Troubleshooting the rabbit ferric chloride-induced arterial model of thrombosis to assess in vivo efficacy of antithrombotic drugs.

INTRODUCTION: The FeCl3-induced arterial model of thrombosis is one of the most widely used animal models to assess arterial efficacy of new antithrombotic drug candidates. This model is well-established in rodents but in a less extent in the rabbit. In this work, we present a methodology for a rabbit FeCl3-induced arterial model of thrombosis derived from our troubleshooting which allows the generation of reliable efficacy data for new antithrombotic drug candidates. METHODS: Rabbits were administered with heparin 4.5U/kg/min, argatroban 10µg/kg/min or saline by intravenous infusion. The blood flow was monitored using a Doppler flow probe. The time from the application of FeCl3 to the recorded zero blood flow was defined as the time to occlusion, with a maximum recording time of 60min post-FeCl3 application. After 30min of infusion, thrombosis was induced by wrapping a FeCl3-saturated filter paper around the carotid artery caudal to the flow probe. Animals were subject to exclusion criteria based on the visual aspect of the artery FeCl3-induced injury and based on changes in blood flow upon FeCl3 application. RESULTS: Following the application of FeCl3, a mean time to occlusion for saline, heparin and argatroban of 24.3±1.8, 52.5±4.8 and 53.5±4.5min was obtained, respectively. Mean time to occlusion for heparin and argatroban administered groups was significantly different when compared to the saline-treated group (p<0.05). These results for the test compounds represent approximately 80% of the maximum possible prolongation. DISCUSSION: The rabbit FeCl3-induced arterial model of thrombosis presented in this paper derived from our troubleshooting is sensitive and reproducible for the generation of accurate and reliable efficacy data in the assessment of new antithrombotic agents in preclinical drug development.

[Prolactinoma and pregnancy. Six cases and review of the literature]. / Prolactinome et grossesse. Mise au point à propos de 6 observations.

Prolactinoma is the most frequent of secreting pituitary adenomas. It is often discovered among women of childbearing-age presenting an association of amenorrhea and galactorrhea. Data in the literature from large series indicate the current risks of interaction between prolactinoma and pregnancy. Risks have been overestimated in the past and it is now recognized that pregnancy can be allowed providing strict follow-up is assured. Dopaminergic drugs have no teratogenic side-effects and are known to allow tumoral control and recovery of fertility in the majority of cases. The use of these medications explains the reduction of indications for surgery. Microprolactinomas are highly influenced by pregnancy and can even lead to tumor retrogression. Macroprolactinomas give complications more often, and require a good tumor control and a rigorous follow-up.

[Modification of hemorheological parameters in microvascular complications of diabetes]. / Modification des paramètres hemorhéologiques au cours des complications microangiopathiques du diabète.

The aim of the present study was to assess the possible modifications in the parameters of red cell aggregation and blood and plasma viscosity in 92 diabetic patients compared to 82 non diabetic control subjects. Based on the presence of microalbuminuria (> 30 mg/24 h) and/or retinopathy each group of diabetic patients was divided into two subgroups. This study shows increased red cell aggregation and blood viscosity among diabetic patients with microangiopathy. There was a very good correlation between fibrinogen level and the different rheological measurements. The results of this study confirm the importance of the blood rheology abnormalities observable in diabetes. These disorders increase peripheral vascular resistances and ischemia and therefore worsen diabetic nephropathy and retinopathy.

[Stenosing esophagitis in Zollinger-Ellison syndrome]. / Oesophagite sténosante au cours du syndrome de Zollinger-Ellison.

Three patients with the Zollinger-Ellison syndrome and severe oesophagitis are reported. Intractable oesophageal stricture developed, leading to oesophago-gastrectomy in two patients and iterative oesophageal dilatations in the third. The retrospective analysis of these 3 cases led us to recommend, in case of oesophagitis in patients who have or might have the Zollinger-Ellison syndrome, to quickly institute a major antisecretory treatment, by parenteral route if necessary, to precociously and repeatedly control the efficacy of the antisecretory treatment mainly by measuring basal acid output and to avoid unjustified treatment discontinuance and gastric intubations.