A prospective, randomized, placebo-controlled trial of prednisone and allopurinol in the prevention of ERCP-induced pancreatitis

BACKGROUND AND STUDY AIMS: Acute pancreatitis is the most frequent and difficult-to-avoid complication of endoscopic retrograde cholangiopancreatography (ERCP). Corticosteroids, potent anti-inflammatory drugs, and allopurinol--a xanthine oxidase inhibitor that blocks the generation of oxygen-derived free radicals--may be potentially effective in preventing post-ERCP pancreatitis. The aim of this prospective study was to determine the effect of prophylactic oral corticosteroids and allopurinol on the incidence and severity of procedure-induced pancreatitis. PATIENTS AND METHODS: 300 patients were randomly assigned to receive oral prednisone (40 mg), allopurinol (200 mg), or placebo 15 h and 3 h prior to ERCP. The diagnosis and grading of ERCP complications were based on commonly accepted criteria. Patients receiving prednisone or allopurinol were compared with the placebo group in a search for differences in pancreatitis rates associated with endoscopic techniques. RESULTS: The overall incidence of pancreatitis was 10.7 %, with 12 % in the prednisone group, 12.1 % in the allopurinol group, and 7.9 % in the placebo group. There were no statistical differences in the incidence or distribution of severity grades between the groups, although severe pancreatitis occurred only in the prednisone and allopurinol groups. Multiple cannulations and prolonged manipulations of the papilla of Vater were identified as risk factors for ERCP-induced pancreatitis. CONCLUSIONS: Neither prednisone nor allopurinol showed a beneficial influence on the incidence and severity of post-ERCP pancreatitis.     

Ecarin chromogenic assay: an innovative test for quantitative determination of direct thrombin inhibitors in plasma

The ecarin chromogenic assay (ECA) was developed for quantitative determination of direct thrombin inhibitors. As a further development of the ecarin clotting time (ECT), the ECA is based on the same principle, the activation of prothrombin by ecarin a snake venom from Echis carinatus. In the ECA the prothrombin activation products meizothrombin and meizothrombin-desF1 cleave a chromogenic substrate, whereas in the clotting assay ECT plasma fibrinogen is converted to fibrin. The activity of meizothrombin/meizothrombin-desF1 is inhibited in a concentration-dependent fashion by direct thrombin inhibitors. The ECA can be used as ECA-H for quantitative determination of hirudin and as ECA-T for determination of synthetic thrombin inhibitors. As shown for hirudin, argatroban and melagatran, the ECA turned out as a very precise and sensitive method, which combines the advantages of ECT with those of chromogenic assays. In ECA very low interindividual variations were found compared to aPTT and even ECT. The ECA is independent of the variations of the coagulation variables prothrombin and fibrinogen.     

Myocardial Perfusion Imaging is Feasible for Infarct Size Quantification in Mice Using a Clinical Single-photon Emission Computed Tomography System Equipped with Pinhole Collimators

Introduction

The aim of this study is to evaluate a non-invasive method for measuring myocardial perfusion defect size in mice using a clinical single-photon emission computed tomography system equipped with pinhole collimators (pinhole SPECT).

Materials and Methods

Thirty days after ligation of the left anterior descending coronary artery, 13 mice (C57BL/6J) were imaged following intravenous injection of 370 MBq [99mTc]sestamibi. Eight control mice without myocardial infarction were likewise investigated. Image quality optimization had been achieved by repeated scanning of a multiple point phantom, with varying zoom factors, number of projection angles, and pinhole diameter. Volumetric sampling was used to generate polar maps, in which intensity was normalized to that of a standard septal region of interest (ROI), which was set at 100%. Receiver operating characteristic analyses were performed to define an optimal threshold as compared to histologically measured defect sizes, which were considered as gold standard.

Results

A spatial resolution of 1.9 mm was achieved using a pinhole diameter of 0.5 mm, a zoom factor of 2, and 6° projection angles. Histological results were best reproduced by a 60% threshold relative to the septal reference ROI. By applying this threshold, SPECT perfusion defect sizes revealed very high correlation to the histological results (R ²?=?0.867) with excellent intra- and interobserver reproducibility (intraclass correlation coefficients of 0.84 and 0.82).

Conclusions

We achieved a spatial resolution of 1.9 mm in myocardial perfusion imaging in mice using a clinical SPECT system mounted with pinhole collimators. Compared to a histological gold standard, the infarct sizes were accurately estimated, indicating that this method shows promise to monitor experimental cardiac interventions in mice.     

Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells

We previously reported that mitochondrial function, intracellular ATP levels, and complex I activity are decreased in renal proximal tubular cells (RPTC) after oxidant (tert-butyl hydroperoxide; TBHP)-induced injury. This study examined the hypothesis that succinate supplementation decreases mitochondrial dysfunction, ameliorates energy deficits, and increases viability in TBHP-injured RPTC. Basal and uncoupled respirations in injured RPTC decreased 33 and 35%, respectively, but remained unchanged in injured RPTC supplemented with 10 mM succinate (electron donor to respiratory complex II). State 3 respiration supported by electron donors to complex I decreased 40% in injured RPTC but improved significantly by succinate supplements. The activity of mitochondrial complex I in TBHP-injured RPTC decreased 48%, whereas complex II activity remained unchanged. Succinate supplementation prevented decreases in complex I activity. ATP levels decreased 43% in injured RPTC but were maintained in injured cells supplemented with succinate. Lipid peroxidation increased 19-fold in injured RPTC but only 9-fold in injured cells supplemented with succinate. Exposure of primary cultures of RPTC to TBHP produced 24% cell injury and lysis but no apoptosis. In contrast, no cell lysis was found in RPTC supplemented with succinate. We conclude that mitochondrial dysfunction and energy deficits in oxidant-injured RPTC are ameliorated by succinate, and we propose that succinate supplementation may prove therapeutically valuable. Succinate 1) uses an alternate pathway of mitochondrial energy metabolism, 2) improves activity of complex I and oxidation of substrates through complex I, and 3) decreases oxidative stress and cell lysis in oxidant-injured RPTC.