bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an in vitro Primary Screen for Skin Depigmentation and Antimelanoma Agents
Authors: Dooley Thomas P. , Gadwood Robert C. , Kilgore Ken , Thomasco Lisa M.
Published: April 2009

An in vitro cell culture assay was developed to identify inhibitors of melanogenesis and agents which produce cytostatic or cytotoxic effects specifically in melanocytes. A total of 50 compounds related to tyrosine, dihydroxyphenylalanine, and hydroquinone (HQ) were tested in vitro in order to determine their effects upon a murine melanocyte cell line, Mel-Ab, that produces copious amounts of melanin in culture. The agents that demonstrated an inhibition of growth or pigment production by 50% (IC50) at < 100 µg/ml were considered active. The cytotoxicity of melanocyte-active compounds were also tested in vitro on a control nonmelanocyte cell line (HT 1080), using a simple crystal violet staining method to quantitate adherent cell number after treatment. The cell culture assay was validated with known potent melanocyte cytotoxic agents, including HQ and 4-S-cysteaminylphe-nol (4-S-CAP). Although most cytotoxic chemicals were nonspecific in this primary screen (i.e. killing both Mel-Ab and HT-1080 cells), several of the compounds tested exhibited high melanocyte-specific cytotoxicity, similar to HQ and 4-S-CAP. Potentially these compounds may be useful as either antimelanoma or skin depigmentation agents. All of the compounds identified as active in this primary screen were cytotoxic or cytostatic to melanocytes, except for the methyl ester of gentisic acid, which uniquely inhibited the de novo synthesis of melanin without cytotoxicity.
Differential Effect of Medium Potent Nonhalogenated Double-Ester-Type and Conventional Glucocorticoids on Proliferation and Chemotaxis of Fibroblasts in vitro
Authors: Hein Rüdiger , Korting Hans Christian , Mehring Thomas
Published: April 2009

Recently several attempts have been made to develop glucocorticoids which show less pronounced side effects. We intended, therefore, to use experimental systems to examine the influence of newly developed nonhalogenated glucocorticoids and conventional fluorinated congeners, demonstrating similar anti-inflammatory activity in vivo, on biosynthetic capacities of human fibroblasts. Fibroblasts were kept in monolayer cultures and exposed to different concentrations of the active compounds for 6 days to analyze the influence on proliferation. Chemotaxis of fibroblasts was studied in blind well Boyden chambers. Fibroblast-conditioned medium was used as chemoattractant. All glucocorticoids tested influenced fi-broblast proliferation at high (10-5M) and low (10-9M) concentration. Yet the effect was clearly more marked with fluorinated compounds. Basically, the same applied for chemotaxis. At the low concentration, however, nonfluorinated glucocorticoids exerted almost no influence. These results suggest that modifications of steroidal structure can specifically influence their effects on biosynthetic capacities of fibroblasts.
Reactions of Human Keratinocytes in vitro after Application of Nicotine
Authors: Theilig C. , Bernd A. , Ramirez-Bosca A. , Görmar F.F. , Bereiter-Hahn J. , Keller-Stanislawski B. , Sewell A.C. , Rietbrock N. , Holzmann H.
Published: April 2009

Nicotine is rapidly taken up by human keratinocytes (HaCaT cells) and after 3 h the uptake is approximately 50% of maximum. Cotinine, a metabolite of nicotine, was detected, thus demonstrating the metabolism of nicotine in HaCaT cells. Low nicotine concentrations (0.1–200 µg/ml) did not influence the incorporation rate of thymidine into DNA or ami-no acids into proteins. Inhibition of DNA and protein synthesis was only observed at concentrations > 200 µg/ml. After application of 400 µg/ml nicotine, the cells were vacuolated. This process was reversed after nicotine withdrawal. At low nicotine concentrations, no changes in microtubules and actin filaments could be detected. However, in the presence of nicotine (1-10µg/ml), keratin filaments showed a more orderly pattern that controls, and the expression of the suprabasal keratins 1 and 10/11 was induced and increased according to the concentration of nicotine. The number of cornified envelopes also increased markedly. Nicotine concentrations > 100 µg/ml led to a disarrangement of keratin filaments and to a decrease in keratin expression and cornified envelope formation. Our results suggest that nicotine at concentrations up to 100 µg/ml is not an irritant but may induce cornification of the skin.
Role of Exogenous Oxygen in Cutaneous Barrier Repair
Authors: Jackson Simon M. , Mao-Qiang Man , Elias Peter M. , Feingold Kenneth R.
Published: April 2009

Occlusion of the skin with a water-vapor-impermeable membrane following disruption of the permeability barrier prevents the epidermal changes which lead to the restoration of barrier function, suggesting that water transit could be an important regulatory signal for barrier repair. However, occlusion with a water-vapor-impermeable membrane also prevents the movement of gases, which could also potentially influence permeability barrier homeostasis. Since O2 is known to have an effect on epidermal cell function, we have determined the effect of gases containing different levels of O2 on barrier repair 6 h following topical treatment of hairless mice with acetone. The disrupted barrier of air-exposed animals (O2 ∼ 20%) recovered by 50.8 ± 3.4% (mean ± SEM) after 6 h. Under flowing air (O2 ∼ 20%), O2/CO2 95/5 % and argon (O2 = 0%) the barrier recovered by 43.9 ± 28, 36.2 ± 8.5 and 39.2 ± 4.6%, respectively. These values were not statistically different from each other. The slightly lower levels of recovery at 6 h with the flowing gases in comparison to exposure to static air probably can be attributed to a slight cooling of the skin caused by the flowing gases. These results suggest that exogenous O2 is neither required for barrier repair nor a signal for barrier repair.
Testing of Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors, Drugs with Immunomodulating Properties and Some Reference Antipsoriatic Drugs in the Modified Mouse Tail Test, an Animal Model of Psoriasis
Authors: Bosman Brigitte
Published: April 2009

