35 results on '"FÁRMACOS IMUNOSSUPRESSORES"'
Search Results
2. Nanostructured lipid carrier co-delivering tacrolimus and TNF-α siRNA as an innovate approach to psoriasis
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Juliana Santos Rosa Viegas, Ana Vitoria Pupo Silvestrini, Fabíola Silva Garcia Praça, Angelo Luis Caron, Isabella Suzuki, Marcelo Kravicz, Wanessa Silva Garcia Medina, José Orestes Del Ciampo, Maria Vitória Lopes Badra Bentley, Viegas, J, Praça, F, Caron, A, Suzuki, I, Silvestrini, A, Medina, W, Del Ciampo, J, Kravicz, M, and Bentley, M
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Male ,medicine.medical_treatment ,Down-Regulation ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Administration, Cutaneous ,030226 pharmacology & pharmacy ,Tacrolimus ,Mice ,03 medical and health sciences ,FÁRMACOS IMUNOSSUPRESSORES ,Gene therapy ,Nanoparticle ,0302 clinical medicine ,In vivo ,Psoriasis ,medicine ,Animals ,Viability assay ,Particle Size ,RNA, Small Interfering ,Psoriasi ,Mice, Inbred BALB C ,Imiquimod ,Tumor Necrosis Factor-alpha ,Chemistry ,Drug Synergism ,021001 nanoscience & nanotechnology ,medicine.disease ,Controlled release ,Topical application ,Calcineurin ,Disease Models, Animal ,Cytokine ,Delayed-Action Preparations ,Tacrolimu ,Liposomes ,NIH 3T3 Cells ,Nanoparticles ,Female ,Tumor necrosis factor alpha ,0210 nano-technology - Abstract
Since psoriasis is an immuno-mediated skin disease, long-term therapies are necessary for its treatment. In clinical investigations, tacrolimus (TAC), a macrolide immunosuppressive inhibitor of calcineurin, arises as an alternative for the treatment of psoriasis, acting in some cytokines involved in the pathogenesis of the disease. Here, we aim to study the psoriasis treatment with TAC and siRNA for one of most cytokines expressed in psoriasis, the TNF-alpha. A multifunctional nanostructure lipid carrier (NLC) was developed to co-delivery TAC and siRNA. Results showed that the particle size and zeta potential were around 230 nm and + 10 mV, respectively. The release study demonstrated a controlled release of TAC, and the permeation and retention profile in the skin tissue show to be promising for topical application. The cell viability and uptake in murine fibroblast presented low toxicity associated to uptake of NLC in 4 h, and finally, the in vivo animal model demonstrates the efficiency of the NLC multifunctional, exhibiting a reduction of the cytokine TNF-alpha expression about 7-fold and presenting a synergic effect between the TAC and TNF-alpha siRNA. The developed system was successfully to treat in vivo psoriatic animal model induced by imiquimod and the synergic combination was reported here for the first time.Graphical abstract
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- 2020
3. In Vitro antifungal activity of LL-37 analogue peptides against Candida spp
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Gladys Pinilla, Yenifer Tatiana Coronado, Gabriel Chaves, Liliana Muñoz, Jeannette Navarrete, Luz Mary Salazar, Carlos Pelleschi Taborda, and Julián E. Muñoz
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Microbiology (medical) ,FÁRMACOS IMUNOSSUPRESSORES ,antimicrobial peptides ,LL-37 ,analogue peptides ,antifungal therapy ,candidiasis ,Candida spp ,Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
Fungal infections have increased in recent decades with considerable morbidity and mortality, mainly in immunosuppressed or admitted-to-the-ICU patients. The fungal resistance to conventional antifungal treatments has become a public health problem, especially with Candida that presents resistance to several antifungals. Therefore, generating new alternatives of antifungal therapy is fundamental. One of these possibilities is the use of antimicrobial peptides, such as LL-37, which acts on the disruption of the microorganism membrane and promotes immunomodulatory effects in the host. In this study, we evaluated the in vitro antifungal activity of the LL-37 analogue peptides (AC-1, LL37-1, AC-2, and D) against different Candida spp. and clinical isolates obtained from patients with vulvovaginal candidiasis. Our results suggest that the peptides with the best ranges of MICs were LL37-1 and AC-2 (0.07 µM) against the strains studied. This inhibitory effect was confirmed by analyzing the yeast growth curves that evidenced a significant decrease in the fungal growth after exposure to LL-37 peptides. By the XTT technique we observed a significant reduction in the biofilm formation process when compared to yeasts untreated with the analogue peptides. In conclusion, we suggest that LL-37 analogue peptides may play an important antimicrobial role against Candida spp.
