Fish melanocortin system

Melanocortin signalling is mediated by binding to a family of G protein-coupled receptors that positively couple to adenylyl cyclase. Tetrapod species have five melanocortin (MC₁–MC₅) receptors. The number of receptors varies in fish, zebrafish, for example, having six melanocortin receptors, with two copies of the melanocortin MC₅ receptor, while pufferfish have 4 receptors with no melanocortin MC₃ receptor and one copy of melanocortin MC₅ receptor. Fish genomes also exhibit orthologue genes for agouti-signalling protein (ASP) and -related protein (AGRP). AGRP expression is confined to a small area in the hypothalamus but ASP is expressed in the skin. Fish melanocortin MC₂ receptor is specific for ACTH and requires the cooperation of accessory proteins (MRAP) to reach functional expression. The four other melanocortin MC receptors distinctively bind MSHs. The interaction of α-MSH and melanocortin MC₁ receptor plays a key point in the control of the pigmentation and mutations of melanocortin MC₁ receptor are responsible for reduced melanization. Both melanocortin MC₄ and MC₅ receptor are expressed in the hypothalamus, and central melanocortin MC₄ receptor expression is thought to regulate the energy balance through the modulation of feeding behaviour. In addition, the peripheral melanocortin system also regulates lipid metabolism by acting at hepatic melanocortin MC₂ and MC₅ receptors. Both sea bass melanocortin MC₁ and MC₄ receptors are constitutively expressed in vitro and both ASP and AGRP work as inverse agonists but only after inhibition of the phosphodiesterase system. Accordingly, the overexpression of AGRP and ASP transgenes promotes obesity and reduces melanization in zebrafish, respectively.     

咖啡牛奶色斑

咖啡牛奶色斑是人群中常见的色素异常性疾病，大量咖啡牛奶色斑常提示有系统性疾病的存在，其表皮黑素细胞增多，可见巨大的黑素体。发病机制可能与DNA错配修护基因的突变有关，多种细胞因子，如肝细胞生长因子、干细胞生长因子也参与咖啡牛奶色斑的形成。激光治疗的成功率变化很大，常见复发。咖啡牛奶色斑的发病机制及治疗等尚有待进一步的研究。     

Expressional changes in the intracellular melanogenesis pathways and their possible role in the pathogenesis of vitiligo

BACKGROUND: Main pathway in human melanocytes through which signal from the melanocortin system reaches the melanogenesis enzymes is cAMP/PKA pathway and it is modulated by Wnt and MAPK pathways. In our previous study we established significant increase of melanocortin receptor expression in unaffected skin of vitiligo patients compared to healthy subjects. OBJECTIVE: The aim of this study was to assess the gene expression profile of the intracellular signalling pathways linking melanocortin system with enzymes involved in melanogenesis. METHODS: Using QRT-PCR method, mRNA expression levels of eight genes related to signal transduction from the melanocortin system to melanogenesis enzymes was measured in lesional and non-lesional skin of vitiligo patients and in the skin of healthy control subjects. Following genes were analyzed in the study: MITF, CREB1, p38, USF1, PIK3CB (PI3K), RPS6KB1, LEF1 and BCL2. RESULTS: The mRNA levels of MITF, LEF1, p38, PIK3CB and RPS6KB1 were decreased in lesional skin of vitiligo patients compared to skin of healthy control subjects. We also found increased expression of USF1 and BCL2 in non-lesional skin of vitiligo patients compared to skin of healthy control subjects. mRNA levels of MITF and BCL2 were decreased in lesional skin of vitiligo patients compared to non-lesional skin of vitiligo patients. CONCLUSIONS: Present study indicates increased expression of the genes of the intracellular melanogenesis pathway in the non-lesional skin of vitiligo patients. This finding suggests activation of melanogenesis pathway in the non-lesional skin of vitiligo.     

Clinical and Laboratory Findings of Pigmented Purpuric Dermatoses

Background

Pigmented purpuric dermatoses (PPD) are chronic, recurrent group of disorders characterized by petechial and pigmentary macules usually localized on the lower limbs. Its etiopathogenesis is unknown. There are very few clinical and etiological studies on PPD in the literature.

Objective

We aim to examine the etiopathogenetic factors of PPD retrospectively.

