消痤Ⅰ号冲剂对金黄地鼠性激素水平与皮脂腺斑组织形态的影响

目的探讨消痤Ⅰ号冲剂治疗寻常痤疮的作用机理.方法选用金黄地鼠侧背部皮脂腺斑作为动物模型,把金黄地鼠随机分成3组,分别用消痤Ⅰ号冲剂、蒸馏水、泰尔丝灌胃,用游标卡尺测量左右皮脂腺斑的最大横径和最大纵径,采集血清检测睾酮、雌二醇的激素水平,观察皮脂腺斑的显微结构.结果3组皮脂腺斑的最大横径×最大纵径的比较无显著差异;消痤Ⅰ号冲剂组较蒸馏水组睾酮水平明显降低;组织形态学也证实,消痤Ⅰ号冲剂组的皮脂腺厚度较蒸馏水组、泰尔丝组薄,排列较松散,液化囊形成数目多.结论消痤Ⅰ号冲剂可抑制皮脂腺的功能,从而影响皮脂腺斑的增生,疗效优于泰尔丝组.     

Possible Existence of Melanocytes or Melanoblasts in Human Sebaceous Glands

Background

Melanocytes are present in both basal epidermis and hair follicles. Melanocyte stem cells have been found in hair follicle bulge. During embryogenesis, the outer cells of the bulge differentiate into the sebaceous gland (SG) and proliferate.

Objective

To identify and determine the distribution and morphological characteristics of melanocytes in human SGs.

Methods

A total of 171 biopsy specimens of face and scalp were studied. Of these specimens, 103 samples contained SGs. We conducted a retrospective review of slides stained with H&E, F-M, anti-S100, anti-c-kit, anti-HMB-45, anti-CD1a, anti-MITF, and anti-tyrosinase. The presence and distribution of melanocytes in human SGs was also evaluated by electron microscopy. In addition, melanocytes were isolated from SGs for primary culture.

Results

S-100-positive cells were observed mainly at the periphery of SGs in 34 of 54 specimens. We did not find F-M-positive and HMB-45-positive cells in SGs. CD1a-positve cells were identified in two specimens. We also found c-kit-, MITF-, and tyrosinase-positive cells in SGs. Electron micrograph showed the presence of melanocytes in the suprabasal portion of SGs. These melanocytes showed fewer melanin-containing granules than the melanocytes of basal epidermis. However, the individually distributed melanosomes in suprabasal melanocytes were larger than those in epidermal melanocytes. Primary culture of melanocytes derived from SGs showed morphologically homogeneous, slender cell bodies with few dendrites.

Conclusion

Our study confirms the presence of non-melanogenic melanocytes and Langerhans cells in human SGs. In addition, the characteristics of the melanocytes in SGs were found to be different from those of the epidermal melanocytes.     

Sebaceous glands in acne patients express high levels of neutral endopeptidase

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. To examine the possible involvement of neurogenic factors in the etiology of acne, we used immunohistochemistry to compare the distribution of SP-containing nerve fibers around sebaceous glands and the expression of neutral endopeptidase in sebaceous acini of the facial skin of acne patients and of healthy subjects. More numerous substance P immunoreactive nerve fibers in close apposition to the sebaceous glands and an increase in expression of neutral endopeptidase in sebaceous acini were observed in acne patients compared with the controls. Immunoelectron microscopy revealed that the subcellular localization of neutral endopeptidase was restricted to the Golgi apparatus and the endoplasmic reticulum within sebaceous germinative cells. In addition, in vitro experiments using an organ culture system demonstrated that substance P induced expression of neutral endopeptidase in sebaceous glands in a dose dependent manner. This study reveals that substance P and its degrading enzymes are involved in the pathogenesis of acne, which in turn might partially explain the pathologic significance of neurogenic and psychogenic aspects in the disease process.     

Presenile diffuse familial sebaceous hyperplasia successfully treated with low‐dose isotretinoin: A report of two cases and review of the published work

Presenile diffuse familial sebaceous hyperplasia (PDFSH) presents as extensive yellowish papules with central umbilication on the face without involvement of periorificial regions and occurs in adolescents or young adults with a positive family history. Thirteen cases of PDFSH have been reported in the English‐language published work, 10 of which responded to oral isotretinoin from 0.5 to 1 mg/kg per day but recurrences were often observed. Herein, we report two cases of PDFSH, which were successfully managed without recurrence with prolonged low‐dose isotretinoin (0.2 mg/kg per day, a cumulative dose of 41 and 64 mg/kg, respectively). Treatment protocols among different published works were reviewed to verify the efficacy of isotretinoin.     

