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Carlos Walter Sobrado, Lucas Faraco Sobrado
Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches...
July 2016: Arquivos Brasileiros de Cirurgia Digestiva: ABCD, Brazilian Archives of Digestive Surgery
Xiao-Sheng Zhang, Hong-Dou Luo, Yang Tao, Yue-Yue Wang, Xin-Hang Jiang, Hui Jiang, Yong-Quan Li
FK506 (tacrolimus), which is produced by many Streptomyces strains, is clinically used as an immunosuppressive agent and for treatment of inflammatory skin diseases. Here, we identified that the FK506 biosynthetic gene cluster in an industrial FK506-producing strain Streptomyces tsukubaensis L19 is organized as eight transcription units. Two pathway-specific regulators, FkbN and Tcs7, involved in FK506 biosynthesis from S. tsukubaensis L19 were characterized in vivo and in vitro. FkbN activates the transcription of six transcription units in FK506 biosynthetic gene cluster, and Tcs7 activates the transcription of fkbN...
October 18, 2016: Journal of Industrial Microbiology & Biotechnology
Felix Krenzien, Markus Quante, Timm Heinbokel, Midas Seyda, Koichiro Minami, Hirohito Uehara, Hector Rodriguez Cetina Biefer, Jeroen M Schuitenmaker, Steven Gabardi, Katrin Splith, Moritz Schmelzle, Athena K Petrides, Haruhito Azuma, Johann Pratschke, Xian C Li, Abdallah ElKhal, Stefan G Tullius
Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor Tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T-cells. Old recipient mice exhibited prolonged skin graft survival when compared to young animals following TAC administration. More importantly, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce pro-inflammatory IFN-γ cytokine production and promote IL-10 production in old CD4(+) T-cells...
October 18, 2016: American Journal of Transplantation
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 post-kidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On days 0-27, patients received prolonged-release tacrolimus (initially 0.2mg/kg/day), corticosteroids and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose-reduction on Day 42) plus sirolimus (Arm 2)...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Paula Schaiquevich, Paula Taich, Natalia Riva, Francisco Leone, Nora Paternoster, Gabriel Mato, Paulo Cáceres Guido
Objective Determine the status of analytical laboratories that quantify immunosuppressants in transplant patients who are under therapeutic drug monitoring (TDM) for these drugs in Argentina in order to identify potential perfectible areas for action. Methods A survey of the clinical and analytical TDM centers in Argentina was conducted between September 2013 and November 2014 under the direction of the Garrahan Hospital Clinical Pharmacokinetics Unit and the National Unified Central Institute for Ablation and Implant Coordination...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Jiang-Tao Tang, Brenda C de Winter, Dennis A Hesselink, Ferdi Sombogaard, Lan-Lan Wang, Teun van Gelder
AIM: Elderly transplant recipients have a lower incidence of acute rejection, and a higher risk to die from infectious complications. Potentially this may be caused by differences in the pharmacokinetics (PK) or pharmacodynamics (PD) of the immunosuppressive drugs they are taking. This study was designed to comprehensively evaluate the influence of age on the PK and PD of mycophenolic acid (MPA). METHODS: In this study the PK and PD of MPA was studied in 26 elderly and 54 younger renal transplant recipients treated with mycophenolate mofetil and tacrolimus...
October 18, 2016: British Journal of Clinical Pharmacology
Lucy Chen, Lisa Liberatore, Tom Chin, Scott Walker, Helen Fanous, Michelle M Nash, Lindita Rapi, Jennie Huckle, Jeffrey S Zaltzman, G V Ramesh Prasad
BACKGROUND: Ensuring reliable gastrointestinal drug absorption of orally-administered immunosuppressive medications posttransplant is critical to ensuring graft survival. METHODS: A 66 year old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy. The Gastrointestinal Quality of Life Index and Gastrointestinal Rating Scale questionnaires were administered to gauge immunosuppressive medication-related side effects in the absence of a stomach...
September 29, 2016: Transplantation
Frane Banovic, Keith E Linder, Maarja Uri, Michael A Rossi, Thierry Olivry
BACKGROUND: Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized. HYPOTHESIS/OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, histopathology and immunological findings of 10 dogs with GDLE. METHODS: Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recurrent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich interface dermatitis)...
October 16, 2016: Veterinary Dermatology
Gorden Muduma, Isaac Odeyemi, Richard Fulton Pollock
BACKGROUND: As of 2014, there were approximately 8300 patients with a functioning liver transplant in the UK Transplant Registry, with 880 liver transplants performed in 2013-2014 alone. Tacrolimus, typically used in combination with steroids and mycophenolate mofetil, currently represents the cornerstone of post-transplant immunosuppression in liver transplant recipients. OBJECTIVES: The objective of the present study was to evaluate the cost-effectiveness of prolonged-release (PR) tacrolimus (Advagraf(®), Astellas Pharma Inc...
March 2016: Drugs—Real World Outcomes
Zhuo Wu, Qinxia Xu, Xiaoyan Qiu, Zheng Jiao, Ming Zhang, Mingkang Zhong
PURPOSE: The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. METHODS: Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis...
October 17, 2016: European Journal of Clinical Pharmacology
Sharon Seth, David A Khan
BACKGROUND: Patients who have failed traditional treatment of chronic urticaria may require trials of alternative medications. Safety profiles, continuous laboratory monitoring, and physician comfort are often barriers to treatment. OBJECTIVES: To evaluate the safety of alternative agents used in chronic urticaria. METHODS: A retrospective chart review of electronic medical records from a single-center allergy and immunology clinic in a major academic hospital was conducted...
