bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil Inflammation and Activation in Bronchiectasis: Comparison with Pneumonia and Idiopathic Pulmonary Fibrosis
Authors: Schaaf Bernhard , Wieghorst Alescha , Aries Sven-Philip , Dalhoff Klaus , Braun Jörg 
Published: April 2003

<i>Background:</i> Pulmonary inflammation in bronchiectasis, pneumonia and idiopathic pulmonary fibrosis (IPF) is dominated by neutrophils. Pathophysiologic differences are seen in the degree of airway and tissue destruction. Neutrophil activation and neutrophil proteolytic activity might differ between bronchiectasis, pneumonia and IPF. <i>Objective:</i> The aim of this study was to determine whether levels of inflammatory and protective markers in bronchoalveolar lavage (BAL) differed among cases of bronchiectasis, pneumonia and IPF. <i>Methods:</i> We studied 11 bronchiectasis patients (group 1), 30 pneumonia patients (group 2), 15 IPF patients (group 3) and 12 healthy volunteers (group 4). In the bronchoalveolar lavage fluid, concentrations of α<sub>1</sub>-proteinase inhibitor, myeloperoxidase (MPO) and elastase-α<sub>1</sub>PI complex were determined using immunoluminometric assays. Elastase inhibition capacity (EIC) and elastase activity were determined using a colorimetric assay. <i>Results:</i> No EIC, but free elastase activity, was found in 82% of group 1, 20% of group 2, 20% of group 3 and 0% of group 4. Median MPO concentration was highest in group 1: 7,951 ng/ml (16th–84th percentile [16–84%]: 256–36,342) vs. 692 ng/ml (106–2,279; group 2), 332 ng/ml (98–1,657; group 3), and 0.12 ng/ml (0.08–0.26; group 4). Bronchiectasis patients with bronchial <i>Pseudomonas</i> infection showed higher amounts of neutrophils (p < 0.01) and higher elastase activity (p < 0.05) than patients with sterile lavage. <i>Conclusion:</i> Bronchiectasis patients show a severe imbalance between neutrophil activity and protective molecules leading to possible lung destruction. Chronic <i>Pseudomonas</i> infection might trigger neutrophil activation. Future research and treatment strategies should focus on increased bacterial clearance and inhibition of neutrophil toxicity.
LINAC Radiosurgery for Cavernous Sinus Meningiomas
Authors: Chang, Steven D. , Adler Jr. John R. , Martin David P. 
Published: April 2003

Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors. Since 1989, 24 patients with cavernous sinus meningiomas have been treated at Stanford University Medical Center with linear accelerator (LINAC) radiosurgery. The mean age of the patients was 47.8 years (range 28–78). The mean volume treated was 6.83 cm<sup>3</sup> (range 0.45–22.45 cm<sup>3</sup>), covered with an average of 2.3 isocenters (range 1–5).Radiation dose averaged 17.7 Gy (range 14–20 Gy). This group of patients was retrospectively studied by sending clinical questionnaires to both the patient/family and referring physicians, and reviewing clinic charts. In addition, follow-up imaging studies were obtained to measure residual tumor volume. Follow-up averaged 45.6 months (range 19–80). Tumor control (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on MRI imaging 1–3 years after radiosurgery. Neurologic status was improved in 10 patients (42%) and unchanged in 12 patients (50%). There was 1 case of symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All other complications were transient, including 4 cases of trigeminal hypesthesia and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was 100%. Although follow-up is still short, this experience corroborates prior reports that radiosurgery can be used to treat selected small cavernous sinus meningiomas with good to excellent clinical results and minimal morbidity.
Validation of Freeze-Drying to Visualize Percutaneous <sup>3</sup>H-Estradiol Transport: The Influence of Skin Hydration on the Efficacy of the Method
Authors: Neelissen Jan A.M. , Arth Christoph , Schrijvers Ad H.G.J. , Junginger Hans E. , Boddé Harry E. 
Published: April 2003

A study was made of the validity of freeze-drying to visualize the distribution of <sup>3</sup>H-estradiol in human stratum corneum after topical application of a dry dose, a patch or a buffer solution. Each of these donor formulations was applied to human dermatomed skin for 24 h using Franz permeation cells. Subsequently, small pieces of skin were subjected to cryofixation, freeze-drying, osmium tetroxide vapor fixation, Spurr resin embedding and electron microscopic autoradiography. Stratum corneum from dry dose and patch application experiments was well preserved by freeze-drying, allowing an accurate localization of <sup>3</sup>H-estradiol. In contrast, stratum corneum from buffer solution experiments suffered from cryofixation artifacts due to excessive hydration of the skin. The corresponding autoradiographs showed strong redistribution of <sup>3</sup>H-estradiol. Thus, the visualization method under investigation has its limitations regarding the hydration level of the skin.
Effects of Systemic Treatment with Liarozole on Cutaneous Inflammation, Epidermal Proliferation and Differentiation in Extensive Plaque Psoriasis
Authors: van Pelt J.P.A. , de Jong E.M.G.J. , de Bakker E.S.M. , van de Kerkhof P.C.M. 
Published: April 2003

