Role Of Melanin Research Articles

Melanin and nicotine: A review of the literature

The role of melanin in nicotine uptake and metabolism has received little attention. Because nicotine has been shown to accumulate in tissues containing melanin, exploring links between melanin and nicotine may provide additional clues to understanding smoking behavior and disease effects. To examine the scientific literature on the relationship between melanin and nicotine, we conducted a PubMed search. We also searched online archives of internal tobacco industry documents. We retrieved and reviewed 82 published research papers related to melanin and nicotine or melanin and metabolism of other drugs, and 150 relevant internal tobacco industry documents. The published literature suggests that nicotine may accumulate in human tissues containing melanin and this retention may increase melanin synthesis. Existing research on the relationship between melanin and nicotine lacks an adequate consideration of this relationship's potential impact, if any, on nicotine metabolism, level of nicotine dependence, and ability to quit smoking. Differential accumulation of nicotine in melanin-containing tissues could have implications for individuals with high levels of melanin.

Role of melanin in mechanical properties of Glycera jaws

The remarkable mechanical prowess of the jaws of the bloodworm Glycera dibranchiata appears to be a consequence of a robust cross-linked network of organic molecules, notably melanin and proteins, as well as small amounts of unmineralized Cu and a Cu-based mineral. The present study focuses on the role of melanin. Mechanical properties of untreated jaws and the constituent melanin are probed through nanoindentation, both in air and underwater. Complementary information is obtained from density and porosity measurements and attempts at Cu removal from the jaws using EDTA, an effective metal chelator in most biological systems. In near-tip regions of the jaws, mechanical properties attain the highest values and diminish only slightly when wet (by 15–25%), in contrast to the behavior of other organic biomaterials. The melanin constituent contributes significantly to the mechanical integrity of the jaw; its hardness and elastic modulus are about half those of untreated jaws. Although melanin may be the dominant shape-determining component of the structure, it remains to be shown whether jaw assembly is mediated by protein deposition on a melanin scaffold or, conversely, by melanin deposition on a protein scaffold. The inability of EDTA to chelate Cu from the jaws and the relatively high density of the jaws and the melanin support the notion of a highly cross-linked molecular structure. Finally, based on the metric H 3/ E 2 ( H being hardness and E the Young’s modulus), the results suggest that the abrasion resistance of the jaws is superior to all engineering polymers and competitive with the hardest metallic alloys.

Quantitative Scattering of Melanin Solutions

The optical scattering coefficient of a dilute, well-solubilized eumelanin solution has been accurately measured as a function of incident wavelength, and found to contribute <6% of the total optical attenuation between 210 and 325 nm. At longer wavelengths (325–800 nm), the scattering was less than the minimum sensitivity of our instrument. This indicates that ultraviolet and visible optical density spectra can be interpreted as true absorption with a high degree of confidence. The scattering coefficient versus wavelength was found to be consistent with Rayleigh theory for a particle radius of 38 ± 1 nm. Our results shed important light on the role of melanins as photoprotectants.

PneumocystisMelanins Confer Enhanced Organism Viability

Pneumocystis continues to represent an important opportunistic fungal pathogen of those with compromised immunity. Thus, it is crucial to identify factors that affect its viability and pathogenicity. We previously reported the first identification of melanins in Pneumocystis. In the present study, we sought to further characterize these components and define the function for these melanins. Melanins extracted from Pneumocystis and melanized Pneumocystis cells were analyzed by electron spin resonance spectroscopy, revealing spectra consistent with melanins from other fungi. Immunofluorescence assays using anti-melanin monoclonal antibodies showed that melanins are widely present across Pneumocystis host species, including mouse-, ferret-, and human-derived Pneumocystis organisms, as well as Pneumocystis carinii derived from rat. Using immunoelectron microscopy, melanins were found to localize to the cell wall and cytoplasm of P. carinii cysts, as well as to intracystic bodies within mature cysts. Next, the role of melanins on the maintenance of Pneumocystis viability was determined by using quantitative reverse transcription-PCR measurement of the heat shock protein mRNA under adverse environmental conditions. Using a new method to promote the melanization of Pneumocystis, we observed that strongly melanized Pneumocystis retained viability to a greater degree when exposed to UV irradiation or desiccation compared to less-pigmented organisms. These studies support our previous identification of Pneumocystis melanins across the genus, further characterize these Pneumocystis components, and demonstrate that melanins protect Pneumocystis from environmental stressors.

