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Sample records for subjects starting immunosuppressive

  1. Immunosuppressants

    Science.gov (United States)

    ... treatment recommendations. Print Email Read related articles 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 Foundation (NKF) ...

  2. Prophylactic effect of bacteriophages on mice subjected to chemotherapy-induced immunosuppression and bone marrow transplant upon infection with Staphylococcus aureus.

    Science.gov (United States)

    Zimecki, Michał; Artym, Jolanta; Kocieba, Maja; Weber-Dabrowska, Beata; Borysowski, Jan; Górski, Andrzej

    2010-05-01

    Due to the increased resistance of bacteria to antibiotics, phage therapy may be an alternative to treat or prevent suppurative infections in immunocompromised patients. The authors' recent studies indicated that such an approach is particularly beneficial in immunosuppressed mice. A5/L bacteriophages, specific for the Staphylococcus aureus strain L, were tested for their ability to protect CBA mice subjected to myeloablative (busulfan) and immunosuppressive (cyclophosphamide) conditioning followed by a syngeneic bone marrow transplantation (BMT) and infected with a sublethal or lethal dose of bacteria. The application of phages to immunocompromised mice given BMT led to a significant (>90%) reduction in bacterial load in the spleen and liver. Moreover, 72% of such mice attained long-term survival versus 8.2% survival of mice not treated with phages. Analysis of leukocyte number and blood cell type composition revealed that phage application increased the leukocyte numbers and neutrophil content in the circulating blood. Moreover, phage application led to an increased content of the myelocytic cell lineage in the bone marrow. The protective effects of phages in immunosuppressed mice are both direct (bacteriolytic) and indirect (by stimulation of myelopoiesis). The results suggest a potential benefit of phage therapy in immunocompromised patients subjected to bone marrow transplant procedures.

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

    Science.gov (United States)

    Demange, Valérie; Wild, Pascal; Zmirou-Navier, Denis; Tossa, Paul; Bohadana, Abraham; Barbaud, Annick; Paris, Christophe

    2010-07-06

    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? 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. 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. 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.

  4. Dogs, zoonoses and immunosuppression.

    Science.gov (United States)

    Robinson, R A; Pugh, R N

    2002-06-01

    Dogs are the source of a wide range of zoonotic infections that pose a significant threat to human health. This is particularly the case for immunocompromised people, although there are few robust studies that determine immunosuppression as a risk factor for transmission of zoonoses from dogs to humans. An increasing proportion of human society is immunodeficient, principally through the advent of HIV infection and through more people, particularly the expanding elderly group, being subjected to immunosuppressive agents. This is happening at a time when more such people are capitalizing on the acknowledged benefits of dog ownership, making for a potentially dangerous mix. Enteric pathogens (for example, Salmonella, Campylobacter and Cryptosporidium species, that may be canine derived) are a frequent risk to the health of immunocompromised persons. Veterinarians and physicians can be criticised for not communicating with each other, and for not providing adequate risk assessment to pet owners. There is scope for voluntary groups to provide information and support for the immunosuppressed who wish to keep their dogs. Key recommendations are to maintain a clean personal environment and intact mucocutaneous barriers. Public health professionals could help rectify the current communications gap between veterinary and medical staff and so facilitate in the appropriate management of dog-owning immunocompromised people.

  5. Testing of a Loop Heat Pipe Subjective to Variable Accelerations. Part 1; Start-up

    Science.gov (United States)

    Ku, Jentung; Rogers, Paul; Hoff, Craig

    2000-01-01

    The effect of accelerating forces on the performance of loop heat pipes (LHP) is of interest and importance to terrestrial and space applications. They are being considered for cooling of military combat vehicles and for spinning spacecraft. In order to investigate the effect of an accelerating force on LHP operation, a miniature LHP was installed on a spin table. Variable accelerating forces were imposed on the LHP by spinning the table at different angular speeds. Several patterns of accelerating forces were applied, i.e. continuous spin at different speeds and periodic spin at different speeds and frequencies. The resulting accelerations ranged from 1.17 g's to 4.7 g's. This paper presents the first part of the experimental study, i.e. the effects of a centrifugal force on the LHP start-up. Tests were conducted by varying the heat load to the evaporator, sink temperature, magnitude and frequency of centrifugal force, and LHP orientation relative to the direction of the accelerating force. The accelerating force seems to have little effect on the loop start-up in terms of temperature overshoot and superheat at boiling incipience. Changes in these parameters seem to be stochastic with or without centrifugal accelerating forces. The LHP started successfully in all tests.

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

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    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.

  7. 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

  8. [Infections in immunosuppressed patients].

    Science.gov (United States)

    Marcos, María Angeles; Alvarez-Martínez, Miriam J; Niubó, Jordi; Pumarola, Tomàs

    2008-07-01

    Molecular biology techniques represent a major advance in the microbiologic diagnosis of infectious diseases, since these methods are able to detect etiological microorganisms with high sensitivity. Moreover, these procedures can also establish prognostic and therapeutic efficacy markers with a sufficiently short turnaround time for the results to have a real impact on the clinical management of immunosuppressed patients. However, these techniques still have substantial limitations that should be solved in the near future: lack of standardization, inter- and intra-assay variability, the difficulty of comparing results among different laboratories and low positive predictive value, due to their high sensitivity, leading to problems in the interpretation of results. The present article reviews the usefulness of molecular biology techniques in the diagnosis and clinical management of infectious diseases caused by human cytomegalovirus, Epstein-Barr virus, human herpes viruses 6 and 7, JC and BK viruses, Toxoplasma gondii and Pneumocystis jiroveci in immunosuppressed patients.

  9. Immunosuppressive Therapy, 1987

    OpenAIRE

    Kahan, Barry D.

    1987-01-01

    The use of cyclosporine in transplant practice has at least doubled graft survival in renal transplantation, and has improved patient survival as well. In cardiac transplants, cyclosporine was first used in combination with prednisone to achieve immunosuppression by inhibition of the synthesis of lymphokines. When stimulated in vitro, lymphocytes from cyclosporine-treated patients display an impaired ability to produce the critical lymphokine interleukin-2. When there is in vitro inhibition, ...

  10. Starting position and stretching velocity effects on the reflex threshold angle of stretch reflex in the soleus muscle of normal and spastic subjects.

    Science.gov (United States)

    Chou, Shih-Wei; Abraham, Lawrence D; Huang, Ing-Shiou; Pei, Yu-Cheng; Lai, Cheng-Hsiu; Wong, Alice M K

    2005-07-01

    Although both starting position and stretching velocity play an important role in reflex response, their interaction with stretch reflexes has not been thoroughly investigated. This study examined the interaction effect of starting position and stretching velocity on the reflex threshold angle (RTA) of the stretch reflex in the soleus muscle of normal and spastic subjects. The spastic group included 11 ankles from 7 subjects with a history of upper motor neuron lesions. Their ages ranged from 22 to 40 years. Another 10 healthy subjects served as the control group. RTAs of the stretch reflex in the soleus muscle were measured for a matrix of starting positions and stretching velocities. The matrix design enabled the use of a 2-way analysis model to investigate the effect of starting position and stretching velocity on the RTA. No interaction effect was found in either the phasic stretch reflex (PSR) or the tonic stretch reflex (TSR) in the spastic group, or in the PSR in the normal group. The RTA of the PSR in both spastic and normal groups was significantly affected by starting position but not by stretching velocity. In contrast, the RTA of the TSR in the spastic group was affected by both starting position and stretching velocity. Stretching velocity and starting position played independent roles in determining the RTA of both the PSR and the TSR of the spastic group and in the PSR of the normal group. The lack of interaction between length-sensitive and velocity-sensitive muscle spindles in both normal and spastic subjects supports the hypothesis that they independently modulate the stretch reflex. Results for the RTA of the TSR demonstrated that spasticity results in disinhibition of motoneuron excitability with different thresholds.

  11. 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.

  12. 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.

  13. New Immunosuppressive Therapies in Uveitis Treatment

    Science.gov (United States)

    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

  14. Review papers immunosuppressive treatment

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    Anna Kryś

    2014-03-01

    Full Text Available Sebaceous carcinoma (sebaceous gland carcinoma – SC is a very aggressive malignant skin tumor that arises from the epithelium of sebaceous glands. Sun exposure and long-term immunosuppression, mainly in organ transplant recipients, are the most common risk factors. The tumor was first well described by Allaire in 1891. Sebaceous carcinoma is rare and accounts for less than 1% of all cutaneous malignancies and from 1% to 5.5% of all eyelid malignancies. The most common localization is the eyelids, where it derives from the Meibomian and Zeiss glands. Most cases occur in woman between 60 and 80 years of age, but the tumor can be seen at any age, even in childhood. It appears mostly as a small, slowly growing, painless and firm mass, sometimes as a small yellowish plaque or ulceration. SC has a tendency for local recurrence and distant metastases. The local recurrence rate ranges from 9 to 36% and tends to appear within the first 5 years from diagnosis. The most effective method of treatment is surgical excision (Mohs’ microsurgical excision if it is possible. The rate of metastases is about 14-25%. The sites of metastases are usually lymph nodes, liver, lungs, bones, and brain. The mortality rate is about 22% but it increases to 50% at 5 years in patients with metastatic disease.

  15. Subjectivity

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    Jesús Vega Encabo

    2015-11-01

    Full Text Available In this paper, I claim that subjectivity is a way of being that is constituted through a set of practices in which the self is subject to the dangers of fictionalizing and plotting her life and self-image. I examine some ways of becoming subject through narratives and through theatrical performance before others. Through these practices, a real and active subjectivity is revealed, capable of self-knowledge and self-transformation. 

  16. Immunosuppressive treatment of Graves' ophthalmopathy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    1992-01-01

    Glucocorticoids and retrobulbar irradiation are the most employed immunosuppressive treatment modalities in Graves' ophthalmopathy. The response rate is approximately 60%. Efficacy is good for improvement of appearance and visual acuity, moderate for correction of extraocular muscle dysfunction, and

  17. [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 <500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%. The majority of subjects with 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.

  18. 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

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    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.

  19. Picornavirus infection leading to immunosuppression

    OpenAIRE

    Cusick, Matthew F; Libbey, Jane E.; Fujinami, Robert S.

    2014-01-01

    Viruses, such as HIV, hepatitis A, poliovirus, coxsackievirus B3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. In addition, we propose that gaining a better insight into how ...

  20. Impact of immunosuppression and chemotherapy on reactivation of Viral hepatitis

    OpenAIRE

    Fallahian Farahnaz; Alavian Seyed-Moayed; Fallahian Vida; Zamani Farhad

    2010-01-01

    Chemotherapy drugs, biological medications that are used to treat cancer, may cause hepatic side effects. Patients with pre-existing viral hepatitis may be more susceptible to exacer-bation of their underlying liver disease, and risk of drug-induced hepatotoxicity. We conducted a search on immunosuppression, and its impact on reactivation of viral hepatitis, using the electro-nic medical databases. Before starting chemotherapy, it is recommended to record the past history of liver disease and...

  1. Review on immunosuppression in liver transplantation

    OpenAIRE

    Moini, Maryam; Schilsky, Michael L; Tichy, Eric M

    2015-01-01

    The optimal level of immunosuppression in solid organ transplantation, in particular for the liver, is a delicate balance between the benefit of preventing rejection and the adverse side effects of immunosuppression. There is uncertainty about when this level is achieved in any individual recipient. Immunosuppression regimens vary between individual centers and changes with time as new agents and data are available. Presently concerns about the adverse side effects of calcineurin inhibitor, t...

  2. 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.

  3. Immunosuppression – tough ally in torrid time

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    Elżbieta Ograczyk

    2015-12-01

    Full Text Available Immunosuppression is a condition characterized by weakened or inhibited immune response. It occurred both in humoral and cellular response. This is related to the variable levels of deficiency for each antibody class (IgG, IgM, IgA and a decrease in the number and function of immune cells, mainly T cells which results in the inhibition of cytokine production, signaling transduction and clonal expansion. Immunosuppressive therapy is used in many fields of medicine, such as transplantology, oncology, autoimmune disorders. Immunosuppression can be induced in several ways, by the surgical resection of the organs of the immune system, physical methods using X-rays or chemical methods using pharmacological agents. The most common way to induce immunosuppression is the administration of immunosuppressive drugs, amongst others: glucocorticoids, cytostatic drugs, immunophilin-binding agents, monoclonal antibodies. Unfortunately, the desired therapeutic effects of immunosuppression may be accompanied by a number of side effects associated with both impaired immunity (susceptibility to infections, including those caused by opportunistic microorganisms, toxic effects on the tissues (nephrotoxicity, neurotoxicity, or with a direct impact on the processes of malignancy. This harmful influence can be limited by the modification of the existing drugs, looking for new ones or developing new methods for the controlled kinetics of releasing the immunosuppressive pharmaceuticals. The personalization of immunosuppressant treatment according to genetic/genomic characteristics of individual patient represents the quite innovative look into the issue of immunosuppression.

  4. 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.

  5. Effects of immunosuppression induced by thalidomide and cyclosporine in heterotopic heart transplantation in rabbits.

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    Carvalho, J B V; Petroianu, A; Travolo, E; de Oliveira, B H; Duarte, A B B; Alberti, L R

    2007-06-01

    Because of its anti-inflammatory and immunodepressive effects, thalidomide has been used for the treatment of dermatologic diseases and of host-versus-graft reactions in patients undergoing bone marrow transplantation. We evaluated the immunosuppressive action of thalidomide alone or in combination with cyclosporine on the prevention of rejection of heterotopic cardiac allografts in rabbits. Fifty rabbits were used including 25 donors and 25 recipients. Recipient animals were divided into five groups (n = 5 each): group 1 (control), non-immunosuppressed animals; group II, animals immunosuppressed with cyclosporine (10 mg/kg per day); group III, immunosuppressed with thalidomide (100 mg/kg per day); group IV, immunosuppressed with cyclosporine (5.0 mg/kg per day); and group V, immunosuppressed with cyclosporine (5.0 mg/kg per day) in combination with thalidomide (50 mg/kg per day). The medications were administered through an orogastric catheter starting on the day before the transplant. The heart of the donor was implanted into the recipient's abdomen. The combination of thalidomide and cyclosporine showed the lowest histopathological rejection score (P cyclosporine was effective against rejection, significantly increasing survival (P < .01). Thalidomide may be considered to be an adjuvant immunosuppressant.

  6. to start

    Indian Academy of Sciences (India)

    Click here to start. Table of contents. Slide 1 · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19.

  7. Immunosuppression and Chagas disease: a management challenge.

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    María-Jesús Pinazo

    Full Text Available Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been

  8. Immunosuppression and Chagas disease: a management challenge.

    Science.gov (United States)

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally

  9. 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!”

  10. to start

    Indian Academy of Sciences (India)

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  11. Starting electronics

    CERN Document Server

    Brindley, Keith

    2005-01-01

    Starting Electronics is unrivalled as a highly practical introduction for hobbyists, students and technicians. Keith Brindley introduces readers to the functions of the main component types, their uses, and the basic principles of building and designing electronic circuits. Breadboard layouts make this very much a ready-to-run book for the experimenter; and the use of multimeter, but not oscilloscopes, puts this practical exploration of electronics within reach of every home enthusiast's pocket. The third edition has kept the simplicity and clarity of the original. New material

  12. Cytomegalovirus in Immunosuppressed Patients: A Silent and ...

    African Journals Online (AJOL)

    Cytomegalovirus (CMV) is a recognized cause of morbidity and mortality among immunocompromised individuals. This review will concentrate on understanding the pathogenesis, clinical manifestations and laboratory diagnostic options for CMV infection. Keywords: Review, Cytomegalovirus, Immunosuppressed ...

  13. Head Start.

    Science.gov (United States)

    Greenman, Geri

    2000-01-01

    Discusses an art project in which students created drawings of mop heads. Explains that the approach of drawing was more important than the subject. States that the students used the chiaroscuro technique, used by Rembrandt and Caravaggio, in which light appears out of the darkness. (CMK)

  14. Immunosuppressive therapies after heart transplantation--The balance between under- and over-immunosuppression.

    Science.gov (United States)

    Söderlund, Carl; Rådegran, Göran

    2015-07-01

    Since the first heart transplantation (HT) in 1967, survival has steadily improved. Issues related to over- and under-immunosuppression are, however, still common following HT. Whereas under-immunosuppression may result in rejection, over-immunosuppression may render other medical problems, including infections, malignancies and chronic kidney disease (CKD). As such complications constitute major limiting factors for long-term survival following HT, identifying improved diagnostic and preventive methods has been the focus of many studies. Notably, research on antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) has recently led to the development of nomenclatures that may aid in their diagnosis and treatment. Moreover, novel immunosuppressants (such as mammalian target of rapamycin [m-TOR] inhibitors) and strategies aimed at minimizing the use of calcineurin inhibitors (CNIs) and corticosteroids (CSs), have provided alternatives to the traditional combination maintenance immunosuppressive therapy of CSs, cyclosporine (CSA) or tacrolimus (TAC), and azathioprine (AZA) or mycophenolate mofetil (MMF). Research within this field of medicine is not only extensive, but also in constant progress. The purpose of the present review was therefore to summarize some major points regarding immunosuppressive therapies after HT and the balance between under- and over-immunosuppression. Transplant immunology, rejection, common medical problems related to over-immunosuppression, as well as induction and maintenance immunosuppressive drugs and therapies, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. 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.

  16. Impact of immunosuppression and chemotherapy on reactivation of viral hepatitis.

    Science.gov (United States)

    Fallahian, Farahnaz; Alavian, Seyed-Moayed; Fallahian, Vida; Zamani, Farhad

    2010-07-01

    Chemotherapy drugs, biological medications that are used to treat cancer, may cause hepatic side effects. Patients with pre-existing viral hepatitis may be more susceptible to exacerbation of their underlying liver disease, and risk of drug-induced hepatotoxicity. We conducted a search on immunosuppression, and its impact on reactivation of viral hepatitis, using the electro-nic medical databases. Before starting chemotherapy, it is recommended to record the past history of liver disease and check for hepatitis B virus (HBV) and hepatitis C virus (HCV) serology. In immunosuppressed patients, radiation toxicity, graft versus host disease, hepatic veno-occlusive disease, acalculous cholecystitis, tumor infiltration, ischemia, other viruses such as CMV and her-pes virus, and systemic infection should also be considered. Transplant recipients with serologic evidence of previous infection with hepatitis B or C, or those who receive organs from a seropositive donor, should have viral load levels monitored before and after transplantation and, may also require treatment. We believe that there is a role for prophylactic use of antiviral treatment in patients at risk for HBV reactivation.

  17. Impact of immunosuppression and chemotherapy on reactivation of Viral hepatitis

    Directory of Open Access Journals (Sweden)

    Fallahian Farahnaz

    2010-01-01

    Full Text Available Chemotherapy drugs, biological medications that are used to treat cancer, may cause hepatic side effects. Patients with pre-existing viral hepatitis may be more susceptible to exacer-bation of their underlying liver disease, and risk of drug-induced hepatotoxicity. We conducted a search on immunosuppression, and its impact on reactivation of viral hepatitis, using the electro-nic medical databases. Before starting chemotherapy, it is recommended to record the past history of liver disease and check for hepatitis B virus (HBV and hepatitis C virus (HCV serology. In immunosuppressed patients, radiation toxicity, graft versus host disease, hepatic veno-occlusive disease, acalculous cholecystitis, tumor infiltration, ischemia, other viruses such as CMV and her-pes virus, and systemic infection should also be considered. Transplant recipients with serologic evidence of previous infection with hepatitis B or C, or those who receive organs from a seropo-sitive donor, should have viral load levels monitored before and after transplantation and, may also require treatment. We believe that there is a role for prophylactic use of antiviral treatment in patients at risk for HBV reactivation.

  18. Renal transport and drug interactions of immunosuppressants

    NARCIS (Netherlands)

    El-Sheikh, Azza Ali Kamel

    2008-01-01

    Immunosuppressants are drugs that are used to treat inflammatory diseases, organ transplantation rejection, and cancer. These drugs are given to patients as single drugs, in combination, or together with other medications to treat accompanying diseases. Several severe side effects may result due to

  19. Immune tolerance and immunosuppression in solid organ ...

    African Journals Online (AJOL)

    Organ transplantation is the treatment of choice for patients with end-stage organ failure. Most of them will require lifelong immunosuppression to prevent both acute and chronic rejection. T-cell recognition of the allograft major histocompatibility complex antigens is the central event initiating cellular rejection of the allograft, ...

  20. 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.

  1. Optimizing the immunosuppressive regimen in heart transplantation.

    Science.gov (United States)

    Eisen, Howard; Ross, Heather

    2004-05-01

    The use of immunosuppression regimens containing a calcineurin inhibitor (CNI), an adjunct immunosuppressant (e.g., azathioprine, everolimus or mycophenolate mofetil) and corticosteroids has effectively reduced the risk of early graft loss due to acute rejection in heart transplant recipients. At present, late graft loss due to cardiac allograft vasculopathy (CAV) remains a major challenge for transplant teams. CAV is characterized by intimal hyperplasia as a result of endothelial cell injury. Factors relating to the transplant procedure itself (e.g., ischemic time and reperfusion injury), cardiovascular risks (e.g., donor age, hypertension, hyperlipidemia, pre-existing diabetes and new-onset diabetes after transplantation), immunologic risks (e.g., acute rejection episodes, anti-HLA antibodies) and the side effects of immunosuppression with CNIs or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity) have all been implicated in the development of CAV. The 2 main approaches to the prevention of CAV are modification of underlying risk factors (e.g., treatment with anti-hypertensive agents and lipid-lowering drugs, and optimizing the immunosuppressive regimen) and improvement in immunosuppression. CNIs remain the cornerstone of immunosuppressive regimens in heart transplantation, but new parameters for monitoring CNI exposure and new immunosuppressive regimens hold the promise of reduced overall CNI exposure with consequent reductions in vascular toxicity and improved clinical outcomes. Traditionally, trough levels of cyclosporine (C(0)) have been used to monitor exposure to cyclosporine and to assess the need for dose adjustment. However, optimal cyclosporine exposure can now be achieved through monitoring of cyclosporine levels 2 hours after dosing (C(2) monitoring). Furthermore, in a pivotal trial in heart transplantation, the new proliferation signal inhibitor, everolimus, plus full-dose cyclosporine and corticosteroids, has been shown to have

  2. Corticosteroid-sparing agents: conventional systemic immunosuppressants.

    Science.gov (United States)

    Kruh, Jonathan; Foster, C Stephen

    2012-01-01

    The introduction of corticosteroids in the mid-20th century to control inflammatory eye disease revolutionized treatment practices. As long-term use of corticosteroids became the backbone of immunosuppressive therapy, it soon became evident that it was associated with significant morbidity to the patient. For this reason, other immunosuppressant agents were sought. Thereafter, the first generation of immunosuppressive agents were born. The main action of all such agents involves the inhibition of lymphoid proliferation. The agents can be further subdivided into the following categories based on their specific mechanism of action: alkylating (cyclophosphamide and chlorambucil), antimetabolite (methotrexate, mycophenolate mofetil and azathioprine), and antibiotic/calcineurin inhibitor (cyclosporine, tacrolimus and sirolimus). These immunomodulating agents serve as the foundation to modern corticosteroid-sparing immunosuppressive therapy. Many times, these agents are now even indicated as first-line therapy for the treatment of systemic inflammatory diseases with destructive ocular sequela, e.g. Behçet's disease and granulomatosis with polyangiitis (Wegener's). Choosing the most appropriate immunomodulatory agent to initiate therapy can often be difficult; a multifactorial approach in the decision-making process is essential. Special attention must be given to the patient's medical history, type and severity of inflammatory disease, social history, compliance, age, and sex. Oftentimes, it takes a joint effort between the ophthalmologist and multiple sub-specialists (rheumatology, oncology, and hematology) to administer and monitor these therapies. Even though each of these systemic immunosuppressive agents has its own array of potential side effects, with careful monitoring and titration of dosages, such potential side effects can be minimized or avoided altogether. Ultimately, these patients are afforded a much more favorable long-term outcome, free of the

  3. Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis.

    Science.gov (United States)

    Sumyuen, M H; Garin, Y J; Derouin, F

    1996-01-01

    To evaluate the potential risk of dissemination or reactivation of toxoplasmosis following the administration of immunosuppressive therapy we examined the effect of corticoids, azathioprine, and cyclosporine given alone or in combination on the course of murine acute and chronic toxoplasmic infection. Swiss Webster mice were infected perorally with a high-level inoculum of cysts of the C strain of Toxoplasma gondii. The evolution of the kinetics of parasite loads in the blood, brain, and lungs of infected and immunosuppressed mice was then sequentially followed. In mice with orally acquired infections initiated 2 days after the beginning of drug treatment, immunosuppression led to the persistence of parasites, especially in the lungs, which was most marked in mice treated with azathioprine and/or cortisol acetate. Administration of immunosuppressive therapy in mice previously infected with T. gondii resulted in a brief resurgence of parasite loads when treatment was started early after infection. Finally, under our experimental conditions we found that the immunosuppressive drugs that were given altered the natural course of infection with a prolonged persistence of parasites in the lungs but did not significantly affect parasite loads in the brain or lead to disseminated infection with detectable parasitemia.

  4. Kaposi′s sarcoma following immunosuppressive therapy for vasculitis

    Directory of Open Access Journals (Sweden)

    Tarik Bouattar

    2011-01-01

    Full Text Available Kaposi′s sarcoma (KS is widely reported to develop after renal transplantation and is induced by activation of a latent human herpes virus 8. We report the clinical features and outcome of a 50-year-old woman who presented with KS 18 weeks after starting immuno-suppressive therapy for vasculitis. She had positive-titer IgG antibody to human herpes virus 8. Cyclophosphamide pulses were interrupted, and prednisone was decreased gradually to 10 mg/day. Skin lesions showed important regression with stabilization of the general state and renal function. Eight months later, the patient presented with a diffuse cutaneous KS that required the discontinuation of steroids. Within 1 month, her general status and renal function deteriorated, and she died with a disseminated intravascular coagulation syndrome.

  5. 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

  6. Immunosuppressive decalin derivatives from red yeast rice.

    Science.gov (United States)

    Zhu, Lin; Lu, Jing-Guang; Li, Ting; Zhu, Guo-Yuan; Han, Quan-Bin; Hsiao, Wen-Luan; Liu, Liang; Jiang, Zhi-Hong

    2012-04-27

    Five new decalin derivatives (1-5), together with two known compounds (6 and 7), were isolated from the ethyl acetate extract of red yeast rice. Their structures were elucidated by means of NMR and mass spectroscopic analyses. Monascusic lactone A (1) is the first reported naturally occurring decalin derivative possessing a spiro lactone at the C-1 position. The immunosuppressive effects of all these isolates (1-7) on human T cell proliferation were investigated, and all, especially monascusic acids B (2), C (3), D (4), and A (6) and heptaketide (7), suppressed human T cell proliferation in a dose-dependent manner from 10 to 100 μM. This is the first report on the immunosuppressive activity of decalin derivatives. © 2012 American Chemical Society and American Society of Pharmacognosy

  7. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......A markedly increased risk of cervical cancer is known in women immunosuppressed due to AIDS or therapy following organ transplantation. The aim of this review is to determine the association between other conditions affecting the immune system and the risk of cervical cancer. Patients with end......-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...

  8. Immunity and immunosuppression in experimental visceral leishmaniasis

    OpenAIRE

    Goto H; Lindoso J.A.L.

    2004-01-01

    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 viscera...

  9. 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.

  10. 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.

  11. Immunosuppression associated with chronic inflammation in the tumor microenvironment

    Science.gov (United States)

    Wang, Dingzhi; DuBois, Raymond N.

    2015-01-01

    Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID:26354776

  12. The Starting Early Starting Smart Story.

    Science.gov (United States)

    Casey Family Programs, Seattle, WA.

    Starting Early Starting Smart (SESS) is an early childhood public/private initiative designed to identify new, empirical knowledge about the effectiveness of integrating substance abuse prevention, addictions treatment, and mental health services with primary health care and childcare service settings (e.g., Head Start, day care, preschool) to…

  13. Management of Sepsis-Induced Immunosuppression.

    Science.gov (United States)

    Venet, Fabienne; Rimmelé, Thomas; Monneret, Guillaume

    2018-01-01

    It is now well established that profound immunosuppression develops within a few days after sepsis onset in patients. This should be considered additional organ failure because it is associated with increased rate of nosocomial infections, mortality, and long-term complications, thus constituting the rationale for immunomodulation in patients. Nevertheless, the demonstration of the efficacy of such therapeutic strategy in improving deleterious outcomes in sepsis remains to be made. Results from clinical trials based on interleukin 7 and granulocyte macrophage colony-stimulating factor immunoadjuvant therapies in septic shock patients are expected for 2018. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Persistent Inflammation, Immunosuppression and Catabolism Syndrome.

    Science.gov (United States)

    Mira, Juan C; Brakenridge, Scott C; Moldawer, Lyle L; Moore, Frederick A

    2017-04-01

    Following advances in critical care, in-hospital multiple organ failure-related mortality is declining. Consequently, incidence of chronic critical illness is increasing. These patients linger in the intensive care unit, have high resource utilization, and poor long-term outcomes. Within this population, the authors propose that a substantial subset of patients have a new phenotype: persistent inflammation, immunosuppression, and catabolism syndrome. There is evidence that myelodysplasia with expansion of myeloid-derived suppressor cells, innate and adaptive immune suppression, and protein catabolism with malnutrition are major contributors. Optimal care of these patients will require novel multimodality interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death.

    Science.gov (United States)

    Karvellas, Constantine J; Cardoso, Filipe S; Gottfried, Michelle; Reddy, K Rajender; Hanje, A James; Ganger, Daniel; Lee, William M

    2017-01-01

    Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P > .17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Within a cohort study of patients with

  16. 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.

  17. 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

  18. Immunosuppressive and biologic therapy for ulcerative colitis.

    Science.gov (United States)

    Ardizzone, Sandro; Cassinotti, Andrea; de Franchis, Roberto

    2012-12-01

    Recent insight into the pathogenesis of ulcerative colitis have led to the development of new treatment options. A better understanding of IBD pathophysiology has progressively led to a more frequent use of immunosuppressants and biologics. The use of the conventional immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate, cyclosporine and tacrolimus, and anti-TNF-α agents, such as infliximab and adalimumab, in the treatment of ulcerative colitis are reviewed. Moreover, the ongoing studies evaluating the efficacy of emerging immunosuppressants in treating patients with ulcerative colitis are discussed. An effort is made to explore some critical areas in which early and more diffuse use of these agents may be advocated. Ulcerative colitis is a chronic condition mainly affecting young people in their more productive age, and determining high indirect costs to the patient and to society. Thus, there is a need for optimizing and renewing our traditional therapeutic approach to UC, and new therapies beyond conventional treatment options possibly aiming to change the poor clinical course of many patients with ulcerative colitis. Keeping in mind this potentially new therapeutic scenario, there are some critical areas in which early and more diffuse use of conventional and emerging new immunomodulators is advocated.

  19. 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.

  20. Cardiac transplantation. Selection, immunosuppression, and survival.

    Science.gov (United States)

    Stevenson, L W; Laks, H; Terasaki, P I; Kahan, B D; Drinkwater, D C

    1988-01-01

    Cardiac transplantation has evolved from an experiment to an accepted therapy for severe heart failure. Increasing competition for donor organs mandates a greater emphasis on selection and timing for transplantation and paradoxically forces more reliance on aggressive medical therapy for all patients after evaluation. The growth of recipient and donor pools may enhance the opportunity for assessing histocompatibility, for which distinguishing between autoantibodies and human leukocyte antigen-determined reactivity is important, and some general nonresponders may be detected. Therapy with cyclosporine has improved the outcome after transplantation, but further refinement is needed, perhaps with pharmacologic synergy, to minimize nephrotoxicity and maximize specific immunosuppression. Survival is more than 80% at 1 year, after which the incidence of acute rejection and infection declines and accelerated atherosclerosis becomes prominent. Although resuming employment is not always possible, the overall quality of life is excellent after cardiac transplantation. Images PMID:3074557

  1. 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.

  2. Viruses in cancers among the immunosuppressed.

    Science.gov (United States)

    Arroyo Mühr, Laila Sara; Bzhalava, Zurab; Hortlund, Maria; Lagheden, Camilla; Nordqvist Kleppe, Sara; Bzhalava, Davit; Hultin, Emilie; Dillner, Joakim

    2017-12-15

    Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably nonmelanoma skin carcinoma (NMSC). We followed all 13,429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). The sequences were analyzed for viruses based on two bioinformatics algorithms (paracel-blast (sensitive for detection of known viruses) and hidden Markov model (HMM; sensitive for distantly related viruses)). Among the 62 NMSCs, the virus family detected in the largest proportion of specimens was Mimiviridae (9/62 NMSCs). The majority of the virus-related reads belonged to Papillomaviridae. The HMM analysis identified 86 additional previously not described viral contigs related to 11 virus families, with reads related to Mimiviridae being the most common (detected in 28/62 NMSCs) with the most prevalent contig (Mimivirus SE906, 1937 bp) detected in 17/62 NMSCs. Among the 27 other cancers, viral sequences were detected in only 5 specimens by blast analysis, compared to in all 27 specimens by HMM (Mimiviridae, Poxviridae, Phycodnaviridae and virus-related sequences yet unclassified to any family). 99% of the virus reads belonged to a single previously not described sequence (Mimivirus SE996, 911 bp). A multitude of viruses is readily detectable in specimens with cancers occurring among the immunosuppressed, with sequences related to Mimiviridae being the most prevalent. Further research would be needed to elucidate the biological significance of the viruses. © 2017 UICC.

  3. Treatment with immunosuppressive therapy in patients with pars planitis: experience of a reference centre in Mexico.

    Science.gov (United States)

    Serna-Ojeda, Juan Carlos; Pedroza-Seres, Miguel

    2014-11-01

    To evaluate the clinical course of the patients with pars planitis that received immunosuppressive drugs. We retrospectively analysed the data of 10 years from 374 patients with pars planitis in a large reference centre in Mexico City and included 49 patients (92 eyes). Median age at presentation was 8 years. 35 patients (71.4%) were male and 43 patients (87.7%) had bilateral disease. Diverse immunosuppressive medications were used, mainly methotrexate (69.4%) and azathioprine (63.3%) with 18 patients requiring more than one drug. The main indications for starting immunosuppressive therapy were lack of response to initial treatment and advance disease at presentation. The results showed good response with steroid reduction (69.3% of patients), visual acuity improvement (51% of patients) and inflammatory disease reduction (59.1% of patients). In 25 patients (51%), steroids were started previous to immunosuppressors and in 24 (49%) at the same time without significant difference in clinical improvement (p=0.210) or visual outcome (p=0.498). Thirteen patients (26.5%) presented mild adverse effects. The median of the final visual acuity was 20/40. The median follow-up time was 44 months (range 13-115 months). Immunosuppressive therapy allows an adequate control of inflammatory disease in pars planitis, with clinical and visual improvement and steroid dose reduction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. 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.

  5. [Immunosuppressive therapy and fertility preservation: Indications and methods].

    Science.gov (United States)

    Choux, C; Cavalieri, M; Barberet, J; Samson, M; Bonnotte, B; Fauque, P; Sagot, P

    2018-02-27

    Fertility preservation is routinely performed in cancerology but less systematically used in the field of immune diseases, even though the use of gonadotoxic treatments in young patients may be required and even though the disease itself can alter fertility. This review aimed to clarify the indications and methods of fertility preservation in this context. Cyclophosphamide is the only immunosuppressive drug requiring fertility preservation in women. In men, fertility preservation should be proposed before treatment with cyclophosphamide, methotrexate, mycophenolate mofetil or mTOR inhibitors. Other factors inherent to the disease or the patient may alter fertility. Thus, screening for infertility and fertility preservation have to be implemented as much as possible to increase the chances of successful procreation in patients with immune disease. For women, the choice between the different preservation methods depends on the patient's age, disease activity, the time available before the start of treatment, the possibility of future pregnancy and the woman's and even couple's wishes. Before puberty, the only accepted method is cryopreservation of ovarian tissue. After puberty, the first-line method is the cryopreservation of mature oocytes. If the treatment has to be started in an emergency, if ovarian hyperstimulation/oocyte retrieval is contraindicated or if the patient refuses this option, cryopreservation of ovarian tissue or GnRH agonists could be proposed. For men, the accepted method is sperm cryopreservation. For prepubertal boys, the cryopreservation of spermatogonia after testicular biopsy is still experimental. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  6. 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.

  7. Imunossupressores na Dermatologia Immunosuppressive agents in Dermatology

    Directory of Open Access Journals (Sweden)

    Aline Lopes Bressan

    2010-02-01

    Full Text Available Os imunossupressores são drogas que agem na divisão celular e têm propriedades anti-inflamatórias. Sendo assim, são essencialmente prescritos na prevenção de rejeição de transplantes e no tratamento das doenças autoimunes e inflamatórias crônicas, que, na Dermatologia, têm a psoríase como maior representante. Nesta sessão serão descritas as principais drogas imunossupressoras, com orientações para seu manejo adequado.Immunosupressants are drugs that act in cell division and have anti-inflammatory effects. Therefore, they are essentially prescribed in the prevention of transplant rejection and in the treatment of autoimmune disorders and chronic inflammatory diseases, whose main example in Dermatology is psoriasis. In this work the most important immunosuppressive drugs and orientation to properly administer them are going to be described.

  8. Immunosuppression during Rhizobium-legume symbiosis.

    Science.gov (United States)

    Luo, Li; Lu, Dawei

    2014-01-01

    Rhizobium infects host legumes to elicit new plant organs, nodules where dinitrogen is fixed as ammonia that can be directly utilized by plants. The nodulation factor (NF) produced by Rhizobium is one of the determinant signals for rhizobial infection and nodule development. Recently, it was found to suppress the innate immunity on host and nonhost plants as well as its analogs, chitins. Therefore, NF can be recognized as a microbe/pathogen-associated molecular pattern (M/PAMP) like chitin to induce the M/PAMP triggered susceptibility (M/PTS) of host plants to rhizobia. Whether the NF signaling pathway is directly associated with the innate immunity is not clear till now. In fact, other MAMPs such as lipopolysaccharide (LPS), exopolysaccharide (EPS) and cyclic-β-glucan, together with type III secretion system (T3SS) effectors are also required for rhizobial infection or survival in leguminous nodule cells. Interestingly, most of them play similarly negative roles in the innate immunity of host plants, though their signaling is not completely elucidated. Taken together, we believe that the local immunosuppression on host plants induced by Rhizobium is essential for the establishment of their symbiosis.

  9. Renoprotective strategies in lupus nephritis: beyond immunosuppression.

    Science.gov (United States)

    Griffin, B; Lightstone, L

    2013-10-01

    Lupus nephritis needs to be diagnosed promptly and treated specifically with appropriate immunosuppression. However, all patients with lupus nephritis have by definition chronic kidney disease (CKD) as they will have proteinuria with varying degrees of renal impairment. CKD requires careful additional management, not only to reduce the risk of progression to end-stage renal disease but also because it is probably the strongest risk for cardiovascular morbidity and mortality. This review focuses on the evidence underscoring strategies to prevent progression of CKD beyond the "simple" treatment of the lupus nephritis. The strategies include immaculate control of blood pressure, inhibition of the renin-angiotensin system to reduce blood pressure and proteinuria, and the benefits of lifestyle modifications such as tackling smoking, obesity and exercise. We also review the literature on control of dyslipidaemias which, although clearly of cardiovascular benefit, provide less compelling data for offering renoprotection. We touch on the emerging area of the importance of controlling urate levels in protecting against progressive renal impairment. Finally, there is a reminder about the importance of considering the nephrotoxicity of all medications prescribed for patients with lupus nephritis - above all the need to avoid the use of non-steroidal anti-inflammatory drugs. Overall, the theme is that there is much more to the management of patients with lupus nephritis than "just" the nephritis - a multidisciplinary approach involving nephrologists as well as rheumatologists is more likely to provide the appropriate wider care required for all patients with lupus nephritis.

  10. Impact of Laboratory Practices on Interlaboratory Variability in Therapeutic Drug Monitoring of Immunosuppressive Drugs.

