Encephalitis due to emerging viruses: CNS innate immunity and potential therapeutic targets.

The emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. The recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious CNS infections. Many RNA viruses enter the CNS by evading the BBB due to axonal transport from the periphery. The systemic adaptive and CNS innate immune systems express pattern recognition receptors PRR (TLRs, RiG-1 and MDA-5) that detect viral nucleic acids and initiate host antiviral response. However, several emerging viruses (West Nile Fever, Influenza A, Enterovirus 71 Ebola) are recognized and internalized by host cell receptors (TLR, MMR, DC-SIGN, CD162 and Scavenger receptor B) and escape immuno surveillance by the host systemic and innate immune systems. Many RNA viruses express viral proteins WNF (E protein), Influenza A (NS1), EV71 (protein 3C), Rabies (Glycoprotein), Ebola proteins (VP24 and VP 35) that inhibit the host cell anti-virus Interferon type I response promoting virus replication and encephalitis. The therapeutic use of RNA interference methodologies to silence gene expression of viral peptides and treat emerging virus infection of the CNS is discussed.

Supplementation with a new therapeutic oxygen carrier reduces chronic fibrosis and organ dysfunction in kidney static preservation.

Static preservation is currently the most widely used organ preservation strategy; however, decreased donor organ quality is impacting outcome negatively. M101 is an O2 carrier with high-oxygen affinity and the capacity to function at low temperatures. We tested the benefits of M101 both in vitro, on cold preserved LLC-PK1, as well as in vivo, in a large white pig kidney autotransplantation model. In vitro, M101 supplementation reduced cold storage-induced cell death. In vivo, early follow-up demonstrated superiority of M101-supplemented solutions, lowering the peak of serum creatinine and increasing the speed of function recovery. On the longer term, supplementation with M101 reduced kidney inflammation levels and maintained structural integrity, particularly with University of Wisconsin (UW). At the end of the 3-month follow-up, M101 supplementation proved beneficial in terms of survival and function, as well as slowing the advance of interstitial fibrosis. We show that addition of M101 to classic organ preservation protocols with UW and Histidine-Tryptophane-Ketoglutarate, the two most widely used solutions worldwide in kidney preservation, provides significant benefits to grafts, both on early function recovery and outcome. Simple supplementation of the solution with M101 is easily translatable to the clinic and shows promises in terms of outcome.

Aparasitemic serological suspects in Trypanosoma brucei gambiense human African trypanosomiasis: a potential human reservoir of parasites?

The serological and parasitological tests used for Trypanosoma brucei gambiense human African trypanosomiasis (HAT) diagnosis have low specificity and sensitivity, respectively, and in the field, control program teams are faced with subjects with positive serology but negative parasitology who remain untreated. The aim of this work was to explore, using PCR tool, the significance of these aparasitemic serological suspects. Since discordant PCR results have been observed earlier with different extraction methods, two DNA extraction methods were compared (the Chelex 100 resin and the DNeasy Tissue kit). The study was conducted on 604 blood samples: 574 from parasitologically confirmed patients, aparasitemic serological suspects and endemic controls collected in Côte d'Ivoire and 30 from healthy volunteers collected in France. No significant differences were observed between the PCR results obtained with the two extraction methods. Concerning PCR, problems of reproducibility and discordances with both serological and parasitological test results were observed, mainly for the aparasitemic serological suspects. In addition to previous results that pointed to the existence of non-virulent or non-pathogenic trypanosome strains and of individual susceptibility leading to long term seropositivity without detectable parasitaemia but positive PCR, the results of this study support the notion of a long lasting human reservoir that may contribute to the maintenance or periodic resurgences of HAT in endemic foci.

[Clinical and biological evolution of myasthenia gravis after thymectomy in a 13-year-old girl]. / Evolution clinique et biologique d'une myasthénie grave après thymectomie chez une jeune fille de 13 ans.

A 13-year-old girl suffering from rhumatoid arthritis developed a myasthenia gravis. Her circulating anti-acetylcholine receptor antibodies were observed before and after thymectomy. Surgical removal of the thymus was followed by complete clinical remission associated with a progressive decrease of the antibody level; these antibodies did not disappear completely even as late as 2 years after the operation.