52-year old patient with skin discoloration

Zusammenfassung Das antiarrhythmisch wirksame Medikament Amiodaron kann nach l?ngerer Anwendung dosisabh?ngig zu einer Dyschromie an den lichtexponierten Arealen der Haut führen. Die Pigmentgranulae im oberen und mittleren Korium sind Komplexe aus Phaeomelanin, Lipochromen und unbekannten jodhaltigen Amiodaronmetaboliten. Eine aggravierende Funktion kommt UVA- und UVB-Licht zu. Mit einer spontanen Abblassung ist erst nach mehreren Jahren zu rechnen. Meidung von UV-Licht, topischer Lichtschutz und die begleitende Gabe von 300 mg Pyridoxin/Tag werden empfohlen. Da die Ablagerung der Pigmentgranulae im Korium sehr sensitiv durch eine Hautbiopsie erfasst werden kann, empfehlen wir bei Vorliegen einer therapeutischen Alternative zus?tzlich eine histologische Untersuchung (Masson-Fontana-F?rbung) eines Hautbiopsates aus einem lichtexponierten Areal.     

Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus

Melanin concentrating hormone (MCH) and the orexins (A and B) have been identified as neuropeptides localized to the lateral hypothalamic area (LHA) and are potential regulators of energy homeostasis. Potential factors regulating expression of both MCH and the orexins include fasting and leptin. Previous studies have generated conflicting data and, as there is little leptin receptor expressed in the lateral hypothalamus, it is likely that any observed leptin effects on these peptides are indirect. In this study, we examined MCH and preproorexin expression in mice in physiological states of starvation, with or without leptin administration, in addition to characterizing MCH and preproorexin expression in well-known obesity models, including ob/ob and UCP-DTA mice. Neuropeptide Y (NPY) expression in the arcuate nucleus was used as a positive control. After a 60-h fast, expression of both NPY and MCH mRNA was increased (by 148 and 33%, respectively) while preproorexin expression in the murine LHA did not change. Leptin administration to fasted mice blunted the rise in MCH and NPY expression towards control levels. In contrast, there was a 78% increase in preproorexin expression in fasted mice in response to peripheral leptin administration. MCH expression was increased (by 116%) in ob/ob mice at baseline, as we have previously reported. In addition, leptin treatment of ob/ob mice blunted the increase in MCH expression. In contrast, preproorexin expression did not differ in the leptin-deficient ob/ob mice or in the obese hyperleptinemic brown adipose tissue deficient (UCP-DTA) mice in comparison with controls. In summary, MCH expression is increased in two states of decreased leptin, fasting and ob/ob mice, and leptin replacement blunts MCH expression in both paradigms. Thus, MCH expression appears to be regulated by leptin. In contrast, preproorexin expression does not respond acutely to fasting, although it is acutely increased by leptin treatment during fasting. These preproorexin responses are in contrast to those seen with well-characterized orexigenic neuropeptides, such as NPY and AgRP, suggesting that appetite regulation may not be a significant physiological role of orexins. This conclusion is further supported by the observation that orexin ablated mice have arousal and not feeding deficits.     

The transdermal inhibition of melanogenesis by a cell-membrane-permeable peptide delivery system based on poly-arginine

