This study compares the toxic effects of native cyclosporia A (CyA) with those of targeted CyA that is conjugated with the anti-rat-thymocyte antibody of rabbit origin via the N-(2-hydroxypropyl)methacrylamide (HPMA) carrier bearing digestible, reactive oligopeptide side chains. Ten toxic doses of native CyA (50 mg/kg i.p.) given to young adult rats in the course of 14 d produced a severe renal lesion-diffuse microvacuolization of the proximal tubules in the deep cortex, and hypergranulation of juxtaglomerular regions. Severe atrophy of the thymic medulla was documented by morphometry. In the cortex the epithelial reticular (but not deep interdigitating) cells showed ultrastructural signs of severe degeneration and lysis. The immature CD4+8+ double-positive cortical lymphocytes were preserved whereas the single-positive medullary thymocytes were greatly depleted; there was also a restriction of MHC class II antigen expression in the medulla. The number of medullary B cells was increased. The cytokeratin net was focally shrunken in the cortex and almost negative in the medulla, with loss of Hassall's corpuscles. After ten corresponding doses of antibody-targeted conjugated CyA no damage to the renal tubules and arterioles appeared and the antiGBM or immune-complex deposition was absent. The thymus had a normal medulla with numerous mature thymocytes and the cortical epithelial reticulum remained well preserved. Thus, the main toxic effects of CyA could be eliminated by targeting. The T-cell-targeted drug was tested for preserved immunosuppressive properties and non-toxic character of HPMA copolymer carrier.

• MeSH
• cyklosporin toxicita   MeSH
• cyklosporiny toxicita   MeSH
• imunokonjugáty toxicita   MeSH
• imunosupresiva toxicita   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   MeSH
• nosiče léků toxicita   MeSH
• potkani Wistar MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• thymus účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklosporin MeSH
• cyklosporiny MeSH
• imunokonjugáty MeSH
• imunosupresiva MeSH
• nosiče léků MeSH

In the decade 1979-1988, 658 biopsies were collected from 568 cadaveric renal allografts. In 118 grafts a non-proliferative insudative vasculopathy (IVA) was found in afferent vessels. Immunosuppression was based on azathioprine (AZA) or on cyclosporin A (CsA), from 1983. The prevalence and extent of IVA has increased significantly since 1984. Light microscopy showed fibrinoid and hyaline masses of varying extent; transmural insudative "knobs", intimal oedema with metachromasia, and microthrombosis were also seen with CsA. The ultrastructure of the insudates was unremarkable but CsA grafts displayed early oedema and hypergranulation of endothelial cells with a disarray of smooth muscle cell (SMC) microfibrils, and pronounced degenerative changes of SMC. Rebiopsy showed stationary IVA in AZA grafts and progression in one-half of CsA-treated patients. Nephrectomy specimens revealed, however, a marked predominance of late rejection endarteritis; in only 3 cases was IVA and/or microthrombosis the possible cause of nephrectomy. The mean donor age was higher in severe IVA in CsA grafts and the mean post-transplantation interval at the time of diagnosis of IVA was significantly shorter in CsA-treated patients. No important differences in cumulative graft survival were seen between grafts with absent, moderate or severe IVA. Unused cadaveric donors' kidneys of comparable age exhibited normal arterioles or a slight focal insudative or hyaline lesion.

• MeSH
• arterie účinky léků   patologie   ultrastruktura   MeSH
• arterioly účinky léků   patologie   ultrastruktura   MeSH
• arterioskleróza epidemiologie   etiologie   patologie   MeSH
• cyklosporiny škodlivé účinky   terapeutické užití   MeSH
• elektronová mikroskopie MeSH
• fluorescenční protilátková technika MeSH
• homologní transplantace MeSH
• imunosupresivní léčba MeSH
• ledviny krevní zásobení   účinky léků   patologie   MeSH
• lidé MeSH
• prevalence MeSH
• rejekce štěpu účinky léků   MeSH
• transplantace ledvin škodlivé účinky   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklosporiny MeSH