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Acta dermato-venereologica. Supplementum最新文献

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Basal cell carcinoma--new aspects of diagnosis and treatment. 基底细胞癌——诊断和治疗的新方面。
A M Wennberg

The incidence of basal cell carcinoma is increasing. New aspects of diagnosis and treatment are discussed in this thesis. Interferon can be used for the treatment of BCC. In paper I, 15 patients received 13.5 x 10(6) IU of alfa-2b-interferon intralesionally. Four patients healed completely whereas a 75% reduction was seen in 5 cases. Intralesional alfa-2b-interferon can reduce the number of excisions during Mohs Micrographic Surgery. Topical photodynamic therapy involves the application of ALA on the skin. In tumour cells selectively, formation of the photosensitizer Pp IX occurs. After 4 hours of occlusion of ALA the area is irradiated with light at a wavelength of 630 nm. Tumour cells are selectively destroyed during this procedure. 144/157 SBCC healed in this series and 14/18 Mb Bowen (paper II). The method is only suited for thin BCCs as the result on thicker lesions is poor (2/10 healed). The cosmetic result was generally good or excellent. Another way of utilising the tumour selectivity of Pp IX is for diagnostic purposes. Instead of illuminating with 630 nm, 365, 366 and 405 nm are used to induce a specific fluorescence. In the present paper (III), 50% of facial BCCs with ill-defined borders could be completely visualised and another 23% partly outlined. The technique did not seem to work in 27% of the cases. The critical factor using ALA is probably the relatively poor penetrance through the skin. In paper IV, microdialysis is used for pharmacokinetic studies of ALA for the first time. The concentration of ALA increases rapidly in lesional skin whereas there is virtually no penetration in healthy skin. Also, the blood perfusion in BCCs was investigated by means of laser Doppler Perfusion Imager. The perfusion in skin overlying a BCC was 2.5 fold higher compared to normal skin. For BCCs with ill-defined borders Mohs Micrographic Surgery is generally recommended. Regarding Mohs Micrographic Surgery, Sweden is underserved as only 1% of BCCs are treated with Mohs Micrographic Surgery as opposed to 30% in the US. Consequently, the Swedish cases are probably more severe. The long-term results are reported in paper V. Two hundred and twenty-eight tumours were followed for at least 5 years. The rate of recurrence was 8%. This figure is slightly higher than in international materials but surprisingly low considering the type of tumours.

基底细胞癌的发病率呈上升趋势。本文讨论了诊断和治疗的新方面。干扰素可用于治疗基底细胞癌。在论文1中,15例患者接受13.5 × 10(6) IU的α -2b干扰素局部注射。4例患者完全愈合,而5例患者减少了75%。在莫氏显微摄影术中,病灶内α -2b-干扰素可减少切除次数。局部光动力疗法包括在皮肤上应用ALA。在肿瘤细胞中选择性地形成光敏剂ppix。在ALA遮挡4小时后,用波长为630 nm的光照射该区域。在这个过程中,肿瘤细胞被选择性地破坏。144/157 SBCC在本系列和14/18 Mb Bowen中愈合(论文II)。该方法仅适用于薄的bccc,因为较厚的病变结果较差(2/10愈合)。美容效果一般是好的或极好的。另一种利用ppix的肿瘤选择性的方法是用于诊断目的。用365、366和405 nm来诱导特定的荧光,而不是用630 nm来照明。在本文(III)中,50%边界不明确的面部bcc可以完全可视化,另外23%可以部分勾画。这项技术似乎在27%的病例中不起作用。使用ALA的关键因素可能是相对较差的皮肤穿透率。在论文IV中,微透析首次用于ALA的药代动力学研究。ALA的浓度在病变皮肤中迅速增加,而在健康皮肤中几乎没有渗透。同时用激光多普勒血流成像仪观察bcc的血流灌注情况。覆盖基底细胞癌的皮肤灌注量是正常皮肤的2.5倍。对于边界不明确的基底细胞癌,一般建议采用莫氏显微摄影手术。关于莫氏显微手术,瑞典的服务不足,只有1%的bcc接受了莫氏显微手术治疗,而美国的这一比例为30%。因此,瑞典的病例可能更为严重。长期研究结果发表在论文v中。对228例肿瘤患者进行了至少5年的随访。复发率为8%。这个数字略高于国际资料,但考虑到肿瘤的类型,这个数字低得惊人。
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引用次数: 0
Analysis of HLA antigens in Croatian patients with psoriasis. 克罗地亚银屑病患者HLA抗原分析。
Pub Date : 2000-01-01 DOI: 10.1080/00015550050500040
M. Kaštelan, F. Gruber, E. Čečuk, V. Kerhin-Brkljačić, L. Brkljačić-Šurkalović, Andrija Kaštelan
In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.
与大多数自身免疫性疾病一样,牛皮癣与一些HLA抗原有关。我们研究了克罗地亚银屑病患者HLA抗原的分布:108例患者根据家族史和发病年龄分组。采用聚合酶链反应分析HLA抗原和HLA- c等位基因。我们发现银屑病患者中HLA-A2、-B17、-B37和-B13抗原显著升高,HLA-Cw*0602和DR7抗原显著升高。1型银屑病患者(早发、家族史阳性)与Cw*0602呈极显著相关[p < 0.00001];相对危险度(RR) = 14.45]和DR7 (p < 0.00001);RR = 15.09)抗原。2型银屑病患者(发病晚、无家族史)与Cw*03抗原有显著相关性(p = 0.008;Rr = 0.17)。综上所述,HLA-B13、-B17、Cw*0602和-DR7抗原与克罗地亚人群中牛皮癣的显著风险相关,其中Cw*0602等位基因与牛皮癣的相关性最强,尤其与I型牛皮癣相关。
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引用次数: 31
The skin barrier from a lipid perspective. 从脂质角度看皮肤屏障。
Pub Date : 2000-01-01 DOI: 10.1080/000155500750042835
S Engström, K Ekelund, J Engblom, L Eriksson, E Sparr, H Wennerström

