bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo Human Skin Barrier Modulation by Topical Application of Fatty Acids
Authors: Tanojo Hanafi , Boelsma Esther , Junginger Hans E. , Ponec Maria , Boddé Harry E.
Published: April 2003

The in vivo effects of fatty acids on skin barrier function were assessed by measuring: (i) transepidermal water loss (TEWL), (ii) diffusion lag times for hexyl nicotinate (HN), and (iii) irritant skin response using laser Doppler velocimetry (LDV) in combination with visual scoring. Two classes of fatty acids have been investigated: straight-chain saturated fatty acids (SFA), having 6–12 carbon atoms, and unsaturated fatty acids (UFA): oleic, linoleic, α-linolenic and arachidonic acids. It has been reported that these acids can enhance the permeation of various compounds across the skin. After topical and occlusive application as a solution in propylene glycol (PG) for 3 h on the volar arm of human subjects, SFA only caused a slight irritation and increase in TEWL. The diffusion lag times of HN were reduced by the application SFA to the same extent as and not more than by the application of the pure solvent PG. In contrast, the application of UFA caused a significant increase in TEWL and LDV (irritation) responses. The TEWL values after oleic acid application were higher than those observed for the other three acids, while the irritation potential of arachidonic acid was the highest among UFA. As with SFA, sites treated with UFA did not show significantly different lag times of HN diffusion from PC-treated sites. The data suggest that the degree of irritation and the degree of barrier modulation for fatty acids are not necessarily correlated.
Cutaneous Microdialysis in the Rat: Insertion Trauma and Effect of Anaesthesia Studied by Laser Doppler Perfusion Imaging and Histamine Release
Authors: Groth Lotte , Jørgensen Aksel , Serup Jørgen
Published: April 2003

Microdialysis makes it feasible to study compounds in the extracellular space of cutaneous tissue in vivo. The insertion of the microdialysis probe causes a trauma, which may be anticipated to influence the microdialysis process. The effect of anaesthesia on basal skin blood flow and the trauma in the skin after insertion of a microdialysis probe were investigated. Hairless rats were anaesthetized either with halothane or pentobarbital sodium. Basal skin blood flow and the effect of insertion of a microdialysis probe were measured by laser Doppler perfusion imaging. Trauma-induced histamine release was investigated. Rats anaesthetized with pentobarbital sodium showed a stable skin perfusion in contrast to rats anaesthetized with halothane. A significant increase in blood flow was seen after insertion of the microdialysis probe in the dermis of rats anaesthetized with pentobarbital sodium, while a change in skin blood flow was not observed in rats anaesthetized with halothane. Probe insertion caused histamine release in rats. A minimum equilibration period of 30 min between probe insertion and the start of the experiment is recommended in future studies, allowing immediate events of the trauma to subside and stabilize.
Dithranol Embedded in Crystalline Monoglycerides Combined with Phototherapy (UVB): A New Approach in the Treatment of Psoriasis
Authors: Gerritsen Marie-Jeanne P. , Boezeman Jan B.M. , Elbers Maria E. , van de Kerkhof Peter C.M.
Published: April 2003

Treatment of psoriasis with dithranol as monotherapy or dithranol in combination with UVB phototherapy is an effective and safe approach for the management of psoriasis. Recently a new formulation of dithranol embedded in crystalline monoglycerides (Micanol) has become available. It was shown that this formulation combines adequate efficacy with low irritation and staining properties. The aim of the present study was to compare and contrast three treatment schedules with respect to clinical efficacy and tolerability: Micanol monotherapy, Micanol in combination with UVB phototherapy and placebo combined with UVB phototherapy. The study design was a partly open, partly double-blind, randomized, left-right comparison. In total 36 patients were included and 24 body halves were available for each of the three treatments. The combination of Micanol with UVB resulted in clearance of lesions in 54% of the patients (body halves). Combination therapies with Micanol and either of the two other therapies were highly effective. However, with the number of patients investigated, a statistically significant difference between the three therapeutic approaches with respect to efficacy could not be shown. The three treatments resulted in a grosso modo comparable clinical improvement. Severe irritation was observed in 8% and staining of the skin in 29% of the patients treated with the combination therapy Micanol/UVB, which is far less compared to the irritation and staining by the conventional short contact approaches. The efficacy and tolerability of Micanol make this active substance an important tool in the management of psoriasis.
Epidermal Enzymes: Their Role in Homeostasis and Their Relationships with Dermatoses
Authors: Redoules D. , Tarroux R. , Périé J.
Published: April 2003

This review underlines the importance of different enzymes (β-glucocerebrosidase, phospholipase A2, proteases and cholesterol sulfatase) in the formation and maintenance of the epidermal barrier function. Certain diseases may be characterized by the lack or excess of one or more of these different enzyme activities, altering the homeostatic equilibrium of the epidermis. In addition to this, particular enzymes may show potential in the development of novel dermocosmetic strategies.
Influence of Endothelial Cells on Structure, Biochemistry and Functionality of Epidermis Reconstructed on Synthetic Porous Membrane
Authors: Pouliot R. , Robert M. , Germain L. , Noël-Hudson M.-S. , Lindenbaum A. , Juhasz J. , Auger F.A. , Wepierre J.
Published: April 2003

