"Extramammary-Type" Paget Disease of the Breast.

BACKGROUND: Mammary Paget disease and extramammary Paget disease (EMPD) have different prognoses. Because they are indistinguishable on histopathological grounds, they must be distinguished on a topographical basis. OBJECTIVE: To study cases of Paget disease of the breast, which show similarities to EMPD. METHODS: Cases were selected by 2 different approaches: (1) those with an exceptionally good evolution and no evidence of subjacent tumor and (2) those expressing MUC5AC. RESULTS: Five cases were collected. All cases showed an indolent behavior with a known long clinical history in 2 cases (9 and 25 years, respectively) and a long follow-up in all cases but one (4-8 years). In all cases but one, surgery was performed, and no parenchymal tumor was found (either intraductal or infiltrating). All cases expressed cytokeratin 7 and MUC5AC without expression of MUC2, S100, or p40. LIMITATIONS: The short number of cases is a limitation of this study. In addition, case 5 is recent, so we have a very short follow-up. CONCLUSIONS: Some cases of mammary Paget disease behave like EMPD with slow progression and with no underlying associated tumor. Immunoexpression of MUC5AC might be a clue to identify them.

Oral administration of Polypodium leucotomos delays skin tumor development and increases epidermal p53 expression and the anti-oxidant status of UV-irradiated hairless mice.

Chronic exposure to ultraviolet radiation (UVR) induces skin tumors in hairless mice. Daily oral administration of a Polypodium leucotomos (PL) extract significantly delayed tumor development in PL-treated versus non-PL-treated mice. UVR and/or PL treatment modified several oxidative stress markers. In all irradiated mice, erythrocytic glutathione S-transferase (GST) activity and glutathione disulphide (GSSG) content increased and in all PL-treated mice GSSG content decreased, specially in non-irradiated animals, and total plasma anti-oxidant capacity (ORAC) increased. In dorsolateral non-tumoral skin of all irradiated mice, glutathione reductase (GR) and glutathione peroxidase (GPx) activities increased and GSSG decreased in non-irradiated PL-treated animals. UVR induced a steep increase of p53 expression in epidermal cells. In non-tumoral skin, this increase was significantly higher in PL-treated animals than in non-treated mice and can contribute in delaying tumor development, either by repairing the damaged DNA or by increasing apoptosis. These results reinforce the usefulness of PL as systemic photoprotective agent, especially in patients highly sensitive to UVR.

Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice.

A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties.

Preliminary evaluation of benign vascular lesions using in vivo reflectance confocal microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) is a novel noninvasive imaging technique for in vivo evaluation of cutaneous lesions at near-histologic resolution. The applicability of RCM for various neoplastic and inflammatory skin diseases has been shown, but a descriptive evaluation of different vascular lesions has not yet been performed. OBJECTIVES: To define specific RCM criteria for congenital and acquired vascular lesions and to determine whether these criteria may assist in their differential diagnosis. MATERIALS AND METHODS: Seven patients with a clinical diagnosis of vascular lesion, including spider angioma, venous lake, cherry angioma, pyogenic granuloma, port wine stain, angiokeratoma, and lymphangioma, participated in this study. Skin sites were systematically analyzed using RCM, and biopsy was obtained for clinically indeterminate lesions. RESULTS: For each entity, characteristic RCM criteria could be identified and selected parameters correlated well to established histopathologic findings. The most relevant criteria included the diameter of the vessels and degree of vascular tortuosity or dilation. Additional findings such as flow velocity, inflammation, and disruption of the epidermal architecture could be documented. CONCLUSION: The findings of this preliminary evaluation indicate that RCM may aid in the noninvasive characterization of inflammatory, proliferative, and ectatic vascular malformations in vivo.

Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

INTRODUCTION: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination. MATERIAL AND METHODS: We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site. RESULTS: Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms. CONCLUSION: Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.

The Sonozotz project: Assembling an echolocation call library for bats in a megadiverse country.