    Science.gov (United States)

    Christians, Uwe; Vinks, Alexander A; Langman, Loralie J; Clarke, William; Wallemacq, Pierre; van Gelder, Teun; Renjen, Varun; Marquet, Pierre; Meyer, Eric J

    2015-12-01

    The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate, and precise test methods are therefore essential to effectively monitor levels and to make proper dose adjustments. Data from proficiency testing programs have shown substantial interlaboratory variability. Only few attempts have been made to study the underlying causes. The aim of this study was to systematically document current practices used for immunosuppressant drug TDM in clinical laboratories and identify methodological and practice differences, which may cause the variability observed among laboratories. Data collection was primarily conducted by a structured Web-based survey. Invitations to participate in the survey were distributed to clinical laboratories providing immunosuppressant drug TDM. Surveys were completed by 76 laboratories in 14 countries. The results of our survey suggest that there are 3 main reasons for interlaboratory variability: (1) lack of standardization of laboratory procedures and workflows starting with sample collection and handling, (2) lack of use of appropriate reference materials (eg, isotope-labeled internal standards for liquid chromatography-tandem mass spectroscopy), and (3) poor compliance with internationally accepted good laboratory practice guidelines (eg, related to quality control, quality assurance, validation, training of personnel). The results of the survey also suggest that interlaboratory variability is a multifactorial problem. Technical-level consensus on laboratory operational procedures, quality systems, and personnel training will be of great importance to improve quality and interlaboratory comparability.

  11. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans.

    Science.gov (United States)

    Thanos, S M; Halliday, G M; Damian, D L

    2012-09-01

    The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown. To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans. Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression. High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045). While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  12. Posttransplant metabolic syndrome in the withdrawal of immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial.

    Science.gov (United States)

    Perito, E R; Mohammad, S; Rosenthal, P; Alonso, E M; Ekong, U D; Lobritto, S J; Feng, S

    2015-03-01

    Posttransplant metabolic syndrome (PTMS)-obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance-is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years (IQR 6.4-10.8), and weaned from calcineurin-inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor withdrawal in the WISP-R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP-R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP-R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. FINANCIRANJE START - UP PODJETIJ

    OpenAIRE

    Kraner, Simona

    2016-01-01

    V magistrskem delu ugotavljamo specifike start-up podjetij ter njihov vpliv na dostopnost in primernost posameznih virov financiranja. Ko ugotovimo in razdelamo poglavitne specifike, ki na splošno veljajo za start-up podjetja, se lotimo proučevanja faz financiranja, skozi katera start-up prehajajo. Vsako od sedmih tipičnih faz financiranja start-up podjetij opredelimo z vidika značilnosti, ki za start-up podjetja v specifični razvojni fazi veljajo. Prvo polovico teoretičnega dela zaključi...

  14. [Visceral leishmaniasis, pemphigus and immunosuppressive treatment: case report from Morocco].

    Science.gov (United States)

    Maleb, A; Messaoudi, N; Chbouki, O; Daoudi, N; Oumghar, K; Lahmadi, K; Elmoussaoui, D; Ezzahraoui, K; Ngoh, Akwa E; Benomar, F; Abi, R; Jeaidi, A; Nazih, M; Belmekki, A; Chakour, M

    2011-02-01

    Atypical forms of visceral leishmaniasis associated with immunosuppressive treatment are difficult to diagnose and cause high mortality. The purpose of this report is to describe a case involving a 42-year-old patient living in a leishmaniasis-endemic area, who was undergoing immunosuppressive treatment using corticosteroids and methotrexate for pemphigus. Despite clinical and laboratory findings consistent with visceral leishmaniasis, detection of Leishmania bodies was a coincidental finding of cytological examination of bone marrow during workup for pancytopenia and associated clinical signs. This case argues in favor of systematic screening for this opportunistic parasitic disease before undertaking immunosuppressive treatment in patients presenting risk factors and consistent clinical/laboratory findings.

  15. 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....

  16. 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....

  17. 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...

  18. Comprehensive comparison of three different immunosuppressive regimens for liver transplant patients with hepatocellular carcinoma: steroid-free immunosuppression, induction immunosuppression and standard immunosuppression.

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Liu

    Full Text Available The different choices of immunosuppression (IS regimens influenced the outcomes of liver transplantation. Steroid was applied as a standard IS to prevent and treat rejections. However, steroid-related complications were increasingly prominent. This study compared the efficacy and safety of standard IS regimens with the efficacy and safety of steroid-free IS regimen and induction IS regimen in Chinese liver transplantation recipients for hepatocellular carcinoma (HCC. A total of 329 patients who underwent liver transplantation from January 2008 to December 2012 were retrospectively reviewed. Three different groups of patients received standard triple-drug IS regimen of steroid, tacrolimus (TAC and mycophenolate mofetil (MMF (triple-drug regimen group; n=57, induction-contained IS regimen of basiliximab, steroid, TAC and MMF (BS group; n=241, and induction-contained and steroid-free regimen of basiliximab, TAC and MMF (SF group; n=31, respectively. There were no significant differences in terms of patient, tumor-free and graft survival rates. The acute rejection rate and rejection time were equivalent in different groups. But compared with BS group, higher incidences of biliary complications (11.52% vs. 30.77%, p=0.013 and graft dysfunction (0.48% vs. 13.64%, p=0.003 were observed in SF group. Furthermore, compared with the two groups, incidence of pleural effusion was also higher in SF group (15.79%, 11.96% vs. 45.45%, respectively, both p<0.01. And a trend towards less proportion of De novo diabetes was revealed in SF group. Although it was found that patient, tumor-free and graft survival rates were equivalent among three IS regimens, higher incidences of complications were demonstrated in steroid-free regimen in patients for HCC. These findings suggested that steroid-free IS regimen has no clear advantages in comparison with standard IS regimens for liver transplant recipients with HCC and the postoperative complications should be treated with

  19. Immunosuppression for Mooren's ulcer: evaluation of the stepladder approach--topical, oral and intravenous immunosuppressive agents.

    Science.gov (United States)

    Ashar, Jatin N; Mathur, Anurag; Sangwan, Virender S

    2013-11-01

    To evaluate a step ladder approach for immunosuppressive regimen for Mooren's ulcer. We retrospectively analysed patients of Mooren's ulcer presenting to a tertiary care centre in south India from 1987 to 2010. Patients were analysed for the age, disease severity at time of presentation in terms of the quadrants of peripheral corneal involvement and amount of peripheral corneal thinning. According to the disease severity, patients were instituted either topical steroids (prednisolone acetate 1%) single agent or in combination with oral steroids (prednisolone 1-1.5 mg/kg/day), oral immunomodulators (methotrexate 7.5-12.5 mg/week), intravenous pulsed methyl prednisolone 1 g or pulsed cyclophosphamide 1 g. The main outcome measure was control of disease activity. Topical steroids as a single therapy had a disease resolution rate in 76% of the cases. Cases that required oral steroids, oral methotrexate, intravenous pulsed methyl prednisolone and combination of pulsed methyl prednisolone and cyclophosphamide had a resolution rate of 86%, 78.5%, 71.4% and 73.3%, respectively. The most common complication was secondary infection. Most of the cases that failed therapy had perforation of the cornea and required corneal transplantation. An aggressive immunosuppressive regimen that is tailor made based on disease severity as a first line of therapy improves the chances of disease control even in cases of aggressive Mooren's ulcer.

  20. Circulating and thymic CD4+ CD25+ T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment

    Science.gov (United States)

    Fattorossi, Andrea; Battaglia, Alessandra; Buzzonetti, Alexia; Ciaraffa, Francesca; Scambia, Giovanni; Evoli, Amelia

    2005-01-01

    Accumulating evidence indicates an immunosuppressive role of the thymus-derived CD4+ T-cell population constitutively expressing high level of CD25, T regulatory (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells in the blood is significantly lower in untreated myasthenia gravis patients than in age-matched healthy subjects, whereas it is normal or elevated in patients on immunosuppressive therapy (prednisone frequently associated with azathioprine). Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic alterations that are often associated with myasthenia gravis provided unique material for studying intrathymic Treg cells and correlating them with their peripheral counterparts. We observed that Tx prevents the increase of Treg cells in the circulation that follows immunosuppressive therapy (particularly evident if the thymus is not neoplastic), indicating that the thymus contributes to Treg-cell normalization. However, thymic Treg cells are not modulated by immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in the blood eventually recover. The present findings suggest that a deficiency in Treg cells favours the development of myasthenia gravis and that their normalization is an important clinical benefit of immunosuppressive therapy. Treg normalization appears to be largely thymus independent and possibly reflects the reported capacity of corticosteroids to promote Treg-cell development. PMID:16108825

  1. Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment.

    Science.gov (United States)

    Fattorossi, Andrea; Battaglia, Alessandra; Buzzonetti, Alexia; Ciaraffa, Francesca; Scambia, Giovanni; Evoli, Amelia

    2005-09-01

    Accumulating evidence indicates an immunosuppressive role of the thymus-derived CD4+ T-cell population constitutively expressing high level of CD25, T regulatory (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells in the blood is significantly lower in untreated myasthenia gravis patients than in age-matched healthy subjects, whereas it is normal or elevated in patients on immunosuppressive therapy (prednisone frequently associated with azathioprine). Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic alterations that are often associated with myasthenia gravis provided unique material for studying intrathymic Treg cells and correlating them with their peripheral counterparts. We observed that Tx prevents the increase of Treg cells in the circulation that follows immunosuppressive therapy (particularly evident if the thymus is not neoplastic), indicating that the thymus contributes to Treg-cell normalization. However, thymic Treg cells are not modulated by immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in the blood eventually recover. The present findings suggest that a deficiency in Treg cells favours the development of myasthenia gravis and that their normalization is an important clinical benefit of immunosuppressive therapy. Treg normalization appears to be largely thymus independent and possibly reflects the reported capacity of corticosteroids to promote Treg-cell development.

  2. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation

    DEFF Research Database (Denmark)

    McAlister, V C; Haddad, E; Renouf, E

    2006-01-01

    A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were...

  3. Inferior results with basis immunosuppression with sirolimus in kidney transplantation.

    NARCIS (Netherlands)

    Akker, J.M. van den; Hene, R.J.; Hoitsma, A.J.

    2007-01-01

    BACKGROUND: The introduction of sirolimus has provided the opportunity to develop an immunosuppressive regimen without the nephrotoxic calcineurin inhibitors. METHODS: We conducted a first trial in 30 renal allograft recipients. Ten patients were followed prospectively and received sirolimus, to

  4. Legionella infections in cyclosporine-immunosuppressed cardiac transplants

    National Research Council Canada - National Science Library

    Favor, A; Frazier, O H; Cooley, D A; Okereke, O U; Radovancevic, B; Powers, P; Chandler, L

    1985-01-01

    ... of the care of transplant patients. One such opportunistic Organism, Legionella pneumophila, was responsible for four episodes of infection in three of our patients who survived due to better management of immunosuppression, together...

  5. Legionella Infection in Cyclosporine-Immunosuppressed Cardiac Transplants

    National Research Council Canada - National Science Library

    Favor, Arsenio; Frazier, O.H; Cooley, Denton A; Okereke, O.U. John; Radovancevic, Branislav; Powers, Penny; Chandler, Linda

    1985-01-01

    ... of the care of transplant patients. One such opportunistic Organism, Legionella pneumophila, was responsible for four episodes of infection in three of our patients who survived due to better management of immunosuppression, together...

  6. Engine Cold Start

    Science.gov (United States)

    2015-09-01

    UNCLASSIFIED UNCLASSIFIED ENGINE COLD START INTERIM REPORT TFLRF No. 469 by Douglas M. Yost Gregory A. T. Hansen U.S...not return it to the originator. UNCLASSIFIED UNCLASSIFIED ENGINE COLD START INTERIM REPORT TFLRF No. 469 by Douglas M. Yost...TITLE AND SUBTITLE Engine Cold Start 5a. CONTRACT NUMBER W56HZV-09-C-0100 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Douglas

  7. Head Start in Action.

    Science.gov (United States)

    Riley, Clara M. D.; Epps, Frances M. J.

    Records and observations from a summer Head Start program, conducted in Los Angeles by Delta Sigma Theta, are delineated in this book. It relates firsthand experiences of the participating personnel as they developed and implemented a Head Start program for some 300 children. The book is divided into three sections. Section I,…

  8. Molecular characterization of rotavirus genotypes in immunosuppressed and non-immunosuppressed pediatric patients.

    Science.gov (United States)

    Pereira, Luciane A; Ferreira, Carla E O; Turchetto, Giovana D; Nogueira, Meri B; Vidal, Luine R; Cruz, Cristina R; Debur, Maria C; Almeida, Sergio M de; Raboni, Sonia M

    2013-01-01

    To describe the genotypic variability of group A rotavirus (RVA) found in immunosuppressed and non-immunosuppressed pediatric patients treated at the Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR), Curitiba, Paraná. A cross-sectional study was conducted with 1,140 stool samples collected from April, 2001 to December, 2008 in outpatients and hospitalized patients with acute gastroenteritis referred to the hospital. RVA diagnosis was performed through the latex agglutination method and enzyme immunoassay. Reverse transcription followed by multiplex hemi-nested polymerase chain reaction (PCR) and nucleotide sequencing were used for genotype characterization. Genotype combinations, clinical, epidemiological, laboratory data, and presence of hospital-acquired infections were reported. A total of 80 rotavirus-positive stool samples were analyzed. The most frequent associations between genotypes G and P were: G4 P[8] (38.9%), G1 P[8] (30.5%), G9 P[8] (13.9%), G2 P[4] (6.9%), and G3 P[8] (1.4%). G2 P[4] was the most prevalent genotype after the vaccine implementation in the years 2006 and 2008. A total of 62,5% of infected children were aged less than 12 months. Of these, 55.6% had severe dehydration and 26.7% needed intensive care. A frequency of 12.5% of nosocomial infections was found. No correlation was observed between genotype and severity of infection in the study patients. RVA infections can be associated with severe clinical manifestations, and the surveillance of genotypic variability of this virus is crucial to monitor the emergence of new strains and the impact of the immunization in these patients. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. 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 main...... 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....

  10. [Infectious complications due to immunosuppression in organ transplant patients].

    Science.gov (United States)

    Morelon, Emmanuel; Touraine, Jean-Louis

    2007-10-15

    Prevention and treatment of allograft rejection by immunosuppressive treatments expose organ transplant patients to frequent and sometimes severe infectious complications. Immunosuppressive drugs inhibit both the immune response to alloantigens, and the anti-infectious immunity; they promote intracellular infections, including infections with viruses and with bacterial, parasitic and mycotic agents. Infectious risks are related to duration of immunosuppression exposure, type of immunosuppressive drugs, combination of drugs and trough levels required to control rejection. Assessment of the risk of infectious diseases in transplant patients before transplantation has to take into account past medical history, number of previous transplantations, immunosuppressive regimen, and the risk of infectious diseases transmitted from the donor. After the graft, infectious risks have to be assessed by clinical examination, repeated white blood cell count to detect leucopenia. In high risk population, monitoring for CMV and EBV infections is based on analysis of replication using nucleic acid based assays or antigenemia studies. Prophylactic anti-infectious therapy in high-risk patients has resulted in reduction of the consequences of overimmunosuppression in organ transplantation.

  11. Early Head Start Evaluation

    Data.gov (United States)

    U.S. Department of Health & Human Services — Longitudinal information from an evaluation where children were randomly assigned to Early Head Start or community services as usual;direct assessments and...

  12. Head Start Impact Study

    Data.gov (United States)

    U.S. Department of Health & Human Services — Nationally representative, longitudinal information from an evaluation where children were randomly assigned to Head Start or community services as usual;direct...

  13. FEMA DFIRM Station Start

    Data.gov (United States)

    Minnesota Department of Natural Resources — This table contains information about station starting locations. These locations indicate the reference point that was used as the origin for distance measurements...

  14. 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.

  15. Withdrawal of immunosuppression following pediatric liver transplantation: a Markov analysis.

    Science.gov (United States)

    Mohammad, Saeed; Li, Zhe; Englesbe, Michael; Skaro, Anton; Alonso, Estella

    2014-08-01

    Survivors of pediatric liver transplantation are at risk for developing complications related to posttransplant immunosuppressive medications. Withdrawal is possible in selected patients but carries the risk of graft rejection and loss. We modeled the effect of withdrawing immunosuppressive medications on survival, cost, and quality-adjusted life-years (QALYs) in a hypothetical cohort of pediatric patients who received transplantation for biliary atresia with stable liver enzymes and no recent episodes of rejection, and who were free from immunosuppression-related adverse effects. A decision analysis tree was developed, and Monte Carlo simulations were used to track patients through the model during a 10-year time course with 1-year cycles. Data from the literature were used to assign probabilities to major clinical events and preference-based utility scores to the values of health outcomes. One-way and probabilistic sensitivity analyses were used to evaluate the impact of uncertainty. Patients following the withdrawal strategy had a 10-year survival rate of 95.8% and experienced 8.61 QALYs versus 88.6% survival and 8.01 QALYs for those taking immunosuppressive medications. Each additional QALY is attained at a cost of -$18,992.41 and was therefore cost saving. Patients in our model who had their immunosuppression withdrawn had improved survival and QALYs with lower costs. Although every effort was made to validate the model, it is limited by the accuracy of the underlying assumptions. Therefore, clinical trials are needed to determine predictors of successful immunosuppression withdrawal to allow for personalization of medication regimens.

  16. 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.

  17. Effects of immunosuppressants on immune response to vaccine in inflammatory bowel disease.

    Science.gov (United States)

    Cao, Yuan; Zhao, Di; Xu, An-Tao; Shen, Jun; Ran, Zhi-Hua

    2015-03-20

    response to vaccination in patients with IBD. Vaccination should be made at the time of diagnosis or before starting immunosuppressed therapy.

  18. Comparison of growth during continuous ambulatory peritoneal dialysis and renal transplantation using conventional immunosuppressive drugs in children.

    Science.gov (United States)

    Iitaka, K; Hojo, M; Moriya, S; Sakai, T; Endo, T

    1998-01-01

    Growth during continuous ambulatory peritoneal dialysis (CAPD) and after renal transplantation (Tx) was assessed in children under the age of 12 years. Growth was assessed by calculating the standard deviation score for height of normal children of the same age and gender. Twenty-one patients undergoing CAPD and 13 patients who had received renal Tx at Kitasato University Hospital. Overall growth in those children undergoing CAPD and after renal Tx was not good, but growth during CAPD seemed to be slightly better than after renal Tx using conventional immunosuppressive drugs. Only young children who had started CAPD or received renal Tx before the age of 5 years with functioning graft showed catch-up growth, but the final height of these children may still be smaller than normal. Growth in children with end-stage renal disease is poor but growth during CAPD seems to be slightly better than after renal Tx using conventional immunosuppressive drugs.

  19. ATLAS starts moving in

    CERN Multimedia

    2004-01-01

    The first large active detector component was lowered into the ATLAS cavern on 1 March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day.

  20. Jump Starting Entrepreneurship

    DEFF Research Database (Denmark)

    Burcharth, Ana Luiza Lara De Araújo; Smith, Pernille; Frederiksen, Lars

    -hanging opportunity seeking entrepreneurs”, and 3) the “jump-start entrepreneurs”. Whereas the two first categories could be expected, the third one shows that, despite hesitance to be self-employed, being uneasy with it, risk adverse and having strong identification to the previous organization, these entrepreneurs...

  1. Waco Head Start Program.

    Science.gov (United States)

    Porter, Para

    The Economic Opportunity Act of 1964 led to the formation of three separate Head Start Programs in Waco, Texas. The first year, 1,500 children were involved. Of these, 40 percent were Negro, 30 percent Latin American, and 30 percent white. All teachers received a week of preparatory study at the University of Texas. The program involved four areas…

  2. Starting up the upstarts.

    Science.gov (United States)

    Greene, J

    1997-12-20

    Venture capitalists pour $1 billion a year into health care--and that investment may be the most overlooked indicator of new business opportunities. Signs show that companies focused on consolidation and cost-cutting are off the A list for risk capital. Instead, venture capitalists are targeting start-ups that save money on the front lines by truly managing care.

  3. Getting started with UDOO

    CERN Document Server

    Palazzetti, Emanuele

    2015-01-01

    If you are an Android developer who wants to learn how to use UDOO to build Android applications that are capable of interacting with their surrounding environment, then this book is ideal for you. Learning UDOO is the next great step to start building your first real-world prototypes powered by the Android operating system.

  4. Getting started with Go

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    No, not the Chinese boardgame, the programming language that ironically Google made difficult to google for. You may have heard of Golang, and are wondering whether you should learn it. The answer is that of course you should, and this talk should explain why and point you at the best resources to get started.

  5. Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-03-01

    Full Text Available Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5 infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.

  6. 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...

  7. Immunosuppressive principles from Achillea talagonica, an endemic species of Iran

    Directory of Open Access Journals (Sweden)

    S Saeidnia

    2009-03-01

    Full Text Available ABSTRACT Background and the purpose of study: Achillea talagonica Boiss. (Asteraceae grows in the western and central parts of Iran. This plant has long been used in traditional medicine as an anti-inflammatory agent for treatment of rheumatic pain. Previously, the immunosuppressive activity of the aqueous extract of this endemic plant in experimental animals was reported. In this research, isolation of the main immunologically active components of A. talagonica, which were effective on humoral immune responses in BALB/c mice is elucidated. Methods: In order to find the main immunosuppressive components of A. talagonica, methanol and methanol-water (80% and 50% v:v extracts were injected to BALB/c mice and the hemagglutinating antibody titer was assayed after immunization with SRBC (sheep red blood cells. Guided by this assay, active principles were separated by chromatographic methods. Results: Isolated compounds were identified as caffeic acid 9-O-glucoside (1, quercetin (2, luteolin (3, 3'-methoxy luteolin (4, proline (5 and choline (6 by comparison of their spectral data with those of reported in literatures. Immunosuppressive property of choline (5 mgkg-1 was comparable to those of prednisolone (10 mgkg-1; although, quercetin (20 mgkg-1 and caffeoyl glucoside (20 mgkg-1 decreased anti-SRBC titer in comparison with control groups. Major conclusion: Immunosuppressive effects of A. talagonica are due to some components belonging to betaine, flavonol and phenoilc esters.

  8. Candida meningitis in a suspected immunosuppressive patient - A ...

    African Journals Online (AJOL)

    Candida meningitis in a suspected immunosuppressive patient - A case report. EO Sanya, NB Ameen, BA Onile. Abstract. No Abstract. West African Journal of Medicine Vol. 25 (1) 2006: pp.79-81. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  9. 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.

  10. 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.

  11. Role of immunosuppression in the evolution of Legionnaires' disease.

    Science.gov (United States)

    Pedro-Botet, M L; Sabria-Leal, M; Sopena, N; Manterola, J M; Morera, J; Blavia, R; Padilla, E; Matas, L; Gimeno, J M

    1998-01-01

    The clinical course of legionella pneumonia in immunosuppressed patients is uncertain. This study was undertaken to determine the clinical evolution of legionellosis on the basis of the immune state and to establish the variables associated with death directly related to legionellosis. The study included 78 patients: 28 with chronic disease who had received immunosuppressive treatment (group 1), 24 with chronic disease without immunosuppressive treatment (group 2), and 26 controls. Inclusion criteria were the occurrence of nosocomially acquired pneumonia, Legionella pneumophila infection, and erythromycin therapy that was initiated within 72 hours following diagnosis. Respiratory and extrarespiratory complications were observed more frequently in groups 1 and 2. Bilateral radiological involvement was most frequent in group 1, and recurrence of legionella pneumonia was observed exclusively in group 1. None of these variables achieved statistical significance. The global mortality of the series was 11.5% (17.9%, 12.5%, and 3.8% in groups 1, 2, and 3, respectively). Variables statistically related to mortality were acute renal failure, shock, and need for mechanical ventilation. Although many of the variables analyzed lacked statistical significance, a trend was seen between complications and basal immunosuppression, as previously suggested.

  12. 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

    2018-02-02

    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

  13. Click here to start

    Indian Academy of Sciences (India)

    Click here to start. Table of contents. Slide 1 · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

  14. Getting started with Hazelcast

    CERN Document Server

    Johns, Mat

    2013-01-01

    Written as a step-by-step guide, Getting Started with Hazelcast will teach you all you need to know to make your application data scalable.This book is a great introduction for Java developers, software architects, or developers looking to enable scalable and agile data within their applications. You should have programming knowledge of Java and a general familiarity with concepts like data caching and clustering.

  15. Instant Start Thyratron Switch.

    Science.gov (United States)

    1981-01-01

    COVEHRID Intnt Start Thyratron SicInterim 1st & 2nd Triannual R pt Swich *1 September 1979 - 1 May 1980 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR( S OTAC...White Oak Laboratory Electronic Warfare Lab, ERADCOM ATTN: Library, Code WX-21 White Sand Missile Range, Silver Spring, MD 20910 NM 88002 010 Defense...Documentation Center 001 Defense Communications Agency ATTN: DDC-TCA Technical Library Center Cameron Station (Bldg 5) Code 205 (P.A. Tolovi) Alexandria

  16. Getting started with JUCE

    CERN Document Server

    Robinson, Martin

    2013-01-01

    his book is a fast-paced, practical guide full of step-by-step examples which are easy to follow and implement.This book is for programmers with a basic grasp of C++. The examples start at a basic level, making few assumptions beyond fundamental C++ concepts. Those without any experience with C++ should be able to follow and construct the examples, although you may need further support to understand the fundamental concepts.

  17. Getting started with Simulink

    CERN Document Server

    Zamboni, Luca

    2013-01-01

    This practical and easy-to-understand learning tutorial is one big exciting exercise for students and engineers that are always short on their schedules and want to regain some lost time with the help of Simulink.This book is aimed at students and engineers who need a quick start with Simulink. Though it's not required in order to understand how Simulink works, knowledge of physics will help the reader to understand the exercises described.

  18. Mucosal Immune Responses against Live Newcastle Disease Vaccine in Immunosuppressed Chickens

    OpenAIRE

    Zhengui Yan, Yijun Du1, Qingyou Zhao, Ruifeng Fan, Wenlong Guo, Rongde Ma, Xinjian Wang and Ruiliang Zhu*

    2011-01-01

    To evaluate mucosal immunity of normal and immunosuppressed chickens vaccinated with live Newcastle disease (ND) vaccine, cyclophosphamide (CY) was used to generate immunosuppressed chickens. Normal and immunosuppressed chickens were vaccinated with the Lasota ND vaccine by ocular-nasal route at three weeks of age and challenged with virulent ND virus (vNDV) at day 28 post-vaccination (pv). The immunosuppressed chickens had significantly lower relative weight of the bursa of Fabricius and ser...

  19. Getting started with Arduino

    CERN Document Server

    Banzi, Massimo

    2011-01-01

    Arduino is the open-source electronics prototyping platform that's taken the design and hobbyist world by storm. This thorough introduction, updated for Arduino 1.0, gives you lots of ideas for projects and helps you work with them right away. From getting organized to putting the final touches on your prototype, all the information you need is here! Inside, you'll learn about: Interaction design and physical computingThe Arduino hardware and software development environmentBasics of electricity and electronicsPrototyping on a solderless breadboardDrawing a schematic diagram Getting started

  20. Getting Started with Processing

    CERN Document Server

    Reas, Casey

    2010-01-01

    Learn computer programming the easy way with Processing, a simple language that lets you use code to create drawings, animation, and interactive graphics. Programming courses usually start with theory, but this book lets you jump right into creative and fun projects. It's ideal for anyone who wants to learn basic programming, and serves as a simple introduction to graphics for people with some programming skills. Written by the founders of Processing, this book takes you through the learning process one step at a time to help you grasp core programming concepts. You'll learn how to sketch wi

  1. Getting Started with Roo

    CERN Document Server

    Long, Josh

    2011-01-01

    Spring Roo goes a step beyond the Spring Framework by bringing true Rapid Application Development to Java-just as Grails has done with Groovy. This concise introduction shows you how to build applications with Roo, using the framework's shell as an intelligent and timesaving code-completion tool. It's an ideal RAD tool because Roo does much of the tedious code maintenance. You'll get started by building a simple customer relationship management application, complete with step-by-step instructions and code examples. Learn how to control any part of the application with Roo's opt-in feature, w

  2. En god start

    DEFF Research Database (Denmark)

    Sievertsen, Hans Henrik

    I Danmark er det muligt at afvige fra reglen om, at barnet skal starte i skole det kalenderår, hvor barnet fylder 6 år. Det gør 10-15 procent af en årgang, mens 80-90 procent af børnene følger normen, og 2-3 procent starter i skole et år tidligere end normen, viser en analyse baseret på børn født i...

  3. Getting Started with Netduino

    CERN Document Server

    Walker, Chris

    2012-01-01

    Start building electronics projects with Netduino, the popular open source hardware platform that's captured the imagination of makers and hobbyists worldwide. This easy-to-follow book provides the step-by-step guidance you need to experiment with Netduino and the .NET Micro Framework. Through a set of simple projects, you'll learn how to create electronic gadgets-including networked devices that communicate over TCP/IP. Along the way, hobbyists will pick up the basics of .NET programming, and programmers will discover how to work with electronics and microcontrollers. Follow the projects in

  4. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient].

    Science.gov (United States)

    Riveiro-Barciela, Mar; Buti, María

    2015-01-01

    Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  5. Immunosuppressive drugs for the treatment of autoimmune pancreatitis.

    Science.gov (United States)

    Pezzilli, Raffaele

    2014-01-01

    Autoimmune pancreatitis is one of the few diseases of the pancreas characterized by the possibility of curing the illness using immunosuppressant drugs. In this paper, the therapeutic approach used to treat autoimmune pancreatitis patients and the clinical outcome related to each treatment modality were reviewed. Steroids are useful in alleviating the symptoms of the acute presentation of autoimmune pancreatitis, but some questions remain open, such as a shared definition of the disease's remission as well as autoimmune pancreatitis relapse, the dosage of steroids in the symptomatic phase of the disease and the duration of steroid therapy. Finally, it should be determined if other immunosuppressive nonsteroidal drugs could become first-line therapy in patients with autoimmune pancreatitis without jaundice and without atrophic pancreas.

  6. 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.

  7. [Immunosuppressants for auto-immune diseases and pregnancy].

    Science.gov (United States)

    Elefant, Elisabeth; Cournot, Marie-Pierre; Assari, Faïza; Vauzelle, Catherine

    2008-11-01

    Therapeutic stability of a systemic disease is a priority during pregnancy. To stop an effective treatment, to reduce dosages or to switch to less effective treatments might induce some loss of chance for pregnant women, and eventually harmful consequences for fetuses. Due to the teratogenic effects of some immunosuppressants, childbearing susceptible women should use effective contraception and be informed of risks in case of pregnancy. A pre-conceptional consultation is of interest, allowing an adaptation of treatment and advices before pregnancy is ongoing. Mycophenolate is highly suspected to be teratogenic in humans. Mycophenolate should not be prescribed in women of childbearing potential unless some criteria are met. Maternal (even fetal) infectious conditions can occur during immunosuppressive treatments. Therefore, obstetricians and pediatricians should be aware of the maternal treatment in order to allow adequate monitoring of the mother and the neonate.

  8. 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.

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

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24926266

  10. 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.

  11. 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.

  12. Immunomodulators and Immunosuppressants for Japanese Patients with Ulcerative Colitis

    OpenAIRE

    Shigeki Bamba; Tomoyuki Tsujikawa; Masaya Sasaki; Yoshihide Fujiyama; Akira Andoh

    2011-01-01

    Ulcerative colitis (UC) is characterized by a long-standing chronic course with remissions and exacerbations. Previously, patients do not respond to 5-aminosalicylic acid compounds and corticosteroids are considered for colectomies, however, in recent years, alternative treatments emerged for steroid-refractory or steroid-dependent UC. In this review article, we focus on immunomodulators (such as azathioprine [AZA] and 6-mercaptopurine [6-MP]) and immunosuppressants (such as cyclosporine A [C...

  13. A rationale for age-adapted immunosuppression in organ transplantation

    Science.gov (United States)

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

    2015-01-01

    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 >50 years and organs from elderly donors are more frequently utilized. 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 while the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus following transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors and mTOR 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. PMID:26244716

  14. The Healthy Start project

    DEFF Research Database (Denmark)

    Olsen, Nanna J; Buch-Andersen, Tine; Händel, Mina N

    2012-01-01

    , and to intervene not only by improving diet and physical activity, but also reduce stress and improve sleep quality and quantity. METHODS: Based on information from the Danish national birth registry and administrative birth forms, children were selected based on having either high birth weight, a mother who......-going, but it is estimated that 394 children will be included. The intervention took place over on average 11/2 year, between 2009 and 2011, and consisted of optional individual guidance in optimizing diet and physical activity habits, reducing chronic stress and stressful events and improving sleep quality and quantity....... The intervention also included participation in cooking classes and play arrangements. Information on dietary intake, meal habits, physical activity, sleep habits, and overall stress level was obtained by 4-7 day questionnaire dairies and objective measurements. DISCUSSION: If the Healthy Start project...

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

    Directory of Open Access Journals (Sweden)

    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

  16. Impact of the addition of maintenance steroids to a rapid steroid discontinuation immunosuppressive protocol following acute renal transplant rejection.

    Science.gov (United States)

    Arora, Swati; Marcus, Richard J; Dikkala, Sudharani; Sureshkumar, Kalathil K

    2009-12-01

    Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol. The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejection Compared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97). More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.

  17. SIGNIFICANCE OF THERAPY MONITORING OF IMMUNOSUPPRESSIVE MEDICINES IN RENAL TRANSPLANTATION PATIENTS

    Directory of Open Access Journals (Sweden)

    Vidojko Đorđević

    2009-04-01

    Full Text Available Immunosuppressive medicines are characterized by specific pharmacokinetic profile which requires therapy monitoring by means of measuring their blood concentrations. Therapy monitoring, by means of determining blood concentration of the medicine, enables application of an optimal individual immunosuppressive therapy. Due to its variable pharmacokinetics, and small therapeutic index and potential interaction with numerous other medicines, the post-operative monitoring of immunosuppressive medicines is an essential element of therapy protocol for renal transplantation patients. Therapy monitoring represents an efficient way to reduce adverse effects of immunosuppressive medicines and to prevent transplantation rejection, by means of adapting the doses in renal transplantation patients. Determining the concentration of immunosuppressive medicines is of special importance in the modified dosing for patients with renal insufficiency. Pharmacokinetic analysis is important for proper interpretation of immunosuppressive medicines' blood concentrations. The interpretation of the received results must be multidisciplinary, considering that there are numerous factors of variability of patients and immunosuppressive medicines.

  18. LEP dismantling starts

    CERN Multimedia

    2000-01-01

    Since the end of November, various teams have been getting stuck into dismantling the LEP accelerator and its four experiments. After making the installations safe, the dismantling and removal of 40,000 tonnes of equipment is underway. Down in the tunnel, it is a solemn moment. It is 10 o'clock on 13 December and Daniel Regin, one of those heading the dismantling work, moves in on a magnet, armed with a hydraulic machine. Surrounded by teams gathered there for a course in dismantling, he makes the first cut into LEP. The great deconstruction has begun. In little over than a year, the accelerator will have been cleared away to make room for its successor, the LHC. The start of the operation goes back to 27 November. Because before setting about the machine with hydraulic shears and monkey wrenches, LEP had first to be made safe - it was important to make sure the machine could be taken apart without risk. All the SPS beam injection systems to LEP were cut off. The fluids used for cooling the magnets and superc...

  19. Starting physiology: bioelectrogenesis.

    Science.gov (United States)

    Baptista, Vander

    2015-12-01

    From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic. Copyright © 2015 The American Physiological Society.

  20. An impressive start

    CERN Multimedia

    2011-01-01

    This has been an excellent week for the LHC, with a succession of fills rapidly increasing the number of proton bunches to 194 per beam. This has allowed the experiments to reach a peak luminosity of 2.5 × 1032 cm-2s-1, thereby surpassing the record for 2010 where we reached 2.0 × 1032 cm-2s-1. At the time of writing, the integrated luminosity delivered by the LHC in 2011 is around 28 inverse picobarns, which is already more than half of the total 2010 dataset.   These are impressive numbers, but what impresses me most is how quickly the LHC operators are now able to turn the machine around between fills, and how well LHC running has been incorporated into the overall operation of CERN’s accelerator complex. The flexibility of the LHC was illustrated on Thursday when we started a short phase of running at 1.38 TeV per beam, equivalent to the energy-per-nucleon of a lead-ion run. This lower energy data will be used by the experiments, in particular by ALICE, to compare...

  1. ATLAS starts moving in

    CERN Multimedia

    Della Mussia, S

    2004-01-01

    The first large active detector component was lowered into the ATLAS cavern on 1st March. It consisted of the 8 modules forming the lower part of the central barrel of the tile hadronic calorimeter. The work of assembling the barrel, which comprises 64 modules, started the following day. Two road trailers each with 64 wheels, positioned side by side. This was the solution chosen to transport the lower part of the central barrel of ATLAS' tile hadronic calorimeter from Building 185 to the PX16 shaft at Point 1 (see Figure 1). The transportation, and then the installation of the component in the experimental cavern, which took place over three days were, to say the least, rather spectacular. On 25 February, the component, consisting of eight 6-metre modules, was loaded on to the trailers. The segment of the barrel was transported on a steel support so that it wouldn't move an inch during the journey. On 26 February, once all the necessary safety checks had been carried out, the convoy was able to leave Buildi...

  2. 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…

  3. [Discontinuation of immunosuppressive and immunomodulatory drugs in connective tissue diseases].

    Science.gov (United States)

    Targońska-Stępniak, Bożena

    2015-01-01

    Remission in connective tissue diseases became a realistic goal of therapy nowadays. However, there is lack of recommendations on the management after achieving a remission. Chronic exposure to immunosuppressive or immunomodulatory drugs may be associated with adverse events, that is why temporal withdrawal or discontinuation of treatment is advisable. In patients with rheumatoid arthritis (RA) who achieve sustained remission lasting for 6-12 months, an attempt to withdraw biological disease modifying antirheumatic drugs (bDMARDs) may be considered. In most patients with established RA discontinuation of bDMARDs is accompanied by a disease flare, butthe risk of loss of good therapeutic response is lower in case of slowly tapering by expanding the interval between doses or reducing the dose of bDMARDs. Patients with early RA are more likely to have successful discontinuation of therapy. Discontinuation of conventional DMARDs (cDMARDs) is usually associated with a disease flare, that is why tapering of doses is advised rather than stopping cDMARDs. DMARDs free remission occurs relatively rare, more often in patients with seronegative RA and with early onset of modifying treatment. In lupus nephritis (LN) patients with persistent, long-term remission, progressive tapering of doses of immunosuppressive drugs and glucocorticoids is recommended, with treatment discontinuation as a goal. An attempt of treatment withdrawal may be taken in patients remaining in LN complete remission as a consequence of maintenance therapy for 3 years.The process of slow tapering of doses preceding discontinuation of drugs, may last several months. The therapy with antimalarial drugs may be helpful to maintain remission after the treatment discontinuation. There is few data on treatment discontinuation in patients with systemic lupus erythematosus (SLE) without kidney involvement. Immunosuppressive drugs withdrawal is usually performed in patients with stable serological and clinically

  4. 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

  5. Contribution of dendritic cells to measles virus induced immunosuppression.

    Science.gov (United States)

    Coughlin, Melissa M; Bellini, William J; Rota, Paul A

    2013-03-01

    Measles virus (MV) remains an important pathogen in children worldwide. The morbidity and mortality of MV is associated with severe immune suppression. Dendritic cells (DCs) were identified as initial target cells in vivo, and DCs were efficiently infected by MV in vitro. MV infection of DCs likely contributes to functional deficiency in these cells; therefore playing a role in MV-induced immunosuppression. DCs appeared to mature phenotypically; however, the ability of infected cells to stimulate T cells was compromised. Phenotypic maturation of infected immature DCs was partially controlled by IFN production; however, infected DCs also maintained markers of an immature phenotype such as the continued uptake of antigen and lack of expression of chemokine receptor CCR7. Furthermore, mature DCs did not appear to maintain phenotypic maturation following infection demonstrated by decreased MHC and co-stimulatory molecule expression. Several mechanisms of MV-induced DC dysfunction have been suggested, each likely contributing to the immunosuppressive effect of MV-infected DCs. Infected DCs responded aberrantly to secondary maturation stimuli such as CD40L or TLR4 stimulation. MV infection resulted in apoptosis in DC/T-cell cocultures, which may contribute to a reduced T-cell response. Additionally, the immunological synapse between infected DCs and T cells was compromised resulting in reduced T-cell interaction times and activation signaling. The mechanisms of MV contribution to DC dysfunction appear multifaceted and central to MV-induced immunosuppression. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  6. [Triple immunosuppressive therapy in the treatment of severe ulcerative colitis].

