Skip Areas of Retained Melanin: A Clue to the Histopathological Diagnosis of Idiopathic Guttate Hypomelanosis

Biopsy findings in 55 cases of idiopathic guttate hypomelanosis (IGH) are reported. Most cases had a flat epidermis with loss of the rete pattern and a thickened orthokeratotic basket weave stratum corneum. The epidermis had markedly decreased to absent melanin in the basal layer and reduced numbers of melanocytes at the dermoepidermal junction. One-third of patients had a sparse perivascular lymphocytic infiltrate, whereas the rest had no significant dermal inflammation. These findings are in concordance with current literature. However, small foci of retained melanin in the basal layer (skip areas) alternating with larger areas of melanin loss were present in almost 80% of cases. This finding has not been reported earlier and appears to be quite specific to IGH and may be used as a clue to differentiate IGH from other similar conditions such as vitiligo and guttate morphea.     

子宫内膜异位症和（或）子宫腺肌症与面部色素斑发生的关系

目的研究子宫内膜异位症（简称内异症）和（或）子宫腺肌症（腺肌症）不孕与患者面部色素斑发生的关系,初步探讨内异症和（或）腺肌症表型特征及可能机制。方法选择150例内异症和（或）腺肌症相关不孕患者及200例非内异症或腺肌症不孕患者作为研究对象,分别设为内异症和（或）腺肌症组和对照组。分析两组患者年龄、体质量指数（BMI）、血清基础雌二醇（E2）水平及面部色素斑发生情况（阳性率）;比较内异症和（或）腺肌症组内面部色素斑阳性与阴性者的血清基础E2、癌抗原125（CA125）水平和抗子宫内膜抗体（AEmAb）阳性率。结果内异症和（或）腺肌症组患者面部色素斑阳性率明显高于对照组（47.33%vs19.00%）（P〈0.05）;内异症和（或）腺肌症组各年龄段患者面部色素斑阳性率均显著高于对照组（P〈0.05）;两组患者年龄、BMI、血清基础E2水平比较差异均无统计学意义（P〉0.05）。内异症和（或）腺肌症组中面部色素斑阳性者与阴性者比较,血清基础E2和CA125水平以及AEmAb阳性率略有升高,但差异均无统计学意义（P〉0.05）。结论内异症和（或）腺肌症与患者面部色素斑产生有一定关系,但是否独立于体内基础雌激素并反映内异症和（或）腺肌症的病情程度,尚有待于进一步探讨。     

Oxidative stress regulated heme-oxygenase-1 and glutathione S-transferase-m1 gene expression changes in cell lines exposed to melanins

To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson’s disease, we treated neuroblastoma cells (SK-N-SH) and glioma cells with Fenton’s reagent, iron chelating agent, neuromelanin and dopamine melanin. We investigated the changes in expression of nine oxidative stress-related genes and proteins. The levels of mRNAs for heme-oxygenase-1 and glutathione S-transferase-m1 were significantly reduced in SK-N-SH cells exposed to oxidative stress, and increased in glial cells treated with deferoxamine. These results revealed that SK-N-SH neurons react sensitively to oxidative stress, which implies different outcomes between these two types of cells in the substantia nigra. Moreover, the influences of neuromelanin and dopamine melanin on cell function are varied, and dopamine melanin is not a good model for neuromelanin.     

Binding of Betaxolol,Metoprolol and Oligonucleotides to Synthetic and Bovine Ocular Melanin,and Prediction of Drug Binding to Melanin in Human Choroid-Retinal Pigment Epithelium

Purpose To characterize the binding of betaxolol, metoprolol and oligonucleotides to synthetic and bovine ocular melanin, and to predict the binding to melanin in human choroid-retinal pigment epithelium (RPE). Materials and Methods The shape, size and specific surface area of synthetic melanin and isolated melanin granules from bovine choroid-retinal pigment epithelium (RPE) were characterized by SEM, laser diffractometry and BET. The binding of betaxolol, metoprolol, fluorescein isothiocyanate (FITC)-labeled phosphodiesther oligonucleotides and 6-carboxyfluorescein (6-CF) to melanin was determined. The binding of beta-blockers to melanin in human choroid-RPE was estimated based on binding parameters and the melanin content in human choroid-RPE. Results Bovine melanin granules were round or oval with a mean diameter of ca. 1 μm. Synthetic granules were slightly smaller and irregular and had a two times higher specific surface area than bovine melanin. Synthetic melanin bound more betaxolol and metoprolol than bovine melanin and both melanin types showed a high affinity and a low affinity binding sites. The human choroid-RPE was predicted to contain 3–19 times more melanin bound drug than unbound drug at typical therapeutic concentrations (1–1,000 ng/ml). FITC-labeled oligonucleotides and 6-CF did not bind to melanin. Conclusions The binding of lipophilic drugs to biological melanin differs from that of synthetic melanin. Lipophilic beta-blockers are expected to bind significantly to melanin in human choroid-RPE: only a small fraction of the drug being in active free form. In contrast, phosphodiesther oligonucleotides do not seem to bind to melanin.     

