bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral and Central Mediators of Itch
Authors: Hägermark Östen
Published: April 2009

Since the majority of itching skin diseases are inflammatory or allergic, it has been assumed that release or activation of inflammatory mediators, stimulating the itch receptors, play an essential role in the pathophysiology of itch. In this review some of the possible mediators are discussed. Histamine induces itch upon intradermal injection, but urticaria is the only itching dermatosis which is significantly relieved by antihistamines. Serotonin is much weaker than histamine in provoking itch upon intradermal injection. Serotonin acting in synergism with prostaglandins may cause itch in polycythaemia vera. Neuropeptides release histamine from skin mast cells, but it remains to be determined whether neurogenic peptides are resopnsible for clinical pruritus. Prostaglandins enhance pruritus induced by intradermal histamine (and serotonin) but are weak pruritogens per se. Lymphocytes are present in many itching skin diseases and it could be assumed that lymphokines are involved in the pathogenesis of itch. Supporting this theory is the finding that ciclosporin A, an inhibitor of lymphokine production, reduces itch in atopic dermatitis. Central mechanisms are essentially unknown, but there are indications that opioid peptides might be involved in the central transmission of itch.
Comparison of Infrared and Helium-Neon Lasers in the Measurement of Blood Flow in Human Skin by the Laser-Doppler Technique
Authors: Coulson M.L. , Hayes N.A. , Foreman J.C.
Published: April 2009

Histamine-induced changes in blood flow in normal human skin were assessed by laser-Doppler velocimetry using 2 lasers of different wavelengths: 780 nm infrared and 633 nm helium-neon. The visible flare response in skin was also measured by planimetry. Laser-Doppler velocimetry was shown to detect both the magnitude of the change in blood flow caused by histamine and also the extent of the changes in the skin. Both parameters were related to the dose of histamine, which ranged between 25 and 750 pmol/site. There was good correlation between the magnitude of the histamine-induced blood flow change and the extent of the response. The flare induced by histamine and measured by planimetry was similar in extent to the blood flow change recorded by laser-Doppler velocimetry. No difference in either the magnitude or the extent of blood flow changes in response to histamine, as measured by laser-Doppler velocimetry, were found when lasers of different wavelengths were used.
Topical and Systemic Absorption of Sodium Pyrithione following Topical Application to the Nails of the Rhesus Monkey
Authors: Mayer Philip R. , Couch Ronald C. , Erickson Mary K. , Wooldridge Bradley , Brazzell R.K.
Published: April 2009

A study was performed to investigate the local penetration into the nail, the systemic absorption into the rest of the body, and the routes of excretion of sodium pyrithione following topical application to the nail. Approximately 20 µ1 of a film-forming 3% sodium 14C-pyrithione solution was applied once daily to 5 fingernails and 5 toenails of 4 rhesus monkeys for 6 or 7 days. Following dose removal on study day 7, 2 animals were sacrificed, and the treated nails were analyzed for radioactivity. The other 2 monkeys received the topical dose for 1 more day and were monitored during the postdosing period. Sodium 14C-pyrithione was absorbed slowly into and across the nail following topical application, with the nails serving as reservoirs for the drug. Further evidence of the slow movement of sodium pyrithione across the nail was provided by peak plasma 14C equivalents obtained on day 9, 1 day after the last dose had been removed from the nails. Only slight drug concentrations were measurable in plasma, with no radioactivity observed beyond day 12. The urinary excretion data exhibited a delay in peak urinary excretion (days 8 and 9), and an elimination half-life of 2 days, so that approximately 90% of the absorbed drug was eliminated within 1 week following treatment. Including a minor excretion pathway through the feces, total excretion as a percent of dosage was 8.5 %, indicating that less than 10% of the applied topical dose of sodium pyrithione was absorbed systemically. Because monkey and human nails have similar absorptive characteristics, it is likely that corresponding levels of sodium pyrithione equivalents would be absorbed across human nails treated with sodium pyrithione.
Repeated Application of Dinitrochlorobenzene to the Ears of Sensitized Guinea Pigs: A Preliminary Characterization of a Potential New Animal Model for Contact Eczema in Humans
Authors: Boyera N. , Covey D. , Bouclier M. , Burg G. , Rossio P. , Hensby C.
Published: April 2009

We have evaluated a subchronic model of contact hypersensitivity in the guinea pig to mimic human chronic/recurrent eczema. Repeated challenges of the ears of previously sensitized guinea pigs with 0.1 % dinitrochlorobenzene (once a week for 4 weeks) induced a typical oedema response, which increased during the first 48 h after each challenge. Crusts were detectable (48 h after challenge) and histological observations (72 h after challenge) revealed hyperplasia, papillomatosis, hyperkeratosis and some mononuclear cell infiltrates in the dermis. In agreement with clinical observations in humans, topical treatment of challenged animals with corticosteroid (1 % hydrocortisone) reduced the oedema, hyperplasia, papillomatosis, and leucocyte infiltrates, while application of 5% bufexamac (a non-steroidal drug) was associated with a slight enhancement of the inflammatory response. Thus, this model presents clinical and histological similarities with human eczema. Its pharmacological relevance is also suggested, although further investigations are required to better define its selectivity.
Principles and Criteria in the Development and Optimization of Topical Therapeutic Products
Authors: Shah Vinod P. , Behl Charan R. , Flynn Gordon L. , Higuchi William I. , Schaefer Hans
Published: April 2009

