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‣ Estudo da incidência da infecção por citomegalovírus através da técnica de antigenemia, em uma coorte de pacientes transplantados renais

Deboni, Luciane Monica
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Dissertação Formato: application/pdf
Português
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O citomegalovírus (CMV), está entre os principais agentes infecciosos que acometem pacientes transplantados renais. A infecção por CMV está relacionada ao status sorológico do doador e receptor, bem como o tipo e intensidade da imunossupressão utilizada. A infecção, e em especial a doença citomegálica, determinam aumento da morbi-mortalidade após o transplante. O espectro da doença varia desde formas assintomáticas até a doença sistêmica grave com comprometimento de vários órgãos. A doença por CMV é diagnosticada através da evidência laboratorial de infeção, associada a quadro clínico compatível. A técnica da antigenemia identifica a presença do antígeno viral p65 em leucócitos do sangue periférico através de reação de imunoperoxidase utilizando-se anticorpos monoclonais. O objetivo principal deste trabalho foi o de determinar a incidência de infecção por CMV em uma coorte de pacientes transplantados renais usando a antigenemia como ferramenta diagnóstica. Secundariamente buscou-se avaliar o impacto desta infecção nas sobrevidas dos pacientes e dos enxertos em 6 anos de acompanhamento. No período de inclusão no estudo, janeiro de 1994 a fevereiro de 1995, foram realizados 74 transplantes renais na Santa Casa de Porto Alegre–RS. As amostras de sangue para a detecção da antigenemia foram obtidas semanalmente durante a internação hospitalar e posteriormente...

‣ Combined effects of cyclosporin and nifedipine on gingival overgrowth in rats is not age dependent

Spolidorio, L. C.; Spolidorio, D. M.; Benatti, C.; Sampaio, J. E.; Almeida, O. P.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 375-379
Português
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Background: Cyclosporin A and nifedipine cause gingival overgrowth in rat, and the combined use of these drugs increases the overgrowth severity. Objective: The purpose of this study was to compare gingival overgrowth of rats of differents ages treated with cyclosporin A and nifedipine alone or given concurrently. Materials and methods: Rats 15, 30, 60 and 90 d old were treated with 10 mg/kg body weight of cyclosporin A and/or 50 mg/kg body weight of nifedipine in the chow. Results: Young rats showed evident gingival overgrowth with nifedipine, cyclosporin A, and cyclosporin A and nifedipine given concurrently. Adult rats did not show significant gingival alterations when treated with cyclosporin A and nifedipine alone. Nevertheless evident gingival overgrowth with alterations of the epithelium and connective tissue were observed when treated simultaneously with cyclosporin A and nifedipine. Conclusion: These results suggest that the combined effects of cyclosporin A and nifedipine on gingival overgrowth in rat is not age dependent.

‣ Efeito da Ciclosporina A associada à infusão de nó-de-cachorro (Heteropterys aphrodisiaca, O. Mach, 1949) na próstata de ratos Wistar; Effect of Cyclosporin A associated with nó-de-cachorro (Heteropterys aphrodisiaca, O. Mach, 1949) infusion on Wistar rats ventral prostate

Karine Moura Freitas
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 18/02/2011 Português
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A Ciclosporina A (CsA) é um imunossupressor amplamente utilizado no tratamento pós-transplante de órgãos e contra doenças auto-imunes. Entretanto, diversos efeitos colaterais estão relacionados ao tratamento com esta droga, dentre eles nefrotoxicidade, hepatoxicidade, tremor, hipertensão, hiperlipidemia, hipercalcemia, hipertricose e hiperplasia gengival. Além destes, danos à reprodução masculina como redução na produção de testosterona e disfunção testicular são extensivamente documentados. Heteropterys aphrodisiaca é uma planta arbustiva típica do Cerrado brasileiro. É conhecida como nó-de-cachorro, sendo utilizada popularmente como tônica e afrodisíaca. Estudos anteriores confirmam a eficiência da infusão de H. aphrodisiaca contra os efeitos colaterais a CsA nos testículos. Visto isso, o objetivo do presente trabalho foi determinar os possíveis efeitos colaterais da CsA na próstata ventral de ratos Wistar e verificar se a infusão de H. aphrodisiaca seria eficiente em minimizá-los. Trinta ratos Wistar adultos (90 dias) foram divididos em cinco grupos (n=6 em cada): Grupo I (controle): tratado com água; grupo II: tratado com CsA; grupo III: tratado com infusão de H. aphrodisiaca; grupo IV: tratamento simultâneo de CsA e H. aphrodisiaca; e grupo V: tratamento com CsA e H. aphrodisiaca em dias alternados. A CsA foi administrada na dose de 15 mg/kg/dia e a infusão de nó-de-cachorro no volume de 0...