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- 2022
4. Uso de rituximab em glomerulopatias. [Editorial]
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Woronik, Viktoria
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2022
5. Current aspects of renal dysfunction after liver transplantation
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Mazo, Daniel F
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2022
6. Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil
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Kallas, Esper Georges
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2022
7. Deposition of immune complexes in gingival tissues in the presence of periodontitis and systemic lupus erythematosus
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J. R. Pires, Mariana Schützer Ragghianti Zangrando, Carla Andreotti Damante, Adriana Campos Passanezi Sant'Ana, Débora Regina Fernandes Degand, Adauto José Ferreira Nunes, Maria Renata Sales Nogueira, Larissa Costa de Moraes Pessoa, Maria Lúcia Rubo de Rezende, and Sebastião Luiz Aguiar Greghi
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Adult ,Male ,lcsh:Immunologic diseases. Allergy ,Pathology ,medicine.medical_specialty ,immune complex ,diagnosis ,Immunology ,Gingiva ,Lupus nephritis ,Fluorescent Antibody Technique ,Antigen-Antibody Complex ,Comorbidity ,Severity of Illness Index ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,FÁRMACOS IMUNOSSUPRESSORES ,systemic lupus erythematosus ,Risk Factors ,immune system diseases ,Humans ,Lupus Erythematosus, Systemic ,Immunology and Allergy ,Medicine ,skin and connective tissue diseases ,periodontitis ,Gingival recession ,Original Research ,030203 arthritis & rheumatology ,Periodontitis ,Autoimmune disease ,Proteinuria ,business.industry ,Disease Management ,030206 dentistry ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Immune complex ,Clinical attachment loss ,inflammation ,Female ,Disease Susceptibility ,medicine.symptom ,lcsh:RC581-607 ,business ,Biomarkers - Abstract
Systemic lupus erythematosus (SLE) is a complex chronic autoimmune disease characterized by tissue damage and widespread inflammation in response to environmental challenges. Deposition of immune complexes in kidneys glomeruli are associated with lupus nephritis, determining SLE diagnosis. Periodontitis is a chronic inflammatory disease characterized by clinical attachment and bone loss, caused by a microbial challenge – host response interaction. Deposition of immune complex at gingival tissues is a common finding in the course of the disease. Considering that, the primary aim of this study is to investigate the deposition of immune complexes at gingival tissues of SLE patients compared to systemically healthy ones, correlating it to periodontal and systemic parameters. Twenty-five women diagnosed with SLE (SLE+) and 25 age-matched systemically healthy (SLE–) women were included in the study. Detailed information on overall patient's health were obtained from file records. Participants were screened for probing depth (PD), clinical attachment loss (CAL), gingival recession (REC), full-mouth bleeding score (FMBS) and plaque scores (FMPS). Bone loss was determined at panoramic X-ray images as the distance from cementenamel junction to alveolar crest (CEJ-AC). Gingival biopsies were obtained from the first 15 patients submitted to surgical periodontal therapy of each group, and were analyzed by optical microscopy and direct immunofluorescence to investigate the deposition of antigen-antibody complexes. Eleven (44%) patients were diagnosed with active SLE (SLE-A) and 14 (56%) with inactive SLE (LES-I). Mean PD, CAL and FMBS were significantly lower in SLE+ than SLE–(p< 0.05; Mann Whitney). The chronic use of low doses of immunosuppressants was associated with lower prevalence of CAL >3 mm. Immunofluorescence staining of markers of lupus nephritis and/or proteinuria was significantly increased in SLE+ compared to SLE–, even in the presence of periodontitis. These findings suggest that immunomodulatory drugs in SLE improves periodontal parameters. The greater deposition of antigen-antibody complexes in the gingival tissues of patients diagnosed with SLE may be a marker of disease activity, possibly complementing their diagnosis.
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- 2021
8. Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer
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Wouter H. P. Driessen, Anupama Hooda-Nehra, Wadih Arap, Prashant Dogra, Massimo Cristofanilli, Diana N. Nunes, Vittorio Cristini, Emmanuel Dias-Neto, Martin Trepel, Javier Ruiz-Ramírez, Robin L. Anderson, Fernanda I. Staquicini, Zhihui Wang, Marina Cardó-Vila, Gabriel Hortobagy, Juri G. Gelovani, Zaver M. Bhujwalla, Stephen K. Burley, Daniela I. Staquicini, Mauro Cortez, Amin Hajitou, Renata Pasqualini, Bettina Proneth, Maria Hoh, Richard L. Sidman, Mohammed Jaloudi, Bedrich L. Eckhardt, Israel Tojal da Silva, Jaqueline Ramalho Buttura, and Christopher Markosian
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0301 basic medicine ,Mouse ,Cell ,Triple Negative Breast Neoplasms ,PDIA3 ,Ligands ,Calcitriol receptor ,tumor-associated macrophage ,0302 clinical medicine ,Tumor-Associated Macrophages ,Tumor Microenvironment ,Biology (General) ,Triple-negative breast cancer ,Mice, Inbred BALB C ,Vitamin D-Binding Protein ,General Neuroscience ,General Medicine ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Systemic administration ,triple-negative breast cancer ,Medicine ,Female ,Oligopeptides ,Research Article ,Signal Transduction ,QH301-705.5 ,Science ,Protein Disulfide-Isomerases ,Mice, Nude ,Antineoplastic Agents ,Tumor-associated macrophage ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immune system ,Breast cancer ,FÁRMACOS IMUNOSSUPRESSORES ,Cell Line, Tumor ,medicine ,Animals ,Humans ,vitamin D receptor ,ddc:610 ,General Immunology and Microbiology ,business.industry ,medicine.disease ,Xenograft Model Antitumor Assays ,Triple-negative Breast Cancer ,Tumor-associated Macrophage ,Vitamin D Receptor ,Enzyme Activation ,030104 developmental biology ,Cancer research ,business - Abstract
Triple-negative breast cancer (TNBC) is an aggressive tumor with limited treatment options and poor prognosis. We applied the in vivo phage display technology to isolate peptides homing to the immunosuppressive cellular microenvironment of TNBC as a strategy for non-malignant target discovery. We identified a cyclic peptide (CSSTRESAC) that specifically binds to a vitamin D receptor, protein disulfide-isomerase A3 (PDIA3) expressed on the cell surface of tumor-associated macrophages (TAM), and targets breast cancer in syngeneic TNBC, non-TNBC xenograft, and transgenic mouse models. Systemic administration of CSSTRESAC to TNBC-bearing mice shifted the cytokine profile toward an antitumor immune response and delayed tumor growth. Moreover, CSSTRESAC enabled ligand-directed theranostic delivery to tumors and a mathematical model confirmed our experimental findings. Finally, in silico analysis showed PDIA3-expressing TAM in TNBC patients. This work uncovers a functional interplay between a cell surface vitamin D receptor in TAM and antitumor immune response that could be therapeutically exploited.