IS MELANIN A DEFENSE AGAINST FEATHER-FEEDING LICE?

Abstract The adaptive basis of plumage color has received much attention, including the finding that color can reveal information about parasite loads to potential mates. A related possibility, that color may be a direct defense against parasites, has received less attention. Melanin makes feathers tough and more resistant to wear and tear. Melanin may also make feathers more difficult for feather-feeding parasites to eat. We explored the role of melanin as a possible ectoparasite defense using Rock Pigeons (Columba livia) and their feather-feeding lice (Insecta: Phthiraptera). Rock Pigeons are an ideal species for such work because of the extreme variation in the feathers of different color morphs, ranging from melanin-rich black to melanin-free white individuals. We tested the effect of melanin on lice in several ways. First, we compared the natural louse loads of free-ranging pigeons to see whether the more melanistic color morphs had fewer lice. We also did laboratory assays in which we measured the s...

Alkylating benzamides with melanoma cytotoxicity: role of melanin, tyrosinase, intracellular pH and DNA interaction

N-(2-Dialkylaminoethyl)benzamides have been shown to selectively accumulate in melanoma metastases with high uptake capacity. Therefore, this class of compound has previously been evaluated as a transporter for cytostatic drugs. It has been demonstrated that this significant targeting effect improves the cytotoxicity against melanoma cells. Although these agents are not accumulated by non-melanoma cells, they have been found to be toxic. In order to identify mechanistic reasons for this effect, we investigated the DNA and melanin binding affinities of a selection of four benzamide-drug conjugates, together with their parental cytostatics. An investigation of the influence of the melanin content on the cytotoxicity of these substances in B16 melanoma and Morris hepatoma (MH3924A) cells was performed, together with their influence on melanosomal pH and tyrosinase activity. The suppression of melanin formation with phenylisothiourea and the saturation of melanin binding sites with chloroquine were also investigated. These experiments demonstrated high DNA binding and low melanin affinity, in accordance with the toxicity against tumour cells. Melanin has a concentration-dependent scavenging effect, thereby reducing cytotoxicity. These compounds lead to an increase in the acidic pH of melanosomes, resulting in an increase in tyrosinase activity. The consequence of this reaction chain is an amplification of the scavenging effect for the benzamide-drug conjugates. These effects may be considered as limiting factors for the targeting characteristics of this class of compound, necessitating further modifications to the carrier system.

Role and modulation of tyrosinase/tyrosinase related protein‐1 complex and PKC beta‐I in melanogenesis

Role and modulation of tyrosinase/tyrosinase related protein‐1 complex and PKC beta‐I in melanogenesis

Role of melanin and artificial hair color in preventing photo‐oxidative damage to hair

