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Topical Application (topical + application)
Kinds of Topical Application Selected AbstractsPhotodynamic Therapy of Cutaneous Lymphoma Using 5-Aminolevulinic Acid Topical ApplicationDERMATOLOGIC SURGERY, Issue 8 2000Arie Orenstein MD Background. Photodynamic therapy (PDT) with topical application of 5-aminolevulinic acid (ALA) is a new and effective modality for treatment of superficial basal and squamous cell carcinomas. Objective. We present the kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of ALA PDT treatment on two patients with different stages (stage I and stage III) of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). Methods. ALA-Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence measurements of PP accumulation were carried out before, during, and 1 hour after photoirradiation (580,720 nm) using the VersaLight system. Results. Different patterns of PP fluorescence kinetics were observed in patients with early and advanced stages of the disease. During photoirradiation the intensity of fluorescence decreased depending on the lesion thickness. One hour after the photoirradiation procedure no PP fluorescence was observed in the stage I MF lesion, while in the thick stage III MF lesions, PP fluorescence reappeared; after an additional 10,15 minutes of irradiation PP fluorescence disappeared. Complete response with excellent cosmetic results was observed in the stage I lesion after a single irradiation with a light dose of 170 J/cm2; in five stage III lesions, complete response was achieved after fractionated irradiation with a total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively). Conclusion. The results showed a high response of both stage I and stage III MF lesions to ALA PDT. This modality appears to be very effective and can be used successfully for MF treatment. [source] Methemoglobinemia and CNS Toxicity after Topical Application of EMLA to a 4-Year-Old Girl with Molluscum ContagiosumPEDIATRIC DERMATOLOGY, Issue 6 2006S. MINTEGI RASO M.D. No abstract is available for this article. [source] Study of Protoporphyrin IX (PpIX) Pharmacokinetics After Topical Application of 5-Aminolevulinic Acid in Urethral Condylomata Acuminata,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2007Xiu-Li Wang The pharmacokinetics of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in lesions of urethral condylomata acuminata were investigated. Sixty patients (20 to 60 years old, 48 male and 12 female) were divided randomly into five groups and received topic application of different concentrations of ALA solution (0.5%, 1%, 3%, 5% or 10%). Biopsy was performed between 1 and 7 h and specimens were subjected to histological, PpIX fluorescence and human papillomavirus (HPV) DNA typing analyses. Fluorescence examination confirmed that ALA-induced PpIX fluorescence was dominantly distributed in the HPV-infected epidermis. In contrast, only a minimal amount of PpIX fluorescence was detected in the dermis. The maximal fluorescence intensity was detected at 5 h incubation. Higher ALA concentration (e.g. 5% and 10%) produced a stronger intensity. These results suggest that the topical application of 5,10% ALA solution for 3,5 h is the optimal condition for the photodynamic therapy of urethral condylomata acuminata. The selective damage of the condylomata acuminata lesions in the epidermis without damaging the dermis ensures a better control of recurrence and side effects such as ulceration or scarring. DNA typing showed that all patients were positive for low risk-HPV DNA and among them 18.3% of patients harbored high risk-HPV DNA. [source] Protoporphyrin IX Fluorescence Kinetics and Localization after Topical Application of ALA Pentyl Ester and ALA on Hairless Mouse Skin with UVB-Induced Early Skin CancerPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2000Johanna T. H. M. van den Akker ABSTRACT In order to improve the efficacy of 5-aminolevulinic acid-based (ALA) photodynamic therapy (PDT), different ALA derivatives are presently being investigated. ALA esters are more lipophilic and therefore may have better skin penetration properties than ALA, possibly resulting in enhanced protoporphyrin IX (PpIX) production. In previous studies it was shown that ALA pentyl ester (ALAPE) does considerably enhance the PpIX production in cells in vitro compared with ALA. We investigated the in vivo PpIX fluorescence kinetics after application of ALA and ALAPE to hairless mice with and without UVB-induced early skin cancer. ALA and ALAPE (20% wt/wt) were applied topically to the mouse skin and after 30 min, the solvent was wiped off and PpIX fluorescence was followed in time with in vivo fluorescence spectroscopy and imaging. At 6 and 12 h after the 30 min application, skin samples of visible lesions and adjacent altered skin (UVB-exposed mouse skin) and normal mouse skin were collected for fluorescence microscopy. From each sample, frozen sections were made and phase contrast images and fluorescence images were recorded. The in vivo fluorescence kinetics showed that ALAPE induced more PpIX in visible lesions and altered skin of the UVB-exposed mouse skin, but not in the normal mouse skin. In the microscopic fluorescence images, higher ALAPE-induced PpIX levels were measured in the stratum corneum, but not in the dysplastic layer of the epidermis. In deeper layers of the skin, PpIX levels were the same after ALA and ALAPE application. In conclusion, ALAPE does induce higher PpIX fluorescence levels in vivo in our early skin cancer model, but these higher PpIX levels are not located in the dysplastic layer of the epidermis. [source] Topical Application of Calcium Channel Blockers to Reduce the Progression of Experimentally Induced Myringosclerosis and TympanosclerosisTHE LARYNGOSCOPE, Issue 