Alberto Signore

Troglitazone prevents insulin dependent diabetes in the non-obese diabetic mouse

Troglitazone has recently been introduced in the treatment of Type 2 diabetes. In addition to its anti-diabetic effects it acts as a perixosome proliferator activated receptor-gamma (PPAR-gamma) agonist and has anti-inflammatory properties by inhibiting macrophage tumour necrosis factor-alpha (TNF-alpha) secretion. It also inhibits the production of endothelial selectin (e-selectin). Troglitazone also reduces interleukin-1alpha induced nitric oxide production in pancreatic beta-cells, which may be relevant in preventing nitric oxide mediated damage to these cells in the Type 1 diabetes process. We tested troglitazone in the spontaneous model of autoimmune diabetes, the non-obese diabetic (NOD) mouse, to determine its effect on the disease process. When administered by gavage from weaning at a dose of 400 mg/kg body weight (n = 32), troglitazone reduced the incidence of diabetes by 16 weeks compared to controls (n = 32) in a pattern that was maintained up to the conclusion of the experiment at 31 weeks of age (p < 0.05). Insulitis was unaltered (index = 1.05 +/- 0.71 vs. 1.13 +/- 0.82, treated vs. controls, p = 0.78). The study was repeated using troglitazone in the diet of NOD mice (n = 24) to give a dose of approximately 200 mg/kg body weight in order to provide a more consistent level of troglitazone during the time course of the experiment. There was a reduction of diabetes incidence in this group but it did not reach significance. Insulin levels were reduced in gavage treated mice although such reduction did not reach significance (p < 0.07). We conclude that, in view of its effect on this model of autoimmune diabetes and because of its known function as an insulin sensitiser, troglitazone might be considered for potential use in those patients with Type 1 masquerading as Type 2 diabetes.

Targeting cytokine/chemokine receptors: a challenge for molecular nuclear medicine

Abstract. Radiolabelled cytokines and chemokines are a group of radiopharmaceuticals that, by highlighting in vivo the binding to specific high-affinity receptors expressed on selected cell populations, allow the molecular and functional characterisation of immune-mediated processes Recently, several authors have described the use of radiolabelled cytokines and chemokines not only for imaging of inflammation and infection, but also as an approach to study in vivo the biology of primary and metastatic cancer cells. The latter avenue of research has been pursued particularly to help oncologists in therapeutic decision making and to follow up the efficacy of new immune therapies. In this paper we describe the characteristics of cytokines and chemokines, focussing on their role as radiopharmaceuticals for the imaging of cancer cells in vivo, a new challenge for molecular nuclear medicine.

Erratum to: Peptide radiopharmaceuticals for diagnosis and therapy

It has come to the authors’ attention that two paragraphs were not optimally placed within our occasional survey. The single-sentence paragraph “Insulin-like growth factor-1 (IGF-I) [41] has also shown good uptake on receptor-overexpressing tumour cells.” within the section “G-protein-coupled receptor radioligands” should in fact have been included in the third paragraph within the section “Tyrosine kinase receptor radioligands”. That paragraph should thus have commenced “Insulin-like growth factor-1 (IGF-I) [41] has also shown good uptake on receptor-overexpressing tumour cells. des(1–3)IGF-I, which lacks the N-terminal tripeptide Gly-Pro-Glu....” The subsequent paragraph within the section “G-protein-coupled receptor radioligands”, commencing “The integrin-binding peptide RDG (Arg-Gly-Asp) and related sequences represent a novel class of peptides able to bind to the v3 and v5 integrins...”, should have appeared as the first paragraph in the section “Other peptide radiopharmaceuticals”. We apologise for any confusion that may have been caused.

Standardizing Experiments with NOD Mice

We would like to provoke discussion on the standardization of experiments involving NOD mice, with a possible view to an international workshop on the subject at a future date.