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

Detection of anticardiolipin and antinuclear antibodies in juvenile idiopathic arthritis and their relation to disease activity

Juvenile Idiopathic Arthritis [JIA] is an autoimmune disorder. The American College of Rheumatology defined juvenile arthritis as a chronic condition that causes inflammation in one or more joints and begins before the age of sixteen. Juvenile arthritis may be difficult to diagnose because children often compensate well for loss of function and may not complain of pain. Observations of limping, stiffness when awakening, reluctance to use a limb or reduced activity level may be clues. Anticardiolipin antibodies [aCL] have been demonstrated in a large spectrum of autoimmune diseases. However, its occurrence in childhood, in particular in JIA, is not well established. The present study addressed the frequency and clinical significance of aCL and to find an association of aCL and antinuclear antibodies [ANA] with JIA and their correlation to clinical picture, functional capacity and disease activity. Thirty five children were included in this study. The patients group consisted of 20 children [6 boys and 14 girls] with JIA according to the American College of Rheumatology [ACR] 1987 criteria and fulfilling the criteria for diagnosis of JIA [Cassidy and Pretty, 1990]. Their mean age was 12.0 years [yr] +/- 2.6 SD, ranged from 8.3 to 16 yr, with a mean of disease duration 3.4 yr +/- 1.1SD, ranged from 1.4 to 5.0 yr. The control group consisted of 15 healthy children [6 boys and 9 girls] with a mean age of 11.9 [yr] +/- 2.2 SD, their ages ranged from 7.3 to 15.3 yr. The JIA patients group was further classified into two subgroups according to the onset of the disease into systemic onset [no.= 7] and polyarticular-pauciarticular [P-P] [no.= 13]. All groups were subjected to complete history taking and physical assessment of local articular and systemic manifestations. Assessment of the degree of disease activity for JIA patients was performed according to Mallya and Mace scale [1981]. The functional capacity in all subjects was assessed according to Juvenile Arthritis Function Assessment Scale [JAFAS]; this scale ranged from 0 to 20. Blood samples were collected and subjected to the following tests: Complete blood count [CBC], ESR, C- reactive protein, Latex agglutination slide test for RF, and assessment of aCL [IgG and IgM] antibodies and ANA using ELISA method. There was increased incidence of disease in females rather than males [nearly double] and the P-P in patients represented 65%. There was a significant increase of ESR and serum levels of ANAs, aCL [IgG and IgM] autoantibodies and JAFAS [p<0.05] in the JIA patient groups as compared to the control group. There was a significant increase of ESR, AI and activity grade in systemic onset group as compared to P-P patients group [p<0.05]. The correlation study in P-P patients group determined a significant negative correlation between aCL- IgG with patient's age of onset and morning stiffness [p<0.05]. A significant positive correlation was found between disease duration with age [p=0.03] and no. of swollen joints [p=0.009]. In the systemic onset patients group, there was a non-significant correlation of aCL-IgG with any clinical or laboratory data [p>0.05], while significant negative correlations was found between aCL-IgM with age, age of onset, JAFAS and ANAs [p<0.05]. There was a positive significant correlation between ANAs and no. of swollen joint [r=0.79, p=0.04] and JAFAS [r=0.78, p=0.04]. We encountered two JIA female patients having positive aCL and ANA antibodies who manifested as P-P onset of the disease. They should have clinical follow up and regular ophthalmologic examination as they are highly susceptible for uveitis. The presence of aCL was not associated with ANA. The relation of aCL with the clinical parameters, could not be established. Age of disease onset, sex, disease activity, and JAFAS could be a prognostic indicator rather than immunological profile tests

Enhancement of bleomycin induced cytoggenetic damage in blood cultures after griseofulvin therapy

Griseofulvin [GF], a naturally occurring food contaminant and a widely prescribed cheap and effective antifungal drug, was tested for its potential mutagenicity using the conventional cytogenetic method to assess the frequency of chromosomal aberrations [CA] in the cultured blood cells of GF treated patients receiving the drug in a dose of 12.5 mg/kg/d. Fourteen patients complaining of Tinea capitis and corporis were divided into two groups according to the duration of therapy [four to six weeks and eight weeks]. Ten healthy control subjects of matched age and sex, who did not receive GF served as blood donors for bleomycin [BLM] tests. It might be considered as a co-mutagen, when there is concomitant exposure of patients receiving GF therapy for a long duration to any radiomimetic agent, as GF amplified their cytogenetic damage. The study recommended the integration of bleomycin test for chromosomal fragility with other cytogenetic assays during the evaluation of the genotoxicity of any chemical agent, as it reflects its possible interaction with any radiomimetic agent