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1.
Front Hum Neurosci ; 10: 437, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27630553

RESUMO

Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one's own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged faces, led to more positive evaluations of competence. The results are discussed within the context of an age-related decline in the differentiation of faces in memory. Our findings have important implications for a better understanding of age-related perceptual factors and cognitive determinants of social interactions with unfamiliar others across the adult lifespan.

2.
PLoS One ; 11(1): e0146084, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26726800

RESUMO

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.


Assuntos
Potenciais Evocados Visuais , Esclerose Múltipla/fisiopatologia , Nervo Óptico/fisiopatologia , Adulto , Estudos Transversais , Progressão da Doença , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Neurite Óptica/etiologia , Neurite Óptica/fisiopatologia , Tempo de Reação , Análise Espectral/métodos
3.
Int Endod J ; 49(10): 915-25, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26356580

RESUMO

AIM: To compare 2D with 3D radiography in assessing the treatment outcome 1 year after periapical surgery. METHODOLOGY: In this prospective study, periapical radiographs (PA) and cone beam computed tomography (CBCT) were performed 1 year after periapical surgery. Three calibrated observers independently evaluated the radiographs for the presence and type of periapical radiolucencies. Ratings in PA were compared to those in bucco-lingual and mesio-distal CBCT images (coronal and sagittal planes), and the ratings of the latter two were also compared between each other. Further, maximum size diameters of radiolucencies were measured on CBCT scans, and the calculated means were correlated with the types of radiolucency. Statistical analysis was completed using Friedman rank sum tests, the Wilcoxon signed rank test and the Pearson correlation coefficient. RESULTS: A total of 61 roots in 54 patients were eligible for the final assessment. On average, the intra-observer ratings were identical in 59.6% when comparing PA and CBCT (kappa 0.112 to 0.192). A very high intra-observer agreement (93.4%) was noted when comparing bucco-lingual and mesio-distal CBCT ratings (kappa 0.797 to 1). Interobserver agreement was higher for PA (68.8%) than for CBCT (bucco-lingual 45.9%, mesio-distal 47.5%), but without reaching significant differences. The calculated mean size of persistent radiolucencies in CBCT scans correlated well with the assigned types of radiolucency. CONCLUSION: CBCT images showed in nearly a third of the evaluated cases a worse situation than PA. There is a need to define criteria to assess the 'radiographic healing' in CBCT following periapical surgery.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Periodontite Periapical/cirurgia , Tecido Periapical/diagnóstico por imagem , Radiografia Dentária Digital/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tecido Periapical/fisiologia , Tecido Periapical/cirurgia , Cicatrização
4.
Respir Res ; 12: 56, 2011 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-21521503

RESUMO

BACKGROUND: Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs. METHODS: A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors. RESULTS: Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R=0.610-0.671 and p<0.05) and of obliteration of the bronchial lumen (R=0.698 and p<0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (p<0.05), or bronchial wall (p<0.05). CONCLUSIONS: In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.


Assuntos
Brônquios/transplante , Bronquiolite Obliterante/imunologia , Movimento Celular , Rejeição de Enxerto/imunologia , Transplante de Pulmão/imunologia , Mucosa Respiratória/transplante , Quimeras de Transplante , Animais , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Brônquios/patologia , Bronquiolite Obliterante/genética , Bronquiolite Obliterante/patologia , Bronquiolite Obliterante/prevenção & controle , Modelos Animais de Doenças , Feminino , Marcadores Genéticos , Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Hibridização in Situ Fluorescente , Masculino , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Coloração e Rotulagem , Sus scrofa , Fatores de Tempo , Tolerância ao Transplante , Transplante Homólogo , Cromossomo Y
5.
Br Poult Sci ; 51(3): 326-34, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20680867