‣ The role of antifungals agents on Candida glabrata biofilms matrix composition

Silva, Sónia Carina; Lourenço, T.; Negri, M.; Henriques, Mariana; Azeredo, Joana; Oliveira, Rosário
Fonte: Universidade do Minho Publicador: Universidade do Minho
Tipo: Conferência ou Objeto de Conferência
Publicado em //2010 Português
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Candida glabrata was considered, for years, a relatively non-pathogenic saprophyte of the normal flora of healthy individuals and as no causative agent of serious infection in humans. However, its high mortality rate and its quick spread confirm the opposite. In fact, due to the widespread and increased use of immunosuppressive therapy together with broad-spectrum antifungal treatments, the frequency of mucosal and systemic infections caused by C. glabrata has increased significantly. Furthermore, biofilms are described as surface associated communities of microorganisms within an extracellular matrix, generally composed of carbohydrate and proteins. Biofilm formation is an important virulence factor for a number of Candida species, as it confers significant resistance to antifungal therapy by limiting the penetration of substances through the matrix and protecting cells from host immune responses. Moreover, little is known about the role of antifungals on C. glabrata biofilms. Thus, the aim of this work was to study the role of fluconazole, itraconazole and amphotericin B on 24 h pre-formed C. glabrata biofilms and specially on their matrix composition. A total of 3 C. glabrata strains isolated from oral, urinary and vaginal tract were used...

‣ Ocular allergy latin american consensus

Santos,Myrna Serapião dos; Alves,Milton Ruiz; Freitas,Denise de; Sousa,Luciene Barbosa de; Wainsztein,Ricardo; Kandelman,Sérgio; Lozano,Mauricio; Beltrán,Francisco; Lozada,Oscar Baça; Santacruz,Concepción; Guzzo,Giovanni; Zaccarelli Filho,Carlos Albe
Fonte: Conselho Brasileiro de Oftalmologia Publicador: Conselho Brasileiro de Oftalmologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2011 Português
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PURPOSE: To establish current definition, classification and staging, and to develop diagnosis and treatment recommendations for ocular allergy, by using Delphi approach. METHODS: Ten Latin American experts on ocular allergy participated in a 4-round Delphi panel approach. Four surveys were constructed and answered by panelists. A two-thirds majority was defined as consensus. Definition, classification, staging and diagnosis and treatment recommendations were the main outcomes. RESULTS: "Ocular allergy" was proposed as the general term to describe ocular allergic diseases. Consensus regarding classification was not reached. Signs and symptoms were considered extremely important for the diagnosis. It was consensus that a staging system should be proposed based on the disease severity. Environmental control, avoidance of allergens and the use of artificial tears were recommended as first line treatment. The secondary treatment should include topical anti-histamines, mast cell stabilizers and multi actions drugs. Topical non-steroidal anti-inflammatory and vasoconstrictors were not recommended. Topical corticosteroids were recommended as third line of treatment for the most severe keratoconjunctivitis. Consensus was not reached regarding the use of systemic corticosteroids or immunosuppressant. Surgical approach and unconventional treatments were not recommended as routine. CONCLUSION: The task of creating guidelines for ocular allergies showed to be very complex. Many controversial topics remain unsolved. A larger consensus including experts from different groups around the world may be needed to further improve the current recommendations for several aspects of ocular allergy.

