Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing.
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PURPOSE: To investigate the suitability of chitosan films prepared using two different solvents, acetic acid (Chitosan-AA) and lactic acid (Chitosan-LA), for wound dressing, in comparison with a commercial preparation, Omiderm. METHODS: The mechanical and in-vitro bioadhesive strength properties of Chitosan-AA, Chitosan-LA, and Omiderm were investigated using texture analyzer equipment. The vapour permeability of chitosan films was determined using a method for evaluation of moisture permeability of containers and packaging material described in USP XXII. In addition, the biological evaluations were performed via primary skin irritation, intracutaneous, and systemic injection tests. RESULTS: The three preparations differed significantly in terms of the mechanical and bioadhesive strength properties. Chitosan-LA exhibited a lower tensile strength, but more flexible and bioadhesive than Chitosan-AA. Chitosan film was found to be permeable to water vapour. Chitosan-LA and Omiderm were non-irritant and did not cause any skin allergic reaction. In contrast, Chitosan-AA films inflicted adverse skin reactions. Nevertheless, no gross sign of toxicity was encountered from the systemic injection of the extracts of the three preparations. CONCLUSION: Chitosan films demonstrated significantly different mechanical and bioadhesive strength properties from Omiderm. Chitosan-LA was more soft, flexible, pliable and bioadhesive when compared to Chitosan-AA films. Furthermore, Chitosan-LA did not cause erythema, edema and systemic toxicity. Hence, Chitosan-LA film is suitable to be used in the management of wound healing and skin burn. (+info)
Peptide-binding assessment using mass spectrometry as a new screening method for skin sensitization.
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Skin sensitization potential of low molecular weight chemicals was assessed by analyzing peptide-conjugate formation. Chemicals were incubated with a peptide, glutathione, and resultant mixtures were analyzed by mass spectrometry. Eighteen chemicals were assessed, and new peaks corresponding to chemical-peptide conjugates were detected for 13 of 14 known sensitizers. Conjugates were not detected for 4 negative chemicals. The method has advantages as a simple screening assay for assessing the sensitization potential of chemicals. (+info)
Preliminary pharmacological study of purified snake enzymatic cream isolated from Agkistrodon Halys venom.
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To investigate the pharmacological and toxicological actions of purified snake enzymatic cream (PSE) isolated from Agkistrodon Halys Venom, erythematous dermatitis was induced by applying dinitrofluorobenezene (DNFB) on the back skin of guinea pigs. Consequent local alterations at different doses of PSE were observed and compared using negative control methods. In skin irritation and acute toxicological experiments, 500 times the effective doses were used in artificially lesioned skin. The marking criteria in the former were based on local manifestations, and in the latter, on changes of some indicators including body weight, breath, and heart rate before and after the experiments. PSE significantly alleviated erythematous dermatitis (p < 0.01, t test) without systemic or local adverse drug reactions within 7 days. PSE as a new drug candidate poses a bright prospect in the prevention and treatment of dermatitis. (+info)
Comparison of poultice-type and tape-type patches containing ketoprofen on human skin irritation.
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Although the patch test for visual skin observation is widely used clinically, it does not allow the mechanisms of side effects to be assessed. In this study, we examined poultice-type KP801 and tape-type KP-T patches containing ketoprofen. The parameters to measure side effects on skin were peeling intensity, amount of stripped stratum corneum, skin moisture and redness of skin color under various mechanical conditions. Since the amount of stripped stratum corneum with the tape-type KP-T patch was higher than with the poultice-type KP801 patch, the bio-adhesive strength of the latter was concluded to be lower. A clear relationship exists between the amount of stripped stratum corneum and skin moisture after tape-type patch removal, but this was not found with the poultice-type patch because of its hydration effects. Peeling intensity, one parameter to predict pain at the time of patch removal, was higher with the KP-T. As for mechanical conditions, when the patch is removed, it is important to remove it as slowly as possible and horizontally, and to avoid any rise in skin temperature. Finally, when a patch is applied to a region with little skin moisture, the amount of stripped stratum corneum may increase accordingly. (+info)
Optimisation of the EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests.
