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Sample records for subjects starting immunosuppressive

  1. Management of HBV Infection During Immunosuppressive Treatment

    OpenAIRE

    Marzano, Alfredo

    2009-01-01

    The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), b) the treatment with antivirals (therapy) of active carriers, c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if...

  2. Immunosuppression in Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Tian Rong; Kuang Anren; Qin Weishi; Zhang Huimin

    2000-01-01

    Objective: Graves' ophthalmopathy (GO) is a disease that seriously threatens the health of patients. But up to now, no optimal therapies have been established. Immunosuppressive treatment is usually used in the management of GO, but they may cause side effects. Recently, 99 Tc-MDP, commercially named 'Yun Ke', is used in the management of autoimmune disease. Therefore, a randomized trial was done to compare the values in the treatment of GO with between Yun Ke and immunosuppression. Methods: 42 consecutive patients with moderate or severe GO were randomly assigned to receive either Yun Ke therapy or immunosuppressive therapy. The degree of ocular involvement and responses to the treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Therapy outcome was assessed 4 months after the start of treatment by the change in the highest NOSPECS class and OI. Data analysis was performed with the SPASS statistic software. Chi-square test was used to compare percentages, logistic regression was performed to identify which variables might correlated with the treatment outcome. Results: The remarkably effective outcome was observed in 14 (67%) cases in immunosuppression treated group and 13 (62%) cases in Yun Ke treated group. There were no significant differences in the degree of improvements in ocular involvements. There was a marked decrease of thyroid antibody titres in both groups. The variables found to correlated significantly with treatment outcome were thyroid antibody titres and GO activity. Side effects were more frequent and severe during immunosuppressive therapy. No side effects were found during Yun Ke treatment. Conclusion: Yun Ke and immunosuppression appeared to be equally effective in the management of GO, but Yun Ke is safer for patients during treatment

  3. Immunosuppressive drugs and fertility.

    Science.gov (United States)

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-10-21

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.

  4. New Immunosuppressive Therapies in Uveitis Treatment

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    Salvador Mérida

    2015-08-01

    Full Text Available Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines.

  5. New Immunosuppressive Therapies in Uveitis Treatment

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    Mérida, Salvador; Palacios, Elena; Navea, Amparo; Bosch-Morell, Francisco

    2015-01-01

    Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines. PMID:26270662

  6. Nanoparticles and direct immunosuppression

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    Ngobili, Terrika A

    2016-01-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  7. Immunosuppressive strategies and management

    Institute of Scientific and Technical Information of China (English)

    Shi-hui PAN

    2008-01-01

    Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival.However,chronic allograft failure,antibody mediated rejection,recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life.New immunosuppressive agents and protocols are being evaluated to combat these problems.Importantly,clinicians must work to manage post-transplant complications and avoid complex medication regimens,which will potentiate drug interactions and non.compliance.Different organs have different immunogenicities and each recipient has a unique clinical and immunologic profile.The clinician must recognize these variations and customize the immunosuppressive regimens and treatment protocols based on the individual condition.The general principles of an individualized immunosuppressive protocol should take the following factors into account:organ type,donor and recipient characteristics,quality of the donor organ,recipienVs medical history,recipient's undedying disease,immunologic risk for acute rejection,potential co-morbidity related to immunosuppression,significant druginteractions,medication costs and patient compliance.In addition,the combination of immunosuppressive drugs must have a pharmacologic rationale to achieve the desired goal of suppressing the individual's immune system to render the patient tolerant to the allograft while minimizing co-morbidities.For the past few years,many clinical strategies have been applied in an attempt to improve graft survival or to reduce immunsuppressants induced side-effects.Specific protocols include steroid or CNI avoidance,minimization or withdraw,desensitization,and treatment for antibody mediated rejection,disease specific,and pediatric specific.The short-term outcomes from these different strategies are promising but the long-term results remain to be determined.Unfortunately,current immunosuppressive agents or strategies

  8. Immunosuppressive agents are associated with peptic ulcer bleeding.

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    Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2017-05-01

    Peptic ulcer bleeding can be fatal. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and immunosuppressive agents are administered for long-term usage. The present study assessed the association between peptic ulcer bleeding and administration of NSAIDs, corticosteroids and immunosuppressive agents. Furthermore, the efficacy of lowering the risk of peptic ulcer bleeding with proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was evaluated. Medical records were retrospectively analyzed for patients subjected to an upper gastrointestinal (GI) endoscopy performed at the National Hospital Organization Shimoshizu Hospital (Yotsukaido, Japan) from October 2014 to September 2015. During this period, a total of 1,023 patients underwent an upper GI endoscopy. A total of 1,023 patients, including 431 males (age, 68.1±12.9 years) and 592 females (age, 66.4±12.3 years), who had been administered NSAIDs, corticosteroids, immunosuppressive agents, PPIs and H2RAs, were respectively enrolled. Endoscopic findings of the patients were reviewed and their data were statistically analyzed. Logistic regression analysis was used to determine the odds ratio of peptic ulcer bleeding for each medication; immunosuppressive agents had an odds ratio of 5.83, which was larger than that for NSAIDs (4.77). The Wald test was applied to confirm the correlation between immunosuppressive agents and peptic ulcer bleeding. Furthermore, χ 2 tests were applied to the correlation between peptic ulcer bleeding and administration of PPIs or H2RAs. Immunosuppressive agents had the largest χ 2 , and the P-value was 0.03. Administration of PPIs was significantly correlated with non-peptic ulcer bleeding (P=0.02); furthermore, a tendency toward non-peptic ulcer bleeding with administration of H2RA was indicated, but it was not statistically significant (P=0.12). In conclusion, immunosuppressive agents were correlated with peptic ulcer bleeding and PPIs were effective at

  9. Immunosuppressants

    Science.gov (United States)

    ... Brain Death HIV and Kidney Transplantation/Donation Incompatible Blood Types and Paired Exchange Programs Knowing Your Immunosuppressive (anti-rejection) Medications Organ and Tissue Donation The National Kidney ...

  10. AChR-specific immunosuppressive therapy of myasthenia gravis.

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    Luo, Jie; Lindstrom, Jon

    2015-10-15

    Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Pancreatic islet allograft in spleen with immunosuppression with cyclosporine. Experimental model in dogs.

    Science.gov (United States)

    Waisberg, Jaques; Neff, Charles Benjamin; Waisberg, Daniel Reis; Germini, Demetrius; Gonçalves, José Eduardo; Zanotto, Arnaldo; Speranzini, Manlio Basilio

    2011-01-01

    To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. In the animals with immunosuppression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.

  12. Psychosocial Variables Associated with Immunosuppressive Medication Non-Adherence after Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Jennifer Felicia Scheel

    2018-02-01

    Full Text Available IntroductionNon-adherence to immunosuppressive medication is regarded as an important factor for graft rejection and loss after successful renal transplantation. Yet, results on prevalence and relationship with psychosocial parameters are heterogeneous. The main aim of this study was to investigate the association of immunosuppressive medication non-adherence and psychosocial factors.MethodsIn 330 adult renal transplant recipients (≥12 months posttransplantation, health-related quality of life, depression, anxiety, social support, and subjective medication experiences were assessed, and their associations with patient-reported non-adherence was evaluated.Results33.6% of the patients admitted to be partially non-adherent. Non-adherence was associated with younger age, poorer social support, lower mental, but higher physical health-related quality of life. There was no association with depression and anxiety. However, high proportions of clinically relevant depression and anxiety symptoms were apparent in both adherent and non-adherent patients.ConclusionIn the posttransplant follow-up, kidney recipients with lower perceived social support, lower mental and higher physical health-related quality of life, and younger age can be regarded as a risk group for immunosuppressive medication non-adherence. In follow-up contacts with kidney transplant patients, physicians may pay attention to these factors. Furthermore, psychosocial interventions to optimize immunosuppressive medication adherence can be designed on the basis of this information, especially including subjectively perceived physical health-related quality of life and fostering social support seems to be of importance.

  13. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

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    James A. Bourgeois

    2014-01-01

    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  14. Clinical aspects of immunosuppression in poultry.

    Science.gov (United States)

    Hoerr, Frederic J

    2010-03-01

    Chickens, turkeys, and other poultry in a production environment can be exposed to stressors and infectious diseases that impair innate and acquired immunity, erode general health and welfare, and diminish genetic and nutritional potential for efficient production. Innate immunity can be affected by stressful physiologic events related to hatching and to environmental factors during the first week of life. Exposure to environmental ammonia, foodborne mycotoxins, and suboptimal nutrition can diminish innate immunity. Infectious bursal disease (IBD), chicken infectious anemia (CIA), and Marek's disease (MD) are major infectious diseases that increase susceptibility to viral, bacterial, and parasitic diseases and interfere with acquired vaccinal immunity. A shared feature is lymphocytolytic infection capable of suppressing both humoral and cell-mediated immune functions. Enteric viral infections can be accompanied by atrophic and depleted lymphoid organs, but the immunosuppressive features are modestly characterized. Some reoviruses cause atrophy of lymphoid organs and replicate in blood monocytes. Enteric parvoviruses of chickens and turkeys merit further study for immunosuppression. Hemorrhagic enteritis of turkeys has immunosuppressive features similar to IBD. Other virulent fowl adenoviruses have immunosuppressive capabilities. Newcastle disease can damage lymphoid tissues and macrophages. Avian pneumovirus infections impair the mucociliary functions of the upper respiratory tract and augment deeper bacterial infections. Recognition of immunosuppression involves detection of specific diseases using diagnostic tests such as serology, etiologic agent detection, and pathology. Broader measurements of immunosuppression by combined noninfectious and infectious causes have not found general application. Microarray technology to detect genetic expression of immunologic mediators and receptors offers potential advances but is currently at the developmental state. Control

  15. IL-10 is an effector molecule mediating urocanic acid-induced immunosuppression

    Czech Academy of Sciences Publication Activity Database

    Krulová, Magdalena; Kuffová, Lucia; Zajícová, Alena; Filipec, M.; Holáň, Vladimír

    1999-01-01

    Roč. 31, - (1999), s. 1218-1219 ISSN 0041-1345 R&D Projects: GA MZd IZ3964; GA ČR GA310/97/1261; GA MŠk VS97099 Keywords : immunosuppression, urocanic acid Subject RIV: EC - Immunology Impact factor: 0.590, year: 1999

  16. Fatal tick-borne encephalitis in an immunosuppressed 12-year-old patient

    Czech Academy of Sciences Publication Activity Database

    Chmelík, V.; Chrdle, A.; Růžek, Daniel

    2016-01-01

    Roč. 74, 1 January (2016), s. 73-74 ISSN 1386-6532 R&D Projects: GA ČR GAP502/11/2116 Institutional support: RVO:60077344 Keywords : Tick-borne encephalitis * immunosuppressed patient * fatal case * haemophagocytic lymphohistiocytosis Subject RIV: EE - Microbiology, Virology Impact factor: 3.051, year: 2016

  17. Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

    Science.gov (United States)

    Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

    2016-06-02

    To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under

  18. Immunosuppressive drugs and fertility

    OpenAIRE

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior ...

  19. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

    Science.gov (United States)

    Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

    2017-06-01

    Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

  20. Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?

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    Gajofatto, Alberto; Benedetti, Maria Donata

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies. PMID:26244148

  1. Induction immunosuppressive therapies in renal transplantation.

    Science.gov (United States)

    Gabardi, Steven; Martin, Spencer T; Roberts, Keri L; Grafals, Monica

    2011-02-01

    Induction immunosuppressive therapies for patients undergoing renal transplantation are reviewed. The goal of induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, particularly in patients at high risk for poor short-term outcomes. All of the induction immunosuppressive agents currently used are biological agents and are either monoclonal (muromonab-CD3, daclizumab, basiliximab, alemtuzumab) or polyclonal (antithymocyte globulin [equine] or antithymocyte globulin [rabbit]) antibodies. Although antithymocyte globulin (rabbit) is not labeled for induction therapy, it is used for this purpose more than any other agent. Basiliximab is not considered as potent an immunosuppressive agent but has a much more favorable adverse-effect profile compared with antithymocyte globulin (rabbit) and is most commonly used in patients at low risk for acute rejection. Rituximab is being studied for use as induction therapy but to date has not demonstrated any significant benefits over placebo. While head-to-head data are available comparing most induction agents, the final decision on the most appropriate induction therapy for a transplant recipient is highly dependent on preexisting medical conditions, donor characteristics, and the maintenance immunosuppressive regimen to be used. No standard induction immunosuppressive regimen exists for patients undergoing renal transplantation. Antithymocyte globulin (rabbit) is the most commonly used agent, whereas basiliximab appears safer. The choice of regimen depends on the preferences of clinicians and institutions.

  2. Immunomodulator, immunosuppression of radiation and immune reconstruction

    International Nuclear Information System (INIS)

    Mao Jianping; Fang Jing; Zhou Ying; Cui Yufang; Jiang Zhujun; Du Li; Ma Qiong

    2010-01-01

    There is a refined and complicated regulatory network between immune cells, and between immune cells and secretory factors. The immune system is kept in a homeostasis and equilibrium by positive activation and negative inhibition. In recent years, the mechanisms of immunosuppression in depth for successful allograft transplantation were studied, and many immunosuppressants and immunosuppressive drugs have been developed for clinical use. Most of them are targeting T cell receptors and three kinds of singnal pathways. The receptors of the immunosuppression were either found highly expressed in immune cells after irradiation. To relieve the suppression by regulating the receptors could help the immune reconstruction out of radiation damage. Many new immunoenhancers have been discovered to improve the immune system function for radiation by Toll-like receptors. The search for new immunoenhancers and agents for relieving immunosuppression is of great importance to immune construction for radiation sickness. (authors)

  3. Urinary Transforming Growth Factor-beta 1 as a marker of response to immunosuppressive treatment, in patients with crescentic nephritis

    Directory of Open Access Journals (Sweden)

    Sotsiou Florentia

    2005-12-01

    Full Text Available Abstract Background Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment. Methods Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA. TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange. Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. Results Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively. In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p 1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence

  4. Generic immunosuppression in transplantation: current evidence and controversial issues.

    Science.gov (United States)

    El Hajj, Sandra; Kim, Miae; Phillips, Karen; Gabardi, Steven

    2015-05-01

    The overall success of organ transplantation in the 21st century has been predicated, in part, on the use of newer, more potent, and selective immunosuppressive agents. However, the high cost of lifelong immunosuppression represents a financial burden for many patients. In the past 15 years, regulatory agencies in Europe and America have approved several generic immunosuppressants. One concern is whether the conversion between innovator and generic immunosuppressants will prove to be problematic. This manuscript aims to compare and contrast the bioequivalence requirements among regulatory authorities in the USA, Europe, and Canada, evaluate published studies of generic immunosuppressants in transplant recipients, summarize consensus statements made by transplant organizations and discuss how to engage patients in discussion regarding the choice between innovator and generic immunosuppressants.

  5. Current trends in immunosuppressive therapies for renal transplant recipients.

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    Lee, Ruth-Ann; Gabardi, Steven

    2012-11-15

    Current trends in immunosuppressive therapies for renal transplant recipients are reviewed. The common premise for immunosuppressive therapies in renal transplantation is to use multiple agents to work on different immunologic targets. The use of a multidrug regimen allows for pharmacologic activity at several key steps in the T-cell replication process and lower dosages of each individual agent, thereby producing fewer drug-related toxicities. In general, there are three stages of clinical immunosuppression: induction therapy, maintenance therapy, and treatment of an established acute rejection episode. Only immunosuppressive therapies used for maintenance therapy are discussed in detail in this review. The most common maintenance immunosuppressive agents can be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids. Immunosuppressive regimens vary among transplantation centers but most often include a CNI and an adjuvant agent, with or without corticosteroids. Selection of appropriate immunosuppressive regimens should be patient specific, taking into account the medications' pharmacologic properties, adverse-event profile, and potential drug-drug interactions, as well as the patient's preexisting diseases, risk of rejection, and medication regimen. Advancements in transplant immunosuppression have resulted in a significant reduction in acute cellular rejection and a modest increase in long-term patient and graft survival. Because the optimal immunosuppression regimen is still unknown, immunosuppressant use should be influenced by institutional preference and tailored to the immunologic risk of the patient and adverse-effect profile of the drug.

  6. Chlorphenesin: an antigen-associated immunosuppressant.

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    Whang, H Y; Neter, E

    1970-07-01

    Chlorphenesin (3-p-chlorophenoxy-1,2-propanediol), when injected intravenously together with either of two common bacterial antigens, inhibits the antibody response of the rabbit. The antigens studied are those common to Enterobacteriaceae and to gram-positive bacteria. The immunosuppression is contingent upon incubation of chlorphenesin and antigen in vitro prior to administration, since separate injection of antigen and inhibitor or of mixtures without prior incubation yields undiminished antibody response. Chlorphenesin, as shown by hemagglutination-inhibition tests, does not alter the antigenic determinants, because antibody neutralization occurs in the presence or absence of the drug. The immunosuppressive effect is reversible, since precipitation of chlorphenesin at 4 C substantially restores immunogenicity. Animals immunized with antigen-drug mixtures, which fail to respond with significant antibody production, nonetheless are immunologically primed. It is concluded that chlorphenesin represents another example of antigen-associated immunosuppressants.

  7. Immunosuppressive effects of sesquiterpene lactones from Laser trilobum (L.) Borkh

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Harmatha, Juraj; Vokáč, Karel; Kmoníčková, Eva

    2009-01-01

    Roč. 75, č. 9 (2009), s. 905-905 ISSN 0032-0943. [International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research /57./. 16.08.2009-20.08.2009, Geneva] R&D Projects: GA ČR GA305/07/0061 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50390512 Keywords : immunosuppressive effects * Laser trilobum Subject RIV: CC - Organic Chemistry

  8. Merkel Cell Carcinoma in Immunosuppressed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Janice E. [Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States); Brewer, Jerry D., E-mail: brewer.jerry@mayo.edu [Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States)

    2014-06-27

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients.

  9. Merkel Cell Carcinoma in Immunosuppressed Patients

    International Nuclear Information System (INIS)

    Ma, Janice E.; Brewer, Jerry D.

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients

  10. Oral candidiasis in immunosuppressed children and young adults after liver or kidney transplantation.

    Science.gov (United States)

    Olczak-Kowalczyk, Dorota; Pawłowska, Joanna; Garczewska, Barbara; Smirska, Ewa; Grenda, Ryszard; Syczewska, Małgorzata; Kowalczyk, Wojciech

    2010-01-01

    Candidiasis is an infectious complication in organ transplant recipients resulting from the patients' immunodeficiency and virulence of fungi pathogens. The purpose of this study was to evaluate the frequency of Candida spp. and identify their presence in the oral lesions of graft recipients. This study included 185 patients, 1.5 to 25.2 years of age (mean = 13.1 +/- 4.2 years) who were receiving combined immunosuppression treatment after kidney or liver transplantation and 70 control subjects. Evaluation included clinical oral examination, mycology, and statistical analysis. Candida spp. colonies were found in the oral mucosa of 63 (34%) graft recipients and in 19 (27%) control subjects. Candida albicans was the most prevalent species. This study showed that, regardless of the type of the organ transplant and immunosuppression, frequent, regular oral follow-up and mycologic tests are recommended. Diagnosing increased density of Candida spp. colonies in the oral cavity will help initiate early antifungal treatment. Candida spp. prevalence in the oral cavity in transplant recipients was higher than in immunocompetent control subjects. Kidney or liver transplantation predisposes one to the development of an increased density of Candida spp. colonies.

  11. Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors

    Directory of Open Access Journals (Sweden)

    Hyun Chul Lee

    2012-06-01

    Full Text Available Postrenal transplantation diabetes mellitus (PTDM, or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

  12. A Nonimmunosuppressant Approach on Asia Psoriasis Subjects: 5-Year Followup and 11-Year Data Analysis

    Directory of Open Access Journals (Sweden)

    Tony Yuqi Tang

    2012-01-01

    Full Text Available Mono- or combine immunosuppressants are commonly used for psoriasis; however the side effect caused by potent systemic immunosuppressants frequently incurred; moreover the inflammation flares up shortly after immunosuppressants are discontinued. An alternative nonimmunosuppressive therapy was introduced to psoriasis subjects. A retrospective observational study consisted of 1583 psoriasis patients who were treated with Herose Psoria capsule 1440 mg three times daily at two clinical centres, one in China, the other in Singapore, from 1 January 2000 to 1 January 2011. Psoriasis lesion evolution was photographed at monthly visit, and efficacy and safety were assessed using psoriasis area severity index PASI score grading, renal and liver function testing, and adverse event reporting and supplemented by information obtained during targeted telephone interviews. The effectiveness of Herose on psoriasis was inversely associated to prior immunosuppressants exposure (r=0.9154, significant improvements occurred in non-immunosuppressants subjects, and complete clearance was achieved in 8 months (87.5%, 14 of 16; the wavelike evolution of psoriatic lesion appeared in prior immunosuppressants subjects.

  13. Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

    Science.gov (United States)

    Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan

    2014-05-01

    To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

    Directory of Open Access Journals (Sweden)

    Viktor Fleming

    2018-03-01

    Full Text Available The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME, which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.

  15. Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

    2004-01-01

    A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...... indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case...

  16. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    Science.gov (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  17. Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis.

    Science.gov (United States)

    Cui, Xin; Morales, Renee-Tyler Tan; Qian, Weiyi; Wang, Haoyu; Gagner, Jean-Pierre; Dolgalev, Igor; Placantonakis, Dimitris; Zagzag, David; Cimmino, Luisa; Snuderl, Matija; Lam, Raymond H W; Chen, Weiqiang

    2018-04-01

    Glioblastoma (GBM) is the most lethal primary adult brain tumor and its pathology is hallmarked by distorted neovascularization, diffuse tumor-associated macrophage infiltration, and potent immunosuppression. Reconstituting organotypic tumor angiogenesis models with biomimetic cell heterogeneity and interactions, pro-/anti-inflammatory milieu and extracellular matrix (ECM) mechanics is critical for preclinical anti-angiogenic therapeutic screening. However, current in vitro systems do not accurately mirror in vivo human brain tumor microenvironment. Here, we engineered a three-dimensional (3D), microfluidic angiogenesis model with controllable and biomimetic immunosuppressive conditions, immune-vascular and cell-matrix interactions. We demonstrate in vitro, GL261 and CT-2A GBM-like tumors steer macrophage polarization towards a M2-like phenotype for fostering an immunosuppressive and proangiogenic niche, which is consistent with human brain tumors. We distinguished that GBM and M2-like immunosuppressive macrophages promote angiogenesis, while M1-like pro-inflammatory macrophages suppress angiogenesis, which we coin "inflammation-driven angiogenesis." We observed soluble immunosuppressive cytokines, predominantly TGF-β1, and surface integrin (α v β 3 ) endothelial-macrophage interactions are required in inflammation-driven angiogenesis. We demonstrated tuning cell-adhesion receptors using an integrin (α v β 3 )-specific collagen hydrogel regulated inflammation-driven angiogenesis through Src-PI3K-YAP signaling, highlighting the importance of altered cell-ECM interactions in inflammation. To validate the preclinical applications of our 3D organoid model and mechanistic findings of inflammation-driven angiogenesis, we screened a novel dual integrin (α v β 3 ) and cytokine receptor (TGFβ-R1) blockade that suppresses GBM tumor neovascularization by simultaneously targeting macrophage-associated immunosuppression, endothelial-macrophage interactions, and

  18. Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

    Science.gov (United States)

    Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

    2014-06-12

    After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse

  19. Association of time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected bacteria of patients after solid organ transplantation.

    Science.gov (United States)

    Schmalz, G; Berisha, L; Wendorff, H; Widmer, F; Marcinkowski, A; Teschler, H; Sommerwerck, U; Haak, R; Kollmar, O; Ziebolz, D

    2018-05-01

    Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT). 169 Patients after SOT (lung, liver or kidney) were included and divided into subgroups according their time under (0-1, 1-3, 3-6, 6-10 and >10 years) and form of immunosuppression (Tacrolimus, Cyclosporine, Mycophenolate, Glucocorticoids, Sirolimus and monotherapy vs. combination). Periodontal probing depth (PPD) and clinical attachment loss (CAL) were assessed. Periodontal disease severity was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were investigated for eleven selected potentially periodontal pathogenic bacteria using polymerasechainreaction. The mean PPD and CAL as well as prevalence of Treponema denticola and Capnocytophaga species was shown to be different but heterogeneous depending on time under immunosuppression (pperiodontal condition compared to patients without Cyclosporine (pperiodontal and microbiological parameters of patients after SOT. Patients under Cyclosporine medication should receive increased attention. Differences in subgingival biofilm, but not in clinical parameters were found for Glucocorticoids, Mycophenolate and combination therapy, making the clinical relevance of this finding unclear.

  20. Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

    2004-01-01

    A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...... indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case...... of tuberculosis. We suggest that RD1 based tests are evaluated further in immunocompromised patients....

  1. A tacrolimus-related immunosuppressant with reduced toxicity.

    Science.gov (United States)

    Dumont, F J; Koprak, S; Staruch, M J; Talento, A; Koo, G; DaSilva, C; Sinclair, P J; Wong, F; Woods, J; Barker, J; Pivnichny, J; Singer, I; Sigal, N H; Williamson, A R; Parsons, W H; Wyvratt, M

    1998-01-15

    Tacrolimus (FK506) has potent immunosuppressive properties reflecting its ability to block the transcription of lymphokine genes in activated T cells through formation of a complex with FK506 binding protein-12, which inhibits the phosphatase activity of calcineurin. The clinical usefulness of tacrolimus is limited, however, by severe adverse effects, including neurotoxicity and nephrotoxicity. Although this toxicity, like immunosuppression, appears mechanistically related to the calcineurin inhibitory action of the drug, a large chemistry effort has been devoted to search for tacrolimus analogs with reduced toxicity but preserved immunosuppressive activity that might have enhanced therapeutic utility. Here, we report on the identification of such an analog, which was synthetically derived from ascomycin (ASC), the C21 ethyl analog of tacrolimus, by introducing an indole group at the C32 position. The profile of biological activity of indolyl-ASC was characterized in rodent models of immunosuppression and toxicity. Indolyl-ASC was found to exhibit an immunosuppressive potency equivalent to that of tacrolimus in T-cell activation in vitro and in murine transplant models, even though indolyl-ASC bound about 10 times less to intracellular FK506 binding protein-12 than tacrolimus or ASC. Further evaluation of indolyl-ASC revealed that it is threefold less potent than tacrolimus in inducing hypothermia, a response that may reflect neurotoxicity, and in causing gastrointestinal transit alterations in mice. Moreover, indolyl-ASC was at least twofold less nephrotoxic than tacrolimus upon 3-week oral treatment in rats. Altogether, these data indicate a modest but definite improvement in the therapeutic index for indolyl-ASC compared with tacrolimus in rodent models.

  2. [Clinical views from the forefront of immunosuppressive drugs].

    Science.gov (United States)

    Kobayashi, Eiji

    2005-11-01

    Recently, many immunosuppressants have been developed and some of them have already been introduced in clinical organ transplantation. With a new concept of immunoregulation, which focuses on prevention of rejection and over-immunosuppression, the latest protocol has been conducted. Chimeric or humanized antibodies targeting the lymphocyte surface molecule such as CD19, 20, 25, 40, and 52 are administrated in the induction phase, and calcineurin inhibitors (cyclosporin and tacrolimus) are used as key drugs. For tapering the doses of them, the combined application of anti-metabolic agents of azathioprine, mizoribine, or mycophenolate mofetil (MMF) has been proved effective. Lymphocyte forming drugs induce unique immunoregulation, targeting at sphingosine 1-phosphate (SlP) receptors. FTY720 is now in the procedure of clinical trial to compare with MMF. KRP203 is also a candidate for more specific SIP receptor agonist. In this issue, I reviewed the recent immunosuppressive strategy and focused on the advance of novel immunosuppressive drugs.

  3. Immunosuppressive T-cell antibody induction for heart transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Gustafsson, Finn

    2013-01-01

    Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

  4. Cutaneous toxoplasmosis in an immunosuppressed dog

    Directory of Open Access Journals (Sweden)

    T.S. Oliveira

    2014-06-01

    Full Text Available A seven-year-old female spayed Schnauzer was presented with cutaneous ulcerated nodular lesions shortly after the beginning of an immunosuppressive treatment for immune-mediated hemolytic disease. Cytology was performed and a great number of neutrophils and banana-shaped organisms were observed. Biopsy showed a neutrophilic and histiocytic dermatitis and panniculitis with myriads of intralesional bradyzoites cysts and tachyzoites. PCR analysis was positive for Toxoplasma gondii and negative for Neospora caninum. Immunohistochemistry confirmed intralesional T. gondii antigens. This study reports a rare case of cutaneous toxoplasmosis in an immunosuppressed dog.

  5. Incidence of herpes zoster amongst adults varies by severity of immunosuppression.

    Science.gov (United States)

    Schröder, Carsten; Enders, Dirk; Schink, Tania; Riedel, Oliver

    2017-09-01

    We examined the incidence of herpes zoster in immunocompromised adults (≥18 years) with different severities of immunosuppression and assessed the prevalence of complications and of various kinds of healthcare resource utilisation. German claims data from more than ten million adults were used to calculate annual incidence rates of herpes zoster for the years 2006-2012 and to analyse the prevalence of complications, physician visits, hospitalisations, and antiviral and analgesic treatments using a cohort design. The analyses were stratified by age, sex, and severity of immunosuppression, defined by immunocompromising conditions and drug therapies. The incidence rate per 1000 person-years of herpes zoster was almost twice as high in immunocompromised patients (11.5 (95% confidence interval (CI): 11.4-11.6)) compared to immunocompetent subjects (5.9 (95% CI: 5.8-5.9)). The incidence rate was higher in highly immunocompromised patients (13.4 (95% CI: 13.2-13.6)) than in patients with a low severity of immunosuppression (10.0 (95% CI: 9.8-10.1)). These differences were observed for both sexes and in all age groups. Complications, outpatient physician visits, hospitalisations, and analgesic treatments occurred more frequently in immunocompromised patients as well. Our results show that immunocompromised individuals are affected by the disease in particular and that the burden of herpes zoster is highest in severely immunocompromised patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Immunosuppressive effect of total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bendel, V.; Medizinische Hochschule Hannover

    1981-01-01

    Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

  7. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    Science.gov (United States)

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    vaccination. Conclusions: Immunomodulators may impair the immune response to vaccination in patients with IBD. Vaccination should be made at the time of diagnosis or before starting immunosuppressed therapy.

  9. The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious uveitis in childhood.

    Science.gov (United States)

    Little, Jessica A; Sen, Ethan S; Strike, Helen; Hinchcliffe, Annie; Guly, Catherine M; Lee, Richard W J; Dick, Andrew D; Ramanan, Athimalaipet V

    2014-01-01

    To assess the safety and efficacy of noncorticosteroid triple immunosuppressive therapy in the treatment of refractory chronic noninfectious childhood uveitis. Subjects were retrospectively selected from a database. Patients were included if they were diagnosed with chronic, noninfectious uveitis at 16 years of age or under and treated with triple immunosuppressive therapy for at least 6 months (following failure of a combination of 2 immunosuppressants). Patient demographics, diagnoses, duration of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were recorded. Efficacy outcomes for triple therapy were recorded at 6 months. Thirteen patients with bilateral uveitis were included. Using Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%) had a 2-step improvement in anterior chamber cell inflammation (n = 26). In addition, 2 patients required additional oral corticosteroid treatment. There were 4 significant infectious adverse events during a total of 21.9 patient-years (PY) on triple therapy (0.18 events per PY). In this group of children with refractory uveitis, addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.

  10. Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs on Distinct T Cell Subopulations

    Czech Academy of Sciences Publication Activity Database

    Hájková, Michaela; Heřmánková, Barbora; Javorková, Eliška; Boháčová, Pavla; Zajícová, Alena; Holáň, Vladimír; Krulová, Magdaléna

    2017-01-01

    Roč. 13, č. 1 (2017), s. 104-115 ISSN 1550-8943 R&D Projects: GA ČR(CZ) GA14-12580S; GA MŠk(CZ) LO1508; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : mesenchymal stem cells * immunosuppressive drugs * stem cell therapy Subject RIV: FF - HEENT, Dentistry OBOR OECD: Immunology Impact factor: 2.967, year: 2016

  11. Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

    Directory of Open Access Journals (Sweden)

    Li Wei

    Full Text Available OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

  12. Awareness of memory impairment increases the adherence to immunosuppressants in kidney transplant recipients.

    Science.gov (United States)

    Cheng, C-Y; Lin, B Y-J; Chang, K-H; Shu, K-H; Wu, M-J

    2012-04-01

    Nonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients. All data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259-4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients. In summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Low Adherence to Immunosuppressants Is Associated With Symptom Experience Among Kidney Transplant Recipients.

    Science.gov (United States)

    Lee, S Y; Chu, S H; Oh, E G; Huh, K H

    2015-11-01

    The purpose of this study was to investigate the relationship between immunosuppressant-related symptom experience (SE) and adherence to immunosuppressant regimens among kidney transplant (KT) recipients. A total of 239 KT recipients on an immunosuppressant regimen who were followed up after transplantation participated in this study. Data was collected through a self-reported questionnaire survey (medication adherence, SE, and quality of life) and medical record review. Low adherence in the immunosuppressant group was associated with longer time since KT, less comorbidity (adherence among KT recipients showed significantly greater overall symptom occurrence (P = .001) and symptom distress (P = .002) levels than patients with high or medium adherence after adjusting for a number of covariates. The most common symptom both in terms of occurrence (96.4%) and distress (91.1%) among poorly adherent KT recipients was tiredness. Low adherence to an immunosuppressant regimen was significantly associated with high SE among KT recipients. Strategies to decrease immunosuppressant-related SE are needed to improve adherence to immunosuppressants. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Influence Of Ginger (Zingiber Officinale) Supplementation Against GAMMA Rays Induced Immunosuppression In Male Rats

    International Nuclear Information System (INIS)

    Mangood, S.A.; Kassab, F.M.A.

    2013-01-01

    The influence of ginger (Zingiber officinale) supplementation against gamma rays-induced immunosuppression in male albino rats was investigated in the present study. Twenty four male albino rats were divided into four equal groups; control group (receiving no treatment), ginger group where the rats received ginger orally at a dose of 15 g/rat/day for 120 consecutive days, gamma radiation group which subjected to a single 6 Gy whole body gamma radiation and gamma radiation plus ginger group where each rat after taking daily 15 g of ginger for 120 consecutive days was subjected to 6 Gy whole body irradiation. Complete blood pictures and immunoglobulin G (IgG) and M (IgM) were estimated and spleen tissue was also examined histologically. The data obtained revealed that exposure to 6 Gy of gamma radiation caused significant decrease in the body weight, spleen weight, IgG, IgM, erythroide and leucoid elements and produced histological damage in spleen tissue. On the other hand, ginger as a protective agent, caused significant amelioration in the changes produced by irradiation especially immunoglobulins leading to the conclusion that ginger supplementation for 120 days caused modulation of the humoral immune response in irradiated rats. In conclusion, these findings indicated that ginger has the regulatory effect against gamma rays-induced immunosuppression.

  15. Electronically-measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation*

    Science.gov (United States)

    Israni, Ajay K.; Weng, Francis L.; Cen, Ye-Ying; Joffe, Marshall; Kamoun, Malek; Feldman, Harold I.

    2013-01-01

    Background Non-adherence with immunosuppressive medications can result in allograft rejection and eventually allograft loss. Methods In a racially diverse population, we utilized microelectronic cap monitors to determine the association of adherence with a single immunosuppressive medication and kidney allograft outcomes post-transplantation. This prospective cohort study enrolled 243 patients from eight transplant centers to provide adherence and kidney allograft outcomes data. To determine the association of adherence with change in estimated glomerular filtration rate (eGFR), we fit mixed effects models with the outcome being change in eGFR over time. We also fit Cox proportional hazards models to determine the association of adherence with time to persistent 25% and 50% decline in eGFR. Results The distribution of adherence post-transplant was as follows: 164 (68%), 49 (20%) and 30 (12%) had >85–100%, 50–85% and adherence, respectively. 79 (33%) and 36 (15%) of the subjects experienced a persistent 25% decline in eGFR or allograft loss and 50% decline in eGFR or allograft loss during follow-up. Adherence was not associated with acute rejection or 25% decline or 50% decline in eGFR. In the adjusted and unadjusted model, adherence and black race were not associated with change in eGFR over time. Conclusions Non-adherence with a single immunosuppressive medication, was not associated with kidney allograft outcomes. PMID:20977496

  16. Electronically measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation.

    Science.gov (United States)

    Israni, Ajay K; Weng, Francis L; Cen, Ye-Ying; Joffe, Marshall; Kamoun, Malek; Feldman, Harold I

    2011-01-01

    Non-adherence with immunosuppressive medications can result in allograft rejection and eventually allograft loss. In a racially diverse population, we utilized microelectronic cap monitors to determine the association of adherence with a single immunosuppressive medication and kidney allograft outcomes post-transplantation. This prospective cohort study enrolled 243 patients from eight transplant centers to provide adherence and kidney allograft outcomes data. To determine the association of adherence with change in estimated glomerular filtration rate (eGFR), we fit mixed effects models with the outcome being change in eGFR over time. We also fit Cox proportional hazards models to determine the association of adherence with time to persistent 25% and 50% decline in eGFR. The distribution of adherence post-transplant was as follows: 164 (68%), 49 (20%), and 30 (12%) had >85-100%, 50-85%, and adherence, respectively. Seventy-nine (33%) and 36 (15%) of the subjects experienced a persistent 25% decline in eGFR or allograft loss and 50% decline in eGFR or allograft loss during follow-up. Adherence was not associated with acute rejection or 25% decline or 50% decline in eGFR. In the adjusted and unadjusted model, adherence and black race were not associated with change in eGFR over time. Non-adherence with a single immunosuppressive medication was not associated with kidney allograft outcomes. © 2010 John Wiley & Sons A/S.

  17. Generic maintenance immunosuppression in solid organ transplant recipients.

    Science.gov (United States)

    Ensor, Christopher R; Trofe-Clark, Jennifer; Gabardi, Steven; McDevitt-Potter, Lisa M; Shullo, Michael A

    2011-11-01

    Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

  18. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide.

    Science.gov (United States)

    Kanakry, Christopher G; Bolaños-Meade, Javier; Kasamon, Yvette L; Zahurak, Marianna; Durakovic, Nadira; Furlong, Terry; Mielcarek, Marco; Medeot, Marta; Gojo, Ivana; Smith, B Douglas; Kanakry, Jennifer A; Borrello, Ivan M; Brodsky, Robert A; Gladstone, Douglas E; Huff, Carol Ann; Matsui, William H; Swinnen, Lode J; Cooke, Kenneth R; Ambinder, Richard F; Fuchs, Ephraim J; de Lima, Marcos J; Andersson, Borje S; Varadhan, Ravi; O'Donnell, Paul V; Jones, Richard J; Luznik, Leo

    2017-03-09

    The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression. However, patients who develop GVHD require supplemental treatment. We assessed the longitudinal requirement for immunosuppressive therapy in 339 patients treated with this transplantation platform: 247 receiving busulfan/cyclophosphamide (BuCy) conditioning (data collected retrospectively) and 92 receiving busulfan/fludarabine (BuFlu) conditioning (data collected prospectively). Approximately 50% of MRD patients and 30% of MUD patients never required immunosuppression beyond PTCy. In patients requiring further immunosuppression, typically only 1 to 2 agents were required, and the median durations of systemic pharmacologic immunosuppression for the BuCy MRD, BuFlu MRD, BuCy MUD, and BuFlu MUD groups all were 4.5 to 5 months. For these 4 groups, 1-year probabilities of being alive and off all systemic immunosuppression were 61%, 53%, 53%, and 51% and 3-year probabilities were 53%, 48%, 49%, and 56%, respectively. These data suggest that PTCy minimizes the global immunosuppressive burden experienced by patients undergoing HLA-matched alloBMT.

  19. Immunity and immunosuppression in experimental visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  20. Symptom Experience Associated With Immunosuppressive Medications in Chinese Kidney Transplant Recipients.

    Science.gov (United States)

    Teng, Sha; Zhang, Shuping; Zhang, Wenxin; Lin, Xiaohong; Shang, Yabin; Peng, Xiao; Liu, Hongxia

    2015-09-01

    Kidney transplant recipients require lifelong treatment with immunosuppressive medications to avoid graft rejection and graft loss. Symptoms experienced may influence recipients' perceived quality of life and medication adherence. The purpose of this study was to evaluate the symptom experience associated with immunosuppressive medications in adult kidney transplant recipients and to explore the association between the symptom experience and adherence to immunosuppressive medications. A cross-sectional design was used. The study was conducted in a general hospital in China from October 2013 to September 2014. A total of 231 recipients with a follow-up of at least 1 year after kidney transplantation were included. Symptom experience associated with immunosuppressive medications was measured by the 13-item Symptom Experience of Immunosuppressive-related Side Effects Scale. Self-reported adherence to immunosuppressive medications was assessed using the Adherence with Immunosuppressive Medication Scale. Ridit analysis was used to rank symptom distress items. A proportion of 60.6% of recipients were male; the time after kidney transplantation was arbitrarily divided into a short-term cohort (1-4 years) and a long-term cohort (4-16 years) according to the median duration of follow-up (4 years). High blood pressure, hair loss, and tiredness were the three most distressing symptoms over all items of the whole sample. High blood pressure was the most distressing symptom for the 1- to 4-year cohort and the 4- to 16-year cohort. For men high blood pressure was the most distressing symptom, whereas for women hair loss was the most distressing symptom. Recipients in the 4- to 16-year cohort perceived a higher level of symptom distress compared with those in the 1- to 4-year cohort, especially in excess hair growth and difficulty sleeping. A negative relationship was found between symptom distress and adherence to immunosuppressive medications (r = -.541, p = .000). Recipients

  1. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  2. Genetic factors for individual administration of immunosuppressants in organ transplantation

    Institute of Scientific and Technical Information of China (English)

    Song-Feng Yu; Li-Hua Wu; Shu-Sen Zheng

    2006-01-01

    BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug eflfux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conlficting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immuno-suppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

  3. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    International Nuclear Information System (INIS)

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-01-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced

  4. Immunosuppression in the elderly renal allograft recipient

    DEFF Research Database (Denmark)

    Montero, Nuria; Pérez-Sáez, María José; Pascual, Julio

    2016-01-01

    BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression...... strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus...... receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account...

  5. Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship

    Science.gov (United States)

    2010-01-01

    Background Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma? Methods Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed. Results Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy. Conclusions Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question. PMID:20604945

  6. CCL2 is critical for immunosuppression to promote cancer metastasis.

    Science.gov (United States)

    Kudo-Saito, Chie; Shirako, Hiromi; Ohike, Misa; Tsukamoto, Nobuo; Kawakami, Yutaka

    2013-04-01

    We previously found that cancer metastasis is accelerated by immunosuppression during Snail-induced epithelial-to-mesenchymal transition (EMT). However, the molecular mechanism still remained unclear. Here, we demonstrate that CCL2 is a critical determinant for both tumor metastasis and immunosuppression induced by Snail(+) tumor cells. CCL2 is significantly upregulated in various human tumor cells accompanied by Snail expression induced by snail transduction or TGFβ treatment. The Snail(+) tumor-derived CCL2 amplifies EMT events in other cells including Snail(-) tumor cells and epithelial cells within tumor microenvironment. CCL2 secondarily induces Lipocalin 2 (LCN2) in the Snail(+) tumor cells in an autocrine manner. CCL2 and LCN2 cooperatively generate immunoregulatory dendritic cells (DCreg) having suppressive activity accompanied by lowered expression of costimulatory molecules such as HLA-DR but increased expression of immunosuppressive molecules such as PD-L1 in human PBMCs. The CCL2/LCN2-induced DCreg cells subsequently induce immunosuppressive CD4(+)FOXP3(+) Treg cells, and finally impair tumor-specific CTL induction. In murine established tumor model, however, CCL2 blockade utilizing the specific siRNA or neutralizing mAb significantly inhibits Snail(+) tumor growth and metastasis following systemic induction of anti-tumor immune responses in host. These results suggest that CCL2 is more than a chemoattractant factor that is the significant effector molecule responsible for immune evasion of Snail(+) tumor cells. CCL2 would be an attractive target for treatment to eliminate cancer cells via amelioration of tumor metastasis and immunosuppression.

  7. Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

    Institute of Scientific and Technical Information of China (English)

    Rita Diehl; Fabienne Ferrara; Claudia Müller; Antje Y Dreyer; Damian D McLeod; Stephan Fricke; Johannes Boltze

    2017-01-01

    Almost every experimental treatment strategy using non-autologous cell,tissue or organ transplantation is tested in small and large animal models before clinical translation.Because these strategies require immunosuppression in most cases,immunosuppressive protocols are a key element in transplantation experiments.However,standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species.Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation.This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects.It also summarizes contemporary knowledge of novel immunomodulatory strategies,such as the use of mesenchymal stem cells or antibodies.Thus,this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

  8. Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation.

    Science.gov (United States)

    Martin, Spencer T; Tichy, Eric M; Gabardi, Steven

    2011-04-01

    In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long-term use in renal transplant recipients. The costimulatory pathway (signal 2) of T-cell activation and proliferation is produced by stimulation of the T-cell surface marker, CD28, and is essential to the immune system's cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7-1 (CD80) and B7-2 (CD86) ligands present on antigen-presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living- and deceased-donor renal transplants, as well as in patients receiving kidneys transplanted from extended-criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy-proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin-based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein-Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long-term risks of belatacept are needed to better define its role as

  9. UVB-induced systemic immunosuppression: role of mast cells and histamine

    International Nuclear Information System (INIS)

    Hart, P.H.; Grimbaldeston, M.A.; Finlay-Jones, J.J.

    1999-01-01

    Full text: UVB radiation (290-320 nm) is immunosuppressive by multiple mechanisms allowing the outgrowth of UV-induced tumours in both mouse and man. Furthermore, patients with non-melanoma skin cancers have a higher risk of death from other cancers which could be explained by UV-induced immunomodulation. The mechanism(s) of suppression by UVB depend on whether the sensitising antigen is applied to the irradiated site ('local') or to non-irradiated sites ('systemic'). In the former, the activity of UV-induced TNFα is important as it affects the migration of Langerhans cells to draining lymph nodes. In contrast, histamine from dermal mast cells is critical to the early events by which UVB can suppress systemic immune responses. The prevalence of dermal mast cells in 7 strains and substrains of mice correlates directly with their susceptibility to UVB-induced systemic immunosuppression. Furthermore, mast cell depleted mice (Wf/Wf) are resistant to UVB-induced systemic immunomodulation. However, they become susceptible after reconstitution of the site to be irradiated with bone marrow derived mast cell precursors. The mice also gain susceptibility to cis-urocanic acid-induced systemic immunomodulation. There is considerable evidence that histamine is the mast cell product critical to downstream immunosuppressive events. Firstly, physiological concentrations of histamine suppress contact hypersensitivity responses. Secondly, histamine receptor antagonists halve UVB-induced systemic immunosuppression. Thirdly, mice with different UVB-susceptibilities are equally susceptible to histamine-induced immunosuppression, and finally, histamine can suppress contact hypersensitivity responses in Wf/Wf mice. We suggest that histamine may be immunomodulatory by multiple pathways. Histamine can induce the production of immunosuppressive prostanoids from keratinocytes. A lymphocyte-derived, histamine-induced suppressor factor was reported in the 1970's. More recently histamine has

  10. Prevention and treatment of Encephalitozoon cuniculi infection in immunosuppressed rabbits with fenbendazole.

    Science.gov (United States)

    Abu-Akkada, S S; Oda, S S

    2016-01-01

    This study was conducted to evaluate the efficacy of oral administration of fenbendazole (20 mg/kg body weight) prior to and after experimental infection of immunosuppressed rabbits with Encephalitozoon cuniculi . A total of thirty rabbits were divided into five groups: NN (non-immunosuppressed; non-infected), IN (immunosuppressed; non-infected), IPI (immunosuppressed; protected-infected), ITI (immunosuppressed; treated-infected), and II (immunosuppressed; infected) groups. Fenbendazole was administered as a prophylactic for seven successive days before infection with E. cuniculi and as a treatment for four weeks initiated on the 28th day post-challenge (PC). Experimental rabbits were infected with intraperitoneal injection of 2 × 10 5 E. cuniculi spores. Parameters evaluated were body weight, detection of spores in urine, serum antibody assay, hematological, biochemical and histopathological changes. The IPI and ITI groups showed a significant better final bwt than the II group. Spores were detected in urine of all infected rabbits from the 28th day PC until the end of the study. The IPI group showed the least values of antibodies (IgG) compared to the ITI and II groups. Concerning histopathological changes, the intensity of the lesions was marked particularly in the II rabbits and to a lesser extent in the ITI rabbits. Noticeable improvement was found in the IPI rabbits. It could be concluded that fenbendazole was effective to some extent in protection of rabbits against E. cuniculi infection, while when administered as a therapeutic no significant effects were observed.

