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1.
Biochem Pharmacol ; 157: 33-42, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30056139

RESUMO

The discovery of the endocannabinoid system nearly three decades ago generated great interest among pain scientists. Moreover, its analogy with the opioid system in terms of evolutionary preservation, tissue localization and analgesic activity enabled a vast new field for the development of medicines addressed to those types of pain that still nowadays are difficult to manage. However, the main disadvantage that hampers the use of cannabinergic drugs as analgesics is their identification with recreational use, besides their psychotomimetic actions. Pain has traditionally been classified attending to the ailment duration (acute or chronic) and drugs are used according to the intensity of the pain to treat, but it is also important to target the mechanism involved despite the intensity or duration of pain. The present chapter reviews the study and use of cannabinoids attending separately to four classic types of pain: nociceptive, inflammatory, neuropathic and oncological, considering basic research (pain animal models) as well as clinical practice.


Assuntos
Canabinoides/uso terapêutico , Dor Crônica/tratamento farmacológico , Analgésicos/uso terapêutico , Animais , Dor do Câncer/tratamento farmacológico , Humanos , Neuralgia/tratamento farmacológico , Dor Nociceptiva/tratamento farmacológico
2.
Artigo em Francês | MEDLINE | ID: mdl-26781159

RESUMO

INTRODUCTION: New continuous digital workflow protocols of guided and computer-assisted implant surgery improve accuracy of implant positioning. TECHNICAL PROCEDURE: The design of the future prosthesis is based on the available prosthetic space, gingival height and occlusal relationship with the opposing and adjacent teeth. The implant position and length depend on volume, density and bone quality, gingival height, tooth-implant and implant-implant distances, implant parallelism, axis and type of the future prosthesis. The crown modeled on the software will therefore serve as a guide to the future implant axis and not the reverse. The guide is made by 3D printing. The software determines surgical protocol with the drilling sequences. The unitary or plural prosthesis, modeled on the software and built before surgery, is loaded directly after implant placing, if needed. DISCUSSION: These protocols allow for a full continuity of the digital workflow. The software provides the surgeon and the dental technician a total freedom for the prosthetic-surgery guide design and the position of the implants. The prosthetic project, occlusal and aesthetic, taking the bony and surgical constraints into account, is optimized. The implant surgery is simplified and becomes less "stressful" for the patient and the surgeon. Guided and computer-assisted surgery with continuous digital workflow is becoming the technique of choice to improve the accuracy and quality of implant rehabilitation.


Assuntos
Implantação Dentária Endóssea/métodos , Prótese Dentária Fixada por Implante/métodos , Arcada Edêntula/cirurgia , Cirurgia Assistida por Computador/métodos , Fluxo de Trabalho , Implantação Dentária Endóssea/instrumentação , Planejamento de Prótese Dentária/instrumentação , Planejamento de Prótese Dentária/métodos , Prótese Dentária Fixada por Implante/instrumentação , Humanos , Imageamento Tridimensional , Maxila/cirurgia , Modelos Anatômicos , Software
3.
Am J Transplant ; 16(5): 1569-78, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26613555

RESUMO

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT.


Assuntos
Cardiopatias/complicações , Transplante de Coração/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Seguimentos , Cardiopatias/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo
4.
Rev Stomatol Chir Maxillofac Chir Orale ; 115(2): 105-10, 2014 Apr.
Artigo em Francês | MEDLINE | ID: mdl-24674931

RESUMO

INTRODUCTION: Pre-implant bone graft in posterior mandibular segments is difficult because of masticatory and lingual mechanical constraints, because of the limited bone vascularization, and because of the difficulty to cover it with the mucosa. The formwork technique is especially well adapted to this topography. TECHNICAL NOTE: The recipient site is abraded with a drill. Grooves are created to receive and stabilize the grafts. The bone grafts were harvested from the ramus. The thinned cortices are assembled in a formwork and synthesized by mini-plates. The gaps are filled by bone powder collected during bone harvesting. DISCUSSION: The bone volume reconstructed with the formwork technique allows anchoring implants more than 8mm long. The proximity of the inferior alveolar nerve does not contra indicate this technique. The formwork size and its positioning on the alveolar crest can be adapted to prosthetic requirements by using osteosynthesis plates. The lateral implant walls are supported by the formwork cortices; the implant apex is anchored on the native alveolar crest. The primary stability of implants is high, and the torque is important. The ramus harvesting decreases operative risks.


