白毛黑眼兔等四种实验兔黑色素分布的组织学观察与比较

目的分析包括白毛黑眼兔在内的四个品种实验兔的虹膜和皮肤组织中的黑色素分布情况和相互之间的差异。方法通过组织切片和硫酸亚铁染色,对四个品种实验兔的虹膜和皮肤组织中的黑色素含量和分布进行了观察与比较。结果与其背景白化品种相比,白毛黑眼兔不仅在虹膜组织中出现了类型完整的黑色素,而且在其表型为白色的皮肤的毛囊中也出现了低含量的黑色素。结论本结果为白毛黑眼兔突变表型机理研究提供了一定线索。     

半夏泻心汤对2型糖尿病大鼠葡萄糖稳态的影响

目的 探讨半夏泻心汤(BD)对2型糖尿病大鼠糖原合成及垂体黑素皮质激素受体(MC4R)表达的影响以及维持葡萄糖代谢平衡的作用机制.方法 采用SD大鼠建立糖尿病模型,造模成功的大鼠按完全随机法分为糖尿病模型组、二甲双胍组(0.3 g/kg)、BD高剂量组(1.7g/kg)、BD中剂量组(0.85g/kg)、BD低剂量组(0.425 g/kg),另设正常对照组饲以正常饮食,1周后测定各组大鼠空腹体重、垂体MC4R及肝糖原的含量.结果 连续给药1周后,半夏泻心汤高、中、低剂量组大鼠的体重分别为(296.62±1.14)g、(293.83±2.17)g、(286.75±1.91)g,与糖尿病模型组(284.73±2.91)g比较,差异有统计学意义(P＜0.01);MC4R表达分别为(29.69±1.64) ng/L、(29.38±1.88) ng/L、(30.04±1.24) ng/L,与糖尿病模型组(25.95±2.24) ng/L比较,表达均增强(P均＜0.05);肝糖原含量分别(15.94±0.82) mg/g、(11.52±0.56) mg/g、(10.48±0.45) mg/g,与糖尿病模型组(9.05±0.44) mg/g比较含量均增加(P＜0.01、P＜0.01、P＜0.05).结论 半夏泻心汤各剂量组通过增加外周组织对糖的利用、提高MC4R表达,调节大鼠摄食行为.     

Link between facultative melanin and tobacco use among African Americans

Nicotine's affinity for melanin-containing tissues may result from its precursor function in melanin synthesis or the irreversible binding of melanin and nicotine. The objective of this study was to investigate a hypothesized association of tobacco use, dependence, and nicotine exposure with melanin pigmentation among African American smokers. A criterion-based sample was employed to collect data from a study of 147 adult African American current smokers. Carbon monoxide, saliva cotinine samples, and skin reflectance measures were obtained from each participant. Questionnaire data on demographic, sociological and behavioral questions related to smoking and skin color were gathered. The three dependent measures were the average number of cigarettes per day (CPD), Fagerström Test of Nicotine Dependence (FTND) score, and cotinine concentration. Analysis of variance, Pearson Correlations, and Multiple Linear Regression were conducted to analyze findings. The mean constitutive melanin reading was 56.3 and 66.5 for facultative melanin. Respondents on average smoked 19 CPD, had a mean FTND of 5.6, and a cotinine concentration of 435 ng/ml. Facultative melanin level was correlated with CPD and cotinine concentration in the bivariate analysis. The multiple linear regression results revealed that facultative melanin was significantly and positively related to CPD, the FTND, and cotinine. The results of this analysis support the hypothesis of a positive association between melanin levels and tobacco use, dependence, and exposure among African American smokers. This analysis may have important implications for research and interventions on tobacco dependence and disease outcomes. Further research on melanin and nicotine among African Americans as well as other population groups is warranted.     

复方木尼孜其颗粒对小鼠B16黑素瘤细胞酪氨酸酶活性及黑素合成的影响

目的 研究复方木尼孜其颗粒对小鼠B16黑素瘤细胞酪氨酸酶活性及黑素合成的影响.方法 培养小鼠B16黑素瘤细胞,采用MTT法测定不同浓度复方木尼孜其颗粒对细胞增殖的影响,采用L-DOPA氧化法测定其对细胞酪氨酸酶活性的影响,采用NaOH裂解法检测细胞黑素含量.结果 复方木尼孜其颗粒高剂量组能明显抑制小鼠B16黑素瘤细胞黑素的合成,但是对酪氨酸酶活性无影响.结论 复方木尼孜其颗粒能抑制小鼠B16黑素瘤细胞黑素的合成,在治疗色素性皮肤病中有一定前景.     

Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities

Background

p-Coumaric acid (PCA) inhibits human tyrosinase (TYR) activity and melanin synthesis in human epidermal melanocytes.

Objective

The purpose of the current study was to examine the potential of PCA and its hydrophobic derivative, methyl p-coumarate (MPC), as hypopigmenting agents for topical use.

