ABSTRACT
Background: Azathioprine is one of the earliest immunosuppressants prescribed for several autoimmune diseases. Yet there is a lack of research on the impact of azathioprine on pulp healing following the pulp capping procedure. Aim: This study aimed to investigate the effect of azathioprine on the healing ability of mechanically exposed dogs' dental pulps following direct pulp capping with mineral trioxide aggregate (MTA), bio-aggregates (BA), and Calcium hydroxide (Ca(OH)2). Methods: Four mongrel dogs were randomly assigned to two groups (two dogs/30 teeth in each group): immunosuppressed (group I) and control (group II). Group I received azathioprine for two months before surgical treatments and until the dogs were euthanized. Fifteen class V buccal cavities were performed in each dog. Each group was randomly divided into three subgroups (10 teeth each) based on the pulp capping substance. The pulps in subgroups A, B, and C were immediately capped with MTA, BA, and Ca(OH)2, respectively. Inflammation and dentine bridge development were histopathologically evaluated and scored at one and two months. The data were statistically analyzed. Results: The immunosuppressed group exhibited statistically greater inflammatory cell count and decreased dentine bridge thickness, compared to the control group in all subgroups (p < 0.05). Conclusion: Azathioprine has an adverse effect on the healing of exposed dogs' dental pulp following direct pulp capping with MTA, BA, and Ca(OH)2. Therefore, patients using azathioprine as an immunosuppressive medication may experience delayed healing of mechanically exposed pulps following capping with MTA, BA, or Ca(OH)2.
Subject(s)
Azathioprine , Calcium Compounds , Calcium Hydroxide , Dental Pulp Capping , Immunosuppressive Agents , Oxides , Silicates , Animals , Dogs , Azathioprine/pharmacology , Azathioprine/therapeutic use , Dental Pulp Capping/veterinary , Oxides/pharmacology , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Silicates/pharmacology , Calcium Compounds/pharmacology , Calcium Hydroxide/pharmacology , Calcium Hydroxide/therapeutic use , Dog Diseases/drug therapy , Aluminum Compounds/pharmacology , Dental Pulp/drug effects , Drug Combinations , Male , Wound Healing/drug effects , Pulp Capping and Pulpectomy Agents/pharmacology , FemaleABSTRACT
Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal homeostasis. Altered PCs function is associated with diverse intestinal pathologies, including ileal Crohn's disease (CD). CD patients with ileal involvement have been previously demonstrated to display impairment in PCs and decreased levels of anti-microbial peptides. Although the immunosuppressive drug Azathioprine (AZA) is widely used in CD therapy, the impact of AZA on IEC differentiation remains largely elusive. In the present study, we hypothesized that the orally administered drug AZA also exerts its effect through modulation of the intestinal epithelium and specifically via modulation of PC function. AZA-treated CD patients exhibited an ileal upregulation of AMPs on both mRNA and protein levels compared to non-AZA treated patients. Upon in vitro AZA stimulation, intestinal epithelial cell line MODE-K exhibited heightened expression levels of PC marker in concert with diminished cell proliferation but boosted mitochondrial OXPHOS activity. Moreover, differentiation of IECs, including PCs differentiation, was boosted in AZA-treated murine small intestinal organoids and was associated with decreased D-glucose consumption and decreased growth rates. Of note, AZA treatment strongly decreased Lgr5 mRNA expression as well as Ki67 positive cells. Further, AZA restored dysregulated PCs associated with mitochondrial dysfunction. AZA-dependent inhibition of IEC proliferation is accompanied by boosted mitochondria function and IEC differentiation into PC.
