T‐cell homeostasis in chronic HCV‐infected patients treated with interferon and ribavirin or an interferon‐free regimen

Direct‐acting antiviral has replaced pegylated interferon‐α and ribavirin‐based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon‐α is immune modulating and causes lymphopenia, interferon‐free regimens seem to be well‐tolerated. This study aimed to compare T‐cell homeostasis before, during, and after HCV treatment with or without interferon‐α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon‐α and ribavirin, and six patients were treated with an interferon‐free regimen. All patients were treated for a minimum of 12 weeks. Interferon‐α treatment caused an increase in the density of the receptor for IL‐7 (IL‐7Rα) during treatment, while interferon‐free regimens caused a decrease in IL‐7Rα density. After a sustained viral response, proportions of IL‐7Rα+ T cells and IL‐7Rα density decreased compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T‐cell homeostasis during treatment were relatively similar in patients receiving interferon‐based treatment and in patients receiving interferon‐free treatment, and alterations during and after treatment seem to illustrate a reduced need for high levels of T cells aimed at controlling infection.     

Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms

INTRODUCTION: Tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are significantly elevated in patients with congestive heart failure (CHF). Pentoxifylline, a xanthin-derived agent, is known to inhibit the production of TNF-alpha and IL-6. Recent studies have shown that pentoxifylline produces an increase in ejection fraction, a decrease in left-ventricular chamber size and an improvement in clinical status in patients with idiopathic-dilated cardiomyopathy. Therefore, we studied the effects of pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy. METHODS: Primary endpoint was left-ventricular ejection fraction (LVEF) assessed by contrast 2D echocardiography. Secondary endpoints were concentrations of TNF-alpha, IL-6, brain natriuretic peptide, maximal oxygen uptake (VO(2 max)) assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire score or New York Heart Association scale. RESULTS: Forty-seven patients (31.9% ischemic, 21.3% hypertensive, 10.6% ischemic and hypertensive, 36.2% idiopathic-dilated cardiomyopathy) were randomly assigned to pentoxifylline 600 mg BID (n=23) or placebo (n=24) if they had a compensated CHF with a LVEF less than or equal to 40% and had taken their standard treatment consisting of angiotensin-converting enzyme inhibitors, diuretics and beta-blockers for at least 3 months. Baseline demographic and clinical characteristics of each group were similar. Forty-one patients completed the study protocol and were analysed for primary and secondary endpoints. After 6 months of treatment, LVEF was unchanged in the pentoxifylline group compared with placebo (29+/-7 to 33+/-10% vs. 27+/-9 to 34+/-9%, respectively, P=NS). Also the secondary endpoints did not significantly change during follow-up. CONCLUSION: Additional treatment with pentoxifylline is neutral with regard to left-ventricular function, inflammatory cytokines and symptoms in patients with ischemic, hypertensive and idiopathic-dilated cardiomyopathy.     

Loading into and electro-stimulated release of peptides and proteins from chondroitin 4-sulphate hydrogels.

Chondroitin 4-sulphate (CS) hydrogels were examined as potential matrices for the electro-controlled delivery of peptides and proteins. A CS hydrogel, cross-linked with ethylene glycol diglycidyl ether, and with a swelling ratio of 20, was used to study the influence of molecular size and shape of guest molecules on loading and release rates. Three positively charged molecules of different molecular weights (vasopressin MW 1084, aprotinin MW 6512 and lysozyme MW 14,400), and one negatively charged protein (bovine serum albumin MW 67,000) were used as model solutes. The hydrogels were loaded by equilibrium swelling. As a result, the three positively charged peptide and proteins were found to be concentrated in the gels, most likely due to ionic attraction between the negative charges in the gel polymeric backbone and the positively charged solutes. No such concentration of solute in the gel was seen for the negatively charged albumin. The latter is presumably loaded passively by diffusing in the water phase of the gel. The loading efficiency (indicated by the loading rate and the total amount of solute loaded in the gel) was found to increase with decreasing molecular size of solute. Electro-stimulated release of the loaded peptide and proteins was followed for 3 h during which an electric field was applied in pulses of 5 V (pulse duration and pulse interval were both of 20 min). The release of lysozyme and aprotinin from CS hydrogels responded to electrical pulses. On the other hand, vasopressin and albumin were largely released by passive diffusion and their release could not be electrically controlled. This work shows that the size of the guest molecule is an important parameter when electrically-stimulated drug release is desired, but further work obviously needs to be carried out with a larger range of molecular weights and conformations.     

Dietary supplementation with an extract of lycopene-rich tomatoes does not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

Tomatoes are rich in lycopene and other carotenoids which have shown beneficial effects on CVD in epidemiological and intervention studies. In the present study the effect of an extract of lycopene-rich tomatoes, Lyc-O-Mato on atherosclerosis was studies in Watanabe Heritable Hyperlipidemic rabbits. The rabbits were fed a control diet, a control diet supplemented with the tomato extract or a control diet supplemented with a mixture of plant oils for 16 weeks. Lycopene was detected only in plasma of rabbits receiving tomato extract. The tomato extract had no effect on cholesterol and triacylglycerol levels measured in total plasma, lipoprotein fractions and on aortic atherosclerosis evaluated biochemically and by microscopy. Oxidation of lipids in unfractionated plasma also was unaffected by the intake of tomato extract. In conclusion, the tomato extract increased plasma levels of lycopene in rabbits, but had no effect on hypercholesterolaemia, oxidation of plasma lipids or aortic atherosclerosis.