Cellular interactions of functionalized superparamagnetic iron oxide nanoparticles on oligodendrocytes without detrimental side effects: Cell death induction, oxidative stress and inflammation.

Iron oxide nanoparticles have the capability to cross Blood Brain Barrier (BBB) and hence are widely investigated for biomedical operations in the central nervous system. Before being used for the biomedical purpose, it is necessary to investigate its biocompatibility, dosimetry and biological interaction. In the present study, in-house synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were functionalized using the polymer, PolyEthylene Glycol (PEG) and a fluorophore (Rhodamine). The interaction of these nanoparticles with murine oligodendrocytes 158N was studied using different assays. The nanoparticles were taken up by the cells via endocytosis and there was a dose-dependent increase in the intracellular iron content as revealed by flow cytometry, transmission electron microscopy and confocal microscopy. Nanoparticles remained stable inside cells even after 24 h. Cell sorting capacity using a magnet depended on the number of particles interact per cell. SPIONs exhibited good biocompatibility as no toxicological responses, including morphological changes, loss of viability, oxidative stress or inflammatory response (IL-1ß, IL-6 secretion) were observed. Together, these data show that the in-house synthesized SPIONs have no side effects on 158N cells, and constitute interesting tools for biomedical applications across brain, including cellular imaging and targeting.

Importance of vector-borne infections in different production systems: bovine trypanosomosis and the innovation dynamics of livestock producers in Senegal.

In Senegal, a project has been undertaken to eradicate a population of tsetse flies (Glossina palpalis gambiensis) from a prime area for intensifying livestock production--the coastal region of Niayes. The project is intended to remove the constraint of trypanosomosis and allow the ecological intensification of cattle production. A cross-sectional analysis of ten case studies was the inductive phase of an assessment to gauge the impact of removing trypanosomosis on livestock production strategies. The methodology used was comprehensive analysis, with participatory epidemiology tools to understand farmers' rationales. The authors analysed the strategies of three main types of livestock producer (agro-pastoralists, mixed crop/livestock farmers and intensive dairy farmers). The strategies were in line with the farmers' goals and their ability to mobilise the socio-technical network. The risk management of trypanosomosis has been incorporated into livestock management practices through the use of trypanotolerant breeds, medical prophylaxis or placing livestock in low-risk areas. Removing the risk of disease would therefore have a major impact on decisions about the composition and strategic direction of herds. This change in the animal health environment would steer livestock production along different routes of intensification in a highly competitive environment. The indicators of innovation capacity revealed by this study will be used to quantitatively monitor various change scenarios, taking livestock producers' reasoning into account, in order to assess the socio-economic impact of eradicating the tsetse fly population in this area. The methodology presented in the study can be used to understand the impact of controlling other vector-borne infections on the innovation dynamics of livestock producers.

High prevalence of diabetes mellitus and hospital-related hyperglycaemia in French general wards.

AIM: The study evaluated the in-hospital prevalence of diabetes and hospital-related hyperglycaemia in a variety of French general wards. METHODS: The multicentre cross-sectional study involving nine French hospitals measured venous fasting plasma glucose (FPG) on a single day in patients hospitalized in adult medical and surgical short-term wards. Diabetes status and length of stay were recorded. RESULTS: Of the 2141 inpatients included in the study, 355 (16.5%) had known diabetes, 156 (7.3%) had screened diabetes (FPG ≥7 mmol/L with no diabetes history), 515 (24.1%) had impaired fasting glucose (IFG; FPG 5.5-6.9 mmol/L) and 1115 (52.1%) had normal glucose values (FPG < 5.5 mmol/L). Diabetes prevalence varied from 11% in hospitals in the west of France to 21% in hospitals in northern and eastern regions. The highest known diabetes prevalence was observed in units for cardiovascular surgery (33%), infectious diseases (27%) and kidney disorders (26%). In cancer units, one-fifth of patients had screened diabetes and one-sixth had known diabetes. Among the known diabetes patients, 127 (36%) were already being treated with insulin, while an additional 41 (12%) started insulin therapy during their hospital stay. Patients with known and screened diabetes were older (70.8 ± 12.2 and 71.1 ± 15.6 years, respectively) than the normal-glucose patients (65.6 ± 18.9 years; P<0.001). Average length of stay was no different between known diabetes and normal-glucose patients after adjusting for age (11.3 ± 7.7 vs 10.0 ± 7.4 days; NS). CONCLUSION: Overall, metabolic glucose disorders (known or screened diabetes and IFG) were found in 48% of inpatients in various French hospital general wards.

Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level.

TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which mainly occurs at the death-inducing signaling complex (DISC) level, through enhanced caspase-8 recruitment and activation, is compromised by c-FLIP expression and is independent of the mitochondria. Importantly, TRAIL-R4 expression prevents TRAIL-induced tumor regression in nude mice, but tumor regression induced by TRAIL can be restored with chemotherapy. Our results clearly support a negative regulatory function for TRAIL-R4 in controlling TRAIL signaling, and unveil the ability of TRAIL-R4 to cooperate with c-FLIP to inhibit TRAIL-induced cell death.

Easy route to functionalize iron oxide nanoparticles via long-term stable thiol groups.

The functionalization of superparamagnetic iron oxide nanoparticles (SPIOs) by meso-2,3-dimercaptosuccinic acid (DMSA) was investigated. Under ambient conditions, the thiol groups from DMSA are not stable and do not allow a direct functionalization without storage in stringent conditions or a chemical regeneration of free thiols. In this study, we have developed a protocol based on poly(ethylene glycol) (PEG) grafting of SPIO prior to DMSA anchoring. We have observed that PEG helps to increase the stability of thiol groups under ambient conditions. The thiol functionalized SPIOs were stable under physiological pH and ionic strength as determined by Ellman's essay and allowed us to graft a thiol reactive fluorescent dye: tetramethylrhodamine-5-maleimide (TMRM).

Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.

The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.