  11. Effect of Increased Immunosuppression on Developmental Outcome of Opsoclonus Myoclonus Syndrome (OMS).

    Science.gov (United States)

    Mitchell, Wendy G; Wooten, Amelia A; O'Neil, Sharon H; Rodriguez, Jenny G; Cruz, Rosa E; Wittern, Rachael

    2015-07-01

    Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal. © The Author(s) 2014.

  12. Scheduling with target start times

    NARCIS (Netherlands)

    Hoogeveen, J.A.; Velde, van de S.L.; Klein Haneveld, W.K.; Vrieze, O.J.; Kallenberg, L.C.M.

    1997-01-01

    We address the single-machine problem of scheduling n independent jobs subject to target start times. Target start times are essentially release times that may be violated at a certain cost. The goal is to minimize an objective function that is composed of total completion time and maximum

  13. A Danish nationwide questionnaire study of hepatitis B virus screening before immunosuppressive therapy

    DEFF Research Database (Denmark)

    Bunyoz, Kristine Ifigenia; Krarup, Henrik; Weis, Nina

    2017-01-01

    INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation of immunos......INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation...... of immunosuppressive therapy and to explore HBV treatment strategies. METHODS: All Danish units of haematology, oncology, dermatology, rheumatology and gastroenterology using immunosuppressive agents were invited to fill out a questionnaire for The Danish Database for Hepatitis B and C. RESULTS: A total of 28 (53...

  14. Immunosuppression and tolerance after total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-01-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR

  15. Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

    Science.gov (United States)

    Zhao, Chan; Zhang, Meifen

    2017-04-10

    Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and

  16. A Danish nationwide questionnaire study of hepatitis B virus screening before immunosuppressive therapy

    DEFF Research Database (Denmark)

    Bunyoz, Kristine Ifigenia; Krarup, Henrik; Weis, Nina

    2017-01-01

    INTRODUCTION: Difficulty in identifying patients who are at risk for hepatitis B virus (HBV) reactivation makes it import-ant to screen for HBV before initiating immunosuppressive therapy. The aim of this study was to investigate screening procedures for HBV infection before initiation...... of immunosuppressive therapy and to explore HBV treatment strategies. METHODS: All Danish units of haematology, oncology, dermatology, rheumatology and gastroenterology using immunosuppressive agents were invited to fill out a questionnaire for The Danish Database for Hepatitis B and C. RESULTS: A total of 28 (53......%) of the 53 included units answered the questionnaire, of which 25 (89.3%) had a guideline regarding screening for HBV serological markers prior to immunosuppressive therapy, but only ten (37%) had a guideline that is in line with the joint guidelines from the national Danish Societies of Infectious Diseases...

  17. Cyclosporine A-loaded and stem cell-seeded electrospun nanofibers for cell-based therapy and local immunosuppression

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Chudíčková, Milada; Trošan, Peter; Svobodová, Eliška; Krulová, Magdalena; Kubinová, Šárka; Syková, Eva; Širc, Jakub; Michálek, Jiří; Juklíčková, M.; Munzarová, M.; Zajícová, Alena

    2011-01-01

    Roč. 156, č. 3 (2011), s. 406-412 ISSN 0168-3659 R&D Projects: GA AV ČR KAN200520804; GA ČR GAP304/11/0653; GA ČR(CZ) GAP301/11/1568; GA ČR GD310/08/H077; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40500505; CEZ:AV0Z50520514 Keywords : nanofibers * immunosuppression * cell transfer Subject RIV: EC - Immunology Impact factor: 5.732, year: 2011

  18. Plasma levels of immunosuppressive mediators during cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    E. Borrelli

    1996-01-01

    Full Text Available The aim of this study was to evaluate plasma levels of two mediators with immunosuppressive properties, complement fraction C3a (C3a and transforming growth factor-β1 (TGF-β1, during extracorporeal circulation. The proliferation index after phytohaemagglutinin (PHA stimulation of isolated peripheral blood mononuclear cells was also investigated. Sixteen patients undergoing hypothermic (n = 8, group 1 and normothermic (n = 8, group 2 cardiopulmormry bypass (CPB were enrolled in this study. As a control, we evaluated four patients undergoing thoracovascular operations without CPB. Blood samples were collected before CPB but after anaesthesia, every 30 min during CPB, at the end of CPB and 10 min after protamine administration. Both C3a and TGF-β1 increased significantly during CPB and after protamine administration in the hypothermic as well as the normothermic group. In the latter case the increase of C3a and TGF-β1, although more prominent, was not significantl higher than in the former group. Conversely, the proliferation, index of peripheral mononuclear cells had already decreased 30 min after CPB was started and remained depressed throughout the CPB time. These results suggest a possible role of C3a and TGF-β1 in the immunological changes occurring during extracorporeal circulation.

  19. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    enzymes such as indoeamine-2,3-dioxygenase (IDO). The possible therapeutic targeting of these pathways is also discussed. Exciting new strategies that might affect future antileukemia immunotherapy include monoclonal antibodies that block inhibitory T-cell pathways (PD-1/PD-L1) and the prevention...... of tryptophan depletion by IDO inhibitors. Furthermore, the clinical effect of several chemotherapeutic drugs may arise from the targeting of immunosuppressive cells. Evidence for a new feedback mechanism to suppress the function of regulatory immune cells was recently provided by the identification...... and characterization of spontaneous cytotoxic T lymphocyte (CTL) responses against regulatory immune cells. Such specific CTLs may be immensely useful in anticancer immunotherapy (for example, by anticancer vaccination). The targeting of one or more immunosuppressive pathways may be especially interesting...

  20. Neurologic emergencies in HIV-negative immunosuppressed patients.

    Science.gov (United States)

    Guzmán-De-Villoria, J A; Fernández-García, P; Borrego-Ruiz, P J

    HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Effective long-term immunosuppression in rats by subcutaneously implanted sustained-release tacrolimus pellet: Effect on spinally grafted human neural precursor survival

    Czech Academy of Sciences Publication Activity Database

    Ševc, J.; Goldberg, D.; van Gorp, S.; Leerink, M.; Juhás, Štefan; Juhásová, Jana; Marsala, S.; Hruška-Plocháň, Marian; Hefferan, M. P.; Motlík, Jan; Rypáček, František; Machová, Luďka; Kakinohana, O.; Santucci, C.; Johe, K.; Lukáčová, N.; Yamada, K.; Bui, J. D.; Marsala, M.

    2013-01-01

    Roč. 248, October (2013), s. 85-99 ISSN 0014-4886 R&D Projects: GA TA ČR TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 ; RVO:61389013 Keywords : immunosuppression * xenograft * human neural precursors Subject RIV: FH - Neurology; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 4.617, year: 2013

  2. Immunosuppressive potential of bardoxolone methyl using a modified murine local lymph node assay (LLNA).

    Science.gov (United States)

    Kitsukawa, Mika; Tsuchiyama, Hiromi; Maeda, Akihisa; Oshida, Keiyu; Miyamoto, Yohei

    2014-08-01

    2-Cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl) is one of the synthetic oleanane triterpenoids (SOs). It is known that it is the strongest Nrf2/ARE signaling inducer of SOs and slightly inhibits immune response. Little was known about the immunomodulatory action of CDDO-Me in vivo. We assessed its immunosuppressive potential by using the modified mouse lymph node assay (LLNA) including immunosuppression-related gene expression analysis. In the modified LLNA, CDDO-Me showed a significant decrease in lymph node weight and changes in expressions of the immunosuppression-related genes, Zfp459 and Fmo2. It has been already reported that a decrease in lymph node weight was induced by several types of immunosuppressive chemicals such as calcineurin inhibitors, antimetabolites, steroids, and alkylators. In addition, changes in Zfp459 and Fmo2 expression was reported in response after only treatment of antimetabolites. From these results, CDDO-Me is considered to have an immunosuppressive action and similar mechanism to antimetabolites.

  3. Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

    Science.gov (United States)

    Constantiner, Melissa; Rosenthal-Asher, Deborah; Tedla, Fasika; Salifu, Moro; Cukor, Judith; Wyka, Katarzyna; Hartono, Choli; Serur, David; de Boccardo, Graciela; Cukor, Daniel

    2018-03-01

    Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

  4. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Cutaneous lymphoproliferative disorder complicating infectious mononucleosis in an immunosuppressed patient.

    Science.gov (United States)

    Owen, Cindy England; Callen, Jeffrey P; Bahrami, Soon

    2011-01-01

    Infectious mononucleosis is the syndrome produced by primary infection with Epstein-Barr virus during adolescence or early adulthood. In immunosuppressed individuals, depressed T-cell function allows the Epstein-Barr virus-driven B-cell proliferation to continue unabated, potentially leading to a lymphoproliferative disorder. A 15-year-old girl with a history of ulcerative colitis treated with 6-mercaptopurine and mesalamine presented with the acute onset of a rapidly enlarging, ulcerative nodule on her left lower eyelid 4 weeks following recovery from infectious mononucleosis. The biopsy revealed an Epstein-Barr virus-positive lymphoproliferative disorder. Systemic disease was absent. Following discontinuation of 6-mercaptopurine, the patient was treated with two courses of intravenous cyclophosphamide. The lesion resolved completely and she remains disease free at 14 months following diagnosis. We report a solitary cutaneous lesion of an immunosuppression-related lymphoproliferative disorder (IR-LPD) occurring as a complication of infectious mononucleosis, and review the pathogenesis and reported cases of Epstein-Barr virus-related immunosuppression-related lymphoproliferative disorder arising in the setting of inflammatory bowel disease. It is important for dermatologists and dermatopathologists to be aware of the occurrence of IR-LPD in patients being treated for inflammatory conditions, including inflammatory bowel disease. Given the role of primary infection with Epstein-Barr virus in the development of IR-LPD, consideration may be given to assessing Epstein-Barr virus status prior to initiating immunosuppressive therapy in young patients. © 2010 Wiley Periodicals, Inc.

  6. Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

    Science.gov (United States)

    Kumari, P; Nigam, R; Singh, A; Nakade, U P; Sharma, A; Garg, S K; Singh, S K

    2017-09-01

    Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

  7. Persistent Hypotony Associated with Immunosuppressive Therapy in Glaucoma Drainage Implant Surgery

    Directory of Open Access Journals (Sweden)

    Susana Duch

    2016-09-01

    Full Text Available Purpose: To describe the histopathology of non-valved implant capsules in three cases of persistent postoperative hypotony after the restrictive tube ligature was released in patients receiving immunosuppressive therapy. Observations: The macroscopic appearance of the capsules 3 and 4 months postoperatively was immature and loose. Microscopic examination disclosed extremely irregular thin tissue, with thicknesses ranging from 0.02 to 0.6 mm, depending on the capsular location studied. Withdrawal of immunosuppressive therapy did not facilitate rebuilding of new capsules. Replacement with a valved implant device was necessary in two cases; the third case recovered with tapering of prednisone. Conclusions and Importance: The use of chronic systemic immunosuppressive therapy might interfere with capsular formation around the plates of drainage devices inducing persistent hypotony. In these cases, the use of valved implants might be safer.

  8. Photobiomodulation with Pulsed and Continuous Wave Near-Infrared Laser (810 nm, Al-Ga-As Augments Dermal Wound Healing in Immunosuppressed Rats.

    Directory of Open Access Journals (Sweden)

    Gaurav K Keshri

    Full Text Available Chronic non-healing cutaneous wounds are often vulnerable in one or more repair phases that prevent normal healing and pose challenges to the use of conventional wound care modalities. In immunosuppressed subject, the sequential stages of healing get hampered, which may be the consequences of dysregulated or stagnant wound inflammation. Photobiomodulation (PBM or low-level laser (light therapy (LLLT emerges as a promising drug-free, non-invasive biophysical approach for promoting wound healing, reduction of inflammation, pain and restoration of functions. The present study was therefore undertaken to evaluate the photobiomodulatory effects of 810 nm diode laser (40 mW/cm2; 22.6 J/cm2 with pulsed (10 and 100 Hz, 50% duty cycle and continuous wave on full-thickness excision-type dermal wound healing in hydrocortisone-induced immunosuppressed rats. Results clearly delineated that 810 nm PBM at 10 Hz was more effective over continuous and 100 Hz frequency in accelerating wound healing by attenuating the pro-inflammatory markers (NF-kB, TNF-α, augmenting wound contraction (α-SM actin, enhancing cellular proliferation, ECM deposition, neovascularization (HIF-1α, VEGF, re-epithelialization along with up-regulated protein expression of FGFR-1, Fibronectin, HSP-90 and TGF-β2 as compared to the non-irradiated controls. Additionally, 810 nm laser irradiation significantly increased CCO activity and cellular ATP contents. Overall, the findings from this study might broaden the current biological mechanism that could be responsible for photobiomodulatory effect mediated through pulsed NIR 810 nm laser (10 Hz for promoting dermal wound healing in immunosuppressed subjects.

  9. IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

    Directory of Open Access Journals (Sweden)

    E. A. Starikova

    2015-01-01

    Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

  10. Immunosuppression by non-ionising and ionising radiation - are there similarities?

    International Nuclear Information System (INIS)

    Reeves, V.

    2003-01-01

    Solar UV radiation, the ubiqitous environmental non-ionising radiation, initiates its immunomodulating effects almost entirely in the skin. In direct contrast, ionising radiation penetrates much more efficiently, and has a multitude of internal targets throughout the body. As a consequence, the mechanisms underlying UV-induced immunosuppression have been more readily characterised, whereas surprisingly little is known about immunosuppression resulting from ionising radiation. Photoimmunological studies in mice during the past 20-30 years have established the action spectrum for UV-induced immunosuppression, implicating the UVB waveband, 290-320 nm. Controversy rages over the immunosuppressive potential of the UVA waveband, 320-400 nm, but we demonstrate that environmentally relevant doses of UVA not only are immunologically innocuous, but provide protection against UVB-immunosuppression. Increasingly larger UVA exposures increasingly immunosuppress mice. The UVA immunoprotective effect is strongly dependent on the induction of a cutaneous redox-regulated enzyme, haem oxygenase (heat shock protein 32) that is known to protect cells from oxidative stress, and it is consistent that a number of exogenous antioxidants (vitamin E, vitamin C, green tea polyphenols, isoflavones) can protect effectively from photoimmuno-suppression. Thus the UV-immunosuppressed state is promoted by oxidative damage and depletion of endogenous antioxidant molecules. It is also associated with cutaneous cytokine derangements, such that Th-2 cytokines (IL-4, IL-10) are increased at the expense of Th-1 cytokines (IFN-gamma, IL-12), and with histamine and inflammatory prostaglandin activity. In contrast, immunoprotective UVA irradiation protects the cutaneous cytokine array, inhibits IL-10 upregulation and increases IFN-gamma and IL-12 expression. On the other hand, while ionising radiation is known to cause immunosuppression, large doses target the bone marrow and haemopoiesis lethally and

  11. Pulmonary tuberculosis in a patient with rheumatoid arthritis undergoig immunosuppressive treatment: case report

    Directory of Open Access Journals (Sweden)

    Sandro Ceratti

    2014-02-01

    Full Text Available Rheumatoid arthritis is a disease which characteristically affects the joints. Because it is an autoimmune disease, immunosuppressive drugs are widely used in its treatment. The present case report illustrates the association of immunosuppressive treatment with the development of opportunistic infections in a 64-year-old patient.

  12. A systematic checklist approach to immunosuppression risk management: An audit of practice at two clinical neuroimmunology centers.

    Science.gov (United States)

    Mori, Amelia M; Agarwal, Smriti; Lee, Monique W M; Rafferty, Martina; Hardy, Todd A; Coles, Alasdair; Reddel, Stephen W; Riminton, D Sean

    2017-11-15

    There is no consensus approach to safety screening for immune intervention in clinical neuroimmunology. An immunosuppression risk evaluation checklist was used as an audit tool to assess real-world immunosuppression risk management and formulate recommendations for quality improvements in patient safety. Ninety-nine patients from two centres with 27 non-MS diagnoses were included. An average of 1.9 comorbidities with the potential to adversely impact morbidity and mortality associated with immunosuppression were identified. Diabetes and smoking were the most common, however a range of rarer but potentially life-threatening co-morbid disorders in the context of immunosuppression were identified. Inadequate documentation of risk mitigation tasks was common at 40.1% of total tasks across both cohorts. A routine, systematic immunosuppression checklist approach should be considered to improve immunosuppression risk management in clinical neuroimmunology practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Varicella-zoster virus immunity in dermatological patients on systemic immunosuppressant treatment.

    LENUS (Irish Health Repository)

    Hackett, C B

    2012-02-01

    BACKGROUND: Primary varicella infection is caused by varicella-zoster virus (VZV). It is a common childhood infection, which is usually benign but can occasionally cause morbidity and mortality. In immunosuppressed adults, atypical presentation and disseminated disease can occur with significant morbidity and mortality. A VZV vaccine is available. OBJECTIVES: This study was designed to measure the prevalence of immunity to VZV and to determine the predictive value of a self-reported history of varicella infection in a population of dermatological patients receiving systemic immunosuppressant therapy. We sought to assess the need for routine serological testing for varicella-zoster immunity in this cohort. METHODS: Serological testing for VZV immunity was done on 228 patients receiving systemic immunosuppressive treatment for a dermatological condition. Information regarding a history of previous primary VZV infection was obtained from each patient. RESULTS: Two hundred and twenty-eight patients had VZV serology performed. The mean age of the patients was 49.6 years. The prevalence of VZV seropositivity in this cohort was 98.7%. One hundred and two patients (44.7%) reported having a definite history of primary VZV. The sensitivity of a self-reported history of VZV infection was 45.3% with a specificity of 100%. The positive and negative predictive values of a self-reported history of VZV for serologically confirmed immunity were 100% and 2.3%, respectively. CONCLUSIONS: The prevalence of VZV IgG antibodies in our cohort of Irish dermatology patients receiving immunosuppressive therapy is 98.7%. A recalled history of varicella infection is a good predictor of serological immunity. This study has shown that there are VZV-susceptible individuals within our cohort. These patients did not have a clear history of previous infection. We recommend serological testing of patients without a clear history of infection prior to the commencement of immunosuppressive therapy and

  14. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2015-01-01

    Full Text Available Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1 or fibroblasts (FB, group 2 under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001 without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.

  15. A Rationale for Age-Adapted Immunosuppression in Organ Transplantation.

    Science.gov (United States)

    Krenzien, Felix; ElKhal, Abdallah; Quante, Markus; Rodriguez Cetina Biefer, Hector; Hirofumi, Uehara; Gabardi, Steven; Tullius, Stefan G

    2015-11-01

    Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants.Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors.This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

  16. Effects of immunosuppression on circulating adeno-associated virus capsid-specific T cells in humans.

    Science.gov (United States)

    Parzych, Elizabeth M; Li, Hua; Yin, Xiangfan; Liu, Qin; Wu, Te-Lang; Podsakoff, Gregory M; High, Katherine A; Levine, Matthew H; Ertl, Hildegund C J

    2013-04-01

    In humans adeno-associated virus (AAV)-mediated gene transfer is followed by expansion of AAV capsid-specific T cells, evidence of cell damage, and loss of transgene product expression, implicating immunological rejection of vector-transduced cells, which may be prevented by immunosuppressive drugs. We undertook this study to assess the effect of immunosuppression (IS) used for organ transplantation on immune responses to AAV capsid antigens. Recipients of liver or kidney transplants were tested before and 4 weeks after induction of IS in comparison with matched samples from healthy human adults and an additional cohort with comorbid conditions similar to those of the transplant patients. Our data show that transplant patients and comorbid control subjects have markedly higher frequencies of circulating AAV capsid-specific T cells compared with healthy adults. On average, IS resulted in a reduction of AAV-specific CD4⁺ T cells, whereas numbers of circulating CD8⁺ effector and central memory T cells tended to increase. Independent of the type of transplant or the IS regimens, the trend of AAV capsid-specific T cell responses after drug treatment varied; in some patients responses were unaffected whereas others showed decreases or even pronounced increases, casting doubt on the usefulness of prophylactic IS for AAV vector recipients.

  17. High immunosuppressive burden in advanced hepatocellular carcinoma patients: Can effector functions be restored?

    Science.gov (United States)

    Lugade, Amit A; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2013-07-01

    The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

  18. Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

    Science.gov (United States)

    Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

    2016-03-01

    Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant. © The Author(s) 2015.

  19. Does Pre-Operative Multiple Immunosuppressive Therapy Associate with Surgical Site Infection in Surgery for Ulcerative Colitis.

    Science.gov (United States)

    Uchino, Motoi; Ikeuchi, Hiroki; Bando, Toshihiro; Hirose, Kei; Hirata, Akihiro; Chohno, Teruhiro; Sasaki, Hirofumi; Takahashi, Yoshiko; Takesue, Yoshio; Hida, Nobuyuki; Hori, Kazutoshi; Nakamura, Shiro

    2015-01-01

    Almost all surgeries for ulcerative colitis (UC) are performed under immunosuppressive conditions. Immunomodulators or biologics, with the exception of corticosteroids, do not appear to be risk factors for post-operative infectious complications. However, many patients are on multiagent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressives on the occurrence of surgical site infection (SSI) in UC. We reviewed surveillance data from 181 patients who underwent restorative proctocolectomy between January 2012 and March 2014. The incidences of SSI and the possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. The incidence of incisional (INC) SSI was 13.3% and that of organ/space (O/S) SSI was 7.2%. The number of immunosuppressives did not significantly correlate with each incidence. Total prednisolone administration ≥12,000 mg (OR 2.6) and an American Society of Anesthesiologists score ≥3 (OR 2.8) were shown to be independent risk factors for overall SSI, whereas corticosteroid use in INC SSI (OR 17.4) and severe disease (OR 5.2) and a large amount of blood loss (OR 3.9) in O/S SSI were identified as risk factors. Although a correlation between multiple immunosuppressive therapy and SSIs was not found, it is not recommended that all patients be treated with multiple immunosuppressive therapy. Treatment strategy should be applied based on the patient's condition. © 2015 S. Karger AG, Basel.

  20. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.

    Science.gov (United States)

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Wojciuk, Bartosz; Wojciechowska-Koszko, Iwona; Roszkowska, Paulina; Krasnodębska-Szponder, Barbara; Paczkowska, Edyta; Safranow, Krzysztof; Gołembiewska, Edyta; Machaliński, Bogusław; Ciechanowski, Kazimierz

    2016-01-01

    In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system - the thymus and the spleen. The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner.

  1. 24-h monitoring of calcineurin phosphatase activity in healthy subjects

    DEFF Research Database (Denmark)

    Koefoed-Nielsen, P.B.; Karamperis, N.; Jørgensen, Kaj Anker

    2005-01-01

    The calcineurin inhibitors cyclosporine and tacrolimus are the cornerstone immunosuppressants used in solid organ transplantation. Studies investigating calcineurin (CaN) activity in renal transplanted patients have been published, but basic properties of the enzyme activity in healthy subjects...... remain to be described. The aim of this study was to investigate whether CaN displays circadian variation or sex difference is present in healthy subjects. Twenty subjects had blood samples drawn every 4 h for a 24-h period. CaN activity was determined in whole blood as the release of 32P from...

  2. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification.

    Science.gov (United States)

    Seto, Wai-Kay

    2015-04-28

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.

  3. Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

    Science.gov (United States)

    Sindhi, R; Webber, S; Venkataramanan, R; McGhee, W; Phillips, S; Smith, A; Baird, C; Iurlano, K; Mazariegos, G; Cooperstone, B; Holt, D W; Zeevi, A; Fung, J J; Reyes, J

    2001-09-15

    The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

  4. Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders.

    Science.gov (United States)

    Loechelt, Brett J; Green, Michael; Gottlieb, Peter A; Blumberg, Emily; Weinberg, Adriana; Quinlan, Scott; Baden, Lindsey R

    2015-09-01

    Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder. Although these agents hold promise for amelioration or cure of this disease, they have the potential to facilitate infectious complications. There are limited data regarding the prospective assessment of infectious risks with these agents in trials of this nature. Pediatric subjects may be at greater risk due to the higher likelihood of primary infection. A subgroup of experts associated with TrialNet (a National Institutes of Health [NIH]-funded Type 1 diabetes mellitus research network) with expertise in infectious diseases, immunology, and diagnostics developed an approach for screening and monitoring of immunosuppression-associated infections for prospective use in clinical trials. The goals of these recommendations are to provide a structured approach to monitor for infections, to identify specific laboratory testing and surveillance methods, and to consider therapies for treatment of these potential complications. Prospective evaluations of these infectious risks allow for greater scientific rigor in the evaluation of risk, which must be balanced with the potential benefits of these therapies. Our experience supports an important role for investigators with expertise in infections in immunocompromised individuals in protocol development of immunosuppressive trials in type 1diabetes and potentially other autoimmune diseases.

  5. Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bryony Jenkins

    2016-12-01

    Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

  6. Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bryony Jenkins

    2017-02-01

    Full Text Available To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II, and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of pMHC formation or TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

  7. Side Effects of Transplant Immunosuppressive Therapy in Post Renal Transplant Recipients, Mazandaran, Northern Iran

    Directory of Open Access Journals (Sweden)

    Abazar Akbarzadeh Pasha

    2017-04-01

    Full Text Available Background Post-kidney transplant survival relies on patient adherence to the intake of immunosuppressive medication. This study was performed to investigate complications associated with immunosuppressive therapy in renal transplantation. Methods This cross-sectional study was conducted on 188 transplanted patients in Shahid Beheshti hospital of Babol in 2013. Check list and demographic questionnaire for data collecting were used. Then the data using were analyzed in SPSS.18 software by using chi-square test. Results A total of 188 transplanted patients, 115 (61.2% was male and mean age was 12.9 ± 42.9 years. 181 (96.3% of the subjects had at least one complication. The most common complication in 142 cases (75.5% was “excessive hair growth” and after this complication “increased blood sugar” had higher frequency and 119 (63.3% had this complication. Severe form of gingival overgrowth in women was significantly that more than men (22 (30.1, 14 (12.2, P = 0.004, and the other side effect was not significant difference between men and women or different age groups (P > 0.05 Conclusions Finding show that nearly all transplanted recipients suffered from one complication which need to recognize, control and treatment. It suggested that period visiting for early diagnosis and education to patient was recommend.

  8. From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2017-01-01

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Nonadherence to immunosuppression: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Moreso F

    2015-06-01

    Full Text Available Francesc Moreso,1 Irina B Torres,1 Gemma Costa-Requena,2 Daniel Serón1 1Nephrology Department, 2Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, Barcelona, Spain Abstract: Nonadherence to immunosuppressant treatment is common after renal transplantation involving >20% of patients. It is associated with cellular rejection, appearance of donor-specific antibodies, and chronic rejection. It has been estimated that nonadherence can be detected in approximately 50% of failing grafts. Since the evaluation of sociodemographic factors do not allow characterizing the target population, it is necessary to combine different measures of adherence (self-reporting and collateral reporting, pill counts, biological monitoring of blood samples, or others to increase its diagnostic accuracy. During the last decade, it has been shown that the implementation of a multidimensional intervention including information, motivation, and behavioral interventions may lead to an improvement of adherence to treatment. On the other hand, it has been shown that one-off feedback from a nurse, simplification of treatment, or financial assistance programs offered little improvement. Thus, increasing the effectiveness of adherence interventions might have a far greater impact on the long-term outcome of renal transplants than any improvement in specific medical treatments. This will require coordinated action from health professionals, researchers, health planners, and policy makers. Keywords: renal transplantation, nonadherence, immunosuppressive treatment

  10. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    International Nuclear Information System (INIS)

    Holland, G.N.; O'Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-01-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease

  11. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Holland, G.N.; O' Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-06-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

  12. Malaria in immuno-suppressed individuals on antiretroviral therapy ...

    African Journals Online (AJOL)

    Malaria in immuno-suppressed individuals on antiretroviral therapy (ART) in north-central Nigeria. C.R. Pam, B.T. Abubakar, G.O. Inwang, G.A. Amuga. Abstract. The immune deficiency caused by HIV infection reduces the immune response to malaria parasitaemia and therefore leads to an increased frequency of clinical ...

  13. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-12-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

  14. Immunosuppressive compounds from a deep water marine sponge, Agelas flabelliformis.

    Science.gov (United States)

    Gunasekera, S P; Cranick, S; Longley, R E

    1989-01-01

    Two immunosuppressive compounds, 4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol and 4,5-dibromo-2-pyrrolic acid were isolated from a deep water marine sponge, Agelas flabelliformis. Their structures were determined by comparison of their spectral data with those of samples isolated from other organisms. Both compounds were highly active in suppression of the response of murine splenocytes in the two-way mixed lymphocyte reaction (MLR) with little to no demonstrable cytotoxicity at lower doses. In addition, 4,5-dibromo-2-pyrrolic acid suppressed the proliferative response of splenocytes to suboptimal concentrations of the mitogen, concanavalin A (Con A). These results describe for the first time compounds isolated from the marine sponge A. flabelliformis that possess potent in vitro immunosuppressive activity.

  15. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  16. Intestinal strongyloidiasis in a psoriatic patient following immunosuppressive therapy: Seeing the unforeseen

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    Poongodi Lakshmi Santhana Kumaraswamy

    2016-01-01

    Full Text Available Strongyloides stercoralis , an intestinal nematode, has a complicated life cycle. Mostly asymptomatic, if symptomatic it has nonspecific, transient clinical manifestations. The two aggressive forms of the disease are: Hyperinfection syndrome (HS or disseminated syndrome (DS. Several risk factors have been associated with strongyloidiasis including immunosuppressive therapy, human immunodeficiency virus (HIV infection, diabetes, alcoholism, tuberculosis, impaired bowel motility, surgically created intestinal blind loops, chronic obstructive pulmonary disease, and chronic renal failure. We describe a case of intestinal strongyloidiasis in a psoriatic patient treated with immunosuppressive therapy.

  17. Pneumonia in immunosuppressed patients; Pneumonien bei immunsupprimierten Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Solyanik, O.; Gaass, T.; Hellbach, K. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Dinkel, J. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer klinische Radiologie, Muenchen (Germany); Comprehensive Pneumology Center Munich (CPC-M), Muenchen (Germany)

    2017-01-15

    Pulmonary infections are a common complication in immunosuppressed patients with a frequently fatal prognosis despite modern prophylactic therapy. An early and correct diagnosis is important for initiation of the appropriate therapy. Chest radiography is the preferred initial imaging examination but is not accurate enough for the detection of pulmonary infections in immunosuppressed patients. Pneumonia is caused by a broad spectrum of pathogens in immunocompromised patients. In addition to imaging, the clinical history and epidemiology also play an important role in the diagnostics. Using epidemiological and anamnestic information, computed tomography (CT) shows a significantly better sensitivity and specificity particularly for the diagnosis of atypical forms of pneumonia. Due to the exact imaging of the different infiltration patterns CT provides an increased sensitivity with respect to the etiological classification of pulmonary infections. This article reviews in particular the radiological findings of commonly occurring pulmonary infections in immunosuppressed patients. (orig.) [German] Pneumonien bei immunsupprimierten Patienten sind haeufige Komplikationen, die trotzt moderner Prophylaxe toedlich verlaufen koennen. Eine korrekte Diagnose ist daher von entscheidender Bedeutung, um die richtige Therapie einleiten zu koennen. Die Roentgenthoraxaufnahme ist selten spezifisch genug fuer die genaue Einordnung atypischer Pneumonien in Folge einer Immunsuppression. Pneumonien unter Immunsuppression werden durch ein sehr breites Erregerspektrum verursacht. Eine wichtige Rolle bei der Diagnosefindung spielen neben der Bildgebung auch die klinische Anamnese und Epidemiologie. Mithilfe der klinischen Anamnese und Epidemiologie bietet die Computertomographie (CT) bei immunsupprimierten Patienten zum einen eine erhoehte Sensitivitaet bei der Detektion insbesondere atypischer Pneumonien. Zum anderen weist die CT durch die exakte Abbildung unterschiedlicher Infiltratmuster

  18. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Garred, Peter

    2013-01-01

    -stage renal disease seem to be at an increased risk of cervical cancer. A higher risk of cervical precancerous lesions was found in patients with some autoimmune diseases; particularly if treated with immunosuppressants. Among behavioral factors weakening the immune system, smoking appeared to strongly...... increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent...

  19. Merkel cell carcinoma in an immunosuppressed patient.

    Science.gov (United States)

    Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da

    2017-01-01

    Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

  20. Immunosuppressive therapy for transplant-ineligible aplastic anemia patients.

    Science.gov (United States)

    Schrezenmeier, Hubert; Körper, Sixten; Höchsmann, Britta

    2015-02-01

    Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials.

  1. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

    Directory of Open Access Journals (Sweden)

    E. A. Drozdova

    2014-07-01

    Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

  2. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

    Directory of Open Access Journals (Sweden)

    E. A. Drozdova

    2012-01-01

    Full Text Available Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years who received low dose methotrexate — 7.5-20 mg once a week (n=79 cyclosporine A 3.5-5.0 mg/kg/d (n=21 with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% of patients with chronic uveitis. Control of acute inflammation was achived in 71.1% patients, who received methotrexate in combination with prednisolone. Cyclosporine A was more effective in controlling inflammatory of the eye: remission of uveitis was achived in 85.7% in combination with glucocorticoids. No significant side effects have been noted.Conclusion: Methotrexate and cyclosporine A with low dose of prednisolone are well tolerated immunosuppressive agents andrather effective in the treatment of non-infectious uveitis and retinovasculitis that fails to respond to conventional steroid treatment.

  3. Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression

    OpenAIRE

    MCCANN, SHAUN

    2002-01-01

    PUBLISHED Background: Aplastic anemia may develop during pregnancy and sometimes improves spontaneously after delivery. The effects of pregnancy on aplastic anemia after immunosuppressive treatment and of aplastic anemia on the outcome of pregnancy have not been described. Objective: To determine the outcome of pregnancy and the disease course among women with aplastic anemia who received immunosuppressive therapy. Design: Retrospective multicenter study. Setting: Twelve cen...

  4. Future immunosuppressive agents in solid-organ transplantation.

    Science.gov (United States)

    Gabardi, Steven; Cerio, Jeffrey

    2004-06-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

  5. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  6. Effects of immunosuppressive treatment on protein expression in rat kidney

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    Kędzierska K

    2014-09-01

    Full Text Available Karolina Kędzierska,1 Katarzyna Sporniak-Tutak,2 Krzysztof Sindrewicz,2 Joanna Bober,3 Leszek Domański,1 Mirosław Parafiniuk,4 Elżbieta Urasińska,5 Andrzej Ciechanowicz,6 Maciej Domański,1 Tomasz Smektała,2 Marek Masiuk,5 Wiesław Skrzypczak,6 Małgorzata Ożgo,6 Joanna Kabat-Koperska,1 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology, and Internal Medicine, 2Department of Dental Surgery, 3Department of Medical Chemistry, 4Department of Forensic Medicine, 5Department of Pathomorphology, Pomeranian Medical University, 6Department of Physiology, Cytobiology, and Proteomics, West Pomeranian University of Technology, Szczecin, Poland Abstract: The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents' toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins' synthesis. Very slight differences

  7. Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Galvao, M.M.; Ianhez, L.E.; Sabbaga, E. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

    1982-02-01

    The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic /sup 131/I as a pre-transplantation immunosuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunosuppressive therapy. Significant differences were observed between the two groups regarding such factors as incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunosuppressive action, its administration being advised for receptors of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel.

  8. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth

    OpenAIRE

    Han Zhipeng; Jing Yingying; Zhang Shanshan; Liu Yan; Shi Yufang; Wei Lixin

    2012-01-01

    Abstract Mesenchymal stem cells (MSCs) have acquired great interests for their potential use in the clinical therapy of many diseases because of their functions including multiple lineage differentiation, low immunogenicity and immunosuppression. Many studies suggest that MSCs are strongly immunosuppressive in vitro and in vivo. MSCs exert a profound inhibitory effect on the proliferation of T cells, B cells, dendritic cells and natural killer cells. In addition, several soluble factors have ...

  9. Rat allotransplantation of epigastric microsurgical flaps: a study of rejection and the immunosuppressive effect of cyclosporin A

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    Carramaschi Fábio R.

    2000-01-01

    Full Text Available The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1 Wistar Furth isogenic donors and receptors (control set; (2 Brown Norway donors and Wistar Furth receptors (rejection set; and (3 Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set. Cyclosporin A (10 mg/kg/d treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.

  10. Cancer immunotherapy by immunosuppression

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    Prehn Liisa M

    2010-12-01

    Full Text Available Abstract We have previously suggested that the stimulatory effect of a weak immune reaction on tumor growth may be necessary for the growth of incipient tumors. In the present paper, we enlarge upon and extend that idea by collecting evidence in the literature bearing upon this new hypothesis that a growing cancer, whether in man or mouse, is throughout its lifespan, probably growing and progressing because of continued immune stimulation by a weak immune reaction. We also suggest that prolonged immunosuppression might interfere with progression and thus be an aid to therapy. While most of the considerable evidence that supports the hypothesis comes from observations of experimental mouse tumors, there is suggestive evidence that human tumors may behave in much the same way, and as far as we can ascertain, there is no present evidence that necessarily refutes the hypothesis.

  11. Immunosuppressive therapy in glomerular diseases: major accomplishment of Tadeusz Orłowski and his school.

    Science.gov (United States)

    Smogorzewski, Mirosław J; Lao, Mieczysław; Gradowska, Liliana; Rowińska, Danuta; Rancewicz, Zofia

    2009-05-01

    Glomerulopathies are the third most common cause of end-stage renal failure. Immunosuppressive treatment of glomerulonephritis in a systematic way was introduced in Poland by Professor Tadeusz Orłowski in the early 1960s. The studies were conducted at the First Department of Medicine and at the Transplantation Institute of the Medical Academy in Warsaw in the years 1962-1988. This paper critically reviews the results of studies on the use of combined, triple-drug (prednisone/chlorambucil/azathioprine), immunosuppressive protocol in various pathological forms of glomerulopathies. We conclude that immunosuppressive protocols pioneered by Tadeusz Orłowski continue to be the backbone of the treatment of glomerulonephritis, especially the one with nephrotic syndrome, progressive impairment of kidney function and poor prognosis.

  12. Survival predictors in paraquat intoxification and role of immunosuppression

    Directory of Open Access Journals (Sweden)

    Keng-Hee Koh

    2014-01-01

    In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4% compared to historical control (30 out of 52 patients (57.7% (p = 0.885 in those with eGFR > 50 ml/min/1.73 m2 or WBC 11,000/μL.

  13. Immunosuppressive medication adherence in kidney transplant patients.

    Science.gov (United States)

    Lalić, Jelena; Veličković-Radovanović, Radmila; Mitić, Branka; Paunović, Goran; Cvetković, Tatjana

    2014-01-01

    To assess the degree of immunosuppressive medication adherence in kidney transplant patients (KTPs) and to determine if there is a difference in the rate of adherence to tacrolimus (Tac), cyclosporine (CsA) and sirolimus (Sir). From a total of 63 KTPs treated at the Clinic of Nephrology, Clinical Centre Niš, Serbia, 60 participated in the study by responding to questionnaires. They were divided into the adherence group (n = 43) and the nonadherence group (n = 17) according to their degree of adherence which was measured using a validated survey form, the simplified medication adherence questionnaire. The KTP adherence to the different immunosuppressive regimens (Tac, CsA and Sir) was compared. Statistical analysis was performed using the Student t test. Adherence was observed in 43 (71.7%) patients, and only 17 (28.3%) did not follow the prescribed therapy. The estimated glomerular filtration rate was significantly lower in the nonadherence group (38.52 ± 18.22 ml/min) than in the adherence group (52.43 ± 16.91 ml/min, p adherers and the nonadherers (6.30 ± 2.06 vs. 5.0 ± 1.52 ng/ml, p adherence. Nonadherence was associated with worse graft function and a lower Tac level. Knowledge about the degree of adherence could help the early identification of nonadherent patients and the development of strategies to improve this. © 2014 S. Karger AG, Basel

  14. Biomechanical Analysis of the Swim-Start: A Review

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    Julien Vantorre, Didier Chollet, Ludovic Seifert

    2014-06-01

    Full Text Available This review updates the swim-start state of the art from a biomechanical standpoint. We review the contribution of the swim-start to overall swimming performance, the effects of various swim-start strategies, and skill effects across the range of swim-start strategies identified in the literature. The main objective is to determine the techniques to focus on in swimming training in the contemporary context of the sport. The phases leading to key temporal events of the swim-start, like water entry, require adaptations to the swimmer’s chosen technique over the course of a performance; we thus define the swim-start as the moment when preparation for take-off begins to the moment when the swimming pattern begins. A secondary objective is to determine the role of adaptive variability as it emerges during the swim-start. Variability is contextualized as having a functional role and operating across multiple levels of analysis: inter-subject (expert versus non-expert, inter-trial or intra-subject (through repetitions of the same movement, and inter-preference (preferred versus non-preferred technique. Regarding skill effects, we assume that swim-start expertise is distinct from swim stroke expertise. Highly skilled swim-starts are distinguished in terms of several factors: reaction time from the start signal to the impulse on the block, including the control and regulation of foot force and foot orientation during take-off; appropriate amount of glide time before leg kicking commences; effective transition from leg kicking to break-out of full swimming with arm stroking; overall maximal leg and arm propulsion and minimal water resistance; and minimized energy expenditure through streamlined body position. Swimmers who are less expert at the swim-start spend more time in this phase and would benefit from training designed to reduce: (i the time between reaction to the start signal and impulse on the block, and (ii the time in transition (i

  15. The role of basiliximab in the evolving renal transplantation immunosuppression protocol

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    Paola Salis

    2008-06-01

    Full Text Available Paola Salis, Chiara Caccamo, Roberto Verzaro, Salvatore Gruttadauria, Mary ArteroDivision of Nephrology and Division of Abdominal Transplantation, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, ItalyAbstract: Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2 receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR inhibitors for calcineurin inhibitors.Keywords: basiliximab, renal transplantation, IL-2 receptor antagonists, induction, immunosuppression, corticosteroids, calcineurin inhibitors

  16. Understanding alterations in drug handling with aging: a focus on the pharmacokinetics of maintenance immunosuppressants in the elderly.

    Science.gov (United States)

    Gabardi, Steven; Tullius, Stefan G; Krenzien, Felix

    2015-08-01

    This review presents current knowledge of the impact of age on the pharmacokinetics of maintenance immunosuppressants. Over the past decade, there has been a steady increase in older patients on organ transplant waiting lists. As a result, the average age of transplant recipients has significantly increased. The survival and quality-of-life benefits of transplantation in the elderly population have been demonstrated. Advancing age is associated with changes in immune responses, as well as changes in drug handling. Immunosenescence is a physiological part of aging and is linked to reduced rejection rates, but also higher rates of diabetes, infections and malignancies. Physiologic changes associated with age can have a significant impact on the pharmacokinetics of the maintenance immunosuppressive agents. Taken together, these age-related changes impact older transplant candidates and may have significant implications for managing immunosuppression in the elderly. Despite the lack of formal efficacy, safety and pharmacokinetic studies of individual immunosuppressants in the elderly transplant population, there are enough data available for practitioners to be able to adequately manage their older patients. A proficient understanding of the factors that impact the pharmacokinetics of the immunosuppressants in the elderly is essential to managing these patients successfully.

  17. The use of irradiated food for immuno-suppressed hospital patients

    International Nuclear Information System (INIS)

    Pryke, D.C.

    1994-01-01

    The treatment of leukaemia and other forms of haematological malignancies involves destruction of the bone marrow followed by bone-marrow transplant. This results in patients becoming severely immuno-suppressed. Other diseases result in a similar condition, most notably Acquired Immuno-Deficiency Syndrome (AIDS). Irradiation using radioactive sources or machines has been proposed as a method for preparing foods for immuno-suppressed patients and other high risk groups. Doses of around 30 kGy ensure a total sterility whilst a dose of 10 kGy (the recommended maximum for food available to the general public) results in a significant reduction in the number of pathogenic microorganisms. Irradiation has a number of advantages over other processing methods, in particular that flavour, texture and nutritional changes are limited. This is important as patients are often in a compromised state and need clinical assistance in returning to normal eating habits. In recognition of the potential of irradiated foods for hospital patients this use has been specifically exempted from regulatory control in the UK. This paper reviews the experience in the UK of irradiation-sterilized foods in hospitals. It was found that for practical reasons use is currently restricted. The future prospects for food irradiated at non-sterilized doses are also considered. It is concluded that as well as providing greater choice for consumers (high risk and the general public as a whole) irradiated foods could extend and improved the diets of immuno-suppressed hospital patients; this could be an important factor in recovery. (author)

  18. De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

    Directory of Open Access Journals (Sweden)

    F. Friedersdorff

    2010-04-01

    Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

  19. Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

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    JG Machado

    2010-01-01

    Full Text Available Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-γ, IL-2, IL-4 and IL-10 by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

  20. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

    2013-01-01

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

  1. Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

    Directory of Open Access Journals (Sweden)

    Nils Schoof

    Full Text Available Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs in 43 genes (39 genomic regions related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=0.0004, thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

  2. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

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    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  3. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.L.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  4. Cervical HPV prevalence and genotype distribution in immunosuppressed Danish women

    DEFF Research Database (Denmark)

    Roensbo, Mette T; Blaakær, Jan; Skov, Karin

    2018-01-01

    INTRODUCTION: Women receiving immunosuppressive treatment due to organ transplantation are at increased risk of Human papilloma virus (HPV)-related diseases, including cervical neoplasia. This pilot study aimed to describe the cervical HPV prevalence and genotype distribution in immunosuppressed...... in 2014 had three cervical cytologies performed; one before and two after transplantation. The samples were examined for cytological abnormalities and tested for HPV using Cobas(®) HPV Test and CLART(®) HPV2 Test. RESULTS: Of 94 eligible cases we included 60 RTR and BMTR. The overall prevalence of high......-risk HPV was 15.0 (95% CI; 7.1-26.6) and the prevalence was higher among BMTR (29.4, CI; 10.3-56.0) than in RTR (9.3%, CI; 2.6-22.1) although this was not statistically significant (p=0.10). The distribution of high-risk HPV was broad with HPV 45 as the most common genotype (3.3%). The prevalences of high...

  5. Factors that determine self-reported immunosuppressant adherence in kidney transplant recipients: a correlational study.

    Science.gov (United States)

    Weng, Li-Chueh; Yang, Ya-Chen; Huang, Hsiu-Li; Chiang, Yang-Jen; Tsai, Yu-Hsia

    2017-01-01

    To determine the factors related to immunosuppressant therapy adherence in kidney transplant recipients in Taiwan. Adherence to immunosuppressant treatment is critical after kidney transplantation. Thus, the factors associated with self-reported medication adherence in kidney transplant recipients warrant investigation. The study used a cross-sectional and correlation design. A convenience sample of 145 kidney transplant recipients was included. Structured questionnaires were used to collect data during 2012-2013. Multivariate linear regression was used to examine the factors related to immunosuppressant therapy adherence. Over half of the participants were female (54·5%), mean age was 45·5 years, and mean year after transplant was 7·4. The mean score for medication adherence was 29·73 (possible score range 7-35). The results of the multivariate linear regression analysis showed that gender (male), low income with a high school or college education, years after transplantation and concerns about medication taking were negatively associated with adherence. Medication self-efficacy was positively associated with adherence. Therapy-related factors, partnerships with healthcare professionals and having private healthcare insurance did not significantly relate to immunosuppressant therapy adherence. Kidney transplant recipients demonstrated a high level of adherence. Strategies to enhance patients' self-efficacy and alleviate concerns about medication may promote medication adherence. Male patients, those with a lower income and those with a higher education level, should be a focus of efforts to maintain adherence to the medication regimen. © 2016 John Wiley & Sons Ltd.