    Science.gov (United States)

    Castro, B; Crespo, J; García-Suárez, C; Fábrega, E; Casafont, F; Pons-Romero, F

    2004-01-01

    Severe episodes of steroid-refractory ulcerative colitis (UC) were considered an indication for surgery until the introduction of new immunosuppressive agents such as cyclosporine. 1) To confirm the efficacy of intravenous cyclosporine in inducing remission in severe episodes of steroid-refractory UC; 2) To analyze the efficacy of triple immunosuppressive therapy with cyclosporine, azathioprine and prednisone in the maintenance of remission induced by intravenous cyclosporine. Fourteen patients diagnosed with a severe episode of steroid-refractory UC were treated with intravenous cyclosporine at a dose of 4 mg/kg/day. In all patients, after response was induced, this regimen was substituted by oral cyclosporine plus azathioprine at a dose of 2-2.5 mg/kg/day and decreasing doses of corticoids. Neoral cyclosporine was progressively reduced until discontinuation within 3 months, coinciding with a simultaneous decrease of oral steroids. All patients showed response to intravenous cyclosporine with a significant reduction in the Truelove index calculated before and after treatment. After remission was induced, all patients followed triple immunosuppressive therapy for 3 months. In the follow-up for a mean of 24 months (range: 14-34) only two patients required admission for a new episode of UC and colectomy was finally indicated in only one. None of the 14 patients treated with cyclosporine showed severe adverse effects attributable to the drug. Intravenous cyclosporine is a safe and effective alternative in the treatment of severe episodes of steroid-refractory UC. Early initiation of oral administration associated with azathioprine is useful in maintaining response, reducing subsequent relapses and the need for colectomy during the follow-up of these patients.

  7. [Immunosuppression--a tightrope walk between iatrogenic harm and therapy].

    Science.gov (United States)

    Berchtold, P; Seitz, M

    1996-09-21

    The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna

  8. Getting started with ADIFOR

    Energy Technology Data Exchange (ETDEWEB)

    Bischof, C.; Corliss, G.; Griewank, A.; Hovland, P. [Argonne National Lab., IL (United States). Mathematics and Computer Science Div.; Carle, A. [Rice Univ., Houston, TX (United States). Center for Research on Parallel Computation

    1993-06-01

    ADIFOR is a source translator that, given a collection of subroutines to compute a function f, generates Fortran 77 code for computing the derivatives of this function. This paper describes step by step how to use ADIFOR to generate derivative code. It also describes common misunderstandings as well as workarounds for current shortcomings. Familiarity with UNIX{trademark} and Fortran 77 is assumed. Also desirable is a basic understanding of automatic differentiation. ADIFOR is a research project, and thus likely to be subject to many changes. This document will change to reflect the ADIFOR changes. New users are advised to make sure that the manual version in hand is the current up-to-date one.

  9. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda.

    Science.gov (United States)

    Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K; Porcella, Stephen F; Martens, Craig; Bruno, Daniel; Skolasky, Richard L; Okonkwo, Ozioma C; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Quinn, Thomas C

    2014-06-01

    HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results.

  10. Immunosuppressive Activity of 8-Gingerol on Immune Responses in Mice

    OpenAIRE

    Wenhui Qian; Guoren Huang; Xuming Deng; Guanghong Xie; Xue Shen; Shuang Guan; Jing Lu

    2011-01-01

    8-Gingerol is one of the principal components of ginger, which is widely used in China and elsewhere as a food, spice and herb. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. In the present study, we found that 8-gingerol suppressed lipopolysaccharide (LPS) and concanavalin A (ConA)-stimulated splenocyte proliferation in vitro. In vivo, 8-gingerol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation (P < 0.05) but a...

  11. The immunosuppressive activity and solution structures of ubiquitin fragments.

    Science.gov (United States)

    Jaremko, Lukasz; Jaremko, Mariusz; Pasikowski, Paweł; Cebrat, Marek; Stefanowicz, Piotr; Lisowski, Marek; Artym, Jolanta; Zimecki, Michał; Zhukov, Igor; Szewczuk, Zbigniew

    2009-06-01

    Recently, ubiquitin was suggested as a promising anti-inflammatory protein therapeutic. We found that a peptide fragment corresponding to the ubiquitin(50-59) sequence (LEDGRTLSDY) possessed the immunosuppressive activity comparable with that of ubiquitin. CD and NMR spectroscopies were used to determine the conformational preferences of LEDGRTLSDY in solution. The peptide mixture, obtained by pepsin digestion of ubiquitin, was even more potent than the intact protein. Although the peptide exhibited a well-defined conformation in methanol, its structure was distinct from the corresponding 50-59 fragment in the native ubiquitin molecule. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 423-431, 2009.

  12. Effect of carnosine on the immunosuppressive effect of histamine

    Energy Technology Data Exchange (ETDEWEB)

    Sharpan, Yu. V.

    1985-04-01

    This paper studies the ability of carnosine (beta-imidazole-lactate) to affect histamine-induced immunosuppression of proliferative activity of various lymphocyte subpopulations and the realization of this effect through surface histamine receptors of the cells. The experiments were carried out on mice; lymphocytes were incubated with tritium-labeled thymidine for 4 h, after which their radioactivity was determined on a scintillation counter. The results show that histamine has an inhibitory action on antigen-induced proliferation of T suppressor lymphocytes through H-2 histamine receptors, for this effect was considerably inhibited by the H-2 histamine blockers metiamide, but not by the H-1 histamine blocker mepyramine.

  13. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    to evade otherwise effective T-cell responses. A growing number of immune evasion mechanisms have been characterized mainly in solid tumors. In hematological malignancies, less is known about how different immune escape mechanisms influence tumor immune evasion and the extent of their impact on ongoing...... immune responses. The present review highlights the potential role of three well-defined immunosuppressive mechanisms in hematological malignancies: (i) inhibitory T-cell pathways (especially programmed death ligand 1/programmed death 1 (PD-L1/PD-1)), (ii) regulatory immune cells, and (iii) metabolic...

  14. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide.

    Science.gov (United States)

    Damian, Diona L; Patterson, Clare R S; Stapelberg, Michael; Park, Joohong; Barnetson, Ross St C; Halliday, Gary M

    2008-02-01

    UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub

  15. Changes in mouse circulating leukocyte numbers in C57BL/6 mice immunosuppressed with dexamethasone for Cryptosporidium parvum oocyst production.

    Science.gov (United States)

    Miller, Thomas A; Schaefer, Frank W

    2007-11-10

    The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone-tetracycline is one published method for immunosuppressing mice for the production of C. parvum oocysts. However, dexamethasone-induced immunosuppression is variable, because it is dependent on the total daily water consumption of each individual mouse. The changes in circulating leukocytes and other immune system associated organs before, during and after dexamethasone suppression were analyzed for comparison with a new single injection methylprednisolone acetate (MPA) suppression model. The dexamethasone-induced immunocompromised state was associated with a greater than 90% sustained drop in circulating T-lymphocytes, a greater than 700% increase in circulating mature segmented neutrophils and a severe depletion of circulating monocytes. The thymus and spleen decreased in size by over 80%. Oocyst shedding in suppressed mice started within 4 days of oocyst inoculation and persisted for 6 days post-dexamethasone treatment. Seven days after dexamethasone withdrawal, circulating neutrophils still were 549% higher than controls. Circulating CD3 and CD4 lymphocytes remained depressed by 85-90% while on dexamethasone and for 7 days after discontinuing dexamethasone. CD8 lymphocyte numbers initially decreased by 90%, but rose even while on dexamethasone and even with severe thymic involution. At day 7 post-dexamethasone treatment, the spleen was 119 mm(3), approximating the same size as controls. Fourteen days post-dexamethasone treatment, which was 8 days after oocyst shedding had ceased, the CD8 counts per 5000 events were only 1.6% below controls, while the CD3 and CD4 counts were still depressed by 66%. The thymus now was about one quarter smaller than the controls. The rise in circulating CD8

  16. Adherence to immunosuppressive therapy following liver transplantation: an integrative review

    Directory of Open Access Journals (Sweden)

    Ramon Antônio Oliveira

    Full Text Available ABSTRACT Objective: to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. Method: integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. Results: were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. Conclusion: there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill.

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

    DEFF Research Database (Denmark)

    Roensbo, Mette T; Blaakaer, 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...

  18. The Consistency and Reporting of Quality-of-Life Outcomes in Trials of Immunosuppressive Agents in Kidney Transplantation: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Howell, Martin; Wong, Germaine; Turner, Robin M; Tan, Ho Teck; Tong, Allison; Craig, Jonathan C; Howard, Kirsten

    2016-05-01

    Shared decision making regarding immunosuppression in kidney transplantation requires an understanding of effects on quality of life (QoL). Our aim was to review the frequency and reliability of QoL measures reported in randomized controlled trials of maintenance immunosuppression following kidney transplantation. Systematic literature review. Kidney transplant recipients enrolled in randomized trials of maintenance immunosuppression. Systematic search of the Cochrane Kidney and Transplant register, CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL databases to January 2014 identifying maintenance immunosuppression trials. An EQUATOR Network-endorsed checklist was used to assess QoL reporting and effect sizes estimated. Maintenance immunosuppression (comparative studies, dose adjustment, and agent withdrawal). Any quantitative patient-reported measure of physical, emotional, or social well-being. Of 2,272 reports, 41 (2%; involving 4,549 participants from 23 trials) included QoL outcomes using 22 instruments (8 generic, 2 disease specific, and 12 symptom specific). Reporting was incomplete for the majority with 1 (4%) addressing all 11 items of the checklist, 4 (17%) addressing clinical significance, and 15 (65%) reporting outcomes selectively. Almost all (n = 96 [95%]) effect size estimates for 101 QoL outcomes (18 trials; 3,919 participants) favored the interventions, with 37 (37%) statistically significant. In comparison, 30 (73%) clinical outcomes favored the intervention and 13 (31%) were significant. QoL outcomes are commonly secondary outcomes and may not be indexed or found using text word searches. Effect sizes were estimated from different QoL measures, populations, and interventions. The small number of trials limits the ability to identify statistically significant associations between effect size and study-/patient-related factors. QoL is infrequently reported in immunosuppression trials in kidney transplantation, appears subject to major biases, and thus

  19. 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...

  20. Starting a New Chapter

    Directory of Open Access Journals (Sweden)

    Loza-Murguia Manuel G.

    2011-08-01

    Full Text Available In this new stage we want to improve the magazine to make it useful for readers, on the one hand we intend to maintain their accreditation project of the contents of the magazine and on the other hand, the boost in indexing websites popularity, who raise the visibility and therefore coverage to authors and readers who have honored us with their support and we receive frequent visits. Obviously all the works received will remain subject to internal assessment and peer review as usual. Your acceptance will be based on significance, originality and validity of the material presented. The journal is indexed by the time DIALNET. The half-yearly, from 2012 we intend to be a leader in information that is intended to finding solutions to the problems latent, on the other side seeks to raise awareness among professionals and researchers that the publication is a prerequisite to in order to will be clear what is being done as has research in the region. The Journal of the Selva Andina Research Society is a journal founded no more than two years, having failed to publish any number of this enormous amount of material in all this time. We are currently under evaluation by the SciELO Project, Bolivia and have the confidence to be meeting all the criteria that are required to be visible on the website of international prestige. We want to be a reference publication in the journal Public areas both in the international literature (particularly in Latin America and in Bolivia. As Director and Editor in Chief continued in front of it, I thank the Board of the Supreme Council on Science and Biotechnology Research Society Selva Andina renewed confidence in me during these early years, all the items they want be published should be sent to infoselvandina@gmail.com or boliviamanloza@yahoo.com. Following the usual guidelines and rules are expressed in the publication. There is an Editorial Board comprised of leading national and international professional experts who

  1. The effect of ego depletion on sprint start reaction time.

    Science.gov (United States)

    Englert, Chris; Bertrams, Alex

    2014-10-01

    In the current study, we consider that optimal sprint start performance requires the self-control of responses. Therefore, start performance should depend on athletes' self-control strength. We assumed that momentary depletion of self-control strength (ego depletion) would either speed up or slow down the initiation of a sprint start, where an initiation that was sped up would carry the increased risk of a false start. Applying a mixed between- (depletion vs. nondepletion) and within- (before vs. after manipulation of depletion) subjects design, we tested the start reaction times of 37 sport students. We found that participants' start reaction times decelerated after finishing a depleting task, whereas it remained constant in the nondepletion condition. These results indicate that sprint start performance can be impaired by unrelated preceding actions that lower momentary self-control strength. We discuss practical implications in terms of optimizing sprint starts and related overall sprint performance.

  2. Cytomegalovirus retinitis in a seronegative patient with systemic lupus erythematosus on immunosuppressive therapy

    OpenAIRE

    Kelkar, Aditya; Kelkar, Jai; Kelkar, Shreekant; Bhirud, Shilpa; Biswas, Jyotirmoy

    2011-01-01

    Aim The purpose of this study is to report a rare case of cytomegalovirus (CMV) retinitis in a seronegative patient with systemic lupus erythematosus (SLE) on immunosuppressive therapy. Methods A seronegative patient with SLE who was on immunosuppressive therapy developed CMV retinitis. The immunosuppressive therapy was tapered, and the patient was given intravitreal ganciclovir and foscarnet in addition to systemic ganciclovir. The follow-up visits were documented. Result The patient respond...

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

    Science.gov (United States)

    Hajkova, Michaela; Hermankova, Barbora; Javorkova, Eliska; Bohacova, Pavla; Zajicova, Alena; Holan, Vladimir; Krulova, Magdalena

    2017-02-01

    Immunosuppressive drugs are widely used to treat undesirable immune reaction, however their clinical use is often limited by harmful side effects. The combined application of immunosuppressive agents with mesenchymal stem cells (MSCs) offers a promising alternative approach that enables the reduction of immunosuppressive agent doses and simultaneously maintains or improves the outcome of therapy. The present study aimed to determinate the effects of immunosuppressants on individual T cell subpopulations and to investigate the efficacy of MSC-based treatment combined with immunosuppressive drugs. We tested the effect of five widely used immunosuppressants with different action mechanisms: cyclosporine A, mycophenolate mofetil, rapamycin, and two glucocorticoids - prednisone and dexamethasone in combination with MSCs on mouse CD4+ and CD8+ lymphocyte viability and activation, Th17 (RORγt+), Th1 (T-bet+), Th2 (GATA-3+) and Treg (Foxp3+) cell proportion and on the production of corresponding key cytokines (IL-17, IFNγ, IL-4 and IL-10). We showed that MSCs modulate the actions of immunosuppressants and in combination with immunosuppressive drugs display distinct effect on cell activation and balance among different T lymphocytes subpopulations and exert a suppressive effect on proinflammatory T cell subsets while promoting the functions of anti-inflammatory Treg lymphocytes. The results indicated that MSC-based therapy could be a powerful strategy to attenuate the negative effects of immunosuppressive drugs on the immune system.

  4. Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy.

    Science.gov (United States)

    Diwan, Tayyab S; Lichvar, Alicia B; Leino, Abbie D; Vinks, Alexander A; Christians, Uwe; Shields, Adele R; Cardi, Michael A; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Kaiser, Tiffany; Woodle, E Steve; Alloway, Rita R

    2017-06-01

    Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics. This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRD patients post-LSG. Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI; 89.6%-119.6%) for AUC0-24 and 92.5% (90% CI; 80.4%-106.4%) for Cmax . PK parameters were similar between ER-TAC and IR-TAC, except for Cmin (P=.004) and Cmax (P=.04). MPA AUC0-24 was similar when given with either ER-TAC or IR-TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24 values vs those with CYP3A5*3/*3 (IR-TACPTACP=.008). Genotype did not impact MPA PK. Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Celiac Crisis in an Adult on Immunosuppressive Therapy

    Directory of Open Access Journals (Sweden)

    Owayed Al Shammeri

    2008-01-01

    Full Text Available ‘Celiac crisis’ is a rare presentation of celiac disease with manifestations that include severe diarrhea, and severe metabolic and electrolyte abnormalities. It is most frequently seen in children younger than two years of age and has been rarely described in adults. A case of a 50-year-old woman who presented with diarrhea, severe dehydration, hypokalemia and metabolic acidosis is described. Based on positive serology and small bowel biopsy, she was diagnosed with celiac disease. She also had histological evidence of lymphocytic colitis. Microscopic colitis has not previously been described in association with celiac crisis, but it may have contributed to the presentation of celiac crisis in the current case. The patient was on corticosteroids and azathioprine for autoimmune hepatitis at the time of her presentation. The current case demonstrates that modest immunosuppression does not prevent a celiac crisis, although previous reports have shown that patients may respond rapidly to high-dose corticosteroids.

  6. [Kidney transplantation before starting dialysis therapy].

    Science.gov (United States)

    Segoloni, G P; Piccoli, G B; Leonardi, G

    2002-01-01

    The rate of the clinical adoption of the so-called pre-emptive transplantation is widely different among countries. In North America it represents 25 % of the total living donor transplantations; in Norway and Sweden it is 15 % and 9 %, respectively, of all grafts performed; in Italy it is less than 1%, whilst in countries like Austria, Germany and Ireland pre-emptive transplantation is nonexistent. Some concern on this type of transplantation was raised in the Seventies and were mainly based on the evidence that uraemia has an immunosuppressive effect, which could be weaker in the pre-dialysis period. Several clinical observations in the pre- cyclosporin era supported this assumption. Starting from the Eighties, however, several studies have demonstrated that pre-emptive transplantation may yield better recipient and graft survival. Moreover, a recent retrospective study, based on higher than 8000 living donor grafts that included both treated and untreated by long-term dialysis before transplantation, showed in the pre-emptive cohort a 52 % reduction in graft losses after the first year and also a lower incidence of acute rejections. Among the advantages of pre-emptive transplantation we find better rehabilitation and especially a lower risk of job loss. The risk of poorer patient compliance, as initially pointed out, has no longer been reported and can be overcome by adequate psychological preparation of the patient. Most centres performing pre-emptive transplantation favour the use of living donor because of the general shortage of cadaver kidney vs. the increasing number of dialysed patients on the waiting list. Nevertheless, in special circumstances (national programs with short waiting lists, uremic type I diabetics, children, primary type I hyperoxaluria), some AA also recommend the use of the cadaver donor.

  7. 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

  8. Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome.

    Science.gov (United States)

    Moore, Frederick A; Phillips, Stuart M; McClain, Craig J; Patel, Jayshil J; Martindale, Robert G

    2017-04-01

    Despite tremendous advances in critical care, multiple-organ failure continues to be a significant problem. However, in recent years, far fewer patients with multiple-organ failure die early, but many experience ongoing immune dysregulation and are developing persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Most PICS patients are discharged to nonhome destinations, fail to rehabilitate, and succumb to indolent death. From a nutrition perspective, patients with PICS experience persistent inflammation-induced cachexia despite evidenced-based recommended intensive care unit nutrition support. Recent basic and translational research indicates that prolonged expansion of myeloid-derived suppressor cells plays a central role in the pathogenesis of PICS. Myeloid-derived suppressor cells express arginase 1, which depletes arginine, causing immunosuppression and impaired wound healing. This is the rationale for arginine supplementation in PICS. Other nutrition support recommendations for PICS are based on inferences made from other patient populations who experience similar persistent inflammation-induced cachexia. These include patients with established cancers, major burns, and sarcopenia. These patients experience anabolic resistance, but studies show that this can be overcome by providing higher levels of protein and certain specific amino acids. Nutrition support guidelines recommend provision of >1.5 g/kg/d of protein and indicate that higher levels may be needed. Protein composition is also important. There is good evidence that leucine can promote anabolism in patients with cancer and sarcopenia. Finally, anabolic interventions-including intensive insulin, oxandrolone, propranolol, and resistance exercise-have proven to be effective in patients with major burns and are likely relevant in combating PICS cachexia.

  9. The Data Subject

    DEFF Research Database (Denmark)

    Blume, Peter

    2015-01-01

    This article considers whether it is fortunate that data protection rules, as a starting point, apply to all physical persons as data subjects, or whether it would be better to differentiate between kinds of persons on grounds of their ability to act as a data subject. In order to protect all...... persons, it is argued that a principle of care should be part of data protection law....

  10. 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.

  11. Oral immunosuppressive drugs in the treatment of atopic dermatitis : improving performance and safety

    NARCIS (Netherlands)

    Garritsen, F.M.

    2018-01-01

    In this thesis the treatment of atopic dermatitis (AD) by the use of oral immunosuppressive drugs is discussed in order to improve the performance and safety. In the first part of this thesis we evaluated the qualitative and quantitative prescribing of oral immunosuppressive drugs in the

  12. Anti-inflammatory effect of a retrovirus-derived immunosuppressive peptide in mouse models.

    Science.gov (United States)

    Tolstrup, Martin; Johansen, Claus; Toft, Lars; Pedersen, Finn S; Funding, Anne; Bahrami, Shervin; Iversen, Lars; Østergaard, Lars; Duch, Mogens

    2013-11-18

    Short dimeric or mulitmeric peptides derived from a highly conserved stretch of amino acids from gammaretroviral envelope proteins has been found to have immunosuppressive properties in vitro. Here we test the hypothesis that such immunosuppressive peptides may serve as immunomodulatory reagents for treatment of inflammatory disorders. The anti-inflammatory effect of a synthetic retrovirus-derived immunosuppressive peptide of 17 amino acids was tested in two murine skin inflammation models, a TPA-induced acute toxic contact eczema model and an oxazolone-induced allergic contact dermatitis. Overall, mice (n = 24) treated with a topically applied cream containing the dimeric immunosuppressive peptide exhibited a reduction of 28.8% in ear thickness (range 20.1-42.5), whereas the application of a scrambled peptide dimer or a monomer of the immunosuppressive peptide remained without effect (p = 0.028). Furthermore, ear biopsies from mice treated with the dimeric immunosuppressive peptide showed a significant reduction in mRNA of the pro-inflammatory cytokines TNF-α, IL-17C, and IL-6 as well as the chemokine CXCL2 compared to mice treated with control peptides. Using two murine skin inflammation models, we show that an immunosuppressive retroviral peptide is capable of reducing inflammatory disorders. The results indicate that virus-derived immunosuppressive peptides capable of down-regulating several proinflammatory cytokines may represent a novel class of drugs for the treatment of excess inflammation.

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

    NARCIS (Netherlands)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Levesque, Herve; Nemes, Laszlo; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kuehne, Angela; Aspoeck, Gerold; Heistinger, Max; Knobl, Paul; Makipernaa, Anne; Andre, Helene; Aouba, A; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; dOiron, Roseline; Gautier, Philippe; Gay, Valerie; Girault, Stephane; Gruel, Yves; Guerin, Viviane; Hezard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Levesque, Herve; Lifermann, Francois; Marlu, Raphael; Ninet, J.; Peynet, Jocelyne; Quemeneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sebastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Huth-Kuhne, Angela; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Nemes, Laszlo; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Baudo, Francesco; Caimi, T.; Contino, L.; D'Angelo, Armando; Crippa, Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Matteo Nicola Dario; D'inca, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; De Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyak, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W.G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P.W.G; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; Del Campo, Raquel; Ferreiro Arguelles, M.; Gonzalez Boullosa, Rosario; Gutierrez Pimentel, Maria Jose; Jimenez-Yuste, Victor [No Value; Jose-Felix, Lucia; Marco, Pascual; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia z; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana Maria; Maranon, HGUG [No Value; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Tengborn, Lilian; Boehlen, Francoise; Korte, Wolfgang; Chowdary, Pratima; Collins, Peter; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan

    2012-01-01

    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

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

    NARCIS (Netherlands)

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela; Aspoeck, Gerold; Heistinger, Max; Knöbl, Paul; Makipernaa, Anne; André, Hélène; Aouba, Achille; Bellucci, Sylvia; Beurrier, Philippe; Borg, Jeanne Yvonne; Darnige, Luc; Devignes, Jean; d'Oiron, Roseline; Gautier, Philippe; Gay, Valérie; Girault, Stéphane; Gruel, Yves; Guerin, Viviane; Hézard, Nathalie; Khellaf, Mehdi; Koenig, Martial; Lifermann, François; Marlu, Raphael; Ninet, Jacques; Peynet, Jocelyne; Quéméneur, Thomas; Rothschild, Chantal; Schleinitz, Nicolas; Sigaud, Marianne; Trouillier, Sébastien; Voisin, Sophie; Giebl, Andreas; Holstein, Katharina; Loreth, Ralph M.; Steigerwald, Udo; Tiede, Andreas; Theodossiades, George; Radvanyi, Gaspar; Schlammadinger, Agota; Barillari, Giovanni; Pasca, Samantha; Caimi, Teresa; Contino, Laura; D'Angelo Armando, Crippa Luciano; Fattorini, Annalisa; Di Minno, Giovanni; Cerbone, Anna Maria; Di Minno, Dario; D'incà, Marco; Falanga, Anna; Maggioni, Anna; Lerede, Teresa; Franchini, Massimo; Gaidano, Gianluca; de Paoli, Lorenzo; Gamba, Gabriella; Ghirardi, Raffaele; Girotto, Mauro; Tasca, Delios; Grandone, Elvira; Tiscia, Giovanni; Imberti, Davide; Iorio, Alfonso; Landolfi, Raffaele; Di Gennaro, Leonardo; Novarese, Linda; Mariani, Guglielmo; Lapecorella, Mario; Marietta, Marco; Pedrazzi, Paola; Mazzucconi, Maria Gabriella; Santoro, Cristina; Morfini, Massimo; Linari, Silvia; Moratelli, Stefano; Paolini, Rossella; Piseddu, Gavino; Poggio, Renzo; Pogliani, Enrico; Carpenedo, Monica; Remiddi, Chiara; Santagostino, Elena; Mancuso, Maria Elisa; Santoro, Rita; Papaleo, Giuseppina; Schinco, Piercarla; Borchiellini, Alessandra; Valeri, Federica; Scortechini, Anna Rita; Siragusa, Sergio; Sottilotta, Gianluca; Squizzato, Alessandro; Tagariello, Giuseppe; Sartori, Roberto; Tagliaferri, Anna Rita; Di Perna, Caterina; Rivolta, Gianna Franca; Testa, Sophie; Paoletti, Oriana; Toschi, Vincenzo; Zanon, Ezio; Brandolin, Barbara; Hamulyák, Karly; Kamphuisen, Pieter; Laros-van Gorkom, Britta; Leebeek, Frank W. G.; Marten, Nijziel; Novakova, Irena; Schutgens, Roger; van der Linden, P. W. G.; van Esser, Joost; van der Meer, J.; Ypma, Paula; Campos, Manuel; Aguilar, Carlos; Altisent, Carmen; Bermejo, Nuria; del Campo, Raquel; Ferreiro Argüelles, María; González Boullosa, Rosario; Gutiérrez Pimentel, María José; Jiménez-Yuste, Victor; Jose-Felix, Lucia; Mingot, Maria Eva; Perez Garrido, Rosario; Perez Gonzale, Noelia Z.; Prieto Garcia, Manuel; Rodriguez-Huerta, Ana María; Sedano, Carmen; Tolosa Munoz, Alexandra; Baghaei, Fariba; Boehlen, Françoise; Korte, Wolfgang; Chowdary, Pratima; Evans, Gillian; Pavord, Suzanne; Rangarajan, Savita; Wilde, Jonathan

    2012-01-01

    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

  15. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Prescription drugs used in immunosuppressive... HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment...

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

    OpenAIRE

    Keshri, Gaurav K.; Gupta, Asheesh; Yadav, Anju; Sharma, Sanjeev K; Singh, Shashi Bala

    2016-01-01

    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 hea...

  17. Recombinant Human Thrombopoietin Treatment Promotes Hematopoiesis Recovery in Patients with Severe Aplastic Anemia Receiving Immunosuppressive Therapy

    Directory of Open Access Journals (Sweden)

    Huaquan Wang

    2015-01-01

    Full Text Available Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO in severe aplastic anemia (SAA patients receiving immunosuppressive therapy (IST. Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000 U, subcutaneously, three times a week. rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared. Results. Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.. Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011, resp.. The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups. Conclusion. rhTPO could improve hematologic response and promote bone marrow recovery in SAA patients receiving IST.

  18. Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

    Science.gov (United States)

    Netski, Dale M; Mao, Qing; Ray, Stuart C; Klein, Robert S

    2008-10-01

    We tested the hypothesis that HIV-related immunosuppression alters the host-hepatitis C virus (HCV) interaction, resulting in fewer amino acid-changing substitutions in HCV viral variants. Higher HCV RNA levels in persons coinfected with HIV compared with HCV infection alone suggest increased viral replication. If this increase is dependent on decreased immune selective pressure, then a reduced rate of nucleotide changes resulting in amino acid replacements (nonsynonymous changes, dN) would be expected. We investigated HCV envelope sequences over time in 79 persons with chronic HCV infection who were HIV negative (group 1) or HIV positive with (group 3) or without (group 2) severe immunodeficiency. We amplified a 1026-nt region of the HCV genome, which encodes a portion of the envelope glycoproteins E1 and E2, including hypervariable region-1 for direct sequence analysis. The overall divergence between paired sequences, dS, dN, and dN/dS, all showed no significant differences among the 3 groups. By measuring nucleotide substitutions in HCV sequences over time, we found no significant differences in the genetic divergence between HCV-monoinfected control subjects and HIV/HCV-coinfected subjects with various levels of immunodeficiency as measured by CD4+ T-cell counts.

  19. The START III bargaining space

    Energy Technology Data Exchange (ETDEWEB)

    Karas, T.H.

    1998-08-01

    The declining state of the Russian military and precarious Russian economic condition will give the US considerable advantages at the START III bargaining table. Taking the US-RF asymmetries into account, this paper discusses a menu of START III measures the US could ask for, and measures it could offer in return, in attempting to negotiate an equitable treaty. Measures the US might seek in a START III treaty include: further reductions in deployed strategic nuclear warheads, irreversibility of reductions through warhead dismantlement; beginning to bring theater nuclear weapons under mutual control, and increased transparency into the Russian nuclear weapons complex. The US may, however, wish to apply its bargaining advantages to attempting to achieve the first steps toward two long-range goals that would enhance US security: bringing theater nuclear weapons into the US-RF arms control arena, and increasing transparency into the Russian nuclear weapons complex. In exchange for measures relating to these objectives, the US might consider offering to Russia: Further strategic weapons reductions approaching levels at which the Russians believe they could maintain a degree of parity with the US; Measures to decrease the large disparities in potential deliver-system uploading capabilities that appear likely under current START II/START III scenarios; and Financial assistance in achieving START II/START III reductions as rapidly as is technically possible.

  20. Immunosuppressive therapy does not prevent the occurrence of immunoglobulin E-mediated allergies in children and adolescents with organ transplants.

    Science.gov (United States)

    Dehlink, Eleonora; Gruber, Saskia; Eiwegger, Thomas; Gruber, Diego; Mueller, Thomas; Huber, Wolf-Dietrich; Klepetko, Walter; Rumpold, Helmut; Urbanek, Radvan; Szépfalusi, Zsolt

    2006-09-01

    Allogeneic organ transplantation has become a common procedure in acute and chronic organ failure. The major limitation, rejection of the allograft by the host's immune system, can be limited by various immunosuppressive drugs that target the adaptive T-cell response. Most of these drugs are used in the treatment of allergic diseases as well, suggesting that transplant recipients under long-term immunosuppressive therapy should not develop any sensitizations or at least not show any clinical signs of allergy. Surprisingly, organ-transplanted children and adults do report symptoms of type 1 allergies, such as allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far, mainly case reports and series on the occurrence of allergy after orthotopic liver transplantation exist. Our purpose with this study was to evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated sensitizations and type 1 allergies in solid organ-transplanted children and adolescents and to identify risk factors. Seventy-eight organ-transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 +/- 5.94 years; range 1.42 to 24.25 years) were studied by standardized interviews (modified International Study of Asthma and Allergies in Childhood [ISAAC] criteria), skin-prick tests, and measurement of specific and total serum immunoglobulin E. Nineteen patients (24.4%) were found to be sensitized to > or = 1 common inhalant or food allergens, as reflected by elevated specific immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects (10.3%) additionally reported a corresponding present history of atopic diseases. No severe anaphylactic reactions were reported. No statistically significant associations with gender, kind of transplanted organ, distinct immunosuppressive therapies, and age at time of transplantation or age at investigation were found (chi2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively). Multiple

  1. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis.

    Science.gov (United States)

    Mancardi, Gianluigi; Sormani, Maria Pia; Muraro, Paolo A; Boffa, Giacomo; Saccardi, Riccardo

    2017-11-01

    In the majority of relapsing multiple sclerosis patients, the disease can be quite easily controlled by already available, approved therapies. There are, however, some aggressive cases who continue to have clinical and magnetic resonance imaging (MRI) activity in spite of the treatment. These are the cases who may now receive benefit from intense immunosuppression followed by autologous haematopoietic stem cell transplantation (aHSCT). In this review, we describe the method and the rationale of aHSCT, the more recently published studies that demonstrate its efficacy in selected multiple sclerosis cases, the problems related to safety and the transplant-related mortality risk of the procedure. A description of the ideal patient who can take advantage of aHSCT is outlined and, finally, the ongoing studies which are near to completion or are close to starting are briefly reported.

  2. Universal Design: Places to Start

    National Research Council Canada - National Science Library

    Jay Dolmage

    2015-01-01

    Beginning with a series of possible ways to introduce an essay on Universal Design for Learning, this contribution instead resolves to offer a long listing or inventory of different places to start...

  3. Immunosuppressive Activity of 8-Gingerol on Immune Responses in Mice

    Directory of Open Access Journals (Sweden)

    Wenhui Qian

    2011-03-01

    Full Text Available 8-Gingerol is one of the principal components of ginger, which is widely used in China and elsewhere as a food, spice and herb. It shows immunosuppressive activity on the immune responses to ovalbumin (OVA in mice. In the present study, we found that 8-gingerol suppressed lipopolysaccharide (LPS and concanavalin A (ConA-stimulated splenocyte proliferation in vitro. In vivo, 8-gingerol not only significantly suppressed Con A-, LPS- and OVA-induced splenocyte proliferation (P < 0.05 but also decreased the percentage of CD19+ B cells and CD3+ T cell (P < 0.05 at high doses (50, 100 mg/kg. Moreover, OVA-specific IgG, IgG1 and IgG2b levels in OVA-immunized mice were reduced by 8-gingerol at doses of 50, 100 mg/kg. These results suggest that 8-gingerol could suppress humoral and cellular immune responses in mice. The mechanism might be related to direct inhibition of sensitized T and B lymphocytes.

  4. The role of apoptosis in immunosuppression of dogs with demodicosis.

    Science.gov (United States)

    Singh, Shanker K; Dimri, Umesh; Sharma, Mahesh C; Swarup, Devendra; Sharma, Bhaskar; Pandey, Hari Om; Kumari, Priyambada

    2011-12-15

    The aim of the present study was to evaluate the status of apoptosis in peripheral blood leukocytes of dogs with demodicosis. A total of 26 dogs suffering from demodicosis, and positive for Demodex canis mites by skin scraping, participated in the study, 13 with localized demodicosis (LD) and 13 with generalized demodicosis (GD). A further 13 clinically healthy dogs, all of whom were negative for mites upon skin scraping, were used as controls. The dogs with GD revealed significantly higher (P ≤ 0.0001) percentage of leukocytes with externalization of phosphatidylserine (PS) and depolarized mitochondrial membrane potentials (ΔΨm) as compared with the dogs with LD and healthy controls. These dogs also revealed significantly lower values (P ≤ 0.0001) of hematological parameters viz. hemoglobin, total erythrocytes count total leukocytes count, lymphocytes, monocytes and neutrophils. Significantly higher (P ≤ 0.0001) percentages of leukocytes with externalization of PS and depolarized ΔΨm were also found in dogs with LD as compared with the healthy controls. These dogs also revealed significantly lower values of Hb (P ≤ 0.0001), TEC (P=0.025), TLC (P ≤ 0.0001), lymphocytes (P=0.008), monocytes (P ≤ 0.0001) and neutrophils (P=0.03). It is concluded that premature apoptosis of PBL may be implicated in the immunosuppression of the dogs with demodicosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Frequent hepatitis E in the Netherlands without traveling or immunosuppression.

    Science.gov (United States)

    Koot, H; Hogema, B M; Koot, M; Molier, M; Zaaijer, H L

    2015-01-01

    In several Western countries, silent endemic hepatitis E virus (HEV) infection is common among blood donors. Immunocompromised persons may develop chronic hepatitis E, but the relevance of endemic HEV for immunocompetent persons remains largely unknown. We investigated the immune status and travel history in cases of hepatitis E in the Netherlands. Between January 2009 and May 2014, physicians throughout the Netherlands submitted samples from 4067 hepatitis patients to Sanquin Diagnostic Services for HEV antibody testing. For the 144 patients testing positive for HEV IgM and HEV RNA, travel behavior and immune status were assessed. Complete information was obtained for 81 patients. Surprisingly, the majority of patients (52/81, 64%) were immunocompetent and did not travel outside Europe. HEV genotyping was obtained for 47 non-traveling patients, all concerned HEV genotype 3. Our findings suggest that currently in Western countries the impact of hepatitis E for non-traveling, immunocompetent persons is underestimated. Historically cases of hepatitis A, B and C, but not cases of hepatitis E, are notifiable and warrant preventive measures. However, in parts of Western Europe HEV may have become the most important source of viral hepatitis, in immunocompetent and in immunosuppressed persons. Pending measures against the ongoing transmission of HEV genotype 3 in parts of Europe, physicians should consider hepatitis E in dealing with new hepatitis patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. HHV-8 prevalence, immunosuppression and Kaposi's sarcoma in South Italy.

    Science.gov (United States)

    Crispo, A; Tamburini, M; De Marco, M R; Ascierto, P; Silvestro, P; Ronga, D; Tridente, V; Desicato, S; Carbone, S; Fabbrocini, G; Spiteri, D; Montella, M

    2001-05-01

    The identification of HHV-8 has opened the way for numerous epidemiological studies aimed at determining both the prevalence of HHV-8 in various sub-groups of the population (affected or not by KS) and at identifying possible cofactors necessary for the development of KS. We set up a study to evaluate the prevalence of HHV-8 in the South of Italy in KS cases, hospital patients and blood donors and to verify the role of immunosuppression in KS. In KS patients the prevalence of lytic and latent antigens were both 91% (29 positive cases). Lytic and latent antigens have prevalence rates of 20% and 15% respectively in hospital patients. In the donor group the rates were 16% for lytic antigens and 2% for latent antigens. The most recurrent chronic pathology in KS patients was cardiopathy (5 cases). The pathological case histories report 4 cases of Herpes Zoster, 6 of diabetes, one case of hepatitis C who had also had gonorrea. There was also a case, negative to HHV-8, who had had malaria after residing for three years in Oristano in Sardinia (a zone with high endemic malaria). Our study confirms that in Southern Italy there are relatively high prevalences of HHV-8 both in the general population and in blood donors and that immunodysregulation may be involved in the pathogenesis of KS. Other studies are necessary to confirm the sexual transmission of the HHV-8 virus and to better understand the natural history of HHV-8 infection.

  7. Orally administered immunosuppressants modify intestinal uptake of nutrients in rabbits.

    Science.gov (United States)

    Dias, V C; Madsen, K L; Yatscoff, R W; Doring, K; Thomson, A B

    1994-12-15

    The effect on intestinal nutrient transport of the immunosuppressive drugs cyclosporin A (CsA), cyclosporin G (CsG), and rapamycin (RAP) was determined in New Zealand white rabbits. Rabbits received oral doses of CsA (20 mg/kg/day), CsG (10 mg/kg/day), or RAP (1 mg/kg/day) for 10 days. Animals receiving RAP had decreased food intake and weight gain compared with controls. This correlated with a decrease in both total ileal weight and corresponding mucosal weight. CsA and CsG administration had no effect on food intake, total weight gain, or intestinal weight. Villus surface area was significantly decreased in all groups as compared with controls. Jejunal uptake of D-glucose as well as 1 medium and 4 long chain fatty acids was not affected by drug administration, while both mucosal-to-serosal and net 3-0-methylglucose fluxes were increased (P nutritional importance, as these animals gained weight normally. In addition, in these animals the changes mainly occurred in the ileum, not in the jejunum, where most glucose is absorbed, and the associated alterations in the values of the Vmax and Km* would lead to reciprocal changes in the rates of uptake of varying luminal concentrations of glucose. In contrast, these changes are likely to be of more importance in RAP-treated animals, since they failed to gain weight normally. The significance of these findings needs to be established in chronically treated animals.