Subject(s)
Azathioprine , Cell Differentiation , Crohn Disease , Intestinal Mucosa , Paneth Cells , Crohn Disease/drug therapy , Crohn Disease/pathology , Crohn Disease/metabolism , Azathioprine/pharmacology , Paneth Cells/metabolism , Paneth Cells/drug effects , Paneth Cells/pathology , Humans , Cell Differentiation/drug effects , Animals , Mice , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Female , Male , Ileum/drug effects , Ileum/metabolism , Ileum/pathology , Adult , Organoids/drug effects , Organoids/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Cell Proliferation/drug effects , Middle Aged , Cell Line , Severity of Illness IndexSubject(s)
Humans , Male , Adult , Sarcoidosis/etiology , Atrioventricular Block/diagnostic imaging , Heart Diseases/complications , Heart Diseases/diagnostic imaging , Azathioprine/pharmacology , Time Factors , Echocardiography , Magnetic Resonance Spectroscopy , Methotrexate/toxicity , Tachycardia, Ventricular/complications , Bisoprolol/chemistry , Adrenal Cortex Hormones/administration & dosage , Computed Tomography Angiography , Heart Failure/complications , Amiodarone/chemistry , Anticoagulants/chemistryABSTRACT
OBJETIVO: Avaliar os efeitos da azatioprina sobre o sistema mucociliar em um modelo de secção e anastomose brônquica em ratos. MÉTODOS: Trinta e seis ratos machos da raça Wistar-Furth foram submetidos à secção e anastomose brônquica esquerda e separados aleatoriamente em dois grupos para receberem solução salina ou azatioprina. Após 7, 15 e 30 dias de terapia, seis animais de cada grupo foram sacrificados, e foram realizadas as medidas da velocidade de transporte mucociliar in situ, da transportabilidade do muco in vitro e do ângulo de contato do muco nos brônquios direito (intacto) e esquerdo (seccionado). RESULTADOS: A velocidade de transporte mucociliar in situ foi significativamente menor nos brônquios seccionados do que nos brônquios intactos (p < 0,001). Houve redução da velocidade de transporte mucociliar in situ nos brônquios intactos dos animais tratados com azatioprina por 7 dias (p < 0,05), havendo completa recuperação após 30 dias de terapia. O ângulo de contato do muco foi maior nos brônquios seccionados dos animais tratados com solução salina por 30 dias (p < 0,001), estando de acordo com a redução da transportabilidade do muco in vitro observada nos mesmos animais (p < 0,001). CONCLUSÕES: Concluímos que, nos brônquios seccionados de ratos, a terapia com azatioprina causa um prejuízo apenas transitório do transporte mucociliar, enquanto a administração de solução salina prejudica o transporte mucociliar por até 30 dias. Além disso, a azatioprina contribui para prevenir alterações nas propriedades da superfície do muco.
OBJECTIVE: To evaluate the effects of azathioprine on the mucociliary system in a model of bronchial section and anastomosis in rats. METHODS: Thirty-six male Wistar-Furth rats were submitted to left bronchial section and anastomosis and divided into two groups to receive either saline solution or azathioprine. After 7, 15 and 30 days of treatment, six animals from each group were killed, after which in situ mucociliary transport velocity, in vitro mucus transportability, and contact angle of mucus in the right (intact) and left (sectioned) bronchi were measured. RESULTS: In situ mucociliary transport velocity was significantly lower in the sectioned bronchi than in the intact bronchi (p < 0.001). In situ mucociliary transport velocity was lower in the intact bronchi of the animals treated with azathioprine for 7 days (p < 0.05), and those bronchi presented full recovery after 30 days of treatment. The contact angle was higher in the mucus samples collected from the sectioned bronchi of the animals treated with saline solution for 30 days (p < 0.001), which is in accordance with the decreased in vitro mucus transportability observed in the same animals (p < 0.001). CONCLUSIONS: We conclude that, in the sectioned bronchi of rats, treatment with azathioprine causes only transitory impairment of mucociliary transport, whereas administration of saline solution impairs mucociliary transport for up to 30 days. In addition, azathioprine protects against alterations in mucus surface properties.
Subject(s)
Animals , Male , Rats , Azathioprine/pharmacology , Immunosuppressive Agents/pharmacology , Mucociliary Clearance/drug effects , Anastomosis, Surgical , Drug Evaluation, Preclinical , Lung Transplantation/immunology , Models, Theoretical , Rats, Wistar , Sodium ChlorideABSTRACT
Immunosuppressive therapy aims to protect transplanted organs from host responses. The success achieved during the last two decades in patient and graft survival is mainly related to the development and clinical use of efficacious immunosuppressive drugs. Nevertheless, the challenge of achieving a balance of adequate graft protection while minimizing the adverse consequences of excessive immunosuppression in the long-term continues. Current maintenance immunosuppression for renal transplant recipients generally consists of a calcineurin inhibitor plus an adjunctive antiproliferative agent, and steroids. The addition of induction therapy with a variety of monoclonal or polyclonal antibodies provides a more potent immunosuppression and its use is more relevant in patients with a high immunological risk. More recently, mammalian target of rapamycin inhibitors have been incorporated in different schemes proven its efficacy in a number of protocols. The incidence of acute rejection is now in its lower historical percentage and excellent results are reported from many transplant centers all over the world due mainly to a judicious combination of these drugs evaluated through many clinical studies. However, long-term use of immunosuppressive drugs convey inherent risks which translate in an increase of cancers and infections, among others. Ongoing investigations and clinical protocols involving new immunosuppressive drugs and biological agents are yielding important information on how to obtain tolerance or the nearest to this goal. Furthermore, there should be a continuous improvement in patient and graft survival, as the use of different immunosuppressive agents for induction and maintenance are individualized (adapted to each patient).
