Cardiac Glucose and Fatty Acid Transport After Experimental Mono- and Polytrauma

OBJECTIVE The aim of this study was to define the influence of trauma on cardiac glucose and fatty acid transport. The effects were investigated in vivo in a porcine mono- and polytrauma model and in vitro in human cardiomyocytes, which were treated simultaneously with different inflammatory substances, mimicking post-traumatic inflammatory conditions. METHODS AND RESULTS In the porcine fracture- and polytrauma model, blood glucose concentrations were measured by blood gas analysis during an observation period of 72 h. The expression of cardiac glucose and fatty acid transporters in the left ventricle was determined by RT-qPCR and immunofluorescence. Cardiac and hepatic glycogen storage was examined. Furthermore, human cardiomyocytes were exposed to a defined trauma-cocktail and the expression levels of glucose- and fatty acid transporters were determined. Early after polytrauma, hyperglycaemia was observed. After 48 h and 72 h, pigs with fracture- and polytrauma developed hypoglycaemia. The propofol demand significantly increased post trauma. The hepatic glycogen concentration was reduced 72 h after trauma. Cardiac glucose and fatty acid transporters changed in both trauma models in vivo as well as in vitro in human cardiomyocytes in presence of proinflammatory mediators. CONCLUSIONS Monotrauma as well as polytrauma changed the cardiac energy transport by altering the expression of glucose and fatty acid transporters. In vitro data suggest that human cardiomyocytes shift to a state alike myocardial hibernation preferring glucose as primary energy source in order to maintain cardiac function

Delayed Hyponatremia is the Most Common Cause of 30-Day Unplanned Readmission After Transsphenoidal Surgery for Pituitary Tumors

BACKGROUND: Unplanned readmission after surgical procedures is an important quality metric. Yet, readmission rates and causes have not been evaluated for patients after transsphenoidal surgery for pituitary tumors. OBJECTIVE: To analyze unplanned 30-day readmissions at a pituitary center and to encourage the development of effective clinical pathways to prevent readmission. METHODS: A retrospective review of adult patients who underwent transsphenoidal surgery for pituitary lesions at Barrow Neurological Institute (January 2011-March 2014) was performed to identify causes of unplanned readmission within 30 days of surgery. Patient demographics, tumor details, surgical complications, and endocrine function were documented. RESULTS: Of 303 patients who had transsphenoidal surgery, 27 (8.9%) were readmitted within 30 days. Most of the 27 (15 [55.6%]) had delayed hyponatremia. Other causes were diabetes insipidus (4 [14.8%]), adrenal insufficiency (2 [7.4%]), and cerebrospinal fluid leak, epistaxis, cardiac arrhythmia, pneumonia, urinary tract infection, and hypoglycemia (1 each [3.7%]). Outpatient sodium screening was performed as needed. In cases of hyponatremia, the mean postoperative day of readmission was day 8 (range, 6-12 days) and the mean serum sodium was 119 mmol/L (range, 111-129 mmol/L). Numerous patient and surgical factors were examined, and no specific predictors of readmission were identified. We developed an outpatient care pathway for managing hyponatremia with the goal of improving readmission rates. CONCLUSION: This study establishes a quality benchmark for readmission rates after transsphenoidal surgery for pituitary lesions and identifies delayed hyponatremia as the primary cause. Implementation of an outpatient care pathway for managing hyponatremia may improve readmission rates

Goodness-of-fit indices for the theoretical models proposed.

<p>χ² = Chi square; <i>df</i>  =  degrees of freedom; CFI  =  Comparative Fit Index; TLI  =  Tucker-Lewis Index; RMSEA  =  Root Mean Square Error of Approximation; WRMR =  Weighted Root Mean Square Residual. Note: </p

Measurement invariance across groups for three-dimensional model proposed by Raine et al., [37].

<p>χ² = Chi square; <i>df</i>  =  degrees of freedom; CFI  =  Comparative Fit Index; TLI  =  Tucker-Lewis Index; RMSEA  =  Root Mean Square Error of Approximation; WRMR =  Weighted Root Mean Square Residual Note: </p

Increased glucose disposal and AMP-dependent kinase signaling in a mouse model of hemochromatosis

