Gastric Bypass Surgery Improves the Skeletal Muscle Ceramide/S1P Ratio and Upregulates the AMPK/ SIRT1/ PGC-1α Pathway in Zucker Diabetic Fatty Rats.

Purpose: Roux-en-Y gastric bypass (RYGB) is associated with remission of type 2 diabetes. However, the cellular and molecular mechanisms remain unknown. We hypothesized that RYGB would increase peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (SIRT1), AMPK/pAMPK, and citrate synthase (CS) protein expression and decrease insulin resistance and these changes would be mediated by sphingolipids, including ceramides and the sphingolipid metabolite sphingosine-1 phosphate (S1P).

Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Pancreatic Islets from Zucker Diabetic Fatty Rats.

Purpose: Diabetes and obesity are associated with inflammasome-mediated low-grade, chronic inflammation that may induce pancreatic beta-cell dysfunction and apoptosis. We examined the effects of Roux-en-Y gastric bypass (RYGB) surgery on NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome-related genes from pancreatic islets of Zucker diabetic fatty rats.

Materials And Methods: Islets were collected from Zucker diabetic fatty sham control and RYGB, 30 days after surgery.

Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue from Obese Rats.

Objective: Obesity is associated with low-grade chronic inflammation. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery would reduce activation of the NLRP3 inflammasome in metabolically active adipose tissue (AT) of obese rats, and this change would be related to decreases in body weight and improved glycemic control.

Methods: Omental, mesenteric and subcutaneous fat depots were collected from Sprague-Dawley rats: Sham control and RYGB; 90-days after surgery.

Gastrostomy tube placement in gastric remnant at gastric bypass: a rat model for selective gut stimulation.

Background: Roux-en-Y gastric bypass (RYGB) surgery achieves high remission rates of type 2 diabetes mellitus in obese diabetic patients. It has been hypothesized that the changes in bowel nutrient exposure after RYGB results in altered release of gut hormones and improved glucose homeostasis. Our objective was to assess the feasibility of, and report on, our technique and initial experience with selective gut stimulation in a gastric bypass rat model at an academic medical center in the United States.

Ten-month laryngeal allograft survival with use of pulsed everolimus and anti-alphabeta T-cell receptor antibody immunosuppression.

Objectives: The risks of daily immunosuppression limit the use of laryngeal transplantation as a reconstructive option. Pulsed immunosuppressive dosing can lessen these risks. The study objective was to develop a long-term pulsing regimen that minimizes exposure to immunosuppressive agents.

Long-term laryngeal allograft survival using low-dose everolimus.

Objective: The purpose of this study was to explore the mechanism and utility of everolimus as a single-agent therapy in preventing mouse laryngeal allograft rejection.

Study Design: Prospective animal study.

Setting: Academic research at a tertiary medical center.

Decoy NF-kappaB fortified immature dendritic cells maintain laryngeal allograft integrity and provide enhancement of regulatory T cells.

Objectives/hypothesis: The increased risk of malignancy associated with post-transplant immunosuppression limits the potential of laryngeal transplantation as a reconstructive option. This risk may be mitigated by utilizing decoy nuclear factor kappa B (NF-kappaB) immature dendritic cells (iDC) to provide donor-specific tolerance. The purpose of this study was to explore whether tolerogenic properties of iDC can be applied to composite tissue transplantation.

A new mouse laryngeal transplantation rejection grading system.

Objectives/hypothesis: Development of a rat laryngeal transplantation model allowed for the first total human laryngeal transplantation by the senior author in 1998. In an effort to further our knowledge of the immune system's role in laryngeal rejection, a change to the mouse model was required. Prior to initiating immunosuppressive research protocols, a reliable mouse larynx rejection classification had to be established.

New mouse model for studying laryngeal transplantation.

Objectives: Laryngeal transplantation research has been studied in various animal models. For in-depth, immunology-based transplantation research, however, a thoroughly studied animal model must exist. The purpose of this study was to develop a reliable surgical technique in mice to serve as a model for further study of laryngeal transplantation.

Induction with T-cell receptor antibody leads to long-term laryngeal allograft function.

Purpose: The use of induction therapy with alphabeta T-cell receptor (alphabetaTCR) monoclonal antibody in association with tacrolimus in an allogeneic rat laryngeal transplant model permits rigorous long-term evaluation of potential short-term synergism offered by these agents.

Materials And Methods: The allogeneic model consisted of 19 Brown Norway larynges transplanted to Lewis recipients. Treatment consisted of tacrolimus (1.

Laryngeal transplantation in the setting of cancer: a rat model.

Objective: Traditional immunosuppressive regimens make laryngeal transplantation in cancer patients prohibitive because of the increased risk of recurrence. Everolimus, a recently developed immunosuppressant, has demonstrated significant antitumor properties. The purpose of this study was to examine the effects of everolimus alone and in combination with other immunosuppressants on tumor growth in a combined laryngeal transplantation and tumor model.