  8. Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity

    Science.gov (United States)

    Klinker, Matthew W.; Marklein, Ross A.; Lo Surdo, Jessica L.; Wei, Cheng-Hong

    2017-01-01

    Human mesenchymal stromal cell (MSC) lines can vary significantly in their functional characteristics, and the effectiveness of MSC-based therapeutics may be realized by finding predictive features associated with MSC function. To identify features associated with immunosuppressive capacity in MSCs, we developed a robust in vitro assay that uses principal-component analysis to integrate multidimensional flow cytometry data into a single measurement of MSC-mediated inhibition of T-cell activation. We used this assay to correlate single-cell morphological data with overall immunosuppressive capacity in a cohort of MSC lines derived from different donors and manufacturing conditions. MSC morphology after IFN-γ stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-γ enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-γ–enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function. PMID:28283659

  9. Mucosal Immune Responses against Live Newcastle Disease Vaccine in Immunosuppressed Chickens

    Directory of Open Access Journals (Sweden)

    Zhengui Yan, Yijun Du1, Qingyou Zhao, Ruifeng Fan, Wenlong Guo, Rongde Ma, Xinjian Wang and Ruiliang Zhu*

    2011-10-01

    Full Text Available To evaluate mucosal immunity of normal and immunosuppressed chickens vaccinated with live Newcastle disease (ND vaccine, cyclophosphamide (CY was used to generate immunosuppressed chickens. Normal and immunosuppressed chickens were vaccinated with the Lasota ND vaccine by ocular-nasal route at three weeks of age and challenged with virulent ND virus (vNDV at day 28 post-vaccination (pv. The immunosuppressed chickens had significantly lower relative weight of the bursa of Fabricius and serum antibody HI titers compared to CY-untreated chickens. Compared with normal chickens, significant lower levels of IgA antibodies were detected in tracheal washings, duodenal washings and bile of immunosuppressed chickens in the whole experimental period. Immuno-histochemical experiment also showed that small numbers of IgA positive cells were found in intestinal tissues of immunosuppressed chickens at day 28 pv. There was only a partial protective effect on immunosuppressed chickens post challenge with virulent ND virus (vNDV. These findings increase our understanding of the protective mucosal immune response against ND vaccine and suggest that mucosal immunity play an important role against NDV infection.

  10. Immunosuppressive drugs modulate the replication of hepatitis B virus (HBV in a hydrodynamic injection mouse model.

    Directory of Open Access Journals (Sweden)

    Junzhong Wang

    Full Text Available Hepatitis B virus (HBV reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.

  11. 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...

  12. Efficacy of caspofungin in neutropenic and corticosteroid-immunosuppressed murine models of invasive pulmonary mucormycosis.

    Science.gov (United States)

    Lewis, Russell E; Leventakos, Konstantinos; Liao, Guangling; Kontoyiannis, Dimitrios P

    2011-07-01

    Caspofungin (CFG) was tested in neutropenic and corticosteroid-immunosuppressed mice challenged with a lethal sinopulmonary inoculum of Rhizopus oryzae. Compared to untreated controls, CFG administered at 1 mg/kg of body weight/day significantly improved survival (54% versus 19%; P = 0.003) and reduced median R. oryzae fungal burden by 1.5 log(10) for conidial equivalent DNA in neutropenic but not corticosteroid-immunosuppressed animals. CFG administered at 16 mg/kg/day was not significantly better than a saline control for treatment of invasive pulmonary mucormycosis (IPM) in either neutropenic or corticosteroid-immunosuppressed animals.

  13. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naïve recipients

    Science.gov (United States)

    Yusuf, Nabiha; Katiyar, Santosh K; Elmets, Craig A

    2013-01-01

    Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4+ and CD8+ T-cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, non-tumor bearing CD4 knockout (CD4−/−) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg/kg Pc4, 110 J/cm2 light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4−/− mice as compared to WT mice. We next examined the role of CD8+ T-cells in Pc4-PDT induced immunosuppression using CD8−/− mice following the same treatment regimen used for CD4−/− mice. Similar to CD4−/− mice, CD8−/− mice exhibited less immunosuppression than WT mice. Pc4-PDT induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (p<0.05) and was mediated primarily by T cells, although macrophages were also found to play a role. Procedures that limit PDT induced immunosuppression but do not affect PDT induced regression of tumors may prove superior to PDT alone in promoting long term anti-tumor responses. PMID:18208456

  14. Dimeric analogs of immunosuppressive decapeptide fragment of ubiquitin.

    Science.gov (United States)

    Kluczyk, Alicja; Cydzik, Marzena; Biernat, Monika; Bąchor, Remigiusz; Pasikowski, Paweł; Stefanowicz, Piotr; Artym, Jolanta; Zimecki, Michał; Szewczuk, Zbigniew

    2012-07-01

    Our previous studies revealed that ubiquitin and its decapeptide fragment with the LEDGRTLSDY sequence, located on the exposed molecule loop, strongly suppressed the immune response. This suggested that the loop may serve as a functional epitope of ubiquitin molecule and that a possible mechanism of biological action of the synthesized peptides is associated with interfering in interactions of ubiquitin with other molecules. Ubiquitin is known to exist in oligomeric forms, which can interact with various oligomeric receptors. We designed and synthesized new dimeric analogs of the ubiquitin fragment, to probe whether dimeric peptides may have higher affinity towards the ubiquitin receptors responsible for immunosuppression, which are believed to form oligomeric structures. Three dimerization strategies, N-terminus to N-terminus, C-terminus to C-terminus, and N-terminus to C-terminus (head-to-tail) via PEG derivatives were used to synthesize the dimeric peptides on solid support. In the course of our research, we developed a new and straightforward procedure of dimerization where α-amino groups of the C-terminal lysine residues of two peptide fragments were linked by PEG spacer directly on solid support. The effect of dimeric analogs on the immunological response was tested in the AFC in vitro experiment. The immunological tests showed that the head-to-tail dimerization caused a more profound increase in the biological activity than other tested dimerization methods. Our results suggest that such orientation of peptide components may correspond to orientation of the hypothetic ubiquitin receptors responsible for the immunomodulatory activity. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  15. MS14, a Marine Herbal Medicine, an Immunosuppressive Drug in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Ebrahimi Kalan, Abbas; Soleimani Rad, Jafar; Kafami, Laya; Mohamadnezhad, Daryoush; Khaki, Amir Afshin; Mohammadi Roushandeh, Amaneh

    2014-07-01

    Cytokines are secreted signaling proteins which play essential roles in immune responses during experimental autoimmune encephalomyelitis (EAE), a demyelinating model that mimics many features of multiple sclerosis (MS). Interleukin 6 (IL-6) is a multifunctional cytokine produced by different cells, mediating inflammatory reactions and immune-mediated processes. Several studies have described immunosuppressive potentials of several herbal medicines. MS14 as an Iranian marine herbal medicine has anti-inflammatory and immunomodulatory activities. The present study investigated the immunosuppressive potential of MS14 as an herbal drug as well as the IL-6 level in EAE model. We hope it will be a new approach for neurologic diseases and autoimmune originated diseases therapy. The present experimental study was a collaboration between Department of Anatomical Sciences of Tabriz University of Medical Sciences and Shefa Neuroscience Research Center of Tehran. We used 30 C57BL/6 mice. The animals were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce EAE and treated with MS14-containing (30%) diets. Subjects were selected by simple random sampling and then they were randomly allocated to two groups. EAE symptoms were assessed using the standard 10-point EAE scoring system from the seventh to the 35th day after immunization. Afterwards, the spleen was removed and its cells were cultured with or without MOG 35-55; then, the IL-6 level was analyzed by ELISA. In addition, histopathological studies were carried out for demyelination lesion evaluation in the spinal cord. MS14 significantly improved clinical symptoms of EAE compared with the control (P < 0.05). It also suppressed proliferative responses of T cells and decreased IL-6 expression (16.93 ± 2.7 vs. 21.4 ± 3.33) (P < 0.05). Our results strongly suggested that IL-6 as a potential molecule could have a role in neuroimmunology and neuroinflammation, which is in congruent with previous studies. Therefore

  16. When to Start Antiretroviral Therapy

    Science.gov (United States)

    ... Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets When to Start Antiretroviral Therapy Search ... Vaccine? What is a Preventive HIV Vaccine? HIV/AIDS Clinical Trials ... HIV Treatment HIV Treatment: The Basics Just Diagnosed: Next Steps ...

  17. Starting School: A Community Endeavor

    Science.gov (United States)

    Dockett, Sue; Perry, Bob

    2008-01-01

    Much of the current debate about children's transition to school focuses on children's readiness for school. Indeed, Boethel (2004, p. 17) describes transition as the "focal point of readiness." Typically, this focus extends to considering children's competencies--particularly their skills and abilities--at the time of starting school.…

  18. Off to a Good Start.

    Science.gov (United States)

    Hoffman, Carl

    1994-01-01

    Caring Start is a mobile-clinic program that provides prenatal care, well-baby clinics, childhood immunizations, counseling services, and contraceptives to rural poor families in northwest Pennsylvania. Before the mobile clinic, many rural women (mostly teenagers) went without prenatal health care due to lack of transportation. (LP)

  19. Emergence of cutaneous neosporosis in a dog receiving immunosuppressive therapy: molecular identification and management.

    Science.gov (United States)

    Legnani, Sara; Pantchev, Nikola; Forlani, Annalisa; Zini, Eric; Schares, Gereon; Balzer, Jörg; Roccabianca, Paola; Ferri, Filippo; Zanna, Giordana

    2016-02-01

    Neosporosis is a multisystemic disease caused by the intracellular protozoan Neospora caninum. In dogs the disease primarily affects the central nervous system. Canine cutaneous neosporosis is a rare condition often associated with old age or concurrent immunosuppressive treatments for different underlying conditions. A 10-year-old female spayed golden retriever dog affected by primary immune-mediated myelofibrosis and treated with immunosuppressive therapies for 6 weeks that developed severe cutaneous lesions. Definitive diagnosis was based on several investigation techniques including serology (immunoblotting), immunohistochemistry (IHC), species-specific conventional and real-time PCR, and DNA sequencing. Remission of cutaneous neosporosis was obtained with the administration of clindamycin while the concurrent immunosuppressive therapy was maintained to manage the underlying primary condition. To the best of the authors' knowledge this is the first report of species-specific PCR and DNA sequencing used as diagnostic methods for canine cutaneous neosporosis emerging in a dog receiving immunosuppressive therapy. © 2015 ESVD and ACVD.

  20. 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.

  1. Cytomegalovirus retinitis in a seronegative patient with systemic lupus erythematosus on immunosuppressive therapy.

    Science.gov (United States)

    Kelkar, Aditya; Kelkar, Jai; Kelkar, Shreekant; Bhirud, Shilpa; Biswas, Jyotirmoy

    2011-09-01

    The purpose of this study is to report a rare case of cytomegalovirus (CMV) retinitis in a seronegative patient with systemic lupus erythematosus (SLE) on immunosuppressive therapy. A seronegative patient with SLE who was on immunosuppressive therapy developed CMV retinitis. The immunosuppressive therapy was tapered, and the patient was given intravitreal ganciclovir and foscarnet in addition to systemic ganciclovir. The follow-up visits were documented. The patient responded to the treatment and there was complete resolution. CMV retinitis is a rapidly progressive condition and patients on immunosuppressive therapy should be referred to an ophthalmologist for periodic check-up for early diagnosis and treatment of this devastating ophthalmic condition. For clinically resistant CMV retinitis in seronegative patients with SLE, a combination therapy of intravitreal foscarnet with oral and intravenous ganciclovir is useful.

  2. [Immunological aspects of corneal graft rejection and own experience in immunosuppressive therapy in high risk patients].

    Science.gov (United States)

    Kamińska, Anna; Szaflik, Jerzy; Minkiewicz-Timler, Grazyna; Sybilska, Małgorzata; Pawluczyk-Dyjecińska, Martyna; Smolarek, Monika

    2004-01-01

    The aim of the study was to present factors responsible for immune privilege of corneal graft, pathogenesis of immunological corneal graft rejection, and the influence of immunosuppressive therapy on keeping clarity of corneal graft. We also present retrospective evaluation of prophylactic immunosuppressive therapy in high-risk patients and in cases of graft rejection, in group of patients after corneal transplantation performed in Department of Ophthalmology in years 2001-2003. 349 cases of penetrating keratoplasty, lamellar or penetrating with limbal transplantation were analyzed. Condition requiring keratoplasty, surgical procedures, profile of immunosuppressive therapy, number of recurrences of corneal graft rejection and changes of visual acuity were evaluated. Immunosuppressive therapy with oral corticosteroids and systemic Cyclosporine allow to keep clarity of corneal graft and useful visual acuity in 60% cases of high-risk patients.

  3. Optimizing immunosuppression with mTOR inhibitors in renal transplant recipients

    NARCIS (Netherlands)

    Moes, Dirk Jan Alie Roelof

    2014-01-01

    The aim of this thesis was to optimize immunosuppressive therapy, especially everolimus therapy in renal transplantation recipients by identifying pharmacological and pharmacogenetic risk factors influencing pharmacokinetics, and dynamics such as side effects and patient outcome. Therapeutic Drug

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

    Directory of Open Access Journals (Sweden)

    Han Zhipeng

    2012-03-01

    Full Text Available 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 been reported to involved in the immunosuppressive effects by MSCs such as TGF-β, HGF, PGE2, IDO and iNOS. These results suggest that MSCs can be used in the therapy of immune disorder diseases, prevention of organ transplantation rejection and tissue injury. In recent study, we demonstrated that MSCs in tumor inflammatory microenvironment might be elicited of immunosuppressive function. Thus, the application of MSCs in cancer therapy might have negative effect by helping tumor cells escaping from the immune surveillance.

  5. The role of donor bone marrow infusions in withdrawal of immunosuppression in adult liver allotransplantation.

    Science.gov (United States)

    Tryphonopoulos, Panagiotis; Tzakis, Andreas G; Weppler, Debbie; Garcia-Morales, Rolando; Kato, Tomoaki; Madariaga, Juan R; Levi, David M; Nishida, Seigo; Moon, Jang; Selvaggi, Gennaro; Regev, Arie; Nery, Caio; Bejarano, Pablo; Khaled, Amr; Kleiner, Gary; Esquenazi, Violet; Miller, Joshua; Ruiz, Philip; Ricordi, Camillo

    2005-03-01

    We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.

  6. 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.

  7. Non-typhoidal Salmonella bacteraemia: Epidemiology, clinical characteristics and its' association with severe immunosuppression

    Directory of Open Access Journals (Sweden)

    Fatt Quek

    2009-05-01

    Full Text Available Abstract Background Non-typhoidal Salmonella (NTS is increasingly recognized as an important pathogen associated with bacteraemia especially in immunosuppressed patients. However, there is limited data specifically describing the clinical characteristics and outcome amongst the immunosuppressed patients. Methods A total of 56,707 blood culture samples and 5,450 stool samples were received by the microbiology laboratory at a tertiary referral hospital in Malaysia, during a 4-year study period. Out of these samples, 55 non-duplicate NTS isolates were identified from blood and 121 from stool. A retrospective analysis of the 55 patients with NTS bacteraemia was then conducted to determine the predominant NTS serovars causing bacteraemia and its' blood invasive potential, epidemiological data, clinical characteristics and antimicrobial susceptibility. Patients were then grouped as immunosuppressed and non-immunosuppressed to determine the association of severe immunosuppression on clinical features. Data was analyzed using the Statistical Package for Social Sciences (SPSS version 15.0 using the non-parametric Mann-Whitney test, Fisher's exact test or Chi-squared test. The odds ratio (OR and its 95% confidence intervals (CI were calculated. The P-value Results Out of 55 NTS bacteraemia cases identified, 81.8% (45/55 were community-acquired. Salmonella enterica serovar Enteritidis had the highest blood invasiveness. An extra-intestinal focus of infection was noted in 30.9% (17/55 of the patients, most commonly involving the lungs and soft tissue. 90.9% (50/55 of the patients had an underlying disease and 65.5% (36/55 of the patients had severe clinical immunosuppressive condition with malignancy and HIV being the most common. Immunosuppressed patients had higher mortality (P = 0.04, presented more commonly with primary bacteraemia (P = 0.023, leukopenia (P = 0.001 and opportunistic infections (P = 0.01. In contrast, atherosclerotic conditions (P = 0

  8. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  9. Immunizations in Children with Inflammatory Bowel Disease Treated with Immunosuppressive Therapy

    OpenAIRE

    Lu, Ying; Bousvaros, Athos

    2014-01-01

    The vast majority of patients with inflammatory bowel disease (IBD) will receive immunosuppressive therapy at some point for their disease, whether for the short term (such as a course of corticosteroids) or long term (such as maintenance therapy with immunomodulators or biologics). The systemic immunosuppression places patients at increased risk for infections. Therefore, it is important that patients are up-to-date with immunizations to minimize vaccine-preventable infections. However, the ...

  10. Visual loss resulting from immunosuppressive therapy in patients with syphilitic uveitis

    OpenAIRE

    Afonso, Vivian Cristina Costa; Nascimento, Heloisa; Belfort, Rubens M.; Sato, Emilia Inoue; Muccioli, Cristina; Belfort Jr., Rubens

    2015-01-01

    ABSTRACT Permanent visual loss can be caused by improper use of immunosuppressive therapy in cases of uveitis without differential diagnosis of syphilitic uveitis. We present four cases of syphilitic uveitis that were incorrectly diagnosed as being secondary to rheumatic diseases and were subsequently treated with immunosuppressive therapy, leading to permanent visual loss. These cases highlight the importance of ruling out syphilis in the differential diagnosis of inflammatory ocular disease...

  11. 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.

  12. Immunosuppressant prescription pattern and trend in kidney transplantation: A multicenter study in Korea.

    Science.gov (United States)

    Chang, Ji-Yeun; Yu, Jihyun; Chung, Byung Ha; Yang, Jaeseok; Kim, Sung-Joo; Kim, Chan-Duck; Lee, Sang-Ho; Lee, Jong Soo; Kim, Joong Kyung; Jung, Cheol Woong; Oh, Chang Kwon; Yang, Chul Woo

    2017-01-01

    The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear. We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy. Most patients (n = 621, 97.6%) received induction therapy often comprising basiliximab (n = 542, 85.2%). The triple therapy including calcineurin inhibitor, mycophenolic acid, and steroids was the major initial maintenance immunosuppression (n = 518, 81.4%), but its proportion decreased by 14% (81.4% to 67.5%) after 1 year. Almost 40% of patients changed immunosuppressive regimen during the 1-year follow-up, most often at an early period (60.2% within the first 4 months). The primary reason for the change was gastrointestinal discomfort (n = 113, 29.8%), followed by infection (112, 29.6%). The most common changing pattern was mycophenolic acid withdrawal (n = 155, 39.1%). The initial immunosuppressive regimen is prone to change within the first year of kidney transplantation. Further studies are needed to evaluate the benefits and risks in patients who changed immunosuppressants.

  13. Immunosuppressant prescription pattern and trend in kidney transplantation: A multicenter study in Korea.

    Directory of Open Access Journals (Sweden)

    Ji-Yeun Chang

    Full Text Available The actual prescription pattern of immunosuppressive agents in kidney transplantation is unclear.We investigated the pattern and trend of immunosuppressive treatment for kidney transplant patients in South Korea. A total of 636 patients at nine transplant centers were enrolled and followed for one year. We reviewed medical records and evaluated induction therapy, as well as the changing pattern and cause of maintenance therapy.Most patients (n = 621, 97.6% received induction therapy often comprising basiliximab (n = 542, 85.2%. The triple therapy including calcineurin inhibitor, mycophenolic acid, and steroids was the major initial maintenance immunosuppression (n = 518, 81.4%, but its proportion decreased by 14% (81.4% to 67.5% after 1 year. Almost 40% of patients changed immunosuppressive regimen during the 1-year follow-up, most often at an early period (60.2% within the first 4 months. The primary reason for the change was gastrointestinal discomfort (n = 113, 29.8%, followed by infection (112, 29.6%. The most common changing pattern was mycophenolic acid withdrawal (n = 155, 39.1%.The initial immunosuppressive regimen is prone to change within the first year of kidney transplantation. Further studies are needed to evaluate the benefits and risks in patients who changed immunosuppressants.

  14. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen

    2012-01-01

    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa...

  15. Sigmoid Colectomy for Acute Diverticulitis in Immunosuppressed vs Immunocompetent Patients: Outcomes From the ACS-NSQIP Database.

    Science.gov (United States)

    Al-Khamis, Ahmed; Abou Khalil, Jad; Demian, Marie; Morin, Nancy; Vasilevsky, Carol-Ann; Gordon, Philip H; Boutros, Marylise

    2016-02-01

    The management of acute diverticulitis in immunosuppressed patients is increasingly debated. The appropriate timing and type of operation remains controversial. This study examines the impact of immunosuppression on mortality and morbidity following colectomies for diverticulitis in the emergency and elective settings. With the use of the American College of Surgeons National Surgical Quality Improvement Program database, the outcomes of immunosuppressed compared with immunocompetent patients who underwent colectomy for acute diverticulitis were compared. The multi-institutional database was queried for patients who underwent colectomy for acute diverticulitis from 2005 to 2012. The impact of immunosuppression on mortality, major morbidity, organ space infection, infectious complications, and wound dehiscence was assessed. Of 26,987 patients, 1332 were immunosuppressed and 25,655 were immunocompetent; 4271 patients had emergency (596 immunosuppressed and 3675 immunocompetent) and 22,716 patients had elective (736 immunosuppressed and 21,980 immunocompetent) colectomies for diverticulitis. In both groups, mortality and major morbidity were significantly higher in the emergency (immunosuppressed 16% and 45%, immunocompetent 4% and 28%) compared with the elective setting (immunosuppressed 2% and 25%, immunocompetent 0.4% and 12%), p < 0.001. On multivariate regression for the emergency setting, immunosuppression significantly increased mortality (OR, 1.79; 95% CI, 1.17-2.75) and did not significantly increase morbidity. On multivariate regression for the elective setting, mortality was similar in immunosuppressed and immunocompetent groups; however, major morbidity (OR, 1.46; 95% CI, 1.17-1.83) and wound dehiscence (OR, 2.69; 95% CI, 1.63-4.42) were significantly increased in immunosuppressed compared with immunocompetent patients. The retrospective design and standardized outcomes are based on heterogeneous data. Emergency colectomy for diverticulitis is associated

  16. Calcineurin phosphatase activity and immunosuppression. A review on the role of calcineurin phosphatase activity and the immunosuppressive effect of cyclosporin A and tacrolimus

    DEFF Research Database (Denmark)

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

    2003-01-01

    The mode of immunosuppressive action of tacrolimus (FK506) and cyclosporin A has been elucidated. Both drugs bind to proteins in the cytoplasm to form complexes, which in turn inhibit the phosphatase activity of calcineurin, an important limiting step in the activation of T cells. The association...

  17. Adherence to immunosuppressive therapy following liver transplantation: an integrative review.

    Science.gov (United States)

    Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

    2016-08-29

    to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. investigar as evidências disponíveis na literatura sobre a não adesão à terapêutica imunossupressora entre pacientes submetidos ao transplante de fígado. revisão integrativa da literatura, que incluiu investigações cuja amostra era composta por pacientes com idade igual ou superior a 18 anos, submetidos a transplante de fígado. Excluíram-se as que continham pacientes submetidos a transplantes de múltiplos órgãos. Para a seleção dos artigos foram consultadas as bases Medline/Pubmed, CINAHL, LILACS, Scopus e Embase. O período de busca determinado correspondeu à data inicial de indexação das

  18. Getting started with Drupal commerce

    CERN Document Server

    Jones, Richard

    2013-01-01

    A simple yet concise step-by-step tutorial that starts from scratch and builds up your knowledge with focused examples that will enable you to set up and run an e-commerce website.This book is for beginners and will take you through the installation and configuration of Drupal Commerce from scratch, but some familiarity with Drupal 7 will be an advantage. All examples are based on development on a local computer - you do not need a hosted Drupal environment.

  19. Getting started with Twitter Flight

    CERN Document Server

    Hamshere, Tom

    2013-01-01

    Getting Started with Twitter Flight is written with the intention to educate the readers, helping them learn how to build modular powerful applications with Flight, Twitter's cutting-edge JavaScript framework.This book is for anyone with a foundation in JavaScript who wants to build web applications. Flight is quick and easy to learn, built on technologies you already understand such as the DOM, events, and jQuery.

  20. School start times for adolescents.

    Science.gov (United States)

    2014-09-01

    The American Academy of Pediatrics recognizes insufficient sleep in adolescents as an important public health issue that significantly affects the health and safety, as well as the academic success, of our nation's middle and high school students. Although a number of factors, including biological changes in sleep associated with puberty, lifestyle choices, and academic demands, negatively affect middle and high school students' ability to obtain sufficient sleep, the evidence strongly implicates earlier school start times (ie, before 8:30 am) as a key modifiable contributor to insufficient sleep, as well as circadian rhythm disruption, in this population. Furthermore, a substantial body of research has now demonstrated that delaying school start times is an effective countermeasure to chronic sleep loss and has a wide range of potential benefits to students with regard to physical and mental health, safety, and academic achievement. The American Academy of Pediatrics strongly supports the efforts of school districts to optimize sleep in students and urges high schools and middle schools to aim for start times that allow students the opportunity to achieve optimal levels of sleep (8.5-9.5 hours) and to improve physical (eg, reduced obesity risk) and mental (eg, lower rates of depression) health, safety (eg, drowsy driving crashes), academic performance, and quality of life. Copyright © 2014 by the American Academy of Pediatrics.

  1. Starting apparatus for internal combustion engines

    Science.gov (United States)

    Dyches, G.M.; Dudar, A.M.

    1995-01-01

    This report is a patent description for a system to start an internal combustion engine. Remote starting and starting by hearing impaired persons are addressed. The system monitors the amount of current being drawn by the starter motor to determine when the engine is started. When the engine is started the system automatically deactivates the starter motor. Five figures are included.

  2. Pharmacokinetics, pharmacodynamics, and pharmacogenomics of immunosuppressants in allogeneic hematopoietic cell transplantation: Part I

    Science.gov (United States)

    McCune, Jeannine S.; Bemer, Meagan J.

    2015-01-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic hematopoietic cell transplant (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared to solid organ transplant, alloHCT is unique because of the potential for bi-directional reactions (i.e., host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATG) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants’ pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source, and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressives deserves to be explored in depth. The development of sophisticated

  3. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses

    Science.gov (United States)

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-01-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  4. Use of transfer factor in immunosuppressed surgical patients.

    Science.gov (United States)

    Garritano, Celia Regina Oliveira; Nubila, Francesco di; Couto, Renata M; Fiorelli, Rossano Kepler Alvim; Aun, Luciana Berti

    2017-01-01

    to evaluate the action of Transfer Factor on the immune response of patients with malignant neoplasm submitted to surgery, chemotherapy and radiotherapy. we analyzed the variations of leukocytes, total lymphocytes, T-lymphocytes and CD4 counts in 60 patients submitted to immunostimulation with a single, daily dose of 0.5mg sublingual Transfer Factor, started simultaneously with chemotherapy and/or radiotherapy. there were statistically significant increases in the counts of all cell lines studied, more pronounced after 12 months of use of the medication. the Transfer Factor restored immune response and showed no side effects.

  5. 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

  6. Getting Started with Hibernate 3

    CERN Document Server

    Elliott, James

    2008-01-01

    Hibernate has clearly arrived. Are you ready to benefit from its simple way of working with relational databases as Java objects? This PDF updates the introductory material from the award-winning Hibernate: A Developer's Notebook to teach you how to jump right in and get productive with the current release of Hibernate. You'll be walked through the ins and outs of setting up Hibernate and some related tools that make it easier to use--and that may give you new ideas about how to store information in your Java programs. In short, this PDF gives you exactly the information you need to start u

  7. Getting started With Amazon Redshift

    CERN Document Server

    Bauer, Stefan

    2013-01-01

    Getting Started With Amazon Redshift is a step-by-step, practical guide to the world of Redshift. Learn to load, manage, and query data on Redshift.This book is for CIOs, enterprise architects, developers, and anyone else who needs to get familiar with RedShift. The CIO will gain an understanding of what their technical staff is working on; the technical implementation personnel will get an in-depth view of the technology, and what it will take to implement their own solutions.

  8. Association of HIV-Induced Immunosuppression and Clinical ...

    African Journals Online (AJOL)

    The participants had a complete clinical evaluation, thick and thin blood films for malaria parasites and CD4 cell count quantification. Clinical malaria was defined as having fever (temperature ≥ 37.5oC or history of fever within 48 hours) and a malaria parasite density above the median value obtained for subjects with ...

  9. The start of the harvest

    CERN Multimedia

    2011-01-01

    The first major particle physics summer conference has just started this week in Grenoble. After the Quark-Matter conference, the Europhysics Conference on High-Energy Physics marks the start of a promising harvest for the LHC experiments.   For the first time, the collaborations will be presenting their latest results based on all luminosity taken until end of June, which will provide more precise measurements in many areas. Thanks to the excellent performance of the LHC, the experiments have already accumulated a substantial quantity of data allowing them to push back the known limits and refine measurements in many fields ranging from b physics to the search for the Higgs boson and for dark matter. At the time of writing, the LHC collaborations are about to present these new results in an energy range which has never previously been explored. I have congratulated all the teams involved in getting the LHC into operation in record time with great efficiency. Today I would like to acknowledge the...

  10. Rapid starting methanol reactor system

    Science.gov (United States)

    Chludzinski, Paul J.; Dantowitz, Philip; McElroy, James F.

    1984-01-01

    The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

  11. Starting point anchoring effects in choice experiments

    DEFF Research Database (Denmark)

    Ladenburg, Jacob; Olsen, Søren Bøye

    Anchoring is acknowledged as a potential source of considerable bias in Dichotomous Choice Contingent Valuation studies. Recently, another stated preference method known as Choice Experiments has gained in popularity as well as the number of applied studies. However, as the elicitation...... of preferences in Choice Experiments resembles the Dichotomous Choice format, there is reason to suspect that Choice Experiments are equally vulnerable to anchoring bias. Employing different sets of price levels in a so-called Instruction Choice Set presented prior to the actual choice sets, the present study...... finds that preferences elicited by Choice Experiments can be subject to starting point anchoring bias. Different price levels provoked significantly different distributions of choice in two otherwise identical choice set designs. On a more specific level, the results indicate that the anchoring...

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

    Science.gov (United States)

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

    2017-03-01

    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. 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. 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 and Gastroenterology and Hepatology. Nineteen (76%) units had a strategy regarding treatment for reactivation before initiating immunosuppressive therapy in case of positive HBV serology. It was not possible to determine the number of HBV reactivations as this was not registered in the ICD-10 system. The Danish Medicines Agency had one report of reactivation. A minority of the units had screening guidelines for HBV reactivation that were in line with the guidelines of the national scientific societies. Screening in accordance with these recommendations should be a goal for all Danish units in order to prevent HBV reactivation. none. not relevant.

  13. The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation.

    Science.gov (United States)

    Rangel, Erika B

    2012-12-01

    Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups. This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed. Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.

  14. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans.

    Science.gov (United States)

    Yiasemides, Eleni; Sivapirabu, Geetha; Halliday, Gary M; Park, Joohong; Damian, Diona L

    2009-01-01

    Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.

  15. Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Natarajaswamy Kalleda

    2016-07-01

    Full Text Available Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.

  16. Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.

    Science.gov (United States)

    Aguiar, Diego; Martínez-Urbistondo, Diego; Baroja-Mazo, Alberto; de la Mata, Manuel; Rodríguez-Perálvarez, Manuel; Rubín, Angel; Puchades, Lorena; Serrano, Trinidad; Montero, Jessica; Cuadrado, Antonio; Casafont, Fernando; Salcedo, Magdalena; Rincón, Diego; Pons, Jose A; Herrero, Jose I

    2017-05-02

    BACKGROUND Long-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice. MATERIAL AND METHODS In this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function. RESULTS Fifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients. CONCLUSIONS Immunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers.

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

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    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.

  18. SUBJECT INDEX

    Indian Academy of Sciences (India)

    Subject Index. Variation of surface electric field during geomagnetic disturbed period at Maitri, Antarctica. 1721. Geomorphology. A simple depression-filling method for raster and irregular elevation datasets. 1653. Decision Support System integrated with Geographic. Information System to target restoration actions in water-.

  19. Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity.

    Science.gov (United States)

    Yamahara, J; Shimoda, H; Matsuda, H; Yoshikawa, M

    1996-09-01

    Potent immunosuppressants, the dimeric sesquiterpene thioalkaloids, 6-hydroxythiobinupharidine (2), 6,6'-dihydroxythiobinupharidine (3), 6-hydroxythionuphlutine B (5) and 6'-hydroxythionuphlutine B (6), were isolated from a natural medicine, Nupharis Rhizoma, the rhizoma of Nuphar pumilum (TIMM.) DC., through bioassay-guided separation together with five quinolizidine alkaloids (8, 9, 10, 11, 12). Dimeric sesquiterpene thioalkaloids (2, 3, 5, 6) were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mice spleen cells at 10(-6) M concentration. At this concentration, 2, 5 and 6 were found to exhibit no cytotoxicity to mice spleen cells, and 3 also showed only a little cytotoxicity. In addition, the inhibitory activity of several Nuphar alkaloids, dimeric sesquiterpene thioalkaloids (1, 4, 7, 8), and monomeric sesquiterpene alkaloids (9, 10, 11, 12) on anti-sheep erythrocyte plaque forming cell formation was examined and some structural requirement of Nuphar alkaloid for immunosuppressive activity was determined.

  20. Ingredients: where pet food starts.

    Science.gov (United States)

    Thompson, Angele

    2008-08-01

    Every clinician is asked "What should I feed my pet?" Understanding the ingredients in pet food is an important part of making the best recommendation. Pet food can be as simple as one ingredient or as complicated as containing more than 60 ingredients. Pet food and its ingredients are regulated by the Food and Drug Administration and state feed officials. Part of that regulation is the review and definition of ingredients. Existing ingredients change and new ingredients become available so the need for ingredient definitions grows. Ingredients for product formulations are chosen based on their nutrient content, digestibility, palatability, functionality, availability, and cost. As an example, a typical, nutritionally complete dry dog food with 42 ingredients is examined and the ingredients are discussed here. Safe, healthy pet food starts with safe ingredients sourced from well-monitored suppliers. The ultimate goal of both veterinarians and pet food manufacturers is the same--long healthy lives for dogs and cats.

  1. 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.

  2. Modified Aloe Polysaccharide Restores Chronic Stress-Induced Immunosuppression in Mice.

    Science.gov (United States)

    Lee, Youngjoo; Im, Sun-A; Kim, Jiyeon; Lee, Sungwon; Kwon, Junghak; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2016-09-30

    Chronic stress generally experienced in our daily lives; is known to augment disease vulnerability by suppressing the host immune system. In the present study; the effect of modified Aloe polysaccharide (MAP) on chronic stress-induced immunosuppression was studied; this Aloe compound was characterized in our earlier study. Mice were orally administered with MAP for 24 days and exposed to electric foot shock (EFS; duration; 3 min; interval; 10 s; intensity; 2 mA) for 17 days. The stress-related immunosuppression and restorative effect of MAP were then analyzed by measuring various immunological parameters. MAP treatment alleviated lymphoid atrophy and body weight loss. The numbers of lymphocyte subsets were significantly normalized in MAP-treated mice. Oral administration of MAP also restored the proliferative activities of lymphocytes; ovalbumin (OVA)-specific T cell proliferation; antibody production; and the cell killing activity of cytotoxic T lymphocytes. In summary; oral administration of MAP ameliorated chronic EFS stress-induced immunosuppression.

  3. 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.

  4. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B

    2016-01-01

    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.......5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry....... 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 genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according...

  5. 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.

  6. Beta-cell replacement in immunosuppressed recipients: old and new clinical indications.

    Science.gov (United States)

    Bertuzzi, Federico; Ricordi, Camillo

    2007-12-01

    Islet transplantation is an appealing procedure able to improve glycemic control in type 1 diabetic patients. However, the possible side effects that may be induced by immunosuppressive therapy limit its application to a select number of patients for whom the risk of immunosuppressants' side effects can be justified. For patients with type 1 diabetes mellitus-who will take immunosuppressants regardless, as they require a solid organ transplant-islet infusion can be an interesting therapeutic option for improving metabolic compensation, whenever pancreas transplant is not possible. Hence, islet infusion can be an important therapeutic option for patients with secondary diabetes mellitus even when a minor pancreatic endocrine function remains. For these patients, results may be better than those obtained with islet infusion for patients with type 1 diabetes mellitus thanks to the lack of autoimmune reaction to the infused islets. The final result is the improvement of the glycemic compensation and most likely also an extension of the graft survival.

  7. Sunlight-induced immunosuppression in humans is initially because of UVB, then UVA, followed by interactive effects.

    Science.gov (United States)

    Poon, Terence S C; Barnetson, Ross St C; Halliday, Gary M

    2005-10-01

    Solar-simulated ultraviolet radiation (ssUV) suppresses immunity in humans. The ultraviolet B (UVB) waveband is recognized as immunosuppressive; however the relative significance of UVA to ssUV immunosuppression is unknown. We created dose and time-response curves for UVB-, UVA-, and ssUV-induced suppression of memory immunity to nickel in humans. UVB caused immunosuppression within 24 h. UVA immunosuppression required 48 h and was normalized by 72 h. UVB alone accounts for ssUV immunosuppression at 24 h, but both UVB and UVA contributed at 48 h. By 72 h neither waveband accounted for ssUV immunosuppression. An interaction between these wavebands was therefore the major contributor. To confirm this dose-response curves were used to determine immune protection factors (IPF) for sunscreens with nickel challenge 72 h following ssUV. A sunscreen with good UVA protection had an IPF twice that of a poor UVA protector, despite providing similar protection from sunburn. Thus UVA was a major contributor to ssUV-induced immunosuppression at 72 h but only with the cooperation of UVB. Hence, UVB initiates immunosuppressive signals within 24 h, followed by UVA at 48 h, then an interaction between UVB and UVA. By 72 h following ssUV exposure, neither UVB nor UVA, but an interaction between them is the major cause of sunlight-induced immunosuppression.

  8. Interleukin-2 receptor antagonist immunosuppression and consecutive viral management in living-donor liver transplantation for human immunodeficiency virus/hepatitis C-co-infected patients: a report of 2 cases.

    Science.gov (United States)

    Maki, Harufumi; Kaneko, Junichi; Akamatsu, Nobuhisa; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Tanaka, Tomohiro; Tamura, Sumihito; Sugawara, Yasuhiko; Tsukada, Kunihisa; Kokudo, Norihiro

    2016-02-01

    Management of immunosuppression for human immunodeficiency virus/hepatitis C (HIV/HCV) in living-donor liver transplantation (LDLT) has not been established. We performed LDLT for two patients with HIV/HCV-co-infected end-stage liver disease. The immunosuppression protocol consisted of early calcineurin inhibitor-free and interleukin-2 receptor antagonist (IL2Ra) induction and methylprednisolone. Maintenance low-dose tacrolimus was started and anti-retroviral therapy for HIV was re-started 1 week after LDLT. Consecutively, pegylated interferon and ribavirin therapy were successfully added as pre-emptive therapy for HCV. HIV-RNA and HCV-RNA were undetectable on anti-retroviral therapy and HCV treatment at 17 and 8 months after LDLT, respectively, with normal liver function. This study is the first report of early calcineurin inhibitor-free and IL2Ra induction with methylprednisolone immunosuppression in LDLT for HIV/HCV-co-infected patients with a favorable outcome. Consecutive HIV/HCV treatment was well tolerated.

  9. Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naïve Mice.

    Directory of Open Access Journals (Sweden)

    Isaac G Sakala

    2015-12-01

    Full Text Available Orthopoxviruses (OPV, including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV, the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. We used the mouse pathogen ectromelia virus (ECTV, the agent of mousepox and a close relative of VARV to investigate virus persistence in inbred mice. We provide evidence that ECTV causes a persistent infection in some susceptible strains of mice in which low levels of virus genomes were detected in various tissues late in infection. The bone marrow (BM and blood appeared to be key sites of persistence. Contemporaneous with virus persistence, antiviral CD8 T cell responses were demonstrable over the entire 25-week study period, with a change in the immunodominance hierarchy evident during the first 3 weeks. Some virus-encoded host response modifiers were found to modulate virus persistence whereas host genes encoded by the NKC and MHC class I reduced the potential for persistence. When susceptible strains of mice that had apparently recovered from infection were subjected to sustained immunosuppression with cyclophosphamide (CTX, animals succumbed to mousepox with high titers of infectious virus in various organs. CTX treated index mice transmitted virus to, and caused disease in, co-housed naïve mice. The most surprising but significant finding was that immunosuppression of disease-resistant C57BL/6 mice several weeks after recovery from primary infection generated high titers of virus in multiple tissues. Resistant mice showed no evidence of a persistent infection. This is the strongest evidence that ECTV can persist in inbred mice, regardless of their resistance

  10. 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.

