To determine the temporal effect of ractopamine (Rac), a phenethanolamine, on adipose lipogenic enzyme activity and gene expression, 20 crossbred barrows were fed Rac (20 mg/kg of diet) for 0, 1, 8, or 24 d before slaughter (105 +/- 1 kg). Ractopamine had no effect (P > .05) on the activity of acetyl-coenzyme A carboxylase or malic enzyme in either the middle or outer layers of subcutaneous adipose tissue. Similarly, mRNA abundance for acetyl-coenzyme A carboxylase and the glucose transport proteins Glut 1 and Glut 4 were not affected by Rac in either adipose depot. Despite the inability of Rac to affect adipose tissue metabolism, Rac increased nitrogen retention, longissimus muscle area, and alpha-actin gene expression in skeletal muscle. Results indicate that Rac was not a functional beta-adrenergic agonist toward adipose tissue in this study. We suggest that the response to Rac in adipose tissue is masked by a combination of factors including tissue insensitivity, Rac-dose limitation, inherent partial agonism of Rac, and beta-adrenoceptor down-regulation.
Summary:Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti-CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full-donor chimerism. The incidence of acute II-IV GVHD was 11% in the CD25 group vs 33% in the control group (P ¼ 0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease-free survival at 2 years was 53% with a median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.
Summary:Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versusgraft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 g/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34 + and CFU-GM cells, reduced total lymphocytes and reversed the CD4 + /CD8 + ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 ؎ 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.