The model of keratinocytes cultured on a synthetic porous membrane at the air-liquid interface leads to the formation of a pluristratified and cornified epidermis with histological and biochemical characteristics near those observed in vivo. In the present study, we evaluated the effect of proliferative endothelial cells on epidermalization. Keratinocytes were grown in three culture conditions: in defined medium (DM; control), in medium previously conditioned by proliferative endothelial cells (CM) and in medium with proliferative endothelial cells (pEC). The structures of reconstructed epidermis were analyzed by electron microscopy, their biochemistry by DNA, protein and cytokine analyses and finally their functionality was evaluated by estradiol and water absorption testing. Ultrastructural analysis showed a well-developed and cornified epidermis for each culture condition. In addition, living epidermis was thinner in the presence of endothelial cells, revealing faster epidermal differentiation. DNA and protein analyses were in accordance with these results. Secreted soluble factors varied according to culture conditions. At 37°C, the permeability of reconstructed epidermis in DM, in CM or with pEC was 5- to 10-fold higher than that of native human epidermis with both tracers. Laminin coating of the inserts led to similar absorption results except for the DM where the barrier function to estradiol was decreased 2-fold. At 32°C, reconstructed and native epidermis were, respectively, 1.5- and 2-fold less permeable to estradiol compared to 37°C. In conclusion, this model is adequate for fundamental and pharmacological studies since it allows the study of interactions between two cell types without their direct contact as well as percutaneous absorption tests directly performed in the modified culture chamber.
Dehydrogenation of 3-Phenoxybenzyl Alcohol in Isolated Perfused Rabbit Skin, Skin Homogenate and Purified Dehydrogenases
Authors: Bast G.E. , Kampffmeyer H.G.
Published: April 2003

The formation of 3-phenoxybenzoic acid from 3-phenoxybenzyl alcohol was determined in (a) rabbit ears, single-pass perfused with a protein-free buffer, pH 7.4; (b) the microsomal fraction and its supernatant from homogenized rabbit skin; and (c) purified alcohol dehydrogenase from horse liver and baker’s yeast. The inhibition of product formation in (a) was about 60% by various 4-methylpyrazole concentrations, but metyrapone had no effect. Following ultracentrifugation, only the supernatant of homogenized skin showed product formation (apparent Vmay: 32 pmol/min per cm2 skin; apparent Km: 64 µM). 3-Phenoxybenzyl alcohol and ethanol dehydrogenation was similar by alcohol dehydrogenase from horse liver (apparent Km: 0.7 vs. 0.4 mM; apparent Vmax: 0.3 vs. 0.2 U/µg protein). In baker’s yeast, the apparent Km of 3-phenoxybenzoic acid formation was several times larger than that for ethanol dehydrogenation. The KI of 4-methylpyrazole for alcohol dehydrogenase from horse liver was 0.6 (3-phenoxybenzyl alcohol) vs. 0.04 µM (ethanol). The KI for ethanol in baker’s yeast was 470 µM. In conclusion dehydrogenation is an important metabolic pathway in the skin for xenobiotics with an aliphatic alcohol at a side chain.
Drug Monitoring of Orally Administered 8-Methoxypsoralen in Patients Treated with Extracorporeal Photopheresis
Authors: Balogh A. , Merkel U. , Looks A. , Vollandt R. , Wollina U.
Published: April 2003

Recently extracorporeal photopheresis (ECP), a new therapy involving extracorporeal activation of orally administered 8-methoxypsoralen (8-MOP), has been established for the treatment of different skin diseases. The pharmacokinetic profile of 8-MOP has been pursued in a clinical study which aimed to assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. However, the enormous intraindividual variations in plasma as well as buffy coat concentrations affect the efficacy of oral 8-MOP therapy. Therefore, the introduction of a liquid 8-MOP formulation enabling the direct administration of the drug into the treatment bag of the ECP device is challenging.
Modulation of Human Stratum Corneum Properties by Salicylic Acid and All-trans-Retinoic Acid
Authors: Piérard-Franchimont Claudine , Goffin Véronique , Piérard Gérald E.
Published: April 2003

Topical all-trans-retinoic acid (RA) has been reported to decrease the in vivo skin response to sodium lauryl sulfate (SLS). The converse was also shown with a synergistic effect of RA following prior applications of SLS. The reason for such effects is not clear. We employed measures of transepidermal water loss (TEWL), squamometry and sequential corneosurfametry to explore the protective activity of a 0.05% RA cream at the level of the stratum corneum. Nonionic oil-in-water emulsions with or without 5% salicylic acid (SA) served as test product references. Data indicated that the RA formulation was responsible for a stochastic impairment in the TEWL and for an increased intercorneocyte cohesion. SA and the unmedicated emulsion did not lead to similar TEWL changes. The squamometry test proved to be very sensitive to disclose the effects of SA and RA without, however, allowing to distinguish the difference in the physiological processes involved. The corneosurfametry bioassay did not show any protection or synergistic effect between RA or SA and SLS challenge on the stratum corneum. This is in contrast to a previous work showing a positive protective effect afforded by retinol against SLS. The combined effects of irritant compounds affecting the stratum corneum are complex. The precise reason for some of their biological consequences remains a conundrum. On balance, products such as SA and RA do not appear to afford protection or impairment to a surfactant challenge at the level of the stratum corneum.
Comparative Analgesic Efficacy of Nimesulide and Diclofenac Gels after Topical Application on the Skin
Authors: Sengupta S. , Velpandian T. , Sapra P. , Mathur P. , Gupta S.K.
Published: April 2003

