Incidence of human cytomegalovirus in breast carcinoma tissues is associated with a higher expression of growth factor receptor-bound protein 2

Background: female mammary carcinoma is the second most common cancer incidence among women and the fifth most common leading cause of cancer death worldwide. Premenopausal young women are more frequently targeted by inflammatory breast cancer (IBC), which is the most lethal form of breast cancer. The human cytomegalovirus (HCMV) has been identified as one of the viral infection with a higher frequency in carcinoma tissues of IBC than in non-IBC. The adaptor protein growth factor receptor-bound protein 2 (Grb2), was found to be upregulated in HCMV-infected cells and play as crucial role in cancer progression. Objective: this study aimed to assess the expression level of Grb2 in carcinoma tissues of IBC and non-IBC with HCMV infection. Patients and Methods: overall, 135 female diagnosed with breast carcinoma were enrolled in this study. Using conventional and real time polymerase chain reaction (PCR), we determined the incidence of HCMV and assessed the expression level of Grb2 mRNA in the breast cancer tissue samples. Results: Grb2 mRNA was significantly upregulated in HCMV+ IBC higher than in HCMV+ non-IBC. According to the molecular subtype, Grb2 mRNA was significantly higher upregulated in breast carcinoma tissues of HCMV+ hormonal positive (HP) than in triple negative (TN) counterparts. Conclusion: HCMV infection is associated with a high expression of Grb2 mRNA in IBC and that HP HCMV+ mammary carcinoma tissues confer upregulated Grb2 mRNA, suggesting a potential role of HCMV infection in enhancing of Grb2 mRNA expression in breast cancer with HP

Evaluation of fungal and bacterial aerosols in cotton dust in a spin factory in El-Minia city and its relation to pulmonary function changes among workers

Background: High concentration of airborne viable particles [bacteria and fungi] are being aerosolized in industrial environments. Inhalation of cotton dust, flax or hemp dust, by textile workers has been known to cause acute reversible bronchoconstriction, which on repeated exposure leads to chronic pulmonary disease called byssinosis. The present study was done in order to determine the concentration of bacteria and fungi in cotton dust and to assess their effect on the severity of pulmonary symptoms and functions

Methods: The present study was carried out on 208 workers. All participants were subjected to full history taking and clinical examination. Pulmonary function tests and sputum culture were done for symptomatic cases. Measurements of concentration of bacteria and fungi were carried out in the main working areas

Results: Mean concentration of total collected fungi was 1215 cfu/m[3] while Gram -negative bacteria was found in low concentration [17.5 cfu/m[3]]. Increased incidence of chest tightness, dyspnea and significant decline in FEV1 % and PEF % were found among exposed workers

Conclusion: Increased incidence of chronic respiratory illness and significant impairment of lung functions were observed among highly exposed workers and smoking appears to be another risk factor

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

Clinical utility of paraoxonase in atherosclerotic coronary artery disease

The scope of this study was to evaluate the significance of serum paraoxonase [PON] assay in diagnosing coronary artery disease [CAD] and to investigate its reliability in determining the severity and progression of CAD. Furthermore, the diagnostic reliability of this marker was compared to that of routinely used conventional lipid parameters and apolipoproteins A1 and B. This study included 65 male patients suffering from anginal pain and were subjected to coronary angiography in addition to 20 age matched healthy males. The coronary angiography of 20 angina patients revealed normal coronary arteries and they were considered as pathological controls. The remaining 45 patients were proved to have atherosclerotic CAD, 15 of them had single vessel affected [SVD], 14 had double vessels affected [DVD] and 16 had multiple vessels affected [MVD]. Routine lipid profile, apolipoprotein A1 [apo-A1], apolipoprotein B [apoB] and serum PON were assayed in all subjects. Serum PON was assayed using a prepared solid phase competitive enzyme immunoassay. Apolipoprotein A1 [apo-A1] and apoB were assayed on the Olympus AU400 system by an immunoturbidimetric endpoint method. Routine lipid parameters were measured on the Synchron CX7 autoanalyzer. Our results showed that all angina subjects were similarly exposed to hypertension, diabetes mellitus and smoking as risk factors for CAD. Serum lipid profile did not vary significantly among the subjects suffering from chest pain. However, when compared to healthy controls, patients with anginal pain showed significantly lowered HDL-C and apo-A1 serum levels and significantly higher atherosclerotic, risk ratio. Moreover, all assayed lipid parameters failed to show any significant difference between different subgroups of CAD patients. In the present study, serum PON levels decreased progressively with the progression of CAD being significantly lower in MVD and DVD subgroups than in SVD. Serum PON levels correlated significantly with nearly all angiographic parameters. Moreover, serum PON had a diagnostic sensitivity, specificity and efficacy of 95.6%, 93.2% and 94.6%, respectively at a cut-off level of 91.0 microg/mL in detecting CAD patients when compared to controls and was proved to be the best discriminating marker for CAD using the multiple regression analysis. As regards apo-A1, the diagnostic efficacy was 67.6% at a cutoff level of 120 mg/dL and it was the second discriminating parameter that could differentiate CAD patients from healthy subjects using the multiple regression analysis and showed a significant correlation with some angiographic parameters and with PON. Finally, routine lipid profile parameters and apoB did not show any significant correlation neither with PON nor with the angiographic parameters. In conclusion, the current study revealed that serum PON was the best predictive marker for CAD risk and the best diagnostic tool for severity for atherosclerotic CAD

