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1.
BACKGROUND: Many different patch systems are available for predicting contact dermatitis. It is important to determine the ideal patch to meet the objective of the testing method. OBJECTIVE: The 21-day cumulative irritation test is well accepted for predicting irritation after repeated exposures. The patch type must allow separation of materials to predict irritation potential in the marketplace. Three patch systems were compared to determine which best provides this separation and prediction. METHODS: Four test materials were evaluated using 3 patch systems in a 21-day cumulative irritation test. Tested were water, 0.06% sodium lauryl sulfate (SLS), and 2 underarm products (UAP), one having lower and one having higher irritation potential. The patch types were; Webril pad and 8-mm and 12-mm Finn Chambers. RESULTS: Both the 12-mm Finn Chamber and Webril pad showed the ability to differentiate the higher irritating UAP and the 0.06% SLS from the lower irritation UAP product and water. The 8-mm Finn chamber was less discriminating, showing the 0.06% SLS to be the same as water and the lower-irritating UAP. CONCLUSION: The Webril pad and the 12-mm Finn Chamber are better at discriminating irritation potential than is the 8-mm Finn Chamber. The 12-mm Finn Chamber might also allow discrimination with a lower degree of irritation.  相似文献   

2.
BACKGROUND: Test chambers for irritant patch testing are usually larger than those used in allergic patch testing. In general, larger areas show stronger skin reactions than smaller areas. OBJECTIVE: This study investigated whether this difference is of practical relevance, when a model irritant is applied in small and large Finn chambers and evaluated by measurement of transepidermal water loss (TEWL). METHODS: Patch testing was performed with 2 concentrations of sodium lauryl sulfate (SLS) (0.25% and 0.5%) on forearms of healthy volunteers. Large (inner diameter, 12 mm) and small (inner diameter, 8 mm) chambers were used. RESULTS: A variance analysis (3 factors, 2-tailed) showed that the test outcome, as assessed by TEWL, was strongly dependent on SLS test concentration and test chamber size. The larger chambers gave approximately 30% to 50% higher values than the smaller. CONCLUSIONS: This may be explained by the fact that with the small chambers, the adjacent small area of nontreated skin was also assessed by the evaporimeter, biasing the results. A formula estimating TEWL value of the large chamber from values of the small chambers has been proposed.  相似文献   

3.
BACKGROUND: When evaluating transepidermal water loss (TEWL) in patch testing, the occlusive effect of the patch must be considered as an important artificial impairment of the measurement. OBJECTIVES: To investigate the time course of effects of occlusion. METHODS: Epicutaneous patches with sodium lauryl sulphate (SLS) 0.25%, SLS 0.5%, water and an empty test chamber (control) were applied on the volar forearm for different time intervals (12, 24, 48 h). Test reactions were evaluated by measurement of TEWL immediately, every 15 min during the first hour, every 30 min during the following 3 h and 24 h after patch removal. RESULTS: After patch removal, TEWL values showed a steep increase. When compared with basal values, TEWL values after SLS patch testing remained increased for 24 h, whereas TEWL values on water patch sites were only significantly increased for up to 180 min, and on empty patch sites for only up to 120 min after patch removal. The prolonged increase in TEWL values in SLS patch testing seemed to be induced by barrier function damage caused by SLS itself, as shown in various earlier studies. After the initial increase, TEWL values showed a significant decrease for all patches from 0 to 120 min after patch removal. Patch testing with water gave a significant decrease in TEWL values up to 180 min, and for empty chambers (control) up to 150 min after removal of patches. These data suggest that the occlusive effect on TEWL in patch testing ends 3 h after the removal of test chambers. CONCLUSIONS: We recommend TEWL measurement in SLS patch testing after a period of at least 3 h after patch removal. For practical purposes a 24-h period after patch removal may be useful.  相似文献   