Assuntos
Transplante Ósseo , Prótese Mandibular , Reconstrução Mandibular/métodos , Procedimentos de Cirurgia Plástica/métodos , Ajuste de Prótese/métodos , Aumento do Rebordo Alveolar , Transplante Ósseo/instrumentação , Transplante Ósseo/métodos , Feminino , Humanos , Reconstrução Mandibular/instrumentação , Pessoa de Meia-Idade , Desenho de Prótese
5.
Neurochem Int ; 61(1): 119-27, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22521773

RESUMO

Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-γ (PPARγ), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARγ. Our results show that daidzein (0.05-5 µM) decreases cell death induced by exposure to oxygen-glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARγ antagonist T0070907 (1 µM). In addition, this phytoestrogen activated PPARγ in neuronal cultures, as shown by an increase in PPARγ transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARγ competitive binding assay. Conversely, daidzein increased PPARγ nuclear protein levels and decreased cytosolic ones, suggesting nuclear translocation. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARγ activity not mediated by direct binding to the receptor ligand-binding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.


Assuntos
Isoflavonas/farmacologia , Fármacos Neuroprotetores/farmacologia , PPAR gama/metabolismo , Animais , Benzamidas/farmacologia , Células Cultivadas , Glucose/metabolismo , Ligantes , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxigênio/metabolismo , PPAR gama/agonistas , Piridinas/farmacologia , Ratos
6.
Rev Stomatol Chir Maxillofac ; 113(2): 108-14, 2012 Apr.
Artigo em Francês | MEDLINE | ID: mdl-22398191

RESUMO

INTRODUCTION: Pre-implant reconstruction techniques of edentulous molar mandibular ridges take into account the height and the width of the initial ridge, but not the initial geometry. The Simplant(®) software allows modeling these techniques by taking into account this geometry. TECHNICAL NOTE: Four surgical techniques for crestal volume reconstruction (apposition, interposition, distraction, formwork) were used on seven hemi-mandibles and modeled with the Simplant(®) software. This reconstructed volume was visualized according to the initial crestal geometry. The average gain in height was 4.1mm for the onlay graft, 2.3mm for the interposition graft, 4mm for distraction, 5.1mm for the boxing. The average gain of crestal width was -0.3mm for the onlay graft, 1mm for the interposition, -0.5mm for the distraction, and 1.3mm for the boxing. DISCUSSION: Modeling with the Simplant(®) software shows that boxing technique gives the closest bone reconstruction to the ideal crestal geometry, whatever the initial crestal geometry.


Assuntos
Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Simulação por Computador , Software , Aumento do Rebordo Alveolar/instrumentação , Transplante Ósseo/instrumentação , Implantação Dentária Endóssea/métodos , Implantes Dentários , Prótese Dentária Fixada por Implante/instrumentação , Prótese Dentária Fixada por Implante/métodos , Humanos , Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Mandíbula/cirurgia , Boca Edêntula/diagnóstico por imagem , Boca Edêntula/patologia , Boca Edêntula/cirurgia , Tamanho do Órgão , Radiografia , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos
8.
Transplant Proc ; 42(8): 3001-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20970593

