"Bleeding Hearts: How Revising a Mediocre Screenplay Helped Me Find My Voice" examines the development of Joseph Pudas’ feature screenplay Bleeding Hearts. It tracks the course of how Bleeding Hearts was written and provides a candid look at the creative process, specifically how the writing and rewriting of this particular screenplay helped Pudas discover truths about his sensibilities and limitations. In his two years at the University of Texas, Pudas took the opportunity to experiment with different genres and tones in order to pinpoint his strengths and weaknesses as a screenwriter. Bleeding Hearts was initially intended as a straightforward romantic comedy set in the political sphere, but early on Pudas encountered difficulties with tone and genre (romantic comedy vs. cynical political satire) that would continue to persist throughout the bloated first draft. With the assistance of his peers and thesis committee, Pudas reworked the concept and wrote a more streamlined, romantic draft closer in line to what he originally envisioned the project to be. / text

Inotropic support for the failing myocardium as the therapy for xi congestive heart failure (CHF) is intended to achieve an increase in cardiac output via positive responses in myocardial contractility and vasodilation. A novel approach to differentiate these two responses is the use of an animal with an implanted total artificial heart (TAH). Three inotropic drugs, dobutamine, enoximone, and pimobendan, were tested in eight animals with their natural heart intact and five animals implanted with a TAH. Baseline values of the TAH and natural heart (NH) were compared to determine their hemodynamic similarities. Each of the three drugs was given randomly to the animals in dosages similar to human clinical doses. Peak responses were recorded and analyzed. All three drugs caused an increase in contractility and cardiac output in the NH animals. Dobutamine and pimobendan also caused a significant increase in heart rate at higher dosages whereas enoximone did not. Dobutamine caused an increase in left ventricle work, as did pimobendan at the first dose given; at higher doses of pimobendan, the left ventricular work returned to baseline. However, at the doses tested, the left ventricular stroke work during enoximone administration decreased. Vasodilation (the only drug stimulation response in the TAH model) was also observed with the administration of the drugs in T AH animals, and all three caused decreases in systemic and pulmonary vascular resistance. Dobutamine and pimobendan caused an increase in left and right atrial pressures (because of the mechanical heart not being adjusted to compensate the increased return). There was also a reduction in systemic and pulmonary resistance. Enoximone caused severe pulmonary hypertension in the TAH animals, possibly due to stimulus of platelets to release vasoconstrictive substances. Thus, dobutamine, enoximone, and pimobendan significantly contribute to increases in output by vasodilation in animals with a natural heart. Similarly, dobutamine and pimobendan's vasodilatory action is identified in an animal with a TAH. However, enoximone's hypertensive action on the pulmonary vasculature of a TAH animal may offer an insight to the toxicity of enoximone when used after recent surgery.

No description available.

Class of 2009 Abstract / OBJECTIVES: The objective of this study was to characterize the Hyaluronidase (HYA) gene family throughout gestational development of murine hearts to provide greater insight regarding its role in cardiac morphogenesis. METHODS: Microdissection of murine embryos was accomplished to extract embryonic heart tissue. RNA was extracted using the standard Trizol protocol. cDNA templates were created using a standard protocol. Polymerase chain reaction (PCR) was used to verify presence of HYA, isolate a sample for insertion into a cloning plasmid to make a recombinant clone. A TOPO cloning reaction followed by a double DNA digest was accomplished to verify gene sequencing and orientation in the clone. SYBR Green real time RT- PCR was used to quantify gene expression relative to 18S RNA. RESULTS: RT-PCR provided qualitative data indicating HYA1, HYA2, and HYA3 are present at all observed time points (E8.5, E9.5, E10.5, E11.5, E12.5, E13.5, E14.5, E15.5, and E16.5). Real time RT-PCR data results characterizing relative expression for HYA2: E9.0 (Rel. Exp. = 1.00; SD = 0), E10.5 (Rel. Exp. = 1.33; SD = 0.577), E12.5 (Rel. Exp. = 2.00; SD = 0), E13.5 (Rel. Exp. = 2.66; SD = 0.577), E14.5 (Rel. Exp. = 3.00; SD = 0), E15.0 (Rel. Exp. = 2.00; SD = Error). CONCLUSIONS: HYA1, HYA2, and HYA3 are present at al time points observed in embryonic heart tissue. Relative expression of HYA2 progressively increased from E9.0 until E14.5 and then started tapering downward at time point E15.0.