The report differentiates between dermatological and transdermal products, identifies and discusses the principles involved in the development and optimization of topical drug products. The regulatory concerns in the evaluation of topical dermatological products with respect to bioequivalence and quality control are also discussed.
The Lipoxygenase Inhibitor 2-Phenylmethyl-1-Naphthol (DuP 654) Is a 12(S)-Hydroxyeicosatetraenoic Acid Receptor Antagonist in the Human Epidermal Cell Line SCL-II
Authors: Arenberger Petr , Raap Achim , Armah Benjamin , Kemény Lajos , Ruzicka Thomas
Published: April 2009

The lipoxygenase inhibitor 2-phenylmethyl-1 -naphthol (DuP 654) has been shown to be an active anti-inflammatory drug in a murine skin inflammation model. Since 12-HETE is as-sumed to have a pathophysiological role in inflammatory skin diseases, and epidermal cells possess high affinity binding sites for 12(S)-HETE, we studied the effect of DuP 654 on 12(S)-HETE binding to the human epidermal cell line SCL-II. DuP 654 antagonized 12(S)-HETE binding in a dose-dependent manner with a Ki of 3.41 ± 0.23 nM. The antagonistic effect was reversible. After 1- and 24-hour preincubation, the drug had no more significant inhibitory effect at concentrations between 10-10 and 10-5M on specific 12(S)-HETE binding (Bmax of 215,000 ± 21,000 receptors per cell) or on receptor affinity (Kd of 3.25 ± 0.42 nM). Our results show that DuP 654, in addition to its 5-lipoxygenase inhibitory activity, exhibits 12-HETE receptor antagonist effect, and therefore may be of benefit in skin diseases with elevated 12-HETE levels.
2-in-1 Shampoo Technology: State-of-the-Art Shampoo and Conditioner in One
Authors: Rushton H. , Gummer C.L. , Flasch H.
Published: April 2009

Consumers have expressed a need for cleaning and conditioning in one step. Conventional shampoo technology using anionic surfactants and cationic conditioners results in charge interaction and complexing of the ingredients. Neither shampoo nor conditioner achieves the desired result. The successful solution was to incorporate charge neutral dimethicone conditioning ingredients, suspended as microfme droplets within complex crystal lattices, into anionic surfactant shampoo technology. The same solution has also been applied to amphoteric surfactant systems. This provides complete cleaning, and hair conditioning fully equal to separate conditioners without the problems of sebum interactions and conditioner build-up. This was achieved by keeping the dimethicone in suspension throughout the shampoo process. During rinsing, excess water breaks the crystaline lattice and allows deposition of the dimethicone droplets onto the hair. Full cleaning and conditioning are, therefore, achieved in one application. Dimethicone build-up is not encountered as subsequent washes first remove soil and previously deposited dimethicone. Neither do neutral dimethicones show any reactions with sebum. The development of effective 2-in-1 technology has had a major impact on shampoo technology and consumer habits and practices. This has significantly changed the way consumers care for their hair.
Recent Advances in Hair Transplantation
Authors: Lucas Manfred W.G.
Published: April 2009

Mini- and micrografts produce esthetic results in the treatment of alopecia androgenetica which cannot be achieved using conventional methods. It is for this reason that they should be used exclusively. Their fineness furthermore opens up new vistas in plastic reconstructive surgery, making treatments possible which were previously inconceivable.
Dose-Response Curve of the Effects of Serotonin and Ketanserin on the Functional Morphology of Skin in vitro
Authors: Beele Hilde , Thierens Hubert , de Ridder Leo
Published: April 2009

A cumulative dose-response curve of the effects of serotonin and its 5-HT2 receptor antagonist ketanserin in embryonic chick skin has been set up using morphological analysis and incorporation of 3H-thymidine as parameters. The resemblance between the results of the morphological analysis and those of the functional analysis was striking. From the results of these experiments, we could deduce new arguments in favor of the hypothesis that a 5-HT2 receptor is involved in the effects of serotonin and ketanserin in embryonic chick skin observed in vitro.
Comparison of Narrow-Band Reflectance Spectrophotometric and Tristimulus Colorimetric Measurements of Skin Color
Authors: Takiwaki Hirotsugu , Overgaard Lina , Serup Jørgen
Published: April 2009

Two types of portable reflectance instruments, tristimulus colorimeters (Chroma Meter CR-200®) and narrow-band spectro-photometers (Dermaspectrometer®), have recently become available for the quantification of skin color. In order to know the difference and the relationship between the different color systems, the CIE L*a*b* system and the erythema melanin (E/M) indices, respectively, adopted by the two, the variations in skin color were measured at 23 different anatomical sites of 10 healthy Caucasian male subjects. The reddish tint of the skin color of the face, palm and sole was readily detected by either of them in the increase in the a* value or in the E index, and a strong linear correlation (r = 0.92, p < 0.001) was noted between the two values. The fair color appearance of the trunk was detected in the high L* value and in the low M index, but the correlation between the two was much less significant (r = -0.56, p < 0.001). Although the mean b* values were highest in the trunk, they are significantly lower on the non-light-exposed side than those on the light-exposed side of the arm. The correlation between the b* value and the M index was weak.
Variation in Color and Blood Flow of the Forearm Skin during Orthostatic Maneuver
Authors: Takiwaki Hirotsugu , Serup Jørgen
Published: April 2009