  6. Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?

    OpenAIRE

    Passweg, Jakob R.; Tichelli, André

    2009-01-01

    The combination of antithymocyte globulin of horse origin and cyclosporine A is the standard treatment for aplastic anemia in patients not eligible for bone marrow transplantation. In this perspective article, Drs. Passweg and Tichelli discuss the current immunosuppressive therapy of aplastic anemia. See related article on page 348.

  7. Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study

    OpenAIRE

    Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Ant?nio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

    2015-01-01

    Background Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Methods Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adher...

  8. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    Christine eNeudoerfl

    2013-02-01

    Full Text Available In the context of kidney transplantation, little is known about the involvement of NK cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e. calcineurin-inhibitors like CyclosporinA vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56dim NK cells was observed with significant differences between CyclosporinA- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR and increased CD94/NKG2A expression in CD56dim NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with PBMC of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and IFN--production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus,NK cells can serve as sensors

  9. Effect of β-3-Thienylalanine on Antibody Synthesis V. Immunosuppression in Mice by Short Diet and Drug Treatments

    Science.gov (United States)

    Misefari, Aldo; La Via, Mariano F.

    1971-01-01

    The analogue of phenylalanine, β-3-thienylalanine, depresses severely the primary and secondary immune response to sheep erythrocytes in mice when administered for a few days immediately before and after each injection of antigen. For this immunosuppression to occur, animals must be maintained on a phenylalanine-free diet during the times of drug injection since dietary phenylalanine will restore anamnestic response. With these experimental conditions, the number of direct and indirect plaque-forming cells is greatly reduced during immune responses. The finding that marked immunosuppression can be obtained with a very short drug and diet treatment points to a potential usefullness of the analogue as a powerful immunosuppressant. PMID:5154884

  10. [Treatment with immunosuppressive and biologic drugs of pregnant women with systemic rheumatic or autoimmune disease].

    Science.gov (United States)

    Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Ferrer-Oliveras, Raquel

    2016-10-21

    Rheumatic and systemic autoimmune diseases occur in women and, to a lesser degree, men of reproductive age. These disorders have to be clinically nonactive before conception, which is usually only possible after anti-inflammatory and immunosuppressive treatment. We must be alert since 50% of pregnancies are unplanned. Physicians should know the embryo-foetal toxicity of these drugs during pregnancy and lactation. This January 2016-updated review allows us to conclude that the majority of immunosuppressives available -anti-TNF inhibitors included- can be used before and during pregnancy, with the exception of cyclophosphamide, methotrexate, mycophenolate and leflunomide. Lactation is permitted with all drugs except methotrexate, leflunomide, mycophenolate and cyclophosphamide. Although data on abatacept, belimumab, rituximab, tocilizumab and anakinra are scant, preliminary reports agree on their safety during pregnancy and, probably, lactation. Cyclophosphamide and sulfasalazine apart, no negative effects on sperm quality, or embryo-foetal anomalies in men treated with immunosuppressives have been described. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Immunosuppression following radiation therapy for carcinoma of the nasopharynx

    International Nuclear Information System (INIS)

    Wara, W.M.; Phillips, T.L.; Wara, D.W.; Ammann, A.J.; Smith, V.

    1975-01-01

    Eleven patients treated for nasopharyngeal carcinoma with standard radiation therapy were found to have depressed cell mediated immunity. Post-treatment their total lymphocyte count was decreased by 60 percent. Eight of 11 patients had depressed T-cell rosettes, and 9 of 10 had abnormal lymphocyte response to PHA. Immunosuppression was probably related to irradiation of large blood volumes, irradiation of the thymus, and malnutrition. (U.S.)

  12. Fungemia Due to Fusarium sacchari in an Immunosuppressed Patient

    Science.gov (United States)

    Guarro, Josep; Nucci, Marcio; Akiti, Tiyomi; Gené, Josepa; Barreiro, M. Da Gloria C.; Gonçalves, Renato T.

    2000-01-01

    The fungus Fusarium sacchari was isolated repeatedly from the blood of an immunosuppressed host. The infection was treated successfully with a small dose of amphotericin B. The strain was resistant to this antifungal in vitro. MICs and minimum fungicidal concentrations of six antifungals for the clinical isolate are provided. To our knowledge, this is the first report involving this fungus in a case of fungemia. PMID:10618130

  13. Immunosuppressive sesquiterpenes from Buddleja daviddi.

    Science.gov (United States)

    Zhang, Wen; Yao, Zhi; Zhang, Yan Wen; Zhang, Xing Xiang; Takaishi, Yoshihisa; Duan, Hong Quan

    2010-11-01

    Six new sesquiterpenes, 2,6(12),10-humulatrien-7β-ol-1-one (1), 2 α-acetoxy-5α-methoxy-enantio-caryophylla-8(15)-en-3-one (2), 2α-acetoxy-5α-hydroxy-enantio-caryophylla-8(15)-en-3-one (3), 2α-acetoxy-4β,5α-hydroxy-enantio-caryophylla-8(15)-en-3-one ( 4), 2α-acetoxy-4β,5β-hydroxy-enantio-caryophylla-8(15)-en-3-one (5), 2β-acetoxy-4-caryophyllen-8β-ol-3-one (6), and nineteen known compounds were isolated from the ethanol extract of Buddleja daviddi. The structures were elucidated by spectroscopic methods. Compounds 8-11, 14, 16, 17, and 20 showed significant immunosuppressive activities, and 8-11 and 14 were cytotoxic on HeLa and L929 cell lines. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression

    International Nuclear Information System (INIS)

    Blum, J.E.; de Silva, S.M.; Rachman, D.B.; Order, S.E.

    1988-01-01

    Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity

  15. Immunosuppressive therapy in patients with aplastic anemia: a single-center retrospective study.

    Directory of Open Access Journals (Sweden)

    Hasan Jalaeikhoo

    Full Text Available Aplastic anemia (AA is a rare disease in which hematopoietic stem cells are severely diminished resulting in hypocellular bone marrow and pancytopenia. Etiology of AA includes auto immunity, toxins, infection, ionizing radiation, drugs and rare genetic disorders, but in the majority of cases no cause can be identified. In the present study we assessed response rate, survival, relapse and clonal evolution in patients with AA treated with immunosuppressive therapy.Patients with AA who received immunosuppressive therapy between May 1998 and September 2013 were included in this study. Patients with non-severe AA (NSAA were treated with cyclosporine (CsA and danazol while patients with severe AA (SAA as well as patients with NSAA who progressed to SAA after beginning of the treatment, were candidates for receiving antithymocyte globulin in addition to CsA and danazol.Among the 63 studied patients, 29 (46% had NSAA and 34 (54% had SAA. Three months after treatment, overall response was 58.6% in NSAA and 12.9% in patients with SAA. Survival of all patients at 5, 10 and 15 years were 73%, 55% and 49%, respectively. Survival rates were significantly higher in patients with NSAA compared to patients with SAA as well as in patients who responded at 6 months compared to non-responders. The relapse risk was 39.7% at 10 years. Relapse occurred in patients who discontinued the therapy more than those who continued taking CsA (p value<0.01. The risk of clonal evolution was 9.9% at 10 years and 22.8% at 15 years after treatment.This long-term retrospective study indicated that immunosuppressive therapy should be recommended to patients with AA. Also, our experience indicated that immunosuppressive therapy should not be discontinued after response to therapy in patients with both NSAA and SAA due to high risk of relapse. Low dose of CsA should be continued indefinitely.

  16. Geranylated flavonoids from the roots of Campylotropis hirtella and their immunosuppressive activities.

    Science.gov (United States)

    Shou, Qing-Yao; Fu, Run-Zhong; Tan, Qing; Shen, Zheng-Wu

    2009-08-12

    In an effort to identify new immunosuppressive agents from natural sources, 12 new geranylated flavonoids, 5,7,4'-trihydroxy-3'-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavone (1), a racemate of 5,7,2',4'-tetrahydroxy-3'-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavanone (2), 2''(S)-5,7-dihydroxy-[2''-methyl-2''-(4-methyl-3-pentenyl)pyrano]-5'',6'':3',4'-isoflavone (3), (2''S,3''R,4''S)-5,7,3'',4''-tetrahydroxy[2''-methyl-2''-(4-methyl-3-pentenyl)pyrano]-5'',6'':3',4'-isoflavone (4), a racemate of 3'-geranyl-5,7,2',4'-tetrahydroxyisoflavanone (5), a racemate of 3'-geranyl-4'-methoxy-5,7,2'-trihydroxyisoflavanone (6), 3'-geranyl-5,7,4',5'-tetrahydroxyisoflavone (8), 3'-geranyl-5,7,2',5'-tetrahydroxyisoflavone (9), 3'-geranyl-4'-methoxy-5,7,2'-trihydroxyisoflavone (10), 2(R),3(R)-3'-geranyl-2,3-trans-5,7,4'-trihydroxyflavonol (12), (2R,3R)-6-methyl-3'-geranyl-2,3-trans-5,7,4'-trihydroxyflavonol (13), and 5,7-dihydroxy-4'-O-geranylisoflavone (14), were isolated from the roots of Campylotropis hirtella (Franch.) Schindl. together with three previously described flavonoids. Their structures were elucidated by spectroscopic measurements, including two-dimensional nuclear magnetic resonance (NMR) techniques. The immunosuppressive effects of these compounds were assessed using mitogen-induced splenocyte proliferation, and the cytotoxicity of the compounds was also examined. The IC50 values of the compounds were found to be in the range of 1.49-61.23 microM for T lymphocyte suppression and 1.16-73.07 microM for B lymphocyte suppression. An analysis of their structure-activity relationships revealed that an isoflavonoid carbon skeleton with a C10 substituent at the C3' position was necessary for the activity. As many of the compounds exhibited good immunosuppressive activities, they may be promising as novel immunosuppressive agents.

  17. Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

    Science.gov (United States)

    Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M

    2011-09-01

    To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2

  18. Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy

    Institute of Scientific and Technical Information of China (English)

    Kohtaro Ooka; Joseph K.Lim

    2016-01-01

    With 185 million people chronically infected globally,hepatitis C is a leading bloodborne infection.All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable.However,trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation.Yet,these patients-most often suffering from malignancy or autoimmune diseases-could stand to benefit from these treatments.In this study,we systematically review the literature on the treatment of hepatitis C in these neglected populations.Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically.Our systematic review produced 2273 unique works,of which 56 met our inclusion criteria and were used in our review.The quality of data was low;only 3 of the 56 studies were randomized controlled trials.Sustained virologic response was reported sporadically.Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals.Severe adverse effects and death were rare.Data on all-oral regimens were sparse,but in the most robust study,rates of sustained virologic response were again comparable to immunocompetent individuals (40/41).Efficacy and safety of interferoncontaining regimens and all-oral regimens were similar to rates in immunocompetent individuals;however,there were few interventional trials.The large number of case reports and case series makes conclusions vulnerable to publication bias.While firm conclusions are challenging,given the dearth of high-quality studies,our results demonstrate that antiviral therapy can be safe and effective.The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects.Preliminary data reveal that these regimens may confer such benefits in immunosuppressed individuals as well

  19. Non-adherence to immunosuppressive medications in kidney transplantation: intent vs. forgetfulness and clinical markers of medication intake.

    Science.gov (United States)

    Griva, Konstadina; Davenport, Andrew; Harrison, Michael; Newman, Stanton P

    2012-08-01

    Although adherence to immunosupressive medication after transplantation is important to maximize good clinical outcomes it remains suboptimal and not well-understood. The purpose of this study was to examine intentional and unintentional non-adherence to immunosuppression medication in kidney transplant patients. A cross-sectional sample of N=218 patients [49.6 ± 12.3 years] recruited in London, UK (1999-2002) completed measures of medication beliefs, quality-of-life, depression, and transplantation-specific emotions. Adherence was measured with self-report and serial immunosuppressive assays. Intentional non-adherence was low (13.8 %) yet 62.4 % admitted unintentional non-adherence and 25.4 % had sub-target immunosuppressive levels. The risk of sub-target serum immunosuppressive levels was greater for patients admitting unintentional non-adherence (OR=8.4; p=0.004). Dialysis vintage, doubts about necessity, and lower worry about viability of graft explained R(2)=16.1 to 36 % of self-report non-adherence. Depression was related only to intentional non-adherence. Non-adherence is common in kidney transplantation. Efforts to increase adherence should be implemented by targeting necessity beliefs, monitoring depression, and promoting strategies to decrease forgetfulness.

  20. Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression.

    Science.gov (United States)

    Aron Badin, R; Vadori, M; Vanhove, B; Nerriere-Daguin, V; Naveilhan, P; Neveu, I; Jan, C; Lévèque, X; Venturi, E; Mermillod, P; Van Camp, N; Dollé, F; Guillermier, M; Denaro, L; Manara, R; Citton, V; Simioni, P; Zampieri, P; D'avella, D; Rubello, D; Fante, F; Boldrin, M; De Benedictis, G M; Cavicchioli, L; Sgarabotto, D; Plebani, M; Stefani, A L; Brachet, P; Blancho, G; Soulillou, J P; Hantraye, P; Cozzi, E

    2016-07-01

    Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. A targeted mutation within the feline leukemia virus (FeLV) envelope protein immunosuppressive domain to improve a canarypox virus-vectored FeLV vaccine.

    Science.gov (United States)

    Schlecht-Louf, Géraldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valérie; Poulet, Hervé; Heidmann, Thierry

    2014-01-01

    We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagation in vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the "mechanical" function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressive in vivo and that this immunosuppressive activity can be "switched off" by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-γ)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-γ/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressive in vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.

  2. aPKC-ι/P-Sp1/Snail signaling induces epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma.

    Science.gov (United States)

    Qian, Yawei; Yao, Wei; Yang, Tao; Yang, Yan; Liu, Yan; Shen, Qi; Zhang, Jian; Qi, Weipeng; Wang, Jianming

    2017-10-01

    Cholangiocarcinoma (CCA) is a highly malignant bile duct cancer that tends to invade and metastasize early. The epithelial-mesenchymal transition (EMT) has been implicated in cancer cell invasion and metastasis, as well as in cancer cell evasion of host immunity. In this study, we investigated the interaction between atypical protein kinase C-iota (aPKC-ι) and Snail in the regulation of EMT and its relationship to CCA immunosuppression. Our results demonstrated that aPKC-ι, Snail, and infiltrated immunosuppressive cells were significantly up-regulated in CCA tumor tissues and linked to poor prognosis. aPKC-ι induced EMT and immunosuppression by regulating Snail in vitro and in vivo, although aPKC-ι did not directly interact with Snail in coimmunoprecipitation experiments. To further clarify the molecular interaction between aPKC-ι and Snail in relation to EMT, quantitative iTRAQ-based phosphoproteomic analysis and liquid chromatography-tandem mass spectrometry were conducted to identify the substrates of aPKC-ι-dependent phosphorylation. Combined with coimmunoprecipitation, we showed that specificity protein 1 (Sp1) was directly phosphorylated by aPKC-ι on Ser59 (P-Sp1). Both Sp1 and P-Sp1 were up-regulated in CCA tumor tissues and associated with clinicopathological features and poor prognosis in CCA patients. Moreover, using chromatin immunoprecipitation assays, we found that P-Sp1 regulated Snail expression by increasing Sp1 binding to the Snail promoter. P-Sp1 also regulated aPKC-ι/Snail-induced EMT-like changes and immunosuppression in CCA cells. Our findings further indicated that CCA cells with EMT-like features appear to generate immunosuppressive natural T regulatory-like cluster of differentiation 4-positive (CD4 + )CD25 - cells rather than to increase CD4 + CD25 + natural T regulatory cells, in part by mediating T regulatory-inducible cytokines such as transforming growth factor β1 and interleukin 2. These results demonstrate that a

  3. Cost utility analysis of immunosuppressive regimens in adult renal transplant recipients in England and Wales

    Directory of Open Access Journals (Sweden)

    Muduma G

    2014-11-01

    Full Text Available Gorden Muduma,1 Jane Shaw,2 Warren M Hart,3 Abayomi Odeyemi,3 Isaac Odeyemi21Astellas Pharma Europe Limited, Chertsey, UK; 2Astellas Pharma Limited, Chertsey, UK; 3EcoStat Consulting UK Limited, London, UKBackground: End-stage renal disease is the irreversible final stage of chronic kidney disease and is fatal when not managed by either transplantation or dialysis. Transplantation is generally preferred over dialysis. However, to prevent graft rejection or loss, lifelong immunosuppression is required. Tacrolimus is currently the cornerstone of post-transplantation immunosuppression. The study aim was to carry out an economic evaluation of immunosuppression, including more recent agents such as a once-daily prolonged-release formulation of tacrolimus (Advagraf™ and belatacept, relative to a twice-daily immediate-release formulation of tacrolimus (Prograf™.Methods: A model was constructed comprising six states: onset of biopsy-confirmed acute rejection, functioning graft with or without a biopsy-confirmed acute rejection, non-functioning graft (dialysis, re-transplantation, and death. Data on clinical effectiveness were derived from a systematic literature review and the model captured the effects of patient adherence to immunosuppressant therapy on graft survival using relative risk of graft survival and published data on adherence in patients using Advagraf and Prograf. In the base case, the time horizon was 25 years and one-way and probabilistic sensitivity analyses were conducted.Results: The analysis demonstrated that Prograf was cost-effective when compared with cyclosporin and belatacept and was more effective than sirolimus, but would not be considered cost-effective against sirolimus. The modeled improvement in the adherence profile of patients using Advagraf relative to Prograf resulted in both improved clinical outcomes and reduced costs. Conclusion: Prograf was more clinically effective than cyclosporin, belatacept, and sirolimus

  4. Assessment of readiness for clinical decision support to aid laboratory monitoring of immunosuppressive care at U.S. liver transplant centers.

    Science.gov (United States)

    Jacobs, J; Weir, C; Evans, R S; Staes, C

    2014-01-01

    Following liver transplantation, patients require lifelong immunosuppressive care and monitoring. Computerized clinical decision support (CDS) has been shown to improve post-transplant immunosuppressive care processes and outcomes. The readiness of transplant information systems to implement computerized CDS to support post-transplant care is unknown. a) Describe the current clinical information system functionality and manual and automated processes for laboratory monitoring of immunosuppressive care, b) describe the use of guidelines that may be used to produce computable logic and the use of computerized alerts to support guideline adherence, and c) explore barriers to implementation of CDS in U.S. liver transplant centers. We developed a web-based survey using cognitive interviewing techniques. We surveyed 119 U.S. transplant programs that performed at least five liver transplantations per year during 2010-2012. Responses were summarized using descriptive analyses; barriers were identified using qualitative methods. Respondents from 80 programs (67% response rate) completed the survey. While 98% of programs reported having an electronic health record (EHR), all programs used paper-based manual processes to receive or track immunosuppressive laboratory results. Most programs (85%) reported that 30% or more of their patients used external laboratories for routine testing. Few programs (19%) received most external laboratory results as discrete data via electronic interfaces while most (80%) manually entered laboratory results into the EHR; less than half (42%) could integrate internal and external laboratory results. Nearly all programs had guidelines regarding pre-specified target ranges (92%) or testing schedules (97%) for managing immunosuppressive care. Few programs used computerized alerting to notify transplant coordinators of out-of-range (27%) or overdue laboratory results (20%). Use of EHRs is common, yet all liver transplant programs were largely

  5. Renal Transplant Recipients: The Factors Related to Immunosuppressive Medication Adherence Based on the Health Belief Model.

    Science.gov (United States)

    Kung, Pen-Chen; Yeh, Mei Chang; Lai, Ming-Kuen; Liu, Hsueh-Erh

    2017-10-01

    Kidney transplant failures are caused primarily by lack of adherence to immunosuppressive medication regimens by patients after transplantation. A number of studies have indicated that health-related beliefs are an effective predictor of health-related behavior. The aim of this study is to understand the influence of the personal characteristics and health-related beliefs of patients on adherence to treatment with immunosuppressive medication based on the Health Belief Model. This cross-sectional study distributed questionnaires to patients who had been recruited via purposive sampling at one medical center in Taipei. All of the potential participants had undergone kidney transplantation at least 6 months previously. The self-developed questionnaire collected data in three areas: personal characteristics, health-related beliefs regarding transplant rejection, and adherence to the immunosuppressive medication regimen. One hundred twenty-two valid questionnaires were received. The collected data were analyzed using descriptive statistics, independent t test, one-way analysis of variance, Pearson's correlation, and multiple regression. Participants who had received dialysis treatment or had experienced rejection perceived susceptibility to rejection more strongly than those who had not. Participants who had undergone transplantation in Taiwan, had experienced more drug-related symptoms, or had contracted severe to extremely severe infections in the past showed lower rates of adherence to treatment with immunosuppressive medication. Adherence to medication regimens correlated negatively with length of time since transplantation. Length of time since transplantation, drug-related symptoms, perceived susceptibility to rejection, and perceived benefits of treatment were identified as major predictors of adherence to immunosuppressive medication regimens. The results partially conformed to the concepts of the Health Belief Model. Perceived susceptibility to rejection and

  6. Transplantation of co-aggregates of Sertoli cells and islet cells into liver without immunosuppression.

    Science.gov (United States)

    Takemoto, Naohiro; Liu, Xibao; Takii, Kento; Teramura, Yuji; Iwata, Hiroo

    2014-02-15

    Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable. Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation. The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days. The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.

  7. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

    LENUS (Irish Health Repository)

    Olaitan, Oyedolamu K

    2010-02-01

    To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.

  8. Immunosuppressive therapy in non-infections uveitis and retinovasculitis

    OpenAIRE

    E. A. Drozdova

    2012-01-01

    Purpose: to evaluate the efficacy and safety of the immunosuppressive therapy for severe forms of non-infections uveitis and retinovasculitis.Methods: 107 patients (62 males and 45 females aged 9 to 54 years) who received low dose methotrexate — 7.5-20 mg once a week (n=79) cyclosporine A 3.5-5.0 mg/kg/d (n=21) with prednisone or other antimetabolites and local corticosteroid therapy for severe forms of inflammatory eye diseases.Results: the efficacy of methotrexate as monotherapy was 51.8% o...

  9. Directional preference and functional outcomes among subjects classified at high psychosocial risk using STarT.

    Science.gov (United States)

    Werneke, Mark W; Edmond, Susan; Young, Michelle; Grigsby, David; McClenahan, Brian; McGill, Troy

    2018-03-14

    Physiotherapy has an important role in managing patients with non-specific low back pain who experience elevated psychosocial distress or risk for chronic disability. In terms of evidence-based physiotherapy practice, cognitive-behavioural approaches for patients at high psychosocial risk are the recommended management to improve patient treatment outcomes. Evidence also suggests that directional preference (DP) is an important treatment effect modifier for prescribing specific exercises for patients to improve outcomes. Little is known about the influence of treatment techniques based on DP on outcomes for patients classified as high psychosocial risk using the Subgroups for Targeted Treatment (STarT) Back Screening Tool. This study aimed to examine the association between functional status (FS) at rehabilitation discharge for patients experiencing low back pain classified at high STarT psychosocial risk and whose symptoms showed a DP versus No-DP. High STarT risk patients (n = 138) completed intake surveys, that is, the lumbar FS of Focus On Therapeutic Outcomes, Inc., and STarT, and were evaluated for DP by physiotherapists credentialed in McKenzie methods. The FS measure of Focus On Therapeutic Outcomes, Inc., was repeated at discharge. DP and No-DP prevalence rates were calculated. Associations between first-visit DP and No-DP and change in FS were assessed using univariate and multivariate regression models controlling for 11 risk-adjusted variables. One hundred nine patients classified as high STarT risk had complete intake and discharge FS and DP data. Prevalence rate for DP was 65.1%. A significant and clinically important difference (7.98 FS points; p = .03) in change in function at discharge between DP and No-DP was observed after controlling for all confounding variables in the final model. Findings suggest that interventions matched to DP are effective for managing high psychological risk patients and may provide physiotherapists with an

  10. Why do Patients Forget to Take Immunosuppression Medications and Miss Appointments: Can a Mobile Phone App Help?

    OpenAIRE

    Israni, Ajay; Dean, Carl; Kasel, Brian; Berndt, Lisa; Wildebush, Winston; Wang, C Jason

    2016-01-01

    Background Kidney transplant recipients must adhere to their immunosuppressive medication regimen. However, non-adherence remains a major problem. Objective The aim of this paper is to determine how kidney transplant recipients remember to take their medications, and assess their perception and beliefs about adherence to immunosuppressive medications and barriers to medication adherence. In addition, we aim to assess perception and beliefs about willingness to use a hypothetical, mobile phone...

  11. Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Douglas C Heimburger

    Full Text Available BACKGROUND: Patients starting antiretroviral therapy (ART for acquired immunodeficiency syndrome (AIDS in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. METHODOLOGY/PRINCIPAL FINDINGS: An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI <16 kg/m(2 or CD4(+ lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43, compared to 1.06 mmol/L (IQR: 0.89, 1.27 among those who died (p<0.01. Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95. The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. CONCLUSIONS/SIGNIFICANCE: Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.

  12. Self-efficacy beliefs, locus of control, religiosity and non-adherence to immunosuppressive medications in kidney transplant patients.

    Science.gov (United States)

    Silva, Andresa Nascimento; Moratelli, Lucas; Tavares, Paula Liziero; Marsicano, Elisa De Oliveira; Pinhati, Renata Romanholi; Colugnati, Fernando Antonio Basile; Lucchetti, Giancarlo; Sanders-Pinheiro, Helady

    2016-11-01

    Adherence to immunosuppressive medication is essential for favourable kidney transplant outcomes. The present study aims to investigate how self-efficacy beliefs, health locus of control and religiosity are associated with adherence to immunosuppressives in post kidney transplant recipients. This is a cross-sectional study with 88 recipients with more than 1 year after transplantation. Three methods were used to classify patients as adherent or non-adherent: Basel Assessment of Adherence Scale for Immunosuppressives - BAASIS, the collateral report and blood levels of immunosuppressive medications. Self-efficacy, health locus of control, and religiosity were evaluated applying General Perceived Self-Efficacy Scale, Multidimensional Health Locus of Control Scale and Duke University Religion Index, respectively. Non-adherence was modelled by uni- and multivariated analysis. Sixty-three percent of the patients were male, age 47.2 ± 12.9 years, and median post-transplant time 108.71 (49.0-266.0) months. We found 70.5% of patients were non-adherent through at least one method. Adherent patients presented higher self-efficacy scores (45.1 ± 4.9 vs 38.3 ± 8.6; P locus of control (OR 1.23, IC 1.04-1.45, P = 0.016) and lower intrinsic religiosity (OR 0.56, IC 0.38-0.84, P = 0.006). Our study showed that self-efficacy, chance locus of control, and intrinsic religiosity were associated with non-adherence to immunosuppressives. A broader perception of the kidney transplant patient´s integrality can help health professionals to design strategies to promote adherence in this population. © 2015 Asian Pacific Society of Nephrology.

  13. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

    Science.gov (United States)

    Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

    2011-11-15

    The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

  14. Abnormal chest shadow on CT in immunosuppressed patients

    International Nuclear Information System (INIS)

    Tanaka, Nobuyuki; Matsumoto, Tsuneo; Nakamura, Hiroshi

    1992-01-01

    An abnormal chest shadow was observed on CT scans in 25 cases of 23 immunosuppressed patients. Pulmonary disease was pathologically confirmed to be pneumocystis carinii pneumonia (PC pneumonia) in four patients, cytomegalovirus pneumonia (CMV pneumonia) in one, bacterial pneumonia in seven, fungal infection in three, miliary tuberculosis in one, leukemic infiltration in two, lymphangitis carcinomatosa in three, drug-induced pneumonitis in three, and ARDS in one. In almost all patients, especially those with infectious diseases such as PC pneumonia, CMV pneumonia, and bacterial pneumonia, the abnormal shadow was wide and visible in the bilateral lung fields. We presumed that such findings as lobular shadow, centrilobular shadow, and mosaic pattern reflected the extension of disease via the respiratory tract, and that those findings are typical of infectious diseases. Because such findings as abnormal linear shadow and swelling of a broncho-vascular bundle were very frequently recognized in patients with lymphangitis carcinomatosa and frequently recognized in those with drug-induced pneumonitis, these diseases may be distinguished from other diseases. An area of slightly increased density was frequently recognized in patients with PC pneumonia, bacterial pneumonia, and drug-induced pneumonitis. Such lesions were pathologically confirmed to be located in the interstitium and/or alveolus. CT was extremely useful in comprehending the character and extension of particular diseases among various diseases. As the number of patients studied was small, the utility of CT in immunosuppressed patients requires further investigation in a larger number of patients. (author)

  15. Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.

    Science.gov (United States)

    Krenzien, F; Quante, M; Heinbokel, T; Seyda, M; Minami, K; Uehara, H; Biefer, H R C; Schuitenmaker, J M; Gabardi, S; Splith, K; Schmelzle, M; Petrides, A K; Azuma, H; Pratschke, J; Li, X C; ElKhal, A; Tullius, S G

    2017-05-01

    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 compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4 + T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4 + T cells more effectively while inhibiting the proliferation of CD4 + T cells in old mice. Both TAC-treated murine and human CD4 + T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca 2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8 + T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4 + T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4 + T cell mediated. The suppression of calcineurin levels and Ca 2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  16. [Mechanisms of retroviral immunosuppressive domain-induced immune modulation].

    Science.gov (United States)

    Blinov, V M; Krasnov, G S; Shargunov, A V; Shurdov, M A; Zverev, V V

    2013-01-01

    Immunosuppressive domains (ISD) of viral envelope glycoproteins provide highly pathogenic phenotypes of various retroviruses. ISD interaction with immune cells leads to an inhibition of a response. In the 1980s it was shown that the fragment of ISD comprising of 17 amino acids (named CKS-17) is carrying out such immune modulation. However the underlying mechanisms were not known. The years of thorough research allowed to identify the regulation of Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR cellular pathways as a result of ISD interaction with immune cells. By the way, this leads to decrease of secretion of stimulatory cytokines (e.g., IL-12) and increase of inhibitory, anti-inflammatory ones (e.g., IL-10). One of the receptor tyrosine kinases inducing signal in these pathways acts as the primary target of ISD while other key regulators--cAMP and diacylglycerol (DAG), act as secondary messengers of signal transduction. Immunosuppressive-like domains can be found not only in retroviruses; the presence of ISD within Ebola viral envelope glycoproteins caused extremely hard clinical course of virus-induced hemorrhagic fever. A number of retroviral-origin fragments encoding ISD can be found in the human genome. These regions are expressed in the placenta within genes of syncytins providing a tolerance of mother's immune system to an embryo. The present review is devoted to molecular aspects of retroviral ISD-induced modulation of host immune system.

  17. Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

    Science.gov (United States)

    Kurti, Zsuzsanna; Lovasz, Barbara Dorottya; Gecse, Krisztina Barbara; Balint, Anita; Farkas, Klaudia; Morocza-Szabo, Agnes; Gyurcsanyi, Andras; Kristof, Katalin; Vegh, Zsuzsanna; Gonczi, Lorant; Kiss, Lajos Sandor; Golovics, Petra Anna; Lakatos, Laszlo; Molnar, Tamas; Lakatos, Peter Laszlo

    2015-12-01

    There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

  18. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients.

    Science.gov (United States)

    Fairfield, Cameron; Penninga, Luit; Powell, James; Harrison, Ewen M; Wigmore, Stephen J

    2018-04-09

    Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017. Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed-effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a

  19. In Silico Characterization and Structural Modeling of Dermacentor andersoni p36 Immunosuppressive Protein

    Directory of Open Access Journals (Sweden)

    Martin Omulindi Oyugi

    2018-01-01

    Full Text Available Ticks cause approximately $17–19 billion economic losses to the livestock industry globally. Development of recombinant antitick vaccine is greatly hindered by insufficient knowledge and understanding of proteins expressed by ticks. Ticks secrete immunosuppressant proteins that modulate the host’s immune system during blood feeding; these molecules could be a target for antivector vaccine development. Recombinant p36, a 36 kDa immunosuppressor from the saliva of female Dermacentor andersoni, suppresses T-lymphocytes proliferation in vitro. To identify potential unique structural and dynamic properties responsible for the immunosuppressive function of p36 proteins, this study utilized bioinformatic tool to characterize and model structure of D. andersoni p36 protein. Evaluation of p36 protein family as suitable vaccine antigens predicted a p36 homolog in Rhipicephalus appendiculatus, the tick vector of East Coast fever, with an antigenicity score of 0.7701 that compares well with that of Bm86 (0.7681, the protein antigen that constitute commercial tick vaccine Tickgard™. Ab initio modeling of the D. andersoni p36 protein yielded a 3D structure that predicted conserved antigenic region, which has potential of binding immunomodulating ligands including glycerol and lactose, found located within exposed loop, suggesting a likely role in immunosuppressive function of tick p36 proteins. Laboratory confirmation of these preliminary results is necessary in future studies.

  20. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  1. Pharmacodynamic Monitoring of Tacrolimus-based Immunosuppression in CD14+ Monocytes after Kidney Transplantation

    NARCIS (Netherlands)

    N.M. Kannegieter (Nynke); D.A. Hesselink (Dennis); M. Dieterich (Marjolein); G.N. de Graav (Gretchen); R. Kraaijeveld (Rens); A.T. Rowshani (Ajda); P.J. Leenen (Pieter); C.C. Baan (Carla)

    2017-01-01

    markdownabstractBackground: Monocytes significantly contribute to ischemia-reperfusion injury and allograft rejection after kidney transplantation. However, the knowledge about the effects of immunosuppressive drugs on monocyte activation is limited. Conventional pharmacokinetic methods for

  2. Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer

    NARCIS (Netherlands)

    J. Jans (Judith); G.A. Garinis (George); W. Schul; A. van Oudenaren (Adri); M.J. Moorhouse (Michael); M. Smid (Marcel); Y.-G. Sert (Yurda-Gul); A. van der Velde (Albertina); Y.M. Rijksen (Yvonne); F.R. de Gruijl (Frank); P.J. van der Spek (Peter); A. Yasui (Akira); J.H.J. Hoeijmakers (Jan); P.J. Leenen (Pieter); G.T.J. van der Horst (Gijsbertus)

    2006-01-01

    textabstractCyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type

  3. Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression

    OpenAIRE

    Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

    2016-01-01

    Background To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Methods Retrospective multicenter study using the Swiss ...

  4. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    International Nuclear Information System (INIS)

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-01-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease

  5. Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice.

    OpenAIRE

    Bartlett, M S; Edlind, T D; Lee, C H; Dean, R; Queener, S F; Shaw, M M; Smith, J W

    1994-01-01

    Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150...

  6. Surveillance of polyomavirus BK in relation to immunosuppressive therapy in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cristina Costa

    2012-03-01

    Full Text Available Introduction. Reactivation of polyomavirus BK in kidney transplant recipients has been associated to the development of nephropathy (polyomavirus-associated nephropathy, PVAN, possibly leading to the loss of the transplanted organ. Immunosuppression is the condicio sine qua non for the onset of PVAN; however, a lower incidence of BK viremia has been reported with low-level tacrolimus based immunosuppressive protocols in comparison to cyclosporine A.Aim of this study was to compare the two immunosuppressive protocols. Methods. Virological monitoring of BK was performed in 468 consecutive renal transplant patients over a period of 3 years (2370 urine e 2370 serum specimens: in particular, 1780 specimens from 362 patients treated with tacrolimus and 590 from 106 treated with cyclosporine A. Results. BK viremia was evidenced in 124 (7.0% and 12 (2.0% specimens from 40 (11.0% and 11 (10.4% patients treated with tacrolimus and cyclosporine A, respectively; similarly, BK viruria in 289 (16.2% and 58 (9.8% specimens from 67 (18.5% and 27 (25.5% patients, being the difference of incidence highly significant (p <0.0001 for both viremia and viruria at comparison between specimens and not significant for patients. No case of PVAN was diagnosed at histophatology evaluation. Conclusions. The incidence of viremia and viruria was similar to that previously reported. Our results evidenced that with low-level tacrolimus-based protocols the overall incidence of reactivation in renal transplant patients is not significantly different and there is no increased risk of PVAN, nevertheless the higher incidence of episodes of reactivation.

  7. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

    OpenAIRE

    Seto, Wai-Kay

    2015-01-01

    Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negati...

  8. Forging a link between oncogenic signaling and immunosuppression in melanoma.

    Science.gov (United States)

    Khalili, Jahan S; Hwu, Patrick; Lizée, Gregory

    2013-02-01

    Immunosuppressive tumor microenvironments limit the efficacy of T cell-based immunotherapy. We have recently demonstrated that the inhibition of BRAF V600E with vemurafenib relieves interleukin-1 (IL-1)-induced T-cell suppression as mediated by melanoma tumor associated fibroblasts (TAFs). These results suggest that inhibitors of the MAPK pathway in combination with T cell-based immunotherapies may induce long-lasting and durable responses.

  9. Hidden sources of grapefruit in beverages: potential interactions with immunosuppressant medications.

    Science.gov (United States)

    Auten, Ashley A; Beauchamp, Lauren N; Joshua Taylor; Hardinger, Karen L

    2013-06-01

    The interaction between grapefruit-containing beverages and immunosuppressants is not well defined in the literature. This study was conducted to investigate possible sources of grapefruit juice or grapefruit extract in common US-manufactured beverages. The goal was to identify those products that might serve as hidden sources of dietary grapefruit intake, increasing a transplant patient's risk for drug interactions. A careful review of the ingredients of the 3 largest US beverage manufacturer's product lines was conducted through manufacturer correspondence, product labeling examination, and online nutrition database research. Focus was placed on citrus-flavored soft drinks, teas, and juice products and their impact on a patient's immunosuppressant regimens. Twenty-three beverages were identified that contained grapefruit. Five did not contain the word "grapefruit" in the product name. In addition to the confirmed grapefruit-containing products, 17 products were identified as possibly containing grapefruit juice or grapefruit extract. A greater emphasis should be placed upon properly educating patients regarding hidden sources of grapefruit in popular US beverages and the potential for food-drug interactions.

  10. The release of immunosuppressive factor(s) in young males following exercise.

    Science.gov (United States)

    Tian, Ye; Nie, Jinlei; Tong, Tom K; Baker, Julien S

    2012-01-01

    It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years) were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th-9th min post-exercise eluates (P exercise may lead to generation of immunosuppressive factor(s) in young males.

  11. The Release of Immunosuppressive Factor(s in Young Males Following Exercise

    Directory of Open Access Journals (Sweden)

    Julien S. Baker

    2012-05-01

    Full Text Available It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years were taken before and immediately after ten sets of exercise consisting of 15 free and 30 10-kg loaded squat jumps in each set. The suppression of lymphocyte proliferation was analysed with high pressure liquid chromatography. It was noted from the result of gel chromatography columns that the post-exercise values of the suppression of lymphocyte proliferation, in comparison to corresponding pre-exercise values, were generally greater with significant differences observed in 7.5th–9th min post-exercise eluates (P < 0.05. Such findings suggest that intense eccentric type exercise may lead to generation of immunosuppressive factor(s in young males.

  12. Sequential kidney/islet transplantation using prednisone-free immunosuppression.

    Science.gov (United States)

    Kaufman, Dixon B; Baker, Marshall S; Chen, Xiaojuan; Leventhal, Joseph R; Stuart, Frank P

    2002-08-01

    Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet-after-kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8-10,000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet-after-kidney transplantation is described using the steroid-free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265,888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95% (trypan blue exclusion); and d) mean islet potency (static low-high glucose challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty-four-hour continuous glucose monitoring confirmed moment-to-moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

  13. CEFTRIAXONE EFFICIENCY AMONG PATIENTS, SUFFERING FROM JUVENILE ARTHRITIS AND RECEIVING IMMUNOSUPPRESSIVE THERAPY

    Directory of Open Access Journals (Sweden)

    A.M. Chomakhidze

    2007-01-01

    Full Text Available The article is dedicated to diagnostics and treatment of infectious complications among children with juvenile rheumatoid arthritis, receiving immunosuppressive therapy. The research involves 92 children with different variants of the illness run, who received immunosuppressive therapy. All the patients showed development of the systemic inflammatory response manifestations. The researchers used the definition of the procalcytonine levels as a marker for the bacterial infectiondevelopment. All the patients showed it higher than 0,5 ng/ml, while 7 patients — higher than 10 ng/ml. keeping in mind several courses of the antibacterial therapy in the anamnesis and presence of the combined bacterial infection, ceftriaxone was prescribed to all the children. As a result of the ceftriaxone based therapy, reduction of the clinical and laboratory manifestations of the bacterial infection was noted among more than 90% of patients. The development of the allergic reaction was noted in 1 case, and leukopenia was also found in 1 patient.Key words: children, juvenile rheumatoid arthritis, ceftriaxone.

  14. Pulmonary aspergillosis in immunosuppressed patients with haematological malignancies.

    Science.gov (United States)

    Spearing, R L; Pamphilon, D H; Prentice, A G

    1986-06-01

    Invasive pulmonary aspergillosis as a cause of mortality and morbidity in patients with haematological malignancies is becoming more common. Predisposing factors are powerful immunosuppressive chemotherapy, neutropenia and synergistic combinations of antibiotics of great potency and wide spectrum of activity. Clinical and radiological signs are heterogeneous, sometimes misleading and often absent. Treatment is often empirical on suspicion alone. Amphotericin B is the only effective drug but it has marked toxicity, mainly renal. Infection is usually fatal without adequate treatment. This paper describes eight cases of invasive pulmonary aspergillosis seen in one centre in two years, reviews the literature and assesses associated problems.

  15. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    Science.gov (United States)

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

  16. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

    Science.gov (United States)

    Salinas-Carmona, Mario Cesar; Rosas-Taraco, Adrian Geovanni; Welsh, Oliverio

    2012-10-01

    Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma.

  17. Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

    Science.gov (United States)

    Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

    2012-07-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

  18. Start-up of spherical tokamak without a center solenoid

    International Nuclear Information System (INIS)

    Maekawa, Takashi; Nagata, Masayoshi

    2012-01-01

    For low-aspect tokamak reactors, spherical tokamak reactors, ST-type FESF/CTFs, it is essential to remove or minimize a central solenoid (CS). Even with the minimized CS, non-inductive start up of the plasma current is required. Rapid increase in the spontaneous plasma current at the final stage of current start-up drives ignition. At the initial stage, formation of plasma and magnetic surfaces are required. As non-inductive plasma start-up scenarios, ECH/ECCD, LHCD, HHFW, DC HELICITY injection, plasma merging and NBI have been studied. In the present article, the present status and future prospect of experimental and theoretical works on these subjects. (author)

  19. Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin

    Energy Technology Data Exchange (ETDEWEB)

    Murahashi, Masataka; Simizu, Siro; Morioka, Masahiko [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan); Umezawa, Kazuo, E-mail: umezawa@aichi-med-u.ac.jp [Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195 (Japan)

    2016-08-05

    15-Deoxyspergualin (DSG) is an immunosuppressive agent being clinically used. Unlike tacrolimus and cyclosporine A, it does not inhibit the calcineurin pathway, and its mechanism of action and target molecule have not been elucidated. Therefore, we previously prepared biotinylated derivative of DSG (BDSG) to fish up the target protein. In the present research, we identified poly(rC) binding protein 2 (PCBP2) as a DSG-binding protein using this probe. DSG was confirmed to bind to PCBP2 by pull-down assay. Intracellular localization of PCBP2 was changed from the nucleus to the cytoplasm by DSG treatment. DSG inhibited the cell growth, and over-expression of PCBP2 reduced the anti-proliferative activity of DSG. PCBP2 is known to regulate various proteins including STAT1/2. Thus, we found PCBP2 as the first target protein of DSG that can explain the immunosuppressive activity. -- Highlights: •Fifteen-deoxyspergualin (DSG) is an immunosuppressive agent clinically used. •We have identified PCBP2, an RNA-binding protein, as a molecular target of DSG. •Alteration of PCBP2 activity may explain the immunosuppressive activity of DSG.

  20. Exploring risk factors of non-adherence to immunosuppressive medication in kidney transplant recipients : improving methodology & reorienting research goals

    OpenAIRE

    Denhaerynck, Kris

    2006-01-01

    8.1. Background and aim of the research program Non-adherence to the immunosuppressive therapy is an important issue in kidney transplant patients. About 20% of the kidney transplant patients are non-adherent to the immunosuppressive regimen. Non-adherence contributes to 20% of late acute rejection episodes and 16% of the graft losses, and results in a decreased number of quality adjusted life years. A strategy to increase long-term successful outcome after transplantation i...

  1. Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Elisa Oliveira Marsicano

    Full Text Available Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system.Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods (self-report [i.e., The Basel Adherence Scale for Assessment of Immunossupressives-BAASIS], collateral report, and immunosuppressive blood levels. Multilevel correlations of non-adherence were assessed (macro, meso, micro and patient level. Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence.Our sample consisted primarily of male (65%, Caucasians (72% with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%, with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages (21.6 vs. 4%; OR 6.46 [1.35-30.89], p = 0.009; patient level, and having access to private health insurance (35.3% vs. 18.4%; OR 2.42 [0.96-6.10], p = 0.04; meso level were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model (OR 5.0; IC: 1.01-25.14; p = 0.04.Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously.

  2. Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study.

    Science.gov (United States)

    Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Antônio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

    2015-01-01

    Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods (self-report [i.e., The Basel Adherence Scale for Assessment of Immunossupressives-BAASIS], collateral report, and immunosuppressive blood levels). Multilevel correlations of non-adherence were assessed (macro, meso, micro and patient level). Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence. Our sample consisted primarily of male (65%), Caucasians (72%) with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%), with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages (21.6 vs. 4%; OR 6.46 [1.35-30.89], p = 0.009; patient level), and having access to private health insurance (35.3% vs. 18.4%; OR 2.42 [0.96-6.10], p = 0.04; meso level) were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model (OR 5.0; IC: 1.01-25.14; p = 0.04). Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously.

  3. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    Science.gov (United States)

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia. Copyright© Ferrata Storti Foundation.

  4. Risk of Herpes Zoster and Disseminated Varicella Zoster in Patients Taking Immunosuppressant Drugs at the Time of Zoster Vaccination.

    Science.gov (United States)

    Cheetham, T Craig; Marcy, S Michael; Tseng, Hung-Fu; Sy, Lina S; Liu, In-Lu Amy; Bixler, Felicia; Baxter, Roger; Donahue, James G; Naleway, Allison L; Jacobsen, Steven J

    2015-07-01

    To determine the risks associated with zoster vaccine when administered to patients taking immunosuppressant medications. Patients enrolled in 1 of 7 managed care organizations affiliated with the Vaccine Safety Datalink between January 1, 2006, and December 31, 2009, were eligible. The exposure of interest was zoster vaccination in patients with current or remote immunosuppressant drug use. The primary outcomes were disseminated varicella zoster virus (VZV) and herpes zoster in the 42 days after vaccination. Automated data were collected on immunosuppressant drugs and baseline medical conditions. A logistic regression model using inverse probability treatment weights was used to estimate the odds of developing VZV or herpes zoster. A total of 14,554 individuals had an immunosuppressant medication dispensed around the time of vaccination, including 4826 with current use and 9728 with remote use. Most patients were taking low-dose corticosteroids. No cases of disseminated VZV were found in the current or remote users. The risk of herpes zoster was elevated in the 42 days after vaccination in current vs remote users (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70). We found that patients taking immunosuppressant medications at the time of vaccination had a modest increased risk of herpes zoster in the 42 days after vaccination. The development of herpes zoster within 42 days after vaccination suggests that this is more likely due to reactivation of latent zoster virus than dissemination of the vaccine-derived varicella virus. These findings support the current zoster vaccination guidelines. Copyright © 2015 Mayo Foundation for Medical Education and Research. All rights reserved.

  5. Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

    LENUS (Irish Health Repository)

    Gabardi, Steven

    2011-09-01

    To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.

  6. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

    Science.gov (United States)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

    2012-07-05

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

  7. Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

    Science.gov (United States)

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  8. A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Atiyah Patel

    2016-01-01

    Full Text Available Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi’s sarcoma.

