Heme oxygenase‐1 (HO‐1) induction in, or carbon monoxide (CO), or bilirubin administration to, donors and/or recipients frequently lead to long‐term survival (>100 days) of DBA/2 islets into B6AF1 recipients. We tested here whether similar treatments show value in a stronger immunogenetic combination, i.e. , BALB/c to C57BL/6, and attempted to elucidate the mechanism accounting for tolerance. Induction of HO‐1, administering CO or bilirubin to the donor, the islets or the recipient, prolonged islet allograft survival to different extents. Combining all the above treatments (the “combined” protocol) led to survival for >100 days and antigen‐specific tolerance to 60% of the transplanted grafts. A high level of forkhead box P3 (Foxp3) and transforming growth factor β (TGF‐β) expression was detected in the long‐term surviving grafts. With the combined protocol, significantly more T regulatory cells (Tregs) were observed surrounding islets 7 days following transplantation. No prolongation of graft survival was observed using the combined protocol when CD4 ⁺ CD25 ⁺ T cells were predepleted from the recipients before transplantation. In conclusion, our combined protocol led to long‐term survival and tolerance to islets in the BALB/c to C57BL/6 combination by promoting Foxp3 ⁺ Tregs;these cells played a critical role in the induction and maintenance of tolerance in the recipient.—Lee S. S., Gao, W., Mazzola, S., Thomas, M. N., Csizmadia, E., Otterbein, L. E., Bach, F. H., and Wang H. Heme oxygenase‐1, carbon monoxide, and bilirubin induce tolerance in recipients toward islet allografts by modulating T regulatory cells. FASEB J. 21, 3450–3457 (2007)

Rationale: We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED). Objectives: To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology. Methods: Five mechanically ventilated swine were connected to a custom-made circuit optimized for R-ED, consisting of a hemofilter, a membrane lung, and an electrodialysis cell. Electrodialysis regionally modulates blood electrolyte concentration to convert bicarbonate to CO2 before entering the membrane lung, enhancing membrane lung CO2 extraction. All animals underwent three repeated experimental sequences, consisting of four steps: baseline (1 h), conventional ECCO2R (2 h), R-ED (2 h), and final NO-ECCO2R (1 h). Blood and gas flow were 250 ml/min and 10 L/min, respectively. Tidal volume was set at 8 ml/kg, and respiratory rate was adjusted to maintain arterial Pco2 at 50 mm Hg. Measurements and Main Results: During R-ED, chloride and H+ concentration increased in blood entering the membrane lung, almost doubling CO2 extraction compared with ECCO2R (112 ± 6 vs. 64 ± 5 ml/min, P < 0.001). Compared with baseline, R-ED and ECCO2R reduced minute ventilation by 50% and 27%, respectively. Systemic arterial gas analyses remained stable during the experimental phases. No major complication occurred, but there was an increase in creatinine level. Conclusions: In this first in vivo application, we proved electrodialysis feasible and effective in increasing membrane lung CO2 extraction. R-ED was more effective than conventional ECCO2R technology in controlling ventilation. Further studies are warranted to assess the safety profile of R-ED, especially regarding kidney function.

The aim of this pilot study was to document the effects of endurance training at different intensities on heart rate (HR), blood count, serum cortisol, and maximal temperatures of different body locations, namely eye, crown, pastern pasterns, gluteus and longissimus dorsi muscle (mm), measured by infrared thermography technique (IRT) in horses trained for endurance. Possible associations among the studied parameters were also investigated. Our hypothesis was that temperature, measured by IRT after endurance training of different intensities would vary depending on the intensity and would be positively correlated with HR and serum cortisol. Eight horses were tested before and after training of different intensities (low, moderate, and high). The results partially supported our hypothesis; all the studied parameters increased after training (p < 0.05), eye temperature (ET) correlated positively with HR (p < 0.01), and crown temperature (CT) correlated positively with cortisol (p < 0.01). However, only HR and white blood cells increased with the intensity of the exercise (p = 0.0016 and p = 0.0142, respectively). Our findings suggest the evaluation of ET and CT may become a useful non-invasive tool to detect physiological stress during training and to evaluate how the horses cope with the training. Infrared thermography technique may also become a useful tool for the early identification of horses that are not fit to compete or to continue the competition. However, further studies should be conducted on a larger number of horses and during competitions to ascertain our preliminary findings.