Expression of IFNγ, coexpression of TNFα and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare

Abstract Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-á as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-· and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3⁺ lymphocytes express interferon-á. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3⁺ lymphocytes and CD68⁺ macrophages contained tumor necrosis factor-·. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-· coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-á⁺ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-α and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells. Received: 23 November 1999 / Received after revision: 28 March 2000 / Accepted: 14 April 2000     

Clinical and pathological features of 31 cases of lipedematous scalp and lipedematous alopecia

Little is known about lipedematous scalp (LS) and lipedematous alopecia (LA). We investigated the clinical and histopathological features of LS and LA with a 7-year retrospective re-evaluation of 31 patients. 23 cases were LS and 8 LA, with 25 females and 6 males. The overweight and obese groups contained 15 patients with 16 within the normal weight range. Scalp thickness varied between 9-18 mm in our patients by magnetic resonance imaging. Thickening of the subcutaneous adipose tissue layer was present in all cases. Dermal edema was seen in 22 patients, lymphatic dilatation in 17 and elastic fiber fragmentation in 21. When the relationship between dermal edema and elastic fibers was investigated, elastic fiber fragmentation was found in 86.4% of cases with dermal edema. Collagen fragmentation and coarsening were seen in two cases, and collagen was normal in 24 cases. The number of follicles was decreased in 9 cases and normal in 17. The clinical and histopathological findings were not statistically different between LS and LA groups (p>0.05). The majority of the patients in our study were females, suggesting an underlying hormonal pathology. The association with obesity suggested that anatomical differences can be present in lipid distribution. Dermal edema and lymphatic dilatation suggested the primary pathology is lymphatic system.     

International of Dermatology and Venereology征稿启事

International of Dermatology and Venereology是中国大陆第一本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jefferson University的JouniUitto教授担任名誉主编。目前已经建成了一个国际性编辑团队,除了在中国医学科学院皮肤病医院建立本土的编辑部以外,分别在美国Thomas Jefferson University和英国King's College London建立了海外办公室。国际编委会由来自8个国家20位知名皮肤病学专家组成,覆盖遗传学、皮肤病理、疱病、黑素瘤、皮肤镜等多个领域.     

International Journal of Dermatology and Venereology征稿启事

International Journal of Dermatology and Venereology是中国大陆第一本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jefferson University的JouniU itto教授担任名誉主编。目前已经建成了一个国际性编辑团队,除了在中国医学科学院皮肤病医院建立本土的编辑部以外,分别在美国Thomas Jefferson University和英国King's College London建立了海外办公室。国际编委会由来自8个国家20位知名皮肤病学专家组成,覆盖遗传学、皮肤病理、疱病、黑素瘤、皮肤镜等多个领域。     

International Journal of Dermatology and Venereology 征稿启事

International Journal of Dermatology and Venereology是中国大陆第一本皮肤性病学方面的开放获取英文期刊,旨在搭建-个高水平的国际学术交流平台,本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jefferson University的Jouni Uitt。     

International Journal of Dermatology and Venereology征稿启事

Ientiond Joural of Dermatalogy and Venerealono是中国内地第一本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教投担任主编,美国Thomus Jeferom Universily的Joumi Uito教授担任名誉主编。     

International Journal of Dermatology and Venereology征稿启事

International Journal of Dermatology and Venereology是中国内地第一本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jefferson University的Jouni Uitto教授担任名誉主编。     

International Journal of Dermatology and Venereology征稿启事

International Journal of Dermatology and Venereology是目前中国(未包括香港地区、台湾地区)唯一一本皮肤性病学开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院王宝玺教授担任主编。国际编委会由来自10个国家20位知名皮肤病学专家组成,覆盖遗传学、皮肤病理、疱病、黑素瘤、皮肤镜等众多领域。     

International Journal of Dermatology and Venereology 征稿启事

International Journal of Dermatology and Venereology是中国大陆第一本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jefferson University的Jouni Uitto教授担任名誉主编。     