Nimesulide is a newer non-steroidal anti-inflammatory drug (NSAID) with selective cyclo-oxygenase (COX)-2 blocking property and has demonstrated a potent analgesic and anti-inflammatory activity on oral and rectal administration. However, the Cmax through both these routes is reached only after 3 h of administration. Dose-dependent gastrointestinal side effects also limit the concentration of drug that can be achieved at the site of inflammation when administered through these routes. The present study was conducted to evaluate the antinociception induced by a new gel formulation of nimesulide when applied on the skin. Efficacy of topical nimesulide gel 1% (w/w) was studied on mice in the acetic-acid-induced writhing, tail flick latency (TFL) test and formalin-induced pain models. The antinociceptive effect of nimesulide was compared to diclofenac gel (1% w/w). Both the drugs induced dose-dependent analgesia with peak effect seen between 90 and 120 min after treatment. Greater antinociceptive effect (expressed as percent maximum possible effect) was seen in the writhing test than in the TFL test, indicating the peripheral action of both drugs. Nimesulide evidenced significant protection in the first phase of formalin-induced pain indicating modulation of peripheral nociceptors unlike other conventional NSAIDs. This suggests that COX-2 may be a primary contributor to afferent evoked increase in prostanoid-mediated changes in pain processing. Antinociception seen following drug application on the skin was lower than that seen on intraperitoneal administration, indicating localised action following topical application. The findings of the present study suggest that the transgel formulation of nimesulide provides significant analgesic activity when applied topically.
cis-Urocanic Acid Induces Mast Cell Degranulation and Release of Preformed TNF--α: A Possible Mechanism Linking UVB and cis-Urocanic Acid to Immunosuppression of Contact Hypersensitivity
Authors: Wille John J. , Kydonieus Agis F. , Murphy George F.
Published: April 2003

The search for effective inhibitors of transdermal drug-induced contact sensitization was directed to dermal mast-cell-degranulating agents (MCDA). Human skin organ cultures were employed to test whether cis-urocanic acid (C-UA) and other potential MCDAs cause mast cell degranulation. These were then tested for their ability to inhibit the induction phase of the contact hypersensitivity reaction (CHR). C-UA at 1 μg/ml significantly depleted mast cell chymase, whereas trans-urocanic acid (T-UA) was relatively ineffective. C-UA, but not T-UA, induced local effects of liberated mast cell TNF-α, as detected by E-selectin expression on the microvascular dermal endothelium. C-UA significantly reduced (>70%) the ear swelling response in Balb/c mice, when applied 24 h prior to application of a sensitizing amount of dinitrochlorobenzene (DNCB), and induced a prolonged (>3 weeks) state of immune tolerance (>40%). Similar effects on local immunosuppression of CHR were observed with topical chloroquine and capsaicin, while cromolyn, a mast cell membrane stabilizer, was unable to inhibit DNCB-induced CHR. It is suggested that MCDAs may interfere with downstream events associated with accessory cell function.
Release of Amino Acids, Fluorescamine-Reactive Substances and Substance P from the Epidermis of the Living Animal
Authors: Wormser Uri , Shoham Shai , Brodsky Berta
Published: April 2003

The present study demonstrates a procedure for extraction and determination of stratum corneum amines in the living animal. A nonleaky well, containing 10 mM Tris-HCl buffer, pH 7.0, was constructed on the shaved backs of anesthetized animals. It was found that Ser, Ala, Gly and Pro are mainly released from the stratum corneum of 4-month-old guinea pigs, and in 2-month-old rats, Gly, Ser and Arg show the highest degree of release. Much lower amino acid concentrations were observed in 20-month-old rats. This was also reflected by the high levels of fluorescamine-reactive substances released from young rat skin as compared to the old animals. The release of the neuropeptide substance P into the aqueous medium was increased 3.2 times upon heat stimulus as compared to control skin. Amines and other compounds released from the skin may serve as markers for skin aging or for certain skin disorders, leading to a new approach for their treatments.
Variegate Porphyria: Past, Present and Future
Authors: Frank Jorge , Christiano Angela M.
Published: April 2003

Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. For a long time, this disease has caused confusion among the porphyrias because it presents with clinical symptoms and biochemical findings that can be similar to those found in other types of porphyrias. Here, we provide an overview of historical, clinical, biochemical, genetical, and other aspects of variegate porphyria that might be helpful in providing more insight into this rare disorder.
Porphyria cutanea tarda
Authors: Fritsch C. , Lang K. , von Schmiedeberg S. , Bolsen K. , Merk H. , Lehmann P. , Ruzicka T.
Published: April 2003

Porphyria cutanea tarda (PCT) is the most frequent form of porphyria. The underlying enzymatic defect in PCT is a reduced activity of the enzyme uroporphyrinogen decarboxylase (Uro-D). Four different types of Uro-D disturbances are known. Pseudoporphyrias such as porphyria cutanea uraemica or drug-induced PCT-like skin symptoms are distinguished from PCT. Porphyrinogens such as estrogens or alcohol, or other inducers of P450 isoenzymes provoke PCT. Polymorphisms of P450 isoenzymes, iron overload and infection with hepatitis C virus play an important role in the etiopathogenesis of disease manifestation. Dominant clinical symptoms are bullae, increased cutaneous vulnerability, hypertrichosis and elastosis. Biochemically, total porphyrin levels in urine are increased with a predominance of uroporphyrin and heptacarboxylic porphyrin. Isocoproporphyrin is demonstrable in feces. Best therapeutic strategies are the oral administration of chloroquine 125 mg twice a week and repetitive bloodlettings or the combination of both.
Photodynamic Diagnosis and Therapy in Dermatology
Authors: Fritsch C. , Lang K. , Neuse W. , Ruzicka T. , Lehmann P.
Published: April 2003

