Serum paraoxonase 1 level and genetic polymorphisms in chronic hepatitis patients

Paraoxonase [PON] is an ester hydrolase that catalyzes the hydrolysis of organophosphorus compounds, unsaturated aliphatic esters and carbamates. PON gene family contains three members: PON1, PON2 and PON3. PON I is tightly bound to HDL in serum to confer protection for LDL against oxidation. The liver plays a key role in PON1 synthesis as PON1 gene expression was only observed in the liver. The aim of this work was to investigate the relationship between serum PON1 level and the degree of liver damage in patients with chronic hepatitis, to study the genetic variability of serum PON1 and to evaluate the efficiency of serum PON1 assay in comparison with standard liver function tests in the assessment of liver damage. Thirty seven chronic hepatitis patients were included in this study. They were classified into; Group I: chronic hepatitis patients without cirrhosis [n = 21] and Group II: chronic hepatitis patients with cirrhosis [n = 16] and their results were compared to those of 15 healthy controls. Serum PON1 assay and PON1 genotyping for transitions at 192 and 54 positions were done for all subjects in addition to standard liver function tests including : total protein [TP], serum albumin [sAlb.], aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], total bilirubin [T bil.] and direct bilirubin [D bil.]. PON1 serum levels were significantly decreased in Group I compared to controls [p < 0.01, 52.5% decrease] and such decrease was even exaggerated in Group II when compared to controls [p < 0.01, 67% decrease]. Moreover, serum PON1 had significant positive correlations with TP and sAlb. and significant negative correlations with AST, ALT, ALP, T bil. and D bil. in patients' group [Group I and II together]. Regarding genotypes and allele frequencies for PONl enzyme at two polymorphic positions PONl[192] and PONl[54] in patients' and control groups, there were no significant differences in genotype or allele frequencies between patients and controls for either polymorphic site. Moreover the mean percent change of PONl level in different genotypes compared to controls in liver disease patients when reclassified according to genotypes was similar to percent decrease of PONl level independent of genotypes compared to controls [-52% in PONl in relation to 192 transition and -55% in PONl level in relation to 54 transition]. Moreover, different PONl genotypes [QQ, QR and RR for PONl[192] and LL, LM and MM for PON[154]] had significant positive correlations with TP and sAlb. and significant negative correlations with AST, ALT, ALP, T bil. and D bil. in patients' group. Stepwise multiregression analysis was performed in this study which revealed that serum PONl, AST and serum albumin constitute the best panel which can predict the presence of liver disease [F = 42.6, p < 0.01]. Moreover, diagnostic reliability for serum PONl and standard liver function tests were done at various cut off levels, Receiver Operator Characteristic Curve [ROC] was illustrated and area under the curve [AUC] was calculated for each parameter. In Group I, serum PONl had the best performance at 208 micro g/ml [80% sensitivity, 95% specificity and AUC = 0.89] followed by AST at 48 IU/L [72% sensitivity, 90% specificity and AUC - 0.85] and AUC for both parameters were significantly higher than AUC for the remaining parameters [p < 0.05]. In Group II, serum PONl performance was even better at cut off 139 micro g/ml [85% sensitivity, 95% specificity and AUC = 0.96] and its AUC was significantly higher than other parameters [p < 0.05]. There was a significant decrease of serum PONl level in chronic hepatitis patients [Group I and Group II] related to the degree of hepatic dysfunction irrespective of allele or genotype differences at positions 192 and 54 amino acids. Moreover, serum PONl, AST and sAlb. were found to be the best panel to predict the presence of chronic liver disease. Supporting this issue, the diagnostic performance of serum PONl followed closely by AST was the best in Group I, while the performance of serum PONl was far superior to that of other tests in Group II indicating a better over all performance for PONl for diagnosis of chronic liver disease specially severe forms [liver cirrhosis]. Hence, the addition of serum PONl assay to the current battery of liver function tests may improve the evaluation of chronic hepatitis patients

Chemokine receptor 3 and eosinophilir cationic protein: as novel laboratoyt markers for assessment of airway inflammation in bronchial asthma

