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Cyclosporin "immune mediated"

Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
Jianyu Zhu, Degang Yang, Chao Shi, Zhichun Jing
AbstractErythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months...
June 2017: American Journal of Tropical Medicine and Hygiene
Franco Locatelli, Maria Ester Bernardo, Alice Bertaina, Carla Rognoni, Patrizia Comoli, Attilio Rovelli, Andrea Pession, Franca Fagioli, Claudio Favre, Edoardo Lanino, Giovanna Giorgiani, Pietro Merli, Daria Pagliara, Arcangelo Prete, Marco Zecca
BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci...
August 2017: Lancet Oncology
L Brambilla, A Tourlaki, G Genovese
AIMS: Kaposi's sarcoma (KS) is a lymphoangioproliferative multicentric disorder. Among its four distinct clinical variants, iatrogenic KS (iKS) typically affects patients who have received immunosuppressant regimens for organ transplants, proliferative disorders, or immune-mediated diseases. The aim of the current study was to examine the characteristics of a cohort of patients with iKS, evaluating the differences in terms of epidemiological and clinical features, management and outcomes between organ transplant recipients (OTR) and patients immunosuppressed for other medical conditions...
June 10, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
Serpil Pirmit, Nahide Onsun, Ozlem Su, Dilek B Ozkaya
BACKGROUND: Psoriasis is a chronic immune-mediated disease and treatment of psoriasis includes conventional immunosuppressive agents and biological agents. There are a few data on the relationship between psoriasis and melanocytic lesions. Either benign or malignant proliferations may be seen with immunosuppressive treatment. Eruptive nevi and malignant melanoma (MM) have been reported also associated with biological agents There is raising link biological treatment and malignancies. The objective of this paper is to examine the effects of biological agents versus conventional drugs on melanocytic nevi count and dermoscopical features...
April 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
F O Cummings, S A Rizzo
OBJECTIVES: The objective of this study was to compare hospitalisation duration, survival times, adverse events and cost of therapy in dogs with presumptive primary immune-mediated thrombocytopenia undergoing therapy with mycophenolate mofetil and corticosteroids versus cyclosporine and corticosteroids. METHODS: A retrospective study of medical case records of dogs with presumed primary immune-mediated thrombocytopenia was conducted. Data collected included signalment, presenting complaints, haematologic and biochemical profiles, vector-borne disease testing, thoracic and abdominal radiographs, abdominal ultrasound, medications administered, duration of hospitalisation, 30- and 60-day survival, adverse events and cost of therapy...
February 2017: Journal of Small Animal Practice
Frank H Zhu, Jocelyn Y Ang
Kawasaki disease is an acute, self-limited vasculitis of childhood and has become the leading cause of acquired pediatric heart disease in the USA. Prompt treatment is essential in reducing cardiac-related morbidity and mortality. The underlying etiology remains unknown. The disease itself may be the characteristic manifestation of a common pathway of immune-mediated vascular inflammation in susceptible hosts. The characteristic clinical features of fever for at least 5 days with bilateral nonpurulent conjunctivitis, rash, changes in lips and oral cavity, changes in peripheral extremities, and cervical lymphadenopathy remain the mainstay of diagnosis...
September 2016: Current Infectious Disease Reports
G H Wabnitz, E Balta, S Schindler, H Kirchgessner, B Jahraus, S Meuer, Y Samstag
Cytotoxic T-cells (CTLs) play an important role in many immune-mediated inflammatory diseases. Targeting cytotoxicity of CTLs would allow to interfere with immune-mediated tissue destruction. Here we demonstrate that WF-10, a pro-oxidative compound, inhibits CTL-mediated cytotoxicity. WF-10 did not influence early steps of target-cell killing, but impaired the ability of CTLs to detach from the initial target cell and to move to a second target cell. This reduced serial killing was accompanied by stronger enrichment of the adhesion molecule LFA-1 in the cytolytic immune synapse...
2016: Cell Death Discovery
Feng Liu, Ping Cai, Imir Metushi, Jinze Li, Tetsuya Nakayawa, Libia Vega, Jack Uetrecht
Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks...
September 2016: Journal of Immunotoxicology
Paolo Gisondi, Micol Del Giglio, Giampiero Girolomoni
Psoriasis is an immune-mediated inflammatory skin disease frequently associated with metabolic disorders, including diabetes, dyslipidaemia and metabolic syndrome. Moreover, a growing number of studies confirm the association between psoriasis and obesity. It has been found that obesity, as measured by body mass index >30 kg/m(2), can double the risk of incident psoriasis. A positive correlation between different measures of adiposity and the severity of psoriasis has also been reported. Epidemiologic studies have also provided robust evidence confirming the association between obesity and psoriatic arthritis...
December 2016: American Journal of Clinical Dermatology
A Scott, K Morris, J Butler, A K Mills, G A Kennedy
BACKGROUND: Aplastic anaemia (AA) is a rare acquired bone marrow failure syndrome resulting from the immune-mediated destruction of haemopoietic stem cells. For adults in whom first-line haemopoietic progenitor cell transplantation is not feasible, combination anti-thymocyte globulin (ATGAM) plus cyclosporine A is standard therapy; however, there are minimal data available regarding the optimal ATGAM dosage in terms of efficacy and survival. AIMS: Our institutions have historically used different dosing protocols of ATGAM in the treatment of AA...