This contribution summarises the results from a number of investigations undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of some stratum corneum lipids revealed phase separation of the lipids in the typical case and the ability of cholesterol to reduce the line tension between phases. A theoretical model was developed describing the response of an oriented stack of polar lipid bilayers in the presence of a gradient in water chemical potential (water solution to humid air). The gradient gives rise to an inhomogeneous water swelling, and presumably to a liquid crystal-to-gel transition in the lamellar region closest to humid air. Skin penetration enhancers such as Azone and oleic acid cause phase transformations in lipid bilayer systems which may be relevant in the context of skin permeation.

这篇文章总结了在1994年由Forslind提出的领域马赛克模型的精神下进行的一系列调查的结果。原子力显微镜(AFM)对某些角质层脂质的二维相行为的研究揭示了典型情况下脂质的相分离和胆固醇降低相间线张力的能力。建立了一个理论模型,描述了在水化学势(水溶液到潮湿空气)梯度存在下极性脂质双分子层定向堆叠的响应。这种梯度引起了不均匀的水膨胀,并可能在最靠近潮湿空气的层状区域产生了液晶到凝胶的转变。皮肤渗透促进剂如氮酮和油酸引起脂质双分子层系统的相变,这可能与皮肤渗透有关。
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引用次数: 19
Atopy and contact sensitization in psoriasis. 银屑病的特应性和接触致敏。
Pub Date : 2000-01-01 DOI: 10.1080/00015550050500077
P. Pigatto
The allergen-specific IgE antibody was determined in 20 men and 120 women with psoriasis and the results were correlated with a history of current and previous allergic disease. Allergic disease was reported in 21% of the patients, but a positive RAST test was obtained in 44%. In chronic plaque-type psoriasis a positive RAST test was significantly more common (58%) than in active psoriasis (22%). Grass pollen and house dust mite were the most prevalent sensitizing allergens, with frequencies of 64% and 53%, respectively in the sensitized subjects. Sensitization increased with age and polysensitization was common. Contact dermatitis was verified with patch tests in 12 men and 20 woman, of whom 10 had chronic plaque-type psoriasis and 22 active psoriasis. Tar, nickel sulphate, corticosteroid mixture and thiomersal were the most common allergens. No irritant reactions were seen at the concentrations used. Atopic allergic diseases and contact sensitization were therefore common among our psoriatic patients.
在20名男性和120名女性牛皮癣患者中检测了过敏原特异性IgE抗体,结果与当前和既往变态反应性疾病史相关。21%的患者报告过敏性疾病,但44%的患者获得RAST检测阳性。慢性斑块型银屑病患者RAST检测阳性的比例(58%)明显高于活动性银屑病患者(22%)。草花粉和屋尘螨是最常见的致敏变应原,分别占致敏对象的64%和53%。致敏性随年龄增加而增加,多致敏性很常见。在12名男性和20名女性中,通过斑贴试验证实了接触性皮炎,其中10名患有慢性斑块型牛皮癣,22名患有活动性牛皮癣。焦油、硫酸镍、皮质类固醇混合物和硫柳汞是最常见的过敏原。在所使用的浓度下未见刺激性反应。因此,特应性变态反应性疾病和接触致敏在我们的银屑病患者中很常见。
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引用次数: 33
Assessment of perforin expression in peripheral blood lymphocytes in psoriatic patients during exacerbation of disease. 银屑病加重期患者外周血淋巴细胞穿孔素表达的评价
Pub Date : 2000-01-01 DOI: 10.1080/00015550050500059
Larisa Prpić, N. Strbo, V. Sotošek, F. Gruber, E. Podack, D. Rukavina
