Epigallocatechin-3-gallate exhibits anti-inflammatory effects in a human interface dermatitis model-implications for therapy.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has been proven effective in treating viral warts. Since anticarcinogenic as well as anti-inflammatory properties are ascribed to the substance, its use has been evaluated in the context of different dermatoses. The effect of EGCG on interface dermatitis (ID), however, has not yet been explored. OBJECTIVES: In this study, we investigated the effect of EGCG on an epidermal human in vitro model of ID. METHODS: Via immunohistochemistry, lesional skin of lichen planus patients and healthy skin were analysed concerning the intensity of interferon-associated mediators, CXCL10 and MxA. Epidermal equivalents were stained analogously upon ID-like stimulation and EGCG treatment. Monolayer keratinocytes were treated likewise and supernatants were analysed via ELISA while cells were processed for vitality assay or transcriptomic analysis. RESULTS: CXCL10 and MxA are strongly expressed in lichen planus lesions and induced in keratinocytes upon ID-like stimulation. EGCG reduces CXCL10 and MxA staining intensity in epidermis equivalents and CXCL10 secretion by keratinocytes upon stimulation. It furthermore minimizes the cytotoxic effect of the stimulus and downregulates a magnitude of typical pro-inflammatory cytokines that are crucial for the perpetuation of ID. CONCLUSIONS: We provide evidence concerning anti-inflammatory effects of EGCG within a human in vitro model of ID. The capacity to suppress mediators that are centrally involved in disease perpetuation suggests EGCG as a potential topical therapeutic in lichen planus and other autoimmune skin diseases associated with ID.

Pathological effects of cyanobacteria on sea fans in southeast Florida.

In early August 2008, observations by divers indicated that sea fans, particularly Gorgonia ventalina, Gorgonia flabellum, and Iciligorgia schrammi, were being covered by benthic filamentous cyanobacteria. From August 2008 through January 2009 and again in April 2009, tissue samples from a targeted G. ventalina colony affected by cyanobacteria and from a nearby, apparently healthy (without cyanobacteria) control colony, were collected monthly for histopathological examination. The primary cellular response of the sea fan to overgrowth by cyanobacteria was an increase in the number of acidophilic amoebocytes (with their granular contents dispersed) that were scattered throughout the coenenchyme tissue. Necrosis of scleroblasts and zooxanthellae and infiltration of degranulated amoebocytes were observed in the sea fan surface tissues at sites overgrown with cyanobacteria. Fungal hyphae in the axial skeleton were qualitatively more prominent in cyanobacteria-affected sea fans than in controls.

Very high finesse optical-feedback cavity-enhanced absorption spectrometer for low concentration water vapor isotope analyses.

So far, cavity-enhanced absorption spectroscopy (CEAS) has been based on optical cavities with a high finesse F that, however, has been limited by mirror reflectivity and by cavity transmission considerations to a few times 10,000. Here, we demonstrate a compact near-infrared optical-feedback CEAS instrument for water vapor isotope ratio measurements, with F>140,000. We show that this very high finesse can be effectively exploited to improve the detection sensitivity to the full extent predicted by the increased effective path length to reach a noise equivalent absorption sensitivity of 5.7×10(-11) cm(-1) Hz(-1/2) for a full spectrum registration (including possible effects of interference fringes and fit model inadequacies).

Management of dermatofibrosarcoma protuberans with fibrosarcomatous transformation: an evidence-based review of the literature.

Fibrosarcomatous transformation represents a rare event in dermatofibrosarcoma protuberans (DFSP) with unpredictable biological behaviour. No guidelines for the adequate treatment of patients with this rare neoplasm have been published. Herein, we present a comprehensive review of the literature comprising 157 patients with transformed DFSP focussing on surgical and adjuvant treatment modalities for this tumour. In the cohort examined, local recurrence occurred in 36% of cases and was significantly lower in patients treated by wide excision with margins ≥2 cm when compared with those treated with local excision without defined margins (P = 0.01). Consistently, negative margin status was associated with a lower recurrence rate when compared with positive or unknown margin status (P = 0.01). Distant metastases were detected in 13% of patients, which is significantly higher when compared with ordinary dermatofibrosarcoma protuberans. Systemic dissemination was preceded by local recurrence in 81% of cases, and is therefore strongly associated with tumour recurrence (P ≤ 0.001). The present data confirm that wide excision with margins ≥ 2 cm represent the gold standard in the treatment of transformed dermatofibrosarcoma protuberans, and prevents recurrence as well as metastasis. When R0-resection is not feasible, adjuvant radiation should be considered for cases with incomplete resection or unknown surgical margins. Irresectable or metastatic transformed DFSP harbouring the COL1A1-PDGFB fusion gene should be treated with imatinib in the palliative setting or as an adjunctive treatment before surgery, although responses may be short-lasting.

Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy.

Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of melanoma patients-from the patients' as well as from the physicians' perspective. The dual blockade of the mitogen-activated protein kinase pathway by B-Raf proto-oncogene serine/threonine kinase and mitogen-activated protein kinase inhibitors and the immune checkpoint inhibition by anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated protein-4 monoclonal antibodies constitute the current standard systemic approaches to combat locally advanced or metastatic melanoma. Here, the preclinical data and clinical evidence of these systemic therapies are reviewed in terms of their potential gonadotoxicity, teratogenicity, embryotoxicity and fetotoxicity. Recommendations for routine fertility and contraception counseling of melanoma patients at fertile age are provided in line with interdisciplinary recommendations for the diagnostic work-up of these patients and for fertility-protective measures. Differentiated recommendations for the systemic therapy in both the adjuvant and the advanced, metastatic treatment situation are given. In addition, the challenges of pregnancy during systemic melanoma therapy are discussed.

Deletion of ADAM-9 in HGF/CDK4 mice impairs melanoma development and metastasis.

ADAM-9 is a metalloproteinase expressed in peritumoral areas by invading melanoma cells and by adjacent peritumoral stromal cells; however, its function in stromal and melanoma cells is not fully understood. To address this question in vivo in a spontaneous melanoma model, we deleted ADAM-9 in mice carrying the hepatocyte growth factor (Hgf) transgene and knock-in mutation Cdk4R24C/R24C, demonstrated to spontaneously develop melanoma. Spontaneous melanoma arose less frequently in ADAM-9-deleted mice than in controls. Similarly reduced tumor numbers (although with faster growth kinetics) were detected upon induction of melanoma with 7,12-dimethylbenz[a]anthracene (DMBA). However, more lesions were induced at early time points in the absence of ADAM-9. Increased initial and decreased late tumor numbers were paralleled by altered tumor cell proliferation, but not apoptosis or inflammation. Importantly, significantly reduced lung metastases were detected upon ADAM-9 deletion. Using in vitro assays to address this effect mechanistically, we detected reduced adhesion and transmigration of ADAM-9-silenced melanoma cells to/through the endothelium. This implies that ADAM-9 functionally and cell autonomously mediates extravasation of melanoma cells. In vitro and in vivo we demonstrated that the basement membrane (BM) component laminin ß3-chain is a direct substrate of ADAM-9, thus contributing to destabilization and disruption of the BM barrier during invasion. In in vitro invasion assays using human melanoma cells and skin equivalents, depletion of ADAM-9 resulted in decreased invasion of the BM, which remained almost completely intact, as shown by continuous staining for laminin ß3-chain. Importantly, supplying soluble ADAM-9 to the system reversed this effect. Taken together, our data show that melanoma derived ADAM-9 autonomously contributes to melanoma progression by modulating cell adhesion to the endothelium and altering BM integrity by proteolytically processing the laminin-ß3 chain. This newly described process and ADAM-9 itself may represent potential targets for anti-tumor therapies.

[Anorectal malignant melanoma : Treatment recommendations]. / Das anorektale maligne Melanom : Eine Therapieempfehlung.

BACKGROUND: Anorectal malignant melanoma is a rare tumor with a poor prognosis. Typical symptoms (bleeding, pain, perianal mass) are characteristic of hemorrhoids. This, together with the high rate of amelanotic tumors, often delays diagnosis. No therapy guidelines exist. MATERIALS AND METHODS: Based on our own experience of surgically treated patients and an extensive literature search, we present a stage-dependent therapeutic concept. RESULTS: Eight patients (six women) with a mean age of 65 ± 8 years were treated at our institution. Six underwent abdominoperineal resection; two had local excision. Two patients additionally underwent inguinal lymph node dissection. Median survival was 12 months with a disease-free survival of 6 months. Forty treatment studies with a total of 1,970 cases could be identified. Prognostic factors are age, time to correct diagnosis, tumor extent, tumor stage, and perineural invasion. The impact of lymph node metastases and R0 resection varies. Surgery is the only effective therapy. Local excision is sufficient when free resection margins are achieved. CONCLUSIONS: Locally limited tumors should be resected; if possible using local excision. Larger tumors or tumors with sphincter infiltration often require abdominoperineal resection with curative intent. When regional lymph node metastases are present, we advise regional lymphadenectomy of the affected area. In the case of distant metastases, palliative surgery is needed for metastasectomy and in cases of incontinence or refractory pain.

Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria.

OBJECTIVE: To examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia. STUDY DESIGN: Retrospective cohort study. Data from all hospitalized pregnant women between 2009 and 2014 with new onset isolated proteinuria of over 300 mg/24 h at admission were obtained. Follow-up was performed from the time of admission to the hospital to the time of discharge postpartum. Obstetrical, maternal and neonatal outcomes were obtained. RESULT: Ninety-five pregnant women diagnosed with new onset isolated proteinuria were followed to term. Thirteen women developed pre-eclampsia during pregnancy and eight developed pre-eclampsia postpartum. Maternal characteristics for progression to pre-eclampsia were greater maximal values of proteinuria. Earlier pre-eclampsia onset was associated with early-onset proteinuria and multiple gestation. Although greater values of proteinuria were associated with increased risk for intrauterine growth restriction and lower Apgar scores, maternal outcome was favorable, regardless of pre-eclampsia progression. Isolated proteinuria progressing to pre-eclampsia was associated with late pre-eclampsia onset and favorable maternal and neonatal outcomes. CONCLUSION: A significant proportion of women with new onset isolated proteinuria will develop pre-eclampsia. In these women, close follow-up is recommended until after delivery.

Classification and identification of Pfiesteria and Pfiesteria-like species.

Dinoflagellates can be classified both botanically and zoologically; however, they are typically put in the botanical division Pyrrhophyta. As a group they appear most related to the protistan ciliates and apicomplexans at the ultrastructure level. Within the Pyrrhophyta are both unarmored and armored forms of the dominant, motile flagellated stage. Unarmored dinoflagellates do not have thecal or wall plates arranged in specific series, whereas armored species have plates that vary in thickness but are specific in number and arrangement. In armored dinoflagellates, the plate pattern and tabulation is a diagnostic character at the family, subfamily, and even genus levels. In most cases, the molecular characterization of dinoflagellates confirms the taxonomy on the basis of external morphology; this has been demonstrated for several groups. Together, both genetic and morphological criteria are becoming increasingly important for the characterization, separation, and identification of dinoflagellates species. Pfiesteria and Pfiesteria-like species are thinly armored forms with motile dinospore stages characterized by their distinct plate formulae. Pfiesteria piscicida is the best-known member of the genus; however, there is at least one other species. Other genetically and morphologically related genera, now grouped under the common names of "Lucy," "Shepherd's crook," and cryptoperidiniopsoid, are being studied and described in separate works. All these other heterotrophic dinoflagellate groups, many of which are thought to be benign, co-occur in estuarine waters where Pfiesteria has been found.

Tyrosine kinase-mediated activation of cytosolic calcium oscillations and phasic myometrial contractions.

These studies sought to test the hypothesis that tyrosine kinase-stimulated phasic myometrial contractions are mediated by activation of the phosphatidylinositol (PI)-signaling pathway and the generation of cytosolic calcium oscillations. For these studies, uterine tissue was obtained from adult female Sprague-Dawley white rats during the proestrus/estrus phase of the cycle. In vitro contraction studies were performed using pervanadate (a tyrosine phosphatase inhibitor) with and without inhibitors of the PI-signaling pathway, including 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (a phospholipase C inhibitor), thimerosal (an inositol-trisphosphate receptor/channel inhibitor), and Ruthenium red (a ryanodine receptor inhibitor), and with oxytocin or prostaglandin F2 alpha (two classic uterotonic agonists). Cytosolic calcium studies were performed using Fura-2-loaded myometrial strips. During these studies, pervanadate was observed to produce cytosolic calcium oscillations and phasic contractions in myometrial tissue comparable to those produced in response to oxytocin and prostaglandin F2 alpha. The pervanadate-stimulated phasic contractions were significantly suppressed in response to inhibition of phospholipase C, the inositol-trisphosphate receptor, and the ryanodine receptor, thereby confirming the importance of the PI-signaling pathway during tyrosine kinase-associated myometrial activity. Further confirming the important and shared role for the PI-signaling pathway during pervanadate-stimulated myometrial contractions, no significant additive effects were observed when classic uterotonic agonists such as oxytocin or prostaglandin F2 alpha were combined with pervanadate.

