砷剂对角质形成细胞生长和IL-8、TNF-α分泌的影响

目的研究不同浓度砷剂对角质形成细胞生长和IL-8、TNF-α分泌的影响。方法以体外培养的角质形成细胞株为对象,不同浓度砷剂处理细胞后,用MTT比色分析法反映细胞增殖的变化。ELISA方法测定细胞上清中IL-8分泌,用L929细胞检测上清TNF-α的生物活性。结果0.5～5μmol/L三氧化二砷对角质形成细胞株HaCaT细胞有明显抑制作用,并呈剂量依赖关系。在0.001μmol/L至0.015μmol/L药物浓度范围内,同对照组相比细胞增殖加快;未药物处理的对照组HaCaT细胞可分泌一定水平的IL-8和TNF-α,低浓度砷剂(0.001～0.015μmol/L)可刺激其分泌增加。结论低浓度砷剂可促进角质形成细胞株HaCaT细胞的生长,但高浓度能抑制增殖和影响细胞活性。并在一定浓度范围刺激IL-8和TNF-α的合成分泌,可能在砷相关皮肤病的发病机制中具有重要意义。     

砷剂对角质形成细胞CDK2、CDK4和Cyclin-E蛋白表达的影响

目的：研究砷剂对角质形成细胞细胞周期调控因子蛋白表达的影响。方法：以体外培养的角质形成细胞株为对象，一定浓度砷剂处理细胞后，用免疫印迹方法研究HaCaT细胞周期蛋白依赖激酶2（CDK2）、周期蛋白依赖激酶4（CDK4）和细胞周期蛋白E（Cyclin—E）的表达情况及砷剂对其表达的影响。结果：未受到砷剂处理的对照组细胞稳定表达CDK2、CDK4和Cyclin—E，当1nmol／L三氧化二砷处理24h后，HaCaT细胞表达CDK4、Cyclin—E水平升高，但CDK2的表达水平无明显变化。结论：一定浓度砷剂可刺激角质形成细胞增殖，可能与其升高细胞周期调控因子CDK4、Cyclin—E蛋白表达，导致S期细胞比例升高有关。     

砷对角质形成细胞DNA合成及E2F1表达的影响

目的探讨砷剂对角质形成细胞DNA合成和相关转录因子E2F1表达的影响。方法以体外培养的角质形成细胞株为对象,不同浓度砷剂处理后,采用3H-TdR实验检测角质形成细胞DNA合成,并用RT-PCR方法研究细胞E2F1表达情况。结果在0.5～16 nmol/L药物浓度范围内,DNA合成加速,促进细胞增殖。但随着砷剂浓度继续升高,3H-TdR掺入量降低,逐渐回到基线水平;RT-PCR结果显示:DNA合成加速的HaCaT细胞组,伴有E2F1mRNA水平的上调。结论一定浓度范围内的砷剂可促进角质形成细胞株HaCaT细胞的DNA合成加速,增强转录因子E2F1的表达,可能是砷相关皮肤病的病理机制之一。     

维A酸对砷刺激角质形成细胞增殖的拮抗作用

目的研究维A酸药物对三价砷刺激角质形成细胞增殖的拮抗作用及其机制。方法以体外培养的角质形成细胞为对象,低浓度三价砷预处理细胞刺激增殖,并用3H-TdR掺入法分析不同维A酸药物对细胞增殖的拮抗效应,进一步用流式细胞仪检测细胞周期变化。结果一定浓度三价砷可刺激角质形成细胞增殖,加入不同浓度芳维A酸氨丁三醇、依曲替酸处理24h,显示0.01~1μmol/L维A酸可不同程度拮抗砷剂的刺激增殖效应,芳维A酸氨丁三醇作用强于依曲替酸。流式细胞仪检测细胞周期分布变化,显示维A酸处理后S期细胞比例降低,G0-G1期细胞比例升高。结论低浓度的三价砷可刺激角质形成细胞增殖,而维A酸可拮抗砷剂的刺激增殖作用,使S期细胞比例降低,可能是维A酸类药物治疗砷相关皮肤病的机制之一。     

三氧化二砷对体外培养的HaCaT细胞基因表达的影响

通过饮水、燃煤、药物、职业等因素长期接触砷,可引起皮肤、肺和膀胱等组织器官的肿瘤发生。砷的致病或致癌是一个缓慢长期的过程,我们先前的研究表明,一定浓度的砷通过相关信号传导途径影响细胞周期,刺激角质形成细胞增殖^[1,2].为进一步全面了解砷对角质形成细胞的影响,采用基因表达谱芯片技术,对低剂量长期砷处理角质形成细胞的基因改变进行了研究.     

