Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function. P-CgA after a major burn injury is an independent and better predictor of organ dysfunction assessed as SOFA score than the traditionally used TBSA% burned. The results also suggest that the extent of neuroendocrine activation is related to organ dysfunction, and this motivates a more extensive effort to evaluate P-CgA as a prognostic marker with respect to mortality and long-term outcome. P-NT-proBNP exhibited a complex pattern with considerable inter-individual and day-to-day variations. Values of P-NT-proBNP were related to size of burn, water accumulation and systemic inflammatory response. A considerable covariation with trauma response and SOFA scores was observed in day by day analyses, but with weight change only on day 2. Maximum P-NT-proBNP showed a stronger correlation with SOFA score on day 14, with mortality, and with LOS, than did age and TBSA% burned. High values were also independent predictors of all subsequent SOFA scores up to two weeks after injury. P-NT-proBNP and NT-proANP reflect and predict organ function after burn injury similarly, notwithstanding a significantly larger intra-individual variability for P-NT-proBNP. P-NT-proBNP, but not NT-proANP, reflects the systemic inflammatory trauma response. Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was, at least in part, related to its effect on organ function. This thesis points to the fact that the stress response is richly interwoven, and cannot be adequately assessed by one biomarker only. All biomarkers studied here can be viewed as representing efferent limbs of the stress reaction, and they would need to be supplemented by biomarkers representing individual physiologic responses that follow the stress signaling.

It has been known that anthracycline-based chemotherapy has the potential to cause cardiac dysfunction in breast cancer patients; however, recently evidence has shown that the addition of trastuzumab increases this risk. The study objective was to compare the cost-effectiveness of monitoring for cardiotoxicity with B-type natriuretic peptide (BNP), multi-gated acquisition scanning (MUGA), echocardiography (ECHO) or no monitoring from a payer’s prospective. Cost-effectiveness was compared between alternatives using an incremental cost-effectiveness ratio with outcomes of 1) quality-adjusted life-years and 2) percentage of patients diagnosed with each monitoring strategy. Costs estimates (in 2010 U.S. Dollars) of each strategy (obtained from the Center for Medicare and Medicaid Services website [www.cms.gov]) included the cost of the test, cost of treating heart failure once discovered (which includes medications, routine office visits, medication management) and the cost of potential acute care (which includes emergency department visits and hospitalizations). Estimates for the probabilities of heart failure development, disease progression, need for acute care, and mortality, as well as utility estimates for all disease stages were obtained from published literature. A 15-year time-frame was used with a 3% discount rate for both costs and QALYs. In the base-case analysis, the average costs and QALYs for monitoring patients were $10,062/ 6.92 QALY, $13,627/4.22 QALY, $14,739/ 6.61 QALY and $15,656/ 6.49 QALY for BNP, No Monitoring, ECHO and MUGA respectively. When comparing all alternatives to BNP, the ICER values were negative, indicating that BNP was the dominant monitoring strategy. Percent detection was similar between the three monitoring methods [21-22 % for HER-2(-) and 30-31% for HER-2(+) patients]. Again BNP was dominant over the other monitoring strategies. Sensitivity analyses were robust to changes in discount rate, probability of patients testing HER-2 (+), probability of patients being diagnosed in an asymptomatic stage, incidence of cardiac dysfunction in patients receiving anthracycline therapy ± trastuzumab and estimate of disutility associated with additional testing. A probabilistic sensitivity analysis conducted via Monte Carlo simulation led to the same conclusion as the base-case analysis; BNP was the dominant strategy over all monitoring alternatives. / text

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Natriuretic peptides are a group of hormones, including atrial-, brain-, and C-type- natriuretic peptides (ANP, BNP, CNP). BNP can bind to two NP receptors (NPRs) denoted NPR-A (activates guanylyl cyclase) and NPR-C (activates inhibitory G- proteins). This study investigated the electrophysiological effects of BNP on isolated mouse atrial myocytes. Current-clamp experiments show that BNP had no effect on action potential (AP) parameters in basal conditions; however, when pre-stimulated with the ?-adrenergic receptor agonist isoproterenol (ISO), BNP prolonged AP duration. Voltage-clamp experiments demonstrate that BNP increased L-type calcium current (ICa,L) in the presence of ISO without altering cardiac potassium currents. The BNP effect on ICa,L was blocked by A71915 (a selective NPR-A antagonist), maintained in myocytes lacking NPR-C receptors and blocked by the phosphodiesterase-3 (PDE-3) inhibitor milrinone. These data demonstrate that BNP prolongs AP duration and increases ICa,L in atrial myocytes by activating NPR-A, increasing intracellular cGMP, and inhibiting PDE- 3.