October 2016: Internal Medicine Journal
Brian J Nankivell, Chow H PʼNg, Philip J OʼConnell, Jeremy R Chapman
BACKGROUND: The contribution of calcineurin inhibitors (CNI) nephrotoxicity to progressive kidney transplant injury remains debated, with little long-term data from the modern tacrolimus (TAC) era using lower doses. METHODS: This longitudinal cohort study evaluated histological evidence of CNI nephrotoxicity from normal donor kidneys of successful kidney-pancreas transplant recipients during cyclosporine (CSA) and TAC eras, analyzed by intention-to-treat. RESULTS: From 200 patients, 1622 adequate prospective protocol (84...
August 2016: Transplantation
Zümrüt Uysal, Mehmet Ertem, Dilber Talia İleri, Figen Doğu, Fatih Mehmet Azık, Aydan İkincioğulları, Sevgi Gözdaşoğlu
Autoimmune lymphoproliferative syndrome (ALPS) is a rare childhood disorder characterized by chronic non-malignant lymphoproliferation and autoimmunity. Patients with ALPS frequently exhibit episodic and intermittent, severe autoimmune- induced hemolytic anemia, thrombocytopenia or combined cytopenias. The co-occurrence of immune-mediated cytopenias, autoimmune thrombocytopenia and autoimmune hemolytic anemia is also known as Evans syndrome. This report describes a child who presented with Evans syndrome symptoms and who, after the detection of increased percentage of double negative T cell population in the peripheral blood, was diagnosed as ALPS...
June 5, 2007: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Seung Woon Park, Soon Ho Um, Han Ah Lee, Sang Hyun Kim, Yura Sim, Sun Young Yim, Yeon Seok Seo, Ho Sang Ryu
Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored...
June 2016: Clinical and Molecular Hepatology
Brian Camilleri, Julie M Bridson, Ahmed Halawa
The introduction of the calcineurin inhibitors cyclosporine and tacrolimus in the immunosuppressive regimens for kidney transplant has been associated with substantial reductions in the incidence of acute rejection, with a subsequent improvement in 1-year graft survival. However, this has not directly correlated with improvements in long-term allograft survival. Immunosuppressive medications are associated with toxicities related directly to immunosuppressive effects, and these are similar among different agents...
October 2016: Experimental and Clinical Transplantation
Justin W Garyu, Eric Meffre, Chris Cotsapas, Kevan C Herold
It has been more than 30 years since the initial trials of Cyclosporin A to treat patients with new onset Type 1 diabetes (T1D). Since that time, there have been insights into genetic predisposition to the disease, the failures of immune tolerance, and mechanisms that cause the immune mediated β cell destruction. The genetic loci associated affect lymphocyte development and tolerance mechanisms. Discoveries related to the roles of specific immune responses gene such as the major histocompatibility complex, PTPN22, CTLA-4, IL-2RA, as well as the mechanisms of antigen presentation in the thymus have suggested ways in which autoreactivity may follow changes in the functions of these genes that are associated with risk...
July 2016: Journal of Autoimmunity
G Barsotti, T Vezzosi
A 6-year-old, intact, male English cocker spaniel was referred for treatment of chronic conjunctivitis and unilateral keratitis. The dog was diagnosed with bilateral immune-mediated keratoconjunctivitis sicca, treated with topical cyclosporine 0·2% ointment and sodium hyaluronate eye drops and improved considerably. After 2 months, pulmonic stenosis was diagnosed, and the dog commenced treatment with oral atenolol; the ophthalmological disease worsened dramatically within a few days. The ophthalmic signs rapidly improved after discontinuation of atenolol, and there was bilateral complete remission after 3 weeks...
July 2016: Journal of Small Animal Practice
Fabio Timeus, Nicoletta Crescenzio, Luiselda Foglia, Alessandra Doria, Paola Saracco
Paroxysmal nocturnal haemoglobinuria (PNH) is very rare in children. The review of the literature shows some peculiarities of paediatric age: high incidence of bone marrow failure at diagnosis, dark urines uncommon, diagnosis often delayed. The thrombosis incidence is variable in the different reports, but in general lower than in adults. The presence of glycosil phosphatidyl-inositol (GPI)-negative populations in acquired aplastic anaemia (AA) at diagnosis has been correlated with a favourable response to immune-suppressive therapy (IST) in adults, whereas the literature data in children are discordant...
April 1, 2016: Current Drug Targets
Shonda A Foster, Baojin Zhu, Jiaying Guo, Enkeleida Nikai, Clement Ojeh, William Malatestinic, Orin Goldblum, Lori J Kornberg, Jashin J Wu
BACKGROUND: Psoriasis is a chronic, incurable, and immune-mediated skin disorder that is characterized by erythematous scaly papules and plaques. Understanding of psoriasis at the molecular level has led to the development of biologic agents that target disease-specific inflammatory mediators in psoriatic lesions. Biologic agents have become important components of the psoriasis armamentarium, but some patients become refractory to these agents over time or fail to respond to subsequent biologics...
April 2016: Journal of Managed Care & Specialty Pharmacy
Jie Zhang, Kan He, Lining Cai, Yu-Chuan Chen, Yifan Yang, Qin Shi, Thomas F Woolf, Weigong Ge, Lei Guo, Jürgen Borlak, Weida Tong
Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium...
August 5, 2016: Chemico-biological Interactions
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