Mitochondrial Dysfunction Increases Oxidative Stress and Decreases Chronological Life Span in Fission Yeast

Background: Oxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria. Methodology/Principal Findings: We analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells. Conclusion/Significance: Individual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes.This work was supported by Dirección General de Investigación of Spain Grant BFU2006-02610, and by the Spanish program Consolider-Ingenio 2010 Grant CSD 2007-0020 to E.H

The Schnitzler syndrome

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections

Reducing the Activity and Secretion of Microbial Antioxidants Enhances the Immunogenicity of BCG

BACKGROUND:In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS:To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE:We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB

A new technique of bladder enlargement and continent urinary diversion using the ceco-appendicular unit

The authors developed a new technique using the cecum with in-situ appendix to simultaneously achieve bladder enlargement and continent urinary diversion (CUD) in five cases of neuropathic bladder or serious complications of abdominopelvic trauma. The cecoplasty provides a large-capacity, low-pressure reservoir; the submucosally-embedded appendix gives complete continence with 3 to 5 intermittent catheterizations daily. It is an alternative to the Mitrofanoff principle when bladder augmentation and CUD are necessary, and easier to achieve when faced with a neuropathic bladder where the thickness of the detrusor makes appendicular implantation difficult

Paludisme des aéroports : particularités thérapeutiques à propos de 6 cas relatés en 1994

Depuis 1977, 44 cas de paludisme des aéroports ont été rapportés en Europe. Cette affection rare reste d'actualité compte tenu de sa gravité et de sa difficulté diagnostique. Au cours du mois d'août 1994, 6 nouveaux cas de paludisme autochtone à #Plasmodium falciparum contractés dans les environs de l'aéroport Roissy-Charles de Gaulle (France) ont été diagnostiqués chez 5 hommes et 1 femme, âgés de 23 à 51 ans. Les signes initiaux à l'admission étaient caractérisés par leur exceptionnelle gravité : fièvre à 40°C (6/6), frissons, céphalées, troubles digestifs (4/6) ; 2 d'entre eux présentaient un accès pernicieux palustre selon les critères de l'Organisation Mondiale de la Santé avec état confusionnel post-critique, syndrome méningé. Sur le plan biologique, ont été observés une thrombopénie de 15 à 50 Gg/l chez tous les patients, des troubles électrolytiques avec hyponatrémie (5/6), hypocalcémie de 1,5 mmol/l à 1,89 mmol/l (4/6), hypoprotidémie (4/6), tableau de coagulation intra-vasculaire disséminée (1/6). L'examen parasitologique du sang met en évidence la présence de trophozoïtes intra-érythrocytaires de #Plasmodium falciparum avec une parasitémie variant de 1,1 à 50%. Devant la gravité de la symptomatologie, tous les patients ont été traités par quinine IV (1,6 g/j) pendant 48 heures à 7 jours puis relais par halofantrine (4/6) ou association avec la doxycycline (1/6). L'évolution favorable sur le plan clinique et biologique dans les premiers jours du traitement (avec négativation de la parasitémie en 3 à 5 jours pour 5 des 6 patients) a été suivie pour 5 d'entre eux par une aggravation secondaire avec réapparition de la fièvre (3/6), encéphalopathie (2/6), décès (1/6). Le paludogramme de 3 isolats a montré la chloroquinorésistance d'une des souches, la sensibilité vis à vis de la quinine, la mefloquine et l'halofantrine. En l'absence d'antécédent de séjour en zone d'endémie palustre, 3 modes de contamination ont été identifiés, piqûre sur l'aéroport par des anophèles infectées (3/6), piqûre au cours de l'ouverture de conteneur à la poste de l'aéroport (1/6), piqûre par des anophèles transportées par les véhicules d'employés de l'aéroport (2/6). Cette étude souligne l'efficacité de la quinine à dose optimale et prolongée ainsi que l'importance du suivi des recommandations de l'Organisation Mondiale de la Santé sur la désinsectisation des avions en provenance de zones d'endémie. (Résumé d'auteur

Step up converter for electromagnetic vibrational energy scavenger

This paper introduces a voltage multiplier (VM) circuit which can step up a minimum voltage of 150 mV (peak). The operation and characteristics of this converter circuit are described. The voltage multiplier circuit is also tested with micro and macro scale electromagnetic vibrational generators and the effect of the VM on the optimum load conditions of the electromagnetic generator is presented. The measured results show that 85% efficiency can be achieved from this VM circuit at a power level of 18 ?W.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/EDA-Publishing