This research is a multifaceted study which investigates not only the role of melanin in providing photostability to natural hair color and hair proteins, but also the claim that the presence of specific artificial colors in hair slows down the rate of photodegradation of hair proteins. In earlier studies, the extractability of protein from photodegraded hair was investigated and showed that many of the cleaved proteins could not be extracted because of photo‐oxidative cross‐linking. The current study investigates the effect of the amount of melanin in hair of different ethnicity and the presence of artificial hair colors on the extractability of the main classes of hair proteins. Furthermore, the data are used in the interpretation of the effect of these components in being able to prevent photo‐oxidative damage to hair proteins.When exposed to sunlight, hair undergoes changes in chemical, mechanical and morphological properties. The UVB and UVA regions of the solar spectrum are the most damaging to human hair. Of these two, the UVA region is predominant in the solar spectrum at low altitudes. Hair of different ethnicity responds differently to the damaging radiation of the solar spectrum, because of different amounts of melanin present in hair. Melanin absorbs the impinging radiation (especially at the lower wavelengths (254–350 nm), and converts it by some complex internal mechanism into heat. Because of this, melanin provides a photochemical protection to natural hair color and hair proteins and prevents their photodegradation. However, the melanin pigments act sacrificially and become themselves degraded in the process of protecting the proteins from light. As a result, this «protective» effect of the melanin pigments does not last during long‐term intense exposure, when, regardless of the amount of melanin in hair, most matrix, intermediate filament and high molecular weight hair proteins undergo photo‐oxidative cross‐linking into higher molecular weight species, and their extractability from hair decreases significantly.The goal of this study is to demonstrate how UV‐radiation affects natural and artificial hair color during long‐term exposures. Bright‐field and UV‐microspectrophotometry and an electrophoretic separation technique (SDS‐PAGE) were chosen as investigative techniques for these studies, because they are well‐suited to accurately and reproducibly investigate the initial properties of a specific hair sample and the changes in these properties as a result of long‐term light‐exposure. The goal of this paper is not to relate this to the content and type of melanin in hair. Electrophoresis, while not measuring the exact quantitative amount of protein extracted, is a semi‐quantitative method, where increases in brightness of the bands represent increased amounts of proteins that were extracted of that specific protein from hair. This electrophoretic study attempts to determine whether the presence of natural or artificial color in hair influences the protein extractability in unaltered hair and the photo‐oxidative cross‐linking during light‐exposure.The bright‐field microspectrophotometric study showed that high concentrations of melanin provide protection to the melanin itself and that they prevent loss of natural hair color during light‐exposure. However, neither large amounts of melanin in hair of different ethnicity, nor artificial hair colors (even a dye with an absorption in the UV region) provide protection to the hair proteins against photodegradation under the conditions used in this study.UV‐microspectrophotometry has suggested the formation of high levels of photo‐oxidized proteins as a result of light‐exposure. Electrophoresis revealed photo‐oxidative cross‐linking of most matrix, intermediate filament and high molecular weight hair proteins into their higher molecular weight analogues, rendering them less extractable due to their lowered diffusivity. Only very low levels of low molecular weight matrix proteins could be extracted.

Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round?

Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long-term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV-induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self-renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.

The Antimicrobial Properties of Melanocytes, Melanosomes and Melanin and the Evolution of Black Skin

A biological issue that has not been satisfactorily resolved is the role of melanin in skin and other animal tissues. A hypothesis is outlined here to account for the evolution of black skin and the ubiquity of melanin in vertebrate tissues. Evidence is presented that melanization of skin and other tissues forms an important component of the innate immune defense system. A major function of melanocytes, melanosomes and melanin in skin is to inhibit the proliferation of bacterial, fungal and other parasitic infections of the dermis and epidermis. This function can potentially explain (a) the latitudinal gradient in melanization of human skin; (b) the fact that melanocyte and melanization patterns among different parts of the vertebrate body do not reflect exposure to radiation; (c) provide a theoretical framework for recent empirical findings concerning the antimicrobial activity of melanocytes and melanosomes and their regulation by known mediators of inflammatory responses.

Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage

Perhaps the most obvious manifestation of the complex interplay between environmental cues, signal transduction pathways, and transcription factors underlying the genesis and differentiation of a cell lineage is provided by the enormous diversity of genetically determined pigmentation patterns. Because melanocytes, the cells responsible for skin, hair, and eye color, are dispensable for viability, the highly visible consequences of mutations affecting the melanocyte lineage (Fig. 1) has allowed over 90 independent genes to be implicated in the genesis of mouse coat color (Mouse Genome Informatics: http:// www.informatics.jax.org/). The 30 or so of these genes that have been cloned to date (http://www.cbc.umn. edu/ifpcs/micemut.htm) not only encode proteins required for the manufacture of the pigment melanin and the function of the melanosome, but also encode signaling molecules and transcription factors that play critical roles in the development of the melanocyte lineage. This unusually large genetic resource which extends to a wide variety of species has made the regulation of melanocyte development an attractive system for understanding how the coordination of gene expression required for the commitment and differentiation of a specific cell lineage is achieved. Melanocytes originate as nonpigmented precursors termed melanoblasts in the mouse neural crest at around embryonic day 10.5 (E10.5), and following migration and proliferation reach the limb buds by E12 and enter the epidermis at the level of the lateral trunk by E13/E14 (Mayer 1973). Melanocytes are found as mature pigment cells in the skin and hair follicles, as well as a range of other sites where their role as pigment-producing cells is less understood. Thus, melanocytes are present in the choroid layer of the eye, the Harderian gland, the anal canal, and in the stria vascularis of the inner ear where they are crucial for hearing because they play a vital role in the endolymph-controlled generation of action potentials (Steel and Barkway 1989; Tachibana 1999). The effects of mutations affecting genes playing a key role in the melanocyte lineage may therefore be manifest at several levels: Mutations may affect genes required for differentiation-specific functions such as the genesis of pigment, or more interestingly from the developmental perspective, any step from the specification and commitment to the melanocyte lineage, to the survival, proliferation, and migration of melanoblasts from the neural crest. Interest in the melanocyte system is also afforded by the impact on melanocytes of ultraviolet (UV) light. In humans, epidermal melanocytes respond to UV irradiation by increasing the synthesis of melanin in membrane-bound structures termed melanosomes that are transferred to surrounding keratinocytes, a process known as the tanning response. At least one role for melanin is likely to be in protection against UV-induced DNA damage (Hill 1992). The incidence of UV-induced DNA damage, however, correlates with the risk of transformation of the melanocyte to a malignant melanoma, an aggressive and increasingly common form of cancer for which a proportion of the population have a genetic predisposition. The difficult path towards understanding the molecular and genetic basis of the progression from a melanocyte to a malignant melanoma has been made easier with recent observations that link the genesis of melanoma to deregulation of pathways operating in melanocyte development. The aim of this review is to provide an overview of how gene expression in neural crest-derived melanocytes is controlled by the interplay between specific transcription factors and signal transduction pathways. Because of limitations of space, the review focuses on the regulation of the expression and function of the Microphthalmia-associated transcription factor, Mitf. For the same reason, the development of the retinal pigment epithelium (RPE), the pigmented layer of cells lying immediately behind the retina which arises via differentiation of the posterior part of the optic cup, is not discussed.