三氧化二砷下调JAK3表达并抑制淋巴细胞增殖

目的 研究三氧化二砷对淋巴细胞增殖和JAK3表达的影响.方法 以分离培养的外周血淋巴细胞为对象,不同浓度砷剂处理后,采用3H-TdR方法 检测淋巴细胞增殖;并进一步探讨其影响淋巴细胞增殖的机制,用Realtime-PCR方法 研究细胞JAK3表达情况.结果 0.01,0.1,1μmol/L砷剂组,摄入的同位素活性不同程度降低,其中0.01μmol/L砷剂组同对照组相比,差异无统计学意义(P>0.05),而0.1和1μmol/L砷剂组与对照组相比,差异均有统计学意义(P<0.05);Realtime-PCR结果 显示:增殖抑制的淋巴细胞组,JAK3 mRNA水平下调. 结论 一定浓度的砷剂可下调JAK3的表达,抑制淋巴细胞增殖,从而影响机体的免疫功能.     

砷剂激活角质形成细胞信号调节激酶及相关的信号传导途径

砷是常见的致癌物,由于饮水、药物、职业等因素长期接触砷,可引起皮肤、肺和膀胱等组织器官的肿瘤发生。尤其在皮肤蓄积,出现色素沉着、皮肤角化等相关皮肤病^[1]。近年来,国外对砷剂的致癌机制做了较多工作,特别是与细胞增殖、转化有关的信号传导途径是人们研究的热点。我们采用免疫印迹的方法,通过对表皮生长因子(EGF)相关的信号传导途径中主要环节的阻断,研究了亚砷酸钠对细胞外信号调节激酶(extracel-luarsignal-regulated kinase,ERK)激活的影响。     

亚砷酸对角质形成细胞增殖及凋亡的影响

目的：研究亚砷酸对不同角质形成细胞增殖及凋亡的影响。方法：以体外培养的角质形成细胞株为对象，不同浓度的亚砷酸处理细胞后，用MTT比色分析法反映细胞增殖变化，用光镜和电镜观察细胞形态，流式细胞仪测定细胞周期分布及凋亡峰的出现，Annexin-V染色荧光照相证实凋亡的发生。结果：0.5-10μmol/L亚砷酸对良性角质形成细胞株HaCaT细胞有明显抑制作用，并呈时间和剂量依赖关系，而该浓度砷剂对A431细胞无明显影响。光镜及HE染色后观察均显示随浓度升高、时间延长，凋亡细胞增多。高于上述范围HaCaT细胞变性死亡增多，流式细胞仪检测细胞周期分布变化，G2M期细胞比例及亚G1期凋亡明显升高，Annexin-V法显示有绿色荧光的阳性细胞。而A431细胞无明显形态和细胞周期分布变化。结论：一定浓度的亚砷酸可抑制HaCaT细胞增殖，并具有诱导凋亡作用，对皮肤鳞状细胞癌A431细胞无明显影响，提示良性表皮角质形成细胞株HaCaT对亚砷酸的处理比鳞状细胞癌A431细胞株更敏感。     

原发性皮肤T淋巴细胞瘤的治疗选择

原发性皮肤T细胞淋巴瘤是一组原发于皮肤的淋巴细胞异常增殖性疾病,蕈样肉芽肿是其中最常见的类型.原发性皮肤T细胞淋巴瘤的治疗选择,主要取决于世界卫生组织-欧洲癌症研究和治疗组织-国际皮肤淋巴瘤学会制定的TNMB分期与分类标准,其他需要考虑的因素包括,治疗方法的有效率、起效与持续缓解时间,治疗耐受性与相关毒副作用,治疗实施的难易程度及治疗费用等.原发性皮肤T细胞淋巴瘤早期主张支持治疗和局部治疗为主,晚期则要进行联合化疗,或根据病情辅以免疫调节治疗.一些特异的细胞因子、单克隆抗体和融合毒素也逐步试用于治疗原发性皮肤T细胞淋巴瘤.     

五倍子对角质形成细胞、黑素细胞和成纤维细胞体外增殖的影响

目的 了解中药五倍子治疗瘢痕疙瘩的药用成分和药用机制以及可能存在的不良反应。方法 用MTT比色试验研究五倍子单宁酸对正常人皮肤中的角质形成细胞、黑素细胞和成纤维细胞体外增殖的影响。并与秋水仙碱及红花和芦荟进行了比较。结果 ①五倍子单宁酸与五倍子生药醇提物对人成纤维细胞的增殖具有相似的抑制作用。在20μg/mL及以上质量浓度时,对人皮肤黑素细胞的抑制作用较大,其细胞增殖率是不加药对照组的73.6%～68%。在50μg/mL以下的质量浓度对人角质形成细胞的体外增殖有轻微的促进作用(111%～112%)。②红花生药醇提物和芦荟水提液在实验浓度下均可促进人角质形成细胞的体外增殖,芦荟水提液还可促进人成纤维细胞的体外增殖。结论 单宁酸是五倍子醇提物中的主要活性物质,其对黑素细胞的抑制作用提示五倍子单宁酸可能存在毒副作用。     