  11. A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE Immunosuppression.

    Science.gov (United States)

    Zandman, Daniel; Hahn, William; Moss, Steven

    2013-10-01

    The increasingly widespread use of novel immunosuppressive drugs may lead to unexpected infectious complications. We report a case of persistent Helicobacter pylori (H. pylori) infection that failed to respond to antimicrobial therapy in a patient receiving omalizumab (Xolair™, Genentech USA Inc., San Francisco, CA and Novartis Pharmaceuticals, Basel, Switzerland), an anti-IgE monoclonal antibody approved by the FDA for treatment of severe persistent asthma. To our knowledge, this is the first case report linking an immunosuppressive regimen containing anti-IgE biologic therapy to persistent H. pylori infection.

  12. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China

    Directory of Open Access Journals (Sweden)

    Yu Xue

    2016-01-01

    Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL and more frequently immunosuppressants than the asymptomatic group (P 1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

  13. 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.

  14. [Neurectodermal malignant tumor of the soft tissues after treatment with immunosuppressive agents of lipoid nephrosis].

    Science.gov (United States)

    Parlier, G; Bensman, A; Leverger, G; Boccon-Gibod, L; Gruner, M

    1992-02-01

    Immunosuppressive drugs are known to increase the risk of inducing neoplasia, especially acute leukaemia when high doses are used. A case of nephrosis in a 10 year-old boy treated with chlormethine (cumulative dose: 0.8 mg/kg) and chlorambucil (cumulative dose: 10 mg/kg) is reported. Four years after the beginning of the treatment an extraskeletal Ewing's sarcoma occurred. Since the review of literature failed to find any malignancy induced by such an immunosuppressive treatment for nephrosis, the question whether or not this extraskeletal Ewing's sarcoma was attributable to this treatment remains unanswered.

  15. From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

    Directory of Open Access Journals (Sweden)

    Oana Draghiciu

    2011-01-01

    Full Text Available Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

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

    Directory of Open Access Journals (Sweden)

    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

  17. Start and the restriction point.

    Science.gov (United States)

    Johnson, Amy; Skotheim, Jan M

    2013-12-01

    Commitment to division requires that cells sense, interpret, and respond appropriately to multiple signals. In most eukaryotes, cells commit to division in G1 before DNA replication. Beyond a point, known as Start in yeast and the restriction point in mammals, cells will proceed through the cell cycle despite changes in upstream signals. In metazoans, misregulated G1 control can lead to developmental problems or disease, so it is important to understand how cells decipher the myriad external and internal signals that contribute to the fundamental all-or-none decision to divide. Extensive study of G1 control in the budding yeast Saccharomyces cerevisiae and mammalian culture systems has revealed highly similar networks regulating commitment. However, protein sequences of functional orthologs often indicate a total lack of conservation suggesting significant evolution of G1 control. Here, we review recent studies defining the conserved and diverged features of G1 control and highlight systems-level aspects that may be common to other biological regulatory networks. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. 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.

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

    Science.gov (United States)

    Keshri, Gaurav K; Gupta, Asheesh; Yadav, Anju; Sharma, Sanjeev K; Singh, Shashi Bala

    2016-01-01

    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.

  20. Fibrillary glomerulonephritis with small fibrils in a patient with the antiphospholipid antibody syndrome successfully treated with immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Tagboto Senyo

    2007-05-01

    Full Text Available Abstract Background Fibrillary glomerulonephritis is a rare cause of progressive renal dysfunction, often leading to the need for dialysis within a few years. The role of immunosuppressive treatment is still uncertain although this has been tried with variable success. Case presentation A 56 year old woman with the antiphospholipid antibody syndrome (IgM anticardiolipin antibodies was seen in the nephrology clinic with haematuria, proteinuria, and worsening renal function. A renal biopsy demonstrated a mesangial proliferative glomerulonephritis on light microscopy and smaller fibrils (10.6–13.8 nm in diameter than is usual for fibrillary glomerulonephritis (typically 18–22 nm on electron microscopy. Amyloidosis was excluded following detailed evaluation. On account of rapidly worsening renal failure she was started on cyclophosphamide and prednisolone which led to the partial recovery and stabilization of her renal function. Conclusion This case highlights the need for routine electron microscopy in native renal biopsies, where the differential diagnosis is wide and varied and the light and immunofluorescence microscopic findings may be non specific.

  1. Vanadium air-pollution - a cause of malabsorption and immunosuppression in cattle

    CSIR Research Space (South Africa)

    Gummow, B

    1994-12-01

    Full Text Available and immunosuppression were the basis of the pathogenesis in affected animals. Eight months after the commencement of the investigation, adult cows began showing evidence of emaciation, reduced milk production and an apparent increase in the number of abortions...

  2. 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; Somerton, Stephen; Wiesinger, Holly; Zandieh, Iman; Caenepeel, Philip; Claessens, Christophe; de Suray, Nicolas; andre, Jacques Defl; Holvoet, Jan; Vergauwe, Philippe

    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

  3. Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation

    Directory of Open Access Journals (Sweden)

    Catić-Đorđević Aleksandra

    2017-01-01

    Full Text Available Immunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection as well as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients’ quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized. Therapeutic drug monitoring (TDM for immunosuppressive drugs is an essential, but at the same time insufficient tool due to low predictability of drug exposition and marked pharmacokinetic variability. Parallel therapeutic, biochemical and clinical monitoring may successfully optimize and individualize therapy for transplanted recipients, providing optimal medical outcomes. Modern pharmacotherapy management should include new biomarkers with better sensitivity and specificity that can identify early cell damage. The aim of this study was to point out the importance of finding new biomarkers that would enable early detection of adverse drug events and cell damage in organ transplant recipients. We wanted to confirm the importance of routine biochemical monitoring in improving the safety of immunosuppressive treatment.

  4. Cancer Screening of Renal Transplant Patients Undergoing Long-Term Immunosuppressive Therapy.

    Science.gov (United States)

    Demir, T; Ozel, L; Gökçe, A M; Ata, P; Kara, M; Eriş, C; Özdemir, E; Titiz, M I

    2015-06-01

    With this study we aimed to research the effects of immunosuppressive drugs, their cumulative doses, and viral infections on development of malign tumors in patients who have undergone treatment for 5 years. We examined 100 patients who underwent renal transplantation from 2004 to 2009. Patients had mycophenolate mofetil and steroid in addition to cyclosporine, sirolimus, or tacrolimus as immunosuppressive treatment. For malignancy screening, physical examination, radiologic and endoscopic screening were done, and immunosuppressive drugs and their cumulative doses, age, sex, body mass index (BMI), dialysis history, and viral infection history were investigated. The mean age of patients was 42.03 ± 11.30 years. There were 1 colon cancer patient, 1 retroperitoneal liposarcoma, 1 renal oncocytoma, 3 Kaposi sarcoma patients treated with cyclosporine; in those treated with Tac there were 1 basal cell carcinoma, 1 Kaposi sarcoma, 2 thyroid carcinoma, 1 breast carcinoma, 1 bladder carcinoma, 1 renal cell carcinoma, and 1 colon carcinoma patients. The mean age of patients having carcinoma was statistically significant compared with those without cancer (P cancer. The risk of carcinoma increases with increasing drug dose and time period of the immunosuppressive drug. There was not a negative effect on cancer prevalence in patients with cyclosporine or tacrolimus. But the cumulative dose of steroids significantly increased malignancy occurence. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

    NARCIS (Netherlands)

    A. Yoshimi (Ayami); M.M. van den Heuvel-Eibrink (Marry); I. Baumann (Irith); S. Schwarz (Stephan); I. Simonitsch-Klupp (Ingrid); P. de Paepe (Pascale); V. Campr (Vit); G. Kerndrup (Gitte); M.J. O'Sullivan (Maureen); R. Devito (Rita); P. Leguit; M. Hernandez (Manuel); M.N. Dworzak (Michael); B. de Moerloose (Barbara); J. Stary (Jan); H. Hasle (Henrik); O.P. Smith (Owen Patrick); M. Zecca (Marco); F. Catala; M. Schmugge; F. Locatelli (Franco); M. Führer (Monika); A. Fischer (Alexandra); A. Guderle (Anne); P. Nöllke (Peter); B. Strahm (Brigitte); C.M. Niemeyer (Charlotte)

    2014-01-01

    textabstractRefractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with

  6. Dexamethasone immunosuppression results in turkey clostridial dermatitis: A retrospective analysis of 7 studies, 1998 - 2009

    Science.gov (United States)

    We have been studying the etiology of turkey osteomyelitis complex (TOC) for the past 20 years and have determined that this syndrome is caused by the inability of some fast-growing male turkeys to cope with production stressors. While immunosuppressive viruses have often been associated with suscep...

  7. [Etiopathogenesis of aplastic anemia and of the severe form treated with immunosuppression and bone marrow transplantation].

    Science.gov (United States)

    Dulley, F L; Lotério, H A; Massumoto, C M; Llacer, P E; Chamone, D de A

    1989-01-01

    Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.

  8. 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.

  9. Look Different: Effect of Radiation Hormesis on the Survival Rate of Immunosuppressed Mice.

    Science.gov (United States)

    Alavi, M; Taeb, S; Okhovat, M A; Atefi, M; Negahdari, F

    2016-09-01

    Hormesis is defined as the bio-positive response of something which is bio-negative in high doses. In the present study, the effect of radiation hormesis was evaluated on the survival rate of immunosuppressed BALB/c mice by Cyclosporine A. We used 75 consanguine, male, BALB/c mice in this experiment. The first group received Technetium-99m and the second group was placed on a sample radioactive soil of Ramsar region (800Bq) for 20 days. The third group was exposed to X-rays and the fourth group was placed on the radioactive soil and then injected Technetium-99m. The last group was the sham irradiated control group. Finally, 30mg Cyclosporine A as the immunosuppressive agent was orally administered to all mice 48 hours after receiving X-rays and Technetium-99m. The mean survival rate of mice in each group was estimated during time. A log rank test was run to determine if there were differences in the survival distribution for different groups and related treatments. According to the results, the survival rate of all pre-irradiated groups was more than the sham irradiated control group (p Ramsar region for 20 days and then injected Technetium-99m. This study confirmed the presence of hormetic models and the enhancement of survival rate in immunosuppressed BALB/c mice as a consequence of low-dose irradiation. It is also revealed the positive synergetic radioadaptive response on survival rate of immunosuppressed animals.

  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, we...

  11. Response of transplant recipients to influenza vaccination based on type of immunosuppression: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Reza Karbasi-Afshar

    2015-01-01

    Full Text Available Influenza vaccination is widely used in transplant recipients, but there is little known about the significance and correlating factors of its effectiveness. In the current study, we reviewed the existing literature on clinical trials performed in transplant recipients on the effectiveness of influenza vaccination and to evaluate the relevance of the type of immunosuppression employed in these patients on the humoral reaction to the vaccine. A comprehensive search of the literature was performed through Pubmed and Google Scholar to find reports indicating immunogenicity of influenza vaccination in transplant patients. Finally, data from 15 published clinical trials were included in the meta-analysis. Data of 947 transplant recipients retrieved from 15 clinical trials investigating the immunogenicity of influenza vaccination were analyzed in this meta-analysis. Analysis showed significantly lower rates of sero-conversion among transplant recipients receiving mycophenolate mofetil (MMF than other immunosuppressive agents (relative risk: 0.724; 95% confidence interval: 0.596-0.880; P = 0.001. No significant correlation was found with tacrolimus, sirolimus, cyclosporine and azathioprine. Different immunosuppressive agents seem to have different effects on the humoral response rate to influenza vaccination, with MMF having the most significant deleterious effect. The limited and controversial data available in the literature do not support any differential effect for other immunosuppressive agents.

  12. Clinical Challenges of Tacrolimus for Maintenance Immunosuppression Post-Lung Transplantation.

    Science.gov (United States)

    Ivulich, S; Dooley, M; Kirkpatrick, C; Snell, G

    2017-11-01

    Lung transplantation (LTx) is a successful treatment option for end-stage lung disease, and immunosuppressant regimens, utilized to prevent rejection of the transplanted graft, are paramount to maintaining long-term graft survival. Immunosuppression can be classified as induction, maintenance, and antirejection therapy. This article focuses on maintenance immunosuppression that includes a combination of a calcineurin inhibitor (CNI), cell cycle inhibitor, and corticosteroid. CNIs remain the cornerstone of immunosuppression following LTx, and tacrolimus is now the preferred CNI, based on a better adverse effect profile and some limited evidence for enhanced efficacy. Tacrolimus is associated with a number of unique challenges post-LTx, with erratic and highly variable absorption making it difficult to achieve and maintain therapeutic levels. Current methods of therapeutic drug monitoring are extrapolated from models in liver and kidney transplants and are not validated in the LTx population. Alternative methods of delivering tacrolimus can address some of the issues associated with their use and can be utilized in particular clinical scenarios. Long-term toxicities attributed to tacrolimus, such as nephrotoxicity and neurotoxicity, can limit the long-term success of tacrolimus in preventing allograft rejection. This article emphasizes the current clinical challenges faced when managing LTx recipients with tacrolimus, offers strategies to manage these issues, and highlights the areas that need further research. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  13. Immunoregulatory function of lactoferrin in immunosuppressed and autoimmune animals.

    Science.gov (United States)

    Zimecki, Michał; Artym, Jolanta; Chodaczek, Grzegorz; Kocieba, Maja; Kuryszko, Jan; Houszka, Marek; Kruzel, Marian L

    2007-01-01

    In this article we review our recent results on the effects of lactoferrin (LF), given orally, on the immune status of mice subjected either to chemotherapy or immobilization stress as well as on rats with experimentally induced autoimmune encephalomyelitis (EAE). We demonstrated that LF accelerated reconstitution of the immune system function after administration of a sublethal dose cyclophosphamide (CP) and normalized the ratio of major blood cell types in that model. Also, after application of methotrexate (MTX) LF was effective to speed up reconstitution of the cellular and humoral immune response. Mice treated with lethal dose of busulfan (Bu) and CP and reconstituted with bone marrow cells (BMC) were able to quicker develop optimal immune responses when administered LF. In addition LF was shown to accelerate engraftment of bone marrow cells from syngeneic donors in that model. Using immobilization stress model was shown that LF accelerates reconstitution of the cellular and humoral immune response. In rats with EAE lactoferrin lowered the clinical score of the disease and diminished pathohistological changes in the spinal cord. In summary, in a series of studies we demonstrated a benefit of orally administered LF in immunocompromised animals.

  14. 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

    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...

  15. Testosterone treatment is immunosuppressive in superb fairy-wrens, yet free-living males with high testosterone are more immunocompetent.

    OpenAIRE

    Peters, A

    2000-01-01

    The immunocompetence handicap hypothesis proposes that the immunosuppressive effect of testosterone enforces honesty of sexual signalling via a physiological trade-off between signal intensity and immunocompetence. However, evidence that testosterone is immunosuppressive is scant, particularly in birds. I studied the correlation between immunocompetence and testosterone in superb fairy-wrens (Malurus cyaneus), a species with intense intersexual selection. Males are seasonally dichromatic and ...

  16. Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Hallas, Jesper

    2015-01-01

    Severely immunosuppressed individuals have a strongly increased risk of cervical cancer. In patients with autoimmune diseases (AID), who have defects in their immune system and receive immunosuppressants, the risk of cervical cancer is less clear. We conducted a cohort study, using Danish...

  17. 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

  18. Effect of immunosuppressant blood levels on serum concentration of interleukin-17 and -23 in stable liver transplant recipients.

    Science.gov (United States)

    Fábrega, E; López-Hoyos, M; San Segundo, D; Casafont, F; Benito, M J; Pons-Romero, F

    2009-04-01

    T(H)17 cells have been recently described to be involved in inflammatory and immune-mediated diseases, but there is no evidence of their role in human liver transplantation. Interleukin (IL)-23 is considered an inducer cytokine, whereas IL-17 is the main cytokine released by T(H)17 cells. The aim of our study was to measure the serum levels of IL-17 and IL-23 in stable liver transplant recipients and examine the influence of immunosuppressant concentrations. Serum levels of IL-23 and IL-17 were determined in 38 healthy subjects and 35 stable hepatic transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the simultaneous blood levels of cyclosporine (n = 20) or tacrolimus (n = 15). No significant differences were observed in the serum levels of IL-17 and IL-23 between healthy subjects and transplanted patients. In addition, patients with low blood levels of tacrolimus (<6 ng/mL), but not cyclosporine, showed significantly lower serum levels of the 2 cytokines. These preliminary results suggested a lack of activation of the T(H)17 pathway, which was more pronounced among the patient subgroup treated with tacrolimus.

  19. 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...

  20. 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

  1. Naltrexone antagonizes the analgesic and immunosuppressive effects of morphine in mice.

    Science.gov (United States)

    Carr, D J; Gerak, L R; France, C P

    1994-05-01

    A study was undertaken to investigate the relationship between morphine-induced analgesia and immunosuppression after acute administration. In male CD1 mice, morphine (10.0-100.0 mg/kg s.c.) produced a U-shaped immunosuppressive dose-effect curve on splenic natural killer (NK) activity. Morphine also induced dose-related analgesia, as measured by an increase in tail-flick latency during thermal application; these analgesic effects were antagonized by naltrexone (1.0-10.0 mg/kg). In addition, morphine-induced suppression of splenic NK activity was antagonized in a dose-dependent manner and, at one dose of naltrexone (10.0 mg/kg), splenic NK activity was augmented. To investigate further the relationship between naltrexone antagonism of morphine-induced analgesia and immunomodulation, single doses of morphine (10.0-100.0 mg/kg) were administered to mice pretreated with naltrexone (0.01-10.0 mg/kg) or saline. A dose of 10.0 mg/kg of morphine produced 35% of the maximal possible effect in the analgesia study and no immunosuppression, whereas a dose of 32.0 mg/kg produced a maximal analgesic effect and significant suppression of NK activity. Naltrexone blocked morphine-induced analgesia and immunosuppression in a dose-dependent fashion. Moreover, the combination of 1.0 mg/kg of naltrexone and 32.0 mg/kg of morphine elevated splenic NK activity. A large dose of morphine (100.0 mg/kg) elicited full analgesia and had no effect on splenic NK activity in saline- or naltrexone-pretreated mice. Collectively, these results support the view that, in mice, morphine-induced analgesia and immunosuppression are mediated through a common opioid receptor type.

  2. Outcomes of cataract surgery with/without vitrectomy in patients with pars planitis and immunosuppressive therapy.

    Science.gov (United States)

    Albavera-Giles, Tania; Serna-Ojeda, Juan Carlos; Jimenez-Corona, Aida; Pedroza-Seres, Miguel

    2017-06-01

    The purpose of this study was to evaluate the characteristics and outcomes of cataract surgery with/without vitrectomy in patients with pars planitis who received immunosuppressive therapy. This was a retrospective case series, single-center study. Twenty-two patients with pars planitis who received immunosuppressive therapy were included, with a median age at presentation of 9.5 years, having had cataract surgery. The following data was collected: age at presentation and at cataract surgery, time of follow-up, best-corrected visual acuity (BCVA) before the surgery and at 1 week, 1 and 6 months after the procedure, immunosuppressive therapy, complications and causes for failed visual improvement. The variables associated with an improvement in visual acuity were evaluated. All patients had phacoemulsification with intraocular lens implantation. The most common immunosuppressive therapy used for the patients was methotrexate in nine patients (40.9%). The BCVA improved from a median of 20/400 to 20/100 after 6 months of follow-up (p = 0.0005); 14 patients (63.6%) improved two lines of vision or more. No significant risk factors were found for the association with improvement in visual acuity after the surgery. No improvement in visual acuity was attributed to posterior segment manifestations or amblyopia; the most common complication was posterior capsule opacification in 11 eyes (50%). The median follow-up after the surgery was 32 months. Phacoemulsification was the procedure for all the patients. Visual acuity improved in patients with pars planitis treated with immunosuppressive drugs who underwent cataract surgery, except for the patients with posterior segment complications or amblyopia.

  3. 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

  4. Sepsis Pathophysiology, Chronic Critical Illness, and Persistent Inflammation-Immunosuppression and Catabolism Syndrome.

    Science.gov (United States)

    Mira, Juan C; Gentile, Lori F; Mathias, Brittany J; Efron, Philip A; Brakenridge, Scott C; Mohr, Alicia M; Moore, Frederick A; Moldawer, Lyle L

    2017-02-01

    To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research. Literature search using PubMed, MEDLINE, EMBASE, and Google Scholar. Sepsis remains one of the most debilitating and expensive illnesses, and its prevalence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness, rarely fully recover, and often experience an indolent death. Patients with chronic critical illness often exhibit "a persistent inflammation-immunosuppression and catabolism syndrome," and it is proposed here that this state of persisting inflammation, immunosuppression and catabolism contributes to many of these adverse clinical outcomes. The underlying cause of inflammation-immunosuppression and catabolism syndrome is currently unknown, but there is increasing evidence that altered myelopoiesis, reduced effector T-cell function, and expansion of immature myeloid-derived suppressor cells are all contributory. Although newer therapeutic interventions are targeting the inflammatory, the immunosuppressive, and the protein catabolic responses individually, successful treatment of the septic patient with chronic critical illness and persistent inflammation-immunosuppression and catabolism syndrome may require a more complementary approach.

  5. Learning relay start strategies in swimming: What feedback is best?

    Science.gov (United States)

    Fischer, Sebastian; Braun, Claudia; Kibele, Armin

    2017-04-01

    In the past, studies and book recommendations on relay starts in swimming have been predominantly focused on the change-over time (COT) as a performance criterion. Aside from the circular backswing start with parallel foot placement, few studies have analysed differences in the take-off movement including step approaches as well. Although trends could be identified, the results remained still somewhat inconclusive. In contrast, no study has examined as has examined whether a reduction of COT in between wall contact of the income swimmer and the take-off of the outgoing swimmer is an optimal relay start strategy, as advocated by various swimming experts. Therefore, the purpose of this study was to compare two different relay start strategies: offensive strategy minimizing COT and conservative strategy to maximize horizontal peak force (HPF). In this regard, a learning intervention with 24 elite-level swimmers (12 females, 12 male) was conducted to compare both strategies regarding relay start time, HPF and COT. Subjects were randomly assigned to two feedback groups: COT versus HPF at take-off. The results of this study showed a clear advantage for HPF feedback for relay start performance measured by wall contact of the incoming swimmer and head passage at 7.5 m of the outgoing swimmer. In addition, similar reductions in COTs were found in both training groups. In conclusion, swimmers should focus on force production rather than minimizing COT. For the latter, deteriorating consequences for force production must be considered.

  6. 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…

  7. 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…

  8. A Data Scientist's Guide to Start-Ups.

    Science.gov (United States)

    Provost, Foster; Webb, Geoffrey I; Bekkerman, Ron; Etzioni, Oren; Fayyad, Usama; Perlich, Claudia

    2014-09-01

    In August 2013, we held a panel discussion at the KDD 2013 conference in Chicago on the subject of data science, data scientists, and start-ups. KDD is the premier conference on data science research and practice. The panel discussed the pros and cons for top-notch data scientists of the hot data science start-up scene. In this article, we first present background on our panelists. Our four panelists have unquestionable pedigrees in data science and substantial experience with start-ups from multiple perspectives (founders, employees, chief scientists, venture capitalists). For the casual reader, we next present a brief summary of the experts' opinions on eight of the issues the panel discussed. The rest of the article presents a lightly edited transcription of the entire panel discussion.

  9. Extended Deterrence, Nuclear Proliferation, and START III

    Energy Technology Data Exchange (ETDEWEB)

    Speed, R.D.

    2000-06-20

    Early in the Cold War, the United States adopted a policy of ''extended nuclear deterrence'' to protect its allies by threatening a nuclear strike against any state that attacks these allies. This threat can (in principle) be used to try to deter an enemy attack using conventional weapons or one using nuclear, chemical, or biological weapons. The credibility of a nuclear threat has long been subject to debate and is dependent on many complex geopolitical factors, not the least of which is the military capabilities of the opposing sides. The ending of the Cold War has led to a significant decrease in the number of strategic nuclear weapons deployed by the United States and Russia. START II, which was recently ratified by the Russian Duma, will (if implemented) reduce the number deployed strategic nuclear weapons on each side to 3500, compared to a level of over 11,000 at the end of the Cold War in 1991. The tentative limit established by Presidents Clinton and Yeltsin for START III would reduce the strategic force level to 2000-2500. However, the Russians (along with a number of arms control advocates) now argue that the level should be reduced even further--to 1500 warheads or less. The conventional view is that ''deep cuts'' in nuclear weapons are necessary to discourage nuclear proliferation. Thus, as part of the bargain to get the non-nuclear states to agree to the renewal of the Nuclear Non-Proliferation Treaty, the United States pledged to work towards greater reductions in strategic forces. Without movement in the direction of deep cuts, it is thought by many analysts that some countries may decide to build their own nuclear weapons. Indeed, this was part of the rationale India used to justify its own nuclear weapons program. However, there is also some concern that deep cuts (to 1500 or lower) in the U.S. strategic nuclear arsenal could have the opposite effect. The fear is that such cuts might undermine extended

  10. Synthesis and characterization of an epimer of tacrolimus, an immunosuppressive drug

    DEFF Research Database (Denmark)

    Skytte, Dorthe Mondrup; Frydenvang, Karla Andrea; Hansen, Liselotte

    2010-01-01

    8-Epitacrolimus (2), a new l-pipecolic acid macrolide lactone, was obtained by base-catalyzed epimerization of tacrolimus (FK-506, 1), an important immunosuppressive drug, and its structure determined by a single-crystal X-ray diffraction method. The compound was fully characterized by spectrosco......8-Epitacrolimus (2), a new l-pipecolic acid macrolide lactone, was obtained by base-catalyzed epimerization of tacrolimus (FK-506, 1), an important immunosuppressive drug, and its structure determined by a single-crystal X-ray diffraction method. The compound was fully characterized...... by spectroscopic techniques. The epimer is of importance due to its potential biological effects as well as because of its possible formation during formulation, handling, and use of tacrolimus products....

  11. Severe diarrhoea due to Cystoisospora belli in renal transplant patient on Immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    A Marathe

    2013-01-01

    Full Text Available Cystoisospora belli , formerly known as Isospora belli, protozoal parasite endemic to many regions of the world including the Caribbean, Central and South America, Africa, and South-East Asia. It is frequently encountered in patients with acquired immunodeficiency syndrome (AIDS and is considered to be an AIDS-defining illness. Chronic severe watery diarrhoea due to C. belli has also been reported in other immunodeficiency states. C. belli infection in immunosuppressed patients has rarely been described. We describe severe diarrhoea due to C. belli in a human immunodeficiency virus-negative renal transplant recipient on immunosuppressive drugs. Oocysts of C. belli were detected in direct smear preparation of the diarrheic stool sample of the patient. The patient responded to combination treatment with Bactrim-double-strength (trimethoprim-sulfamethoxazole and Nitazoxanide.

  12. 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.

  13. Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Martínez, Carmen; Millán, Olga; Rovira, Montserrat; Fernández-Avilés, Francesc; López, Anna; Suárez-Lledó, María; Carreras, Enric; Urbano-Ispízua, Álvaro; Brunet, Mercè

    2017-04-01

    Information on pharmacodynamic monitoring after allogeneic hematopoietic cell transplantation (allo-SCT) to evaluate individual responses to immunosuppressive drugs is scarce. We studied the relationship between a panel of pharmacodynamic markers monitored during the first 3 months after transplant and the occurrence of graft-versus-host disease (GVHD). Lymphocyte activation assessed by intracellular ATP concentration in CD4(+) T cells, a high percentage of CD8(+) effector T cells, and a low percentage of CD4(+) regulatory T (Treg) cells correlated significantly with GVHD. A cutoff value of 0.5 for the CD8(+) effector T/Treg ratio provided the most accurate diagnosis of GVHD (sensitivity 58.8%, specificity 91%). These pharmacodynamic markers may provide an efficient complement to standard pharmacokinetic monitoring of immunosuppressive drugs after allo-SCT.

  14. Chronic inflammation drives glioma growth: cellular and molecular factors responsible for an immunosuppressive microenvironment

    Directory of Open Access Journals (Sweden)

    Joseph P Antonios

    2014-09-01

    Full Text Available This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell types and molecules present also correlate with the grade of malignancy. An overall "type 2" chronic inflammatory microenvironment develops that facilitates glioma promotion and contributes to the neo-vascularization characteristic of gliomas. An immunosuppressive microenvironment shields the tumor mass from clearance by the patient's own immune system. Here, we provide suggestions to deal with a chronically-inflamed tumor microenvironment and provide recommendations to help optimize adjuvant immune- and gene therapies currently offered to glioma patients.

  15. Food safety for the solid organ transplant patient: preventing foodborne illness while on chronic immunosuppressive drugs.

    Science.gov (United States)

    Obayashi, Patricia A C

    2012-12-01

    Issues regarding food safety are seen increasingly in the news; outbreaks of foodborne illness have been associated with public health concerns ranging from mild illness to death. For the solid organ transplant patient, immunosuppressive and antibacterial drugs, which maintain transplant organ function, can expose the transplant patient to increased risk of foodborne illness from bacteria, viruses, fungi, and parasites. This review article describes the clinical consequences, sources of foodborne illness, and food safety practices needed to minimize risks to the solid organ transplant patient who must take lifelong immunosuppressive drugs. All members of the transplant team share responsibility for education of the solid organ transplant patient in preventing infections. The registered dietitian, as part of the transplant team, is the recognized expert in providing food safety education in the context of medical nutrition therapy to solid organ transplant patients, the patients' caregivers, and other healthcare providers.

  16. Collagenase enzymatic fasciotomy for Dupuytren contracture in patients on chronic immunosuppression.

    Science.gov (United States)

    Waters, Michael J; Belsky, Mark R; Blazar, Philip E; Leibman, Matthew I; Ruchelsman, David E

    2015-11-01

    Collagenase enzymatic fasciotomy is an accepted nonsurgical treatment for disabling hand contractures caused by Dupuytren disease. We conducted a study to investigate use of collagenase in an immunosuppressed population. We retrospectively reviewed data from 2 academic hand surgical practices. Eight patients on chronic immunosuppressive therapies were treated with collagenase for digital contractures between 2010 and 2011. Thirteen collagenase enzymatic fasciotomies were performed in these 8 patients. Mean preinjection contracture was 53.0°. At mean follow-up of 6.7 months, mean magnitude of contracture improved to 12.9°. Mean metacarpophalangeal joint contracture improved from 42.0° to 4.2°. Mean proximal interphalangeal joint contracture improved from 65.8° to 21.7°. Three of the enzymatic fasciotomies were complicated by skin tears. There were no infections. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated prospectively.

  17. A case of necrotising fasciitis caused by Serratia marsescens: extreme age as functional immunosuppression?

    Science.gov (United States)

    Cope, Thomas Edmund; Cope, Wei; Beaumont, David Martin

    2013-03-01

    We report the case of a 97-year-old woman who had a prolonged hospital admission for the treatment of right-sided heart failure. During her stay she experienced a rapid deterioration, characterised by shortness of breath, cardiovascular compromise and a hot, red, swollen calf. Post-mortem examination demonstrated that this was caused by necrotising fasciitis due to Serratia marcescens as a single pathogen. This is only the second reported case of this condition in the absence of diabetes or immunosuppression, and clinical deterioration was much more rapid. The case underlines the importance of circumspection and regular review in the diagnosis of the elderly patient. It reminds us that these patients should be viewed as functionally immunosuppressed, and that some or all of the haematological markers of infection can be absent even in severe disease.

  18. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD)

    Science.gov (United States)

    2014-01-01

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection. PMID:24490832

  19. Vernal keratoconjunctivitis: culmination of management using immunosuppression, surgical and prosthetic therapy over quarter century.

    Science.gov (United States)

    Das, Shilpa; Pasari, Anand S; Sangwan, Virender S

    2016-11-23

    A 22-year-old male patient presented in 1988 with active vernal keratoconjunctivitis. He was treated with topical mast cell stabilisers and corticosteroids. Chronic inflammation despite topical treatment necessitated oral immunosuppressants. Active disease came under control with this; however, the patient gradually developed limbal stem cell deficiency. He underwent bilateral pannus resection with amniotic membrane transplantation that resulted in improved ocular surface. In 2007, patient was found to have significant bilateral posterior subcapsular cataracts and underwent bilateral cataract surgery with intraocular lens implantation with good visual outcome. In 2016, he was provided with scleral lens prosthetic device, which further improved vision. At last follow-up, more than 25 years after his initial visit, his visual acuity was 20/25 in both eyes with a stable surface. With a comprehensive approach using immunosuppression, surgical therapy and scleral lens prosthetic device, chronic vernal keratoconjunctivitis can be well managed as illustrated in this case. 2016 BMJ Publishing Group Ltd.

  20. 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.

  1. 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.

    2012-01-01

    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. PMID:22547544

  2. Perioperative use of immunosuppressive medications in patients with Crohn's disease in the new "biological era"

    Science.gov (United States)

    Shen, Bo

    2017-01-01

    Abstract Crohn’s disease (CD) is characterized by transmural inflammation of the gastrointestinal tract leading to inflammatory, stricturing and/or and fistulizing disease. Once a patient develops medically refractory disease, mechanical obstruction, fistulizing disease or perforation, surgery is indicated. Unfortunately, surgery is not curative in most cases, underscoring the importance of bowel preservation and adequate perioperative medical management. As many of the medications used to treat CD are immunosuppressive, the concern for postoperative infectious complications and anastomotic healing are particularly concerning; these concerns have to be balanced with preventing and treating residual or recurrent disease. We herein review the available literature and make recommendations regarding the preoperative, perioperative and postoperative administration of immunosuppressive medications in the current era of biological therapy for CD. Standardized algorithms for perioperative medical management would greatly assist future research for optimizing surgical outcomes and preventing disease recurrence in the future. PMID:28852521

  3. 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).

  4. Synthesis and biological evaluation of α,β-unsaturated lactones as potent immunosuppressive agents.

    Science.gov (United States)

    Lee, Sun-Mi; Lee, Won-Gil; Kim, Young-Chul; Kim, Yong-Chul; Ko, Hyojin

    2011-10-01

    Compounds having α,β-unsaturated lactones display a variety of biological activities. Many research groups have tested both natural and unnatural α,β-unsaturated lactones for as-yet undiscovered biological properties. We synthesized α,β-unsaturated lactones with various substituents at the δ-position and studied their immunosuppressive effects, that is, the inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized, the benzofuran-substituted α,β-unsaturated lactone 4h showed the best inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes (IC(50)=66.9 nM) without cytotoxicity at 10 μM. The results indicated that 4h may be useful as a potent immunosuppressive agent, as well as in IL-2-related studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Pancolitis with Ischemic Injury as a Complication of Immunosuppressive Treatment in a Patient with Autoimmune Hepatitis: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Dalbeni

    2012-01-01

    Full Text Available Ischemic colitis is a serious drug-induced adverse event. There are only few cases of immunosuppression-associated ischemic colitis described in the literature, but none with a pancolitis-like manifestation. We report the case of a 72-year-old female patient who developed a pancolitis with ischemic injury on immunosuppressive treatment with steroids and azathioprine for autoimmune hepatitis. The patient presented with massive rectal bleeding. Colonoscopy confirmed the diagnosis of pancolitis. The results of histological examination indicated drug-induced ischemic colitis involving the entire colon. This is the first case of ischemic pancolitis mimicking an inflammatory bowel disease (IBD in a patient with immunosuppressive therapy.

  7. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    Science.gov (United States)

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

  8. Genipin attenuates sepsis-induced immunosuppression through inhibition of T lymphocyte apoptosis.

    Science.gov (United States)

    Kim, Joon-Sung; Kim, So-Jin; Lee, Sun-Mee

    2015-07-01

    Sepsis, a systemic inflammatory response to infection, initiates a complex immune response consisting of an early hyperinflammatory response and a subsequent hypoinflammatory response that impairs the removal of infectious organisms. The importance of sepsis-induced immunosuppression and its contribution to mortality has recently emerged. Apoptotic depletion of T lymphocytes is a critical cause of immunosuppression in the late phase of sepsis. Genipin is a major active compound of gardenia fruit that has anti-apoptotic and anti-microbial properties. This study investigated the mechanisms of action of genipin on immunosuppression in the late phase of sepsis. Mice received genipin (1, 2.5 and 5mg/kg, i.v.) at 0 (immediately) and 24h after cecal ligation and puncture (CLP). Twenty-six hours after CLP, the spleen and blood were collected. Genipin improved the survival rate compared to controls. CLP increased the levels of FADD, caspase-8 and caspase-3 protein expression, which were attenuated by genipin. Genipin increased the level of anti-apoptotic B-cell lymphoma-2 protein expression, while it decreased the level of pro-apoptotic phosphorylated-Bim protein expression in CLP. CLP decreased the CD4(+) and CD8(+) T cell population, while it increased the regulatory T cell (Treg) population and the level of cytotoxic T lymphocyte-associated antigen 4 protein expression on Treg. These changes were attenuated by genipin. The splenic levels of interferon-γ and interleukin (IL)-2 were reduced, while the levels of IL-4 and IL-10 increased after CLP. Genipin attenuated these alterations. These findings suggest that genipin reduces immunosuppression by inhibiting T lymphocyte apoptosis in the late phase of sepsis. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Biliary diseases in heart transplanted patients: a comparison between cyclosporine a versus tacrolimus-based immunosuppression

    Directory of Open Access Journals (Sweden)

    Stief J

    2009-05-01

    Full Text Available Abstract A cyclosporine (CsA-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ± 11 years. Data were compared to 57 patients (47 male, 10 female, mean age: 58 ± 11 years who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25, of gallstones 28% (7 of 25. In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51 and gallstones in 25% (13 of 51. Nine of 42 males in the CsA group (21% and eight of 20 males in the Tac group (40% developed either gallstones or sludge (n.s. Six of nine females in the CsA group (67%, but none of five females in the Tac group (0% developed either gallstones or sludge (p = 0.01. In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.

  10. A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE Immunosuppression

    OpenAIRE

    Zandman, Daniel; Hahn, William; Moss, Steven

    2013-01-01

    The increasingly widespread use of novel immunosuppressive drugs may lead to unexpected infectious complications. We report a case of persistent Helicobacter pylori (H. pylori) infection that failed to respond to antimicrobial therapy in a patient receiving omalizumab (Xolair?, Genentech USA Inc., San Francisco, CA and Novartis Pharmaceuticals, Basel, Switzerland), an anti-IgE monoclonal antibody approved by the FDA for treatment of severe persistent asthma. To our knowledge, this is the firs...

  11. Post-transplant aspergillosis and the role of combined neurosurgical and antifungal therapies under belatacept immunosuppression

    DEFF Research Database (Denmark)

    Ekkehard, Kasper; Bartek, Jiri; Johnson, Jesper Scott

    2011-01-01

    Opportunistic CNS-infection represent a major threat to patients after organ transplantation due to the need for ongoing immunosuppression and belatacept is a novel CTL4A inhibitor, which is increasingly used for patients following cadaveric kidney transplantation. Among the CNS infections, intra...... with intraoperative image guidance was performed for a gross total resection of the lesion. Twenty-four months from resection, she remains on voriconazole with no evidence of recurrence and complete neurologic recovery and preserved renal function....

  12. 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.

  13. Trial of complete weaning from immunosuppression for liver transplant recipients: factors predictive of tolerance.

    Science.gov (United States)

    de la Garza, Rocío García; Sarobe, Pablo; Merino, Juana; Lasarte, Juan J; D'Avola, Delia; Belsue, Virginia; Delgado, José A; Silva, Leyre; Iñarrairaegui, Mercedes; Sangro, Bruno; Sola, Jesus J; Pardo, Fernando; Quiroga, Jorge; Herrero, J Ignacio

    2013-09-01

    Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4(+) , CD8(+) , and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range = 8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P = 0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P = 0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n = 7 for an interval > 10 years and an SI  10 years and an SI > 20 or an interval  20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables-the time from transplantation and the SI-may help to identify these patients. © 2013 American Association for the Study of Liver Diseases.

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

    OpenAIRE

    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants). Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: "inflammatory bowel disease (IBD)" OR "Crohn′s dise...

  15. Immunosuppression and Chagas disease; experience from a non-endemic country.

    Science.gov (United States)

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  16. Biliary diseases in heart transplanted patients: a comparison between cyclosporine a versus tacrolimus-based immunosuppression

    Science.gov (United States)

    2009-01-01

    A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ± 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ± 11 years) who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01). In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare. PMID:19541577

  17. Personalization of the immunosuppressive treatment in renal transplant recipients: the great challenge in "omics" medicine.

    Science.gov (United States)

    Zaza, Gianluigi; Granata, Simona; Tomei, Paola; Dalla Gassa, Alessandra; Lupo, Antonio

    2015-02-17

    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.

