bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D3 and Its Synthetic Analogue Secocholestra-Trien-1,2,24-Triol Influence the Metabolism and the Isomerization of Retinoic Acid inHuman Keratinocytes
Authors: Jugert F.K. , Roos T.C. , Notzon I. , Merk H.F.
Published: April 2003

Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D3 – VD3) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol – TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 mM Ca for 24 h, followed by the addition of 10–6, 10–8 or 10–10 M VD3 or TAC, we added 10–5 M 13-cis-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD3 (10–6 M) inhibited the isomerization of 13-cis-RA to all-trans-RA (tretinoin) and 9-cis-RA independently from the Ca concentration in the culture medium. 10–6–10–10 M TAC equally inhibit the 4-hydroxylation of all-trans-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-all-trans-RA, leading to a higher persistence of all-trans-RA, the active hormone. Both VD3 and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD3 which prolongs the persistence of 13-cis-RA, and TAC elevating the intracellular concentration of all-trans-RA.
In vitro Cross-Linking of Recombinant Human Involucrin
Authors: LaCelle Peter T. , Lambert Adam , Ekambaram Meenakshi C. , Robinson Nancy A. , Eckert Richard L.
Published: April 2003

Human involucrin (hINV) is a constituent of the scaffolding of the cornified envelope. In the present study, we describe an in vitro model system to study the role of hINV in scaffold formation. We characterize the in vitro cross-linking of full-length (585 amino acid) recombinant hINV, rhINV(1–585). When reacted with detergent-solubilized, particulate transglutaminase type 1 (TG1) or partially purified type 2 transglutaminase (TG2), rhINV(1–585) functions as a TG substrate in a calcium-dependent manner. When the reaction is supplemented with 14C-putrescine tracer, the radiolabeled cosubstrate is incorporated into a high-molecular-weight product in a calcium-, rhINV(1–585)- and time-dependent manner. 35S-rhINV(1–585) is also cross-linked to form a high-molecular-weight product. These results suggest that rhINV(1–585) is extensively multimerized. Products having a molecular weight smaller than authentic rhINV(1–585) are also formed, providing evidence for intramolecular cross-link formation. Transmission electron microscopy of cross-linked product reveals immunoreactive large-molecular-weight loop-string-loop and branched structures. Our studies (1) show that rhINV(1–585) is a substrate for both TG1 and TG2, (2) indicate that rhINV(1–585) can be cross-linked to form macromolecular products having distinct structural features, (3) demonstrate that rhINV(1–585) forms intramolecular cross-links when hINV concentration is limiting and (4) establish that hINV possesses reactive Gln and Lys residues.
Photoallergenicity of a Fluoroquinolone Antibacterial Agent with a Fluorine Substituent at the 8-Position in Guinea Pigs Exposed to Long-Wavelength UV Light
Authors: Marutani Kiyoshi , Otabe Yohko , Nagamuta Masahiro , Matsubara Shuzo , Otani Hajime
Published: April 2003

The 8-position of the quinolone ring of balofloxacin (BLFX), one of fluoroquinolones, was replaced with fluorine to obtain the 8-F. When an aqueous solution of bovine serum albumin (BSA) containing the 8-F was exposed to long-wavelength UV light (UVA) at a rate of 2.5 J/cm2, the absorbance of BSA at 300 nm or longer wavelengths increased markedly in comparison to that of native BSA. In addition, when a homogenate of skin tissue from Hartley guinea pigs was exposed to UVA (2.5 J/cm2) in the presence of the 8-F and then injected subcutaneously into guinea pigs, the animals produced IgG class antibody specific to the 8-F and its UVA-irradiation product. No such phenomenon, however, was observed when the parent compound, i.e., BLFX which possesses a methoxy group at the 8-position, was used instead of the 8-F. In a subsequent experiment, the 8-F was administered either orally or topically to the shaved neck of guinea pigs and then irradiated with UVA (5 J/cm2) once daily for 5 days. When the treated animals were challenged by a combination of UVA irradiation (5 J/cm2) and either an oral or intradermal administration of the 8-F, 2 and 3 of the 5 animals showed redness and erythema on the irradiated area, respectively. However, no change was observed when BLFX was used instead of the 8-F. These results suggest that the introduction of a fluorine substituent to the 8-position of quinoline ring of fluoroquinolones induces photoallergic responses in which the fluoroquinolone or its photo-denatured product(s) act as an allergen.
Several Different Ion Channel Modulators Abrogate Contact Hypersensitivity in Mice
Authors: Wille John J. , Kydonieus Agis , Kalish Richard S.
Published: April 2003

A major obstacle in transdermal delivery of drugs is the development of adverse skin sensitization reactions. We tested the concept that ion channel modulators as a class of agents suppress contact hypersensitivity in a mouse model. Mice were sensitized to several contact sensitizing chemicals including dinitrochlorobenzene (DNCB) and a sensitizing drug, nadolol. We report our successful use of several ion channel modulators in suppressing contact hypersensitivity, including amiloride, ethacrynic acid (ECA), nifedipine and verapamil. For this purpose, Balb/c female mice were sensitized with DNCB, and abrogation of induction of contact hypersensitivity reaction (CHR) was examined by topical pretreatment of the target-sensitized skin with amiloride, nifedipine and pairwise combinations of these agents with ECA, a potassium ion channel blocker. Abrogation of induction of CHR was observed in all cases. In addition, suppression of contact hypersensitivity was observed in nadolol-sensitized mice pretreated with either verapamil or nifedipine. The results indicate that ion channel inhibitors are broadly effective inhibitors of allergic contact dermatitis and may be useful for facilitating the transdermal delivery of therapeutic drugs that have sensitization potential.
Bioavailability of Clobetasol Propionate – Quantification of Drug Concentrationsin the Stratum Corneum by Dermatopharmacokinetics UsingTape Stripping
Authors: Weigmann H.-J. , Lademann J. , Pelchrzim R.v. , Sterry W. , Hagemeister T. , Molzahn R. , Schaefer M. , Lindscheid M. , Schaefer H. , Shah V.P.
Published: April 2003