International Journal of Dermatology and Venereology征稿启事

International Journal of Dermatology and Venereology是中国内地第--本皮肤性病学方面的开放获取英文期刊,旨在搭建一个高水平的国际学术交流平台。本刊由中国医学科学院整形外科医院党委书记王宝玺教授担任主编,美国Thomas Jfferson University的Jouni Uitto教授担任名誉主编。目前已经建成了-个国际性编辑团队,除了在中国医学科学院皮肤病医院建立本土的编辑部以外.分别在美国Thomas Jefferson University和英国King's Collge London建立了海外办公室。国际编委会由来自8个国家20位知名皮肤病学专家组成.覆盖遗传学、皮肤病理、疱病黑素瘤皮肤镜等多个领域。     

Development and characterization of phyto-vesicles of β-sitosterol for the treatment of androgenetic alopecia

Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of alopecia, which affects millions of men and women worldwide, and is an androgen driven disorder. To study the effect of β-sitosterol phyto-vesicles on AGA, the testosterone-induced alopecia model was used. For the study, the albino rats were used and the period of study was 21 days. β-Sitosterol is a phytosterol which is chemically similar to cholesterol. This compound was found suitable for the preparation of phyto-vesicles by the process involving its complexation with phosphatidyl choline. Pharmacokinetic studies of β-sitosterol reveal its poor absorption through the intestine. The objective of the present study is to enhance the bioavailability of β-sitosterol by its complexation with phosphatidyl choline and then to formulate it as phyto-vesicles for the treatment of alopecia. The complex of β-sitosterol was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, TLC, UV, IR and NMR spectroscopy. This complex was then formulated as phyto-vesicles and then characterized. The results revealed that effect on alopecia is better in case of phyto-vesicles as compared to the complex, physical mixture and the β-sitosterol itself. Enhanced bioavailability of the β-sitosterol complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and β-sitosterol, in terms of better absorption and improved activity for the treatment of alopecia.     

Levels of matrix metalloproteinase-2, −9 and −8 in the skin,serum and saliva of smokers and non-smokers

Smoking induces skin ageing, affects wound healing and inflammatory responses in skin and mucous membranes but the mechanisms behind these adverse effects of smoking are not clear. The objective was to elucidate the mechanisms of smoking-related tissue damage, by comparing the levels of matrix metalloproteinases (MMPs) −2, −9, and −8 in the skin, serum and saliva of smokers and non-smokers. The study population consisted of 47 current smokers and 51 non-smokers, all males of Finnish origin. Skin samples from the upper inner arm were frozen in liquid nitrogen. Levels of MMP-2 and MMP-9 protein in the skin were assessed by zymography and MMP-8 isoforms were determined by Western blotting. From the serum samples, MMP-2 and MMP-9 were assessed by zymography and MMP-8 levels by time-resolved immunofluorometric assay (IFMA). From the salivary samples, MMP-8 levels were analysed by IFMA and MMP-9 levels by capture activity assay. In skin tissue, lower levels of both the pro and active forms of MMP-9 and of the active forms of MMP-8 were found in the smokers compared to the non-smokers. In serum, higher levels of proMMP-2 and proMMP-9 were found in the smokers compared to the non-smokers (P=0.001 and P<0.001, respectively), whereas MMP-8 levels did not differ significantly between the groups. Active forms of MMP-9 and MMP-2 could not be found in serum. In saliva, the amount of total MMP-9 was significantly lower in the smokers (156.0 U/ml) compared to the non-smokers (223.9 U/ml, P=0.032), whereas the levels of MMP-8 or active MMP-9 did not differ significantly between the groups. We conclude that smoking alters the levels of matrix metalloproteinases in skin tissue, serum and saliva, which may affect the turnover of extracellular matrix of skin even though the clinical impact of our findings is not clear.     

