Central tolerance induction in natural immunoglobulin-allotype-specific T cells

While self toleance is induced to IgG(b)(2a) in Igh(b / b) mice, an anti-IgG(b)(2a) T cell activity emerges in their Igh(a / a) congenic counterparts. This activity is revealed by postnatal transfer of Igh(a / a) T splenocytes into Igh(a / b) F(1), in which total suppression of IgG(2a)(b) expression is established. Here, we sought to determine whether the natural T cell unresponsiveness to IgG(2a)(b) in Igh(b / b) mice involved a central tolerance. Based on the kinetics of postnatal thymic C(gamma2a)(b) gene expression in Igh(b / b) mice, we transplanted thymi from Igh(b / b) donors of diverse ages into tolerogen-free Igh(a / a) nu / nu recipients. The state of T cell tolerance or responsiveness to IgG(2a)(b) in these reconstituted nu / nu hosts was determined by monitoring the capacity of their splenocytes to induce suppression in Igh(a / b) F(1). These experiments demonstrated that: (i) in the Igh(a / a) nu / nu recipients of adult Igh(b / b) thymi, 33 to 65 % T splenocytes were from nu / nu recipient origin, but these peripheral Igh(a / a) T cells were rendered tolerant to IgG(2a)(b) during their differentiation through the adult Igh(b / b) thymi, (ii) circulating IgG(2a)(b) was not a prerequisite for this tolerance induction, (iii) Igh(b / b) thymic epithelium was unable to induce tolerance to IgG(2a)(b) and (iv) IgG(2a)(b)-producing / presenting cells, colonizing the Igh(b / b) thymi, were certainly responsible of full tolerance induction to IgG(2a)(b).     

In vitro and in situ intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells lining a polyester fabric

In order to improve long-term patency of vascular grafts, the promising concept of endothelial cell seeding is actually under investigation. Our laboratory tested a polyester coated with albumin and chitosan which permits a rapid colonization by human umbilical vein endothelial cells (HUVEC) and it seems relevant to test in vitro the expression of adhesive molecules expressed by cells with regard to the inflammatory process. We studied intercellular adhesion molecule-1 (ICAM-1) expression and focused our work on the determination of ICAM-1 sites expressed per adherent cell lining the biomaterial, thus in situ, in comparison to control HUVEC on plastic wells: the results obtained by binding experiments were correlated to flow cytometry analyses and showed that the polyester does not induce a proinflammatory state and that HUVEC covering the structure are able to respond to a stimulus.     

Cost-sparing effect of twice-weekly targeted endurance training in type 2 diabetics: a one-year controlled randomized trial

OBJECTIVE: We evaluated the effects of targeted, moderate endurance training on healthcare cost, body composition and fitness in type 2 diabetes patients routinely followed within the French healthcare system. DESIGN AND METHODS: A total of 25 type 2 diabetic patients was randomly assigned to one of two groups: 13 underwent a training programme (eight sessions, followed by training twice a week for 30-45 minutes at home at the level of the ventilatory threshold [V(T)]); and 12 received their usual routine treatment. Both groups were followed for one year to evaluate healthcare costs, exercise effectiveness and a six-minute walking test. RESULTS: The training prevented loss of maximum aerobic capacity, which decreased slightly in the untrained group (P=0.014), and resulted in a higher maximum power output (P=0.041) and six-minute walking distance (P=0.020). The Voorrips activity score correlated with both V(O2max) (r=0.422, P<0.05) and six-minute walking distance (r=0.446, P<0.05). Changes in V(O2max) were negatively correlated with changes in body weight (r=0.608, P<0.01). Training decreased the insulin-resistance index (HOMA-IR) by 26% (P<0.05). Changes in percentages of fat were correlated to changes in waist circumference (r=0.436, P<0.05). The total healthcare cost was reduced by 50% in the trained group (euro 1.65+/-1 per day versus euro 3.00+/-1.47 per day in the untrained group; P<0.02) due to fewer hospitalizations (P=0.05) and less use of sulphonylureas (P<0.05). CONCLUSION: Endurance training at V(T) level prevented the decline in aerobic working capacity seen in untrained diabetics over the study period, and resulted in a marked reduction in healthcare costs due to less treatments and fewer hospitalizations.     

