Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The quality of bone may be as important as its quantity, influencing bone strength and turnover. Using quantitative BSE (backscattered electron) imaging, we have found changes in the mineral density of bone with age, the proportion of denser bone increasing, and discontinuities occurring in the mineral phase between packets of bone. SEM of resorptive fields showed that severing of trabeculae occurs with deep, vertical excavations; their thinning is by long, narrow, resorption grooves extending from node to node. Grooved regions may become deeper, undercut and burrowing. In vitro, we showed that larger osteoclasts made larger pits. However, the volume of tissue resorbed per nucleus did not increase, and could decrease. Interactions between osteoclasts and autologous osteoblastic cells were observed by time-lapse video microscopy in vitro. Message-mediated contact behaviour, dependent upon the state of activation of both cell types, resulted in changes in the territory of the responding cell. The numbers and sizes of gap junctions between rat parietal bone cells in situ were investigated using confocal fluorescence and reflection microscopy and polyclonal antisera to connexin-43 peptides. The junctions reached approximately 1.3 microns in diameter, with 0.2 microns as the limit of detection. The extent of connectivity and communication may also affect bone quality.
 ...
PMID:Questions of quality and quantity--a morphological view of bone biology. 809 41

Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive MI, rats were randomized to cell (1.5x10(6)) transplantation (n=11) or culture medium injection (n=16) into the myocardial scar. Echocardiography study was performed before and 53+/-3 days after implantation to assess left ventricular (LV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P=0.12). X-gal staining, BrdU and alpha -SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against alpha -SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning, LV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive MI in a rat model attenuate LV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months after grafting.
 ...
PMID:Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. 1143 38

The cis benzopyran compound tonabersat (SB-220453) has previously been reported to inhibit connexin26 expression in the brain by attenuating the p38-mitogen-activated protein kinase pathway. We show here that tonabersat directly inhibits connexin43 hemichannel opening. Connexin43 hemichannels have been called "pathological pores" based upon their role in secondary lesion spread, edema, inflammation, and neuronal loss following central nervous system injuries, as well as in chronic inflammatory disease. Both connexin43 hemichannels and pannexin channels released adenosine triphosphate (ATP) during ischemia in an in vitro ischemia model, but only connexin43 hemichannels contributed to ATP release during reperfusion. Tonabersat inhibited connexin43 hemichannel-mediated ATP release during both ischemia and reperfusion phases, with direct channel block confirmed using electrophysiology. Tonabersat also reduced connexin43 gap junction coupling in vitro, but only at higher concentrations, with junctional plaques internalized and degraded via the lysosomal pathway. Systemic delivery of tonabersat in a rat bright-light retinal damage model (a model for dry age-related macular degeneration) resulted in significantly improved functional outcomes assessed using electroretinography. Tonabersat also prevented thinning of the retina, especially the outer nuclear layer and choroid, assessed using optical coherence tomography. We conclude that tonabersat, already given orally to over 1000 humans in clinical trials (as a potential treatment for, and prophylactic treatment of, migraine because it was thought to inhibit cortical spreading depression), is a connexin hemichannel inhibitor and may have the potential to be a novel treatment of central nervous system injury and chronic neuroinflammatory disease.
 ...
PMID:Tonabersat Prevents Inflammatory Damage in the Central Nervous System by Blocking Connexin43 Hemichannels. 2856 Jul 8