4 2008Adin Selcuk MD Abstract Objectives: This study aimed to evaluate the ability of topically applied calcium channel blockers (diltiazem) to reduce the progression of experimentally induced myringosclerosis and tympanosclerosis. Study Design: Animal model. Experimental prospective study. Methods: The study included 25 adult albino guinea pigs that were bilaterally myringotomized and inoculated with a suspension of Streptococcus pneumonia type 3. The right ears were treated with topical application of diltiazem, and the untreated left ears served as the control group. Otomicroscopy and remyringotomy were conducted every week. One animal was sacrificed after 1 week and the remaining at the end of 6 weeks. Temporal bones were dissected, and tympanic bullae were analyzed with light microscopy. Results: The untreated control ears showed evidence of extensive myringosclerosis on otomicroscopy, and the ears treated with calcium channel blockers did as well although to a lesser degree. Under light microscopy, the lamina propria of both tympanic membranes and middle ear mucosae of the control group exhibited thicker (P < .1 and P < .05, respectively) and larger (P < .01 and P < .01, respectively) sclerotic tissue in comparison with the treatment group. Conclusion: The results suggest that calcium channel blockers had an influence in the prevention of tympanosclerosis. [source] In vivo Skin Irritation Potential of a Castanea sativa (Chestnut) Leaf Extract, a Putative Natural Antioxidant for Topical ApplicationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2008Isabel F. Almeida However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40°. The IC50 found for the iron chelation and DPPH scavenging assays were 132.94 ± 9.72 and 12.58 ± 0.54 µg/ml (mean ± S.E.M.), respectively. The total phenolic content was found to be 283.8 ± 8.74 mg GAE/g extract (mean ± S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application. [source] Behavioural observations of Pieris brassicae larvae indicate multiple mechanisms of action of analogous drimane antifeedantsENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2000L. Messchendorp Abstract We tested 11 analogous synthetic drimane antifeedant compounds for their feeding inhibiting effects on larvae of the large white butterfly Pieris brassicae L. (Lepidoptera: Pieridae) in no-choice tests on the host plant Brassica oleracea L. Furthermore, we observed larval feeding behaviour in no-choice tests to analyze temporal effects of five drimanes. The results show that the five analogous antifeedants differentially influence feeding behaviour and locomotion activity. Warburganal and polygodial are most likely sensory mediated antifeedants. Habituation to these compounds occurs soon after the onset of the tests (i.e., within 0.5,1.5 h). Compound 5 and confertifolin are probably not direct, sensory mediated antifeedants. After 0.5,1.5 h of exposure, these compounds inhibit not only feeding, but also locomotion behaviour, indicating postingestive, toxic effects. Isodrimenin inhibits feeding from the onset of the test and is probably a sensory mediated antifeedant. No habituation occurs to this compound, indicating that isodrimenin is either a very strong antifeedant or that it additionally has postingestive, toxic effects. Topical application of the drimanes on the larval cuticle revealed feeding inhibiting effects, but these could not be related to the occurrence of postingestive feeding inhibiting effects, indicating that this method is inappropriate to show possible postingestive effects of drimanes in P. brassicae. In conclusion, the behavioural observations performed in this research indicate that analogous drimanes inhibit feeding by P. brassicae larvae through multiple mechanisms of action. The results show that, when developing a structure activity relationship (SAR) for a series of antifeedants, it is important to distinguish the mode of action which underlies inhibition of feeding. [source] Sensitization of meningeal nociceptors: inhibition by naproxenEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Dan Levy Abstract Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A,- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N -[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A,- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. [source] Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversibleEXPERIMENTAL DERMATOLOGY, Issue 7 2005Amanda Greatens Abstract:, Skin pigmentation results in part from the transfer of melanized melanosomes synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins and their glycoconjugates expressed by these epidermal cells are critical molecules involved in this transfer process. In addition, the derivative of vitamin B3, niacinamide, can inhibit melanosome transfer and induce skin lightening. We investigated the effects of these molecules on the viability of melanocytes and keratinocytes and on the reversibility of melanosome-transfer inhibition induced by these agents using an in vitro melanocyte,keratinocyte coculture model system. While lectins and neoglycoproteins could induce apoptosis in a dose-dependent manner to melanocytes or keratinocytes in monoculture, similar dosages of the lectins, as opposed to neoglycoproteins, did not induce apoptosis to either cell type when treated in coculture. The dosages of lectins and niacinamide not affecting cell viability produced an inhibitory effect on melanosome transfer, when used either alone or together in cocultures of melanocytes,keratinocytes. Cocultures treated with lectins or niacinamide resumed normal melanosome transfer in 3 days after removal of the inhibitor, while cocultures treated with a combination of lectins and niacinamide demonstrated a lag in this recovery. Subsequently, we assessed