La terapia inmunosupresora empleada en receptores de trasplante tiene el objetivo de proteger el injerto de la respuesta inmunoloógica generada por parte del huésped. El éxito logrado en el transcurso de las últimas dos décadas en la supervivencia de receptores e injertos, ha dependido en gran medida del desarrollo y uso clínico de fármacos inmunosupresores de probada eficacia. Empero el enorme beneficio que han representado, el reto continúa para mantener un balance adecuado entre la protección inmunológica del injerto y la minimización de las consecuencias adversas derivadas de su indispensable utilización a largo plazo. La terapia inmunosupresora actual de mantenimiento en receptores de trasplante renal consiste habitualmente en la administración de un inhibidor de calcineurina, un agente antiproliferativo, como adyuvante, y esteroides. La adición de terapia de inducción, con modalidades biológicas de anticuerpos mono o policlonales, proveen un mayor grado de inmunosupresión y su empleo adquiere gran relevancia en pacientes con mayor riesgo inmunológico. En una etapa más reciente, los inhibidores del blanco de rapamicina han sido introducidos en varios esquemas después de probar su eficacia en múltiples protocolos. La incidencia de rechazo agudo ha alcanzado sus más bajos índices históricos y los resultados alcanzados en muchos centros de trasplante del mundo son excelentes, derivados en gran medida de la combinación juiciosa de estos fármacos, evaluados en una gran variedad de estudios. El empleo crónico de estos fármacos conlleva riesgos inherentes que se traducen en riesgos incrementados para el desarrollo de infecciones y neoplasias, entre otros. Así, mientras esperamos nuevos avances derivados de una gran profusión de estudios de investigación y protocolos clínicos con nuevas drogas inmunosupresoras y compuestos biológicos, encaminados a obtener tolerancia o lo más cercano a este propósito, deberemos ser capaces de continuar mejorando la vida funcional de la mayoría de los injertos y, desde luego, de sus receptores, "individualizando" (de acuerdo con los riesgos de cada paciente) el empleo de los agentes inmunosupresores disponibles para inducción y mantenimiento.
Subject(s)
Humans , Immunosuppression Therapy/methods , Kidney Transplantation/immunology , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal/therapeutic use , Azathioprine/pharmacology , Azathioprine/therapeutic use , Calcineurin/antagonists & inhibitors , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Graft Rejection/prevention & control , Growth Inhibitors/pharmacology , Growth Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Protein Kinases/drug effects , /antagonists & inhibitors , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases , Tacrolimus/pharmacology , Tacrolimus/therapeutic useABSTRACT
In order to evaluate whether immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine would differently influence the outcome of the renal transplants, we prospectively analyzed the incidence of acute rejection episodes, cytomegalovirus infection within the first 6 months following renal transplantation and 5 yr graft survival rate after minimizing influences of donor factors by grafting the same cadaveric donor kidney. There was no significant difference in sex, HLA mismatch, cold ischemic time, and patients' weight between the two groups. Contrary to the previous studies which demonstrated that MMF could lower the incidence of acute rejection episodes and improved graft survival rate, the two groups showed no significant difference in the incidence of acute rejection episodes and 5-yr graft survival rate as well. This discrepancy in these results might explain that donor factors could be important to cadaveric renal transplantation. Thus, we suggest that the influences of donor factors should be considered in further clinical studies of cadaveric renal transplantation.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , ABO Blood-Group System , Azathioprine/pharmacology , Body Weight , Cadaver , Cytomegalovirus/metabolism , Cytomegalovirus Infections/metabolism , Graft Rejection , Graft Survival , Histocompatibility Testing , Immunophenotyping , Immunosuppressive Agents/pharmacology , Ischemia , Kidney Diseases/mortality , Kidney Transplantation/methods , Mycophenolic Acid/analogs & derivatives , Prospective Studies , Time Factors , Tissue Donors , Treatment OutcomeABSTRACT