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- 2021
9. Assessment of the hypoglycemic effect of Bixin in alloxan-induced diabetic rats: in vivo and in silico studies
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Rodolfo Bortolozo Serafim, Silvana Giuliatti, Irlon M. Ferreira, Andrés Navarrete Castro, Matheus Mercês Ramos, Hady Keita, Cleydson B. R. Santos, José Carlos Tavares Carvalho, Gabriel Monteiro da Silva, Elias Carvalho Padilha, Jesús Rafael Rodríguez Amado, Univ Fed Amapa, Univ Sierra, Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), and Univ Nacl Autonoma Mexico
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biology ,In silico ,Bixin ,General Medicine ,Pharmacology ,Hypoglycemia ,medicine.disease ,biology.organism_classification ,PPAR gamma ,chemistry.chemical_compound ,Bixa ,in vivo ,FÁRMACOS IMUNOSSUPRESSORES ,hypoglycemia ,chemistry ,Structural Biology ,In vivo ,in silico ,Alloxan ,medicine ,Molecular Biology - Abstract
Made available in DSpace on 2020-12-10T19:49:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-12 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Procad Amazonia Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The objectives of this study were to extract and purify Bixin from the seeds of Bixa orellana and to evaluate its hypoglycemic activity in vivo, as well as, to conduct an in silico study of selectivity on peroxisome proliferator-activated receptors via molecular docking and molecular dynamics simulations. Oral administration of Bixin (10 mg/kg) significantly reduced their glucose level that was alloxan-induced diabetic rats. Bixin showed in silico selectivity on peroxisome proliferator-activated receptors (PPARs), particularly by the peroxisome proliferator-activated receptor gamma (PPAR gamma), which supports the hypoglycemic activity of Bixin. From the results obtained, it can be inferred that Bixin presents hypoglycemic characteristics, which was confirmed by the results obtained from the in vivo and in silico tests. Bixin may act by other pathways to control blood glucose and thus it is possible that it presents a different toxicity profile than troglitazone, rosiglitazone and pioglitazone. However, more studies on the activity and toxicity of Bixin are needed to evaluate for further clinical use. Univ Fed Amapa, Dept Biol Sci & Hlth, Lab Drugs Discovery, Macapa, Brazil Univ Sierra, Div Postgrade, Ixtlan De Juarez, Mexico Univ Fed Amapa, Dept Biol Sci & Hlth, Lab Modeling & Computat Chem, Macapa, Brazil Univ Fed Amapa, Res Grp Biocatalysis & Apllied Organ Synth, Macapa, Brazil Sao Paulo State Univ, Dept Nat Act Principles & Toxicol, Fac Pharmaceut Sci, Araraquara, SP, Brazil Univ Sao Paulo, Dept Cellular & Mol Biol, Ribeirao Preto Med Sch, Ribeirao Preto, Brazil Univ Nacl Autonoma Mexico, Fac Chem, Dept Pharm, Lab Pharmacol Nat Prod, Mexico City, DF, Mexico Univ Sao Paulo, Ribeirao Preto Med Sch, Bioinformat Grp, Dept Genet, Ribeirao Preto, Brazil Sao Paulo State Univ, Dept Nat Act Principles & Toxicol, Fac Pharmaceut Sci, Araraquara, SP, Brazil CAPES: PNPD/20130076-14001012005P1 Procad Amazonia: Auxpe - 1723/2018 CNPq: 407768/2013-0
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- 2020
10. Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient
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Ana Solange Vasconcelos de Sousa, Hareton Teixeira Vechi, Jeffrey Jon Shaw, Kleber Giovanni Luz, and Mirella Alves Cunha
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Male ,Asplenia ,medicine.medical_specialty ,Combination therapy ,Pentamidine Isethionate ,Meglumine antimoniate ,medicine.medical_treatment ,030231 tropical medicine ,Splenectomy ,Antiprotozoal Agents ,Gastroenterology ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Pharmacotherapy ,FÁRMACOS IMUNOSSUPRESSORES ,Splenectomized Adult Patient ,Bone Marrow ,Virology ,Internal medicine ,Amphotericin B ,medicine ,Humans ,Intestinal Mucosa ,Pentamidine ,Visceral leishmaniasis ,Meglumine Antimoniate ,business.industry ,Leishmaniasis ,Articles ,Middle Aged ,medicine.disease ,Infectious Diseases ,Leishmaniasis, Visceral ,Parasitology ,Drug Therapy, Combination ,Lymph Nodes ,business ,medicine.drug - Abstract
In immunocompromised patients, visceral leishmaniasis (VL) can present with atypical clinical symptoms that include poor response to treatment. No optimal therapeutic regimen is available for such cases. In a splenectomized male patient, we observed a disseminated form of the disease in the liver, bone marrow, lymph nodes, and gastrointestinal tract. There was an apparent clinical improvement when he was initially treated with liposomal amphotericin B (L-AmB), but this was followed by a relapse involving severe clinical symptoms. He was finally treated successfully with a combination of L-AmB, meglumine antimoniate, and pentamidine isethionate. It is important to include asplenia as an immunosuppressive condition that induces exotic VL pathologies. In such cases, combination anti-Leishmania drug therapy should be considered.
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- 2019
11. Zika Virus Meningoencephalitis in an Immunocompromised Patient
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Luciano Neder, Fernando Crivelenti Vilar, Silvia Moreira Ayub-Ferreira, Pedro V. Schwartzmann, Marilia Farignoli Romeiro, Ross Arena, Leandra Naira Zambelli Ramalho, Osvaldo Massaiti Takayanagui, Marcus Vinicius Simões, André Schmidt, Luiz Tadeu Moraes Figueiredo, and Antônio Carlos dos Santos
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Heart transplantation ,Microcephaly ,biology ,business.industry ,medicine.medical_treatment ,Outbreak ,Meningoencephalitis ,Autopsy ,General Medicine ,medicine.disease ,biology.organism_classification ,Virology ,Zika virus ,03 medical and health sciences ,Flaviviridae ,FÁRMACOS IMUNOSSUPRESSORES ,0302 clinical medicine ,Cerebrospinal fluid ,Medicine ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery - Abstract
The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barre syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.
