ABSTRACT
Background: the induction of apoptosis for the virus-infected cells is an important host defense mechanism against invading pathogens. Activated T cells express Fas receptor; virus-infected hepatocytes bear the receptor as well. Both immune mediated reaction and cytopathic effects of HCV may be involved in pathogenesis. The apoptosis in immune or non-immune tissue and the mechanism of liver damage in chronic HCV infection remains uncertain
Aim: to assess the relationship between serum concentrations of adhesion and apoptotic-related soluble structures in patients affected by Hepatitis C Virus [HCV]. Investigate serum levels of soluble Fas antigen [sFas], soluble intercellular adhesion molecules-1 [sICAM-1]; study their roles in pathogenesis and liver cell damage in chronic hepatitis C patients
Patients and methods: sixty chronic hepatitis C patients [78.33% male vs. 22.66% female] and twenty controls recruited, they were positive for anti-HCV, and HCV-RNA by quantitative PCR. Liver biopsies were fixed and examination. Patients were classified into Group A [n=23] Chronic Hepatitis C minimal activity [0-3], Group B [n=19] mild activity [4 -8], and Group C [n=13] moderate and severe activity [9-13, and >13] depending on Histological Activity Index [HAI] score, then, assessment of hepatic [periportal, intra-lobular and total] was done. Patients were categorized into cirrhotic group [n=18] and non-cirrhotic group [n=42]. Tissue Fas [tFas] was assessed using anti-Fas antibody. Serum Soluble Fas [sFas] and [sICAM-1] were measured using EIA kits
Result: sFas was significantly increased in patients subgroups compared to controls [p<0.001] and in comparing cirrhotic to no cirrhotic [p<0.01]. tFas showed rising significance with disease activity [p<0.01].Both studied parameters of Fas were not correlated with ALT level [r=0.04, 0.03]. sICAM-1 revealed significant correlation of albumin levels in Group B [mild activity], with sFas antigen in non-cirrhotic patients group correlation not yet reach significance. No correlation was found between viral load, Fas parameters and sICAM [r=0.19, 0.16 and 0.21] respectively, while correlated with HAI [r=0.91, 0.96] respectively, expect in patients group A of [minimal activity]. In addition, sFas correlated significantly with tFas expect group A
Conclusion: Fas studied parameters can reflect severity of liver inflammation and play a crucial role in HCV infection. Equally, Soluble Fas and sICAM-1may serve as serological indicator of active inflammation. Strategies to prevent Fas-mediated apoptosis during inflammation might offer exciting therapeutic potential
ABSTRACT
Background: a growing body of evidence indicates that many trace elements an play important role in a number of carcinogenic processes that proceed through various mechanisms. Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver functions. Hepatitis infection may alter serum content of several trace elements e.g. Iron, Cupper, Manganese and Zinc. This alteration may play a role on ongoing liver fibro genesis. Serum metal levels, such as cupper [Cu], zinc [Zn], iron [Fe] and manganese [Mn] have been reported to be highly sensitive in the diagnosis of some diseases
Aim of work to evaluate the level of some trace metals in HCV and HCC patients, also correlating their levels with HCC tumor size
Patients and methods: sixty liver disease patients and fifteen healthy subjects served as a healthy control group. Patients were classified into Group A [n=20] chronic hepatitis C virus infection [compensated], Group B [n=20] patients [un compensated HCV], and Group C [n=20] patients diagnosed as hepatocellular carcinoma. After verbal consent, all patients detection of subjected to full history taking, clinical examination, and routine laboratory testing, in addition to viral hepatitis markers for the presence of HCV-Ab by linked immune sorbent assay [ELISA], the presence of HCV-RNA by PCR, alpha-fetoprotein, abdominal ultrasonography and estimation of serum minerals [Fe, Cu, Mn, and Zn] using atomic absorption spectrophotometry