4.
The aim of the study was to compare the effects of a SLS toothpaste formulation with and without betaine on skin and oral mucosa using electrical bioimpedance (IMP). Two groups, in total 47 participants, were recruited. In the skin group (27 participants) four test sites on the volar forearms were used: SLS paste, SLS + betaine paste, betaine paste, and one unoccluded control site. In the oral group (20 participants) the same toothpaste formulations were used. The test substances were applied in 12 mm Finn chambers for 24 hours at randomised test sites on the skin, and in 18 mm Finn chambers for 15 minutes on the oral mucosa. Visual examination and readings with IMP were taken before application and 24 hours after removal of the chambers for the skin, and for the oral mucosa before and 15 minutes after exposure. Information was extracted from the impedance spectra using four indices based on magnitude and phase at 2 frequencies, emphasising different aspects of the impedance properties of the tissues. The SLS‐containing pastes showed for both skin and oral mucosa some positive visual grade 1 reactions. Significant changes were found for the impedance indices, and the reaction patterns of the indices differed between the skin and the oral mucosa. We conclude that very slight reactions of skin and oral mucosa are detected by IMP. Furthermore, betaine containing toothpaste does not irritate neither skin nor oral mucosa, but the effect together with SLS is insignificant.  相似文献   

5.
This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and "stone-like" structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.  相似文献   

6.
Purpose: To compare laser Doppler perfusion imaging (LDPI) measurements in experimentally induced allergic contact reactions and irritant contact reactions. The degree of correlation between visual scores and LDPI measurements was also studied.
Methods: Fifteen patients with known contact allergy to nickel or fragrance were patch tested with nickel sulfate 5% pet., fragrance mix 8% pet., sodium lauryl sulfate (SLS) 0.5% pet., SLS 1.0% pet. and two empty control chambers. Visual readings and LDPI measurements were taken at 0, 48 and 96 h.
Results: There was a positive correlation between visual scores and LDPI measurement in the nickel sulfate and fragrance mix patch test sites. However, no correlation between visual scores and LDPI measurements was seen in the SLS 0.5% and SLS 1.0% patch test sites. There was no significant difference ( P =0.125) in LDPI measurements between contact-allergic reactions and contact-irritant reactions.
Conclusion: LDPI correlates with visual scoring in contact-allergic reactions, but not in irritant reactions. LDPI is not useful in distinguishing between allergic and irritant reactions.  相似文献   

7.
We used light and electron microscopic immunocytochemistry to study distributional changes in the human Langerhans cell (LC) system during the first 14 days of a mild irritancy caused by sodium lauryl sulphate (SLS). A marked initial decrease in epidermal LC was noted possibly resulting from migration from the epidermis to the dermis and from irreversible cell damage. Several studies have previously found an unchanged number of LC in SLS-induced contact irritant dermatitis, but these studies may not have taken into account the fact that SLS is effectively absorbed from the test chamber. Unless certain precautions are taken the SLS concentration rapidly falls to topical levels that have no effect on the LC system. Simultaneously with the decrease in the epidermis we observed an increase in dermal CD1a+ cells, confirming an often reported finding. There is, however, no consensus as to the identity of these cells, and several authors have reported that such cells lack LC granules and thus these cells have often been classed as indeterminate cells. We found that, during irritant contact dermatitis, provided an adequate number of sections were scrutinized in the electron microscope, all dermal CD1+ cells contained Birbeck granules.  相似文献   

8.
Reading of doubtful patch test reactions can be improved by comparing them to dened negative, allergic and irritant controls. For the latter, an irritant patch test is needed that gives sufficiently reproducible results. In our double-blind, placebo-controlled, randomized study, we have analysed the synchronous reproducibility of patch tests with 0%, 0.0625%, 0.125%, 0.25%, 0.5% and 1.0% sodium lauryl sulfate (SLS). Tests and readings were done according to ESCD guidelines. 139 patients (75 women, 64 men) 18 to 77 years old were tested. The % of positive patients as well as the % of reproducible positive reactions increased with rising concentrations of SLS to a maximum of approximately 90% and 85%, respectively, with 1 % SLS. Time courses of reactions were also related to the concentration of SLS: with 1 % SLS, plateau-type time courses were most common (65%), followed by decrescendo- (23%) and crescendo-type reactions (12%). With 1% SLS, very similar mild to moderate reactions were obtained on days 2 and 3. The reaction threshold and reproducibility of tests were not related to age and sex of patients or to their own assessment of skin irritability. We conclude that 1% SLS is appropriate for an irritant patch test that gives sufficiently reproducible results.  相似文献   