Topical therapy is the most favored form of treatment for whitening against hyper-pigmentation and sunburn because it lends itself to self-administration, patient compliance and an absence of systemic adverse effects. However, high-molecular-weight, hydrophilic chemicals are difficult to use as transdermal delivery drugs and the use of topical drugs has been highly limited. There are now many potent tyrosinase inhibitors, for example, sulfite or kojic acid, but the efficacy of their skin transduction remains a big problem. Furthermore, melanogenesis inhibitors from natural sources have great potential, as they are considered to be safe and largely free from adverse side effects. We applied 11-arginine (11R), a cell-membrane-permeable peptide, as a transdermal delivery system with a skin delivery enhancer, pyrenbutyrate. We performed intracellular screening for melanogenesis inhibitors with 11R fused with several kinds of tyrosinase inhibitory peptides from natural sources. Of 28 tyrosinase peptides, 13 melanin synthesis inhibitory peptides were selected. Peptide No. 10 found in gliadin protein, a wheat component, most strongly inhibited melanin production. This No. 10 peptide, of only 8 amino acids, fused to 11R showed no cytotoxicity and inhibited melanin synthesis as determined through melanin content measured using an absorption spectrometer and observation with a transmission electron microscope. Next, we transduced this 11R-No. 10 into skin with an 11R transdermal delivery system after previous treatment with pyrenbutyrate and performed daily repetitive topical application for two weeks against a UV-induced sun-tanning guinea pig model. We observed a whitening effect in a model skin sample by Masson-Fontana staining and the 11R-No. 10 peptide-applied area showed significant melanogenesis inhibition. These results show that 11R using a transdermal drug delivery system with melanogenesis inhibitory peptide is a very safe and promising method for applications from cosmetics to the pharmaceutical industry.     

窄谱中波紫外线治疗前后照射区浅表角质层细胞中黑素颗粒的变化研究

目的：探讨窄谱中波紫外线治疗前后照射区浅表角质层细胞中黑素颗粒的临床变化。方法：对我院收治住院的9例白癜风患者采用窄谱中波紫外线治疗,观察治疗前后照射区浅表角质层细胞中黑素颗粒的分布、形态等变化。结果：治疗前后对称皮损复色皮肤黑素面积分布比例比较均有统计学差异,P＜0．05;治疗结束后对称皮损复色区域内可见较多黑素颗粒分布,浅表角质层黑素颗粒含量明显增多,颜色加深,与周围正常皮肤颜色基本一致。结论：窄谱中波紫外线照射治疗能改善白癜风浅表角质层细胞中黑素颗粒的形态,具有较好的应用价值。     

Clinical outcomes and 5-year follow-up results of keratosis pilaris treated by a high concentration of glycolic acid

BACKGROUNDKeratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice. Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen, which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation. Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes. It also promotes skin metabolism and accelerates the melanin metabolism. The therapeutic effect is related to the glycolic acid concentration.AIMTo evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris, and to observe the outcomes at 5-year of follow-up.METHODSTwenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites. High concentrations of glycolic acid (50% or 70%) were applied to a circular area (d = 8 cm, S = 50 cm²) and repeated four times, on days 0, 20, 40 and 60. Before each treatment and 20 d after the last treatment, on days 0, 20, 40, 60, and 80 and at a 5-year follow-up, The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined. At the same time, the participants provided subjective evaluations of treatment efficacy and safety.RESULTSTreatment effectiveness was indicated by the percentage of keratotic papules in the test site, on days 20, 40, 60 and 80, which were 8%, 12%, 36%, and 60%, respectively. Compared with day 0, each difference was significant (P < 0.05). Compared with day 0, differences in melanin content (M) in the skin and skin lightness (L) on days 40, 60 and 80, the were statistically significant (P < 0.05); skin hemoglobin content (E) on days 60 and 80 was statistically different as compared with before treatment (P < 0.05). There were no significant differences in the number of keratotic papules, M, L, and E in 9 participants at the 5-year follow-up compared with before treatment (P > 0.05%).CONCLUSIONA high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris. The treatment was relatively safe, but there was no significant difference at the 5-year follow-up compared to before treatment.     

