RESUMEN
Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours.
Asunto(s)
Neoplasias/patología , Factor A de Crecimiento Endotelial Vascular/farmacología , Empalme Alternativo , Animales , Carcinoma de Células Renales/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Células Endoteliales/efectos de los fármacos , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias/irrigación sanguínea , Neovascularización Patológica , Próstata/citología , Próstata/efectos de los fármacos , Neoplasias de la Próstata/patología , Isoformas de Proteínas , Sarcoma de Ewing/patología , Transfección , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
The objective of the audit was to examine the increased morbidity associated with elective tonsillectomy with single-use instruments in a district general hospital in England. Retrospective audit of consecutive case notes of 145 patients who underwent tonsillectomy in a 6-week period after the introduction of single-use instruments was carried out. The main outcome measure was incidence of secondary haemorrhage. In total, 9.5% of patients required re-admission indicated by secondary haemorrhage, 4% required emergency surgery and 43% of the total group had haemostasis achieved with ties. None of these was re-admitted. Out of the total group, 57% had haemostasis achieved with single-use bipolar forceps; 16.8% of these patients were re-admitted, with 7% of this group requiring emergency surgery to control the haemorrhage. Animal tissue experiments and design analysis of the single-use bipolar diathermy highlighted the deficiencies of the initial single-use bipolar diathermy. This was replaced by a new design of single-use diathermy forceps. A second audit was performed which revealed a significant reduction in postoperative morbidity. Complications associated with the introduction of new instruments can be identified by repeated audit cycles.
Asunto(s)
Equipos Desechables , Hemorragia/etiología , Auditoría Médica , Tonsilectomía/instrumentación , Animales , Electrocoagulación/efectos adversos , Electrocoagulación/instrumentación , Diseño de Equipo , Hemorragia/epidemiología , Técnicas Hemostáticas , Morbilidad , Estudios Retrospectivos , Tonsilectomía/efectos adversosRESUMEN
The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reaction are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37 degrees C and 22 degrees C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37 degrees C and 22 degrees C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37 degrees C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37 degrees C.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Colinesterasas/sangre , Insecticidas/farmacología , Compuestos Organofosforados , Compuestos Organotiofosforados , Activación Enzimática , Humanos , Técnicas In Vitro , Factores de TiempoRESUMEN
Psoriasis remains a disease of unknown aetiology. It is common, has a chronic course with exacerbations and remissions, and may present at any age. There are a number of clinical types recognized and an association with arthritis has been noted. Treatment is directed at control of the disease to enable the person to live and cope with his disease state. This can often be achieved with topical therapy, but it may at times require hospitalization. More severe forms of psoriasis may require potentially dangerous medication.