  18. Immunosuppressant-driven de novo malignant neoplasms after solid-organ transplant.

    Science.gov (United States)

    Billups, Kelsey; Neal, Jennifer; Salyer, Jeanne

    2015-06-01

    Solid-organ transplant recipients are at a 3- to 5-fold increased risk of a de novo malignant neoplasm developing compared with the general population. The most frequently developed virus-associated malignant neoplasms are Kaposi sarcoma (standardized incidence ratio [SIR], 208.0), nonmelanoma skin cancer (SIR, 28.6), and posttransplant lymphoproliferative disorder, primarily non-Hodgkin lymphoma (SIR, 8.1). Immunosuppressive agents such as corticosteroids, antimetabolites, calcineurin inhibitors, and mammalian target of rapamycin (mTOR) inhibitors play a key role in either causing or preventing this complication. It is hypothesized that some of these regimens can impair cancer surveillance, facilitate the action of oncogenic viruses, and promote direct oncogenic activity. Evolving research has shown promising dual antitumor and immunosuppressive properties of the mTOR inhibitor class. The effective management of posttransplant neoplasms most likely involves the use of these medications among other preventative options. These measures include monitoring certain viral loads as well as immunosuppressant drug levels. Reducing these levels to as low as possible for healthy engraftment and altering regimens when appropriate are management strategies that could lessen this complication of solid-organ transplant. More studies examining the effects of therapeutic drug monitoring are needed to determine specific plasma drug concentrations that will ensure organ engraftment without the development of de novo malignant neoplasms.

  19. Immunosuppression is an independent prognostic factor associated with aggressive tumor behavior in cutaneous melanoma.

    Science.gov (United States)

    Donahue, Tracy; Lee, Christina Y; Sanghvi, Asmi; Obregon, Roxana; Sidiropoulos, Michael; Cooper, Chelsea; Merkel, Emily A; Yélamos, Oriol; Ferris, Laura; Gerami, Pedram

    2015-09-01

    A number of factors other than those identified by the American Joint Committee on Cancer (AJCC) may have prognostic significance in the evaluation of melanoma. We sought to evaluate commonly recorded clinical features potentially associated with aggressive melanoma. We conducted a retrospective case-control study. We included patients given a diagnosis of cutaneous melanoma with at least 5 years of follow-up or documented metastases. Patients were divided into nonaggressive and aggressive groups. Univariate and multivariate statistical analyses were performed to evaluate the association of multiple clinical and histologic parameters and metastases. We included 141 patients. Significant prognostic factors in univariate analysis associated with nonaggressive disease included history of dysplastic nevus syndrome and ABCDE criteria. Significant factors in univariate analysis associated with aggressive disease included age and immunosuppression. Only age and immunosuppression remained significant in multivariate analysis when controlled across statistically significant histologic variables from AJCC. The study is retrospective and has a small sample size. Older patients and those with a history of immunosuppression may be at higher risk for aggressive disease and should be closely monitored after an initial diagnosis of melanoma. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

    Science.gov (United States)

    Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert; Van Ranst, Marc; Verbeken, Erik; Hooper, Jay W; Maes, Piet

    2017-10-01

    Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

  1. 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.

  2. Immunosuppressive and antiparasitic effects of cyclosporin A on Hymenolepis nana infection in mice.

    Science.gov (United States)

    Matsuzawa, K; Nakamura, F; Abe, M; Okamoto, K

    1998-04-01

    The effect of cyclosporin A, which is known to act both as immunosuppressant and as an antiparasitic drug in many host-parasite systems, was examined in a mouse-Hymenolepis nana system. When BDF1 mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) every 48 h from 11 days p.i. with eggs, expulsion of the adult worms from the intestines of mice was prevented completely until at least 30 days p.i. Worm burden, dry weight and the number of gravid proglottids were not significantly reduced. By contrast, in untreated mice most of the worms were eliminated by 19 days p.i. The drug also completely abolished acquired resistance to a challenge infection with eggs when mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) around the time of challenge infection (Days -2, -1, 0, 1 and 2 relative to challenge). Such immunosuppressive effects of cyclosporin A on worm expulsion and protective immunity to reinfection were similar to those of another immunosuppressant, cyclophosphamide. As for the antiparasitic action of cyclosporin A against H. nana, a smaller number of cysticercoids developed from eggs in mice given cyclosporin A (100 mg kg-1 day-1) for 5 days beginning 1 day before infection, than in untreated controls.

  3. 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.

  4. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression.

    Science.gov (United States)

    Wang, Jinheng; De Veirman, Kim; Faict, Sylvia; Frassanito, Maria Antonia; Ribatti, Domenico; Vacca, Angelo; Menu, Eline

    2016-06-01

    Multiple myeloma (MM) pathogenesis and progression largely rely on the cells and extracellular factors in the bone marrow (BM) microenvironment. Compelling studies have identified tumour exosomes as key regulators in the maintenance and education of the BM microenvironment by targeting stromal cells, immune cells, and vascular cells. However, the role of MM exosomes in the modification of the BM microenvironment and MM progression remains unclear. Here, we explored the functions of MM exosomes in angiogenesis and immunosuppression in vitro and in vivo. Murine MM exosomes carrying multiple angiogenesis-related proteins enhanced angiogenesis and directly promoted endothelial cell growth. Several pathways such as signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase, and p53 were modulated by the exosomes in endothelial and BM stromal cells. These exosomes promoted the growth of myeloid-derived suppressor cells (MDSCs) in naive mice through activation of the STAT3 pathway and changed their subsets to similar phenotypes to those seen in MM-bearing mice. Moreover, MM exosomes up-regulated inducible nitric oxide synthase and enhanced the immunosuppressive capacity of BM MDSCs in vivo. Our data show that MM exosomes modulate the BM microenvironment through enhancement of angiogenesis and immunosuppression, which will further facilitate MM progression. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. To immunosuppress or not: Behcet's syndrome presenting as an eosinophilic pleural effusion

    Directory of Open Access Journals (Sweden)

    Shakti Kumar Bal

    2017-01-01

    Full Text Available Etiologic diagnosis of an eosinophilic pleural effusion (EPE presents a diagnostic challenge when intrapleural air and blood have been ruled out as its proximate causes. Among the causes of EPE, those that require immunosuppression for the underlying disease include connective tissue diseases, sarcoidosis, vasculitis, and eosinophilic pneumonia. We present a case of clinically suspected Behcet's syndrome based on a 10-year history of recurrent multiple oral ulcers and human leukocyte antigen-B51 positivity who presented with only an EPE. Computed tomography pulmonary angiogram ruled out central thoracic vein thrombosis but was inconclusive in ruling out a subsegmental pulmonary embolism. The patient declined immunosuppressants and while on follow-up developed bilateral extensive acute lower limb deep venous thrombosis and pulmonary embolism. Upper infrarenal inferior vena cava demonstrated chronic thrombosis suggestive of its antecedent role in pulmonary embolism-related EPE during the first instance. Behcet's syndrome-related EPE can be associated with venous thromboembolism, and immunosuppressive therapy prevents the subsequent thrombotic episodes.

  6. Immunosuppression reactivates viral replication long after resolution of woodchuck hepatitis virus infection.

    Science.gov (United States)

    Menne, Stephan; Cote, Paul J; Butler, Scott D; Toshkov, Ilia A; Gerin, John L; Tennant, Bud C

    2007-03-01

    Resolution of hepatitis B virus (HBV) infection is characterized by coordinated humoral and cellular immune responses. Immunity is durable over decades, protecting the host from reinfection and potential activation of residual HBV. Woodchucks infected at birth with woodchuck hepatitis virus (WHV) cleared viremia and developed antibodies to surface antigen (anti-WHs). Woodchucks became seronegative for anti-WHs 3-6 years later, but in some, WHV DNA was detected in serum, liver, and/or peripheral blood mononuclear cells (PBMCs). Those with WHV DNA had increased in vitro cellular immune responses to viral antigens, CD4 and CD8 markers, and Th1-type cytokines, suggesting active WHV-specific T lymphocytes. Immunosuppression for 12 weeks using cyclosporine A in such woodchucks resulted in transient reactivation of WHV replication. Serum of 1 woodchuck that became positive for WHV DNA during immunosuppression was inoculated into WHV-susceptible woodchucks, and a productive infection was demonstrated. The results indicate that after infection durable cellular immunity to WHV is essential for the long-term control of viral replication and is probably maintained by continuous priming from residual virus. These experimental observations demonstrate the potential of immunosuppression to reactivate HBV after resolution of infection.

  7. Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J; Long-Boyle, Janel

    2016-05-01

    Part I of this article included a pertinent review of allogeneic hematopoietic cell transplantation (alloHCT), the role of postgraft immunosuppression in alloHCT, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of the calcineurin inhibitors and methotrexate. In this article (Part II), we review the pharmacokinetics, pharmacodynamics, and pharmacogenomics of mycophenolic acid (MPA), sirolimus, and the antithymocyte globulins (ATG). We then discuss target concentration intervention (TCI) of these postgraft immunosuppressants in alloHCT patients, with a focus on current evidence for TCI and on how TCI may improve clinical management in these patients. Currently, TCI using trough concentrations is conducted for sirolimus in alloHCT patients. Several studies demonstrate that MPA plasma exposure is associated with clinical outcomes, with an increasing number of alloHCT patients needing TCI of MPA. Compared with MPA, there are fewer pharmacokinetic/dynamic studies of rabbit ATG and horse ATG in alloHCT patients. Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include '-omics'-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses.

  8. 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.

  9. Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala

    Science.gov (United States)

    Chen, Liang; Yang, Yang; Yuan, Pulong; Yang, Yifu; Chen, Kaixian; Jia, Qi; Li, Yiming

    2014-01-01

    Cinnamon barks extracts have been reported to regulate immune function; however, the component(s) in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s) that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F) and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD-1), parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB) induced delayed-type hypersensitivity (DTH) response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-γ and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases. PMID:25530780

  10. Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2014-01-01

    Full Text Available Cinnamon barks extracts have been reported to regulate immune function; however, the component(s in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD-1, parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB induced delayed-type hypersensitivity (DTH response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-γ and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases.

  11. [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.

  12. 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.

  13. Advances in the understanding and treatment of sepsis-induced immunosuppression.

    Science.gov (United States)

    Venet, Fabienne; Monneret, Guillaume

    2018-02-01

    Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences. Scientific advances have highlighted the role of metabolic failure, epigenetic reprogramming, myeloid-derived suppressor cells, immature suppressive neutrophils and immune alterations in primary lymphoid organs (the thymus and bone marrow) in sepsis. An improved understanding of the mechanisms underlying this immunosuppression as well as of the similarities between sepsis-induced immunosuppression and immune defects in cancer or immunosenescence has led to novel therapeutic strategies aimed at stimulating immune function in patients with sepsis. Trials assessing the therapeutic benefit of IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF) and antibodies against programmed cell death protein 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) for the treatment of sepsis are in progress. The reappraisal of sepsis pathophysiology has also resulted in a novel approach to the design of clinical trials evaluating sepsis treatments, based on an evaluation of the immune status and biomarker-based stratification of patients.

  14. Non-specific aortoarteritis: long-term follow-up on immunosuppressive therapy.

    Science.gov (United States)

    Talwar, K K; Vasan, R S; Sharma, S; Chopra, P; Shrivastava, S; Malhotra, A

    1993-04-01

    Thirteen patients with non-specific aortoarteritis and endomyocardial biopsy evidence of myocarditis were followed-up on immunosuppressive therapy comprising of prednisolone and cyclophosphamide in addition to conventional treatment for hypertension and/or congestive heart failure. Serial determinations of erythrocyte sedimentation rate, chest roentgenogram, radionuclide ventriculogram and hemodynamic study including endomyocardial biopsy were carried out at 12, 24 and 52 weeks of therapy. Arterial lesions were also assessed by digital subtraction angiography at 0 and 52 weeks of immunosuppressive therapy. At the end of a year of treatment all patients with congestive heart failure (10/13) showed symptomatic improvement by at least one New York Heart Association (NYHA) class. There was a significant fall in erythrocyte sedimentation rate (48 +/- 12 mm/1st h to 31 +/- 12 mm/1st h, P < 0.05), pulmonary artery pressure (32 +/- 14 mmHg to 20 +/- 9 mmHg, P < 0.05), left ventricular filling pressure (20 +/- 11 mmHg to 11 +/- 7 mmHg, P < 0.05) and increase in left ventricle ejection fraction (39 +/- 16% to 51 +/- 14%, P < 0.05) associated with resolution of morphological changes on endomyocardial biopsy. Arterial lesions remained static with neither progression nor appearance of new lesions. No significant complications of therapy were noticed in any patient. Our uncontrolled observations suggest that immunosuppressive therapy is safe and results in clinical, hemodynamic and myocardial morphological improvement in a subset of patients with non-specific aortoarteritis and associated myocarditis.

  15. [Persistent inflammation immunosuppression catabolism syndrome: a special type of chronic critical illness].

    Science.gov (United States)

    Ding, Renyu; Ma, Xiaochun

    2016-07-01

    After the concept of "chronic critical illness (CCI)" was proposed, the new concept persistent inflammation immunosuppression catabolism syndrome (PICS) is present recently. Patients with PICS are manifested by fast decreasing body weight, poor nutritional status, long-term immunosuppression and repeated nosocomial infections. These patients are faced with great challenges of persistent inflammation, acquired immunosuppression and high catabolism, which finally results in repeated nosocomial infections, prolonged hospital stay and increased mortality. At present, main problems of PICS diagnosis standard include varying length of ICU stay, difference in normal C reactive protein value, poor value of nutrition indexes, absence of clinical verification. Though associated pathophysiology mechanism is not clear, PICS is preventable and magageable with certain therapy, including early comprehensive prevention and treatment focused on infection control for CCI patients to stop the progression of PICS, application of immune modulator to improve immune function and prognosis of patients, and reasonable nutritional support and treatment. Besides, through the analysis of the association between PICS and CCI, authors draw a conclusion that PICS is a new phenotype of CCI, and immune paralysis is its main feature.

  16. Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model.

    Science.gov (United States)

    Steinborn, Carmen; Klemd, Amy Marisa; Sanchez-Campillo, Ann-Sophie; Rieger, Sophie; Scheffen, Marieke; Sauer, Barbara; Garcia-Käufer, Manuel; Urech, Konrad; Follo, Marie; Ücker, Annekathrin; Kienle, Gunver Sophia; Huber, Roman; Gründemann, Carsten

    2017-01-01

    Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML) was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.

  17. Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model.

    Directory of Open Access Journals (Sweden)

    Carmen Steinborn

    Full Text Available Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC activity and thereby escape from immune responses. The impact of mistletoe (Viscum album extracts (VAE, which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays. Furthermore, we examined whether VAEI was able to counteract tumor-induced immunosuppression within this cellular system using a renal cancer cell model. The role of mistletoe lectin (ML was analyzed using ML-specific antibodies and ML-depleted VAEI. VAEI and VAEA augmented the maturation of dendritic cells. VAEI abrogated tumor-induced immunosuppression of dendritic cells and both processes were partially mediated by ML since ML-depleted VAEI and ML-specific antibodies almost neutralized the rehabilitative effects of VAEI on DC maturation. Using these settings, co-culture experiments with purified CD4+ T cells had no influence on T cell proliferation and activation but did have an impact on IFN-γ secretion. The study provides a potential mode-of-action of VAE as an additive cancer therapy based on immunomodulatory effects. However, the impact on the in vivo situation has to be evaluated in further studies.

  18. Impact of preoperative immunosuppressive agents on postoperative outcomes in Crohn's disease.

    Science.gov (United States)

    Ahmed Ali, Usama; Martin, Sean T; Rao, Abhishek D; Kiran, Ravi P

    2014-05-01

    Immunosuppressive agents are essential in the management of Crohn's disease. Their safety before surgery, however, is still controversial. The aim of this study is to evaluate whether the preoperative use of immunosuppressive agents is associated with increased postoperative complications in Crohn's disease. A literature search of PubMed, EMBASE, and The Cochrane Library was undertaken in February 2013. All studies describing postoperative outcomes of patients undergoing bowel resections for Crohn's disease were included if they reported data comparing patients on preoperative immunosuppressive agents with an appropriate control group. All immunosuppressive agents used to manage Crohn's disease were studied. The main outcomes measured were total overall complications and total infectious complications. Twenty-one eligible studies (20 retrospective and 1 prospective) with 6899 patients were included. When individual studies were examined, only 2/14 (14%), 4/13 (31%), and 1/8 (13%) studies found an association between postoperative complications and preoperative anti-tumor necrosis factor agents, corticosteroids, and thiopurines. In meta-analyses, patients on anti-tumor necrosis factor agents (risk ratio, 1.29; 95% CI, 1.07-1.55), and corticosteroids (risk ratio, 1.55; 95% CI, 1.23-1.95) were found to have a higher risk of postoperative infectious complications. The use of anti-tumor necrosis factor agents was also significantly associated with wound infection (risk ratio, 1.62; 95% CI, 1.12-2.34) and septic shock (risk ratio, 1.81; 95% CI, 1.03-3.17). There was no association between the use of thiopurines or combined immunomodulator drugs and postoperative complications. Most studies were retrospectively designed, and there were large variations in the patient populations and outcome definitions. Patients with Crohn's disease on preoperative immunosuppressive agents are at higher risk for complications. Both corticosteroids and anti-tumor necrosis factor agents may

  19. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Kirby Sean

    2012-03-01

    Full Text Available Abstract Background After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications. Methods A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications. Results The incidence of neoplasia on lung biopsy was 0.4% (9 cases, which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases, and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2% cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03. Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns. Conclusions Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with

  20. Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity.

    Science.gov (United States)

    Boehmer, L N; Wu, M-F; John, J; Siegel, J M

    2004-08-01

    All Doberman pinschers and Labrador retrievers homozygous for a mutation of the hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal conditions. Degenerative changes and increased display of major histocompatibility complex class II antigens have been linked to symptom onset in genetically narcoleptic Doberman pinschers. This suggests that the immune system may contribute to neurodegenerative changes and narcoleptic symptomatology in these dogs. We therefore attempted to alter the course of canine genetic narcolepsy, as an initial test of principle, by administering a combination of three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune response globally. Experimental dogs were treated with a combination of methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks after birth, and raised in an environment that minimized pathogen exposure. Symptoms in treated and untreated animals were quantified using the food elicited cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to cataplexy onset more than doubled, time spent in cataplexy during tests was reduced by more than 90% and nighttime sleep periods were consolidated. Short-term drug administration to control dogs did not reduce cataplexy symptoms, demonstrating that the drug regimen did not directly affect symptoms. Treatment was stopped at 6 months, after which experimental animals remained less symptomatic than controls until at least 2 years of age. This treatment is the first shown to affect symptom development in animal or human genetic narcolepsy. Our findings show that hcrtr2 mutation is not sufficient for the full symptomatic development of canine genetic narcolepsy and suggest that the immune system may play a role in the development of this disorder.

  1. starting infants on antiretroviral therapy clinical: paediatrics

    African Journals Online (AJOL)

    CHARACTERISTICS OF CHILDREN STARTING ART. A literature review of 30 paediatric studies or treatment programmes found that children receiving ART ranged from infants aged 2 months to adolescents aged 15 years.5 Of 26 studies that reported age at ART initiation,. 19 (73%) showed a mean or median age at start ...

  2. Lean and global technology start-ups

    DEFF Research Database (Denmark)

    Tanev, Stoyan; Rasmussen, Erik Stavnsager; Zijdemans, Erik

    2015-01-01

    In this paper the authors introduce the concept of Lean Global Start-up (LGS) as a way of emphasizing the impossibility for new technology start-ups to deal separately with business development, innovation and early internationalization. For a newly established technology firm the task of being...

  3. When Do Start-Ups Make Sense?

    Science.gov (United States)

    Langemeyer, Clement J.

    2005-01-01

    The start-up has received considerable attention in the last few years. While the National Research Council of Canada has generated many start-ups over its 88-year history, the creation of a formal entrepreneurship programme in the mid-1990s dramatically accelerated the pace at which they were created. Many factors come into play in the decision…

  4. 76 FR 14841 - Head Start Program

    Science.gov (United States)

    2011-03-18

    ... eligibility information. Programs should be especially sensitive to any potential domestic violence issues... HUMAN SERVICES Administration for Children and Families 45 CFR Part 1305 RIN 0970-AC46 Head Start Program AGENCY: Office of Head Start (OHS), Administration for Children and Families (ACF), Department of...

  5. Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis.

    Science.gov (United States)

    Rodríguez-Perálvarez, Manuel; Guerrero-Misas, Marta; Thorburn, Douglas; Davidson, Brian R; Tsochatzis, Emmanuel; Gurusamy, Kurinchi Selvan

    2017-03-31

    As part of liver transplantation, immunosuppression (suppressing the host immunity) is given to prevent graft rejections resulting from the immune response of the body against transplanted organ or tissues from a different person whose tissue antigens are not compatible with those of the recipient. The optimal maintenance immunosuppressive regimen after liver transplantation remains uncertain. To assess the comparative benefits and harms of different maintenance immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until October 2016 to identify randomised clinical trials on immunosuppression for liver transplantation. We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adult participants undergoing liver transplantation (or liver retransplantation) for any reason. We excluded trials in which participants had undergone multivisceral transplantation or participants with established graft rejections. We considered any of the various maintenance immunosuppressive regimens compared with each other. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We included a total of 26 trials (3842 participants) in the review, and 23 trials (3693 participants) were included in one or more outcomes in the review. The vast majority of the participants underwent primary liver transplantation. All of the trials were at high risk of bias, and all of the evidence was

  6. Differential effects of immunosuppressive drugs on COX-2 activity in vitro and in kidney transplant patients in vivo

    DEFF Research Database (Denmark)

    Jespersen, Bente; Thiesson, Helle C; Henriksen, Charlotte

    2009-01-01

    BACKGROUND: It was hypothesized that calcineurin inhibitors suppress vascular cyclooxygenase (COX)-2 and exert a reciprocal influence on in vivo prostacyclin and thromboxane. This could contribute to cardiovascular morbidity in transplanted patients. METHODS: The ability of immunosuppressives to ...

  7. Outcomes of Liver Transplant Recipients With Autoimmune Liver Disease Using Long-Term Dual Immunosuppression Regimen Without Corticosteroid

    Directory of Open Access Journals (Sweden)

    Sanjaya K. Satapathy, MBBS, MD, DM

    2017-07-01

    Conclusions. Dual immunosuppression protocol in LT recipients with autoimmune liver disease without corticosteroid maintenance had acceptable rates of survival and ACR without predisposing patients to the adverse effects of long-term steroid therapy.

  8. Interferon alpha and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS.

    Science.gov (United States)

    Zagury, D; Lachgar, A; Chams, V; Fall, L S; Bernard, J; Zagury, J F; Bizzini, B; Gringeri, A; Santagostino, E; Rappaport, J; Feldman, M; Burny, A; Gallo, R C

    1998-03-31

    HIV type 1 (HIV-1) not only directly kills infected CD4(+) T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon alpha (IFNalpha) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNalpha and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNalpha and extracellular Tat. We, therefore, suggest that IFNalpha and Tat may be critical targets for anti-AIDS strategies.

  9. CHANGES IN MOUSE CIRULATING LEUKOCYTE NUMBERS IN C57BL/6 MICE IMMUNOSUPPRESSED FOR CRYPTOSPORIDIUM PARVUM OOCYST PRODUCTION

    Science.gov (United States)

    The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised Nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone - tetracy...

  10. O professor intérprete de língua de sinais em sala de aula: ponto de partida para se repensar a relação ensino, sujeito e linguagem/The sign language teacher/interpreter in the classroom: the starting point for a re-evaluation of teaching, subject and language relations

    Directory of Open Access Journals (Sweden)

    Regina Maria de Souza

    2007-01-01

    Full Text Available O presente trabalho discute a necessária participação educativa do intérprete de língua de sinais em sala de aula. A partir da teoria do Acontecimento Didático sobre o ensino e das idéias de Derrida sobre o ato interpretativo, defende a tese de que tentar estabelecer limites para a atuação do intérprete educacional - na tentativa de fazer com que não se confunda com a figura do/a professor/a em sala de aula - é submeter-se a uma formação discursiva de ensino que o reduz ou ao currículo, ou ao método (técnicas ou a intervenções que consideram tão somente a “capacidade” cognitiva do sujeito. The present paper discusses the necessary educational participation by the sign language interpreter in the classroom. Based on the Didactic Event teaching theory and Derrida´s ideas on the interpretive act, we argue that by setting limits for the educational interpreter’s performance – in an attempt to prevent him/her from being mistaken for a teacher in the classroom –, a discursive position about teaching is adopted, which restricts him/her to the curriculum, to the (technical method or to the interventions that take into account only the cognitive “capacity” of the subject.

  11. Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Andreassen, Arne K; Andersson, Bert

    2017-01-01

    BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or CNI-free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after....... CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function seem dissociated; hence, the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression....

  12. Halo naevi and café au lait macule regression in a renal transplant patient on immunosuppression.

    Science.gov (United States)

    Lolatgis, Helena; Varigos, George; Braue, Anna; Scardamaglia, Laura; Boyapati, Ann; Winship, Ingrid

    2015-11-01

    A case of halo naevi and café au lait macule regression in a renal transplant patient receiving long-term immunosuppressive therapy is described. We propose the direct transfer of an auto-reactive antibody, CD8 T-cells or tumour necrosis factor α from the transplant donor to the recipient as a possible cause. We have also considered insufficient immunosuppressive therapy as a possible mechanism. © 2014 The Australasian College of Dermatologists.

  13. 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.

  14. 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.

  15. Immunoblotting using Strongyloides venezuelensis larvae, parthenogenetic females or eggs extracts for the diagnosis of experimentally infected immunosuppressed rats.

    Science.gov (United States)

    Goulart de Carvalho, Edson Fernando; Neto de Sousa, José Eduardo; Gonçalves, Ana Lúcia Ribeiro; da Cunha-Junior, Jair Pereira; Costa-Cruz, Julia Maria

    2015-10-01

    The nematode Strongyloides stercoralis is responsible for strongyloidiasis in humans. Diagnosis of infection occurs through detection of larvae in feces, but low elimination of larvae often hampers the detection of disease, particularly in cases of patient immunosuppression. Immunodiagnostic tests have been developed; however obtaining S. stercoralis larvae for the production of homologous antigen extract is technically difficult. Thus, the use different developmental forms of Strongyloides venezuelensis has become an alternative method for the production of antigen extracts. The aim of this study was to evaluate immunoblotting using alkaline extracts from S. venezuelensis L3 larvae, parthenogenetic females or eggs to test detection of experimental strongyloidiasis associated with immunosuppression. Immunocompetent and immunosuppressed male rats were experimentally infected, and serum sample from all animals were obtained at 0, 5, 8 13, and 21 days post infection (d.p.i.). Immunoblotting was evaluated for use in detection of anti-S. venezuelensis IgG in both experimental rat groups. The larval extract immunoblotting profile had the most immunoreactive fractions in the immunosuppressed group beginning at 5 d.p.i., while the immunocompetent group reactivity began on 8 d.p.i. Immunoreactive protein fractions of 17 kDa present in larval alkaline extract presented as possible markers of infection in immunosuppressed rats. It is concluded that all extracts using immunoblotting have diagnostic potential in experimental strongyloidiasis, particularly larval extract in immunosuppressed individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Competition between immune function and lipid transport for the protein apolipophorin III leads to stress-induced immunosuppression in crickets.

    Science.gov (United States)

    Adamo, S A; Roberts, J L; Easy, R H; Ross, N W

    2008-02-01

    Intense physical activity results in transient immunosuppression in a wide range of animals. We tested the hypothesis that competition between immune function and lipid transport for the protein apolipophorin III (apoLpIII) can cause transient immunosuppression in crickets. Both flying, an energetically demanding behavior, and an immune challenge reduced the amount of monomeric (free) apoLpIII in the hemolymph of crickets. Because both immune function and flying depleted free apoLpIII, these two phenomena could be in competition for this protein. We showed that immune function was sensitive to the amount of free apoLpIII in the hemolymph. Reducing the amount of free apoLpIII in the hemolymph using adipokinetic hormone produced immunosuppression. Increasing apoLpIII levels after flight by pre-loading animals with trehalose reduced immunosuppression. Increasing post-flight apoLpIII levels by injecting purified apoLpIII also reduced flight-induced immunosuppression. These results show that competition between lipid transport and immune function for the same protein can produce transient immunosuppression after flight-or-fight behavior. Intertwined physiological systems can produce unexpected trade-offs.

  17. Begin and start: aspect and complement choice

    Directory of Open Access Journals (Sweden)

    Tünde Nagy

    2008-01-01

    Full Text Available The paper offers a semantic analysis of begin and start and their non-finite complementation: the to-infinitive and –ing constructions. The core idea of the paper is that the aspectual constructions ‘begin+ to infinitive’, ‘begin + ing’, ‘start+ to infinitive’, and ‘start+ ing’ have both a schematic and a prototypical meaning, and that the subtle differences between them are motivated by several factors, like viewing (perfectivity vs. imperfectivity, temporality (future orientation vs. ongoing reading dynamicity (graduality vs. abruptness, agentivity, etc.

  18. Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2014-12-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Berthold Klein,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch11Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyObjective: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR containing immunosuppressive regimen.Methods: A total of 381 patients (age ≥18 years receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA and azathioprine (AZA was replaced by CsA and mycophenolate mofetil (MMF in 2001 and by tacrolimus (TAC and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus were applied since 2003.Results: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total. Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%, 56 patients with noncutaneous malignancy only (14.7%, and 16 patients with both cutaneous and noncutaneous malignancy (4.2%. Statistically significant

  19. Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three Swiss Travel Clinics.

    Science.gov (United States)

    Huber, Fabienne; Ehrensperger, Benoît; Hatz, Christoph; Chappuis, François; Bühler, Silja; Eperon, Gilles

    2018-01-01

    Patients increasingly benefit from immunosuppressive/immunomodulatory medications for a range of conditions allowing them a lifestyle similar to healthy individuals, including travel. However, the administration of live vaccines to immunodeficient patients bears the risk of replication of the attenuated vaccine microorganism. Therefore, live vaccines are generally contraindicated on immunosuppression. Data on live vaccinations on immunosuppressive/immunomodulatory medication are scarce. We identified all travellers seeking pre-travel advice in three Swiss travel clinics with a live vaccine during immunosuppressive/immunomodulatory therapy to ascertain experienced side effects. A retrospective and multi-centre study design was chosen to increase the sample size. This study was conducted in the travel clinics of the University of Zurich; the Swiss TPH, Basel; and Geneva University Hospitals. Travellers on immunosuppressive/immunomodulatory therapy who received live vaccines [yellow fever vaccination (YFV), measles/mumps/rubella (MMR), varicella and/ or oral typhoid vaccination (OTV)] between 2008 and 2015 were identified and interviewed. A total of 60 age- and sex-matched controls (matched to Basel/Zurich travel clinics travellers) were included. Overall, 197 patients were identified. And 116 patients (59%) and 60 controls were interviewed. YFV was administered 92 times, MMR 21 times, varicella 4 times and OTV 6 times to patients on immunosuppressive/immunomodulatory therapy. Most common medications were corticosteroids (n = 45), mesalazine (n = 28) and methotrexate (n = 19). Live vaccines were also administered on biological treatment, e.g. TNF-alpha inhibitors (n = 8). Systemic reactions were observed in 12.2% of the immunosuppressed vs 13.3% of controls; local reactions in 7.8% of the immunosuppressed vs 11.7% of controls. In controls, all reactions were mild/moderate. In the immunosuppressed, 2/21 severe reactions occurred: severe local pain on interferon

  20. A Healthy Start Can Begin Now

    Science.gov (United States)

    A healthy pregnancy begins before you ever become pregnant. Give yourself the best chance for a healthy pregnancy and healthy baby before you start down the road to motherhood. If you smoke, now’s a great time to quit.

  1. Drug Abuse Prevention Starts with Parents

    Science.gov (United States)

    ... Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Use Young Adult Healthy Children > Ages & Stages > Teen > Substance Use > Drug Abuse Prevention Starts with Parents Ages & Stages Listen Español ...

  2. Start small and build toward business intelligence.

    Science.gov (United States)

    Kirby, Sean; Robertson, Brian

    2009-01-01

    To use business intelligence effectively, healthcare organizations should start small, align organizationally, and leverage success. Organizations should determine which measures they need and how to present them. Organizations should reinvest savings to continually improve.

  3. 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.

  4. Renoprotective immunosuppression by pioglitazone with low-dose cyclosporine in rat heart transplantation.

    Science.gov (United States)

    Tanaka, Yosuke; Hasegawa, Tomomi; Chen, Zhi; Okita, Yutaka; Okada, Kenji

    2009-09-01

    The peroxisome proliferator-activated receptor gamma activator pioglitazone has recently been reported to possess pleiotropic cardioprotective and renoprotective actions. We hypothesized that pioglitazone would reduce a dose of the immunosuppressant cyclosporine after heart transplantation, resulting in beneficial protective effects for both cardiac allografts and recipient kidneys. Experiments were performed by using an allomismatched rat heterotopic heart transplantation model. Recipients were treated with cyclosporine with or without pioglitazone and were divided into one of 4 groups: group I, no treatment; group II, low-dose cyclosporine (2 mg x kg(-1) x d(-1)); group III, high-dose cyclosporine (5 mg x kg(-1) x d(-1)); and group IV, low-dose cyclosporine with pioglitazone (3 mg x kg(-1) x d(-1)). Cyclosporine-treated rats showed significantly longer graft survival and less graft rejection but severe renal damage in a dose-dependent manner. Compared with group II, treatment with pioglitazone with low-dose cyclosporine (group IV) significantly suppressed graft infiltration of CD4/CD8 T lymphocytes and serum concentrations of interleukin 2 and interferon gamma, leading to extended graft survival up to 60 days. These immunosuppressive effects in group IV were equivalent to those in group III. In addition, recipient kidneys in group IV had few apoptotic cells, possibly through upregulation of peroxisome proliferator-activated receptor gamma and downregulation of transforming growth factor beta1, and maintained stable renal functions, as evidenced by a normalization of blood urea nitrogen, creatinine, and creatinine clearance values. In vitro experiments also confirmed the renoprotective effects of pioglitazone on cyclosporine-induced toxicity. Collectively, pioglitazone can reduce a dose of cyclosporine with sufficient immunosuppressive effects. Pioglitazone treatment with low-dose cyclosporine has synergistic protective effects for cardiac allografts and recipient

  5. 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

  6. Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent.

    Science.gov (United States)

    Qi, Guoyan; Liu, Peng; Dong, Huimin; Gu, Shanshan; Yang, Hongxia; Xue, Yinping

    2017-03-09

    BACKGROUND Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. MATERIAL AND METHODS MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. RESULTS Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. CONCLUSIONS The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma.

  7. [Correlation of the manifestations of tuberculosis and the degree of immunosuppression in patients with HIV].

    Science.gov (United States)

    Kouassi, B; N'Gom, A; Horo, K; Godé, C; Ahui, B; Emvoudou, N M L; Koffi, N; Anon, J C; Konaté, K F; Itchi, M; Koffi, M O; Ano, A; Manewa, S F; Gro Bi, A; Aka-Danguy, E; Gnazé, A; Touré, K

    2013-09-01

    Correlation of the manifestations of tuberculosis and the degree of immunosuppression in patients with HIV. The advent of HIV has contributed to the increase in the number of people with tuberculosis. The clinical and paraclinical of TB/HIV co-infected are polymorphic and function of immune status. To determines the clinical and paraclinical characteristics of TB related to different levels of CD4 lymphocytes. A retrospective case series based on analysis of 450 patients with both TB/HIV co-infections. It focused on the records of patients with pulmonary smear-positive (TPM +) with a positive HIV status. The effect of immunosuppression was analyzed in groups based on the CD4 count (350/mm(3)), in a chronological fashion from April to September 2010 until there were 150 patients in each CD4 group. Among the 450 patients, 71.1% were between 25 and 45years old. The clinical signs were more significant as the level of CD4 fell. The clinical signs were predominantly fever (93%) and weight loss (62.7%). Pulmonary cavitation (59.3%), infiltrates (38.7%) and the location of the lesions at the lung apex (72%) were more common in the third group patients. By contrast, extra pulmonary lesions (mediastinal lymphadenopathy, pleurisy) and normal x-ray (9.3%) were more frequent in patients of the first group. The scarcity of cavitations (22.3% compared to 59.3% CD4>350) and the increase in associated lesions became more marked if patients were immunocompromised. Hematologic, hepatic, renal disorders were more frequent and severe in the most immunocompromised patient group. HIV-associated tuberculosis has an atypical clinical, radiological, biological presentation and is more severe when there is significant immunosuppression. Copyright © 2013. Published by Elsevier Masson SAS.

  8. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests

    DEFF Research Database (Denmark)

    Hammer, J H; Nielsen, Hans Jørgen; Moesgaard, F

    1992-01-01

    The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four tim....... In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days....

  9. Inflammatory myositis complicating hypocomplementemic urticarial vasculitis despite on-going immunosuppression.

    Science.gov (United States)

    Chew, Gary Y J; Gatenby, Paul A

    2007-08-01

    We present a patient with previously diagnosed hypocomplementemic urticarial vasculitis syndrome, with skin, lung, and renal involvement, who presented with congestive cardiac failure. During the course of her hospitalization, she was also found to have profound proximal muscle weakness in both upper and lower limbs associated with raised creatinine kinase levels. A muscle biopsy was performed, which demonstrated evidence of an inflammatory myositis with vasculitis, which had returned despite on-going immunosuppression. This occurrence of a new autoimmune disease may well be an example of the "waste disposal" hypothesis.

  10. VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection.

    Science.gov (United States)

    Gebremariam, Teclegiorgis; Wiederhold, Nathan P; Fothergill, Annette W; Garvey, Edward P; Hoekstra, William J; Schotzinger, Robert J; Patterson, Thomas F; Filler, Scott G; Ibrahim, Ashraf S

    2015-12-01

    We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. The nutritional status of patients starting specialized predialysis care.

    Science.gov (United States)

    Westland, Gjalt J; Grootendorst, Diana C; Halbesma, Nynke; Dekker, Friedo W; Verburgh, Cornelis A

    2015-05-01

    To examine the prevalence of and risk factors for malnutrition at the start of specialized predialysis care. The present analysis was performed on cross-sectional data collected at inclusion in the study. The study included 25 outpatient clinics delivering specialized predialysis care in the Netherlands. Three hundred seventy-six incident patients with advanced chronic kidney disease attending one of the participating outpatient clinics. Subjective global assessment (SGA) of nutritional status. At the start of specialized predialysis care, 11% of patients suffer from moderate protein-energy wasting as measured by SGA. Independent risk factors are age >75 years (Odds ratio [OR], 3.88 [1.74-8.66]), female gender (OR, 2.95 [1.37-6.32]), and having a body mass index 75 years, female gender, and BMI <25 kg/m(2). Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  12. Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression.

    Science.gov (United States)

    Hovakimyan, M; Müller, J; Wree, A; Ortinau, S; Rolfs, A; Schmitt, O

    2012-09-01

    Functional replacement of specific neuronal populations through transplantation of neural tissue represents an attractive therapeutic strategy for treating neurodegenerative disorders like Parkinson's disease (PD). Even though the brain is a partially immune privileged site, immunosuppression is still needed for the prevention of host immune response, and thus, xenograft rejection. Here, we investigated the fate of human ventral mesencephalon derived immortalized cell line ReNcell VM upon unilateral transplantation into the intact rat striatum with or without immunosuppression with cyclosporine A (CsA). The status of xenografted human ReNcell VM cells was analysed by immunohistochemistry/immunofluorescence 4 and 6weeks after transplantation. Four weeks after transplantation, ReNcell VM cells could be detected in both groups, although the number of survived cells was significantly higher in brains of immunosuppressed rats. In contrast, only 2 out of 6 brains grafted without immunosuppression revealed human ReNcell VM cells 6weeks post grafting, whereas a considerable number of human cells could still be found in all the brains of immunosuppressed rats. Immunohistochemical analysis of grafted cells showed almost no evidence of neuronal differentiation, but rather astroglial development. In summary, we have shown that the immunosuppression is needed for the survival of human VM derived progenitor cells in the rat striatum. CsA affected cell survival, but not differentiation capacity: in both groups, grafted either with or without immunosuppression, the ReNcell VM cells lacked neuronal phenotype and developed preferentially into astroglia. Copyright © 2012 Elsevier GmbH. All rights reserved.

  13. 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.