<p>Plant natriuretic peptides (PNPs) are a novel class of extracellular, systemically mobile molecules that elicit a number of plant responses important in homeostasis and growth. Natriuretic peptides were first identified in vertebrates where they play a role in the regulation of salt and water balance. Subsequent experimental investigations have identified the presence of a natriuretic peptide hormone system in plants. While PNPs have been implicated in various physiological responses such as stomatal guard cell movements and regulation of net water uptake, its biological role has remained elusive. Here we have used co-expression and promoter content analysis tools to understand the biological role of the Arabidopsis thaliana PNP (AtPNP-A). The analysis of AtPNP-A and its co-expressed genes revealed that genes annotated as part of the systemic acquired resistance (SAR) pathway were over-represented, thus suggesting that AtPNP-A may function as a component of plant defense responses and specifically, SAR. The results further show that AtPNP-A shares many characteristics with pathogenesis related (PR) proteins in that its transcription is strongly induced in response to pathogen challenges, thus implying a newly described role for AtPNP-A in pathogen attack. Additional tissue expression analysis also indicated distinct localization of PNP activity in sepals and transcriptional meta-analysis showed that AtPNP-A may play a role in starch breakdown. Therefore, together with the finding that AtPNP-A plays a role in regulating phloem transport, we also hypothesize that AtPNP-A may play a role in phloem unloading in sepals to assist processes such as seed formation in plants. In plants, the second messenger, guanosine 3&rsquo / ,5&rsquo / -cyclic monophosphate (cGMP) mediates a whole range of important processes including salinity tolerance, disease resistance, drought tolerance and responses to light. Since PNPs regulate water and salt homeostasis via a cGMP-dependent signaling pathways, it is thus important to analyse the transcriptome induced by the second messenger (cGMP) in Arabidopsis thaliana to give a better understanding of its mechanism of action. This study was also supplemented by the analysis of the gibberellic acid (GA) dependent transcriptome, since cGMP also plays a role its transcription pathway. This data analysis, together with promoter content investigation, revealed that genes upregulated after cGMP treatment and down-regulated in the GA insensitive mutant (ga1-3) were enriched with a GA response element (GARE), while no GARE enrichment were observed in genes up-regulated in the ga1-3 mutant. These findings suggest that GARE is indicative of GA-induced and cGMP-dependent transcriptional up-regulation. Gene ontology analysis confirmed previous reports that cGMP is involved in ion homeostasis and indicated that the transcriptional cGMP response is bi-polar in the sense that both genes up- and down-regulated in response to cGMP is involved in cation transport. Additionally, ab initio analysis of genes transcriptionally dependent on cGMP identified CHX8 as a hub gene and promoter content of CHX8 co-expressed genes show enrichment of the GARE motif. The fact that CHX8 has its highest expression levels during male gametogenesis and pollen tube growth, together with our findings, suggest that GA-induced and cGMP- dependent genes may play a key role in ion and water homeostasis in the male gametophyte. Finally, we propose that the type of analysis undertaken here can yield new insights into gene regulation networks and inform experimental strategies to unravel complex transcription regulatory systems under different developmental and stimulus specific conditions.</p>

C-type Natriuretic Peptide (CNP), a relatively new member of the natriuretic peptide family, is found throughout the central nervous system. Circumstantial evidence associates CNP with learning and memory, as its expression is highest in brain regions known to be involved in memory and associated with hippocampal physiology. Here, the first study housed rats in an enriched environment, regarded as providing an 'informal' learning experience, for either 14 or 28 days of housing in enrichment in six regions of interest, which was attributed to changes in the degradation of CNP. The second study examined a group of rats trained on object -recognition task – the bow-tie maze. A difference was found in CNP production in the limbic medial prefrontal cortex over repeated exposures to novel objects relative to controls that received 'yoked learning' an exposure only to the test room. CNP concentrations also tended to be lower in rats with better levels of discrimination between familiar objects. Together, these studies provide some initial evidence that CNP influences learning –induced plasticity in the intact brain.

No description available.

Dissertation (Ph.D.)--University of South Florida, 2006. / Title from PDF of title page. Document formatted into pages; contains 142 pages. Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 1997. / "May 1997" Typescript. Vita. Includes bibliographical references (l. 117-131). Also available on the Internet.

Universiẗat, Diss., 2004--München.