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Evidences of percutaneous absorption of a novel topical cyclosporin a formulation
114
Poster Presentations
MAMMARY AND EXTRAMAMMARY PAGET‘S DISEASE: AN IMMUNOCYTOCHEMICAL STUDY USINO ANTI-TUMOR ANTIBODIES. Zxkw Tsuii and Naokl Otake, Depatmenr of Dermatology, Nagoya City University Medical School, Nagoya. Japan The parhogenesls of mammary (MPD) and extramammary (EMPD) Paget’s disease has remained controversial; and debate has intensified in recent years as data has accumulated from immunocy~ochem~cal investigations. In the present study. we used monoclonal anfibodles to three different tumor antigens (Ca 15-3, Ca 19-9 and SLX) which had not teen used 10 Pa&s disease and cornoared with each olher and CEA. Surgically removed and‘formahn-fixed paraffin-embedded tissues from seven mammary, five vulvar. two scrotal, and two axillar Paget’s disease were studied for mxouno.zvtochemical anneens. Page; cells sramed wzh the anti-r2 15-3 anohody. The mtensity of the stammg was strong. Staining with this antibody was also observed in the duccal and secretory portions of the eccrine and apocrine glands, and in sebaceous gland cells. Staining with antiCa 19-9 antibody was mainly observed in the eccnne duc1, but not in other skin components. The Paget cells stained with anti-SLX antibody strongly. Staining wtb this antibody was also observed in the apocrine secretory coils, lacriferous ducts. epidennal dendritic cells, dennal iibroblasts and inflammatory infiltrates. lmmonoreactivity with anti0 15-3 antibody was more reproducible and reliable than that wth antibody against CBA because a positive reacdon for CEA was weaker than that of Ca 15.3 and was not always found I” all Paget cells. When compared with antibody to Ca 15.3, that to SLX was less useful because the latter had immonoreaclivi~y with epidermal dendmic cells and many infilualing cells m the denis. Thus, antibody 10 Ca 1S-3 seems most useful among four wmor markers 10 stain Paget cells. Depending on the staining pattern of the antibodies 11IS suggested that Lhe origin of Paget cells is secretory cells of apocrine sweat glands m EMPD. and luminal lactiferous ducts in MPD.
NETABOLIC NEFBRrx*THY.
N.
CHANGES IN I. Schakhtmeister,
Nevero”,
noscow. We
S.
Grachev,
PBORIASIB
AND
PSORIATIC
K. Golov, M. Ryabinina. Sechenov Medical Academy,
Russia
EFFECTS OF TOPIULLY @PLIED SPIRONOLbCmNEON mNDROGEN STIMUUTED SEBACEOUS GLANDS IN THEHlWSTER PINNA. Taisuke Seki and Masaaki Morohashi. Department of Dernatalogr.
Faculty
of Medicine.
Toyama Medical and Pharmaceutical
the role of carbonhydrate, lipid and $nalvsed in clinical ;nd morphological purine abriormelities features of psoriatic nephropathy for‘ three groups of patients namely GII with proteinuria (0.05-3.8 9/l), patients psoriatic nicroalbuminuria and lx* with without proteinuria and microalbuminuria (Gr3). and Gr2 we observed significantly higher levels of serum and urine uric acid, serum triglycerides, total increased (VLDL+LDL)/HDL ratio in comparicholesterol, son with Gr3. Besides that in GrZ comparing to Grl and Gr3 there were significantly increased levels of qlycemia and basal qlomerular filtration rate (GFR), decreato acute protein sed renal ~‘eseue (i.e. GFR response correlation of glycemia and uric acid load), positive study of renal levels with basal GFR. Morphological biopsy in WI (34 cases) revealed various types of qlomerulonephritis and focal and segmental qlomerulOSclerosis with LDL-depositions (4 cases) and uric acid crythickened stals (1 case). in Gr2 (8 cases) it revealed qlomer&rbasement membrane and mesangium proliferation mainly in area of glomerular hilus. The hyperlipidemia with increased (VtDL+LDL)/HDL ratio, uric acid and hyperperfusion due to hyperglycemia and hyperuricemia iS supposed to cause morphological changes in Grl and Gr2.
