33 research outputs found
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
Self-Administration of Medicines and Dietary Supplements Among Female Amateur Runners: A Cross-Sectional Analysis
Participação do estado contrĂĄtil e do relaxamento miocĂĄrdico na disfunção ventricular durante a transição hipertrofia-falĂȘncia cardĂaca Myocardial function during the transition from compensated left ventricular hypertrophy to failure
OBJETIVO: Avaliar a participação do estado contrĂĄtil e do relaxamento miocĂĄrdico na disfunção do mĂșsculo cardĂaco durante a transição hipertrofia-falĂȘncia cardĂaca em ratos espontaneamente hipertensos (SHR). MĂTODOS: MĂșsculos papilares isolados do ventrĂculo esquerdo de SHR com insuficiĂȘncia cardĂaca (SHR-IC) e sem falĂȘncia cardĂaca (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contraçÔes isomĂ©trica e isotĂŽnica, em solução de Krebs-Henseleit (1,25 mM Ca2+, 28ÂșC). RESULTADOS: Os valores da tensĂŁo mĂĄxima desenvolvida (TD) e da velocidade mĂĄxima de encurtamento (VmĂĄx) foram menores nos SHR-IC e SHR, em relação aos WKY (p<0,05). TD e VmĂĄx foram semelhantes nos SHR-IC e SHR (p>0,05). A rigidez passiva do mĂșsculo aumentou significantemente nos SHR-IC (p<0,05 vs WKY e SHR); esta variĂĄvel nĂŁo diferiu entre WKY e SHR (p>0,05). CONCLUSĂO: Os dados obtidos mostram que a transição da fase de hipertrofia estĂĄvel para insuficiĂȘncia cardĂaca nos ratos espontaneamente hipertensos estĂĄ associada ao aumento da rigidez passiva do miocĂĄrdio e nĂŁo Ă piora da função contrĂĄtil do mĂșsculo cardĂaco.<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 28ÂșC. 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