Bat acoustic libraries are important tools that assemble echolocation calls to allow the comparison and discrimination to confirm species identifications. The Sonozotz project represents the first nation-wide library of bat echolocation calls for a megadiverse country. It was assembled following a standardized recording protocol that aimed to cover different recording habitats, recording techniques, and call variation inherent to individuals. The Sonozotz project included 69 species of echolocating bats, a high species richness that represents 50% of bat species found in the country. We include recommendations on how the database can be used and how the sampling methods can be potentially replicated in countries with similar environmental and geographic conditions. To our knowledge, this represents the most exhaustive effort to date to document and compile the diversity of bat echolocation calls for a megadiverse country. This database will be useful to address a range of ecological questions including the effects of anthropogenic activities on bat communities through the analysis of bat sound.

Potential of Jatropha curcas as a source of renewable oil and animal feed.

Jatropha curcas (L.) is a perennial plant of the spurge family (Euphorbiaceae). Recently, it has received much attention as a potential source of vegetable oil as a replacement for petroleum, and, in particular, the production of biodiesel. Despite the interest that is being shown in the large-scale cultivation of J. curcas, genetic resources remain poorly characterized and conserved and there has been very little plant breeding for improved traits. At present, the varieties being used to establish plantations in Africa and Asia are inedible. The meal obtained after the extraction of oil cannot, therefore, be used as a source of animal feed. Naturally existing edible varieties are, however, known to occur in Mexico. The toxic components of J. curcas seeds, the potential for plant breeding to generate improved varieties, and the suitability of J. curcas oil as a feedstock for biodiesel production are discussed.

Mucinous carcinoma of the skin: evaluation of lymphatic invasion with D2-40.

Primary cutaneous mucinous carcinoma is a rare adnexal sweat gland neoplasm that mainly affects elderly people. Differential diagnosis includes mammary and gastrointestinal metastatic mucinous carcinoma (MC) and secondary cutaneous involvement by underlying neoplasms. An 83-year-old woman presented with an 8-year history of slow-growing infiltrate plaque in her right hemithorax, with ulceration on supraclavicular area, right upper limb edema and palpable axillary lymphadenopathies. She underwent partial excision of the tumor and local radiotherapy. Imaging studies showed widespread cutaneous dissemination with enlargement of ipsilateral axillary lymph nodes but without evidence of underlying breast cancer. Histopathological examination showed large amounts of mucin in the dermis including small islands of epithelial cells. They stained positive for cytokeratin 7, carcinoembryonic antigen, epithelial membrane antigen, gross cystic disease fluid protein-15, and c-erbB-2. Lymphatic invasion was demonstrated by D2-40-immunostained sections. A diagnosis of primary cutaneous mucinous carcinoma was made. Our aim was to reevaluate the differential clinical, histopathological, and immunohistochemical criteria for distinguishing primary cutaneous mucinous carcinoma from skin metastases of visceral mucinous carcinoma, especially those arising in breast. We also propose D2-40 as a reliable marker to detect lymphatic invasion that indicates a strong aggressive trend with shorter recurrence-free and predicts nodal metastases.

Photodynamic therapy of cancer. Basic principles and applications.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved for clinical treatment of several types of cancer and non-oncological disorders. In PDT, a compound with photosensitising properties (photosensitiser, PS) is selectively accumulated in malignant tissues. The subsequent activation of the PS by visible light, preferentially in the red region of the visible spectrum (lambda>or=600 nm), where tissues are more permeable to light, generates reactive oxygen species, mainly singlet oxygen ((1)O(2)), responsible for cytotoxicity of neoplastic cells and tumour regression. There are three main mechanisms described by which (1)O(2) contributes to the destruction of tumours by PDT: direct cellular damage, vascular shutdown and activation of immune response against tumour cells. The advantages of PDT over other conventional cancer treatments are its low systemic toxicity and its ability to selectively destroy tumours accessible to light. Therefore, PDT is being used for the treatment of endoscopically accessible tumours such as lung, bladder, gastrointestinal and gynaecological neoplasms, and also in dermatology for the treatment of non-melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic keratosis). Photofrin, ALA and its ester derivatives are the main compounds used in clinical trials, though newer and more efficient PSs are being evaluated nowadays.