RESUMO

INTRODUCTION: The incidence of skin cancer in heart transplant (HT) patients is higher than in the general population, reversing the proportion of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with a predominance of the former. The etiologic role of new immunosuppressants is not well known. We sought to ascertain the incidence of SCC and BCC in HT patients and the risk factors for its occurrence. PATIENTS AND METHODS: We report the incidence of all types of post-HT skin cancer, SCC, and BCC among adult HT patients in Spain (4089 subjects) as well as the influence of gender, age at heart transplant, immunosuppression, and sunlight exposure. RESULTS: The incidence rates of SCC and BCC, per 1000 persons/year, were 8.5 and 5.2, respectively. Males had a higher risk of SCC but not BCC. Induction therapy increased the risk of SCC and BCC. The relative risk of mycophenolate mofetil (MMF) was 0.3 (0.2-0.6; P<.0005) and azathioprine (AZA) 1.8 (1.2-2.7; P<.0032) for SCC, whereas tacrolimus and cyclosporine showed no difference. The relative risk of BCC was not affected by any immunosuppressant. CONCLUSION: Age at transplantation>45 years, induction therapy use, and high sunshine zone were risk factors for both SCC and BCC. Different immunosuppressive agents have different risks of nonmelanoma skin cancer, as AZA increases the risk of SCC and MMF is a protective factor. The relative risk of BCC was not affected by any immunosuppressor.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Masculino , Fatores de Risco , Neoplasias Cutâneas/etiologia , Espanha/epidemiologia
9.
Adv Urol ; : 782381, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19009036

RESUMO

Some tumors are known to have a definite cause-effect etiology, but renal cell carcinoma (RCC) is not one of them precisely. With regard to RCC we can only try to identify some clinical and occupational factors as well as substances related to tumorigenesis. Smoking, chemical carcinogens like asbestos or organic solvents are some of these factors that increase the risk of the RCC. Viral infections and radiation therapy have also been described as risk factors. Some drugs can increase the incidence of RCC as well as other neoplasms. Of course, genetics plays an outstanding role in the development of some cases of kidney cancer. Chronic renal failure, hypertension, and dialysis need to be considered as special situations. Diet, obesity, lifestyle, and habits can also increase the risk of RCC. The aim of this review is to summarize the well-defined causes of renal cell carcinoma.

10.
Am J Transplant ; 8(5): 1031-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18416739

RESUMO

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.


Assuntos
Transplante de Coração/efeitos adversos , Neoplasias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha , Fatores de Tempo
11.
Am J Transplant ; 7(7): 1842-8, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17511763

RESUMO

The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation. MICA antibodies were detected by CDC test on recombinant cell lines and by the newly developed Luminex MICA antibody detection assay. Additionally, MICA expression was analyzed by 'real time' RT-PCR and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had HLA antibodies post-transplant. Nevertheless, MICA antibodies were found in a significant number of subjects. The prevalence of MICA antibodies was significantly higher among those with severe acute rejection (AR) than in those without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020 by Luminex). In most cases, the appearance of MICA antibodies post-transplant precedes AR. Following transplantation, MICA up-regulation correlated with histological evidence of severe rejection. Monitoring for MICA antibodies post-transplant may be useful to establish new risk factors for acute rejection.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Adulto , Linfócitos B/imunologia , Biópsia , Linhagem Celular , Feminino , Antígenos HLA/imunologia , Células HeLa , Transplante de Coração/patologia , Humanos , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Espanha
12.
Neurosci Lett ; 326(3): 163-6, 2002 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-12095647

RESUMO

Our aim was to study the involvement of 5-hydroxytryptamine (5-HT)(3) and 5-HT(4) receptors in two models of gastrointestinal transit (GIT) in mice: the 5-hydroxytryptophan (5-HTP)-induced diarrhea and intestinal inflammation produced by an irritant agent, croton oil (CO). 5-HTP (10 mg/kg) produced diarrhea that was significantly inhibited after pretreatment with ondansetron (5-HT(3) antagonist) or RS 39604 (5-HT(4) antagonist) (1-5 mg/kg). The GIT speed was increased after CO and 5-HTP administration. 5-HT(3-4) antagonists decreased GIT after 5-HTP-treatment but not after CO-treatment. Our results show that 5-HT(3) and 5-HT(4) receptors are involved in 5-HTP-induced diarrhea. This may be the reason why 5-HT(3-4) antagonists could be useful in the treatment of carcinoid syndrome diarrhea. 5-HT(3-4) antagonists were not effective in the modifications of GIT; nevertheless, they could be useful in the treatment of inflammatory bowel diseases because some symptoms as abdominal pain, discomfort or abnormal bowel function are modulated via 5-HT(3).


