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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.

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Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres.

Background and aims: The extracellular calcium sensing receptor (CaR) plays a key role in the calcium homeostatic system and is therefore widely expressed in tissues involved in calcium metabolism. However, the CaR has also been identified in other tissues where its role is less clear. We have investigated the presence of the CaR in the human pancreas. Methods: Messenger RNA for the CaR was detected by reverse transcription-polymerase chain reaction and the protein was localised by immunostaining. CaR function was assayed in Capan-1 cells by measuring intracellular calcium and [

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Ϫ secretion may be physiologically important in terms of limiting the hydrostatic pressure developed within the ducts and in terms of switching off pancreatic secretion after a meal. Substance P (SP) inhibits secretin-stimulated HCO 3Ϫ secretion by modulating a Cl Ϫ -dependent HCO 3 Ϫ efflux step at the apical membrane of the duct cell (Hegyi P, Gray MA, and Argent BE. Am J Physiol Cell Physiol 285: C268 -C276, 2003). In the present study, we have shown that SP is present in periductal nerves within the guinea pig pancreas, that PKC mediates the effect of SP, and that SP inhibits an anion exchanger on the luminal membrane of the duct cell. Secretin (10 nM) stimulated HCO 3 Ϫ secretion by sealed, nonperfused, ducts about threefold, and this effect was totally inhibited by SP (20 nM). Phorbol 12,13-dibutyrate (PDBu; 100 nM), an activator of PKC, reduced basal HCO 3 Ϫ secretion by ϳ40% and totally blocked secretin-stimulated secretion. In addition, bisindolylmaleimide I (1 nM to 1 M), an inhibitor of PKC, relieved the inhibitory effect of SP on secretin-stimulated HCO 3 Ϫ secretion and also reversed the inhibitory effect of PDBu. Western blot analysis revealed that guinea pig pancreatic ducts express the ␣-, ␤ I-, ␦-, ⑀-, -, -, -, and -isoforms of PKC. In microperfused ducts, luminal H 2DIDS (0.5 mM) caused intracellular pH to alkalinize and, like SP, inhibited basal and secretinstimulated HCO 3 Ϫ secretion. SP did not inhibit secretion further when H 2DIDS was present in the lumen, suggesting that SP and H2DIDS both inhibit the activity of an anion exchanger on the luminal membrane of the duct cell.pancreas; Cl Ϫ /HCO 3 Ϫ exchanger; inhibition; epithelium THE PANCREATIC DUCTAL EPITHELIUM secretes an alkaline fluid that may contain up to 140 mM NaHCO 3 (4, 5). While the regulatory pathways that stimulate pancreatic ductal HCO 3 Ϫ secretion have been described well in the literature (4, 5), much less is known about inhibitory pathways. Such inhibitory pathways may be physiologically important in terms of limiting the hydrostatic pressure within the lumen of the duct (thus preventing leakage of enzymes into the parenchyma of the gland) and in terms of switching off pancreatic secretion after a meal (1). Both somatostatin (20, 32) and peptide YY (1, 34) have been shown to inhibit secretion from the intact pancreas and probably work by interfering with the neural and/or hormonal mechanisms that control the gland. In contrast, substance P (SP) (6, 18), 5-hydroxytryptamine (45), arginine vasopressin (29), and basolateral ATP (22) all have been shown to inhibit fluid and/or HCO 3 Ϫ secretion from isolated pancreatic ducts. Therefore, these agents must exert their effects directly on the ductal epithelium.SP has been identified in the pancreas of the dog, rat, and mouse (36), and the peptide has been shown to inhibit secretion from the intact gland of the dog (26, 31) and rat (27). Moreover, SP is a potent inhibitor of basal fluid secretion from isolated rat pancreatic ducts as well as of fluid secretion stimulated by secr...

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