Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation. Leukocyte migration into tissues is vital for efficient defense against insulting pathogens and foreign antigens. Nevertheless, the same phenomenon is also crucial to inappropriate inflammation and tissue destruction in several types of acute and chronic inflammatory and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, organ transplant rejection, and ischemia-reperfusion injury. Leukocytes enter from the blood circulation into the tissues by passing through the walls of blood vessels. An essential step in this process is binding of leukocytes to the innermost layer of the blood vessel wall, the endothelium, by adhesion molecules. Multiple adhesion molecules on the leukocytes interact concertedly with their counter-receptors on the endothelium during the adhesion and the subsequent transmigration process.1,2 A change in the functional expression of adhesion molecules on the endothelial surface is an early and specific indicator of inflammation. In fact, recent studies suggest that radioactively labeled monoclonal antibodies against specific endothelial adhesion molecules can be used in the diagnosis of inflammation by nuclear imaging methods. 3,4Human vascular adhesion protein-1 (VAP-1), originally defined by 1B2 monoclonal antibody, is a 170-kd endothelial sialoglycoprotein.5 VAP-1 is inflammation inducible and mediates the early phases of interaction between lymphocytes and endothelium. 6 The expression pattern of VAP-1 in normal and inflamed human tissues has been described 7,8 and the role of VAP-1 in human leukocyte adhesion has been shown in vitro. 5,9 However, practically nothing is known about the translocation of VAP-1 from the inside of the cells to the functional position on the cell surface as well as the significance of VAP-1 in leukocyteendothelium interactions in vivo.The anti-human-VAP-1 mAb 1B2 does not recognize VAP-1 of small laboratory animals such as mouse, rat, or rabbit. However, preliminary screening experiments revealed that 1B2 antibody does recognize porcine and canine blood vessels. That encouraged us to study whether the antigens recognized by 1B2 are the porcine and canine homologues o...

Aims/hypothesis The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. Methods In the validation study, pigs were imaged using In the clinical study, GU was measured in different regions of the intestine in lean (n=8) and morbidly obese (n=8) humans at baseline and during euglycaemic hyperinsulinaemia.

14( R, S)-[(18)F]Fluoro-6-thia-heptadecanoic acid ([(18)F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [(18)F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [(18)F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [(18)F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [(18)F]FTHA metabolite analysis. Fractional [(18)F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring (18)F in the tissue samples. Fractional [(18)F]FTHA uptake rates based on the analysis of tissue samples were 0.56+/-0.17 ml g(-1) min(-1) and 0.037+/-0.007 ml g(-1) min(-1) for myocardium and skeletal muscle (mean +/- SD), respectively. The myocardial results obtained from the PET data (0.50+/-0.11 ml g(-1) min(-1)) were similar to the values obtained from the tissue samples ( r=0.94, P=0.002). We also found that 89%+/-23% (mean+/-SD, n=7) of the (18)F entered mitochondria in myocardium, as compared with only 36%+/-15% (mean+/-SD, n=7) in skeletal muscle. Intracellular [(18)F]FTHA metabolite analysis showed that a major part of [(18)F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that ~89% of [(18)F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [(18)F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only ~36% of [(18)F]FTHA accumulated in skeletal muscle appears to directly enter mitochondria; the majority is taken up by the other cell fractions, suggesting that in skeletal muscle [(18)F]FTHA traces FFA uptake but not specifically FFA beta-oxidation.