精神刺激对皮肤功能的调节

人类早就注意到精神因素对疾病(包括皮肤病)的影响。基础研究显示,精神因素对角质形成细胞的增生和皮肤的免疫有调节作用。临床研究证明,精神刺激可以诱发或加重某些皮肤病。保持良好的精神状态可使某些皮肤疾病得以缓解。正确地了解精神因素对皮肤的影响,对于某些皮肤病的防治具有指导意义。     

Oxidative stress in the pathogenesis of skin disease

Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, the skin is a major target for toxic insult by a broad spectrum of physical (i.e. UV radiation) and chemical (xenobiotic) agents that are capable of altering its structure and function. Many environmental pollutants are either themselves oxidants or catalyze the production of reactive oxygen species (ROS) directly or indirectly. ROS are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders including photosensitivity diseases and some types of cutaneous malignancy. ROS act largely by driving several important molecular pathways that play important roles in diverse pathologic processes including ischemia-reperfusion injury, atherosclerosis, and inflammatory responses. The skin possesses an array of defense mechanisms that interact with toxicants to obviate their deleterious effect. These include non-enzymatic and enzymatic molecules that function as potent antioxidants or oxidant-degrading systems. Unfortunately, these homeostatic defenses, although highly effective, have limited capacity and can be overwhelmed thereby leading to increased ROS in the skin that can foster the development of dermatological diseases. One approach to preventing or treating these ROS-mediated disorders is based on the administration of various antioxidants in an effort to restore homeostasis. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.     

Relationship between arsenic intake and internal malignant neoplasms

An attempt has been made to assess the carcinogenic effect of arsenic intake by analyzing a group of patients who were treated with arsenic for various skin diseases in the 1930s. When compared with the expected incidence of malignant internal neoplasms, based on figures obtained from the Danish Cancer Registry, a significant increase in the incidence of internal malignant neoplasms was observed in females with multiple basal cell carcinomas. A group comprising 53 patients with arsenic keratoses presented a considerable increase in the incidence of internal malignant neoplasms. However, these patients were so specifically selected that no regular statistical analysis can be made of this group. It may be said that arsenic has a carcinogenic effect even in the relatively small doses applied in dermatological therapy.     

UVA1治疗皮肤病的现状

在过去的30年中,UVA1因能进入皮肤深层诱导T细胞凋亡,下调多种细胞因子,激活内皮细胞并促进血管新生,逐渐被用于治疗各种皮肤疾病.目前有随机对照队列研究证据的疾病包括特应性皮炎、局限性硬皮病、系统性红斑狼疮,其他的适应证还有皮肤T细胞淋巴瘤、系统性硬皮病、胫前黏液性水肿、结节性痒疹等.相比其他光疗法,UVA1的近期不良反应相对较少,远期副作用目前尚无报道,仍需跟踪随访.     

局限性硬皮病的UVA-1和PUVA治疗进展

局限性硬皮病是一种结缔组织病,以局限性或弥漫性皮肤硬化或伴有内脏器官纤维化为特征,治疗方法包括物理治疗、药物治疗、紫外线和光化学疗法.其中紫外线和光化学疗法由于效果明显且不良反应小而成为近期研究的热点.大量临床及基础试验证明,紫外线可阻止纤维化进程,使硬化的皮肤斑块变软,尤其是UVA-1(340～400 nm)和光化学治疗PUVA更是取得了很好的效果.但是,目前的大多数试验在实验设计和效果评价方面尚没有统一的标准.

Abstract：

Localized scleroderma (LS) is a connective tissue disease characterized by localized or diffused sclerosis of skin with or without the fibrosis of various internal organs.The management of LS includes physical treatment,drugs and phototherapy.Because of high efficiency and few side effects,phototherapy has become a hot spot of recent researches.Numerous clinical and basic researches have proved that phototherapy can block fibrosis progression,induce softening of already existing sclerotic lesions by suppressing inflammatory cell infiltration.In particular,long wave ultraviolet A1 (340-400 nm) and photochemotherapy (PUVA) have shown a satisfactory effect.However,no uniform standard is available for the design of trials and evaluation of efficacy.     