the effect of niacinamide on facial hyperpigmented spots using a vehicle-controlled, split-faced design human clinical trial. Topical application of niacinamide resulted in a dose-dependent and reversible reduction in hyperpigmented lesions. These results suggest that lectins and niacinamide at concentrations that do not affect cell viability are reversible inhibitors of melanosome transfer. [source] Topical ascorbic acid on photoaged skin.EXPERIMENTAL DERMATOLOGY, Issue 3 2003Clinical, topographical, ultrastructural evaluation: double-blind study vs. placebo Abstract:, Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the ,global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing. [source] The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunizationIMMUNOLOGY, Issue 1 2002Maria E. Baca-Estrada Summary Topical application of antigen induces antigen-specific humoral and cellular immune responses. In this study we examined whether expansion of dendritic cells (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune responses following transcutaneous immunization. Mice were treated intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower HEL-specific cellular and humoral immune responses than PBS-treated mice. However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and transcutaneous immunization, Flt3L-treated mice developed significantly higher cellular and humoral immune responses to HEL when compared to PBS-treated mice. We assessed whether the immunomodulatory effects of CT were a result of activation of epidermal dendritic cells (Langerhans' cells; LC). Our results indicate that within 8,12 hr of topical application of CT, epidermal LC cells lose their dendritic morphology and become rounder in appearance. In addition, we observed enhanced expression of major histocompatibility complex (MHC) class II, and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1). Our observations support the concept that the state of activation of DC in the skin is central to the regulation of immune responses. This information is relevant to the design of effective transcutaneous vaccination strategies. [source] Trehalose and trehalose-hydrolyzing enzyme in the haemolymph of Locusta migratoria infected with Metarhizium anisopliae strain CQMa102INSECT SCIENCE, Issue 4 2007HUA ZHAO Abstract Topical application of the Metarhizium anisopliae var. acridum specialist strain CQMa102 to the locust Locusta migratoria manilensis results in changes of the concentrations of trehalose and glucose in the haemolymph. Micrographs of the locust haemolymph shows Metarhizium anisopliae can effectivly penetrate the external skeleton of locust and after 2 days infection, the hyphae body will appear in the haemolymph of infected insects. The time in decrease of trehalose concentration coincided with that in increase of trehalose-hydrolysing enzyme activity in the haemolymph of the fungus-infected insects. Overlay gel analysis indicated there was considerably more trehalose-hydrolysing activity in the haemolymph of locusts infected by fungus than in controls. A comparable isoform was identified in in vitro culture of the fungus, suggesting a fungal origin for the in vivo enzyme. Haemolymph trehalose decreased significantly during mycosis of locusts by M. anisopliae. All these results suggested that this fungus may take advantage of competing nutrient utilization against the insect by its trehalose-hydrolyzing enzyme secretion. It may provide fundamental knowledge for fungal pathogenesis. [source] Effects of a Brazilian herbal compound as a cosmetic eyecare for periorbital hyperchromia ("dark circles")JOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2009Samara Eberlin PhD Summary Background, Evidence suggests that periorbital hyperchromia (dark circles) occurs mainly as a consequence of postinflammatory hemodynamic congestion producing a typical bruising aspect on the lower eyelids. Aims, To evaluate the clinical effects of Pfaffia paniculata/Ptychopetalum olacoides B./Lilium candidum L.-associated compound (PPLAC) on periorbital hyperchromia and to study in vitro its underlying anti-inflammatory and antioxidant mechanisms. Methods, Twenty-one volunteers presenting with periorbital hyperchromia received a serum sample containing 5.0% PPLAC, which was applied topically in the periorbital area twice a day for 28 days. Skin color was measured using variations in the individual typological angle (,ITA0) and skin luminance (,L*) calculated in the area around the eyes and in the adjacent area. Colorimetric readings were taken at the onset and end of the 28-day treatment. Volunteers were also asked to fill out a questionnaire concerning the improvement in "dark circles." The anti-inflammatory and antioxidant effects of PPLAC were measured by quantification of prostaglandin E2, leukotriene B4, histamine, and superoxide dismutase levels using an in vitro model of human skin culture. Results, Topical application of PPLAC led to a significant improvement in skin luminance and tone in the periorbital area, which was demonstrated by increased values of ITA0 and L* in about 90% of volunteers. In addition, subjects reported reduced intensity and improved appearance of "dark circles." A dose-dependent decreased production of inflammatory mediators, concomitant to increased antioxidant enzyme levels, was observed in our in vitro studies, under basal and lipopolysaccharide-stimulated conditions. Conclusions, Although the precise mechanisms related to PPLAC remain to be clarified, our results indicate that the reduction in the inflammatory process as well as the antioxidant protection against deleterious elements may be considered as an integral approach to preserve the integrity of vascular endothelium, preventing the hemodynamic congestion that culminates in the formation