The aim of this work was to trace and follow up the profile of the chemokine receptor3 [CXCR3], eosinophilic cationic protein [ECP] and immunoglobulin E [IgE] in atopic asthmatic patients during and between the attacks and to outline their relations to other parameters denoting disease activity and severity. Moreover, this study also aimed at testing the ability of the three markers to monitor the patients response to treatment in order to tailor relevant therapeutic modalities to alleviate the patients' allergic condition. Thirty seven atopic asthmatic patients [Group 1] were enrolled in this study. They were sub classified according to their peak expiratory flow [PEF] into mild, moderate and severe asthmatics [subgroups IA, IB and IC, respectively]. Their results were compared to those of 13 healthy subjects [Group II]. For all subjects; number of eosinophils in peripheral blood, serum total lgE, serum ECP and plasma CXCRJ% expression by flow cytometry were estimated. For group I only laboratory parameters and PEF were done twice; during acute asthmatic attack and between the attacks [controlled condition after one week of efficient treatment of corticosteroids and supportive therapy]. Highly significant results were found in asthmatic patients' group [Group I] during the attack regarding the number of eosinophils, ECP values and CXCR3% [decrease], while only a significant difference was found regarding IgE levels when compared to healthy controls [Group II]. Comparative study between patients' subgroups was done revealing highly significant differences for patients in subgroups IB and IC regarding CXCR3%, ECP and IgE [in subgroup IC only], when compared to control group. While, in subgroup IA highly significant difference was found regarding ECP values and significant differences were found regarding.. CXCR3% [decrease] and IgE values when compared to controls. Similar results were found when patients subgroups results were compared to each others. Paired t test was used to compare patients' results during acute attack and between attacks [after treatment] to monitor the inflammatory events in both situations, where highly significant differences were found regarding CXCR3% [increase] and ECP levels [decrease], while only a significant difference was found for IgE levels [decrease]. Correlation matrix was performed for patients' results during acute attack revealing strong negative correlations between CXCR3% expression and ECP, IgE and number of eosinophils in peripheral blood [r= -0.8, -0.7 and -0.5, respectively]. While, ECP values had strong positive correlation with IgE [r=0.7] and a weak positive correlation with number of eosinophils in peripheral blood [r= 0.4]. Stepwise multi regression analysis was done to choose the best parameter [s] which can be used for monitoring patients' good response to treatment, where both CXCR3 and ECP were found to be the best for that purpose [F=7.8, p<0.01]. One way analysis of variance [ANOVA] testing and positive likelihood ratio were done to choose the best parameter [s] which can discriminate patients with severe asthma among other asthmatics. ANOVA test revealed that CXCR3% was the best for this purpose [F=47.2, p<0.01] followed by ECP, lgE and number of eosinophuls in peripheral blood [p<0.01, <0.01 and <0.05, respectively]. Moreover, positive likelihood ratio revealed that both CXCR3% and ECP had comparable excellent ratios [ratio =10, respectively] followed by IgE [ratio=7]. This study revealed an integrated explanation of the immunoinflammatory events in acute atopic asthma. Where, a drop of CXCR3 expression paves the way for the immediate hypersensitivity reaction of allergy including T helper2 [Th2] cells with their chemokine receptors leading to eosinophilic recruitment and degranulation releasing ECP with the help of IgE bound on their cell surface resulting in airway inflammatory response and typical allergic reaction of asthma. Hence, new therapeutic modalities for asthmatic patients should include agonists for CXCR3 or Th2 antagonists to alleviate the patient's condition. Moreover, this study demonstrated that short term oral corticosteroids modulate the balance of chemokine receptors' expression in favor of CXCR3 in asthmatic patients. In addition, this work provides evidence that CXCR3 and ECP assays can be used efficiently for monitoring of treatment efficacy in such patients. Lastly, CXCR3, ECP and to a lesser extent IgE assays were found to be good prognostic markers to distinguish patients with severe asthma among other asthmatic patients

Crystalloid versus blood-enriched cardioplegia: clinical and biochemical markers of myocardial injury

In this study, two methods of myocardial preservation were compared. Sixty patients were enrolled in this study and categorized into two groups: Group I, 28 patients received cold crystalloid cardioplegia and group II, 32 patients received cold blood enriched cardioplegia. The two groups of patients [all underwent mitral valve replacement] were comparable as regards age sex, New York Heart Association class [NYHA], ejection fraction, pulmonary artery pressure, left atrial size, ischemic and cardiopulmonary bypass times. Myocardial protection has been assessed from the evolution of hemodynamic parameters, reperfusion arrhythmias and the postoperative need for inotropic support. The extent of myocardial injury was also estimated by monitoring the postoperative leakage of the MB isoenzyme of creatinine kinase [CK-MB] and the more recently used cardiac troponin T [cTnT]