The Langendorff perfused murine heart has become an increasingly important research model in cardiovascular physiology and pharmacology. However, the model remains relatively poorly characterised when compared with the widely employed rat preparation. The purpose of the research within this thesis was initially two-fold: 1) to characterise the functional and substrate-dependent properties of the murine model; and 2) to characterise the relationships between glycolysis, ischaemic tolerance and adenosine-mediated cardioprotection in the mouse. Initial studies, confirmed by simultaneous/subsequent work in other laboratories, revealed the frequent occurrence of regular cyclic oscillations in contractile function and coronary flow in glucose-perfused isovolumically contracting hearts. This phenomenon (labelled 'cycling') was unaltered by inhibition of ?-adrenergic receptors, prostaglandins, and nitric oxide synthase. However, A1/A2 adenosine receptor agonism did abolish the oscillations in flow and reduced contractile oscillations by 50%. Importantly, cycling was eliminated by addition of 50 IU/l insulin to perfusion fluid, or provision of 5 mM pyruvate as a co-substrate with glucose. These data suggest that functional 'cycling' in glucose-perfused murine hearts likely occurs as a result of a mismatch between substrate metabolism (energy supply) and myocardial energy demand. It may be that glycolysis with exogenous glucose is insufficient to ensure appropriate matching of myocardial energy supply and demand. For this reason, it is advisable to employ a co-substrate such as pyruvate in studies of murine hearts. Further studies performed within this thesis generally employ this co-substrate addition. Addition of pyruvate as co-substrate removes 'cycling' but is also known to inhibit/modify glycolysis, which may affect ischaemic tolerance and/or cardioprotection mediated by adenosine. Experiments throughout this thesis demonstrated that pyruvate-perfusion improved tolerance to both ischaemia (delayed time to onset of ischaemic contracture; TOC) and reperfusion (reduced diastolic dysfunction and cell death). The delay in TOC as a result of pyruvate-perfusion also suggests that contracture is not solely influenced by anaerobic glycolysis (as outlined in current paradigms). To test the relevance of glycolysis to ischaemic injury hearts were subjected to various forms of glycolytic inhibition. Glycolysis was inhibited by use of 10 mM pyruvate, (iodoacetic acid) IAA treatment, and glycogen depletion by pre-ischaemic substrate-free perfusion (all groups employing pyruvate as sole-substrate). Each form of glycolytic modification resulted in significant delays in TOC, in complete contrast to findings from other models and species. Glycogen depletion also reduced the peak level of contracture. These findings indicate that the mouse is either unique in terms of substrate metabolism and mechanisms of contracture (an unlikely possibility), or raise serious questions regarding current models of contracture development during ischaemia (theorised to be delayed by prolonging anaerobic glycolysis). Modification of glycolysis also altered post-ischaemic outcome, with pyruvate perfusion and glycogen depletion both enhancing functional recoveries. However, IAA treated hearts, despite near-identical ischaemic tolerance (ie contracture development) to pyruvate-perfused hearts, displayed very poor functional recovery, which was below that for all other groups. These data clearly reveal that blocking glycolysis improves tolerance to ischaemia (as evidenced by reduced contracture), provide evidence of dissociation of ischaemic injury or contracture from post-ischaemic recovery, and confirm the key importance of glycolysis in enhancing recovery from ischaemia. Since tolerance to ischaemia/reperfusion was shown to be glycolysis dependent, and since it has been theorised that adenosine protects hearts through modulating glycolysis, the relationships between glycolytic inhibition and adenosine-mediated cardioprotection was tested. In a number of studies, exogenously applied adenosine was shown to protect both glucose- and pyruvate-perfused hearts (supporting no dependence of adenosinergic protection on glycolysis). However, to more equivocally test the role of glycolysis effects of IAA were studied and were shown to markedly limit protection with adenosine. The effects of adenosine during ischaemia were abolished by IAA treatment, and effects on post-ischaemic recovery were reduced (but not eliminated). Similar results were acquired for protection with endogenous adenosine (using iodotubercidin to block adenosine phosphorylation). Collectively, these data reveal that adenosinergic protection during ischaemia depends entirely upon glycolysis while protection during reperfusion likely involves glycolysis dependent and independent processes. However, glycolysis is required for full recovery of function during reperfusion. Further studies assessed the involvement of glycolysis in cardioprotection afforded by transgenic A1 adenosine receptor (A1AR) overexpression. It was found that pyruvate-perfusion provided the same protection as A1AR overexpression, and the two responses (to pyruvate and A1AR overexpression) were not additive. Thus, it is probable that common mechanisms are targeted in both responses (likely glycolysis). Finally, the effects of adenosine and pyruvate on oxidant injury were studied, testing whether interactions between adenosine and pyruvate observed in prior work within this thesis could be explained by alterations in anti-oxidant responses. It was found that adenosine has quite profound anti-oxidant responses in glucose-perfused hearts, with very selective effects on markers of damage. Pyruvate also had some anti-oxidant effects but interestingly it reduced the anti-oxidant effects of adenosine. In conclusion, the work entailed within this thesis demonstrates that the isolated mouse heart model may possess unique properties and should be further characterised by potential users in order to improve its utility, and the reliability of experimental findings (chiefly when studying ischaemia-reperfusion). Other work within thesis demonstrates that modification of glycolysis is important in dictating recovery from ischaemia-reperfusion, and also impacts on adenosine-mediated protection (principally but not exclusively during ischaemia itself). The manner in which glycolysis is modified and contributes to protection remains unclear.