9.
Contact allergen-induced migration of epidermal Langerhans cells (LCs) to draining lymph nodes is dependent upon receipt by LCs of at least two cytokine signals provided by tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. It has been reported previously that intradermal injection of healthy human volunteers with homologous TNF-alpha or IL-1beta each induces a significant reduction in LC frequency, as measured in epidermal sheets prepared from 6-mm punch biopsies. In the current experiments, we have compared the frequency of LCs in punch biopsies with those obtained concurrently in epidermal sheets from the roofs of suction blisters isolated from the sun-protected buttock skin of healthy adult volunteers. There was a significant, approximately 30%, reduction in CD1a(+) LC numbers in suction blister roofs compared with punch biopsies. Injection of homologous recombinant IL-1beta, a stimulus that provokes measurable epidermal LC mobilization in punch biopsy sites, failed to provoke further LC migration in suction blister sites. These data suggest that the mechanical trauma to the skin caused by the creation of suction blisters provokes the degree of cutaneous inflammation necessary for LC mobilization. The responsive cells (only a proportion of resident LCs, approximately 30%) have already migrated, thus addition of an exogenous cytokine signal (IL-1beta) is without further effect. It is not possible therefore to measure the regulation of LC mobilization by exogenous cytokines in suction blister roofs. However, this technique provides an opportunity to profile induced changes in the cutaneous cytokine environment, with cytokine expression measured by a multiple cytokine array system. Using this technique, intradermal injection of IL-1beta was found to cause a marked upregulation of proinflammatory cytokines including TNF-alpha, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10 in fluid from suction blisters raised at the site of injection. In conclusion, the suction blister technique appears to be a powerful tool for measurement of induced changes in cutaneous cytokines.  相似文献   

10.
BACKGROUND: Sulphur mineral waters may have anti-inflammatory effects on human skin. We evaluated the anti-inflammatory effects of Leopoldine spa water, a salso-sulphate water (Table 1), on human skin tested with sodium lauryl sulphate (SLS). PATIENTS AND METHODS: Ten healthy, Caucasian volunteers 28-53 years old were enrolled in this study. SLS was tested on the right arm, in two concentrations (0.5% and 1%) dissolved in both double-distilled nonpyrogenic water and Leopoldine spa water in four separate test tubes; 0.02 mL of each solution was applied via the testing apparatus (Vand der Bend chambers, four squares measuring 1 x 1 cm), which was fixed and remained in contact with the skin surface. The anti-inflammatory effect was measured via the variations of redness (chromometry, parameter a*), using a Minolta CR 200 chromometer. RESULTS: At base condition the values of a* of the areas that were tested ranged from 7.11 to 9.30 with a mean of 7.97. In regard to the reaction caused by SLS dissolved in double-distilled water, the values of a* ranged from 8.98 to 9.53, mean 9.24, for 0.5% SLS and from 12.81 to 14.33, mean 13.59, for 1% SLS. The a* values for the cutaneous reaction caused by SLS dissolved in Leopoldine spa water ranged from 7.22 to 9.60 (mean 8.20) for 0.5% SLS and from 10.8 to 12.36 (mean 11.68) for the 1% SLS. CONCLUSIONS: These data show the potential anti-inflammatory effects of Leopoldine mineral water on human skin affected by modest inflammatory reactions caused by the direct application of the chemical irritant SLS. Leopoldine spa water can, thus, be considered a natural therapeutic alternative for the treatment of inflammatory skin conditions.  相似文献   

