Abstract:
:The present study was undertaken to examine a possible effect of aprotinin, a 6.5-kDa polypeptide with an inhibitory effect on proteolysis, on aminoglycoside nephrotoxicity. Experimental animals (female Sprague-Dawley rats, 175-200 g body wt) were treated for 4 days with 40 mg/kg gentamicin given ip at 12-hr intervals. Aprotinin (40,000 kIU per animal) was infused i.v. over a period of 8 days, using subcutaneously implanted miniosmotic pumps. In protocol A, infusion pumps were placed 4 days before starting gentamicin treatment. In protocol B, pumps were implanted 15-18 hr prior to first gentamicin administration. In addition to rats exposed to both gentamicin and aprotinin (GAP), animals were treated with gentamicin ip+saline i.v. (G), saline ip+aprotinin i.v. (AP), or received only saline by both routes of administration (C). All rats were terminated 4 days after the end of gentamicin dosing. One hour before sacrifice, 200 microCi of [3H]thymidine was given ip to each animal in order to monitor cell turnover in renal tissue. The kidneys were analyzed with respect to (i) histopathological alterations and renal dysfunction, (ii) aminoglycoside tissue accumulation, and (iii) tubular regeneration (measurement of cell proliferation). In animals receiving aprotinin alone, histological examination of renal cortex on paraffin sections disclosed mild tubular injury with focal cell necrosis. In plastic-embedded tissue, proximal tubule epithelium was characterized by the presence of numerous inclusions densely stained with toluidine blue. At the ultrastructural level, these inclusions appeared filled with amorphous electron-dense material. In gentamicin-treated animals, cortical drug accumulation reached values higher than 0.3 mg/g renal tissue, but a significant 30-40% decrease of gentamicin accumulation was noted in GAP groups, compared to G groups. Histological examination of renal cortex (paraffin sections) revealed the development of acute tubular necrosis in both G and GAP groups. Tubular injury was accompanied by mild renal dysfunction, as shown by the level of serum creatinine which was increased almost 3-fold in the G group, compared to C and AP groups. Aprotinin infusion produced a further increase of serum creatinine, particularly in protocol A where it was 72% higher for the GAP group than for the G group. In both G and GAP groups, postnecrotic tubular regeneration was evidenced by determining the rate of DNA synthesis and the frequency of S-phase cells in renal cortex. Both methods gave consistent results and showed a 8- to 13-fold increase of cell proliferation in groups receiving gentamicin alone, compared to C groups.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Exp Mol Patholjournal_title
Experimental and molecular pathologyauthors
Morin NJ,Frau A,Nonclercq D,Toubeau G,Zanen J,Heuson-Stiennon JA,Bergeron MG,Beauchamp D,Laurent Gdoi
10.1006/exmp.1994.1018subject
Has Abstractpub_date
1994-06-01 00:00:00pages
197-213issue
3eissn
0014-4800issn
1096-0945pii
S0014-4800(84)71018-5journal_volume
60pub_type
杂志文章abstract:BACKGROUND:New drugs targeting specific genes required for unregulated growth and metastases have improved survival rates for patients with metastatic colorectal cancer. Resistance to monoclonal antibodies specific for the epidermal growth factor receptor (EGFR) has been attributed to the presence of activating point m...
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更新日期:2013-08-01 00:00:00
abstract::The hypoxia-inducible factor-1alpha (HIF-1alpha) is expressed in response to hypoxia and has been recently demonstrated in a variety of cells such as tumor cells and tumor-associated macrophages. Several characteristics of leishmanial lesions in humans and in animal models, such as microcirculation impairment, metabol...
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/0014-4800(92)90043-b
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1995.1018
更新日期:1995-06-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Experimental and molecular pathology
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doi:10.1016/j.yexmp.2015.01.007
更新日期:2015-04-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.2000.2322
更新日期:2000-10-01 00:00:00
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doi:10.1016/j.yexmp.2015.07.006
更新日期:2015-10-01 00:00:00
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journal_title:Experimental and molecular pathology
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doi:10.1006/exmp.2002.2460
更新日期:2002-10-01 00:00:00
abstract::Apolipoprotein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the progression of glomerulosclerosis (GS). We conducted this investigation to explore whether all-trans retinoic acid (ATRA) could regulate the apoE expression in the pathological process of GS. 120 Wistar rats w...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2011.03.001
更新日期:2011-06-01 00:00:00
abstract::Integrins are a family of cell surface glycoproteins that act as receptors for ECM proteins or for membrane bound counter-receptors on other cells. The integrin receptor family of vertebrates includes at least 16 distinct alpha subunits and at least 8 beta subunits which can associate to form more than 20 distinct int...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2005.04.004
更新日期:2005-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.yexmp.2007.05.004
更新日期:2007-12-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2009.01.013
更新日期:2009-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.yexmp.2012.10.003
更新日期:2013-02-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2006.01.002
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1994.1027
更新日期:1994-10-01 00:00:00
abstract::In this comparative study, rat hearts were perfused at 37 degrees C with three clearly defined protocols: the Ca2+ paradox, the O(2) paradox, and with 20 mM caffeine. Each protocol involved an initial priming (Ca(2+)(0) depletion or anoxia; stage 1) and subsequent full activation (Ca(2+)(0) repletion, caffeine or reox...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.1999.2275
更新日期:1999-10-01 00:00:00
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doi:10.1016/j.yexmp.2019.04.010
更新日期:2019-06-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
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更新日期:2003-12-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1006/exmp.2001.2402
更新日期:2001-12-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer mortality globally. HCC incidence has doubled in Egypt in the past 10 years, which could be attributed to the high prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV), although HBV rates have declined af...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2009.09.012
更新日期:2010-02-01 00:00:00
abstract:RATIONALE:The rat carotid balloon-injury (BI) model is a widely used model of intimal hyperplasia (IH) and vascular remodeling. A variable degree of IH after BI has been previously reported, and we have encountered technical challenges and suboptimal results with the original method. OBJECTIVE:To evaluate the original...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2011.06.011
更新日期:2011-10-01 00:00:00
abstract::Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are involved in the initiation and control of the immune response to antigens present at the interface with the environment. A limited number of groups have studied DCs in human and animal conjunctiva but no data is available concerning the dif...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2007.04.007
更新日期:2007-10-01 00:00:00
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journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2005.08.002
更新日期:2005-12-01 00:00:00
abstract::As the fifth most common cancer and the second leading cause of cancer related deaths worldwide, hepatocellular carcinoma (HCC) causes up to one million deaths annually. Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are becoming the two major risk factors because both may develop liver fibro...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2019.04.002
更新日期:2019-06-01 00:00:00
abstract::Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significant...
journal_title:Experimental and molecular pathology
pub_type: 杂志文章
doi:10.1016/j.yexmp.2006.05.001
更新日期:2006-10-01 00:00:00