of "dark circles" around the eyes. [source] Studies on the effects of lactate transport inhibition, pyruvate, glucose and glutamine on amino acid, lactate and glucose release from the ischemic rat cerebral cortexJOURNAL OF NEUROCHEMISTRY, Issue 1 2001J. W. Phillis A rat four vessel occlusion model was utilized to examine the effects of ischemia/reperfusion on cortical window superfusate levels of amino acids, glucose, and lactate. Superfusate aspartate, glutamate, phosphoethanolamine, taurine, and GABA were significantly elevated by cerebral ischemia, then declined during reperfusion. Other amino acids were affected to a lesser degree. Superfusate lactate rose slightly during the initial ischemic period, declined during continued cerebral ischemia and then was greatly elevated during reperfusion. Superfusate glucose levels declined to near zero levels during ischemia and then rebounded beyond basal levels during the reperfusion period. Inhibition of neuronal lactate uptake with ,-cyano-4-hydroxycinnamate dramatically elevated superfusate lactate levels, enhanced the ischemia/reperfusion evoked release of aspartate but reduced glutamine levels. Topical application of an alternative metabolic fuel, glutamine, had a dose dependent effect. Glutamine (1 mm) elevated basal superfusate glucose levels, diminished the decline in glucose during ischemia, and accelerated its recovery during reperfusion. Lactate levels were elevated during ischemia and reperfusion. These effects were not evident at 5 mm glutamine. At both concentrations, glutamine significantly elevated the superfusate levels of glutamate. Topical application of sodium pyruvate (20 mm) significantly attenuated the decline in superfusate glucose during ischemia and enhanced the levels of both glucose and lactate during reperfusion. However, it had little effect on the ischemia-evoked accumulation of amino acids. Topical application of glucose (450 mg/dL) significantly elevated basal superfusate levels of lactate, which continued to be elevated during both ischemia and reperfusion. The ischemia-evoked accumulations of aspartate, glutamate, taurine and GABA were all significantly depressed by glucose, while phosphoethanolamine levels were elevated. These results support the role of lactate in neuronal metabolism during ischemia/reperfusion. Both glucose and glutamine were also used as energy substrates. In contrast, sodium pyruvate does not appear to be as effectively utilized by the ischemic/reperfused rat brain since it did not reduce ischemia-evoked amino acid efflux. [source] Acceleration of ALA-induced PpIX fluorescence development in the oral mucosaLASERS IN SURGERY AND MEDICINE, Issue 3 2003Sirintra Charoenbanpachon Abstract Background and Objectives The development of 5-aminolevulinic acid (ALA)-induced tissue fluorescence is optimal 2,4 hours after ALA application. Goal of this work was to develop a means of accelerating oral topical ALA-induced tissue fluorescence. Study Design/Materials and Methods In 300 hamsters, DMBA (9,10 dimethyl-1,2-benzanthracene) cheek pouch carcinogenesis produced dysplasia in 3,5 weeks. Topical application of 20% ALA in Eucerin was followed by localized ultrasound treatment (1, 3.3 MHz) in 150 animals. In 75 animals, ALA was applied in an Oral Pluronic Lecithin Organogel (OPLO,an absorption enhancer) vehicle. Seventy-five animals received only topical ALA in Eucerin. Hamsters were sacrificed and cryosections underwent fluorescence measurements, histological evaluation, 20,180 minutes after ALA application. One-way ANOVA detected independent effects of pathology on laser-induced fluorescence (LIF). Two-way ANOVA tested for independent effect of pathology and of OPLO, ultrasound, and interaction effects. Results Ultrasound significantly (P,<,0.05) accelerated tissue fluorescence development. Conclusions Low-frequency ultrasound can accelerate ALA-induced fluorescence development. Lasers Surg. Med. 32:185,188, 2003. © 2003 Wiley-Liss, Inc. [source] In Vitro and In Vivo Transfer of bcl-2 Gene into Keratinocytes Suppresses UVB-induced Apoptosis,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2001Hidetoshi Takahashi ABSTRACT Bcl-2 is a member of the large Bcl-2 family and protects cells from apoptosis. Ultraviolet B (UVB) irradiation induces apoptosis of keratinocytes that is known as "sunburn cells." Previously we reported that UVB irradiation induces apoptosis accompanied by sequential activation of caspase 8, 3 and 1 in keratinocytes, and that the process is inhibited by various caspase inhibitors. Using bcl-2,expressing adenovirus vector we investigated the effect of Bcl-2 on UVB-induced apoptosis. Adenovirus vector efficiently introduced bcl-2 gene in cultured normal mouse keratinocytes (NMK cells); almost all NMK cells (1 × 106) were transfected at 1 × 108 plaque-forming unit (PFU)/mL. Bcl-2,transfected NMK cells were significantly resistant to UVB-induced apoptosis with the suppressive effect dependent on the Bcl-2 expression level. Following UVB irradiation caspase 8, 3 and 9 activities were stimulated in NMK cells, whereas in bcl-2,transfected cells only caspase 8, but not caspase 3 or 9, activity was stimulated. In order to investigate the effect of Bcl-2 in vivo topical application of Ad-bcl-2 on tape-stripped mouse skin was performed. Following the application Bcl-2 was efficiently overexpressed in almost all viable keratinocytes. The expression was transient with the maximal expression of Bcl-2 on the first day following the application of 1 × 109 PFU in 200 ,L. The introduced Bcl-2 remained at least for 6 days. UVB irradiation (1250 J/m2) induced apoptosis within 12 h and the maximal effect was observed at 24 h in control mouse skin. Both bcl-2,transfected and topical caspase 3 inhibitor-treated mice skin were resistant to UVB-induced