The Role of Melanin in the Induction of Oxidative DNA Base Damage by Ultraviolet A Irradiation of DNA or Melanoma Cells

Highly pigmented, dark skin is more resistant to the harmful effects of solar ultraviolet radiation than light-colored human skin. The extent to which tanning protects skin from harmful effects including induction of skin cancer is not known, however. We have investigated whether the skin pigment, melanin, sensitizes or protects isolated DNA or nuclear DNA in melanoma cells from the induction of the premutagenic oxidative DNA base damage, 8-hydroxy-deoxyguanosine, by ultraviolet A irradiation. Synthetic eumelanin sensitized isolated DNA to induction of the oxidative DNA base damage by ultraviolet A, but it also induced the oxidative DNA base damage in the dark. To study the role of natural melanin in mammalian melanoma cells in the induction of oxidative DNA base damage, melanin synthesis was modulated 5-7-fold in the human melanoma cells GLL19 and IGR1 (which contain both pheomelanin and eumelanin) as well as in the mouse melanoma cells B16 (which contain mainly eumelanin). Increased melanin synthesis clearly did not protect against ultraviolet A-induced oxidative DNA base damage in cells. On the contrary, the human melanoma cells with high melanin content accumulated two times more 8-hydroxy-deoxyguanosine after ultraviolet A irradiation than cells with low melanin content. Furthermore, preirradiation of the human melanoma cells, IGR1, with ultraviolet A 4 h before a second ultraviolet A exposure produced an altered amount of induced 8-hydroxy-deoxyguanosine dependent on the melanin content of the cells. We conclude that stimulation of melanin synthesis, but probably not melanin itself, increases the susceptibility of human melanoma cells to induction of premutagenic oxidative DNA base damage by ultraviolet A irradiation.

Aging in Epidermal Melanocytes: Cell Cycle Genes and Melanins

With aging, melanocytes become unevenly distributed in the epidermis. In light skin individuals, hypopigmentation is found in association with focal hyperpigmentation (lentigo senilis). Apparently this results from progressive loss of active melanocytes and focal increase in melanocyte proliferation and/or aggregation. This paper summarizes the present knowledge on aging of melanocytes in vivo and in vitro, with a focus on the role of melanin as a determinant for proliferation and terminal differentiation. We describe that excessive melanin deposition by cyclic AMP-inducing agents results in increased expression of the cyclin-dependent kinase inhibitors p27Kp-1 and p21SDI-1/Waf-1, increased binding of p16 to CDK4, and terminal differentiation. Importantly, the efficiency with which the melanocytes exit the cell cycle depends on the melanin background of the donor's cells. Melanocytes from skin types IV-VI that accumulate large amounts of brown black melanin (eumelanin), lose expression of the transcription factors E2F1 and E2F2, two key regulatory proteins, and withdraw from the cell cycle more rapidly than melanocytes from skin types I and II that accumulate red/yellow melanin (pheomelanin). Thus, we propose that terminal differentiation is a tumor suppressor mechanism that becomes less efficient under imperfect eumelanization.

