New therapeutics for the prevention and reduction of scarring

Published literature shows that both physicians and patients are highly concerned about scarring and value even small improvements in scar appearance. Both severe and relatively minor scars can have a significant psychological impact on patients, irrespective of whether or not they are hidden by clothing. There is no universal standard of care for scarring and, currently, no marketed pharmaceuticals for the prophylactic reduction of scarring. Novel approaches are under development, with the furthest progressed being avotermin (Juvista; transforming growth factor beta 3). The scar-improvement efficacy of this agent, administered at the time of surgery, has been demonstrated in robust, well-controlled, randomized human studies. Avotermin and other agents in development represent a new class of prophylactic medicines promoting the regeneration of normal skin and improving scar appearance.     

Fractionated delivery systems for difficult to treat clinical applications: acne scarring, melasma, atrophic scarring, striae distensae, and deep rhytides

Fractional resurfacing or laser therapy (FLT) represents a technology that seeks to address the limitations of both ablative resurfacing and nonablative treatments. Many companies now offer versions of fractionated erbium or carbon dioxide lasers. The purpose of this paper is to examine FLT for difficult to treat applications such as melasma, acne scarring, atrophic scarring, striae distensae, and deep rhytides. Fractional laser therapy is a truly novel approach to many conditions, especially those with dermal pathology. Although published peer review data is limited, the ability to effectively and safely treat these conditions in all skin types appears to have been significantly enhanced with this new modality. We are early in our scientific explorations of what is possible with FLT.     

皮肤微生态与皮肤疾病研究进展

皮肤是人体最大的器官,其结构从内到外依次为皮下组织、真皮层和表皮层。皮肤表面及腺体等部位定植着众多微生物,统称为皮肤微生物组。不同微生物其组成和分布在一定范围内维持动态平衡,并通过增殖、分泌等方式与宿主的皮肤及免疫系统进行相互调节,构成了皮肤微生态系统。当皮肤菌群失调时,会引发微生态紊乱,导致疾病的发生。通过微生态角度进行治疗,不仅能有效减少病症,还可避免细菌耐药性扩散等情况。综述了皮肤微生态相关的近期研究成果,并着重介绍皮肤微生物与皮肤疾病的关联,以及微生态治疗在皮肤疾病中的应用,旨在为相关研究提供参考。     

Skin permeability

The histochemical and physicochemical aspects of skin permeability and transdermal drug permeation are reviewed under preponderant consideration of the past years' literature supplied by relevant investigations from the author's laboratories. The chemical composition and the physical order of the horny layer lipids as well as the interactions of drugs and vehicle components with these lipids are the basis of understanding drug penetration, its influencing by vehicles and penetration enhancement. By means of measuring drug concentration profiles in human skin the mechanisms of vehicle effects and penetration enhancement are demonstrated. The consequences of increased permeability and xenobiotic enrichment in pathologically altered skin are discussed.     

齐墩果酸对兔耳增生性瘢痕的治疗作用

目的研究齐墩果酸（oleanolicacid）对兔耳增生性瘢痕的治疗作用。方法用打孔器产生创面建立兔耳增生性瘢痕模型。齐墩果酸（2．5％、5％、10％）外用给药,1次／d,连续22d。给药结束后切除瘢痕组织进行组织学检测并且测定I型和Ⅲ型胶原、基质金属蛋白酶．1（MMP-1）和生长转化因子βl（TGF-βl）的水平以及瘢痕增生指数（scarelevationindex,SEI）。结果用不同质量浓度的齐墩果酸给药22d后发现其对兔耳肥厚性瘢痕有显著的治疗作用,TGF-βl、I型和Ⅲ型胶原水平显著降低,MMP-1在瘢痕组织中显著增加,SEI明显降低。组织形态观察结果显示齐墩果酸对瘢痕有明显的改善作用。结论齐墩果酸对兔耳增生性瘢痕有治疗作用,可能成为治疗人类增生性瘢痕的活性药物。     

头孢菌素类药物皮肤过敏的试验及皮试方法的研究

目的观察和分析头孢菌素类药物皮肤过敏的实验以及皮试方法。方法选择我院2010年1月至2011年1月接收的治疗过程中使用头孢菌素类药物的500例住院患者,随机平均分成皮试组与非皮试组,分别观察患者用药后的情况。结果有青霉素过敏史的患者占19.80%,皮试阳性占有率中,其他物质过敏史的占12.02%,无过敏史的占0.55%;皮试阴性组用药后发生的不良用药反应以及过敏反应明显低于非皮试组患者,两组数据差异显著,具有统计学意义。结论影响头孢菌素类药物出现不良药物反应以及皮试阳性发生率的主要因素是患者的过敏史,因此,对具有过敏史患者用药前应该对患者进行采取拟用药皮试。     

Predicting Skin Permeability

Published permeability coefficient (K _p) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (K _oct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physicochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of K _p upon MV (or MW) and K _oct. It is found that the existence of an aqueous-polar (pore) pathway across the SC is not necessary to explain the K _p values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected K _p. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to >750, and log K _oct ranging from –3 to + 6), the postulated upper limiting value of K _p for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal K _p values. Overall, then, we present a facile interpretation of a considerable body of skin permeability measurements that (a) very adequately describes the dependence of K _p upon permeant size and lipophilicity, (b) generates parameters of considerable physicochemical and mechanistic relevance, and (c) implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.     