There are very few data concerning the role played by cell-mediated cytotoxicity, particularly at the molecular level, in the course of psoriasis. Both cytotoxic T lymphocytes (CTL) and natural killer cells contain in their granules the cytolytic protein perforin, a mediator in cell-mediated cytotoxicity reactions. The aim of this study was to analyze perforin expression in various sets and subsets of perforin-positive peripheral blood lymphocytes in 17 patients with chronic psoriasis vulgaris in the exacerbation phase. The results were compared with those of an age- and sex-matched healthy control group (n = 21). Perforin (intracellular antigen) and cell surface antigens were detected using the simultaneous double-staining method. We found a significant increase in perforin (P) expression in the patient group for CTL (CD3+P+ cells), which are located mostly in the CD8+ population of T lymphocytes (CD8+P+).
关于细胞介导的细胞毒性,特别是在分子水平上,在牛皮癣过程中所起的作用的数据很少。细胞毒性T淋巴细胞(CTL)和自然杀伤细胞的颗粒中都含有细胞溶解蛋白穿孔素,穿孔素是细胞介导的细胞毒性反应的介质。本研究旨在分析17例慢性寻常型银屑病患者急性加重期穿孔素阳性外周血淋巴细胞中不同组和亚群穿孔素的表达。将结果与年龄和性别匹配的健康对照组(n = 21)进行比较。同时双染色法检测穿孔素(细胞内抗原)和细胞表面抗原。我们发现,患者组的CTL (CD3+P+细胞)的穿孔素(P)表达显著增加,这些细胞主要位于T淋巴细胞的CD8+群(CD8+P+)中。
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引用次数: 16
Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis. 双盲,安慰剂对照,随机,右-左研究比较钙化三醇单药治疗与钙化三醇和戊酸二氟落酮联合治疗慢性斑块型银屑病。
Pub Date : 2000-01-01 DOI: 10.1080/00015550050500022
W. Salmhofer, H. Maier, H. Soyer, H. Hönigsmann, S. Hödl
A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone.
本研究采用双盲随机临床研究,比较每日2次局部钙化三醇与每日1次早晨联合使用钙化三醇、晚间联合使用戊酸双氟落酮的疗效和耐受性。63例临床诊断为慢性斑块型银屑病和身体两侧类似银屑病病变的患者被纳入研究。在1周的洗脱期后,银屑病病变在身体一侧使用钙化三醇软膏治疗4周,每天两次,另一侧使用钙化三醇和戊酸双氟落酮软膏联合治疗。治疗期后4周不进行任何治疗。采用银屑病面积及严重程度指数(PASI)对两组患者进行比较。此外,总体治疗结果由研究人员和患者独立评估。两种治疗方案都显示出显著的、几乎相同的PASI减少。单独使用钙化三醇的平均PASI在基线时为5.7,治疗4周后为1.9,随访结束时为3.8。对于联合治疗,这些值分别为5.7、1.8和3.8。在第1周和第2周,钙化三醇和戊酸地氟落酮联合治疗有统计学意义(p < 0.05);然而,在治疗阶段结束时,两种疗法之间的差异并不显著。研究者和患者对疗效的主观评价显示两种治疗方法之间没有差异。两组的副作用(如刺激)发生率均较低。综上所述,两种治疗方法对慢性斑块型银屑病病变均有效。钙化三醇和局部类固醇联合使用似乎能产生更快的临床反应,并被证明与单独使用钙化三醇一样有效。
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引用次数: 9
Insights into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models. 从角质层脂质模型的红外光谱研究中洞察皮肤屏障中脂质的分子组织。
Pub Date : 2000-01-01 DOI: 10.1080/000155500750042817
D J Moore, M E Rerek

In order to gain some insight into the molecular organization of lipids in the skin barrier we used Fourier transform infrared (FTIR) spectroscopy to investigate models of the stratum corneum (SC) containing deuterated hexadecanoic acid, cholesterol, and ceramide 2 or ceramide 5. In both models there is clear evidence of separate conformationally ordered domains of ceramide and fatty acids. In addition, these chains are packed in orthorhombic subcells at physiological temperatures. The ceramide headgroup behavior indicates distinct hydrogen bonding patterns between the ceramide 2 and ceramide 5 models. In the ceramide 2 model the amide I mode is split into two components suggesting strong transverse intermolecular hydrogen bonding between headgroups. In contrast, no amide splitting is observed for ceramide 5 although the amide frequencies are indicative of strong hydrogen bonding. These observations on the molecular organization of SC lipids are discussed in terms of skin barrier function.

