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R Bottino

Publications and source records attributed to R Bottino.

At least 37 records · Page 2Linked to original sources

Improved human islet isolation using a new enzyme blend, liberase.

Enzymatic digestion of donor pancreases is a vital step in human and large mammalian islet isolation. The variable enzymatic activities of different batches of commercially available collagenase is a major obstacle in achieving reproducibility in islet isolation procedures. In the present work, the effectiveness of Liberase, a standardized mixture of highly purified enzymes recently developed for the separation of human islets, was compared with that of a traditional collagenase preparation (type P). The results of 50 islet isolations using Liberase enzyme were compared with those of 36 isolations with collagenase, type P. No significant differences in donor age, cold ischemia time, digestion time, or weight of the pancreases were observed between the two groups. Islet yield was significantly higher in the group where the Liberase enzyme was used. All parameters examined (islet number, islet number per gram of tissue, islet equivalent number, and islet equivalent number per gram of tissue) were significantly improved when Liberase enzyme was used. Different lots of Liberase enzyme were tested, and no difference was observed. Islets isolated with Liberase enzyme were also of larger size and were much less fragmented, suggesting a gentler enzymatic action and better preservation of anatomical integrity. Islets isolated with Liberase enzyme, assessed both in vitro and in vivo, revealed a functional profile similar to that of islets separated with collagenase. Liberase enzyme appears, therefore, to represent a new powerful tool for improving the quality of human islet isolation.

Adult↗

Liver transplantation without immunosuppression: future perspectives.

It has been hypothesized that a state of microchimerism in recipients of organ transplants may result in donor-specific tolerance to the graft. Numerous studies show that infusion of donor-derived bone marrow cells can, indeed, achieve systemic chimerism in the recipient and effectively prolong allograft survival. We have compared organ and patient survival in recipients of liver allografts alone (controls) or in combination with single or multiple infusions of donor bone marrow cells; recipients were infused either at day 0 (perioperatively) or at day 0 and 11 post-transplant. The incidence of rejection episodes and survival of the liver allograft were significantly reduced in recipients of two bone marrow infusions compared to controls; recipients of one infusion, conversely, experienced a higher number of rejection episodes when compared to controls, pointing to a possible sensitizing role of a single bone marrow infusion if administered perioperatively. Variables such as timing, number and composition of the bone marrow inocula still remain to be elucidated but may be of critical importance for the attainment of a state of donor-specific tolerance without the need for immunosuppressive therapy in recipients of organ allografts.

Animals↗

Antenatal risk factors for germinal matrix hemorrhage and intraventricular hemorrhage in preterm infants.

OBJECTIVES: This study was designed to evaluate the effect of antenatal risk factors on the occurrence of germinal matrix hemorrhage or intraventricular hemorrhage in preterm infants. STUDY DESIGN: Antenatal factors were evaluated in 302 infants delivered between 24 and 33 completed weeks gestation. Ultrasonographic screening of intracranial hemorrhage was carried out in all the infants. The association between risk factors and neonatal intracranial hemorrhage was evaluated with both univariate and multivariate models. RESULTS: In stepwise logistic regression analysis, birthweight was a better predictor of neonatal germinal matrix hemorrhage than gestational age. Conversely, gestational age better predicted intraventricular hemorrhage than did birthweight. Risk factors for neonatal germinal matrix hemorrhage and intraventricular hemorrhage were dissimilar. A history of heavy (> 10 cigarettes/day) maternal smoking on admission increased the risk of germinal matrix hemorrhage three-fold (odds ratio = 3.35; 95% C.I. 1.24-9.07). Antenatal corticosteroid use reduced the risk of intraventricular hemorrhage by 76% (odds ratio = 0.24; 95% C.I. 0.09-0.61). Among patients with spontaneous preterm delivery or premature rupture of fetal membranes, the presence of labor was a significant effect modifier of the gestational-age associated risk of germinal matrix hemorrhage-intraventricular hemorrhage. CONCLUSIONS: Risk factors for neonatal germinal matrix hemorrhage are different from those for intraventricular hemorrhage. Most antenatal factors, especially those affecting fetal maturity, could influence the progression rather than the onset of intracranial hemorrhage.

Adult↗