Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.

BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology

Regression of atherosclerosis in cholesterol-fed rabbits: Effects of fish oil and verapamil

AbstractPrevious studies have shown that either fish oil or verapamil can attenuate the development of atherosclerosis in the lipid-fed rabbit. The present study was designed to evaluate the individual and combined effects of these two interventions on regression.Seventy New Zealand rabbits in seven groups (10 each) were fed a 0.3% cholesterol diet for 10 weeks. Control group C10 was then killed. Control group C20 was fed a 0.3% cholesterol diet and the other five groups were fed a normal diet for an additional 10 weeks. Group F in three treated groups received 2 ml/day of fish oil (Proto-Chol, eicosapentaenoic acid, 180 mg/ml and docosahexaenoic acid, 120 mg/ml) by gavage. Group V received verapamil, 2 g/1,000 ml drinking water, and group FV received both fish oil and verapamil for an additional 10 weeks. Group CF (control for fish oil) received 2 ml/day of water by gavage and group CV (control for verapamil) received water without gavage for an additional 10 weeks.The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the four control groups (C20, C10, CF and CV) was 57 ± 22, 40 ± 15, 40 ± 14 and 33 ± 25%, respectively. The fish oil or verapamil groups (F, V, FV) showed a significant reduction in aortic lesions: 15 ± 17%, p < 0.05; 16 ± 12%, p < 0.05; and 26 ± 24%, p = NS, respectively. The area of pulmonary artery lesions was significantly higher in the control group (CF, 24 ± 9%) than in group F (11 ± 9%, p < 0.05), group V (12 ± 9%, p < 0.05) and group FV (17 ± 14%, p = NS).These data demonstrate that either fish oil or verapamil can decrease atherosclerosis in cholesterol-fed rabbits placed on a normal diet. However, there was no additive effect of fish oil and verapamil. Although not statistically significant, there was a suggestive antagonistic effect between fish oil and verapamil

Correlations in the (Sub)Mil1imeter Background from ACT x BLAST

We present measurements of the auto- and cross-frequency correlation power spectra of the cosmic (sub)millimeter background at: 250, 350, and 500 microns (1200, 860, and 600 GHz) from observations made with the Balloon-borne Large Aperture Submillimeter Telescope, BLAST; and at 1380 and 2030 microns (218 and 148 GHz) from observations made with the Atacama Cosmology Telescope, ACT. The overlapping observations cover 8.6 deg(sup 2) in an area relatively free of Galactic dust near the south ecliptic pole (SEP). The ACT bands are sensitive to radiation from the CMB, the Sunyaev-Zel'dovich (SZ) effect from galaxy clusters, and to emission by radio and dusty star-forming galaxies (DSFGs), while the dominant contribution to the BLAST bands is from DSFGs. We confirm and extend the BLAST analysis of clustering with an independent pipeline, and also detect correlations between the ACT and BLAST maps at over 25(sigma) significance, which we interpret as a detection of the DSFGs in the ACT maps. In addition to a Poisson component in the cross-frequency power spectra, we detect a clustered signal at 4(sigma), and using a model for the DSFG evolution and number counts, we successfully fit all our spectra with a linear clustering model and a bias that depends only on red shift and not on scale. Finally, the data are compared to, and generally agree with, phenomenological models for the DSFG population. This study represents a first of its kind, and demonstrates the constraining power of the cross-frequency correlation technique to constrain models for the DSFGs. Similar analyses with more data will impose tight constraints 011 future models

Interferometric Mapping of Magnetic Fields in Star-forming Regions I. W51 e1/e2 Molecular Cores

We present the first interferometric polarization map of the W51 e1/e2 molecular cores obtained with the BIMA array at 1.3 mm wavelength with approximately 3 arcsecond resolution. The polarization angle varies smoothly across the double cores with an average position angle of 23+-5 degrees for W51 e1 and 15+-7 degrees for W51 e2. The inferred magnetic field direction is parallel to the minor axis of the double cores, which is consistent with the theoretical picture that clouds collapse along the field lines. However, the magnetic field may not determine the axis of angular momentum of these two cores as the field directions of the two cores significantly differ with the previously measured directions of rotational axes. The polarization percentage decreases toward regions with high intensity, suggesting that the dust alignment efficiency decreases toward high density regions. The field directions are highly ordered, and the small dispersion of the polarization angles implies that magnetic fields are strong ($\gtrsim$ 1 mG) and perhaps dominate turbulence in W51 e1/e2.Comment: 9 pages, 3 figures. Accepted for publication in the Astrophysical Journal, Nov 10, 2001 issu

972-107 L-Arginine Decreases Infarct Size in Rats Exposed to Environmental Tobacco Smoke

We previously showed that environmental tobacco smoke (ETS) increased myocardial infarct size in a rat model of ischemia and reperfusion. If reduced reperfusion was caused by endothelial cell damage and increased vascular tone, we postulated that L-arginine (ARG) would increase nitric oxide and better protect the heart. 60 rats were randomly divided into 4 groups: ETS or Control (C) with and without ARG (2.25% ARG in drinking water). The ETS groups were exposed (4 Marlboro cigarettes per 15 minutes. 6 hours a day) for 6 weeks. During ETS-exposure, average air nicotine, carbon monoxide and total particulate concentrations were 1304 μg/m3, 78 ppm and 31 mg/m3, respectively. After 6 weeks, all rats were subjected to 35 min LAD occlusion (0) and 120 min reperfusion, with hemodynamic monitoring via the carotid artery. Aortic rings were harvested to evaluate vascular reactivity. Infarct size (infarct mass/risk area x 100%) decreased significantly in the ETS with ARG group compared to the ETS without ARG group. There were no significant differences among groups in heart rate (HR), systolic pressure (SP), and rate pressure product. Tlere were positive correlations between infarct size and heart rates from baseline to reperfusion 120 min (r = 0.4-0.6. p = 0.01-0.001). There was no relationship between vascular reactivity and infarct size.GroupNo. of RatsInf/LV (%)Inf/RA (%)0-35’HR (beats/m)0-35'SP (mmHg)Max Relax (%)C1125±351±6408±11120±784±11C+ ARG1025±252±3415±10103±11112±15ETS1034±464±6427±16108±8128±16ETS + ARG1122±3*42±6*410±17106±10127±18Values are Means±SEM*p&lt;0.05, p values from two-way ANOVAConclusionL-arginine decreases myocardial infarct size after ischemia and reperfusion in ETS-exposed rats. This effect does not appear to be secondary to alterations in hemodynamics

Creativity out of chaos

Creativity is said to be highly desired in post-modern and post-industrial organizations Creativity and anarchy on the one hand, and managerialism, on the other, can be seen as different forms of knowledge, two opposed ideals. In many organizational as well as societal reforms we currently observe it is the managerialist ideal that wins over the anarchic. In this paper, we wonder if people fear anarchy? We reflect on the possible reasons for the fear, and we also try to explain why we believe that anarchic organizing should not be avoided or feared