No disponible
Subject(s)
Humans , Azathioprine/chemistry , Skin Diseases/drug therapy , Azathioprine/pharmacology , Azathioprine/metabolism , Azathioprine/administration & dosage , Homeopathic Dosage , Drug InteractionsABSTRACT
Los cánceres de cabeza y cuello representan el 15 por ciento de todos los tumores malignos en los pacientes trasplantados. La principal causa que justifica este incremento de incidencia con relación a la población general, es el significativo aumento de los cánceres de labio. En el presente trabajo se documentan dos casos de carcinoma epidermoide oral desarrollados en pacientes sometidos a un trasplante renal. Se realiza una revisión sobre la cuestión, definiendo aquellos aspectos de mayor trascendencia clínica para el odonto-estomatólogo. (AU)
Subject(s)
Aged , Male , Humans , Carcinoma, Squamous Cell/etiology , Mouth Neoplasms/etiology , Lip Neoplasms/etiology , Kidney Transplantation/adverse effects , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/epidemiology , Renal Insufficiency, Chronic/surgery , Azathioprine/pharmacology , Azathioprine/administration & dosage , Prednisone/administration & dosage , Prednisone/pharmacology , Immunosuppression Therapy , Incidence , Glossectomy/methods , Mouth Neoplasms/epidemiology , Mouth Neoplasms/diagnosis , Mouth Neoplasms/surgery , Lip Neoplasms/epidemiology , Lip Neoplasms/diagnosis , Lip Neoplasms/surgeryABSTRACT
Os autores relatam quatro casos graves de psoríase resistentes às terapias convencionais que apresentaram boa resposta ao tratamento com azatioprina. Esclarecem ainda os aspectos farmacológicos, bem como os efeitos colaterias e uso terapêutico da droga, e destacam a azatioprina como alternativa terapêutica nos casos mais graves e resistentes de psoríase em um país como o Brasil, onde fatores como alcoolismo e hepatite limitam o uso do metotrexate e da ciclosporina
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Azathioprine/adverse effects , Azathioprine/pharmacology , Azathioprine/therapeutic use , Cyclosporine , Methotrexate , Psoriasis/drug therapy , Drug Resistance, Multiple , Drug Monitoring , Risk FactorsABSTRACT
In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha1-antitypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immuno-suppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg(-1) week(-1) while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 + 0.73 U vs 0.37 + 0.13 U (control children), P<0.001 and vs 0.23 + 0.12 U (control adults), P<0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4 percent). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 + 0.24 U, 0.76 + 0.43 U, 0.95 + 0.52 U, respectively, P<0.05). IgA values exceeding normal levels for age were found in 14 percent of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P<0.01), alpha1-acid-glycoprotein (r = 0.45, P<0.01), alpha1-antichymotrypsin (r = 0.52, P<0.01), alpha1-antitrypsin (r = 0.40, P<0.01) and IgA (r = 0.56, P<0.01) was established.
Subject(s)
Child , Child, Preschool , Female , Humans , Adolescent , alpha 1-Antitrypsin/drug effects , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/physiopathology , Azathioprine/pharmacology , Azathioprine/therapeutic use , Immunosuppressive Agents/pharmacology , Methotrexate/pharmacology , Methotrexate/therapeutic use , Antirheumatic Agents , Azathioprine/blood , Immunosuppressive Agents/therapeutic use , Methotrexate/bloodABSTRACT
A azatioprina foi sintetizada em 1959 e três anos após já era administrada em receptores de alotransplantes renais. Nos últimos 30 anos, tem sido usada em vários tipos de transplantes de órgäos, prevenindo a rejeiçäo aguda ou reaçäo enxerto versus hospedeiro e no tratamento de várias doenças auto-imunes. Pouco tem sido publicado sobre esta droga, embora o seu uso seja universal. O objetivo desta publicaçäo foi rever os aspectos farmacológicos: apresentaçäo, administraçäo, absorçäo, metabolismo, mecanismo de açäo, excreçäo, efeitos terapêuticos, indicaçöes clínicas, efeitos colaterais e interaçöes medicamentosas.