  9. A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

    Science.gov (United States)

    Patel, Atiyah; Mudenda, Victor; Lakhi, Shabir; Ngalamika, Owen

    2016-01-01

    Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi's sarcoma. PMID:26881148

  10. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    Science.gov (United States)

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  11. Improving NPT safeguards. Particularly at the natural uranium starting point

    International Nuclear Information System (INIS)

    Harry, J.; Klerk, P. de

    1996-03-01

    According to the Non Proliferation Treaty (NPT) all nuclear material is subject to safeguards, but according to INFCIRC/153 the full range of safeguards is only applied beyond the 'starting point of safeguards', that is: The point at which nuclear material has reached a composition and purity suitable for fuel fabrication or enrichment. This paper addresses the two questions: (a) is the starting point adequately defined, and (b) what mesures could be applied to nuclear material before the starting point? Those questions have been asked before, some of the answers in this paper are new. (orig.)

  12. Improving NPT safeguards. Particularly at the natural uranium starting point

    Energy Technology Data Exchange (ETDEWEB)

    Harry, J. [Netherlands Energy Research Foundation (ECN), Petten (Netherlands); Klerk, P. de [Ministry of Foreign Affairs, The Hague (Netherlands)

    1996-03-01

    According to the Non Proliferation Treaty (NPT) all nuclear material is subject to safeguards, but according to INFCIRC/153 the full range of safeguards is only applied beyond the `starting point of safeguards`, that is: The point at which nuclear material has reached a composition and purity suitable for fuel fabrication or enrichment. This paper addresses the two questions: (a) is the starting point adequately defined, and (b) what mesures could be applied to nuclear material before the starting point? Those questions have been asked before, some of the answers in this paper are new. (orig.).

  13. Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy

    International Nuclear Information System (INIS)

    Martins, Flavia Paiva Proenca; Gutfilen, Bianca

    2001-01-01

    Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed 99m Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

  14. Microwave – assisted reduction of racemic intermediates potential immunosuppressant

    Directory of Open Access Journals (Sweden)

    Wender A. Silva

    2012-06-01

    Full Text Available Immunosuppressant are drugs that reduce the immune response, as important in the treatment of autoimmune diseases and rejection attenuators in organ transplants, the structural point of view generally have a high complexity. Within this context it is indispensable structural simplifications, new molecules are proposed with potential action on a stage is a necessary, reduction system α,β-unsaturated specifically, chalcone, to their respective alcohol saturated. Therefore, a new method was developed for microwave assisted subsequently coupling to other fragments to the total synthesis of the novel compounds.

  15. Acute Hepatitis E Virus infection with coincident reactivation of Epstein-Barr virus infection in an immunosuppressed patient with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Schultze, Detlev; Mani, Bernhard; Dollenmaier, Günter; Sahli, Roland; Zbinden, Andrea; Krayenbühl, Pierre Alexandre

    2015-10-29

    Hepatitis E virus (HEV) is the most recently discovered of the hepatotropic viruses, and is considered an emerging pathogen in developed countries with the possibility of fulminant hepatitis in immunocompromised patients. Especially in the latter elevated transaminases should be taken as a clue to consider HEV infection, as it can be treated by discontinuation of immunosuppression and/or ribavirin therapy. To our best knowledge, this is a unique case of autochthonous HEV infection with coincident reactivation of Epstein-Barr virus (EBV) infection in an immunosuppressed patient with rheumatoid arthritis (RA). A 68-year-old Swiss woman with RA developed hepatitis initially diagnosed as methotrexate-induced liver injury, but later diagnosed as autochthonous HEV infection accompanied by reactivation of her latent EBV infection. She showed confounding serological results pointing to three hepatotropic viruses (HEV, Hepatitis B virus (HBV) and EBV) that could be resolved by detection of HEV and EBV viraemia. The patient recovered by temporary discontinuation of immunosuppressive therapy. In immunosuppressed patients with RA and signs of liver injury, HEV infection should be considered, as infection can be treated by discontinuation of immunosuppression. Although anti-HEV-IgM antibody assays can be used as first line virological tools, nucleic acid amplification tests (NAAT) for detection of HEV RNA are recommended--as in our case--if confounding serological results from other hepatotropic viruses are obtained. After discontinuation of immunosuppressive therapy, our patient recovered from both HEV infection and reactivation of latent EBV infection without sequelae.

  16. Ultraviolet spectral energy differences affect the ability of sunscreen lotions to prevent ultraviolet-radiation-induced immunosuppression

    International Nuclear Information System (INIS)

    Roberts, L.K.; Beasley, D.G.; Learn, D.B.; Giddens, L.D.; Beard, J.; Stanfield, J.W.

    1996-01-01

    Acute exposure to UV radiation causes immunosuppression of contact hypersensitivity (CH) responses. Past studies conducted with unfiltered sunlamps emitting non-solar spectrum UV power (wavelengths below 295 nm) or using excessive UV doses have suggested sunscreens may not prevent UV-induced immunosuppression in mice. This study was thus designed to evaluate critically the effects of different UV energy spectra on the immune protection capacity of sunscreen lotions. Minimum immune suppression doses (MISD), i.e. the lowest UV dose to cause ∼ 50% suppression of the CH response to dinitrofluorobenzene in C3H mice, were established for three artificial UV sources. The MISD for each UV source was 0.25 kJ/m 2 for unfiltered FS20 sunlamps (FS), 0.90 kJ/m 2 for Kodacel-filtered FS20 sunlamps (KFS), which do not emit UV power at wavelengths 2 for a 1000 W filtered xenon arc lamp solar simulator. Using MISD as baseline, sunscreens with labeled sun protection factors (SPF) of 2, 8, 15 and 30 were tested with each UV source to establish their relative immune protection factors. The immune protection factor of each sunscreen exceeded its labeled SPF in tests conducted with the solar simulator, which has a UV power spectrum (295-400 nm) similar to that of sunlight. Conversely, sunscreen immune protection factors were significantly less than the labeled SPF in tests conducted with FS and KFS. Comparison of the immunosuppression effectiveness spectra showed that relatively small amounts of nonsolar spectrum UV energy, i.e. UVC (200-290 nm) and/or shorter wavelength UVB (between 290 and 295 nm), produced by FS and KFS contributes significantly to the induction of immunosuppression. (Author)

  17. Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival

    International Nuclear Information System (INIS)

    Burkhardt, K.; Loughnan, M.S.; Diamantstein, T.; Mandel, T.E.

    1988-01-01

    Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes

  18. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  19. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  20. Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia

    Science.gov (United States)

    Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Hama, Asahito; Kawashima, Nozomu; Wang, Xinan; Narita, Atsushi; Doisaki, Sayoko; Xu, Yinyan; Muramatsu, Hideki; Yoshida, Nao; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Nakamura, Kazuhiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2014-01-01

    Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5–16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41–69%) and 97% (95%CI: 87–99%), respectively. Median telomere length in responders was −0.4 standard deviation (SD) (−2.7 to +3.0 SD) and −1.5 SD (−4.0 to +1.6 (SD)) in non-responders (Paplastic anemia. PMID:24816243

  1. Monitoring the patient off immunosuppression. Conceptual framework for a proposed tolerance assay study in liver transplant recipients.

    Science.gov (United States)

    Thomson, A W; Mazariegos, G V; Reyes, J; Donnenberg, V S; Donnenberg, A D; Bentlejewski, C; Zahorchak, A F; O'Connell, P J; Fung, J J; Jankowska-Gan, E; Burlingham, W J; Heeger, P S; Zeevi, A

    2001-10-27

    The mission of the recently established Immune Tolerance Network includes the development of protocols for the induction of transplant tolerance in organ allograft recipients and the development of assays that correlate with and may be predictive of the tolerant state. The state of clinical organ transplant tolerance seems to already exist in a small minority of conventionally immunosuppressed liver and, more rarely, kidney transplant patients. Immunosuppressive drug therapy has been withdrawn from these patients for a variety of reasons, including protocolized weaning for a uniquely large group of liver patients at the University of Pittsburgh. In this study, we propose to evaluate the validity of a variety of in vitro immunologic and molecular biologic tests that may correlate with, and be predictive of, the state of organ transplant tolerance in stable liver patients off immunosuppression. Only peripheral blood will be available for the execution of these tests. Both adult and pediatric liver graft recipients will be studied, in comparison to appropriate controls. We shall examine circulating dendritic cell (DC) subsets [precursor (p) DC1 and p DC2] including cells of donor origin, and assess both the frequency and function of donor-reactive T cells by ELISPOT and by trans-vivo delayed-type hypersensitivity analysis in a surrogate murine model. Cytokine gene polymorphism and alloantibody titers will also be investigated. It is anticipated that the results obtained may provide physicians with a tolerance assay "profile" that may determine those patients from whom immunosuppressive therapy may be safely withdrawn.

  2. CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    International Nuclear Information System (INIS)

    Wang, Ding; Chen, Ke; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying

    2010-01-01

    Here, the effect of CD14 + monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-γ (IFN-γ) secretion capacities of CD4 + and CD8 + T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E 2 (PGE 2 ) as an important soluble mediator. CD14 + monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1β, either exogenously added or produced by CD14 + monocytes in culture, could trigger expression of high levels of PGE 2 by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE 2 expression, but also reversed the promotional effect of CD14 + monocytes and partially restored CD4 + and CD8 + T cell proliferation and IFN-γ secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  3. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.

    Science.gov (United States)

    van Gelder, Teun; Gabardi, Steven

    2013-08-01

    Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  4. Shift concept for starting clutch in powershift transmission; Schaltkonzept fuer Anfahrkupplungen in Lastschaltgetrieben

    Energy Technology Data Exchange (ETDEWEB)

    Grad, Karl; Cappellaro, Thomas [ZF Friedrichshafen AG, Passau (Germany); Oberbuchner, Thomas

    2013-07-15

    In powershift transmissions for tractors the starting clutch represents a core assembly, which is subjected to the highest stresses in use. ZF Friedrichshafen introduces a design in which the thermal stress on the starting clutches can be significantly reduced by changing the clutch actuation. This enables the starting clutches to be dimensioned substantially lighter or to save more space or their function can even be integrated into the powershift clutches.

  5. Clinical aspects of immunosuppression in poultry

    Directory of Open Access Journals (Sweden)

    Rеsаnоvić Rаdmilа

    2015-01-01

    Full Text Available Immunity is ability to stop an infection. Immunosupression is a status where the immunity is reduced. Humoral (antibodies and/or cell immunity may be depressed. Immunosupression can be caused by infectious agents, improper feeding balance (deficiencies, lack of biosecurity, management failures, stress or by a combination of these factors. Each of these possible causes must be seriously worked out to prevent the consequences of immunosupression on profitability. Environmental factors and numerous infectious pathogens have been identified as a multi-factorial cause of various degrees of immunosupression. Mainly subclinical character and coinfections make the diagnosis of the primary immunosuppressive agents difficult. On the other hand, early diagnosis and identification of contributing factors are important to develop strategies to fight immunosupression in birds successfully. A combination of biosecurity measures, optimized housing condition and stress reduction together with appropriate vaccination strategies is necessary for the successful control of immunosupression in commercial poultry.

  6. Selective immunosuppression by radiation

    International Nuclear Information System (INIS)

    Chanana, A.D.; Cronkite, E.P.; Joel, D.D.

    1976-01-01

    The historical aspects of selective irradiation of lymphocytes are reviewed as well as the problems concerned with dosimetry and the radiosensitivity of circulating blood elements other than lymphocytes. The possibilities of perturbations in steady-state lymphocytopoiesis which might be triggered by products of radiation-induced cell death are presented; however, the parameters investigated thus far, such as the degree of lymphocytopenia, thoracic duct lymphocyte output, and cell-cycle times of thoracic duct lymphocytes, have failed to reveal any such perturbations. Studies in adrenalectomized calves have failed to confirm the notion that lymphocytopenia after extracorporeal irradiation of blood and lymph might primarily be accounted for by stress-induced corticosteroid hormonal activity. Of the various techniques, only local-graft irradiation and extracorporeal irradiation of blood (ECIB) have found clinical application. The results obtained are encouraging and indicate a need for additional, well-controlled clinical trials, especially concerning the role of ECIB as an adjunct to standard immunosuppressive therapy. The experimental results with extracorporeal irradiation of lymph have also established the potential of this technique for clinical application. There is an urgent need for studying the influence of irradiation on various subpopulations of lymphocytes with regard to their functional capabilities and in particular with regard to their reproductive potential. Possible influence of selective blood irradiation on circulating stem cells in blood needs to be evaluated

  7. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  8. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  9. Richter transformation driven by Epstein-Barr virus reactivation during therapy-related immunosuppression in chronic lymphocytic leukaemia.

    Science.gov (United States)

    García-Barchino, Maria J; Sarasquete, Maria E; Panizo, Carlos; Morscio, Julie; Martinez, Antonio; Alcoceba, Miguel; Fresquet, Vicente; Gonzalez-Farre, Blanca; Paiva, Bruno; Young, Ken H; Robles, Eloy F; Roa, Sergio; Celay, Jon; Larrayoz, Marta; Rossi, Davide; Gaidano, Gianluca; Montes-Moreno, Santiago; Piris, Miguel A; Balanzategui, Ana; Jimenez, Cristina; Rodriguez, Idoia; Calasanz, Maria J; Larrayoz, Maria J; Segura, Victor; Garcia-Muñoz, Ricardo; Rabasa, Maria P; Yi, Shuhua; Li, Jianyong; Zhang, Mingzhi; Xu-Monette, Zijun Y; Puig-Moron, Noemi; Orfao, Alberto; Böttcher, Sebastian; Hernandez-Rivas, Jesus M; Miguel, Jesus San; Prosper, Felipe; Tousseyn, Thomas; Sagaert, Xavier; Gonzalez, Marcos; Martinez-Climent, Jose A

    2018-05-01

    The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV - tumours, EBV + DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV + DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV + DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2 -/- IL2γc -/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV + B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV + DLBCL in patients. Accordingly, clonally related and unrelated EBV + DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV + DLBCL. Copyright © 2018 Pathological

  10. Presentation of hemophagocytic lymphohistiocytosis due to a novel MUNC 13–4 mutation masked by partial therapeutic immunosuppression

    Directory of Open Access Journals (Sweden)

    Garrett Jackie P-D

    2012-05-01

    Full Text Available Abstract Hemophagocytic lymphohistiocytosis is a potentially fatal disease characterized by excessive macrophage and lymphocyte activity. Patients can be affected following immune activation after an oncologic, autoimmune or infectious trigger. An associated gene mutation may be found which impairs cytolytic lymphocyte function. We describe a pediatric case of hemophagocytic lymphohistiocytosis with a novel mutation of MUNC 13–4 whose diagnosis was confounded by concurrent immunosuppression. Clinical reassessment for hemophagocytic lymphohistiocytosis is necessary in persistently febrile patients with laboratory derangements in the setting of immunosuppressive agent exposure.

  11. Extracellular Purine Metabolism Is the Switchboard of Immunosuppressive Macrophages and a Novel Target to Treat Diseases With Macrophage Imbalances

    Directory of Open Access Journals (Sweden)

    Anna Ohradanova-Repic

    2018-04-01

    Full Text Available If misregulated, macrophage (Mϕ–T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA. We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF- and Mϕ colony-stimulating factor (M-CSF-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ, adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73. Since we observed a misbalance between immunosuppressive and immunostimulatory Mϕs in human and murine arthritic joints, we devised a new strategy for RA treatment based on targeted delivery of a novel methotrexate (MTX formulation to the immunosuppressive FRβ+CD39+CD73+ Mϕs, which boosts adenosine production and curtails the dominance of proinflammatory Mϕs. In contrast to untargeted MTX, this approach leads to potent alleviation of inflammation in the murine arthritis model. In conclusion, we define the Mϕ extracellular purine metabolism as a novel checkpoint in Mϕ cell fate decision-making and an attractive target to control pathological Mϕs in immune-mediated diseases.

  12. Efficacy of interventions for adherence to the immunosuppressive therapy in kidney transplant recipients: a meta-analysis and systematic review.

    Science.gov (United States)

    Zhu, Yichen; Zhou, Yifan; Zhang, Lei; Zhang, Jian; Lin, Jun

    2017-10-01

    Immunosuppressive treatment regimens are complex and require ongoing self-management. Medication adherence can be difficult to achieve for several reasons. The current meta-analysis and systematic review investigated whether adherence interventions improved immunosuppressive treatment adherence in kidney transplant recipients. Medline, Cochrane, EMBASE, and Google Scholar were searched until October 17, 2016 using the following search terms: kidney transplantation, compliance, adherence, and immunosuppressive therapy. Randomized controlled trials and two-arm prospective, retrospective, and cohort studies were included. The primary outcomes were adherence rate and adherence score. Eight studies were included with a total for 546 patients. Among participants receiving intervention, the adherence rate was significantly higher than the control group (pooled OR=2.366, 95% CI 1.222 to 4.578, p=0.011). Participants in the intervention group had greater adherence scores than those in the control group (pooled standardized difference in means =1.706, 95% CI 0.346 to 3.065, p=0.014). Sensitivity analysis indicated that findings for adherence rate were robust. However, for adherence score, the significance of the association disappeared after removing one of the studies indicating the findings may have been overly influenced by this one study. Intervention programs designed to increase immunosuppressive adherence in patients with kidney transplant improve treatment adherence. Copyright © 2017 American Federation for Medical Research.

  13. Personalization of the Immunosuppressive Treatment in Renal Transplant Recipients: The Great Challenge in “Omics” Medicine

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    2015-02-01

    Full Text Available Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%–5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, “omics” techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient’s genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies.

  14. Homologous tracheal transplantation with grafts previously exposed to high doses of gamma radiation in dogs without immunosuppressive agents

    International Nuclear Information System (INIS)

    Yokomise, Hiroyasu; Inui, Kenji; Kure, Toshio; Wada, Hiromi; Itomi, Shigeki

    1993-01-01

    The study was designed to determine whether previous high doses irradiation of gamma radiation would contribute to tracheal transplantation with no use of immunosuppressive agents. Twenty mongrel dogs were used as experimental animals. Five rings of thoracic tracheas, which were extracted from recipients, were exposed to 20000, 50000, or 100000 cGy in each 5 dogs. Five other non-irradiated dogs served as controls. Irradiated tracheal grafts were transplanted and covered with pedicled omentum. After transplantation, no immunosuppressive agents were given to dogs. All dogs in the control group died of tracheal stenosis due to graft-host rejection within one month. All but one long-term survivor died of tracheal stenosis, as well, in both the 20000 cGy and 50000 cGy groups. In the 100000 cGy group, grafts became viable in 4 dogs, and three of these survived one year or more. In conclusion, previous irradiation with high doses of 100000 cGy allowed homologous tracheal transplantation even when no immunosuppressive agents are given. (N.K.)

  15. Strategies to improve the immunosuppressive properties of human mesenchymal stem cells

    OpenAIRE

    Lee, Myoung Woo; Ryu, Somi; Kim, Dae Seong; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2015-01-01

    Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases because of their immunosuppressive capacities. However, few clinical trials of MSCs have yielded satisfactory results. A number of clinical trials using MSCs are currently in progress worldwide. Unfortunately, protocols and methods, including optimized culture conditions for the harvest of MSCs, have not been standardized. In this regard, complications in the ex vivo expansion of MSCs and MSC...

  16. A pilot study to examine the effect of chronic treatment with immunosuppressive drugs on mucociliary clearance in a vagotomized murine model.

    Directory of Open Access Journals (Sweden)

    Abhiram R Bhashyam

    Full Text Available Previously, we have demonstrated that mucociliary clearance (MCC is diminished within the first months after surgery in lung transplant patients and the explanation for the reduction in MCC is unknown. We hypothesized that chronic treatment with a commonly prescribed regimen of immunosuppressive drugs significantly impairs MCC. We tested this hypothesis in a murine model of lung transplantation.Fifteen C57BL/6 mice underwent vagotomy on the right side to simulate denervation associated with lung transplantation in humans. For 6 days, seven mice (controls were intraperitoneally injected with three 100 µL doses of phosphate buffered saline and eight mice (immunosuppressed were injected with three 100 µL injections of tacrolimus (1 mg/kg, mycophenolate mofetil (30 mg/kg, and prednisone (2 mg/kg once daily. Then, mice inhaled the radioisotope (99mtechnetium and underwent gamma camera imaging of their lungs for 6.5 hrs. Counts in the right lung at 1-1.5 hrs and at 6-6.5 hrs were first background-corrected and then decay-corrected to time 0 counts. Decay-corrected counts were then divided by time 0 counts. Retention at each time point was subtracted from 1.00 and multiplied by 100% to obtain percent removed by mucociliary clearance.Although there was a slowing of MCC at 1-1.5 hrs for the immunosuppressed mice, there was no statistical difference in MCC measured at 1-1.5 hrs for the two groups of mice. At 6-6.5 hrs, MCC was significantly slower in the immunosuppressed mice, compared to controls, with 7.78±5.9% cleared versus 23.01±11.7% cleared, respectively (p = 0.006.These preliminary results suggest that chronic treatment with immunosuppressive medications significantly slows MCC in vagotomized C57BL/6 mice. These findings could shed light on why MCC is reduced in lung transplant patients whose lungs are denervated during surgery and who are chronically treated with immunosuppressive drugs post surgery.

  17. Stored blood--an effective immunosuppressive method for transplantation of kidneys from unrelated donors. An 11-year follow-up.

    Science.gov (United States)

    Galvão, M M; Peixinho, Z F; Mendes, N F; Sabbaga, E

    1997-06-01

    Thirty-seven patients were submitted to kidney transplantation after transfusion at 2-week intervals with 4-week stored blood from their potential donors. All patients and donors were typed for HLA-A-B and DR antigens. The patients were also tested for cytotoxic antibodies against donor antigens before each transfusion. The percentage of panel reactive antibodies (PRA) was determined against a selected panel of 30 cell donors before and after the transfusions. The patients were immunosuppressed with azathioprine and prednisone. Rejection crises were treated with methylprednisolone. The control group consisted of 23 patients who received grafts from an unrelated donor but who did not receive donor-specific pretransplant blood transfusion. The incidence and reversibility of rejection episodes, allograft loss caused by rejection, and patient and graft survival rates were determined for both groups. Non-parametric methods (chi-square and Fisher tests) were used for statistical analysis, with the level of significance set at P transplant days did not differ significantly between groups. The actuarial graft and patient survival rates at five years were 56% and 77%, respectively, for the treated group and 39.8% and 57.5% for the control group. Graft loss due to rejection was significantly higher in the untreated group (P = 0.0026) which also required more intense immunosuppression (P = 0.0001). We conclude that transfusions using stored blood have the immunosuppressive effect of fresh blood transfusions without the risk of provoking a widespread formation of antibodies. In addition, this method permits a reduction of the immunosuppressive drugs during the process without impairing the adequate functioning of the renal graft.

  18. Radiostrontium-induced oncogenesis and the role of immunosuppression. Pt. 2

    International Nuclear Information System (INIS)

    Bierke, P.; Nilsson, A.

    1990-01-01

    The significance of depressed immune function for the development and progression of tumours induced by 90 Sr (mainly osteosarcomas and malignant lymphomas) was investigated in a series of experiments by comparing the tumour responses in normal mice with those in immunocompromised mice. The present paper (part II) reports on lympho-reticular (LR) and extraskeletal neoplastic lesions in male CBA/SU mice after exposure to different single doses of 90 Sr with or without additional immunosuppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. Neoplastic lesions in bone were reported in part I. The status of the animal's immune system and responsive ability were examined in parallel experiments. The tumor yields were analysed in relation to the dosage of 90 Sr and the immunosuppressive treatments employed. Although the incidences and latency times of induced tumours were clearly dose-dependent, they were never significantly influenced by ATx/ALG treatments. Thus, no substantial support was gained for the theory that the immune system plays a controlling or modifying role in 90 Sr carcinogenesis. The results, which are in agreement with the bone tumour responses, suggest that 90 Sr induced tumours either do not express the antigens necessary for immune rejection or that the decline in immune responsiveness induced by ATx/ALG was of little consequence for tumour development and spread. The pathogenesis of 90 Sr induced malignant lymphomas (MLs) and their immunophenotypes are discussed. (orig.)

  19. Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions.

    Science.gov (United States)

    Belinky, Frida; Rogozin, Igor B; Koonin, Eugene V

    2017-09-29

    Reconstruction of the evolution of start codons in 36 groups of closely related bacterial and archaeal genomes reveals purifying selection affecting AUG codons. The AUG starts are replaced by GUG and especially UUG significantly less frequently than expected under the neutral expectation derived from the frequencies of the respective nucleotide triplet substitutions in non-coding regions and in 4-fold degenerate sites. Thus, AUG is the optimal start codon that is actively maintained by purifying selection. However, purifying selection on start codons is significantly weaker than the selection on the same codons in coding sequences, although the switches between the codons result in conservative amino acid substitutions. The only exception is the AUG to UUG switch that is strongly selected against among start codons. Selection on start codons is most pronounced in evolutionarily conserved, highly expressed genes. Mutation of the start codon to a sub-optimal form (GUG or UUG) tends to be compensated by mutations in the Shine-Dalgarno sequence towards a stronger translation initiation signal. Together, all these findings indicate that in prokaryotes, translation start signals are subject to weak but significant selection for maximization of initiation rate and, consequently, protein production.

  20. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    Directory of Open Access Journals (Sweden)

    Welling JD

    2012-04-01

    Full Text Available John D Welling, Ahmad B Tarabishy, John ChristoforidisDepartment of Ophthalmology, Havener Eye Institute, Ohio State University, Columbus, OH, USAAbstract: Cytomegalovirus (CMV retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants.Keywords: cytomegalovirus retinitis, central retinal vein occlusion, immunosuppression, solid organ transplant, venous stasis, risk factor

  1. CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ding, E-mail: qqhewd@gmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Chen, Ke, E-mail: chenke_59@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Du, Wei Ting, E-mail: duwtpumc@yahoo.com.cn [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); Han, Zhi-Bo, E-mail: zhibohan@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); Ren, He, E-mail: knifesharp2000@hotmail.com [National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, TEDA, Tianjin (China); Chi, Ying, E-mail: caizhuying@hotmail.com [The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020 (China); TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin (China); and others

    2010-09-10

    Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  2. Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study.

    Science.gov (United States)

    Brito, Daniela Cristina Sampaio de; Marsicano, Elisa Oliveira; Grincenkov, Fabiane Rossi Dos Santos; Colugnati, Fernando Antônio Basile; Lucchetti, Giancarlo; Sanders-Pinheiro, Helady

    2016-01-01

    : Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P transplantation patients and should be considered among the strategies for reducing nonadherence.

  3. Severe neuro-Behcet's disease treated with a combination of immunosuppressives and a TNF-inhibitor.

    Science.gov (United States)

    Korkmaz, Fatma Nur; Ozen, Gulsen; Ünal, Ali Uğur; Kahraman Koytak, Pınar; Tuncer, Nese; Direskeneli, Haner

    2016-01-01

    Abstract/ Resumo Behcet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD), is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI) findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days) and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day), iv cylophosphamide (1g) and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day) and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in NBD. Although

  4. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Kazuhiko (Yamato Seiwa Hospital, Kanagawa (Japan)); Rapaport, F.T.

    1992-12-01

    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author).

  5. Total lymphoid irradiation assessed for possible enhancement of immunosuppression in hyperimmunized dogs receiving renal allografts

    International Nuclear Information System (INIS)

    Sonoda, Kazuhiko; Rapaport, F.T.

    1992-01-01

    With performed antibodies to human leukocyte antigens (HLA) appearing in an increasing number of patients today, hyperimmunization constitutes a major problem in clinical transplantation. In adult beagle dogs hyperimmunized with skin allografts and buffy coat injection, we performed renal allograft transplantation to assess the efficacy of total lymphoid irradiation (TLI) employed as a preoperative measure in combination with cyclosporine (CyA) and methyl-prednisolone (MPL) in effecting immunosuppression. The mean survival period were 6.5 days in dogs withheld preliminary treatment, 9.0 days in the dogs receiving CyA and MPL, 26.7 days in those administered one-stage TLI, and 68 days (terminated by euthanasia) of the dogs given two-stage TLI. TLI administered two stages is considered an effective method of enhancing immunosuppression sufficiently to enable the attenuation of adverse reaction to renal allograft in hyperimmunized recipients. (author)

  6. The Release of Immunosuppressive Factor(s) in Young Males Following Exercise

    OpenAIRE

    Tian, Ye; Nie, Jinlei; Tong, Tom K.; Baker, Julien S.

    2012-01-01

    It has been shown that a suppressive protein, acting as an immune suppressor, is generated in animals and humans under particular stresses. However, studies related to immunosuppressive factors in response to the stress resulting from acute exercise are limited. This study compares the effects of pre- and post-exercise human serum on concanavalin A stimulated lymphocyte proliferation of mice. In the present study, blood samples in eight male undergraduates (age 21 ± 0.7 years) were taken befo...

  7. Sternoclavicular Osteomyelitis in an Immunosuppressed Patient: A Case Report and Review of the Literature.

    Science.gov (United States)

    Khan, Kamran; Wozniak, Susan E; Mehrabi, Erfan; Giannone, Anna Lucia; Dave, Mitul

    2015-12-28

    BACKGROUND Sternoclavicular osteomyelitis is a rare disease, with less than 250 cases identified in the past 50 years. We present a rare case of sternoclavicular osteomyelitis in an immunosuppressed patient that developed from a conservatively treated dislocation. CASE REPORT A 62-year-old white man with a history of metastatic renal cell carcinoma presented to the emergency department (ED) with a dislocated left sternoclavicular joint. He was managed conservatively and subsequently discharged. However, over subsequent days he began to experience pain, fever, chills, and night sweats. He presented to the ED again and imaging revealed osteomyelitis. In the operating room, the wound was aggressively debrided and a wound vac (vacuum-assisted closure) was placed. He was diagnosed with sternoclavicular osteomyelitis and placed on a 6-week course of intravenous Nafcillin. CONCLUSIONS Chemotherapy patients who sustain joint trauma normally associated with a low risk of infection should be monitored thoroughly, and the option to discontinue immunosuppressive therapy should be considered if signs of infection develop.

  8. Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Won-Jae [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Hah, Young-Sool [Biomedical Research Institute, Gyeongsang National University Hospital, Jinju (Korea, Republic of); Ock, Sun-A. [Animal Biotechnology Division, National Institute of Animal Science, RDA, Suwon 441-706, Gyeonggi (Korea, Republic of); Lee, Jae-Hoon; Jeon, Ryong-Hoon; Park, Ji-Sung [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sang-Il [Department of Internal Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju (Korea, Republic of); Rho, Na-Young [Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 4S7 (Canada); Rho, Gyu-Jin [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Lee, Sung-Lim, E-mail: sllee@gnu.ac.kr [College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701, Gyeongnam (Korea, Republic of)

    2015-05-01

    The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice. - Highlights: • Immunosuppressive capacity of BM-, SM-, and SF-MSCs was evaluated in an RA model. • Proliferation, pluripotency and chondrogenic differentiation capacity were higher in SF-MSCs. • SF-MSCs exhibited improved therapeutic effects than BM-MSCs. • SF-MSCs may have applications as immunosuppressive therapy in autoimmune diseases.

  9. Seronegative Bilateral Symmetrical Inflammatory Polyarthritis: Think Twice Before Starting Immunosuppression

    Directory of Open Access Journals (Sweden)

    Omar Alsaed

    2018-06-01

    Full Text Available The most common cause of bilateral symmetrical polyarthritis in the small joints is rheumatoid arthritis. However, if seronegative arthritis is involved, it could be the case that other underlying causes need to be diagnosed. This is particularly important for those coming from or living in developing countries where infectious causes should always be considered. The case of a young Nepali woman is presented in this article. She was referred as a case of seronegative rheumatoid arthritis for DMARDs therapy but this was not the case due to her origin from Nepal and seronegativity for RF, Anti-ccp, and ANA as well as faint macular skin lesions over her face and upper extremities, which the patients are not aware of. Consequently, skin biopsy was carried out which subsequently confirmed that the infectious cause of her polyarthritis was leprosy.

  10. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  11. Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

    NARCIS (Netherlands)

    Khanna, Reena; Bressler, Brian; Levesque, Barrett G.; Zou, Guangyong; Stitt, Larry W.; Greenberg, Gordon R.; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J.; Donner, Allan; Vandervoort, Margaret K.; Morris, Joan C.; Feagan, Brian G.; Anderson, Frank; Atkinson, Kenneth; Bacchus, Rahman; Berezny, Gary; Borthistle, Bruce; Buckley, Alan; Chiba, Naoki; Cockeram, Alan; Elkashab, Magdy; Fashir, Baroudi; Gray, James; Hemphill, Douglas; Hoare, Connie; Holland, Stephen; Hurowitz, Eric; Kaal, Nuri; Laflamme, Pierre; Borromee, Saint-Charles; Lau, Helena; McMullen, William; Memiche, Reshat; Menon, Krishna; Miller, D. Alexander; O'Hara, William; Oravec, Michael; Penner, Robert; Petrunia, Denis; Pluta, Henryk; Prabhu, Umesh; Prest, Marcia; Shaaban, Hani; Sheppard, Duane; Shulman, Scott

    2015-01-01

    Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of

  12. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Schnitzbauer, Andreas A; Adam, Rene; Bechstein, Wolf O; Becker, Thomas; Beckebaum, Susanne; Chazouillères, Olivier; Cillo, Umberto; Colledan, Michele; Fändrich, Fred; Gugenheim, Jean; Hauss, Johann P; Zuelke, Carl; Heise, Michael; Hidalgo, Ernest; Jamieson, Neville; Königsrainer, Alfred; Lamby, Philipp E; Lerut, Jan P; Mäkisalo, Heikki; Margreiter, Raimund; Mazzaferro, Vincenzo; Mutzbauer, Ingrid; Graeb, Christian; Otto, Gerd; Pageaux, Georges-Philippe; Pinna, Antonio D; Pirenne, Jacques; Rizell, Magnus; Rossi, Giorgio; Rostaing, Lionel; Roy, Andre; Turrion, Victor Sanchez; Schmidt, Jan; Rochon, Justine; Troisi, Roberto I; Hoek, Bart van; Valente, Umberto; Wolf, Philippe; Wolters, Heiner; Mirza, Darius F; Scholz, Tim; Steininger, Rudolf; Soderdahl, Gunnar; Strasser, Simone I; Bilbao, Itxarone; Jauch, Karl-Walter; Neuhaus, Peter; Schlitt, Hans J; Geissler, Edward K; Burra, Patrizia; Jong, Koert P de; Duvoux, Christophe; Kneteman, Norman M

    2010-01-01

    The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2 1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from

  13. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Roy Andre

    2010-05-01

    Full Text Available Abstract Background The potential anti-cancer effects of mammalian target of rapamycin (mTOR inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC-free patient survival in liver transplant (LT recipients with a pre-transplant diagnosis of HCC. Methods/Design The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously

  14. Early Introduction of Everolimus Immunosuppressive Regimen in Liver Transplantation with Extra-Anatomic Aortoiliac-Hepatic Arterial Graft Anastomosis

    Directory of Open Access Journals (Sweden)

    Emanuele Felli

    2014-01-01

    Full Text Available Liver transplantation is the treatment of choice for patients with acute and chronic end-stage liver disease, when no other medical treatment is possible. Despite high rates of 1- to 5-year survival, long-term adverse effects of immunosuppressant agents remain of major concern. Current research and clinical efforts are made to develop immunosuppressant agents that minimize adverse effects along with a low rate of graft rejection. Tailoring immunosuppressive therapy to individual patients by the use of proliferation signal inhibitors seems to be the best way to minimize toxicity and increase efficacy. Recently everolimus has been introduced in clinical practice; among its adverse effects an increased incidence of arterial graft thrombosis in renal transplants, vascular anastomosis leakage, impaired wound healing, and thrombotic microangiopathy have been reported. We present the case of a 54-year-old patient submitted to liver transplantation for end-stage liver disease treated by an extra-anatomic aortoiliac-hepatic arterial graft anastomosis and early postoperative introduction of everolimus for acute renal failure. Postoperative period was characterized by two abdominal collections and reactivation of cytomegalovirus infection that were treated by percutaneous drainage and antiviral therapy, respectively; the patient is well after 8-month followup with patency of the arterial conduit and no leakage.

  15. CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Nicolas Espagnolle

    2017-04-01

    Full Text Available Summary: Mesenchymal stromal cells (MSCs sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy. : Mesenchymal stromal cells (MSCs are promising for cell-based therapy in inflammatory disorders by switching off the immune response. Varin and colleagues demonstrate that MSCs and inflammatory macrophages communicate via an unconventional but functional interaction that strongly increases the immunosuppressive capacities of MSCs. This new communication between the innate immune system and MSCs opens new perspectives for MSC-based cell therapy. Keywords: macrophages, bone marrow mesenchymal stromal cells, functional interaction, CD54, immunosuppression, indoleamine 2,3-dioxygenase, cell therapy

  16. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  17. The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice.

    Science.gov (United States)

    Hong, Se Hyang; Ku, Jin Mo; In Kim, Hyo; Ahn, Chang-Won; Park, Soo-Hyun; Seo, Hye Sook; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-09-01

    Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. 6-methylprednisolone does not impair anti-thymocyte globulin (ATG) immunosuppressive activity in non-human primates

    NARCIS (Netherlands)

    Preville, [No Value; Sick, E; Beauchard, S; Ossevoort, M; Tiollier, J; Revillard, JP; Jonker, Margreet

    2001-01-01

    Background: Induction treatments with anti-thymocyte globulin (ATG) in solid organ transplantation may enhance the efficacy of maintenance immunosuppressive therapy. Since ATG can trigger Fas (CD95) mediated T cell apoptosis, a process antagonized in vitro by corticosteroids, an important issue is

  19. Anxiety about starting three-shift work among female workers: findings from the Female Shift Workers' Health Study.

    Science.gov (United States)

    Kubo, Tatsuhiko; Maruyama, Takashi; Shirane, Kiyoyumi; Otomo, Hajime; Matsumoto, Tetsuro; Oyama, Ichiro

    2008-03-01

    In 1999, the Japanese Law on Equal Employment Opportunity and Conditions was amended and the previous prohibition of the assignment of female workers to night work was abolished. Subsequently, the number of female shift workers has been increasing in Japan, necessitating greater attention to the health care of this population. The aim of the current study is to evaluate the relationship between anxiety expressed about starting three-shift work and background characteristics among female workers who were being assigned to three-shift work for the first time. The subjects were 38 middle-aged female workers (age range: 44 to 59 years) who were working at a chemical plant. The women completed a self-administered questionnaire before starting three-shift work. Levels of anxiety about starting three-shift work were assessed by the question 'Do you feel anxious about starting three-shift work?' The available responses were: 'Very agree', 'Considerably agree', 'Rather agree', 'Slightly agree' and 'Not agree at all', and 63% of the subjects gave one of the first two answers, which were defined as indicating anxiety. We also acquired information regarding lifestyle and occupation for each subject, including the following factors: frequency of breakfast consumption, subjective sleep insufficiency, previous experience of similar work before beginning shift work, previous experience of two-shift work, and responsibility for household duties. In the study, we found a marginally statistically significant trend association between frequent breakfast consumption and anxiety about starting three-shift work (P(trend) = 0.09). Anxiety was also high among subjects with sleep disorders, especially those suffering from subjective sleep insufficiency (P = 0.08). Due to the small study population, these results should be interpreted with caution and confirmed by future studies.

  20. Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression.

    Science.gov (United States)

    Nijhoff, M F; Engelse, M A; Dubbeld, J; Braat, A E; Ringers, J; Roelen, D L; van Erkel, A R; Spijker, H S; Bouwsma, H; van der Boog, P J M; de Fijter, J W; Rabelink, T J; de Koning, E J P

    2016-01-01

    Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Start-up performance of parabolic trough concentrating solar power plants

    DEFF Research Database (Denmark)

    Ferruzza, Davide; Topel, Monika; Basaran, Ibrahim

    2017-01-01

    Concentrating solar power plants, even though they can be integrated with thermal energy storage, are still subjected to cyclic start-up and shut-downs. As a consequence, in order to maximize their profitability and performance, the flexibility with respect to transient operations is essential...

  2. Prevention of Intraabdominal Adhesions by Local and Systemic Administration of Immunosuppressive Drugs

    Science.gov (United States)

    Peker, Kemal; Inal, Abdullah; Sayar, Ilyas; Sahin, Murat; Gullu, Huriye; Inal, Duriye Gul; Isik, Arda

    2013-01-01

    Background: Intraperitoneal adhesion formation is a serious postsurgical issue. Adhesions develop after damage to the peritoneum by surgery, irradiation, infection or trauma. Objectives: Using a rat model, we compared the effectiveness of systemic and intraperitoneally administered common immunosuppressive drugs for prevention of postoperative intraperitoneal adhesions. Materials and Methods: Peritoneal adhesions were induced in 98 female Wistar-Albino rats by cecal abrasion and peritoneal excision. Rats were randomly separated into seven groups, each containing fourteen rats, and the standard experimental model was applied to all of rats. 14 days later, rats were euthanized, intraperitoneal adhesions were scored and tissues were examined histologically using hematoxylin/eosin and Masson’s trichrome staining. Results: Throughout the investigation, no animal died during or after surgery. In all of experimental groups, decrease in fibrosis was statistically significant. Decrease in fibrosis was most prominently in intraperitoneal tacrolimus group (P = 0.000), and decrease was least in intraperitoneal cyclosporine group (P = 0.022). Vascular proliferation was significantly decreased in all experimental groups (P < 0.05) except for systemic tacrolimus group (P = 0.139). Most prominent reduction in vascular proliferation was in intraperitoneal tacrolimus group (P = 0.000). Conclusions: Administration of immunosuppressive drugs is effective for prevention of intraperitoneal adhesions. PMID:24693396

  3. Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

    Science.gov (United States)

    Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

    2017-01-01

    Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

  4. Menopause in women with chronic immunosuppressive treatment - how to help those patients.

    Science.gov (United States)

    Cyganek, Anna; Pietrzak, Bronisława; Wielgoś, Mirosław; Grzechocińska, Barbara

    2016-03-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

  5. Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative

    Directory of Open Access Journals (Sweden)

    Marcin Mączyński

    2018-06-01

    Full Text Available This work describes the synthesis of a new series of isoxazole derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10 was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The isoxazole derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA-induced proliferation of peripheral blood mononuclear cells (PBMCs to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenylmethylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3 compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS-induced tumor necrosis factor (TNF α production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.

  6. Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction.

    Science.gov (United States)

    Gharagozloo, Marjan; Majewski, Slawomir; Foldvari, Marianna

    2015-05-01

    Autoimmune diseases are chronic, destructive diseases that can cause functional disability and multiple organ failure. Despite significant advances in the range of therapeutic agents, especially biologicals, limitations of the routes of administration, requirement for frequent long-term dosing and inadequate targeting options often lead to suboptimal effects, systemic adverse reactions and patient non-compliance. Nanotechnology offers promising strategies to improve and optimize autoimmune disease treatment with the ability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we focus on nanomedicine-based delivery strategies of biological immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis and type 1 diabetes. This comprehensive review details the concepts and clinical potential of novel nanomedicine approaches for inducing immunosuppression and immunological tolerance in autoimmune diseases in order to modulate aberrant and pathologic immune responses. The treatment of autoimmune diseases remains a significant challenge. The authors here provided a comprehensive review, focusing on the current status and potential of nanomedicine-based delivery strategies of immunomodulatory agents for the treatment of autoimmune disorders including psoriasis, rheumatoid arthritis, systemic lupus erythematous, scleroderma, multiple sclerosis, and type 1 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effect of Mesenchymal Stromal Cells on T Cells in a Septic Context: Immunosuppression or Immunostimulation?

    Science.gov (United States)

    Le Burel, Sébastien; Thepenier, Cédric; Boutin, Laetitia; Lataillade, Jean-Jacques; Peltzer, Juliette

    2017-10-15

    Sepsis is a complex process, including a first wave of damage partially due to the body's response to pathogens, followed by a phase of immune cell dysfunction. The efficacy of a pharmacological approach facing a rapidly evolving system implies a perfect timing of administration-this difficulty could explain the recent failure of clinical trials. Mesenchymal stromal cells (MSCs) are usually defined as immunosuppressive and their beneficial effects in preclinical models of acute sepsis have been shown to rely partly on such ability. If nonregulated, this phenotype could be harmful in the immunosuppressed context arising hours after sepsis onset. However, MSCs being environment sensitive, we hypothesized that they could reverse their immunosuppressive properties when confronted with suffering immune cells. Our objective was to evaluate the effect of human MSCs on activated human lymphocytes in an in vitro endotoxemia model. Peripheral blood mononuclear cells (PBMCs) underwent a 24-h lipopolysaccharide (LPS) intoxication and were stimulated with phytohemagglutinin (PHA) in contact with MSCs. MSCs induced a differential effect on lymphocytes depending on PBMC intoxication with LPS. Unintoxicated lymphocytes were highly proliferative with PHA and were inhibited by MSCs, whereas LPS-intoxicated lymphocytes showed a low proliferation rate, but were supported by MSCs, even when monocytes were depleted. These data, highlighting MSC plasticity in their immunomodulatory activity, pave the way for further studies investigating the mechanisms of mutual interactions between MSCs and immune cells in sepsis. Thus, MSCs might be able to fight against both early sepsis-induced hyperinflammatory response and later time points of immune dysfunction.

  8. Discrepancies between beliefs and behavior: a prospective study into immunosuppressive medication adherence after kidney transplantation.

    Science.gov (United States)

    Massey, Emma K; Tielen, Mirjam; Laging, Mirjam; Timman, Reinier; Beck, Denise K; Khemai, Roshni; van Gelder, Teun; Weimar, Willem

    2015-02-01

    Nonadherence to immunosuppressive medication after kidney transplantation is a behavioral issue and as such it is important to understand the psychological factors that influence this behavior. The aim of this study was to investigate the extent to which goal cognitions, illness perceptions, and treatment beliefs were related to changes in self-reported immunosuppressive medication adherence up to 18 months after transplantation. Interviews were conducted with patients in the outpatient clinic 6 weeks (T1; n=113), 6 months (T2; n=106), and 18 months (T3; n=84) after transplantation. Self-reported adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale Interview. Psychological concepts were measured using the Brief Illness Perceptions Questionnaire, Beliefs about Medicines Questionnaire, and questions on the importance of adherence as a personal goal, conflict with other goals, and self-efficacy for goal attainment. Nonadherence significantly increased over time to 31% at T3. Perceived necessity of medication, perceived impact of transplant on life (consequences) and emotional response to transplantation significantly decreased over time. Participants who reported low importance of medication adherence as a personal goal were more likely to become nonadherent over time. Illness perceptions can be described as functional and supportive of adherence which is inconsistent with the pervasive and increasing nonadherence observed. There appears therefore to be a discrepancy between beliefs about adherence and actual behavior. Promoting (intrinsic) motivation for adherence goals and exploring the relative importance in comparison to other personal goals is a potential target for interventions.

  9. A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

    Directory of Open Access Journals (Sweden)

    Lorf Thomas

    2010-04-01

    Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

  10. Menopause in women with chronic immunosuppressive treatment ? how to help those patients

    OpenAIRE

    Cyganek, Anna; Pietrzak, Bronis?awa; Wielgo?, Miros?aw; Grzechoci?ska, Barbara

    2016-01-01

    Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General ...

  11. The cannabinoid receptor type 2 as mediator of mesenchymal stromal cell immunosuppressive properties.

    Directory of Open Access Journals (Sweden)

    Francesca Rossi

    Full Text Available Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive properties of human mesenchymal stromal cells have attracted much attention from immunologists, stem cell biologists and clinicians. Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated. Endocannabinoids, mainly acting through the cannabinoid receptor subtype 2, are able to modulate cytokine release and to act as immunosuppressant when added to activated T lymphocytes. In the present study, we have investigated, through a multidisciplinary approach, the involvement of the endocannabinoids in migration, viability and cytokine release of human mesenchymal stromal cells. We show, for the first time, that cultures of human mesenchymal stromal cells express all of the components of the endocannabinoid system, suggesting a potential role for the cannabinoid CB2 receptor as a mediator of anti-inflammatory properties of human mesenchymal stromal cells, as well as of their survival pathways and their capability to home and migrate towards endocannabinoid sources.

  12. Two rare cases of Epstein-Barr virus-associated lymphoproliferative disorders in inflammatory bowel disease patients on thiopurines and other immunosuppressive medications.