丹参酮对人皮脂腺细胞增殖、脂质合成及雄性激素受体mRNA表达的影响

目的探讨丹参酮治疗痤疮的机制。方法用四甲基偶氮唑盐(MTT)法检测不同浓度的隐丹参酮、丹参酮ⅡΑ在作用24、48及72h对SZ95细胞增殖的影响;用流式细胞仪检测尼罗河红荧光染色的SZ95细胞中脂质含量的变化;用半定量逆转录PCR(RT-PCR)检测药物对SZ95细胞中AR mRNA表达的影响。结果隐丹参酮浓度在0.5～12.5μmol/L之间呈时间和剂量依赖性抑制SZ95细胞增殖,其半数抑制浓度为7.473μmol/L(48h)和2.146μmol/L(72h);丹参酮ⅡΑ浓度在1.25μmol/L～12.5μmol/L呈时间和剂量依赖性抑制SZ95细胞增殖,其半数抑制浓度为6.021μmol/L(48h)和2.250mol/L(72h)。0.125μmol/L丹参酮ⅡΑ作用SZ95细胞48h后,尼罗河红荧光染色的平均荧光强度较对照组明显下降(P<0.05);此外,1μmol/L和0.1μmol/L隐丹参酮以及1μmol/L丹参酮ⅡΑ对SZ95细胞AR mRNA的表达显示出抑制作用(P<0.01,P<0.05,P<0.01)。结论隐丹参酮、丹参酮ⅡΑ可能通过直接抑制皮脂腺细胞的增殖、脂质合成或间接下调皮脂腺细胞雄激素受体mRNA的表达而具有抗皮脂腺活性的作用,这可能是丹参酮治疗痤疮的机制之一。     

Gender differences and effects of sex steroids and dehydroepiandrosterone on androgen and oestrogen alpha receptors in mouse sebaceous glands

BACKGROUND: It is generally believed that the sebaceous gland is an intracrine organ which synthesizes its own active hormones to meet its local needs. OBJECTIVES: To understand further the mechanisms of sex steroid action in mouse sebaceous glands. METHODS: We have used immunocytochemistry to examine the expression of oestrogen receptor alpha (ERalpha) and androgen receptor (AR) in mouse sebaceous glands. RESULTS: In intact males AR is exclusively localized in the nuclei of basal and mature sebocytes, while in females it is present at a lower level in both the nuclei and the cytoplasm. Three weeks following gonadectomy (GDX), a marked decrease of AR labelling is observed in male sebocytes, while no change occurs in female sebocytes. Treatment of GDX animals with dihydrotestosterone (DHT) or dehydroepiandrosterone (DHEA) increases AR expression, while 17beta-estradiol (E2) decreases the stimulatory effect of DHT and DHEA. ERalpha is detected only in basal sebocytes of intact females but not in males. Following treatment with E2, ERalpha expression becomes visible in GDX males while DHT and DHEA inhibit the effect of E2. CONCLUSIONS: The present data show gender differences and demonstrate that DHT, E2 and DHEA exert specific effects on the expression of AR and ERalpha in mouse sebocytes.     

Modelling the remission of individual acne lesions in vitro

BACKGROUND: Acne lesions spontaneously remit, but the mechanism of this remission has not been elaborated. It is known, however, that the remission is associated with a de-differentiation of sebocytes, causing a cessation of sebum secretion specific to that particular pilosebaceous unit. We have previously described the cytokines that will promote in vitro the lesions of acne. OBJECTIVES: To show that those same cytokines may also promote a de-differentiation of sebocytes analogous to that seen during remission of some lesions. METHODS: Human chest sebaceous glands were maintained in vitro as whole organs. We then chronicled the effects of the appropriate cytokines and growth factors on the glandular rates of (i) lipogenesis and (ii) DNA synthesis, as well as on (iii) glandular morphology, (iv) the expression patterns of the proliferation marker Ki-67, (v) keratinocyte-specific markers, and (vi) the sebocyte marker epithelial membrane antigen. RESULTS: We have shown that the same cytokines that promote comedogenesis (interleukin-1alpha), expression of infundibular intercellular adhesion molecule-1 and human leucocyte-associated antigen-DR (tumour necrosis factor-alpha and interferon-gamma), and infundibular disruption (epidermal growth factor/transforming growth factor-alpha) in human infundibula in vitro, will also inhibit sebaceous lipogenesis in vitro and will also induce, histologically, a de-differentiation of human sebocytes into a keratinocyte-like phenotype. CONCLUSIONS: These results confirm our hypothesis that the cytokines that induce the infundibular changes in acne may also inhibit the secretion of lipid from the sebaceous gland and thus, on diffusing down to the gland, contribute to the remission of the individual lesions. These findings help to explain the known natural history of the disease.     

An update on the microbiology,immunology and genetics of seborrheic dermatitis

The underlying mechanism of seborrheic dermatitis (SD) is poorly understood but major scientific progress has been made in recent years related to microbiology, immunology and genetics. In light of this, the major goal of this article was to summarize the most recent articles on SD, specifically related to underlying pathophysiology. SD results from Malassezia hydrolysation of free fatty acids with activation of the immune system by the way of pattern recognition receptors, inflammasome, IL-1β and NF-kB. M. restricta and M. globosa are likely the most virulent subspecies, producing large quantities of irritating oleic acids, leading to IL-8 and IL-17 activation. IL-17 and IL-4 might play a big role in pathogenesis, but this needs to be further studied using novel biologics. No clear genetic predisposition has been established; however, recent studies implicated certain increased-risk human leucocyte antigen (HLA) alleles, such as A*32, DQB1*05 and DRB1*01 as well as possible associations with psoriasis and atopic dermatitis (AD) through the LCE3 gene cluster while SD, and SD-like syndromes, shares genetic mutations that appear to impair the ability of the immune system to restrict Malassezia growth, partially due to complement system dysfunction. A paucity of studies exists looking at the relationship between SD and systemic disease. In HIV, SD is thought to be secondary to a combination of immune dysregulation and disruption in skin microbiota with unhindered Malassezia proliferation. In Parkinson's disease, SD is most likely secondary to parasympathetic hyperactivity with increased sebum production as well as facial immobility which leads to sebum accumulation.     