11.
The dose- and time-related effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration was studied using 3 radiolabeled tracer compounds with different physicochemical properties: tritiated water, hydrocortisone and nickel. Human cadaver abdominal skin from caucasian women was used as membrane in static in vitro penetration cells. Simultaneous application of SLS together with 1 of the tracer compounds showed, after 48 h, a significant dose-effect relationship between SLS concentration (0.25%, 2% and 10%) and penetration of tritiated water or nickel ( p < 0.001, Spearman), whereas SLS had no significant effect on penetration of hydrocortisone. When 4% SLS was applied as pretreatment, a significant time-effect relationship, after 48 h, was found between pretreatment time (0.5, 2 and 8 h) and penetration of tritiated water. A similar relationship was not found for penetration of nickel or hydrocortisone. Pretreatment of the skin with SLS for 2 h using 3 concentrations (0.25%, 4% and 10%) showed, after 48 h, a significant dose-effect relationship between SLS treatment and penetration of tritiated water or nickel ( p < 0.001, Spearman). Pretreatment had no effect on penetration of hydrocortisone. Pretreatment simulates a cleaning-washing situation. The present in vitro skin penetration model, using human cadaver skin, described the dose-effect and time-effect relationships for SLS on the penetration profiles of 3 different compounds. The model may be extended to other compounds with suspected irritant/damaging effect on the skin barrier. It should be kept in mind that the model uses a dead skin membrane without the barrier repair mechanisms of live skin.  相似文献   

12.
用包被有羊抗鼠IgG的磁珠结合鼠抗白念单抗后,对白念珠菌,类星形念珠菌,类星形念珠菌,热带念珠菌,新生隐球菌,光滑念珠菌菌悬液及白念珠菌与新生隐球菌两菌混悬液进行了分离纯化研究。结果:免疫磁球和白念珠菌,类星形念珠菌结合尤为明显,与热带念珠菌少量结合而不和新生隐球菌,光滑念珠菌结合。  相似文献   

13.
Abstract In order to define the influence of contact allergens on the fluid-phase endocytosis (FPE) of soluble molecules of murine epidermal Langerhans cells (LC), we studied the internalization of FITC-labeled bovine serum albumin (FITC-BSA), TRITC-labeled dextrane (TRITC-DEX) as well as horseradish peroxidase by LC. A 3-parameter flow-cytometric technique was performed for quantification of internalized FITC-BSA in LC using quantum red-labeled reagents for detection of la-antigen expression by LC and propidium iodide for exclusion of dead cells from analysis. A temperature-dependent rapid accumulation of FITC-BSA was noticed in time-course studies reaching a plateau between 1 and 2 h of in vitro culture at 37°C. The quantity of FPE under stimulation with phorbol 12-myristate 13-acetate (PMA), concanavalin A (Con A), sta-phylococcal enterotoxin B (SEB) and contact sensitizers (DNFB, Kathon CG, K2Cr2O7) as well as the irritant SLS was determined. Treatment of LC with PMA and Con A resulted in a significant increase of total FITC-BSA uptake. The contact sensitizers as well as SEB and SLS failed to mediate augmented fluid-phase endocytosis. By use of the pH-insensitive soluble marker, TRITC-DEX and a microscope photometer for evaluation these findings could be confirmed. This excluded any artificial influence of differences in pH values in endocytotic compartments which might have influenced the fluorescence intensity of the pH-sensitive fluoro-chrome FITC. For qualitative analysis of FPE, the intracellular distribution of internalized horseradish peroxidase in LC was studied. An aggregated pattern became apparent in untreated LC and did not change under stimulation with any of the substances used. This was in sharp contrast to a modulation of receptor-mediated endocytosis of antibody-crosslinked MHC class II molecules under the influence of contact sensitizers, and suggested that haplen-mediated endocytotic activation of LC was restricted to this mechanism of inlernalization.  相似文献   

