Stem-cell-based Therapies for Improving Islet Transplantation Outcomes in Type 1 Diabetes.

INTRODUCTION: Beta-cell replacement by human islets or whole pancreas offers a life-saving therapeutic remedy for patients suffering from type 1 diabetes, providing considerable advantages with respect to diminishing total daily insulin dose and lowering frequencies of debilitating hypoglycemic reactions as well as preventing chronic micro- and macrovascular complications. Although remarkable progress has been made in this area, several hurdles remain, hampering its wide-spread applicability. Such hurdles include a limiting supply of islets, the necessity of several donors to achieve enough islet mass for insulin independence, and graft failure because of metabolic pressure, continued autoimmunity, alloimmunity, high concentrations of immunosuppressive drugs as well as oxidative stress caused by hypoxia or inflammation. On the other hand, the islet transplant procedure provides the possibility to undertake multiple practical and beneficial manipulations of the beta cells before engraftment with the intention to reach improved graft survival results. CONCLUSION: We have focused on the current status of various obstacles in islet transplantation and on the potential of (stem)cell-based treatments able to stimulate islet graft outcome in pre-clinical and clinical transplantation settings in which specific attention is given to the engraftment-enhancing and immunomodulatory potential of various types of stem cells..

Renal and cardiorespiratory effects of treatment with lactated Ringer's solution or physiologic saline (0.9% NaCl) solution in cats with experimentally induced urethral obstruction.

OBJECTIVE: To compare the renal and cardiorespiratory effects of IV treatment with lactated Ringer's solution (LRS) or physiologic saline (0.9% NaCl) solution (PSS) in severely decompensated cats with urethral obstruction (UO). ANIMALS: 14 cats (4 cats were used only to establish infusion rates). PROCEDURES: An occluded urethral catheter was used to induce UO in each cat. After development of severe metabolic acidosis, hyperkalemia, and postrenal azotemia, the obstruction was relieved (0 hours); LRS or PSS (5 cats/group) was administered IV (gradually decreasing rate) beginning 15 minutes before and continuing for 48 hours after UO relief. Ten minutes before urethral catheter placement (baseline), at start of fluid therapy (SFT), and at intervals during fluid administration, various physical and clinicopathologic evaluations were performed. RESULTS: Metabolic acidosis was detected in the PSS-treated group at SFT and 2 hours after relief of UO and in the LRS-treated group only at SFT The PSS-treated group had significantly lower blood pH and bicarbonate concentrations at 8 through 48 hours and lower base excess values at 2 through 48 hours, compared with the LRS-treated group. Hypocalcemia and hypernatremia were detected in the PSS-treated group at 2 and 12 hours, respectively. Absolute serum potassium and chloride concentrations did not differ significantly between groups at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with LRS or PSS appeared to be safe and effective in cats with experimentally induced UO; however, LRS was more efficient in restoring the acid-base and electrolyte balance in severely decompensated cats with UO.