Gábor Rácz

Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects

Objective:Short-term mechanical ventilation has been proven to reduce diaphragm force and fiber dimensions. We hypothesized that intermittent spontaneous breathing during the course of mechanical ventilation would minimize the effects of mechanical ventilation on diaphragm force and expression levels of transcription factors (MyoD and myogenin). Design:Randomized, controlled experiment. Setting:Animal basic science laboratory. Subjects:Male Wistar rats, weighing 350–500 g. Interventions:Anesthetized and tracheotomized rats were submitted to either 24 hrs of spontaneous breathing (SB, n = 5), 24 hrs of continuous controlled mechanical ventilation (CMV, n = 7), or controlled mechanical ventilation with intermittent spontaneous breathing: 60 mins every 5 hrs of mechanical ventilation repeated four times (ISB60, n = 8) or 5 mins every 5 hrs 55 mins of mechanical ventilation repeated four times (SB5, n = 9). They were compared with control animals free from intervention (C, n = 5). Measurements and Main Results:The profile of the diaphragm force-frequency curve of the controls and SB group was significantly different from that of the ISB and CMV groups; especially, the mean asymptotic force was less in the ISB and CMV compared with controls and SB. CMV resulted in a significant decrease in the diaphragm type I (−26%, p < .05 vs. C) and type IIx/b (−39%, p < .005 vs. C and SB) cross-sectional area, whereas this was not observed in the ISB groups. Diaphragm MyoD protein expression was significantly decreased after ISB60 (−35%, p < .0001 vs. C and SB) and even more after CMV (−73%, p < .0001 vs. others). The same pattern was observed with myogenin protein levels. Positive relationships between diaphragm MyoD and myogenin protein levels and diaphragm force were observed. Conclusions:The data demonstrated that intermittent spontaneous breathing during the course of mechanical ventilation may minimize the deleterious effect of controlled mechanical ventilation on diaphragm force, fiber dimensions, and expression of transcription factors.

Localization of the α-chemokine SDF-1 and its receptor CXCR4 in idiopathic inflammatory myopathies ☆

Abstract We studied the distribution of stromal cell-derived factor 1 isoforms α and β, and their receptor CXCR4, in polymyositis, sporadic inclusion body myositis and dermatomyositis using in situ hybridization, immunohistochemistry, immunofluorescence and Western blotting. In control muscle, polymyositis and sporadic inclusion body myositis, stromal cell-derived factor-1α expression was noted in muscle fibers, while stromal cell-derived factor-1β and CXCR4 were predominantly localized to capillaries and arterioles. In dermatomyositis, stromal cell-derived factor-1β immunoreactivity of blood vessels was focally increased. The vast majority of inflammatory cells in idiopathic inflammatory myopathies were CXCR4 positive. A subset of helper T-cells and macrophages expressed stromal cell-derived factor-1α, while only rare inflammatory cells expressed stromal cell-derived factor-1β. A significant increase of stromal cell-derived factor-1α and CXCR4 was observed in protein extracts of idiopathic inflammatory myopathies in comparison with normal controls. The abundance of both CXCR4 and its ligand stromal cell-derived factor-1 implicates their interaction in the pathogenesis of idiopathic inflammatory myopathies and identifies these proteins as possible targets for selective immune therapy.

Expression and distribution of the nitric oxide synthases in idiopathic inflammatory myopathies

Different immune effector mechanisms have been characterised in the idiopathic inflammatory myopathies (IIM): in polymyositis (PM) and sporadic inclusion body myositis (sIBM), T-cell-mediated cytotoxicity targets nonnecrotic muscle fibres, whereas in dermatomyositis (DM) the complement-mediated immune response is directed against the microvasculature. As nitric oxide (NO) has an important function in cell signalling and in the cytotoxicity displayed by activated macrophages, it is potentially involved in the immunopathogenesis of IIM. Using immunohistochemical, in situ hybridisation and Western blotting techniques, we visualised the three isoforms of NO synthase (NOS) in muscle tissues from normal controls and from patients diagnosed with IIM. The levels of both constitutive isoforms of NOS (endothelial, i.e., eNOS, and neuronal, i.e., nNOS) were unchanged in IIM as compared with normal muscle. Both protein and mRNA of the inducible form (iNOS) were detected in half of the control biopsies. Constant and increased iNOS protein expression was found in endomysial infiltrates of PM and sIBM, whereas perimysial inflammatory cells in DM were largely negative. We developed a quantitative Western blotting protocol which confirmed the constitutive nature of nNOS and eNOS and the significant induction of iNOS in PM. Our results appoint iNOS with a dual function: a limited and transient role in normal muscle physiology and an active cytotoxic role in PM and sIBM.

Anyai és újszülöttkori B12-vitamin-hiány felismerése kiterjesztett újszülöttkori szűréssel

Absztrakt: Bevezetes: A csecsemőkori B12-vitamin-hiany sulyos neurodegenerativ betegsegkent jelenhet meg, es rendszerint vegetarianus etrend vagy anaemia perniciosa kovetkezteben letrejovő anyai hiany okozza. Korai felismeresevel es kezelesevel a potencialisan sulyos es irreverzibilis neurologiai karosodas megelőzhető. Biokemiailag a B12-vitamin-hiany metil-malonsav-, homocisztein- es propionil-karnitin-felhalmozodashoz vezet. A tandem tomegspektrometrias kiterjesztett ujszulottkori szűres azonosithatja az ujszulottkori es anyai B12-vitamin-hianyt, a propionil-karnitinnek es egyeb metabolitoknak az ujszulottek beszaritott vercseppmintajaban tortenő meresevel. Celkitűzes: A B12-vitamin-hiany szűresevel nyert tapasztalataink osszefoglalasa. Modszer: Retrospektiv modon elemeztuk a Szegedi Szűrőkozpontban diagnosztizalt B12-vitamin-hianyos csecsemők klinikai es laboratoriumi adatait. Eredmenyek: Magyarorszagon a kiterjesztett ujszulottkori szűres 2007-ben kerult bevezetesre. Kozpontunkban azota korulbelul 395...