‣ The Novel Immunosuppressive Agent Mycophenolate Mofetil Markedly Potentiates the Antiherpesvirus Activities of Acyclovir, Ganciclovir, and Penciclovir In Vitro and In Vivo

Neyts, Johan; Andrei, Graciela; De Clercq, Erik
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/1998 Português
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The immunosuppressive agent mycophenolate mofetil (MMF) has been approved for use in kidney transplant recipients and may thus be used concomitantly for the treatment of intercurrent herpesvirus infections with drugs such as acyclovir (ACV), ganciclovir (GCV), and penciclovir (PCV). We found that MMF and its parent compound mycophenolic acid (at concentrations that are attainable in plasma) strongly potentiate the antiherpesvirus (herpes simplex virus [HSV] type 1 [HSV-1], HSV-2, thymidine kinase-deficient [TK−] HSV-1, both wild-type and TK− varicella-zoster virus, and human cytomegalovirus) activities of ACV, PCV, and GCV (up to 350-fold increases in their activities). The mechanism of potentiation was found to reside in the depletion of endogenous dGTP pools, which favored the inhibitory effect of the triphosphate of ACV, GCV, or PCV on the viral DNA polymerase. The combination of topically applied 5% MMF with 0.1% ACV strongly protected against HSV-1-induced cutaneous lesions in hairless mice, whereas therapy with either compound used singly had no protective effect. Interestingly, the combination of topically applied 5% MMF with 5% ACV was also highly effective in protecting against TK− HSV-2-induced cutaneous lesions (that were refractory to ACV treatment) in athymic nude mice. Topical therapy with MMF was very well tolerated...

‣ CB2 cannabinoid receptor agonist, JWH-015 triggers apoptosis in immune cells: Potential role for CB2 selective ligands as immunosuppressive agents

Lombard, Catherine; Nagarkatti, Mitzi; Nagarkatti, Prakash
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2 selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.

‣ Cyclosporine Inhibits Mouse Cytomegalovirus Infection via a Cyclophilin-Dependent Pathway Specifically in Neural Stem/Progenitor Cells▿

Kawasaki, Hideya; Mocarski, Edward S.; Kosugi, Isao; Tsutsui, Yoshihiro
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
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The potential of neural stem and progenitor cell (NSPC) transplantation in neurodegenerative disease raises a concern about immunosuppressive agents and opportunistic neurotropic pathogens that may interfere with engraftment. Cytomegalovirus (CMV) is an important opportunistic pathogen infecting the central nervous system, where it may remain latent for life, following transplacental transmission. Cyclosporine (Cs), an immunosuppressive drug used in organ transplantation, where its use is associated with CMV reactivation, suppressed murine CMV (MCMV) infection in cultured NSPCs but not in fibroblasts. This activity of Cs appears to be mediated via cyclophilin (CyP) rather than via calcineurin. First, the calcineurin-specific inhibitor FK506 failed to suppress replication. Second, the CyP-specific inhibitor NIM811 strongly suppressed replication in NSPC. NSPCs maintained in the presence of NIM811 retained viral genomes for several weeks without detectable viral gene expression or obvious deleterious effects. The withdrawal of NIM811 reactivated viral replication, suggesting that the inhibitory mechanism was reversible. Finally, inhibition of endogenous CyP A (CyPA) by small interfering RNA also inhibited replication in NSPCs. These results show that MCMV replication depends upon cellular CyPA pathways in NSPCs (in a specific cell type-dependent fashion)...

‣ Gordon Wilson lecture. The prevention of immune rejection of islet transplants without the use of immunosuppressive drugs.