Assuntos
Diarreia/tratamento farmacológico , Trânsito Gastrointestinal/fisiologia , Intestinos/efeitos dos fármacos , Receptores de Serotonina/metabolismo , 5-Hidroxitriptofano/farmacologia , Animais , Antidiarreicos/farmacologia , Óleo de Cróton/farmacologia , Fármacos Dermatológicos/farmacologia , Diarreia/induzido quimicamente , Masculino , Camundongos , Morfina/farmacologia , Ondansetron/farmacologia , Receptores 5-HT3 de Serotonina , Receptores 5-HT4 de Serotonina , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia
13.
Claves odontol ; 7(45): 12-4, mayo-jun. 2001. ilus
Artigo em Espanhol | LILACS | ID: lil-289184

RESUMO

Es una alternativa al método convencional de aislamiento absoluto que se comenzó a utilizar hace aproximadamente 8 años. Técnica totalmente atraumática, fácil y económica. Consideraciones: el isobutil cianoacrilato permite suturar heridas de labio que involucren epidermis, mucosa y músculos. Es bicompatible, ayuda a la hemostasia, polimeriza en presencia de sangre, carece de toxicidad, tiene bajo costo y es de fácil aplicación. La utilización del producto sebre tejidos duros y blandos debe realizarse sobre campo seco y sin aplicar calor a la zona. Es irritante para la mucosa conjuntival. El Isobutil Cianoacrilato no necesita calor para su polimerización y lo hace en presencia de oxígeno, por el contrario, los isobutiles comunes requieren altas temperaturas para polimerizar. Requerimientos: Goma dique, porta goma, perforador de goma, aplicador Microbrush o similar, adhesivo instantáneo. Técnica: se selecciona el elemento a tratar y se comienza con la perforación de la goma siempre con el orificio de menor diámetro para que la goma entre a presión sobre la superficie a tratar. Se seca el campo y se aplica el adhesivo con el microbrush contactando el adhesivo en parte con la goma y en parte con el elemento dentario, de esta forma el adhesivo polimeriza produciendo una exotermia suave que funde el látex de la goma sobre el diente brindando aislamiento absoluto. Se retira luego la goma hacia el exterior de la cavidad bucal, y si existieran rastros de adhesivo los mismos se retiran con una cureta o explorador. En conclusión esta técnica permite realizar tratamientos en elementos dentarios permanentes que no se puedan aislar con la técnica convencional


Assuntos
Bucrilato/química , Diques de Borracha/normas , Dentição Permanente , Restauração Dentária Permanente/métodos , Restauração Dentária Permanente/normas , Dente Decíduo
14.
Bol. Asoc. Argent. Odontol. Niños ; 30(1): 16-8, mar. 2001. ilus
Artigo em Espanhol | LILACS | ID: lil-288814

RESUMO

Es una alternativa al método convencional de aislamiento absoluto que se comenzó a utilizar hace aproximadamente 8 años. Técnica totalmente atraumática, fácil y económica. Consideraciones: El Isobutil Cianoacrilato permite suturar heridas de labio que involucren epidermis, mucosa y músculos. Es biocompatible, ayuda a la hemostasia, polimeriza en presencia de sangre, carece de toxicidad, tiene bajo costo y es de fácil aplicación. La utilización del producto sobre tejidos duros y blandos debe realizarse sobre campo seco y sin aplicar calor a la zona. Es irritante para la mucosa conjuntival. El Isobutil Cianoacrilato no necesita calor para su polimerización y lo hace en presencia de oxígeno, por el contrario, los isobutiles comunes requieren altas temperaturas para polimerizar. Requerimientos: goma dique, porta goma, perforador de goma, aplicador Microbrush o similar, Adhesivo instantáneo. Técnica: Se selecciona el elemento a tratar y se comienza con la perforación de la goma siempre con el orificio de menor diámetro para que la goma entre a presión sobre la superficie a tratar. Se seca el campo y se aplica el adhesivo con el microbrush contactando el adhesivo en parte con la goma y en parte con el elemento dentario, de esta forma el adhesivo polimeriza produciendo una exotermia suave que funde el látex de la goma sobre el diente brindando aislamiento absoluto. Se retira luego la goma hacia el exterior de la cavidad bucal, y si existieran rastros de adhesivo los mismos se retiran con una cureta o explorador. En conclusión esta técnica permite realizar tratamientos en elementos dentarios permanentes que no se puedan aislar con la técnica convnecional