评介《Color Atlas and Synopsis of Blistering and Pustular Diseases》

喜读人民卫生出版社出版发行的(水疱性与脓疱性皮肤病的彩色图谱与概要).该书是由中国医学科学院皮肤病医院靳培英教授主编.靳教授治学严谨,博览群书,医术高明,患者至上,是中国医学科学院的十大名医之一.靳教授从医五十余载,特别对大疱性及脓疱性皮肤病有很深的造诣,本书是她丰富临床经验的概括与总结.全书内容翔实、文字简洁,图文并茂、印刷精良,对自身免疫性大疱性皮肤病及遗传性大疱性皮肤病均有精辟的论述,此外,对各类临床上以水疱、大疱及脓疱为特点的皮肤病也都作了介绍,使本书具有很高的可读性及实用性.     

Clinical and histopathological characters of 22 cases of subungual melanoma北大核心

Objective: To analyze the clinical and histological characters of subungual melanoma. Methods: Retrospective analysis of 22 cases of subungual melanoma was made at the Department of Dermatology, Xijing Hospital from 2003 to 2009. Results: The clinical data showed all patients were adult (9 males, 13 females). Nine lesions were located on thumbs, 5 on index fingers, 4 on the first toes and 4 distributed on other fingers or toes. Sixteen cases showed darkening of skin around nail, 10 damage of nail plate, nodules or ulceration, 6 cases presented as melanonychia. Histological data showed 10 cases were melanoma in situ and 12 invasive melanoma. Conclusion: Subungual melanoma always appears in adults, especially in the senile. Thumbs, index fingers and the first toes were the most predilection sites. Its early stage always presented as broad melanonychia with uneven color. Its late stage always involves skin around the nail, or forms nodules or ulceration. Subungual melanoma in situ showed proliferations of single cells distributed at very high level in matrix or nail bed. The neoplasm cells always show dense chromatin, prominent dendrites and contained coarse pigment. Subungal invasive melanoma involves dermis and shows infiltrative growth pattern, maturation of melanocytes is not existed and cellular polymorphism is prominent.     

Parallel development and course of pheochromocytoma and giant squamous cell carcinoma of the leg: a new paraneoplastic syndrome?

Paraneoplastic syndromes (PS) are diseases or symptom complexes associated with malignancy, usually of internal origin, but not directly related to mass effects, invasion, or metastatic spread. Rarely, cutaneous squamous cell carcinoma (SCC) may be associated with PS. We present a patient with a giant SCC located on the right leg and a pheochromocytoma. Considering the concurrent onset and parallel course of both pheochromocytoma and SCC in this patient, and the complete resolution of the endocrine abnormalities after resection of the skin tumor, it was possible to conceive of the pheochromocytoma as a paraneoplastic phenomenon. To our knowledge, this association has not been previously described.     

Role of Oxidative and Nitrosative Stress in Pathophysiology of Toxic Epidermal Necrolysis and Stevens Johnson Syndrome—A Pilot Study

Background:

Oxidative and nitrosative stress caused by drug metabolism may be a trigger for keratinocyte apoptosis in the epidermis seen in toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS).

Aims:

To estimate oxidative damage in the serum and to examine the role of nitric oxide in mediating epidermal damage in patients with TEN and SJS.

Materials and Methods:

A prospective study was conducted among TEN and SJS patients and controls in a tertiary care center between January 2006 and February 2010. Patients with a maculopapular drug rash without detachment of skin constituted the control group 1 (drug exposed). Patients without a drug rash constituted the control group 2 (drug unexposed). The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were measured. Two-group comparison with the non-parametric Mann–Whitney U test was used. Significance of differences if any was established using Pearson''s Chi-square test.

Results:

Ten patients in the SJS-TEN group (study group), 8 patients in control group 1 and 7 patients in control group 2 were included. More than one drug was implicated in 4/10 patients in group 1 and 3/8 patients in group 2. SCORTEN of 0, 1 and 3 at admission were seen in 2, 6 and 2 patients, respectively. The serum values of protein carbonyls, malondialdehyde, conjugated diene and nitrates were not significantly increased in the study group when compared to the controls.

Conclusions:

There was no elevation of oxidative stress markers in patients with TEN and SJS as compared to the control population.