No abstract

BackgroundType 1 and Type 2 diabetes mellitus (T1DM and T2DM) are caused by beta(β)-cell loss and functional impairment. Identification of mechanisms of β-cell death and therapeutic interventions to enhance β-cell survival are essential for prevention and treatment of diabetes. Oxidative stress is a common feature of both T1DM and T2DM; elevated biomarkers of oxidative stress are detected in blood, urine and tissues including pancreas of patients with DM. Islet transplantation is a promising treatment for diabetes. However, exposure to stress (chemical and mechanical) and ischemia-reperfusion during isolation and transplantation causes islet loss by generation of reactive oxygen species (ROS). Human intracellular antioxidant enzymes and related molecules are essential defenses against ROS. Antioxidant enzyme levels including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) have been shown to be low in islet cells. However, little is known about the expression and function of antioxidant enzymes within islet cell subsets. We evaluated the expression of the key antioxidant enzymes in β- and alpha(α)-cell and accessed effects of oxidative stress, islet isolation and transplantation on β/α-cell ratio and viability in human islets.MethodsHuman pancreata from T1DM, T2DM and non-diabetic deceased donors were obtained and analyzed by confocal microscopy. Isolated islets were (I) transplanted in the renal sub-capsular space of streptozotocin-induced diabetic nude mice (in vivo bioassay), or (II) exposed to oxidative (H2O2) and nitrosative (NO donor) stress for 24 hrs in vitro. The ratio, % viability and death of β- and α-cells, and DNA damage (8OHdG) were measured.Results and conclusionsCatalase and GPX expression was much lower in β- than α-cells. The β/α-cell ratio fells significantly following islet isolation and transplantation. Exposure to oxidative stress caused a significantly lower survival and viability, with higher DNA damage in β- than α-cells. These findings identified the weakness of β-cell antioxidant capacity as a main cause of vulnerability to oxidative stress. Potential strategies to enhance β-cell antioxidant capacity might be effective in prevention/treatment of diabetes.

The prognosis for patients with fulminant (FHF) or subfulminant hepatic failure (SFHF) has improved since the introduction of liver transplantation. However, the death rate of patients awaiting liver transplantation is high, possibly because of the difficulty in obtaining grafts in a timely manner, given the relative shortage of cadaveric donors. Between June 1990 and June 1999, 106 patients underwent living-related liver transplantation (LRLT) at Shinshu University Hospital. Among them, 8 patients had FHF and 6 had SFHF; these 14 patients are the subjects of this report. The graft volumes (GV) ranged from 231 mL to 625 mL, corresponding to 35% to 105% of the recipients' standard liver volume (SLV). The postoperative courses of all donors were uneventful. Following liver transplantation, all grafts functioned favorably, with normalization of serum total bilirubin within 3 to 5 days and normalization of coagulation profiles within 4 to 7 days. Thirteen of the 14 recipients are still alive. The actuarial 6-month, 1-year, and 5-year survival rates were 100%, 90%, and 90%, respectively. In the present study, when the ratio of the GV to the recipient's SLV was more than 35%, the graft was able to support the patient's metabolic demand after liver transplantation for FHF or SFHF. Because of the urgent nature of liver transplantation in this clinical condition, concerns over informed consent may be even greater than for elective LRLT. Nevertheless, the high success rate and low donor risk may justify this option for pediatric patients, as well as for a limited population of adult patients suffering from FHF or SFHF. (HEPATOLOGY 1999;30:1521-1526.)The prognosis for patients with fulminant hepatic failure (FHF) and subfulminant hepatic failure (SFHF) has improved since the introduction of orthotopic liver transplantation. 1 The survival rate of patients with these conditions who undergo liver transplantation is in the range of 56% to 80%, 2-4 compared with the 15% to 20% survival rate of patients who do not undergo transplantation, even with improved medical treatment. 5 Because FHF is rapidly progressive and irreversible, the need for liver transplantation is urgent. The death rate of patients awaiting liver transplantation is as high as 40% 6 or 62%, 7 possibly as a result of the difficulty of obtaining grafts in a timely manner, given the relative shortage of cadaveric donors.Living-related liver transplantation (LRLT) has been developed as an alternative to cadaveric liver transplantation. To avoid ethical dilemmas in LRLT, including any potential coercion of the live donor candidates, we have pursued a strict policy of ensuring that the participants in LRLT are fully informed of all aspects and risks of the procedure before we obtain their consent. As favorable results for LRLT have accumulated, reluctance toward the procedure has gradually subsided. Given this success, it is worth considering LRLT for patients with FHF, provided that each situation is considered with special care because of the short amount of time...

Female sex and metabolic disease may be factors contributing to hepatic artery thrombosis after living-donor liver transplantation. More intensive anticoagulation therapy for this patient population might decrease the incidence of hepatic artery thrombosis and, thus, posttransplant recipient mortality.