Assuntos
Restauração Dentária Permanente/normas , Diques de Borracha , Bucrilato/química , Cianoacrilatos/química , Cianoacrilatos/uso terapêutico , Dentição Permanente , Dente Decíduo
15.
Nefrologia ; 20(4): 383-6, 2000.
Artigo em Espanhol | MEDLINE | ID: mdl-11039266

RESUMO

Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared.


Assuntos
Insuficiência Renal/etiologia , Escleroderma Sistêmico/complicações , Pele/irrigação sanguínea , Vasculite/etiologia , Idoso , Anticorpos Anticitoplasma de Neutrófilos/análise , Feminino , Humanos , Peroxidase/imunologia , Insuficiência Renal/tratamento farmacológico , Transtornos Respiratórios/etiologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Vasculite/tratamento farmacológico
16.
J Immunol ; 163(3): 1382-9, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10415038

RESUMO

Nasal-associated lymphoid tissue (NALT), a mucosal inductive site for the upper respiratory tract, is important for the development of mucosal immunity locally and distally to intranasally introduced Ag. To more fully understand the induction of nasal mucosal immunity, we investigated the addressins that allow for lymphocyte trafficking to this tissue. To investigate the addressins responsible for naive lymphocyte binding, immunofluorescent and immunoperoxidase staining of frozen NALT sections were performed using anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1), anti-peripheral node addressin (PNAd), and anti-VCAM-1 mAbs. All NALT high endothelial venules (HEV) expressed PNAd, either associated with MAdCAM-1 or alone, whereas NALT follicular dendritic cells expressed both MAdCAM-1 and VCAM-1. These expression profiles were distinct from those of the gut mucosal inductive site, Peyer's patches (PP). The functionality of NALT HEV was determined using a Stamper-Woodruff ex vivo assay. The anti-L-selectin MEL-14 mAb blocked >90% of naive lymphocyte binding to NALT HEV, whereas the anti-MAdCAM-1 mAb, which blocks almost all naive lymphocyte binding to PP, minimally blocked binding to NALT HEV. NALT lymphocytes exhibited a unique L-selectin expression profile, differing from both PP and peripheral lymph nodes. Finally, NALT HEV were found in increased amounts in the B cell zones, unlike PP HEV. These results suggest that NALT is distinct from the intestinal PP, that initial naive lymphocyte binding to NALT HEV involves predominantly L-selectin and PNAd rather than alpha4beta7-MAdCAM-1 interactions, and that MAdCAM-1 and VCAM-1 expressed by NALT follicular dendritic cells may play an important role in lymphocyte recruitment and retention.


Assuntos
Antígenos de Superfície/fisiologia , Endotélio Linfático/imunologia , Imunoglobulinas/fisiologia , Linfonodos/imunologia , Mucoproteínas/fisiologia , Mucosa Nasal/imunologia , Receptores de Retorno de Linfócitos/fisiologia , Animais , Antígenos de Superfície/biossíntese , Antígenos de Superfície/metabolismo , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/fisiologia , Adesão Celular/imunologia , Moléculas de Adesão Celular , Movimento Celular/imunologia , Endotélio Linfático/citologia , Endotélio Linfático/metabolismo , Imunoglobulinas/biossíntese , Imunoglobulinas/metabolismo , Imunofenotipagem , Selectina L/biossíntese , Selectina L/metabolismo , Selectina L/fisiologia , Linfonodos/citologia , Linfonodos/metabolismo , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Mucoproteínas/biossíntese , Mucoproteínas/metabolismo , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/fisiologia
17.
J Immunol ; 160(9): 4465-72, 1998 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-9574552