Methods

PCA and MPC were comparatively tested against in vitro human TYR enzyme activity and cellular melanin synthesis in human epidermal melanocytes. Permeation studies were undertaken using an artificial lipophilic membrane and an excised porcine skin. In vivo hypopigmenting efficacy was assessed on the skin of melanin-possessing hairless mice exposed to UVB.

Results

Although PCA was a stronger inhibitor than MPC against TYR activity in vitro, the former inhibited cellular melanin synthesis less effectively than the latter. A non-cell based permeability assay indicated that PCA was practically impermeable through the lipophilic barrier while MPC was highly permeable. In contrast, an ex vivo skin permeation study demonstrated that topically applied PCA in the form of a cream can diffuse into the aqueous medium underneath the skin. No MPC was released from a MPC cream but PCA was released instead as a bio-converted product. Topical application of PCA cream attenuated the UVB-induced erythema formation and pigmentation in mice models, more effectively compared with MPC cream.

Conclusion

PCA may be useful as an active ingredient for topical applications for a hypopigmenting effect. MPC has potential as a hypopigmenting agent but requires rather invasive methods for its delivery to the target cells.     

Design, synthesis and evaluation of PEGylated lipoic acid derivatives with functionality as potent anti-melanogenic agents

The novel PEGylated lipoic acid (LA) derivatives with functionality were synthesized in satisfactory yield by simple procedures and evaluated about its anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the water solubility and functionality to incorporate the other bioactive moieties. We have found that derivatives showed inhibition of melanin formation by up to 36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition, it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is higher than LA. These data suggest that the novel PEGylated LA derivatives with functionality may thus serve as a potentially effective anti-melanogenic and anti-aging agent.     

Functional effects of neuromelanin and synthetic melanin in model systems

Summary. The function of the dark polymer pigment neuromelanin found in catecholaminergic neurons of the human brain is not understood, especially as most published data are based upon a synthetic model melanin which differs structurally to the native pigment. Nevertheless human neuromelanin has been shown to efficiently bind transition metals such as iron, as well as other potentially toxic molecules. The pigment may have a protective function in the healthy brain by, for example, contributing to iron homeostasis within pigmented nuclei. We have demonstrated that synthetic dopamine melanin stimulates cell damage in both cell lines and primary cells in vitro, an effect associated with increased hydroxyl radical production and apoptosis. In contrast, at low iron concentrations native neuromelanin does not induce cell damage but rather protects cells in culture from oxidative stress. This protective function appears to be lost at high iron concentrations where neuromelanin saturated with iron functions as a source of oxidative load, rather than an iron chelator. Changes to neuromelanin and tissue iron load in Parkinson’s disease may decrease the protective potential of the pigment, thus increase the potential for cell damage in this disorder.     

Gingival melanin depigmentation by Er:YAG laser: A literature review

Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO₂, diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.     

Preliminary approach to elucidate the role of pigment as a binding site for drugs and chemicals in anagen hairs: pigments as carriers for 3H-haloperidol in HaCaT/Sk-Mel-1 co-cultures

In view of the melanin-binding characteristics of haloperidol and its differential uptake by pigment- and non-pigment-producing cells, a co-culture of HaCaT with Sk-Mel-1 cell lines was performed to investigate whether melanosomes act as carriers for drug molecules associated with the pigments. Initially, HaCaT and Sk-Mel-1 cells were separately cultivated in the presence of ³H-haloperidol (400 pmol/ml medium ) for 28 days followed by subsequent co-cultivation in the absence of ³H-haloperidol for 5 days. The transfer of pigments into the keratinocytes during co-culture was confirmed by transmission electron microscopy. After the co-culture experiments a striking increase (≥ 50%) of ³H-haloperidol was observed in the pigmented HaCaT cells compared to the unpigmented keratinocytes. The present study proved the role of pigments as carriers for melanin-associated drug molecules. The results supported the hypothesis that hair pigment might be a factor affecting the outcome of hair assays for particular categories of commonly used licit and illicit substances. The chosen cell lines and the developed co-culture system may represent suitable in vitro models to study differential drug uptake into cell populations present in the skin or in the growing hair follicle as well as to elucidate drug uptake due to melanocyte-keratinocyte interactions. Received: 13 November 2000 / Accepted: 31 May 2001     

A melanotic desmoplastic medulloblastoma: Report of a rare case and review of the literature

A 28-year-old man had a desmoplastic medullo-blastoma in the vermis and left cerebellum. This tumor was composed of nodular, reticulin-free zones (pale islands) surrounded by densely packed, highly proliferative cells that produced a dense intercellular reticulin network. Some of the cells were heavily pigmented, and this pigment proved to be melanin. Adult age, desmoplastic nature, and melanin pigmentation are some of the rare features of this tumor that need documentation. Further, this pigment was in the primitive cells, unlike in the published cases, in which it was present in the tubular or tubulopapillary component. To the best of our knowledge, this is the first published case of desmoplastic pigmented medulloblastoma, and the patient is the oldest reported to have this tumor.