Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.     

Serum levels of alpha-tocopherol (vitamin E) in Parkinson's disease.

To elucidate the possible role of vitamin E in the pathogenesis of Parkinson's disease (PD), we compared serum levels of alpha-tocopherol (vitamin E), measured by high-performance liquid chromatography, and the vitamin E/cholesterol ratio of 42 Parkinson's disease (PD) patients using their spouses as the control group. The serum levels of vitamin E did not differ significantly between the groups (13.84 +/- 0.56 micrograms/ml for PD and 14.80 +/- 0.57 micrograms/ml for controls), nor did the vitamin E/cholesterol ratio (0.64 +/- 0.03 for both groups). There was no influence of antiparkinsonian therapy on vitamin E or the vitamin E/cholesterol ratio. Serum levels of the vitamin E and vitamin E/cholesterol ratio did not correlate with age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the Hoehn and Yahr staging in the PD group. These results suggest that serum vitamin E concentrations do not play a role in the pathogenesis of PD.     

P-fimbriae vaccines

To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with fimbriae purified from either Escherichia coli strain ER2 or strain JR1. The vaccinated animals showed elevated antibody titers to P-fimbriae from each of the E. coli strains used, suggesting cross-reactivity as was expected from the results of immunoprecipitation of the fimbriae. Enzyme-linked immunosorbent assay inhibition by heterologous P-fimbriae proved this to be true immunologic cross-reactivity.     

The Chemical Protecting Group Concept Applied in Crosslinking of Natural Tissues with Glutaraldehyde Acetals

This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected.     

Determining the Alveolar Component of Nitric Oxide in Exhaled Air: Procedures and Reference Values for Healthy Persons

Nitric oxide (NO) production has been described using a 2-compartment model for the synthesis and movement of NO in both the alveoli and the airways. The alveolar concentration of NO (Ca_NO), an indirect marker of the inflammatory state of the distal portions of the lung, can be deduced through exhalation at multiple flow rates. Our objective was to determine reference values for Ca_NO. The fraction of exhaled NO (Fe_NO) was measured in 33 healthy individuals at a rate of 50 mL/s; the subjects then exhaled at 10, 30, 100, and 200 mL/s to calculate Ca_NO. A chemiluminescence analyzer (NIOX Aerocrine) was used to perform the measurements. The mean (SD) Fe_NO was 15 (6) ppb. The mean Ca_NO was 3.04 (1.30) ppb. These values of Ca_NO measured in healthy individuals will allow us to analyze alveolar inflammatory behavior in respiratory and systemic processes.     

Endocrinology: Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome in an in-vitro fertilization programme

A cohort study was undertaken to compare the effect at the timeof oocyte retrieval of the i.v. administration of either 1000ml of lactated Ringer' solution or 1000 ml of a 5% solutionof human albumin on in-vitro fertilization patients at riskfor severe ovarian hyperstimulation syndrome (OHSS). A totalof 207 patients with an oestradiol concentration > 10 000pmol/l and/or > 15 follicles (>10 mm diameter) on theday of human chorionic gonadotrophin (HCG) injection were reviewed.Of these, 158 women received 500 ml of lactated Ringer’ssolution both before and after egg retrieval, and 49 women receivedtwo infusions of 500 ml of 5% human albumin in normal salineat the time of egg retrieval. Severe OHSS developed in two patientswho received human albumin and in 10 women who did not receivethe albumin. This difference was not statistically significant.There were no differences between the two groups in terms ofage, number of follicles punctured at transvaginal oocyte retrievalor oestradiol concentration at the time of HCG injection. Theadministration of a 5% human albumin solution does not preventthe development of severe OHSS in at risk patients. It doesappear to blunt the severity of the condition.