The topical application of δ-aminolevulinic acid (ALA) induces porphyrin formation in the skin, preferentially in tumor tissues. Irradiation of the porphyrin-enriched tumor tissue with Wood’s light leads to emission of a brick-red fluorescence. This principle may be used as a diagnostic procedure which may be termed photodynamic diagnosis (PDD). In ALA-PDD, tumors and precancerous lesions of the skin reveal a homogeneous, intensive red fluorescence. Psoriatic lesions also show a strong but inhomogeneous porphyrin fluorescence. ALA-induced porphyrin fluorescence in preoperative planning is a valuable method to determine the peripheral borders of a given tumor. The histopathological extensions of the tumors correlate well with the borders detected by the tumor-specific fluorescence. The main indications of PDD are the delineation of clinically ill-defined skin tumors and the control of the efficacy of other tumor therapies. Photodynamic therapy (PDT) utilizes exogenously applied or endogenously formed photosensitizers and their activation by light to induce cell death via formation of singlet oxygen and other free radicals. PDT is highly efficient in the treatment of solar keratoses and superficial basal cell carcinomas. Initial squamous cell carcinomas also show good response to ALA-PDT. During the last decade, numerous studies on PDT for dermatologic diseases were published, the more important ones are reviewed here.
Acute Intermittent Porphyria: Mutation Analysis and Identification of Gene Carriers in a German Kindred by PCR-DGGE Analysis
Authors: Petrides Petro E.
Published: April 2003

Acute intermittent porphyria (AIP) is the most frequent acute porphyria. Symptomatic patients and asymptomatic gene carriers are characterized by a reduction of their porphobilinogen-deaminase (PBG-D) activity to 50%, which is sufficient for porphyrin biosynthesis. PBG-D is encoded by two different mRNAs which are expressed in a tissue-specific manner. In classical AIP, the enzyme activity is reduced in erythroblasts and all other heme-forming body cells, whereas in the variant form of AIP, the PBG-D activity in erythroid tissues remains normal. Acute porphyria attacks can occur in gene carriers when the biosynthesis of heme is increased by drugs, low calory intake, alcohol consumption or infections. Under these conditions, PBG-D cannot convert the precursors adequately so that PBG and δ-aminolevulinate accumulate. This may lead to neurovisceral symptoms and other neurological complications which are potentially life threatening. In patients with AIP, mutation analysis by PCR-DGGE (denaturing gradient gel electrophoresis) is becoming increasingly important since it also permits rapid identification of their presymptomatic relatives. Using this technique, more than 120 mutations have been identified in the PBG-D gene. When identified, the family members are informed about their genetic predisposition and are taught how to prevent porphyric attacks. Here, I illustrate this preventive strategy by describing a German kindred of an affected patient with the variant form of AIP with 17 family members.
Laboratory Assessment of Hair Follicle Growth
Authors: Stenn K.S.
Published: April 2003

This article reviews the methods currently used to assess hair growth properties of a compound. The methods exploit in vivo, in vitro and ex vivo methodology. The challenge for the field remains to develop a purely in vitro system which reflects in detail the in vivo state.
Alterations of Rat Liver Phospholipid Composition Induced by Oral Thalidomide
Authors: Kalofoutis A. , Monastirli A. , Papapanagiotou A. , Georgiou S. , Pasmatzi E. , Sakkis T. , Bolsen K. , Goerz G. , Merk H.F. , Tsambaos D.
Published: April 2003

In an attempt to elucidate the effects of oral thalidomide on liver phospholipid composition, doses of 1 and 3 mg/kg/day of thalidomide were orally administered to two groups of female Wistar rats (7 animals each), respectively, over a period of 60 days. Control animals (n = 7) received corresponding quantities of the vehicle alone. Chromatographic analysis and quantitative determination of the isolated phospholipid classes revealed statistically significant alterations of phospholipid fractions in the liver of the animals treated with the higher thalidomide dose (3 mg/kg/day). These alterations may be associated with changes in the metabolic activity, ionic transport and cell-cell interactions of the hepatic cellular components.
Changes in the Skin Moisture Contents, Skin Color, and Skin Protein Conformational Structures of Sprague-Dawley Rats after Ultraviolet B Irradiation
Authors: Li Mei-Jane , Lin Shan-Yang , Liang Run-Chu
Published: April 2003

The influence of ultraviolet B (UVB) irradiation on the skin moisture contents, skin color, and protein secondary structure in the skin of alive Sprague-Dawley (SD) rats was investigated. The UVB irradiation source emitted 725 ± 10 μW/cm2 of UVB range with a peak at 302 nm during the exposure course of 6 h/day for 3 successive days. The moisture content of SD rat’s skin first decreased with the UVB irradiation, then returned to normal level on days 1 and 2, and, finally, decreased significantly with the increase of UVB irradiation on day 3. After the 6-hour irradiation on days 1 and 2, the moisture contents of the irradiated skin of SD rat returned to normal values, suggesting repairability of the irradiated skin of SD rat during the following 18 hour period without irradiation. By increasing frequency and duration of UVB irradiation, the skin color parameters exhibited a lower L* value, a greater a* value, and a higher ΔE value, indicating that the skin color darkened and reddened. The slight modification of protein secondary structure of the skin of SD rats after repeated UVB irradiation was evidenced. However, the infrared spectrum during the initial course of irradiation, from day 1 to day 3, exhibited a similar pattern. Thus, the alive SD rat’s skin was repairable during the 18-hour period without irradiation.
Studies on Constituents of Moisturizers: Water-Binding Properties of Urea and NaCl in Aqueous Solutions
Authors: Miettinen Heije , Johansson Gunnar , Gobom Sylvia , Swanbeck Gunnar
Published: April 2003

