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Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (ϩ223%), and this effect was maintained along 45 min of renal arterial blockade. After reperfusion, NO concentration fell below preischemic values and remained stable for the remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl ester (L-NAME) decreased significantly basal NO concentration before ischemia, but it did not modify the rise in NO levels observed during ischemia. In rats pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient increase in renal NO concentration that fell to preischemic values 20 min before reperfusion. A similar response was observed when the kidney was illuminated 40 min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine with BSO ϩ L-NAME restored the increase in NO levels observed during renal ischemia and prevented the depletion of renal thiol groups. These results demonstrate that the increase in renal NO concentration observed during ischemia originates from thiol-dependent tissue stores. voltammetry; nitrosothiols; N-acetyl-L-cysteine; buthionine sulfoximine; photosensitive nitric oxide release IT HAS BEEN REPORTED THAT arterial ischemia produces an abrupt and significant increase in tissue nitric oxide (NO) concentration, which can last as long as ischemia is maintained and returns to preischemic levels during reperfusion. This phenomenon has been observed in kidney (27), liver (16), heart (40), gastric tissue (15), and brain (39); although its physiological relevance is unclear, it may generate the high levels of peroxynitrite anion formed during reperfusion when a burst of superoxide anion reacts with the high levels of NO accumulated during ischemia (21), thus contributing to reperfusion damage. The mechanism responsible for these increased NO levels during renal ischemia is unknown, although it seems to be partially insensitive to NO synthesis inhibition, at least in liver and kidney (16,27). This is not surprising because NO synthase (NOS) requires molecular oxygen. Therefore, during ischemia, NO must be released from other sources, such as tissue NO stores (22,26,31).In the presence of oxygen, NO is synthesized from Larginine through the action of NOS, and this gaseous hormone acts in the kidney by stimulating guanylyl cyclase and by inhibiting cytochrome P-450 (18). However, as soon as it is synthesized, NO avidly react...

Abstract. The quality of business process models is an increasing concern as enterprise-wide modelling initiatives have to rely heavily on non-expert modellers. Quality in this context can be directly related to the actual usage of these process models, in particular to their understandability and modifiability. Since these attributes of a model can only be assessed a posteriori, it is of central importance for quality management to identify significant predictors for them. A variety of structural metrics have recently been proposed, which are tailored to approximate these usage characteristics. In this paper, we address a gap in terms of validation for metrics regarding understandability and modifiability. Our results demonstrate the predictive power of these metrics. These findings have strong implications for the design of modelling guidelines.

Background: Process orientation is one of the essential elements of quality management systems, including those in use in healthcare. Business processes in hospitals are very complex and variable. BPMN (Business Process Modelling Notation) is a user-oriented language specifically designed for the modelling of business (organizational) processes. Previous experiences of the use of this notation in the processes modelling within the Pathology in Spain or another country are not known. We present our experience in the elaboration of the conceptual models of Pathology processes, as part of a global programmed surgical patient process, using BPMN.