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An ECVAM-funded prevalidation study (PV) was conducted during 1999 and 2000 to identify in vitro tests capable of reliably distinguishing between skin irritants (I) and non-irritants (NI) according to European Union risk phrases ("R38" or no classification). The tests evaluated were EpiDerm, EPISKIN, PREDISKIN, the non-perfused pig ear method, and the mouse skin integrity function test (SIFT). Whereas reproducibility of the two human skin model tests and SIFT was acceptable, none of the methods was deemed ready to enter a formal validation study due to their low predictivity. The ECVAM Skin Irritation Task Force therefore suggested improvements of protocols and prediction models for these tests. Furthermore, it was agreed that experience gained with the two human-skin models be shared, and a common protocol should be developed for EpiDerm and EPISKIN (Zuang et al., 2002). When we applied an improved EPISKIN protocol (Portes et al., 2002) to the EpiDerm model, an acceptable specificity (80%) was achieved, whereas the sensitivity (60%) was far too low. In 2003, the EPISKIN protocol was further refined by extension of the post-incubation period following chemical exposure. In the current study, we evaluated this EPISKIN refinement by applying it to EpiDerm. In addition, we developed technical improvements for the application of the test chemicals and rinsing procedure, which reduced the variability of results and increased the percentage of correct predictions. A set of twenty non-coded reference substances from the ECVAM prevalidation study phase III (Fentem et al., 2001) was tested with the final protocol in three independent runs. Both high sensitivity (80%) and high specificity (78%) were achieved, and the statistical probability of correct classifications was high, so that the test is now regarded ready for formal validation. (+info)
Essential oils from sweet basil (Ocimum basilicum) as novel enhancers to accelerate transdermal drug delivery.
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The purpose of this study was to evaluate the essential oils from sweet basil (Ocimum basilicum, OB) as skin permeation enhancers to promote the percutaneous absorption of drugs. The in vitro and in vivo irritancy of the essential oils was also examined. Terpenes with various carbon numbers (mono-, sesqui-, di-, and tri-) were identified in both the lower-polarity fraction (OB-1) and higher-polarity fraction (OB-2). In vitro skin permeation and deposition of indomethacin were significantly enhanced after treatment with OB essential oils. The enhancing effect of OB-1 was greater than that of OB-2 in the in vitro permeation and in vivo cutaneous microdialysis analyses as well as in the plasma concentration of indomethacin. On the other hand, the in vivo study showed that OB-2 had a greater ability to retain the drug within the skin than did OB-1. Enhancement of the skin permeation of drugs by OB essential oils might be mainly due to improvement in the partitioning of the drugs to the stratum corneum. Both in vitro cell cultures (keratinocytes and skin fibroblasts) and in vivo transepidermal water loss showed no or only negligible irritation to skin by OB essential oils. (+info)
T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation.
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Interleukin (IL)-10 is a regulator of inflammatory responses and is secreted by a variety of different cell types including T cells. T regulatory cells have been shown to suppress immune responses by IL-10-dependent, but also IL-10-independent, mechanisms. Herein, we address the role of T cell-derived IL-10 in mice with an inactivation of the IL-10 gene restricted to T cells generated by Cre/loxP-mediated targeting of the IL-10 gene. Splenocytes from this T cell-specific mutant secrete increased amounts of proinflammatory cytokines after activation in vitro compared with show enhanced contact hypersensitivity reactions, and succumb to severe immunopathology upon infection with Toxoplasma gondii. Despite intact IL-10 genes in other cell types, the dysregulation of T cell responses observed in the T cell-specific IL-10 mutant closely resembles the phenotype in complete IL-10 deficiency. However, in contrast to complete IL-10 deficiency, sensitivity to endotoxic shock and irritant responses of the skin are not enhanced in the T cell-specific IL-10 mutant. Our data highlight the importance of T cell-derived IL-10 in the regulation of T cell responses and demonstrate that endotoxic shock and the irritant response of the skin are controlled by IL-10 from other cell types. (+info)
Toxicity of some phenolic derivatives--in vitro studies.
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Cytotoxicity of 5 phenol derivatives (phenol, catechol, resorcinol, hydroquinone and phloroglucinol) was tested using a mouse 3T3 fibroblast cell line. Its relationships with structural and physicochemical properties were investigated. Linear regression analysis and Pearson's correlation coefficient were used to characterise the relationship between cytotoxicity (expressed by IC(50) values) and physicochemical parameters of compounds or their toxicity in vivo expressed by LD(50) values. The studies showed that physicochemical properties of compounds seemed to have less influence on their cytotoxic potency than structural properties. Cytotoxicity of the compounds probably depends on the number of -OH groups and their location in the aromatic ring more than on physicochemical properties of compounds. The best correlation was obtained for IC(50) values and LD(50) values determined following rabbit skin administration and experimental skin irritation score. (+info)