The melanin biosynthesis genes of Alternaria alternata can restore pathogenicity of the melanin-deficient mutants of Magnaporthe grisea.

The phytopathogenic fungi Magnaporthe grisea and Alternaria alternata produce melanin via the polyketide biosynthesis, and both fungi form melanized colonies. However, the site of melanin deposition and the role of melanin in pathogenicity differ between these two fungi. M. grisea accumulates melanin in appressoria, and their melanization is essential for host penetration. On the other hand, A. alternata produces colorless appressoria, and melanin is not relevant to host penetration. We examined whether the melanin biosynthesis genes of A. alternata could complement the melanin-deficient mutations of M. grisea. Melanin-deficient, nonpathogenic mutants of M. grisea, albino (Alb-), rosy (Rsy-), and buff (Buf-), were successfully transformed with a cosmid clone pMRB1 that carries melanin biosynthesis genes ALM, BRM1, and BRM2 of A. alternata. This transformation restored the melanin synthesis of the Alb- and Buf- mutants, but not that of the Rsy- mutant. The melanin-restored transformants regained mycelial melanization, appressorium melanization, and pathogenicity to rice. Further, transformation of Alb- and Buf- mutants with subcloned ALM and BRM2 genes, respectively, also produced melanin-restored transformants. These results indicate that the Alternaria genes ALM and BRM2 can restore pathogenicity to the mutants Alb- and Buf-, respectively, due to their function during appressorium development in M. grisea.

Laccase and melanin in the pathogenesis of Cryptococcus neoformans.

Cryptococcosis, caused by an encapsulated fungus, Cryptococcus neoformans, has emerged as a life threatening infection in HIV positive individuals and other immunocompromised hosts. The present review describes laccase and its product melanin as an important virulence factor of Cryptococcus neoformans and illustrates the approaches used in elucidating the pathogenesis of cryptococcosis. Characterization of the biochemical pathways leading to melanin synthesis is summarized using biochemical and biomolecular approaches. Melanin synthesis is dependent on a single copper-dependent enzyme, laccase. Since the mammalian host does not contain this enzyme, laccase is an attractive candidate for the study of fungal pathogenesis, as well as a drug target. The cloning of the CNLAC1 gene and construction of CNLAC1 gene knock-out strains has confirmed its role in the virulence of Cryptococcus. Also described is the role of melanin in the host-pathogen interactions. Melanin may protect Cryptococcus cells by a variety of methods including anti-oxidant or cell wall surface effects thereby offering protection against numerous effectors of cellular immunity.

Delayed neurogenesis in the albino retina: evidence of a role for melanin in regulating the pace of cell generation

Delayed neurogenesis in the albino retina: evidence of a role for melanin in regulating the pace of cell generation

Melanin, melanin "ghosts," and melanin composition in Cryptococcus neoformans

Melanin synthesis is associated with virulence for the pathogenic fungus Cryptococcus neoformans. Exposure of nonmelanized C. neoformans 4067 cells to 4 M guanidinium isothiocyanate followed by 6 M HCl at 100 degrees C resulted in complete solubilization of cellular structures. However, exposure of melanized C. neoformans 24067 to the same conditions produced a suspension of black particles. Analysis of black particles with transmission and scanning electron microscopy revealed cell "ghosts" with electron-dense walls. Electron spin resonance (ESR) spectroscopy of suspensions of black particles revealed a signal indicative of a stable free radical population. The magnitude of the ESR signal was increased by illumination, Zn2+ ions, and basic pH. Boiling the black particles produced only a small reduction in the magnitude of the ESR signal. These ESR changes are characteristic of melanin. Exposure of melanized black cells to 0.1 or 0.5% NaOCl bleached the cells white and abolished the ESR signal, consistent with melanin disruption. ESR spectroscopy was used to study the rate of stable free radical formation, taken as an index of melanization, of C. neoformans 24067 cells growing in medium with 1.0 mM L-dopa at 30 and 37 degrees C over the course of 14 days. Melanization was slower at 37 degrees C. but by day 14, cells grown at 30 and 37 degrees C. had comparable levels or melanin. ESR spectroscopy of seven melanized C. neoformans strains revealed that some strains differed by up to eightfold in melanin content. The ESR spectra of C. neoformans 24067 grown in minimal medium containing either 1.0 mM catechol, dopamine, or L-dopa revealed large differences in signal amplitude. The relative melanin contents were 0.05, 0.45, and 1.0 for C. neoformans grown in media with catechol, dopamine. and L-dopa, respectively. Quantitative analysis revealed that melanin comprised 15.4% of the dry mass of the cell after 10 days of growth in medium containing 1.0 mM L-dopa. The results suggest (i) a useful protocol for isolating C. neoformans melanin, (ii) a role for melanin in maintaining cell wall integrity, (iii) disruption of melanin by NaOCl, (iv) strain differences in melanin content after growth in L-dopa, and (v) quantitative and/or qualitative differences in the melanin produced after growth in various substrates.