To investigate the influence of arm position on the color and blood flow of the forearm skin, the CIE L*a*b* values, the erythema and melanin indices, and laser-Doppler blood flow values were recorded at three different arm positions (lowered, heart level and raised) in 15 healthy subjects using three kinds of optoelectronic instruments. The values of almost all color parameters, including the melanin index, changed stepwise significantly following the change in the arm position, and blood flow values decreased significantly during arm lowering. These results are most likely due to complex changes in the volume, flow rate and oxygen saturation level of the blood in the superficial vascular plexus, and their influences on each parameter were discussed. To use these instruments effectively for the quantitative evaluation of skin test reactions, a standardized arm position should be kept when the test is carried out in the forearm.
Drug and Vehicle Deposition from Topical Applications: Localization of Minoxidil within Skin Strata of the Hairless Mouse
Authors: Tsai J.-C. , Weiner N. , Flynn G.L. , Ferry J.J.
Published: April 2009

The cutaneous bioavailability of topical 2% minoxidil solution was verified in live hairless mice. Minoxidil and propy-lene glycol deposition on the skin surface, epidermis and der-mis from the single-dose in vivo study were compared with the results from previous in vitro studies. A distinct difference is apparent in the epidermis where the in vitro values are 11–22 times higher than the in vivo values for minoxidil and 8–16 times higher for propylene glycol. The differences were not as great in the dermis. Percutaneous absorption of the drug appeared to be a very small fraction of the applied dose. Similarly shaped stratum corneum and plasma concentration profiles and the relatively constant dermal profiles of minoxidil and propylene glycol open the possibility of transappendageal routes being involved in percutaneous absorption. The greater amount of drug and vehicle found in the dermis from in vitro studies can be explained by the absence of dermal clearance. The overestimation in the amount of drug found in the epidermis in vitro may also be attributable to poor dermal clearance. On the whole, the study raises questions about the use of in vitro tissue dispositions for bioavailability assessment and bioequivalence demonstration.
Inhibition of Cytokine Gene Expression in Mouse Skin by Subcutaneous Injection of Cyclosporine
Authors: Kono Takeshi , Kondo Seiji , Venner Thomas J. , Sauder Daniel N. , McKenzie Roderick C.
Published: April 2009

Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of action is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonstrated in vitro that CsA inhibits cell proliferation and suppresses cytokine gene expression in keratinocytes. In this study, we report the in vivo effects of CsA on skin cytokine gene expression as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleu-kin (IL)-1Α and tumor necrosis factor Α gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited expression of all three genes by 80-90% relative to control levels. These data show that CsA can inhibit constitutive cytokine gene expression in mouse skin.
Dapsone Inhibits the Generation of 5-Lipoxygenase Products in Human Polymorphonuclear Leukocytes
Authors: Wozel Gottfried , Lehmann Bodo
Published: April 2009

Dapsone (4,4’-diaminodiphenylsulfone) is effective in treating inflammatory skin diseases. Several lines of evidence suggest that the anti-inflammatory properties of this sulfone are partially due to modulation of functions of polymorphonuclear leukocytes (PMN). The goal of the present investigation is therefore to ascertain possible inhibitory effects of dapsone upon human 5-lipoxygenase (5-LOX) pathway. PMN of healthy donors were pretreated with dapsone in different concentrations (1.6-100 μM) for 5 min following by adding Ca ionophore A 23187 (10 μM) and subsequent incubation for 10 min. Thereupon the eicosanoids were assessed by reversed-phase high-performance liquid chromatography (RP-HPLC). Dapsone exhibited dose-dependent inhibitory activity showing 50% inhibition at 15 μM for leukotriene B4 (LTB4) with 5 × 106 PMN. The IC50 (half maximum inhibition concentration) of dapsone for 5-hydroxyeicosatetraenoic acid (5-HETE) and ω-OH-LTB4 amounted to similar values (5-HETE: 9 μM; (ω-OH-LTB4: 11 μM). The inhibition of the conversion of arachidonic acid to several eicosanoids mainly suggests an effect on the 5-LOX enzyme. The comparison of inhibition values between intact PMN and a cell-free system (by sonification) indicates an additional effect of dapsone upon enzymes other than 5-LOX. Since the concentrations used are comparable with therapeutic conditions, dapsone may exert part of its anti-inflammatory effect by prevention of the generation of 5-LOX metabolities.
Novel Steroid Derivative Modulates Gene Expression of Cytokines and Growth Regulators
Authors: Michel Günter , Nowok Katja , Beetz Axel , Ried Christine , Kemény Lajos , Ruzicka Thomas
Published: April 2009

Topical steroid treatment is a common therapy for psoriasis. Steroids are known to bind to specific cytoplasmic receptors and to influence gene expression. We investigated the effects of the novel steroid derivative mometasone furoate on the expression of putative target genes in normal human epidermal cells (KC). Gene expression was measured by semiquanti-tative mRNA-PCR. In addition, cytokine receptor characteristics were assessed by ligand binding studies. We found a dose-dependent downregulation of proinflammatory mediators (IL-8, TNFα). Genes involved in growth regulation (HER-2, p53) were also modulated. IL-8 binding to KC was inhibited. We conclude that modulation of the expression of cytokine, cytokine receptor and growth factor genes may contribute to the antipsoriatic action of steroids.
Skin Surface Lipid and Skin Friction: Relation to Age, Sex and Anatomical Region
Authors: Cua Anastasia B. , Wilhelm Klaus-P. , Maibach Howard I.
Published: April 2009