Influence of habitat suitability and sex-related detectability on density and population size estimates of habitat-specialist warblers.

Knowledge about the population size and trends of common bird species is crucial for setting conservation priorities and management actions. Multi-species large-scale monitoring schemes have often provided such estimates relying on extrapolation of relative abundances in particular habitats to large-scale areas. Here we show an alternative to inference-rich predictive models, proposing methods to deal with caveats of population size estimations in habitat-specialist species, reed warblers (Acrocephalus scirpaceus and Acrocephalus arundinaceus). Reed warblers were only found in pure reedbeds within riparian woodlands or in riparian vegetation scattered within or around reedbed patches, as expected according to their habitat specialization. The proportion of individuals located in reedbed associated with lotic and lentic waters differed between species, and no reed warbler was recorded in reedbed located along dry streams. This indicates that microhabitat features or their effects on reedbed structure and other factors made a proportion of the apparently available habitat unsuitable for both warbler species. Most warblers detected were males performing territorial singing (females seldom sing and do not perform elaborate territorial song, and are undistinguishable from males by plumage). The regional population sizes of the warbler species (~4000 individuals of A. scirpaceus and ~ 1000 individuals of A. arundinaceus) were much smaller than those estimated for the same area by transforming relative abundance obtained at a national scale to population size through extrapolation by habitat at a regional scale. These results highlight the importance of considering the habitat actually used and its suitability, the manner of sex-related detection, population sex-ratio and their interactions in population estimates. Ideally, the value of predictive methods to estimate population size of common species should be tested before conducting large-scale monitoring, rather than a posteriori. Although logistically challenging, this can be achieved by designing monitoring programs including an intensive sampling of abundance in ad hoc reference areas of variable size.

Assessment of the efficacy and tolerance of an innovative regenerative serum on cutaneous regeneration, following fractional laser procedure using Erbium:YAG.

INTRODUCTION: Cutaneous regeneration, fractional laser, medical device, cellular proliferation cutaneous changes linked to photoaging are currently treated with physical treatments, such as fractional laser, which may induce epidermal alteration. OBJECTIVE: To determine the efficacy and safety of a regenerative serum (Matricium® , Laboratoire Bioderma, France) after laser procedure. METHODS: Prospective, double-blind, controlled, and randomized study in subjects with photoaged skin. The regenerative serum of treatment was used after a fractional laser session twice daily for 2 months on 1 side of the face and the placebo on the other side. The main variable to determine efficacy was the improvement of clinical signs and histological and immunological results. RESULTS: A superior quality of epidermal regeneration on the treated side compared to the placebo side was observed. Likewise, a superior and faster clinical improvement on static wrinkles was observed on the hemiface on which the regenerative serum was used. After 60 days, the investigator and the subjects observed a moderate to significant improvement of the skin on the treated side and a mild to moderate improvement on the placebo side. Histological examinations showed a superior thickness of epidermis and higher cellular proliferation rate (Ki67 markers) as well as a superior thickness of dermis with higher increase in elastin density with the regenerative serum compared to placebo. CONCLUSION: The use of the regenerative serum after fractional laser on the face accelerated and improved the cutaneous regeneration on both the clinical and histological level and maximized the benefits of the laser procedure.

Two-dimensional discrete solitons in rotating lattices.

We introduce a two-dimensional discrete nonlinear Schrödinger (DNLS) equation with self-attractive cubic nonlinearity in a rotating reference frame. The model applies to a Bose-Einstein condensate stirred by a rotating strong optical lattice, or light propagation in a twisted bundle of nonlinear fibers. Two types of localized states are constructed: off-axis fundamental solitons (FSs), placed at distance R from the rotation pivot, and on-axis (R=0) vortex solitons (VSs), with vorticities S=1 and 2 . At a fixed value of rotation frequency Omega , a stability interval for the FSs is found in terms of the lattice coupling constant C , 0

Erythema nodosum leprosum: reactional leprosy.