Growth and pigmentation in genetically related Cloudman S91 melanoma cell lines treated with 3‐isobutyl‐1‐methyl‐xanthine and β‐melanocyte‐stimulating hormone

4 clonal sublines of Cloudman S91 melanoma cells, S91/mel, S91/I3, S91/6 and S91/amel, were evaluated for changes in growth, pigment content and plating efficiency during and after treatment with a cyclic-AMP phosphodiesterase inhibitor-melanin-stimulating agent, 3-isobutyl-1-methyl-xanthine (IBMX) plus beta-melanocyte stimulating hormone (beta-MSH) or IBMX alone. After combined treatment, increases in melanin content on day 3 were 48, 27, 11, and 2 pg/cell in the four cell lines respectively. In each case IBMX alone was less effective than IBMX plus beta-MSH. Doubling time increased and plating efficiency decreased with increased melanization. The increases in doubling time and decreases in plating efficiency were cell line dependent. The greatest rate of increase in doubling time and decrease in plating efficiency as a function of melanin content were seen in S91/amel, which produced the least pigment. The lowest rates of increase/decrease were seen in S91/mel, which produced the most pigment. Melanin pigment induced in the cells was classified as eumelanin by EPR determination. The differential response to induction of pigmentation makes these cell lines suitable models for comparative studies on the role of melanin in pigment cell biology.

In Vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin Provides Strong Contrast

Confocal scanning laser microscopy of live human skin was performed to investigate the correlation of in vivo cellular and morphologic features to histology, the effect of wavelength on imaging, and the role of melanin as a contrast agent. We built a video-rate confocal scanning laser microscope for in vivo imaging of human skin. Using a 100 x microscope objective, we imaged high-contrast optical "sections" of normal skin, vitiliginous skin, and a compound nevus. In vivo "confocal histology" correlated well with conventional histology. The maximum imaging depth increased with wavelength: the epidermis was imaged with visible 400-700-nm wavelengths; the superficial papillary dermis and blood cells (erythrocytes and leukocytes) in the deeper capillaries were imaged with the near infrared 800-900-nm wavelengths. For confocal reflectance imaging, melanin provided strong contrast by increased backscattering of light such that the cytoplasm in heavily pigmented cells imaged brightly. In vivo confocal microscopy potentially offers dermatologists a diagnostic tool that is instant and entirely non-invasive compared to conventional histopathology.

The chemistry of melanins and melanogenesis.

Some twenty years have passed since Swan reviewed the chemistry of melanins for Vol. 31 of this series (1). Although some of the questions which he aired at that time have remained unanswered, our knowledge and appreciation of the field have increased dramatically in the intervening years (2, 3). Considerable steps forward have been made in practically all areas of melanin research, including the molecular biology of pigment-related genes (4, 5). Concurrent with these advances, research has begun to explore in earnest some fascinating phenomena at the interface between chemistry and biology, such as the origin of skin colour differences in man, the role of melanins in photoprotection and in a variety of genetic and acquired pigmentary disorders that are of great social concern. Some of these alterations are well known and include albinism, vitiligo, mongolian spots and melanoma. The latter is a tumor of the melanin producing cells whose increasing incidence, aggressive behaviour, and resistance to conventional therapeutic regimens represent a challenge to the whole scientific community.KeywordsPigment CellCarboxyl ContentMelanin PigmentationQuinone MethidePigment PolymerThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.