RESUMO

1. Ammonia (NH(3)) is an important gaseous pollutant generated from manure in commercial poultry farms and has been an environmental, ecological, and health concern. Poultry manure also releases carbon dioxide (CO(2)), which is a greenhouse gas and is often used as a tracer gas to calculate building ventilation. 2. A 38-d laboratory study was conducted to evaluate the characteristics of NH(3) and CO(2) releases from layer hen manure using 4 manure reactors (122 cm tall, 38 cm internal diameter), which were initially filled with 66 cm deep manure followed by weekly additions of 5 cm to simulate manure accumulation in commercial layer houses. 3. The average daily mean (ADM) NH(3) and CO(2) release fluxes for the 4 reactors during the entire study were 1615 +/- 211 microg/s.m(2) (ADM +/- 95% confidence interval) and 100 +/- 03 mg/s.m(2), respectively. The daily mean NH(3) and CO(2) releases in individual reactors varied from 352 to 6791 microg/s.m(2) and from 66 to 205 mg/s.m(2), respectively. 4. The ADM NH(3) release flux was within the range of those obtained in 4 high-rise layer houses by Liang et al. (2005, Transactions of the ASAE, 48). However, the CO(2) release flux in this study was about 10 to 13 times as high as the data reported by Liang et al. (2005). Fresh manure had greater NH(3) release potential than the manure in the reactors under continuous ventilation. Manure with higher contents of moisture, total nitrogen, and ammonium in the 4th weekly addition induced 11 times higher NH(3) and 75% higher CO(2) releases immediately after manure addition compared with pre-addition releases.


Assuntos
Poluentes Atmosféricos/análise , Amônia/análise , Dióxido de Carbono/análise , Galinhas , Esterco , Animais , Concentração de Íons de Hidrogênio , Nitrogênio/análise , Compostos de Amônio Quaternário/análise , Ventilação
6.
Mediators Inflamm ; 2009: 510254, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19503785

RESUMO

The local immunoreactivity of C-reactive protein (CRP) was studied in a heterotopic porcine model of posttranplant obliterative bronchiolitis (OB). Bronchial allografts and control autografts were examined serially 2-28 days after subcutaneous transplantation. The autografts stayed patent. In the allografts, proliferation of inflammatory cells (P < .0001) and fibroblasts (P = .02) resulted in occlusion of the bronchial lumens (P < .01). Influx of CD4+ (P < .001) and CD8+ (P < .0001) cells demonstrated allograft immune response. CRP positivity simultaneously increased in the bronchial walls (P < .01), in macrophages, myofibroblasts, and endothelial cells. Local CRP was predictive of features characteristic of OB (R = 0.456-0.879, P < .05-P < .0001). Early obliterative lesions also showed CRP positivity, but not mature, collagen-rich obliterative plugs (P < .05). During OB development, CRP is localized in inflammatory cells, myofibroblasts and endothelial cells probably as a part of the local inflammatory response.


Assuntos
Brônquios/imunologia , Brônquios/transplante , Bronquiolite Obliterante/imunologia , Bronquiolite Obliterante/metabolismo , Proteína C-Reativa/metabolismo , Regulação da Expressão Gênica , Animais , Brônquios/patologia , Bronquiolite Obliterante/patologia , Regulação da Expressão Gênica/imunologia , Imuno-Histoquímica , Suínos , Transplante Autólogo , Transplante Homólogo/efeitos adversos
7.
J Heart Lung Transplant ; 27(4): 400-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18374876

RESUMO

BACKGROUND: Epithelial cell injury, inflammation, fibrosis and airway obliteration result in remodeling of terminal bronchi in post-transplant obliterative bronchiolitis. Tenascin as an extracellular matrix glycoprotein is expressed in several remodeling processes. METHODS: Heterotopic bronchial allografts of pigs were studied to assess tenascin expression during development of post-transplant obliterative bronchiolitis. A total of 157 allografts or autograft controls were serially obtained 2 to 28 days after transplantation and processed for histology and immunocytochemistry for tenascin, CD4, CD8 and macrophages. Epithelial tenascin index was calculated by multiplying the percentage of positive cells by the grade of tenascin intensity (1 to 3). RESULTS: Epithelial tenascin expression occurred during the initial ischemic damage to the respiratory epithelium. After partial recovery and before total epithelial loss and subsequent airway obliteration, tenascin expression peaked in allografts (p < 0.001). Epithelial tenascin index on Day 7 was predictive of subsequent epithelial damage, bronchial wall inflammation and the number of (CD4(+) and CD8(+)) cells, fibroproliferation, and obliteration of the bronchial lumen (R > or = 0.47, p < or = 0.01). Tenascin expression in the bronchial wall was more intense in allografts (p < 0.001), paralleling proliferation of fibroblasts and influx of inflammatory cells, and was predictive of inflammatory alterations also in the early obliterative lesions (R > or = 0.45, p < 0.05). Expression decreased during maturation of fibrosis (p < 0.05). CONCLUSIONS: Epithelial tenascin was predictive of features observed in post-transplant obliterative bronchiolitis, demonstrating a role for tenascin in the development of obliterative bronchiolitis. Tenascin may have relevant properties in serving as a clinical marker for early obliterative bronchiolitis.