The different clinical forms of leprosy are mainly related to the variety of immunological responses to the infection. Thus, lepromatous leprosy occurs in patients with a poor cell-mediated immunity to Mycobacterium leprae, whereas tuberculoid leprosy is associated with a high resistance to leprosy bacillus. Intermediate forms, including borderline tuberculoid leprosy, borderline lepromatous leprosy, and borderline leprosy, are a continuous and unstable spectrum of the disease. Leprosy reactions are rare and not well-known states that interrupt the usual chronic course and clinical stability of patients with leprosy. They are expressions of immunological perturbations. Attending to the clinical and histopathological manifestations, leprosy reactions may be separated in 2 or 3 different variants: reverse reaction (type I), erythema nodosum leprosum (type II), erythema polymorphous (type II) and Lucio's phenomenon, mainly considered a type II reaction, but sometimes designated type III. Type I leprosy reaction, also named "upgrading reaction," occurs in borderline leprosy states and is associated with a shift toward the tuberculoid pole. Type II reaction usually occurs in lepromatous leprosy, and there are 3 different clinical variants, including erythema nudosum leprosum, erythema polymorphous-like reaction, and Lucio's phenomenon.

Motion of discrete solitons assisted by nonlinearity management.

We demonstrate that time-periodic modulation of the nonlinearity coefficient in the discrete nonlinear Schrödinger equation strongly facilitates creation of traveling solitons in the lattice. We predict this possibility in a semi-qualitative form analytically, and test it in direct numerical simulations. Systematic computations reveal several generic dynamical regimes, depending on the amplitude and frequency of the time modulation, and on the initial thrust which sets the soliton in motion. These regimes include irregular motion of the soliton, regular motion of a decaying one, and regular motion of a stable soliton. The motion may occur in both the straight and reverse directions, relative to the initial thrust. In the case of stable motion, extremely long simulations in a lattice with periodic boundary conditions demonstrate that the soliton keeps moving indefinitely long without any visible loss. Velocities of moving stable solitons are in good agreement with the analytical prediction, which is based on requiring a resonance between the ac drive and motion of the soliton through the periodic lattice. The generic dynamical regimes are mapped in the model's parameter space. Collisions between moving stable solitons are briefly investigated too, with a conclusion that two different outcomes are possible: elastic bounce, or bounce with mass transfer from one soliton to the other. The model can be realized experimentally in a Bose-Einstein condensate trapped in a deep optical lattice.

Clinical and histopathological improvement of psoriasis with oral chondroitin sulfate: a serendipitous finding.

We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.

Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study.

BACKGROUND: The current standard diagnostic procedure for basal cell carcinoma (BCC) is histologic examination after invasive biopsy. Reflectance-mode confocal microscopy (RCM) offers noninvasive high-resolution imaging of human skin in vivo. OBJECTIVE: The objective of this study was to explore the sensitivity and specificity of RCM for diagnosis of BCC. METHODS: This was a retrospective study of RCM images from 4 institutions of 152 skin lesions representing a variety of benign and malignant diagnoses. These 152 lesions were examined clinically, with biopsies recorded for all the 83 BCCs detected. Based on a previous study, a set of 5 histologically correlated confocal imaging criteria for diagnosing BCC was established, eg, the presence of elongated monomorphic nuclei. Blinded retrospective analysis of the images from the 152 lesions was carried out by a single novice reviewer to determine the sensitivity and specificity of these 5 RCM criteria for diagnosing BCC. The accuracy of combining the probability of BCC based on examination of clinical photographs with the predicted probability of BCC based on confocal criteria was also evaluated. RESULTS: The presence of two or more criteria is 100% sensitive for the diagnosis of BCC, and with 4 or more RCM criteria present the specificity was 95.7% and sensitivity was 82.9%. These results were found to have little variability across study sites and across BCC subtypes. The combination of RCM with photography-based predictions of clinical probability of BCC significantly improved the accuracy for noninvasive diagnosis of BCC. CONCLUSION: RCM offers a sensitive and specific tool for the noninvasive diagnosis of BCC in vivo.