  14. Urinary tract infections in the era of newer immunosuppressant agents : A tertiary care center study

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    Khanna Pallavi

    2010-01-01

    Full Text Available We studied the incidence and the risk factors predisposing to post transplantation urinary tract infection (UTI and the association with use of different immunosuppressive regimens. We performed a retrospective analysis of 152 recipients of renal transplantation over a period of two years. Seventy one (46.71% patients had culture positive UTI, Escherichia coli (45.1% being the commonest. Thirty four (22.39% patients had acute rejection and 14.4% of those had suffered UTI in the early post transplant period. Immunosuppression included induction with various anti-bodies and maintenance on antirejection medications. Trimethoprim-sulphamethoxazole was given as prophylaxis throughout the period. The UTI was treated according to microbiological sensitivity. 2.8% died due to urosepsis. In our retrospective analysis renal transplant recipients under the age of 45, female gender and diabetics suffered more UTI. Combination therapy with micro-emulsion form of cyclosporine A, prednisolone and azathioprine developed more UTI (P= 0.0418.

  15. Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Kuczmarski, Thomas; Stommel, Elijah W; Riley, Kristen; Tandan, Rup; Chaudhry, Vinay; Clawson, Lora; Caller, Tracie A; Henegan, Patricia L; Facciponte, Dominic N; Bradley, Walter G; Andrew, Angeline S

    2017-08-01

    A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22-0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50-1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.

  16. 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.

  17. Hidden Sources of Grapefruit in Beverages: Potential Interactions with Immunosuppressant Medications

    Science.gov (United States)

    Auten, Ashley A.; Beauchamp, Lauren N.; Joshua Taylor

    2013-01-01

    Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:24421511

  18. T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies.

    Science.gov (United States)

    Hess, Constanze; Winkler, André; Lorenz, Alexandra K; Holecska, Vivien; Blanchard, Véronique; Eiglmeier, Susanne; Schoen, Anna-Lena; Bitterling, Josephine; Stoehr, Alexander D; Petzold, Dominique; Schommartz, Tim; Mertes, Maria M M; Schoen, Carolin T; Tiburzy, Ben; Herrmann, Anne; Köhl, Jörg; Manz, Rudolf A; Madaio, Michael P; Berger, Markus; Wardemann, Hedda; Ehlers, Marc

    2013-09-01

    Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell-dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell-independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity.

  19. Radiographic assessment of photodynamic therapy as an adjunctive treatment on induced periodontitis in immunosuppressed rats

    Science.gov (United States)

    FERNANDES, Leandro Araújo; MARTINS, Thiago Marchi; de ALMEIDA, Juliano Milanezi; THEODORO, Letícia Helena; GARCIA, Valdir Gouveia

    2010-01-01

    Objective The aim of this study was to assess radiographically the effect of photodynamic therapy (PDT) as an adjunctive treatment to scaling and root planing (SRP) on induced periodontitis in dexamethasone-induced immunosuppressed rats. Material and Methods The animals were divided into 2 groups: ND group (n=60): saline treatment; D group (n=60): dexamethasone treatment. In both ND and D groups, periodontal disease was induced by the placement of a ligature in the left first mandibular molar. After 7 days, ligature was removed and all animals received SRP, being divided according to the following treatments: SRP: saline and PDT: phenothiazinium dye (TBO) plus laser irradiation. Ten animals per treatment were killed at 7, 15 and 30 days. The distance between the cementoenamel junction and the height of the alveolar bone crest in the mesial surface of the mandibular left first molars was determined in millimeters in each radiograph. The radiographic values were analyzed statistically by ANOVA and Tukey's test at a p value periodontitis in dexamethasone-induced immunosuppressed rats. PMID:20857000

  20. Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression.

    Science.gov (United States)

    Dai, Jun; Kumbhare, Ajinkya; Youssef, Dima; Yao, Zhi Q; McCall, Charles E; El Gazzar, Mohamed

    2017-11-01

    Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs. Moreover, C/EBPβ-reconstituted myeloid cells expressed IL-10 and reduced T cell proliferation and function, similar to control MDSCs that express C/EBPβ. Exogenous expression of miR-21 and miR-181b in the C/EBPβ-deficient myeloid progenitors from septic mice produced similar results. Notably, NFI-A-dependent transactivation of NF-kB MDSC generating pathway was reversed in the C/EBPβ-deficient myeloid progenitors from septic mice. Together, these results support that decreasing C/EBPβ expression prevents MDSC generation and decreases immunosuppression in septic mice, providing a target for sepsis treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Anal Squamous Cell Carcinoma in a Patient with Myasthenia Gravis: Is Immunosuppression the Main Underlying Etiology?

    Science.gov (United States)

    Masab, Muhammad; Saif, Muhammad W

    2017-11-15

    Patients who are immunocompromised by diseases such as human immunodeficiency virus (HIV) infection are more prone to develop some malignancies such as Kaposi's sarcoma and central nervous system (CNS) lymphomas. Historically, anal squamous cell carcinoma (SCC) was also included on the list as an acquired immunodeficiency syndrome (AIDs)-defining cancer.  Similarly, compromised immune disorders including severe immunosuppression, haematologic malignancies, and solid organ transplantation have been identified as important risk factors for the development of anal SCC. Review of the medical literature showed only sporadic cases of anal SCC in patients with pre-existing myasthenia gravis (MG), with or without thymoma.  We present here a case of anal SCC in a patient with several years history of MG who was receiving intravenous immunoglobulin (IVIG).  We believe this association is explained by the autoimmune nature of the disease and the use of immunosuppressive medications to treat it. To further support our case, we also present a review of the literature associating anal SCC with MG.

  2. Mesenchymal stem cell infusion on skin wound healing of dexamethasone immunosuppressed wistar rats

    Directory of Open Access Journals (Sweden)

    Betânia Souza Monteiro

    Full Text Available ABSTRACT: To evaluate the therapeutic contribution of MSC intravenous infusion to surgical wound healing in dexamethasone-immunosuppressed rats, thirty-five rats were randomly divided into 2 groups: in the Control Group (CG, five rats received normal saline as 0.2ml subcutaneous (SC injections every 24 hours, for 30 consecutive days and, in the Dexamethasone Group (DG, 30 rats were given 0.2mL subcutaneous dexamethasone (0.1mg kg-1 every 24 hours, for 30 consecutive days. After 30 days, all rats underwent surgery to create an experimental skin wound. The 30 animals of the DG group were divided into two equal groups, which received different treatments: the dexamethasone group (DG received a single application of 0.5ml normal saline, via the intravenous route (IV, 48 hours after wound creation; and the Mesenchymal Stem Cells Dexamethasone group (MSCDG received MSC transplantation at a concentration of 9x106 cells in a single IV application, 48 hours after wound creation. The surgical wounds of CG rats closed on average 14.75 days after creation and DG rats had wounds closed within 22 days; whereas, the surgical wounds of MSCDG rats were closed in 14 days. MSC infusion in dexamethasone-immunosuppressed patients contributed positively to epithelial healing in less time.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Dai Cheng

    2017-07-01

    Full Text Available 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.

  5. Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites.

    Directory of Open Access Journals (Sweden)

    Erwin Berthier

    Full Text Available The secondary metabolome provides pathogenic fungi with a plethoric and versatile panel of molecules that can be deployed during host ingress. While powerful genetic and analytical chemistry methods have been developed to identify fungal secondary metabolites (SMs, discovering the biological activity of SMs remains an elusive yet critical task. Here, we describe a process for identifying the immunosuppressive properties of Aspergillus SMs developed by coupling a cost-effective microfluidic neutrophil chemotaxis assay with an in vivo zebrafish assay. The microfluidic platform allows the identification of metabolites inhibiting neutrophil recruitment with as little as several nano-grams of compound in microliters of fluid. The zebrafish assay demonstrates a simple and accessible approach for performing in vivo studies without requiring any manipulation of the fish. Using this methodology we identify the immunosuppressive properties of a fungal SM, endocrocin. We find that endocrocin is localized in Aspergillus fumigatus spores and its biosynthesis is temperature-dependent. Finally, using the Drosophila toll deficient model, we find that deletion of encA, encoding the polyketide synthase required for endocrocin production, yields a less pathogenic strain of A. fumigatus when spores are harvested from endocrocin permissive but not when harvested from endocrocin restrictive conditions. The tools developed here will open new "function-omic" avenues downstream of the metabolomics, identification, and purification phases.

  6. Intensive Pharmacological Immunosuppression Allows for Repetitive Liver Gene Transfer With Recombinant Adenovirus in Nonhuman Primates

    Science.gov (United States)

    Fontanellas, Antonio; Hervás-Stubbs, Sandra; Mauleón, Itsaso; Dubrot, Juan; Mancheño, Uxua; Collantes, María; Sampedro, Ana; Unzu, Carmen; Alfaro, Carlos; Palazón, Asis; Smerdou, Cristian; Benito, Alberto; Prieto, Jesús; Peñuelas, Iván; Melero, Ignacio

    2010-01-01

    Repeated administration of gene therapies is hampered by host immunity toward vectors and transgenes. Attempts to circumvent antivector immunity include pharmacological immunosuppression or alternating different vectors and vector serotypes with the same transgene. Our studies show that B-cell depletion with anti-CD20 monoclonal antibody and concomitant T-cell inhibition with clinically available drugs permits repeated liver gene transfer to a limited number of nonhuman primates with recombinant adenovirus. Adenoviral vector–mediated transfer of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene was visualized in vivo with a semiquantitative transgene-specific positron emission tomography (PET) technique, liver immunohistochemistry, and immunoblot for the reporter transgene in needle biopsies. Neutralizing antibody and T cell–mediated responses toward the viral capsids were sequentially monitored and found to be repressed by the drug combinations tested. Repeated liver transfer of the HSV1-tk reporter gene with the same recombinant adenoviral vector was achieved in macaques undergoing a clinically feasible immunosuppressive treatment that ablated humoral and cellular immune responses. This strategy allows measurable gene retransfer to the liver as late as 15 months following the first adenoviral exposure in a macaque, which has undergone a total of four treatments with the same adenoviral vector. PMID:20087317

  7. T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodies

    Science.gov (United States)

    Hess, Constanze; Winkler, André; Lorenz, Alexandra K.; Holecska, Vivien; Blanchard, Véronique; Eiglmeier, Susanne; Schoen, Anna-Lena; Bitterling, Josephine; Stoehr, Alexander D.; Petzold, Dominique; Schommartz, Tim; Mertes, Maria M.M.; Schoen, Carolin T.; Tiburzy, Ben; Herrmann, Anne; Köhl, Jörg; Manz, Rudolf A.; Madaio, Michael P.; Berger, Markus; Wardemann, Hedda; Ehlers, Marc

    2013-01-01

    Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell–dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell–independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity. PMID:23979161

  8. Coffea arabica Seed Extract Stimulate the Cellular Immune Function and Cyclophosphamide-induced Immunosuppression in Mice

    Science.gov (United States)

    Rafiul Haque, Mohammad; Ansari, Shahid Hussain; Rashikh, Azhar

    2013-01-01

    In this study, we investigate the immunostimulatory effects of alcoholic extract of the coffee seed on cell-mediated immune response and cyclophosphamide-induced (CP) immunosuppressed mice. The assessment of cellular immune function was carried out by the measurement of delayed-type hypersensitivity (DTH) response. According to the literature survey, cyclophosphamide has only suppressing effect on the lymphoid organ, white blood cell (WBC) and other parts of humoral immunity. Humoral immunity was assessed by the hemagglutination antibody titre. Mice were treated with three doses of extract (50, 150 and 250 mg/Kg body weight per os). Relative organ weight and WBC counts were also studied in these animals. At doses of 50 and 150, a significant increase (p < 0.05) in relative organ weight of spleen and thymus was observed but there was no effect on kidney and liver weights. WBC counts was also increased significantly (p < 0.001) in all doses of the plant extract. Coffea arabica extract elicited a significant (p < 0.001) increase in the DTH response at doses of 50 and 150 mg/Kg, but the change at higher dose of 250 mg/Kg was not statistically significant. In the HT test, plant extract also showed modulatory effect at all doses groups. Over all, coffee seed showed the stimulatory effect on cellular immune function and cyclophosphamide induced immunosuppression in mice. PMID:24250577

  9. 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.

  10. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus

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    Borysowski Jan

    2009-08-01

    Full Text Available Abstract Background Bacteriophages can be successfully applied to treat infections caused by antibiotic-resistant bacteria. Until now no attempts have been undertaken to treat infections in immunosuppressed patients with phages. In this work we investigated the prophylactic efficacy of specific bacteriophages in CBA mice treated with cyclophosphamide (CP and infected with Staphylococcus aureus. Results High numbers of bacterial colony-forming units in the organs as well as elevated tumor necrosis factor and interleukin-6 serum concentrations in CP-treated and S. aureus-infected mice were significantly lowered upon application of phages. The phages markedly increased the percentage of circulating neutrophils and immature cells from the myelocytic and lymphocytic lineages in CP-treated, S. aureus-infected mice as well as of myelocytes and immature neutrophils in the bone marrow. In addition, phages stimulated in such mice generation of specific agglutinins against S. aureus. Conclusion Application of specific phages to immunosuppressed mice prior to infection with S. aureus proved very effective, suggesting a potential benefit of phage therapy in immunocompromised patients experiencing bacterial infections.

  11. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus.

    Science.gov (United States)

    Zimecki, Michał; Artym, Jolanta; Kocieba, Maja; Weber-Dabrowska, Beata; Borysowski, Jan; Górski, Andrzej

    2009-08-17

    Bacteriophages can be successfully applied to treat infections caused by antibiotic-resistant bacteria. Until now no attempts have been undertaken to treat infections in immunosuppressed patients with phages. In this work we investigated the prophylactic efficacy of specific bacteriophages in CBA mice treated with cyclophosphamide (CP) and infected with Staphylococcus aureus. High numbers of bacterial colony-forming units in the organs as well as elevated tumor necrosis factor and interleukin-6 serum concentrations in CP-treated and S. aureus-infected mice were significantly lowered upon application of phages. The phages markedly increased the percentage of circulating neutrophils and immature cells from the myelocytic and lymphocytic lineages in CP-treated, S. aureus-infected mice as well as of myelocytes and immature neutrophils in the bone marrow. In addition, phages stimulated in such mice generation of specific agglutinins against S. aureus. Application of specific phages to immunosuppressed mice prior to infection with S. aureus proved very effective, suggesting a potential benefit of phage therapy in immunocompromised patients experiencing bacterial infections.

  12. Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study.

    Science.gov (United States)

    Santangelo, Michele L; Criscitiello, Carmen; Renda, Andrea; Federico, Stefano; Curigliano, Giuseppe; Dodaro, Concetta; Scotti, Alessandro; Tammaro, Vincenzo; Calogero, Armando; Riccio, Eleonora; Pisani, Antonio; Carlomagno, Nicola

    2015-01-01

    Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome, data so far are not robust enough to justify a correlation between immunodeficiency and multiple primary malignancies in transplanted patients.

  13. Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study

    Directory of Open Access Journals (Sweden)

    Michele L. Santangelo

    2015-01-01

    Full Text Available Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome, data so far are not robust enough to justify a correlation between immunodeficiency and multiple primary malignancies in transplanted patients.

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

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    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.

  15. Combined long-term steroid and immunosuppressive treatment regimen in granulomatous mastitis.

    Science.gov (United States)

    Konan, Ali; Kalyoncu, Umut; Dogan, Ismail; Kiliç, Yusuf A; Karakoç, Derya; Akdogan, Ali; Kiraz, Sedat; Kaynaro Lu, Volkan; Onat, Demirali

    2012-08-01

    Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. It is related to various etiological factors. The treatment of IGM is challenging as there is a lack of consensus in the literature and treatment options vary widely. Conservative treatment with antibiotics, glucocorticoids and immunosuppressive drugs, and surgery are used in the management of the disease. In this article we report our experience with IGM patients receiving immunosuppressive treatment. The medical records of patients with IGM receiving systemic therapy at the Hacettepe University Hospital between October 2007 and May 2010 were reviewed. 15 cases of histopathologically proven IGM were identified. The data was examined for risk factors and success of treatment. 14 patients were given prednisolone together with azathioprine, and 1 patient who was pregnant at the time of diagnosis received only prednisolone (30 mg/day). 11 (73%) patients had a complete response to systemic therapy. 2 patients had a relapse, of whom 1 required surgical drainage and 1 was treated with a higher dose of glucocorticoids. Systemic therapy is a safe and effective treatment for IGM. The addition of azathioprine to glucocorticoid therapy permits quick tapering of the steroid doses and increases the treatment success.

  16. Effects of an immunosuppressive treatment in the GRMD dog model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Barthélémy, Inès; Uriarte, Ane; Drougard, Carole; Unterfinger, Yves; Thibaud, Jean-Laurent; Blot, Stéphane

    2012-01-01

    The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

  17. Effects of an immunosuppressive treatment in the GRMD dog model of Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Inès Barthélémy

    Full Text Available The GRMD (Golden retriever muscular dystrophy dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy, using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage and prednisolone (2 mg/kg/d during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

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

    Science.gov (United States)

    Galipeau, Jacques; Nooka, Ajay K.

    2013-01-01

    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. PMID:24350294

  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. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.

    Science.gov (United States)

    Cardenas, M E; Hemenway, C; Muir, R S; Ye, R; Fiorentino, D; Heitman, J

    1994-01-01

    The peptidyl-prolyl isomerases FKBP12 and cyclophilin A (immunophilins) form complexes with the immunosuppressants FK506 and cyclosporin A that inhibit the phosphatase calcineurin. With the yeast two hybrid system, we detect complexes between FKBP12 and the calcineurin A catalytic subunit in both the presence and absence of FK506. Mutations in FKBP12 surface residues or the absence of the calcineurin B regulatory subunit perturb the FK506-dependent, but not the ligand-independent, FKBP12-calcineurin complex. By affinity chromatography, both FKBP12 and cyclophilin A bind calcineurin A in the absence of ligand, and FK506 and cyclosporin A respectively potentiate these interactions. Both in vivo and in vitro, the peptidyl-prolyl isomerase active sites are dispensable for ligand-independent immunophilin-calcineurin complexes. Lastly, by genetic analyses we demonstrate that FKBP12 modulates calcineurin functions in vivo. These findings reveal that immunophilins interact with calcineurin in the absence of exogenous ligands and suggest that immunosuppressants may take advantage of the inherent ability of immunophilins to interact with calcineurin. Images PMID:7529175

  1. 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.

  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 coping strategies may have implications for understanding and managing nonadherent behavior among transplantation patients and should be considered among the strategies for reducing nonadherence.

  3. Importance of liver biopsy findings in immunosuppression management: biopsy monitoring and working criteria for patients with operational tolerance.

    Science.gov (United States)

    2012-10-01

    Obstacles to morbidity-free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of the original disease and malignancies, and unexplained chronic hepatitis and graft fibrosis. Many programs attempt to minimize chronic exposure to IS by reducing dosages and stopping steroids. A few programs have successfully weaned a highly select group of recipients from all IS without apparent adverse consequences, but long-term follow-up is limited. Patients subjected to adjustments in IS are usually followed by serial liver chemistry tests, which are relatively insensitive methods for detecting allograft damage. Protocol biopsy has largely been abandoned for hepatitis C virus-negative recipients, at least in part because of the inability to integrate routine histopathological findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsy samples, the Banff Working Group on Liver Allograft Pathology has reviewed the literature, pooled the experience of its members, and proposed working definitions for biopsy changes that (1) are conducive to lowering IS and are compatible with operational tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased IS during or after IS weaning. The establishment of guidelines should help us to standardize analyses of the effects of various treatments and/or weaning protocols and more rigorously categorize patients who are assumed to show OT. Long-term follow-up using standardized criteria will help us to determine the consequences of lowering IS and to define and determine the incidence and robustness of OT in liver allografts. Copyright © 2012 American Association for the Study of Liver Diseases.

  4. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

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    Wen-Pyng Wu

    Full Text Available 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%, P<0.001. The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001. Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001. Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  5. 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.

  6. Immunosuppression of allogenic mesenchymal stem cells transplantation after spinal cord injury improves graft survival and beneficial outcomes.

    Science.gov (United States)

    Torres-Espín, Abel; Redondo-Castro, Elena; Hernandez, Joaquim; Navarro, Xavier

    2015-03-15

    Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Mesenchymal stem cells (MSC) have demonstrated beneficial effects following transplantation in animal models of SCI. However, despite the immunoprivilege properties of the MSC, their survival in the injured spinal cord is reduced due to the detrimental milieu in the damaged tissue and immune rejection of the cells. The limited survival of the engrafted cells may determine the therapy success. Therefore, we compared two strategies to increase the presence of the cells in the injured spinal cord in rats: increasing the amount of MSC transplants and using immunosuppressive treatment with FK506 after transplantation. Functional outcomes for locomotion and electrophysiological responses were assessed. The grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that immunosuppression improved grafted cells survival. A cell-dose effect was found regarding locomotion recovery and tissue protection independent of immunosuppression. Nevertheless, immunosuppression enhanced the electrophysiological outcomes and allowed filling of the cavity formed after injury by new regenerative tissue and axons. These results indicate that MSC transplantation combined with immunosuppression prolongs the survival of engrafted cells and improves functional and morphological outcomes after SCI.

  7. Long-Term Impact of Different Immunosuppressive Drugs on QT and PR Intervals in Renal Transplant Patients.

    Science.gov (United States)

    Ikitimur, Baris; Cosansu, Kahraman; Karadag, Bilgehan; Cakmak, Huseyin Altug; Avci, Burcak Kilickiran; Erturk, Emre; Seyahi, Nurhan; Ongen, Zeki

    2015-09-01

    Sudden cardiac deaths due to arrhythmias are thought to be an important cause of mortality in patients with renal transplants. Exposure to immunosuppressive drugs may lead to QT or PR interval abnormalities which may consequently cause arrhythmias. Our study investigated the long term impact of four different immunosuppressive drugs on PR and corrected QT intervals (QTc) in renal transplant patients The study population consisted of 98 kidney transplant recipients. Study patients were receiving immunosuppressive management with tacrolimus, cyclosporine A, everolimus or azathioprine according to the local protocols. QTc and PR intervals obtained from the most recent post-transplant electrocardiograms were compared with the pre-transplant intervals dated before the transplantation procedure. Post-transplant QTc intervals had prolonged significantly in comparison to the pre-transplant QTc intervals in all groups. However, there were no significant differences between the immunosuppressive agents with regard to post-transplant QTc interval prolongation (p > 0.05). There were no significant differences between the groups with regard to the pre and post-transplant PR interval changes (p > 0.05). QT interval prolongation, a marker of risk for arrhythmias and sudden death, is highly prevalent among kidney transplant patients receiving different classes of immunosuppressive drugs. © 2014 Wiley Periodicals, Inc.

  8. Guidelines for starting today's private practice

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    Schmitz ED

    2012-11-01

    Full Text Available No abstract available. Article truncated at 150 words. Starting a new practice may seem like a daunting task. The purpose of this article is to demystify the process of creating a new practice from the beginning. The cardinal rule is to keep costs low and not to outsource work that can easily be performed by any competent physician and staff. You do not need a manager, lawyer, business partner, coder or biller individually; you may be able to perform many of these services yourself. What you do need is a commitment to making your practice a success. Do not spend too much on your office space, furnishings or equipment. Start with the bare essentials. Immediately start applying to all insurance companies especially Medicare. Request an employer identification number. Set up a basic business banking account and submit the account number to the insurance companies you plan to work with. You can purchase an entire electronic healthcare record (EHR …

  9. Two-Man Bobsled Push Start Analysis

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    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.

  10. Company start-up costs and employment

    OpenAIRE

    Christopher Pissarides

    2002-01-01

    I study the role of company start-up costs for employment performance. The model is search equilibrium with a new concept for firms. Agents have an innate managerial ability and make a career choice to become either managers or workers. Managers set up firms, post jobs and match with workers. Managers set up firms, post jobs and match with workers. I show that in equilibrium, career choice and job creation are jointly determined. Higher start-up costs reduce overall employment but increase th...

  11. Getting started with Microsoft Lync server 2013

    CERN Document Server

    Volpe, Fabrizio

    2013-01-01

    This book has a practical approach with a lot of step-by-step guides and explanations as to where and why we're doing the various operations.Getting Started with Microsoft Lync Server 2013 is a starting point for system administrators, IT pros, unified communication technicians, and decision makers in companies or in the consultancy business. For people who have never managed Lync (or a U.C. product), the book will guide you through the basic concepts and mistakes. If you are already managing a Lync deployment you will find important explanations and ideas put together in a single text. If you

  12. Smart or Diverse Start-up Teams?

    DEFF Research Database (Denmark)

    Hoogendoorn, Sander; Parker, Simon C.; Van Praag, Mirjam

    2017-01-01

    This paper explores the relationship between cognitive abilities and team performance in a start-up setting. We argue that performance in this setting hinges on three tasks: opportunity recognition, problem solving, and implementation. We theorize that cognitive ability at the individual level has...... by assigning students to teams based on their measured cognitive abilities. Each team performed a variety of tasks, often involving complex decision making. The key result of the experiment is that the performance of start-up teams first increases and then decreases with ability dispersion. Strikingly, average...

  13. The Lean and Global Start-up

    DEFF Research Database (Denmark)

    Tanev, Stoyan; Rasmussen, Erik Stavnsager

    For several decades researchers have studied start-up companies with a focus on international markets, suppliers and networks from their inception and on companies that are establishing new, agile business models. This has resulted in two streams of research: The Born Global and International New...... Ventures research and research with a focus on the Lean Start-up company. It is our intention in this paper to give a short presentation of the two research streams and show how they can be merged into one with a focus on newly established technology oriented firms that are lean and global from...

  14. Impulsive started flow by a jellyfish

    OpenAIRE

    市川, 誠司; 望月, 修; Seiji, ICHIKAWA; Osamu, MOCHIZUKI; 東洋大; Toyo University

    2008-01-01

    The purpose of this study is to understand the relation between circulation of a vortex ring generated by a disk starting impulsively and necessary force to move the disk. We measured the velocity vector field around the disk by using a PIV method to estimate circulation of the starting vortex ring. It was found that the circulation increased with the square root of the generated energy which is necessary to move the disk. This showed the same relation of the energy of a vortex ring and its c...

  15. Entrepreneur How to Start an Online Business

    CERN Document Server

    Tobin, Lucy

    2012-01-01

    The secrets of the UK’s biggest online entrepreneurs revealed   Thinking of starting a business? Already have a business online and looking to take it to the next level? The wonderful world wide web has made creating a start-up that much easier. Thousands of people are out there reaping the rewards the web can bring. If you want to join them, you’ve come to the right place.  Profiling today’s foremost web entrepreneurs, Lucy Tobin - who meets successful business founders every week writing an enterprise column for The Evening Standard – takes us throug

  16. ULTRASOUND MONITORING IN THE EVALUATION OF THE FUNCTIONAL STATE OF A KIDNEY TRANSPLANT AT DIFFERENT IMMUNOSUPPRESSION THERAPIES

    Directory of Open Access Journals (Sweden)

    L.E. Belyaeva

    2009-01-01

    Full Text Available This article covers one of the most important spheres in medicine — transplantation of a kidney from a live relative donor. The appearance of new generation immunosuppressive medicines has made it possible to boost the survivability of both the kidney and the recipient. The present research has allowed the authors to evaluate the functional state of a kidney transplant at the use of different immuno-suppression protocols (induction therapy with alemtuzumab in the first group and with daclizumab in the second one by means of a non invasive examination method. Moreover, the authors have defined ultrasound signs of transplant rejection depending on the type (interstitial or vascular.Key words: kidney transplantation, transplant dysfunction, evaluation of the transplant function, immunosuppression.

  17. Resveratrol promotes recovery of immune function of immunosuppressive mice by activating JNK/NF-κB pathway in splenic lymphocytes.

    Science.gov (United States)

    Lai, Xin; Cao, Mei; Song, Xu; Jia, Renyong; Zou, Yuanfeng; Li, Lixia; Liang, Xiaoxia; He, Changliang; Yin, Lizi; Yue, Guizhou; Ye, Gang; Yin, Zhongqiong

    2017-06-01

    Resveratrol, a natural compound found in over 70 plants, is known to possess immunoregulatory effects and anti-inflammatory activity. It has been shown that resveratrol has regulatory effects on different signaling pathways in different diseases. However, few reports have evaluated the effects of resveratrol on reinforcing immunity recovery via activating nuclear factor-κB (NF-κB) pathway and Jun N-terminal kinases (JNK) pathway. The present study aimed to assess immune-enhancing activity and underlying mechanism of resveratrol in immunosuppressive mice. Previously, we reported that resveratrol could promote mouse spleen lymphocyte functions to recover the immune system effectively. In the present study, we show that resveratrol could upregulate the expressions of NF-κB, IκB kinase, JNK, and c-jun in splenic lymphocytes of immunosuppressive mice. Taken together, our results indicate that resveratrol could promote recovery of immunologic function in immunosuppressive mice by activating JNK/NF-κB pathway.

  18. 76 FR 70009 - Head Start Program

    Science.gov (United States)

    2011-11-09

    ..., health, nutritional, and social needs of the children and families they serve and meet program and... administered by the Office of Head Start (OHS), Administration for Children and Families (ACF), Department of... that indicate the great importance of the early years of a child's growth and development. On December...

  19. 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 Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... required; (2) Used in the presence of open flames or burning flame safety lamps, or when welding or cutting...

  20. Starting wages respond to employer's risk

    NARCIS (Netherlands)

    Berkhout, P.; Hartog, J.; van Ophem, H

    2009-01-01

    Firms hiring fresh graduates face uncertainty on the future productivity of workers. Theory suggests that starting wages reflect this, with lower pay for greater uncertainty. We use the dispersion of exam grades within a field of education as an indicator of the unobserved heterogeneity that

  1. Addressing Tooth Decay in Head Start Children

    Science.gov (United States)

    Knowlden, Adam P.; Hill, Lawrence F.; Alles-White, Monica L.; Cottrell, Randall R.

    2012-01-01

    Tooth decay is the most prevalent chronic disease of childhood. Oral health education and dental services are crucial to reducing the number of children afflicted with dental cavities. Due to limited access to preventative care, Head Start children are particularly vulnerable to tooth decay. This article outlines practical implications of a…

  2. How to Start Intergenerational Programs in Communities.

    Science.gov (United States)

    2002

    This document is designed for use by community organizers in creating, developing and maintaining an intergenerational program. Starting with a brief overview of the Maryland Intergenerational Coalition, the document describes (in short, bulleted entries) the activities and accomplishments of various intergenerational programs in Maryland, such as…

  3. START to Get Ready for Breastfeeding

    Science.gov (United States)

    Breastfeeding is a great way to give your baby the nutrients he or she needs to grow and develop. Breastfeeding also can help you and your baby form a special bond. Breastfeeding can be good for both of you if you know where to S-T-A-R-T.

  4. Systematic clustering of transcription start site landscapes

    DEFF Research Database (Denmark)

    Zhao, Xiaobei; Valen, Eivind; Parker, Brian J

    2011-01-01

    Genome-wide, high-throughput methods for transcription start site (TSS) detection have shown that most promoters have an array of neighboring TSSs where some are used more than others, forming a distribution of initiation propensities. TSS distributions (TSSDs) vary widely between promoters...

  5. Can Students Predict Starting Salaries? Yes!

    Science.gov (United States)

    Webbink, Dinand; Hartog, Joop

    2004-01-01

    We use Dutch panel data in which students have been asked to state their expected starting salary and confront these with realisations four years later. Both level and structure of expectations and realisations are remarkably close: we barely find systematic under- or overestimation effects.

  6. Verifying the INF and START treaties

    Energy Technology Data Exchange (ETDEWEB)

    Ifft, Edward [School of Foreign Service, Georgetown University, Washington, DC 20057 (United States)

    2014-05-09

    The INF and START Treaties form the basis for constraints on nuclear weapons. Their verification provisions are one of the great success stories of modern arms control and will be an important part of the foundation upon which the verification regime for further constraints on nuclear weapons will be constructed.

  7. From Jam to Start-up

    DEFF Research Database (Denmark)

    Bering Kjæhr, Emil; Lyngbye Hvid Jensen, Jane; Schoenau-Fog, Henrik

    2015-01-01

    the foundation for new start-up companies. There are, however, an even larger group of very creative and innovative games and artifacts with great potential that go unpublished. This potentially leads to a loss of entrepreneurial opportunities and ultimately the jobs and careers such games could have fostered...

  8. Single phase induction motor with starting performance

    Energy Technology Data Exchange (ETDEWEB)

    Popescu, M.; Demeter, E. [Research Institute for Electrical Machines, ICPE-ME, Bucharest (Romania); Navrapescu, V. [University `Politehnica` Bucharest, Electrical Engineering Faculty Splaiul Independentei, Bucharest (Romania)

    1997-12-31

    The paper presents problems related to a special type of single phase induction motor. The main novelty consists in the use of a conducting (aluminium casted) shell distributed on the periferic region of the rotor. As a result the starting performance, as well as the rated ones, is much improved in comparison with the conventional construction. (orig.) 4 refs.

  9. Start-Up Success: Collection Development

    Science.gov (United States)

    Awe, Susan C.

    2010-01-01

    All those who dream of working for themselves and being their own boss, whether they are fresh college graduates, recently unemployed, or newly retired from one career, have a thousand questions about where and how to begin. New entrepreneurs especially will need professional, expert help to start and run a small business effectively and…

  10. Getting started with OrientDB

    CERN Document Server

    Tesoriero, Claudio

    2013-01-01

    A standard tutorial aimed at making you an OrientDB expert, through the use of practical examples, explained in a step-by-step format.Getting Started with OrientDB 1.3.0 is great for database designers, developers, and systems engineers. It is assumed that you are familiar with NoSQL concepts, Java, and networking principles.

  11. Start-up incentives the Netherlands

    NARCIS (Netherlands)

    Bekker, S.; van den Eijnden, J.

    2014-01-01

    Generally, there are three different types of start-up incentive for unemployed and inactive people in the Netherlands. The first is a set of incentives for potential entrepreneurs receiving Unemployment Benefits (UB) (Werloosheidwet - WW). Such incentives have existed since 2006 and were adjusted

  12. Starting Salary Outcomes of Cooperative Education Graduates.

    Science.gov (United States)

    Gardner, Philip D.; And Others

    1992-01-01

    Comparison of 370 engineering co-op graduates with 1,037 nonco-op engineering graduates showed that co-op participants had higher starting salaries; 5 or fewer terms of co-op had better effects. Women, especially electrical, mechanical, or chemical majors, had substantially better salaries with co-op experience. (SK)

  13. Ultraviolet radiation-induced murine tumors produced in the absence of ultraviolet radiation-induced systemic tumor immunosuppression.

    Science.gov (United States)

    Menzies, S W; Greenoak, G E; Reeve, V E; Gallagher, C H

    1991-06-01

    Using micro-UV-irradiation versus whole-dorsal irradiation for inducing cutaneous carcinomas in Skh:HRI mice and an assay for UV radiation (UVR)-induced systemic tumor immunosuppression, the dependence upon systemic immunosuppression for the growth of UVR-induced carcinomas was examined. Squamous cell carcinomas were produced by repeated microirradiation of 0.8-cm2 middorsal skin with xenon are solar-simulated UVR. These tumors were excised from tumor-bearing animals who 7 days later were inoculated ventrally with a cloned UVR-induced squamous cell carcinoma cell line, the T51/6. This cell line only grows in UVR-induced immunosuppressed Skh:HRI mice. In two separate experiments T51/6 inocula failed to grow significantly in the previously tumor-bearing animals (1 of 13) and in unirradiated mice (0 of 19), whereas it grew in 100% (15 of 15) of animals given a whole-dorsal subcarcinogenic UVR dose from a filtered fluorescent tube solar simulator. No sinecomitant immune response to the T51/6 was found in previously UVR-induced tumor-bearing animals. In contrast to whole-dorsal UVR-induced tumors, microirradiation-induced squamous cell carcinomas, whose original growth environment lacked UVR-induced systemic tumor immunosuppression, did not grow preferentially in mice given an immunosuppressive dose of UVR. However both the whole-dorsal and microirradiation-induced tumors were shown to be poorly antigenic, since they lacked preferential growth in athymic nude mice. These observations provide evidence that UVR-induced systemic tumor immunosuppression is not necessary for the production of UVR-induced tumors. However, it does cause a positive selection pressure during tumor formation, independent of the carcinogenic effect of UVR, which affects the transplantation biology of a tumor.

  14. Early Start DENVER Model: A Meta - analysis

    Directory of Open Access Journals (Sweden)

    Jane P. Canoy

    2015-11-01

    Full Text Available Each child with Autism Spectrum Disorder has different symptoms, skills and types of impairment or disorder with other children. This is why the word “spectrum” is included in this disorder. Eapen, Crncec, and Walter, 2013 claimed that there was an emerging evidence that early interventions gives the greatest capacity of child’s development during their first years of life as “brain plasticity” are high during this period. With this, the only intervention program model for children as young as 18 months that has been validated in a randomized clinical trial is “Early Start Denver Model” (ESDM. This study aimed to determine the effectiveness of the outcome of “Early Start Denver Model” (ESDM towards young children with Autism Spectrum Disorders. This study made use of meta-analysis method. In this study, the researcher utilized studies related to “Early Start Denver Model (ESDM” which is published in a refereed journal which are all available online. There were five studies included which totals 149 children exposed to ESDM. To examine the “pooled effects” of ESDM in a variety of outcomes, a meta-analytic procedure was performed after the extraction of data of the concrete outcomes. Comprehensive Meta Analysis Version 3.3.070 was used to analyze the data.  The effectiveness of the outcome of “Early Start Denver Model” towards young children with Autism Spectrum Disorders (ASD highly depends on the intensity of intervention and the younger child age. This study would provide the basis in effectively implementing an early intervention to children with autism such as the “Early Start Denver Model” (ESDM that would show great outcome effects to those children that has “Autism Spectrum Disorder”.

  15. 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....

  16. 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.

  17. 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 re...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....... 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...

  18. Interaction with Intestinal Epithelial Cells Promotes an Immunosuppressive Phenotype in Lactobacillus casei

    Science.gov (United States)

    Tiittanen, Minna; Keto, Joni; Haiko, Johanna; Mättö, Jaana; Partanen, Jukka; Lähteenmäki, Kaarina

    2013-01-01

    Maintenance of the immunological tolerance and homeostasis in the gut is associated with the composition of the intestinal microbiota. We here report that cultivation of Lactobacillus casei ATCC 334 in the presence of human intestinal epithelial cells promotes functional changes in bacteria. In particular, the interaction enhanced the immunosuppressive phenotype of L. casei as demonstrated by the ability of L. casei to generate functional regulatory T cells (CD4+CD25+FoxP3+) and production of the anti-inflammatory cytokine interleukin-10 by human peripheral blood mononuclear cells. The results indicate microbe-host cross-talk that changes features of microbes, and suggest that in vitro simulation of epithelial cell interaction can reveal functional properties of gut microbes more accurately than conventional cultivation. PMID:24244309

  19. Immunosuppressive activity of ethanolic extract of seeds of Moringa oleifera Lam. in experimental immune inflammation.

    Science.gov (United States)

    Mahajan, Shailaja G; Mehta, Anita A

    2010-07-06

    Traditionally, the plant Moringa oleifera Lam. (Moringaceae) is used for the treatment of ascites and rheumatism, while the dried seeds of the plant are used as an 'anti-allergic' agent. The aim of the study was to assess the efficacy of ethanolic extract of seeds from Moringa oleifera Lam. in experimental immune inflammation. Circulatory and splenic leukocyte counts, delayed-type hypersensitivity reactions and humoral antibody responses were measured in mice using SRBC as the antigen. In addition, macrophage phagocytosis was measured by the carbon clearance test. The extract dose-dependently (50, 100 and 200mg/kg) inhibited spleen weight as well as circulatory leukocyte and splenocyte counts. The delayed-type hypersensitivity reaction was significantly inhibited (PMoringa oleifera have immunosuppressive activity. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  20. 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.

  1. Longitudinal analysis of the associations between antiretroviral therapy, viraemia and immunosuppression with lipid levels

    DEFF Research Database (Denmark)

    Kamara, David A; Smith, Colette; Ryom, Lene

    2016-01-01

    BACKGROUND: Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear....... METHODS: Participants from the D:A:D study with at least one TG/TC/HDL-C measurement were included. Linear mixed effect models were used to determine the association of ART, viral load (VL), nadir and current CD4(+) T-cell count and previous AIDS diagnosis with lipids. RESULTS: Of 49,717 participants, 90...... with the worst TG profile, (27.2% higher levels compared to atazanavir; 95% CI 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared with emtricitabine/tenofovir, whereas...