Ilniwrsit". .lacan
A NEW MODEL FOR CYCLOPHOSPHAMIDE-INDUCED ALOPECIA AND ITS MANIPULATION BY CYCLQSPORlNE A ANDTOPICAL DEXAh4EWASONE. &Stefan Eicvaod M.Caas&& Dermatology, Bori Handiis Universitv Hosoilal R. &bow. Freie UnivetiULt Be& D-1000 Berlin 65 Aiopec& as a side-effect of chemorherapy rem&s a major problem in clinical oncology. Reliable scrceniog systems for the detection of effativc means to block ibe devclopmeoc of rbis alopecia am required. Here, we introduce cyclophosphamide (CYP)-induced alopecia io the C 57 BM rnoux as one ~atticolarly attractive model. It assesses the effects of P single intrapritooeal injection of CYP (Im 150 mgikg) o(1 the growrh. pigmentation and recovery of malure. dcpilafion-induced aoagen VI hair follicles in adolescent animals. This was followed over time and analyzed by assessing hair cycle-dependent changes in skin color, by bislological morphomerry and by electron microscopy. CYP-treated mice display macroscopic and histological phenomena that strikingly resemble the characteristic hair follicle pathology seen with CYP-induced alopcia in man: patchy alopecia of rapid onset. melanin clumping and incontinence, dental papilla swelling, and distension of the follicular canal. Also, the pattern of follicle recovery and repigmentatioo follows that occunng under clinical conditions. Anagen VI follicles respond to CYP by the induction of dySb@ic anagen and catagen, and there are regional diierences in the follieular vulncmbili~y to CYP. Ulfrastmcturally, cell damage to hair matrix temtinocytes and dennal papillafibmblasts and extraccllularly localed. abnormal mclanosorncs were seen in CYP-treated mice. CYP-induced alaoccia could be attenuated by intraoeritosesl application of cyclmporiae A (3 x.5 mgtmousc) sad enhsooed by &p&l &xmxtethaso~%(O.l%). Due to its similaritv with CYP-induced alooecia in man. this is the clinically rnoft relevanl animal model &ailabls @date for studying the pathobiology of chemotherapy-induced alopecia and for snecaing for drugs that modulate this alvia.
ELECTRONMICROSCOPIC STUDY OF THE EFFECT OF SHORT-TERM TOPICAL TRETlNOM ON PHOTODAMAGED SKIN. -1s -L. ‘Dept. of Derm., Nagasald University School of Medicine, Nagasaki, Japan. acpt. of Den%, Univashy ofPenmylvania. Philadelphis. U.S.A. There have been many reports of the corrective effects of topical tretinoin on phdcdamaged skin. Previocs reports have employed tnwment schedules of six owntIm and Ionnet. To determine the imomvement obtained after a short-rnn topical applica&oftntinoin, fivemales,'agesX?to 61,withsevereIyphotodamag~skin received 0.05% tretinoin awn twice d&Iv for one month to the s!& of the dorsal forearm.Ihe following prooedorrs were &e before andaftertreatmeat: (1)3 mm punch biopsies for histochemisny and mmsmisskm clectmo mic-py. (2) sticky slidcs for mclnnization of emneceytes, (3) detergent scrubs for comcocyte sir&q and
In Gr1
UPa
Spironolactane
is a diuretic
antihrpertensive
drug which acts at the
aidosterone-dependent sodium-potassium exchange site in the distal
renal tubule. effects recwtor
by cowetitvely
inhibiting
le
investigated
sites.
spiranolactane
convoluted
Spironolactone has been also shorn to produce antiandrwenic dihydrotestosterone the effects
at the andrwen
of topically
applied
o,n the andraeen stimulated sebaceous glands br measuring the
post-application
sire of the sebaceous acinus as an index of the effect using
whole MUnt techniques in adult male golden hanrters. Topically applied spironolactone induced a 23% reduction of the sebaceous gland sire with a significantly
higher suppression rate
of the matching placebo in androgen atilrmlated baster Increased
sebaceous
petbogenesis
of
dihydrotestosterone suggest
potential
acne
secretion. vulgaris.
one of the various is
to androgen rerxptors usefulness
I ~(0.01 1 than that
riinnae.
induced
factors
by the
in the skin.
in the
binding
of
Tbua these results
of topicallyapplied spironolactonein the
treateent of acnevulgaris.
layas wxs Iedueed after treabnent. u1tIast?ocIuzaI1y. there were many villu54ike pmjcctions(VPs) on the comeooyte before atinom. The number of VR was demeaed and &smcsomal bcdies in stratum comelml innesscd after tmrtmcnL Dennalchangeswercinsigniiicant. S gIanulrswithincam~were~ pigmented spots. Despite these sinwuml cements, the eQn==w= we+x SnaaY swollen in size and incgolar in sl!ape. reflezang an abmrmal s!xntum -urn ban&. The plnicular effects of topical trerinoin on the epidennal abnommlitics of phdodpmagsdsldneanbediganvdaftcrallymlemonlhofaeamaa.
