CCR5△32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C

AIM: To study whether CCR5△32 mutation was associated with viral infection and severity of liver disease.METHODS: Two hundred and fifty two histologically proven, chronic HCV patients (mean age: 41 ± 14 years;M/F: 164/88) were genotyped. PCR based genotyping of 32 bp deletion at the CCR5 locus was done. Fourhundred and eight matched healthy controls were studied to assess susceptibility to HCV infection. To assess correlation of immune gene polymorphism with severity of HCV related liver disease, patients with chronic HCV infection were divided into those with a fibrosis score of ≤ 2 (mild) or ＞ 2 (severe) and histological activity index (HAI) of ≤ 5 or ＞ 5. For correlation between CCR5△32 mutations and response to therapy, 129 patients who completed therapy were evaluated.RESULTS: The majority (89.4%) of the patients were infected with genotype 3. The frequency of homozygous CCR5△32 mutants was comparable to HCV patients as compared to the healthy controls (0.7% vs 0%, P = 0.1).Further more, the frequency of CCR5△32 mutation was comparable in patients with mild or severe liver disease.(P = NS). There was also no association observed with response to therapy and CCR5△32 mutation.CONCLUSION: CCR5△32 mutation does not have a role in disease susceptibility, severity or response to therapy in patients with chronic hepatitis C infection.     

A study of immunological profile,disease characteristics and socioeconomic status of a population of rheumatoid arthritis patients in Sri Lanka

ObjectiveTo study the immunological profile, disease characteristics and socioeconomic status of a population of patients with rheumatoid arthritis (RA) in Sri Lanka.MethodsA case-control study was undertaken to characterize the immunoglobulin profiles of 105 RA and, age and gender matched osteoarthritis (OA) patients (n = 30) from the National Hospital, Sri Lanka. Healthy, non-arthritic individuals (n=30) served as controls. Sera were assayed for immunoglobulins [IgG, IgM, IgE and IgA isotypes] by establishing sandwich type ELISA. IgM, IgG and IgA rheumatoid factors (RFs) of 162RA patients were assayed by indirect ELISA. Disease characteristics and socioeconomic factors were accrued via an interviewer-administered questionnaire.ResultsHigher IgG, IgM, IgE, IgA and lower IgG1, IgG2 levels were observed in RA sera compared with controls (P < 0.05). Novel correlations between disease characteristics and immunoglobulins, as well as group-specific correlation matrices of immunoglobulins and RFs (P < 0.05) of seropositive and seronegative patients, were found. Higher IgM-RF and IgA-RF levels in seropositives and IgG-RF in seronegatives were evident compared with controls (P < 0.05). Immunoglobulin and RF profiles did not reflect gender disparity of RA (P > 0.05). Proportions of seropositives with nodules and erosions were significantly higher than seronegatives (P < 0.05). While IgM-RF and erosions positively correlated in the seropositives (P < 0.05), the seronegatives showed an inverse correlation between IgG-RF and erosions (P < 0.01). Familial clustering imposed a relative risk of 4.7 for developing seropositive RA.ConclusionsThis model study provides baseline information on pathogenetic aspects of RA in Sri Lanka, which may have implications for further research on management of the disease.     

Effects of serial plasmapheresis on serum IgA levels in IgA-deficient blood donors with IgA-suppressor T cells

Seventeen IgA-deficient blood donors, without antibodies to IgA, underwent plasmapheresis four to eight consecutive times at intervals of 8 weeks or less to provide fresh-frozen plasma for patients with anti-IgA. Blood samples, drawn for analysis no more than 1 hour before plasmapheresis and again at the conclusion of each procedure, were analyzed for lymphocyte subpopulations and serum IgA levels. Five lymphocyte subpopulations, including natural killer cells, the suppressor-inducer CD4 subset, the suppressor-precursor CD8 subset, non-major histocompatibility complex (MHC)-restricted cytotoxic T cells, and CD5+ B cells, were all decreased significantly after plasmapheresis (p less than 0.05). In a subgroup of IgA-deficient donors with excessive IgA-suppressor T-cell activity, serum IgA increased to levels exceeding 0.05 g per L following the fourth consecutive plasmapheresis procedure. Serum IgA levels did not similarly increase in IgA-deficient donors without excessive IgA-suppressor T-cell activity or in controls without IgA deficiency. Our study shows the potential, in a subpopulation of IgA-deficient donors who undergo frequent plasmapheresis, for a transient increase in serum IgA to a level no longer considered IgA deficient.     

Comparative evaluation of ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole in three acute gastric ulcer models in rats

Summary— Ulcer prevention efficacy of orally, rectally and sublingually administered omeprazole was evaluated and compared using ulcer index and percentage inhibition of ulcerogenecity in three different acute gastric ulcer models viz, indomethacin, 0.6N HCl and aspirin (after pylorus ligation) induced ulcers in rats. The ulcer prevention efficacy after oral, rectal and sublingual administration were statistically significant ( P < 0.01) in all the models. The differences in ulcer index and percentage inhibition of ulcerogenecity for rectal and sublingual administration were insignificant ( P < 0.05) in indomethacin and HCl induced ulcers and were significant ( P < 0.05) in aspirin induced ulcers. The ulcer prevention activity was significantly higher ( P < 0.05) after rectal and sublingual routes when compared to oral administration in all three models evaluated. Results revealed a faster onset and higher extent of pharmacodynamic activity of omeprazole after rectal and sublingual administration.     

Host microenvironment in breast cancer development: Extracellular matrix–stromal cell contribution to neoplastic phenotype of epithelial cells in the breast

Epithelial–mesenchymal interactions play an important role both in normal mammary gland development and during neoplastic transformation. Perturbations in the production, deposition and degradation of the extracellular matrix occurring during neoplastic transformation and progression have been implicated to arise from alterations in the stromal response. These changes in the stroma exhibit a dominant regulatory role, via microenvironmental epigenetic effectors, to contribute to the development of the tumorigenic epithelial phenotype. The role of stromally derived microenvironmental epigenetic effectors in modulating epithelial growth, hormonal response, morphogenesis and epithelial plasticity is discussed.     

Risk of leukemic transformation in PV and ET patients

Despite a prolonged survival of around 15 years linked to a prolonged complete remission induced by myelosuppression, myeloproliferative syndromes such as polycythemia vera (PV) and essential thrombosis (ET) remain at risk of lethal adverse affects such as thrombotic events and acute transformation. The major risk at diagnosis, in the absence of treatment, is essentially thrombosis. Different therapeutic trials have shown the necessity to maintain circulating blood cells (RBC and platelets counts) near normal levels to avoid thrombosis. Phlebotomies alone in PV lead in the long run to metaplasia and increased platelet counts and should only be kept for emergency cell count reduction. Myelosuppression is thus until recently the most widely accepted effective alternative. However, the effects of long term chronic administration of myelosuppresive agents needs to be analyzed and monitored as the biological changes which appear during the course of these diseases linked or not to the intrinsic clonal haematopoietic abnormality may lead to malignant transformation. Thus, alternative therapies need to be evaluated and predisposition factors taken in account.