The concentration of clobetasol propionate in the stratum corneum after application of three different formulations was determined, quantifying the influence of the formulations on the bioavailability of the drug. The stratum corneum was sampled by tape stripping. The concentrations of clobetasol propionate were determined quantitatively by HPLC. After application of Clobetasol Propionate Cream USP, 0.05%, and Temovate Cream, 0.05%, identical amounts of the drug were found in the stratum corneum, whereas after application of Temovate ε Emollient, 0.05%, the quantity was clearly decreased. From results obtained measuring the drug concentration in the adjacent sites of the skin where the creams had not been applied, it became clear that clobetasol propionate in Temovate ε Emollient, migrated to a large extent in the lateral direction. This explains the lower concentration measured for this formulation in the skin areas where the cream had been applied. In general, a lateral distribution of the applied drug must be taken into account when positioning the application areas on the forearm.
Topical Anti-Inflammatory Activity of Human Recombinant Epidermal Growth Factor
Authors: Casacó A. , Ledón N. , González A. , Merino N. , Pérez R.
Published: April 2003

The topical anti-inflammatory activity of epidermal growth factor (EGF) was evaluated in inflammation models induced by 12-Otetradecanoylphorbol-13-acetate, croton oil and arachidonic acid. When EGF (1.5, 3 or 6 μg/ear) was coapplied with each inflammatory agent, there was a dose-related decrease in inflammation as assessed by ear punch weights, myeloperoxidase activity as well as by histopathological studies. The precise anti-inflammatory action of EGF is yet unclear, but we believe that interference with arachidonic acid metabolism may play an important role.
A Qualitative Estimate of the Influence of Halcinonide Concentration and Urea on the Reservoir Formation in the Stratum Corneum
Authors: Clarys P. , Gabard B. , Barel A.O.
Published: April 2003

The existence of a stratum corneum reservoir for topically applied substances is well known. Data concerning the stratum corneum retention time are important for the elaboration of optimal topical treatment. We used the re-occlusion technique followed by skin colour measurements (Chromametry) for the evaluation of the stratum corneum retention time of halcinonide. We found a significant reservoir for halcinonide up to 5 days after the initial application. The retention was found to be corticosteroid concentration and formulation dependent.
The Genetic Bases of the Porphyrias
Authors: Frank Jorge , Christiano Angela M.
Published: April 2003

The porphyrias are disorders that result from the inherited or acquired dysregulation of one of the eight enzymes in the porphyrin-heme biosynthetic pathway. The different types of porphyrias often show overlapping findings with regard to clinical and/or biochemical features. Therefore, the establishment of screening methods for the identification of underlying mutations on the basis of direct DNA analysis may provide a more reliable approach for diagnosis of the different types of porphyrias. Here, we provide an overview of molecular biological screening techniques for mutations and the molecular bases of the porphyrias.
Retinoid Therapy: Compatible Skin Care
Authors: Appa Yohini
Published: April 2003

Topically applied tretinoin (a retinoid) has been used for over 25 years to treat acne and disorders of keratinization. Now, tretinoin emollient cream, 0.05% (Renova®), may be prescribed for the treatment of photodamaged and chronologically aged skin, in conjunction with appropriate skin care and sun protection routines. Mild to moderate cutaneous side effects to topical tretinoin, such as xerosis, peeling, erythema and subjective irritation, are experienced by a majority of patients undergoing retinoid therapy. Results of clinical compatibility testing show that concomitant use of effective moisturizers, mild cleansers and daily sunscreens greatly enhance skin tolerance and patient comfort. A frequently prescribed regimen for topical treatment of photodamaged skin includes a combination of tretinoin and glycolic acid. While many clinicians report the use of both these agents for the management of their patients, little information exists in the literature about their compatibility in concomitant use. The results of a double-blind clinical study demonstrate that daytime usage of one of two 8% glycolic acid lotions in addition to nightly applications of Renova was well tolerated as part of a comprehensive skin care and sun protection program.
Treatment of Porphyria cutanea tarda with Oral Thalidomide
Authors: Monastirli A. , Georgiou S. , Bolsen K. , Pasmatzi E. , Papapanagiotou A. , Goerz G. , Kalofoutis A. , Merk H.F. , Tsambaos D.
Published: April 2003