    Science.gov (United States)

    Subramaniam, K; Cherian, M; Jain, S; Latimer, M; Corbett, M; D'Rozario, J; Pavli, P

    2013-12-01

    The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  13. Thorax irradiation triggers a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells

    International Nuclear Information System (INIS)

    Wirsdörfer, Florian; Cappuccini, Federica; Niazman, Muska; Leve, Simone de; Westendorf, Astrid M; Lüdemann, Lutz; Stuschke, Martin; Jendrossek, Verena

    2014-01-01

    Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but their contribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on the T cell compartment with a focus on immunosuppressive regulatory T cells (Treg). C57BL/6 wild type mice (WT) received anesthesia only (sham controls, 0 Gy) or were exposed to a single dose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes were collected 10 to 84 days post-irradiation and phenotypically characterized by flow cytometry. Whole thorax irradiation provoked an increased influx of CD3+ T cells at 42 and 84 days post-irradiation. In contrast, local irradiation caused a sustained reduction in CD3+ T cells in peripheral lymphoid tissues. Interestingly, we observed a significant local and systemic increase in the fraction of CD4+ T cells expressing the transcription factor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulation of Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment and immunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able to suppress CD4+ effector T cells to a similar extent as Treg isolated from control mice. The response of the adaptive immune system to whole thorax irradiation is characterized by local immunoactivation and systemic immunosuppression. The transient accumulation of immunosuppressive CD4+ FoxP3+ Treg may be required to protect the lung against excessive inflammation-induced tissue damage. Further investigations shall define the mechanisms underlying the accumulation of Treg and their role for the pathogenesis of radiation-induced lung disease

  14. Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Stefan Jenkins

    2013-12-01

    Full Text Available Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP and aqueous normal phase (ANP chromatographic separations, as well as electrospray ionization (ESI and atmospheric pressure chemical ionization (APCI sources for detection in both ion polarities. Unsupervised principle component analysis (PCA and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published

  15. Severe neuro-Behcet’s disease treated with a combination of immunosuppressives and a TNF-inhibitor.

    Directory of Open Access Journals (Sweden)

    Fatma Nur Korkmaz

    2016-10-01

    Full Text Available Abstract/ Resumo Behcet's disease (BD is a multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The nervous system involvement of BD, neuro-Behcet's disease (NBD, is one of the important causes of mortality of the disease. Herein, we present a 29-year-old male with parenchymal NBD who has progressed rapidly and was managed with an uncommon aggressive immunosuppresive combination therapy. The patient first presented six years ago with vertigo and difficulty in talking and walking. On examination, he had oral ulcers, acneiform lesions on the torso, genital ulcer scar, dysartria, and ataxia. Along with the magnetic resonance imaging (MRI findings, the patient was diagnosed as NBD. After pulse methylprednisolone (1g/day, 3 days and 8 courses of 1g/month iv cylophosphamide therapy, he was put on azathioprine and oral methlyprednisolone. On the 4th year of the maintenance therapy, he was admitted with NBD relapse which was treated with 3 days of iv 1g pulse methlyprednisolone. One year after the last relapse, the patient voluntarily stopped medications and presented with global aphasia, right hemihypoesthesia and quadriparesis. MRI findings were suggestive of NBD relapse. After exclusion of infection, pulse methylprednisolone was started but no improvement was observed. Considering the severity of the NBD, the patient was put on methylprednisolone (1mg/kg/day, iv cylophosphamide (1g and adalimumab 40 mg/14 days subcutaneously with appropriate tuberculosis prophylaxis. Neurological examination and MRI findings after 4 weeks showed dramatic improvement however patient developed pulmonary tuberculosis. Methylprednisolone dose was decreased (0.5mg/kg/day and quadruple antituberculosis therapy was started. Patient was discharged with 5/5 muscle strength in extremities without any respiratory symptoms 2 months after first presentation. Prompt introduction of immunosuppressive therapy is crucial in

  16. The central effect of biological Amines on immunosuppressive effect of restraint stress in rat

    Directory of Open Access Journals (Sweden)

    Zeraati F

    2000-10-01

    Full Text Available The effects of some histaminergic agents were evaluated on stress- induced immunosuppression in immunized nale rats. In rat immunized with sheep red blood cells ( SRBCs. Restraint stress (RS prevented the booster-induced rise in anti-SRBC antibody titre and cell immunity response. Intracerebroventicular (I.C>V injection of histamine (150 µg/rat induced a similar effect with RS. Pretreatment with chlorpheniramine (50 µg/rat reduced the inhibitory effect of Ras on immune function. Also histamine could inhibit the effect of RS on immune function. Also histamine could inhibitory the effect of chlorpheniramine when injected simultaneously. Pretreatment with ranidine (10 µg/rat had not a significant effect. Serotonin (3 µg/rat and dopamine (0.2 µg/rat could reverse the effects of chlorpheniromine when injected with chlorpheniramine (P<0.05. Epinephrine (0.2 µg/rat had not a significant effect. The results indicate that histamine mediates the immunosuppression of restraint stress by influencing the histamine H1 receptor in the brain and this effects of histamine may be modulated by serotoninergic and dopaminergic system.

  17. Why START?

    International Nuclear Information System (INIS)

    Mendelsohn, J.

    1991-01-01

    Barring some major unexpected downturn in US-Soviet relations, it seems likely that the long-awaited Strategic Arms Reduction Talks (START) treaty will be signed sometime in 1991. Under negotiation for the past nine years, public acceptance and Senate approval of a START treaty will be facilitated by the generally less confrontational East-West relationship which has evolved over that time, by the growing constraints on the US defense budget, and by the obvious merits of the treaty itself. Not only will the nearly complete START treaty be an extremely useful and powerful arms control agreement, it is also decidedly advantageous to US security interests. First and foremost, a START treaty will cap and reduce the steady buildup of nuclear weapons that has characterized the last 30 years of the US-Soviet strategic relationship. As a result of the basic outline originally agreed to at the Reykjavik summit, START will take a 25 to 35 percent bite out of existing nuclear arsenals, impose approximately a 50 percent cut in overall Soviet ballistic missile warheads and throw-weight (lifting power or payload capacity), and produce an exact 50 percent cut in Soviet SS-18 missiles

  18. From Head Start to Sure Start: Reflections on Policy Transfer

    Science.gov (United States)

    Welshman, John

    2010-01-01

    This article uses the history of debates over the US Head Start programme (1965), Early Head Start (1994) and the UK Sure Start initiative (1998), as a window on to policy transfer. In all the three, the aim was that early intervention could offer a means of boosting children's educational attainment and of countering the wider effects of poverty…

  19. Synergistic immunosuppressive effects of the mTOR inhibitor sirolimus and the phytochemical curcumin.

    Science.gov (United States)

    Deters, M; Hütten, H; Kaever, V

    2013-01-15

    The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not-human cell lines. Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. To answer this question we investigated the interaction of both these substances on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation. OKT3-induced human PBMC proliferation was determined by measuring (3)H-thymidine incorporation. Influence of curcumin on interleukin-2 (IL-2) release and IκB-phosphorylation in PBMC was determined by ELISA and western blot, respectively. Curcumin-induced apoptosis and necrosis was analyzed by FACS analysis. Whereas curcumin completely inhibited OKT3-induced PBMC proliferation in a dose-dependent manner with an IC(50) of 2.8 μM, sirolimus could reduce PBMC proliferation dose-dependently only to a minimum of 28% at a concentration of 5 ng/ml (IC(50) 1.1 ng/ml). When curcumin was combined at concentrations of 1.25-2.5 μM with sirolimus at concentrations from 0.63 to 1.25 ng/ml the effects were synergistic. Combination of curcumin (1.25-2.5 μM) with sirolimus (5 ng/ml) showed additive effects. The effects after combination of curcumin at 5 μM with each sirolimus concentration and sirolimus at 10 ng/ml with each curcumin concentration were presumably antagonistic. We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3-activated PBMC. Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models. Copyright © 2012 Elsevier GmbH. All rights reserved.

  20. Evidence of immunosuppression by Demodex canis.

    Science.gov (United States)

    Barriga, O O; al-Khalidi, N W; Martin, S; Wyman, M

    1992-04-01

    Three clinically normal beagles, 3 beagles with localized demodectic mange (LDM), and 3 beagles with generalized demodectic mange (GDM) were investigated simultaneously 1-3 and 4-6 weeks from the appearance of the clinical signs. Blood clinical examination and reactivity of peripheral lymphocytes to Con A and PHA were investigated in the first instance, and reactivity to Con A, PHA, and LPS in the second. Eight aliquots were used in each blastogenesis assay for each dog. All dogs were negative for rheumatoid factor. The results of blastogenesis showed that many observations were distributed non-normally, and that not all dogs in each group responded homogeneously. Comparison of blastogenesis results between dogs demands careful statistical analysis. Responses to mitogens were normal in all dogs at 1-3 weeks except for the LDM dogs that showed an increased response to PHA. Only the response to Con A was moderately inhibited in the LDM dogs at 4-6 weeks. All responses were severely depressed in the GDM dogs at 4-6 weeks. This means that immunosuppression follows rather than precedes the clinical manifestations of GDM, and implies that the phenomenon is induced by the parasite or the host's reaction to it.

  1. African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

    Science.gov (United States)

    Malat, Gregory E; Culkin, Christine; Palya, Aniruddha; Ranganna, Karthik; Kumar, Mysore S Anil

    2009-10-22

    Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors

  2. Endogenous nocardial endophthalmitis in an immunosuppressed patient: A serious warning of an underlying life threatening and blinding disorder

    Directory of Open Access Journals (Sweden)

    Hemant Trehan

    2017-01-01

    Conclusion: Ocular nocardiosis is a serious vision and life threatening disorder, particularly in patients on immunosuppressive therapy. A high index of suspicion is required for successful treatment.

  3. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp

    DEFF Research Database (Denmark)

    Pierdomenico, Laura; Bonsi, Laura; Calvitti, Mario

    2005-01-01

    ) as a potential source of MSCs instead of bone marrow (BM). METHODS: Flow cytometric analysis showed that DP-MSCs and BM-MSCs were equally SH2, SH3, SH4, CD29 and CD 166 positive. The in vitro proliferative kinetics of MSCs were measured by 3H-thymidine incorporation uptake. The immunosuppressive function of MSCs...

  4. Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

    2018-01-01

    Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE

  5. Polyketides with Immunosuppressive Activities from Mangrove Endophytic Fungus Penicillium sp. ZJ-SY₂.

    Science.gov (United States)

    Liu, Hongju; Chen, Senhua; Liu, Weiyang; Liu, Yayue; Huang, Xishan; She, Zhigang

    2016-11-25

    Nine polyketides, including two new benzophenone derivatives, peniphenone ( 1 ) and methyl peniphenone ( 2 ), along with seven known xanthones ( 3 - 9 ) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY₂ isolated from the leaves of Sonneratia apetala . Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Compounds 1 , 3 , 5 , and 7 showed potent immunosuppressive activity with IC 50 values ranging from 5.9 to 9.3 μg/mL.

  6. Large belt conveyors: starting them and keeping them going

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-03-15

    Although heavy-duty conveyor drives are subjected to some of the most severe operating conditions, it is still possible to achieve reliability and low maintenance. Some areas where choices in design and construction can make a difference include thermal capacity, sealing, lubrication and strength. Dodge recently brought out its redesigned Global Series 750 CST - controlled start transmission - a multi-stage gear reducer with an internal clutch designed for smooth starting of high inertia loads on long-distance conveyors. The Antelope Mine in Wyoming's Powder River Basin first installed Dodge CST units in 1984 and has added more units over the years. CSTs have also been successfully employed in Australian coal mines. 1 fig., 1 photo.

  7. Cancer-Associated Fibroblasts from lung tumors maintain their immuno-suppressive abilities after high-dose irradiation

    Directory of Open Access Journals (Sweden)

    Laia eGorchs

    2015-05-01

    Full Text Available Accumulating evidence supports the notion that high-dose (>5 Gy radiotherapy (RT regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study we have investigated the effects of high-dose irradiation (HD-RT on the immunomodulating functions of cancer-associated fibroblasts (CAFs. Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays and T-cell cytokine production. Additionally, CAF-secreted immuno-regulatory factors were studied by multiplex protein arrays, ELISAs and by LC-MS/MS proteomics. In all functional assays we observed a powerful immuno-suppressive effect exerted by CAF-conditioned medium on activated T-cells (p>0,001, and this effect was sustained after a single radiation dose of 18 Gy. Relevant immuno-suppressive molecules such as prostaglandin E2, interleukin-6 and -10, or transforming growth factor-β were found in CAF conditioned medium, but their secretion was unchanged after irradiation. Finally, immunogenic cell death responses in CAFs were studied by exploring the release of high motility group box-1 and ATP. Both alarmins remained undetectable before and after irradiation. In conclusion, CAFs play a powerful immuno-suppressive effect over activated T-cells, and this effect remains unchanged after HD-RT. Importantly, CAFs do not switch on immunogenic cell death responses after exposure to HD-RT.

  8. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

    DEFF Research Database (Denmark)

    Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard

    2015-01-01

    BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...

  9. Healthy rabbits are susceptible to Epstein-Barr virus infection and infected cells proliferate in immunosuppressed animals.

    Science.gov (United States)

    Khan, Gulfaraz; Ahmed, Waqar; Philip, Pretty S; Ali, Mahmoud H; Adem, Abdu

    2015-02-18

    Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of several human malignancies. However, due to the lack of a suitable animal model, a number of fundamental questions pertaining to the biology of EBV remain poorly understood. Here, we explore the potential of rabbits as a model for EBV infection and investigate the impact of immunosuppression on viral proliferation and gene expression. Six healthy New Zealand white rabbits were inoculated intravenously with EBV and blood samples collected prior to infection and for 7 weeks post-infection. Three weeks after the last blood collection, animals were immunosuppressed with daily intramuscular injections of cyclosporin A at doses of 20 mg/kg for 15 days and blood collected twice a week from each rabbit. The animals were subsequently sacrificed and tissues from all major organs were collected for subsequent analysis. Following intravenous inoculation, all 6 rabbits seroconverted with raised IgG and IgM titres to EBV, but viral DNA in peripheral blood mononuclear cells (PBMCs) could only be detected intermittently. Following immunosuppression however, EBV DNA could be readily detected in PBMCs from all 4 rabbits that survived the treatment. Quantitative PCR indicated an increase in EBV viral load in PBMCs as the duration of immunosuppression increased. At autopsy, splenomegaly was seen in 3/4 rabbits, but spleens from all 4 rabbit were EBV PCR positive. EBER-in situ hybridization and immunoshistochemistry revealed the presence of a large number of EBER-positive and LMP-1 positive lymphoblasts in the spleens of 3/4 rabbits. To a lesser extent, EBER-positive cells were also seen in the portal tract regions of the liver of these rabbits. Western blotting indicated that EBNA-1 and EBNA-2 were also expressed in the liver and spleen of infected animals. EBV can infect healthy rabbits and the infected cells proliferate when the animals are immunocompromised. The infected cells expressed several EBV

  10. Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

    Science.gov (United States)

    Castro-Manrreza, Marta E.; Mayani, Hector; Monroy-García, Alberto; Flores-Figueroa, Eugenia; Chávez-Rueda, Karina; Legorreta-Haquet, Victoria; Santiago-Osorio, Edelmiro

    2014-01-01

    Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM—the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BM-MSCs and UCB-MSCs significantly inhibited the proliferation of both CD4+ and CD8+ activated T cells in a cell–cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-γ, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4+CD25+CTLA-4+. Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications. PMID:24428376

  11. The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

    Science.gov (United States)

    Conic, Ruzica Z; Napekoski, Karl; Schuetz, Heidi; Piliang, Melissa; Bergfeld, Wilma; Atanaskova Mesinkovska, Natasha

    2017-06-01

    Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). This was a single center, retrospective study. SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Subject Agreement-Dependency of Accusative Case in Turkish or Jump-starting Grammatical Machinery

    NARCIS (Netherlands)

    Keskin, C.

    2009-01-01

    A work which argues that there is a link between the presence of subject agreement in a construction and the availability of accusative case in that construction. The empirical domain is various types of nominalization in Turkish. Adopts a cross-linguistic perspective to a certain degree, studying

  13. Assessing and improving health in the workplace: an integration of subjective and objective measures with the STress Assessment and Research Toolkit (St.A.R.T. method

    Directory of Open Access Journals (Sweden)

    Panari Chiara

    2012-09-01

    Full Text Available Abstract Background The aim of this work was to introduce a new combined method of subjective and objective measures to assess psychosocial risk factors at work and improve workers’ health and well-being. In the literature most of the research on work-related stress focuses on self-report measures and this work represents the first methodology capable of integrating different sources of data. Method An integrated method entitled St.A.R.T. (STress Assessment and Research Toolkit was used in order to assess psychosocial risk factors and two health outcomes. In particular, a self-report questionnaire combined with an observational structured checklist was administered to 113 workers from an Italian retail company. Results The data showed a correlation between subjective data and the rating data of the observational checklist for the psychosocial risk factors related to work contexts such as customer relationship management and customer queue. Conversely, the factors related to work content (workload and boredom measured with different methods (subjective vs. objective showed a discrepancy. Furthermore, subjective measures of psychosocial risk factors were more predictive of workers’ psychological health and exhaustion than rating data. The different objective measures played different roles, however, in terms of their influence on the two health outcomes considered. Conclusions It is important to integrate self-related assessment of stressors with objective measures for a better understanding of workers’ conditions in the workplace. The method presented could be considered a useful methodology for combining the two measures and differentiating the impact of different psychological risk factors related to work content and context on workers’ health.

  14. Assessing and improving health in the workplace: an integration of subjective and objective measures with the STress Assessment and Research Toolkit (St.A.R.T.) method.

    Science.gov (United States)

    Panari, Chiara; Guglielmi, Dina; Ricci, Aurora; Tabanelli, Maria Carla; Violante, Francesco Saverio

    2012-09-20

    The aim of this work was to introduce a new combined method of subjective and objective measures to assess psychosocial risk factors at work and improve workers' health and well-being. In the literature most of the research on work-related stress focuses on self-report measures and this work represents the first methodology capable of integrating different sources of data. An integrated method entitled St.A.R.T. (STress Assessment and Research Toolkit) was used in order to assess psychosocial risk factors and two health outcomes. In particular, a self-report questionnaire combined with an observational structured checklist was administered to 113 workers from an Italian retail company. The data showed a correlation between subjective data and the rating data of the observational checklist for the psychosocial risk factors related to work contexts such as customer relationship management and customer queue. Conversely, the factors related to work content (workload and boredom) measured with different methods (subjective vs. objective) showed a discrepancy. Furthermore, subjective measures of psychosocial risk factors were more predictive of workers' psychological health and exhaustion than rating data. The different objective measures played different roles, however, in terms of their influence on the two health outcomes considered. It is important to integrate self-related assessment of stressors with objective measures for a better understanding of workers' conditions in the workplace. The method presented could be considered a useful methodology for combining the two measures and differentiating the impact of different psychological risk factors related to work content and context on workers' health.

  15. Menopause in women with chronic immunosuppressive treatment – how to help those patients

    Directory of Open Access Journals (Sweden)

    Anna Cyganek

    2016-03-01

    Full Text Available Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

  16. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    Energy Technology Data Exchange (ETDEWEB)

    Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  17. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    International Nuclear Information System (INIS)

    Easterling, K.J.; Trumble, T.E.

    1990-01-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

  18. A better START for low-acuity victims: data-driven refinement of mass casualty triage.

    Science.gov (United States)

    Cross, Keith P; Petry, Michael J; Cicero, Mark X

    2015-01-01

    Methods currently used to triage patients from mass casualty events have a sparse evidence basis. The objective of this project was to assess gaps of the widely used Simple Triage and Rapid Transport (START) algorithm using a large database when it is used to triage low-acuity patients. Subsequently, we developed and tested evidenced-based improvements to START. Using the National Trauma Database (NTDB), a large set of trauma victims were assigned START triage levels, which were then compared to recorded patient mortality outcomes using area under the receiver-operator curve (AUC). Subjects assigned to the "Minor/Green" level who nevertheless died prior to hospital discharge were considered mistriaged. Recursive partitioning identified factors associated with of these mistriaged patients. These factors were then used to develop candidate START models of improved triage, whose overall performance was then re-evaluated using data from the NTDB. This process of evaluating performance, identifying errors, and further adjusting candidate models was repeated iteratively. The study included 322,162 subjects assigned to "Minor/Green" of which 2,046 died before hospital discharge. Age was the primary predictor of under-triage by START. Candidate models which re-assigned patients from the "Minor/Green" triage level to the "Delayed/Yellow" triage level based on age (either for patients >60 or >75), reduced mortality in the "Minor/Green" group from 0.6% to 0.1% and 0.3%, respectively. These candidate START models also showed net improvement in the AUC for predicting mortality overall and in select subgroups. In this research model using trauma registry data, most START under-triage errors occurred in elderly patients. Overall START accuracy was improved by placing elderly but otherwise minimally injured-mass casualty victims into a higher risk triage level. Alternatively, such patients would be candidates for closer monitoring at the scene or expedited transport ahead of other

  19. Accuracy of C - Reactive protein as a bacterial infection marker in critically immunosuppressed patients: A systematic review and meta-analysis.

    Science.gov (United States)

    de Oliveira, Vanessa Martins; Moraes, Rafael Barberena; Stein, Airton Tetelbom; Wendland, Eliana Márcia

    2017-12-01

    There is a need for a better understanding of the role of C-reactive protein (CRP) as a valid marker for the detection of bacterial infections in critically immunosuppressed patients. A high negative predictive value of CRP is also needed to rule out sepsis and bacterial infections in immunocompetent patients. However, few studies have evaluated the performance of CRP in immunocompromised hosts. The aim of the present study was to evaluate the performance of CRP as a marker of infection in critically immunosuppressed patients. The inclusion criterion was immunosuppression for which CRP was used as a bacterial infection marker. Searches were performed in the Cochrane Register, MEDLINE, EMBASE, SCOPUS, Web OF Science, LILACS and CINAHL databases. We applied the Quality Assessment of Diagnostic Accuracy Studies tool 2 (QUADAS 2) to evaluate the quality of the articles and evaluated the test accuracy parameters using hierarchical summary receiver operating characteristic (HSROC) curves and bivariate random effect models. Only 13 of 21 studies produced quantitative results. We analyzed all studies using the random effects method (restricted maximum likelihood) and obtained a joint diagnostic odds ratio (DOR) of 3.04 (95% confidence interval [CI] 1.71-5.40) with heterogeneity (I 2 =91%, Q=181.48, p<0.001). Therefore, a bivariate model was applied. Analyzing the tuberculosis carrier, steroid user, or presence of opportunistic infection subgroups, as described in the proposal, was not possible due to the lack of information on these topics included in the articles. CRP appears to be a good screening tool for sepsis in critically immunosuppressed patients. Submitted PROSPERO 2015: CRD42015019329. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Raghavan Chinnadurai

    2013-01-01

    Full Text Available The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS, linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs.

  1. DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.

    Science.gov (United States)

    Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

    2016-07-01

    Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  2. Lean start-up

    DEFF Research Database (Denmark)

    Rasmussen, Erik Stavnsager; Tanev, Stoyan

    2016-01-01

    The risk of launching new products and starting new firms is known to be extremely high. The Lean Start-up approach is a way of reducing these risks and enhancing the chances for success by validating the products and services in the market with customers before launching it in full scale. The ma...... and the final business model. In other words: The start-up must first nail the problem together with the customers, then develop the solution and test, and then in the end scale it to a full-grown business model.......The risk of launching new products and starting new firms is known to be extremely high. The Lean Start-up approach is a way of reducing these risks and enhancing the chances for success by validating the products and services in the market with customers before launching it in full scale. The main...

  3. Key parameters of the swimming start and their relationship to start performance.

    Science.gov (United States)

    Tor, Elaine; Pease, David L; Ball, Kevin A

    2015-01-01

    The swimming start is typically broken into three sub-phases; on-block, flight, and underwater phases. While overall start performance is highly important to elite swimming, the contribution of each phase and important technical components within each phase, particularly with the new kick-start technique, has not been established. The aim of this study was to identify technical factors associated with overall start performance, with a particular focus on the underwater phase. A number of parameters were calculated from 52 starts performed by elite freestyle and butterfly swimmers. These parameters were split into above-water and underwater groupings, before factor analysis was used to reduce parameter numbers for multiple regression. For the above-water phases, 81% of variance in start performance was accounted for by take-off horizontal velocity. For the underwater water phase, 96% of variance was accounted for with time underwater in descent, time underwater in ascent and time to 10 m. Therefore, developing greater take-off horizontal velocity and focussing on the underwater phase by finding the ideal trajectory will lead to improved start performance.

  4. From START to NEW START. The dilemma and future of nuclear disarmament; Von START zu NEW START. Das Dilemma und die Zukunft der Nuklearen Abruestung

    Energy Technology Data Exchange (ETDEWEB)

    Plettenberg, Lars

    2012-07-01

    The report describes the existing four agreements on nuclear disarmament: START I (1991). START II (1993), SORT (2002) and NEW START (2010). The chapter on the dependence between nuclear disarmament and strategic stability covers the issues mutual assured destruction (MAD), credibility, overkill capacity; the role of nuclear weapons in the national strategies of the USA and NATO, Russia, Great Britain, France, China and the other nuclear states. Ways out of MAD include disarmament, de-alerting and mutual assured protection (MAP).

  5. Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

    Directory of Open Access Journals (Sweden)

    Asami Hanazawa

    2018-02-01

    Full Text Available The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs, and tumor-associated macrophages (TAMs that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg mouse strain, human interleukin (hIL-6-expressing NOG mice (NOG-hIL-6 transgenic mice. After transplantation of human hematopoietic stem cells (HSCs, the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF, and vascular endothelial growth factor (VEGF, into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1, IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory/immunosuppressive

  6. Genetic variation in the immunosuppression pathway genes and breast cancer: a pooled analysis of 42,510 cases and 40,577 controls from the Breast

    OpenAIRE

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison Margaret; Easton, Douglas Frederick; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien

    2015-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate g...

  7. Engraftment versus immunosuppression: cost-benefit analysis of immunosuppression after intrahepatic murine islet transplantation.

    Science.gov (United States)

    Marzorati, Simona; Melzi, Raffaella; Citro, Antonio; Cantarelli, Elisa; Mercalli, Alessia; Scavini, Marina; Piemonti, Lorenzo

    2014-05-27

    Immunosuppression (IS) in islet transplantation (Tx) is a double-edged sword: it prevents immunoreaction but has the potential to impair islet engraftment. The aim of this study was to identify in murine animal models the IS platform with the best balance between these two opposite effects. To study the impact of IS on islet engraftment diabetic C57BL/6 mice were transplanted with 350 syngeneic islets through the portal vein and treated once-daily with either rapamycin (RAPA; 0.1-0.5-1 mg/kg ip), tacrolimus (FK506; 0.1-0.5-1 mg/kg ip), mycophenolate mofetil (MMF; 60-120-300 mg/kg oral) or vehicle for 14 days. Islet function was evaluated by measuring not-fasting glycemia and by performing an IVGTT on days 15 and 30 post-Tx. RAPA ≥0.5 mg/Kg, FK506 ≥0.5 mg/Kg, and MMF ≥120 mg/kg had detrimental effects on islet engraftment but not on the function of islets already engrafted in the liver. The effect on engraftment was irreversible and persisted even after IS withdrawal. The lower dose of IS that did not affect engraftment was tested for preventing rejection in the full mismatch allogeneic Tx BALB/c to C57BL/6 model. RAPA and/or FK506 were inefficient in preventing rejection, even when anti-IL2R mAb was added to the IS regimen. On the other hand, MMF alone or in association with FK506 significantly prolonged the time to islet rejection. IS showed profound dose-dependent deleterious effects on islet cell engraftment. The MMF/FK506 combination proved the best balance with less toxicity at the time of engraftment and more efficacy in controlling graft rejection.

  8. Symptom experience associated with immunosuppressive drugs after liver transplantation in adults : possible relationship with medication non-compliance?

    NARCIS (Netherlands)

    Drent, Gerda; Moons, P.; De Geest, S.; Kleibeuker, J. H.; Haagsma, E. B.

    2008-01-01

    Symptom experience (occurrence and perceived distress) associated with side effects of immunosuppressive medications in organ transplant patients may well be associated with poorer quality of life and medication non-compliance. The aims of this study were: first, to assess symptom experience in

  9. Skin cancer in immunosuppressed transplant patients:Vigilance matters

    Institute of Scientific and Technical Information of China (English)

    Ozan Unlu; Emir Charles Roach; Alexis Okoh; May Olayan; Bulent Yilmaz; Didem Uzunaslan; Abdullah Shatnawei

    2015-01-01

    Liver transplantation (LT) is a widely-accepted, definitivetherapy of irreversible liver diseases including hepatitisC, alcoholic liver disease and metabolic liver disease.After transplantation, patients generally use a varietyof immunosuppressive medications for the rest of theirlives to prevent rejection of transplanted liver. Mortalityafter LT is mainly caused by recurrence of alcoholichepatitis which is mostly seen in the patients whoresume heavy drinking. On the other hand, de-novomalignancies after LT are not seldom. Skin cancers makeup 13.5% of the de-novo malignancies seen in thesepatients. Malignancies tend to affect survival earlier inthe course with a 53% risk of death at 5 years afterdiagnosis. We aimed to report a case who underwentLT secondary to alcoholic liver disease and developedsquamous cell carcinoma of the skin eighteen yearsafter transplantation. In summary, transplant recipientsare recommended to be educated on self examinationfor skin cancer; health care providers should be furthersuspicious during routine dermatological examinations ofthe transplant patients and biopsies of possible lesionsfor skin cancer is warranted even many years aftertransplantation.

  10. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  11. Immunosuppressant therapeutic drug monitoring by LC-MS/MS: workflow optimization through automated processing of whole blood samples.

    Science.gov (United States)

    Marinova, Mariela; Artusi, Carlo; Brugnolo, Laura; Antonelli, Giorgia; Zaninotto, Martina; Plebani, Mario

    2013-11-01

    Although, due to its high specificity and sensitivity, LC-MS/MS is an efficient technique for the routine determination of immunosuppressants in whole blood, it involves time-consuming manual sample preparation. The aim of the present study was therefore to develop an automated sample-preparation protocol for the quantification of sirolimus, everolimus and tacrolimus by LC-MS/MS using a liquid handling platform. Six-level commercially available blood calibrators were used for assay development, while four quality control materials and three blood samples from patients under immunosuppressant treatment were employed for the evaluation of imprecision. Barcode reading, sample re-suspension, transfer of whole blood samples into 96-well plates, addition of internal standard solution, mixing, and protein precipitation were performed with a liquid handling platform. After plate filtration, the deproteinised supernatants were submitted for SPE on-line. The only manual steps in the entire process were de-capping of the tubes, and transfer of the well plates to the HPLC autosampler. Calibration curves were linear throughout the selected ranges. The imprecision and accuracy data for all analytes were highly satisfactory. The agreement between the results obtained with manual and those obtained with automated sample preparation was optimal (n=390, r=0.96). In daily routine (100 patient samples) the typical overall total turnaround time was less than 6h. Our findings indicate that the proposed analytical system is suitable for routine analysis, since it is straightforward and precise. Furthermore, it incurs less manual workload and less risk of error in the quantification of whole blood immunosuppressant concentrations than conventional methods. © 2013.

  12. Post-therapeutic recovery of serum interleukin-35 level might predict positive response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Huang, Zhen; Tong, Hongfei; Li, Yuan; Zhou, Haixia; Qian, Jiangchao; Wang, Juxiang; Ruan, Jichen

    2017-08-01

    The predictive value of interleukin-35 (IL-35) on efficacy of immunosuppressive therapy (IST) in aplastic anemia (AA) has not been well investigated. The aim of the study was to evaluate the association between serum IL-35 level and response to IST in pediatric AA. A total of 154 children with AA and 154 controls were included between January 2012 and December 2013. Blood and bone marrow fluid specimens were collected. Serum level of IL-35 was determined by enzyme-linked immunosorbent assay. Patients were treated with IST, and response to therapy was evaluated during 180-day follow-up period after starting therapy. Serum levels of IL-35 at admission decreased significantly in patients compared with that in controls (10.9 ± 5.5 pg ml -1 and 45.3 ± 8.8 pg ml -1 , p < 0.001). After starting IST, serum levels of IL-35 in patients recovered 30.7 ± 9.7 pg ml -1 in the first 28 days (p < 0.001). During the follow-up period, increased range of serum IL-35 level ≥30.7 pg ml -1 in the first 28 days was associated with effective response to therapy (odds ratio 7.97, 95% confidence interval 3.82-16.79). In addition, Fas/FasL protein expression in bone marrow mononuclear cells dropped significantly in the same group of patients in the first 28 days (p < 0.05). The study revealed that post-therapeutic recovery of circulating IL-35 concentration might be an independent predictor for effective response to IST in pediatric AA. Moreover, apoptosis might be involved in such a forecasting process.

  13. Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals.

    Science.gov (United States)

    Stanjek-Cichoracka, A; Żegleń, S; Ramos, P; Pilawa, B; Wojarski, J

    2018-06-01

    The immunosuppressive drugs used in solid organ transplantation or autoimmunological processes were studied by electron paramagnetic resonance (EPR) spectroscopy to estimate their free radical scavenging activity. The interactions of immunosuppressants with free radicals were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free radicals. The EPR spectra of DPPH and DPPH interacting with individual drugs were compared. Kinetic studies were performed, and the effect of ultraviolet (UV) irradiation on the free radical scavenging activity of the tested drugs was determined. The free radical scavenging activity of non-irradiated drugs decreased in the order: rapamycin > mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the free radical scavenging activity of all the tested immunosuppressive drugs, and the effect was highest for tacrolimus. For the non-irradiated samples, the speed of free radical interactions decreased in the order: ciclosporin > tacrolimus > mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the speed of interactions of the immunosuppressive drugs with the model DPPH free radicals. Electron paramagnetic resonance spectroscopy is useful for obtaining information on interactions of immunosuppressive drugs with free radicals. We hypothesized that the long-term immunosuppressive effects of these drugs after transplantation or during autoimmune disorders may be mediated by anti-inflammatory action in addition to the known receptor/cell cycle inhibition. © 2018 John Wiley & Sons Ltd.

  14. Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON-RD1 test

    DEFF Research Database (Denmark)

    Ravn, Pernille; Munk, Martin E; Andersen, Ase Bengaard

    2004-01-01

    A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive...

  15. Candidal carriage predicts candidiasis during topical immunosuppressive therapy: a preliminary retrospective cohort study.

    Science.gov (United States)

    Tejani, Sara; Sultan, Ahmed; Stojanov, Ivan; Woo, Sook-Bin

    2016-10-01

    To determine (1) the prevalence of candidal carriage in patients with oral mucosal disease to be treated with topical immunosuppressive therapy, and (2) the incidence of oral candidiasis among carriers and noncarriers after initiation of therapy to assess any correlation between carriage and the development of candidiasis. Records of patients who underwent swab cultures for Candida between January 2009 and October 2014 at the Brigham and Women's Hospital in Boston, Massachusetts, were retrospectively reviewed. The prevalence of candidal carriage and incidence of candidiasis were determined by using descriptive statistics. Of 99 evaluable patients, 20 (20.2%) were Candida positive and 79 (79.8%) were Candida negative. Of 44 patients with follow-up, 7 (15.9%) were Candida positive and 37 (84.1%) were Candida negative; five (11.4%) developed candidiasis. Four of seven (57.1%) Candida-positive patients developed candidiasis, whereas only one of 37 (2.7%) Candida-negative patients developed candidiasis (P = .0012). The overall prevalence of candidal carriage was low (20.2%), and there was a significant difference in the incidence of candidiasis between carriers and noncarriers (P = .0012) after topical immunosuppressive therapy. Therefore, patients who are candidal carriers should be monitored closely for the development of secondary candidiasis and may be candidates for prophylactic antifungal therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Adenosinergic Immunosuppression by Human Mesenchymal Stromal Cells Requires Co-Operation with T cells.

    Science.gov (United States)

    Kerkelä, Erja; Laitinen, Anita; Räbinä, Jarkko; Valkonen, Sami; Takatalo, Maarit; Larjo, Antti; Veijola, Johanna; Lampinen, Milla; Siljander, Pia; Lehenkari, Petri; Alfthan, Kaija; Laitinen, Saara

    2016-03-01

    Mesenchymal stem/stromal cells (MSCs) have the capacity to counteract excessive inflammatory responses. MSCs possess a range of immunomodulatory mechanisms, which can be deployed in response to signals in a particular environment and in concert with other immune cells. One immunosuppressive mechanism, not so well-known in MSCs, is mediated via adenosinergic pathway by ectonucleotidases CD73 and CD39. In this study, we demonstrate that adenosine is actively produced from adenosine 5'-monophosphate (AMP) by CD73 on MSCs and MSC-derived extracellular vesicles (EVs). Our results indicate that although MSCs express CD39 at low level and it colocalizes with CD73 in bulge areas of membranes, the most efficient adenosine production from adenosine 5'-triphosphate (ATP) requires co-operation of MSCs and activated T cells. Highly CD39 expressing activated T cells produce AMP from ATP and MSCs produce adenosine from AMP via CD73 activity. Furthermore, adenosinergic signaling plays a role in suppression of T cell proliferation in vitro. In conclusion, this study shows that adenosinergic signaling is an important immunoregulatory mechanism of MSCs, especially in situations where ATP is present in the extracellular environment, like in tissue injury. An efficient production of immunosuppressive adenosine is dependent on the concerted action of CD39-positive immune cells with CD73-positive cells such as MSCs or their EVs. © 2016 AlphaMed Press.

  17. The Immunosuppressant Effect Comparation Between Ethyl Acetate and n-Butanol Fractions of Kalanchoe Pinnata (Lmk Pers In 2,6,10,14 Tetramethylpentadecane-Treated Mice

    Directory of Open Access Journals (Sweden)

    Niken Indriyanti

    2017-07-01

    Full Text Available Immunosuppressant drugs are the main treatment of lupus patient. The ACR and SLICC treatment guidelines are able to increase the quality of life, but the outcome is not satisfying since the off-label therapy of corticosteroids and cytotoxic drugs give a lot of side effects. Many breakthrough efforts still develop in order to find the safe and effective drugs for lupus, such as finding immunosuppressant drugs from natural resources. One of the potential resources is Kalanchoe pinnata (Lmk Pers, which have immunosuppressant, anti-inflammatory, antinociceptive, and antioxidant effects. Thus, in the previous study, we found the effect of the aqueous extract of Kalanchoe pinnata (Lmk Pers is active to repair the lupus manifestation in 2,6,10,14 tetramethylpentadecane (TMPD-treated mice. Then, this research was focused on the in vivo immunosuppressant effect of a flavonoid-rich fraction of the extract which was consisted of the ethyl acetate (FE and n-butanol (FB fractions. The induction method and the extraction procedure were the same as the previous study and then the fractionation was performed by using liquid-liquid extraction. After 2-week treatment of both fractions, we obtained the differences in the total leukocytes, organ indexes, and also the spleen, kidney, and joint structure parameters. The total leukocyte of the FE group was 3,600±264 cells/mm3, which was lower than that in the FB group. The spleen and kidney indexes increased after the administration of FB fraction, while the FE fraction was not. At last, despite the histology observation of spleen resembled mild structural changes differences, the clear differences between both treatment groups occurred in the kidney and joint histology. The differences led to a conclusion that the FE fraction has the better immunosuppressant effect in TMPD-treated mice.

  18. Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro.

    Science.gov (United States)

    Martina, M N; Ramirez Bajo, M J; Bañon-Maneus, E; Moya Rull, D; Hierro-Garcia, N; Revuelta, I; Campistol, J M; Rovira, J; Diekmann, F

    2016-11-01

    Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27 + CD24 + phenotype was not modified by any immunosuppressive treatment. Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation. Copyright © 2016. Published by Elsevier Inc.

  19. Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: clues for possible immunosuppression-related or infectious etiology.

    Science.gov (United States)

    Shiels, Meredith S; Engels, Eric A

    2012-10-01

    Malignancies that occur in excess among human immunodeficiency virus (HIV)-infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS). Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population-based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression). Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression). The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Copyright © 2012 American Cancer Society.

  20. Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

    International Nuclear Information System (INIS)

    Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

    2008-01-01

    CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

  1. Transcultural adaptation and initial validation of Brazilian-Portuguese version of the Basel assessment of adherence to immunosuppressive medications scale (BAASIS) in kidney transplants.

    Science.gov (United States)

    Marsicano, Elisa de Oliveira; Fernandes, Neimar da Silva; Colugnati, Fernando; Grincenkov, Fabiane Rossi dos Santos; Fernandes, Natalia Maria da Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

    2013-05-21

    Transplant recipients are expected to adhere to a lifelong immunosuppressant therapeutic regimen. However, nonadherence to treatment is an underestimated problem for which no properly validated measurement tool is available for Portuguese-speaking patients. We aimed to initially validate the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS®) to accurately estimate immunosuppressant nonadherence in Brazilian transplant patients. The BAASIS® (English version) was transculturally adapted and its psychometric properties were assessed. The transcultural adaptation was performed using the Guillemin protocol. Psychometric testing included reliability (intraobserver and interobserver reproducibility, agreement, Kappa coefficient, and the Cronbach's alpha) and validity (content, criterion, and construct validities). The final version of the transculturally adapted BAASIS® was pretested, and no difficulties in understanding its content were found. The intraobserver and interobserver reproducibility variances (0.007 and 0.003, respectively), the Cronbach's alpha (0.7), Kappa coefficient (0.88) and the agreement (95.2%) suggest accuracy, preciseness and reliability. For construct validity, exploratory factorial analysis demonstrated unidimensionality of the first three questions (r = 0.76, r = 0.80, and r = 0.68). For criterion validity, the adapted BAASIS® was correlated with another self-report instrument, the Measure of Adherence to Treatment, and showed good congruence (r = 0.65). The BAASIS® has adequate psychometric properties and may be employed in advance to measure adherence to posttransplant immunosuppressant treatments. This instrument will be the first one validated to use in this specific transplant population and in the Portuguese language.

  2. Immunosuppressive mechanisms in protein-calorie malnutrition

    International Nuclear Information System (INIS)

    Redmond, H.P.; Shou, J.; Kelly, C.J.; Schreiber, S.; Miller, E.; Leon, P.; Daly, J.M.

    1991-01-01

    Protein-calorie malnutrition (PCM) induces immunosuppression leading to increased mortality rates. Impaired macrophage respiratory burst activity (superoxide anion [O2-] generation) occurs in PCM, but cellular mechanisms are unclear. The major pathway resulting in O2- production involves inositol lipid-dependent signal transduction. This study examined the effect of mild versus severe PCM on macrophage O2- generating signal transduction pathways specific for responses to Candida albicans. Mice (CFW/Swiss Webster: n = 300) were randomized to either control or low protein diets for 3 or 8 weeks. Peritoneal macrophages were harvested for O2- production, mannose-fucose receptor (MFR) expression, membrane phospholipid analysis, arachidonic acid (AA) content, prostaglandin E2 (PGE2) production, and protein kinase C levels. O2- release was impaired in both mild and severe PCM. MFR expression was also decreased at these time points. Inositol lipid content was significantly lower at the 8-week time point only, although PGE2 and AA were significantly higher in the low protein diet group at 3 weeks. Protein kinase C levels were unchanged by PCM. Thus, mild PCM significantly increases macrophage-PGE2 production secondary to increased AA phospholipid content, with subsequent inhibition of O2- and MFR expression. Severe PCM inhibits macrophage (O2-) through depletion of critical membrane phospholipid components with subsequent impairment in signal transduction

  3. Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

    Directory of Open Access Journals (Sweden)

    Michaud L

    2016-12-01

    Full Text Available Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20 might have lower medication adherence than noncomplex patients (INTERMED≤20. Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20. Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11 and noncomplex patients (N=21 were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value. Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly

  4. Feasibility of ionizing radiation decontamination of ready to eat fresh vegetable salads for immunosuppressed patients

    International Nuclear Information System (INIS)

    Horak, Celina I.; Narvaiz, Patricia; Kairiyama, Eulogia; Adeil Pietranera, Maria S.; Gimenez, Palmira; Gronostajsky, D.

    2003-01-01

    In the last years consumer trends have increased for fresh like and minimally processed foods. Also, foods are frequently requested without or reduced chemical preservatives. Minimally processed foods have a limited shelf life and mainly rely on HACCP and refrigeration for preservation. However, over the last years, the detection of food borne illness outbreaks associated with fresh vegetables and fruits has increased. This is possible because these product characteristics, high moisture and their cut surface, provide excellent conditions for microorganisms growth. As the feasibility of applying ionizing radiation to inactivate microorganisms is well known, this project will contribute to define the minimal and maximum doses in order to assure the hygienic quality and shelf life of this fresh pre-cut vegetables and fruits. Immunosuppressed patients have different classes of diets, depending on the immunosuppression grade. The hygienic quality was determined on the basis of levels 2 and 3, for (recovery and ambulatory patients respectively). The products investigated were carrots and tomatoes and the irradiation facility was a Cobalt Source. The microorganisms analysed were TBC, Mould and Yeasts, Total coliforms and faecal coliforms. Sensorial evaluation was carried out on the basis of a hedonic scale. (author)

  5. Later Start, Longer Sleep: Implications of Middle School Start Times

    Science.gov (United States)

    Temkin, Deborah A.; Princiotta, Daniel; Ryberg, Renee; Lewin, Daniel S.

    2018-01-01

    Background: Although adolescents generally get less than the recommended 9 hours of sleep per night, research and effort to delay school start times have generally focused on high schools. This study assesses the relation between school start times and sleep in middle school students while accounting for potentially confounding demographic…

  6. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Adam Gassas

    2011-01-01

    Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

  7. Dynamic factors and electromyographic activity in a sprint start

    Directory of Open Access Journals (Sweden)

    M Čoh

    2009-07-01

    Full Text Available The aim of the study was to establish the major dynamic parameters as well as the EMG activation of muscles in a sprint start as the first derivative of sprint velocity. The subject of the analysis was block velocity, the production of force in the front and rear starting blocks, the block acceleration in the first two steps and the electromyographic activity (EMG of the following muscles: the erector spinae muscle, gluteus maximus muscle, rectus femoris muscle, vastus medialis muscle, vastus lateralis muscle, biceps femoris muscle and gastrocnemius–medialis muscle. One international-class female sprinter participated in the experiment. She performed eight starts in constant laboratory conditions. The 3-D kinematic analysis was made using a system of nine Smart-e 600 cameras operating at a frame rate of 60 Hz. Dynamic parameters were established by means of two separate force platforms to which the starting blocks were fixed. A 16-channel electromyograph was used to analyse electromyographic activity (EMG. It was established that the block velocity depended on the absolute force produced in the front and rear starting blocks and that it was 2.84±0.21 m.s-1. The maximal force on the rear and front blocks was 628±34 N and 1023±30 N, respectively. In view of the total impulse (210±11 Ns the force production/time ratio in the rear and front blocks was 34%:66%. The erector spinae muscle, vastus lateralis muscle and gastrocnemius–medialis muscle generate the efficiency of the start. The block acceleration in the first two steps primarily depends on the activation of the gluteus maximus muscle, rectus femoris muscle, biceps femoris muscle and gastrocnemius–medialis muscle. A sprint start is a complex motor stereotype requiring a high degree of integration of the processes of central movement regulation and an optimal level of biomotor abilities.

  8. Very late relapse of PTLD 10 yrs after allogeneic HSCT and nine yrs after stopping immunosuppressive therapy

    DEFF Research Database (Denmark)

    Helgestad, Jon; Rosthøj, Steen; Pedersen, Morten Høgild

    2014-01-01

    the fever settled, the PET scan normalized, and the M-component disappeared. Without any ongoing immunosuppressive therapy, PTLD relapsed nine yr later with large intra-abdominal lymph node masses causing ureteric obstruction with bilateral hydronephrosis. Pathological features were identical to the primary...

  9. Impurity control and its impact upon start-up and transformer recharging in NET

    International Nuclear Information System (INIS)

    Harrison, M.F.A.

    1985-01-01

    Control of the release of impurities and their subsequent ingress and exhaust from tokamak plasmas has been the subject of intensive studies aimed at both the prediction of reactor burn condition and the interpretation of results from present experiments. Control concepts which are specific to current-initiation, current ramp-up and RF heating during start-up of a reactor such as NET have to date received little attention, according to the author. This paper presents an inductive start-up scenario which is typical of those presently being considered for NET. Shown are plasma configurations during start-up. Particularly significant issues are the advantages of forming the divertor configuration at the earliest practicable stage and the problems expected due to contamination of the limiter with divertor material

  10. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

    Science.gov (United States)

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

    2016-10-15

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Time program using in automatization of steam turbines start-up

    International Nuclear Information System (INIS)

    Lejzerovich, A.Sh.; Melamed, A.D.