Acetoside inhibits α‐MSH‐induced melanin production in B16 melanoma cells by inactivation of adenyl cyclase

Objectives The aim of the study was to determine the mechanism of the whitening effect of acteoside. Methods We used tyrosinase activity and melanin production stimulated in B16 melanoma cells by α‐melanocyte stimulating hormone (α‐MSH) or forskolin to measure the whitening effect of acteoside. Key findings Acteoside did not directly inhibit mushroom tyrosinase activity, but dose‐dependently inhibited tyrosinase activity and melanin production in B16 melanoma cells stimulated by 1 μmol/l α‐MSH. Acteoside also reduced cyclic AMP levels in cells stimulated by 1 μmol/l α‐MSH, suggesting direct inhibition of adenyl cyclase. Acteoside also inhibited productionofbothmelanin and cyclic AMP in cells stimulated by 1 μmol/l forskolin, an adenyl cyclase activator. Acteoside showed antioxidant activity in a cell‐free DPPH (1‐diphenyl‐2‐picrylhydroazyl) assay and inhibited generation of intracellular reactive oxygen species. Conclusions These results suggest that the whitening activity of acteoside results from inhibition of adenyl cyclase and α‐MSH signalling.     

火棘果实提取物的美白作用

目的:研究火棘Pyracantha fortuneana(Maxim.)Li果实提取物的美白作用并观察其对大鼠腹腔肥大细胞释放组胺的影响,探讨可能的作用机制。方法:采用熊果苷为抑制酪氨酸酶活性的标准对照,以酪氨酸酶法探讨火棘果实提取物对酪氨酸酶活性及B16细胞黑色素合成的影响,评价火棘果实提取物的美白作用。利用高效液相库仑阵列电化学检测系统(HPLC-ECD)测定Compound 48/80刺激大鼠腹腔肥大细胞释放组胺,评价火棘果实提取物对肥大细胞释放组胺的影响。结果:火棘果实提取物对酪氨酸酶活性具有明显抑制作用,能显著减少小鼠B16细胞内黑色素的含量。此外,火棘果实提取物对Compound 48/80刺激大鼠腹腔肥大细胞释放组胺呈剂量依赖性抑制作用。结论:火棘果实提取物显著抑制酪氨酸酶活性和肥大细胞释放组胺,为火棘果实作为美白添加剂提供了实验依据。     

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

We examined the wavelength dependence of ultraviolet (UV) ra-diation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.     

Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures

Abstract

Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8⁺ IL-17⁺ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.     

Plasticity in vagal afferent neurones during feeding and fasting: mechanisms and significance

The ingestion of food activates mechanisms leading to inhibition of food intake and gastric emptying mediated by the release of regulatory peptides, for example cholecystokinin (CCK), and lipid amides, e.g. oleylethanolamide from the gut. In addition, there are both peptides (e.g. ghrelin) and lipid amides (e.g. anandamide) that appear to signal the absence of food in the gut and that are associated with the stimulation of food intake. Vagal afferent neurones are a common target for both types of signal. Remarkably, the neurochemical phenotype of these neurones itself depends on nutritional status. CCK acting at CCK1 receptors on vagal afferent neurones stimulates expression in these neurones of Y2-receptors and the neuropeptide CART, both of which are associated with the inhibition of food intake. Conversely, in fasted rats when plasma CCK is low, these neurones express cannabinoid (CB)-1 and melanin concentrating hormone (MCH)-1 receptors, and MCH, and this is inhibited by exogenous CCK or endogenous CCK released by refeeding. The stimulation of CART expression by CCK is mediated by the activation of CREB and EGR1; ghrelin inhibits the action of CCK by promoting nuclear exclusion of CREB and leptin potentiates the action of CCK by the stimulation of EGR1 expression. Vagal afferent neurones therefore constitute a level of integration outside the CNS for nutrient-derived signals that control energy intake and that are capable of encoding recent nutrient ingestion.