Lacy, P. E.
Fonte: American Clinical and Climatological Association Publicador: American Clinical and Climatological Association
Tipo: Artigo de Revista Científica
Publicado em //1984 Português
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The findings in this series of investigations indicate that the passenger leukocyte concept applies to islet transplants. Six methods have been developed which prevent rejection of islet allografts in rats and mice without requiring the continuous use of immunosuppressive drugs in the recipient. Initial studies indicate that the passenger leukocyte concept also applies to the prevention of rejection of islet allografts in the dog. Thus the problems remaining with respect to human application are two. One is to determine which of the six methods will completely prevent rejection of islet allografts in dogs and could serve as a model for human application. The second is to modify and adapt the Velcro technique and the automated procedure for mass isolation of islets to the human pancreas. When we have been successful in modifying these isolation procedures so that we can obtain at least 100-150,000 islets, then human islets will be transplanted into the omentum of diabetic subjects who have received a kidney transplant and are already being treated with immunosuppressive agents. The purpose of these initial studies in humans will be to determine whether a sufficient mass of endocrine islet tissue has been transplanted to maintain normoglycemia and normal carbohydrate metabolism in these individuals. We hope that by the time these studies are completed we will have finished the studies in dogs on the selection of the optimal method for preventing rejection and will then be able to initiate human islet transplants without the use of immunosuppressive drugs. Dr. Davie and I also believe that these methods may be applicable to the prevention of rejection of other tissues and organs. It should be quite easy to apply these procedures to transplants of the parathyroid. Dr. Lafferty already has evidence that parathyroid tissue is present in established allografts of thyroid in mice following in vitro culture of the thyroid in 95% O2. It is possible that the procedures will also apply to other endocrine tissue such as the adrenal...

‣ Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

Huang, Li-Juan; Zhu, Qin; Lei, Min; Cao, Qian
Fonte: The WJG Press Publicador: The WJG Press
Tipo: Artigo de Revista Científica
Português
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AIM: To investigate immunosuppressive agents used to treat inflammatory bowel disease (IBD) in East China.

‣ Generation of Epstein-Barr virus–specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506)

De Angelis, Biagio; Dotti, Gianpietro; Quintarelli, Concetta; Huye, Leslie E.; Zhang, Lan; Zhang, Ming; Pane, Fabrizio; Heslop, Helen E.; Brenner, Malcolm K.; Rooney, Cliona M.; Savoldo, Barbara
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 26/11/2009 Português
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Adoptive transfer of autologous Epstein-Barr virus–specific cytotoxic T lymphocytes (EBV-CTLs) to solid organ transplant (SOT) recipients has been shown safe and effective for the treatment of EBV-associated posttransplantation lymphoproliferative disorders (PTLDs). SOT recipients, however, require the continuous administration of immunosuppressive drugs to prevent graft rejection, and these agents may significantly limit the long-term persistence of transferred EBV-CTLs, precluding their use as prophylaxis. Tacrolimus (FK506) is one of the most widely used immunosuppressive agents in SOT recipients, and its immunosuppressive effects are largely dependent on its interaction with the 12-kDa FK506-binding protein (FKBP12). We have knocked down the expression of FKBP12 in EBV-CTLs using a specific small interfering RNA (siRNA) stably expressed from a retroviral vector and found that FKBP12-silenced EBV-CTLs are FK506 resistant. These cells continue to expand in the presence of the drug without measurable impairment of their antigen specificity or cytotoxic activity. We confirmed their FK506 resistance and anti-PTLD activity in vivo using a xenogenic mouse model, suggesting that the proposed strategy may be of value to enhance EBV-specific immune surveillance in patients at high risk of PTLD after transplantation.

‣ Lentivectors Encoding Immunosuppressive Proteins Genetically Engineer Pancreatic β Cells to Correct Diabetes in Allogeneic Mice

Kojaoghlanian, Tsoline; Joseph, Aviva; Follenzi, Antonia; Zheng, Jian Hua; Leiser, Margarita; Fleischer, Norman; Horwitz, Marshall S.; DiLorenzo, Teresa P.; Goldstein, Harris
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with β cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted β cells from an alloimmune attack. The insulin-producing β cell line βTC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RIDα/β. The efficiency of lentiviral transduction of βTC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I MHC expression by over 90%, while RIDα/β expression inhibited cytokine-induced Fas upregulation by over 75%. βTC-tet cells transduced with gp19K and RIDα/β lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c SCID mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of β cells using gp19K and RIDα/β expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents currently necessary for prolonged engraftment with transplanted islets.