Anti-malarial chloroquine stimulate P53-apoptotic pathway in rat hepatocytes

This study investigated rat liver injury produced by anti-malarial dose of chloroquine [CQ] and elucidated if CQ could induce DNA damage and subsequently p53-dependent apoptosis in rat hepatocytes or not. The effect of anti-malarial CQ on p53-apoptotic pathway of rat liver cells after different time intervals [1, 2 and 3 days] was studied. Apoptosis was assessed in whole liver tissue using ELISA technique and at single cell level using TUNEL technique. The level of expression of p53 was measured quantitatively by ELISA. The results found that CQ induced DNA damage and rat hepatocytes apoptosis in a time dependent manner. Secondly, p53 expression was associated with CQ administration in time dependent manner. Thus, anti-malarial dose of CQ induces DNA damage and apoptosis of rat liver cells and the expression of p53 could be considered as a normal response of hepatocytes suffering from CQ genotoxic stress

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

Assessment Of regional diastolic dysfunction in coronary artery disease by tissue doppler during dobutamine stress echocardiography

The present study aimed to evaluate the role of tissue Doppler imaging in diagnosis of diastolic dysfunction during Dobutamine stress echocardiography and to compare it with coronary angiography. Sixty patients were included in this study, 40 of them were with ischemic heart disease according to the result of coronary angiography and 20 of them were coronary arteries free also according to the coronary angiography. All patients were subjected to thorough clinical examination, resting ECG, conventional transthoracic echocardiography and Dobutamine stress echocardiography. Dose of Dobutamine was 5 micro g/kg/min in each stage [3 min for each stage] up to 50 micro g/kg/min or target heart rates achieved, detection of wall motion abnormality or dangerous arrhythmias occur [Mc Neil et al., 1992] [1]. Tissues Doppler echocardiography was used at baseline, low dose and peak stress. Tissue Doppler echocardiography wave form at mitral annulus in 4 left ventricular sectors [lateral, septal, anterior and inferior] were used to measure early filling wave [Em cm/sec], late filling wave [Am cm/s] and deceleration time [DTm ms]. Coronary angiography was performed to each patient and control.1- Higher association of ischemic heart disease and male sex, diabetes, hypercholesterolemia and positive family history for ischemia.2- Low accuracy of mitral E/A ratio for diagnosis of coronary artery disease, as there was non-significant difference between both groups.3- The presence of heterogeneity of regional contraction and relaxation in control group.4- Reduced Em wave in ischemic area when comparing it with the corresponding wall in healthy subject.5- Biphasic response of Em wave in ischemic region during Dobutamine stress test i.e. increase with low dose and decreased with high dose.6-Progressive increment of Am wave in each work step of Dobutamine infusion in both healthy and ischemic patients.7- Shorter DTm in ischemic group when it compared with that of control group.8- Progressive decrement of DTm during Dobutainine stress from low to peak in ischemic patients.9- Low accuracy of wall motion score index in diagnosis of coronary artery disease when compared it with tissue Doppler accuracy.10- Higher agreement between tissue Doppler and results of coronary angiography, which is the golden standard for diagnosis of ischemic heart disease. The presents study demonstrate the usefulness and advantage of combining these techniques in diagnosis of ischemic heart disease. The biphasic response of Em velocity is characteristic and diagnostic of ischemic heart disease

Oncostatin-M and matrix metalloproteinase-3 production in rheumatoid arthritis and osteoarthritis

To evaluate the significance of measuring serum levels of Oncostatin-M [OS-M] and matrix metalloproteinase-3 [MMP-3] in the assessment of rheumatoid arthritis [RA] and osteoarthritis [OA]. The study was performed on 15 RA, 15 OA patients and 10 controls age and sex matched. Laboratory and clinical data for all the patients were assessed and serum MMP-3 and OS-M were measured in all subjects. Statistical analysis and correlations were done for all the data. Serum levels of MMP-3 and OS-M were higher in RA than OA patients and controls. The difference was of a high statistical significance [p<0.001, p<0.001]. In RA patients OS-M level correlated positively with MMP-3 level [r=0.826] but OS-M and MMP-3 did not correlate with any parameters of disease activity. There was a significant difference in serum levels of OS-M and MMP-3 in patients taking steroid therapy and those who were not on steroid therapy. In OA patients, serum MMP-3 and OS-M were also higher than those of controls and the difference was highly significant. MMP-3 in OA patients correlated positively with ESR [r=0.77] and this was higher in patients with severe erosive changes. Measuring serum MMP-3 and OS-M is necessary for evaluating synovial inflammation and cartilage destruction in RA and OA patients. Using MMP inhibitor may be useful to stop the progression of synovitis and erosions

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]