349 research outputs found

    Case Study of Multiyear Precipitation Variations and the Hydrology of Fort Cobb Reservoir

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    Impacts of decadal precipitation variations on reservoir inflow, flood releases, and pool elevation were investigated for the Fort Cobb Reservoir, which controls runoff from a 787 km2 agricultural watershed in central Oklahoma. The difference in mean annual precipitation between multiyear dry and wet periods was 33% of the long-term mean and led to a corresponding 100% change in mean reservoir inflow, 170% change in mean annual flood releases from the reservoir, and a maximum drop in conservation pool elevation of 2 m. From a reservoir operations perspective, only the frequency of controlled flood releases was impacted by decadal precipitation variations. These flood releases were sporadic in nature, and the more frequent releases during wet periods were not believed to appreciably enhance stream habitat and riparian vegetation downstream of the reservoir. It was further reasoned that large differences in annual reservoir inflow due to decadal precipitation variations would likely be accompanied by related changes in upstream soil erosion and reservoir sediment loading. With regard to hydrologic and environmental modeling, it was argued that decadal precipitation variations had important implications for model calibration, verification, and subsequent application. Overall, this case study demonstrated watershed and reservoir hydrology were sensitive to decadal precipitation variations and suggested that decadal precipitation variations deserved careful consideration in hydrologic and water quality investigations in central Oklahoma

    Myocardial creatine levels do not influence response to acute oxidative stress in isolated perfused heart

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    Background: Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury. Objectives: To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS) exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare worse. Methods and Results: CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo 1 H– MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H2O2 0.5 mM (30 min), or the anti-neoplastic drug doxorubicin 15 mM (100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCd expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wildtype controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction. Conclusions: Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity

    Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale

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    New Findings What is the central question of this study? There is an ethical imperative to optimize analgesia protocols for laboratory animals, but this is impeded by our inability to recognize pain reliably. We examined whether the Mouse Grimace Scale (MGS) provides benefits over a standard welfare scoring system for identifying a low level of pain in the frequently used murine surgical model of myocardial infarction. What is the main finding and its importance? Low-level pain, responsive to analgesia, was detected by MGS but not standard methods. In this model, most of the pain is attributable to the thoracotomy, excepted in mice with very large infarcts. This approach represents a model for assessing postsurgical analgesia in rodents. The Mouse Grimace Scale (MGS) was developed for assessing pain severity, but the general applicability to complex postsurgical pain has not been established. We sought to determine whether the MGS provides benefits over and above a standard welfare scoring system for identifying pain in mice following experimental myocardial infarction. Female C57BL/6J mice (n = 60), anaesthetized with isoflurane, were subjected to thoracotomy with ligation of a coronary artery or sham procedure. A single s.c. dose of buprenorphine (1.1 mg kg−1) was given at the time of surgery and pain assessed at 24 h by MGS and a procedure-specific welfare scoring system. In some animals, a second dose of 0.6 mg kg−1 buprenorphine was given and pain assessment repeated after 30 min. The MGS was scored from multiple photographs by two independent blinded observers with good correlation (r = 0.98). Using the average MGS score of both observers, we identified a subset of mice with low scores that were not considered to be in pain by the welfare scoring system or by single observer MGS. These mice showed a significant improvement with additional analgesia, suggesting that this low-level pain is real. Pain attributable to the myocardial injury, as opposed to thoracotomy, persisted at 24 h only in mice with large infarcts >40%. In conclusion, the use of a multi-observer, post hoc version of the MGS is a sensitive tool to assess the efficacy of postsurgical analgesic protocols. Following surgical induction of myocardial infarction, we identified a significant proportion of mice that were in low-level pain at 24 h that were not identified by other assessment methods

    New potential for the Leitz Infinity Coordinate Measuring Machine

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    The following study is realised within the frame of the PACMAN project: a study on Particle Accelerator Components Metrology and Alignment to the Nanometre scale, which is a Marie Curie program supported by the European commission and hosted by CERN (European Organisation for Nuclear Research). The aim of this program is to develop and build a pre-alignment bench on which each component is aligned to the required level in one single step using a stretched wire. During the operation, the centre of the stretched wire is aligned with the magnetic axis of the magnet. Then, the position of the wire is measured to the highest possible accuracy using a 3D Coordinate Measuring Machine (CMM) Leitz PMM-C Infinity from HEXAGON Metrology. The research described in this paper is two-fold: on one hand we apply a strong magnetic field to the head of the CMM and evaluate its influence on the measurement accuracy; on the other hand we measure the positio

    MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation.

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    PURPOSE: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. METHODS: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. RESULTS: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. CONCLUSION: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines
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