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- 2017
12. Immune-mediated rippling muscle disease in a patient with treated hypothyroidism
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Paulo José Lorenzoni, Leonardo G. Leão, Marcelo Rezende Young Blood, Rosana Herminia Scola, Renata Dal-Prá Ducci, Cláudia Suemi Kamoi Kay, Mariz Vainzof, and Lineu Cesar Werneck
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0301 basic medicine ,medicine.medical_specialty ,Pathology ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Rippling muscle disease ,03 medical and health sciences ,FÁRMACOS IMUNOSSUPRESSORES ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Text mining ,Immune system ,Neurology ,Internal medicine ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Published
- 2017
13. Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients
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Alvaro Cerda, Alice Cristina Rodrigues, Jose O. Medina-Pestana, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata, Claudia Rosso Felipe, Fabiana Dalla Vecchia Genvigir, N. Oliveira, Patricia C Salgado, Sonia Q. Doi, Elena Y.F. Luo, Helio Tedesco-Silva, and Camila Alves
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Adult ,Male ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Adolescent ,Pharmacogenomic Variants ,Renal function ,Kidney ,Kidney Function Tests ,030226 pharmacology & pharmacy ,Gastroenterology ,Tacrolimus ,Young Adult ,03 medical and health sciences ,FÁRMACOS IMUNOSSUPRESSORES ,0302 clinical medicine ,Polymorphism (computer science) ,Internal medicine ,Genotype ,Genetics ,medicine ,Cytochrome P-450 CYP3A ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Allele ,CYP3A5 ,Molecular Biology ,Genetics (clinical) ,Kidney transplantation ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Transplantation ,Treatment Outcome ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,business ,Brazil ,Immunosuppressive Agents - Abstract
BACKGROUND Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment. OBJECTIVE The aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes. MATERIAL AND METHODS Brazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T) and rs776746 (g.6986A>G), ABCB1 rs1128503 (c.1236C>T), rs1045642 (c.3435C>T), and rs2032582 (c.2677G>T/A) polymorphisms. RESULTS Frequencies of CYP3A4 g.20230A, CYP3A5 g.31611C, and g.6986A were 0.37, 0.26, and 0.28, respectively. These alleles were associated with TAC rapid metabolization and were used for CYP3A4/5 genetic score construction. A higher CYP3A4/5 genetic score was associated with higher TAC dose and lower concentrations for dose administered (Co/D, P
- Published
- 2016
14. Regulation of Adipocyte and Macrophage Functions by mTORC1 and 2 in Metabolic Diseases
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William T. Festuccia
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0301 basic medicine ,Adipose Tissue, White ,Adipose tissue ,Mechanistic Target of Rapamycin Complex 2 ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,mTORC2 ,03 medical and health sciences ,chemistry.chemical_compound ,FÁRMACOS IMUNOSSUPRESSORES ,Metabolic Diseases ,Adipocyte ,Adipocytes ,Animals ,Humans ,Obesity ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,030109 nutrition & dietetics ,biology ,Macrophages ,Cell biology ,030104 developmental biology ,chemistry ,Lipotoxicity ,Lipogenesis ,biology.protein ,Inflammation Mediators ,Food Science ,Biotechnology - Abstract
Scope Evidence gathered in the last decades suggests that lipotoxicity and inflammation are the main factors connecting adipose tissue dysfunction to the development of metabolic diseases such as insulin resistance, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, and certain types of cancer, among others. The mechanistic target of rapamycin (mTOR) is a serine threonine kinase that functions as the catalytic entity of two multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). These complexes are important components of signaling pathways activated by nutrients, growth factors, and inflammatory mediators and are therefore directly involved in the regulation of adipocyte and macrophage metabolism and function. Methods and results In this article, studies that evaluate the involvement of mTORC1 and 2 in the regulation of macrophage and adipocyte function and their implication in the development of metabolic-disease-associated adipose tissue dysfunction are reviewed. Conclusion In adipocytes, optimal levels of mTORC1 activity are required for its pro-lipogenic actions, while in macrophages, mTORC1 regulates features of both M1 and M2 polarization. mTORC2, on the other hand, promotes glucose uptake and de novo lipogenesis in adipocytes and counteracts macrophage inflammatory response.
- Published
- 2020
15. Evaluation of Ca 2+ Binding Sites in Tacrolimus by Infrared Multiple Photon Dissociation Spectroscopy
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Pierre Archirel, Thiago C. Correra, Maria Angélica C. Masson, Philippe Maître, Renan Karpfenstein, Diogo Oliveira-Silva, Jean-Marie Teuler, Laboratoire de Chimie Physique D'Orsay (LCPO), and Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Coordination sphere ,Chemistry ,Infrared spectroscopy ,010402 general chemistry ,01 natural sciences ,Dissociation (chemistry) ,0104 chemical sciences ,Surfaces, Coatings and Films ,03 medical and health sciences ,030104 developmental biology ,FÁRMACOS IMUNOSSUPRESSORES ,[CHIM.ANAL]Chemical Sciences/Analytical chemistry ,Potential energy surface ,Materials Chemistry ,Molecule ,Physical chemistry ,[CHIM]Chemical Sciences ,Density functional theory ,Physical and Theoretical Chemistry ,Spectroscopy ,ComputingMilieux_MISCELLANEOUS ,Natural bond orbital - Abstract
Tacrolimus (TAC) is an efficient immunosuppressant used in organ transplantation procedures. There is an intrinsic correlation between TAC and Ca2+ because of the dependence of its action mechanism on calcium and calcineurin, and the role of ion coordination on TAC identification and quantitation. To depict the Ca2+ binding sites in TAC, this work carried out gas-phase vibrational infrared multiple photon dissociation spectroscopy of [Ca(TAC)]2+ and of three other TAC mimetic molecules (probes 1-3). Density functional theory (DFT) and Monte Carlo (MC) simulations were also used to support the experimental data assignment, and natural bond orbital (NBO) analysis was carried out to depict the coordination sphere. PM3 and B3LYP/6-31G(d) levels of theory displayed similar trends during the MC simulations, suggesting that PM3 is a viable alternative to more expensive DFT calculations, at least during the conformational analysis step. Infrared spectroscopy of the [Ca(probe X)1]2+ and [Ca(probe X)3]2+ ( X = 1-3) complexes allowed for a useful guide for building guess geometries and for the band assignment of the [Ca(TAC)]2+ complex. Nevertheless, the MC approach was particularly useful for exploring the potential energy surface. The lowest energy conformation for [Ca(TAC)]2+ was found by MC simulations and is 32.92 kJ mol-1 lower in energy than the one found by comparing the results obtained for Ca2+ coordination in probes, despite the calculated spectra being virtually identical. Both approaches are good ways to depict the coordination sites, and these results suggest that using small molecules as models is a reliable approach to depict the geometry or coordination sites of extensive ions, yielding a robust correlation between experimental and theoretical spectra. Furthermore, MC survey produced a lower energy conformation with a good match to the experimental results. Both methods depict the Ca2+ coordination sphere as a hexacoordinated environment where the main coordination centers are carbonyl groups.