  2. Oral cancer after prolonged immunosuppression for multiorgan chronic graft-versus-host disease

    Directory of Open Access Journals (Sweden)

    Renata Lins Fuentes de Araujo

    2014-01-01

    Full Text Available Long-term survivors of hematopoietic stem cell transplantation are recognized as a risk group for malignization. Malignant oral neoplasms are increasingly being reported in the literature as a consequence of lesions of chronic graft-versus-host disease, and prolonged multidrug treatment to control its manifestations. This report describes a 43-year-old patient who, after allogeneic bone marrow transplantation, developed an oral squamous cell carcinoma secondary to the use of azathioprine, cyclosporine, prednisone, and tacrolimus, associated with multiorgan chronic graft-versus-host disease involving the oral mucosa, skin, eyes, and liver. This report aims to discuss the possible role of immunosuppressant therapy for chronic graft-versus-host disease on the development of oral squamous cell carcinoma, and the relevance of a close oral follow-up of patients to detect dysplastic or malignant alterations at an early stage.

  3. Extramedullary plasmacytoma presenting as a nasal mass in an immunosuppressed patient: treatment after failed primary radiotherapy.

    Science.gov (United States)

    Dempewolf, Ryan; Lee, John H

    2008-04-01

    Most of the recent evidence suggests that extramedullary plasmacytoma should be treated initially with radiation, as response rates have exceeded 90% in many studies. Surgery is not considered a primary treatment modality for such tumors. We report the case of a chronically immunosuppressed 43-year-old man with bilateral extramedullary plasmacytomas of the nasal cavities. The right-sided mass was surgically excised, while the left-sided mass was initially treated with radiation. However, the left mass proved to be radioresistant, and it was subsequently excised surgically The patient showed no evidence of recurrence of either mass at 42 months of follow-up. We believe that the particulars of this case, combined with the results of some recent studies, provide good evidence that surgery should be considered in the treatment of certain cases of extramedullary plasmacytoma.

  4. Poor response to tuberculosis treatment with regimens without rifampicin in immunosuppressed AIDS patients

    Directory of Open Access Journals (Sweden)

    O'Donnel M.M.

    2002-01-01

    Full Text Available A prospective study was conducted on 79 advanced immunosuppressed AIDS patients from 1997 to 1999, during which nine cases of tuberculosis (TB were diagnosed. The main clinical and laboratory characteristics and the response to TB treatment were reviewed. The clinical manifestations of TB were: pulmonary (six cases, extrapulmonary (two cases and disseminated (one case. These patients were being treated with highly active antiretroviral treatment (HAART and were not responding. In three cases an optional regimen without rifampicin (RMP was indicated to maintain HAART during TB treatment. A clinical response to TB treatment (disappearance of fever was observed in 6/9 patients during a mean of 73 days (SD = 96. The three unresponsive patients were those treated without RMP. A switch to TB regimens containing RMP was proposed and successful. In our study, though it was limited by a small sample size, the response to TB regimens without rifampin was poor in immunossupressed patients failing HAART.

  5. Poor response to tuberculosis treatment with regimens without rifampicin in immunosuppressed AIDS patients

    Directory of Open Access Journals (Sweden)

    M.M. O'Donnel

    Full Text Available A prospective study was conducted on 79 advanced immunosuppressed AIDS patients from 1997 to 1999, during which nine cases of tuberculosis (TB were diagnosed. The main clinical and laboratory characteristics and the response to TB treatment were reviewed. The clinical manifestations of TB were: pulmonary (six cases, extrapulmonary (two cases and disseminated (one case. These patients were being treated with highly active antiretroviral treatment (HAART and were not responding. In three cases an optional regimen without rifampicin (RMP was indicated to maintain HAART during TB treatment. A clinical response to TB treatment (disappearance of fever was observed in 6/9 patients during a mean of 73 days (SD = 96. The three unresponsive patients were those treated without RMP. A switch to TB regimens containing RMP was proposed and successful. In our study, though it was limited by a small sample size, the response to TB regimens without rifampin was poor in immunossupressed patients failing HAART.

  6. 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

    BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) are currently being investigated in preclinical and clinical settings because of their multipotent differentiative capacity or, alternatively, their immunosuppressive function. The aim of this study was to evaluate dental pulp (DP...... characteristics of DP-MSCs may prompt future studies aimed at using these cells in the treatment or prevention of T-cell alloreactivity in hematopoietic or solid organ allogeneic transplantation....... was then tested by coculturing PHA-stimulated allogeneic T cells with or without MSCs for 3 days. RESULTS: BM-MSCs could be differentiated in vitro into osteogenic, chondrogenic and adipogenic lineages. DP-MSCs showed osteogenic and adipocytic differentiation, but did not differentiate into chondrocytes. Although...

  7. 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.

  8. Protective effects of Picrorhiza kurroa on cyclophosphamide-induced immunosuppression in mice.

    Science.gov (United States)

    Hussain, Arshad; Shadma, Wahab; Maksood, Ali; Ansari, Shahid Hussain

    2013-01-01

    To study the immunomodulatory effect of ethanolic and aqueous extract of the rhizomes of Picrorrhiza kurroa (Scrophulariaceae) in normal and immunosuppressed mice models. The rhizomes extract of Picrorrhiza kurroa was administered orally according to their body weight in mice. The study was carried out by various hematological and serological tests. The assessment of immunomodulatory activity on specific and non-specific immunity was studied by administration of test extract. The method of cyclophasphamide-induced immunosuppression was employed with slight modification to study the immunomodulatory potential of the extract. Plant extracts were administered by oral feeding canula to the test groups (groups III-VI), group I (control animals) and group II (model control animals) received same volume of normal saline (0.2 ml). Humoral antibody response to SRBC measurement of antibody titer by hemagglutination reaction was done. The mice belonging to the all groups were antigenically challenged with SRBC (0.5×10(9) cells/ml/100 g) on 10(th) day intraparitoneally. Cellular immune response (Foot pad reaction test) the edema was induced by injecting SRBC (0.025×10(9) cells) in left paw, and 0.025 ml of saline was injected in right paw. The plant extract showed protective effects on humoral immunity. The change in percentage deduction in footpad volume was also found significant (P<0.001). Administration of extract remarkably ameliorated both cellular and humoral antibody response. It is concluded that the test extracts possessed promising immunostimulant properties. But, the alcoholic extract is more potent than aqueous extract in producing delayed type hypersensitivity response.

  9. A decade (1982 to 1992) of pediatric cardiac transplantation and the impact of FK 506 immunosuppression

    Science.gov (United States)

    Armitage, John M.; Fricker, Frederick J.; Nido, Pedro del; Starzl, Thomas E.; Hardesty, Robert L.; Griffith, Bartley P.

    2010-01-01

    The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14 %) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67%. In children with congenital heart disease (>6 months of age) the perioperative (30 day) mortality was 66% before mid-1988 (n = 10) and 0% since mid-1988 (n = 11). The late mortality (>30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66% (n = 14) and 7% since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82% in children with congenital heart disease and 90% in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82% at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60% at 3 and 6 months after transplantation versus 20% and 12%, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p cyclosporine group (p cardiac transplantation and a future wedded to immunosuppression. PMID:7680396

  10. 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.

  11. Antigenic and immunosuppressive properties of a trimeric recombinant transmembrane envelope protein gp41 of HIV-1.

    Directory of Open Access Journals (Sweden)

    Michael Mühle

    Full Text Available The transmembrane envelope (TM protein gp41 of the human immunodeficiency virus-1 (HIV-1 plays an important role during virus infection inducing the fusion of the viral and cellular membranes. In addition, there are indications that the TM protein plays a role in the immunopathogenesis leading to the acquired immunodeficiency syndrome (AIDS. Inactivated virus particles and recombinant gp41 have been reported to inhibit lymphocyte proliferation, as well as to alter cytokine release and gene expression. The same was shown for a peptide corresponding to a highly conserved domain of all retroviral TM proteins, the immunosuppressive domain. Due to its propensity to aggregate and to be expressed at low levels, studies comprising authentic gp41 produced in eukaryotic cells are extremely rare. Here we describe the production of a secreted, soluble recombinant gp41 in 293 cells. The antigen was purified to homogeneity and characterised thoroughly by various biochemical and immunological methods. It was shown that the protein was glycosylated and assembled into trimers. Binding studies by ELISA and surface plasmon resonance using conformation-specific monoclonal antibodies implied a six-helix bundle conformation. The low binding of broadly neutralising antibodies (bnAb directed against the membrane proximal external region (MPER suggested that this gp41 is probably not suited as vaccine to induce such bnAb. Purified gp41 bound to monocytes and to a lesser extent to lymphocytes and triggered the production of specific cytokines when added to normal peripheral blood mononuclear cells. In addition, gp41 expressed on target cells inhibited the antigen-specific response of murine CD8+ T cells by drastically impairing their IFNγ production. To our knowledge, this is the first comprehensive analysis of a gp41 produced in eukaryotic cells including its immunosuppressive properties. Our data provide another line of evidence that gp41 might be directly involved in

  12. Reduction of immunosuppression in UV-irradiated mice by dietary retinyl palmitate plus canthaxanthin.

    Science.gov (United States)

    Gensler, H L

    1989-01-01

    The ability of dietary retinyl palmitate, canthaxanthin or the combination of both, to prevent induction of immunosuppression by UVB irradiation was tested by passive transfer of splenocytes. The basal diet was the American Institute of Nutrition diet 76A, containing 4 IU retinyl palmitate/g diet. Groups of 55 mice were fed this basal diet alone, or supplemented with 120 IU retinyl palmitate/g diet, 1% canthaxanthin or the combination of both. After 18 weeks of these diets, UVB radiation treatments began. The UVB radiation source was a bank of six unfiltered Westinghouse FS40 lamps which delivered an average dose of 4.6 J/m2/s over the wavelength range of 280-340 nm. After 27.5 weeks of UV treatments, and approximately 1.14 X 10(6) J/m2, spleens were removed from mice and used as sources of splenocytes for passive transfer into naive recipients. These recipients were then challenged with an immunogenic, syngeneic UV-induced tumor (UV20). Approximately twice as many tumor challenges grew in recipients of splenocytes from UV-irradiated (19/20), as compared with unirradiated (11/20) donors fed the basal diet. Transfer of splenocytes from UV-irradiated donors fed the basal diet admixed with 1% canthaxanthin, 120 IU retinyl palmitate/g diet or the combination, resulted in 16/20, 13/20 and 10/20 growing tumors, respectively. These values were insignificantly (P = 0.25), marginally (P = 0.054) or significantly (P less than 0.02) different from the positive control value, respectively. Thus, dietary supplementation with retinyl palmitate plus canthaxanthin prevented the transfer of UV-induced immunosuppression with splenocytes from UV-irradiated mice.

  13. Immunosuppressive effects of ginsenoside-Rd on skin allograft rejection in rats.

    Science.gov (United States)

    Wang, Li; Zhang, Yunxin; Chen, Jiajia; Li, Sijia; Wang, Yanhong; Hu, Lamei; Wang, Lihua; Wu, Yongjie

    2012-07-01

    Organ transplantation is a life-saving procedure for patients with organ failure. However, the side effects of long-term application of classic immunosuppressant remain major obstacles for successful transplantation. Therefore, new and safe immunosuppressive drugs against acute and chronic rejection are eagerly awaited. In the present study, we detected the effect of ginsenoside-Rd on mitogen-induced mouse spleen lymphocytes proliferation in vitro and observed the effect of ginsenoside-Rd on allograft rejection in a rat skin transplantation model. Th1/Th2 type cytokines secretion and T-cell subsets were also detected. The results showed that ginsenoside-Rd could markedly inhibit Concanavalin A (ConA)-induced mouse spleen T lymphocytes proliferation. Also, ginsenoside-Rd could significantly prolong the mean survival time of skin allograft and improve the skin allograft pathological damage. Furthermore, ginsenoside-Rd could markedly suppress alloantigen-specific production of Th1 cytokines IL-2 and IFN-γ as well as proinflammatory cytokines TNFα and IL-12. In parallel, Th2 cytokine IL-10 production in serum of rat recipients was markedly up-regulated. Ginsenoside-Rd at a dose of 25 mg/kg could significantly reduce the percentages of CD4(+) T cells and CD8(+) T cells in peripheral blood of rat recipients. Our results suggest that ginsenoside-Rd can effectively antagonize transplant rejection, which might qualify ginsenoside-Rd as a putative, therapeutic drug for the treatment of Th1-driven diseases, including transplant rejection. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Citalopram enhances B cell numbers in a murine model of morphine-induced immunosuppression.

    Science.gov (United States)

    Nguyen, Thao; Kramer, Jeffery; Vallejo, Ricardo; Stanton, George; Heidenreich, Byron A; Benyamin, Ramsin; Vogel, Laura A

    2009-01-01

    Patients with chronic pain are often challenged with depression stemming from the long-term psychophysiological effects of their condition. Consequently, patients with chronic pain are often treated with morphine, which can induce immunosuppression, along with an antidepressant. The antidepressant citalopram (CTP; Sigma-Aldrich Chemical, St. Louis, MO, U.S.A.) is a serotonin reuptake inhibitor that is reported to have immunomodulatory effects. Thus, we investigated whether CTP administration impacted immunity in morphine-treated animals. Adult mice were pretreated for 7 days with either saline or CTP (10 or 30 mg/kg intraperitoneal injections twice daily), followed by subcutaneous implantation of a 25 mg morphine pellet for 48 hours. Spleen, thymus, and lymph nodes were harvested to analyze total cell numbers, relative lymphocyte populations, and lymphocyte function. In this study, CTP had no effect on either total cell counts or lymphocyte populations in the thymus. However, in the spleen, total splenocyte numbers in all CTP-treated animals displayed an increasing trend over saline-treated animals. Interestingly, although more cells were found in the spleen, distribution of splenic lymphocyte populations did not differ between treatments. Despite no increase in total cell number, a high dose of CTP (30 mg/kg) resulted in a significantly higher B cell population in the lymph nodes, while T cell and NK cell numbers were not different. CTP did not significantly reverse morphine-induced weight loss or splenic B cell antibody secretion in vitro. Additionally, CTP treatment demonstrated a slight but not significant increase in both splenic B and T cell mitogen-induced proliferation in vitro. In summary, CTP may have a specific potential in the attenuation of morphine's immunosuppressive effect by enhancing splenocyte numbers and lymph node B cell populations.

  15. 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.

  16. Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection.

    Directory of Open Access Journals (Sweden)

    Dimitra Peppa

    2010-12-01

    Full Text Available NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB, allowing them to kill hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to 31 healthy controls. We found that, in contrast to their upregulated TRAIL expression and maintenance of cytolytic function, NK cells had a markedly impaired capacity to produce IFN-γ in CHB. This functional dichotomy of NK cells could be recapitulated in vitro by exposure to the immunosuppressive cytokine IL-10, which was induced in patients with active CHB. IL-10 selectively suppressed NK cell IFN-γ production without altering cytotoxicity or death ligand expression. Potent antiviral therapy reduced TRAIL-expressing CD56(bright NK cells, consistent with the reduction in liver inflammation it induced; however, it was not able to normalise IL-10 levels or the capacity of NK cells to produce the antiviral cytokine IFN-γ. Blockade of IL-10 +/- TGF-β restored the capacity of NK cells from both the periphery and liver of patients with CHB to produce IFN-γ, thereby enhancing their non-cytolytic antiviral capacity. In conclusion, NK cells may be driven to a state of partial functional tolerance by the immunosuppressive cytokine environment in CHB. Their defective capacity to produce the antiviral cytokine IFN-γ persists in patients on antiviral therapy but can be corrected in vitro by IL-10+/- TGF-β blockade.

  17. Designer Thiopurine-analogues for Optimised Immunosuppression in Inflammatory Bowel Diseases.

    Science.gov (United States)

    Atreya, Imke; Diall, Alexandra; Dvorsky, Radovan; Atreya, Raja; Henninger, Christian; Grün, Mathias; Hofmann, Ute; Schaeffeler, Elke; López-Posadas, Rocío; Daehn, Ilse; Zenker, Stefanie; Döbrönti, Michael; Neufert, Clemens; Billmeier, Ulrike; Zundler, Sebastian; Fritz, Gerhard; Schwab, Matthias; Neurath, Markus F

    2016-10-01

    The clinical use of azathioprine and 6-mercaptopurine is limited by their delayed onset of action and potential side effects such as myelosuppression and hepatotoxicity. As these drugs specifically target the Vav1/Rac1 signalling pathway in T lamina propria lymphocytes via their metabolite 6-thio-GTP, we studied expression and optimised suppression of this pathway in inflammatory bowel diseases [IBD]. Rac1 and Vav1 expressions were analysed in mucosal immune cells in IBD patients. Targeted molecular modelling of the 6-thio-GTP molecule was performed to optimise Rac1 blockade; 44 modified designer thiopurine-analogues were tested for apoptosis induction, potential toxicity, and immunosuppression. Activation of the Vav1/Rac1 pathway in lymphocytes was studied in IBD patients and in lamina propria immune cells in the presence or absence of thiopurine-analogues. Several thiopurine-analogues induced significantly higher T cell apoptosis than 6-mercaptopurine. We identified a compound, denoted B-0N, based on its capacity to mediate earlier and stronger induction of T cell apoptosis than 6-mercaptopurine. B-0N-treatment resulted in accelerated inhibition of Rac1 activity in primary peripheral blood T cells as well as in intestinal lamina propria immune cells. Compared with 6-thio-GTP and 6-mercaptopurine, B-0N-treatment was associated with decreased myelo- and hepatotoxicity. The Vav1/Rac1 pathway is activated in mucosal immune cells in IBD. The designer thiopurine-analogue B-0N induces immunosuppression more potently than 6-mercaptopurine. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Herpes viruses and tumours in kidney transplant recipients. The role of immunosuppression.

    Science.gov (United States)

    Ponticelli, Claudio

    2011-06-01

    Herpes virus infections are frequent in renal transplant recipients. Some herpes viruses are not only responsible for life-threatening infections and renal graft injury but can also increase the risk of malignancy. Three herpes viruses, namely cytomegalovirus (CMV) or human herpes virus 5, Epstein-Barr virus (EBV) or herpes virus 4 and human herpes virus 8 (HHV8), may play an oncogenic role. The oncogenic role of CMV is controversial. However, there is growing evidence showing that CMV can infect cancer cells and favour their resistance to the immune system and chemotherapy. B cells infected by EBV can have uncontrolled proliferation eventually resulting in polyclonal polymorphic or monomorphic post-transplant lymphoproliferative diseases (PTLD), which are particularly frequent in children and in EBV-negative recipients. In some ethnicities, the carriers of HHV8 are susceptible to develop Kaposi's sarcoma after transplantation. The intensity of immunosuppression therapy plays a critical role in mediating infections from oncogenic herpes viruses. However, the type of immunosuppressive drugs can also influence the risk of virus-mediated neoplasias. An aggressive induction therapy aimed at depleting lymphocytes may favour the reactivation and dissemination of oncogenic herpes viruses, while anti-CD25 monoclonal antibodies have little impact on virus reactivation. Calcineurin inhibitors can increase the risk of viral infections and malignancy. Mycofenolate salts may perhaps protect from EBV-related PTLD. Finally, the inhibitors of the mammalian target of rapamycine may reduce the risk of viral disease by inhibiting the cascade of kinases that govern the proliferation and replication of oncogenic herpes viruses.

  19. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy.

    Science.gov (United States)

    Huang, Yuhui; Yuan, Jianping; Righi, Elda; Kamoun, Walid S; Ancukiewicz, Marek; Nezivar, Jean; Santosuosso, Michael; Martin, John D; Martin, Margaret R; Vianello, Fabrizio; Leblanc, Pierre; Munn, Lance L; Huang, Peigen; Duda, Dan G; Fukumura, Dai; Jain, Rakesh K; Poznansky, Mark C

    2012-10-23

    The recent approval of a prostate cancer vaccine has renewed hope for anticancer immunotherapies. However, the immunosuppressive tumor microenvironment may limit the effectiveness of current immunotherapies. Antiangiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy, but they often are used at high doses in the clinic to prune tumor vessels and paradoxically may compromise various therapies. Here, we demonstrate that targeting tumor vasculature with lower vascular-normalizing doses, but not high antivascular/antiangiogenic doses, of an anti-VEGF receptor 2 (VEGFR2) antibody results in a more homogeneous distribution of functional tumor vessels. Furthermore, lower doses are superior to the high doses in polarizing tumor-associated macrophages from an immune inhibitory M2-like phenotype toward an immune stimulatory M1-like phenotype and in facilitating CD4(+) and CD8(+) T-cell tumor infiltration. Based on this mechanism, scheduling lower-dose anti-VEGFR2 therapy with T-cell activation induced by a whole cancer cell vaccine therapy enhanced anticancer efficacy in a CD8(+) T-cell-dependent manner in both immune-tolerant and immunogenic murine breast cancer models. These findings indicate that vascular-normalizing lower doses of anti-VEGFR2 antibody can reprogram the tumor microenvironment away from immunosuppression toward potentiation of cancer vaccine therapies. Given that the combinations of high doses of bevacizumab with chemotherapy have not improved overall survival of breast cancer patients, our study suggests a strategy to use antiangiogenic agents in breast cancer more effectively with active immunotherapy and potentially other anticancer therapies.

  20. Resistance of a lizard (the green anole, Anolis carolinensis; Polychridae) to ultraviolet radiation-induced immunosuppression

    Science.gov (United States)

    Cope, R.B.; Fabacher, D.L.; Lieske, C.; Miller, C.A.

    2001-01-01

    The green anole (Anolis carolinensis) is the most northerly distributed of its Neotropical genus. This lizard avoids a winter hibernation phase by the use of sun basking behaviors. Inevitably, this species is exposed to high doses of ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B (UV-B) radiation secondary to stratospheric ozone depletion and habitat perturbation potentially place this species at risk of UVR-induced immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85 kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative doses of 192 kJ/m2 UV-B, 2.04 × 103 kJ/m2 UV-A) did not suppress the anole's acute or delayed type hypersensitivity (DTH) response to horseshoe crab hemocyanin. In comparison with the available literature UV-B doses as low as 0.1 and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans, respectively. Exposure of anoles to UVR did not result in the inhibition of ex vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2 have been reported to suppress murine splenic/peritoneal macrophage phagocytosis and nitric oxide production. These preliminary studies demonstrate the resistance of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin contained two peaks in the ultraviolet wavelength range that could be indicative of photoprotective substances. However, the resistance of green anoles to UVR is probably not completely attributable to absorption by UVR photoprotective substances in the skin but more likely results from a combination of other factors including absorption by the cutis and absorption and reflectance by various components of the dermis.

  1. 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.

  2. Starting apparatus for internal combustion engines

    Science.gov (United States)

    Dyches, Gregory M.; Dudar, Aed M.

    1997-01-01

    An internal combustion engine starting apparatus uses a signal from a curt sensor to determine when the engine is energized and the starter motor should be de-energized. One embodiment comprises a transmitter, receiver, computer processing unit, current sensor and relays to energize a starter motor and subsequently de-energize the same when the engine is running. Another embodiment comprises a switch, current transducer, low-pass filter, gain/comparator, relay and a plurality of switches to energize and de-energize a starter motor. Both embodiments contain an indicator lamp or speaker which alerts an operator as to whether a successful engine start has been achieved. Both embodiments also contain circuitry to protect the starter and to de-energize the engine.

  3. Sleep-wake pattern of medical students: early versus late class starting time

    OpenAIRE

    Lima, P.F.; Medeiros, A.L.D.; Araujo, J.F.

    2002-01-01

    The sleep-wake cycle of students is characterized by delayed onset, partial sleep deprivation and poor sleep quality. Like other circadian rhythms, the sleep-wake cycle is influenced by endogenous and environmental factors. The aim of the present study was to determine the effects of different class starting times on the sleep-wake pattern of 27 medical students. The data were collected during two medical school semesters having different class starting times. All subjects answered the Portug...

  4. Complexity and Chaos in Surgical Start Times

    Directory of Open Access Journals (Sweden)

    Dennis J. Baumgardner

    2016-08-01

    Full Text Available In discussing an article investigating the causes for delay of first-case operating room start times included in this issue of the Journal of Patient-Centered Research and Reviews, the editor uses elements of complexity science and chaos theory to explain that such stubborn problems rarely stem from one of a few isolated causes. Taking a whole systems approach that utilizes flexibility, cross training, enhanced communication, common sense and perhaps mathematical models is suggested to effect positive change.

  5. Starting and developing a surveying business

    CERN Document Server

    Imber, Austen

    2013-01-01

    Starting and Developing a Surveying Business shows how surveyors can develop their own successful small business. For surveyors thinking of taking this step, guidance is provided on the pros and cons which will help the right decision to be made, and the key factors which help see the business through its early stages. For surveyors already running their own small business, consideration is given to factors which will help profitability and growth potential.

  6. New START: The Contentious Road to Ratification

    Directory of Open Access Journals (Sweden)

    Elizabeth Zolotukhina

    2011-01-01

    Full Text Available Senate ratification of the New START treaty re-established effective bilateral inspection and monitoring of American and Russian nuclear holdings and has the potential to further enhance U.S.-Russian cooperation on key issues, including containing the Iranian nuclear program, and further reductions in the two countries' arsenals. Although the accord was widely heralded as a foreign policy success of the Obama administration, the contentious Senate ratification may impede future progress on arms control.

  7. The 2002 Starting Artificial Intelligence Researchers Symposium

    OpenAIRE

    Vidal, Thierry

    2003-01-01

    During the 2002 European Conference on Artificial Intelligence (ECAI-02) was introduced the Starting Artificial Intelligence Researchers Symposium STAIRS), the first-ever international symposium specifically aimed at Ph.D. students in AI. The outcome was a thorough, high-quality, and successful event, with all the features one usually finds in the best international conferences: large international committees, comprehensive coverage, published proceedings, renowned speakers and panelists, sub...

  8. Getting started with nopCommerce

    CERN Document Server

    Atkinson, Brandon

    2013-01-01

    A friendly, tutorial style book, which will help you learn your way through creating a live storefront with nopCommerce in a step-by-step manner.Getting Started with nopCommerce is for anyone who wants to sell products online using nopCommerce. If you are a non-technical person and are discouraged by the complexity of this powerful e-commerce application, then this book is for you.

  9. New Start of “Psychological Thought”

    Directory of Open Access Journals (Sweden)

    Stanislava Stoyanova

    2012-05-01

    Full Text Available The history and the mission of Psychological Thought are presented. The scientific journal “Psychological Thought” started its existence as an idea of the colleagues at the Department of Psychology at South-West University “Neofit Rilski” in 2006. Seven print issues were published from 2006 to 2009 (2 issues per year. Each issue included average ten articles published in Bulgarian or in English.

  10. "Go" signal intensity influences the sprint start.

    Science.gov (United States)

    Brown, Alexander M; Kenwell, Zoltan R; Maraj, Brian K V; Collins, David F

    2008-06-01

    Loud sounds can decrease reaction time (RT) and increase force generated during voluntary contractions. Accordingly, we hypothesized that the loud starter's pistol at the Olympic Games allows runners closer to the starter to react sooner and stronger than runners farther away. RT for the 100/110 m athletics events at the 2004 Olympics were obtained from International Association of Athletics Federations archives and binned by lane. Additionally, 12 untrained participants and four trained sprinters performed sprint starts from starting blocks modified to measure horizontal force. The "go" signal, a recorded gunshot, was randomly presented at 80-100-120 dB. Runners closest to the starter at the Olympics had significantly lower RT than those further away. Mean RT for lane 1 (160 ms) was significantly lower than for lanes 2-8 (175 +/- 5 ms), and RT for lane 2 was significantly lower than that for lane 7. Experimentally, increasing "go" signal intensity from 80-100-120 dB significantly decreased RT from 138 +/- 30 to 128 +/- 25 to 120 +/- 20 ms, respectively. Peak force was not influenced by sound intensity. However, time to peak force was significantly lower for the 120 dB compared to the 80-dB "go" signal for untrained but not trained participants. When a startle response was evoked, RT was 18 ms lower than for starts with no startle. Startle did not alter peak force or time to peak force. Graded decreases in RT may reflect a summation-mediated reduction in audiomotor transmission time, whereas step-like decreases associated with startle may reflect a bypassing of specific cortical circuits. We suggest that procedures presently used to start the Olympic sprint events afford runners closer to the starter the advantage of hearing the "go" signal louder; consequently, they react sooner but not more strongly than their competitors.

  11. Getting started with MariaDB

    CERN Document Server

    Bartholomew, Daniel

    2013-01-01

    A practical, hands-on, beginner-friendly guide to installing and using MariaDB.Getting Started with MariaDB is for anyone who wants to learn more about databases in general or MariaDB in particular. No prior database experience is required. It is assumed that you have basic knowledge of software installation, editing files with a text editor, and using the command line and terminal.

  12. Sensibility and Subjectivity: Levinas’ Traumatic Subject

    Directory of Open Access Journals (Sweden)

    Rashmika Pandya

    2011-02-01

    Full Text Available The importance of Levinas’ notions of sensibility and subjectivity are evident in the revision of phenomenological method by current phenomenologists such as Jean-Luc Marion and Michel Henry. The criticisms of key tenants of classical phenomenology, intentionality and reduction, are of a particular note. However, there are problems with Levinas’ characterization of subjectivity as essentially sensible. In “Totality and Infinity” and “Otherwise than Being”, Levinas criticizes and recasts a traditional notion of subjectivity, particularly the notion of the subject as the first and foremost rational subject. The subject in Levinas’ works is characterized more by its sensibility and affectedness than by its capacity to reason or affect its world. Levinas ties rationality to economy and suggests an alternative notion of reason that leads to his analysis of the ethical relation as the face-to-face encounter. The ‘origin’ of the social relation is located not in our capacity to know but rather in a sensibility that is diametrically opposed to the reason understood as economy. I argue that the opposition in Levinas’ thought between reason and sensibility is problematic and essentially leads to a self-conflicted subject. In fact, it would seem that violence characterizes the subject’s self-relation and, thus, is also inscribed at the base of the social relation. Rather than overcoming a problematic tendency to dualistic thought in philosophy Levinas merely reverses traditional hierarchies of reason/emotion, subject/object and self/other. 

  13. Sanskrit Grammarians and the 'Speaking Subjectivity'

    OpenAIRE

    Aussant, Emilie

    2013-01-01

    International audience; Starting from the grammatical terminology, I give in this paper a panorama of the speaking subjectivity manifestationsaccording to Sanskrit grammatical texts, from the Aṣṭādhyāyī of Pāṇini to the Paramalaghumañjūṣā of Nāgeśa.

  14. The effect of infectious bursal disease virus induced immunosuppression on vaccination against highly pathogenic avian influenza virus

    Science.gov (United States)

    Poor efficacy of avian influenza virus (AIV) vaccines in chickens has been documented in the field in spite of good results in experimental settings. Although the causes are multi-factorial and complex, one contributing factor may be prior infection with immunosuppressive viruses. In an effort to ...

  15. 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.

    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

  16. 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

  17. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    NARCIS (Netherlands)

    Garritsen, Floor M.; Van der Schaft, Jorien; Van den Reek, Juul M.; Politiek, Klaziena; Van Osmedendorp, Harmieke; Van Dijk, Marijke; Hijnen, Dirk J.; De Graaf, Marlies; Bruijnzeel-Koomen, Carla A.; De Jong, Elke M.; Schuttelaar, Marie-Louise A.; De Bruin-Weller, Marjolein S.

    There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  18. Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

    NARCIS (Netherlands)

    Garritsen, F.M.; Schaft, J. van der; Reek, J.M.P.A. van den; Politiek, K.; Os-Medendorp, H. van; Dijk, M.; Hijnen, D.J.; Graaf, M de; Bruijnzeel-Koomen, C.A.; Jong, E.M.G.J. de; Schuttelaar, M.A.; Bruin-Weller, M.S. de

    2017-01-01

    There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the

  19. Neurological complications after liver transplantation as a consequence of immunosuppression: univariate and multivariate analysis of risk factors.

    Science.gov (United States)

    Rompianesi, Gianluca; Montalti, Roberto; Cautero, Nicola; De Ruvo, Nicola; Stafford, Anthony; Bronzoni, Carolina; Ballarin, Roberto; De Pietri, Lesley; Di Benedetto, Fabrizio; Gerunda, Giorgio E

    2015-07-01

    Neurological complications (NCs) can frequently and significantly affect morbidity and mortality of liver transplant (LT) recipients. We analysed incidence, risk factors, outcome and impact of the immunosuppressive therapy on NC development after LT. We analysed 478 LT in 440 patients, and 93 (19.5%) were followed by NCs. The average LOS was longer in patients experiencing NCs. The 1-, 3- and 5-year graft survival and patient survival were similar in patients with or without a NC. Multivariate analysis showed the following as independent risk factors for NC: a MELD score ≥20 (OR = 1.934, CI = 1.186-3.153) and an immunosuppressive regimen based on calcineurin inhibitors (CNIs) (OR = 1.669, CI = 1.009-2.760). Among patients receiving an everolimus-based immunosuppression, the 7.1% developed NCs, vs. the 16.9% in those receiving a CNI (P = 0.039). There was a 1-, 3- and 5-year NC-free survival of 81.7%, 81.1% and 77.7% in patients receiving a CNI-based regimen and 95.1%, 93.6% and 92.7% in those not receiving a CNI-based regimen (P < 0.001). In patients undergoing a LT and presenting with nonmodifiable risk factors for developing NCs, an immunosuppressive regimen based on CNIs is likely to result in a higher rate of NCs compared to mTOR inhibitors. © 2015 Steunstichting ESOT.

  20. Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity.

    NARCIS (Netherlands)

    Buf-Vereijken, P.W.G. du; Wetzels, J.F.M.

    2004-01-01

    BACKGROUND: A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of

  1. 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.

  2. 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...

  3. 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

  4. 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...

  5. 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.

  6. Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study.

    Science.gov (United States)

    Lin, W T; Chen, Y M; Chen, D Y; Lan, J L; Chang, C S; Yeh, H Z; Yang, S S

    2018-01-01

    Objective We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy. Methods We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation. Results During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis. Conclusions The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

  7. The relation of the number of hydrogen-bond acceptors with recoveries of immunosuppressants in DBS analysis

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Botma, Rixt; Greijdanus, Ben; Uges, Donald R. A.; Kosterink, Jos G. W.; Touw, Daan J.

    2015-01-01

    BACKGROUND: We investigated the influence of the number of hydrogen-bond acceptors on the recovery of immunosuppressant drugs and their structural analogs. This hypothesis was tested by evaluation of the extraction recoveries of tacrolimus, ascomycin, sirolimus, everolimus and temsirolimus with 12,

  8. Prevention of ultraviolet radiation‑induced immunosuppression by sunscreen in Candida albicans‑induced delayed‑type hypersensitivity.

    Science.gov (United States)

    Chen, Quan; Li, Runxiang; Zhao, Xiaoxia; Liang, Bihua; Ma, Shaoyin; Li, Zhenjie; Zhu, Huilan

    2016-07-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans‑induced delayed‑type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub‑erythema dose of solar‑simulated radiation. Delayed‑type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi‑quantitatively detected using Western blotting and immunohistochemical assays. The delayed‑type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non‑sunscreen group were 24.39 and 65.85%, respectively (Psunscreen group, compared with those in the non‑sunscreen group. UV exposure reduced Candida albicans antigen‑induced delayed‑type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells.

  9. Tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation: systematic review with meta-analyses and trial sequential analyses of randomised trials

    DEFF Research Database (Denmark)

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

    2010-01-01

    We conducted a systematic review of randomized trials to compare the benefits and harms of tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation.......We conducted a systematic review of randomized trials to compare the benefits and harms of tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation....

  10. [Analogies between "fraction P" with immunosuppressive properties in pregnant females and a protein fraction induced by estradiol treatment in the amphibian Salamandra salamandra L].

    Science.gov (United States)

    Badet, M T

    1980-12-08

    A "fraction P" analogue possessing immunosuppressive properties during pregnancy in the Salamandra, can be induced by treating males and females with oestradiol. Both fractions possess the same physiochemical characteristics, and equally react against a Rabbit immune serum anti "fraction P" of pregnant Salamandra. But the proteic fraction induced by hormonal treatment does immunosuppressive properties.

  11. 76 FR 50813 - Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures

    Science.gov (United States)

    2011-08-16

    ... Federal Transit Administration Major Capital Investment Projects; Guidance on News Starts/Small Starts... policy guidance on the New and Small Starts capital project review and evaluation process and criteria...) published by FTA in June 2010, which sought public comment on the New Starts and Small Starts project...

  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. No adaptation to UV-induced immunosuppression and DNA damage following exposure of mice to chronic UV-exposure.

    Science.gov (United States)

    Steerenberg, Peter A; Daamen, Frieda; Weesendorp, Eefke; Van Loveren, Henk

    2006-07-03

    It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity.

  14. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans.

    Science.gov (United States)

    Sivapirabu, G; Yiasemides, E; Halliday, G M; Park, J; Damian, D L

    2009-12-01

    Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown. To determine the effects and mechanisms of topical nicotinamide on UV-induced suppression of delayed type hypersensitivity (DTH) responses in humans. Healthy Mantoux-positive volunteers in four randomised, double-blinded studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0.2% or 5%) or its vehicle were applied immediately after each irradiation. Mantoux testing was performed at irradiated sites and adjacent unirradiated control sites 48 h after the first irradiation and measured 72 h later. Immunosuppression was calculated as the difference in Mantoux-induced erythema and induration at test sites compared to control sites. Human keratinocyte cell cultures, with and without ssUV and nicotinamide, were used for quantitative real-time reverse transcriptase-polymerase chain reaction assessment of TP53 and enzymes that regulate oxidative phosphorylation. Nicotinamide cooperated with ssUV to increase enzymes involved in cellular energy metabolism and p53, and significantly protected against immunosuppression caused by UVB, longwave UVA and single and repeated ssUV exposures. Longwave UVA, which is poorly filtered by most sunscreens, was highly immune suppressive even at doses equivalent to 20 min of sun exposure. Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.

  15. Power plant start-up demands productive methods and practices

    Energy Technology Data Exchange (ETDEWEB)

    Follett, R.E.

    1993-05-01

    This article examines the factors affecting power plant start-up. The article addresses cogeneration plants in particular. The topics of the article include the start-up schedule, start-up program administration, safety tagging procedure, system boundary identification, mechanical test procedures, electrical test procedures, pre-operational tests, loop calibration reports, performance test procedure, instrument calibration, checkout philosophy, plant start-up organization, plant start-up sequence, operator training, and typical plant start-up conditions.

  16. Take Control of Getting Started with Dreamweaver

    CERN Document Server

    Keller, Arnie

    2009-01-01

    Learn fundamental Web design principles and become comfortable working in Dreamweaver's complex interface! Dreamweaver 8 is a great Web design tool for pros, but newcomers may be overwhelmed by its interface or want to know more about how to work creatively and intelligently in the program. Help is at hand in Take Control of Getting Started with Dreamweaver, which offers a detailed tutorial for making your first site in Dreamweaver. Author Arnie Keller, who teaches Web design at the University of Victoria, shows you how to style type the smart way with CSS, create a sophisticated page layout

  17. Getting started with Zurb Foundation 4

    CERN Document Server

    Patterson, Andrew D

    2013-01-01

    The book starts with the basics of Foundation and helps you build your skills as you advance from installation to design, configuration, and customization with examples at every step.This book will be of great benefit to web architects, designers, and builders. While it helps to be a programmer, it isn't necessary for this book. You should be familiar with the basic principles of responsive web design and have a desire to create a professional website that looks great on both mobile devices and regular displays.

  18. Getting started with the Lazarus IDE

    CERN Document Server

    Person, Roderick

    2013-01-01

    This book is written in a simple, easy-to-understand format with lots of screenshots and step-by-step explanations.This book is geared toward developers that have a familiarity with Delphi or Free Pascal and would like to start using the open source Lazarus Integrated Development Environment. You should have knowledge of creating a console and GUI applications as well as creating basic components. Example source code and projects are provided to help learn the differences between Delphi and Lazarus projects.

  19. Getting started with ownCloud

    CERN Document Server

    Patawari, Aditya

    2013-01-01

    This is a standard, precise, and short tutorial for setting up ownCloud and includes advanced topics like encryption, user management, and server security. This ownCloud book would be an ideal starting point for anyone who wants to store their data and also share it.This book is for first time users as well as administrators who are interested or responsible for managing an ownCloud instance. You do not need any prior experience with any of the technology, including Linux/Windows, Apache/IIS, SQLite/MySQL, or even PHP. It is a beginner-friendly book, written with a first time user in mind.

  20. Successful start-ups & key success factors

    OpenAIRE

    Brillois, Bertrand

    2000-01-01

    Almost everyday we can read about or listen to the radio the creation of a new company, which is of course successfull and just started several months ago. One succeed but for how many other failures. In our everyday life we only know the companies which exist. We never consider all the high number of companies that have failed. In addition to that, by analyzing some cases, we can notice that some"good"companies, with good team, good concept can failed too. In order to understand the views th...