Eight male patients with overt clinical and biochemical features of porphyria cutanea tarda (PCT) were orally treated with 300 mg/day thalidomide for 1 week and with 200 mg/day for 3 more weeks. Already after the first week of treatment no new vesicles and/or bullae could be observed. Spontaneous blisters completely disappeared, increased skin fragility subsided and skin hyperpigmentation receded about 2 months after completion of therapy, whereas hypertrichosis persisted. There was a rapid decrease in the urinary total porphyrin excretion which reached normal levels in all patients by the end of the fourth week of therapy, whereas the posttreament chromatographic pattern of urinary porphyrins revealed a slight reduction of higher carboxylated porphyrin metabolites and an increase in the amount of the excreted coproporphyrin, as compared to the pretreatment period. Somnolence, intermittent constipation and dry mouth occurred in all patients, 2 patients additionally experienced dizziness. No evidence of peripheral neuropathy could be detected and laboratory investigations revealed no abnormalities, as compared to the pretreatment period. During the 16- to 28-month follow-up of the patients, no clinical or biochemical relapse was observed. In view of the encouraging results of the present investigation, further studies are now warranted in order to definitely answer the question whether oral thalidomide may be regarded as an effective alternative approach to the treatment of PCT.
Kinetics of Plasma and Tissue Distribution of 9-cis-Retinoic Acid in Rat
Authors: Disdier B. , Marchetti M.N. , Bun H. , Placidi M. , Durand A.
Published: April 2003

The biotransformation and tissue distribution of 9-cis-retinoic acid was investigated in hairless rats. Indeed, only limited information is available about the pharmacokinetics of 9-cis-retinoic acid. Assuming that the target site for retinoids is the skin, tissue distribution study is therefore particularly justified. Following single oral administration of 30 mg/kg of 9-cis-retinoic acid, the parent drug and five metabolites were detected in plasma. Additionally, concentrations of 9-cis-retinoic acid and metabolites were determined in the skin and seven other tissues. The distribution of 9-cis-retinoic acid was rapid in all of the organs studied (Tmax ≤2 h). In skin, unchanged 9-cis-retinoic acid was still measurable up to 168 h after administration and was undetectable in other organs and plasma after 48 h.
Inhibition of Irritation and Contact Hypersensitivity by Phenoxyacetic Acid Methyl Ester in Mice
Authors: Wille John J. , Kydonieus Agis , Kalish Richard S.
Published: April 2003

New anti-irritant treatments are required to prevent irritation and sensitization reactions to consumer medicines and dermatological drugs. We report here that phenoxyacetic acid methyl ester (PAME) is an effective agent to prevent and treat irritant and allergic contact dermatitis. Balb/c mice skin-treated with 1% PAME do not lose weight relative to vehicle-treated mice, nor is it irritating to mouse skin. Topical PAME prevents skin irritation to a wide variety of irritants including: arachidonic acid, capsaicin, sodium lauryl sulfate (SLS), disodium laureth sulfosuccinate and tetradecanoylphorbol-13-acetate. Histological studies showed that 1% PAME greatly diminished dermal neutrophilic infiltration and dermal capillary vessel dilation, and prevented epidermal hyperproliferation and hyperkeratosis that accompanies detergent (SLS)-induced skin irritation. Topical PAME inhibited ear swelling following ear challenge during the elicitation phase of contact hypersensitivity in mice sensitized with 1-chloro-2,4-dinitrochlorobenzene (DNCB), oxazolone and the hair coloring dye ρ-phenylenediamine (PPD). Finally, topical administration of 1% PAME prior to PPD or DNCB sensitization prevented the induction phase of contact hypersensitivity. These results indicate that PAME represents a potential new category of potent topical anti-inflammatory agents.
Cutaneous Inflammation and Proliferation in vitro: Differential Effects and Mode of Action of Topical Glucocorticoids
Authors: Lange Katharina , Kleuser Burkhard , Gysler Anja , Bader Michael , Maia Claudia , Scheidereit Claus , Korting Hans Christian , Schäfer-Korting Monika
Published: April 2003

The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristics of this steroid, a new compound created according to an identical concept, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halogenated monoester desoximetasone 21-cinnamate (DCE) were tested and compared to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammatory processes in the epidermis, fibroblasts of the same origin were used to investigate the atrophogenic potential. Inflammation was induced by TNFα, resulting in an increased interleukin 1α (Il-1α) synthesis. As quantified by ELISA, all drugs significantly reduced Il-1α production. But PC and BMV appeared particularly potent, followed by DM and the two new congeners, which revealed minor anti-inflammatory activity. Glucocorticoid esters including PEP are rapidly degraded in keratinocytes (85% within 12 h). Hence, a ribonuclease protection assay of Il-1α mRNA was performed allowing short incubation times and thus minimizing biodegradation. This assay confirmed the anti-inflammatory potency of native PC and BMV. In contrary DCE and PEP did not reduce Il-1α mRNA to a significant extent. Therefore PEP acts as a prodrug only. In fibroblasts, Il-1α and Il-6 syntheses indicate proliferation and inflammation, respectively. Whereas PC and PEP inhibited Il-1α and Il-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly affected by the conventional glucocorticoids BMV and DM, but also by DCE. The minor unwanted effect of PC and PEP on fibroblasts was also reflected by their low influence on cell proliferation as derived from 3H-thymidine incorporation. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticoids. In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of Il-1α) and antiproliferative effects in fibroblasts (suppression of Il-1α and Il-6; 3H-thymidine incorporation) was analyzed. Here, PC is revealed as the only glucocorticoid with an improved benefit/risk ratio. Native PEP is shown to be almost ineffective and DCE presents exactly the opposite features of PC. It is tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts.
Diffusion of Water across Human Skin in the Presence of Two Barrier Creams
Authors: van der Bijl Pieter , van Eyk Armorel D. , Cilliers Jacques , Stander Ilse A.
Published: April 2003

