Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

ANALYSE DE LA PROPAGATION D'ONDES ACOUSTIQUES DANS LES STRUCTURES PÉRIODIQUES À L'AIDE DE LA MÉTHODE DES ÉLÉMENTS FINIS

The finite element method has been extended to model, with the help of the ATILA code, the propagation of plane harmonic waves in an infhite elastic medium, with a bi or tri-dimensional periodicity. This article briefly describes the formalism and provides results obtained for a periodic array of square inclusions.La méthode des éléments finis a été étendue pour modéliser, avec l'aide du code ATILA, la propagation d'ondes planes harmoniques dans un milieu élastique, infini, périodique dans deux ou trois directions de l'espace. Cette communication décrit brièvement le formalisme puis présente les résultats obtenus pour un réseau d'inclusions carrées

Homogénéisation de matériaux périodiques à l'aide de la méthode des éléments finis, dans la limite des grandes longueurs d'onde

Un modèle numérique a été développé pour étudier la propagation d'ondes planes harmoniques dans un matériau périodique dans une, deux ou trois directions de l'espace. Les propriétés homogénéisées de matériaux poreux sont déterminées sur un modèle anisotrope, dans la limite des grandes longueurs d'onde. Une validation a été faite sur des plaques perforées périodiquement par la mesure des fréquences de résonance.A numerical model has been developed to study the propagation of plane harmonic waves in single, doubly or triply periodic materials. The homogenized properties of porous materials are determined with the help of an anisotropic model, in the limit of large wavelengths. A validation has been carried out with periodically perforated plates, the resonance frequencies of which have been measured

Weekly pegylated interferon alpha-2b vs daily interferon a-2b versus standard regimen of interferon a-2b in the treatment of patients with chronic hepatitis C virus infection.

BACKGROUND AND STUDY AIMS: The combination of Pegylated (PEG)interferon alpha-2b and ribavirin is considered to be the standard treatment for naïve chronic hepatitis C patients. Study aims are to evaluate the differences between standard interferon and PEG-interferon by conducting a multi-centre, controlled randomized trial comparing 3 groups. Group A : daily interferon alfa-2b at a dose of 4 MIU + ribavirin, Group B : PEG-interferon alfa-2b at a dose of 100 mcg/week + ribavirin; Group C: interferon alfa-2b at a dose of 3 MIU TIW + ribavirin PATIENTS AND METHODS: Multicentrer, open label study including naïve chronic Hepatitis C Virus patients randomised in three groups with a ratio of 2:2:1. Group A: daily interferon alpha-2b (4 MIU s.c. for patients > 65 kg or 0.06 MIU/kg 65 kg or 1.5 microg/kg weekly for patients < 65 kg) and ribavirin and group C (reference arm) : interferon alpha-2b (3MIU s.c. TWI) and ribavirin. The duration of the treatment was 48 weeks for all 3 groups, with a 6 month follow-up period. 336 patients were enrolled in the study and included in the intention-to-treat analysis; 78 never started treatment (35 in group A, 28 in group B and 15 in group C): 101 in group A, 98 in group B and 59 in group C. RESULTS: Demographic data, PCR results and reasons for early withdrawal have been statistically analysed. At baseline, the 3 groups did not show any statistical difference regarding age, gender, race, genotypes and METAVIR score. At week 24 on treatment, HCV ribonucleic acid RNA was undetectable in 87% in group A, in 79% in group B and in 69% in group C. At the end of treatment, 73% 74% and 58% respectively, had a negative PCR result. At week 24 of follow-up, these results were 71%, 64% and 48%, respectively. When comparing the efficacy of the daily interferon (+ ribavirin) and the PEG-interferon (+ ribavirin) regimen, no statistical difference was found (p = 0.32). In group A, 38% of drop-outs were due to adverse events compared to 37% in group B and 58% in group C. No statistical differences were observed regarding safety. CONCLUSION: Daily weight based interferon alpha-2b dosing and PEG interferon alpha-2b weighed based dosing once weekly both in combination with Ribavirin offer the same efficacy and safety rates

The management of patients with mild hepatitis C.

Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver disease. However, the identification of these patients with mild hepatitis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are persistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probability of response and the motivation of the patient

The management of patients with mild hepatitis C

Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver disease. However, the identification of these patients with mild hepatitis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are persistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probability of response and the motivation of the patient