Differences in the skin surface lipid content (SSL) and the dynamic friction coefficient (µ) were investigated with respect to age, sex, and anatomical region in 29 volunteers. The group consisted of (a) 7 young adult females (24.9 ± 1.1 years old, mean ± SD), (b) 7 old females (75.3 ± 2.4 years old), (c) 7 young adult males (28.7 ± 0.5 years old), and (d) 8 old males (73.8 ± 1.9 years old). Measurements were obtained on 11 anatomical regions, namely, the forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper and lower back, thigh, and ankle. Skin surface lipid content data were compared with µ measurements to determine the relative contribution of the former to frictional properties of skin, µ and SSL were not statistically different between age groups on all regions except for the ankle, where lipid content was lower in the elderly. Similarly, µ did not vary between sex groups. Skin surface lipid content was statistically lower on the forehead, dorsal forearm and postauricular area in females. Both parameters, however, showed considerable regional variability. A significant linear correlation was established between µ and SSL combining all regions from all volunteers. When µ was plotted against SSL among individual anatomic sites, only the forehead and postauricular area showed significant linear correlations between the two parameters. These data suggest that surface lipid content plays a limited role in frictional properties of skin.
Effects of Hypertrichotic Agents on Follicular and Nonfollicular Cells in vitro
Authors: Kurata Sotaro , Uno Hideo , Allen-Hoffmann Lynn
Published: April 2009

Our previous studies revealed that topical minoxidil induced an increased rate of DNA synthesis in both dermal papilla and follicular germinal cells in early anagen and bulbar matrix as well as outer root sheath and perifollicular fibrocytic cells in mid and late anagen follicles in the bald scalp of the stump-tailed macaque. However, the epidermis and dermal fibrocytes showed no response. To determine the specific action of hypertrichotic agents on follicular cells, we examined the effects of two potent hypertrichotic agents, minoxidil and cyclosporin, on the DNA synthesis of cultured cells derived from either follicular cells (dermal papular, perifollicular fibrocytic and outer root sheath cells) obtained from human and macaque scalps or nonfollicular cells (fibrocytes and epidermal keratinocytes) from human and macaque foreskin, palm and sole regions and the 3T3 cell line. Cultured subconfluent cells from the above follicular and nonfollicular specimens were incubated with either minoxidil (0.01-2 mM) or cyclosporin (0.01-100 mM) in medium (serum-free DMEM) for 48 h, then 3H-fhymidine was added for the final 6 h. Minoxidil induced a significant increase in DNA synthesis in all follicular cells in a dose-specific manner (maximum rate at 0.5 mM for dermal papilla and perifollicular fibrocytic cells and 0.1 mM for outer root sheath cells). The perifollicular fibrocytic cells appeared to have a potentiality similar to that of the dermal papilla cells. Nonfollicular cells showed no response to minoxidil; 3T3 cells were rather suppressed. Cyclosporin appeared to have rather suppressive effects on both follicular and nonfollicular cells. These results suggest that minoxidil has a specific affinity to hair follicular cells and induced their cell proliferation. Although cyclosporin is known as a potent hypertrichotic agent, our studies on cultured follicular cells showed no direct proliferative effect. The hypertrichotic mechanism of cyclosporin appeared to be different from that of minoxidil.
Vaginal Keratinization during the Estrous Cycle in Rats: A Model for Evaluating Retinoid Activity
Authors: Chateau Danielle , Geiger Jean-Marie , Samama Brigitte , Boehm Nelly
Published: April 2009

A model is described for evaluating the activity of a retinoid based on its effect on the keratinization of the vaginal epithelium that occurs on estrus (day 4) of a 4-day cycle in female rats. This keratinization process is dependent on the endogenous estradiol (E2) secreted between the evening of diestrus 2 (day 2) and that of proestrus (day 3). Various doses of all-trans-retinoic acid (tRA) were injected at different time points during the estrous cycle and the vaginal keratinization was assessed by microscope examination of unstained native or Papanicolaou-stained smear preparations. Additionally, the preovulatory E2 secretion was measured and ovaries were histologically examined. A single injection of 10 mg/kg tRA either on diestrus 2 (evening) or on proestrus (early morning) was able to induce a complete inhibition of the vaginal keratinization in more than 80% of the cases. This can be considered as a direct effect on the vaginal epithelial differentiation since neither the E2 secretion nor the ovulatory process were affected. The inhibition of vaginal keratinization can be used as a rapid and convenient in vivo model for screening retinoid candidates with antikeratinizing activity.
Diethylene Glycol Monoethyl Ether (Transcutol®) Displays Antiproliferative Properties Alone and in Combination with Xanthines
Authors: Levi-Schaffer Francesca , Dayan Nava , Touitou Elka
Published: April 2009