- Published
- 2018
16. Early pregnancy factor, chaperonin 10 and rheumatoid arthritis; the story unravels
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Yee S. Poo, Helder I. Nakaya, Thuy T. Le, Thiago Dc Hirata, and Andreas Suhrbier
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FÁRMACOS IMUNOSSUPRESSORES ,biology ,business.industry ,Rheumatoid arthritis ,Immunology ,biology.protein ,Medicine ,Early pregnancy factor ,business ,medicine.disease ,Chaperonin - Published
- 2018
17. The use of biosimilar medicines in oncology - position statement of the Brazilian Society of Clinical Oncology (SBOC)
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D.V. Araujo, Cinthya Sternberg, Markus A.C. Gifoni, R.A. Gil, Roger Chammas, Gustavo Dos Santos Fernandes, and Gilberto Lopes
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Physiology ,Immunology ,Biophysics ,Ocean Engineering ,Cancer management ,Medical Oncology ,Biochemistry ,Pharmacovigilance ,03 medical and health sciences ,FÁRMACOS IMUNOSSUPRESSORES ,0302 clinical medicine ,Biosimilar Pharmaceuticals ,Neoplasms ,Internal medicine ,Health care ,medicine ,Humans ,Product (category theory) ,General Pharmacology, Toxicology and Pharmaceutics ,lcsh:QH301-705.5 ,Societies, Medical ,Clinical Trials as Topic ,lcsh:R5-920 ,Evidence-Based Medicine ,Therapeutic antibodies ,business.industry ,General Neuroscience ,Biosimilar ,Immunobiologicals ,Antibodies, Monoclonal ,Concepts and Comments ,Cell Biology ,General Medicine ,Evidence-based medicine ,Access ,030104 developmental biology ,Biopharmaceutical ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Position paper ,business ,lcsh:Medicine (General) ,Brazil - Abstract
A biosimilar is a biologic product that is similar to a reference biopharmaceutical product, the manufacturing process of which hinders the ability to identically replicate the structure of the original product, and therefore, it cannot be described as an absolute equivalent of the original medication. The currently available technology does not allow for an accurate copy of complex molecules, but it does allow the replication of similar molecules with the same activity. As biosimilars are about to be introduced in oncology practice, these must be evaluated through evidence-based medicine. This manuscript is a position paper, where the Brazilian Society of Clinical Oncology (SBOC) aims to describe pertinent issues regarding the approval and use of biosimilars in oncology. As a working group on behalf of SBOC, we discuss aspects related to definition, labeling/nomenclature, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, and the potential impact on financial burden in healthcare. We take a stand in favor of the introduction of biosimilars, as they offer a viable, safe, and cost-effective alternative to the biopharmaceutical products currently used in cancer. We hope this document can provide valuable information to support therapeutic decisions that maximize the clinical benefit for the thousands of cancer patients in Brazil and can contribute to expedite the introduction of this new drug class in clinical practice. We expect the conveyed information to serve as a basis for further discussion in Latin America, this being the first position paper issued by a Latin American Oncology Society.
- Published
- 2018
18. Ceftriaxone versus ceftriaxone plus a macrolide for community-acquired pneumonia in hospitalized patients with HIV/AIDS: a randomized controlled trial
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Claudia Figueiredo-Mello, Marinella Della Negra, Anna S. Levin, and Pontus Naucler
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Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Randomization ,HIV Infections ,Placebo ,law.invention ,03 medical and health sciences ,FÁRMACOS IMUNOSSUPRESSORES ,0302 clinical medicine ,Randomized controlled trial ,Community-acquired pneumonia ,law ,Internal medicine ,Pneumonia, Bacterial ,Medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,business.industry ,Hazard ratio ,Ceftriaxone ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,Clinical trial ,Community-Acquired Infections ,Hospitalization ,Infectious Diseases ,030228 respiratory system ,Relative risk ,Drug Therapy, Combination ,Female ,Macrolides ,business ,medicine.drug - Abstract
Objectives To evaluate if treatment with ceftriaxone and a macrolide, improved patient outcome when compared with monotherapy with ceftriaxone, in hospitalized patients with human immunodeficiency virus/acquired immunodeficient syndrome (HIV/AIDS) with community-acquired pneumonia (CAP). Methods Adult patients with HIV hospitalized due to suspected CAP were randomized to receive one of two regimens, ceftriaxone plus macrolide or ceftriaxone plus placebo, at a 1:1 proportion (Brazilian Clinical Trials Registry: RBR-8wtq2b). The primary outcome was in-hospital mortality and the secondary outcomes were mortality within 14 days, need for vasoactive drugs, need for mechanical ventilation, time to clinical stability and length of hospitalization. Results A total of 227 patients were randomized, two were excluded after randomization; 225 patients were analysed (112 receiving ceftriaxone plus placebo and 113 receiving ceftriaxone plus macrolide). The frequency of the primary outcome, in-hospital mortality, was not statistically different between the regimens: 12/112 (11%) patients who received ceftriaxone plus placebo and 17/113 (15%) who received ceftriaxone plus macrolide died during hospitalization (hazard ratio 1.22, 95% CI 0.57–2.59). We did not find differences between the regimens for any of the secondary outcomes, including mortality within 14 days, which occurred in 5/112 (4%) patients with ceftriaxone plus placebo and in 12/113 (11%) patients with ceftriaxone plus macrolide (relative risk 2.38, 95% CI 0.87–6.53). Conclusions Among hospitalized patients with HIV/AIDS with CAP, treatment with ceftriaxone and a macrolide did not improve patient outcomes, when compared with ceftriaxone monotherapy.
- Published
- 2017
19. Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis
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Fernando Silva Ramalho, Carlos Henrique Tomich de Paula da Silva, Teresa Dalla Costa, Michael Niehues, Nerry T. Cecilio, Bruna Gaelzer Silva Torres, Fernando Q. Cunha, Maria Cristina Nonato, José C. Alves-Filho, Thiago M. Cunha, Flavio da Silva Emery, Gabriela A. Buqui, Gabriela B. Santos, Valquíria A. P. Jabor, Raphael S. Peres, Norberto Peporine Lopes, and Paulo Louzada-Junior
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,Oxidoreductases Acting on CH-CH Group Donors ,Dihydroorotate dehydrogenase ,Arthritis ,Lymphocyte proliferation ,Pharmacology ,Lymphocyte Activation ,DMARDs ,Arthritis, Rheumatoid ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,FÁRMACOS IMUNOSSUPRESSORES ,In vivo ,medicine ,Animals ,Humans ,Rats, Wistar ,Rheumatoid arthritis ,Lapachol ,Leflunomide ,Cell Proliferation ,Inflammation ,Chemistry ,digestive, oral, and skin physiology ,medicine.disease ,equipment and supplies ,Arthritis, Experimental ,In vitro ,3. Good health ,Rats ,Pyrimidine metabolism ,Mice, Inbred C57BL ,Molecular Docking Simulation ,030104 developmental biology ,Mice, Inbred DBA ,Immunology ,Collagen-induced arthritis ,human activities ,Immunosuppressive Agents ,medicine.drug ,Naphthoquinones ,Research Article - Abstract
Background The inhibition of pyrimidine biosynthesis by blocking the dihydroorotate dehydrogenase (DHODH) activity, the prime target of leflunomide (LEF), has been proven to be an effective strategy for rheumatoid arthritis (RA) treatment. However, a considerable proportion of RA patients are refractory to LEF. Here, we investigated lapachol (LAP), a natural naphthoquinone, as a potential DHODH inhibitor and addressed its immunosuppressive properties. Methods Molecular flexible docking studies and bioactivity assays were performed to determine the ability of LAP to interact and inhibit DHODH. In vitro studies were conducted to assess the antiproliferative effect of LAP using isolated lymphocytes. Finally, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA) models were employed to address the anti-arthritic effects of LAP. Results We found that LAP is a potent DHODH inhibitor which had a remarkable ability to inhibit both human and murine lymphocyte proliferation in vitro. Importantly, uridine supplementation abrogated the antiproliferative effect of LAP, supporting that the pyrimidine metabolic pathway is the target of LAP. In vivo, LAP treatment markedly reduced CIA and AIA progression as evidenced by the reduction in clinical score, articular tissue damage, and inflammation. Conclusions Our findings propose a binding model of interaction and support the ability of LAP to inhibit DHODH, decreasing lymphocyte proliferation and attenuating the severity of experimental autoimmune arthritis. Therefore, LAP could be considered as a potential immunosuppressive lead candidate with potential therapeutic implications for RA. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1236-x) contains supplementary material, which is available to authorized users.