Assuntos
Brônquios/metabolismo , Brônquios/transplante , Bronquiolite Obliterante/etiologia , Complicações Pós-Operatórias , Mucosa Respiratória/metabolismo , Tenascina/metabolismo , Animais , Brônquios/patologia , Bronquiolite Obliterante/patologia , Bronquite/etiologia , Bronquite/patologia , Proliferação de Células , Fibroblastos/patologia , Fibrose , Imuno-Histoquímica , Transplante de Órgãos/efeitos adversos , Período Pós-Operatório , Valor Preditivo dos Testes , Mucosa Respiratória/patologia , Suínos , Fatores de Tempo , Transplante Homólogo
8.
Exp Lung Res ; 33(6): 303-20, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17694440

RESUMO

The expression of platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, and connective tissue growth factor (CTGF) and the effect of imatinib, an agent inhibiting PDGF receptors, were assessed in a porcine bronchial transplantation model of obliterative bronchiolitis (OB). Up-regulation of PDGF-A, PDGF receptors alpha and beta, and TGF-beta expression occurred in allografts, whereas PDGF-B and CTGF expression was similar in allo- and autografts. Imatinib modified the inflammatory responses and expression patterns of PDGF-A and PDGF receptors. This study further confirms PDGF and TGF-beta as mediators of OB and supports the concept of the importance of the pathways signaled through PDGF receptors in post-transplant OB.


Assuntos
Brônquios/metabolismo , Bronquiolite Obliterante/metabolismo , Rejeição de Enxerto/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Benzamidas , Brônquios/efeitos dos fármacos , Brônquios/patologia , Brônquios/transplante , Bronquiolite Obliterante/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Fator de Crescimento do Tecido Conjuntivo , Modelos Animais de Doenças , Rejeição de Enxerto/patologia , Mesilato de Imatinib , Imuno-Histoquímica , Macrófagos/patologia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Sus scrofa , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo
9.
Int Endod J ; 39(10): 800-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16948666

RESUMO

AIM: To evaluate the haemostatic efficacy and the histologic tissue responses after the application of different haemostatic agents used in periradicular surgery. METHODOLOGY: The study was conducted in the calvarium of six rabbits. Standardized bone defects (diameter 4 mm) were trephined, and different haemostatic agents were applied and compared with control defects: bone wax (left for 10 min), Stasis (ferric sulphate, left for 5 s), Expasyl (aluminium chloride, left for 2 min and left permanently in situ), and a combination of Expasyl (2 min) and Stasis (5 s). The sites were photographed before the application and after the removal of the haemostatic agents. Three independent examiners judged the initial and final bleeding (on the photographs) using a bleeding score for each site and treatment. The results were compared using Wilcoxon's signed rank test. For the histologic analysis, three animals were killed after 3 weeks and three animals after 12 weeks. Transverse, nondecalcified sections were stained with combined basic fuchsin and toluidine blue for descriptive histology. RESULTS: The most efficient haemorrhage control was provided by Expasyl in combination with Stasis and by Expasyl alone, whereas bone wax had the weakest bleeding reduction effect. The histologic analysis after 3 weeks demonstrated an inflammatory and foreign body tissue response towards all haemostatic agents. At 12 weeks, this tissue response was less pronounced but still present in sites treated with bone wax or Expasyl. In general, the inflammatory tissue reactions were limited to the bone defects, and never extended into the surrounding tissues. CONCLUSIONS: Expasyl alone or in combination with Stasis appeared to be the most efficient of tested agents to control the bleeding within the bony defects created in a rabbit calvarium model.