The in vitro permeability of tritiated water through fresh and frozen human skin was evaluated in the presence and absence of two different barrier creams. Treated (10 min) and untreated fresh and frozen human skin disks (4 mm in diameter) were mounted in flow cells of a continuous flow-through diffusion apparatus. Buffer/tritiated water was collected from the acceptor chambers at 2-hour intervals for a total of 20 h and counted in a liquid scintillation counter. The results indicated that both barrier creams lowered the average flux rates of tritiated water through fresh and frozen skin, but no significant differences could be detected between the two preparations. However, different results may be obtained when compounds with molecular weights much higher than water are used.
Comparative Study of the Efficacy of Various Moisturizers on the Skin of the ASR Miniature Swine
Authors: O’Goshi Ken-Ichiro , Tabata Nobuko , Sato Yoshihisa , Tagami Hachiro
Published: April 2003

The skin of the back of the ASR hairless miniature swine shows a rough and scaly fissured appearance. Clinically it resembles that of ichthyosis vulgaris or senile xerosis in humans. By using the skin of this animal, we developed an assay system to evaluate the efficacy of different moisturizers. The study was carried out in winter months from January to March. To establish this system, we studied various topical agents including such ordinary emollients as petrolatum and 10% salicylic acid in petrolatum as well as those available as pseudodrugs from cosmetic companies or prescription drugs from pharmaceutical companies such as heparinoid- containing creams (w/o and o/w) and 10% urea creams. Applying 0.01 g of each agent to 7 randomly selected skin areas (2 × 2 cm2) on the back of a 6-month-old swine once daily for various periods of time, we measured high-frequency conductance, the parameter for the hydration state of the skin surface. As a result, we have established a simple assay system. It consists of applications of topical agents once daily for 5 days from Monday to Friday in the first week and of subsequent measurement of the skin surface hydration state once every week. Evaluation measurements were performed from day 14 to day 21 depending upon their moisturizing effects. We found that heparinoid-containing creams exerted highly effective moisturizing effects on the dry pig skin that lasted even over 3 weeks after discontinuation of the treatments that were carried out for the first 5 days.
Several Selective Protein Kinase C Inhibitors Including Procyanidins Promote Hair Growth
Authors: Takahashi Tomoya , Kamimura Ayako , Shirai Akio , Yokoo Yoshiharu
Published: April 2003

We have previously reported that procyanidin oligomers selectively promote growth of murine hair epithelial cells in vitro and stimulate anagen induction in vivo. We report here the possible relationship between the protein kinase C-inhibiting activity of procyanidins and their hair-growing activity. Of the procyanidins, procyanidin B-2 and procyanidin C-1, which selectively inhibit protein kinase C, intensively promote hair epithelial cell proliferation in vitro and stimulate anagen induction in vivo. On the other hand, procyanidins, which inhibit both protein kinase C and A, showed relatively low activity in in vitro and in vivo evaluations. We also found that calphostin C, which is a selective inhibitor of protein kinase C, possesses hair epithelial cell growth-promoting activity in vitro and anagen phase-inducing hair-growing activity in vivo. Other selective protein kinase C inhibitors, such as hexadecylphosphocholine, palmitoyl-DL-carnitine chloride, and polymyxin B sulfate, also show marked anagen phase-inducing hair-growing activity in vivo. Nonselective protein kinase inhibitors, such as staurosporine and K252a, inhibit the growth of hair epithelial cells. 1,2-Dioctanoyl-sn-glycerol, a protein kinase C activator, dose-dependently decreases the growth of hair epithelial cells. Forskolin, an adenylate cyclase activator, promotes hair epithelial cell growth and boosts the growth-promoting effect of procyanidin B-2. It is speculated that the hair-growing activity of procyanidins is related to their protein kinase C-inhibiting activity.
Differential Modulation of Transforming Growth Factor-β by Betamethasone-17- Valerate and Isotretinoin: Corticosteroid Decreases and Isotretinoin Increases the Level of Transforming Growth Factor-β in Suction Blister Fluid
Authors: Leivo T. , Arjomaa P. , Oivula J. , Vesterinen M. , Kiistala U. , Autio P. , Oikarinen A.
Published: April 2003

Retinoids and glucocorticoids are known to have a potential to modulate the expression of transforming growth factor-β (TGF-β). We investigated the effect of oral isotretinoin (13-cis-retinoic acid) on the expression of two distinct isoforms of TGF-β, TGF-β1 and TGF-β2, in suction blister fluid and serum in acne patients. We also investigated the effect of topical glucocorticoid (betamethasone-17-valerate) and age on suction blister fluid TGF-β1 in healthy volunteers. Six weeks of isotretinoin treatment caused a statistically significant 19% increase in suction blister fluid TGF-β1. The suction blister fluid TGF-β2 level remained below the sensitivity level of the immunoassay in many cases. Isotretinoin did not affect the serum TGF-β1 or TGF-β2 level. Betamethasone-17-valerate pretreatment for 3 days twice a day caused a statistically significant 17% decrease in suction blister fluid TGF-β1. The active form of TGF-β1 represented 5% of the total TGF-β1 in suction blister fluid. Our diffusion calculations suggest that all TGF-β1 and TGF-β2 detected in suction blister fluid have diffused from systemic circulation. The increase in suction blister fluid TGF-β1 after isotretinoin treatment seems to be of local origin, while the decrease in suction blister fluid TGF-β1 after glucocorticoid pretreatment seems to be due to glucocorticoid-induced vasoconstriction resulting in decreased diffusion of TGF-β1 from the circulation. Modulation of local interstitial fluid TGF-β1 concentration may be one mechanism by which isotretinoin and glucocorticoids mediate their effects in skin.
Evaluation of Dermal Irritancy Potential of Benzanthrone-Derived Dye Analogs: Structure Activity Relationship
Authors: Singh Ravindra P. , Das Mukul , Khanna Raj , Khanna Subhash K.
Published: April 2003

