RESUMEN
With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.
Asunto(s)
Anemia Aplásica/terapia , Busulfano/uso terapéutico , Antígenos HLA/análisis , Inmunosupresores/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Histocompatibilidad , Humanos , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Donante no Emparentado , Adulto JovenRESUMEN
Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Aloinjertos , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Ciclosporina/uso terapéutico , Supervivencia sin Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Histocompatibilidad , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Incidencia , Infecciones/etiología , Infecciones/mortalidad , Estimación de Kaplan-Meier , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Linfocitos T/inmunología , Donante no EmparentadoRESUMEN
The aim of this study is to develop a novel decellularization method using aqueous extract of soap nut pericarp (SPE) and its evaluation using hematoxylin-eosin staining, scanning electron microscopy, diamidino-2-phenylindol (DAPI) staining, mechanical testing, sodium dodecyl sulfate polyacrylamide gel electrophoresis and DNA quantification. The presently available decellularization agent raises some concerns due to the potential for presence of residual cytotoxic agents in the extracellular matrix. Histological analysis of hematoxylin and eosin and masson's trichrome stained processed aortic samples shows complete decellularization with preservation of extracellular matrix microarchitecture at 120 h. Further, staining of tissue samples with DAPI demonstrates complete removal of DNA fragments. Quantitative evaluation of DNA in the decellularized aorta tissues demonstrated a significant (P < 0.01) decrease in DNA content as compared to native tissues. Collagen quantification assay indicate no significant (P> 0.05) difference in its content between native and decellularized caprine aorta. Tensile strength of the decellularized scaffolds decreased non-significantly (P > 0.05) when compared to native tissues. There was no significant (P > 0.05) difference in young's modulus of elasticity, stiffness and stretch ratio between native aortic tissues and decellularized aortic scaffolds. Histological and scanning electron microscopic examination of in vitro cultured scaffold demonstrated the cell viability and proliferation of primary chicken embryo fibroblasts. SPE treatment is thus capable of producing cytocompatible decellularized caprine aorta scaffold with preservation of extracellular matrix architecture for vascular tissue engineering and could be applied widely as one of the decellularization agent.
Asunto(s)
Aorta/citología , Separación Celular/métodos , Extractos Vegetales , Sapindus , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Fenómenos Biomecánicos , Supervivencia Celular , Embrión de Pollo , Colágeno , Matriz Extracelular , Fibroblastos/metabolismo , Frutas/química , Cabras , Histocompatibilidad , Microscopía Electrónica de Rastreo , Extractos Vegetales/química , Medicina Regenerativa , Sapindus/químicaRESUMEN
BACKGROUND: Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. METHODS: Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. CONCLUSION: These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/terapia , Donante no Emparentado , Adolescente , Adulto , Anciano , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Causas de Muerte , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Histocompatibilidad , Humanos , Incidencia , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact. METHODS: To investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation. RESULTS: The group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection. CONCLUSIONS: Desensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.