apoptosis. The suppressive effect of Bcl-2 was more potent than that of caspase 3 inhibitor application. Topical application of empty adenovirus vector alone had no effect on Bcl-2 expression or UVB-induced apoptosis. These results indicate that adenovirus vector is an efficient gene delivery system into keratinocytes and that Bcl-2 is a potent inhibitor of UVB-induced apoptosis both in vitro and in vivo. [source] Ergocalciferol promotes in vivo differentiation of keratinocytes and reduces photodamage caused by ultraviolet irradiation in hairless micePHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2004Hiroaki Mitani Background: Ergocalciferol (VD2) is usually administered orally and it is metabolized to produce its biologically active metabolites in the liver and kidney. Active vitamin D is a well-known potent regulator of cell growth and differentiation. Purpose: Active vitamin D such as 1,25-dihydroxyvitamin D3 (1,,25(OH)2D3) prevents photodamage, including wrinkles and morphologic alterations. However, its clinical and cosmetic use is limited because of its potent, associated effect on calcium metabolism. We examined the efficacy of vitamin D analogues with few adverse effects for preventing skin photodamage. Method: Topical application of VD2 to hairless mouse dorsal skin, and exposure to solar-simulating ultraviolet (UV) radiation at a dose of 10.8 J/cm2 (UVA) were performed for 15 weeks, five times a week on weekdays. At the end of the final irradiation, histological and analytical studies were performed. Results: Topical application of VD2 significantly prevented wrinkle formation and abnormal accumulation of extracellular matrix components. In addition, VD2 suppressed excessive secretion of IL-6 induced by UV irradiation in cultured human normal keratinocytes, in a dose-dependent manner. Conclusion: VD2 promoted keratinocytes differentiation in the epidermis and showed diverse physiological effects, the same as the active form of VD3. The results suggested that the suppression of skin photodamage involved the promotion of keratinocytes differentiation and suppression of IL-6 secretion induced by exposure to UV. Topical application of VD2 may become an effective means to suppress solar UV-induced human skin damage. [source] Liposomes in investigative dermatologyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2001Daniel B. Yarosh Liposomes are microscopic spheres, usually composed of amphiphilic phospholipids. They may be useful without skin penetration if they simply protect or sequester compounds that would otherwise be unstable in the formulation. Liposomes that remain on the skin surface are useful as light-absorbers, agents to deliver color or sunscreens, or as depots for timed-release. Liposomes that penetrate the stratum corneum have the potential to interact with living tissue. Topically applied liposomes can either mix with the stratum corneum lipid matrix or penetrate the stratum corneum by exploiting the lipid-water interface of the intercellular matrix. There are at least four major routes of entry into the skin: pores, hair follicles, columnular spaces and the lipid:water matrix between squames. A major force driving liposome penetration is the water gradient, and flexible liposomes are best able to exploit these delivery opportunities. Some liposomes release their contents extracellularly. Topical application of photosensitizers may be enhanced by encapsulation in liposomes. Higher and longer-lasting drug concentrations may be produced in localized areas of skin, particularly at disease sites where the stratum corneum and the skin barrier function are disrupted. The liposome membrane should be designed to capture lipophilic drugs in the membrane or hydrophilic drugs in the interior. Other types of liposomes can be engineered to be taken up by cells. Once inside cells, the lysosomal sac and clatherin-coated pit are the dead-end destinations for liposomes unless an escape path has been engineered into the liposome. A novel method has been developed to allow delivery into cells of the skin, by escape from the lysosomal sac. These liposomes have been used to topical deliver active DNA repair enzymes from liposomes into epidermal cells and to enhance DNA repair of UV-irradiated skin. From these studies a tremendous amount has been learned about the relationship of DNA damage and skin cancer. Both mutations and immunosuppression appear to be essential to skin cancer and both are induced by DNA damage. DNA damage produces immediate effects by inducing the expression of cytokines, which means that DNA damage can induce signaling in neighboring, undamaged cells. The repair of only a fraction of the DNA damage has a disproportionate effect on the biological responses, clearly demonstrating that not all DNA damage is equivalent. This technology demonstrates that biologically active proteins can be delivered into the cells of skin, and opens up a new field of correcting or enhancing skin cell metabolism to improve human health. [source] Topical application of Pya -AKH stimulates lipid mobilization and locomotion in the flightless bug, Pyrrhocoris apterus (L.) (Heteroptera)PHYSIOLOGICAL ENTOMOLOGY, Issue 1 2002Dalibor Kodrík Abstract Two different methods of applying Pya -AKH to long-winged (macropterous) females of the firebug, Pyrrhocoris apterus (Linnaeus) (Heteroptera) were compared: both injection and topical application increased the levels of lipids in the haemolymph and stimulated locomotor activity. Lipid mobilization was maximal when 10 pmol was applied by injection or 40,100 pmol by topical application, with the first significant responses occurring 1.5 h after injection and 2 h after topical application. The highest elevations of lipid concentration in the haemolymph were comparable between the treatments, i.e. 