The role of nitric oxide in testosterone-induced vasodilation in pig coronary arteries and rat thoracic aorta

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 25-26).Several studies have provided evidence that the administration of testosterone to vascular tissue causes vasodilation (Costarella, Yue). This study examines the role of nitric oxide (NO) as a potential mechanism of testosterone-induced vasodilation. This report includes a functional study that indirectly examined the role of NO and a study to determine an appropriate experimental set up to directly measure NO in vitro. In the functional study, the right coronary arteries and left anterior descending arteries from exercised and sedentary, female Yucatan Mini-Swine were treated with N[]-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase (NOS). Following blockade of NOS, seven cumulative doses (5 []M to 300 []M) of testosterone produced dose-dependent relaxation and resulted in maximal relaxation. This confirms that NO is not the only mediator of testosterone-induced vasodilation. In addition, this study suggests that NO plays a significant role in the mechanism of testosterone-induced dilation in coronary arteries of exercised pigs, while it plays little or no role in the coronary arteries of sedentary pigs. The second part of this study includes the determination of an appropriate experimental set up to directly measure NO release from the thoracic aorta of male and female Sprague-Dawley rats. The experimental set up has to account for the NO-sensitive probe being temperature sensitive, and responding to mechanical stress, acetylcholine (ACh), and background noise. An in vitro experimental set up involving the insertion of a 30 []m probe (World Precision Instruments) into the lumen of the rat thoracic aorta appears to be the most promising method. To test the viability of the set up, the response of the probe to acetylcholine was measured. A detectable response has not been measured, which indicates that the probe should not respond in the presence of tissue unless NO is released. To date, detectable measurements of NO from tissue following the administration of ACh have not been made. This indicates that the experimental set up needs further modification. In combination with functional studies, the direct measurement of NO could definitively determine the role of NO in testosterone-induced vasodilation

Quercetin and Chlorogenic Acid Mitigate DSS-Induced Changes in Expression of Select Pro-Inflammatory Cytokines and Short Chain Fatty Acid Transporter Genes

Quercetin (Q) and chlorogenic acid (CA), two bioactive compounds found in stonefruits, may protect against inflammation and cancer because of anti-cancer, anti-oxidant, and anti-inflammatory properties. Since these compounds reach the colon undigested, they affect the luminal environment before they are metabolized by the microbiota and transported into epithelial cells. We hypothesized that Q and CA may suppress expression of pro-inflammatory molecules, alter the luminal environment, and alter the cell cycle, thereby protecting against injury/colitis. To test this hypothesis, 63 male weanling rats were given one of three diets (basal, 0.45% Q, 0.05% CA). After 3 wk of acclimation, colitis was induced in 11 rats/diet [3% dextran sodium sulfate (DSS), 48 h, 3 treatments, 2 wk separation] and 10 rats/diet served as control (0% DSS). All rats were terminated at wk 9. Measurements included: fecal moisture content, fecal short chain fatty acid (SCFA) concentrations (gas chromatography), epithelial injury and inflammation in the distal colon, proliferation (PCNA), and NF-kappaB activity (ELISA method) and gene expression (real time RT-PCR) in mucosal scrapings. Fecal moisture content was significantly increased by DSS exposure (p<0.05), and never returned to control levels. Fecal SCFA concentrations also increased with DSS (acetate, p<0.05; butyrate, p<0.05). Increased SCFA concentrations could indicate decreased SCFA uptake. Experimental diets were able to mitigate DSS-induced decreases in SLC5A8 (SCFA transporter) expression. DSS significantly increased injury (p<0.0001) and inflammation (p<0.01) scores. Compared to the basal diet, CA decreased NF-kappaB activity in DSS-treated rats (p<0.05). Q and CA may maintain healthy regulation of NF-kappaB through maintaining expression levels of IkappaBalpha and Tollip, molecules that inhibit NF-kappaB activation. Q and CA mitigated DSS-induced increases in pro-inflammatory cytokine expression, specifically IL-1. Q enhanced expression of injury-repair molecule FGF-2 (p<0.01), but neither diet nor DSS treatment altered proliferation. Although Q and CA did not protect against DSS-induced increases in injury and inflammation scores or fecal SCFA concentrations, their influence on expression of injury repair molecules, pro-inflammatory cytokines, SCFA transport proteins, and NF-kappaB inhibitory molecules suggests beneficial influences on major pathways involved in DSS-induced injury/inflammation. The combined benefit of these compounds could have additive/synergistic effects and, therefore, deserve further examination

Improved cardiac management with a disease management program incorporating comprehensive lipid profiling.