‣ Successful Treatment of Protein-Losing Gastroenteropathy with Steroid Pulse and Immunosuppressive Therapies in a Patient with Sjögren Syndrome

Nasu, Tetsushi; Miyata, Kaori; Uno, Akiko; Kawashima, Akira; Kondo, Michi; Akamizu, Takashi; Nakao, Taisei
Fonte: S. Karger AG Publicador: S. Karger AG
Tipo: Artigo de Revista Científica
Publicado em 08/07/2011 Português
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We report the case of a 59-year-old female who developed facial edema together with hypoproteinemia. On the basis of 99mTc-human serum albumin scintigraphy and a1-antitrypsin clearance, she was diagnosed with protein-losing gastroenteropathy. Furthermore, she was diagnosed with Sjögren syndrome on the basis of eye and oral dryness, positive result with anti-SSA antibody, and salivary gland biopsy. Her symptoms improved with the use of immunosuppressive agents following steroid pulse therapy. Therefore, steroid pulse therapy and immunosuppressive agents should be considered as possible effective treatment strategies for protein-losing gastroenteropathy associated with autoimmune diseases.

‣ Development and Use a Novel combined in-vivo and in-vitro Assay for Anti-inflammatory and Immunosuppressive Agents

Li, Tan; Chen, Hong; Mei, Xin; Wei, Na; Cao, Bo
Fonte: Shaheed Beheshti University of Medical Sciences Publicador: Shaheed Beheshti University of Medical Sciences
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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Contact hypersensitivity (CHS) mouse model induced by 2, 4-dinitrofluorobenzene (DNFB) is thought to be a T helper 1 (Th1)-dominant response and used for investigating anti-inflammatory and immunosuppressive agents. However, it is hardly used for screening large-scale drugs because of the large number of animals and complex mechanisms involved in-vivo. In this study, we focused on whether T lymphocytes from CHS mouse model could maintain the state of immune response in-vitro and explored a suitable time for drugs screening. The results showed that CD4+ T cells of CHS mice were higher compared with those in normal group. The expression of T-bet and GATA3 showed a Th1 shift and the levels of interleukin (IL)-2 and IL-4 also showed similar trend. Furthermore, IL-6 produced by T lymphocytes from CHS mice had a high level too. Then, we detected the effects of dexamethasone (DEX), cyclosporine A (CsA) and mycophenolate mofetil (MMF) on T lymphocytes in-vitro, and the data displayed that these immunosuppressive drugs could all inhibit the proliferation of T lymphocytes significantly. These findings suggested that T lymphocytes from CHS mice could mimic a similar immune response in-vitro, and it’s also a suitable method for screening anti-inflammatory and immunosuppressive agents.

‣ Relationship between vitamin D status and immunosuppressive therapy in kidney transplant recipients

Filipov, Jean Jeanov; Zlatkov, Borelli Kirilov; Dimitrov, Emil Paskalev; Svinarov, Dobrin
Fonte: Taylor & Francis Publicador: Taylor & Francis
Tipo: Artigo de Revista Científica
Português
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There is a growing body of evidence for the protective role of vitamin D in diabetes mellitus (DM), infection, cancer, cardiovascular disease, immune disorders and kidney function. Considering the reported high prevalence of vitamin D insufficiency among kidney transplant recipients (KTRs), the aim of this study was to assess the influence of immunosuppressive therapy and other factors on vitamin D status in such patients. The study included 289 KTRs (189 males and 100 females) who consented to participate. The first test for 25-hydrohyvitamin D [25(OH)D] was performed by a validated liquid chromatography–tandem mass spectrometry method. Influence of immunosuppressive drugs and previously reported predictors on vitamin D status was assessed by descriptive statistics, univariate and multivariate regression. Our results showed that only 53 patients (18.34%) of the studied KTRs were vitamin D sufficient. In addition to a well expected positive association between serum 25(OH)D and summer blood sampling (p < 0.05) and inverse relationship between vitamin D status and DM, gender (female) and body mass index, serum 25(OH)D was found to be inversely associated with calcineurin inhibitors (CNI) (p < 0.05) and unaffected by other immunosuppressive agents. Our study demonstrated high prevalence of vitamin D insufficiency after kidney transplantation in the studied cohort of patients. Apart from female gender...