Donor bone marrow in laryngeal transplantation: results of a rat study.

Introduction: The concept of donor bone marrow transplantation has been successfully used in human solid organ transplantation to increase recipient chimerism. The development of recipient chimerism is associated with a decreased need for immunosuppression and even donor-specific tolerance. In this study, we attempted to augment recipient chimerism by the transfer of donor bone marrow at the time of rat laryngeal transplant.

Quantitative analysis of OX62-positive dendritic cell distribution in the rat laryngeal complex.

Objectives: Dendritic cells (DCs) are key instigators of rejection after transplantation. Their distribution has not been systematically characterized in all locations of the larynx and its surrounding tissues.

Methods: Rat larynges were stained with monoclonal antibodies identifying DCs.

Postallograft donor and recipient dendritic cell trafficking in the rat larynx.

Objectives/hypothesis: Dendritic cells (DC) are potent antigen-presenting cells that instigate allograft rejection. Their migration kinetics vary depending on the type of organ transplanted. The timing of donor and recipient DC trafficking in laryngeal transplants is unknown.

Pulsed immunosuppression with everolimus and anti-alphabeta T-cell receptor: laryngeal allograft preservation at six months.

Objectives: Laryngeal transplantation can restore the voice in patients who have undergone laryngectomy. However, the prospect of lifelong immunosuppression is a drawback to this procedure. We present data from a study aimed at minimizing the need for immunosuppression while maintaining graft viability through a novel pulsed-dosing protocol.

The effect of donor-specific transfusion upon rejection in a rat model of laryngeal transplantation.

Lifelong immunosuppression carries significant morbidity, and techniques to reduce or eliminate such immunosuppression might expand laryngeal transplantation. This study investigates the ability of donor-specific transfusion to establish tolerance in a rat model of laryngeal transplantation. A total of 289 transplants were performed from Lewis-Brown-Norway donors to Lewis recipients.

Direct revascularization is superior for rat parathyroid allotransplantation with FK506.

Parathyroid gland allotransplantation has been a challenging goal for decades. Our objective was to optimize a parathyroid allotransplantation model for analysis of short-term or low-dose immunosuppressive regimens. Rats that had undergone parathyroidectomy received parathyroid allografts either by direct microvascular anastomoses as part of a composite laryngotracheal graft or by direct implantation into hind limb muscle.

Induction of tolerance in a rat model of laryngeal transplantation.

Background: The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression.

Materials And Methods: Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients.

Evaluation of parathyroid hormone as a functional biological marker of rat laryngeal transplant rejection.

Objectives/hypothesis: Short-term immunosuppressive protocols in a preclinical rat model that have led to prolonged survival of the graft in preliminary trials were investigated. Rat allografts, by their heterotopic nature, do not allow direct examination or functional interpretation. The primary objective of the study was to identify a reliable functional biological marker allowing monitoring of graft status.

Immunosuppressive effect of irradiation in the murine laryngeal transplantation model: a controlled trial.

Since the first successful human laryngeal transplantation in 1998, research continues toward developing less-morbid immunosuppressive protocols. Although irradiation of donor organs is known to decrease acute rejection, the most advantageous method of radiation delivery is still unknown. Using a rat laryngeal transplant model, we sought to determine the most beneficial timing and delivery method of irradiation.

Tacrolimus and mycophenolate mofetil provide effective immunosuppression in rat laryngeal transplantation.

Objectives/hypothesis: Tacrolimus is efficacious in several transplantation settings. Some studies have demonstrated improved results using combination therapy with mycophenolate mofetil. Our primary objective was to evaluate the efficacy and optimal dosing of tacrolimus in preventing rejection, using an established rat model of laryngeal transplantation.

Cyclosporine dose, serum trough levels, and allograft preservation in a rat model of laryngeal transplantation.

Using a rat model of laryngeal transplantation, we sought to define the relationships between acute laryngeal rejection grade (RG) and cyclosporin A (CSA) concentration and CSA dosage. Five recipient Lewis rat groups (N = 10 per group) were administered intramuscular CSA doses of 1.0 (group 1), 2.

Rat laryngeal transplant model: technical advancements and a redefined rejection grading system.

The rat laryngeal transplant model, introduced in 1992, laid the basic science foundation that contributed to the first successful human larynx transplant in 1998. Over 1,500 rat transplants later, numerous modifications have improved the model, increasing the initially reported evaluability rate of 50% to almost 100%. The observed histologic rejection process has been altered, as well.

Effects of adding steroids, in vitro irradiation, or both to cyclosporine immunosuppression in the murine laryngeal transplantation model.

Adding oral prednisone or in vitro organ irradiation to an immunosuppressive regimen for laryngeal transplantation may allow cyclosporine dosage to be decreased without compromising organ rejection rates. Using an established rat laryngeal transplant model, we sought to determine whether combined immunosuppressive regimens decreased rejection rates. Twenty-two treatment groups of 10 animals each were studied.