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In this review article, we focus on the most recent applications of nuclear medicine techniques (mainly (99m)Tc/(111)In white blood cells (WBC) scan, [(18)F]-FDG-PET/CT, [(18)F]-FDG-PET/MRI, and (99m)Tc-IL-2 scintigraphy) in the study of children affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel diseases, and type 1 diabetes, owing to recent important published evidences of their role in the management of these diseases. For osteomyelitis in children, both bone scintigraphy and [(18)F]-FDG-PET have a major advantage of assessing the whole body in one imaging session to confirm or exclude multifocal involvement, whereas WBC scan has a limited role. In children with fungal infections, [(18)F]-FDG-PET can help in defining the best location for biopsy and can help in evaluating the extent of the infection and organs involved (also sites that were not yet clinically apparent), although its main role is for therapy monitoring. In inflammatory bowel diseases, and Crohn disease in particular, WBC scan has been successfully used for many years, but it is now used only in case of doubtful magnetic resonance (MR) or when MR cannot be performed and endoscopy is inconclusive. By contrast, there is an accumulating evidence of the role of [(18)F]-FDG-PET in management of children with Crohn disease, and PET/MR could be a versatile and innovative hybrid imaging technique that combines the metabolic information of PET with the high soft tissue resolution of MR, particularly for distinguishing fibrotic from active strictures. Finally, there are several new radiopharmaceuticals that specifically target inflammatory cells involved in the pathogenesis of insulitis aiming at developing new specific immunotherapies and to select children candidates to these treatments for improving their quality of life.

Background: More children are now surviving severe acute malnutrition (SAM), but evidence suggests that early-life malnutrition is associated with increased risk of long-term cardio-metabolic disorders. To better understand potential mechanisms, we studied the metabolite profiles of children seven years after treatment for SAM. Methods: We followed-up children (n=352) treated for SAM in 2006-2007, at Queen Elizabeth Central Hospital, in Malawi. Using nuclear magnetic resonance spectroscopy, tandem mass spectrometry and enzyme-linked immunosorbent assay, we measured circulating metabolites in fasting blood in a subset of SAM survivors (n = 69, 9.6 +/- 1.6 years), siblings (n = 44, 10.5 +/- 2.7 years), and age and sex-matched community controls (n = 37, 9.4 +/- 1.8 years). Data were analysed using univariate and sparse partial least square (sPLS) methods. Differences associated with SAM survival, oedema status, and anthropometry were tested, adjusting for age, sex, HIV, and wealth index. Findings: Based on 194 measured metabolites, the profiles of SAM survivors were similar to those of siblings and community controls. IGF1, creatinine, and FGF21, had loading values >0.3 and ranked stably in the top 10 distinguishing metabolites, but did not differ between SAM survivors and controls with univariate analysis. Current stunting was associated with IGF1 (beta = 15.2, SE = 3.5, partial R-2 = 12%, p < 0.0001) and this relationship could be influenced by early childhood SAM(beta = 17.4, SE = 7.7, partial R-2 = 2.8%, p = 0.025). No metabolites were associated with oedema status, duration of hospital stay, anthropometry measured during hospitalization, nor with changes in anthropometry since hospitalization. Interpretation: In this group of survivors, SAM was not associated with longer-term global metabolic changes 7 years after treatment. However, SAM may influence the relationship between current stunting and IGF1. Further risk markers for NCDs in SAM survivors may only be revealed by direct metabolic challenge or later in life. (C) 2019 The Authors. Published by Elsevier B.V.

The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated, We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal stimulation at 6-9 mo after intrasplenic islet autotransplantation in 8 dogs, as compared with 30 controls, The enteroinsular axis in the recipients was examined by infusion of porcine glucose-dependent insulinotropic polypeptide (GIP) and human glucagon-like peptide-1 (GLP-1) (7-36 amide) under 8.5-mM glycemic clamp conditions in order to mimic the postprandial glycemia after transplantation. The grafts comprised 25% of the native islet mass, and the ISC likewise averaged 25% of the control value, The postprandial insulin response, in contrast, had increased to 140% after transplantation-albeit with a concomitant glucose excursion to approximately 8.5 mM, Insulin action declined on average by 45% posttransplant. The ISC correlated both with the postprandial glucose excursion and insulin action in the grafted dogs, Insulin action did not correlate with the postprandial glucose excursion, Infusion of GIP had no effect, but GLP-1 nearly doubled glucose-stimulated insulin, Thus, a hyperglycemia-enhanced insulinotropic effect of GLP-1, and perhaps other gut hormones, may account for the difference in the insulin response to the intravenous and oral challenges, Because the ISC reflects the engrafted islet mass and appears to be the primary determinant of glucose tolerance, transplantation of higher islet doses should allow prolonged near-normal glucoregulation-at least, in the autotransplant setting. (C) 1997 Elsevier Science Inc.

L6 myotubes expressing the constitutively active Arg(1152)-->Gln insulin receptor (L6(1152)) featured a 31% increased glucose consumption as compared with L6 cells expressing wild-type receptors (L6(WT)). However, insulin treatment decreased glucose consumption of the mutant cells by 20% while increasing that of the L6(WT) by 30%, In the L6WT, insulin elicited a significant increase in glucose transport and GLUT1 and GLUT4 plasma membrane expression, while in the L6(1152), all of these functions were constitutively activated and not further stimulated by insulin, Similarly, glycogen content and glycogen synthase activity were increased by 80 and 125%, respectively, in the L6(1152) versus the L6(WT) and unaffected by insulin (while a 2-fold increase was measured in insulin-exposed L6(WT)), Glucose oxidation and pyruvate dehydrogenase activity were also 25% higher in the mutant compared with the L6(WT), However, in the L6(1152), both functions decreased by 35% in response to insulin (while increasing by 60 and 80%, respectively, in the L6(WT)). Similarly as in the L6(1152), in vivo, forearm glucose uptake in IR(1152) patients was 2-fold higher than in control subjects, This difference was not accounted for by higher plasma glucose levels. We conclude that, in skeletal muscle, glucose storage and oxidation are differentially impaired by the expression of IR(1152), suggesting that their regulation by insulin involves divergent signaling pathways, Muscle expression of IR(1152) may contribute to impairing glucose tolerance in IR(1152) individua