Topical administration of lipoxygenase and cyclooxygenase inhibitors, antipsoriatic drugs and some immunomodulating drugs on adult mouse tail scales showed variable induction of of orthokeratosis. Dithranol and retinoic acid showed ED50 concentrations of 0.5% and 0.23%, respectively. The lipoxygenase inhibitors catechol and octyl gallate showed ED50 of 2.5 and 13.4%. 10% lonapalene showed 20% activity, curcumin, linoleic acid, primrose oil and AA673 10–15% activity, methyl and ethyl gallate 5% activity, nordihydroguaiaretic acid, diethylcarbamazine, ebselen, esculetin, quercetin, AA861, gallic acid, dodecyl gallate and 15-hydroxyeicosatetraenoic acid no activity. The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid and bufexamac were inactive, benoxaprof-en showed 14% activity. The immunomodulating drugs fluo-rouracil and triamcinolone showed > 10% activity, cyclosporin A and thalidomide no activity. Fumaric acid showed 5% activity. The results show that this model could be proposed for screening antipsoriatic drugs.
Use of Human Skin Recombinants as an in vitro Model for Testing the Irritation Potential of Cutaneous Irritants
Authors: Ponec Maria , Kempenaar Johanna
Published: April 2009

Two human skin recombinants, the epidermis reconstructed on the deepidermized dermis (RE-DED) or on fibroblast-populated collagen matrix (Living Skin Equivalent, LSETM), were used to study the irritating effect of sodium lauryl sulfate (SLS). The extent of cytotoxicity induced after a 24-hour exposure period to increasing concentrations of SLS (0-5%) was evaluated on the basis of (1) morphological perturbations, (2) changes in the expression of differentiation-specific protein markers (keratin 1, 10, 6, 16, involucrin and transglutaminase), (3) cell membrane integrity (LDH leakage) and (4) release of proinflammatory mediators (PGE2, IL-1, IL-6 and IL-8). SLS induced significant changes in epidermal morphology and changes in the expression and localization of differentiation-specific protein markers when applied topically in concentrations higher than 1 % on RE-DED and higher than 0.1% on LSE. The exposure of both human skin recombinants to SLS resulted in a dose-dependent release of LDH, PGE2 and IL-1Α and in an increase in keratinocyte intracellular IL-1 levels. Upon application of 5% SLS on RE-DED the total (intra- and extracellular) IL-1 levels remained high but due to cell damage the intracellular IL-1 level was markedly decreased and the extracellular IL-1 level increased. Similar observations have been made with LSE after application of 0.5% SLS. However, with LSE the extracellular IL-1Α levels were found to be about 100 times lower than those measured with RE-DED. Exposure of LSE to SLS induced a marked increase of IL-6 production in fibroblasts incorporated in the collagen matrix. Contrary to LSE, both intra- and extracellular levels of IL-6 were low in unexposed controls and were only marginally modulated by the exposure of the RE-DED to SLS. In addition, a dose-dependent increase in IL-8 release was observed upon application of SLS on RE-DED. The results of the present study indicate that concentrations of SLS required to induce epidermal irritancy in vitro approximate those inducing irritation in human skin in vivo. All parameters used in the present study for evaluation of toxicity can serve as useful endpoints for screening of contact skin irritancy in vitro. Compared to RE-DED, the LSE seems to be more susceptible to SLS. The differences in sensitivity between LSE and RE-DED can be ascribed to reported differences in their stratum corneum barrier function.
Use of Continuous Electrical Capacitance and Transepidermal Water Loss Measurements for Assessing Barrier Function in Neonatal Rat Skin
Authors: Wickett Randall , Nath Veena , Tanaka Reiko , Hoath Steven B.
Published: April 2009

A vital function ofthe skin is to oppose the loss of water to the environment. In this study, two complementary methods, transepidermal water loss (TEWL) and continuous electrical capacitance under occlusion, were used to assess epidermal barrier function in a developmental animal model, the neonatal Sprague-Dawley rat. TEWL monitors barrier function directly while the increase in capacitance under occlusion is related to both the skin’s barrier function and to its water holding capacity. Serial tape stripping of the stratum corneum on 1-day-old rat pups led to a significant increase in both TEWL and continuous capacitance measurements. Anatomic site heterogeneity and the effects of surface temperature were also studied. The ventral skin surface exhibited an increase in the continuous capacitance measurements, an effect possibly due to the thinner stratum corneum on the ventral side. Both TEWL and continuous capacitance values were directly correlated with ambient temperatures within the physiological range.
Study of the Stratum corneum Barrier Function by Transepidermal Water Loss Measurements: Comparison between Two Commercial Instruments: Evaporimeter® and Tewameter®
Authors: Barel A.O. , Clarys P.
Published: April 2009