RESUMO

The proposed usage of replication-deficient adenovirus (Ad) vectors for corrective gene therapy or for mucosal immunization has been limited in part by the host reactivity to the Ad vector, thus limiting repeated Ad instillations. We have recently shown that the reactivity to the Ad vector is in large part due to increased CD4+ Th1 and Th2 responses as well as elevated IgG and mucosal IgA responses. It has been recently proposed that the diminution of transgene expression in respiratory epithelia was due to increased CTL reactivity to expressed Ad proteins. Herein, we report that repeated intratracheal delivery of a second generation Ad2 vector into mice results in no detectable CTL activity in freshly isolated lymphoid cells from lungs, lower respiratory lymph nodes, or spleens or after in vitro restimulation. In contrast, a single dose of Ad2 vector did elicit a robust CTL response. This attenuation of CTL activity was long lived and was not affected by macrophage depletion or due to a reduction in CD4+ or CD8+ T cells. Examination of cytokine production via MHC class I or class II restimulation by lymphoid cells from three intratracheally treated mice showed an attenuation in the production of IFN-gamma by as much as 110-fold. This reduction in IFN-gamma could not be attributed to increased IL-4 or IL-10 production. Thus, this study shows that the CTL response to Ad vectors is attenuated upon repeated administration.


Assuntos
Adenoviridae , Citotoxicidade Imunológica , Terapia Genética/métodos , Vetores Genéticos , Interferon gama/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinação/métodos , Administração por Inalação , Animais , Imunidade nas Mucosas , Masculino , Camundongos , Camundongos Endogâmicos C57BL
18.
AIDS Res Hum Retroviruses ; 13(14): 1187-94, 1997 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-9310285

RESUMO

Previous studies from our group showed that a Salmonella-HIV vector vaccine that expressed recombinant HIV-1 envelope protein gp120 stably in the vector cytoplasm elicited type 1 helper T cell (Th1) responses to gp120. Despite the promise of such vaccines, a major limitation in their use was that multiple immunizations were required to elicit even small responses. For this reason, we sought a modified vector configuration that would induce more potent gp120-specific T cell responses exhibiting a broader spectrum of effector functions after a single inoculation. In this article we describe the construction and immunogenicity of a Salmonella-HIV vector that displays a truncated derivative of HIV-1(IIIB) envelope in the periplasm of the vector. A single oral dose of this Salmonella vector, called H683(pW58-asd+), generated a gp120-specific proliferation response in the spleen 14 days after immunization. In agreement with our previous findings, the gp120-specific splenic CD4+ T cells elicited by H683(pW58-asd+) displayed a Th1 phenotype; however, gp120-specific splenic CD4+ Th2 cells were also evident. In addition, this strain induced strong gp120-specific IgA antibody-secreting cell (ASC) responses in the intestinal lamina propria and mesenteric lymph nodes. As many as 2% of the total lamina propria and mesenteric lymph node IgA ASCs were found to be specific for gp120 28 days after a single oral dose of H683(pW57-asd+). Because the proliferative response following a single dose of H683(pW58-asd+) was comparable to that seen previously after three doses of an analogous construct expressing recombinant gp120 in the cytoplasm, these observations suggest that Salmonella-vectored secreted HIV-1 antigens elicit higher T cell responses than their cytoplasmically bound analogs.


