Mechanobiology and force transduction in scars developed in darker skin types

BACKGROUND: Scarring is a complex process involving many cell types, cytokines and biological pathways including mechanobiology. Some subtle mechanical properties of skin can be assessed by measuring the speed of ultrasound shear wave propagation. The orientation of abnormal skin tension forces can be visualized, particularly in darker skin types, using dermoscopy showing distinct patterns of rete ridges' conformation. AIM: To assess some mechanobiological features of scars in darker skin types. PATIENTS AND METHODS: Large atrophic and hypertrophic surgical scars were examined on the trunk of 35 darker skin subjects. The surrounding skin was used as a comparator. Dermoscopic aspects were recorded. Resonance running time measurements (RRTM) were performed using a shear wave propagation device (Reviscometer). They were performed in four specific directions at given angles with regard to the long axis of the scar. The minimum, maximum and mean RRTM values were recorded at each site. RESULTS: Dermoscopy revealed patterns of melanin deposits in scars distinct from the normal honeycomb network seen in the surrounding skin. Hypertrophic scars showed a patchy pattern of large macular melanoderma dispersed in a lighter background. In these cases, low RRTM values were obtained with little variations according to the orientation of the measurements. By contrast, atrophic scars showed a streaky laddering melanotic pattern under dermoscopy. Higher RRTM values were often obtained, particularly in the transversal direction of the scars. Mechanical anisotropy was greater in the atrophic scars compared with the normal skin. DISCUSSION: Darker skin types represent a model for visualizing the main orientation of the epidermal rete ridges. A correlation was found between the pattern of melanized rete ridges of scars and the main orientation of the intrinsic forces in the skin.     

A simple organ culture method for differentiation of melanocytes in mouse embryonic skin using “origami” membrane filter

Summary A simple organ culture method for culturing embryonic skin was developed. A piece of skin with a part of the neural tube from mouse embryo (11 to 12 d) was placed on a 25 mm d membrane filter. The filter was folded to wrap the explant and inserted into glass tubing. The explant and filter in the glass tubing were placed in a rotating tissue culture tube containing 5 ml culture medium (Ham's F12 supplemented with 15 to 20% fetal bovine serum) and filled with a mixture of 95% air:5% CO₂. In explants cultured for 6 d fully differentiated melanocytes were observed in the epidermis.     

An immunohistochemical and radioimmunological study of the distribution of [met5]- and [leu5]-enkephalin in the gastrointestinal tract.

The identification of opiate-like substances in extracts of the gastrointestinal tract and nervous system of vertebrates suggests that the known endogenous opiate-like peptides [Met⁵]- and [Leu⁵]-enkephalin might have a role in neurotransmission. In this study the gastrointestinal tract of guinea-pigs, rats and hamsters was examined by the immunoperoxidase-bridge method using specific antisera raised against [Met⁵]- and [Leu⁵]-enkephalin. Immunostained nerve fibers were most numerous in Meissner's plexus of the duodenum and in the circular muscle layer of the stomach and rectum of the guinea-pig. Nerve fibers in the guinea-pig esophagus and cardia of the stomach stained with [Met⁵]- but not with [Leu⁵]-enkephalin antiserum. Staining was not observed in any epithelial cells. The regional distribution of these peptides was also examined by radioimmunoassay of extracts of the gut of guinea-pigs and rats. The highest concentrations of [Met⁵]- and [Leu⁵]-enkephalin were found in extracts of guinea-pig duodenum at a ratio of 11:1, respectively.These findings provide evidence for an enkephalinergic nervous system in the gastrointestinal tract.     