Methods

Demographic characteristics, history of co-morbid disorders and drug usage, hepatitis markers, levels of serum lipids, findings of Doppler ultrasonography in lower extremities, and patch test results of the 24 patients of PPD were examined retrospectively. The patch test results, history of drug use, and co-morbid disorders of the patients were compared with those of the control groups.

Results

The male-to-female ratio was 1 : 2, and 83.3% of the patients had Schamberg disease. Seventeen patients had co-morbid disorders and 16 used various drugs, but there was no statistically significant difference between the controls and patients. One patient was positive for hepatitis B surface antigen and 1, for anti-hepatitis C virus antibody. Nine had elevated total cholesterol levels, and 5 had elevated triglyceride levels. Further, 30% of them were positive for at least 1 allergen, while 16% of the control subjects were positive for at least 1 allergen, but statistically significant difference was not found between the 2 groups. Variable degrees of venous insufficiency were detected in 75% of the patients on Doppler ultrasonography of the lower extremities.

Conclusion

Venous insufficiency and hypercholesterolemia might be the basic predisposing factors for PPD. Further studies are needed to show if diabetes mellitus and hypertension may cause perivascular inflammation in PPD.     

冷冻、激光及手术治疗皮肤色素痣的效果比较

目的 比较冷冻、激光及手术治疗皮肤色素痣的临床效果。方法 选择本院2021年1月-2022年 5月收治的120例皮肤色素痣患者为研究对象,按照随机数字表法分成冷冻组、激光组和手术组,每组40 例。冷冻组应用冷冻治疗,激光组应用激光治疗,手术组应用手术治疗,比较三组的临床疗效、复发情况 及并发症发生情况。结果 手术组治疗总有效率为97.50%,高于冷冻组的77.50%和激光组的80.00%,差异有 统计学意义（P＜0.05）;手术组治疗半年后复发率为5.00%,低于冷冻组的27.50%和激光组的25.00%, 差异有统计学意义（P＜0.05）;手术组治疗后不良反应总发生率为5.00%,低于冷冻组的25.00%和激光 组的22.50%,差异有统计学意义（P＜0.05）。结论 在皮肤色素痣的治疗中,手术治疗效果优于冷冻、激 光治疗,且复发率和不良反应发生率均较低,应用安全性较高,可作为皮肤色素痣的首选治疗方式,值 得临床应用。     

皮肤美容对面部烧伤后色素沉着患者的康复治疗作用

目的 分析皮肤美容治疗面部烧伤后色素沉着的临床效果。方法 选择2018年1月-2022年11月我院收治的100例面部烧伤色素沉着患者为研究对象,按照随机数字表法分为对照组与观察组,每组50例。对照组给予常规治疗,观察组给予皮肤美容治疗,比较两组临床疗效、面部外观恢复时间、疾病治愈时间及色素值改善情况。结果 观察组治疗总有效率为96.00%,高于对照组的68.00%（P ＜0.05）;观察组治疗后色素值低于对照组（P ＜0.05）;观察组面部外观恢复、疾病治愈时间均短于对照组（P ＜0.05）。结论 皮肤美容对面部烧伤后色素沉着患者的康复治疗作用良好,可有效改善色素沉着现象,促进皮损恢复,值得临床应用。     

Effect of lipstick on composite resin color at different application times

Objectives

The aim of this study was to evaluate the influence of the contact of two lipsticks, one with common fixer and one with ultra fixer, on the color of a composite resin immediately, 30 min and 24 h after photoactivation.

Material and methods

Ninety specimens were prepared with a composite resin, Filtek-Z350. Specimens were polished and divided into 9 groups (n=10) according to time elapsed after photoactivation (A- immediately; B- 30 min; C- 24 h) and the contact with lipstick (UF- lipstick with ultra fixer; F- lipstick with common fixer). The control group was represented by specimens that did not have any contact with lipstick (C- without lipstick). Color measurements of the specimens were carried out using a spectrophotometer (Easyshade - CIE L* a* b* system). For UF and F groups, the baseline color of the specimens was measured immediately before pigmentation and the lipsticks were applied dry after 1 hour. The excess lipstick was removed with absorbent paper and final color checking was performed, including the control group. Differences between the final and baseline color measurements were calculated and data were analyzed statistically by the Kruskal-Wallis test at 5%.

