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Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice
Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) a...
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Published in: | Virchows Archiv A Pathological Anatomy and Histopathology 1990-11, Vol.416 (6), p.505-511 |
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description | Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types. |
doi_str_mv | 10.1007/BF01600301 |
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However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types.</description><identifier>ISSN: 0174-7398</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/BF01600301</identifier><identifier>PMID: 2110697</identifier><identifier>CODEN: VAAHDJ</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Animals ; Biological and medical sciences ; Cyclosporins - pharmacology ; Female ; Immunomodulators ; Medical sciences ; Mice ; Mice, Nude ; Pharmacology. Drug treatments ; Skin - cytology ; Skin - drug effects ; Skin - ultrastructure ; Skin Transplantation</subject><ispartof>Virchows Archiv A Pathological Anatomy and Histopathology, 1990-11, Vol.416 (6), p.505-511</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c226t-37d7b47187f5fd855e85e1db9bf011cfb173c13603349b852cb9ec7e936b7a7f3</citedby><cites>FETCH-LOGICAL-c226t-37d7b47187f5fd855e85e1db9bf011cfb173c13603349b852cb9ec7e936b7a7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4427067$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2110697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KANITAKIS, J</creatorcontrib><creatorcontrib>RAMIREZ-BOSCA, A</creatorcontrib><creatorcontrib>HAFTEK, M</creatorcontrib><creatorcontrib>THIVOLET, J</creatorcontrib><title>Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice</title><title>Virchows Archiv A Pathological Anatomy and Histopathology</title><addtitle>Virchows Arch A Pathol Anat Histopathol</addtitle><description>Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cyclosporins - pharmacology</subject><subject>Female</subject><subject>Immunomodulators</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Pharmacology. Drug treatments</subject><subject>Skin - cytology</subject><subject>Skin - drug effects</subject><subject>Skin - ultrastructure</subject><subject>Skin Transplantation</subject><issn>0174-7398</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><recordid>eNpFkMFLwzAYxYMoc04v3oUcPAnV72uapj3qcE4YeNFzSdNkdrbJSFJw_70dG_P04L0f7_Aj5BbhEQHE08sCMAdggGdkihlLk5SBOCdTQJElgpXFJbkKYQPAORZ8QiYpIuSlmJLNsg3RdW7dKtlRaRs6dNHLEP2g4uDHThujVQzUGap2qnNh63xr6TN1llrn-xH5HnppafgZ619t3dpLE3WzB6Kjdmg07Vulr8mFkV3QN8ecka_F6-d8maw-3t7nz6tEpWkeEyYaUWcCC2G4aQrOdcE1NnVZG0BUpkbBFLIcGMvKuuCpqkuthC5ZXgspDJuRh8Ov8i4Er0219W0v_a5CqPa-qn9fI3x3gLdD3evmhB4Fjfv9cZdhNGS8tKoNJyzLUgG5YH_kkHML</recordid><startdate>199011</startdate><enddate>199011</enddate><creator>KANITAKIS, J</creator><creator>RAMIREZ-BOSCA, A</creator><creator>HAFTEK, M</creator><creator>THIVOLET, J</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199011</creationdate><title>Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice</title><author>KANITAKIS, J ; RAMIREZ-BOSCA, A ; HAFTEK, M ; THIVOLET, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c226t-37d7b47187f5fd855e85e1db9bf011cfb173c13603349b852cb9ec7e936b7a7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cyclosporins - pharmacology</topic><topic>Female</topic><topic>Immunomodulators</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Pharmacology. Drug treatments</topic><topic>Skin - cytology</topic><topic>Skin - drug effects</topic><topic>Skin - ultrastructure</topic><topic>Skin Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KANITAKIS, J</creatorcontrib><creatorcontrib>RAMIREZ-BOSCA, A</creatorcontrib><creatorcontrib>HAFTEK, M</creatorcontrib><creatorcontrib>THIVOLET, J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Virchows Archiv A Pathological Anatomy and Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KANITAKIS, J</au><au>RAMIREZ-BOSCA, A</au><au>HAFTEK, M</au><au>THIVOLET, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice</atitle><jtitle>Virchows Archiv A Pathological Anatomy and Histopathology</jtitle><addtitle>Virchows Arch A Pathol Anat Histopathol</addtitle><date>1990-11</date><risdate>1990</risdate><volume>416</volume><issue>6</issue><spage>505</spage><epage>511</epage><pages>505-511</pages><issn>0174-7398</issn><eissn>1432-2307</eissn><coden>VAAHDJ</coden><abstract>Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>2110697</pmid><doi>10.1007/BF01600301</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Biological and medical sciences Cyclosporins - pharmacology Female Immunomodulators Medical sciences Mice Mice, Nude Pharmacology. Drug treatments Skin - cytology Skin - drug effects Skin - ultrastructure Skin Transplantation |
title | Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice |
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