‣ Untersuchungen über den Einfluss von immunsuppressiven Substanzen auf die Interaktion dendritischer Zellen mit Aspergillus fumigatus; Investigation of the Impact of Immunosuppressive Agents on the Interaction between monocyte derived dendritic cells and Aspergillus fumigatus

Mickan, Andreas Richard
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Die invasive Aspergillose ist eine gefürchtete, oft letale Infektion bei immundefizienten Patienten. Um die Rolle unterschiedlicher Immunsuppressiva in der Pathogenese der invasiven Aspergillose näher zu beleuchten, wurden deren Effekte durch in vitro- Analysen untersucht. In Vorarbeiten konnte gezeigt werden, dass aus Monozyten generierte, unreife dendritische Zellen nach Inkubation mit Aspergillus-fumigatus-Präparationen in reife dendritische Zellen ausdifferenzieren. Um den Einfluss verschiedener Immunsuppressiva auf diese Ausreifungsreaktion zu untersuchen, wurde die Expression von Zelldifferenzierungsmarkern im Durchflusszytometer analysiert. Ferner wurde deren Einfluss auf die DC-vermittelte, für Aspergillus-fumigatus spezifische, Lymphoproliferation und die Zytokinsekretion (Interleukin 4 und Interferon gamma) der Lymphozyten näher bestimmt. Analysiert wurden die klinisch häufig eingesetzten Immunsuppressiva Dexamethason, Cyclosporin A, Rapamycin und FK 506. Nach Inkubation mit Aspergillus-fumigatus-Hyphen und dem Proteinpräzipitat (PPSAB) des Erregers konnte eine Ausreifungsreaktion mit gesteigerter Oberflächenexpression der Marker CD 80, CD 83, CD 86 und MHC-Klasse II nachgewiesen werden. Für die genannten Immunsuppressiva konnte eine konzentrationsabhängige Hemmung der DC-induzierten Aspergillus-fumigatus-spezifischen Lymphoproliferation gezeigt werden. Die Zytokinausschüttung IFN  in den Überständen wurde durch Cyclosporin A und Rapamycin unterdrückt. Für Interleukin-4 konnte nur unter Cyclosporin A eine geringe Unterdrückung der Ausschüttung gezeigt werden. Bei der Ausreifung dendritischer Zellen nach Inkubation mit Aspergillus-fumigatus-Antigenen bewirkte insbesondere Dexamethason eine Hemmung der DC-Ausreifung. Zusammenfassend konnte im Rahmen dieser Arbeit gezeigt werden...

‣ Cutaneous histoplasmosis as a complication after anti-TNF use - Case report

Zattar,Gabrielle Aline; Cardoso,Fernanda; Soares,Cleverson Teixeira
Fonte: Sociedade Brasileira de Dermatologia Publicador: Sociedade Brasileira de Dermatologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2015 Português
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AbstractAnti-TNF agents are effective in the treatment of psoriasis. However, they render individuals more susceptible to infections. We report an atypical case of histoplasmosis in an immunosuppressed patient due to anti- TNF therapy. A patient who used anti-TNF for the treatment of psoriasis had had a lesion on the right eyebrow since discontinuation of the medication. The diagnostic hypothesis was basal cell carcinoma, but the histopathological examination was compatible with histoplasmosis.