Subject(s)
Humans , Azathioprine/pharmacokinetics , Drug Interactions , Azathioprine/therapeutic use , Azathioprine/pharmacology , TransplantationABSTRACT
Se estudian los resultados globales de sobrevida de paciente e injerto a 5 años plazo y la influencia de la histocompatibilidad HLA en una serie de 100 trasplantes renales primarios donante cadáver. El tratamiento inmunosupresor fue Ciclosporina A, Azatioprina y Prednisona. La sobrevida actuarial a 1 y 54 años de pacientes e injerto fue del 96-91 por ciento y 71-70 por ciento respectivamente. Si bien se observó una tendencia a mejores sobrevidas para mejores compatibilidades HLA-DR, HLA B-DR y HLA A-B y DR, estos resultados no tienen significación estadística
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Graft Survival , Histocompatibility/drug effects , Kidney Transplantation , HLA Antigens , Azathioprine/pharmacology , Cadaver , Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Prednisone/pharmacology , Transplantation, HomologousABSTRACT
El Fk 509 es un macrólido natural con una potente actividad inmunosupresora. Experimentos in vitro han demostrado la supresión de la inmunidad celular mediada por linfocitos T. Experiencias clínicas han demostrado su utilidad como tratamiento en terapia de rescate en pacientes que han recibido un trasplante de hígado, que presentaban rechazo y cuando éste es resistente a las terapias actuales en uso. El objetivo de esta presentación es mostrar lo que sucedió con 15 pacientes que recibieron FK 506 como terapia inmunosupresora principal. Forma parte de un estudio multicéntrico europeo, prospectivo y randomizado, cuyo objetivo es comparar la utilidad de FK 506 v/s CyA en trasplante de hígado. La serie estudiada estuvo constituida por 28 pacientes; 15 recibieron FK 506 y 13 recibieron CyA. Las observaciones que se obtienen en esta evaluación inicial son: a) el FK 506 tiene efectos colaterales adversos en tipo y frecuencia similar a la obtenida en pacientes que son tratados con CyA; b) la incidencia de insuficiencia renal postoperatoria parece estar relacionada con la dosificación y niveles de FK 506; c) para demostrar la superioridad de una alternativa de tratamiento (FK 506) sobre el otro (CyA), se requiere de un gran número de pacientes y seguidos por un período prolongado; d) es probable que el FK 506 sea una buena alternativa para el tratamiento asociado con CyA como terapia de rescate
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Azathioprine/pharmacology , Cyclosporine/pharmacology , Liver Transplantation/immunology , Tacrolimus/pharmacology , Carbohydrates/metabolism , Immunosuppression Therapy/adverse effects , Immunosuppression Therapy/methods , Immunosuppression Therapy/mortalityABSTRACT
Entre 27 pacientes submetidos a transplante cardíaco, no Instituto do Coraçäo do Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo, 4 eram portadores de cardiomiopatia chagásica. As idades situaram-se entre 28 e 43 anos. Três pacientes estavam em grup funcional IV e 1, na classe funcional II, mas apresentando taquiarritmia ventricular refratária. A imunossupressäo foi feita com cilosporina mais corticóide, no 1§ pacientes, e ciclosporina, azatioprina e corticóide, nos outros três. Três pacientes tiveram episódios de rejeiçäo, tratados com pulsoterapia. Um destes pacientes apresentou doença intestinal linfoproliferativa precoce. os 3 pacientes tiveram reagudizaçäo da doença de Chagas no 59§, 81§ e 42§ de pós-operatório, respectivamente, caracterizada por febre, lesöes cutâneas e miocardite. O Trypanosoma cruzi foi encontrado nas biópsias de pele dos 3 pacientes e nas biópsias do miocárdio em 2 pacientes. Um dos pacientes näo teve reagudizaçäo. todos os 4 doentes foram tratados com medicaçäo específica, bem tolerada em todos. As alteraçöes da reagudizaçäo da doença de Chagas revertem em poucos dias. Um dos pacientes, que teve doença linfoproliferativa e cujas doses de imunossupressores foram reduzidas, faleceu no 197§ dia, em crise de rejeiçäo. Os demais estäo bem e em seguimento por 107, 160 e 500 dias, respectivamente
Subject(s)
Humans , Adult , Chagas Cardiomyopathy/surgery , Heart Transplantation/immunology , Immunosuppression Therapy , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Azathioprine/pharmacology , Azathioprine/therapeutic use , Chagas Cardiomyopathy/drug therapy , Cyclosporins/pharmacology , Cyclosporins/therapeutic use , Follow-Up StudiesABSTRACT
Apresenta-se um estudo experimental realizado em cäes, onde observaram as alteraçöes da pequena curvatura do estômago após a Vagotomia Superseletiva, em animais submetidos à imunossupressäo. Os animais do grupo de controle apresentaram evoluçäo pós-operatória sem anormalidades e perfuraçäo da pequena curvatura. Histologicamente, a cicatrizaçäo ocorreu dentro dos parâmentros normais. Entre os sete animais submetidos à imunossupressäo através do uso de corticosteróide e azatioprina, um apresentou perfuraçäo da pequena curvatura do estômago no quarto dia pós-operatório, evoluindo para o óbito com quadro de peritonite e hematêmese. Do ponto de vista histopatológico neste grupo de animais, os elementos de cicatrizaçäo estiveram discretamente presentes, especialmente em relaçäo ao colágeno e à reaçäo inflamatória. Conclue-se que a VSS näo deva ser indicada para pacientes portadores de úlcera duodenal, que estejam sob uso de imunossupressores por tempo prolongado