Poster Presentations
MAMMARY AND EXTRAMAMMARY PAGET‘S DISEASE: AN IMMUNOCYTOCHEMICAL STUDY USINO ANTI-TUMOR ANTIBODIES. Zxkw Tsuii and Naokl Otake, Depatmenr of Dermatology, Nagoya City University Medical School, Nagoya. Japan The parhogenesls of mammary (MPD) and extramammary (EMPD) Paget’s disease has remained controversial; and debate has intensified in recent years as data has accumulated from immunocy~ochem~cal investigations. In the present study. we used monoclonal anfibodles to three different tumor antigens (Ca 15-3, Ca 19-9 and SLX) which had not teen used 10 Pa&s disease and cornoared with each olher and CEA. Surgically removed and‘formahn-fixed paraffin-embedded tissues from seven mammary, five vulvar. two scrotal, and two axillar Paget’s disease were studied for mxouno.zvtochemical anneens. Page; cells sramed wzh the anti-r2 15-3 anohody. The mtensity of the stammg was strong. Staining with this antibody was also observed in the duccal and secretory portions of the eccrine and apocrine glands, and in sebaceous gland cells. Staining with antiCa 19-9 antibody was mainly observed in the eccnne duc1, but not in other skin components. The Paget cells stained with anti-SLX antibody strongly. Staining wtb this antibody was also observed in the apocrine secretory coils, lacriferous ducts. epidennal dendritic cells, dennal iibroblasts and inflammatory infiltrates. lmmonoreactivity with anti0 15-3 antibody was more reproducible and reliable than that wth antibody against CBA because a positive reacdon for CEA was weaker than that of Ca 15.3 and was not always found I” all Paget cells. When compared with antibody to Ca 15.3, that to SLX was less useful because the latter had immonoreaclivi~y with epidermal dendmic cells and many infilualing cells m the denis. Thus, antibody 10 Ca 1S-3 seems most useful among four wmor markers 10 stain Paget cells. Depending on the staining pattern of the antibodies 11IS suggested that Lhe origin of Paget cells is secretory cells of apocrine sweat glands m EMPD. and luminal lactiferous ducts in MPD.
NETABOLIC NEFBRrx*THY.
N.
CHANGES IN I. Schakhtmeister,
Nevero”,
noscow. We
S.
Grachev,
PBORIASIB
AND
PSORIATIC
K. Golov, M. Ryabinina. Sechenov Medical Academy,
Russia
EFFECTS OF TOPIULLY @PLIED SPIRONOLbCmNEON mNDROGEN STIMUUTED SEBACEOUS GLANDS IN THEHlWSTER PINNA. Taisuke Seki and Masaaki Morohashi. Department of Dernatalogr.
Faculty
of Medicine.
Toyama Medical and Pharmaceutical
the role of carbonhydrate, lipid and $nalvsed in clinical ;nd morphological purine abriormelities features of psoriatic nephropathy for‘ three groups of patients namely GII with proteinuria (0.05-3.8 9/l), patients psoriatic nicroalbuminuria and lx* with without proteinuria and microalbuminuria (Gr3). and Gr2 we observed significantly higher levels of serum and urine uric acid, serum triglycerides, total increased (VLDL+LDL)/HDL ratio in comparicholesterol, son with Gr3. Besides that in GrZ comparing to Grl and Gr3 there were significantly increased levels of qlycemia and basal qlomerular filtration rate (GFR), decreato acute protein sed renal ~‘eseue (i.e. GFR response correlation of glycemia and uric acid load), positive study of renal levels with basal GFR. Morphological biopsy in WI (34 cases) revealed various types of qlomerulonephritis and focal and segmental qlomerulOSclerosis with LDL-depositions (4 cases) and uric acid crythickened stals (1 case). in Gr2 (8 cases) it revealed qlomer&rbasement membrane and mesangium proliferation mainly in area of glomerular hilus. The hyperlipidemia with increased (VtDL+LDL)/HDL ratio, uric acid and hyperperfusion due to hyperglycemia and hyperuricemia iS supposed to cause morphological changes in Grl and Gr2.
