Early and rapid prediction of patency of the infarct-related coronary artery by using left ventricular wall thickness as measured by two-dimensional echocardiography

AbstractObjectives. The aim of this study was to determine whether echocardiography can distinguish between persistent coronary occlusion and reperfusion.Background. There are no adequate clinical or noninvasive laboratory markers to accurately predict successful reperfusion in an acute myocardial infarction.Methods. In a closed chest swine model, the effect of reperfusion on myocardial wall thickness was studied by comparing a 150-min total coronary artery occlusion (group 1) with 120 min of occlusion followed by 30 min of reperfusion (group 2) in the area of risk as measured by echocardiography. Wall thickness was measured at baseline and at 90 and 150 min.Results. In group 1 (n = 4), there was no appreciable change in mean wall thickness from 90 min to 150 min of occlusion at either end-diastole or end-systole (0.54 ± 0.02 to 0.52 ± 0.03 cm, 0.55 ± 0.03 to 0.54 ± 0.03 cm, respectively; p = NS). In contrast, in group 2 (n = 6), an increase in mean wall thickness from 0.53 ± 0.02 to 0.97 ± 0.05 cm at end-diastole and from 0.56 ± 0.04 to 1.04 ± 0.07 cm at end-systole was found from 90 min of occlusion to 30 min of reperfusion (p < 0.001). Reperfusion resulted. in an increase in wall thickness of 83 ± 11% at end-diastole and 92 ± 17% at end-systole. In contrast, persistent coronary occlusion showed minimal changes of −3.0 ± 5% at end-diastole and −2.0 ± 6% at end-systole.Conclusions. This study confirms the hypothesis that an increase in wall thickness can accurately distinguish between reperfusion and permanent coronary occlusion

Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery

Abstract Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at th

Extended Lyman alpha emission around bright quasars

Quasars trace the most massive structures at high redshifts and their presence may influence the evolution of the massive host galaxies. We study the extended Lyman alpha emission line regions (EELRs) around seven bright, mostly radio-quiet quasars (QSOs) at 2.7<z<4.5, and compare luminosities with EELRs around radio-loud QSOs reported in the literature. Using integral field spectroscopy, we analyse the morphology and kinematics of the quiescent Lya EELRs around the QSOs. We find evidence for the presence of EELRs around four radio-quiet and one radio-loud QSO. All EELRs appear asymmetric and the optically brightest QSOs also have the brightest Lya nebulae. For the two brightest nebulae we find velocities between ~600 km s^-1 at the QSO position to ~200 km s^-1 at a distance of 3-4 arcsec from the QSO and surface flux densities up to 2-3*10^{-16} erg cm^-2 s^-1 arcsec^-2. The five EELRs have total Lya luminosities which correspond to ~0.5% of the luminosities from the QSOs broad Lya emission lines. This fraction is an order of magnitude smaller than found for EELRs around radio-loud, steep spectrum QSOs reported in the literature. While the nebulae luminosities are correlated with the QSO Lya luminosities, we find that nebulae luminosities are not correlated with the central QSO ionising fluxes. The presence of gas in the EELRs can be interpreted based on two competing scenarios: either from quasar feedback mechanisms, or from infalling matter. Apart from these two effects, the Lya flux around radio-loud objects can be enhanced due to interactions with the radio jets. The relatively fainter nebulae around radio-quiet QSOs compared to lobe-dominated radio-loud QSOs can be ascribed to this effect, or to significant differences in the environments between the two classes.Comment: 15 pages, A&A accepted. Section 4 revise

Potential Modes of Interaction of 9-Aminomethyl-9,10-dihydroanthracene (AMDA) Derivatives with the 5-HT 2A Receptor: A Ligand Structure-Affinity Relationship, Receptor Mutagenesis and Receptor Modeling Investigation

The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT2A receptor models that suggest that members of the DOB-like series can bind to the receptor in two distinct modes that correlate with the compounds’ functional activity. Automated ligand docking and molecular dynamics suggest that all of the AMDA derivatives, the parent of which is a 5-HT2A antagonist, bind in a fashion analogous to that for the sterically demanding antagonist DOB-like compounds. The failure of the F3406.52L mutation to adversely affect the affinity of AMDA and the 3-bromo derivative is consistent with the proposed modes of orientation. Evaluation of ligand-receptor complex models suggest that a valine/threonine exchange between the 5-HT2A and D2 receptors may be the origin of selectivity for AMDA and two substituted derivatives