Assuntos
Hemostáticos/uso terapêutico , Tecido Periapical/cirurgia , Cloreto de Alumínio , Compostos de Alumínio/efeitos adversos , Compostos de Alumínio/uso terapêutico , Animais , Cloretos/efeitos adversos , Cloretos/uso terapêutico , Combinação de Medicamentos , Compostos Férricos/efeitos adversos , Compostos Férricos/uso terapêutico , Reação a Corpo Estranho/etiologia , Hemostáticos/efeitos adversos , Palmitatos/efeitos adversos , Palmitatos/uso terapêutico , Coelhos , Crânio/cirurgia , Estatísticas não Paramétricas , Ceras/efeitos adversos , Ceras/uso terapêutico
10.
Transpl Int ; 18(9): 1100-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16101731

RESUMO

We developed our porcine model to elucidate the cellular rejection mechanisms of xenografts. Bronchial segments from a donor lamb were implanted into domestic pigs. The immunosuppressive regimens consisted of no immusuppression, or of daily oral cyclosporine A (CsA) 15 mg/kg, or of everolimus, 1.5 mg/kg, or of both. Implants were serially harvested during 17 days. Epithelial damage and obliteration were graded histologically, followed by a count of CD4+, CD8+, MHC class II-expressing cells, and macrophages. Furthermore, we studied the pharmocokinetics of everolismus. Epithelial damage preceded luminal obliteration, which was eventually total, except when both drugs had been given. In xenografts, an influx of cells with CD8+ cells dominating peaked on day 9, thereafter declining, except in the combination drug group. There, the immunological reaction was delayed and blunted, with CD4+ cells dominating. More macrophages appeared in xenografts than in allografts except with the combination CsA and everolimus. A dose of 1.5 mg/kg everolimus yields adequate blood concentrations for porcine studies. In this xenograft model, chronic rejection appears to be caused by an immune response to the graft, but it is more short-lived than the response in allografts. The combination of CsA and everolimus was able to blunt the response and delay the subsequent obliteration.


Assuntos
Brônquios/transplante , Transplante Heterólogo/imunologia , Animais , Brônquios/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ciclosporina/uso terapêutico , Everolimo , Rejeição de Enxerto , Antígenos de Histocompatibilidade Classe II/análise , Imuno-Histoquímica , Ovinos , Sirolimo/análogos & derivados , Sirolimo/farmacocinética , Sirolimo/uso terapêutico , Suínos , Transplante Homólogo
11.
J Heart Lung Transplant ; 24(4): 426-32, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15797744

RESUMO

BACKGROUND: Epithelial cell injury, inflammation, fibrosis, and airway obliteration are associated in post-transplant obliterative bronchiolitis. Fibrosis is a consequence of fibroblastic activity and of collagen deposition after disturbances in the balance of protein formation and degradation. Proteolytic enzymes such as the matrix metalloproteinases mediate degradation. To assess matrix metalloproteinases during obliterative bronchiolitis development, we studied porcine, heterotopic bronchial allografts. METHODS: A total of 119 allografts or autografts were harvested serially at 3 to 60 days after transplantation and processed for histology and in situ hybridization for matrix metalloproteinases 2 and 9. Immunocytochemistry for vimentin and alpha-smooth-muscle-cell actin was performed with specific antibodies. RESULTS: Implants had initial ischemic injury to airway epithelium and to the bronchial wall. Recovery was rapid in autografts and in immunosuppressed allografts. In matrix metalloproteinase-2 mRNA activity in fibroblasts, correlation with endothelial expression and expression in macrophages occurred during intense fibroproliferation. We observed intense matrix metalloproteinase-9 positivity during onset of inflammation and fibroproliferation in endothelial cells (p < 0.01), fibroblasts (p < 0.05), macrophages (p < 0.05), and lymphocytes (p < 0.05). Matrix metalloproteinase-9 mRNA activity in fibroblasts correlated with that in endothelial and inflammatory cells and also proved predictive of early obliteration. CONCLUSIONS: Matrix metalloproteinase-2, and especially matrix metalloproteinase-9, gene activity was associated with onset of inflammation and fibroblastic proliferation in allografts, predicting early obliteration. Although this may be the case in the model described, its role in human-allograft post-transplant obliterative bronchiolitis requires further supportive data.