The twelve structural analogs of benzanthrone-derived dyes of commercial use were screened for their dermal irritation potential response using the Draize occlusive patch test. The test dyes, dissolved in DMSO as vehicle, were topically applied on the skin of the male Druckery rats (160 ± 10 g) according to the OECD protocol. The potential dermal hazard was assessed in terms of the primary cutaneous irritation (PCI) index and irritancy. Irritancy was evaluated according to the AFNOR scale. In terms of irritancy, the twelve benzanthrone dyes qualified as moderately irritant (3.0–5.0) according to the above scale. In decreasing order, PCI index of the various dyes was: Navy Blue R (4.5); Jade Green XBN (4.25); 16, 17-dihydroxydibenzanthrone (3.84); Black NB (3.75), Jade Green 2G (3.75); 3-bromobenzanthrone (3.58); Brilliant Purple 4R (3.58); Olive D (3.50); Dark Blue 2R (3.41); Olive Green B (3.33); isodibenzanthrone (3.33), and benzanthrone (3.16). These results indicate that benzanthrone-derived dyes/dye intermediates caused dermal toxicity which appears to be influenced by the number of carbonyl and amino-anthraquinone groups as well as by the presence of functional groups like halogen, nitro, hydroxy and methoxy in the parent molecule, benzanthrone.
Biophysical Characteristics of Healthy Skin and Nonlesional Skin in Atopic Dermatitis: Short-Term Effects of Ultraviolet A and B Irradiation
Authors: Habig Juliane , Vocks Elisabeth , Kautzky Florian , Ring Johannes
Published: April 2003

The present study was designed to evaluate basic differences in surface structure and viscoelastic properties of nonatopic versus atopic skin and facultative acute changes following ultraviolet irradiation. Therefore, biophysical measurements by means of profilometry and cutometry were carried out on sun-protected unaffected gluteal skin areas in both groups before and 24 h after single UVA and UVB irradiations. The results indicate that the clinically unaffected skin of patients with atopic eczema differs from normal skin in terms of increased roughness parameters, but not concerning depth of furrows or viscoelastic properties (viscosity and biological elasticity, cutometrically calculated). Single UVA irradiation with 50 J/cm2 induced neither measurable changes in the skin’s surface structure nor in its viscoelastic properties in both groups after 24 h. However, irradiation with a single erythemogenic dose of 1 MED UVB was followed by a short-term significant increase in the depths of furrows and decrease in biological elasticity in normal and atopic skin, accompanied by an increase in viscosity in normal skin.
The Pig as an Experimental Animal Model of Percutaneous Permeation in Man: Qualitative and Quantitative Observations – An Overview
Authors: Simon Gad A. , Maibach Howard I.
Published: April 2003

The pig has been a well-recognized experimental animal in biomedical research for many centuries. Physiological and anatomical similarities between man and pig made this animal a good model for man in many research areas. Pharmacological and toxicological research on the skin is often based on knowledge of skin absorption and percutaneous permeation. Anatomical, physiological and biochemical similarities are cited and various uses of the pig as a model for man in the investigation of skin permeation are reviewed. Further, several isolated organ models are reviewed. The importance of full details of the experimental animal, namely its age, sex, breed, size (weight) and body region, is emphasized.
Assessment of Toxic Potential of Industrial Chemicals Using a Cultured Human Bioartificial Skin Model: Production of Interleukin 1α and Hydroxyeicosatetraenoic Acids
Authors: Yang Eun Kyung , Yoon Hee Hoon , Lee Doo Hoon , Park Jung Keug
Published: April 2003

Cytotoxicity assays using artificial skin are proposed as alternative methods for in vitro tests to minimize animals used in ocular and dermal irritation testing. The responses of the artificial skins were studied to a well-characterized chemical irritant, such as toluene, glutaraldehyde and sodium lauryl sulfate (SLS), and a nonirritant, such as polyethylene glycol. The evaluation of irritating and nonirritating test chemicals was also compared with responses seen in human dermal fibroblasts and human epidermal keratinocytes grown in monolayer culture. The responses monitored included the MTT mitochondrial functionality assay. In order to better understand the local mechanisms involved in skin damage and repair, the productions of several mitogenic proinflammatory mediators such as interleukin-1α (IL-1α), 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were investigated. Dose-dependent increases in the levels of IL-1α and HETEs were observed in the underlying medium of the skin systems exposed to two skin irritants, glutaraldehyde and SLS. The results of the present study show that both human artificial skins can be used as efficient testing models for the evaluation of skin toxicity in vitro and for screening the contact skin irritancy in vitro.
Penetration Enhancers Assessed by Corneoxenometry
Authors: Goffin Véronique , Henry Frédérique , Piérard-Franchimont Claudine , Piérard Gérald E.
Published: April 2003

