[Organophosphorus poisoning: Towards enzymatic treatments]. / Intoxication aux organophosphorés : vers des traitements enzymatiques.

Organophosphorus compounds (OP) are toxic molecules developed as insecticides and chemical warfare nerve agents (CWNAs). Most OP are neurotoxic and act as nervous system disruptors by blocking cholinergic transmission. They are therefore responsible for many poisonings worldwide. OP toxicity may result either from acute or chronic exposure, and their poisoning effect were evaluated using several animal models. These latter were also used for evaluating the efficacy of antidotes. Strategies based on enzymes that can trap (stoichiometric bioscavengers) or degrade (catalytic bioscavengers) OP, were particularly studied since they allow effective decontamination, without toxicity or environmental impact. This review summarizes the results obtained in vivo with enzymes through three levels: prophylaxis, treatment and external decontamination. The efficiency of enzymatic treatments in different animal models is presented and the relevance of these models is also discussed for a better extrapolation to humans.

[Prevent bacteria from communicating: Divide to cure]. / Empêcher les bactéries de communiquer : diviser pour mieux soigner.

Quorum Sensing (QS) is a communication system used by numerous bacteria to synchronize their behavior according to the cell density. In this way, bacteria secrete and sense small mediating molecules, called autoinducers (AI), which concentration increases in the environment proportionally to bacterial cell number. QS induces major physiological and phenotypic changes such as virulence induction and biofilm formation. Biofilm represents a physical barrier which shelters bacteria poorly sensitive to antimicrobial treatments and favors the apparition of resistance mechanisms. Disturbing QS is referred to as quorum quenching (QQ). This strategy is used by microorganisms themselves to prevent the development of specific group behaviors. Two strategies are mainly employed: the use of quorum sensing inhibitors (QSI) and of quorum quenching enzymes (QQE) that degrades AI. Many studies have been dedicated to identifying QSI (natural or synthetic) as well as QQE and demonstrating their anti-virulence and anti-biofilm effects on numerous bacterial species. Synergistic effects between QQ and traditional treatments such as antibiotherapy or with reemerging phage therapy have been put forward. The efficiency of numerous QSI and QQE was thereby demonstrated either with in vitro or in vivo animal models leading to the development of medical devices containing QSI and QQE to improve already existing treatments.

[Decontamination of organophosphorus compounds: Towards new alternatives]. / La décontamination des organophosphorés : vers de nouvelles alternatives.

Organophosphorus coumpounds (OP) are toxic chemicals mainly used for agricultural purpose such as insecticides and were also developed and used as warfare nerve agents. OP are inhibitors of acetylcholinesterase, a key enzyme involved in the regulation of the central nervous system. Chemical, physical and biological approaches have been considered to decontaminate OP. This review summarizes the current and emerging strategies that are investigated to tackle this issue with a special emphasis on enzymatic remediation methods. During the last decade, many studies have been dedicated to the development of biocatalysts for OP removal. Among these, recent reports have pointed out the promising enzyme SsoPox isolated from the archaea Sulfolobus solfataricus. Considering both its intrinsic stability and activity, this hyperthermostable enzyme is highly appealing for the decontamination of OP.

[Feasibility study for Intercept platelets]. / Étude de faisabilité des plaquettes Intercept.

During 3 months, platelet concentrates prepared by "Établissement français du sang Pyrénées-Méditerranée" (Blood bank) were treated with the Intercept process (CERUS©). This study primarily aimed to measure the organizational impact of this technology on transfusion chain. The introduction of Intercept did not raise any major difficulties, but required some adaptations upstream from the deployment. Prior information of health care institutions and physician was essential to anticipate the practical changes, including the prescription of platelet concentrates (CMV negative, irradiation). This study allowed to analyze also the transfusion consequences for patients, in the form of observational studies. The patients transfused with platelet concentrates treated with Intercept received more platelet concentrates (+12.9%), less rich in platelets (-12.8%), the cumulated quantity of platelet being stable.

[Enzymes for disrupting bacterial communication, an alternative to antibiotics?] / Des enzymes pour bloquer la communication bactérienne, une alternative aux antibiotiques ?

Quorum sensing (QS) is used by bacteria to communicate and synchronize their actions according to the cell density. In this way, they produce and secrete in the surrounding environment small molecules dubbed autoinducers (AIs) that regulate the expression of certain genes. The phenotypic traits regulated by QS are diverse and include pathogenicity, biofilm formation or resistance to anti-microbial treatments. The strategy, aiming at disrupting QS, known as quorum quenching (QQ), has emerged to counteract bacterial virulence and involves QS-inhibitors (QSI) or QQ-enzymes degrading AIs. Differently from antibiotics, QQ aims at blocking cell signaling and does not alter bacterial survival. This considerably decreases the selection pressure as compared to bactericide treatments and may reduce the occurrence of resistance mechanisms. QQ-enzymes are particularly appealing as they may disrupt molecular QS-signal without entering the cell and in a catalytic way. This review covers several aspects of QQ-based medical applications and the potential subsequent emergence of resistance is discussed.