Results

The means between the differences of color values were: AUF: 16.0; AF: 12.4; AC: 1.07; BUF: 9.51; BF: 8.3; BC: 0.91; CUF: 17.7; CF: 12.41; CC: 0.82.

Conclusion

Groups where lipstick was applied showed greater staining than the control group at the three evaluation times. The lipstick with ultra fixer stained more than the lipstick with common fixer. Time elapsed between photoactivation and contact with lipstick had a similar influence on the groups that received lipstick application.     

Pigmentation techniques of a 4YSZ: Effect on the fatigue mechanical behavior of a 4YSZ adhesively luted onto dentin analog

ObjectiveTo characterize the effect of pigmentation techniques on the fatigue behavior of a 4YSZ ceramic adhesively luted onto dentin analog (glass fiber-reinforced epoxy resin).Methods4YSZ ceramic discs (Ø= 10 mm, 1 mm thickness) were allocated into 5 groups: Ctrl – unshaded (IPS e.max ZirCAD MT BL); Manuf – shaded by the manufacturer (IPS e.max ZirCAD MT A2); Brush – unshaded pigmented, pre-sintering, using a brush; Stain – unshaded pigmented, post-sintering, during glaze application; Brush+Stain – combination of both techniques. Color assessments ensured the same perceived color (Vita Classical A2). Dentin analog discs (Ø= 10 mm, 2.5 mm thickness) were obtained, paired with the 4YSZ discs, and adhesively luted using a resin cement. Cyclic fatigue testing (n = 15) was run (20 Hz; 10,000 cycles/step, initial load 200 N; step-size 100 N up to 700 N; then 50 N until specimen failure). Fractographic, roughness and topography analyses were performed.ResultsNo statistical (p > 0.05) detrimental influence were observed for fatigue outcomes (Ctrl = Manuf = Brush = Stain = Brush+Stain). However, the Brush+Stain technique induced inferior statistical (p < 0.05) fatigue performance compared to Stain. All failures were radial cracks with origin at the ceramic intaglio surface. The staining technique triggered statistically higher roughness (p < 0.05). Uniformly sized zirconia crystals were seen in the Ctrl, Manuf and Brush groups, and a smooth vitreous surface with encrusted pigments in the Stain and Brush+Stain groups.SignificancePigmentation techniques (Vita Classical A2 shade) have no detrimental effect on the mechanical fatigue properties of 4YSZ ceramic adhesively luted onto dentin analog.     

Fibroblast morphology,growth rate and gene expression in facial melasma

BackgroundIn addition to melanocytic hyperfunction, changes are observed in the upper dermis of melasma, and fibroblasts play a central role in collagen synthesis and pigmentation induction.ObjectiveTo explore the morphology, growth rate, and gene expression profile of fibroblasts from the skin with melasma in comparison to fibroblasts from the adjacent healthy skin.MethodsTen women with facial melasma were biopsied (lesion and adjacent healthy skin), and the fragments were processed for fibroblast culture. Samples from five participants were seeded to evaluate growth (days 2, 5 and 8) and senescence (SA-β-gal) curves. The samples from the other participants were submitted to real-time PCR to comparatively evaluation of the expression of 39 genes.ResultsCultured fibroblasts from melasma skin were morphologically less fusiform in appearance and on average a 34% (95% CI 4%?63%) greater proportion of cells labeled with SA-β-gal than the fibroblasts from the adjacent skin. The cell growth rate was lower for the melasma samples after eight days (p < 0.01). TheWNT3A, EDN3, ESR2, PTG2, MMP1, and SOD2 genes were up-regulated, whereas the COL4A1, CSF2, DKK3, COL7A1, TIMP4, CCL2, and CDH11 genes were down-regulated in melasma skin fibroblasts when compared to the ones from adjacent healthy skin.Study limitationsSmall sample size; absence of functional tests.ConclusionsFibroblasts from the skin with melasma showed a lower growth rate, less fusiform morphology and greater accumulation of SA-β-gal than those from adjacent photo exposed skin. Moreover, their gene expression profile comprised factors that may contribute to upper dermis damage and sustained melanogenesis.