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

The usefulness of combining antithrombotic agents and radical scavengers in the treatment of reperfusion injury (an almost ideal approach) was substantiated using an ischemic flap model. The cause(s) of reperfusion injury was hypothesized on the basis of differences in effects between antithrombotic agents and radical scavengers in the experimental groups. Flap specimens were also obtained regularly for histologic examination. The experiment was conducted in nine rabbit groups. For continuous treatment with intraarterial antithrombotic agents, both heparin and urokinase were continuously injected at respective administration rates of 20 U/kg/hr and 200 IU/kg/hr for seven consecutive days immediately before reperfusion. For intraarterial radical scavenger treatment, a solution of both 30,000 U/kg SOD and 30,000 U/kg catalase in 5 ml of a lactated Ringer's solution was injected over a period of about 30 min immediately before reperfusion. The ischemic time of the flaps was 10 hr for Group I and 12 hr for Group II. Each group was comprised of subgroups a, b, c, and d: a = control; b = continuous intraarterial antithrombotic agent injection; c = intraarterial lactated Ringer's solution alone; and d = intraarterial radical scavenger injection. For Group II, an additional subgroup e was established, which received continuous injection of both intraarterial antithrombotic agents and injected intraarterial radical scavenger. In the 10-hr ischemic treatment group, an effect was obtained by continuous intraarterial antithrombotic agents alone. In the 12-hr ischemic treatment group, a significant improvement in flap-take ratio was obtained using intraarterial radical scavenger, in combination with antithrombotic agents. Observation of the flaps that survived in subgroups Ib and IIe revealed skin thinning, vascular wall thickening, and muscular tissue degeneration, although the skin architecture was well preserved.
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PMID:Combined therapy with antithrombotic agents and radical scavengers for reperfusion injury of flaps. 189 Jun 81

Any perturbation of the blood brain barrier, whether from changes in cell physiology or from direct injury, may result in microvascular dysfunction and disease. We examined, at the ultrastructural level, microvascular pericyte responses in a well-defined model of traumatic brain injury in the rat. In areas close to the site of impact cortical pericytes underwent a number of changes within the first hour. Approximately 40% of pericytes migrated from their microvascular location. Migration occurred concomitant with a thinning of the abluminal surface of the basal lamina and an accumulation of the receptor for the urokinase plasminogen activator on the leading surface of the migrating cell. Migrated pericytes appeared viable and remained in a perivascular location in the adjacent neuropil. Nonmigrating pericytes in the same section displayed cytoplasmic alterations and nuclear chromatin changes consistent with a rapid degenerative process.
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PMID:Pericyte migration from the vascular wall in response to traumatic brain injury. 1087 15

The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain deficient in urokinase-type plasminogen activator (uPA-/-) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA-/- mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA-/- mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders.
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PMID:The pathophysiology of pelvic floor disorders: evidence from a histomorphologic study of the perineum and a mouse model of rectal prolapse. 1176 Aug 91

Clinical complications of atherosclerosis are often triggered by the rupture of unstable plaques, while thinning of the atherosclerotic vessel wall owing to elastin and collagen degradation and media necrosis may result in aneurysm formation and bleeding. Proteolysis, mediated via the plasminogen/plasmin and/or matrix metalloproteinase (MMP) systems may contribute to neovascularization and rupture of plaques, or to ulceration and rupture of aneurysms. In an in vivo model of atherosclerosis, using mice that had a combined deficiency of apolipoprotein E (ApoE) and urokinase-type plasminogen activator (u-PA) and that were maintained on a cholesterol-rich diet, it was observed that u-PA deficiency protects against aneurysm formation. This was explained by the findings that plasmin, generated from plasminogen by u-PA, activates several macrophage-secreted proMMPs (e.g. proMMP-3, -9, -12 and -13), which in turn cause extracellular matrix degradation. A potential role for MMP-3 (stromelysin-1) was confirmed in a subsequent study using mice with a combined deficiency of ApoE and MMP-3, that were kept on a cholesterol-rich diet. The results suggest that MMP-3 contributes to plaque destabilization, possibly by degrading extracellular matrix components, but also promotes aneurysm formation by degrading the elastic lamina. These effects may be mediated by MMP-3 directly or by activation of other proMMPs or other (proteolytic) systems. A functional role of MMPs is further supported by the finding that deficiency in TIMP-1 (tissue inhibitor of MMPs type 1) reduces atherosclerotic plaque size but enhances aneurysm formation. Taken together, these results suggest that u-PA has an important role in the structural integrity of the atherosclerotic vessel wall, which is likely to involve triggering the activation of MMPs and, furthermore, they suggest that increased u-PA levels are a risk factor for aneurysm formation.
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PMID:Extracellular proteolysis in the development and progression of atherosclerosis. 1202 44