基于皮肤微生态的炎症性皮肤病和衰老治疗策略

皮肤微生态在调控微生物和内稳态方面发挥着关键作用,与炎症性皮肤病及皮肤衰老存在密切联系。本文总结了皮肤微生态的组成与作用、皮肤疾病与微生态之间的关系、炎症性皮肤病和皮肤衰老的微生态调节治疗策略,为皮肤疾病的临床治疗及药物开发提供参考。     

Warfarin-Induced Skin Necrosis

Background:

Warfarin is a frequently used oral anticoagulant in the treatment and prevention of various medical conditions. One uncommon adverse effect that can occur following the initiation of therapy is warfarin-induced skin necrosis. Because it is a rare effect with an undetermined pathophysiology of disease, the treatment is not well established.

Case:

A 52-year-old female was prescribed warfarin and enoxaparin for a newly diagnosed deep vein thrombosis (DVT) in the left lower extremity. On day 4 of therapy, the patient had a supra-therapeutic international normalized ratio (INR), prompting the discontinuation of enoxaparin and a decrease in the warfarin dose. The patient returned to the emergency department on day 7 of treatment with a purple, cold, and extremely painful right foot with punctate areas of necrosis and petechiae proximal to the discoloration. The patient’s INR was found to be 10.64. Following the diagnosis of warfarin-induced skin necrosis, the patient was administered vitamin K intravenously and fresh frozen plasma (FFP) to reverse the effects of warfarin and promote protein C and S synthesis. Once the patient’s INR was no longer supratherapeutic, subcutaneous enoxaparin was re-started as treatment for the known recent DVT. The patient’s necrotic foot began to improve and she was discharged home with an anticipated full recovery.

Conclusions:

Based on the proposed pathophysiology of disease, adequate bridge therapy may decrease the likelihood of developing this life-threatening condition. Early recognition and treatment with intravenous vitamin K, FFP or 4-factor prothrombin complex concentrate, and continued wound care are essential to prevent further complications.     

Skin deep.

Over the past 30 or so years there has been a considerable advance in our knowledge of the mechanisms of skin permeation. This has largely been brought about by the development of sophisticated biophysical techniques and increased computing powers. The advanced technology has clearly provided indications, at a molecular level, about routes of permeation and how the barrier function can be modulated by excipients with which actives are formulated. This publication reviews some of the advances that have been made and mathematical models that have been constructed to predict percutaneous penetration and transdermal delivery. The models also indicate the various enhancement strategies that can be used in dermal penetration. In the past, it has been difficult to identify precise mechanisms of action of the different classes of enhancer but a combination of appropriate biophysical techniques, mathematical modelling and chemometric analysis can help identify the contributing processes. The models can also be used to indicate rate control in transdermal delivery, whether it is in the applied delivery device or in the skin.     

EpiSkin™和Epikutis®模型在体外皮肤刺激性和腐蚀性检测应用中的比较

目的 对Episkin™和Epikutis®模型在体外皮肤刺激性和腐蚀性检测各方面进行对比。方法 参考体外皮肤刺激实验（OECD指导原则439）和体外皮肤腐蚀实验（OECD指导原则431）,对2种模型在质量控制、检测方法、结果判断、运输等方面进行探讨。结果 2种模型在质量控制、检测方法、结果判断等方面存在差异,在实验操作性和成本上也各有优缺点,但2种模型均能满足体外皮肤刺激性和腐蚀性实验要求。结论 2种模型均能很好地用于体外皮肤刺激性和腐蚀性检测。     

Analysis of Drug Penetration Through the Skin by the Two-Layer Skin Mode

A diffusion model for the skin penetration of drug in the finite-dose system was developed considering the skin to be composed of two layers, the outermost layer (stratum corneum) and the lower layer (viable epidermis and dermis). Based on this skin model, the Laplace transforms of the equations for the drug amounts in the receptor, the vehicle, and the skin were derived. The penetration profiles of 6-mercaptopurine (6-MP) through the intact and stripped guinea pig skin were obtained from in vitro diffusion experiments. The computer fitting of those profiles to the Laplace-transformed equations by a nonlinear least-squares program based on a fast inverse Laplace transform algorithm [MULTI-(FILT)] gave parameters such as diffusion coefficients of 6-MP and thicknesses of both layers. The mean transit time (MTT) for each diffusion process was defined based on statistical moment concept and calculated using the obtained parameters. Under the present condition, the process to move from the vehicle to the stratum corneum is demonstrated to have the longest mean time in overall processes of 6-MP penetration.