The measurement of transepidermal water loss (TEWL) is an important noninvasive method in order to assess the barrier function of the stratum corneum. As a consequence, TEWL has been found to be a very useful technique for studying skin irritation induced by various physical and chemical effects. Exposure of the skin to chemicals (detergents) and physical conditions (occlusion and stripping) generally results in an increase of TEWL. Until recently the only commercially available TEWL instrument was the Evaporimeter® developed by ServoMed (Sweden). The instrument is based on the open chamber system with two humidity and temperature sensors which measure the water evaporation gradient at the surface of the skin. Recently a new commercially available instrument based on the same physical principle of measurement was developed by Courage and Khazaka (Tewameter®, FRG). Our aim in this study has been to compare the measuring capacities of both instruments. The accuracy, sensitivity, variability and reproducibility of both instruments were compared in vivo under identical conditions on normal skin and skin damaged by external conditions. The influence of external and environmental factors such as air and probe temperature, relative humidity, air turbulence and pressure of application was evaluated for both instruments. Finally, the two instruments were compared in practice when following the increase in TEWL of the skin after stripping, occlusion and exposure to irritant household detergents. A very good correlation (r = +0.97) was found between the results of the two instruments over a wide range of TEWL values.
Skin Thickness in Patients with Osteoporosis and Controls Quantified by Ultrasound A Scan
Authors: Pedersen Helle , Agner Tove , Storm Tommy
Published: April 2009

In order to study a possible association between skin thickness and osteoporosis, we measured skin thickness by A mode ultrasound scanning in 20 females with osteoporosis and 20 age- and sex-matched controls. Bone mineral content (BMC) of the lumbar spine and the forearm was measured by dual-photon absorptiometry. BMC of the lumbar spine was significantly reduced in the osteoporotic group as compared to controls (p < 0.002). No difference in skin thickness was found between osteoporotic patients and controls. A statistically significant correlation between skin thickness on the forearm and BMC of the forearm was found (p < 0.02), but was opposed by a lack of correlation between skin thickness and BMC of the lumbar spine. We found a correlation between skin thickness and body weight (p < 0.002), which to our knowledge had not been reported earlier.
Anti-Inflammatory Activity of Croconazole, a Broad-Spectrum Antimycotic Agent, in the Arachidonic Acid-Induced Mouse Ear Swelling Test
Authors: Steinmann Dierk , Barth Joachim , Wozel Gottfried
Published: April 2009

Investigations on croconazole, a novel imidazole compound, suggested antiphlogistic properties in vitro. Hence, its anti-inflammatory capacity was tested in vivo using the arachidonic acid-induced mouse ear swelling test, which is a suitable model for screening inhibitors of the lipoxygenase and/or the cyclooxygenase. Topical application of croconazole (1%/ 0.01 %) to the mouse ear induced a maximal inhibition of edema (inhibition: 39%/33%; p = 0.01) which was as strong as the reference nordihydroguaiaretic acid (inhibition: 38.9%; p = 0.01). These results justify further investigations on croconazole to study potential inhibitory effects on proinflammatory arachidonic acid metabolites.
Noninvasive Investigation of Human Skin after in vivo Iontophoresis
Authors: Thysman Sophie , Van Neste Dominique , Préat Véronique
Published: April 2009

The main objective of our study was to investigate skin function and structure in human volunteers after electrical current application in order to demonstrate the safety of iontophoresis in vivo. The direct current was applied for 30 min at a density of 0.1 and 0.2 mA/cm2. Iontophoresis increased cutaneous blood flow as measured by laser Doppler flowmetry (LDF). This increase was reversible within 1 h and was more pronounced at higher current density. Measurements of transepidermal water loss (TEWL) and LDF were the same at the cathode and the anode sites. Except for 5 min at 0.2 mA/cm2 density, TEWL values were not enhanced as compared to control values (no iontophoresis). Attenuated total reflectance-Fourier transform infrared spectroscopy of the stratum corneum structure showed a transient increase (30 min) in hydra-tion after electrode application for 30 min. No alteration in lipid structure could be shown. These results augur the safety of drug delivery by iontophoresis.
Evidence that Diazoxide Promotes Calcium Influx in Mouse Keratinocyte Cultures by Membrane Hyperpolarization
Authors: Xiong Yimin , Harmon Charles S.
Published: April 2009

We have used fura-2/AM to investigate the effect of diazoxide on the cytosolic calcium concentration (Cai) in primary mouse keratinocyte cultures. Treatment of keratinocytes with 100 µM diazoxide induced a transient peak in Cai, followed by a sustained elevation. Depletion of medium calcium by addition of EGTA abolished the diazoxide-induced Cai response, indicating that the agent promoted calcium influx withou release of calcium from intracellular stores. The diazoxide-induced rise in Cai was inhibited both by addition of 60 mM KC1 to the assay buffer and by preincubation with glibenclamide, a specific K+ channel blocker. In addition, studies with the membrane potential-sensitive fluorescent probe bis-oxonol demonstrated that diazoxide hyperpolarized keratinocyte membranes. These findings suggest that keratinocytes possess K+ channels, and that the previously reported proliferation effects of K+ channel openers such as diazoxide on keratinocytes may result from hyperpolarization-induced elevation of Cai.
Optimization of Topical Erythromycin Formulations by Ion Pairing
Authors: Matschiner S. , Neubert R. , Wohlrab W.
Published: April 2009