Results: Mn and Cu levels were significant when correlated with the uncompensated HCV patients viral load [r = -0.65 and = 0.51, p < 0.01 and <0.02 respectively]. While in HCC patients, only Zn correlated significantly with viral load [P<0.01]. No correlation was found between HCV viral load and the studied trace elements in HCV compensated patients. Also, in HCC patients, serum Zn correlated significantly with tumor size greater than 5cm. while Cu serum level was significantly correlated with tumor size less than 5cm. in the uncompensated HCV group, iron serum level showed high significance results when correlated with ALT [r =0.563 , p <0.01]. Regarding correlation of liver function tests with studied trace elements in HCC patients group , the ALK showed high significant correlation with serum Cu level [r = 0.640, P<0.046]. Also, T.BIL/D.BIL showed slight correlation with Cu serum level but not yet reach significance [r = 0.583, p < 0.076]
Conclusion trace elements were verified to have an essential role in liver disease. Serum cupper levels were correlated with the viral load whereas, serum Mn levels showed a promising role in protecting HCV uncompensated patients. Zn might be of importance in regulating viral replication and liver carcinogenesis in HCV patients. While serum Zn levels were correlated with the viral load and liver damage in HCC patients. Further studies have to be performed to confirm the relation between trace elements and HCC development
ABSTRACT
Background: the receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA
Objective: to evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity
Methods: the study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine82serine [G82S] of the RAGE gene
Results: RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE
Conclusion: the levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine82serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions
ABSTRACT
Preeclampsia [PE] a major cause of maternal and neonatal mortality and morbidity worldwide in which hypertensive disorders during pregnancy account for 25.7% of maternal deaths. Both maternal and fetal genetic factors may predispose towards pre-eclamptic pregnancy, especially severe forms. However, preeclampsia is thought to be the result of the interplay between important genetic components and environmental influences; still, factors and mechanisms that lead to preeclampsia remain mysterious. Insertion/deletion [I/D] polymorphism of ACE gene has attracted significant attention and has been extensively investigated with its serum activity in a spectrum of cardiovascular phenotypes
Aim to study the potential association of I/D polymorphism of ACE gene in PE Egyptian women that gets us closer to understanding the disease
Patients and Methods: one hundred hypertensive and age-matched normotensive primigravida were recruited from Minufiya university Hospital. Routine investigations were done for PE diagnosis. DNA was extracted from whole blood of patients and healthy controls. All samples were genotyped for ACE I/D polymorphism according to Rigat et al. using amplification and PCR of known allelic variants. ACE genotype was identified and followed by serum concentration of ACE activity for both groups
Results: ACE DD genotype was found in 60% of PE patients while 34% of normotensive subjects [P 0.05], although D allele was higher among cases than controls, but it did not show significance [P > 0.05]. High significance was revealed when comparing the mean total ACE activity in the hypertensive patients [32.74 IU/l] and normotensive subjects [28.06 IU/l] [P <0.001]. The ACE activity in cases and controls carrying DD allele differed significantly [P<0.001]. In contrast the other ACE genotype ID and II did not show significance between cases and controls
Conclusion: these findings might bear implications for precise management of pregnancy in high-risk DD genotype women. Further large scale evaluation was required to provide added marker for risk assessment for PE patients
ABSTRACT
