A theoretical model for prescription of the patient-specific therapeutic activity for radioiodine therapy of Graves' disease.

A fundamental function of the thyroid is to extract iodine from the blood, synthesize it into thyroid hormones, and release it into the circulation under feedback control by pituitary-secreted hormones. This capability of the thyroid, termed as functionality, can in principle be related to the severity of hyperthyroidism in individual patients. In this paper the uptake and release of 131I by the thyroid following the administration of 131I therapy for Graves' disease has been theoretically studied. The kinetics of iodine in the thyroid and blood have been evaluated using a two-compartment model. This simplified model appears to be adequate for dosimetry purposes and allows one to correlate levels of increased thyroid functionality (hyperthyroidism) with clinically measurable kinetic parameters. An expression has been derived for the rate of change of thyroid mass following therapy; this has the same form as an empirical relationship described in an earlier work. A method is presented for calculation of the amount of radioiodine activity to be administered to individual patients in order to achieve the desired final functionality of the gland. The activity to be administered is based on measurements of 131I kinetics after the administration of a 'low-activity' (1850 kBq) tracer for treatment planning.

An in vivo model of hyperacute rejection: characterization and evaluation of the effect of transgenic human complement inhibitors.

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after I day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1alpha, IL-1beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase dramatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.