Erythromycin (ERY) is used in the topical treatment of acne vulgaris. In order to decrease the amount of microorganisms markedly, the antibiotic must penetrate into the sebaceous follicles. Firstly, the aim of this study was to improve the lipo-philicity of ERY by ion pairing. Secondly, a formulation with optimized penetration of the ion pair was developed. Thirdly, the optimized formulation was compared with formulations containing ethanol and with the commercial product Zine-ryt®. The determination of lipophilicity was based on partition coefficients (PC) and on the penetration of ERY into a modified multilayer membrane system (MMS). It was shwon that the penetration of ERY into a lipophilic acceptor system was three times higher when ion pairing between ERY and octadecansulfonate was used in comparison with the penetration of the ERY base alone. The dosage of the antibiotic used can be markedly reduced by optimizing a vehicle for the ion pair.
Croconazole: An Inhibitor of Eicosanoid Synthesis in A23187-Stimulated Human Polymorphonuclear Leukocytes and Human Whole Blood
Authors: Lehmann Bodo , Wozel Gottfried , Steinmann Dierk , Barth Joachim
Published: April 2009

The aim of this investigation was to ascertain possible inhibitory effects of the antimycotic agent croconazole on eicosanoid biosynthesis. Human polymorphonuclear leukocytes (PMN) and whole blood of healthy donors were pretreated with croconazole in different concentrations (0.8-100 µM) for 5 min followed by the addition of Ca ionophore A23187 (10 µM) and subsequent incubation for 10 min (PMN) and 30 min (whole blood), respectively. Thereupon the eicosanoids were determined by reversed-phase high-performance liquid chromatography. Croconazole exhibited dose-dependent inhibitory activity on the 5-lipoxygenase (5-LOX) of neutrophils. The mean half maximum inhibition concentration (IC50) of croconazole for synthesis of leukotriene B4 (LTB4) and 5-hy-droxyeicosatetraenoic acid (5-HETE) was determined as 7.8 ± 1.7 and 7.6 ± 0.3 µM, respectively. The mean IC50 value for LTB4 estimated in whole blood was distinctly higher (27.0 ± 3.1 µM) compared with that determined in PMN. Additionally, an inhibitory effect (IC50 9.8 ± 2.0 µM) on the production of the cyclooxygenase (COX) product 12-hydroxyhepta-decatrienoic acid (HHT) was demonstrated, whereas the production and/ or releasing of 12-hydroxyeicosatetraenoic acid (12-HETE) was not attenuated by the azole. Our results in the cell-free 5-LOX system favor a direct inhibitory action of croconazole on 5-LOX, with a relatively high portion (45-77%) of reversibility. In spite of distinctly lower inhibitory potency compared with reference inhibitors such as nordihydroguaiaretic acid and indomethacin, croconazole is an effective inhibitor of arachidonic acid metabolism. Our results suggest that croconazole may be of some benefit in anti-inflammatory therapy.
Modulation of in vitro Cytokine Release from Human Leukemic Mast Cells (HMC-1) by Glucocorticoids
Authors: Lippert Undine , Welker Pia , Krüger-Krasagakes Sabine , Möller Annelie , Henz Beate M.
Published: April 2009

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (105M-10-9M), on the IL-1Β, IL-3, IL-8, and tumor necrosis factor Α secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 × 10-7M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.
Human Skin Irritation Studies of a Lecithin Microemulsion Gel and of Lecithin Liposomes
Authors: Dreher F. , Walde P. , Luisi P.L. , Elsner P.
Published: April 2009

Soybean lecithin microemulsion gels offer promising features for the possible use as matrices in transdermal therapeutic systems. In order to assess the skin irritancy potential of the gel, acute and cumulative irriation tests were performed in human subjects in vivo using as comparison an unilamellar soybean lecithin liposome preparation and the solvent isopropyl palmitate (IPP). Acute irritation was tested in 151 volunteers in a 48-hour patch test, whereas cumulative irritation was assessed in a 21-day human repeated insult patch test in 20 volunteers. In the acute irritation test, discrete irritation (erythema only) developed with the gel in 2 subjects (1.3%), with the liposomes in 3 subjects (2.0%), and with IPP in 2 subjects (1.3%). For the assessment of cumulative irritation, the IT50 (irritation time of 50% of the test population) was calculated. IT50 was 13 days for the gel, 14 days for the liposomes and 17 days for IPP. This study shows a very low acute and a low cumulative irritancy potential for the soybean lecithin microemulsion gel making it a candidate matrix for transdermal therapeutic systems also under toxicological aspects.
Effects of Freezing and Azide Treatment of in vitro Human Skin on the Flux and Metabolism of 8-Methoxypsoralen
Authors: Shaikh Naureen A. , Ademola John I. , Maibach Howard I.
Published: April 2009

