The ROS Scavenger, NAC, Regulates Hepatic Vα14iNKT Cells Signaling during Fas mAb-Dependent Fulminant Liver Failure

Uncontrolled systemic activation of the immune system is an early initiating event that leads to development of acute fulminant liver failure (FLF) in mice after treatment with agonistic Fas mAb. In this study, we demonstrate that treatment of mice with N-acetylcysteine (NAC), an ROS scavenger and glutathione (GSH) precursor, almost completely abolished Fas mAb-induced FLF through suppression of Vα14iNKT cell activation, IFN-γ signaling, apoptosis and nitrotyrosine formation in liver. In addition, enrichment of the liver with GSH due to Vα14iNKT cells deficiency, induced an anti-inflammatory response in the liver of Jα18−/− mice that inhibited apoptosis, nitrotyrosine formation, IFN-γ signaling and effector functions. In summary, we propose a novel and previously unrecognized pro-inflammatory and pro-apoptotic role for endogenous ROS in stimulating Th1 signaling in Vα14iNKT cells to promote the development of FLF. Therefore, our study provides critical new insights into how NAC, a ROS scavenger, regulates Th1 signaling in intrahepatic Vα14iNKT cells to impact inflammatory and pathological responses

Cesarianas: percepção de risco e sua indicação pelo obstetra em uma maternidade pública no Município do Rio de Janeiro Cesarean sections: risk perception and indication by attending obstetricians in a public maternity hospital in Rio de Janeiro

A taxa de cesariana entre as maternidades públicas municipais da cidade do Rio de Janeiro no ano de 2000 foi de 30,1%. Com taxas tão elevadas, nossas hipóteses são que as indicações de cesarianas nestas unidades não estão restritas apenas às indicações clínicas. Este artigo tem como objetivo analisar as representações de médicos sobre os riscos inerentes da cesariana que influenciam a sua indicação. Neste estudo qualitativo, realizado com observação participante de plantões e entrevistas com obstetras, pudemos identificar que as indicações feitas pelos obstetras da unidade pública estudada sofrem influência de diversos fatores não obstétricos: a insegurança quanto às manobras obstétricas, a fragmentação do atendimento e o medo da responsabilização jurídica, entre outros. O artigo sugere que a banalização desta intervenção no serviço privado traz para o serviço público um desvio da prática obstétrica que compromete não apenas a qualidade da assistência pública, como pode colocar em risco a vida de mulheres e bebês.<br>The cesarean section rate in municipal public maternity hospitals in the city of Rio de Janeiro in the year of 2000 was 30.1%. With such a high rate, our hypothesis is that attending obstetricians in these units are indicating cesarean sections for reasons not restricted to clinical factors. The article aims to analyze physicians' representations of the inherent risks in cesarean sections that influence the medical decision for their indication. In this qualitative study, conducted through participant observation during ward duty and interviews with obstetricians, we observed that C-section indications by obstetricians are influenced by various non-obstetric factors, including insecurity about performing obstetric maneuvers, fragmented care, and fear of legal liability. The paper suggests that the widespread use of this intervention in private maternity services has fostered a practice in public obstetric services that compromises the quality of public health care and may jeopardize the health of women and infants

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study.

International audienceDigestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia

TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration

Inflammation participates in tissue repair through multiple mechanisms including directly regulating the cell fate of resident progenitor cells critical for successful regeneration. Upon surveying target cell types of the TNF ligand TWEAK, we observed that TWEAK binds to all progenitor cells of the mesenchymal lineage and induces NF-κB activation and the expression of pro-survival, pro-proliferative and homing receptor genes in the mesenchymal stem cells, suggesting that this pro-inflammatory cytokine may play an important role in controlling progenitor cell biology. We explored this potential using both the established C2C12 cell line and primary mouse muscle myoblasts, and demonstrated that TWEAK promoted their proliferation and inhibited their terminal differentiation. By generating mice deficient in the TWEAK receptor Fn14, we further showed that Fn14-deficient primary myoblasts displayed significantly reduced proliferative capacity and altered myotube formation. Following cardiotoxin injection, a known trigger for satellite cell-driven skeletal muscle regeneration, Fn14-deficient mice exhibited reduced inflammatory response and delayed muscle fiber regeneration compared with wild-type mice. These results indicate that the TWEAK/Fn14 pathway is a novel regulator of skeletal muscle precursor cells and illustrate an important mechanism by which inflammatory cytokines influence tissue regeneration and repair. Coupled with our recent demonstration that TWEAK potentiates liver progenitor cell proliferation, the expression of Fn14 on all mesenchymal lineage progenitor cells supports a broad involvement of this pathway in other tissue injury and disease settings