In the present study we have investigated the effects of diethylene glycol monoethyl ether (Transcutol®) in combination with theophylline, caffeine and dyphylline and alone on 3T3 mouse fibroblast proliferation. These three xanthines (1-0.01 mM) inhibited fibroblast proliferation by themselves. Enhancement of the effect was detected by addition of 1 and 0.1 mM Transcutol. Transcutol alone also displayed a dose-dependent inhibition (2-0.01 mM) of both 3T3 and human normal and psoriatic fibroblasts, although normal human fibroblasts were the least sensitive to Transcutol antiproliferative activity. Transcutol was assessed for its antiproliferative effects on YAC lymphoma and P-815 mastocytoma human cell lines. Transcutol inhibited cell proliferation of both these cell lines, being more effective towards P-815 mastocytoma (at 2 mM it displayed 3.95-fold vs. 2.4-fold inhibition towards YAC lymphoma). In conclusion, we have shown that Transcutol has antiproliferative effects on 3T3 murine, human normal and psoriatic fibroblasts and tumour cell lines. In addition it enhances xanthine antiproliferative effects on 3T3 fibroblasts. Therefore it might be a useful topical drug alone or in combination with xanthines in the treatment of skin hyperproliferaive disorders.
A New Method for Assessing the Gloss of Human Skin
Authors: Lentner A. , Wienert V.
Published: April 2009

A new method for an objective assessment of the gloss of human skin is presented. The refiectometric measuring set-up complies with DIN 67530. The principle of this new method is based on a contactless determination of the skin’s reflection of light from a tungsten filament lamp, recorded at an angle of 60° by a silicon photocell. In a comparative study with 30 test persons it was discovered that the forehead, with 2.70 standardised reflectometer units (RU; SD ± 0.59 RU), displayed a significantly higher gloss than the lower arm (1.99 RU, SD 0.28 RU, p < 0.0001). In an investigation into the influence of four different cream bases on the skin gloss it could be determined that the value depends on the percentage of grease, the water concentration and the consistency of the respective base. The method presented permits a fast, contactless, randomly repeatable objective assessment of skin gloss. Since the acceptance of cosmetics and pharmaceutical products depends not least on their skin gloss effect, this method can provide valuable information when estimating the success of old and new products.
Effect of Naftifine on Neutrophil Adhesion
Authors: Choi Tak-Shun , Solomon Barry , Nowakowski Maja , Lee Wei-Li , Geen Susan , Suntharalingam Kamala , Fikrig Senih , Shalita Alan R.
Published: April 2009

Effective methods of fungal treatment involve reduction in fungal infections and host inflammatory responses. Naftifine (NF), a topical antifungal agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN) chemotaxis and respiratory burst activity in an irreversible dose-dependent and time-dependent manner. Since leukocyte adherence to endothelia is believed to be one of the initial crucial events in the recruitment of circulating leukocytes to the site of inflammation, we have investigated the in vitro effect of NF on PMN adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and endothelial mono-layers via three adherence assays. All three assays demonstrated a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the respective media. In particular, NF (at 30-60 μg/ml) significantly inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits PMN adherence to endothelia in our in vitro model system. This inhibition may constitute part of the anti-inflammatory effect of NF.
Influence of Ion Pairing on ex vivo Penetration of Erythromycin into Sebaceous Follicles
Authors: Matschiner S. , Neubert R. , Wohlrab W. , Matschiner F.
Published: April 2009

Microorganisms play an important role in the pathomechanism of acne vulgaris which is treated with antibiotics, particulary erythromycin (ERY). The main problem in the topical use of ERY lies in achieving sufficient penetration of the drug into sebaceous follicles. Doubly enhanced penetration of an ion pair composed of ERY and octadecansulfonate (OS) in contrast to the commonly used ERY base was observed, using a multilayer membrane model (MMM). The aim of the present study was to evaluate the results obtained on the MMM using excised human skin. The amount of ERY penetrating into sebaceous follicles of freshly excised human skin was measured using [N-methyl-14C]erythromycin. The ex vivo penetration of the ion pair ERY/OS into the sebaceous follicles was observed to be doubly enhanced compared with the penetration of the ERY base. The model was shown to be suitable for predicting in vivo penetration of anti-acne formulations into sebaceous glands.
Variation de I’insulinémie en fonction de I’âge chez le rat mâle non traité
Authors: Gommers A. , de Gasparo M.
Published: April 2009

Effect of ageing on insulinemia, determined by radio-immunological method, has been studied in male rats aged 3, 12 and During the intravenous hyperglycemia test, the coefficient of glucose assimilation decreases significantly with age, whereas a hype insulinemia is to be seen. This becomes apparent at the moment of the hyperglycemic peak and still persists 20 min after the beginning of the test. Senescence in the rat is, therefore, accompanied by early decrease in glucose tolerance and abnormally high IRI (immunoreactive insulin) level in the blood.
Lymphocyte Sensitization and Ageing
Authors: Field E.J. , Smith J.K.
Published: April 2009

Lymphocyte sensitization to encephalitogenic factor and cancer basic protein increases with age. No significant sex difference was found. Sensitization to PPD does not change significantly though there is a suggestion it may diminish. Cellular sensitization in general thus appears toparallel circulating ‘auto-antibody’ levels.
Immunological and Clinical-Chemical Investigations on Blood, Urine, and Kidney in Aging Praomys(Mastomys)natalensis with Spontaneous Glomerulonephritis
Authors: van Pelt Frida G. , Blankwater Marie-José
Published: April 2009