特应性皮炎与Th17的研究进展

特应性皮炎是一种慢性复发性、炎症性皮肤疾病,病因复杂,涉及环境、基因及免疫之间的相互作用,其中免疫因素为特应性皮炎发病的重要原因之一。Th17作为一个不同于Th1和2的CD4＋T细胞亚群,已经证实,在特应性皮炎发生发展中起重要的作用。Th17通过分泌白介素-17、21、22等细胞因子诱发炎症反应及免疫反应,参与特应性皮炎发病的免疫学机制。通过物理治疗、药物治疗等手段,可以靶向抑制Th17及相关细胞因子,对治疗特应性皮炎有一定疗效。     

Analysis of the effect of a sunscreen agent on the suppression of natural killer cell activity induced in human subjects by radiation from solarium lamps

Previous studies in rodents have shown that ultraviolet radiation (UVR) may have direct effects on the immune system in the skin and at higher doses may induce systemic suppression of immune responses. We have previously shown that UVR from sun or solarium beds may induce systemic effects in human subjects. The purpose of the present study was to examine whether these systemic effects in human subjects could be prevented by use of commercially available sunscreen agents. Groups of 12 normal subjects were exposed to radiation from solarium lamps after application of a sunscreen agent or the base used in its preparation. Twelve half-hourly exposures induced a depression of natural killer (NK) cell activity against a melanoma and the K562 target cell which was not prevented by use of the sunscreen agent. Changes in functional activity were accompanied by a reduction in NK cell numbers assessed by Leu-11 monoclonal antibodies against the labile Fc receptor. Application of the sunscreen agent also did not protect against effects of solarium exposure on recall antigen skin tests and immunoglobulin production in vitro in pokeweed mitogen-stimulated cultures of B and T cells. These results suggest that further evaluation of the wave-length spectrum of UVR and the effectiveness of sunscreen agents in prevention of UVR-induced effects on the immune system is needed.     

Peripheral vascular diseases resulting from chronic arsenical poisoning

Drinking water contaminated by arsenic remains a major public health problem. Long-term arsenic exposure has been found to be associated with peripheral vascular diseases in a variety of studies. Reports of vascular effects of arsenic in drinking water, which span almost 100 years, have been published in Taiwan, Chile, Mexico, and China. This paper reviewed the association of peripheral vascular diseases resulting from arsenic exposure to drinking water from the clinical and pathological points of view. An endemic peripheral vascular disorder called "blackfoot disease" has been noticed in a limited area in Taiwan. This disease results in gangrene in the extremities. It has been associated with the ingestion of high concentrations of arsenic-tainted artesian well water. Epidemiological studies confirmed a dose-response relationship between long-term arsenic exposure and the occurrence of blackfoot disease. Whereas arsenic has induced various clinical manifestations of vascular effects in Chile, Mexico and China, they do not compare in magnitude or severity to the blackfoot disease found in Taiwan. The pathogenesis of vascular effects induced by arsenic is still controversial. The possible mechanisms include endothelial cell destruction, arsenic-associated atherogenesis, carotene and zinc deficiency, and/or some immunological mechanism. Microcirculatory assessments revealed that deficits of capillary blood flow and permeability exist in clinically normal skin of patients with chronic arsenical poisoning. The vascular effects of chronic arsenic poisoning may involve cardiovascular and cerebrovascular systems as well. In view of the increasing public health problems caused by arsenic exposure, vascular effects should be included in the future study of health effects of arsenic.     

T淋巴细胞在白癜风免疫学发病机制中的研究进展

白癜风是一种皮肤色素脱失性疾病,以表皮功能性黑素细胞破坏为主要特征.目前研究支持其发病与遗传、免疫、氧化应激、神经-体液等机制有关.其中,T淋巴细胞介导的免疫反应在白癜风发病中起重要作用.CD4+T细胞亚群Th1、Th2、Th17、调节性T细胞通过分泌多种细胞因子调节其他免疫细胞的功能、诱导黑素细胞凋亡.CD8+T细胞可经由细胞毒作用直接杀伤黑素细胞.另一方面,自身耐受功能障碍、自身反应性T细胞数量和活性的增加可以增强T细胞对黑素细胞的免疫反应.除此以外,恒定型自然杀伤T细胞、记忆性T细胞等对白癜风免疫相关发病有一定的作用.     

Liposomal systems as drug delivery vehicles for dermal and transdermal applications

Enhancement strategies are necessary to improve the dermal/transdermal bioavailability of drugs applied to the skin due to its amazing barrier, the stratum corneum. Strategies to overcome this barrier, thus improving drug release to the skin include the use of penetration enhancers, specific delivery systems, supersaturated solutions and physical methods (iontophoresis, electroporation and ultrasound). Delivery of active agents to the skin by liposomal carriers has improved topical therapy in the field of dermatology. The interest in these carriers is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Particularly, in recent years liposomes have been shown to be a promising drug-delivery system to the skin. Their use may produce several-fold higher drug concentrations in the epidermis and dermis and lower systemic concentrations when compared to conventional dosage forms. On the other hand, special characteristic vesicles like ethosomes, transfersomes and niosomes may be potential transdermal delivery systems for ionic molecules and polypeptides.