- Published
- 2017
20. Potential Use of Alginate-Based Carriers As Antifungal Delivery System
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Luciana B. Lopes, Cristina de Castro Spadari, and Kelly Ishida
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0301 basic medicine ,Microbiology (medical) ,Drug ,Antifungal ,medicine.drug_class ,media_common.quotation_subject ,Review ,02 engineering and technology ,Pharmacology ,Microbiology ,03 medical and health sciences ,drug delivery systems ,FÁRMACOS IMUNOSSUPRESSORES ,Amphotericin B ,medicine ,alginate ,media_common ,business.industry ,021001 nanoscience & nanotechnology ,amphotericin B ,Biotechnology ,Bioavailability ,030104 developmental biology ,Drug delivery ,nanoparticles ,Delivery system ,Nanocarriers ,0210 nano-technology ,business ,Drug carrier ,antifungal ,medicine.drug - Abstract
Fungal infections have become a major public health problem, growing in number and severity in recent decades due to an increase of immuncompromised patients. The use of therapeutic agents available to treat these fungal infections is limited by their toxicity, low bioavailability, antifungal resistance and high cost of treatment. Thus, it becomes extremely important to search for new therapeutic options. The use of polymeric systems as drug carriers has emerged as a promising alternative to conventional formulations for antifungals. Alginate is a natural polymer that has been explored in the last decade for development of drug delivery systems due to its non-toxicity, biodegradability, biocompatibility, low cost, mucoadhesive and non-immunogenic properties. Several antifungal agents have been incorporated in alginate-based delivery systems, including micro and nanoparticles, with great success, displaying promising ‘in vitro” and “in vivo” results for antifungal activities, reduction in the toxicity and the total drug dose used in the treatment, and improved bioavailability. This review aims at discussing the potential use and benefits of alginate-based nanocarriers and other delivery systems containing antifungal agents in the therapy of fungal infections.
- Published
- 2017
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21. Association Between Readmission After Liver Transplant and Adverse Immunosuppressant Reactions: A Prospective Cohort With a 1-Year Follow-up
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Luana Regina Baratelli Carelli Mendes, Luiz A. D’Albuquerque, Wellington Andraus, Luciana Bertocco de Paiva Haddad, Liliana Ducatti, and K. Andrade
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Drug ,Male ,medicine.medical_specialty ,Time Factors ,Drug-Related Side Effects and Adverse Reactions ,media_common.quotation_subject ,medicine.medical_treatment ,Pharmacist ,030230 surgery ,Liver transplantation ,Patient Readmission ,End Stage Liver Disease ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,FÁRMACOS IMUNOSSUPRESSORES ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,media_common ,Transplantation ,business.industry ,Length of Stay ,Middle Aged ,medicine.disease ,Tacrolimus ,Surgery ,Liver Transplantation ,030211 gastroenterology & hepatology ,Female ,business ,Adverse drug reaction ,Immunosuppressive Agents ,Follow-Up Studies - Abstract
Objective To measure the association between readmission after liver transplantation and corresponding adverse drug reactions. Methods A total of 48 patients undergoing liver transplantation were prospectively followed for 1 year. Of these, 23 were readmitted and evaluated by a pharmacist for causes of adverse drug reaction. The detection of adverse drug reactions was based on a combination of clinical interviews and physical and laboratory exams. Adverse reactions were defined in accordance with the Naranjo algorithm. Results A total of 67.6% of all readmissions were related to adverse drug reactions, with tacrolimus accounting for 80% of the drug reactions. The most common cause of readmission was infection (48.6%), followed by procedure-related reasons (29.7%). Of all patients requiring admission, 39.1% had Model for End-stage Liver Disease (MELD) scores below 21 at the time of transplantation, 17.4% had MELD scores between 21 and 29, and 43.5% had MELD scores above 29. Most (66.7%) of those readmitted more than twice had MELD scores above 29. Conclusion Adverse drug reactions related to immunosuppressants frequently lead to readmission among liver transplant patients, and in our series tacrolimus was the most frequently associated drug.
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- 2017
22. Immunohistochemical Quantification of Inflammatory Cells in Endomyocardial Biopsy Fragments After Heart Transplantation: A New Potential Method to Improve the Diagnosis of Rejection After Heart Transplantation
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Silvia Moreira Ayub-Ferreira, Paulo Roberto Chizzola, Ronaldo Honorato, Guilherme Veiga Guimarães, Pablo Maria Alberto Pomerantzeff, Domingos D. Lourenço-Filho, Fernando Bacal, Sara Michelly Gonçalves Brandão, R.Y. Tanigawa, Luiz Alberto Benvenuti, E A Bocchi, Germano Emilio Conceição Souza, Fátima das Dores Cruz, Alfredo Inácio Fiorelli, and V.S. Issa
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Adult ,Graft Rejection ,Male ,Pathology ,medicine.medical_specialty ,Biopsy ,medicine.medical_treatment ,CD3 ,FÁRMACOS IMUNOSSUPRESSORES ,Antigens, CD ,medicine ,Animals ,Humans ,Lung transplantation ,Myocyte ,Grading (tumors) ,Heart transplantation ,Transplantation ,biology ,Receiver operating characteristic ,business.industry ,CD68 ,Myocardium ,Immunohistochemistry ,Cats ,Leukocytes, Mononuclear ,biology.protein ,Heart Transplantation ,Female ,Surgery ,business - Abstract
Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm 2 ( P = .000) and CD3+ cells/mm 2 ( P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm 2 and CD3+ cells/mm 2 was obtained ( P = .000). One patient with CD3+ and CD68+ cells/mm 2 above the upper limit of the 95% confidence interval for cells/mm 2 found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm 2 areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.
