Differential effects of zidovudine and zidovudine triphosphate on mitochondrial permeability transition and oxidative phosphorylation

1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca²⁺-induced mitochondrial permeability transition (MPT), respiratory control ratio (RCR) and ATP synthesis have been investigated on isolated rat liver mitochondria.
2. ZDV slightly but significantly decreased RCR and ATP synthesis but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and ATP synthesis but strongly inhibited MPT (IC₅₀=3.0±0.9 μM).
3. The effect of ZDV-3P on mitochondrial swelling required a preincubation time. When incubated 10 min with mitochondria, ZDV-3P (8 μM) totally inhibited the rate of swelling.
4. ADP, ATP and atractyloside, which are agents known to interact with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect of ZDV-3P on mitochondrial swelling. Indeed, the IC₅₀ value of ZDV-3P increased from 3.0 to 17.4, 93.6 and 66.5 μM, in the presence of 20 μM, ADP, ATP or atractyloside, respectively.
5. ZDV-3P did not displace [³H]-ATP from its mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that ZDV-3P and [³H]-ATP do not share the same binding sites.
6. ZDV-3P did not affect either mitochondrial respiration or ATP synthesis but inhibited Ca²⁺-dependent mitochondrial swelling. It was concluded that mitochondrial toxic effects observed during the chronic administration of ZDV cannot be related to its active metabolite (ZDV-3P).

     

Outbreak of OXA-48-producing Enterobacterales in a haematological ward associated with an uncommon environmental reservoir,France, 2016 to 2019

The hospital water environment, including the wastewater drainage system, is increasingly reported as a potential reservoir for carbapenemase-producing Enterobacterales (CPE). We investigated a persistent outbreak of OXA-48 CPE (primarily Citrobacter freundii) in a haematological ward of a French teaching hospital by epidemiological, microbiological and environmental methods. Between January 2016 and June 2019, we detected 37 new OXA-48 CPE-colonised and/or ‑infected patients in the haematological ward. In October 2017, a unit dedicated to CPE-colonised and/or ‑infected patients was created. Eleven additional sporadic acquisitions were identified after this date without any obvious epidemiological link between patients, except in one case. Environmental investigations of the haematological ward (June–August 2018) identified seven of 74 toilets and one of 39 drains positive for OXA-48 CPE (seven C. freundii, one Enterobacter sakazakii, one Escherichia coli). Whole genome comparisons identified a clonal dissemination of OXA-48-producing C. freundii from the hospital environment to patients. In addition to strict routine infection control measures, an intensive cleaning programme was performed (descaling and bleaching) and all toilet bowls and tanks were changed. These additional measures helped to contain the outbreak. This study highlights that toilets can be a possible source of transmission of OXA-48 CPE.     

Remote Echography between a Ground Control Center and the International Space Station Using a Tele-operated Echograph with Motorized Probe

Echography is the most appropriate imaging modality for investigating astronauts. Unfortunately, it requires a great deal of training to perform ultrasound examinations, which can be difficult and time consuming, especially if the astronaut does not have a medical background. We designed a new echography system with motorized probes that allows for the majority of exam functions to be controlled by a ground-based sonographer. Using tele-operation, the sonographer controls the orientation of the transducer (tilt, rotation) and echograph settings (gain, depth, freeze) and triggers ultrasound functions (pulsed wave color Doppler, 3-D capture, radiofrequency data collection, elastography). With this system, astronauts are required to hold the motorized probe only at the locations indicated, with the remainder of the exam being conducted by the ground-based sonographer. During spaceflight, ultrasound imaging of the carotid artery, jugular vein, thyroid, liver, gallbladder, biliary tract and portal vein (2-D, 3-D, color, pulsed wave, radiofrequency) were successfully performed.     

Substance use and misuse in a mountain ultramarathon: new insight into ultrarunners population?

Endurance and ultra-endurance events have become increasingly popular. The aim of our study was to explore the use of medication among endurance runners participating in the 2014 Infernal Trail des Vosges. Among the 389 runners engaged, 297 (76.3%) completed a specific questionnaire dealing with substance use/misuse. Our results show a 27% (before the race) and 18% (during the race) prevalence of substance use. The two major classes of substances used were non-steroidal anti-inflammatory drugs (NSAIDs; 9.8%) and painkillers (6.7%), principally because of osteo-articular pain (29.6%) or to prevent pain (28.2%). A positive correlation was found between substance consumption before (past month) and during the race (overall medication: p < 0.0001; NSAIDs: p = 0.008). Our results could be explained by the specific characteristics of ultrarunners predominantly motivated by personal achievement and general health (recreational approach). However, education interventions should further be delivered regarding the risks of substance use in ultra-endurance events.