Communications Biophysics

Contains reports on one research project

Communications Biophysics

Contains reports on one research project.National Institutes of Health (Grant 2 TO1 GM01555-06

Studies of Prevention, Treatment and Mechanisms of Heart Failure in the Aging Spontaneously Hypertensive Rat

The spontaneously hypertensive rat (SHR) is an animal model of genetic hypertension which develops heart failure with aging, similar to man. The consistent pattern of a long period of stable hypertrophy followed by a transition to failure provides a useful model to study mechanisms of heart failure with aging and test treatments at differing phases of the disease process. The transition from compensated hypertrophy to failure is accompanied by changes in cardiac function which are associated with altered active and passive mechanical properties of myocardial tissue; these events define the physiologic basis for cardiac decompensation. In examining the mechanism for myocardial tissue dysfunction, studies have demonstrated a central role for neurohormonal activation, and specifically the renin-angiotensin-aldosterone system. Pharmacologic attenuation of this system at differing points in the course of the process suggests that prevention but not reversal of myocardial tissue dysfunction is possible. The roles of the extracellular matrix, apoptosis, intracellular calcium, beta-adrenergic stimulation, microtubules, and oxygen supply-demand relationships in ultimately mediating myocardial tissue dysfunction are reviewed. Studies suggest that while considerable progress has been made in understanding and treating the transition to failure, our current state of knowledge is limited in scope and we are not yet able to define specific mechanisms responsible for tissue dysfunction. It will be necessary to integrate information on the roles of newly discovered, and as yet undiscovered, genes and pathways to provide a clearer understanding of maladaptive remodeling seen with heart failure. Understanding the mechanism for tissue dysfunction is likely to result in more effective treatments for the prevention and reversal of heart failure with aging. It is anticipated that the SHR model will assist us in reaching these important goals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45828/1/10741_2004_Article_391524.pd

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

Suzaku Observations of Luminous Quasars: Revealing the Nature of High-Energy Blazar Emission in Quiescent States

We present the results from the Suzaku X-ray observations of five flat-spectrum radio quasars (FSRQs), namely PKS0208-512, Q0827+243, PKS1127-145, PKS1510-089 and 3C 454.3. All these sources were additionally monitored simultaneously or quasi-simultaneously by the Fermi satellite in gamma-rays and the Swift UVOT in the UV and optical bands, respectively. We constructed their broad-band spectra covering the frequency range from 10^14 Hz up to 10^25 Hz, and those reveal the nature of high-energy emission of luminous blazars in their low-activity states. The analyzed X-ray spectra are well fitted by a power-law model with photoelectric absorption. In the case of PKS0208-512, PKS1127-145, and 3C 454.3, the X-ray continuum showed indication of hard-ening at low-energies. Moreover, when compared with the previous X-ray observations, we see a significantly increasing contribution of low-energy photons to the total X-ray fluxes when the sources are getting fainter. The same behavior can be noted in the Suzaku data alone. A likely explanation involves a variable, flat-spectrum component produced via inverse-Compton (IC) emission, plus an additional, possibly steady soft X-ray component prominent when the source gets fainter. This soft X-ray excess is represented either by a steep powerlaw (photon indices Gamma ~ 3 - 5) or a blackbody-type emission with temperatures kT ~ 0.1-0.2 keV. We model the broad-band spectra spectra of the five observed FSRQs using synchrotron self-Compton (SSC) and/or external-Compton radiation (ECR) models. Our modeling suggests that the difference between the low and high-activity states in luminous blazars is due to the different total kinetic power of the jet, most likely related to varying bulk Lorentz factor of the outflow within the blazar emission zone.Comment: 36 pages, 8 figures, 11 tables. Accepted for publication in the Astrophysical Journal

Communications Biophysics

Contains research objectives and summary of research on thirteen research projects split into four section.National Institutes of Health (Grant 1 RO1 NS10737-01)National Institutes of Health (Grant 1 ROI NS10916-01)National Institutes of Health (Grant 5 RO1 NS11000-02)National Institutes of Health (Grant 1 RO1 NS11153-01)Harvard M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare, Grant 23-P-55854National Institutes of Health (Grant 1 RO1 NS11680-01)Norlin Music, Inc.Clarence J. LeBel FundNational Institutes of Health (Grant 1 RO1 NS11080-01A1)National Institutes of Health (Grant 5 TO1 GM01555-08)M.I.T. Health Sciences FundBoston City Hospital Purchase Order 1176-05-21335-C

Fermi/LAT discovery of gamma-ray emission from the flat-spectrum radio quasar PKS 1454-354

We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z=1.424). On 4 September 2008 the source rose to a peak flux of (3.5 +/- 0.7)x 10^-6 ph cm^-2 s^-1 (E > 100 MeV) on a time scale of hours and then slowly dropped over the following two days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope ATOM; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.Comment: 8 pages, 5 figures, 2 tables. Accepted for publication on ApJ Main Journa

Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca Myocardial function during the transition from compensated left ventricular hypertrophy to failure

OBJETIVO: Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR). MÉTODOS: Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC) e sem falência cardíaca (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contrações isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ºC). RESULTADOS: Os valores da tensão máxima desenvolvida (TD) e da velocidade máxima de encurtamento (Vmáx) foram menores nos SHR-IC e SHR, em relação aos WKY (p<0,05). TD e Vmáx foram semelhantes nos SHR-IC e SHR (p>0,05). A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p<0,05 vs WKY e SHR); esta variável não diferiu entre WKY e SHR (p>0,05). CONCLUSÃO: Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associada ao aumento da rigidez passiva do miocárdio e não à piora da função contrátil do músculo cardíaco.<br>PURPOSE: To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR). METHODS: Isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF), and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28ºC. RESULTS: Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p<0.05). SHR-F and SHR-NF did not differ. Compared with SHR-NF and WKY, muscle passive stiffness was increased in the failing SHR (p<0.05 versus WKY and SHR-NF). This parameter did not differ between SHR-NF and WKY (p>0.05). CONCLUSION: These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function