Melanotic cerebral astrocytoma: case report and literature review

We describe the case of 47-year-old man with a cystic, melanotic temporal lobe astrocytoma who had a history of complex partial seizures. The tumor mass was made up of two histologically different regions: one consisted of spindle-shaped and pleomorphic cells often with foamy or vacuolated cytoplasm, while the other consisted of fairly uniform spindle-shaped cells, many of which contained dark-brown intracytoplasmic pigment. Desmoplasia was also noted in the latter region of the tumor. No features suggestive of malignancy, such as mitotic figures, necrotic foci or endothelial vascular proliferation, were observed throughout the tumor. Immunohistochemically, the tumor cells in both regions were positive for glial fibrillary acidic protein. Ultrastructural examination of the pigmented region showed the presence of melanosomal melanin in the tumor cells. Apart from the partial pigmentation, the entire histological picture resembled a pleomorphic xanthoastrocytoma. To our knowledge, only two cases of similar melanotic astrocytic tumors have been described previously. Interestingly, the astrocytic tumors in both of these patients were also clinically associated with epilepsy, were located in the temporal lobe, and were histologically benign. Received: 8 July 1996 / Revised, accepted: 10 September 1996     

Melanotic paraganglioma of the orbit: a case report

Summary A paraganglioma of the orbit in a 21-year-old woman is presented, containing oculo-cutaneous melanin in many tumor cells, occasionally adjacent to neurosecretory granules, and in macrophages. This tumor expands the list of neuroectodermal tumors with potential melaninization.     

The effect of sympathectomy upon iris tyrosinase activity

It is generally accepted that interruption of the sympathetic pathway to the eye may result in iris hypochromia in human infants. Weanling Dutch belted rabbits were used as a model system to investigate whether the melanin synthesizing enzyme, tyrosinase, is regulated in the iris of the juvenile animal by adrenergic innervation. Although we did not find a significant decrease in tyrosine activity isolated from the sympathetically denervated iris, we did observe a tenfold fall in iris tyrosine activity between the 30th and 120th days of life in both intact and denervated irides. About 90% of the iris tyrosine activity was localized in the pigmented epithelium and the remaining tyrosinase activity was found in the stromal tissue. This distribution of tyrosine activity was not affected by sympathetic denervation or time.     

Variations in melanin formation by cultured melanocytes from different skin types

Abstract In many laboratories, culturing skin melanocytes has become a routine research activity. However, recent investigations have revealed that the quality and quantity of the pigment formed in the cultured cells may differ significantly from those of the original skin pigment cells. To shed more light on this issue, we examined the influence of different culture media on pigment production. We showed that there were notable passage-to-passage variations in the synthesis of melanin. This was particularly true for phaeomelanin. It is therefore advisable to analyse the melanin in the cells before the start of experiments. In spite of the variations, basic differences in the pigmentation pattern between melanocytes isolated from light-skinned and dark-skinned individuals remained preserved in the corresponding cultures as observed by electron microscopy. Also, the total melanin content was higher in a skin type VI melanocyte culture than in skin type I and II melanocyte cultures. In contrast to total melanin, the phaeomelanin concentration of skin type VI cells was similar to that of the skin type I melanocytes. With higher l-tyrosine concentrations in the medium, as well as increased eumelanin synthesis, phaeomelanogenesis was also stimulated in all cultures tested. This stimulation was particularly prominent in skin type I melanocytes. Our preliminary experiments also showed that a melanocyte culture from atypical naevus cells exhibited a similar preference for phaeomelanogenesis when pigmentation was stimulated. Received: 8 August 1997     

透明细胞肉瘤（附4例电镜观察）

本文对４例透明细胞肉瘤（ＣｌｅａｒＣｅｌｌＳａｒｃｏｍａ，以下简称Ｃ．Ｃ．Ｓ）进行了电镜观察。发现Ｃ．Ｃ．Ｓ肿瘤细胞呈梭形，胞浆透明，有伪足样突起；细胞膜外可见断片状基底膜；核膜凸凹不平，核仁呈网眼状；胞浆内细胞器发达，游离或多聚核糖体多。无论是黑色素性Ｃ．Ｃ．Ｓ还是非黑色素性Ｃ．Ｃ．Ｓ，电镜下均能找到黑素体，二者区别只是黑素体数量和成熟阶段不同；前者数量多，多为Ⅳ型；后者数量少，多为Ⅱ─Ⅲ型。结合免疫组化结果，作者认为Ｃ．Ｃ．Ｓ是一种特殊的软组织肿瘤，具有恶性黑色素瘤的特点。