Clinical and in vitro evidence suggests that the physicochemical properties of the skin influence the process by which drugs are transported through skin. The effects of skin storage, preparation and pretreatment on the permeation and metabolism of (8-methoxypsoralen (8-MOP), as a model penetrant, were studied using the flow-through in vitro cell diffusion system. The metabolites and unchanged drug were estimated by thin-layer chromatography. While the permeability of 8-MOP was similar in fresh (445 cm·• h-1) and azide-treated (449 cm • h-1) skin (p < 0.01), decreased permeability was observed in frozen skin (406 cm·h-1, p < 0.01). A 2.8-fold increase in the cumulative flux of 8-MOP at 24 h through azide-pretreated (2.5 × 10-3 µmol • h-1 • cm-1) versus fresh skin (9.1 × 10-4 µmol·h-1 • cm-1) was observed (p < 0.01). There was a slight increase in the flux of 8-MOP at 24 h when skin was frozen, compared with untreated skin. Increase in the flux of 8-MOP in frozen skin might result from the alteration of the molecular arrangement of the skin components during freezing. In addition to the obvious differences between frozen and fresh skin, these observations discourage the use of frozen skin. There is a moderate relationship between the permeability and flux of 8-MOP through frozen skin. A similar but nonrelated correlation was observed between the permeability and flux of 8-MOP through azide-treated skin samples (r = 0.6). These findings suggest that azide and freezing treatments lower the skin barrier properties to the transport of 8-MOP. Apparently, factors that may affect the inherent permeability of human skin, particularly those related to the handling, storage and pretreatment of skin with solvents and chemicals, can also influence topical drug delivery. The metabolic capacity of frozen skin and fresh skin remained constant during the period of study. These data may be of value in the development of topical methoxypsoralen systems. Further in vitro and in vivo studies are required to ascertain the generalization of this process.
Effects of Calcipotriol and Clobetasol-17-Propionate on UVB-lrradiated Human Skin: An Immunohistochemical Study
Authors: van der Vleuten Carine J.M. , Snijders Clementine G.E.M. , de Jong Elke M.G.J. , van de Kerkhof Peter C.M.
Published: April 2009

Corticosteroids and vitamin D3 analogues inhibit proliferation, enhance normal keratinisation and interfere with cutaneous inflammation in in vitro systems. Both treatments are effective in psoriasis, although several reports suggest that vitamin D3 is less effective in reducing the inflammatory changes compared to its potent effect on keratinocyte growth and differentiation. The aim of the present study was to compare and contrast the effects of the vitamin D3 analogue calcipotriol, clobetasol-17-propionate and a placebo on immunohistochemical markers for epidermal growth, keratinisation and inflammation induced by a standardised single challenge with ultraviolet B (UVB) radiation in normal human skin. Clobetasol proved to inhibit UVB-induced proliferation of epidermal cells, tenascin induction, keratin 16 induction and the accumulation of T lymphocytes and CD la-positive cells. Epidermal thinning due to clobetasol was also observed. No effect of clobetasol was shown on the enhanced terminal differentiation following UVB challenge. In contrast, calcipotriol reduced the member of transglutaminase-positive cells following UVB challenge but increased the thickness of the epidermis without a significant effect on other markers for keratinisation, epidermal proliferation and inflammation. The present study reconfirms the potent effect of topical corticosteroids on various aspects of UVB-challenged skin. In contrast, calcipotriol interfered especially with one differentiation pathway (transglutaminase) without modulation of other UVB-induced changes.
Treatment Options for Photodamaged Skin
Authors: Griffiths Christopher E.M.
Published: April 2009

Photodamage of the skin can be a detriment to physical and psychological health with a consequent negative impact on both personal and professional life. Medical treatments for photodamaged skin include topical all-trans-retinoic acid (tretinoin) as well as moisturizers, chemical peels, dermabrasion, Α hydroxy acids and cosmetic surgery. Of these treatment options, only tretinoin has been subjected to large-scale, controlled studies to substantiate its clinical efficacy and long-term benefits. This review summarizes the use of various therapies and presents available clinical and histologic results of systematic trials, including the few studies of retinoid compounds other than tretinoin. Among the extensive data on topical tretinoin are long-term treatment results that provide evidence of ultrastructural changes. These histologic findings suggest that fundamental cellular effects may be responsible for the clinical benefits, which are sustained even when treatment frequency is reduced. It thus appears that tretinoin therapy at least partially restores photodamaged skin to the predamaged state.
Secondary Antibody-Forming Potential of Aged Mice, with Special Reference to the Influence of Adjuvant on Priming
Authors: Finger H. , Beneke G. , Emmerling P. , Bertz R. , Plager L.
Published: April 2009

Aged (20 months old) NMRI mice, showing a significantly reduced primary immune response to 4 × 108 sheep erythrocytes (SE), reacted to a secondary injection of 4 × 108 SE 1 month after primary immunization with a typical secondary immune response at both the adjuvant cellular and humoral levels. This specific anamnestic response was not found to be diminished, as compared to that of young adult controls (3 months old at the time of primary immunization). When killed cells of Bordetella pertussis were given as an adjuvant together with the primarily injected erythrocyte antigen, the process of priming for the secondary immune response was found to be significantly increased in both the aged and the young adult animals. The impressive restoration of the antibody-forming potential observed following secondary antigenic stimulation was associated with a remarkable restoration of the splenic structure. Splenic amyloidosis did not impair the secondary antibody-forming potential to a significant extent. It is suggested that the suppressed immunological reactivity of aged mice to a primary antigenic stimulus is mainly due to deficiencies in the regulatory factors, such as antigen-processing and antigenic triggering of immunocompetent precursor cells.
Influences on the Structural Stability of Collagen in Relation to Ageing
Authors: Verzár F. , Ackerschott-Strittmatter E. , Moser P.
Published: April 2009