The receptor for advanced glycated end products [RAGE] is a multi-ligand receptor expressed as a cell surface molecule, interacting with diverse ligands. Since soluble RAGE [sRAGE] acts as a competitive receptor for cellular RAGE, the balance between these two types of receptors might be of importance in the pathogenesis of RA. To evaluate the levels of sRAGE in patients with RA compared with healthy controls and to assess the relationship between sRAGE levels and disease characteristics. Also, we assessed the association between the gene variants and the sRAGE level and disease activity. The study included 33 patients with RA and 16 healthy normal controls. All patients and controls are subjected to laboratory investigations including CBC, ESR, urine analysis, kidney function tests, liver function tests, RF and C-reactive protein [CRP]. Soluble RAGE was determined by enzymatic immunoassay and molecular study was done for single nucleotide polymorphisms [SNP] in the glycine 82 serine [G82S] of the RAGE gene. RF was positive in 72.7% of patients and was negative in all controls. CRP was significantly higher in RA patients as compared with controls [p<0.01]. Serum levels of sRAGE were significantly lower in RA patients than controls [840.11 +/- 230.32 versus 1111.59 +/- 143.20, p<0.05]. Genotyping of the RAGE gene showed G82S in 22 out of 33 RA patients, 5 of them were homozygous for the RAGE serine82 allele, while genotyping in the control subjects showed polymorphisms in the G82S in 5 out of 16, only one of them was homozygous for the RAGE G82S allele, indicating significantly increased G82S allele in RA patients as compared with controls [p<0.05]. The G82S allele was related to the CRP and sRAGE in RA patients. The sRAGE levels were significantly lower in RA patients. Linear regression analysis detected CRP and gene polymorphism as significant predictors for sRAGE. The levels of sRAGE were significantly lower in patients with RA and this reduction was correlated with the disease activity and glycine 82 serine gene polymorphism. Thus, the sRAGE may be an important marker of disease activity and can be used as a therapeutic target in these conditions
Subject(s)
Humans , Male , Female , Polymorphism, Genetic , Receptors, Immunologic , Polymerase Chain ReactionABSTRACT
Background: Leptin acts mostly as a signaling factor from adipose tissue to central nervous system regulating food intake. Adiponectin and Resistin produced by adipose cells may have a role in preventing the development of insulin resistance. Polycystic ovary syndrome [PCOS] is characterized by insulin resistance and 50% of women affected are obese
Aim of work: To study adipo-cytokines secretion in women with Polycystic Ovary Syndrome and correlate results with insulin resistance
Subjects and Methods: Thirty-two women with PCOS and matched controls were studied; three adipocytokines were measured compared with controls. Diagnosis of PCOS based on the classic criteria of hyperandrogenism and chronic anovulation. PCOS patients mean age was 26.2+/-1 years and Body Mass Index [BMI] mean was 28.7+/-0.7. years Controls of 20 women mean age 25.1+/-0.7 yrs and mean BMI 28.5+/-0.5. Normal ovulation was assessed by serum progesterone [20nM/l] on days 22-23 of menstrual cycle. Controls and PCOS were subdivided into groups of normal weight [BMI 25]; overweight [BMI 25-30], and obese [BMI 30]. Fasting blood samples used during the follicular phase [08:00-09:00 hr] for measurements of LH, FSH, insulin, glucose, leptin, adiponectin, and resistin using RIAs and EIAs. Insulin resistance was calculated by the quantitative insulin-sensitivity check index [QUICKI]
Results: PCOS women had increased insulin level [19.2 +/- 1.1] [P= 0.01] also a lower QUICKI values than controls [19 +/- 0.5] [P= 0.00], but obese women had a greater degree of insulin resistance. The entire PCOS group had lower levels of adiponectin [8.2 +/- 0.6] [P= 0.05] and higher levels of resistin [6.1 +/- 0.4] [P= 0.05] while leptin levels were not significantly different than controls. Leptin was only significantly higher in the obese group [BMI 30] compared with normal. However, adiponectin correlated only with BMI [r 0.58, P=0.05] but not with insulin [r 0.03] nor with QUICKI [r 0.02], and resistin did not correlate with any of these parameters. Leptin maintains its correlations with BMI, insulin and QUICKI [r=0.72, 0.54 and 0.63, P= 0.01, =0.05 and =0.01 respectively]