A water content of about 10% in the horny layer is necessary for softness and pliability of this part of the epidermis. In conditions with dry skin, emollients of different types are used. It is important that solid data are collected about the effect of the ingredients of emollients and moisturizers. Urea has since long been used in the treatment of dry skin. In the present report, the mixture of urea and sodium chloride has been analyzed with respect to its effect on the water vapor pressure in concentrated solutions. The depression of the water vapor pressure by NaCl and urea was found to be additive. Thus, the decrease in water vapor pressure in aqueous solution of urea-NaCl mixtures can be estimated by adding the decrease of water vapor pressure caused by dissolving the pure compounds. The results indicate that urea and NaCl in aqueous solution do not interact strongly and are, therefore, compatible in moisturizing preparations. They can, therefore, both be expected to be effective in mixtures giving a better than one of them alone.
Transglutaminase Reactivity of Human Involucrin
Authors: Lambert Adam , Ekambaram Meena , Robinson Nancy , Eckert Richard L.
Published: April 2003

Human involucrin (hINV) is assembled into cornified structures via formation of transglutaminase (TG)-dependent interprotein ε-(γ-glutamyl)lysine bonds. The hINV sequence includes 150 glutamine residues that could function as potential sites of cross-link formation. The present studies were designed to evaluate the extent to which hINV can function as a TG substrate under optimal conditions and in the absence of other substrates. Incubation of hINV with TG results in formation of 4–5 isopeptide bonds per hINV molecule. When the small amine donor 14C-putrescine is included in the reaction, 48 Q residues are labled. Isotope distribution and sequence analysis suggests that the 14C-putrescine-labeled sites are located throughout the protein. Our present results show that many hINV Q residues can be utilized for cross-link formation, and that hINV can be cross-linked at very high cross-link densities. These results suggest that, in vivo, factors other than hINV structure limit the number of residues used for cross-link formation.
Induction of Antiproliferative Effects in HaCaT Cells by a Synthetic Hydroperoxide
Authors: Göhring Jürgen , Fröde Dirk , Wohlrab Wolfgang
Published: April 2003

The effects of decylhydroperoxide (DHP) on proliferation were assessed in HaCaT keratinocytes. DHP, a model compound of lipid peroxidation, reduced proliferation dose dependently. The analyses of cell number, DNA synthesis and cell cycle distribution suggest a delayed progression through S-phase of DHP-treated HaCaT cells. It has been proven that necrotic and apoptotic cell death were also causes for the DHP-induced decrease in proliferation. Moreover, in HaCaT cultures treated with the highest DHP concentration, apoptosis occurred to a much greater extent thus playing an overproportional role in the decline in living cell number. Results with the radical scavenger ascorbic acid and the iron chelator deferoxamine support the conclusion that an iron-catalyzed radical formation from DHP may induce the DHP-mediated reduction in proliferation.
Predicting Visual Assessment of Allergic Patch Test Reactions by Non-Invasive Measurements
Authors: Zuang V. , Archer G. , Rona C. , Vignini M. , Mosca M. , Berardesca E.
Published: April 2003

The quantification of allergic patch test reactions to several compounds was evaluated on patients using laser Doppler velocimetry (LDV), transepidermal water loss and colorimetry. The correlation between visual scores and instrumental measurements was investigated by the implementation of a modern statistical method: a classification tree. The LDV showed the highest correlation with the severity of the reaction. The best prediction model was obtained when the data of the three instruments were considered together. Using the classification tree methodology, a model of classification, independent of human observation, was developed. The technique can not only predict an allergic reaction for a new patient, but can also give a measure of how reliable its predictions are. This new method, when entirely standardised and approved, could help in the harmonisation of patch test reactions in different laboratories, thus allowing a more homogenous interpretation of these reactions.
Correlation between in vitro Cyclic Adenosine Monophosphate Phosphodiesterase Inhibition and in vivo Anti-Inflammatory Effect
Authors: Goyarts Earl , Mammone Thomas , Muizzuddin Neelam , Marenus Ken , Maes Daniel
Published: April 2003

We tested the hypothesis that topical adenosine monophosphate phosphodiesterase (cAMP PDE) inhibitors are anti-inflammatory. These can be shown by a correlation between PDE inhibitory and anti-inflammatory function of a series of known PDE inhibitors. The effect of various cAMP PDE inhibitors on PDEs isolated from HaCaT cells was first investigated. These compounds were then tested as anti-irritants against topical 8% Balsam of Peru. A direct correlation was observed between the in vitro EC50 values for PDE inhibition and the in vivo anti-inflammatory potential with a correlation coefficient of r = 0.79. These results stress the value of PDE inhibitors as anti-inflammatory agents in topical use, and also demonstrate that the in vitro PDE assay can be used to predict in vivo anti-inflammatory potential.
Dose-Dependent Inhibition of Ribonuclease P Activity by Anthralin
Authors: Drainas D. , Papadimou E. , Monastirli A. , Tsambaos D. , Merk H.F.
Published: April 2003