Asunto(s)
Abatacept/farmacología , Refuerzo Inmunológico de Injertos/métodos , Rechazo de Injerto/prevención & control , Trasplante de Riñón , Oligopéptidos/farmacología , Inhibidores de Proteasoma/farmacología , Animales , Linfocitos B/inmunología , Médula Ósea/inmunología , Receptores Coestimuladores e Inhibidores de Linfocitos T/efectos de los fármacos , Receptores Coestimuladores e Inhibidores de Linfocitos T/inmunología , Evaluación Preclínica de Medicamentos , Centro Germinal/inmunología , Supervivencia de Injerto , Histocompatibilidad , Memoria Inmunológica/efectos de los fármacos , Inmunosupresores/uso terapéutico , Isoanticuerpos/biosíntesis , Ganglios Linfáticos/inmunología , Activación de Linfocitos/efectos de los fármacos , Macaca mulatta , Masculino , Células Plasmáticas/inmunología , Cuidados Preoperatorios , Trasplante de Piel , Linfocitos T Colaboradores-Inductores/inmunologíaAsunto(s)
Conducta Cooperativa , Prestación Integrada de Atención de Salud/organización & administración , Cooperación Internacional , Trasplante de Riñón , Donadores Vivos/provisión & distribución , Obtención de Tejidos y Órganos/organización & administración , Selección de Donante , Europa (Continente) , Histocompatibilidad , Humanos , Evaluación de Programas y Proyectos de SaludRESUMEN
Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic haematopoietic cell transplantation (allo-HCT) is a potentially curative option, in particular in the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allo-HCT for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This manuscript reports on general considerations regarding allo-HCT for lymphoma and elaborates on the use of alternative donors in this setting.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/normas , Linfoma/terapia , Donantes de Tejidos , Aloinjertos , Resistencia a Antineoplásicos , Francia , Haploidia , Histocompatibilidad , Humanos , Recurrencia , Estudios Retrospectivos , Sociedades MédicasRESUMEN
PURPOSE: The purpose of this study was to evaluate engraftment and adverse events with a conditioning and prophylactic regimen intended to achieve high rates of engraftment with minimal graft-versus-host disease (GVHD) in allogeneic transplantation for chronic granulomatous disease in a single center. METHODS: Forty patients, 37 male, with chronic granulomatous disease were transplanted. Transplant products were matched sibling peripheral blood stem cells (PBSCs) in four and matched unrelated donor (MUD) bone marrow in three, and one patient received mismatched unrelated PBSCs. Thirty-two patients received MUD PBSCs. All patients received a conditioning regimen of busulfan/alemtuzumab (with low-dose total body irradiation for MUD recipients) with sirolimus graft-versus-host disease prophylaxis. RESULTS: Engraftment occured in 38/40 recipients (95%). Acute or chronic GVHD occurred in 18 (45%) and 5 (12.5%), respectively, with 6 episodes of grades III-IV and/or steroid refractory GVHD. Overall survival was 33/40 (82.5%) and event-free survival was 30/40 (80%). Successful engraftment was associated with myeloid and NK cell, but not CD3+ chimerism. Myeloid engraftment was greater than 70% in 30/32 recipients at mean follow-up of 3.4 years. Evidence of persistent immunodeficiency was not seen in successful transplants. Attempts to rescue failed or poorly functioning grafts were associated with unacceptable morbidity and mortality. CONCLUSIONS: A reduced-intensity allogeneic transplant protocol based on alemtuzumab and busulfan with sirolimus GVHD prophylaxis produced high rates of successful engraftment and minimal regimen-related toxicity. Prolonged clinical follow-up has confirmed its efficacy in ameliorating CGD-related disease. Outcomes were not acceptable with donor cell infusion rescue of cause with poor graft function.
Asunto(s)
Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Granulomatosa Crónica/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunoglobulinas Intravenosas/uso terapéutico , Quimerismo , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Granulomatosa Crónica/diagnóstico , Enfermedad Granulomatosa Crónica/mortalidad , Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Estudios Prospectivos , Hermanos , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.
Asunto(s)
Ciclofosfamida/uso terapéutico , Enfermedad de Hodgkin/terapia , Trasplante de Células Madre/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico , Adulto , Trasplante de Células Madre de Sangre del Cordón Umbilical , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped , Antígenos HLA , Histocompatibilidad , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Estudios Retrospectivos , Trasplante de Células Madre/normas , Trasplante Homólogo , Donante no Emparentado/provisión & distribuciónRESUMEN