‣ Pharmacological treatments for thyroid eye disease

Modjtahedi, S.; Modjtahedi, B.; Mansury, A.; Selva-Nayagam, D.; Douglas, R.; Goldberg, R.; Leibovitch, I.
Fonte: Adis International Ltd Publicador: Adis International Ltd
Tipo: Artigo de Revista Científica
Publicado em //2006 Português
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Thyroid eye disease (TED), which affects the majority of patients with Grave's disease, is associated with significant ophthalmic morbidity. In patients with mild disease, supportive treatment with lubricating medication can be sufficient. However, in patients with severe TED and disfiguring proptosis or sight-threatening neuropathy, more aggressive medical or surgical interventions are necessary. Corticosteroids remain the preferred pharmacological treatment modality in the majority of patients with an active inflammatory component. Other immunosuppressive drugs in combination with corticosteroids may be helpful in patients with corticosteroid-resistant TED. Newer agents such as somatostatin analogues have not shown to be of significant clinical benefit; however, initial studies on the use of antioxidants and cytokine antagonists are encouraging.; Sara P. Modjtahedi, Bobeck S. Modjtahedi, Ahmad M. Mansury, Dinesh Selva, Raymond S. Douglas, Robert A. Goldberg and Igal Leibovitch

‣ Effect of the immune modulating agents cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on an animal model of granulomatous bowel disease.

Mitchell, I C; Turk, J L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1990 Português
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This study was undertaken to determine the effect of cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on a model of granulomatous infiltration in the terminal ileum and draining lymph nodes of the guinea pig. Treatment groups of six animals were used and compared to untreated groups of 12. Epithelioid cell granulomas and primary macrophage granulomas were induced by the inoculation of BCG (Pasteur) and irradiated Mycobacterium leprae respectively into the terminal ileum of the guinea pig. The response to purified protein derivative of tuberculin was reduced in both groups of animals receiving any of these agents. Cyclophosphamide and methotrexate treated animals inoculated with BCG or M leprae showed a significant reduction of granulomatous infiltration at the inoculation site (p less than 0.05 and p less than 0.001 respectively). BCG inoculated animals treated with either hydrocortisone or cyclosporin A showed no reduction in granulomatous infiltration at either the inoculation site or the draining lymph nodes. By contrast M leprae inoculated animals receiving either of these agents showed a significant reduction of granulomatous infiltration at both the inoculation site (p less than 0.001) and in the primary draining lymph node (p less than 0.001). Ziehl Neelsen staining showed an increased proportion of animals with detectable acid fast bacilli (AFB) at the inoculation site in the groups receiving hydrocortisone (50%) and methotrexate (67%) compared to untreated controls (8%). No AFB were observed in any of the animals inoculated with M leprae. In conclusion...

‣ How self-tolerance and the immunosuppressive drug FK506 prevent B-cell mitogenesis

Glynne, Richard; Akkaraju, Srinivas; Healy, James I; Rayner, J; Goodnow, Christopher; Mack, David H
Fonte: Macmillan Publishers Ltd Publicador: Macmillan Publishers Ltd
Tipo: Artigo de Revista Científica
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Therapy for transplant rejection, autoimmune disease and allergy must target mature lymphocytes that have escaped censoring during their development. FK506 and cyclosporin are immunosuppressants which block three antigen-receptor signalling pathways (NFAT, NFκB and JNK), through inhibition of calcineurin, and inhibit mature lymphocyte proliferation to antigen. Neither drug induces long-lived tolerance in vivo, however, necessitating chronic use with adverse side effects. Physiological mechanisms of peripheral tolerance to self-antigens provide an opportunity to emulate these processes pharmacologically. Here we use gene-expression arrays to provide a molecular explanation for the loss of mitogenic response in peripheral B-cell anergy, one aspect of immunological tolerance. Self-antigen induces a set of genes that includes negative regulators of signalling and transcription but not genes that promote proliferation. FK506 interferes with calcium-dependent components of the tolerance response and blocks an unexpectedly small fraction of the activation response. Many genes that were not previously connected to self-tolerance are revealed, and our findings provide a molecular fingerprint for the development of improved immunosuppressants that prevent lymphocyte activation without blocking peripheral tolerance.