14.
BACKGROUND: Irritant contact dermatitis (ICD) is one of the most frequent types of occupational dermatitis. Different factors are involved in the development of contact dermatitis. In the food-processing industry, the combined exposure to different irritants may be involved in the development of ICD. Few data have been published regarding the irritant potential of sodium lauryl sulphate (SLS) in combination with cold. OBJECTIVES: The present study was intended to analyse whether cold exposure and low skin temperature influence the development of ICD. METHODS: Twenty (part I) and 12 (part II) healthy volunteers were exposed twice daily for 4 days to SLS alone, different low temperatures alone (4 degrees C six times for 90 s with an interval of 20 s or 15 degrees C for 10 min) or a combination of cold and SLS (19.6 microL SLS 1% cm(-2), part I; or 52.6 microL SLS 0.5% cm(-2), part II) using the tandem repetitive irritation test. Irritant cutaneous reactions were measured by noninvasive biophysical methods with transepidermal water loss as a parameter for permeability barrier function and skin colour reflectance together with visual scoring as parameters for inflammatory reactions. RESULTS: Cold alone caused no significant skin reaction compared with untreated control. Exposure to SLS alone and SLS together with cold (independent of the applied temperature of 4 or 15 degrees C) twice daily induced a clear irritant reaction and barrier disturbance. Reactions did not differ whether SLS was applied before or after cold. Furthermore, 'tandem application' of cold and SLS diminished the barrier disruption and irritant reaction compared with SLS alone. CONCLUSIONS: We conclude that the application of cold may have a protective effect on the development of ICD, at least in our short-term model.  相似文献   

15.
目的评估不同肤色人种皮肤对化学刺激物的敏感性。方法用多个浓度的硫酸月桂酯钠对32例健康志愿者(黑种人8例,白种人16例,黄种人8例)背部皮肤进行斑贴试验。结果显示黑种人组最小红斑刺激量高于白种人组(P<0.05)和黄种人组(P>0.05)。然而在相同浓度的硫酸月桂酯钠刺激部位,黑种人、白种人和黄种人3组经表皮水分散失和真皮浅层微血管血流量值无显著性差异。黑种人、白种人和黄种人3组经表皮水分散失和真皮浅层微血管血流量值分别与硫酸月佳酯钠刺激浓度有明显的剂量应答关系,并且3组经表皮水分散失值与临床观察指数值之间呈显著正相关(黑种人组:r=0.83,P<0.01;白种人组:r=0.92,P<0.01;黄种人组:r=0.89,P<O.01)。结论与白种人和苗种人相比,黑种人皮肤对硫酸月桂酯钠刺激同样较敏感。  相似文献   

16.
The purpose of the present study was to compare 2 experimental models of moisturizer efficacy on the recovery of irritated skin on the hands and the volar forearms. 12 healthy volunteers had their hands immersed in sodium lauryl sulfate (SLS) 10 min 2x daily for 2 days, and at the same time the volunteers had patch tests with SLS (0.125%, 0.25% and 0.5%) applied on their forearms for 24 h. After irritation of the skin, the volunteers had a moisturizer applied on one arm/hand 3x daily for the following 9 days. The other arm/hand served as untreated control. Evaluation was done on days (D) 1, 3, 5, 8 and 12 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry and DermaSpectrometry. Both models were found useful, and the moisturizer was found to accelerate regeneration of the skin barrier function in both the hands (D8, p<0.05) and the volar forearms (0.5% SLS, D5 and D8, p<0.01). When the forearm model is used in the present set-up, a relatively high concentration of SLS (>0.25%) should be used and evaluation measurements are best performed on D5-D8. The forearm model proved reliable and easy to handle and we suggest that this model is used in future studies on moisturizer evaluation.  相似文献   

17.
The effect of a protective cream was tested in a new tandem repeated irritation test with tandem application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene. The irritants were applied twice daily for 30 min to the ventral forearms of 20 volunteers. Irritant cutaneous reactions were quantified by a visual score, transepidermal water loss, chromametry and skin capacitance. Concurrent application of SLS/toluene induced stronger reactions than those caused by twice daily application of each irritant on its own. A protective effect of the protective cream was obtained against all treatment combinations and was significant for SLS/SLS (p < or = 0.01) and SLS/ toluene (p < or = 0.05). Our results indicate that the tandem repetitive irritation test has great potential in the evaluation of skin care products to prevent irritant contact dermatitis.  相似文献   

