Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment.

Despite tremendous efforts to develop stimuli-responsive enzyme delivery systems, their efficacy has been mostly limited to in vitro applications. Here we introduce, by using an approach of combining biomolecules with artificial compartments, a biomimetic strategy to create artificial organelles (AOs) as cellular implants, with endogenous stimuli-triggered enzymatic activity. AOs are produced by inserting protein gates in the membrane of polymersomes containing horseradish peroxidase enzymes selected as a model for natures own enzymes involved in the redox homoeostasis. The inserted protein gates are engineered by attaching molecular caps to genetically modified channel porins in order to induce redox-responsive control of the molecular flow through the membrane. AOs preserve their structure and are activated by intracellular glutathione levels in vitro. Importantly, our biomimetic AOs are functional in vivo in zebrafish embryos, which demonstrates the feasibility of using AOs as cellular implants in living organisms. This opens new perspectives for patient-oriented protein therapy.

[Intracoronary brachytherapy: a meta-analysis]. / Curiethérapie endocoronaire: une méta-analyse.

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.

Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding.

Neonatal herpes affects about 1 in 15,000 newborns and the prognosis for disseminated disease with encephalitis is poor. We investigated whether acyclovir prophylaxis in late pregnancy effectively reduces the risk of viral shedding and, hence, of mother-to-child transmission at delivery. A prospective study was conducted. Pregnant women who had at least one episode of genital herpes during pregnancy were randomly assigned to two groups: group 1 (n=167) received oral acyclovir from 36 weeks of gestation to term; group 2 (n=121) received no treatment. Group 3 (n=201) comprised women not given prophylaxis who had a history of genital herpes, but no active episodes during pregnancy. No specific instruction were set up for obstetrical management except for cesarean section in case of a suspected herpes lesion at the time of labor. The rate of Cesarean section was 8.4% in group 1, 16.5% in group 2, and 9.9% in group 3 (p<0.001). 75% of cesareans in group 2 and 10% in group 3 were done for genital herpes. Percentage of viral shedding was, respectively, 0% (group1), 5% (group2), and 0.5%(group3) (p<0.05). These findings underline the value of antiviral prophylaxis in late pregnancy for women with a known history of genital herpes. Such prophylaxis only partly prevents neonatal herpes infection, because it is not applicable to patients with no known clinical history but may excrete the virus.

Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms.

BACKGROUND: There is a current debate regarding the association of human herpesvirus 6 (HHV-6) infection and drug reaction with eosinophilia and systemic symptoms (DRESS). METHODS: Seven consecutive patients hospitalized with DRESS were enrolled in a prospective study to evaluate evidence of active HHV-6 infection. OBSERVATIONS: The imputable drugs were carbamazepine (5 patients), ibuprofen (1 patient), and sulfasalazine (1 patient). All patients were seropositive for anti-HHV-6 IgG antibodies. Anti-HHV-6 IgM antibodies were detected in 4 of the 7 patients with a seroconversion in 2 patients. Neither anti-cytomegalovirus nor anti-Epstein-Barr virus early antigen IgM antibody was detected. Human herpesvirus 6 genome was not detected by polymerase chain reaction in the first serum sample of all patients. It was weakly detected in skin lesions in the last patient tested by polymerase chain reaction but was not found in uninvolved skin. CONCLUSIONS: The results suggest an association between HHV-6 active infection (primo-infection or reactivation) and severe DRESS. Absence of anti-cytomegalovirus or anti-Epstein-Barr virus early antigen IgM antibodies argues against a nonspecific viral reactivation. Human herpesvirus 6 infection may play a role in the development of DRESS in susceptible patients. Some drugs with reactive metabolites could favor reactivation and propagation of HHV-6.

Two genomic species in Borrelia burgdorferi.

A total of 13 Borrelia burgdorferi strains (responsible for Lyme borreliosis) and representatives of 3 other Borrelia species (B. hermsii, B. parkeri, B. turicatae) associated with relapsing fever were studied by DNA/DNA hybridization and rRNA gene-restriction patterns. Two genomic DNA hybridization groups were observed which could be differentiated by rRNA gene-restriction patterns. Moreover, the number and size of restriction fragments suggest the existence of a single set of 16 and 23 S rRNA genes in Borrelia.