BACKGROUND: Porcine xenografts are a promising source of scarce transplantable organs, but stimulate intense thrombosis of human blood despite targeted genetic and pharmacologic interventions. Current experimental models do not enable study of the blood/endothelial interface to investigate adhesive interactions and thrombosis at the cellular level under physiologic conditions. The purpose of this study was to develop and validate a live-cell, shear-flow based thrombosis assay relevant to general thrombosis research, and demonstrate its potential in xenotransplantation applications. METHODOLOGY/PRINCIPAL FINDINGS: Confluent wild-type (WT, n = 48) and Gal transferase knock-out (GalTKO, which resist hyperacute rejection; n = 11) porcine endothelia were cultured in microfluidic channels. To mimic microcirculatory flow, channels were perfused at 5 dynes/cm2 and 37°C with human blood stained to fluorescently label platelets. Serial fluorescent imaging visualized percent surface area coverage (SA, for adhesion of labeled cells) and total fluorescence (a metric of clot volume). Aggregation was calculated by the fluorescence/SA ratio (FR). WT endothelia stimulated diffuse platelet adhesion (SA 65 ± 2%) and aggregation (FR 120 ± 1 a.u.), indicating high-grade thrombosis consistent with the rapid platelet activation and consumption seen in whole-organ lung xenotransplantation models. Experiments with antibody blockade of platelet aggregation, and perfusion of syngeneic and allo-incompatible endothelium was used to verify the biologic specificity and validity of the assay. Finally, with GalTKO endothelia thrombus volume decreased by 60%, due primarily to a 58% reduction in adhesion (P < 0.0001 each); importantly, aggregation was only marginally affected (11% reduction, P < 0.0001). CONCLUSIONS/SIGNIFICANCE: This novel, high-throughput assay enabled dynamic modeling of whole-blood thrombosis on intact endothelium under physiologic conditions, and allowed mechanistic characterization of endothelial and platelet interactions. Applied to xenogeneic thrombosis, it enables future studies regarding the effect of modifying the porcine genotype on sheer-stress-dependent events that characterize xenograft injury. This in-vitro platform is likely to prove broadly useful to study thrombosis and endothelial interactions under dynamic physiologic conditions.
Asunto(s)
Anticoagulantes/farmacología , Trombosis/inmunología , Animales , Bioensayo , Fenómenos Biomecánicos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Células Endoteliales/inmunología , Endotelio Vascular/inmunología , Xenoinjertos , Histocompatibilidad , Humanos , Cinética , Sus scrofaRESUMEN
INTRODUCTION: Nucleic acid delivery is a complex process that requires transport across numerous extracellular and intracellular barriers, whose impact is often neglected during optimization studies. As such, the development of nonviral vectors for efficient delivery would benefit from an understanding of how these barriers relate to the physicochemical properties of lipoplexes and polyplexes. AREAS COVERED: This review focuses on the evaluation of parameters associated with barriers to delivery such as blood and immune cells compatibility which, as a collective, may serve as a useful prescreening tool for the advancement of nonviral vectors in vivo. An outline of the most relevant rationally developed polyplexes and lipoplexes for clinical application is also given. EXPERT OPINION: The evaluation of scientifically recognized parameters enabled the identification of systemic delivered nonviral vectors' behavior while in blood as one of the key determinants of vectors function and activity both in vitro and in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro-in vivo translation by minimizing false negatives. Further, it can aid in the identification of meaningful structure-function-activity relationships, improve the in vitro screening process of nonviral vectors before in vivo use and facilitate the future development of potent and safe nonviral vectors.
Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Técnicas de Transferencia de Gen , Vectores Genéticos/química , Vectores Genéticos/farmacocinética , Ácidos Nucleicos/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Citocinas/biosíntesis , Evaluación Preclínica de Medicamentos , Hemólisis/efectos de los fármacos , Histocompatibilidad/inmunología , Lipopéptidos/química , Lipopéptidos/farmacocinética , Nanopartículas/química , Polímeros/química , Relación Estructura-ActividadRESUMEN
Hematopoietic stem cell transplantation (HSCT) is the one and only curative therapy available for patient with severe sickle cell disease (SCD). Until today, several hundreds of patients have undergone geno-identical HSCT. More than 200 patients were transplanted in France. The first indication was cerebral vasculopathy. Among both malignant and non-malignant diseases treated with HSCT, the success rate obtained in SCD patients appears as the best one. From the year 2000, more than 95% of transplanted patients survived the HSCT procedure and more than 90% are completely cured and experience a very satisfying health condition post-transplantation. However, the current standard procedure includes a myeloablative conditioning regimen for warranting engraftment. Such regime is linked to severe long-term side effects such as hypofertility. Due to the excellent obtained results, we have to think about a possible widening of indications, a decrease of conditioning intensity and toxicity, and about HSCT from alternative stem cell sources, such as mismatch family donor, unrelated volunteer donor or unrelated cord blood.