Sebaceous Adenomas,Squamous Cell Carcinoma and Skin Infections in a Patient with Carcinoma of the Colon,Rectum and Bladder

Sebaceous adenomas and squamous cell carcinoma developed in a male patient in addition to viral, mycotic and bacterial infections, several years after the removal of three malignant tumors from his lower gastrointestinal and urinary tract. Skin tests with trichophytin, candidin, and mixed bacteria were negative. Various aspects regarding cutaneous changes associated with colorectal and bladder carcinomas are discussed.     

Androgen-induced delay of hair growth in the golden Syrian hamster

The golden Syrian hamster flank organ has been used to study the stimulatory effect of androgens on sebaceous glands and hair. Androgens cause the sebaceous glands and hair follicles in this organ to grow. We have made the novel observation that exogenously administered androgen, testosterone propionate (TP), suppresses hair growth in the area surrounding the flank organ. When given in a time-release (systemic) subcutaneous dosage form (pellet), 25 mg TP inhibited the regrowth of clipped hair in peri-flank organ skin for up to 21 days; however, by 28 days hair grew back to the same extent as in controls. The peak serum level of testosterone in TP-treated animals occurred at 14 days, and declined thereafter. When two separate TP pellets (25 mg/pellet) were administered 14 days apart in order to maintain high serum levels for 28 days, the amount of hair regrowth after 35 days was identical to animals receiving a single TP pellet or placebo. This suggests that the systemic level of testosterone was not the only factor in hair regulation. Hair growing within the flank organ appeared to be unaffected by TP administration. In the golden Syrian hamster, androgen, as in humans, can exert stimulatory and inhibitory effects on hair growth depending on the body site. We conclude that this animal model could serve as a useful system to investigate the mechanisms responsible for the opposing effects of androgen on hair growth.     

The Effect of Methotrexate on the Expression of a Cysteine Protease Inhibitor (Type 2 Cystatin) in Rat Sebaceous Glands

The purpose of this study was to assess whether rat cystatin S, a cysteine proteinase inhibitor, is present in rat sebaceous glands, and to measure the effects of methotrexate on the expression of cystatin in these glands. With methotrexate treatment, the number of skin sebaceous cells expressing cystatin increased from 13.9% to 34.3% (P<.05). A smaller increase (from 15.3% to 23.9%; P=.1) was observed in Zymbal sebaceous glands. Type 2 cystatin could not be detected in the major salivary glands, nor in trachea, lung, stomach, small intestine, large intestine, spleen, liver, kidney, or pancreas, in any of the rats given either saline or methotrexate. Our results suggest that type 2 cystatin is a constituent of normal sebaceous glands, and that the amount of cystatin present in these glands increases with methotrexate administration. We speculate that, in addition to the protective functions ascribed to sebaceous lipids, sebum may augment the physical barrier of skin through secretion of cysteine proteinases that may be pharmacologically modulated.     

盐酸小檗碱、黄芩苷和苦参碱对SZ95皮脂腺细胞增殖及脂质合成的影响

目的 研究中药单体盐酸小檗碱、黄芩苷和苦参碱对永生化人皮脂腺细胞(SZ95)增殖及脂质合成的影响.方法 倒置显微镜观察药物作用24h后细胞形态变化.确定药物的毒性浓度;用四甲基偶氮唑盐(MTT)法检测不同浓度的药物在作用24、48及72h对SZ95细胞增殖的影响;用流式细胞仪检测药物作用48h后尼罗红染色的SZ95细胞内脂质含量的变化.结果 毒性浓度黄芩苷为1×10^-3mol/L,盐酸小檗碱为1×10^-4mol/L,苦参碱在1×10^-3mol/L以下细胞未见形态变化.MTT法显示,盐酸小檗碱呈时间和剂量依赖性抑制SZ95细胞的增殖,IC50值48h为2.9×10^-5mol/L,72h为1.4×10^-5mol/L;黄芩苷在5×10^-4mol/L以下、苦参碱在1×10^-3mol/L以下对SZ95细胞增殖无影响.1×10^-4mol/L儿黄芩苷作用48h使细胞平均荧光强度下降30.1%(P<0.05);1×10^-6mol/L盐酸小檗碱下降7.9%,但差异无统计学意义(P>0.05);1×10^-3mol/L苦参碱则促进脂质合成(26.9%).结论 盐酸小檗碱、黄芩苷等中药单体可能具有抑制皮脂腺细胞增殖或脂质合成的作用.