为了深入了解皮肤屏障中脂质的分子结构,我们使用傅里叶变换红外(FTIR)光谱来研究角质层(SC)中含有氘化十六烷酸、胆固醇和神经酰胺2或神经酰胺5的模型。在这两种模型中,有明确的证据表明神经酰胺和脂肪酸的构象有序结构域是分开的。此外,这些链在生理温度下被包裹在正交亚细胞中。神经酰胺的头基团行为表明神经酰胺2和神经酰胺5模型之间存在明显的氢键模式。在神经酰胺2模型中,酰胺I模式被分成两个组分,表明头基之间存在很强的横向分子间氢键。相反,在神经酰胺5中没有观察到酰胺分裂,尽管酰胺频率表明有很强的氢键。这些关于SC脂质分子组织的观察在皮肤屏障功能方面进行了讨论。
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引用次数: 91
Causes and effects of the chronic inflammation in venous leg ulcers. 下肢静脉性溃疡慢性炎症的原因及影响。
M S Agren, W H Eaglstein, M W Ferguson, K G Harding, K Moore, U K Saarialho-Kere, G S Schultz

The pathogenesis of venous leg ulcers is multifactorial. In this review article new physiological, molecular and cellular abnormalities in venous ulcers related to the chronic inflammation are presented and discussed. Venous hypertension causes disturbed microcirculation and pathological changes of the capillaries, which eventually locks the condition in a self-amplifying, detrimental cascade with persistent elevated levels and activities of pro-inflammatory cytokines and proteases preventing progress into a healing phase. As a consequence fibroblasts senescence and become less responsive to growth factors the older the ulcers become. Current data imply there is no deficiency but rather an unfavorable distribution of growth factors in venous ulcers. An imbalance in proteolytic enzymes and their endogenous inhibitors is a common finding in chronic venous leg ulcers. Variation in disease severity and concomitant ailments in this heterogeneous patient group may explain the contradictory results in the literature. Thus, to advance the areas of research further, longitudinal studies involving larger number of patients are required to identify the major pathogenic factors.