[Kinetic and organization of granulocytes transfusion: a case report]. / Transfusion thérapeutique de granulocytes : cinétique et aspects organisationnels autour d'un cas clinique.

BACKGROUND: Therapeutic granulocyte transfusion remains an indication for neutropenic sepsis associated with prolonged neutropenia. However, harvest complexity and lack of proved efficacy mark the limits of its development. CASE REPORT: A 58-year old man received allogeneic stem cell transplantation for osteomyelofibrosis. Six months later, after a transplant rejection, he presented with perineal cellulitis from hemorrhoid origin, without any microbiological documentation. The evolution was unfavorable despite antibiotic and antifungal therapy. A set of seven granulocytes transfusions was initiated. Re-circulation of granulocytes analysis showed an initial increase (H2) followed by a decrease (H8) reaching the basal rate at H16. No toxicity has been reported during or following the transfusions. Clinical improvement has been reported five days after the first transfusion, scaring over at D15, without any neutrophil recovery. CONCLUSION: In 2014, granulocyte transfusion therapy is indicated for severe infection associated with long-term neutropenia. Minimal circulation of transfused cells in our observation and fast clinical improvement suggest the concentration of granulocytes on the infected area.

Cost-effective treatment solutions for rural areas: design and operation of a new package treatment plant for single households.

The design approach and operation of a newly developed package plant treating domestic sewage from single households were evaluated. Combining submerged aerated filter (SAF) technology with jet aeration and incorporating both into a compact and shallow tank resulted in a cost-effective treatment solution. A trial unit was permanently installed at a rural site, serving a single household. Jet aeration proved to be the best aeration method for the shallow bioreactor design. Further trials revealed a 50% reduction in suspended solids (SS) through the use of a static effluent filter and found that annual plant maintenance was vital to sustain stable operating conditions. Despite high variations in influent conditions, the trial unit produced good effluent quality during steady-state operation. Average effluent BOD5, COD and SS values were 19.6 mg l(-1), 98 mg l(-1) and 32 mg l(-1) achieving overall removal efficiencies of 94.2%, 85.9% and 87.6% respectively. However, effluent ammonia nitrogen (NH4-N) levels were found to be inconsistent varying from 9 mg l(-1) to over 60 mg l(-1).

Moving bed biofilm reactors: a small-scale treatment solution.

The design and operational suitability of the moving bed process for small-scale sewage treatment systems were evaluated. A prototype plant was installed at a new housing development near Winchester, UK, and operated under different conditions over an eight-month period. During normal operation, the MBBR plant produced a good quality effluent with average values for BOD5, COD, SS and NH4-N of 15.6 mg l(-1), 65.9 mg l(-1), 21 mg l(-1) and 4.7 mg l(-1), respectively. The plant was further subjected to organic and hydraulic shock loads. The treatment performance remained high over the organic shock period, however, hydraulic surges of up to 10 times the design flow caused a loss of solids from the final settlement stage. While organic carbon removal resumed to over 80% within a single week after a prolonged power failure, effluent NH4-N values remained high for a period of three weeks. Besides producing a good quality effluent, the MBBR plant proved to be simple and reliable to operate, thus providing a viable treatment solution for small-scale applications.

[Validity of pretransfusion bedside agglutination tests for pretransfusional control]. / Etude régionale de validité, dans les services de soins, du test d'agglutination du contrôle ultime prétransfusionnel.

The incidence rate of ABO hazards of transfusion remains high in France. In this country, bedside pretransfusion controls include an agglutination test for red cells only, although its validity has scarcely been assessed in the practice. 847 nurses from 9 public hospitals and private clinics in a French region participated in a study aimed at measuring the sensitivity and specificity of pretransfusion bedside agglutination tests within hospital wards. Sensitivity was found to be 93.9% +/- 3%. Nondetection of mismatching was increased by two risk factors only: having worked more than 4 years in the same ward, and not having been trained to use this test. The sensitivity of this test might still be improved. This test is found sensitive enough to be kept. Nevertheless, if used alone, it is not a safe protection against recipient's mismatch. Authors recommend both to improve agglutination test sensitivity and to link it strongly to the bedside checking of both transfusion information and the recipient's identity.