    Examples and arguments for developing time programs of changing basic parameters of automated start-up of TPP and NPP high-power steam turbines are considered. Basic parameters subject to controlled changing at automatization of turbine start-up are rotation frequency, loading and temperature of steam supplied to the turbine. Principle facility schemes of program regulation of steam temperature at the start-up are presented. The facility scheme of loading the NPP wet steam turbine is given. The principles of developing time programs, of changing basic parameters of automated start-up enable realizing transient processes close to theoretically optimum processes at arbitrary prestart-up state of the turbine by means of rather simple autatic facilities. In particular, for automated temperature increase of steam supplied to the turbine of TES power units and AES turbine loading, it is advisable to use programs in the form of linear dependence of velocity of changing the controlled parameter on the given value, the initial level, from which the parameter increase with a regulated velocity is realized, is given in the form of analogue dependence on the turbine prestart-up state. The programs described and the schemes of their realization have been approved at the automatization of 300 MW power unit starts up with the K-300-240 turbine and K-220-44 turbine as well as used when creating control system for turbines of 500 MW and higher for designed TPP and NPP power units

  12. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Science.gov (United States)

    2011-06-24

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Capital Investment Program--New Starts... apportionment of the FY 2011 Capital Investment (New Starts and Small Starts) program funds. The funds will be... FY 2011, $1,596,800,000 was appropriated for the Capital Investments Grant Account, which includes...

  13. Protocol for the combined immunosuppression & radiotherapy in thyroid eye disease (CIRTED trial: A multi-centre, double-masked, factorial randomised controlled trial

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    Kingston Laura

    2008-01-01

    Full Text Available Abstract Background Medical management of thyroid eye disease remains controversial due to a paucity of high quality evidence on long-term treatment outcomes. Glucocorticoids are known to be effective initially but have significant side-effects with long-term use and recrudescence can occur on cessation. Current evidence is conflicting on the efficacy of radiotherapy and non-steroid systemic immunosuppression, and the majority of previous studies have been retrospective, uncontrolled, small or poorly designed. The Combined Immunosuppression and Radiotherapy in Thyroid Eye Disease (CIRTED trial was designed to investigate the efficacy of radiotherapy and azathioprine in combination with a standard course of oral prednisolone in patients with active thyroid eye disease. Methods/design Patients with active thyroid eye disease will be randomised to receive (i azathioprine or oral placebo and (ii radiotherapy or sham-radiotherapy in this multi-centre, factorial randomised control trial. The primary outcome is improvement in disease severity (assessed using a composite binary measure at 12 months and secondary end-points include quality of life scores and health economic measures. Discussion The CIRTED trial is the first study to evaluate the role of radiotherapy and azathioprine as part of a long-term, combination immunosuppressive treatment regime for Thyroid Eye Disease. It will provide evidence for the role of radiotherapy and prolonged immunosuppression in the management of this condition, as well as pilot data on their use in combination. We have paid particular attention in the trial design to establishing (a robust placebo controls and masking protocols which are effective and safe for both radiotherapy and the systemic administration of an antiproliferative drug; (b constructing effective inclusion and exclusion criteria to select for active disease; and (c selecting pragmatic outcome measures. Trial registration Current controlled trials

  14. Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons.

    Science.gov (United States)

    Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

    2016-12-01

    Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Dexamethasone-immunosuppressed male mice (6-8weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (Pvirus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Manual wheelchair propulsion patterns on natural surfaces during start-up propulsion.

    Science.gov (United States)

    Koontz, Alicia M; Roche, Bailey M; Collinger, Jennifer L; Cooper, Rory A; Boninger, Michael L

    2009-11-01

    To classify propulsion patterns over surfaces encountered in the natural environment during start-up and compare selected biomechanical variables between pattern types. Case series. National Veterans Wheelchair Games, Minneapolis, MN, 2005. Manual wheelchair users (N=29). Subjects pushed their wheelchairs from a resting position over high-pile carpet, over linoleum, and up a ramp with a 5 degrees incline while propulsion kinematics and kinetics were recorded with a motion capture system and an instrumented wheel. Three raters classified the first 3 strokes as 1 of 4 types on each surface: arc, semicircular (SC), single looping over propulsion (SL), and double looping over propulsion (DL). The Fisher exact test was used to assess pattern changes between strokes and surface type. A multiple analysis of variance test was used to compare peak and average resultant force and moment about the hub, average wheel velocity, stroke frequency, contact angle, and distance traveled between stroke patterns. SL was the most common pattern used during start-up propulsion (44.9%), followed by arc (35.9%), DL (14.1%), and SC (5.1%). Subjects who dropped their hands below the rim during recovery achieved faster velocities and covered greater distances (.016propulsion patterns is a difficult task that should use multiple raters. In addition, propulsion patterns change during start-up, with an arc pattern most prevalent initially. The biomechanical findings in this study agree with current clinical guidelines that recommend training users to drop the hand below the pushrim during recovery.

  16. Infecção experimental pelo Encephalitozoon cuniculi em camundongos imunossuprimidos com dexametasona Experimental Encephalitozoon cuniculi infection in dexamethasone-immunosuppressed mice

    Directory of Open Access Journals (Sweden)

    Maria Anete Lallo

    2002-10-01

    Full Text Available OBJETIVO: O microsporídio Encephalitozoon cuniculi tem sido reconhecido como um patógeno oportunista em indivíduos imunossuprimidos, tais como pacientes com Aids. O objetivo do trabalho foi desenvolver animais farmacologicamente imunossuprimidos como modelo da infecção natural pelo E. cuniculi. MÉTODOS: Foram usados grupos distintos de camundongos Balb-C adultos, imunossuprimidos com diferentes doses de dexametasona (Dx, 3 ou 5 mg/kg/dia por via intraperitoneal ¾ IP e inoculados com esporos de E. cuniculi por via IP. Também foram usados grupos controle (animais inoculados, mas nãoimunossuprimidos, e animais imunossuprimidos, mas não inoculados. Os esporos de E. cuniculi foram previamente cultivados em células MDCK. Os animais foram sacrificados e submetidos à necropsia aos 7, 14, 21, 28 e 35 dias pós-inoculação. Fragmentos teciduais foram coletados e processados para análise por microscopia de luz, utilizando-se as técnicas de coloração de Gram -chromotrope e de hematoxilina-eosina. RESULTADOS: Em todos os animais imunossuprimidos e inoculados, porém especialmente naqueles que receberam 5 mg/kg/dia de Dx, os achados de necropsia mais proeminentes foram hepato e esplenomegalia. A inoculação experimental resultou em uma infecção disseminada e não-letal, caracterizada por lesões granulomatosas em diversos órgãos (fígado, pulmões, rins, intestino, encéfalo, porém mais notadamente no tecido hepático. Esporos de E. cuniculi foram observados em poucos animais tratados com 5 mg/kg/dia de Dx aos 35 dias pós-infecção. CONCLUSÕES: Microsporidiose em camundongos imunossuprimidos com Dx fornece um modelo útil para estudos da infecção por microsporídios, assemelhando-se àquela naturalmente observada em indivíduos imunodeficientes com Aids.OBJECTIVE: Microsporidian Encephalitozoon cuniculi has been recognized as an opportunistic pathogen in immunosuppressed individuals, such as AIDS patients. The objective of the

  17. A fast-start pacing strategy speeds pulmonary oxygen uptake kinetics and improves supramaximal running performance.

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    Tiago Turnes

    Full Text Available The focus of the present study was to investigate the effects of a fast-start pacing strategy on running performance and pulmonary oxygen uptake (VO2 kinetics at the upper boundary of the severe-intensity domain. Eleven active male participants (28±10 years, 70±5 kg, 176±6 cm, 57±4 mL/kg/min visited the laboratory for a series of tests that were performed until exhaustion: 1 an incremental test; 2 three laboratory test sessions performed at 95, 100 and 110% of the maximal aerobic speed; 3 two to four constant speed tests for the determination of the highest constant speed (HS that still allowed achieving maximal oxygen uptake; and 4 an exercise based on the HS using a higher initial speed followed by a subsequent decrease. To predict equalized performance values for the constant pace, the relationship between time and distance/speed through log-log modelling was used. When a fast-start was utilized, subjects were able to cover a greater distance in a performance of similar duration in comparison with a constant-pace performance (constant pace: 670 m±22%; fast-start: 683 m±22%; P = 0.029; subjects also demonstrated a higher exercise tolerance at a similar average speed when compared with constant-pace performance (constant pace: 114 s±30%; fast-start: 125 s±26%; P = 0.037. Moreover, the mean VO2 response time was reduced after a fast start (constant pace: 22.2 s±28%; fast-start: 19.3 s±29%; P = 0.025. In conclusion, middle-distance running performances with a duration of 2-3 min are improved and VO2 response time is faster when a fast-start is adopted.

  18. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

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    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  19. Pharmacogenetics of immunosuppressants: State of the art and clinical implementation - recommendations from the French National Network of Pharmacogenetics (RNPGx).

    Science.gov (United States)

    Woillard, Jean-Baptiste; Chouchana, Laurent; Picard, Nicolas; Loriot, Marie-Anne

    2017-04-01

    Therapeutic drug monitoring is already widely used for immunosuppressive drugs due to their narrow therapeutic index. This article summarizes evidence reported in the literature regarding the pharmacogenetics of (i) immunosuppressive drugs used in transplantation and (ii) azathioprine used in chronic inflammatory bowel disease. The conditions of use of currently available major pharmacogenetic tests are detailed and recommendations are provided based on a scale established by the RNPGx scoring tests as "essential", "advisable" and "potentially useful". Other applications for which the level of evidence is still debated are also discussed. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  20. Angle β of greater than 80° at the start of spirometry may identify high-quality flow volume curves.

    Science.gov (United States)

    Lian, Ningfang; Li, Li; Ren, Weiying; Jiang, Zhilong; Zhu, Lei

    2017-04-01

    The American Thoracic Society (ATS) and European Respiratory Society (ERS) emphasize a satisfactory start in maximal expiratory flow-volume (MEFV) curves and highlight subjective parameters: performance without hesitation and expiration with maximum force. We described a new parameter, angle β for characterization of the start to the MEFV curve. Subjects completed the MEFV curve at least three times and at least two curves met ATS/ERS quality. Subjects were divided into normal, restrictive and obstructive groups according to pulmonary function test results. The tangent line was drawn at the start of the MEFV curve's ascending limb to the x-axis and the angle β between the tangent line and x-axis was obtained. The relationships between tangent of β, pulmonary function parameters (PFPs) and anthropometric data were assessed. The MEFV curves with insufficient explosion at the start were considered as poor-quality MEFV curves. In 998 subjects with high-quality spirometry, although PFP varied in relation to the three aspects: the angle β and its tangent were similar (P > 0.05), the tangent of β did not correlate with PFP or anthropometric measurements (P > 0.05) and the lower limit of normal (LLN) of the angle β was 80° in the group with high-quality spirometry (P < 0.05). Angle β derived from poor-quality MEFV curves was smaller than that from good quality one (P < 0.05). Angle β may function as a parameter to assess the expiratory efforts, which can be used to assess the quality of the MEFV curve start. © 2016 Asian Pacific Society of Respirology.

  1. Stress, coping and adherence to immunosuppressive medications in kidney transplantation: a comparative study

    Directory of Open Access Journals (Sweden)

    Daniela Cristina Sampaio de Brito

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE : Adherence to medication is a key issue relating to outcomes from transplantation and it is influenced by several factors, such as stress and coping strategies. However, these factors have been poorly explored. We aimed to compare stress and coping strategies between adherent and nonadherent renal transplant recipients who were receiving immunosuppression. DESIGN AND SETTING : We conducted a comparative, cross-sectional and observational study at a university-based transplantation clinic in Juiz de Fora, Brazil. METHODS :Fifty patients were recruited and classified as adherent or nonadherent following administration of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Stress was evaluated using the Lipp Stress Symptom Inventory for Adults and coping strategies were assessed using the Ways of Coping Scale. RESULTS : The study included 25 nonadherent patients and 25 controls with a mean age of 44.1 ± 12.8 years and median post-transplantation time of 71.8 months. Stress was present in 50% of the patients. Through simple logistic regression, nonadherence was correlated with palliative coping (OR 3.4; CI: 1.02-11.47; P < 0.05 and had a marginal trend toward significance with more advanced phases of stress (OR 4.7; CI: 0.99-22.51; P = 0.053. CONCLUSION :Stress and coping strategies may have implications for understanding and managing nonadherent behavior among transplantation patients and should be considered among the strategies for reducing nonadherence.

  2. Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Pascher, Andreas; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Brockmann, Jens; Andrassy, Joachim; Banas, Bernhard; Jauch, Karl-Walter

    2012-04-01

    Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S-creatinine at conversion >2mg/dl, CMV naïve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

  3. Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens.

    Science.gov (United States)

    El-Ela, Fatma I Abo; Shany, S A S; El-Deen, Manal B; El-Banna, H A; El-Gendy, A A; Hendy, K; Tohamy, M A

    2016-10-01

    Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. STARTing Again: What Happens After START I Expires?

    International Nuclear Information System (INIS)

    Mladineo, Stephen V.; Durbin, Karyn R.; Eastman, Christina M.

    2007-01-01

    The Strategic Arms Reduction Treaty (START I), a seminal arms control agreement that substantially reduced the levels of deployed strategic nuclear arms in the United States and Russia, will expire in December 2009. At this time, it is unclear what - if anything - will replace it. While the treaty remains relevant, more than a simple extension is appropriate. Instead the authors advocate for a successor regime that builds on the START I legacy but does not rely on the traditional tools of arms control. This paper examines the strategic context in which a successor regime would be developed and proposes several recommendations for future action

  5. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study.

    Science.gov (United States)

    Abedini, Sadollah; Gøransson, Lasse; Cockburn, Elinor; Kilany, Suzanne; Holdaas, Hallvard

    2018-02-01

    This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice. Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events. Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was -0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m 2 ), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal

  6. Metacognitive experience of mathematics education students in open start problem solving based on intrapersonal intelligence

    Science.gov (United States)

    Sari, D. P.; Usodo, B.; Subanti, S.

    2018-04-01

    This research aims to describe metacognitive experience of mathematics education students with strong, average, and weak intrapersonal intelligence in open start problem solving. Type of this research was qualitative research. The research subject was mathematics education students in Muhammadiyah University of Surakarta in academic year 2017/2018. The selected students consisted of 6 students with details of two students in each intrapersonal intelligence category. The research instruments were questionnaire, open start problem solving task, and interview guidelines. Data validity used time triangulation. Data analyses were done through data collection, data reduction, data presentation, and drawing conclusion. Based on findings, subjects with strong intrapersonal intelligence had high self confidence that they were able to solve problem correctly, able to do planning steps and able to solve the problem appropriately. Subjects with average intrapersonal intelligence had high self-assessment that they were able to solve the problem, able to do planning steps appropriately but they had not maximized in carrying out the plan so that it resulted incorrectness answer. Subjects with weak intrapersonal intelligence had high self confidence in capability of solving math problem, lack of precision in taking plans so their task results incorrectness answer.

  7. FUMEX-III Cases by START-3. Final Report

    International Nuclear Information System (INIS)

    Novikov, Vladimir; Bogatyr, Sergey; Kuznetsov, Vladimir; Chulkin, Dmitriy

    2013-01-01

    This document covers ''SUPER-RAMP'' and ''AREVA High-Burnup Idealised case'', cases of FUMEX-III project that were calculated by means of START-3 code. SUPER-RAMP PK-2 rodlets were chosen for calculation because they were subjected to strong power ramp and did not fail, because the main objective of the present calculations was to check the models of fission gas release and gaseous swelling of START-3 in the conditions of the power ramps (we did not intend to get the limit stresses for Zry-4 fuel rods). AREVA high burnup (PRIORITY CASE) case was chosen to check the applicability of the START-3 code to high-burnup PWR fuel rods behavior. Also, in order to check the stability and quality of the changes made into the code during the course of FUMEX-III participation, several simplified cases of FUMEX-II were recalculated. FUMEX-III SUPER-RAMP exercise included up to 49 kW/m power ramps of fuel rods with burnup up to 45 MWd/kgU. START-3 calculations of this exercise are in reasonable agreement with the experiment. AREVA high burnup priority case (∼81.5 MWd/kgU) was calculated and overprediction of the FGR was found. This overprediction is related with the conservative overestimation of rim-structure capability to retain fission gas and can be adjusted implementing a simple correction of this property. To verify the changes made into the code (oxide layer growth model and Zry-4 radiation growth), the corrected version of the code was used to recalculate the FUMEX-II simplified cases 27.2 and satisfactory results were obtained. (author)

  8. [Predictive factors for failure of non-invasive positive pressure ventilation in immunosuppressed patients with acute respiratory failure].

    Science.gov (United States)

    Jia, Xiangli; Yan, Ci; Xu, Sicheng; Gu, Xingli; Wan, Qiufeng; Hu, Xinying; Li, Jingwen; Liu, Guangming; Caikai, Shareli; Guo, Zhijin

    2018-02-01

    To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO 2 ) was significantly decreased, the ratio of oxygenation index (PaO 2 /FiO 2 ) failure of NIPPV. ROC curve analysis showed that the APACHE II score ≥ 20 and PaO 2 /FiO 2 failure of NIPPV, the area under ROC curve (AUC) of the APACHE II score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO 2 /FiO 2 failure of NIPPV in immunocompromised patients.

  9. From START to NEW START. The dilemma and future of nuclear disarmament

    International Nuclear Information System (INIS)

    Plettenberg, Lars

    2012-01-01

    The report describes the existing four agreements on nuclear disarmament: START I (1991). START II (1993), SORT (2002) and NEW START (2010). The chapter on the dependence between nuclear disarmament and strategic stability covers the issues mutual assured destruction (MAD), credibility, overkill capacity; the role of nuclear weapons in the national strategies of the USA and NATO, Russia, Great Britain, France, China and the other nuclear states. Ways out of MAD include disarmament, de-alerting and mutual assured protection (MAP).

  10. Epstein-Barr virus-positive mucocutaneous ulcer in Crohn's disease. A condition to consider in immunosuppressed IBD patients.

    Science.gov (United States)

    Juan, Alba; Lobatón, Triana; Tapia, Gustavo; Mañosa, Míriam; Cabré, Eduard; Domènech, Eugeni

    2017-08-01

    Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity that can affect the oropharyngeal mucosa, the gastrointestinal tract and the skin. The main risk factor for the development of this lesion is immunosuppression. Because its features are similar to other Epstein-Barr virus-associated lymphoproliferative disorders, a differential diagnosis can sometimes prove challenging. Here, we report the case of a man diagnosed with Crohn's disease and treated with azathioprine and infliximab who developed ulceration at the rectum that was refractory to conventional medical treatment. Although the histological characteristics were suggestive of an EBVMCU, lymphoproliferative disease could not be ruled out. The patient did not improve after discontinuation of the treatment, a proctectomy was performed and the diagnosis of this disease was confirmed. Although very few cases of EBVMCU affecting the colon have been reported, its diagnosis should be always considered in refractory cases of inflammatory bowel disease with patients undergoing immunosuppressive treatment. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

    Science.gov (United States)

    Pranteda, G; Carlesimo, M; Bottoni, U; Di Napoli, A; Muscianese, M; Pimpinelli, F; Cordiali, P; Laganà, B; Pranteda, G; Di Carlo, A

    2014-01-01

    A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. © 2014 Wiley Periodicals, Inc.

  12. The impact of dry-land sprint start training on the short track speed skating start.

    Science.gov (United States)

    Haug, William B; Drinkwater, Eric J; Cicero, Nicholas J; Barthell, J Anthony; Chapman, Dale W

    2017-05-05

    This investigation sought to determine the effects of dry-land sprint start training on short track speed skating (STSS) start performance. Nine highly trained short track athletes completed a control period of normal STSS training followed by a four-week training intervention. Before and after the control and intervention periods, athletes performed three electronically timed dry-land and on-ice 14.43 m maximal sprint start efforts. The intervention consisted of two sprint sessions per week consisting of nine electronically timed 14.43 m dry-land sprint starts in addition to normal STSS training. The control period resulted in no substantial change in on-ice start performance (Mean Δ: -0.01 s, 95% Confidence Limits (CL): -0.08 to 0.05 s; Effect Size (ES): -0.05; Trivial) however, a small change was observed in dry-land start performance (Mean Δ: -0.07 s, 95% CL: -0.13 to -0.02 s; ES: -0.49). Following brief specific dry-land sprint start training a small improvement was observed in both on-ice (Mean Δ: -0.07 s, 95% CL: -0.13 to -0.01 s; ES: -0.33) and dry-land (Mean Δ: -0.04 s, 95% CL: -0.09 to 0.00 s; ES: -0.29) start performance. This investigation suggests STSS start performance can be improved through a brief dry-land sprint start training program.

  13. Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study

    Directory of Open Access Journals (Sweden)

    Sadollah Abedini, MD, PhD

    2018-02-01

    Conclusions. There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.

  14. The impact of pancreas and kidney transplant on cardiovascular risk factors (analyzed by mode of immunosuppression and exocrine drainage).

    LENUS (Irish Health Repository)

    Davenport, Colin

    2011-04-06

    The aim of this study was to determine the cardiovascular (CV) risk factor response in Irish patients with type 1 diabetes following simultaneous pancreas and kidney transplantation (SPK), analyzing response based on mode of immunosuppression and surgical drainage in a uniquely homogenous population.

  15. Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

    OpenAIRE

    White, Kimber L.; DeLorme, Michael P.; Beatty, Patrick W.; Smith, Matthew J.; Peachee, Vanessa L.

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (...

  16. TIE-2 and VEGFR kinase activities drive immunosuppressive function of TIE-2-expressing monocytes in human breast tumors.

    Science.gov (United States)

    Ibberson, Mark; Bron, Sylvian; Guex, Nicolas; Faes-van't Hull, Eveline; Ifticene-Treboux, Assia; Henry, Luc; Lehr, Hans-Anton; Delaloye, Jean-François; Coukos, George; Xenarios, Ioannis; Doucey, Marie-Agnès

    2013-07-01

    Tumor-associated TIE-2-expressing monocytes (TEM) are highly proangiogenic cells critical for tumor vascularization. We previously showed that, in human breast cancer, TIE-2 and VEGFR pathways control proangiogenic activity of TEMs. Here, we examine the contribution of these pathways to immunosuppressive activity of TEMs. We investigated the changes in immunosuppressive activity of TEMs and gene expression in response to specific kinase inhibitors of TIE-2 and VEGFR. The ability of tumor TEMs to suppress tumor-specific T-cell response mediated by tumor dendritic cells (DC) was measured in vitro. Characterization of TEM and DC phenotype in addition to their interaction with T cells was done using confocal microscopic images analysis of breast carcinomas. TEMs from breast tumors are able to suppress tumor-specific immune responses. Importantly, proangiogenic and suppressive functions of TEMs are similarly driven by TIE-2 and VEGFR kinase activity. Furthermore, we show that tumor TEMs can function as antigen-presenting cells and elicit a weak proliferation of T cells. Blocking TIE-2 and VEGFR kinase activity induced TEMs to change their phenotype into cells with features of myeloid dendritic cells. We show that immunosuppressive activity of TEMs is associated with high CD86 surface expression and extensive engagement of T regulatory cells in breast tumors. TIE-2 and VEGFR kinase activity was also necessary to maintain high CD86 surface expression levels and to convert T cells into regulatory cells. These results suggest that TEMs are plastic cells that can be reverted from suppressive, proangiogenic cells into cells that are able to mediate an antitumoral immune response. ©2013 AACR.

  17. Colonization and infection with Trichosporon species in the immunosuppressed host.

    Science.gov (United States)

    Haupt, H M; Merz, W G; Beschorner, W E; Vaughan, W P; Saral, R

    1983-02-01

    Trichosporon beigelii and Trichosporon capitatum have recently been recognized as systemic pathogens in the immunosuppressed host. We studied the incidence of colonization and systemic infection with these organisms in 353 highly immunocompromised patients over a 37-month period. Thirteen patients (3.7%) had positive surveillance cultures for Trichosporon species in stool, skin, or urine. Three of the 13 patients developed systemic infections after having positive surveillance cultures. In two of these three patients, urine cultures were positive near the time of systemic infection. The route of entry appeared to have been enteric in two patients and cutaneous in one patient. Both colonizing and infecting organisms showed in vitro susceptibility to amphotericin B and nystatin. This study suggests that positive surveillance cultures for Trichosporon species may correlate with systemic infection in the severely immunocompromised patient and that repeated positive urine cultures may indicate dissemination.

  18. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

    Science.gov (United States)

    Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

    2018-04-19

    We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects.

    Directory of Open Access Journals (Sweden)

    Peter D Burbelo

    Full Text Available Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO, interferon-α (IFN-α, interleukin-2 (IL-2, and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24, matrix (p17, envelope (gp41, and reverse transcriptase (RT were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.

  20. Association of Marek's Disease induced immunosuppression with activation of a novel regulatory T cells in chickens.

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    Angila Gurung

    2017-12-01

    Full Text Available Marek's Disease Virus (MDV is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT, fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour

  1. Effects of feeding bentonite clay upon ochratoxin A-induced immunosuppression in broiler chicks.

    Science.gov (United States)

    Khatoon, Aisha; Khan, Muhammad Zargham; Abidin, Zain Ul; Bhatti, Sheraz Ahmed

    2018-03-01

    A presence of mycotoxins in feed is one of the most alarming issues in the poultry feed industry. Ochratoxins, produced by several Aspergillus and Penicillium species, are important mycotoxin regarding the health status of poultry birds. Ochratoxins are further classified into to several subtypes (A, B, C, etc) depending on their chemical structures, but ochratoxin A (OTA) is considered the most important and toxic. Bentonite clay, belonging to phyllosilicates and formed from weathering of volcanic ashes, has adsorbent ability for several mycotoxins. The present study was designed to study the effects of bentonite clay upon OTA-induced immunosuppression in broiler chicks. For this, 480 day-old broiler chicks were procured from a local hatchery and then different combinations of OTA (0.15, 0.3, or 1.0 mg/kg) and bentonite clay (5, 10, and 20 g/kg) were incorporated into their feed. At 13, 30, and 42 days of age, parameters such as antibody responses to sheep red blood cells, in situ lymphoproliferative responses to mitogen (PHA-P), and in situ phagocytic activity (i.e., via carbon clearance) were determined respectively. The results indicated there was a significant reduction of total antibody and immunoglobulin titres, lymphoproliferative responses, and phagocytic potential in OTA-treated birds, suggesting clear immunosuppression by OTA in birds in a dose-dependent manner. These results were also significantly lower in all combination groups (OTA with bentonite clay), suggesting few to no effects of feeding bentonite clay upon OTA- induced alterations in different immune parameters.

  2. The influence of immunosuppressive treatment on the progression of Graves' disease after radioiodine

    International Nuclear Information System (INIS)

    Jurca, T.; Pirnat, E.; Hojker, S.; Avcin, J.

    1994-01-01

    Radioiodine therapy (RIT) for Graves' disease could produce a rise in autoimmune activity expressed as elevation of antibody against TSH receptors (TSI). In our retrospective study the influence of different immunosuppressive therapy on autoimmune activity was studied. Patients, treated with radioiodine or surgery for the first time, between January 1989 and March 1992 were included in the study, divided in the 5 groups (patients after thyroidectomy, and patients after RIT divided into groups according to treatment with different combinations of corticosteroids and cyclosporine A). Patients were examined and TT 4 , TT 3 TSH and TSI were collected before and 3, 6 and 9 months after treatment. There was no differences between groups before and according to the thyroid status the patients of all groups received antithyroid drugs or substitution therapy after the RIT or surgery. Immunosuppressive therapy was indicated because of Graves' ophthalmopathy. After surgery, the progressive fall of TSI and no relapses of the disease were stated. After first 3 months the situation was very similar in group of patients treated with cyclosporine A after RIT, later after the cessation of treatment, there were a slight elevation of TSI. In all other groups of patients after RIT there was a constant positive trend of TSI and the significant correlation was found between TSI before and after treatment. We conclude, that autoimmune response after RIT is a consequence of activity of T cells and therefore cyclosporine A could be taken in mind when we want to prevent it. Corticosteroids on the other hand had no such an effect. (author)

  3. Late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. III. Disease incidence and life expectancy. [Mice, x radiation

    Energy Technology Data Exchange (ETDEWEB)

    Peter, C P; Perkins, E H; Peterson, W J; Walburg, H E; Makinodan, T

    1975-01-01

    The effect of various immunosuppressive treatments on mean life-span and disease incidence have been studied. Significant life shortening was seen only in mice which received X-irradiation early in life and can be ascribed primarily to an increased incidence of certain malignancies. Marginal life shortening was seen in cyclophosphamide-treated animals, however, survival patterns between those and control animals did not differ until 30 months of age and the magnitude of life-shortening never approached that seen in X-irradiated animals. Thymectomy, splenectomy or cortisone treatment did not alter survival. All immunosuppressive treatments enhanced mortality due to non-neoplastic diseases, however, only a small percentage of animals die with these disease entities. With the exception of cortisone all immunosuppressive treatments increased the incidence of neoplastic disease. However, their effects on various neoplastic processes were variable and unpredictable. Four primary patterns in terms of relative immune competence, disease incidence and life expectancy were seen. Thus, immunodepression may or may not correlate with increased disease incidence, which in turn may or may not have a life-shortening effect. These findings are discussed in terms of the marked reduction of both humoral and cell-mediated immunity normally seen in aged mice and the significance of postulated immune surveillance mechanisms to survival.

  4. School Starting Age and Crime

    DEFF Research Database (Denmark)

    Landersø, Rasmus; Nielsen, Helena Skyt; Simonsen, Marianne

    This paper investigates the effects of school starting age on crime while relying on variation in school starting age induced by administrative rules; we exploit that Danish children typically start first grade in the calendar year they turn seven, which gives rise to a discontinuity in children......’s school starting age. Analyses are carried out using register-based Danish data. We find that higher age at school start lowers the propensity to commit crime, but that this reduction is caused by incapacitation while human capital accumulation is unaffected. Importantly, we also find that the individuals...

  5. Comparison of the performance of polymerase chain reaction and pp65 antigenemia for the detection of human cytomegalovirus in immunosuppressed patients

    Directory of Open Access Journals (Sweden)

    Patrícia Borba Martiny

    2011-06-01

    Full Text Available INTRODUCTION: Human cytomegalovirus (HCMV is often reactive in latently infected immunosuppressed patients. Accordingly, HCMV remains one of the most common infections following solid organ and hemopoietic stem cell transplantations, resulting in significant morbidity, graft loss and occasional mortality. The early diagnosis of HCMV disease is important in immunosuppressed patients, since in these individuals, preemptive treatment is useful. The objective of this study was to compare the performance of the in-house qualitative polymerase chain reaction (PCR and pp65 antigenemia to HCMV infection in immunosuppressed patients in the Hospital de Clínicas of Porto Alegre (HCPA. METHODS: A total of 216 blood samples collected between August 2006 and January 2007 were investigated. RESULTS: Among the samples analyzed, 81 (37.5% were HCMV-positive by PCR, while 48 (22.2% were positive for antigenemia. Considering antigenemia as the gold standard, sensitivity, specificity, positive predictive values and negative predictive values for PCR were 87.5%, 76.8%, 51.8% and 95.5% respectively. CONCLUSIONS: These results demonstrated that qualitative PCR has high sensitivity and negative predictive value (NPV. Consequently PCR is especially indicated for the initial diagnosis of HCMV infection. In the case of preemptive treatment strategy, identification of patients at high-risk for HCMV disease is fundamental and PCR can be useful tool.

  6. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

    Science.gov (United States)

    Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

    2014-01-01

    Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, Ppoisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  7. A New Immunosuppressive Molecule Emodin Induces both CD4+FoxP3+ and CD8+CD122+ Regulatory T Cells and Suppresses Murine Allograft Rejection

    Directory of Open Access Journals (Sweden)

    Feifei Qiu

    2017-11-01

    Full Text Available Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA, a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs, although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity. In this study, we investigated the capacity of emodin, an anthraquinone molecule originally extracted from certain natural plants, to prolong transplant survival in a mouse model and explored the cellular and molecular mechanisms underlying its action. We found that emodin significantly extended skin allograft survival and hindered CD3+ T cell infiltration in the allograft, accompanied by an increase in CD4+Foxp3+ and CD8+CD122+ Treg frequencies and numbers but a reduction in effector CD8+CD44highCD62Llow T cells in recipient mice. Emodin also inhibited effector CD8+ T cells proliferation in vivo. However, CD4+CD25+, but not CD8+CD122+, Tregs derived from emodin-treated recipients were more potent in suppression of allograft rejection than those isolated from control recipients, suggesting that emodin also enhances the suppressive function of CD4+CD25+ Tregs. Interestingly, depleting CD25+ Tregs largely reversed skin allograft survival prolonged by emodin while depleting CD122+ Tregs only partially abrogated the same allograft survival. Furthermore, we found that emodin hindered dendritic cell (DC maturation and reduced alloantibody production posttransplantation. Finally, we demonstrated that emodin inhibited in vitro proliferation of T cells and blocked their mTOR signaling as well. Therefore, emodin may be a novel mTOR inhibitor that suppresses alloimmunity by

  8. The influence of ego depletion on sprint start performance in athletes without track and field experience.

    Science.gov (United States)

    Englert, Chris; Persaud, Brittany N; Oudejans, Raôul R D; Bertrams, Alex

    2015-01-01

    We tested the assumption that ego depletion would affect the sprint start in a sample of N = 38 athletes without track and field experience in an experiment by applying a mixed between- (depletion vs. non-depletion) within- (T1: before manipulation of ego depletion vs. T2: after manipulation of ego depletion) subjects design. We assumed that ego depletion would increase the possibility for a false start, as regulating the impulse to initiate the sprinting movement too soon before the starting signal requires self-control. In line with our assumption, we found a significant interaction as there was only a significant increase in the number of false starts from T1 to T2 for the depletion group while this was not the case for the non-depletion group. We conclude that ego depletion has a detrimental influence on the sprint start in athletes without track and field experience.

  9. Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice.

    Science.gov (United States)

    Madbouly Taha, Noha; Salah A Yousof, Hebat-Allah; El-Sayed, Shaimaa H; Younis, Azza Ibrahim; Ismail Negm, Mohamed Sherif

    2017-10-01

    The present study was conducted on 200 male mice for the detection of the effect of Atorvastatin on Cryptosporidium spp. infection versus the commercially used drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five consecutive days. Parasitological assessment of the drug effect was done using Modified Z-N staining of stool samples collected from mice. Results revealed a reduction of the number of oocysts shed with percentage of reduction on the 21st day post infection by 53.7%, 67.2%, 70.1% &77.5%, respectively, compared to the infected untreated group. The Nitazoxanide treated group showed 52.7% reduction. In addition, examination of small and large intestinal contents after mice scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%, 70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in Nitazoxanide treated group. The histopathological examination of sections from duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant improvement of the histopathological changes in Atorvastatin treated groups and more remarkable improvement in the groups treated with combined drugs as compared to infected untreated group. Accordingly, the combination of Atorvastatin and Nitazoxanide showed a synergistic effect through reduction of the number of oocysts shed and improvement of the histopathological changes induced by Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs of infected immunosuppressed mice in comparison to that induced by either Nitazoxanide or Atorvastatin alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Enhancing the effect of secreted cyclophilin B on immunosuppressive activity of cyclosporine.

    Science.gov (United States)

    Denys, A; Allain, F; Masy, E; Dessaint, J P; Spik, G

    1998-04-27

    Cyclophilin B (CyPB) is a cyclosporine (CsA)-binding protein, located within intracellular vesicles and secreted in biological fluids. In previous works, we reported that CyPB specifically interacts with the T-cell membrane and potentiates the ability of CsA to inhibit CD3-induced proliferation of T lymphocytes. CyPB levels were measured in plasma from healthy donors and transplant patients. The role of extracellular CyPB on the distribution and activity of CsA was investigated first by studies on the uptake of free and CyPB-complexed drug by blood cells, and second by studies on the inhibitory effects of these two compounds on the CD3-induced proliferation of peripheral blood mononuclear cells. A significant increase in plasma CyPB level was observed for CsA-treated patients (13+/-6.4 nM, n=42) in comparison with untreated donors (4.3+/-2.1 nM, n=34). In vitro, extracellular CyPB dose dependently modified CsA distribution between plasma, erythrocyte, and lymphocyte contents, by both retaining the complexed drug extracellularly and promoting its specific accumulation within peripheral blood mononuclear cells. Moreover, the enhanced ability of CyPB-complexed CsA to suppress CD3-induced T-cell proliferation was preserved in the presence of other blood cells, implying specific targeting of the drug to sensitive cells. Furthermore, although a large interindividual variability of sensitivity to the drug was confirmed for 18 individuals, we found that CyPB potentiated the activity of CsA in restoring a high sensitivity to the immunosuppressant. These results suggest that plasma CyPB may contribute to the acceptance and the good maintenance of organ transplantation by enhancing the immunosuppressive activity of CsA through a receptor-mediated incorporation of CyPB-complexed CsA within peripheral blood lymphocytes.

  11. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

    Science.gov (United States)

    Stockis, Julie; Liénart, Stéphanie; Colau, Didier; Collignon, Amandine; Nishimura, Stephen L; Sheppard, Dean; Coulie, Pierre G; Lucas, Sophie

    2017-11-21

    Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

  12. Experimental coccidioidomycosis in the immunosuppressed rat Coccidioidomicose experimental em ratos imunossuprimidos

    Directory of Open Access Journals (Sweden)

    Mirta C. Remesar

    1992-08-01

    Full Text Available C. immitis inoculated rats are known to develop infection restricted to lung whereas cyclophosphamide (CY treatment leads to widespread dissemination with considerable mortality. In this study, an attempt was made to elucidate the mechanisms involved in such behaviour. With this aim, spleen cells were transferred from infected CY-treated to infected untreated rats, achieving significant specific inhibition in footpad swelling to coccidioidin in recipients, attributable to a suppressor T cell subpopulation induced by greater fungal antigen concentration arising from widespread C. immitis dissemination in immunosuppressed animals. NK activity proved similar regardless of CY treatment. Lastly, chronically infected rats presented increased colony forming units count after several weekly doses of CY, as happens in immunosuppressed patients harbouring a previous infection.Ratos adultos inoculados com C. immitis desenvolveram infecção circunscrita ao pulmão sem apresentar mortalidade; no entanto, ao serem imunossuprimidos com CY apresentaram disseminação fúngica em vários órgãos, ausência de granulomas e depressão na resposta celular à coccidioidina junto com uma mortalidade de 50%. Tentou-se determinar os mecanismos envolvidos neste comportamento. Para isso foram medidas as atividades dos linfócitos supressores e células NK. Ao serem transferidos esplenócitos de animais infectados e tratados com CY a ratos somente infectados conseguiu-se significativa inibição específica da resposta à coccidioidina. Este efeito seria devido a uma subpopulação de linfócitos T supressores induzida por maior concentração de antígeno nos animais imunossuprimidos. A atividade NK foi semelhante nos ratos infectados independentemente do tratamento com CY. Por outro lado, tentou-se a reativação da infecção crônica com C. immitis. Os animais infectados apresentaram maior quantidade de unidades formadoras de colônias nos pulmões depois de v

  13. [Evaluation of immunosuppressive treatment on homocystein levels in patients after kidney transplantation during a 2 year observation period].

    Science.gov (United States)

    Aksamit, Dariusz; Janda, Katarzyna; Kuźniewski, Marek; Krzanowski, Marcin; Ignacak, Ewa; Betkowska-Prokop, Alina; Chowaniec, Eve; Sułowicz, Wladysław

    2012-01-01

    The aim of the study was to evaluate the influence of the type of prescribed immunosuppression: cyclosporine A (CsA) vs. tacrolimus (Tac) on remote homocystein levels in patients (pts) after kidney transplantation (Ktx). The study included 51 pts (17 F, 34 M) aged 15 to 62 years (mean 38.1) after cadaver Ktx. The mean observation period equaled 21.2 months (6 -24); while total observation period was 90 personlyears. Before Ktx, 46 pts were treated with maintenance hemodialysis (HD), while 5 by peritoneal dialysis (PD). After Ktx, patients had immunosuppression prescribed according to the following schemes: prednisone (P) + CsA + azathioprine (AZA) - 12 pts; P + CsA + mycophenolate mofetil (MMF) -26 pts; P + Tac + MMF - 11 pts; and P + Tac + AZA - 2 pts. Hcy level was measured using high performance liquid chromatography (HPLC). Serum creatinine level was measured by standard method using the Hitachi 917 analyzer. Creatinine clearance was calculated based on the Cockcroft-Gault formula. Patient's blood was drawn before Ktx and 3, 6, 9, 12,15, 18, 21 and 24 months post procedure. Delayed graft function (DGF) after Ktx was diagnosed in 29 pts (56.9%) and this group required from 4 to 28 HD sessions (mean 14 sessions). Hcy level did not significantly differ between pts requiring (29 pts) and not requiring (22 pts) HD treatment after Ktx. It was also noted that the number of performed HD sessions did not significantly correlate with Hcy levels 24 months after Ktx (R =0.04, p=0.81). No relationship was found (non-parametric Spearman test) between the drop in Hcy level 3 months after Ktx as compare with value before Ktx and ischemia time (R=0.09, p=0.49), number of compatible HLA A and B (R=0.07, p=0.63), and DR antigens (R=0.09, p=0.51). Decrease in Hcy level (before Ktx and 24 months after Ktx) did not significantly correlate with the above parameters, respectively: R=-0.14, p=0.40; R=0.06, p=0.73; R=0.12, p=0.45; R=0.11, p=0.50. Decrease in Hcy level (before Ktx and 3

  14. Reported Nonadherence to Immunosuppressive Medication in Young Adults After Heart Transplantation: A Retrospective Analysis of a National Registry.

    Science.gov (United States)

    Tumin, Dmitry; McConnell, Patrick I; Galantowicz, Mark; Tobias, Joseph D; Hayes, Don

    2017-02-01

    Young adult heart transplantation (HTx) recipients experience high mortality risk attributed to increased nonadherence to immunosuppressive medication in this age window. This study sought to test whether a high-risk age window in HTx recipients persisted in the absence of reported nonadherence. Heart transplantation recipients aged 2 to 40 years, transplanted between October 1999 and January 2007, were identified in the United Network for Organ Sharing database. Multivariable survival analysis was used to estimate influences of age at transplantation and attained posttransplant age on mortality hazard among patients stratified by center report of nonadherence to immunosuppression that compromised recovery. Three thousand eighty-one HTx recipients were included, with univariate analysis demonstrating peak hazards of mortality and reported nonadherence among 567 patients transplanted between ages 17 and 24 years. Multivariable analysis adjusting for reported nonadherence demonstrated lower mortality among patients transplanted at younger (hazards ratio, 0.813; 95% confidence interval, 0.663-0.997; P = 0.047) or older (hazards ratio, 0.835; 95% confidence interval, 0.701-0.994; P = 0.042) ages. Peak mortality hazard at ages 17 to 24 years was confirmed in the subgroup of patients with no nonadherence reported during follow-up. This result was replicated using attained age after HTx as the time metric, with younger and older ages predicting improved survival in the absence of reported nonadherence. Late adolescence and young adulthood coincide with greater mortality hazard and greater chances of nonadherence to immunosuppressive medication after HTx, but the elevation of mortality hazard in this age range persists in the absence of reported nonadherence. Other causes of the high-risk age window for post-HTx mortality should be demonstrated to identify opportunities for intervention.

  15. Immunosuppressive effect of compound K on islet transplantation in an STZ-induced diabetic mouse model.

    Science.gov (United States)

    Ma, Peng-Fei; Jiang, Jie; Gao, Chang; Cheng, Pan-Pan; Li, Jia-Li; Huang, Xin; Lin, Ying-Ying; Li, Qing; Peng, Yuan-Zheng; Cai, Mei-Chun; Shao, Wei; Zhu, Qi; Han, Sai; Qin, Qing; Xia, Jun-Jie; Qi, Zhong-Quan

    2014-10-01

    Islet transplantation is a therapeutic option for type 1 diabetes, but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound (Cpd) K is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4(+) and CD8(+) T cells in spleen and lymph nodes, inhibited inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-γ secretion, and increased transforming growth factor-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  16. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis.

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St; Wadowsky, Robert M; Paterson, David L; McCurry, Kenneth R; Reinhart, Todd A; Husain, Shahid; Rinaldo, Charles R

    2007-02-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.

  17. Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis▿

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St.; Wadowsky, Robert M.; Paterson, David L.; McCurry, Kenneth R.; Reinhart, Todd A.; Husain, Shahid; Rinaldo, Charles R.

    2007-01-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses. PMID:17065270

  18. Dendritic Cells Primed with Paracoccidioides brasiliensis Peptide P10 Are Therapeutic in Immunosuppressed Mice with Paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Leandro B. R. Silva

    2017-06-01

    Full Text Available Paracoccidioidomycosis (PCM is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P. brasiliensis Pb18 to establish the therapeutic efficacy of P10-pulsed DCs. Immunosuppressed and infected animals that received DCs had a reduction in their fungal burden, and this result was most pronounced in mice receiving DCs primed with P10. The efficacy of therapeutic DCs was significantly augmented by concomitant treatment with trimethoprim-sulfamethoxazole. Additionally, primed-DCs with or without the antifungal drug induced a beneficial Th1-biased immune response and significantly reduced tissue damage. In conclusion, these studies with immunocompromised mice demonstrate that P10-pulsed DCs with or without concomitant antifungal drugs are potently effective in combating invasive PCM. These findings support further translational studies to validate the use of P10-primed DCs for PCM in immunocompetent and immunosuppressed hosts.

  19. Starting an aphasia center?

    Science.gov (United States)

    Elman, Roberta J

    2011-08-01

    Starting an aphasia center can be an enormous challenge. This article provides initial issues to review and consider when deciding whether starting a new organization is right for you. Determining the need for the program in your community, the best size and possible affiliation for the organization, and available resources, as well as developing a business plan, marketing the program, and building awareness in the community, are some of the factors that are discussed. Specific examples related to starting the Aphasia Center of California are provided. © Thieme Medical Publishers.

  20. Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation.

    Science.gov (United States)

    Li, Li; Chaudhuri, Abanti; Chen, Amery; Zhao, Xinmeng; Bezchinsky, Maria; Concepcion, Waldo; Salvatierra, Oscar; Sarwal, Minnie M

    2010-12-27

    Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients. Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003). There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection. TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

  1. [Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

    Science.gov (United States)

    Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

    2002-01-01

    To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

  2. Análise da eficácia do laser de baixa potência no tratamento da dor tendínea em ratos imunossuprimidos Analysis of low-level laser therapy efficacy on tendon pain treatment in immunosuppressed rats

    Directory of Open Access Journals (Sweden)

    Fernanda de Oliveira Busarello

    2011-12-01

    Full Text Available O comprometimento do sistema imune, que pode ser apresentado por indivíduos com doenças crônicas, leva à baixa resposta imunológica. Um dos tratamentos utilizados para lesões agudas em tendões é o laser de baixa potência, contudo há uma lacuna em relação ao seu uso em imunodepressão. O objetivo do presente estudo foi analisar se o laser de baixa potência é eficaz para o tratamento da dor em ratos imunodeprimidos submetidos a trauma tendíneo. Foram utilizados 23 ratos, machos, da linhagem Wistar, divididos aleatoriamente em três grupos: grupo controle, placebo e laser. Os animais foram imunodeprimidos (por administração de Ciclosporina A e submetidos à lesão no tendão calcâneo direito, com impacto de cerca de 0,40 J. Para o tratamento, utilizou-se laser de baixa potência, 670 nm, 30 mW e dose de 2 J/cm², durante 3 dias. A avaliação da dor foi realizada pelo teste de incapacidade funcional e por filamento de Von Frey digital. Os resultados apresentaram valores significativos para o grupo laser, com diminuição de dor funcional e da dor à pressão na superfície plantar e no local lesionado (tendão calcâneo direito. Portanto, concluiu-se que o laser de baixa potência é eficaz para reduzir a dor em ratos imunodeprimidos submetidos a trauma tendíneo.The commitment of immune system, which may be presented by individuals with chronic diseases, leading to a low immune response. One of the treatments used for acute injuries in tendons is the low-power laser, however there is a gap in relation to its use in immunosuppression. The objective of this study was to analyze if low-level laser therapy is effective for the treatment of pain in immunosuppressed rats subjected to trauma tendon. We used 23 male rats of Wistar strain, divided randomly in three groups: control group, placebo and laser. The animals were immunosuppressed (by administration of Cyclosporin A and underwent right Achilles tendon injury, with impact of about

  3. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients.