Melanocytes in the Testes of Eupemphix nattereri (Anura,Leiuperidae): Histological,Stereological, and Ultrastructural Aspects

Ectothermic vertebrates have a well‐developed system of melanin‐containing cells, which localize in several organs and tissues and compose an extracutaneous pigmentary system. This research aimed at characterizing histological and ultrastructural patterns of pigmented cells in the testes of the anura Eupemphix nattereri (Steindachner, 1963), including the stereological and quantitative evaluation of this cell type in the gonads. Ten adult males were collected in Nova Itapirema, São Paulo, Brazil, and submitted to morphological studies with light and transmission electron microscopy. The testis presents a great number of large cells with many brown granules and long cytoplasmic processes. The pigmented cells found in the testis are structurally similar to melanocytes, characterized by large amounts of melanosomes. The cells may be in intimate contact with the same cell type, with myoid cells surrounded by a large amount of collagen fibers, Leydig cells, and next to fibroblasts. The distribution and amount of extracutaneous melanocytes is variable when other organs and membranes are analyzed, allowing the establishment of species‐specific patterns for the extracutaneous pigmentary system. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.     

补骨脂对体外黑素细胞黏附和迁移的作用

目的 :研究补骨脂对黑素细胞黏附和迁移的影响。方法 :用补骨脂处理黑素细胞 ,检测其黏附于牛血清纤维结合素和通过微孔滤膜的细胞数量并与生姜和未经药物处理的黑素细胞比较。结果 :补骨脂可显著促进黑素细胞黏附于牛血清纤维结合素和通过微孔滤膜并呈剂量依赖关系 ,但当补骨脂浓度超过 0.2mg·L^-1时这种作用未见增加。补骨脂浓度在 0.01mg·L^-1时 ,黑素细胞黏附并无显著增加 ,但对迁移的影响已可见统计学差异 (P <0.01)。生姜则不具有这样的作用。结论 :在体外 ,补骨脂能明显促进黑素细胞的黏附和迁移 ,这至少可以部分解释应用补骨脂治疗白癜风是有效的。     

Facial-Skin Hyperpigmentation： Histological and Computer Geometric Assessment

Hyper-pigmentation is a common, acquired dermatological skin-disorder manifesting and identifiable as irregular brown or greyish-brown facial discolouration, and sometimes referred to as melanosis, melasma or hypermelanosis. Purpose and Objective： To identify the site of melanin deposition in skin-layers regarding facial hyper-pigmentation, based on a histological study of full-thickness skin-facial biopsies in aged Caucasian-cadavers. Hypothesis： Recalcitrant hyper-pigmentation, is chiefly characterised by hyper-melanosis restricted to the dermal-layer of the integument. Method： The histological features of facial hyper-pigmentation and solar-lentigenes were evaluated in a pilot-study of 5-randomly selected Caucasian-cadavers with pigmentation （15 facial biopsies）, ranging in age between 75 and 102 years （mean 77-years）. Selection-criteria included, both genders, age 〉 75, focal and confluent hyper-pigmented lesions, involving sun-exposed areas of skin （centrifacial, scalp, malar, mandibular and cervical）. Study groups included （Grp-1： Control skin-histology in otherwise normal aged, human-cadavers; Grp-2： Histology of pigmented facial skin-lesions in man; Grp-3： Comparative histological skin-controls in non-human primates）. No obvious hepatic disease was evident in the cohort studied. Twenty-five histological controls were obtained from non-pigmented areas. Histological evaluation of full-thickness skin-biopsies （including the lesion, edge and peri-]esion skin）, was under a Leitz~-light-microscope, and staining included H＆E, Masson-trichrome, Masson-fontana, Alcian-blue and Verhoef technology. Histological-scoring used was on histological deposition of melanin in skin-layers： epidermal, dermal, mixed, and indeterminate melanin-deposition （score 1-4）. Controls included cadaveric skin-biopsies of human races of colour and non-human primate, Cercopethicus Aethiops （latter is known to have predominantly dermal-melanin deposition）. Pigmented and non-pigmented areas were compared in both species. Results： The majority of clinically visible individual and confluent areas of hyper-pigmentation studied were maeroscopically present on the forehead, frontal scalp in hair-receded cadavers, molar and temporal zones. Histologically, documented features of age-related changes without pigment were present in almost all the embalmed cadaver-skins, with a melanin-score of 1. Computer enhanced skin geometry and biometrics confirmed the presence of an aged-skin, pigmentation and features of solar damage. The human embalmed-tissue was well preserved and minimal autolytic changes were present. Special stains of full-thickness biopsies （Masson-Fontana）, showed that melanin in the subhuman-primate is lodged in the deep dermis （reticular dermis）, within the extra-cellular matrix （ECM） and superficial to the hypodermal adipose-tissue （melanin-score 3）. Fifteen pigmented lesions studied in five （5） aged-cadavers （forehead, molar and mandibular areas） all showed predominantly epidermal-deposition of melanin in the basal, suprabasal and stratum corneum with tiny focal areas of dermal melanosis in single-cell macrophages in the papillary-dermis but not reticular-dermis （melanin-score 2）. A melanin-deposition localization ratio of epidermis to dermis was approximately 98 to 2% in cadavers with hyper-pigmentation. Conclusion： The skin-strata localization of the melanin with regards hyper-pigmentation of the face and forehead in this aged, human adult Caucasian, cadaveric-study, was predominantly in the epidermis and sparse in the papillary dermis.     