The effect of five different anthralin concentrations on tRNA biogenesis was investi- gated employing the ribonuclease P (RNase P) of the slime mold Dictyostelium discoideum as an in vitro cell-free experimental system. RNase P is an ubiquitous and essential enzyme that endonucleolytically cleaves all tRNA precursors to produce the mature 5′ end. Anthralin revealed a dose-dependent inhibition of RNase P activity indicating that this compound may have a direct effect on tRNA biogenesis. Taking into account that anthralin has no structural similarities to the substrate (pre-tRNA) of RNase P, it seems reasonable to suggest that this compound may bind to allosteric inhibition sites of the enzyme.
Use of Infrared Attenuated Total Reflectance Spectroscopy for the in vivo Measurement of Hydration Level and Silicone Distribution in the Stratum corneum following Skin Coverage by Polymeric Dressings
Authors: Branagan M. , Chenery D.H. , Nicholson S.
Published: April 2003

The ability of wound dressings to hydrate the stratum corneum has been tested experimentally using attenuated total reflectance (ATR) infrared spectroscopy. A silicone gel dressing was able to hydrate the stratum corneum to the extent that its water content within the sampled volume was >60% after 5 h of contact compared with about 15% of normal exposed skin and about 30% for a highly permeable hydrophilic polyurethane dressing. An ATR method was devised to determine the presence and depth of penetration of silicone in the stratum corneum as a result of skin coverage by the polymeric dressing.
Effect of Internal Wool Lipid Liposomes on Skin Repair
Authors: de Pera M. , Coderch L. , Fonollosa J. , de la Maza A. , Parra J.L.
Published: April 2003

Intercellular lipids of the stratum corneum (SC) play a crucial role in keeping an optimal skin barrier function and in regulating the water-holding capacity. Recently, the internal lipids have been extracted from wool fibre. This lipid extract has a composition similar to that of the SC lipids. Two parameters were used to test the effect of topically applied internal wool lipids (IWL), structured as liposomes, on the water barrier functions of disturbed and intact skin: transepidermal water loss and skin capacitance. Liposomes made up of lipids that simulate the composition of the SC were also applied for comparison. The single application of the IWL liposomes on disturbed skin resulted in an accelerated recovery of water barrier functions. Daily application of these liposomes on intact skin for 5 days reinforced the skin barrier and increased the water-holding capacity. The repairing effect of the IWL enhances their suitability in the treatment, prevention and care of skin.
Investigation of the Stability of Coated Titanium Microparticles Used in Sunscreens
Authors: Lademann J. , Weigmann H.-J. , Schäfer H. , Müller G. , Sterry W.
Published: April 2003

Due to its UV-light-absorbing properties, titanium dioxide is used in many sunscreen products. However, concern has been raised about a possible photocatalytic activity of titanium dioxide on living tissues. To reduce potential adverse effects, titanium dioxide used in cosmetic preparations is often coated. The coating should be stable under conditions of use. In order to verify the coating stability, sunscreen-grade-coated titanium microparticles were investigated by laser-induced plasma spectroscopy. No changes in the mechanical stability of the coated microparticles could be detected during the manufacturing and penetration of the sunscreen. Applying strong forces on the microparticles by centrifugation, exceeding by far in use conditions, resulted only in small changes in the coating.
Structural Modifications in the Stratum corneum by Effect of Different Solubilizing Agents: A Study Based on High-Resolution Low-Temperature Scanning Electron Microscopy
Authors: López O. , Walther P. , Cócera M. , de la Maza A. , Coderch L. , Parra J.L.
Published: April 2003

The action of different solubilizing agents (chloroform-methanol mixtures and the nonionic surfactant octyl glucoside, OG) on the structural organization of the stratum corneum (SC) was investigated by means of the double-layer high-resolution low-temperature scanning electron microscopy technique. Chloroform-methanol mixtures were able to remove mainly the lipid without a significant loss of cohesion in the SC tissue. However, OG treatment caused a partial disaggregation of the corneocytes and their envelopes and, at a macroscopic level, a loss of cohesion in the whole SC tissue. As for lipid domains, after OG treatment the formation of rough structures was detected, probably associated with the disorder in the lipid lamellae. The formation of these new structures could be attributable to the interaction of the lipids with the proteins liberated from the corneocytes. Hence, a direct correlation may be established between the preservation of the structure of the corneocytes and the corneocyte envelope and the cohesion of the whole SC tissue.
New Insights into the Pathomechanisms of Contact Dermatitis by the Use of Transgenic Mouse Models
Authors: Traidl Claudia , Merk Hans F. , Cavani Andrea , Hunzelmann Nicolas
Published: April 2003

Allergic contact dermatitis (ACD) is one of the most common skin diseases with a great socioeconomic impact. Although extensively studied, its pathophysiology and the interaction of different cells and factors which lead to sensitization and elicitation reaction are still not completely understood. The advent of transgenic mouse technology has considerably changed the study of ACD. This technology has been used extensively to investigate biomedically important issues in such diverse areas as mammalian development, neurophysiology and immunology. This new approach has already led to fascinating results which are confirmatory but also contradictory to previous thinking on the role of certain cytokines, adhesion and cell surface molecules in the complex pathophysiologic process of ACD. This review will describe how recent experiments employing mice carrying cytokine and accessory molecule transgenes change our current understanding of contact dermatitis which may lead to improved therapeutic strategies.
Detection of Skin Irritation Potential of Cosmetics by Non-Invasive Measurements
Authors: Zuang Valérie , Rona Claudia , Archer Graeme , Berardesca Enzo
Published: April 2003