Hereditary hemochromatosis is an inherited disorder of increased iron absorption that can result in cirrhosis, diabetes, and other morbidities. We have investigated the mechanisms underlying supranormal glucose tolerance despite decreased insulin secretion in a mouse model of hemochromatosis with deletion of the hemochromatosis gene (Hfe(-/-)). Hfe(-/-) mice on 129Sv or C57BL/6J backgrounds have decreased glucose excursions after challenge compared with controls. In the C57BL/6J/Hfe(-/-), for example, incremental area under the glucose curve is reduced 52% (p < 0.001) despite decreased serum insulin, and homeostasis model assessment insulin resistance is decreased 50% (p < 0.05). When studied by the euglycemic clamp technique 129Sv/Hfe(-/-) mice exhibit a 20% increase in glucose disposal (p < 0.05) at submaximal insulin but no increase at maximal insulin compared with wild types. [1,2-C-13]D-glucose clearance from plasma is significantly increased in Hfe(-/-) mice (19%, p < 0.05), and lactate derived from glycolysis is elevated 5.1-fold in Hfe(-/-) mice (p < 0.0001). Basal but not insulin-stimulated glucose uptake is elevated in isolated soleus muscle from Hfe(-/-) mice (p < 0.03). Compared with controls Hfe(-/-) mice exhibit no differences in serum lipid, insulin, glucagon, or thyroid hormone levels; adiponectin levels are elevated 41% (p < 0.05), and the adiponectin message in adipocytes is increased 83% (p = 0.04). Insulin action measured by phosphorylation of Akt is not enhanced in muscle, but phosphorylation of AMP-dependent kinase is increased. We conclude that supranormal glucose tolerance in iron overload is characterized by increased glucose disposal that does not result from increased insulin action. Instead, the Hfe(-/-) mice demonstrate increased adiponectin levels and activation of AMP-dependent kinase

Reduction of invertebrate herbivory by land use is only partly explained by changes in plant and insect characteristics

Invertebrate herbivory is a crucial process contributing to the cycling of nutrients and energy in terrestrial ecosystems. While the function of herbivory can decrease with land-use intensification, the underlying mechanisms remain unclear. We hypothesize that land-use intensification impacts invertebrate leaf herbivory rates mainly through changes in characteristics of plants and insect herbivores. We investigated herbivory rates (i.e., damaged leaf area) on the most abundant plant species in forests and grasslands and along land-use intensity gradients on 297 plots in three regions of Germany. To evaluate the contribution of shifts in plant community composition, we quantified herbivory rates at plant species level and aggregated at plant community level. We analyzed pathways linking land-use intensity, plant and insect herbivore characteristics, and herbivory rates. Herbivory rates at plant species and community level decreased with increasing land-use intensity in forests and grasslands. Path analysis revealed strong direct links between land-use intensity and herbivory rates. Particularly at the plant community level, differences in plant and herbivore composition also contributed to changes in herbivory rates along land-use intensity gradients. In forests, high land-use intensity was characterized by a larger proportion of coniferous trees, which was linked to reduced herbivory rates. In grasslands, changes in the proportion of grasses, plant fiber content, as well as the taxonomic composition of herbivore assemblages contributed to reduced herbivory rates. Our study highlights the potential of land-use intensification to impair ecosystem functioning across ecosystems via shifts in plant and herbivore characteristics. De-intensifying land use in grasslands and reducing the share of coniferous trees in temperate forests can help to restore ecosystem functionality in these systems.ISSN:0012-9615ISSN:1557-7015ISSN:1741-701

A Familial Mutation Renders Atrial Natriuretic Peptide Resistant to Proteolytic Degradation*

A heterozygous frameshift mutation causing a 12-amino acid extension to the C terminus of atrial natriuretic peptide (ANP) was recently genetically linked to patients with familial atrial fibrillation (Hodgson-Zingman, D. M., Karst, M. L., Zingman, L. V., Heublein, D. M., Darbar, D., Herron, K. J., Ballew, J. D., de Andrade, M., Burnett, J. C., Jr., and Olson, T. M. (2008) N. Engl. J. Med. 359, 158–165). The frameshift product (fsANP), but not wild-type ANP (wtANP), was elevated in the serum of affected patients, but the molecular basis for the elevated peptide concentrations was not determined. Here, we measured the ability of fsANP to interact with natriuretic peptide receptors and to be proteolytically degraded. fsANP and wtANP bound and activated human NPR-A and NPR-C similarly, whereas fsANP had a slightly increased efficacy for human NPR-B. Proteolytic susceptibility was addressed with novel bioassays that measure the time required for kidney membranes or purified neutral endopeptidase to abolish ANP-dependent activation of NPR-A. The half-life of fsANP was markedly greater than that of wtANP in both assays. Additional membrane proteolysis studies indicated that wtANP and fsANP are preferentially degraded by neutral endopeptidase and serine peptidases, respectively. These data indicate that the familial ANP mutation associated with atrial fibrillation has only minor effects on natriuretic peptide receptor interactions but markedly modifies peptide proteolysis