Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus.</p> <p>Case presentation</p> <p>We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion) with the insulin analogue lispro (Humalog^®) in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg) p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI) despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog^®.</p> <p>Conclusion</p> <p>Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog^®), triggered by an unknown endogenous mechanism.</p

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Foerderung von 2-Phasengemischen (fluessig/gasfoermig) mit Kreiselpumpen Zusammenfassender Schlussbericht

Detailed studies were carried out in order to identify changes in the characteristic parameters of gyropumps when pumping gas. For the first time ever, the velocity fields of the liquid and bubbles were measured simultaneously using particle image velocimetry supplemented by laser-induced fluorescence (PIV-LIF). The volume flow redistribution as a function of the gas charge enables conclusions on the individual contributing effects. The dominant effect was the pressure field dependent relative motion of the bubbles and the resulting local gas concentration. Other important effects wre the manner of gas supply, e.g. stratified flow and even distribution of gas bubbles, the speed, and of course the inlet concentration. The results can be transferred to pump flow in general. In cooperation with the Pfleiderer Institute at Brunswick, the basis was thus provided for calibrating simplified, less complex programs for pump calculation. (orig.)Zur Klaerung der Kennwert- bzw. Kennlinienaenderungen von Kreiselpumpen bei Gasbeladung wurde die Pumpendurchstroemung detailliert untersucht. Erstmalig wurden mit Hifle der Particle-Image-Velocimetry unter zusaetzlicher Heranziehung der Laser-Induzierten-Fluoreszenz (PIV-LIF) die Geschwindigkeitsfelder von Fluessigkeit und Blasen simultan bestimmt. Die Volumenstromumverteilung in Abhaengigkeit von der Gasbeladung ermoeglicht Rueckschluesse auf die wirkenden Einzeleffekte. Als dominant erweist sich die druckfeldbedingte Relativbewegung der Blasen und damit im Zusammenhang die oertlich sich einstellende Gaskonzentration. Weiterhin sind von wesentlichem Einfluss die Art der Gaszufuehrung (Schichtenstroemungg bzw. Gasblasengleichverteilung), die Drehzahl (Grad der Dispergierung) und natuerlich die Eintrittskonzentration. Das Ziel einer detaillierten Studie der Foerderung von 2-Phasengemischen mittels Radialkreiselpumpen konnte somit erreicht werden. Die Ergebnisse lassen sich auf Pumpendurchstroemungen allgemein uebertragen. In Uebereinstimmung und gemeinsam mit den am Pfleiderer-Institut Braunschweig gemessenen Schaufeldruckverlaeufen wurde damit auch die Basis fuer eine Kalibrierung vereinfachter, weniger aufwendiger Programme der Pumpenberechnung geschaffen. (orig.)SIGLEAvailable from TIB Hannover: RS 3405(2002,1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekArbeitsgemeinschaft Industrieller Forschungsvereinigungen 'Otto von Guericke' e.V. (AIF), Koeln (Germany); Bundesministerium fuer Wirtschaft und Technologie (BMWi), Berlin (Germany)DEGerman

Characterization of the porcine neonatal Fc receptor--potential use for trans-epithelial protein delivery

The neonatal Fc receptor transports maternal immunoglobulin across the gut wall and has the potential to deliver genetically engineered proteins bearing immunoglobulin Fc domains across the gut to the mucosal immune system. Here we have characterized the porcine neonatal Fc receptor and tested its utility as a model system to study this kind of protein delivery. The complete DNA sequence obtained from an EST revealed 70–80% homology to mouse and human receptors, respectively, and tyrptophan and di-leucine endocytosis motifs were identified in the cytoplasmic tail. Reverse transcription–polymerase chain reaction analysis showed expression of the receptor mRNA in gut, liver, kidney and spleen tissue, aortic endothelial cells and monocytes. Pig kidney cell lines showed saturable pH-dependent binding and uptake of porcine immunoglobulin G (IgG) and also bovine, mouse and human IgG. Polyclonal antibodies raised against the receptor immunoprecipitated a protein of 40 000 MW when the cDNA was expressed in cells and the receptor required assembly with porcine β(2)-microglobulin for transport from the endoplasmic reticulum to recycling and early endosomes. Immunohistochemical analysis showed the receptor expressed in epithelial cells of the gut of young and adult animals. The ability of the receptor to deliver immunoglobulin across the gut was demonstrated by feeding piglets bovine colostrum as a source of bovine IgG. Bovine IgG was delivered into the pig circulation. Pigs express the neonatal Fc receptor and the receptor has the potential to deliver protein antigens to the pig immune system