RESUMEN
The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis.
Asunto(s)
Hialuronoglucosaminidasa/administración & dosificación , Linfangiogénesis/efectos de los fármacos , Vasos Linfáticos/efectos de los fármacos , Linfedema/tratamiento farmacológico , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Glicoproteínas/agonistas , Glicoproteínas/genética , Glicoproteínas/metabolismo , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Inyecciones Intralesiones , Linfangiogénesis/genética , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patología , Linfedema/genética , Linfedema/metabolismo , Linfedema/patología , Glicoproteínas de Membrana/agonistas , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Ratones , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Cola (estructura animal) , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/agonistas , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
This study presents an unusual case of primary lymphedema of the upper extremity in a healthy 28-year-old woman. The onset of swelling of the left upper extremity was observed at birth, but was not accurately diagnosed until the patient visited our department. Diagnostic assessment included evaluating the patient's history and laboratory and radiological data, which were all normal except for the swollen upper extremity and the lymphoscintigraphy findings. The patient was diagnosed as suffering from primary lymphedema of her left arm. Complete decongestive therapy was done and her swelling mildly improved.
Asunto(s)
Linfedema/congénito , Adulto , Brazo , Diagnóstico Diferencial , Femenino , Humanos , Linfedema/diagnóstico , Linfedema/rehabilitación , Modalidades de Fisioterapia , Tomografía Computarizada por Rayos XRESUMEN
Progression to cancer in Barrett's esophageal columnar metaplasia is classically heralded by the presence of epithelial dysplasia. Differentiation of reactive epithelial atypia and mild dysplasia from severe dysplasia, however, may often be difficult especially with limited biopsy material. We performed DNA content analysis of 11 cases of Barrett's esophagus showing variable reactive atypia, 24 cases of Barrett's with low- and high-grade dysplasia, and 30 cases of Barrett's with invasive adenocarcinoma (BCA) using Feulgen-stained paraffin sections and the CAS 200 image analyzer. The mean DNA index of the uniformly diploid BE was 1.06. The 1.26 mean DNA index for the low-grade Barrett's esophagus with dysplasia, 1.62 for high grade, and 1.88 DI for BCA were significantly greater than for variable reactive atypia (P < 0.004) but not different from each other. Six BCA cases (20%) were diploid; 24 cases (80%) were aneuploid. Mean survival of diploid BCA at 20.4 mo was nearly double the survival of 10.6 mo for aneuploid BCA. However, this difference was not statistically significant (P < 0.21) and survival at 3 yr was identical for all BCA cases. Tumor grade, stage, and lymph node status did not significantly correlate with ploidy pattern. Thus, although DNA analysis does not seem to predict ultimate outcome in BCA, aneuploidy and high DNA index are associated with Barrett's esophagus with dysplasia and BCA and may be of significant value in the differentiation from variable reactive atypia in small biopsies.