毛囊内黑素细胞研究进展

黑素母细胞,即黑素前体细胞,起源于神经嵴,部分迁移到毛囊,在毛囊内进一步分化成产色素的黑素细胞。毛囊内包含存在于外根鞘的、可作为黑素细胞“贮库”的未分化的黑素母细胞,以及毛球部有活性的黑素细胞。毛囊黑素细胞数目、寿命、黑素生成活性与毛发生长周期紧密结合在一起。灰发是由于毛囊内黑素干细胞不能完全维系所致。     

Ultrastructure of Amelanotic Melanocytes from Human Hair Follicles

To investigate the ultra structure of amelanotic melanocytes （AMMC）. Methods： The hair follicles obtained from normal human scalp by 0.50% collagenase type V treatment were washed with 0.1 mol/L phosphate buffer salt （PBS）. Hair-follicle cell suspensions were prepared by trypsin treatment and cultured in melanocyte medium. Remaining keratinocytes were removed by differential trypsinization. 100μg/ml geneticin was used to eliminate the contaminating fibroblasts. At third passage, the cells were trypsinized, and then washed in phosphate-buffered saline and processed for transmission electron microscopy. Results： Under transmission electron microscope, the cultured cells showed round or oval shape, with single large nuclear and the karyotheca were double deck. There were obvious euchromosome within the nucleus, and sparse heterochromosome. There were various organelles in the cytoplasm, including plentiful melanosomes with nearly similar size, mitochondria, rough endoplasmic reticule （RER） and ribosome. The electron density granules in most of the melanosomes disposed along concentric circularities. Golgi apparatus in the cells was inconspicuous. Conclusion： The ultra structure of AMMC from human hair follicles is different from that of epidermal melanocytes, and these characteristics determine the functional immature of AMMC.     

慢性饮水型砷中毒人群发、尿、血砷含量及皮肤色素细胞改变特点

目的调查慢性饮水型砷中毒病区砷中毒人群发、尿、血砷含量并进行皮肤病理学检查。方法采用高效液相色谱法测定水砷含量;采用超低温捕获-还原气化-原子吸收分光光度法测定发、尿、血砷含量;皮肤样本进行HE病理学检查。结果砷中毒患者饮用水中三价无机砷(AsIII)、五价无机砷(AsV)、有机砷及总砷(tAs)水平均显著高于无砷暴露对照人群;砷中毒患者毛发中无机砷(iAs)、二甲基砷(DMA)及tAs水平,尿中iAs、甲基砷(MA)、DMA及tAs水平,血液中MA及DMA水平均显著高于相应无砷暴露对照人群。发砷、尿砷及血砷水平男女间无显著差异。皮肤HE病理切片中黑色素细胞出现凋亡并有黑色素产生增多现象。结论砷性皮肤损伤可能与血液中高水平的MA关系密切;砷性皮肤色素脱失可能与黑色素细胞发生凋亡有关。     

The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.