Collagen fibers of tendons show tension with hypermolar salt solution, as 5 M NaClO4. This increases with the age of the animal and also with formaldehyde. The tension is reversible in physiological salt solution (0.85% NaCl). Tension production by hypermolar solution is inhibited by small concentrations of methionine and cysteine. Penicillamine only in higher concentrations .It is discussed whether thetension of collagen fibers is regulated by aldehyde and methionine.
Vertebral Aging in Hypopituitary Dwarf Mice
Authors: Silberberg Ruth
Published: April 2009

Changes occurring in lumbar and lower thoracic vertebrae of aging dwarf mice (dwdw) were compared with those found in non-dwarfs of the same strain (Dwdw or DwDw) and of strain C57B1. Dwarf vertebrae, besides remaining smaller, develop less completely and more slowly than those of non-dwarfs. Retarded development is indicated by the presence of non-resorbed epiphyseal cartilage, by diminished removal of cancellous bone from the vertebral bodies and possibly also by the failure of osseous replacement of the cartilaginous end-plates. The slowing of the aging process manifests itself in decreased degeneration of the growth zones, delayed loss of mucopolysaccharide from the matrix of the articular cartilage and by an attenuated tendency to develop spondylosis.
Lathyrisme chronique
Authors: Bouissou H. , Julian M. , Pieraggi M.T.
Published: April 2009

The action of pyridinol carbamate (PDC) was studied in rats during chronic intoxication with β-aminopropio-nate (BAPN), and also during chronic lathyrism associated with a atherogenic diet; (1) a protective effect of PDC on the aortic wall with regard to the toxic effects of BAPN was noted; (2) PDC retards the development of elastic tissue lesions and reduces their intensity and frequency; (3) with regard to the role of PDC in the prevention of experimental atheroma, this compound has no lipid reducing action but preserves the integrity of the aortic wall and hinders the penetration of fat depots into the media which is the initial site of experimentally induced atherogenic lesions, and (4) PDC can be considered as an anti-atherogenic agent. Because of its protective action, it inhibits one of the most important factors in atherogenesis – the parietal factor. It might be active in the prevention of vascular arteriosclerosis and also aortic atherosclerosis.
Open-Field Behavior in Aging Inbred Mice
Authors: Sprott Richard L. , Eleftheriou Basil E.
Published: April 2009

Open-field activity levels of young (2- to 6-month-old) and older (12- to 30-month-old) C57BL/6J and DBA/2J mice were assessed in two experiments conducted in separate laboratories. A large decrement in activity level was observed with advancing age in mice of both genotypes. The environment in which the subjects were maintained and tested also appeared to be a major contributor to behavioral variability in the openfield.
Age-Related Changes of Acid Mucopolysaccharides in Various Portions of the Renal Artery
Authors: Sawada Terufumi , Inoue Gosuke , Yoshikawa Masaki
Published: April 2009

Acid mucopolysaccharides (AMPS) of the renal arterial system were studied to observe changes with advancing age. The arteries were dissected from cadaver kidneys, made free of lesions, and divided into three portions according to locations. Uronic acid measurements showed that the AMPS contents were significantly different among the three portions, with trend of decrease from proximal towards distal portions. With age there was a linear increase of AMPS, which was most marked in the proximal portion. It should be stressed that the aging process of the vascular system differs in different portions of the renal arterial system.
Response of Liver and Kidney Catalase to α-p-Chloro-phenoxyisobutyrate (Clofibrate) in C57B1/6J Male Mice of Different Ages
Authors: Baird M.B. , Zimmerman J.A. , Massie H.R. , Samis H.V.
Published: April 2009

C57B1/6J male mice of different ages were treated with clofibrate (CPIB) and the effect of the drug upon liver and kidney catalase activity was determined. Enzyme activity in hepatic tissue was induced 2.5-fold in all age groups from similar maintenance levels of activity. There was no age-related lag in enzyme induction, nor were there any age-related differences in the kinetics of induction. This increase in enzyme activity was accompanied by a marked hepatomegaly in all treated animals. CPIB had no effect upon catalase activity in the kidney of young animals. The decreased enzyme activity which is always observed in aging mice is, however, unexpectedly restored to young levels after treatment of old animals with CPIB. These results are reviewed in the context of the Orgel error hypothesis from which it is concluded that the results of this study offer no support for the Orgel hypothesis.
The Meaning of Suffering in Families
Authors: Ok Ja Lee  , Young Sook Choi  , Doucet Thomas J.
Published: April 2009

The authors of this article present the findings of a study about the experience of suffering for 2 families from South Korea with relatives living with chronic mental illness, using the humanbecoming nursing perspective. The central findings of this qualitative descriptive—exploratory study showed that suffering in families with relatives living with mental chronic illness is agonizing trepidation amid calm invigoration, as confident relinquishing of the expected arises with liberating diverse affiliations. The findings are discussed in relation to the themes of the humanbecoming school of thought and related literature. Phenomena of study for further research are suggested.
Being Judicious
Authors: Morrow Mary R.
Published: April 2009

The purpose of this column is to present a uniquely conceived nursing phenomenon inspired by an artform, to discuss its relevance for nursing knowledge development in light of a preliminary review of literature and the creative conceptualization process, and to suggest an appropriate mode for further inquiry.
Judiciary and Good Governance in Bangladesh
Authors: Mollah Md. Awal Hossain
Published: April 2009