Conclusion: Circulating adipo-cytokine levels were different resulting in higher leptin and lower adiponectin, being the most marked change, shows similar levels with no marked change of resistin with increasing BMI. These alterations may due to altered adipose tissue function in women with PCOS, which occurs even with normal BMI
ABSTRACT
To investigate the expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha [HIF-1 alpha] genes in hepatocellular carcinoma and correlate their expression with clinicopathological data. Liver biopsy samples of 30 hepatocellular carcinoma [HCC] subjects. 20 chronic hepatitis C [CHC] and 20 liver biopsy samples from non cancerous tissue [i.e control samples] of HCC were assessed by polymerase chain reaction [RT-PCR] and restriction enzyme analysis for the three genes; wild p53 gene, mutations in p53 at codon 249, exon 7 and hypoxia inducible factor-1 alpha gene. Wild p53 gene was detected in 18/30cases of HCC [60%], 16/20 cases of CHC [80%] and 15/20 cases of control samples [75%] with no significant difference between the studied groups. Mutated p53 gene was detected in 12/30 cases of HCC [40%], 4/20 cases of CHC [20%] and 5/20 cases of control samples [25%], also with no statistically significant difference between the studied groups while HIF-lalpha gene was expressed in 20/30 cases of HCC [66.7%] in comparison to 2/20 cases of CHC [10%] and 3/20 of control samples [15%] with a highly statistically significant difference [p<0.001]. The expression of both wild p53 and the mutated p53 correlated with tumor size but did not correlate with grade of malignancy nor serum alpha fetoprotein level, while the expression of HIF-1 alpha correlated with grade of malignancy and alpha fetoprotein level but not with tumor size. No correlation between expression of all genes and capsule infiltration or presence of cirrhosis was found in all groups. HIF-1 alpha is highly expressed in HCC and is related to grade of malignancy and serum alpha fetoprotein level
Subject(s)
Humans , Male , Female , Genes, p53 , Polymerase Chain Reaction , Cell Hypoxia , Neoplasm Staging , alpha-Fetoproteins , Electrophoresis, Agar GelABSTRACT
To evaluate the triple screening test [using AFP, beta-HCG and uE3] in prenatal diagnosis of Down syndrome through comparing the results of the test with the outcome of pregnancy. We will also compare these results with the results of the double test [using AFP and beta-HCG] or MSAFP test to evaluate the value of combining beta-HCG, alpha-fetoprotein [AFP] and unconjugated estriol with maternal age in this three-analyte maternal serum screening program for Down syndrome. This study was conducted on 50 pregnant women, 35 years or older. Their gestational age ranged from 14th to 19th week of pregnancy detected through 1st day of last menstrual period. Blood samples were taken from them for measurement of alpha-fetoprotein, HCG and unconjugated estriol. Risk ratio was calculated for Down syndrome detection using three protocols: MSAFP alone, MSAFP and HCG, MSAFP, HCG, and unconjugated estriol [triple test] using Prisca software [DPC, France]. The [cut-off] median MoM values in pregnancies with Down syndrome were 0.73 [AFP], 2.02 [beta-HCG] and 0.74 [uE3]. After labour, the newborns of selected women for the study were evaluated clinically for diagnosis of Down syndrome. The results of all tests done before labour are compared with the clinical evidence of cases to evaluate them. The detection rate of triple test, double test, MSAFP test was 75%, 50%, 25% respectively. The false positive rate was 40%, 75% and 94% respectively. The correlation coefficient between each test and actual outcome of pregnancy was 0.626 for triple, 0.267 for double and 0.146 for MSAFP test. Using cut-off value 1:190 kept the same detection rate for triple test and lowered the false positive rate to 25%. Triple screening test using AFP, HCG and uE3 has the upper hand over MSAFP and double test in detection of Down syndrome as it has the highest detection rate and lowest false positive rate. The value of correlation coefficient means that other factors or analytes need to be added to improve the detective power of the tests. It is strongly recommended to lower the cut-off value to be 1:190 instead of 1:270. These results need to be evaluated on a more large scale