Prospectus, November 14, 1984

YOUR COURAGE, DEDICATION AND SACRIFICES ARE NOT FORGOTTEN; Parkland Veterans Honored; Women Veterans receive deserved recognition; Landslide of volunteers hoped for; Recognition needed all year; Blood Drive November; Best Sellers in the Library; PC Happenings; Original performance at Parkland; How to Live to be 1000 is retirees topic; Gallery hosts touring exhibit; EMT refresher workshop scheduled; Parkland, GM cooperate; Student job prospects look great; Man on Street...Question: Did you vote on Tuesday, and whatever you answer, why?; Creative Corner...especially for you!; Doom story...The cataclysm begins; Fluffy White Clouds; Nursing on a psychiatric floor; Ember of Empathy; With Feeling; Hurry Monday!; Contradiction versus deception; the eve of destruction; Homo Sapiens; Essence; Straub has not even begun to hit his stride; Good music sometimes underrated; Anothe Bowie hit; Classifieds; Britter\u27s Knights devastate USA Adidas 113-55 in opener; Lady Cobras finish spectacular season with 39-9-1 clipping; Knights down Nonames 100-30; Cobra cagers have flexibility and depth for \u2784-\u2785 campaign; Stater, Phillips supply one-two punch for Cobrashttps://spark.parkland.edu/prospectus_1984/1004/thumbnail.jp

Bcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage

AbstractThe therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents

Prospectus, October 17, 1984

SPORTS FEATURE LADY COBRAS TAKE IV INVITATIONAL; Assistance available; many services offered; Speech team takes honors; Goal is to overthrow the \u27masculine mind\u27; PC Happenings; Parkland hosts Foley exhibit; TV for Parents and Kids debuts; Workshop focuses on sexual abuse of young children; Career restructuring focus of workshop; Hearing topic for retirees; International students enrich us all; Did You Know...; Creative Corner...Especially for you!!; Paper Dolls Souls; History; Depression; Alone; Being & Becoming; So Much; Breakable Item; Thumbism; Diary; \u27Doom Story\u27-the terror escalates; Excerpts from Some Late Evening Thoughts While Anticipating That First Great Thunderstorm of a Dry Month; Midnight; Strength or weakness; The Ultimate Weapon; Photographer captures essence of traditional, contemporary Latin America; Celebrate the Arts Week; WPCD DJ likes job, Parkland; TV programs for parents scheduled; Classifieds; Peter Pan syndrome causes relationship problems; Experience Blues Explosion; Two comedians better than one; 1978 was cruel summer for Sullivan; 1984 is proving to be a sweet fall; Drive on to educate-issues important; Powell wins invitational; Stewart places 4th; Peterson prefers to use an eight-ironhttps://spark.parkland.edu/prospectus_1984/1008/thumbnail.jp

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD). No liver injury has been observed with tolvaptan treatment in healthy subjects and in non-ADPKD indications, but ADPKD clinical trials showed evidence of drug-induced liver injury (DILI). Although all DILI events resolved, additional monitoring in tolvaptan-treated ADPKD patients is required. In vitro assays identified alterations in bile acid disposition and inhibition of mitochondrial respiration as potential mechanisms underlying tolvaptan hepatotoxicity. This report details the application of DILIsym software to determine whether these mechanisms could account for the liver safety profile of tolvaptan observed in ADPKD clinical trials. DILIsym simulations included physiologically based pharmacokinetic estimates of hepatic exposure for tolvaptan and2 metabolites, and their effects on hepatocyte bile acid transporters and mitochondrial respiration. The frequency of predicted alanine aminotransferase (ALT) elevations, following simulated 90/30 mg split daily dosing, was 7.9% compared with clinical observations of 4.4% in ADPKD trials. Toxicity was multifactorial as inhibition of bile acid transporters and mitochondrial respiration contributed to the simulated DILI. Furthermore, simulation analysis identified both pre-treatment risk factors and on-treatment biomarkers predictive of simulated DILI. The simulations demonstrated that in vivo hepatic exposure to tolvaptan and the DM-4103 metabolite, combined with these 2 mechanisms of toxicity, were sufficient to account for the initiation of tolvaptan-mediated DILI. Identification of putative risk-factors and potential novel biomarkers provided insight for the development of mechanism-based tolvaptan risk-mitigation strategies

A low density of 0.8 g/cc for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees). The asteroid 617 Patroclus is the only known binary Trojan (Merline et al. 2001). The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system centre of mass, describing roughly a circular orbit. Using the orbital parameters, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8 g/cc. The components of Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the solar system.Comment: 10 pages, 3 figures, 1 tabl