18.
Exposure to irritants may cause chronic irritant contact dermatitis (ICD), characterized by irregular epidermal thickening and a predominantly dermal mononuclear cell infiltrate. The mechanisms involved, and why only certain individuals are affected, are not clearly understood. Different irritants may trigger different cellular and molecular interactions between resident skin cells and recruited inflammatory cells. In some individuals these interactions may become self-perpetuating resulting in persistent inflammation in the absence of continued exposure. This study examined Langerhans cell (LC) density in clinically normal skin of 46 patients with chronic ICD and 10 healthy individuals, and compared the action of the two irritants nonanoic acid (NA) and sodium lauryl sulphate (SLS) on the LCs and keratinocytes of clinically normal skin in patients with chronic ICD. There was a higher number of LCs/mm basement membrane in patients compared with controls, although there was no difference in the number of dendrites/LC nor in dendrite length. SLS induced keratinocyte proliferation after 48 h exposure, had no effect on LC number or distribution, and induced keratinocyte apoptosis after 24 and 48 h exposure. In contrast, NA decreased keratinocyte proliferation after 24 h exposure but this returned to basal levels after 48 h, and induced epidermal cell apoptosis after only 6 h exposure. NA dramatically decreased LC number after 24 and 48 h exposure, which was accompanied by basal redistribution and decreased dendrite length. Most significantly, NA induced apoptosis in over half of the LCs present after 24 and 48 h exposure.  相似文献   

19.
Exposure of the skin to surfactant-based products can result in irritation. To control this effect researchers are probing mechanisms of surfactant action. In vitro studies show that mixing surfactants often results in less denaturation (swelling) of stratum corneum. We have explored the in vivo human irritation response (using a 21-day cumulative irritation test) to two of these surfactants-sodium lauryl sulfate (SLS) and (C12-C14) alkyl, 7-ethoxy sulfate (AEOS-7EO). Results demonstrate that addition of AEOS-7EO to a constant dose of SLS results in a significant reduction in erythema, hence producing a milder system. The reason for the synergism is unclear, but may related to experimentally determined alterations in the micellar solution properties of the SLS upon addition of AEOS-7EO.  相似文献   

20.
Background/aims: This study evaluated the efficacy of a dimethicone skin protectant lotion against sodium lauryl sulfate (SLS)-induced irritant contact dermatitis (ICD) by clinical visual grading and bioengineering techniques in 12 healthy humans.
Methods: The flexor aspects of both forearms of the subjects were used as test sites. Each test was duplicated to diminish the variations of the test sites. In a random order and a double-blind manner, two test sites were pretreated either with the testing protectant lotion or with its vehicle control prior to contact with SLS. Thirty minutes later, 0.2 ml of 0.5% SLS in a polypropylene chamber was applied to each pretreated site. One additional test site served as a positive control (without lotion), receiving the irritant only. After 24 h of exposure to the irritant, the chambers were removed. The efficacy of protective effect was determined by four parameters: visual scoring (VS), transepidermal water loss (TEWL), skin color ( a * value), and cutaneous blood flow volume (BFV). All test sites were assessed with the parameters daily for 5 days.
Results: The VS data showed a significant decrease on the site pretreated with protectant lotion in comparison with the SLS-only treated site ( P <0.01) and with the site pretreated with control vehicle ( P <0.05) (overall for 5 days). TEWL value was significantly decreased in comparison with the SLS-only treated site ( P =0.02 at day 2; P =0.008 at day 4; P =0.014 at day 5) and with the site pretreated with the control vehicle ( P <0.05) (day 2, 4 and 5). However, the BFV and a * values did not show a statistical difference between protectant lotion, vehicle, and SLS-only treated sites.
Conclusions: This study demonstrated that appropriate dimethicone skin protection products may provide certain benefits from surfactant ICD. The skin protectant lotion may be used to prevent ICD in home or work environments, where skin irritants may induce dermatitis or eczema.  相似文献   

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