Assuntos
Bronquiolite Obliterante/enzimologia , Transplante de Pulmão/efeitos adversos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Animais , Biomarcadores/metabolismo , Brônquios/enzimologia , Brônquios/patologia , Brônquios/transplante , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/patologia , Proliferação de Células , Modelos Animais de Doenças , Fibroblastos/enzimologia , Fibroblastos/patologia , Imuno-Histoquímica , Hibridização In Situ , Transplante de Pulmão/patologia , Linfócitos/enzimologia , Linfócitos/patologia , Macrófagos/enzimologia , Macrófagos/patologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mucosa Respiratória/enzimologia , Mucosa Respiratória/patologia , Suínos
12.
J Pathol ; 204(3): 340-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15476277

RESUMO

Epithelial cell injury, inflammation, progressive fibrosis, and airway obliteration are histological features of post-transplant obliterative bronchiolitis (OB). Cyclooxygenase (COX)-2 is expressed in acute and chronic inflammatory responses. Our aim was to elucidate the possible role of COX-2 in post-transplant OB by using a heterotopic bronchial porcine model. Bronchial allografts from non-related donors were transplanted subcutaneously into 24 random-bred domestic pigs, each weighing about 20 kg. Groups studied had grafts, non-treated allografts, allografts given cyclosporine A (CsA), methylprednisolone (MP), and azathioprine (Aza), and allografts given CsA, MP, and everolimus. Grafts were serially harvested during a follow-up period of 21 days for histology (H&E) and immunohistochemistry. Immunostaining was performed with monoclonal IgG against human COX-2 peptide, and histological alterations and immunohistochemical positivity were graded on a scale from 0 to 5. Epithelial COX-2 index was calculated by multiplying the percentage of positive cells by grade of epithelial COX-2 intensity. Ischaemic epithelial loss, evident in all implants, recovered rapidly in autografts, and bronchi remained patent. Epithelial loss in non-treated allografts preceded fibroblast proliferation, resulting in total luminal obliteration. In CsA-, MP-, and Aza-treated allografts epithelial destruction and luminal obliteration were delayed, and these were prevented in CsA-, MP-, and everolimus-treated allografts. COX-2 expression due to operative ischaemia was evident in all implants on day 2. Thereafter, the epithelial COX-2 index preceded epithelial injury and obliteration. During the inflammatory response and fibroblast proliferation, COX-2 expression occurred in macrophages and fibroblasts. In conclusion, in the early stage of OB development, COX-2 induction occurred in airway epithelial cells prior to luminal obliteration. In addition, the observation that COX-2 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation indicates a role in OB development, but the causal relationships need further study.


Assuntos
Brônquios/transplante , Bronquiolite Obliterante/enzimologia , Isoenzimas/análise , Prostaglandina-Endoperóxido Sintases/análise , Sirolimo/análogos & derivados , Animais , Azatioprina/uso terapêutico , Brônquios/patologia , Bronquiolite Obliterante/patologia , Condrócitos/enzimologia , Condrócitos/patologia , Ciclo-Oxigenase 2 , Ciclosporina/uso terapêutico , Modelos Animais de Doenças , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Everolimo , Fibroblastos/enzimologia , Fibroblastos/patologia , Fibrose/enzimologia , Fibrose/patologia , Imuno-Histoquímica/métodos , Imunossupressores/uso terapêutico , Macrófagos/enzimologia , Macrófagos/patologia , Metilprednisolona/uso terapêutico , Período Pós-Operatório , Sirolimo/uso terapêutico , Suínos
13.
J Heart Lung Transplant ; 22(9): 1014-22, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12957611