The terms ‘governance’ and ‘good governance’ are increasingly being used in development literature. Intellectuals, bureaucrats and civil society members alike are accepting the spirit of the concept and are conceiving it in the context of their own experience and environment. The Bangladeshi government has recently been under constant pressure from various donor agencies for ensuring good governance. The implementation and achievement of good governance depends upon the transparency, honesty and efficiency of the legislature, executive and judiciary, along with the cooperation of civil society and the private sector. The main concern of this article is to analyse the role of the judiciary in the pursuit of good governance in Bangladesh. The study will focus on the Bangladesh Supreme Court in order to evaluate its role in ensuring good governance.
Volatile Fraction of Ewe's Milk Semi-Hard Cheese Manufactured with and without the Addition of a Cysteine Proteinase
Authors: Mariaca R. G. , Fernandez-Garcia E. , Mohedano A. F. , Nufiez M.
Published: April 2009

A dynamic headspace technique (purge and trap) coupled to gas chromatography-mass spectrometry was used for the study of the volatile fraction of pasteurized ewe's milk cheese. The effect of the addition of the cysteine proteinase of Micrococcus sp. INIA 528 to milk on the formation of volatile aroma compounds in cheese was also evaluated. Forty-five compounds, in total, were identified, including hydrocarbons, alcohols, ketones, aldehydes, esters, terpenes and sulfur compounds. The abundance of most volatile compounds increased significantly (P < 0.05) with ripening time, except those of ethanol and 2,3-butanedione which decreased. Acetaldehyde and some minor components did not vary remarkably during ripening. Acetaldehyde, 2-methyl-I-butanal, 3-methyl-I-butanal, 2-propanol, 2-pentanone and 3-methyl-3-buten-1-ol were the only compounds affected by the addition of cysteine proteinase. The more extensive proteolysis in cheese with cysteine proteinase might have enhanced the formation of volatile compounds derived from amino acids, such as acetaldehyde, 2-methyl-1-butanal and 3-methyl-I-butanal, formed from threonine, isoleucine and leucine breakdown, respectively.
Note. Comparison of Two Rapid Methods of Lipoxygenase Assay in Blanched Green Peas, Green Beans and Potatoes
Authors: Garrote R. L. , Bertone R. A. , Silva E. R. , Avalle A.
Published: April 2009

Two rapid methods, methylene blue bleaching (MBB) and potassium iodide-starch (KI-S), for lipoxygenase assay in blanched green peas, cut green beans and diced potatoes were evaluated and compared, using as a reference a quantitative spectrophotometric procedure for lipoxygenase (LPO) activity determination. Green peas (diameter - 10-II mm), cut green beans (diameter = 10 mm; length = 20 mm) and diced potatoes (cubes of 10 mm) were water blanched at 100 'C; heating times ranged between 10 and 40 seconds. For visual comparison of the methods, two times were registered: starting time, when the color began to change, and final time, when the color change fully developed. Both rapid visual methods (MBB and KI-S) showed good performance in detecting LPO in blanched vegetable samples. KI-S method was more sensitive than MBB procedure, with its detection limit between 0.70 and 1.80 LPO units/g, depending on the product. Additionally, FT was 180 seconds for KI-S method as compared to 600 seconds for MBB procedure, therefore, KI-S method is recommended as the best option for a rapid assay of LPO in the vegetables studied.
Influence of the CO2 Quality in the Antioxidant Activity of Rosemary Extracts Dearomatized by Supercritical Fluid Extraction
Authors: Ibanez E. , Lopez-Sebastian S. , Fernandez J. , Tabera J. , Bueno J. M. , Ballester L. , Reglero G.
Published: April 2009

The effect of the CO2 quality (mainly related to CO2 content) in the antioxidant activity of rosemary extracts deodorized by using a supercritical fluid extraction process is analyzed. A Taguchi experimental design was used to study the influence of the CO2 quality on the antioxidant activity of the rosemary dearomatized extracts. The antioxidant activity of the rosemary extracts obtained in optimal conditions was tested with sunflower oil.
Residual In-plane Mechanical Properties of Transversely Crushed Structural Foams
Authors: Koissin Vitaly , Shipsha Andrey
Published: April 2009

The mechanical properties of structural polymer foams are investigated after crushing in the rise direction (out-of-plane axis of a foam material block). The crushed foams are loaded in uniaxial compression, tension, or shear. All tests are performed in the plane of the foam block, i.e., perpendicular to the crushing direction. For comparison, virgin foams are also characterized. The results are discussed featuring the properties of crushed foams, which can be important for the damage tolerance analysis of a foam core sandwich structure.
Comparing Predictors of Women's Congressional Election Success
Authors: Ondercin Heather L. , Welch Susan
Published: April 2009

Examining all Congressional races from 1992 through 2000, we explore why, over time, some districts are more likely to have women candidates and to elect women than are others. We focus on the obvious, but rarely explored, fact that women's election success is a product of three key stages of the election process: women running, women's successes in the primaries, and finally, women's general election successes. We find that different factors predict success at each stage and that the predictors of women's candidacies and success in open seat races are different than in others.
The mechanisms of atrial fibrillation in hyperthyroidism
Authors: Bielecka-Dabrowa Agata , Mikhailidis Dimitri P , Rysz Jacek , Banach Maciej
Published: April 2009

