Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis C patients: a case control study

BACKGROUND: High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied. METHODS: A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction. RESULTS: Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group. CONCLUSIONS: These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C

Differential effects of lung inflammation on insulin resistance in humans and mice

BACKGROUND: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis. METHODS: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues. RESULTS: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1. CONCLUSIONS: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis

Global stability for a class of virus models with CTL immune response and antigenic variation

We study the global stability of a class of models for in-vivo virus dynamics, that take into account the CTL immune response and display antigenic variation. This class includes a number of models that have been extensively used to model HIV dynamics. We show that models in this class are globally asymptotically stable, under mild hypothesis, by using appropriate Lyapunov functions. We also characterise the stable equilibrium points for the entire biologically relevant parameter range. As a byproduct, we are able to determine what is the diversity of the persistent strains.Comment: 15 page

Finite size scaling study of dynamical phase transitions in two dimensional models : Ferromagnet, symmetric and non symmetric spin glasses

We study the time evolution of two configurations submitted to the same thermal noise for several two dimensional models (Ising ferromagnet, symmetric spin glass, non symmetric spin glass). For all these models, we find a non zero critical temperature above which the two configurations always meet. Using finite size scaling ideas, we determine for these three models this dynamical phase transition and some of the critical exponents. For the ferromagnet, the transition Tc ≃ 2.25 coincides with the Curie temperature whereas for the two spin glass models ( ± J distribution of bonds) we obtain Tc ≃ 1.5-1.7.Nous étudions l'évolution de deux configurations soumises au même bruit thermique pour plusieurs modèles en dimension 2 : ferromagnétisme et verres de spin symétrique et non symétrique. Pour chacun de ces modèles nous obtenons une température critique non nulle au-dessus de laquelle les deux configurations finissent toujours par se rencontrer. En utilisant les lois d'échelle des systèmes finis, nous déterminons pour ces trois modèles cette transition de phase dynamique et certains exposants critiques. Pour le modèle ferromagnétique, la transition à Tc ≃ 2,25 coincide avec la température de Curie tandis que pour les deux modèles de verre de spin (± J) nous obtenons Tc = 1,5-1,7

Domains and distances in magnetic systems

International audienc

Recent approaches to immune networks

Jerne (1974) proposed that the immune system has important network characteristics that are similar in many respects to neural networks. This paper outlines some recent approaches taken by the authors and their colleagues toward the analysis of immune networks. Other approaches have been omitted owing to space limitations, notably that of Coutinho, Stewart, and Varela