Assuntos
Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV/genética , HIV/imunologia , Imunidade nas Mucosas/imunologia , Salmonella typhimurium/genética , Salmonella typhimurium/imunologia , Administração Oral , Animais , Linfócitos T CD4-Positivos/imunologia , Clonagem Molecular , Feminino , Imunização , Ativação Linfocitária/imunologia , Camundongos , Proteínas Recombinantes/imunologia , Baço/citologia , Baço/imunologia
19.
J Immunol ; 159(2): 685-93, 1997 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9218583

RESUMO

Replication-deficient adenovirus (Ad) vectors are effective to specifically target the respiratory epithelium for either corrective gene therapy such as cystic fibrosis or for mucosal immunization. As a consequence of transducing the lower respiratory tract with an E1/E3 deleted Ad5 vector, host responses have been characterized by the duration of transgene expression and by the induction of CTL responses. However, limited emphasis has been devoted to understanding the contribution of CD4+ T cell responses to the Ad vector. Both CD4+ and CD8+ T cells migrate into the lung following sequential intratracheal Ad5 transgene instillations. Isolated CD3+ T lymphocytes from the lungs were predominantly of the Th2 type, and after cell sorting, the IL-4-producing T cells were largely CD4+, while IFN-gamma expression was associated with both CD4+ and CD8+ T cells. Ab responses to the Ad5 vector and to the expressed transgene beta-galactosidase (beta gal) revealed elevated bronchial and serum IgA and IgG Abs with low neutralization titers. Analysis of serum IgG subclass responses showed IgG1 and IgG2b with lower IgG2a Abs to Ad5 and IgG2a and IgG2b Ab responses to beta gal. Ad5-specifc CD4+ T cells produced both Th1 (IFN-gamma and IL-2)- and Th2 (IL-4, IL-5, IL-6)-type cytokines, while beta gal-specific CD4+ T cells secreted IFN-gamma and IL-6. This study provides direct evidence for the concomitant induction of Th2- with Th1-type responses in both the pulmonary systemic and mucosal immune compartments to the Ad5 vector as well as a Th1-dominant response to the transgene.


Assuntos
Adenoviridae , Técnicas de Transferência de Genes , Vetores Genéticos/imunologia , Pulmão/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Terapia Genética , Imunidade Celular , Pulmão/patologia , Pneumopatias/imunologia , Pneumopatias/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Rev Esp Cardiol ; 49(6): 432-8, 1996 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-8753908

RESUMO

BACKGROUND: Coronary stents have proved their efficacy in bail-out situations and restenosis. Nevertheless, the high incidence of subacute thrombosis and vascular and bleeding complications limits its use. OBJECTIVES: To evaluate the clinical complications during the first month of three different types of stents, implanted with high pressure, without ultrasound guidance or anticoagulation. PATIENTS AND METHODS: All stents were implanted in arteries of 3 mm or more. After implantation, all stents were dilated between 15-17 atmospheres, aiming to a residual stenosis lower than 10%. After implantation, all patients received aspirin indefinitely and ticlopidine 250 mg twice daily for one month. The initial success, the ischemic complications (death, myocardial infarction and emergency surgery), acute and subacute thrombosis and vascular and hemorrhagic complications were evaluated. The evaluation was done following the procedure, prior to discharge from the hospital and at 1 month follow-up. RESULTS: In 49 patients, 51 stents were implanted. 70% had unstable angina. In one case the stent was implanted after primary PTCA. In 17.6%, the stent was implanted in a bail-out situation. Of the 51 stents, 32 were Palmaz-Schatz, 12 Wiktor and 7 Gianturco-Roubin. The initial success was 100%. There were no deaths, AMI, nor emergency surgeries in the first month. There was no case of acute or subacute thrombosis. There were 2 minor complications; one vascular: a pseudoaneurysm, and another hemorrhagic: an inguinal hematoma. Neither case needed surgery nor blood transfusion. All patients were discharged within 48 hours. CONCLUSION: Implantation of stents with high pressures, in spite of not using guidance ultrasound nor anticoagulation, is safe and effective, with a clear decrease in vascular complications, and without an increase in the incidence of acute or subacute thrombosis.


Assuntos
Doença das Coronárias/terapia , Complicações Pós-Operatórias/epidemiologia , Stents/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Fatores de Tempo
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