Liarozole is a novel inhibitor of the enzyme cytochrome P<sub>450</sub> which has inhibitory effects on the 4-hydroxylation of retinoic acid. Previous studies have shown that liarozole is effective in the treatment of psoriasis. We performed an immunohistochemical study on the lesional skin from 7 patients with extensive plaque psoriasis, who were treated with systemic liarozole 75 mg BID for a period of at least 2 months. The effects of liarozole treatment on clinical and histological parameters were investigated. In particular, the effect of liarozole on the integrin markers CD11b and CD18 was studied.For immunohistochemistry, three consecutive biopsies were taken: before treatment, after 4, and after 8 weeks of treatment. Clinical scores and side effects were recorded before and during treatment.The medication was well tolerated and only mild side effects were reported, which were comparable with hypervitaminosis A. After 2 months of treatment a statistically significant decrease of the extent of body involvement was observed. In the psoriatic plaque, markers for epidermal proliferation and cutaneous inflammation decreased, and markers for epidermal differentiation increased to values comparable to normal skin. The first therapeutic effects in the psoriatic plaque occurred after 4 weeks of treatment, and consisted of a decreased induration, accompanied by a decrease of the total number of inflammatory infiltrate cells and a decreased epidermal ICAM-1 expression. Already after 4 weeks of treatment, a decrease of CD11b-positive cells was observed. Subsequently, after 8 weeks of treatment the recruitment of cycling epidermal cells and the number of involucrin-positive cell layers decreased.The present study demonstrates that liarozole treatment of psoriasis results in a reduction of aspects of cutaneous inflammation and subsequently a reduction of epidermal proliferation and promotion of differentiation. After 4 weeks of treatment, effects are observed on the epidermal ICAM-1 expression and on the CD11b-positive cell population.
Silver Nitrate: Antimicrobial Activity Related to Cytotoxicity in Cultured Human Fibroblasts
Authors: Hidalgo Eduard , Bartolomé Rosa , Barroso Concepción , Moreno Antonio , Domínguez Carmen 
Published: April 2003

The aims of this study were to ascertain whether silver nitrate (AgNO<sub>3</sub>) concentrations below those used in clinical practice inhibit bacterial growth, and in parallel study the cytotoxic effects on human fibroblasts. The cytoprotective effects of fetal calf serum (FCS) were also evaluated. The cytotoxic effects of eight different silver nitrate concentrations were determined by assessing mitochondrial activity of viable cells capable of cleaving tetrazolium salts. Antimicrobial activity of AgNO<sub>3</sub>, range: 7–550 × 10<sup>–5</sup>%, was tested against <i>Staphylococcus aureus, Citrobacter freundii</i>, and <i>Pseudomonas aeruginosa</i>. Silver nitrate concentrations exerting antimicrobial effects were: <i>S. aureus</i>, >70 × 10<sup>–5</sup>%; <i>P. aeruginosa</i>, ≥270 × 10<sup>–5</sup>%, and <i>C. freundii</i>, ≥550 × 10<sup>–5</sup>%. With 2% FCS, the lowest AgNO<sub>3</sub> concentration studied (7 × 10<sup>–5</sup>%) showed cytotoxic effects (cell survival 71 ± 19%) at only 2 h of incubation. Under these conditions AgNO<sub>3</sub> cytotoxicity was time- and concentration-dependent in all exposure periods. Cytotoxicity was greatly enhanced causing 76% fibroblast growth inhibition at concenctrations of 14 × 10<sup>–5</sup>% and contact time of 2 h. The AgNO<sub>3</sub> concentration of 7 × 10<sup>–5</sup>% was also cytotoxic with 5% FCS in the media compared with controls, although cell survival was higher than with 2% FCS. The cytoprotective action of FCS was clearly shown at the concentration of 10% at which AgNO<sub>3</sub> cytotoxicity of 7 × 10<sup>–5</sup>% to 28 × 10<sup>–5</sup>% was partially or completely inhibited. Our results show that AgNO<sub>3</sub> at concentrations 100–700 times more diluted than that normally used in clinical practice retained effective inhibitory activity against some of the above-mentioned microorganisms. However, even these concentrations are cytotoxic for cultured fibroblasts. Thus, silver nitrate concentrations up to 100 times more diluted can be used, since they possess bacterial growth-inhibiting power, are less cytotoxic and therefore favour wound healing.
Vitamin D<sub>3</sub> and Its Synthetic Analogue Secocholestra-Trien-1,2,24-Triol Influence the Metabolism and the Isomerization of Retinoic Acid inHuman Keratinocytes
Authors: Jugert F.K. , Roos T.C. , Notzon I. , Merk H.F. 
Published: April 2003

Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D<sub>3</sub> – VD<sub>3</sub>) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol – TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 m<i>M</i> Ca for 24 h, followed by the addition of 10<sup>–6</sup>, 10<sup>–8</sup> or 10<sup>–10</sup> <i>M</i> VD<sub>3</sub> or TAC, we added 10<sup>–5</sup> <i>M</i> 13-<i>cis</i>-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD<sub>3</sub> (10<sup>–6</sup> <i>M</i>) inhibited the isomerization of 13-<i>cis</i>-RA to <i>all-trans</i>-RA (tretinoin) and 9-<i>cis</i>-RA independently from the Ca concentration in the culture medium. 10<sup>–6</sup>–10<sup>–10</sup> <i>M</i> TAC equally inhibit the 4-hydroxylation of <i>all-trans</i>-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-<i>all-trans</i>-RA, leading to a higher persistence of <i>all-trans</i>-RA, the active hormone. Both VD<sub>3</sub> and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD<sub>3</sub> which prolongs the persistence of 13-<i>cis</i>-RA, and TAC elevating the intracellular concentration of <i>all-trans</i>-RA.
Treatment of Porphyria cutanea tarda with Oral Thalidomide
Authors: Monastirli A. , Georgiou S. , Bolsen K. , Pasmatzi E. , Papapanagiotou A. , Goerz G. , Kalofoutis A. , Merk H.F. , Tsambaos D. 
Published: April 2003

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

The biotransformation and tissue distribution of 9-<i>cis</i>-retinoic acid was investigated in hairless rats. Indeed, only limited information is available about the pharmacokinetics of 9-<i>cis</i>-retinoic acid. Assuming that the target site for retinoids is the skin, tissue distribution study is therefore particularly justified. Following single oral administration of 30 mg/kg of 9-<i>cis</i>-retinoic acid, the parent drug and five metabolites were detected in plasma. Additionally, concentrations of 9-<i>cis</i>-retinoic acid and metabolites were determined in the skin and seven other tissues. The distribution of 9-<i>cis</i>-retinoic acid was rapid in all of the organs studied (T<sub>max</sub> ≤2 h). In skin, unchanged 9-<i>cis</i>-retinoic acid was still measurable up to 168 h after administration and was undetectable in other organs and plasma after 48 h.
Cutaneous Inflammation and Proliferation in vitro: Differential Effects and Mode of Action of Topical Glucocorticoids
Authors: Lange Katharina , Kleuser Burkhard , Gysler Anja , Bader Michael , Maia Claudia , Scheidereit Claus , Korting Hans Christian , Schäfer-Korting Monika 
Published: April 2003

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

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

The skin of the back of the ASR hairless miniature swine shows a rough and scaly fissured appearance. Clinically it resembles that of ichthyosis vulgaris or senile xerosis in humans. By using the skin of this animal, we developed an assay system to evaluate the efficacy of different moisturizers. The study was carried out in winter months from January to March. To establish this system, we studied various topical agents including such ordinary emollients as petrolatum and 10% salicylic acid in petrolatum as well as those available as pseudodrugs from cosmetic companies or prescription drugs from pharmaceutical companies such as heparinoid- containing creams (w/o and o/w) and 10% urea creams. Applying 0.01 g of each agent to 7 randomly selected skin areas (2 × 2 cm<sup>2</sup>) on the back of a 6-month-old swine once daily for various periods of time, we measured high-frequency conductance, the parameter for the hydration state of the skin surface. As a result, we have established a simple assay system. It consists of applications of topical agents once daily for 5 days from Monday to Friday in the first week and of subsequent measurement of the skin surface hydration state once every week. Evaluation measurements were performed from day 14 to day 21 depending upon their moisturizing effects. We found that heparinoid-containing creams exerted highly effective moisturizing effects on the dry pig skin that lasted even over 3 weeks after discontinuation of the treatments that were carried out for the first 5 days.
Evaluation of Dermal Irritancy Potential of Benzanthrone-Derived Dye Analogs: Structure Activity Relationship
Authors: Singh Ravindra P. , Das Mukul , Khanna Raj , Khanna Subhash K. 
Published: April 2003

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

The present study was designed to evaluate basic differences in surface structure and viscoelastic properties of nonatopic versus atopic skin and facultative acute changes following ultraviolet irradiation. Therefore, biophysical measurements by means of profilometry and cutometry were carried out on sun-protected unaffected gluteal skin areas in both groups before and 24 h after single UVA and UVB irradiations. The results indicate that the clinically unaffected skin of patients with atopic eczema differs from normal skin in terms of increased roughness parameters, but not concerning depth of furrows or viscoelastic properties (viscosity and biological elasticity, cutometrically calculated). Single UVA irradiation with 50 J/cm<sup>2</sup> induced neither measurable changes in the skin’s surface structure nor in its viscoelastic properties in both groups after 24 h. However, irradiation with a single erythemogenic dose of 1 MED UVB was followed by a short-term significant increase in the depths of furrows and decrease in biological elasticity in normal and atopic skin, accompanied by an increase in viscosity in normal skin.