Impact of Interleukin-28B gene polymorphism [rs12979860] on Egyptian patients infected with hepatitis C virus genotype-4

Single nucleotide polymorphisms [SNPs] in the Interleukin [IL]-28B gene, namely rs12979860, could predict response to pegylated interferon-alpha-ribavirin [PR] therapy in hepatitis C virus genotype 1 [HCV-1]-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype [CC] was associated with sustained viral response [SVR] to therapy compared with the homozygous T allele genotype [TT] and the heterozygous genotype [CT]. In the SVR group, the response rate was statistically significantly higher in CC genotypes [58.6%] compared with CT/TT [20.3%]. There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy. We underscore IL28B genotyping as a tool that might increase PR cost-benefit in Egypt

Effect alpha globlin gene deletion and gamma globin gene -158 [C/T] polymorphism in beta-thalassemic patients

The beta-thalassemias [beta- thalassemias] are among the most common autosomal recessive disorders. They have a remarkably high frequency in the Mediterranean region and represent one of the most common genetic diseases in Egypt. In this study, the spectrum of beta-thalassemia mutations and genotype-to-phenotype correlations were defined in 32 beta- thalassemic patients [beta- thlassemias major and intermedia] with varying disease severity in two cities of the Suez Canal region. Ten different mutations were identified and the most frequent ones were: IVSI-6 [T-C] [37.5%], IVSI-110 [G-A] [34.4%] and both IVSI-1 [G-A], IVSII-745 [C-G] and -102 [C-G] [12.5% each]. There was a wide spectrum of phenotypic severity in all patients. We studied the Xmnl polymorphism [C/T] in gamma- globin gene position -158 of beta- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a modulating factor was not evident in our patients. In conclusion, we have been unable to find a molecular basis for the benign clinical course in all our patients. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition

Human telomerase enzyme activity in human hepatoma cell line [HEPG2] and its interaction with the heme oxygenase gene

Objective: to examine the contribution of telomerase and HO-1 in the adaptive cellular response to survive exposure to oxidative stresses in human hepatoma cell line [HepG2]

Materials and Methods: induction and activities of HO and telomerase enzymes were assessed in HepG2 cells in response to oxidative stress [represented by treatment with heme, SnC12 and H202] and in the presence of the HO inhibitor stannic mesoporphyrin [SnMP]. Induction of HO and telomerase mRNA were assessed using RT-PCR and western blotting techniques, while HO and telomerase enzyme activities were assessed spectrophotometrically Cytoprotection against oxidative stress was measured by assessing cell viability using a novel colorimetric method

Results: upregulation of HO-1 provided cytoprotection against oxidative stress while its downregulation increased oxidative stress mediated cell injury without altering telomerase activity. Telomerase was active in hepatocellular carcinoma cell line [HepG2] and human telomerase enzyme catalytic subunit [hTERT] was expressed in telomerase positive cancer cells. However, telomerase activity was not affected by oxidants, heme and H[2]O[2] or downregulation of HO gene activity by SnMP, similarly. hTERT, which is considered as the major regulator of telomerase activity, was not affected by oxidants, inducers or inhibitors of HO activity. On the other hand, HO-1 gene induction stimulated cell proliferation and accelerates cell cycle in HepC2 cells, while inhibition of HO activity augmented the damaging effects of oxidants

Conclusion: Induction of HO-1 gene mediates protection against oxidants and increases cell survival by a mechanism independent of telomerase enzyme activity

Serum transforming growth factor beta1 and prostate specific antigen as markers for localized and metastatic prostate cancer

Objectives: To assess any additional benefits of the estimation of serum TGF-beta 1 over serum prostate specific antigen [PSA] for differentiating localized from metastatic prostatic carcinoma

Patients and Methods: Forty-seven prostate cancer patients [23 with and 24 without metastases] and ten controls were included in the study. Serum PSA was estimated using the chemiluminescent immunometric assay, and serum TGF-beta1 was assessed using the enzyme immunoassay

Results: The mean serum PSA in the localized and metastatic disease groups was significantly higher than that in the control group [p<0.001 and p<0.001, respectively], while the mean serum TGF-beta 1 in the metastatic disease group only was significantly higher than in the control group [p<0.01]. The mean serum PSA and TGF-beta 1 in the metastatic disease group were significantly higher than the values in the localized disease group [p<0.001 and p<0.001, respectively]. Serum PSA was directly correlated with the Gleason score in both patient groups [localized group: r=0.427, p<0.05; and metastatic group: r=0.425, p<0.05], while serum TGF-beta 1 was directly correlated with the Gleason score in the localized disease group only [r=0.686, p<0.001]. Serum PSA was directly correlated with serum TGF-beta 1 in the metastatic disease group only [r=0.418, p<0.05]

Conclusion: Although we found that both serum PSA and TGF-beta 1 are useful markers for metastatic prostate cancer, we could not detect a specific advantage of TGF-beta 1 over PSA. In the localized form of the disease PSA is a more reliable marker

Effect of haemodialysis on prolactin level in chronic renal failure

Hyperprolactinemia occurs frequently in patients with chronic renal failure and it persists despite dialysis treatment. Hence the study of the actual change in PRL level after a hemodialysis set is essentially reported. Thirty non diabetic male patients with chronic renal failure were selected from Dialysis Units of Port-Said and Ismailia General Hospitals where they underwent chronic hemodialysis [CHD] for all cases the following had been done: full medical history, full clinical examination. determination of fasting serum glucose to exclude diabetics as well as serum urea, creatinine, total proteins and PRL before and after a hemodialysis set. The results obtained showed: 1. There is a significant hyperprolactinemia among patients on CHD 2. PRL does not significantly change after the set [insignificantly increased]. 3. Some patients have sexual dysfunction and gynecomastia. Finally from our results we conclude that patients undergoing hemodialysis are prone to have clinically significant hyperprolactinemia that may impair their sexual function. Since this complication diminishes the quality of life and limits psychological rehabiltitation, we recommend treatment with bromocriptine [dopamine agonist] to chronic renal failure patients on hemodialysis with sexual dysfunction and exhibit high prolactin