During its life-span, the multimammate mouse, Praomys (Mastomys) natalensis, may develop glomerulonephritis and a great variety of spontaneous tumors. Their occurrence is found to increase with age. Struck by the similarities at the light microscopic level between the glomerular lesions in Mastomys and those found in NZB mice and in man with systemic lupus erythematosus, an immunological and clinical-chemical investigation was initiated in order to study the pathogenesis of the glomerulonephritis. All data were compared with those described for aging rodents and for NZB mice strains with glomerulonephritis. The randomly bred Mastomys studied did not show hypergammaglobulinemia, hypoalbuminemia, Coombs’ hemolytic anemia, or cryo globulins. The percentage of ANF-positive sera and the extent of proteinuria seem to be normal for a rodent. However, in connection with the high incidence of tumors in Mastomys, it is suggested that the observed granular fluorescent deposits in the glomerulus of the kidneys consist of tumor antigen-antibody complexes.
Age-Dependent Immnnophysiologic Correlates of Chronic Respiratory Disease
Authors: Buckley, III C.E. , Dorsey F.C. , Sieker H.O.
Published: April 2009

Serum levels of IgG, IgA and IgM were evaluated in 688 adult patients with chronic respiratory disease. Diagnoses were verified by retrospective audit of the medical records of the first 372 patients; measures of ventilation were obtained in 110 patients and arterial blood gases in 84 patients who were free of acute infection. Sampling reproducibility was verified by comparison of the audited patients with the second sample of 318 patients. IgG and IgA levels were decreased in patients under 40 years of age. Elevated IgM and IgG occurred in older patients; macroglobulinemia was the most significant change observed. Abnormal serum immunoglobulin levels occurred in 44 % of patients with clinical evidence of emphysema, 66 % of patients with pneumonia, 27 % of patients with chronic bronchitis and 32 % of patients with chronic sinusitis. Patients with chronic sinusitis had decreased IgA. Macroglobulinemia was observed in patients with emphysema. In contrast to alterations associated with the clinical diagnosis, comparisons of immunoglobulin levels within the patient sample with physiologic measures of respiratory function revealed an association between low IgG, hypoxemia and respiratory alkalosis – changes compatible with a ventilation perfusion imbalance. Residual lung volume and total lung capacity were maximum in patients with low IgM – changes compatible with emphysema. These observations suggest that humoral immune surveillance may be important in the pathogenesis of chronic degenerative parenchymal lung disease.
Effects of Age and Isolation on the Intestinal Flora of Mice
Authors: Pesti László , Gordon Helmut A.
Published: April 2009

The gut flora of 4- and 24-month-old ICR mice has been studied in the following groups: (a) conventional mice held in the open environment, (b) conventional mice in germ-free-type isolators and (c) germ-free mice in similar conditions after they have been associated with normal mouse flora following a single microbial exposure. The results indicate that elements of the autochthonous flora populate the gut in young mice, irrespective of the type of housing. Pathogenic organisms (e.g. clostridia, E. coli) were rejected. In older mice held in the open environment – i.e. when re-seeding from the external environment was permitted – these pathogens were established in the gut, while this did not occur in mice protected by the isolator. Age-induced impairment of body defenses might be responsible for this phenomenon.
Emergence of New Antigens in Ageing Tissues
Authors: Field E.J. , Shenton B.K.
Published: April 2009

Ageing both in mice and the human is associated with the emergence of new antigenic determinant(s) which may be recognized by injecting the tissues into guinea pig and studying the sensitization developed by the animal’s lymphocytes, to normal and scrapie mouse brain or spleen. New antigenic determinant(s) appear in ageing tissues sufficiently like those found in scrapie mouse brain or spleen to give cross reactions with the latter. It is possible to use a preparation of lymphocytes or RBC as a ‘biopsy’ material to assess the position of an individual with respect to the emergence of the antigenic determinant(s) associated with ageing. The method might be used to study the influence of disease in general upon ageing in tissues.
Effects of Various Drugs on Longevity in Female C57BL/6J Mice
Authors: Hochschild R.
Published: April 2009

Chlorpromazine, chlorpheniramine, chloroquine, dimethylaminoethyl p-chlorophenoxyacetate, aspirin and acet-aminophen were individually administered at one or more dosage levels, to groups of female C57BL/6J mice from an average age of 10 months to the end of life. Each of the drugs are known or suspected stabilizers of cellular membranes. Except for two cases of apparently toxic effects, differences in life span between drug-treated animals and control animals were not significant at the p < 0.05 level. Dimethylaminoethyl p-chlorophenoxyacetate, which had previously extended the life span of male Swiss Webster albino mice by 27.3% of the period of administration (p = 0.039), produced a modest and not quite significant 5.9% extension (p = 0.077). Weight changes were negligible up to 19 months of age, but several of the drug-treated groups averaged somewhat lighter in weight than control mice by 25 months of age.
Regenerative Properties of Tissues Involved in Chronic Pathological Processes
Authors: Vukas A. , Zambal Z.
Published: April 2009

A deficiency of spontaneous regeneration is a characteristic feature in many chronic pathological skin processes. However, if a degree of vitality of the cells is still present, it is possible to release their inhibited embryonic properties, so that they behave like normal cells, contributing to the restoration of the original tissue architecture and function. The study reported here was performed on the skin of aged human beings and on arterial walls of old dogs and confirmed to a certain extent previous experience.
Effect of Age, Hypophysectomy, Cortisone and Growth Hormone on Amine (Lysyl) Oxidase Activity in Rat Aorta
Authors: Howarth D. , Everitt A.V.
Published: April 2009