Chemical enhancers abating the barrier function of the stratum corneum act in a number of ways. Their relative effects in mixtures are notoriously difficult to determine. Corneoxenometry is a bioassay where xenobiotic interactions with corneocytes are assessed using reflectance colorimetry. It was used to evaluate comparatively the effects of ethanol and laurocapram at various dilutions. In addition, a 10% propylene-glycol-based gel supplemented with N-acetyl-L-cysteine, urea and salicylic acid in various concentrations was tested. The relative index or irritancy (RII) was calculated for each formulation. RII is a surrogate marker of lipid removal and disorganization, and of protein denaturation in the stratum corneum. It is likely a good predictor for barrier function alterations and represents a cheap and rapid alternative to animal testing.
The Stripping Technique: In vitro Absorption and Penetration of Five UV Filters on Excised Fresh Human Skin
Authors: Potard G. , Laugel C. , Schaefer H. , Marty J.-P.
Published: April 2003

This article gives the results of a study whose aim was to compare the compartmental distribution and absorption of 5 UV filters, in vitro, by fresh human skin, after exposure times of 30 min and 16 h. These UV filters from BASF (octyl methoxycinnamate, benzophenone 4, benzophenone 3, octyl triazone and octocrylene) were incorporated separately in a simple oil-in-water emulsion. The composition of the emulsions was designed in order to obtain a sun protection factor of 5. Therefore the UV filters were introduced into the emulsions at different concentrations. We show that the affinity for each skin level [stratum corneum (SC), viable epidermis, dermis and receptor fluid] is different according to the test substance used. Some substances accumulated in the SC, whereas others passed through the skin very quickly and were quantified in the receptor fluid. The stripping technique allowed us to see that more than 94% of the chemical compound in the SC was in the first eight tapes. The problem of individual values below the limit of detection was raised, a correlation between the two exposure times was found (y = 1.702x – 0.105; R = 0.94) and a classification of products according to their affinity for the SC was determined.
Antipruritic and Thermal Sensation Effects of Hydrocortisone Creams in Human Skin
Authors: Zhai Hongbo , Frisch Sherryl , Pelosi Alessandra , Neibart Steven , Maibach Howard I.
Published: April 2003

Few studies evaluate the effect of topical corticosteroids on thermal sensation and in alleviation of itch produced by intradermal injection of histamine. We evaluated the antipruritic effect of hydrocortisone (1% and 2.5%) on histamine-induced itch and sensory effects by measuring itch magnitude, itch duration and thermal thresholds using a computerized thermal sensory analyzer (TSA). This was a double-blind, random, comparative, controlled, single-dose and single-center study. Itch was experimentally induced in both forearms by intracutaneous injection of histamine in 18 subjects. Hydrocortisone 1%, 2.5% and placebo were applied to test sites on both forearms. The thermal threshold for warmth sensation, cold sensation, cold and heat pain was measured with the TSA. Itch magnitude was measured each minute after histamine injection for 10 min with a visual analogue scale (VAS). Itch duration was also recorded. In comparison to placebo, 2.5% hydrocortisone significantly (p = 0.03) reduced itch duration from 12.6 ± 11.0 min (mean ± SD) to 8.6 ± 8.2 min (the reducing rate was 32%) as well as itch magnitude (at minutes 3, 6, 7 and overall). Placebo, 1% and 2.5% hydrocortisone significantly altered (p <0.05) the cold sensation threshold. No treatment altered cold or heat pain thresholds. These data suggest that topical application of 2.5% hydrocortisone may be significantly beneficial for the treatment of histamine-induced itch. The correlation between thermal measurements and antipruritic effects warrants further study.
Study of Calcium Oxalate Crystalluria on Renal and Vesical Urines in Stone Formers and Normal Subjects
Authors: Robert Maxime , Boularan Anne-Marie , Delbos Olivier , Guiter Jacques , Descomps Bernard
Published: April 2003

Objective: The aim of this study is to compare vesical and renal calcium oxalate crystalluria in an attempt to correlate crystal formation with chemical composition and calcium oxalate saturation of renal urine. Material and Methods: Urine specimens were directly collected from the bladder and the kidney, of 11 stone formers and 11 control subjects under general anesthesia. The type of crystals present in urine as well as their size, number by cubic millimeter and state of aggregation were determined. In addition, calcium, magnesium, sodium, chloride, phosphate, citrate, oxalate, pyrophosphate and uric acid were measured in order to evaluate the calcium saturation status (EQUIL V program). Results: Calcium oxalate crystals were detected in 3 stone formers (27%) and 2 control subjects (18%) in vesical urine and in 4 stone formers (36%) and 3 control subjects (27%) in renal urine. Only 2 stone formers presented with simultaneous renal and vesical crystalluria. Subjects of the two groups with and without renal crystalluria were compared in terms of chemical composition and calcium oxalate saturation of renal urine. Crystalluric subjects (n = 7) had significantly higher uricosuria (p = 0.02), calciuria (p = 0.04), magnesiuria (p = 0.04) and calcium oxalate molar product (p = 0.05) than noncrystalluric (n = 15); calcium oxalate saturation was similar (p = 0.5). Conclusions: Beyond theorical considerations on lithogenesis, our observations and in particular the apparent discrepancy between renal and vesical crystalluria pose the problem of the clinical interest of the evaluation of calcium oxalate crystalluria based on freshly voided urine in the assessing the lithogenic risk or in the follow-up of patients who are particularly prone to stone recurrence.
Comparative Study of Therapeutic Effect of Dibenyline, Finasteride, and Combination Drugs for Symptomatic Benign Prostatic Hyperplasia
Authors: Kuo Hann-Chorng
Published: April 2003