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- 2014
23. Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation
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Tannuri, Uenis
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2016
24. Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years
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Carlos Bernardo Tauil, Maria Lucia Brito Ferreira, Maria Iris Moraes Machado, Marcus Goncalves, André Palma da Cunha Matta, Dagoberto Callegaro, Yara Dadalti Fragoso, Soniza Vieira Alves-Leon, Regina Maria Papais-Alvarenga, Amilton Antunes Barreira, Samira Luisa dos Apostolos Pereira, Alessandro Finkelsztejn, Vanessa Daccach Marques, and Sidney Gomes
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Drug ,Male ,medicine.medical_specialty ,Pediatrics ,Multiple Sclerosis ,Adolescent ,media_common.quotation_subject ,Drug Prescriptions ,Disability Evaluation ,FÁRMACOS IMUNOSSUPRESSORES ,Developmental Neuroscience ,medicine ,Humans ,In patient ,Adverse effect ,Child ,media_common ,medicine.diagnostic_test ,business.industry ,Fingolimod Hydrochloride ,Multiple sclerosis ,Magnetic resonance imaging ,medicine.disease ,Fingolimod ,Magnetic Resonance Imaging ,Clinical trial ,Neurology ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Physical therapy ,Observational study ,Female ,Neurology (clinical) ,business ,Brazil ,Immunosuppressive Agents ,medicine.drug ,Follow-Up Studies - Abstract
Background There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Participants and methods Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Results Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Conclusions Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control.
- Published
- 2015
25. Antileishmanial activity evaluation of adunchalcone, a new prenylated dihydrochalcone from Piper aduncum L
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Patricia Sartorelli, Camilla R. Dal Picolo, Mariana Palmeira Bezerra, Kaio S. Gomes, Euder Glendes Andrade Martins, Luiz Felipe Domingues Passero, João Henrique G. Lago, and Márcia Dalastra Laurenti
- Subjects
Stereochemistry ,Microbial Sensitivity Tests ,chemistry.chemical_compound ,FÁRMACOS IMUNOSSUPRESSORES ,Chalcones ,Prenylation ,Drug Discovery ,medicine ,Hydroxybenzoates ,Animals ,Amastigote ,EC50 ,Pharmacology ,Leishmania ,Mice, Inbred BALB C ,Piper aduncum ,biology ,Antiparasitic Agents ,Leishmaniasis ,Dihydrochalcone ,General Medicine ,Piperaceae ,biology.organism_classification ,medicine.disease ,chemistry ,Piper - Abstract
Bioactivity-guided fractionation of EtOH extract from the leaves of Piper aduncum L. (Piperaceae) afforded a new dihydrochalcone, named adunchalcone. Its structure was elucidated on the basis of their spectroscopic data, primarily NMR and MS. Adunchalcone was evaluated against promastigote forms of Leishmania (L.) amazonensis, L. (V.) braziliensis, L. (V.) shawi, and L. (L.) chagasi and displayed 50% effective concentrations (EC50) of 11.03, 26.70, and 11.26 μM, as well as selective indexes of 4.86, 2.01, 4.76 and 0.50, respectively. This compound was also tested against intracellular forms of L. (L.) amazonensis, displaying weak activity, in comparison to reference drug amphotericin B. However, despite reduced effect of adunchalcone against amastigotes of L. (L.) amazonensis, this work opens the perspective to use this particular molecule as a scaffold for the design of novel and selective drug candidates for neglected diseases, mainly leishmaniasis.
- Published
- 2014
26. High Dose of N-Acetylcystein Prevents Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing Myocardial Revascularization
- Author
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Puig, Luiz B.
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2014
27. Liver transplantation: Fifty years of experience
- Author
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Abdala, Edson
- Subjects
FÁRMACOS IMUNOSSUPRESSORES - Published
- 2014
28. An analysis of tacrolimus-related complications in the first 30 days after liver transplantation
- Author
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D′Albuquerque, Luiz A. Carneiro
- Subjects
FÁRMACOS IMUNOSSUPRESSORES - Published
- 2014
29. IgA pemphigus: Case series with emphasis on therapeutic response [Carta]
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Valeria Aoki, Claudia Giuli Santi, Ana Carulina L. Moreno, Takashi Hashimoto, Celina W. Maruta, and Tatiana Villas Boas Gabbi
- Subjects
Immunoglobulin A ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Dermatology ,Antibodies, Monoclonal, Humanized ,Acitretin ,Keratolytic Agents ,FÁRMACOS IMUNOSSUPRESSORES ,Anti-Infective Agents ,medicine ,Humans ,IgA pemphigus ,biology ,business.industry ,Adalimumab ,Tetracycline ,medicine.disease ,Tubulin Modulators ,Anti-Bacterial Agents ,Pemphigus ,biology.protein ,Prednisone ,Drug Therapy, Combination ,Colchicine ,business ,Dapsone ,medicine.drug - Published
- 2014
30. Synthesis and preliminary biological evaluation of a compound library of triazolylcyclitols
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Gonzalo Carrau, Ana Lucia Borges Shimada, Ana Bertucci, Sandra Helena Poliselli Farsky, Carine Cristiane Drewes, Hélio A. Stefani, and David Gonzalez
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Male ,Antifungal Agents ,Cyclitol ,Clinical Biochemistry ,Pharmaceutical Science ,Alkyne ,Toluene dioxygenase ,Antifungal ,Biochemistry ,Hygromycin ,Small Molecule Libraries ,chemistry.chemical_compound ,Mice ,FÁRMACOS IMUNOSSUPRESSORES ,Drug Discovery ,Organic chemistry ,Animals ,Molecular Biology ,Cells, Cultured ,Immunosuppressant ,Cell Proliferation ,Medicine(all) ,chemistry.chemical_classification ,Cycloaddition Reaction ,Molecular Structure ,Organic Chemistry ,Triazoles ,Cycloaddition ,Mice, Inbred C57BL ,chemistry ,Biocatalysis ,Dihydroxylation ,Molecular Medicine ,Hüisgen cycloaddition ,Derivative (chemistry) ,Cyclitols ,Immunosuppressive Agents ,Conduritol - Abstract
A small library of compounds was prepared by a combination of toluene dioxygenase (TDO)-catalyzed enzymatic dihydroxylation and copper(I)-catalyzed Hüisgen cycloaddition. Some compounds were obtained by coupling an alkyne and a conduritol derivative, while more complex structures were obtained by a double Hüisgen reaction of a dialkyne and two molecules of the cyclitol. The compounds were fully characterized and subjected to preliminary biological screening.