    Science.gov (United States)

    Muduma, Gorden; Shupo, Francis C; Dam, Sophie; Hawken, Natalia A; Aballéa, Samuel; Odeyemi, Isaac; Toumi, Mondher

    2016-01-01

    Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients' non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients' HRQoL because of their side effects and the complex chronic medication regimen they represent. To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients' adherence to IT. Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants' responses. Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the

  4. Mumpreneurs: Motivational factors for Swedish mothers to start their own businesses

    OpenAIRE

    Boneberger, Diana; Kirilova, Bogomila

    2015-01-01

    The presented master thesis is an exploratory study on the motivational factors of the Swedish Mumpreneurs to start a business. Providing a nuanced and detailed review of the evolution of the literature on female entrepreneurship, the phenomenon of ‘Mumpreneurship’ is being introduced as a new, internationally widespread concept. Following a close look at this particular contestable subject, the study shows how different internal and external factors can influence the motivation of the Swedis...

  5. 30 CFR 75.1913 - Starting aids.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting aid...

  6. Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Muduma G

    2016-01-01

    Full Text Available Gorden Muduma,1 Francis C Shupo,2 Sophie Dam,3 Natalia A Hawken,3 Samuel Aballéa,3 Isaac Odeyemi,1 Mondher Toumi4 1Astellas Pharma Europe Ltd, Chertsey, 2Creativ-Ceutical Ltd, London, UK; 3Creativ-Ceutical Ltd, Paris, 4Public Health (EA 3279, Faculty of Medicine, Aix-Marseille University, Marseille, France Background: Renal transplantation (RT is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients’ non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients’ HRQoL because of their side effects and the complex chronic medication regimen they represent. Purpose: To elicit key concepts related to adherence to immunosuppressant therapy (IT and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients’ adherence to IT. Materials and methods: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants’ responses. Results: Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember

  7. Subject in Tractatus according to David Pears

    Directory of Open Access Journals (Sweden)

    M Hoseinzadeh Yazdi

    2013-02-01

    Full Text Available Subjectivism is viewed as one of the most fundamental underpinnings of modern philosophy. In modern philosophy, subject takes up a new position in human knowledge. The formation of the concept of subject is a decisive turn with which the modern philosophy starts. Considering the centrality of subjectivism in modern philosophy, this article attempts to explain subject in Tractatus according to David Pears. A review of Wittgenstein’s earlier teachings reveals that he considers a fundamental limitation for language. The subject serves as a point of view from which the language can be understood. The subject is the presupposition of understanding. Another way of putting this would be to say that any experience is understood from a point of view which is not represented in that experience. Regarding this, it seems that earlier Wittgenstein is somehow subjectivist. This specific form of subjectivism is different from Kantian subjectivism.

  8. Press Start

    Science.gov (United States)

    Harteveld, Casper

    This level sets the stage for the design philosophy called “Triadic Game Design” (TGD). This design philosophy can be summarized with the following sentence: it takes two to tango, but it takes three to design a meaningful game or a game with a purpose. Before the philosophy is further explained, this level will first delve into what is meant by a meaningful game or a game with a purpose. Many terms and definitions have seen the light and in this book I will specifically orient at digital games that aim to have an effect beyond the context of the game itself. Subsequently, a historical overview is given of the usage of games with a serious purpose which starts from the moment we human beings started to walk on our feet till our contemporary society. It turns out that we have been using games for all kinds of non-entertainment purposes for already quite a long time. With this introductory material in the back of our minds, I will explain the concept of TGD by means of a puzzle. After that, the protagonist of this book, the game Levee Patroller, is introduced. Based on the development of this game, the idea of TGD, which stresses to balance three different worlds, the worlds of Reality, Meaning, and Play, came into being. Interested? Then I suggest to quickly “press start!”

  9. A Pilot Randomized Controlled Trial to Promote Immunosuppressant Adherence in Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Cukor, Daniel; Ver Halen, Nisha; Pencille, Melissa; Tedla, Fasika; Salifu, Moro

    2017-01-01

    Nonadherence to immunosuppressant medication is a prevalent practice among kidney transplant recipients and has been associated with increased risk for graft failure and economic burden. The aim of this pilot study was to test whether a culturally sensitive cognitive-behavioral adherence promotion program could significantly improve medication adherence to tacrolimus prescription as measured by telephone pill counts among kidney transplant recipients. Thirty-three adult transplant recipients were less than 98% adherent to tacrolimus prescription based on 3 telephone pill counts and were randomized either to the 2-session cognitive-behavioral adherence promotion program or to standard care. The curriculum was developed from an iterative process with transplant recipients into a 2-session group program that provided psychoeducation, addressed barriers to adherence, fostered motivation to improve adherence behavior, and discussed cultural messages on adherence behavior. The intervention group displayed significantly higher levels of adherence when compared to the control group (t = 2.2, p = 0.04) and. similarly, when the amount of change was compared between the groups, the intervention group showed more change than the control condition (F (22,1) = 12.005, p = 0.003). Tacrolimus trough concentration levels were used as a secondary measure of adherence and, while there were no significant between-group differences for mean trough concentration levels, the variability in the trough levels did significantly decrease over time indicating more consistent pill-taking behavior in the intervention group. There is preliminary support for the pilot program as a successful intervention in helping patients with their immunosuppressant medication. © 2016 S. Karger AG, Basel.

  10. Jump Starting Entrepreneurship

    DEFF Research Database (Denmark)

    Burcharth, Ana; Smith, Pernille; Frederiksen, Lars

    How do laid-off employees become entrepreneurs after receiving a dream start into self-employment? This question is relevant for policy makers and entrepreneurship researchers alike since it raises the possibility of a reverse entrepreneurial opportunity, in which the chance of becoming an entrep......How do laid-off employees become entrepreneurs after receiving a dream start into self-employment? This question is relevant for policy makers and entrepreneurship researchers alike since it raises the possibility of a reverse entrepreneurial opportunity, in which the chance of becoming...... an entrepreneur emerges before the discovery of a profitable opportunity. We empirically examine this question on the unique setting of a corporate entrepreneurship program. In the midst of a corporate crisis, Nokia supported laid-off employees to start their own ventures under favorable conditions. We...... persevered in their endeavors and eventually became comfortable with their new career prospects. We discuss the psychological factors that impact career transition after organizational closure and theorize weather they encourage or discourage entrepreneurship....

  11. Cutaneous Alternaria infectoria infection in a dog in association with therapeutic immunosuppression for the management of immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Dedola, C.; Stuart, A.P.G.; Ridyard, A.E.; Else, R.W.; Van den Broek, T.; Choi, J.S.; de Hoog, G.S.; Thoday, K.L.

    2010-01-01

    A 4-year-old, ovariohysterectomized, English springer spaniel on immunosuppressive therapy was re-examined for the review of its immune-mediated haemolytic anaemia and the recent development of skin lesions. For the 3 months since hospital discharge, the dog had been receiving 1.3 mg/kg prednisolone

  12. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    NARCIS (Netherlands)

    Hampras, S.S.; Sucheston-Campbell, L.E.; Cannioto, R.; Chang-Claude, J.; Modugno, F.; Dork, T.; Hillemanns, P.; Preus, L.; Knutson, K.L.; Wallace, P.K.; Hong, C.C.; Friel, G.; Davis, W.; Nesline, M.; Pearce, C.L.; Kelemen, L.E.; Goodman, M.T.; Bandera, E.V.; Terry, K.L.; Schoof, N.; Eng, K.H.; Clay, A.; Singh, P.K.; Joseph, J.M.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Baker, H.; Bean, Y.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Cook, L.S.; Cramer, D.W; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Despierre, E.; Dicks, E.; Doherty, J.A.; Bois, A. du; Durst, M.; Easton, D.; Eccles, D.; Edwards, R.P.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Gronwald, J.; Harrington, P.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hogdall, C.; Hogdall, E.; Hosono, S.; Iversen, E.S.; Jakubowska, A.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.L.M.; Klapdor, R.; Kolomeyevskaya, N.; Krakstad, C.; Kjaer, S.K.; Kruszka, B.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Liu, S.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.A.G.; Matsuo, K.; McGuire, V.; et al.,

    2016-01-01

    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and

  13. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

    DEFF Research Database (Denmark)

    Hampras, Shalaka S; Sucheston-Campbell, Lara E; Cannioto, Rikki

    2016-01-01

    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases a...

  14. Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help?

    Science.gov (United States)

    Nerini, Erika; Bruno, Fulvio; Citterio, Franco; Schena, Francesco P

    2016-10-01

    End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance.

  15. Knowledge-based immunosuppressive therapy for kidney transplant patients--from theoretical model to clinical integration.

    Science.gov (United States)

    Seeling, Walter; Plischke, Max; de Bruin, Jeroen S; Schuh, Christian

    2015-01-01

    Immunosuppressive therapy is a risky necessity after a patient received a kidney transplant. To reduce risks, a knowledge-based system was developed that determines the right dosage of the immunosuppresive agent Tacrolimus. A theoretical model, to classify medication blood levels as well as medication adaptions, was created using data from almost 500 patients, and over 13.000 examinations. This model was then translated into an Arden Syntax knowledge base, and integrated directly into the hospital information system of the Vienna General Hospital. In this paper we give an overview of the construction and integration of such a system.

  16. Comparing subjective and objective quality assessment of HDR images compressed with JPEG-XT

    DEFF Research Database (Denmark)

    Mantel, Claire; Ferchiu, Stefan Catalin; Forchhammer, Søren

    2014-01-01

    In this paper a subjective test in which participants evaluate the quality of JPEG-XT compressed HDR images is presented. Results show that for the selected test images and display, the subjective quality reached its saturation point starting around 3bpp. Objective evaluations are obtained...

  17. Impact of everolimus: update on immunosuppressive therapy strategies and patient outcomes after renal transplantation

    Directory of Open Access Journals (Sweden)

    Helio Tedesco-Silva Jr

    2011-01-01

    Full Text Available Helio Tedesco-Silva Jr, Claudia Rosso Felipe, Tainá Veras de Sandes Freitas, Marina Pontello Cristeli, Carolina Araújo Rodrigues, José Osmar Medina PestanaNephrology Division, Hospital do Rim e Hipertensão, Universidade Federal de São Paulo, BrazilAbstract: Everolimus is an immunosuppressive agent used for the prophylaxis of acute rejection after kidney transplantation. Everolimus inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR, a key enzyme that controls cell growth and metabolism, producing cell cycle arrest from the G1 to S phase. As a consequence, everolimus has antiproliferative and antineoplastic effects. Everolimus is a drug with a narrow therapeutic index. The pharmacokinetics of everolimus indicates a need for twice-daily dosing. Intra- and interindividual variability and drug–drug interactions suggest the need for therapeutic drug monitoring to maximize the efficacy/toxicity ratio. The good correlation between exposure (area under the concentration–time curve and trough concentration indicates that monitoring of everolimus trough concentrations is an adequate strategy after kidney transplantation. Everolimus is indicated for low- to moderate-risk de novo kidney transplant candidates. There are no conclusive studies thus far indicating that everolimus can be used in high-risk patients, such as sensitized patients, retransplants, and African Americans. In de novo kidney transplant recipients, the recommended initial dose of everolimus is 0.75 mg twice daily, adjusted to maintain blood trough concentrations of 3–8 ng/mL, in combination with progressive reduction in blood trough cyclosporine concentrations to 25–50 ng/mL. In combination with reduced trough blood tacrolimus concentrations of 4–7 ng/mL the recommended initial dose of everolimus is 1.5 mg twice daily, adjusted to maintain trough blood concentrations of 3–8 ng/mL. Everolimus can also be used as a conversion strategy

  18. 76 FR 50813 - Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures

    Science.gov (United States)

    2011-08-16

    ... DEPARTMENT OF TRANSPORTATION Federal Transit Administration Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures AGENCY: Federal Transit Administration (FTA... Administration (FTA) to publish policy guidance on the New and Small Starts capital project review and evaluation...

  19. Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

    1988-01-01

    We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

  20. Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses

    Directory of Open Access Journals (Sweden)

    Hsin-Chun Chen

    2016-08-01

    Full Text Available Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC and gas chromatography/mass spectrometry (GC/MS with direct injection (DI/GC or headspace-solid phase microextraction (HS-SPME/GC. In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial. An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases.

  1. How to Hit Mesenchymal Stromal Cells and Make the Tumor Microenvironment Immunostimulant Rather Than Immunosuppressive

    Directory of Open Access Journals (Sweden)

    Alessandro Poggi

    2018-02-01

    Full Text Available Experimental evidence indicates that mesenchymal stromal cells (MSCs may regulate tumor microenvironment (TME. It is conceivable that the interaction with MSC can influence neoplastic cell functional behavior, remodeling TME and generating a tumor cell niche that supports tissue neovascularization, tumor invasion and metastasization. In addition, MSC can release transforming growth factor-beta that is involved in the epithelial–mesenchymal transition of carcinoma cells; this transition is essential to give rise to aggressive tumor cells and favor cancer progression. Also, MSC can both affect the anti-tumor immune response and limit drug availability surrounding tumor cells, thus creating a sort of barrier. This mechanism, in principle, should limit tumor expansion but, on the contrary, often leads to the impairment of the immune system-mediated recognition of tumor cells. Furthermore, the cross-talk between MSC and anti-tumor lymphocytes of the innate and adaptive arms of the immune system strongly drives TME to become immunosuppressive. Indeed, MSC can trigger the generation of several types of regulatory cells which block immune response and eventually impair the elimination of tumor cells. Based on these considerations, it should be possible to favor the anti-tumor immune response acting on TME. First, we will review the molecular mechanisms involved in MSC-mediated regulation of immune response. Second, we will focus on the experimental data supporting that it is possible to convert TME from immunosuppressive to immunostimulant, specifically targeting MSC.

  2. 45 CFR 1308.21 - Parent participation and transition of children into Head Start and from Head Start to public...

    Science.gov (United States)

    2010-10-01

    ... into Head Start and from Head Start to public school. 1308.21 Section 1308.21 Public Welfare... AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START... Standards § 1308.21 Parent participation and transition of children into Head Start and from Head Start to...

  3. Starting Strong: Talent-based Branching of Newly Commissioned U.S. Army Officers

    Science.gov (United States)

    2016-04-01

    security policy formulation. iii v Strategic Studies Institute and U.S. Army War College Press STARTING STRONG: TALENT -BASED BRANCHING OF NEWLY...public release; distribution is unlimited. ***** This publication is subject to Title 17, United States Code , Sections 101 and 105. It is in the public...SSI website at www.StrategicStudiesInstitute.army.mil/newsletter. ***** This volume is the 9th in a series of monographs on officer talent management

  4. [Correlation of SNP of IL-2-330T/G Gene with Genetic Susceptibility and Efficacy of Immunosuppressive Therapy in Patients with Aplastic Anemia].

    Science.gov (United States)

    Zeng, Qiang; Chang, Hong

    2016-10-01

    To investigate the correlation of single nucleotide polymorphism (SNP) of Interleukin-2(IL-2)-330T/G with genetic susceptibility and the efficacy of immunosuppressive therapy in patients with aplastic anemia. The peripheral blood samples from 103 patients with aplastic anemia in our hospital were collected. Out of 103 patients 46 received immuosuppressive therapy and were observed for 4 months, and 100 healthy adults were selected as control. The electrophoresis and DNA sequence were performed. The polymerase chain reaction(PCR) was used to amplify the polymorphic gene segment of IL-2 -330T/G from 103 aplastic anemia patients and 100 healthy adults. The frequencis of IL-2-330 GG genotype and G allele were a little higher in patients with aplastic anemia than that in the healthy adults(12.6% vs 12.0%, P>0.05; 27.7% vs 33.5%, P>0.05), but not statistically significant(P>0.05); in the 103 patients with aplastic anemia, 46 received immunosuppressive therapy, whereas 29 patients showed response, no significant difference was found between the responders and non-responders in the IL-2-330 GG genotype and G allele (31.0% vs 48.3%, P>0.05; 64.8% vs 61.8%, P>0.05). IL-2 -330T/G gene polymorphism may not correlate with the susceptibility of aplastic anemia or the efficacy of immunosuppressive therapy.

  5. DETECTION OF ANTIBODIES TO CANDIDA ALBICANS GERM TUBE BY IMMUNOFLUORESCENCE IN IMMUNOSUPPRESSED MICE WITH EXPERIMENTAL SYSTEMIC CANDIDIASIS

    Directory of Open Access Journals (Sweden)

    F. Zaini

    2007-07-01

    Full Text Available "nThe increasing incidence of systemic candidiasis, which parallels the use of invasive and immunosuppressive medical procedures, necessitates development of rapid and cost effective tests for diagnosis of systemic candidiasis. Therefore in this study 85 mice were first immunosuppressed by cyclophosphamide and then infected by Candida albicans NCPF 3153. Other 85 mice were employed as control. The case and control mice were bled and then autopsied. Hearts and kidneys were checked by direct, histopathological and cultural examination for systemic candidiasis. The 85 sera from histological proven cases and 85 control mice were adsorbed with heat killed blastospores of same strain of C. albicans. Anti-Candida albicans germ tube antibodies were detected by indirect immunofluorescence assay for diagnosis of invasive candidiasis in case and control mice. In addition, sera from 35 mice with proven cryptococcosis were also tested. While 84 mice with proven systemic candidiasis (100% had anti-germ tube antibodies, these antibodies were absent in all controls and mice with cryptococcosis. The specificity was 100%, indicating a high degree of discrimination was possible between systemic candidiasis and cryptococcosis in the mice studied. It must be concluded that anti-germ tube responses did not appear to be significantly reduced in immunocompromised mice.

  6. Fecal Bacteriotherapy: A Case Report in an Immunosuppressed Patient with Ulcerative Colitis and Recurrent  Clostridium difficile Infection

    Directory of Open Access Journals (Sweden)

    Hadeel Zainah

    2012-01-01

    Full Text Available We report a case of ulcerative colitis (UC and recurrent Clostridium difficile infection (CDI where the patient was on immunomodulatory therapy and had successful CDI eradication after fecal transplantation. This is the first case report in the literature documenting successful C. difficile eradication in an immunosuppressed patient. We feel that fecal transplantation should be studied as a treatment option in these patients.

  7. Unusual Case Report of Thrombotic Microangiopathy of the Small Bowel Following Liver Transplantation, a Possible Immunosuppressant-Induced Disease with Histological and Ultrastructural Findings

    Directory of Open Access Journals (Sweden)

    Domenico Piscitelli

    2009-01-01

    Full Text Available Cyclosporin-A (CsA and tacrolimus (FK-506 are immunomodulating agents used to prevent rejection in organ transplantation. They are both associated with several side effects, including nephrotoxicity and severe hypertension due to vascular injury, which often appears as a microvascular occlusive disorder (thrombotic microangiopathy, TMA. We report the first case of a microvascular occlusive disorder with the features of TMA in the small bowel of an orthotopic liver transplant (OLT patient after immunosuppressive therapy with CsA and FK506. The patient presented with severe recurrent abdominal colics and distal subocclusion, requiring aggressive surgical treatment. Histological and ultrastructural analysis of the resected specimen disclosed intestinal TMA. Although rare, such a complication should be considered in the differential diagnosis of abdominal colics in patients undergoing immunosuppressant therapy after OLT.

  8. Pre-start timing information is used to set final linear speed in a C-start manoeuvre.

    Science.gov (United States)

    Reinel, Caroline; Schuster, Stefan

    2014-08-15

    In their unique hunting behaviour, archerfish use a complex motor decision to secure their prey: based solely on how dislodged prey initially falls, they select an adapted C-start manoeuvre that turns the fish right towards the point on the water surface where their prey will later land. Furthermore, they take off at a speed that is set so as to arrive in time. We show here that the C-start manoeuvre and not subsequent tail beating is necessary and sufficient for setting this adaptive level of speed. Furthermore, the C-start pattern is adjusted to independently determine both the turning angle and the take-off speed. The selection of both aspects requires no a priori information and is done based on information sampled from the onset of target motion until the C-start is launched. Fin strokes can occur right after the C-start manoeuvre but are not required to fine-tune take-off speed, but rather to maintain it. By probing the way in which the fish set their take-off speed in a wide range of conditions in which distance from the later catching point and time until impact varied widely and unpredictably, we found that the C-start manoeuvre is programmed based on pre-C-start estimates of distance and time until impact. Our study hence provides the first evidence for a C-start that is fine-tuned to produce an adaptive speed level. © 2014. Published by The Company of Biologists Ltd.

  9. The oncogenic potential of three different 7, 12-dimethylbenz (a)anthracene transformed C3H/10T1/2 cell clones at various passages and the importance of the mode of immunosuppression

    International Nuclear Information System (INIS)

    Saxholm, H.J.K.

    1979-01-01

    The oncogenic potential of C3H/10T1/2 cells which were transformed in vitro with 7,12-dimethylbenz(a)anthracene is reported. The ability of the cells to grow as malignant tumors in syngeneic immunosuppressed mice was used as parameter for oncogenic potential. Cells of types I, II and III were assayed at several dosage levels, i.e., 10 4 , 10 5 or 10 6 cells per inoculum, with or without immunosuppression by antithymocyte serum globulin fraction. The studies were performed in several strains of host animals, i.e., male and female syngeneic C3H mice supplied by the National Cancer Institute, C3H mice supplied by Charles River and nude, athymic female mice. Morphological transformation preceded oncological transformation, and type I cells could not be established as tumors. Type II and type III cells developed oncogenic potential only after several passages in culture. Oncogenic potential was pronounced in the type III cells, and less strongly expressed in type II cells. Also tested were different methods of immunosuppression of the animal against the expression of the oncogenic potential of DMBA transformed C3H/10T1/2 cells from type II and III clones. Immunosuppression by antithymocyte serum globulin fraction was an effective method of preparing the syngeneic host so that cells with a low oncogenic potential would grow as tumors, whereas total body irradiation was not effective. For cells with a high oncogenic potential both ways of immunosuppression were sufficient. Admixing lethally irradiated cells in the cell inoculum slightly enhanced the tumor development from cells with low oncogenic potential and such addition was clearly effective for cells with a higher oncogenic potential, both for the antibody-treated and for the irradiated series. The findings were reproducible. The study stresses the importance of immunosuppression by antithymocyte globulins for detecting in vitro transformed weakly oncogenic cells. (author)

  10. Preschool Facilities - MDC_HeadStart

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A label (point) feature class of Head Start / Early Head Start/ Delegate Agencies/ Child Care Partnership & Family Day Care Homes Programs location in Miami-Dade...

  11. Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a meta-analysis based on Chinese adults.

    Directory of Open Access Journals (Sweden)

    Guoqiang Xie

    Full Text Available Idiopathic membranous nephropathy (IMN is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs meeting the criteria was performed using Review Manager.17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008, partial or complete remission (effective (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003, and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX, leflunomide (LET showed no beneficial effect, mycophenolate mofetil (MMF showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006 but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15.This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

  12. Environmental mitigation for SCC initiation of BWR core internals by hydrogen injection during start-up

    International Nuclear Information System (INIS)

    Dozaki, K.; Abe, A.; Nagata, N.; Takiguchi, H.

    2004-01-01

    Hydrogen injection into the reactor water has been applied to many BWR power stations. Since hydrogen injected accelerates recombination of oxidant generated by water radiolysis, oxidant concentration, such as dissolved oxygen concentration in reactor water can be reduced. As the result of the reduction of oxidant concentration, Electrochemical Corrosion Potential (ECP) at the surface of structural material can be lowered. Lowered ECP moderates Stress Corrosion Cracking (SCC) sensitivity of structural materials, such as stainless steels. As usual, hydrogen injection system begins to work after the plant start-up is finished, when the condition of normal operation is established. Accordingly, Hydrogen Water Chemistry (HWC) does not cover all the period of plant operation. As far as SCC crack growth is considered, loss of HWC during plant start-up does not result in significant crack growth, because of duration of plant start-up is much shorter than that of plant normal operation, when HWC condition is being satisfied. However, the reactor water environment and load conditions during a plant start-up may contribute to the initiation of SCC. It is estimated that the core internals are subjected to the strain rate that may cause susceptibility to SCC initiation during start-up. Dissolved oxygen (DO) and hydrogen peroxide (H 2 O 2 ) has a peak, and ECP is in high levels during start-up. Therefore it is beneficial to perform hydrogen injection during start-up as well in order to suppress SCC initiation. We call it HWC During Start-up (HDS) here. (orig.)

  13. Getting started with Unity

    CERN Document Server

    Felicia, Patrick

    2013-01-01

    Getting Started with Unity is written in an easy-to-follow tutorial format.""Getting Started with Unity"" is for[ 3D game developers[/color] who would like to learn how to use Unity3D and become familiar with its core features. This book is also suitable for intermediate users who would like to improve their skills. No prior knowledge of Unity3D is required.

  14. Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

    International Nuclear Information System (INIS)

    Wijkstrom, Martin; Kirchhof, Nicole; Graham, Melanie; Ingulli, Elizabeth; Colvin, Robert B.; Christians, Uwe; Hering, Bernhard J.; Schuurman, Henk-Jan

    2005-01-01

    Streptozotocin (STZ) is widely applied in animal models of insulin-dependent diabetes mellitus. Adverse effects of STZ mainly concern liver and kidney. In nonhuman primates a single 100-150 mg/kg dose invariably induces diabetes with only rare adverse effects. We report one animal with renal failure necessitating sacrifice. Body weight (age) might be a confounding factor, i.e. older animals might be more vulnerable to STZ-related toxicity. We therefore recommended to administer STZ on a mg/m 2 basis and not on a mg/kg basis. In our islet transplantation program nonhuman primates with STZ-induced diabetes received transplants under chronic immunosuppression including calcineurin inhibitors (cyclosporine, tacrolimus), drugs in the rapamycin class affecting growth factor-induced cell proliferation, and the sphingosine 1-phosphate receptor antagonist FTY720. Four animals developed renal failure and had to be sacrificed, most likely caused by cyclosporine. Kidney histology was typical for cyclosporine toxicity including thrombotic microangiopathy in glomeruli and fibrinoid necrosis of arteries, and for STZ toxicity including acute tubular necrosis and accumulations of erythroid precursors. This adverse effect was observed at a pharmacologically active cyclosporine exposure. Additionally, six diabetic animals without major adverse effects during cyclosporine or tacrolimus treatment are presented. We conclude that cyclosporine facilitates renal dysfunction in animals with STZ-induced diabetes, presumably related to an increased vulnerability to a toxic insult after STZ administration

  15. IMMEDIATE EFFECTS OF DEEP TRUNK MUSCLE TRAINING ON SWIMMING START PERFORMANCE.

    Science.gov (United States)

    Iizuka, Satoshi; Imai, Atsushi; Koizumi, Keisuke; Okuno, Keisuke; Kaneoka, Koji

    2016-12-01

    In recent years, deep trunk muscle training has been adopted in various sports, including swimming. This is performed both in everyday training and as part of the warm-up routine before competitive races. It is suggested that trunk stabilization exercises are effective in preventing injury, and aid in improving performance. However, conclusive evidence of the same is yet to be obtained. The time of start phase of swimming is a factor that can significantly influence competition performance in a swimming race. If trunk stabilization exercises can provide instantaneous trunk stability, it is expected that they will lead to performance improvements in the start phase of swimming. The purpose of this study was to investigate the immediate effect of trunk stabilization exercises on the start phase in swimming. Intervention study. Nine elite male swimmers (mean age 20.2 ± 1.0 years; height 174.4 ± 3.5 cm; weight 68.9 ± 4.1 kg) performed the swimming start movement. The measurement variables studied included flying distance, and the time and velocity of subjects at hands' entry and on reaching five meters. Measurements were taken in trials immediately before and after the trunk stabilization exercises. A comparison between pre- and post-exercise measurements was assessed. The time to reach five meters (T 5m ) decreased significantly after trunk stabilization exercises, by 0.019 s (p = 0.02). Velocity at entry (V entry ) did not demonstrate significant change, while velocity at five meters (V 5m ) increased significantly after the exercises (p = 0.023). In addition, the speed reduction rate calculated from V entry and V 5m significantly decreased by 5.17% after the intervention (p = 0.036). Trunk stabilization exercises may help reduce the time from start to five meters in the start phase in swimming. The results support the hypothesis that these exercises may improve swimming performance. Level 3b.

  16. Clinical features and therapeutic interventions in 17 cases of Bacillus bacteremia in an immunosuppressed patient population.

    OpenAIRE

    Cotton, D J; Gill, V J; Marshall, D J; Gress, J; Thaler, M; Pizzo, P A

    1987-01-01

    We retrospectively examined episodes of Bacillus bacteremia at a hospital with a large proportion of immunosuppressed patients. Seventeen episodes in 9.5 years met our case definition: two of two bottles of one blood culture or one of two bottles of two or more separately obtained blood cultures drawn on the same date. During the same period, there were 59 additional episodes in which a single blood culture had only one of two bottles positive for Bacillus species. Only 2 of 59 such episodes ...

  17. Identification and characterization of two novel Gammapapillomavirus genomes in skin of an immunosuppressed Epidermodysplasia Verruciformis patient.

    Science.gov (United States)

    Dutta, Sankhadeep; Robitaille, Alexis; Aubin, François; Fouéré, Sébastien; Galicier, Lionel; Boutboul, David; Luzi, Fabiola; Di Bonito, Paola; Tommasino, Massimo; Gheit, Tarik

    2018-04-02

    Two novel human gamma-papillomavirus genomes (HPV_MTS3, and HPV_MTS4) were isolated from the skin of an immunosuppressed, late-onset Epidermodysplasia Verruciformis patient and fully cloned. The L1 open reading frames of HPV_MTS3 and HPV_MTS4 were 77% and 91% identical to their closest HPV full genome isolates w18c39 and EV03c60, which belong to the species gamma-22and gamma-7 of the genus Gammapapillomavirus, respectively. Copyright © 2018. Published by Elsevier B.V.

  18. Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    Science.gov (United States)

    Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

    2016-01-01

    Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

  19. Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    Science.gov (United States)

    Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

    Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

  20. Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

    Directory of Open Access Journals (Sweden)

    Alicia J. McLuckie

    2017-03-01

    Full Text Available Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV infection, making the interactions between feline immunodeficiency virus (FIV and Felis catus gammaherpesvirus 1 (FcaGHV1 pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18 or feline leukemia virus (FeLV-infected (P2, n = 57 patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57. In contrast, FIV/FeLV-co-infected cats (P3, n = 5 were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068, and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3 had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4. In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

  1. T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-γ Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma

    Directory of Open Access Journals (Sweden)

    Qiang Zou

    2015-12-01

    Full Text Available USP15 is a deubiquitinase that negatively regulates activation of naive CD4+ T cells and generation of IFN-γ-producing T helper 1 (Th1 cells. USP15 deficiency in mice promotes antitumor T cell responses in a transplantable cancer model; however, it has remained unclear how deregulated T cell activation impacts primary tumor development during the prolonged interplay between tumors and the immune system. Here, we find that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA-induced fibrosarcomas. Excessive IFN-γ production in USP15-deficient mice promotes expression of the immunosuppressive molecule PD-L1 and the chemokine CXCL12, causing accumulation of T-bet+ regulatory T cells and CD11b+Gr-1+ myeloid-derived suppressor cells at tumor site. Mixed bone marrow adoptive transfer studies further reveals a T cell-intrinsic role for USP15 in regulating IFN-γ production and tumor development. These findings suggest that T cell intrinsic USP15 deficiency causes excessive production of IFN-γ, which promotes an immunosuppressive tumor microenvironment during MCA-induced primary tumorigenesis.

  2. Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.

    Science.gov (United States)

    Roux, Clémence; Saviane, Gaëlle; Pini, Jonathan; Belaïd, Nourhène; Dhib, Gihen; Voha, Christine; Ibáñez, Lidia; Boutin, Antoine; Mazure, Nathalie M; Wakkach, Abdelilah; Blin-Wakkach, Claudine; Rouleau, Matthieu

    2017-01-01

    Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4 + FoxP3 + regulatory T (Treg) cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3 + -Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo . They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

  3. Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Clémence Roux

    2018-01-01

    Full Text Available Despite mesenchymal stromal cells (MSCs are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate. Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs, and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4+ FoxP3+ regulatory T (Treg cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3+-Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo. They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

  4. Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang, E-mail: molpharm@163.com; Sun, Yang, E-mail: yangsun@nju.edu.cn

    2013-03-01

    In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

  5. Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

    International Nuclear Information System (INIS)

    Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang; Sun, Yang

    2013-01-01

    In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

  6. Starting out

    NARCIS (Netherlands)

    Ans Merens; Freek Bucx

    2018-01-01

    Original title: Werken aan de start Women in the Netherlands have been outperforming men in education for many years now. However, this superior educational achievement does not translate into a better position on the labour market. More women work today than in the past, but still fewer than men.

  7. ATG-Fresenius S combined with cyclosporine a: an effective immunosuppressive therapy for children with aplastic anemia.

    Science.gov (United States)

    Luo, Cheng-Juan; Gao, Yi-Jin; Tang, Jing-Yan; Zhu, Xiao-Hua; Xue, Hui-Liang; Lu, Feng-Juan; Pan, Ci; Jiang, Hua; Luo, Chang-Ying; Ye, Qi-Dong; Zhou, Min; Chen, Jing

    2014-07-01

    For the first time, we conducted a 2-center retrospective study to show the efficacy of antithymocyte globulin (ATG)-Fresenius S plus cyclosporine treatment of children with severe aplastic anemia. From March 1997 to May 2011, a total of 124 patients (median age, 7.5 y; range, 1.5 to 16 y) from 2 centers with acquired AA treated with an immunosuppressive therapy (IST) regimen, consisting of ATG-Fresenius S (5 mg/kg per day for 5 d) and cyclosporine, were enrolled. The response rate was 55.6%. The median time between IST and response was 6 (0.5 to 18) months. After a median follow-up time of 29 (6 to 153) months, the rates of relapse and clonal evolution were 3.2% and 0.8%, respectively. Overall, 17 patients (13.7%) died in this study: 14 resulted from sepsis, 1 resulted from intracranial hemorrhage, 1 occurred after hematopoietic stem cell transplantation, and 1 resulted from clonal disease progression. The 5-year overall survival rate for the entire cohort was 74.7%. IST responders had a better survival rate (100%) than nonresponders (70.7%). The use of ATG-Fresenius S plus cyclosporine as a first-line immunosuppressive treatment appeared to be effective for children with severe aplastic anemia in our study. ATG-Fresenius S could be another option in the treatment arsenal, especially in countries where the other ATG products are harder to acquire.

  8. Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

    Science.gov (United States)

    Patel, Jaina; Bozeman, Erica N.; Selvaraj, Periasamy

    2013-01-01

    The identification of TIM-3 expression on tumor associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells, however its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings. PMID:23240746

  9. Effect of orally-administered Lactobacillus plantarum LPLM-O1 strain in an immunosuppressed mouse model of urinary tract infection.

    Science.gov (United States)

    de Arellano, A Ramírez; Sánchez, M; Vera, R; Jara, S; González, M; Castro, E

    2012-03-01

    Urinary tract infections (UTIs) affect both healthy and immunocompromised people, and they are treated with antibiotics. However, the high recurrence of UTIs obliges the use of natural mechanisms to regulate the normal microbiota through the use of e.g. lactic acid bacteria. In order to induce a UTI, 20 µl of the Escherichia coli (Ec-01) strain, in doses of 2.7×10(7) cfu/ml, was inoculated by way of the urethra in female Balb/c mice, all of them immunosuppressed with dexamethasone (10 mg/kg). Lactobacillus plantarum LPLM-O1 was used as a treatment, in daily doses of 1×10(7) cfu/ml, which were orally administered for seven days before the infection (preventive) or alongside the infection for seven days (curative). The oral administration of LPLM-O1 did not cause any adverse effects when used in an immunosuppressed animal model. It was observed that, when used as a preventive measure, LPLM-O1 induces a decrease in the infection, in the concentration of urinary leukocytes, and in the bacterial load. This study proposes the use of this lactic bacterium as a probiotic.

  10. Start 2: Thinking one move ahead

    Energy Technology Data Exchange (ETDEWEB)

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush`s historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R&D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  11. Start 2: Thinking one move ahead

    Energy Technology Data Exchange (ETDEWEB)

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush's historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  12. Efficiency of Photodynamic Therapy in the Treatment of Diffuse Facial Viral Warts in an Immunosuppressed Patient: Towards a Gold Standard

    Directory of Open Access Journals (Sweden)

    M. Caucanas

    2010-12-01

    Full Text Available A 64-year-old man with a pulmonary transplant developed diffuse verrucae vulgares of the neck. After the failure of multiple cryotherapy treatments, 3 sessions of photodynamic therapy resulted in rapid therapeutic clinical success. This moderately painful and well-tolerated treatment is reproducible and can be very useful in treating papillomavirus infections in the immunosuppressed patient.

  13. [Barriers to ART initiation in HIV infected subjects and with treatment indication in Spain. Why don't they start their treatment? Bridgap Study].

    Science.gov (United States)

    Viciana-Fernández, Pompeyo; Falcó, Vicenç; Castaño, Manuel; de los Santos-Gil, Ignacio; Olalla-Sierra, Julián; Hernando, Asunción; Deig, Elisabet; Clotet, Bonaventura; Knobel, Hernando; Podzamczer, Daniel; Pedrol, Pere Domingo

    2015-01-01

    In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented. A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART. A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  14. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells

    Science.gov (United States)

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-01

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:26775677

  15. Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

    Science.gov (United States)

    Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

    2015-11-01

    Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

  16. Interferon-gamma improves impaired dentinogenic and immunosuppressive functions of irreversible pulpitis-derived human dental pulp stem cells.

    Science.gov (United States)

    Sonoda, Soichiro; Yamaza, Haruyoshi; Ma, Lan; Tanaka, Yosuke; Tomoda, Erika; Aijima, Reona; Nonaka, Kazuaki; Kukita, Toshio; Shi, Songtao; Nishimura, Fusanori; Yamaza, Takayoshi

    2016-01-18

    Clinically, irreversible pulpitis is treated by the complete removal of pulp tissue followed by replacement with artificial materials. There is considered to be a high potential for autologous transplantation of human dental pulp stem cells (DPSCs) in endodontic treatment. The usefulness of DPSCs isolated from healthy teeth is limited. However, DPSCs isolated from diseased teeth with irreversible pulpitis (IP-DPSCs) are considered to be suitable for dentin/pulp regeneration. In this study, we examined the stem cell potency of IP-DPSCs. In comparison with healthy DPSCs, IP-DPSCs expressed lower colony-forming capacity, population-doubling rate, cell proliferation, multipotency, in vivo dentin regeneration, and immunosuppressive activity, suggesting that intact IP-DPSCs may be inadequate for dentin/pulp regeneration. Therefore, we attempted to improve the impaired in vivo dentin regeneration and in vitro immunosuppressive functions of IP-DPSCs to enable dentin/pulp regeneration. Interferon gamma (IFN-γ) treatment enhanced in vivo dentin regeneration and in vitro T cell suppression of IP-DPSCs, whereas treatment with tumor necrosis factor alpha did not. Therefore, these findings suggest that IFN-γ may be a feasible modulator to improve the functions of impaired IP-DPSCs, suggesting that autologous transplantation of IFN-γ-accelerated IP-DPSCs might be a promising new therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.

  17. Teaching iSTART to Understand Spanish

    Science.gov (United States)

    Dascalu, Mihai; Jacovina, Matthew E.; Soto, Christian M.; Allen, Laura K.; Dai, Jianmin; Guerrero, Tricia A.; McNamara, Danielle S.

    2017-01-01

    iSTART is a web-based reading comprehension tutor. A recent translation of iSTART from English to Spanish has made the system available to a new audience. In this paper, we outline several challenges that arose during the development process, specifically focusing on the algorithms that drive the feedback. Several iSTART activities encourage…

  18. Soft-Starting Power-Factor Motor Controller

    Science.gov (United States)

    Nola, F. J.

    1983-01-01

    Three-phase power-factor controller with soft start is based on earlier version that does not control starting transients. Additional components serve to turn off "run" command signal and substitute gradual startup command signal during preset startup interval. Improved controller reduces large current surge that usually accompanies starting. Controller applies power smoothly, without causing motor vibrations.

  19. What Happens at the Lesson Start?

    Science.gov (United States)

    Saloviita, Timo

    2016-01-01

    Transitional periods, such as lesson starts, are necessary steps from one activity to another, but they also compete with time for actual learning. The aim of the present study was to replicate a previous pilot study on lesson starts and explore possible disturbances. In total, 130 lesson starts in Finnish basic education in grades 1-9 were…

  20. 46 CFR 112.50-3 - Hydraulic starting.

    Science.gov (United States)

    2010-10-01

    ... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be a... 46 Shipping 4 2010-10-01 2010-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping...

  1. Distribution in pregnant mice of radioactivity after injection of 131I, and immunosuppressive effect by the whole body irradiation

    International Nuclear Information System (INIS)

    Sushida, Kiyo; Nakano, Hisao

    1978-01-01

    For the purpose of decreasing resistance to leprous bacilli, 100 μCi of 131 I was injected subcutaneously to 2-3 week pregnant, dd-strain mice. Internal distribution of 131 I was followed up by measuring radioactivity in each organ of parent mice (I-P) and fetal mice (I-F). 300 rad in all of 60 Co was irradiated to 2-3 week pregnant mice (R-P) in two directions from the dorsal side of the abdomen. Immunosuppressive effect of the irradiation was evaluated in the parent mice and their offsprings (R-F) and compared with that in the 131 I-treated mice using a skin graft method. It was shown that 131 I of parent mice stayed in the uterus and was transmitted to their fetus through the placenta, and clarified that 131 I which remained in parent mice was continually supplied to their infant mice through milk still after birth. These findings seem to explaine the result that I-F which had been affected continually by 131 I had higher sensitivity to leprous bacilli than I-P. Immunosuppressive effect on a skin graft disclosed that the chief mechanisms of 131 I are to decrease the function of the reticulo-endothelial system by iodine and to suppress cellular immunity by its radioactivity. The rejecting time for the mouse skin homograft in the untreated mouse was 8.8 days on the average, and the lymph node weight was 33 mg. The order of the duration in the graft survival was R-P>I-F>I-P>R-F> normal mice, while that of lymph node weights was completely inverse. Therefore, the immunosuppressive effect on I-P and I-F mice, when it is compared with normal mice, could be confirmed, and the I-F was said to be favorable further than to I-P when based on this immunity test by transplantation. (Ueda, J.)

  2. IB-12LUNG MASS AND IMMUNOSUPPRESSANT RESPONSIVE SEIZURES: VGKC AUTOIMMUNITY MASQUERADING AS ETIOLOGY OR ACTING AS REACTIVE MARKER?

    OpenAIRE

    Umemura, Yoshie; Bujarski, Krzysztof; Ronan, Lara

    2014-01-01

    Voltage gated potassium channel complex antibody (VGKC Ab) has been associated with many neurological illnesses including seizures. VGKC Ab related seizures are less responsive to antiepileptic drugs alone, and often require immunosuppression to achieve seizure freedom. Recently, specific antigenic targets such as LGI1 and CASPR2 within VGKC have been found and have been associated with specific syndromes. It has also been noted that the term "VGKC Ab" itself is problematic because it groups ...

  3. Longitudinal study of the indirect immunofluorescence and complement fixation tests for diagnosis of chagas' disease in immunosuppressed patients submitted to renal transplantation

    Directory of Open Access Journals (Sweden)

    José Fernando de Castro Figueiredo

    1993-12-01

    Full Text Available Clinical and serological follow-up of 7 patients submitted to renal transplantation and presenting positive serological reactions to Chagas 'disease before immunossupression did not show significant changes in indirect immunofluorescence and complement fixation titres for Chagas ' disease, or signs and symptoms indicating exacerbation of the disease during follow- up. In addition, 18 of 66 recipients of renal transplants considered to be non-chagasic before immunosuppression showed at least one positive result to the indirect immunofluorescence test for Chagas ' disease during the study period. The results suggest that the immunosuppression State induced in chagasic patients submitted to renal transplant did notpromoted exacerbation of the chronic infection in these patients and not interfere with the serological response of chronic chagasics, thus permitting the use of these serologic reactions for diagnostic purposes in these cases. However, the positive results ofthe indirect immunofluorescence test in non- chagasic patients indicate the needforjudicious interpretation ofthe indirect immunofluorescence test for the diagnosis of Chagas' disease in renal transplanted patients.

  4. Predictors of Immunosuppressive Regulatory T Lymphocytes in Healthy Women

    International Nuclear Information System (INIS)

    Hampras, S. S.; Nesline, M.; Davis, W.; Moysich, K. B.; Wallace, P. K.; Odunsi, K.; Furlani, N.

    2012-01-01

    Immunosuppressive regulatory T (Treg) cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and Bio Repository (DBBR) program at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood levels of CD4 + CD25 + FOXP3 + Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI), and hormone replacement therapy (HRT) were found to be significant positive predictors of Treg cell levels in peripheral blood (π≤0.05 ). Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (π<0.05) negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.

  5. Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis-associated severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Aleksandar Savic

    2010-12-01

    Full Text Available Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery.

  6. Irradiation of ice creams for immunosuppressed patients

    International Nuclear Information System (INIS)

    Adeil Pietranera, Maria S.; Narvaiz, Patricia; Horack, C.; Kairiyama, Eulogia; Gimenez, Palmira; Gronostajski, D.

    2003-01-01

    Immunosuppressed patients are very likely to acquire microbial food borne diseases, since due to illness, biological condition or situations generating risks, their natural defences are below what is considered as 'normal limits'. This makes their food intake very restricted, avoiding all those products that could be a source of microorganisms. Gamma radiation applied at sub-sterilizing doses represents a good choice in order to achieve 'clean' diets, and at the same time, it can widen the variety of available meals for these patients, allowing the inclusion of some products normally considered as 'high risk' due to their microbial load, but that can be nutritionally or psychologically adequate. One of these products is ice-cream, a minimally processed type of meal that does not suffer enough microbial inactivation during its processing. Particularly those from natural origin can carry undesirable contamination causing sometimes diseases to the consumer. For that reason, different ice-cream flavours (vanilla, raspberry, peach and milk jam) were exposed to an irradiation treatment at the 60 Co facility of the Ezeiza Atomic Centre. The delivered doses were 3, 6 and 9 kGy. Microbiological determinations were performed, together with sensory evaluations and some chemical analysis: acidity, peroxide value, ultraviolet and visible absorption, thin-layer chromatography and sugar determination, in order to find out if gamma radiation could be applied as a decontamination process without impairing quality. Water-based ice-creams (raspberry and peach) were more resistant to gamma radiation than cream-based ones (vanilla and milk jam), due to their differences in fat content. Gamma irradiation with 3 kGy reduced remarkably the microbial load of these ice-creams and eliminated pathogens without impairing their quality. (author)

  7. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease.

    Science.gov (United States)

    2004-04-01

    Treatment with rasagiline mesylate, an irreversible monoamine oxidase type B inhibitor, improves symptoms of early Parkinson disease (PD). Preclinical studies suggest that this compound may also modify the progression of PD. To compare the effects of early and later initiation of rasagiline on progression of disability in patients with PD. Double-blind, parallel-group, randomized, delayed-start clinical trial. Four hundred four subjects with early PD, not requiring dopaminergic therapy, enrolled at 32 sites in the United States and Canada. Subjects were randomized to receive rasagiline, 1 or 2 mg/d, for 1 year or placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months. Change in total Unified Parkinson's Disease Rating Scale score from baseline to 12 months. Three hundred seventy-one subjects were included in the 1-year efficacy analysis. Subjects treated with rasagiline, 2 mg/d, for 1 year had a 2.29-unit smaller increase in mean adjusted total Unified Parkinson's Disease Rating Scale score compared with subjects treated with placebo for 6 months followed by rasagiline, 2 mg/d, for 6 months (P =.01). The mean adjusted difference between the placebo/rasagiline, 2 mg/d, group and those receiving rasagiline, 1 mg/d, for 1 year was -1.82 unit on the Unified Parkinson's Disease Rating Scale score (P =.05). Subjects treated with rasagiline, 2 and 1 mg/d, for 12 months showed less functional decline than subjects whose treatment was delayed for 6 months.