Interspecies differences with in vitro and in vivo models of vascular tissue engineering

In arterial replacement there is a clear clinical need for a functional substitute possessing appropriate haemocompatible properties to be implanted as small diameter artery. Endothelial cell seeding constitutes an appreciated method to improve blood compatibility on the condition that cells firmly adhere to the support. Along this way, an innovative technique based on multilayered polyelectrolyte films (PEM) as cell adhesive substrate was previously validated in vitro and in vivo in a small-animal model. In this study, we extended the work on a larger animal (sheep) to validate furthermore the paradigm of PEM functionalization for vascular substitutes. We tested in vitro: the efficiency of PEM to induce endothelial progenitor differentiation in sheep endothelial cells; the ability of PEM to sustain cell proliferation and allow resistance to shear stress; the fate of PEM-coated de-endothelialized human saphenous veins under flow conditions, a prerequisite step before in vivo experiments. Despite in vitro differences we were encouraged by testing in vivo PEM-coated prosthesis as carotid replacement in sheep, but without success. In order to explain the implantation failure, an in vitro haemocompatibility evaluation was performed that highlighted interspecies differences able to explain, at least in part, the graft failure obtained.     

Polyethylene terephthalate membrane grafted with peptidomimetics: endothelial cell compatibility and retention under shear stress

The present work aimed to treat a polyethylene terephthalate (PET) surface to make the biomaterial more ‘attractive’ in terms of attachment and shear stress response to endothelial cells with a view to possible applications in vascular grafting. A surface wet-chemistry protocol was applied to graft track-etched PET membranes with RGD peptidomimetics based on the tyrosine template and active at the nano-level vs. isolated human α_vβ₃ receptor, which was monitored by X-ray photoelectron spectroscopy, contact angle measurement and atomic force microscopy for characterization. A primary culture of human saphenous vein endothelial cells was used before and after sterilization of the membranes (heat treatment or γ-ray irradiation) to test the benefit of grafting. The optimal surface concentrations of grafted molecules were around 50?pmol/cm². Compared to GRGDS, the peptidomimetics promoted cell attachment with similar or slightly better performances. Endothelialized grafted supports were further exposed to 2?h of shear stress mimicking arterial conditions. Cells were lost on non-grafted PET whereas cells on grafted polymers sterilized by γ-ray irradiation withstood forces with no significant difference in focal contacts. At the mRNA level, cells on functionalized PET were able to respond to shear stress with NFkB upregulation. Thus, grafting of peptidomimetics as ligands of the α_vβ₃ integrin could be a relevant strategy to improve the adhesion of human endothelial cells and to obtain an efficient endothelialized PET for the surgery of small-diameter vascular prostheses.     

Tumeur ORL responsable de syncopes à répétition : cas clinique

The repeated syncopes in case of head and neck cancer are a complication rarely described in the literature. They occur when the tumor invade the carotid sinus or the afferent fibers of the glossopharyngeal nerve. We report the case of a 62-year-old man presented episodes of syncope synchronous of a recurrent hypopharyngeal tumor scheduled for chemotherapy and gastrostomy. A computerized tomography showed a voluminous tumor expanded to the carotid and parapharyngeal spaces. After treatment by isporenaline chlorhydrate in intensive care unit, a pacemaker was implanted to prevent syncopes and allowed the beginning of the chemotherapy.     

Prognostic utility of pre-transplantation [18F] fluorodeoxyglucose positron emission tomography/computed tomography in patients with diffuse large B-cell lymphoma who underwent rituximab,dexamethasone, high-dose cytarabine,carboplatin salvage chemotherapy

We analysed the outcomes of 62 patients with refractory/relapsed diffuse large B-cell lymphoma (rrDLBCL) who had pre-transplantation fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after R-DHAC (rituximab, dexamethasone, high-dose cytarabine, carboplatin) salvage chemotherapy, and were evaluated using Deauville criteria and total lesion glycolysis (TLG). A positive pre-transplantation PET/CT with Deauville score of 5 was associated with shorter progression-free survival (PFS) (P = 0·01), while a Deauville score of 4 was not predictive of outcome. Only pre-transplant TLG was significantly associated with both PFS (P = 0·005) and overall survival (P = 0·03). TLG deserves to be further investigated in prospective studies.     

In vitro evaluation of an epoxy resin's cytocompatibility using cell lines and human differentiated cells.

The cytocompatibility of a polyepoxy resin (Elf Aquitaine) has been studied using both cell lines and human differentiated cell cultures. The human models were gingival fibroblasts and bone osteoblasts, while the cell lines were Hela cells and 3T3 Balb/c cells. Basal cytocompatibility was assessed by estimation of the cell proliferation, total cell protein content, cell membrane sub-lysis, and cell attachment and spreading. Specific cytocompatibility concerning human osteoblasts, from both alveolar and trabecular bone, was determined by measuring the intracellular alkaline phosphatase activity. Resin colonization by the cells was studied by both TEM and SEM. The behaviour of the two cell lines reveals a significant level of discrepancy, whereas the behaviour of human cells, whatever the model, is comparable; however, osteoblasts look more sensitive. Moreover, the results show that this epoxy resin exhibits a moderate cytocompatibility which could be the result of the cytotoxicity of early released products, associated with the considerable surface roughness.