Objectives: A prospective study was conducted in a community hospital in order to evaluate the therapeutic effect of dibenyline, finasteride, and a combination of the two drugs for symptomatic benign prostatic hyperplasia (BPH). Methods: 190 men suffering from severe prostatism entered this study. They were assessed by IPSS symptom score, digital rectal examination, transrectal sonography of the prostate, uroflowmetry and residual urine. The patients were randomly selected for medical treatment with dibenyline 10 mg b.i.d. (n = 71), finasteride 5 mg q.d. (n = 54), and a combination (n = 65). Clinical assessments were carried out before treatment and 3 and 6 months after starting treatment. Patients who could not complete the treatment and those with prostatic cancer were excluded from the final statistics. The quality of life after 6 months of treatment and side effects were also assessed. Results: A total of 172 patients completed the treatment course and 153 patients completed the periodic clinical assessments. Improvement in IPSS was noted in all 3 groups of patients both at 3 and 6 months. The prostatic volume was found to decrease in the finasteride group and the combination group at 6 months by 24.3 and 10.5%, respectively. Maximal flow rate (Qmax) was significantly improved in the dibenyline and combination groups but not in the finasteride group at 3 months. At 6 months a significant increase in Qmax was noted in all groups with a mean increase of 1.4–1.8 ml/s. The quality of life after treatment was satisfactory in 71.9% of the dibenyline group, 70.4% of the finasteride group and 83.1% of the combination group. Side effects were higher in the dibenyline than the finasteride or combination group. The dropout rate was higher in the dibenyline group (15.5%) than in the finasteride (7.5%) and combination (4.6%) groups. After 6 months of treatment, some of the patients discontinued medication and symptom relapse was noted in 92.6% of the dibenyline group, 57.6% of the finasteride group, and 71% of the combination group. Conclusions: Medical treatment is effective in treating symptomatic BPH. Combination dibenyline and finasteride provides a weak synergistic clinical effect without additive side effects.
Magnesium Hydrogen Carbonate Natural Mineral Water Enriched with K+-Citrate and Vitamin B6 Improves Urinary Abnormalities in Patients with Calcium Oxalate Nephrolithiasis
Authors: Bren Andrej , Kmetec Andrej , Kveder Rado , Kaplan-Pavlovčič Staša
Published: April 2003

The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.
Acquired Renal Cystic Disease and Adenocarcinoma following Renal Transplantation – A Current Urologic Perspective
Authors: Sant Grannum R. , Ucci Jr. Angelo A.
Published: April 2003

Two patients treated with chronic dialysis and renal transplantation developed acute hemorrhage from a native kidney. Bilateral native nephrectomy demonstrated acquired cystic disease and adenocarcinoma in each of the four kidneys. The etiology of acquired cystic kidney disease (ACKD) is unclear and its incidence increases with the duration of dialysis. ACKD patients have a propensity to develop adenomas and adenocarcinomas. The increased incidence of renal neoplasms in ACKD patients warrants careful radiologic monitoring of native end-stage kidneys in selected patients.
Pyelovenous Fistula: An Uncommon Cause of‘Esse ntial Haematuria’
Authors: Al Turki Mohammed , Onuora Vincent C. , Koko Abdelmoniem H. , Al Mosa Mohammed , Al Jawini Nasser
Published: April 2003

Haematuria from obscure lesions of the kidney sometimes pose both diagnostic and therapeutic challenge. Recently, we managed a patient in whom a confident diagnosis of pyelovenous fistula was made.
Pelvic Arteriovenous Aneurysm Caused by Transurethral Resection of the Prostate: Successful Management by Intra-Arterial Embolization
Authors: Suzuki Yasuhiro , Nakada Teruhiro , Ishigooka Manabu , Hashimoto Tohru , Abe Yutaka , Sasagawa Isoji , Kubota Yoko
Published: April 2003

We report a case of pelvic arteriovenous aneurysm caused by transurethral resection of the prostate. An abnormal vascular system was successfully managed by intra-arterial embolization using N-butyl cyanoacrylate in combination with platinum coil.
Increased Transforming Growth Factor β1 Plasma Level in Patients with Renal Cell Carcinoma:A Tumor-Specific Marker?
Authors: Wunderlich H. , Steiner T. , Kosmehl H. , Junker U. , Reinhold D. , Reichelt O. , Zermann D.H. , Schubert J.
Published: April 2003