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- 2013
31. Efeitos da ciclosporina e sirolimus ao nível cardiovascular
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Maio, Diogo António Gonçalves Candeias da Guerra
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Canais de cálcio ,Ciclosporina - Doenças cardiovasculares ,Ciclosporina ,Sirolimus - Doenças cardiovasculares ,Fármacos imunossupressores ,Stress - Hipertensão - Abstract
Submitted by Helena Fortuna (hfortuna@ubi.pt) on 2013-05-17T13:45:43Z No. of bitstreams: 1 Tese_Mestrado_Diogo_Maio.pdf: 3196175 bytes, checksum: a8d488a353105372e9242ef5e0d03b84 (MD5) Made available in DSpace on 2013-05-17T13:45:43Z (GMT). No. of bitstreams: 1 Tese_Mestrado_Diogo_Maio.pdf: 3196175 bytes, checksum: a8d488a353105372e9242ef5e0d03b84 (MD5) Previous issue date: 2012-10
- Published
- 2012
32. GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation
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Verônica Coelho, Pedro M. Moraes-Vieira, Hernandez Moura Silva, Jorge Kalil, David Saitovitch, Maisa C.S. Takenaka, Sandra Maria Monteiro, Francine Brambate Carvalhinho Lemos, and Fabiana Agena
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TBX21 ,Adult ,Male ,Immunology ,GATA3 Transcription Factor ,Biology ,Peripheral blood mononuclear cell ,Transforming Growth Factor beta1 ,Th2 Cells ,FÁRMACOS IMUNOSSUPRESSORES ,Gene expression ,Immunology and Allergy ,Humans ,Regulator gene ,Aged ,Retrospective Studies ,Gene Expression Profiling ,Graft Survival ,GATA3 ,FOXP3 ,Forkhead Transcription Factors ,Middle Aged ,Kidney Transplantation ,Transplantation ,Interleukin 10 ,Leukocytes, Mononuclear ,Female ,Transplantation Tolerance ,Receptors, Transforming Growth Factor beta ,Immunosuppressive Agents - Abstract
Some organ-transplanted patients achieve a state of "operational tolerance" (OT) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, IL10, TGFB1, TGFBR1/ TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups. This predominant REG gene expression profile displayed stability over time. The significant GATA3 gene and protein expressions in OT individuals suggest that a Th2 deviation may be a relevant pathway to OT. Moreover, the capacity of the REG/INFLAMMA gene panel to discriminate OT by peripheral blood analysis indicates that this state has systemic repercussions.
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- 2012
33. Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model
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Pego-Fernandes, Paulo Manuel
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FÁRMACOS IMUNOSSUPRESSORES - Published
- 2011
34. Mixed connestivite tissue disease
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Veiga,Mariana Novais, Sousa,Ana Olívia, Martins,Joana, Carvalho,Claudina, Quintas,Conceição, Mota,Margarida, Gonçalves,Manuel, and Cunha,Emília
- Subjects
immunosupressive drugs ,Case report ,mixed connective tissue disease ,pregnancy ,fármacos imunossupressores ,Conectivite mista ,gravidez - Abstract
Os autores apresentam um caso clínico de Conectivite Mista numa primigesta de 24 anos portadora de hepatite B e pertencente a uma família de risco (Cônjuge Hepatite C Crónica e irmão co-infecção vírus hepatite C (VCH) - vírus imunodeficiência humana (VIH), toxicodependente). O diagnóstico de Conectivite Mista tinha sido confirmado há 3 anos e estava em fase de remissão há mais de 6 meses. Neste caso, e em contraste com o descrito na literatura, houve atingimento grave do Sistema Nervoso Central pondo em risco a sobrevivência materna, pelo que a equipa multidisciplinar que acompanhou a grávida se debateu com dúvidas em relação ao tratamento e eventual uso de fármacos potencialmente teratogénicos assim como quanto aos meios auxiliares de diagnóstico a utilizar e o momento mais indicado para interromper a gestação. Será aconselhável o tratamento agressivo das doenças imunológicas a fim de prevenir uma exacerbação durante a gravidez? The authors report a case of a 24 -year-old female in is first pregnancy, hepatitis B carrier, with mixed connective tissue disease, wich belongs to a very problematic family (husband with chronic hepatitis C and brother with co-infection HIV-HCV and toxicodependent). The diagnosis was confirmed 3 years ago and the disease was in remission for more than 6 months ago. In this case, in constrast to what we found in the literature, there was a very serious complication in the central nervous system putting at risk the mother’s life. The multidisciplinary team had many doubts in decide the best treatment, the use or not of teratogenic drugs and the moment to interrupt the gestation. We wonder if agressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.
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- 2005
35. Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and polymyositis: Immunogenicity independent of therapy and no harmful effect in disease
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Mauricio Levy-Neto, Julio C. B. Moraes, Alexander Roberto Precioso, Clovis A. Silva, Nadia E. Aikawa, Samuel Katsuyuki Shinjo, C. G. S. Saad, Eloisa Bonfa, and Ana Cristina de Medeiros Ribeiro
- Subjects
Adult ,Male ,medicine.medical_specialty ,Visual analogue scale ,medicine.disease_cause ,Polymyositis ,Gastroenterology ,Dermatomyositis ,FÁRMACOS IMUNOSSUPRESSORES ,Influenza A Virus, H1N1 Subtype ,Autoantibody ,Internal medicine ,Immunology and Microbiology(all) ,Influenza A virus ,Medicine ,Humans ,Seroconversion ,Adverse effect ,Autoantibodies ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Vaccination ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,veterinary(all) ,Infectious Diseases ,Influenza Vaccines ,Immunology ,biology.protein ,Molecular Medicine ,Creatine kinase ,Female ,business - Abstract
The goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1±9.9 vs. 43.8±8.4 years, p=0.607) and gender distribution (p=1.00) were comparable between the patients and controls. After 21 days, seroconversion (p=0.394), seroprotection (p=0.08), GMT (p=0.573) and the FI in the GMT (p=0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p=0.20) and aldolase levels (p=0.98), the physicians’ VAS (p=1.00), the patients’ VAS (p=1.00) and the MMT-8 (p=1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p=0.969), GC >0.5mg/kg/day (p=0.395) and GC+immunosuppressors (p=0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p>0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.
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