Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

Striatal trophic activity is reduced in the aged rat brain

Our previous studies demonstrated that the survival of a mesencephalic graft was reduced in aged animals suggesting an age-related decline in target-derived neurotrophic activity. We tested this hypothesis by examining dopamine (DA) and trophic activities from the striatum of intact or unilateral 6-hydroxydopamine (6-OHDA) lesioned rats of increasing age. Fisher 344 rats were 4, 12, 18, and 23 months old (m.o.) at sacrifice. Half the animals had received unilateral 6-OHDA lesions of the mesostriatal DA pathway 8 weeks earlier. Striatal tissue punches were analyzed for DA, homovanillic acid (HVA), and DA activity (HVA/DA) using HPLC. The remainder of the striatal tissue was homogenized to generate tissue extracts which were added to E14.5 ventral mesencephalic cultures to test trophic activity. In the non-lesioned animals, striatal DA was reduced and striatal DA activity was increased in the 18 and 23 m.o. animals relative to the 4 and 12 m.o. animals. Striatal trophic activity was inversely related to age. In the lesioned animals, striatal DA ipsilateral to 6-OHDA infusion was below detection limits while the contralateral striatum exhibited age-related changes in DA similar to those seen in the non-lesioned animals. In 4 m.o. lesioned rats, striatal trophic activity ipsilateral to 6-OHDA infusion was elevated by 26% relative to the contralateral side. The ipsi/contra-lateral differences in striatal trophic activity were reduced in 12 m.o. animals and absent in the 18 and 23 m.o. groups. These data suggest that advancing age is associated with a reduction in striatal DA as well as trophic activity. Moreover, the aged striatum loses its ability to biochemically and trophically compensate for DA reduction and therefore may represent a more challenging environment for the survival, growth, and function of a fetal graft.     

Beacon: a novel gene involved in the regulation of energy balance

The hypothalamus plays a major role in the control of energy balance via the coordination of several neuropeptides and their receptors. We used a unique polygenic animal model of obesity, Psammomys obesus, and performed differential display polymerase chain reaction on hypothalamic mRNA samples to identify novel genes involved in obesity. In this study, we describe a novel gene that encodes a small protein we have termed "beacon." Beacon mRNA gene expression in the hypothalamus was positively correlated with percentage of body fat. Intracerebroventricular infusion of beacon resulted in a dose-dependent increase in food intake and body weight and an increase in hypothalamic expression of neuropeptide Y (NPY). Simultaneous infusion of beacon and NPY significantly potentiated the orexigenic response and resulted in rapid body weight gain. These data suggest a role for beacon in the regulation of energy balance and body weight homeostasis that may be mediated, at least in part, through the NPY pathway.     

Standalone portable xenon-129 hyperpolariser for multicentre clinical magnetic resonance imaging of the lungs

ObjectivesDesign and build a portable xenon-129 (¹²⁹Xe) hyperpolariser for clinically accessible ¹²⁹Xe lung MRI.MethodsThe polariser system consists of six main functional components: (i) a laser diode array and optics; (ii) a B₀ coil assembly; (iii) an oven containing an optical cell; (iv) NMR and optical spectrometers; (v) a gas-handling manifold; and (vi) a cryostat within a permanent magnet. All components run without external utilities such as compressed air or three-phase electricity, and require just three mains sockets for operation. The system can be manually transported in a lightweight van and rapidly installed on a small estates footprint in a hospital setting.ResultsThe polariser routinely provides polarised ¹²⁹Xe for routine clinical lung MRI. To test the concept of portability and rapid deployment, it was transported 200 km, installed at a hospital with no previous experience with the technology and ¹²⁹Xe MR images of a diagnostic quality were acquired the day after system transport and installation.ConclusionThis portable ¹²⁹Xe hyperpolariser system could form the basis of a cost-effective platform for wider clinical dissemination and multicentre evaluation of ¹²⁹Xe lung MR imaging.Advances in knowledgeOur work successfully demonstrates the feasibility of multicentre clinical ¹²⁹Xe MRI with a portable hyperpolariser system.     

Allgemeine Therapie

Ohne Zusammenfassung     

Einfluß der Ultraviolettbestrahlung auf die Malignitätsdisposition des Kaninchenkrebses

Zusammenfassung Faßt man die Ergebnisse beider oben geschilderten Versuche zusammen, so kommt man zu dem Schluß, daß durch UV.-Bestrahlung in einigermaßen vernünftiger Dosierung die Malignitätsdisposition des Kaninchensnicht gesteigert wird. Selbst wenn man zugibt, daß durch extremste Überdosierung unter Umständen Neoplasmen entstehen können, so zeigen doch die eigenen Versuche die Unschädlichkeit einer mäßigen Strahlendosierung. Wir glauben, diese beim Kaninchen gewonnenen Ergebnisse auch auf den Menschen übertragen zu dürfen: Die von einigen Autoren festgestellte Möglichkeit eines Höhensonnen-krebses ist für die Praxisohne jede Bedeutung.Weiterhin aber geht aus den geschilderten Versuchen hervor, daß durch UV.-Bestrahlung allein oder in Kombination mit Eisentherapie die Malignitätsdisposition des Kaninchens in keiner Weise verringert wird.Sieht man von der unter besonderen Versuchsbedingungen geglücktenErzeugung maligner Tumoren durch extreme Bestrahlung ab, kommt man zu dem Schluß:Ultraviolette Strahlen und Carcinomwachstum haben miteinander nichts zu tun.