Asunto(s)
Anemia de Células Falciformes/cirugía , Trasplante de Células Madre Hematopoyéticas , Adolescente , Trasplante de Médula Ósea/estadística & datos numéricos , Niño , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical/estadística & datos numéricos , Preservación de la Fertilidad , Francia , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Histocompatibilidad , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Lactante , Donadores Vivos , Agonistas Mieloablativos/efectos adversos , Calidad de Vida , Hermanos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
Na Medicina, como em muitas áreas da ocupação humana, o oculto tende a encantar. Talvez isso explique, em parte, o grande interesse em torno da sarcoidose, uma doença repleta de incógnitas e desafios ao seu entendimento. Esta revisão teve como objetivo apresentar os principais avanços no entendimento da imunopatogenia, diagnóstico e tratamento da sarcoidose pulmonar. Vários estudos têm enfatizado a importância do alelo DRB1*03 do antígeno leucocitário humano e da exposição ambiental na patogenia da doença. No tocante ao diagnóstico, o ultrassom endoscópico transesofágico, o ultrassom endobrônquico e a tomografia por emissão de pósitrons com 18F fluordesoxiglicose têm sido apresentados como exames promissores, inclusive na avaliação da resposta ao tratamento. Várias recomendações baseadas em evidências têm sugerido o uso de imunobiológicos nos casos de resistência aos corticosteroides, especialmente na sarcoidose refratária ao tratamento. O melhor entendimento da relação entre sarcoidose e exposição ambiental pode auxiliar na diferenciação dos vários fenótipos da doença. É possível que uma abordagem diagnóstica e terapêutica distinta possa ser utilizada em um futuro próximo, com base nesses fenótipos.
Asunto(s)
Humanos , Masculino , Femenino , Terapia Biológica , Histocompatibilidad , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis Pulmonar/epidemiología , Sarcoidosis Pulmonar/inmunología , Sarcoidosis Pulmonar/terapia , Ultrasonografía , Diagnóstico por Imagen , Enfermedades Pulmonares Intersticiales , TerapéuticaRESUMEN
OBJECTIVE: Discussing the chitosan' medical efficiency to treat Gynecology bacteria infectious disease by researching the bacteriostasis, biocompatibility of chitosan and analyzing the chitosan' medical efficiency to Bacterial vaginosis by clinical examination. METHODS: The antibiotic experiment of chitosan to Candida albicans (ATCC 10231), Escherichia Coli (ATCC 25922) and Golden staphylococcus (ATCC 6538) has been studied in this paper. The vaginal irritation experimentation of chitosan to female rabbit and the sensitization experimentation of chitosan to guinea pig also have been conducted. To study the curative effect, we also coat a layer of chitosan in 20 patients' vagina. RESULT: The Antibacterial rate of chitosan to Candida albicans is more than 98% and to Escherichia Coli is more than 99% and to Golden staphylococcus is more than 99%. Cytotoxicity of chitosan to vagina mucosa is grade 1 and sensitization of chitosan to vagina mucosa is none and stimulation of chitosan to vagina mucosa is very slightly. The total efficiency rate to treat Gynecology bacteria infectious disease is 90% and the cure rate is 75%.