14.36 ± 3.59 mg/mL for injection and 14.43 ± 4.07 mg/mL for topical application. However, these maximal elevations were achieved at different times: 3 h after the injection and 7 h after the topical application. Injection of 10 and 40 pmol of Pya -AKH stimulated locomotor activity with maximal activity 3 h later but, surprisingly, injection of 80 pmol showed no effect initially and than a slight inhibitory effect after 6,8 h. Increased locomotor activity was found after topical application of Pya -AKH, but the response was lower than after injection and appeared later, 5,9 h after the hormone application. In addition, the greatest increase in walking activity required topical application of 300 pmol and was still less dramatic than the response to injection. The stimulatory effect of Pya -AKH on locomotion was positively correlated with its effect on lipid mobilization only for injection of the hormone. It is argued that a stress caused by injection could play a role in the appearance of the complex response to adipokinetic hormone. [source] Depigmenting Action of Phenylhydroquinone, an o -Phenylphenol Metabolite, on the Skin of JY-4 Black Guinea-PigsPIGMENT CELL & MELANOMA RESEARCH, Issue 6 2002Kuniaki Tayama The effects of o -phenylphenol (OPP) and its metabolite, phenylhydroquinone (PHQ) on the skin of JY-4 black guinea-pigs were studied. Topical application of 1 or 5% PHQ on the black skin of the back caused marked depigmentation and hypopigmentation of the skin after 5 weeks, whereas OPP applied at the same concentrations had little effect. Depigmented skin had an increased L* (lightness) value in the CIE-L*a*b* color system. This corresponded with a decreased number of melanocytes and melanosomes in the melanocytes and keratinocytes, the disruption of melanosomes in the melanocytes, and destruction of the membranous organelles of the melanocytes. These morphological and numerical changes in epidermal melanocytes indicate that selective melanocyte toxicity occurred. Furthermore, application of PHQ to the skin of white guinea-pigs caused skin irritation, as shown by a colorimetric increase in a* value (redness) and by histological observation of inflammation. This study confirmed that OPP, which is a reported depigmenter, has little depigmenting action, while its metabolite, PHQ, is a potent depigmenter preferentially affecting melanocytes. [source] Effect of topical glyceryl trinitrate on anodermal blood flow in patients with chronic anal fissuresANZ JOURNAL OF SURGERY, Issue 9 2001Keith B. Kua Introduction: Recent studies have highlighted the role of increased internal anal sphincter pressure and decreased anodermal blood flow in the pathogenesis of chronic anal fissures. The duration of the effect of topical 0.2% glyceryl trinitrate (GTN) ointment on anodermal blood flow in fissure and normal areas was investigated in patients with chronic anal fissures. Methods: Six patients with chronic anal fissures in the posterior midline participated in the study. Blood flow measurements were performed on the anoderm using laser Doppler flowmetry before and immediately after the topical application of 0.2% GTN ointment and subsequent readings were taken at 5, 15, 30, 45 and 60 min in all four quadrants. Results: The mean anodermal blood flow in the fissure region is significantly lower than the mean blood flow of the rest of the anoderm before 0.2% GTN ointment is applied (228.7 ± 61.8 flux units vs 439.3 ± 25.5 flux units, respectively; P < 0.05). Immediately after the application of local 0.2% GTN ointment there is a significant increase in anodermal blood flow over the anal fissure region (457.8 ± 56.5 flux units; P < 0.05) compared to the rest of the anoderm (457.4 ± 30.8 flux units). This increase is most marked at 5 min post-GTN ointment application in the fissure area (474.6 ± 41.1 flux units) and the blood flow in the fissure region is consistently above the rest of the anoderm for most of the 60 min. Conclusion: There is clearly reduced blood flow to the chronic anal fissure region compared to the rest of the anoderm. Topical application of glyceryl trinitrate ointment seems to significantly improve the blood flow to the fissured area in the first hour. This may therefore help in the healing of chronic anal fissures. [source] Susceptibility of four field populations of the diamondback moth Plutella xylostella L. (Lepidoptera: Yponomeutidae) to six insecticides in the Sydney region, New South Wales, AustraliaAUSTRALIAN JOURNAL OF ENTOMOLOGY, Issue 4 2008Vincent Y Eziah Abstract Concerns about the failure of insecticides to control the diamondback moth (DBM) Plutella xylostella in the Sydney region of New South Wales, Australia, necessitated the current investigation to establish the susceptibility of four field populations of the DBM to six insecticides. These include two each of organophosphates (OPs), and synthetic pyrethroid insecticides as well as two new products with different modes of action, spinosad and indoxacarb, currently recommended for DBM control in the region. Topical application of the insecticides to the third-instar larvae showed high resistance to pyrethroids (permethrin and esfenvalerate) of 35.0- to 490.0-fold. Resistance to the OPs (methamidophos and chlorpyrifos) and indoxacarb ranged from 12.1- to 36.2-fold and from 11.4- to 34.6-fold, respectively. However, the field populations were susceptible to spinosad (resistance factors only two- to threefold compared with the susceptible strain). A 2 h pre-treatment of the esfenvalerate-resistant strain with the synergists piperonyl butoxide and diethyl maleate increased the toxicity of esfenvalerate by 30.0- and 1.9-fold, respectively, suggesting the involvement of esterases and/or monooxygenases as the key mechanism(s) of insecticide resistance with glutathione