RESUMEN
In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.
Asunto(s)
Conjuntivitis , Preparaciones Farmacéuticas , Niño , Conjuntivitis/tratamiento farmacológico , Conjuntivitis/epidemiología , Hospitales Universitarios , Humanos , Plasminógeno/deficiencia , Enfermedades Cutáneas GenéticasRESUMEN
Our laboratory has previously shown that apelin is mitogenic for endothelial cells. We have postulated that apelin represents an angiogenic factor secreted by tumour cells in order to promote the formation of new vessels necessary for tumour growth. We first demonstrate that apelin and its receptor are not expressed by the mouse TS/A mammary carcinoma cells. We therefore established clones of this tumoral cell type stably overexpressing the apelin cDNA (TS/A-apelin clones). Comparison of the in vitro proliferation rates between TS/A-mock and TS/A-apelin cells did not reveal any difference and confirmed the lack of receptor expression by tumour cells. On the other hand, apelin overexpression clearly increased the in vivo tumour growth and this increase was associated with an earlier onset of tumour development. In tumours derived from TS/A-apelin clones, the expression of the endothelial marker CD31 was increased and revealed the formation of large intratumoral vessels lined with CD31 positive cells. These data suggest that apelin behaves as a potent activator of tumour neoangiogenesis by a paracrine effect on host vessels. The pathological relevance of this finding is demonstrated by hypoxia-induced upregulation of apelin gene and its overexpression in one-third of human tumours.