Hypophysectomy abolishes the activity of amine (lysyl) oxidase in rat aorta, and this is associated with a reduced aldehyde content of soluble collagen in tail tendon. Both amine oxidase activity and the aldehyde content decrease with age. Treatment of the hypophysectomized rat with either cortisone or growth hormone restores the activity of amine (lysyl) oxidase. This work supports the hypothesis that hypophysectomy inhibits collagen aging (cross-linkage) by reducing the activity of lysyl oxidase, the enzyme concerned in the first step of cross-linkage.
Altersbedingte Konzentrationsänderungen saurer Mukopolysaccharide in der Mitralklappe des Menschen
Authors: Sames Klaus , Stegmann Thomas , Rebel Wolfgang
Published: April 2009

The acid glycosaminoglycans of human mitral valves are differentiated histochemically by the critical electrolyte concentrations of alcian blue. Age- dependent changes in the composition of acid mucopolysaccharides in the ground substances of valves are investigated by histophotometric measurements between the free valve edge and the line of closure. With respect to these values, the concentration of the total acid mucopolysaccharides in mitral valves grows with aging. The first increase is seen until to the 4th decade, a second one with the 5th decade reaching its maximum in old age. Sulfomucopolysaccharides show similar variations; increasing until the 4th decade, they are followed by a slight decrease and new increasing until old age. The concentration of more alcianophilic chondroitin sulfates, however, reaches a maximum in the 4th decade, falling off in later life. No acid mucopolysaccharides of higher sulfation grade are detected in mitral valve ground substances. Hyaluronic acid represents the main part of acid mucopolysaccharides in mitral valves. With advancing age the content of hyaluronic acid grows at a rate equal to that of the total acid mucopolysaccharides and reaches its maximum concentration in the 8th and 9th decade. The chondroitin sulfates represents 20–22% of the total acid mucopolysaccharides. This ratio does not change substantially during the aging process.
Rubella Antibody Titer and IgG Concentration in an Aging Population
Authors: Remy Wolfgang , Bockendahl Hans , Antoniadis Grigorios
Published: April 2009

Statistical analysis of rubella titers (values partly from the literature) reveals that about 4% of those between 16 and 30 years of age are without antibodies. Older age groups show complete immunization of all individuals. Mean rubella titers in subjects between 16 and 40 years of age are identical. A group of elderly subjects (60 years) shows decreased titers that could be statistically verified. IgG serum concentrations in individuals over 60 years are significantly elevated if compared with normal medium values. The results are discussed in view of previous studies about antibodies and IgG concentration in the aged.
Variation of Collagenous and Non-Collagenous Proteins of Human Knee Joint Menisci with Age and Degeneration
Authors: Ingman A.M. , Ghosh P. , Taylor T.K.F.
Published: April 2009

The chemical composition has been determined in inner, middle and peripheral zones of 50 human knee joint menisci of ages 0–86 years. Of these, 12 showed areas of degeneration which were analysed separately. On a dry weight basis, normal adult tissues contained 77.9 ± 0.4% collagen, 8.1 ± 0.8% non-collagenous proteins (NCP) and 1.0 ± 0.1 % hexosamine. With aging, the level of collagen increases and NCP declines. In degenerate areas, a statistically significant loss in collagen, and rise in NCP and hexosamines was observed, relative to normal menisci of the same age.
Age-Related Changes in the Bone Marrow and Spleen of SAS/4 Mice
Authors: Coggle J.E. , Gordon M.Y. , Proukakis C. , Bogg C.E.
Published: April 2009

The total number of nucleated cells in the bone marrow of SAS/4 mice increase some twofold between 1 and 24 months of age but when related to body weight remains essentially constant over a wide range of ages. The concentration of CFU-S in femoral marrow is also constant with age and since other bones containing marrow appear, at least in young mice, to have the same CFU-S concentration as the femur it is concluded that the CFU-S compartment size of the whole bone marrow is independent of age when expressed on a body weight basis. In contrast, both the absolute number and the concentration of exogenous CFU-S in the spleen decline markedly in old mice. Similarly there is a decline in the number of endogenous colony-forming cells and the spleens of 24-month-old mice seem virtually devoid of such colonies. Not only were older mice less capable of supporting the growth of endogenous colonies, but their spleens also appear to provide a poorer environment for exogenous colony growth when compared with growth in younger recipient spleens.
Age Differences in Learning, Immediate and One Week Delayed Recall
Authors: Schneider Nina G. , Gritz Ellen R. , Jarvik Murray E.
Published: April 2009

In an initial study, differences in learning and immediate recall were observed for groups of young and aged subjects on several measures. Retest data showed some differential loss for aged subjects after 1 week. Conclusions regarding long-term retention per se were not possible due to the nature of the design. In a second study, additional aged and young groups of subjects were run under delayed recall conditions. The data from these two groups were combined with data from the first study, with care taken to match subjects on a number of variables (health, education, intelligence). The results showed age-related differences for measures of learning and immediate recall but not for delayed 1 week retention.
Biochemical and Histochemical Changes in Energy Supply-Enzyme Pattern of Muscles of the Rat during Old Age
Authors: Bass A. , Gutmann E. , Hanzlíková V.
Published: April 2009