October 13, 2016: Journal of Allergy and Clinical Immunology in Practice
Yihung Huang, Evan Farkash
As both T cell and antibody-mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody-mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy...
September 2016: Advances in Chronic Kidney Disease
M Gastaca, I Bilbao, M Jimenez, J Bustamante, C Dopazo, R Gonzalez, R Charco, J Santoyo, J Ortiz de Urbina
Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2...
September 2016: Transplantation Proceedings
M Pereira, J Guerra, J Gonçalves, A Santana, C Nascimento, A G da Costa
Hyperacute rejection (HAR) is a rare event that can be prevented by crossmatch tests that detect anti-human leukocyte antigen antibodies against the donor. We present the case of a 43-year-old man who underwent a deceased-donor kidney transplantation with a negative complement-dependent cytotoxicity and a negative flow cytometry crossmatch. Luminex technology detected anti-DQ donor-specific antibodies (DSA) with a mean fluorescence intensity of 11,000. A single plasmapheresis session was carried out, followed by immunosuppression with immunoglobulin, antithymocyte globulin, tacrolimus, and methylprednisolone...
September 2016: Transplantation Proceedings
I Laranjinha, P Matias, C Jorge, R Birne, A Weigert, T Adragão, M Bruges, R A Cabrera, J Cassis, S Ramos, A Nogueira, J Godinho, H Messias, D Machado
BACKGROUND: Kidney transplant (KT) recipients have a higher incidence of malignancy than the general population. Smooth muscle tumors (SMT), including leiomyosarcoma, are rare in kidney transplant recipients, and most cases are associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 57-year-old man received a deceased donor kidney transplant at the age of 53 years, with 5 human leukocyte antigen (HLA) mismatches. Before the transplantation, the patient was IgG positive for EBV viral capsid antigen (VCA), negative for IgM EBV VCA, and also negative for IgG EBV nuclear antigen (EBNA), suggesting a prior EBV infection...
September 2016: Transplantation Proceedings
P Barreto, J Malheiro, P Vieira, S Pedroso, M Almeida, L S Martins, L Dias, A C Henriques, A Cabrita
INTRODUCTION: Immunosuppression has a pivotal role in kidney transplantation. The new prolonged-release formulation of tacrolimus was developed to provide a more convenient once-daily dosing to improve patient adherence. METHODS: We selected 60 stable kidney transplant recipients who underwent tacrolimus conversion in our unit. Conversion was made on a 1 mg:1 mg basis in 66.7% of patients (n = 40) and on a 1 mg:1.1 mg basis in the remaining 33.3% (n = 20). Clinical and analytical data at conversion and postconversion was analyzed retrospectively to evaluate the efficacy and safety of conversion from tacrolimus twice-daily to once-daily formulation...
September 2016: Transplantation Proceedings
R N Makroo, Soma Agrawal, Mohit Chowdhry, Brinda Kakkar, Uday K Thakur
BACKGROUND: Liver transplantation is one of the solid organs most commonly being transplanted across the world. The indications, affordability and accessibility have grown manifold. To increase the donor pool, inclusion of ABO incompatible liver donors is being considered. To enhance the graft functioning and survival, immunoadsorption apheresis to reduce the ABO hemagglutination titres are on the rise. CASE REPORT: We report three cases ABO incompatible liver transplantation with immunoadsorption protocol...
September 28, 2016: Transfusion and Apheresis Science
Anton M Kolomeyer, Ken K Nischal, Ellen Mitchell
PURPOSE: To report a case of bilateral cavernous sinus thrombosis (CST) in a patient with tacrolimus-associated posttransplant thrombotic microangiopathy. METHODS: Case report. RESULTS: An 8-year-old boy with a medical history of orthotopic heart transplant, posttransplant lymphoproliferative disease, and recurrent infections was hospitalized for nausea, vomiting, and diarrhea. His ocular history included accommodative esotropia, hyperopia with astigmatism, Molluscum contagiosum lid lesions, and idiopathic intracranial hypertension...
October 13, 2016: European Journal of Ophthalmology
A Mercuri, S Wu, S Stranzinger, S Mohr, S Salar-Behzadi, M Bresciani, E Fröhlich
This work aims to better understand the in vivo behaviour of modified release (MR) formulations (Envarsus(®) tablets and Advagraf(®) capsules) using in vitro properties of tacrolimus and in silico simulations. The in silico concentration profiles of tacrolimus released from the MR formulations were predicted after building a three compartments PK model with GastroPlus™, and using the experimentally determined in vitro physico-chemical properties as input parameters. In vitro-in vivo correlations (IVIVC) were obtained after deconvolution of in vivo data from a clinical trial...
October 11, 2016: International Journal of Pharmaceutics
Huimin Wu, Kaiyuan Wang, Hanning Wang, Fang Chen, Wencong Huang, Yuqi Chen, Jiali Chen, Jin Tao, Xiaoguang Wen, Subin Xiong
The aim was to explore the potential application of novel self-assembled nanoparticles cross-linking thermosensitive hydrogels composed of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and tacrolimus (FK-506) for local therapy of rheumatoid arthritis (RA). The sol-gel transition temperature (Tsol-gel), gelation time, rheological behaviors, in vitro release, in vivo gelation and retention, and therapeutic efficacy against adjuvant-induced arthritis (AIA) rats were compared between the Soluplus hydrogels and widely studied poloxamer 407 (P407) delivery systems...
October 6, 2016: Colloids and Surfaces. B, Biointerfaces
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