Atrial fibrillation (AF) is a complex condition with several possible contributing factors. The rapid and irregular heartbeat produced by AF increases the risk of blood clot formation inside the heart. These clots may eventually become dislodged, causing embolism, stroke and other disorders. AF occurs in up to 15% of patients with hyperthyroidism compared to 4% of people in the general population and is more common in men and in patients with triiodothyronine (T3) toxicosis. The incidence of AF increases with advancing age. Also, subclinical hyperthyroidism is a risk factor associated with a 3-fold increase in development of AF. Thyrotoxicosis exerts marked influences on electrical impulse generation (chronotropic effect) and conduction (dromotropic effect). Several potential mechanisms could be invoked for the effect of thyroid hormones on AF risk, including elevation of left atrial pressure secondary to increased left ventricular mass and impaired ventricular relaxation, ischemia resulting from increased resting heart rate, and increased atrial eopic activity. Reentry has been postulated as one of the main mechanisms leading to AF. AF is more likely if effective refractory periods are short and conduction is slow. Hyperthyroidism is associated with shortening of action potential duration which may also contribute to AF.
Bambini al Centro: Music as a means to promote wellbeing.
Authors: Iadeluca Valentina , Sangiorgio Andrea
Published: April 2009

Bambini al Centro literally Children in the Centre is a project operating since 1999 in Rome, financed by the Italian State. It is a recreational-musical space devoted to children aged 012 months and their families. The principal goal of the Centre is to provide an opportunity for encounter,
relationship, sharing and global growth with, and through, music and dance. This project report aims to illustrate the social and political context in which the project was born and the main features that make it a successful example of community music.
People's media and reform efforts in Thailand
Authors: Brooten Lisa , Klangnarong Supinya
Published: April 2009

A major limitation in the development and protection of people's media in Thailand is the unstable and highly polarized political environment in which governments are short-lived and the constitution is not taken seriously as the fundamental law of the land. As a result, media have
become tools in larger political struggles. This analysis demonstrates that while several foundational elements necessary to promote people's media are emerging in Thailand, others are still lacking. A clear understanding of people's media as distinguished from both state and commercial media
has recently gained strength. Yet, constitutional protections for people's communication rights are nevertheless undermined by politicized media laws that in practice carry more weight than the constitution and prevent people from acting on their communication rights with confidence. This
article explores these issues, and discusses two forms in which people's media have found a space to operate community radio and Internet-based people's media. The analysis finds that while these media still find themselves struggling to survive a complex and constantly shifting policy environment,
the basic concept of communication rights has taken hold, in the process providing lessons for people's media elsewhere.
Review
Authors: Mandel Ruth
Published: April 2009

Communication for Social Change Anthology: Historical and Contemporary Readings, Alfonso Gumucio-Dagron and Thomas Tufte (eds.) (2006) South Orange, NJ: CFSC Consortium, 1067 pp., ISBN 0977035794 (pbk), $120
Outlaws and citizens: indigenous people and the New Media Nation
Authors: Alia Valerie
Published: April 2009

Emerging from the international movement of Indigenous peoples, what the author terms the New Media Nation is linked to the explosion of Indigenous news media, information technology, film, music, and other artistic and cultural developments. The creators of Indigenous media projects experience an array of government, transgovernment, corporate and other policies and pressures: these range from supportive to disinterested, to hostile and sometimes life-threatening. In the most supportive environments, they are able to participate as citizens working within government media policies. In the most hostile environments, they are forced to become outlaws, finding ways to send printed materials, radio signals and Internet transmissions across borders that often artificially (re)construct Indigenous peoples as bounded by nation-states. Indigenous people are using old and new technologies to amplify their voices and expand their power, disseminating information to a rapidly expanding global audience. The article draws on more than 20 years of research in several countries and picks up key themes elaborated in the book,The New Media Nation, now in press.
Policy convergence and online civil society media (CSM) in Japan
Authors: Hadl Gabriele , Tadahisa Hamada
Published: April 2009

In Japan, civil society uses of online technology have a long history: non-profit computer networks preceded the Internet and webcasting was pioneered by civic groups wanting to overcome rigid broadcasting laws. However, online civil society media face great challenges, with government,
market and un-civil society trying to marginalize them against an even more damaging background of general neglect and disregard. The Ministry of Internal Affairs and Communications (MIC) has proposed a new policy framework for the convergence of telecommunication and broadcasting, the basis
for a new law planned for 2010. Varying levels of regulation are foreseen for all content. Online variants of mainstream media such as newspapers and television broadcasting will remain largely self-regulated. Civil society media (CSM) remain unrecognized, facing potentially heavy regulation
as user-generated content. The authors focus on Japanese online civil society media (online CSM), using case studies to illustrate its successes and challenges in the current environment. In Japan, the Internet is considered the natural domain of business, while civil society, individual,
citizens' and personal media, often termed shimin media, are presented as latecomers. The authors will show this to be historically inaccurate and politically dubious. Identifying patterns of enclosure and colonization, the authors argue that despite increases in technological opportunity,
the space for civil society media is shrinking, bringing the Japanese media system to a critical juncture. The authors conclude by outlining suggestions for improving the Japanese communication environment to enhance online civil society media.