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L System (l + system)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Entorhinal Cortex Lesion in the Mouse Induces Transsynaptic Death of Perforant Path Target Neurons

BRAIN PATHOLOGY, Issue 3 2004
Adam D. Kovac
Entorhinal cortex lesion (ECL) is a well described model of anterograde axonal degeneration, subsequent sprouting and reactive synaptogenesis in the hippocampus. Here, we show that such lesions induce transsynaptic degeneration of the target cells of the lesions pathway in the dentate gyrus. Peaking between 24 and 36 hours postlesion, dying neurons were labeled with DeOlmos silver-staining and antisera against activated caspase 3 (CCP32), a downstream inductor of programmed cell death. Within caspase 3-positive neurons, fragmented nuclei were co-localized using Hoechst 33342 staining. Chromatin condensation and nuclear fragmentation were also evident in semithin sections and at the ultrastructural level, where virtually all caspase 3-positive neurons showed these hallmarks of apoptosis. There is a well-described upregulation of the apoptosis-inducing CD95/L system within the CNS after trauma, yet a comparison of caspase 3-staining patterns between CD95 (lpr)- and CD95L (gld)-deficient with non-deficient mice (C57/bl6) provided no evidence for CD95L-mediated neuronal cell death in this setting. However, inhibition of NMD A receptors with MK-801 completely suppressed caspase 3 activation, pointing to glutamate neurotoxicity as the upstream inducer of the observed cell death. Thus, these data show that axonal injury in the CNS does not only damage the axotomized neurons themselves, but can also lethally affect their target cells, apparently by activating glutamate-mediated intracellular pathways of programmed cell death. [source]

Predicting solubility in multiple nonpolar drugs,cyclodextrin system

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2002
Luwei Zhao
Abstract This study presents a model to predict the solubility of a nonpolar drug DA in the presence of other nonpolar drugs D1,Dn in a complexing ligand L system such as hydroxypropyl-,-cyclodextrin (HP,CD). Using an equilibrium approach, the model describes the molecular interactions among these drug species and the ligand. The model indicates that the solubility of DA invariably decreases as a result of the presence of D1,Dn. Furthermore, the decrease in DA solubility is related to the sum of the products of the intrinsic solubilities of the other drugs and drug,ligand complexation constants. To test the model, three steroids (prednisolone, 17,-hydroxyprogesterone, and progesterone) were used as model compounds in HP,CD solutions. The experimental data showed that the solubility of any particular drug decreased in the presence of other drugs. At all tested HP,CD concentrations, these experimental solubility data were in good agreement with the predicted solubility data. This result lends strong support to the reliability and effectiveness of the proposed model. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2301,2306, 2002 [source]

Sodium butyrate induces P53-independent, Fas-mediated apoptosis in MCF-7 human breast cancer cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2002
Valérie Chopin
This study was performed to determine the effect and action mechanisms of sodium butyrate (NaB) on the growth of breast cancer cells. Butyrate inhibited the growth of all breast cancer cell lines analysed. It induced cell cycle arrest in G1 and apoptosis in MCF-7, MCF-7ras, T47-D, and BT-20 cells, as well as arrest in G2/M in MDA-MB-231 cells. Transient transfection of MCF-7 and T47-D cells with wild-type and antisense p53 did not modify butyrate-induced apoptosis. Pifithrin-,, which inhibits the transcriptional activity of P53, did not modify cell growth or apoptosis of MCF-7 and T47-D cells treated with butyrate. These results indicate that P53 was not involved in butyrate-induced growth inhibition of breast cancer cells. Treatment of MCF-7 cells with anti-Fas agonist antibody induced cell death, indicating that Fas was functional in these cells. Moreover, butyrate potentiated Fas-induced apoptosis, as massive apoptosis was observed rapidly when MCF-7 cells were treated with butyrate and anti-Fas agonist antibody. In addition, butyrate-induced apoptosis in MCF-7 cells was considerably reduced by anti-Fas antagonist antibody. Western blot analysis showed that butyrate increased Fas and Fas ligand levels (Fas L), indicating that butyrate-induced apoptosis may be mediated by Fas signalling. These results demonstrate that butyrate inhibited the growth of breast cancer cells in a P53-independent manner. Moreover, it induced apoptosis via the Fas/Fas L system and potentiated Fas-triggered apoptosis in MCF-7 cells. These findings may open interesting perspectives in human breast cancer treatment strategy. British Journal of Pharmacology (2002) 135, 79,86; doi:10.1038/sj.bjp.0704456 [source]

Enhanced star formation in narrow-line Seyfert 1 active galactic nuclei revealed by Spitzer

MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2010
E. Sani
ABSTRACT We present new low-resolution Spitzer mid-infrared spectroscopy of a sample of 20 ROSAT -selected local narrow-line Seyfert 1 galaxies (NLS1s). We detect strong active galactic nucleus (AGN) continuum in all and clear polycyclic aromatic hydrocarbon (PAH) emission in 70 per cent of the sources. The 6.2 ,m PAH luminosity spans three orders of magnitude, from ,1039 to ,1042 erg s,1, providing strong evidence for intense ongoing star formation in the circumnuclear regions of these sources. Using the Infrared Spectrograph/Spitzer archive, we gathered a large number of additional NLS1s and their broad-line counterparts (BLS1s) and constructed NLS1 and BLS1 subsamples to compare them in various ways. The comparison shows a clear separation according to full width at half-maximum (H,) [FWHM(H,)] such that objects with narrower broad H, lines are the strongest PAH emitters. We test this division in various ways trying to remove biases due to luminosity and aperture size. Specifically, we find that star formation activity around NLS1 AGN is larger than around BLS1 of the same AGN luminosity. The above result seems to hold over the entire range of distance and luminosity. Moreover, the star formation rate is higher in low black hole mass and high L/LEdd systems indicating that black hole growth and star formation are occurring simultaneously. [source]