This study analyses the ability of four non-invasive techniques (laser Doppler velocimetry, evaporimetry, chromametry and corneometry) to discriminate between irritant and non-irritant products, when compared to appropriate controls, and to detect subliminal changes in barrier function and erythema. These changes, which remain undetectable in the traditional visual and palpable clinical assessment, can be used as early reactions that are followed by the development of overt skin irritation. Laser Doppler velocimetry and evaporimetry were good discriminators between irritant and non-irritant substances, whereas corneometry and chromametry did not clearly distinguish between them. Laser Doppler velocimetry and evaporimetry detected early stages in the development of an irritant reaction before it became visible, but chromametry was not able to detect an early irritant response. It was concluded that non-invasive measurements could improve the quality and relevance of data obtained from human irritation testing, since the data they provide are objective, quantitative and sometimes subclinical, which also allows the concentration of a positive control to be reduced, resulting in the induction of less skin damage in human volunteers and reducing the ethical concerns related to the deliberate induction of an irritant response in a ‘healthy’ volunteer.
Development of a Turbidimetric Assay to Study the Effect of Urinary Components on Calcium Oxalate Precipitation
Authors: Saso L. , Valentini G. , Casini M.L. , Mattei E. , Panzironi C. , Silvestrini B.
Published: April 2003

The pharmacological treatment of calcium urinary stones, most of which are made of calcium oxalate (CaOx), is only prophylactic. The causes of nephrolithiasis are often unclear, and a number of patients were found to be deficient in physiological inhibitors, e.g. citrate, pyrophosphate, magnesium, and specific proteins. The identification and characterization of these inhibitors can be performed in vitro by a number of methods, most of which are complex and time-consuming. Thus, we developed a simple turbidimetric method based on the precipitation of CaOx from a supersaturated solution. Using this approach, we determined that ionic strengths >0.2 and pH <5 inhibited the precipitation of CaOx. The first observation is of interest if one considers that the osmolarity of urine varies in the range of 50–1,400 mmol/kg, while the effect of pH is not usually seen in vivo because of the influence of other phenomena, such as the precipitation of uric acid. The activity of sodium chloride, magnesium and citrate was displayed at concentrations not far from their normal urinary level. Among several mono-, di- and tricarboxylic acids, like acetic, ascorbic, citric, isocitric, formic, fumaric, gluconic, glutaric, α-ketoglutaric, maleic, malic, malonic, propionic, pyruvic, succinic, and tartaric acid, only isocitric acid was more potent than citric acid. Pyrophosphate was a potent inhibitor in vitro, but its urinary level may not be sufficient for a significant effect in vivo. Amino acids like Ala, Arg, Asp, Glu, Gly, and Ser, which are known to bind calcium, showed little activity. Work is in progress to search for new compounds potentially useful in the treatment of nephrolithiasis.
A Case of Small Cell Lung Cancer Metastasizing to Prostatic Cancer
Authors: Ohmori K. , Nishimura K. , Nishizaka Y.
Published: April 2003

Although the fact that the presence of two or more malignancies in a single patient is not a rare occurrence, metastasis of cancer to cancer is rare. Generally the most frequent donor tumor is a lung cancer, and the most common recipient tumor is a renal cell carcinoma. A rare case of lung cancer with metastasis to prostatic cancer is described. To our knowledge, this report represents the first case of a small cell lung cancer metastasizing to a prostatic cancer.
Extracorporeal Shock Wave Lithotripsy for Vesical Lithiasis
Authors: Kojima Yoshiyuki , Yoshimura Mugi , Hayashi Yutaro , Asaka Hidekazu , Ando Yutaka , Kohri Kenjiro
Published: April 2003

Between 1991 and 1997, 17 male patients with bladder stones underwent extracorporeal shock-wave lithotripsy (ESWL) therapy in our department. One patient required epidural anesthesia and 5 patients were treated under intravenous sedation. Complete fragmentation was achieved after a single session in 9 patients and 4 required 2 sessions. Four patients underwent initial ESWL followed by mechanical cystolithotripsy. No major complications were noted. Fourteen patients were stone-free within 1 week after the procedure. Four patients were treated by transurethral resection of the prostate (TUR-P) on the day after completion ESWL. In conclusion, ESWL therapy is a simple, effective and safe modality for the management of vesical lithiasis.
A Study of Growth Pattern in Giant Condyloma acuminatum
Authors: Yagi Hiroshi , Igawa Mikio , Shiina Hiroaki , Shigeno Kazushi , Yoneda Tatsuaki , Wada Yukihiro , Sumura Masahiro
Published: April 2003

We report a case of giant condyloma acuminatum (CA) of the perianal region. Pathological diagnosis revealed a typical CA with no sign of atypia. In addition, HPV type 11 could be identified by Southern blot analysis. PCNA was highly positive immunohistochemically, but the positivity of p53 protein was not as high as compared with the other control cases. Thus, the high growth rate of tumor cells evaluated by PCNA staining seems to contribute to the marked increase in size, and not only the p53 mutation but also an other cascade may be implicated in cell proliferation.
Oral Calcium Supplement Decreases Urinary Oxalate Excretion in Patients with Enteric Hyperoxaluria
Authors: Takei Kazushiro , Ito Haruo , Masai Motoyuki , Kotake Tadashi
Published: April 2003