RESUMO

BACKGROUND: Epithelial damage is an important feature in the pathogenesis of obliterative airway disease. We investigated the extent of epithelial apoptosis in this process in pig bronchial allografts. METHODS: The bronchial grafts (total, n = 200) were placed subcutaneously into recipients. Three allograft groups were formed: the first group had no immunosuppression therapy; the second received triple therapy with 10 mg/kg/day cyclosporine, 2 mg/kg/day azathioprine, and 20 mg/day methylprednisolone; and the third was given triple therapy in which azathioprine was replaced with 1.5 mg/kg/day everolimus (40-O-[2-hydroxyethyl]-rapamycin). The fourth group, which had allograft and autograft implants, received only 1.5 mg/kg/day everolimus. The implants were serially removed during 3 months of follow-up. We evaluated graft histology and analyzed the apoptotic index percentage (apoptotic cells / total number of cells) of the bronchial epithelium using in situ 3'-end labeling of apoptotic DNA. RESULTS: Epithelial destruction and subsequent obliteration of the bronchial lumen were complete by Day 28 in non-treated allografts and in most allografts with inadequate immunosuppression to prevent these changes (those treated with cyclosporine, azathioprine, and methylprednisolone and those treated with everolimus only). The apoptotic indexes of the epithelium were high (>1% of the cells were apoptotic) and increased with concomitant epithelial destruction. In allografts with adequate immunosuppression to prevent epithelial destruction (those treated with cyclosporine, everolimus, and methylprednisolone) and in autografts, after initial damage, well-pre-served epithelium was maintained with low apoptotic indexes (<1% of the cells apoptotic). CONCLUSIONS: Apoptotic activity increased with progressing epithelial damage preceding bronchial obliteration. Our results give further evidence that apoptotic death of epithelial cells is an important mechanism in events that lead to graft deterioration in obliterative bronchiolitis after lung transplantation.


Assuntos
Apoptose , Bronquiolite Obliterante/etiologia , Transplante de Pulmão/patologia , Mucosa Respiratória/patologia , Animais , Bronquiolite Obliterante/patologia , Modelos Animais , Suínos , Transplante Autólogo , Transplante Homólogo
14.
Transplantation ; 76(3): 516-23, 2003 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-12923437

RESUMO

BACKGROUND: In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-alpha is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-alpha in the development of OB in our heterotopic porcine bronchial transplantation model. METHODS: Three groups were formed: autografts, nontreated allografts, and allografts treated with preoperative anti-TNF-alpha monoclonal antibody (infliximab) infusion. The implants were harvested on days 2, 4, 7, 11, 14, 21, and 28 for histologic and immunohistochemical analysis. RESULTS: TNF-alpha inhibition reduced inflammation, rate of epithelial loss, fibrosis, and obliteration early in the development of OB. In the epithelium, the numbers of TNF-alpha-positive epithelial and inflammatory cells and macrophages were significantly lower in treated than in nontreated allografts on day 4; furthermore, in the epithelium and in the bronchial wall, invasion of CD8+ lymphocytes was significantly decreased during the first week. CONCLUSIONS: These results indicate that TNF-alpha promotes the development of OB, and inhibition of TNF-alpha may prove beneficial in a clinical setting.


Assuntos
Brônquios/transplante , Bronquiolite Obliterante/patologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Brônquios/patologia , Linfócitos T CD8-Positivos/patologia , Imuno-Histoquímica , Inflamação/patologia , Infliximab , Complicações Pós-Operatórias/patologia , Suínos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
15.
Int Endod J ; 36(7): 476-82, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12823703

RESUMO

AIM: This paper describes the initial experiences following the introduction of a rotary engine-driven preparation technique into the undergraduate endodontic programme at the Zurich University Dental Centre. METHODS: Forty third-year students practised the ProFile.04 (PF.04) technique between January and July 2001 in a preclinical course. Between November 2001 and February 2002, 20 of these students (Group A) root-treated 51 teeth in their clinical course using either PF.04, the balanced force technique (BFT) or a combination of both. The second group of 20 students (Group B) similarly treated another 36 randomly selected teeth between April and July 2002. Types of teeth treated by the students and the canal preparation techniques were recorded. The students also completed a short questionnaire, evaluating their opinions of the new course. RESULTS: Of the 87 teeth endodontically treated during the clinical course, 34, 14 and 39 were shaped using PF.04 alone, a combination of PF.04 and BFT and BFT alone, respectively. No rotary instruments were fractured during the 1-year clinical course, although some instruments were fractured during the preclinical laboratory course. Overall, the students rated the rotary technique as positive. CONCLUSION: A rotary technique was successfully introduced into an undergraduate endodontic programme (this will be continued in the foreseeable future). However, the continuity between the preclinical and the clinical courses was poor as a result of the constraints of the general teaching programme.


Assuntos
Educação em Odontologia , Endodontia/educação , Preparo de Canal Radicular/métodos , Ensino/métodos , Competência Clínica , Humanos , Irrigantes do Canal Radicular/uso terapêutico , Obturação do Canal Radicular/métodos , Preparo de Canal Radicular/instrumentação , Suíça
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