Indiana University-Purdue University Indianapolis (IUPUI) / Recent clinical outcome studies demonstrate that Sodium glucose cotransporter 2 inhibitors (SGLT2i) significantly reduce major adverse cardiovascular events and heart failure outcomes in subjects with type 2 diabetes mellitus. At present, several hypotheses have been proposed to explain the observed cardiovascular benefit of SGLT2i, however, the mechanisms responsible remain to be elucidated. This investigation tested the hypothesis that SGLT2i improves cardiac function and efficiency during acute, regional ischemia/reperfusion injury via preferential shifts in myocardial substrate selection and/or inhibition of cardiac sodium/hydrogen exchanger-1 (NHE-1). Our initial investigation evaluated the effects of 24 hour pretreatment of the SGLT2i canagliflozin on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in healthy swine. At the onset of ischemia, canagliflozin increased left ventricular end diastolic and systolic volumes which returned to baseline with reperfusion. This increased end diastolic volume was directly associated with increased stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial substrate uptake of glucose, lactate, fatty acids or ketones were detected between groups. In separate experiments using a longer 60 min coronary occlusion, canagliflozin significantly diminished myocardial infarct size. Subsequent studies investigated the effect of an acute administration (15-30 min pre-treatment) of canagliflozin and the NHE-1i cariporide on cardiac contractile function efficiency in response to myocardial ischemia/reperfusion injury. Similar to our initial studies, canagliflozin increased diastolic filling, stroke work and improved cardiac work efficiency relative to untreated control hearts during the ischemic period. In contrast, cariporide did not alter ventricular filling volume, cardiac output or work efficiency at any time point. Additional examination of AP-1 cells transfected with wild-type NHE-1 showed dose-dependent inhibition of NHE-1 activity by cariporide, while canagliflozin had minimal effect on overall activity. This investigation demonstrates that SGLT2i improves cardiac function and efficiency during acute, regional ischemia in healthy swine. However, the present data fail to support the hypothesis that these SGLT2i-mediated improvements involve either preferential alterations in myocardial substrate utilization or the inhibition of NHE-1 activity.

The legislative procedures regarding wild pigs in the United States are expanding in scope and priority, however, the uniformity of legislation is entropic at best. Each state addresses the issues of wild pigs differently and treatment is based on a priority of resource concerns. An evaluation was conducted at the national level of federal, state, and local policy with regards to wild pig control. Additionally, successful and unsuccessful legislation is evaluated to determine commonalities in the social, economic, and ecological factors contributing to the success or failure of legislation. Information collected provides state legislatures with sample model legislation that can be passed with the support of stakeholders and the citizenry, as well as help guide states into a more uniform system of policy. Furthermore, it provides states without, or with low populations of wild pigs, a proactive suite of legislation to prevent further spread and facilitate eradication of localized populations.

The porcine antral follicle, which consists of an oocyte and surrounding follicular components, including theca, granulosa, and cumulus cells and follicular fluid, is an essential microenvironment for oocyte development and maturation. Investigating cellular and molecular events in the context of the whole follicle will aid in our understanding of interactions between the oocyte and the follicular components. The objective of this dissertation was to develop a novel bioluminescent imaging model to visualize and measure cellular and molecular events in living intact ovarian follicles in vitro. Bioluminescence imaging was employed to facilitate noninvasive, dynamic, and real-time transgene analysis in living intact follicles. The time courses of luciferase-luciferin reactions, effective plasmid DNA and D-luciferin doses and their combinations were determined as the first step toward developing a new real-time bioluminescence imaging model. In addition, the efficient nonviral gene delivery methods: cationic lipid mediated gene transfer (chemical) and electroporation (physical) for the living intact follicles were determined. For the cationic lipid mediated gene transfer method, the 1:3 DNA lipid ratio was optimal. It was also found that the optimal condition of electroporation (4 electric pulses with 100 ms duration at field strength of 100 V/cm) resulted in 15 times higher luciferase activity and increased granulosa cell viability over the cationic lipid mediated gene transfer method. Moreover, increased granulosa cell viability, increased follicular fluid progesterone content, and oocytes with expanded cumulus cells were observed in intact follicles transfected by electroporation at a field strength of 100 V/cm. Finally, bioluminescence imaging was applied to quantify functional and ligand-activated estrogen receptor (ER) activity within living intact follicles. The functional ERs were differentially activated during the different stages of the estrous cycle in the mature sow; the levels of functional ER activity in cultured granulosa cells and intact follicles in vitro were increased from late luteal phase to early follicular phase and then significantly decreased at late follicular phase. The methodology developed herein can be applicable to further our understanding of oocyte and follicle development and oocyte maturation.

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<p> An experimental evaluation of three desulphurisers for pig iron has been conducted. Sodium vapor, blast furnace slag enriched with cerium oxide and a rare earth alloy named misch metal have been used. </p> / Thesis / Master of Engineering (MEngr)

The objective of this study was to investigate the diet-induced metabolic changes that affect the brain tissue of juvenile pigs with NAFLD. This study explored the liver- brain axis and metabolic markers in the frontal cortex (FC) affected by liver damage. 18 male (M) and 20 female (F) Iberian pigs were randomly allocated to 1 of 3 high-fructose high-fat liquid diets (lard, olive oil, and coconut oil) and fed for 10 consecutive weeks. “Healthy” Iberian pigs were fed a eucaloric diet to establish a physiological baseline. Protein precipitation extraction using ultra-performance liquid chromatography-tandem quadrupole mass spectrometry was performed for primary metabolic and bile acid assays on FC samples. Univariate data were analyzed by one-way ANOVA, which included diet as the fixed effect and both replicate and pen nested in the diet as random effects. A more pronounced separation was observed in the PLS-DA between the COC and LAR/OLI diets. LC, C14:0 SM, and kynurenine, all metabolites linked to brain health, showed elevated levels in COC-fed pigs and reduced levels in animals fed OLI. Each of the three diets demonstrated heightened ratios of secondary bile acids to primary bile acids, with OLI-fed pigs showing increased TDCA:CA and TLCA:CA ratios associated with neurodegeneration (MahmoudianDehkordi et al., 2019). In conclusion, results may suggest that LAR could represent a more favorable dietary intervention for promoting brain health in pediatric NAFLD but further research is required.

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Ascorbate (Asc) is a key antioxidant in preventing cardiovascular dysfunction during diseases exacerbated by altered shear stress. According to the literature endothelial responses to hypotonic shock share some characteristics with those induced by shear stress. Thus to study the physiological responses of endothelium to shear stress, the characterization of the Asc release by pig coronary artery endothelial cells in response to hypotonic shock was performed. The pig coronary artery endothelial cells that had been loaded with ^14C Asc and ^3H deoxyglucose, were exposed to buffers of varying osmolality for different time periods and the release of ^14C Asc and ^3H deoxyglucose was examined. Based on various parameters like relative release of ^14C Asc and ^3H deoxyglucose, their rate of release and protein loss, it was decided to use buffer of .67 percent osmolality for 2 min for these characterization studies. The Asc release was authentic and not a result of membrane damage. The hypotonic shock induced Asc release was not due to endogenously released ATP. The inhibition of ATP induced release by anion channel inhibitors niflumic acid and NPPB was complete but only partial in case of hypotonic shock induced release. The release was not inhibited under nominally Ca^2+ free conditions. Additive release by hypotonic shock and ATP or hypotonic shock and Ca^2+ ionophore A23187 suggests that there are two independent Asc release pathways. Asc release by two different mechanisms may help endothelial cells deal with stressful conditions efficiently and preserve endothelial function. / Thesis / Master of Science (MS)