Purpose: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers. Materials and Methods: The level of latent transforming growth factor β1 (TGF-β1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls. Results: In all cases of RCC the levels of latent TGF-β1 in plasma were much higher (n = 20, 41.0 ± 13.9 ng/ml, range 19.3–78.1 ng/ml) than in healthy controls (n = 20, 3.8 ± 2.9 ng/ml, range 0.6–9.9 ng/ml, p < 0.0001). The TGF-β1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 ± 4.64 ng/ml, range 2.9–21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 ± 14.2 ng/ml, range 4.2–46.7 ng/ml, p < 0.001) were also higher than in healthy controls. Conclusion: We conclude that increased levels of latent TGF-β1 are common in the plasma of RCC patients. The TGF-β1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-β1 is a possible tumor-prognostic marker in RCC.
DNA-Flow Cytometric Analysis of Bladder TCC Using Paraffin-Embedded Tissues
Authors: Wu Lujia , Lochhead Alistair , Yang Jia-Lin , Ow Kim T. , Russell Pamela J.
Published: April 2003

A retrospective study of DNA flow cytometry (FCM) in paraffin-embedded tissues of urinary bladder transitional cell carcinoma (TCC) was performed on 239 biopsy samples taken from 81 patients in the period from 1984 to 1994. 210 (87%) were analysable. Of these samples 21 patients had multiple biopsies taken from large tumours and/or bladder mucosa showing an endoscopically normal appearance. DNA-FCM results have been evaluated comparing ploidy and histopathological grade, clinical stage and different clinical status, i.e., first diagnosis, recurrence and patients who died from bladder cancer. Our results indicate that ‘diploid’ FCM correlated with a better prognosis, whilst DNA aneuploid correlated with malignancy and a poorer prognosis. There was a trend to an increasing incidence of DNA aneuploidy as the grade of the tumour rose and the proportion of biopsies with aneuploidy was significantly higher in malignant tissue samples, recurrences and in biopsies from patients who died from TCC than in other groups. In 12 patients from whom several biopsies were obtained, samples from recurrences had significantly higher DNA aneuploidy than those from the first diagnosis.
Relationship of Prostate-Specific Antigen Levels to Prostate Volume and Age in Mass Screening Subjects
Authors: Akimoto Susumu , Ichikawa Tomohiko , Ito Haruo
Published: April 2003

To evaluate the relationship between prostate-specific antigen (PSA) levels and prostate volume and age in a mass screening for prostatic disease, a total of 1,162 examinees from one Japanese prefecture who were over 45 years of age underwent a mass screening for prostatic disease that used the Hybritech (Tandem®RIA) kit, and the prostate volume was estimated by transabdominal ultrasonography. Differences among several groups of men according to prostate volume and age were examined by multiple comparisons using ranks. When some subjects visited several times, the data of the first visit were adopted only. The total number of individual subjects in this study was 589 men. The multiple comparisons using ranks and 10-year age brackets revealed that the levels of PSA showed significant differences between only two pairs of groups stratified by age. In contrast, the levels of PSA showed significant differences among seven pairs of groups stratified by the prostate volume according to 10-ml brackets. When a logarithmic transformation of the serum levels of PSA was used, the results showed the same tendencies. From the results of the present study, it can be said that the PSA reference range calculated with stratified prostate volume might be more useful in the detection of prostate cancer than that calculated with stratified age.
Testicular Relapse after 13 Years of Complete Remission of Acute Lymphoblastic Leukemia
Authors: Franck P. , Duffner U. , Schulze-Seemann W. , Riede U. , Dördelmann M. , Niemeyer C.M.
Published: April 2003

Girls with acute lymphoblastic leukemia appear to have a higher cure rate than boys. This is in part attributable to the reoccurrence of testicular disease in boys. Although the frequency of testicular relapse is less than 5% with current intensive therapy regimens, testicular disease remains of apparent clinical importance. Here we report an unusually late testicular relapse in an 18-year-old male after 12.7 years of continuous complete remission, and review the literature regarding this late failure.
Adrenal Lipoma
Authors: Sharma M.C. , Gill S.S. , Kashyap S. , Nabi G. , Mishra M.C.
Published: April 2003

Lipoma of the adrenal gland is an extremely uncommon tumor detected incidentally at postmortem or during life when the patient undergoes investigations for other reasons. All tumors reported in the literature were very small in size. We report a case of lipoma of the adrenal gland in a 45-year-old male patient who was hypertensive and presented with pain in the abdomen. The symptomatic presentation, large size, laparoscopic removal and rarity of this tumor merit documentation in the literature.
Inguinal Hernia as a Rare Cause of Penile Prosthesis Malfunction
Authors: Tiguert Rabi , Tefilli Marcos V. , Gheiler Edward , Shekarriz Bijan , Upadhyay Jyoti , Dhabuwala C.B.
Published: April 2003

Penile prosthesis malfunction is associated with mechanical failure as well as with infection requiring removal of the prosthesis. We report on the 2 first cases in the literature of inflatable penile prostheses in the presence of inguinal hernia. We advocate early hernia repair in patients with inflatable penile prostheses to avoid malfunction related to hernia.
Micturitional Disturbances due to Labial Adhesion
Authors: Saito Motoaki , Ishida Goro , Watanabe Nobuyuki , Abe Bungo
Published: April 2003

We report 2 cases of micturitional disturbances due to labial adhesion. Two women, aged 78 and 77 years old, visited our hospital with chief complaints of difficult voiding and urinary retention. On examination, their labias were found to be extensively fused. In both cases, the labial adhesions were separated by surgical repair under spinal anesthesia. Gentamicin and steroid ointments were used to prevent readhesion of the labia postoperatively.