S-transferases playing a minor role. [source] A simple and rapid method to assess lycopene in multiple layers of skin samplesBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Luciana B. Lopes Abstract Topical application of lycopene is a convenient way to restore antioxidants depleted from the skin by UV radiation and achieve protection against premature aging and cancer. In this study, a simple, rapid and reproducible method to quantify lycopene in different skin layers was developed, validated and employed to assess this compound after skin penetration studies. Lycopene was extracted from the stratum corneum (SC) and viable epidermis and dermis (ED) by vortex homogenization and bath sonication in a mixture of acetonitrile and methanol (52:48, v/v). Lycopene was assayed by HPLC using a C18 column, and acetonitrile:methanol (52:48, v/v) as mobile phase. The quantification limit of lycopene in samples of SC and ED was 35,ng/mL and the assay was linear from 35 to 2000,ng/mL. Within-day and between-days assays coefficients of variation and relative errors (indicative of precision and accuracy) were less than 15% (or 20% for the limit of quantification). Lycopene recovery from SC and ED was dependent on the spiked concentration: for 50,ng/mL, recoveries were 88.3 and 90.5%; for 100,1000,ng/mL, recoveries were 68.6,74.9%. This method has a potential application for lycopene quantification during formulation development and evaluation in the dermatological field. Copyright © 2009 John Wiley & Sons, Ltd. [source] Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plateBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007M.J. Finnen Summary Background, Topical treatment of nail diseases is hampered by the nail plate barrier, consisting of dense cross-linked keratin fibres held together by cysteine-rich proteins and disulphide bonds, which prevents penetration of antifungal agents to the focus of fungal infection. Acidified nitrite is an effective treatment for tinea pedis. It releases nitric oxide (NO) and other NO-related species. NO can react with thiol (-SH) groups to form nitrosothiols (-SNO). Objectives, To determine whether acidified nitrite can penetrate the nail barrier and cure onychomycosis, and to determine whether nitrosospecies can bind to the nail plate. Methods, Nails were treated with a mixture of citric acid and sodium nitrite in a molar ratio of 0·54 at either low dose (0·75%/0·5%) or high dose (13·5%/9%). Immunohistochemistry, ultraviolet-visible absorbance spectroscopy and serial chemical reduction of nitrosospecies followed by chemiluminescent detection of NO were used to measure nitrosospecies. Acidified nitrite-treated nails and the nitrosothiols S-nitrosopenicillamine (SNAP) and S-nitrosoglutathione (GSNO) were added to Trichophyton rubrum and T. mentagrophytes cultures in liquid Sabouraud medium and growth measured 3 days later. Thirteen patients with positive mycological cultures for Trichophyton or Fusarium species were treated with topical acidified nitrite for 16 weeks. Repeat mycological examination was performed during this treatment time. Results, S-nitrothiols were formed in the nail following a single treatment of low- or high-dose sodium nitrite and citric acid. Repeated exposure to high-dose acidified nitrite led to additional formation of N-nitrosated species. S-nitrosothiol formation caused the nail to become antifungal to T. rubrum and T. mentagrophytes. Antifungal activity was Cu2+ sensitive. The nitrosothiols SNAP and GSNO were also found to be antifungal. Topical acidified nitrite treatment of patients with onychomycosis resulted in > 90% becoming culture negative for T. rubrum. Conclusions, Acidified nitrite cream results in the formation of S-nitrosocysteine throughout the treated nail. Acidified nitrite treatment makes a nail antifungal. S-nitrosothiols, formed by nitrosation of nail sulphur residues, are the active component. Acidified nitrite exploits the nature of the nail barrier and utilizes it as a means of delivery of NO/nitrosothiol-mediated antifungal activity. Thus the principal obstacle to therapy in the nail becomes an effective delivery mechanism. [source] Topical adapalene gel 0·1% vs. isotretinoin gel 0·05% in the treatment of acne vulgaris: a randomized open-label clinical trialBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002D. Ioannides Summary Background Topical application of isotretinoin and adapalene has proved effective in treating acne vulgaris. Both drugs demonstrate therapeutic advantages and less irritancy over tretinoin, the most widely used treatment for acne. They both act as retinoid agonists, but differ in their affinity profile for nuclear and cytosolic retinoic acid receptors. Objectives To compare the efficacy and tolerability of adapalene gel 0·1% and isotretinoin gel 0·05% in the treatment of acne vulgaris of the face, in a randomized open-label clinical trial. Methods Eighty patients were enrolled and were instructed to apply adapalene gel 0·1% or isotretinoin gel 0·05% once daily over a 12-week treatment period. Efficacy determination included noninflammatory and inflammatory lesion counts by the investigator and global evaluation of improvement. Cutaneous tolerance was assessed by determining erythema, scaling and burning with pruritus. Results Adapalene and isotretinoin gels were highly effective in treating facial acne. Adapalene gel produced greater reductions in noninflammatory and inflammatory lesion counts than did isotretinoin gel, but differences between treatments were not statistically significant. Adapalene gel was significantly better tolerated than isotretinoin gel during the whole treatment period. Conclusions The two gels studied demonstrated comparable efficacy. When adapalene and isotretinoin were compared, significantly lower skin