  8. High Time Resolution Measurements of VOCs from Vehicle Cold Starts: The Air Toxic Cold Start Pulse

    Science.gov (United States)

    Jobson, B. T.; Huangfu, Y.; Vanderschelden, G. S.

    2017-12-01

    Pollutants emitted during motor vehicle cold starts, especially in winter in some climates, is a significant source of winter time air pollution. While data exist for CO, NO, and total hydrocarbon emissions from federal testing procedures for vehicle emission certification, little is known about the emission rates of individual volatile organic compounds, in particular the air toxics benzene, formaldehyde, and acetaldehyde. Little is known about the VOC speciation and temperature dependence for cold starts. The US EPA vehicle emission model MOVES assumes that cold start emissions have the same speciation profile as running emissions. We examined this assumption by measuring cold start exhaust composition for 4 vehicles fueled with E10 gasoline over a temperature range of -4°C to 10°C in winter of 2015. The extra cold start emissions were determined by comparison with emissions during engine idling. In addition to CO and NOx measurements a proton transfer reaction mass spectrometer was used to measure formaldehyde, acetaldehyde, benzene, toluene, and C2-alkylbenzenes at high time resolution to compare with the cold start emission speciation profiles used in the EPA MOVES2014 model. The results show that after the vehicle was started, CO mixing ratios can reach a few percent of the exhaust and then drop to several ppmv within 2 minutes of idling, while NOx showed different temporal behaviors among the four vehicles. VOCs displayed elevated levels during cold start and the peak mixing ratios can be two orders higher than idling phase levels. Molar emission ratios relative to toluene were used to compare with the emission ratio used in MOVES2014 and we found the formaldehyde-to-toluene emission ratio was about 0.19, which is 5 times higher than the emission ratio used in MOVES2014 and the acetaldehyde-to-toluene emission ratios were 0.86-0.89, which is 8 times higher than the ones in MOVES2014. The C2-alkylbenzene-to-toluene ratio agreed well with moves. Our results

  9. Application of intelligent soft start in asynchronous motor

    Science.gov (United States)

    Du, Xue; Ye, Ying; Wang, Yuelong; Peng, Lei; Zhang, Suying

    2018-05-01

    The starting way of three phase asynchronous motor has full voltage start and step-down start. Direct starting brings large current impact, causing excessive local temperature to the power grid and larger starting torque will also impact the motor equipment and affect the service life of the motor. Aim at the problem of large current and torque caused by start-up, an intelligent soft starter is proposed. Through the application of intelligent soft start on asynchronous motor, highlights its application advantage in motor control.

  10. Insertion and professional development of starting university professors: the need for spaces for pedagogical discussion

    Directory of Open Access Journals (Sweden)

    Beatriz Maria Boessio Atrib Zanchet

    2016-01-01

    Full Text Available Current paper is the result of a research on twenty-eight starting university teachers in four universities in southern Brazil and seeks to understand their concern on pedagogical discussion spaces as a possible support for the development of their teaching practice. The research started from the point that starting teachers should insert themselves within higher education culture and find pedagogical support to develop their lectures. As a rule, they have recently obtained a doctoral degree, complying with the required academic title for their tenure, but with scanty or no pedagogical preparation. The subjects answered a semi-structured interview, with issues on the challenges, difficulties and possibilities of pedagogical support pointed out when they started their activities. The quantitative data form the corpus analyzed used in the analysis. The paper is based on studies by Garcia (1999, 2009b, Vaillant and Garcia (2012 and others. Results showed that pedagogical education and professional development of university professors, developed through pedagogical spaces, are essential for and welcomed by these teachers. An overall policy is required that valorizes the teaching tasks as fundamental for achieving teaching quality.

  11. Relative reductions in soluble CD30 levels post-transplant predict acute graft function in islet allograft recipients receiving three different immunosuppression protocols.

    Science.gov (United States)

    Hire, Kelly; Hering, Bernhard; Bansal-Pakala, Pratima

    2010-08-01

    Despite advances in islet transplantation, challenges remain in monitoring for anti-islet immune responses. Soluble CD30 (sCD30) has been investigated as a predictor of acute rejection in kidney, lung, and heart transplantation as well as in a single study in human islet cell recipients. In this study, sCD30 levels were retrospectively assessed in 19 allograft recipients treated with three different immunosuppression induction therapies. Soluble CD30 levels were assessed at pre-transplant; early post-transplant (day 4-day 7); one-month post-transplant; and late post-transplant (day 90-day 120) and then correlated with eventual graft outcomes at 1-year follow-up. Results showed no correlation between mean serum sCD30 levels at any point in time pre- or post-transplant and graft function at 1-year follow-up. However, analysis demonstrated that mean sCD30 levels at day 28 or day 90-day 120 decreased from pre-transplant levels in recipients with long-term islet allograft function compared to recipients with partial or non-graft function (a decrease of 43.6+/-25.6% compared to 16.7+/-35.2%, psCD30 levels post-transplant overall. A larger reduction post-transplant correlated with full graft function. The results demonstrate that a relative reduction in sCD30 levels post-transplant may be applicable as a biomarker to monitor graft function in islet allograft recipients. Additionally, knowledge of the impact of various immunosuppression protocols on the timing and extent of changes in post-transplant sCD30 levels could aid in patient-specific tailoring of immunosuppression. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. De-escalatory confidence-building measures after START

    International Nuclear Information System (INIS)

    Stockton, P.N.

    1992-01-01

    The very notion of examining de-escalatory CBMs in the context of the START negotiations appears odd. Given the immense progress in US-Soviet relations, of which the proposed START agreement is emblematic, the risk of the two nations stumbling to the brink of war seems increasingly remote. Why bother analyzing CBMs designed to help resolve such an improbable event? The obvious answer is that relations between the US and the Soviet Union - or whatever array of nations succeed it - could take an unforeseeable turn for the worse. Once ratified, the START agreement is supposed to remain in force for seven years, more than enough time for political tensions to return with a vengeance. This suggests a more prudent question: if our two nations do stumble to the brink of war, will the START agreement affect the prospect of de-escalatory CBMs? And if the US and Soviet Union pursue deeper force-reductions in a follow-on START II agreement, could that agreement be designed to facilitate more effective de-escalatory measures? This paper sets the stage for addressing such questions by outlining the START agreement and offering a brief overview of how START might affect the prospects for CBMs. Then, after examining some specific CBM proposals in light of START, an analysis will be made of the de-escalatory problems and opportunities that a Start II treaty might create

  13. Interventions to increase adherence in patients taking immunosuppressive drugs after kidney transplantation: a systematic review of controlled trials.

    Science.gov (United States)

    Mathes, Tim; Großpietsch, Kirsten; Neugebauer, Edmund A M; Pieper, Dawid

    2017-11-29

    Immunosuppressive drugs have to be taken through the whole duration of kidney transplant survival to avoid rejection. Low adherence can increase the risk of allograft rejection. The objective was to evaluate the effectiveness of adherence-enhancing interventions (AEI) in kidney transplantation recipients taking immunosuppressive drugs. A search was performed in Medline, Embase, CINAHL, and PsycINFO. The search was performed in May 2016. We included comparative studies on AEI for kidney transplant recipients taking immunosuppressive drugs. The primary outcome was medication adherence. All identified articles were screened according to the predefined inclusion criteria. The risk of bias was assessed with the Cochrane risk of bias tool. Study selection and risk of bias assessment were performed by two reviewers independently. Data were extracted in standardized tables. Data extraction was verified by a second reviewer. All discrepancies were resolved through discussion. Data were synthesized in a structured narrative way. There is no registered or published protocol for this systematic review. We identified 12 studies. The number of participants ranged from 24 to 1830. Nine studies included adults, two children, and one adults and children. Risk of bias was high. The main reasons for high risk of bias were inadequate allocation sequence (confounding) and that studies were not blinded. Eleven studies evaluated AEI consisting of educational and/or behavioral components. All these studies showed an effect direction in favor of the intervention. Intervention effect was only moderate. Most adherence measures in studies on educational and behavioral interventions showed statistically significant differences. Studies that combined educational and behavioral intervention components showed larger effects. All studies that were statistically significant were multimodal. Studies that included an individualized component and more intensive interventions showed larger effects. One

  14. Fibroblast Growth Factor-2 Enhances Expansion of Human Bone Marrow-Derived Mesenchymal Stromal Cells without Diminishing Their Immunosuppressive Potential

    OpenAIRE

    Auletta, Jeffery J.; Zale, Elizabeth A.; Welter, Jean F.; Solchaga, Luis A.

    2011-01-01

    Allogeneic hematopoietic stem cell transplantation is the main curative therapy for many hematologic malignancies. Its potential relies on graft-versus-tumor effects which associate with graft-versus-host disease. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties that make them attractive therapeutic alternatives. We evaluated the in vitro immunosuppressive activity of medium conditioned by human MSCs from 5 donors expanded 13 passages with or without FGF-2. FGF-2 supplemen...

  15. Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation.

    Science.gov (United States)

    Weiss, Melissa; Steinbach, Daniel; Zintl, Felix; Beck, James; Gruhn, Bernd

    2015-06-01

    The outcome of cyclosporin A (CSA) alone (n = 19) as graft-versus-host disease (GVHD) prophylaxis was compared to that of CSA combined with methotrexate (MTX) (n = 43) in children with acute leukemia who underwent hematopoietic stem cell transplantation. All respective donors were HLA-identical siblings. All patients received CSA at a dose of 3 mg/kg/day starting on day -1. A CSA level of 80-130 ng/ml was aimed for. The 43 patients in the historical control were given an additional 10 mg/m(2) dosage of MTX on days 1, 3, 6, and 11. Patients who received CSA alone had a significantly reduced cumulative incidence of relapse (5 vs. 40 %; p = 0.002), a significantly increased 5-year event-free survival (84 vs. 35 %; p = 0.001), and a significantly increased 5-year overall survival (84 vs. 42 %; p = 0.004). The incidence of acute GVHD grade II-IV and chronic GVHD in patients in the CSA group was equivalent to the CSA+MTX group (26 vs. 19 %; p = 0.440, and 32 vs. 23 %; p = 0.428). In conclusion, post-transplant immunosuppression consisting of CSA alone is well tolerated and may contribute to a superior outcome.

  16. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-01-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

  17. 46 CFR 112.50-7 - Compressed air starting.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Compressed air starting. 112.50-7 Section 112.50-7... air starting. A compressed air starting system must meet the following: (a) The starting, charging... air compressors addressed in paragraph (c)(3)(i) of this section. (b) The compressed air starting...

  18. Technological start of T-15 tokamak. The start-up diagnostic complex

    International Nuclear Information System (INIS)

    Notkin, G.E.

    1989-01-01

    The T-15 tokamak with superconducting toroidal winding reached the technological start-up phase. The results of the first operating tests of the main tokamak components are reported. Due to improper function of both the vacuum and the cryogenic system, the nominal parameters of the vacuum and of the toroidal magnetic field have not been achieved. The non-optimum vacuum conditions made the discharge start-up difficult even when a pre-ionizing electron beam and a gyrotron generator were used. The pre-discharge plasma parametes were studied by means of a limited set of plasma diagnostic apparatus. Due to substantially deteriorated vacuum conditions, it was not possible to repeat the only one successful discharge with a current of 100 kA, lasting for 50 ms. (J.U.)

  19. Experimental study of starting plumes simulating cumulus cloud flows in the atmosphere

    Science.gov (United States)

    Subrahmanyam, Duvvuri; Sreenivas, K. R.; Bhat, G. S.; Diwan, S. S.; Narasimha, Roddam

    2009-11-01

    Turbulent jets and plumes subjected to off-source volumetric heating have been studied experimentally and numerically by Narasimha and co-workers and others over the past two decades. The off-source heating attempts to simulate the latent heat release that occurs in cumulus clouds on condensation of water vapour. This heat release plays a crucial role in determining the overall cloud shape among other things. Previous studies investigated steady state jets and plumes that had attained similarity upstream of heat injection. A better understanding and appreciation of the fluid dynamics of cumulus clouds should be possible by study of starting plumes. Experiments have been set up at JNCASR (Bangalore) using experimental techniques developed previously but incorporating various improvements. Till date, experiments have been performed on plumes at Re of 1000 and 2250, with three different heating levels in each case. Axial sections of the flow have been studied using standard PLIF techniques. The flow visualization provides us with data on the temporal evolution of the starting plume. It is observed that the broad nature of the effect of off-source heating on the starting plumes is generally consistent with the results obtained previously on steady state flows. More complete results and a critical discussion will be presented at the upcoming meeting.

  20. Start Later, Sleep Later: School Start Times and Adolescent Sleep in Homeschool vs. Public/Private School Students

    Science.gov (United States)

    Meltzer, Lisa J.; Shaheed, Keisha; Ambler, Devon

    2014-01-01

    Homeschool students provide a naturalistic comparison group for later/flexible school start times. This study compared sleep patterns and sleep hygiene for homeschool students and public/private school students (grades 6-12). Public/private school students (n=245) and homeschool students (n=162) completed a survey about sleep patterns and sleep hygiene. Significant school group differences were found for weekday bedtime, wake time, and total sleep time, with homeschool students waking later and obtaining more sleep. Homeschool students had later school start times, waking at the same time that public/private school students were starting school. Public/private school students had poorer sleep hygiene practices, reporting more homework and use of technology in the hour before bed. Regardless of school type, technology in the bedroom was associated with shorter sleep duration. Later school start times may be a potential countermeasure for insufficient sleep in adolescents. Future studies should further examine the relationship between school start times and daytime outcomes, including academic performance, mood, and health. PMID:25315902

  1. PI3K-AKT signaling pathway is involved in hypoxia/thermal-induced immunosuppression of small abalone Haliotis diversicolor.

    Science.gov (United States)

    Sun, Yulong; Zhang, Xin; Wang, Guodong; Lin, Shi; Zeng, Xinyang; Wang, Yilei; Zhang, Ziping

    2016-12-01

    The PI3K-AKT signal pathway has been found to be involved in many important physiological and pathological processes of the innate immune system of vertebrates and invertebrates. In this study, the AKT (HdAKT) and PI3K (HdPI3K) gene of small abalone Haliotis diversicolor were cloned and characterized for the important status of PI3K and AKT protein in PI3K-AKT signaling pathway. The full length cDNAs of HdAKT and HdPI3K are 2126 bp and 6052 bp respectively, encoding proteins of 479 amino acids and 1097 amino acids, respectively. The mRNA expression level of fourteen genes in the PI3K-AKT signaling pathway were detected by quantitative real-time PCR. The results showed that all these fourteen genes were ubiquitously expressed in seven selected tissues. Meanwhile, HdAKT was expressed in haemocytes with the highest expression level (p abalone. The mRNA expression of these genes in gills, haemocytes and hepatopancreas was significantly down-regulated after the Vibrio parahaemolyticus stimulation with environment stimulation (thermal, hypoxia and thermal & hypoxia). These results indicate that the dual/multiple stresses defeat the immune system and lead to immunosuppression in abalone. PI3K-AKT signaling pathway may be involved in hypoxia/thermal-induced immunosuppression of small abalone Haliotis diversicolor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Development of a subjective refraction simulator

    Science.gov (United States)

    Perches, S.; Ares, J.; Collados, M. V.

    2013-11-01

    We have developed simulation software by Matlab (MathworksInc.) with a graphical interface designed for non-expert users. This simulator allows you to complete the process of subjective refraction starting from the aberrometry of the patients and analyse the influence of different factors during the exam. In addition to explain the graphical interface and its working, we show two examples about a complete process of subjective refraction with the influence of high order aberrations and without them showing the retinal image obtained in each step of the refraction process. When the Jackson Cross-Cylinder technique is made with this software, it becomes clear the difficulty of chosen between two images when high order aberrations are present. Therefore, the variability of response during the refraction can be a problem when the examiner has to reach an adequate optical prescription.

  3. Starting a business through a franchise

    OpenAIRE

    Dubravka Mahaček; Maja Martinko Lihtar

    2013-01-01

    A business can be launched by establishing a new entity, purchasing an existing entity or through a franc - hise. There are certain prerequisites for starting a business, the most important ones being a quality idea and start-up capital. Potential start-up difficulties are inadequate financing, existing competition as well as the process of building your own market position. By purchasing an existing business some risks may be avoided and the opportunity for gaining profit may ...

  4. Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells

    International Nuclear Information System (INIS)

    Li Qian; Lauer, Fredine T.; Liu Kejian; Hudson, Laurie G.; Burchiel, Scott W.

    2010-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO 2 (As 3+ ) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO 2 , As 3+ ) was found to produce immunosuppression at concentrations as low as 0.5 μM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na 2 HAsO 4 , As 5

  5. Comparison of outcomes between emergent-start and planned-start peritoneal dialysis in incident ESRD patients: a prospective observational study.

    Science.gov (United States)

    Li, Wen-Yi; Wang, Yi-Cheng; Hwang, Shang-Jyh; Lin, Shih-Hua; Wu, Kwan-Dun; Chen, Yung-Ming

    2017-12-11

    The clinical consequences of starting chronic peritoneal dialysis (PD) after emergent dialysis via a temporary hemodialysis (HD) catheter has rarely been evaluated within a full spectrum of treated end-stage renal disease (ESRD). We investigated the longer-term outcomes of patients undergoing emergent-start PD in comparison with that of other practices of PD or HD in a prospective cohort of new-onset ESRD. This was a 2-year prospective observational study. We enrolled 507 incident ESRD patients, among them 111 chose PD (43 planned-start, 68 emergent-start) and 396 chose HD (116 planned-start, 280 emergent-start) as the long-term dialysis modality. The logistic regression model was used to identify variables associated with emergent-start dialysis. The Kaplan-Meier survival analysis was used to determine patient survival and technique failure. The propensity score-adjusted Cox regression model was used to identify factors associated with patient outcomes. During the 2-year follow-up, we observed 5 (4.5%) deaths, 15 (13.5%) death-censored technique failures (transfer to HD) and 3 (2.7%) renal transplantations occurring in the PD population. Lack of predialysis education, lower predialysis estimated glomerular filtration rate and serum albumin were predictors of being assigned to emergent dialysis initiation. The emergent starters of PD displayed similar risks of patient survival, technique failure and overall hospitalization, compared with the planned-start counterparts. By contrast, the concurrent planned-start and emergent-start HD patients with an arteriovenous fistula or graft were protected from early overall death and access infection-related mortality, compared with the emergent HD starters using a central venous catheter. In late-referred chronic kidney disease patients who have initiated emergent dialysis via a temporary HD catheter, post-initiation PD can be a safe and effective long-term treatment option. Nevertheless, due to the potential complications

  6. Lean Start-up in Established Companies

    DEFF Research Database (Denmark)

    Goduscheit, René Chester

    2018-01-01

    Lean start-up is an emergent perspective on how entrepreneurs can bring new products and services to the market. This approach challenges the dominant role of lengthy business plans, linear product development processes, and seeking complete overview of the potential of the new products....../services before market launch. Instead it suggests that start-ups could benefit from a ‘minimum-viable product’ approach where products and services are launched when they contain critical features. The emphasis in the lean start-up approach is on business models rather than the elaborate business plan...... at the companies (strategy meetings, development workshops etc.). The aim is to shed light on the implications for companies that seek to employ lean start-up. These implications will be aimed at aspects like innovation management, organizational structure, customer relations etc....

  7. Genital Tuberculosis as the Cause of Tuboovarian Abscess in an Immunosuppressed Patient

    Directory of Open Access Journals (Sweden)

    M. Ilmer

    2009-01-01

    Full Text Available Background. Although tuberculosis (TB is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB, and in particular female genital tract infection, remains a rare event. Case Report. A 35-year-old human immunodeficiency virus (HIV seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb. Consequently, antituberculotic therapy was provided. Conclusion. In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present.

  8. Systematic Review and Meta-Analysis of Tacrolimus versus Ciclosporin as Primary Immunosuppression After Liver Transplant.

    Directory of Open Access Journals (Sweden)

    Gorden Muduma

    Full Text Available Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials, but most captured data from randomized controlled trials (RCTs predating recent improvements in waiting list prioritization, induction protocols and concomitant medications. The present study comprised a systematic review and meta-analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000.Searches of PubMed, the Cochrane Library and EMBASE identified RCTs of tacrolimus and ciclosporin as the immunosuppressant in adult primary liver transplant recipients, published between January 2000 and August 6, 2014. A random effects meta-analysis was conducted to evaluate the relative risk of death, graft loss, acute rejection (AR, new-onset diabetes after transplantation (NODAT and hypertension with tacrolimus relative to ciclosporin at 12 months.The literature search identified 11 RCTs comparing ciclosporin with tacrolimus. Relative to ciclosporin, tacrolimus was associated with significantly improved outcomes in terms of patient mortality (risk ratio [RR] with ciclosporin of 1.26; 95% confidence interval [95%CI] 1.01-1.58. Tacrolimus was superior to ciclosporin in terms of hypertension (RR with ciclosporin 1.26; 95%CI 1.07-1.47, but inferior in terms of NODAT (RR with ciclosporin 0.60; 95%CI 0.47-0.77. There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR.Meta-analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension, while ciclosporin was superior in terms of NODAT. No significant differences were identified in terms of graft loss or AR. These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients.

  9. Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer?

    Science.gov (United States)

    COGHILL, Anna E.; SHIELS, Meredith S.; RYCROFT, Randi K.; COPELAND, Glenn; FINCH, Jack L.; HAKENEWERTH, Anne M.; PAWLISH, Karen S.; ENGELS, Eric A.

    2015-01-01

    Objective Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. Design Population-based registry Methods We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991–2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons to the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. Results HIV-infected persons had an excess risk of rectal SCC compared to the general population (SIR=28.9; 95%CI 23.2–35.6), similar to the increase for anal SCC (SIR=37.3). Excess rectal SCC risk was most pronounced among HIV-infected men who have sex with men (MSM, SIR=61.2). Risk was not elevated for rectal non-SCC (SIR=0.88) or colon non-SCC (SIR=0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio=1.86; 95%CI 1.04–3.31). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. Conclusions HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumor location is needed to prove that rectal SCC is a distinct entity. PMID:26372482

  10. Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma patients.

    Science.gov (United States)

    Torrance, Hew Dt; Brohi, Karim; Pearse, Rupert M; Mein, Charles A; Wozniak, Eva; Prowle, John R; Hinds, Charles J; OʼDwyer, Michael J

    2015-04-01

    To explore the hypothesis that blood transfusion contributes to an immunosuppressed phenotype in severely injured patients. Despite trauma patients using disproportionately large quantities of blood and blood products, the immunomodulatory effects of blood transfusion in this group are inadequately described. A total of 112 ventilated polytrauma patients were recruited. Messenger RNA (mRNA) was extracted from PAXGene tubes collected within 2 hours of the trauma, at 24 hours, and at 72 hours. T-helper cell subtype specific cytokines and transcription factors were quantified using real-time polymerase chain reaction. Median injury severity score was 29. Blood transfusion was administered to 27 (24%) patients before the 2-hour sampling point. Transfusion was associated with a greater immediate rise in IL-10 (P = 0.003) and IL-27 (P = 0.04) mRNA levels. Blood products were transfused in 72 (64%) patients within the first 24 hours. There was an association between transfusion at 24 hours and higher IL-10 (P < 0.0001), lower Foxp3 (P = 0.01), GATA3 (P = 0.006), and RORγt (P = 0.05) mRNA levels at 24 hours. There were greater reductions in T-bet (P = 0.03) mRNA levels and lesser increases in TNFα (P = 0.015) and IFNγ (P = 0.035) at 24 hours in those transfused. Multiple regression models confirmed that the transfusion of blood products was independently associated with altered patterns of gene expression. Blood stream infections occur in 15 (20.8%) of those transfused in the first 24 hours, compared with 1 patient (2.5%) not transfused (OR = 10.3 [1.3-81], P = 0.008). The primarily immunosuppressive inflammatory response to polytrauma may be exacerbated by the transfusion of blood products. Furthermore, transfusion was associated with an increased susceptibility to nosocomial infections.

  11. Drug Abuse Prevention Starts with Parents

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Drug Abuse Prevention Starts with Parents Page Content Article Body ... for a time when drugs may be offered. Drug abuse prevention starts with parents learning how to talk ...

  12. Spalling of concrete subjected to blast loading

    Directory of Open Access Journals (Sweden)

    Foglar M.

    2013-09-01

    Full Text Available This paper presents outcomes of the blast field tests of FRC and reinforced concrete specimens, which were performed in cooperation with the Czech Army corps and Police of the Czech Republic in the military training area Boletice. The numerical evaluation of the experiments focused on the spalling of concrete subjected to blast loading started after the first set of the tests, took almost 3 years and required further small-scale experiments performed in the labs of the Czech Technical University.

  13. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

    Science.gov (United States)

    Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

    2018-04-07

    Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Dampak Mentoring Pada Keberhasilan Start-Up Business: Studi Kasus Pada Start-Up Business di Indonesia [Mentoring the Impact of Success of a Start-Up Business: A Case Study of a Start-Up Business in Indonesia

    Directory of Open Access Journals (Sweden)

    Christina Yanita Setyawati

    2016-10-01

    Full Text Available Entrepreneurship is a highly developed science today, as well as in the world of education in Indonesia. Teaching entrepreneurship at the university level, especially at some universities in Surabaya, the second largest city in Indonesia, shows the positive impact that there were 74.03% of start-up businesses that survived and thrived in 2014. Based on the previous observation, some business start-ups are accompanied by a mentor. Mentoring is a process of forming and maintaining lasting relationships that develop intensively among seniors with juniors. The mentoring function includes career and psychosocial functions. The main purpose of this research is to study the relationship between mentoring and the success of a start-up business. This study is a quantitative descriptive study using a random sampling method to obtain 100 samples. The tool used to collect data was a questionnaire. The methodology used to analyze the quantitative description to test the hypothesis. The results of this study indicate that mentoring influences the success of a start-up business that was owned by university students in Surabaya, Indonesia by 32% and 78% was influenced by other variables.

  15. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Directory of Open Access Journals (Sweden)

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  16. Impact of hand forces and start/stop frequency on physiological responses to three forms of pushing and pulling: a South African perspective.

    Science.gov (United States)

    Ai, Todd

    2012-01-01

    There has been limited attention given to the physiological demands of pushing and pulling, especially in industrially developing countries such as South Africa. Two key factors affecting the physiological demands of these tasks are the hand forces exerted and the start/stop frequency. The purpose of the current study was therefore to investigate the physiological responses to pushing and pulling at various loads and start/stop frequencies. 36 male subjects participated in the study and were required to complete a total of 18 conditions (three techniques: pushing, two- and one-handed pulling; three loads: 200, 350 and 500 kg; and two frequencies: 2 and 4 stops per minute). During each condition the heart rate, oxygen uptake and energy expenditure were measured. Pushing was found to elicit significantly lower responses for all three dependent variables than either form of pulling. The start/stop frequency was also found to have a significant impact on subject responses. The findings of this study indicate that the technique adopted to maneuver loads is critical in determining the physical demands placed on the human operator. Furthermore increasing the frequency of start/stops plays an important role, thus the forces exerted during these two phases are important from a physiological perspective.

  17. Modelling of individual subject ozone exposure response kinetics.

    Science.gov (United States)

    Schelegle, Edward S; Adams, William C; Walby, William F; Marion, M Susan

    2012-06-01

    A better understanding of individual subject ozone (O(3)) exposure response kinetics will provide insight into how to improve models used in the risk assessment of ambient ozone exposure. To develop a simple two compartment exposure-response model that describes individual subject decrements in forced expiratory volume in one second (FEV(1)) induced by the acute inhalation of O(3) lasting up to 8 h. FEV(1) measurements of 220 subjects who participated in 14 previously completed studies were fit to the model using both particle swarm and nonlinear least squares optimization techniques to identify three subject-specific coefficients producing minimum "global" and local errors, respectively. Observed and predicted decrements in FEV(1) of the 220 subjects were used for validation of the model. Further validation was provided by comparing the observed O(3)-induced FEV(1) decrements in an additional eight studies with predicted values obtained using model coefficients estimated from the 220 subjects used in cross validation. Overall the individual subject measured and modeled FEV(1) decrements were highly correlated (mean R(2) of 0.69 ± 0.24). In addition, it was shown that a matrix of individual subject model coefficients can be used to predict the mean and variance of group decrements in FEV(1). This modeling approach provides insight into individual subject O(3) exposure response kinetics and provides a potential starting point for improving the risk assessment of environmental O(3) exposure.

  18. Health Coordination Manual. Head Start Health Services.

    Science.gov (United States)

    Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

    Part 1 of this manual on coordinating health care services for Head Start children provides an overview of what Head Start health staff should do to meet the medical, mental health, nutritional, and/or dental needs of Head Start children, staff, and family members. Offering examples, lists, action steps, and charts for clarification, part 2…

  19. EFFECTIVENESS AND SAFETY OF RECOMBINANT HUMAN GRANULOCYTIC COLONY-STIMULATING FACTOR IN TREATMENT OF GRANULOCYTOPENIA DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2010-01-01

    Full Text Available Treatment of patients with severe clinical course of juvenile rheumatoid arthritis (JRA is difficult problem. During the last years genetically engineered biological drugs are used equally with traditional immunosuppressive agents in treatment of severe forms of juvenile arthritis. High effectiveness of these drugs can be accompanied with development of unfavorable effects, for example, febrile neutropenia. The article presents results of a study of effectiveness and safety of recombinant human granulocytic colony-stimulating factor — filgrastim (Leucostim — in treatment of granulocytopenia developed during immunosuppressive therapy in 16 patients with JRA. It was shown that administration of filgrastim arrests leucopenia in 100% of patients and granulocytopenia — in 93% of patients in 24 hours after first injection. High effectiveness of drug was combined with good tolerability and safety.Key words: children, treatment, granulocytopenia, filgrastim, juvenile rheumatoid arthritis.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:94-100

  20. Time-in-a-bottle (TIAB): a longitudinal, correlational study of patterns, potential predictors, and outcomes of immunosuppressive medication adherence in adult kidney transplant recipients.

    Science.gov (United States)

    Russell, Cynthia L; Ashbaugh, Catherine; Peace, Leanne; Cetingok, Muammer; Hamburger, Karen Q; Owens, Sarah; Coffey, Deanna; Webb, Andrew W; Hathaway, Donna; Winsett, Rebecca P; Madsen, Richard; Wakefield, Mark R

    2013-01-01

    This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 yr or older from three kidney transplant centers using a theory-based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using electronic monitoring. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self-efficacy was associated with medication non-adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non-adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory-based, experimental interventions that include a medication self-efficacy component. © 2013 John Wiley & Sons A/S.

  1. Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

    Science.gov (United States)

    Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

    2015-01-01

    Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Automated processing of whole blood samples for the determination of immunosuppressants by liquid chromatography tandem-mass spectrometry.

    Science.gov (United States)

    Vogeser, Michael; Spöhrer, Ute

    2006-01-01

    Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is an efficient technology for routine determination of immunosuppressants in whole blood; however, time-consuming manual sample preparation remains a significant limitation of this technique. Using a commercially available robotic pipetting system (Tecan Freedom EVO), we developed an automated sample-preparation protocol for quantification of tacrolimus in whole blood by LC-MS/MS. Barcode reading, sample resuspension, transfer of whole blood aliquots into a deep-well plate, addition of internal standard solution, mixing, and protein precipitation by addition of an organic solvent is performed by the robotic system. After centrifugation of the plate, the deproteinized supernatants are submitted to on-line solid phase extraction, using column switching prior to LC-MS/MS analysis. The only manual actions within the entire process are decapping of the tubes, and transfer of the deep-well plate from the robotic system to a centrifuge and finally to the HPLC autosampler. Whole blood pools were used to assess the reproducibility of the entire analytical system for measuring tacrolimus concentrations. A total coefficient of variation of 1.7% was found for the entire automated analytical process (n=40; mean tacrolimus concentration, 5.3 microg/L). Close agreement between tacrolimus results obtained after manual and automated sample preparation was observed. The analytical system described here, comprising automated protein precipitation, on-line solid phase extraction and LC-MS/MS analysis, is convenient and precise, and minimizes hands-on time and the risk of mistakes in the quantification of whole blood immunosuppressant concentrations compared to conventional methods.

  3. The physics of tokamak start-up

    International Nuclear Information System (INIS)

    Mueller, D.

    2013-01-01

    Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current

  4. Prognosis of bedridden patients with end-stage renal failure after starting hemodialysis.

    Science.gov (United States)

    Sugaya, Kimio; Hokama, Asanori; Hayashi, Eiri; Naka, Hidekatsu; Oda, Masami; Nishijima, Saori; Miyazato, Minoru; Hokama, Sanehiro; Ogawa, Yoshihide

    2007-06-01

    The mean age of starting hemodialysis (HD) in patients with end-stage renal failure is gradually increasing in Japan. It is not uncommon for HD to be commenced in bedridden elderly patients who cannot give informed consent, because of brain damage. However, we have not been able to provide useful advice to their families because there was no relevant information available about the prognosis of bedridden patients on HD. Therefore, we examined the prognosis of bedridden HD patients. Two hundred and nineteen patients who received HD were enrolled. These subjects were divided into five groups; (aged or=80 years at the commencement of HD), and we compared the overall prognosis between bedridden and nonbedridden patients, as well as that for each age group. There were 76 bedridden patients among the 219 HD patients, and the main cause of their bedridden state before starting HD was cerebrovascular disease. The 50% survival time after the start of HD was 120 months for the nonbedridden patients versus 56 months for bedridden patients. However, the mean (+/-SD) age of the bedridden patients was higher than that of nonbedridden patients (70 +/- 13 versus 64 +/- 14 years). In patients under age 50 years at the start of dialysis, the survival rate was lower in the bedridden than in the nonbedridden patients, but there were no differences between survival rates for bedridden and nonbedridden patients in the other four age groups. The prognosis of HD patients is poor compared with the general life expectancy of the Japanese population, but whether these patients are bedridden or not has little influence on their survival.

  5. University Knowledge Spillovers & Regional Start-up Rates

    DEFF Research Database (Denmark)

    Hellerstedt, Karin; Wennberg, Karl; Frederiksen, Lars

    2014-01-01

    how characteristics of the economic and political milieu within each region influence the ratio of firm births. We find that knowledge spillovers from universities and firm-based R&D strongly affect the start-up rates for both high-tech firms and knowledge-intensive services firms. Further, the start......This chapter investigates how regional start-up rates in the knowledge-intensive services and high-tech industries are influenced by knowledge spillovers from both universities and firm-based R&D activities. Integrating insights from economic geography and organizational ecology into the literature......-up rate of knowledge-intensive service firms is tied more strongly to the supply of university educated individuals and the political regulatory regime within the municipality than start-ups in high-tech industries. This suggests that knowledge-intensive service-start-ups are more susceptible to both...

  6. What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

    Science.gov (United States)

    Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

    2014-05-01

    Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal

  7. Co-housing of Rift Valley fever virus infected lambs with immunocompetent or immunosuppressed lambs does not result in virus transmission

    Directory of Open Access Journals (Sweden)

    Paul J Wichgers Schreur

    2016-03-01

    Full Text Available Rift Valley fever virus (RVFV is transmitted among susceptible animals by mosquito vectors. Although the virus can be isolated from nasal and oral swabs of infected animals and is known to be highly infectious when administered experimentally via oral or respiratory route, horizontal transmission of the virus is only sporadically reported in literature. We considered that immunosuppression resulting from stressful conditions in the field may increase the susceptibility to horizontally transmitted RVFV. Additionally, we reasoned that horizontal transmission may induce immune responses that could affect the susceptibility of contact-exposed animals to subsequent infection via mosquito vectors. To address these two hypotheses, viremic lambs were brought into contact with sentinel lambs. One group of sentinel lambs was treated with the immunosuppressive synthetic glucocorticosteroid dexamethasone and monitored for signs of disease and presence of virus in the blood and target organs. Another group of contact-exposed sentinel lambs remained untreated for three weeks and was subsequently challenged with RVFV. We found that none of the dexamethasone-treated contact-exposed lambs developed detectable viremia, antibody responses or significant increases in cytokine mRNA levels. Susceptibility of immunocompetent lambs to RVFV infection was not influenced by previous contact-exposure. Our results are discussed in light of previous findings.

  8. Making a Simple Self-Starting Electric Motor

    Science.gov (United States)

    Hong, Seok-In; Choi, Jung-In; Hong, Seok-Cheol

    2009-01-01

    A simple electric motor has a problem in that the current applied to the motor per se can rarely trigger its rotation. Usually such motors begin to rotate after the rotor is slightly turned by hand (i.e., manual starting). In a "self-starting" motor, the rotor starts to rotate spontaneously as soon as the current is applied. This paper describes…

  9. Dynamic interaction between STLV-1 proviral load and T-cell response during chronic infection and after immunosuppression in non-human primates.

    Directory of Open Access Journals (Sweden)

    Sandrine Souquière

    Full Text Available We used mandrills (Mandrillus sphinx naturally infected with simian T-cell leukemia virus type 1 (STLV-1 as a model for evaluating the influence of natural STLV-1 infection on the dynamics and evolution of the immune system during chronic infection. Furthermore, in order to evaluate the role of the immune system in controlling the infection during latency, we induced immunosuppression in the infected monkeys. We first showed that the STLV-1 proviral load was higher in males than in females and increased significantly with the duration of infection: mandrills infected for 10-6 years had a significantly higher proviral load than those infected for 2-4 years. Curiously, this observation was associated with a clear reduction in CD4+ T-cell number with age. We also found that the percentage of CD4(+ T cells co-expressing the activation marker HLA-DR and the mean percentage of CD25(+ in CD4(+ and CD8(+ T cells were significantly higher in infected than in uninfected animals. Furthermore, the STLV-1 proviral load correlated positively with T-cell activation but not with the frequency of T cells secreting interferon gamma in response to Tax peptides. Lastly, we showed that, during immunosuppression in infected monkeys, the percentages of CD8(+ T cells expressing HLA-DR(+ and of CD4(+ T cells expressing the proliferation marker Ki67 decreased significantly, although the percentage of CD8(+ T cells expressing HLA-DR(+ and Ki67 increased significantly by the end of treatment. Interestingly, the proviral load increased significantly after immunosuppression in the monkey with the highest load. Our study demonstrates that mandrills naturally infected with STLV-1 could be a suitable model for studying the relations between host and virus. Further studies are needed to determine whether the different compartments of the immune response during infection induce the long latency by controlling viral replication over time. Such studies would provide important

  10. Steroid-free immunosuppression after renal transplantation-long-term experience from a single centre

    DEFF Research Database (Denmark)

    El-Faramawi, Mohamad; Rohr, Nils; Jespersen, Bente

    2006-01-01

    BACKGROUND: A steroid-free immunosuppressive protocol may improve the general well-being of patients, but long-term renal graft survival has been a concern. METHODS: In a retrospective clinical study, 329 consecutive transplantations with renal grafts at our centre during the period 1995-2004, were......, for instance because of primary kidney disease or when calcineurin inhibitor toxicity was suspected. RESULTS: About 71% of the patients did not take steroids at all. Nevertheless, graft survival rates at 1, 5 and 7 years were 95, 77 and 72% for all grafts, including 27% living donor transplants and 27% second...... or subsequent grafts. Ten patients (3.2%) died with functioning grafts. Within the first year of transplantation there were 69 acute rejections in 63 patients (19%). Four cases (1.3%) of post-transplant lymphoproliferative disorder (PTLD) occurred with one graft loss and no deaths. Owing to a high PTLD rate...

  11. Modelling ohmic confinement experiments on the START tokamak

    International Nuclear Information System (INIS)

    Roach, C.M.

    1996-05-01

    Ohmic confinement data from the tight aspect ratio tokamak START has been analysed using the ASTRA transport simulation code. Neoclassical expressions have been modified to describe tight aspect ratio configurations, and the comparison between START data and models of anomalous transport has been made quantitative using the standard χ 2 test from statistics. Four confinement models (T11, Rebut-Lallia-Watkins, Lackner-Gottardi, and Taroni et al's Bohm model) have been compared with the START data. Three of the models are found to simulate START's electron temperature data moderately well, while Taroni et al's Bohm model overestimates electron temperatures in START by an order of magnitude. Thus comparison with START data tends to discriminate against Bohm models; these models are pessimistic or ITER. (author)

  12. University Start-ups: A Better Business Model

    Science.gov (United States)

    Dehn, J.; Webley, P. W.

    2015-12-01

    Many universities look to start-up companies as a way to attract faculty, supporting research and students as traditional federal sources become harder to come by. University affiliated start-up companies can apply for a broader suite of grants, as well as market their services to a broad customer base. Often university administrators see this as a potential panacea, but national statistics show this is not the case. Rarely do universities profit significantly from their start-ups. With a success rates of around 20%, most start-ups end up costing the university money as well as faculty-time. For the faculty, assuming they want to continue in academia, a start-up is often unattractive because it commonly leads out of academia. Running a successful business as well as maintaining a strong teaching and research load is almost impossible to do at the same time. Most business models and business professionals work outside of academia, and the models taught in business schools do not merge well in a university environment. To mitigate this a new business model is proposed where university start-ups are aligned with the academic and research missions of the university. A university start-up must work within the university, directly support research and students, and the work done maintaining the business be recognized as part of the faculty member's university obligations. This requires a complex conflict of interest management plan and for the companies to be non-profit in order to not jeopardize the university's status. This approach may not work well for all universities, but would be ideal for many to conserve resources and ensure a harmonious relationship with their start-ups and faculty.

  13. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    Full Text Available The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined.We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group, and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group.A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05. Flagellar motor switch protein (fliNY and type IV pilus assembly protein pilM (pilM were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity.Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

  14. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen.

    Science.gov (United States)

    Zaza, Gianluigi; Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

    2017-01-01

    The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this objective.

  15. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen

    Science.gov (United States)

    Dalla Gassa, Alessandra; Felis, Giovanna; Granata, Simona; Torriani, Sandra; Lupo, Antonio

    2017-01-01

    Background The gut microbiome is the full set of microbes living in the gastrointestinal tract and is emerging as an important dynamic/fluid system that, if altered by environmental, dietetic or pharmacological factors, could considerably influence drug response. However, the immunosuppressive drug-induced modifications of this system are still poorly defined. Methods We employed an innovative bioinformatics approach to assess differences in the whole-gut microbial metagenomic profile of 20 renal transplant recipients undergoing maintenance treatment with two different immunosuppressive protocols. Nine patients were treated with everolimus plus mycophenolate mofetil (EVE+MMF group), and 11 patients were treated with a standard therapy with tacrolimus plus mycophenolate mofetil (TAC+MMF group). Results A statistical analysis of comparative high-throughput data demonstrated that although similar according to the degree of Shannon diversity (alpha diversity) at the taxonomic level, three functional genes clearly discriminated EVE+MMF versus TAC+MMF (cutoff: log2 fold change≥1, FDR≤0.05). Flagellar motor switch protein (fliNY) and type IV pilus assembly protein pilM (pilM) were significantly enriched in TAC+MMF-treated patients, while macrolide transport system mrsA (msrA) was more abundant in patients treated with EVE+MMF. Finally, PERMANOVA revealed that among the variables analyzed and included in our model, only the consumption of sugar significantly influenced beta diversity. Conclusions Our study, although performed on a relatively small number of patients, showed, for the first time, specific immunosuppressive-related effects on fecal microbiome of renal transplant recipients and it suggested that the analysis of the gut microbes community could represent a new tool to better understand the effects of drugs currently employed in organ transplantations. However, multicenter studies including healthy controls should be undertaken to better address this

  16. ECRH-assisted start-up in ITER

    International Nuclear Information System (INIS)

    Lloyd, B.; Carolan, P.G.; Warrick, C.D.

    1996-07-01

    In ITER, the electric field applied for ionisation and to ramp up the plasma current may be limited to ∼ 0.3 V/m. In this case, based on established theories of the avalanche process, it is shown that ohmic breakdown in ITER is only possible over a narrow range of pressure and magnetic error field. Therefore, ECRH may be necessary to provide robust and reliable start-up. ECRH can ensure prompt breakdown over a wide range of prefill pressure and error field and can also give control over the initial time and location of breakdown. For ECRH-assisted start-up in ITER, the power and pulse length requirements are essentially determined by the need to ensure burnthrough, i.e. complete ionisation of hydrogen and the transition to high ionisation states of impurities. A 0-D code (with inclusion of some 1-D effects) has been developed to analyse burnthrough in ITER. The 0-D simulations indicate that control of the deuterium density is the key factor for ensuring successful start-up in ITER, where the effects of neutral screening and dynamic fuelling by the ex-plasma volume are also crucial. It is concluded that without ECRH, successful start-up will only be possible over a very restricted range of parameters but 3MW of absorbed ECRH power will ensure reasonably robust start-up for a broad range of conditions with beryllium impurity. In the case of carbon impurity, even with an absorbed ECRH power of 5MW one may be restricted to low prefill pressure and/or low carbon concentration for successful start-up. (Author)

  17. Two-Man Bobsled Push Start Analysis

    Directory of Open Access Journals (Sweden)

    Lopes Alexandre Dias

    2016-04-01

    Full Text Available The importance of push start times on bobsled performance was evidenced by some studies, but at this moment there is no article to the authors’ knowledge that describes the bobsled push start. Thus, the objectives of this study were to describe the two-man bobsled push start, analyze the differences between teams, and estimate the most important variable analyzed. We hypothesized that the pilot and brakeman athletes’ movement patterns during a bobsled pushing start can be described. The images used in this study were obtained during the men’s two-man XIV World Championship of Bobsled (2004. Fifteen best teams participating in the championship were recorded, and four start runs for each team were analyzed. The videos were captured by two digital video cameras. The pilot athletes were analyzed during the moment that they touched the lateral push bar of the sled, and the brakemen were analyzed during the first take-off and first landing. The teams were pooled in three groups of five teams using the final ranking of pushing time. We concluded that there was a distinct pattern movement for pilots and brakemen. The initial position of the majority of the pilots was localized slightly behind the bar. After touching the lateral bar, the pilots remained in a semi-squat position, pushing the sled forward in a pattern of marching movement. All brakemen used the board attached to the track as a support for both feet at the start. The brakeman gave the greatest contribution to break the inertia of the sled. There was no significant difference of movement between the three groups analyzed for the pilot and the brakeman.

  18. MANAGEMENT OF HBV INFECTION DURING IMMUNOSUPPRESIVE TREATMENT

    Directory of Open Access Journals (Sweden)

    Alfredo Marzano

    2009-11-01

    Full Text Available

    The literature on hepatitis B virus (HBV in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline, b the treatment with antivirals (therapy of active carriers, c the pre-emptive use of antivirals (prophylaxis in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, d the biochemical and HBsAg monitoring (or universal prophylaxis in case of high risk immunosuppression, as in onco-haematologic patients and bone marrow transplantation in subjects with markers of previous contact with HBV (HBsAg-negative and antiHBc-positive, in order to prevent reverse seroconversion.

    Moreover in solid organ transplants it is suggested a strict adherence to the criteria of allocation based on the virological characteristics of both recipients and donors  and the universal prophylaxis or therapy with nucleos(tides analogs

  19. Research nuclear reactor start-up simulator

    International Nuclear Information System (INIS)

    Sofo Haro, M.; Cantero, P.

    2009-01-01

    This work presents the design and FPGA implementation of a research nuclear reactor start-up simulator. Its aim is to generate a set of signals that allow replacing the neutron detector for stimulated signals, to feed the measurement electronic of the start-up channels, to check its operation, together with the start-up security logic. The simulator presented can be configured on three independent channels and adjust the shape of the output pulses. Furthermore, each channel can be configured in 'rate' mode, where you can specify the growth rate of the pulse frequency in %/s. Result and details of the implementation on FPGA of the different functional blocks are given. (author)

  20. Enhancing start performance in the sport of skeleton

    OpenAIRE

    Colyer, Steffi

    2015-01-01

    A fast start is considered to be crucial in skeleton with marginal gains in start performance perceived to make meaningful improvements to overall chances of success. Currently, knowledge surrounding the underlying determinants of start performance is sparse and training practices are based on limited scientific evidence. A series of investigations were conducted to advance this understanding.Initial observations revealed similarities between dry-land push-starts and those on ice tracks. Howe...