Asunto(s)
Antiinfecciosos/uso terapéutico , Quitosano/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Animales , Antiinfecciosos/farmacología , Candida albicans/efectos de los fármacos , Quitosano/farmacología , Escherichia coli/efectos de los fármacos , Femenino , Histocompatibilidad , Pruebas de Sensibilidad Microbiana , Conejos , Staphylococcus/efectos de los fármacosRESUMEN
Oral administration of Tokishakuyaku-san (TJ-23), a Japanese herbal medicine, induces prolongation of cardiac allograft survival and generates regulatory cells in mice. Because herbal medicines usually have unique odor, and because smell is supposed to modulate the immune system, we examined whether the odor of TJ-23 induced prolonged allograft survival and regulatory cell generation. Naïve CBA mice (H2(k)) and olfactory-dysfunctional CBA mice after a stereotaxic operation underwent transplantation of C57BL/6 (B6, H2(b)) hearts, receiving fumigated water only or TJ-23 until rejection. Untreated or treated with water fumigation CBA mice rejected B6 cardiac grafts acutely (median survival times [MSTs], 7 and 8.5 days). When CBA mice were treated with fumigation of TJ-23, allograft survival was significantly prolonged (MST, 48 days). Olfactory-dysfunctional CBA mice treated with fumigation of TJ-23 rejected grafts acutely (MST, 7 days). Treatment with fumigation of TJ-23 also suppressed splenocytes proliferation and interferon-γ production. Secondary CBA recipients of whole splenocytes or CD4(+) cells from primary TJ-23-treated CBA recipients of B6 cardiac allografts at 30 days after grafting showed prolonged survival of B6 hearts (MST, >60 days). Flow cytometry studies showed increased CD4(+)CD25(+)Foxp3(+) regulatory cells in recipients given fumigation of TJ-23. In conclusion naïve but not olfactory-dysfunctional CBA mice treated with fumigation of TJ-23 displayed prolonged survival of fully allogeneic cardiac allografts and generation of regulatory cells.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón/inmunología , Factores Inmunológicos/farmacología , Odorantes , Olfato , Linfocitos T Reguladores/efectos de los fármacos , Traslado Adoptivo , Animales , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Rechazo de Injerto/inmunología , Rechazo de Injerto/fisiopatología , Histocompatibilidad , Interferón gamma/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Trastornos del Olfato/inmunología , Trastornos del Olfato/fisiopatología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/trasplante , Factores de TiempoRESUMEN
Inchingorei-san (TJ-117), a 6-component herbal medicine, is used in Japan for the treatment of vomiting, urticaria, and liver and kidney disorders with few side effects. In this study we investigated the effect of TJ-117 on alloimmune responses in murine cardiac allograft transplantation. CBA (H2(k)) mice underwent transplantation of a C57BL/6 (B6, H2(b)) heart with oral administration of TJ-117 (or 1 component of TJ-117) from the day of transplantation for 7 days. CBA recipients given 1 g/kg/d of TJ-117 showed prolonged B6 allograft survival (median survival time [MST], 23 days). Naive CBA mice rejected B6 cardiac grafts acutely (MST, 7 days). Moreover, Artemisiae capillaris herba (ACH; 1g/kg/d) 1 component of TJ-117, significantly prolonged B6 allograft survival (MST, > 100 days). However, the other 5 components of TJ-117 were individually less effective than TJ-117 or ACH. ACH also suppressed splenocyte proliferation and interferon-γ production. Secondary CBA recipient showed prolonged survival of B6 hearts after treatments with whole splenocytes from primary ACH-treated CBA recipients carrying B6 cardiac allografts for 30 days (MST, >50 days). Flow cytometry studies showed increased CD4(+)CD25(+)Foxp3(+) regulatory cells in transplant recipients given ACH. In conclusion, ACH, 1 component of TJ-117, as well as TJ-117 induced hyporesponsiveness to fully allogeneic cardiac allografts with generation of CD4(+)CD25(+)Foxp3(+) regulatory cells.
Asunto(s)
Artemisia , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Corazón/inmunología , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Administración Oral , Traslado Adoptivo , Animales , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Rechazo de Injerto/inmunología , Histocompatibilidad , Factores Inmunológicos/administración & dosificación , Interferón gamma/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Extractos Vegetales/administración & dosificación , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/trasplante , Factores de TiempoRESUMEN
In clinical practice, music has been used to decrease stress, heart rate, and blood pressure and to provide a distraction from disease symptoms. We investigated sound effects on alloimmune responses in murine heart transplantation. Naïve and eardrum-ruptured CBA/N (CBA, H2(K)) underwent transplantation of a C57BL/6 (B6, H2(b)) heart and were exposed to 1 of 3 types of music-opera (La Traviata), classical (Mozart), and New Age (Enya)-or 1 of 6 different single sound frequencies for 7 days. An adoptive transfer study was performed to determine whether regulatory cells were generated in allograft recipients. Cell-proliferation, cytokine, and flow cytometry assessments were also performed. CBA recipients of a B6 graft exposed to opera and classical music had significantly prolonged allograft survival (median survival times [MSTs], 26.5 and 20 days, respectively), whereas those exposed to 6 single sound frequencies and New Age did not (MSTs, 7, 8, 9, 8, 8, 8, and 11 days, respectively). Untreated and eardrum-ruptured CBA rejected B6 grafts acutely (MSTs, 7 and 8.5 days, respectively). Adoptive transfer of whole splenocytes, CD4(+) cells, and CD4(+)CD25(+) cells from opera-exposed primary recipients resulted in significantly prolonged allograft survival in naive secondary recipients (MSTs, 36, 68, and >50 days, respectively). Cell-proliferation, interleukin (IL)-2 and interferon-γ were suppressed in opera-exposed mice, whereas IL-4 and IL-10 from opera-exposed recipients were up-regulated. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population in splenocytes from opera-exposed mice. In conclusion, exposure to some types of music may induce prolonged survival of fully allogeneic cardiac allografts and generate CD4(+)CD25(+)Foxp3(+) regulatory cells.
Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Trasplante de Corazón/inmunología , Música , Linfocitos T Reguladores/inmunología , Estimulación Acústica , Traslado Adoptivo , Animales , Proliferación Celular , Citocinas/metabolismo , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Rechazo de Injerto/inmunología , Histocompatibilidad , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Trasplante de Piel/inmunología , Linfocitos T Reguladores/trasplante , Factores de Tiempo , Perforación de la Membrana Timpánica/inmunología , Perforación de la Membrana Timpánica/fisiopatologíaRESUMEN
Since its establishment in 2008, the National Kidney Registry has facilitated 213 kidney transplants between unrelated living donors and recipients at 28 transplant centers. Rapid innovations in matching strategies, advanced computer technologies, good communication and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 91% as a result of changes to the HLA typing requirements for potential donors and improved mechanisms to list unacceptable HLA antigens for sensitized patients. A uniform financial agreement among participating centers eliminated a major roadblock to facilitate unbalanced donor kidney exchanges among centers. The NKR transplanted 64% of the patients registered since 2008 and the average waiting time for those transplanted in 2010 was 11 months.
Asunto(s)
Sistemas de Administración de Bases de Datos , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Donadores Vivos/provisión & distribución , Sistema de Registros , Obtención de Tejidos y Órganos , Agencias Voluntarias de Salud , Autoanticuerpos/inmunología , Conducta Cooperativa , Prestación Integrada de Atención de Salud , Difusión de Innovaciones , Antígenos HLA/inmunología , Accesibilidad a los Servicios de Salud , Histocompatibilidad , Humanos , Relaciones Interinstitucionales , Trasplante de Riñón/economía , Trasplante de Riñón/ética , Trasplante de Riñón/inmunología , Sistema de Registros/ética , Programas Informáticos , Obtención de Tejidos y Órganos/economía , Obtención de Tejidos y Órganos/ética , Estados Unidos , Agencias Voluntarias de Salud/economía , Agencias Voluntarias de Salud/éticaRESUMEN
The aim of the present investigation was to develop and study topical gel delivery of curcumin for its anti-inflammatory effects. Carbopol 934P (CRB) and hydroxypropylcellulose (HPC) were used for the preparation of gels. The penetration enhancing effect of menthol (0-12.5% w/w) on the percutaneous flux of curcumin through the excised rat epidermis from 2% w/w CRB and HPC gel system was investigated. All the prepared gel formulations were evaluated for various properties such as compatibility, drug content, viscosity, in vitro skin permeation, and anti-inflammatory effect. The drug and polymers compatibility was confirmed by Differential scanning calorimetry and infrared spectroscopy. The percutaneous flux and enhancement ratio of curcumin across rat epidermis was enhanced markedly by the addition of menthol to both types of gel formulations. Both types of developed topical gel formulations were free of skin irritation. In anti-inflammatory studies done by carrageenan induced rat paw oedema method in wistar albino rats, anti-inflammatory effect of CRB, HPC and standard gel formulations were significantly different from control group (P < 0.05) whereas this effect was not significantly different for CRB and HPC gels formulations to that of standard (diclofenac gel) formulation (P > 0.05). CRB gel showed better % inhibition of inflammation as compared to HPC gel.