We studied the effect of oral calcium supplementation in patients with enteric hyperoxaluria. Three patients with renal stone events following ileal resection were given oral calcium supplement. One of the three patients was put on a low-fat diet. The treatment reduced urinary oxalate excretion to the normal range. Subsequently, 2 patients reduced the dose of calcium supplementation at their own discretion and consequently developed renal stones again together with hyperoxaluria. Based on these observations, we believe that an adequate dose of calcium can normalize urinary oxalate excretion.
Diagnostic Value of Voided Urine and Bladder Barbotage Cytology in Detecting Transitional Cell Carcinoma of the Urinary Tract
Authors: Konety Badrinath R. , Metro Michael J. , Melham Mona F. , Salup Raoul R.
Published: April 2003

In this article we report on our experience with the use of urine cytology for the screening and diagnosis of transitional cell carcinoma (TCC) of the bladder and upper urinary tracts at our institution between January 1987 and December 1995. A total of 76 patients were included in the study. All patients had voided urine cytology studies read as positive or highly suspicious for malignancy and no prior history of TCC of the urinary tract. All these patients subsequently underwent cystoscopy, bladder/ureteral barbotage cytology, random bladder biopsies, and radiographic studies of the upper tracts. Of the 76 patients with positive urine cytology, 53 also had barbotage urine cytologies which were positive. Six of these patients were found to have cystoscopically evident TCC of the bladder, and 1 patient had upper tract TCC. Three other patients subsequently went on to develop TCC of the bladder at 52, 89 and 111 months of follow-up. An additional patient was diagnosed with upper tract TCC at 12 months of follow-up. Among the 23 patients with negative bladder/ureteral barbotage cytology, 3 patients, 2 at the time of initial cystoscopy, and one 15 months later, showed evidence of TCC. Median patient follow-up was 97 (range 35–132) months. Thus of 76 patients with initial positive voided urine cytology studies, only 9 proved to have TCC at initial work-up, while 5 other patients were diagnosed with TCC during a median follow-up of 97 months. The statistical diagnostic values of the bladder/ureteral barbotage urine cytology studies at the time of cystoscopic work-up were: sensitivity 77%; specificity 31%; positive predictive value 13%, and negative predictive value 91%. Our data suggest that in patients without a previous history of TCC, the diagnostic value of bladder barbotage urine cytology is insignificant, and therefore not cost effective to be included as part of the routine work-up of TCC. Moreover, in patients with initially positive voided urine cytology and negative work-up, if the cytology subsequently becomes negative, the likelihood of the development of TCC is low. However, if the initially positive cytology continues to remain positive, there is a much higher probability of TCC being detected in this population.
Carcinoembryonic Antigen and Carbohydrate Antigen 19-9-Producing Adenocarcinoma of the Prostate: Report of an Autopsy Case
Authors: Kodama Susumu , Itoh Hiroshi , Ide Hisamitsu , Kataoka Hiroaki , Takehara Toshiyuki , Nagano Masashi , Hamasuna Ryoichi , Koono Masashi , Osada Yukio
Published: April 2003

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) are well known as specific tumor markers of prostate cancer, but carcinoembryonic antigen (CEA)- and carbohydrate antigen 19-9 (CA19-9)-producing adenocarcinoma originating in the prostate is rare. We report here a case of prostatic adenocarcinoma positive for these 4 tumor markers in a 50-year-old man who had initially complained about chest pain due to metastatic bone tumor. In spite of the extensive treatment involving hormone and radiation therapy, the patient died of rapid tumor extension only 4 months after initial diagnosis. Autopsy revealed multiple metastases to the bone, liver, lungs and lymph nodes. Histologically, two types of adenocarcinoma were involved in both primary prostate and metastatic sites: one was a poorly differentiated adenocarcinoma positive for PSA and PAP but not CEA or CA19-9, and the other one was a less differentiated adenocarcinoma partially positive for CEA and CA19-9 but not for PSA or PAP. Based on this case and previous cases by review of the literature, CEA- and CA19-9-producing adenocarcinoma of the prostate was suggested to rapidly progress with multiple metastases and to show poor prognosis with strong resistance to any treatment.
Urinary Tract Infection in Diabetic Patients
Authors: Bonadio Mario , Meini Micaela , Gigli Cristina , Longo Benedetta , Vigna Armando
Published: April 2003

Aim: The aim of the study was to compare the epidemiological, microbiological and clinical features of diabetic patients with urinary tract infection (UTI) to those of nondiabetic ones. Methods: A prospective study was performed on 490 consecutive patients with proven UTI. The patients were studied on the basis of a specific questionnaire and hospital records. Results: Of 490 enrolled patients, 89 (18.1%) had diabetes mellitus. The mean age of diabetics and nondiabetics was respectively 64.9 ± 13.2 (SD) and 54.4 ± 23.3 years. Most diabetics had asymptomatic bacteriuria and had undergone bladder catheterization more frequently than the nondiabetics. The most frequent causative agents of UTI in diabetics and nondiabetics were: E. coli (respectively, 56.1 vs. 56.8%), Proteus sp. (7.9% vs. 7.2%), Pseudomonas sp. (6.7 vs. 8.2%), Enterococcus sp. (6.7 vs. 7.2%). More than 50% of the isolated Pseudonomas sp. strains in both groups were resistant to gentamicin, piperacillin and norfloxacin. Both diabetics (52.8%) and nondiabetics (42.2%) had recurrent UTI during the follow-up period; the difference in the incidences did not reach statistical significance. Conclusion: No significant differences in epidemiological, clinical and microbiological evaluated features of diabetics and nondiabetics were pointed out, except for the higher frequency of bladder catheterization of diabetics than nondiabetics. However, the eradication of UTI seemed to be more difficult in diabetics than in nondiabetics.