irritation was noted with adapalene, indicating that adapalene may begin a new era of treatment with low-irritant retinoids. [source] Actinic keratosis treated with an immune response modifier: a case report of six patientsCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2003L. Bianchi Summary Actinic keratoses (AKs) are intraepidermal tumours, which result from the proliferation of transformed neoplastic keratinocytes. They are typically induced by chronic exposure to ultraviolet radiation, and can often develop into squamous cell carcinoma (SCC). Six patients, who presented with AKs located on the head, face and chest, were treated with the immune response modifier, imiquimod, as a 5% cream five times per week for up to 8 weeks. The majority of patients experienced mild to moderate side-effects, consisting of erythema, itching and burning. Topical application of imiquimod for 4,8 weeks resulted in complete clearance in all patients. No new or recurrent lesions were observed during a 6,8 month follow-up period. [source] Interleukin-8 production by polymorphonuclear leukocytes from patients with chronic infected leg ulcers treated with Lactobacillus plantarumCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2010M. C. Peral Clin Microbiol Infect 2010; 16: 281,286 Abstract Bacterial infection impairs the healing process, promoting the chronicity of inflammation and wounds. Because antibiotics fail to eradicate bacteria, especially in biofilm form, new therapeutic modalities may be required. In the present study, the effectiveness of bacteriotherapy with Lactobacillus plantarum on infected chronic venous ulcers was investigated and its effects on interleukin (IL)-8 production by cells from the ulcer bed and neutrophils isolated from peripheral blood that were previously challenged in vitro with Pseudomonas aeruginosa and L. plantarum were studied. Topical application of L. plantarum culture to lesions (25,60 cm2) of 14 diabetic and 20 non-diabetic patients induced debridement, granulation tissue formation and total healing after 30 days in 43% diabetics and in 50% non-diabetics. No significant differences between the groups were observed. The cells from ulcer beds collected after treatment with L. plantarum for 10 days showed a decrease in the percentage of polymorphonuclear, apoptotic and necrotic cells and an enhancement of IL-8 production. IL-8 production by isolated neutrophils from these patients was compared with that in diabetics without ulcers, as well as normal subjects under basal conditions, and after infection of polymorphonuclear cells with P. aeruginosa preincubated either with or without L. plantarum. The basal values in diabetic and ulcer patients were higher than normal (p <0.001) and were increased by P. aeruginosa infection in normal, diabetics (p <0.001) and non-diabetics with ulcers (p <0.01). Preincubation with L. plantarum decreased IL-8 production in patients with ulcers non-diabetic and diabetic (p <0.001). Lactobacillus plantarum treatment reduced wound bacterial load, neutrophils, apoptotic and necrotic cells, modified IL-8 production and induced wound healing. [source] Clove oil cream: a new effective treatment for chronic anal fissureCOLORECTAL DISEASE, Issue 6 2007H. A. Elwakeel Abstract Objective, Anal fissure is a common painful condition affecting the anal canal and causes considerable morbidity and reduction in quality of life. Surgical treatment has been associated with a degree of incontinence in up to 30% of patients. This study discussed the results of clove oil 1% cream in healing of chronic anal fissure. Method, A single-blind randomized comparative trial was setup to compare traditional treatment with stool softeners and lignocaine cream 5% against clove oil 1% cream for 6 weeks. Results, 55 patients were included in this study, 30 patients in clove oil group and 25 patients in control group. Healing had occurred in 60% of patients in clove oil group and in 12% of patients in the control group after 3-month follow up (P < 0.001). Patients in clove oil group showed significant reduction in resting anal pressure and almost all other anorectal manometric pressures compared with patients in control group. Conclusion, Topical application of clove oil cream demonstrated a significant beneficial effect when applied to patients suffering from chronic anal fissure. [source] Erythema multiforme-like generalized allergic contact dermatitis caused by Alpinia galangaCONTACT DERMATITIS, Issue 2 2006Song Jen Hong This study reports a case of localized contact dermatitis and subsequently generalized erythema multiforme-like eruptions after topical application of herbal remedies. Patch tests showed there was an allergen in fresh and dried Alpinia galanga, which is also a popular spice in Southeast Asian cuisines. [source] Enhancing the Growth of Natural Eyelashes: The Mechanism of Bimatoprost-Induced Eyelash GrowthDERMATOLOGIC SURGERY, Issue 9 20102Article first published online: 2 APR 2010, JOEL L. COHEN MD BACKGROUND Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States. OBJECTIVE To review eyelash physiology and the proposed mechanisms by which the topical pros-tamide product bimatoprost enhances eyelash growth. METHODS AND MATERIALS Clinical and preclinical studies pertaining to the efficacy, safety, and mechanisms of action of bimatoprost are presented. RESULTS Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any one time. This probably accounts for its ability to lengthen lashes. Bimatoprost-induced stimulation of melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes. CONCLUSION By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution 0.03% is a safe and effective means of enhancing eyelash growth. Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc. [source] | |||||||||||||||||||||||||||||||