Thesis (D. Min.)--Gordon-Conwell Theological Seminary, 2007. / Includes bibliographical references.

No description available.

Tweedle-Dee and Tweedle-Dum is the first edition of a book for all audiences but especially targeting children. The story follows Tweedle-Dee and Tweedle-Dum as they explore wonderland, encountering famous characters including the Queen of Hearts, the Catepillar, the Mad Hatter, the March Hare, and the White Rabbit, as well as a set of new characters at well. The account is entirely fictional, and any character or event that bares any resemblance to a real person or something that happened in real life is completely and only a coincidence. I would like to give a special thanks to all my friends that helped in the writing process; I would write an extensive list, but not everyone has a facebook and I don't want to spell anyone's name wrong. Thanks guys. The book is meant to be a fun and light read; enjoy.

The signaling mechanisms for muscarinic receptor-mediated vasoconstriction in coronary resistance arteries were studied in KCl-arrested isolated rat hearts perfused at a constant flow rate. The cholinergic agonists acetylcholine and bethanechol were given by bolus injection or constant infusion. The coronary vascular resistance was monitored by measuring the changes in perfusion pressure. The selective muscarinic agonist bethanechol caused a similar vasoconstrictor response as ACh, but with less potency and efficacy. Bolus injection of bethanechol evoked a phasic vasoconstriction in a dose-dependent manner, while infusion of bethanechol evoked a tonic vasoconstriction without producing tachyphylaxis. Coronary vascular responses to bethanechol were further examined in the absence and presence of a specific inhibitor or blocker for the potential signaling components. The bethanechol-induced phasic vasoconstriction was eliminated by perfusion with a Ca2+ -free medium. The maximal vasoconstriction to bethanechol was suppressed by 31% in the presence of the Ca2+ -dependent Cl- -channel blocker A-9-C. The L-type voltage-operated Ca2+ channel blocker nifedipine decreased the maximal constrictor response to bethanechol by 59%, while the putative receptor-operated Ca 2+ channel blocker SK&F 96365 converted this vasoconstriction into vasodilation which was not affected by the nitric oxide synthase inhibitor L-NAME. Coronary vascular responses to bethanechol were almost abolished by a combination of nifedipine and SK&F 96365. The protein kinase C inhibitor chelerythruine reduced bethanechol-evoked peak vasoconstriction by 79%. The bethanechol-induced tonic vasoconstriction was rapidly converted into vasodilation by the concomitant infusion of SK&F 96365 or nifedipine, but the simultaneous infusion of chelerythrine gradually attenuated this response. These data suggest that the novel receptor-operated Ca2+ channel, voltage-operated Ca2+ channel, and protein kinase C are the most crucial signaling components for muscarinic receptor-mediated coronary vasoconstriction in the isolated rat heart. Extracellular Ca 2+ influx via receptor-operated Ca2+ channels and voltage-operated Ca2+ channels is essential to both phasic and tonic vasoconstrictor responses to bethanechol. Protein kinase C plays a pivotal role in the regulation of bethanechol-evoked vasoconstriction by sensitizing the contractile apparatus and modulating the activity of Ca 2+ channels.

Easy Hearts is a novel set in contemporary Texas. Justin Borchard, just paroled after three and-a-half years in prison, returns to his hometown in East Texas where his wife, Melinda, has been tending bar at the Shortleaf Inn. After Melinda confesses to a brief affair with a local oil executive named Waylon Goodwin, an affair she has ended, and facing limited prospects in their hometown, Melinda and Justin make the hard choice to accept a proposition from Waylon: they will leave home for Hearts County, a desolate swatch of hardpan in the Permian Basin of West Texas, where Waylon has arranged steady work for Justin in the oil fields. When Melinda vanishes from their trailer home, Justin must re-cross Texas, avoiding the law and dangerous railway men, so he can confront his troubled past, his increasingly mysterious wife, and the secrets sown around them.