下肢静脉性溃疡的发病机制是多因素的。本文就与慢性炎症有关的静脉溃疡的新的生理、分子和细胞异常进行综述和讨论。静脉高压引起微循环紊乱和毛细血管的病理改变,最终将病情锁定在一个自我放大的有害级联反应中,促炎细胞因子和蛋白酶的水平和活动持续升高,阻止病情进入愈合阶段。结果,成纤维细胞衰老,对生长因子的反应越弱,溃疡越老。目前的数据表明,生长因子在静脉溃疡中没有不足,而是不利的分布。蛋白水解酶及其内源性抑制剂的失衡是慢性静脉性腿部溃疡的常见发现。在这种异质患者群体中,疾病严重程度和伴随疾病的差异可能解释了文献中相互矛盾的结果。因此,为了进一步推进研究领域,需要进行涉及更多患者的纵向研究,以确定主要致病因素。
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引用次数: 0
Subclinical microbial infection in patients with chronic plaque psoriasis. 慢性斑块型银屑病患者的亚临床微生物感染。
Pub Date : 2000-01-01 DOI: 10.1080/00015550050500068
I. Bartenjev, M. R. Butina, M. P. Nik, I. Bartenjev
Epidemiological evidence implicates bacterial infection as a common triggering stimulus for psoriasis. Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for relapse of acute guttate psoriasis but also for a new episode of chronic plaque psoriasis. In this study 195 patients suffering from a severe form of chronic plaque psoriasis hospitalized between 1996 and 1998 were examined. The presence of subclinical microbial infection of the upper respiratory tract was studied by the cultivation of pathogens from this area. Patients with other provoking factors, such as a positive history of taking any drugs that may exacerbate psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus and clinically evident bacterial infection, were excluded. Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group. The results of this study indicate that subclinical bacterial infections of the upper respiratory tract may be an important factor in provoking a new relapse of chronic plaque psoriasis. Searching for, and eliminating, microbial infections could be of importance in the treatment of psoriasis.
流行病学证据暗示细菌感染是牛皮癣的常见触发刺激。最近的研究表明,持续的亚临床链球菌和葡萄球菌感染可能不仅是急性点滴状银屑病复发的原因,也是慢性斑块状银屑病新发作的原因。在这项研究中,195名患有严重慢性斑块型银屑病的患者在1996年至1998年间住院。通过对该地区病原菌的培养,研究了上呼吸道亚临床微生物感染的存在。排除有其他诱发因素的患者,如有任何可能加重银屑病的药物阳性史、内分泌和代谢因素、酗酒、创伤、牙灶和临床明显的细菌感染。在68%的接受检测的患者中检测到亚临床链球菌和/或葡萄球菌感染,而在对照组中仅为11%。本研究结果提示,上呼吸道亚临床细菌感染可能是引起慢性斑块型银屑病复发的重要因素。寻找并消除微生物感染对银屑病的治疗具有重要意义。
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引用次数: 16
In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Studies in hairless rats and human subjects. 体内微透析用于研究真皮中的药物水平和屏障扰动对皮肤药物渗透的影响。无毛大鼠和人类实验对象的研究。
Pub Date : 1999-12-01 DOI: 10.1080/00015555206159
E. Benfeldt
The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage inflicted was quantified by non-invasive measurements of transepidermal, water loss and erythema. The penetration of salicylic acid, applied in an ethanol solution in chambers glued to the skin in the barrier perturbed areas, was measured by microdialysis sampling of the drug level in the underlying dermis. At the end of the experiment, probe depth in the dermis and skin thickness were measured by ultrasound scanning. In humans and hairless rats alike, the cutaneous drug penetration was highly increased in tape stripped skin (157- and 170-fold increased, respectively, in comparison to the penetration in unmodified skin) and in skin with irritative dermatitis (46- and 80-fold increased). Delipidization by acetone led to a doubling of the penetration in humans but had no effect on penetration in hairless rats. In both studies a close correlation between the measurements of barrier perturbation by non-invasive methods and the cutaneous drug penetration in the same area was found. In the huma
论文以回顾章节开始,涉及皮肤中药物含量研究的理论和实践方面。讨论了现有方法的优点和局限性,以及实验部分采用的相对较新的微透析采样方法。影响正常人体皮肤屏障功能的因素被描述为在患病和实验中发现的皮肤屏障功能的改变。微透析技术包括在真皮中引入一根超薄的半透管,即所谓的探针。该管与精密泵相连,该泵以非常低的流量提供稳定的组织相容流体通过探头。组织中较小的分子,其中包括细胞外液中药物含量的非蛋白质结合部分,将被动地扩散穿过膜表面,从而进入灌注液的流动,定期取样并分析。在本文的实验部分中,微透析用于局部和全身给药后皮肤内药物水平的测定。该方法并不适用于所有药物或化合物的研究,因为我们已经证明,如果不进一步发展该方法,用微透析对高蛋白结合药物或非常亲脂的药物进行取样是不可行的。局部给药的研究包括两项模型药物水杨酸的皮肤渗透研究,最初在无毛大鼠中进行,随后在人类志愿者中进行。在这两项研究中,皮肤屏障的扰动是通过物理方法(通过反复剥离胶带去除角质层)或化学方法(用丙酮治疗)或刺激性皮炎(应用十二烷基硫酸钠,一种洗涤剂)进行的。在渗透实验之前,通过非侵入性测量经皮、失水和红斑来量化所造成的屏障损伤。水杨酸的渗透,应用于乙醇溶液的室粘在皮肤的屏障干扰区域,通过微透析取样的药物水平在真皮底层测量。实验结束时,通过超声扫描测量探针在真皮层的深度和皮肤厚度。在人类和无毛大鼠中,胶带剥离的皮肤(与未修饰的皮肤相比,分别增加了157倍和170倍)和刺激性皮炎皮肤(分别增加了46倍和80倍)的皮肤药物穿透性大大增加。丙酮的脱脂作用使人类的穿透力增加了一倍,但对无毛大鼠的穿透力没有影响。在这两项研究中,发现用非侵入性方法测量的屏障扰动与同一区域的皮肤药物穿透之间存在密切的相关性。在人体研究中,无创方法无法测量丙酮处理区域的屏障摄动,而微透析采样测量的药物穿透性明显增加,说明微透析方法在检测和定量皮肤屏障功能摄动方面具有很高的灵敏度。在人体研究中,可以证明用于诱导刺激性皮炎的洗涤剂浓度与随后药物穿透皮肤的增加之间的剂量-反应关系。在对无毛大鼠的研究中,发现了探针在真皮层的深度与药物渗透之间的相关性,表明探针放置得越浅,药物通过皮肤流入的时间就越早。研究了健康志愿者口服2g乙酰水杨酸后的全身药物分布。(抽象截断)
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引用次数: 66
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Acta dermato-venereologica. Supplementum
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