Senile muscles of the rat (28–36 months) show loss of overall activity of glycolytic and aerobic enzymes. However, there is a differential loss and shift of enzyme activity pattern in the three types of muscles. The extensor digitorum longus (EDL) and diaphragm show a decrease of ratios of glycolytic to aerobic-oxidative enzymes. This shift to a more oxidative type of metabolism is not observed in the soleus muscle. Decrease of enzyme activities is least marked in the diaphragm muscle. Biochemical analysis shows a trend to levelling out of metabolic differences between the different muscle types. This trend of ‘dedifferentiation’ is most marked when comparing EDL and soleus, least marked when comparing EDL and diaphragm muscle. The histochemical analysis shows a shift from the original mixed to a more uniform pattern of muscle fibres in the EDL and soleus muscle; this levelling-out of differences between enzymatic activities of different muscle fibres is not observed in the diaphragm muscle. Preferential atrophy and loss of ATPase activity in type II muscle fibres in the soleus muscle and the occurrence of ‘type grouping’ are further characteristic features of senile muscle change. The findings show general (i.e. loss of enzyme activities) and differential trends of biochemical and histochemical enzyme changes in different types of muscles.
A Brief Argument in Opposition to the Orgel Hypothesis
Authors: Baird M.B. , Samis H.V. , Massie H.R. , Zimmerman J.A.
Published: April 2009

The Orgel hypothesis receives considerable attention as a possible explanation for the phenomenon of senescence. Experimental observations which argue in favor of the Orgel hypothesis are discussed, and criticized in part. This is followed by a presentation of experimental data which argue in opposition to the notion. On the basis of the considerable body of data which argue in opposition to the Orgel theory, a call for reappraisal of the applicability of this theory to the phenomenon of senescence is suggested.
Lack of Increase in DNA Crosslinking in Drosophila melanogaster with Age
Authors: Massie H.R. , Baird M.B. , Williams T.R.
Published: April 2009

Adult Drosophila melanogaster fruit flies ranging in age from 2 to 7.5 weeks with a median colony survival time of 6.4 weeks at 25°C showed no increase in DNA crosslinking with age. The purified denatured DNA used for crosslink determinations varied in molecular weight from 2.02 to 3.84 × 105 daltons and was crosslinked to the extent of 6.2–8.8% with no age-related trend.
Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program
Authors: Hoogenkamp Maarten , Lichtinger Monika , Krysinska Hanna , Lancrin Christophe , Clarke Deborah , Williamson Andrew , Mazzarella Luca , Ingram Richard , Jorgensen Helle , Fisher Amanda , Tenen Daniel G. , Kouskoff Valerie , Lacaud Georges , Bonifer Constanze
Published: April 2009

At the cellular level, development progresses through successive regulatory states, each characterized by their specific gene expression profile. However, the molecular mechanisms regulating first the priming and then maintenance of gene expression within one developmental pathway are essentially unknown. The hematopoietic system represents a powerful experimental model to address these questions and here we have focused on a regulatory circuit playing a central role in myelopoiesis: the transcription factor PU.1, its target gene colony-stimulating-factor 1 receptor (Csf1r), and key upstream regulators such as RUNX1. We find that during ontogeny, chromatin unfolding precedes the establishment of active histone marks and the formation of stable transcription factor complexes at the Pu.1 locus and we show that chromatin remodeling is mediated by the transient binding of RUNX1 to Pu.1 cis-elements. By contrast, chromatin reorganization of Csf1r requires prior expression of PU.1 together with RUNX1 binding. Once the full hematopoietic program is established, stable transcription factor complexes and active chromatin can be maintained without RUNX1. Our experiments therefore demonstrate how individual transcription factors function in a differentiation stage–specific manner to differentially affect the initiation versus maintenance of a developmental program.
Avaliação da função pancreática em pacientes com diabetes melito tipo 1 de acordo com a duração da doença
Authors: Dantas Joana R. , Almeida Mirella H. , Barone Bianca , Campos Felipe , Kupfer Rosane , Milech Adolpho , Zajdenverg Lenita , Rodacki Melanie , Oliveira José Egídio P. de
Published: April 2009

Os pacientes com diabetes melito tipo 1 (DM1) podem apresentar secreção residual de insulina por longos períodos, o que tem sido associado a prognóstico mais favorável. OBJETIVO: Avaliar a secreção de insulina por meio da dosagem de peptídeo C (PC) em pacientes com DM1 de curta (<5 anos; grupo 1) e longa (> 5 anos; grupo 2) duração da doença. PACIENTES E MÉTODOS: Voluntários com DM1 coletaram sangue em jejum e 6 minutos após a infusão de glucagon para dosagem de PC, HbA1c e anti-GAD. RESULTADOS: Foram avaliados 43 pacientes, 22 no grupo 1 e 21 no grupo 2. Secreção de insulina preservada (PC > 1,5 ng/mL) foi identificada em seis (13,9%) e oito (18,6%) casos nas coletas basal (PC1) e após estímulo (PC2), sem diferença entre os grupos (p = 0,18 e 0,24). PC1 foi detectável (> 0,5 ng/mL) em 13 (30,2%) e PC2 em 18 (41,9%) casos, mais frequentes no grupo 1 do que no 2 (p = 0,045 para PC1/p = 0,001 para PC2). Os títulos de PC1 (1,4 ±0,8 versus 1,2 ±1,0; p = 0,69) ou PC2 (1,8 ±1,5 versus 1,7 ±0,8; p = 0,91) não diferiram entre os grupos. No grupo 1 houve correlação inversa entre tempo de doença e PC2 (R = -0,58; p = 0,025). CONCLUSÃO: Uma proporção significativa dos pacientes com DM1 apresenta secreção residual de insulina, especialmente nos primeiros cinco anos da doença. Tais indivíduos representam a população ideal para estudos visando à prevenção secundária da doença.