We also found significant correlation between the synovial levels of both IL-1Ra and TNF-alpha in RA when compared to OA patients. The mean level of synovial IL-1Ra in RA patients is about twice that was found in OA patients. Our data reveal a consistent association between IL-1Ra production and disease activity and severity in RA patients. It also reveals a high serum and synovial IL-1Ra and TNF-alpha in OA patients that make us suggest that OA should be considered a disease with a systemic and local inflammatory response. Further studies are needed to determine the association of cytokines and its inhibitors in OA

Circulating levels of pro-inflammatory cytokines in pregnancies complicated by preeclampsia and eclampsia

The purpose of the study was to evaluate the determinant of proinflammatory cytokines status in patients with preeclampsia of different degrees and antepartum eclampsia, also how these cytokines affect one another. Serum tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6] were measured in 40 women in the third trimester of pregnancy; 10 healthy normotensive pregnant women [group I], 10 women documented mild preeclampsia [group II], 10 women documented severe preeclampsia [group III] and 10 women with antepartum eclampsia [group IV] with matched maternal and gestational ages. All women were primigravida with singleton pregnancies. From the results obtained, it was concluded that TNF-alpha interacts in complex ways with the vascular endothelial cells to release IL-6. Both TNF-alpha and IL-6 are likely to be important mediators of pathophysiological derangement seen in this pregnancy disorder