Ilniwrsit". .lacan
A NEW MODEL FOR CYCLOPHOSPHAMIDE-INDUCED ALOPECIA AND ITS MANIPULATION BY CYCLQSPORlNE A ANDTOPICAL DEXAh4EWASONE. &Stefan Eicvaod M.Caas&& Dermatology, Bori Handiis Universitv Hosoilal R. &bow. Freie UnivetiULt Be& D-1000 Berlin 65 Aiopec& as a side-effect of chemorherapy rem&s a major problem in clinical oncology. Reliable scrceniog systems for the detection of effativc means to block ibe devclopmeoc of rbis alopecia am required. Here, we introduce cyclophosphamide (CYP)-induced alopecia io the C 57 BM rnoux as one ~atticolarly attractive model. It assesses the effects of P single intrapritooeal injection of CYP (Im 150 mgikg) o(1 the growrh. pigmentation and recovery of malure. dcpilafion-induced aoagen VI hair follicles in adolescent animals. This was followed over time and analyzed by assessing hair cycle-dependent changes in skin color, by bislological morphomerry and by electron microscopy. CYP-treated mice display macroscopic and histological phenomena that strikingly resemble the characteristic hair follicle pathology seen with CYP-induced alopcia in man: patchy alopecia of rapid onset. melanin clumping and incontinence, dental papilla swelling, and distension of the follicular canal. Also, the pattern of follicle recovery and repigmentatioo follows that occunng under clinical conditions. Anagen VI follicles respond to CYP by the induction of dySb@ic anagen and catagen, and there are regional diierences in the follieular vulncmbili~y to CYP. Ulfrastmcturally, cell damage to hair matrix temtinocytes and dennal papillafibmblasts and extraccllularly localed. abnormal mclanosorncs were seen in CYP-treated mice. CYP-induced alaoccia could be attenuated by intraoeritosesl application of cyclmporiae A (3 x.5 mgtmousc) sad enhsooed by &p&l &xmxtethaso~%(O.l%). Due to its similaritv with CYP-induced alooecia in man. this is the clinically rnoft relevanl animal model &ailabls @date for studying the pathobiology of chemotherapy-induced alopecia and for snecaing for drugs that modulate this alvia.
ELECTRONMICROSCOPIC STUDY OF THE EFFECT OF SHORT-TERM TOPICAL TRETlNOM ON PHOTODAMAGED SKIN. -1s -L. ‘Dept. of Derm., Nagasald University School of Medicine, Nagasaki, Japan. acpt. of Den%, Univashy ofPenmylvania. Philadelphis. U.S.A. There have been many reports of the corrective effects of topical tretinoin on phdcdamaged skin. Previocs reports have employed tnwment schedules of six owntIm and Ionnet. To determine the imomvement obtained after a short-rnn topical applica&oftntinoin, fivemales,'agesX?to 61,withsevereIyphotodamag~skin received 0.05% tretinoin awn twice d&Iv for one month to the s!& of the dorsal forearm.Ihe following prooedorrs were &e before andaftertreatmeat: (1)3 mm punch biopsies for histochemisny and mmsmisskm clectmo mic-py. (2) sticky slidcs for mclnnization of emneceytes, (3) detergent scrubs for comcocyte sir&q and
In Gr1
UPa
Spironolactane
is a diuretic
antihrpertensive
drug which acts at the
aidosterone-dependent sodium-potassium exchange site in the distal
renal tubule. effects recwtor
by cowetitvely
inhibiting
le
investigated
sites.
spiranolactane
convoluted
Spironolactone has been also shorn to produce antiandrwenic dihydrotestosterone the effects
at the andrwen
of topically
applied
o,n the andraeen stimulated sebaceous glands br measuring the
post-application
sire of the sebaceous acinus as an index of the effect using
whole MUnt techniques in adult male golden hanrters. Topically applied spironolactone induced a 23% reduction of the sebaceous gland sire with a significantly
higher suppression rate
of the matching placebo in androgen atilrmlated baster Increased
sebaceous
petbogenesis
of
dihydrotestosterone suggest
potential
acne
secretion. vulgaris.
one of the various is
to androgen rerxptors usefulness
I ~(0.01 1 than that
riinnae.
induced
factors
by the
in the skin.
in the
binding
of
Tbua these results
of topicallyapplied spironolactonein the
treateent of acnevulgaris.
layas wxs Iedueed after treabnent. u1tIast?ocIuzaI1y. there were many villu54ike pmjcctions(VPs) on the comeooyte before atinom. The number of VR was demeaed and &smcsomal bcdies in stratum comelml innesscd after tmrtmcnL Dennalchangeswercinsigniiicant. S gIanulrswithincam~were~ pigmented spots. Despite these sinwuml cements, the eQn==w= we+x SnaaY swollen in size and incgolar in sl!ape. reflezang an abmrmal s!xntum -urn ban&. The plnicular effects of topical trerinoin on the epidennal abnommlitics of phdodpmagsdsldneanbediganvdaftcrallymlemonlhofaeamaa.