Abstract The objective of this study was to evaluate the improved effectiveness of a disease management treatment protocol incorporating comprehensive lipid profiling and targeted lipid care based on lipid profile findings in patients with ischemic heart disease (IHD) or congestive heart failure (CHF) enrolled in a managed care plan. This retrospective cohort study, conducted over a 2-year period, compared outcomes between patients with a standard lipid profile to those evaluated with a comprehensive lipid profile. All adult members of the WellMed Medical Management, Inc. managed care health plan diagnosed with IHD or CHF, and continuously enrolled between July 1, 2006 and June 30, 2008, were included in the study. Cases were defined as those who had at least 1 comprehensive lipid test (the VAP [vertical auto profile] ultracentrifuge test) during this period (n=1767); they were compared to those who had no lipid testing or traditional standard lipid testing only (controls, n=289). Univariate statistics were analyzed to describe the groups, and bivariate t tests or chi-squares examined differences between the 2 cohorts. Multivariate regression analyses were performed to control for potential confounders. The results show that the case group had lower total costs ($4852.62 vs.$7413.18; P=0.0255), fewer inpatient stays (13.1% vs. 18.3% of controls; P=0.0175) and emergency department visits (11.9% vs. 15.6% of controls; P=0.0832). Prescription use and frequency of lipid measurement suggested improved control resulting from a targeted approach to managing specific dyslipidemias. A treatment protocol incorporating a comprehensive lipid profile appears to improve care and reduce utilization and costs in a disease management program for cardiac patients. (Population Health Management 2012;15:46-51)

Studies of a three-stage dark matter and neutrino observatory based on multi-ton combinations of liquid xenon and liquid argon detectors

We study a three stage dark matter and neutrino observatory based on multi-ton two-phase liquid Xe and Ar detectors with sufficiently low backgrounds to be sensitive to WIMP dark matter interaction cross sections down to 10E-47 cm^2, and to provide both identification and two independent measurements of the WIMP mass through the use of the two target elements in a 5:1 mass ratio, giving an expected similarity of event numbers. The same detection systems will also allow measurement of the pp solar neutrino spectrum, the neutrino flux and temperature from a Galactic supernova, and neutrinoless double beta decay of 136Xe to the lifetime level of 10E27 - 10E28 y corresponding to the Majorana mass predicted from current neutrino oscillation data. The proposed scheme would be operated in three stages G2, G3, G4, beginning with fiducial masses 1-ton Xe + 5-ton Ar (G2), progressing to 10-ton Xe + 50-ton Ar (G3) then, dependent on results and performance of the latter, expandable to 100-ton Xe + 500-ton Ar (G4). This method of scale-up offers the advantage of utilizing the Ar vessel and ancillary systems of one stage for the Xe detector of the succeeding stage, requiring only one new detector vessel at each stage. Simulations show the feasibility of reducing or rejecting all external and internal background levels to a level <1 events per year for each succeeding mass level, by utilizing an increasing outer thickness of target material as self-shielding. The system would, with increasing mass scale, become increasingly sensitive to annual signal modulation, the agreement of Xe and Ar results confirming the Galactic origin of the signal. Dark matter sensitivities for spin-dependent and inelastic interactions are also included, and we conclude with a discussion of possible further gains from the use of Xe/Ar mixtures

WOSMIP II- Workshop on Signatures of Medical and Industrial Isotope Production

Medical and industrial fadioisotopes are fundamental tools used in science, medicine and industry with an ever expanding usage in medical practice where their availability is vital. Very sensitive environmental radionuclide monitoring networks have been developed for nuclear-security-related monitoring [particularly Comprehensive Test-Ban-Treaty (CTBT) compliance verification] and are now operational