Microanalysis of senile plaques using nuclear microscopy.

Silver-staining "senile" plaques occurring in the brain are a major part of the pathology of Alzheimer's disease. The elemental composition of these structures, and the possible presence of aluminum and silicon in these structures, has been the subject of an increasing research effort over the last decade. However, the results have often been contradictory. Using a scanning proton microprobe, the elemental composition of senile plaques has been determined. This instrument, similar to an electron probe, uses a focused beam of protons scanned across a sample to map the elements. The technique is absolutely quantitative and is sensitive down to the parts per million level. Tissue from six cases of clinically and pathologically characterized cases of Alzheimer's disease and two aged neurologically normal controls was scanned. It was found that aluminum and silicon occur at a level of 50 ppm or greater in the cores of 20% of senile plaques and that the total occurrence of aluminum or silicon in scans containing plaques was not above background. The major uncertainties affecting interpretation of results of this kind are discussed, and it is suggested that the least controllable factor is contamination in the reagents used to prepare and stain the tissue. This indicates that until plaques can be unambiguously identified and analyzed in untreated tissue, no conclusion can be reached on whether senile plaques contain aluminum and silicon.

The toothbrush and gingival traumatic injury.

This paper explores, by means of clinical observation, toothbrush misuse and its relationship to gingival recession/clefting. The morphology of the lesions created is correlated with the vigor, duration, frequency and direction of the toothbrush abuse. In addition, histologic observations of biopsied tissue from different types of clefts and recessions are used as a basis for discussion of the possible pathogenesis of this type of lesion.

The effect of betamethasone versus dexamethasone on fetal biophysical parameters.

BACKGROUND: Clinical observations suggest that betamethasone reduces maternal perception of fetal movements and short term variability, but that this dose not occur after treatment with dexamethasone. OBJECTIVES: To compare the effect of betamethasone and dexamethasone on fetal biophysical parameters. METHODS: In a randomized, prospective, double blind study, 20 courses of betamethasone and 20 courses of dexamethasone were given in random sequence to patients with imminent preterm labor. During the first 32h after initiation of treatment, fetal movements were counted by the mothers and recorded by ultrasound, and a nonstress test was performed. RESULTS: Betamethasone induced a significant decrease in fetal movements as perceived by the mother and observed by ultrasound. Fetal breathing movements also decreased. Dexamethasone did not change fetal body movements. Neither drug changed the short term variability. CONCLUSIONS: Unlike betamethasone, dexamethasone does not induce a decrease in fetal movements. Dexamethasone might, therefore, be preferred for enhancement of lung maturation in imminent preterm labor.

Etiologies, observations and reporting of estuarine finfish lesions.

Lesions in estuarine finfish are associated with a variety of organisms including parasites and bacterial, viral, and fungal infectious agents. In addition, trauma, suboptimal water quality, and other abiotic stress factors may result in the loss of homeostasis. We have observed solitary ulcerative lesions on menhaden sampled from the Chesapeake Bay, Maryland, the Pimlico River, North Carolina, and the St. Johns River, Florida. Histologically, the lesions demonstrated a marked chronic inflammatory infiltrate and granulomas in response to fungal hyphae throughout large areas of exposed necrotic muscle. Gram-negative rod-shaped bacteria were also observed in the lesions, a common finding in ulcers of aquatic organisms. Similar observations in menhaden and other species have been described previously in the literature as ulcerative mycosis, mycotic granulomatosis, red spot disease, and epizootic ulcerative syndrome. Despite the many different known causes of fish lesions, the popular press and the scientific literature have recently emphasized Pfiesteria piscicida and other Pfiesteria-like dinoflagellates (and their bioactive compounds) as the primary causative agent for finfish lesions, particularly mycotic granulomatous ulcers in Atlantic menhaden. While some laboratory data suggest that Pfiesteria may play a role in field-observed lesions, much more cause-and-effect evidence is needed to determine the importance of other risk factors, both alone or and in combination with Pfiesteria. In order to better understand the etiology of lesion initiation and progression in estuarine finfish, accurate assessments of environmental conditions collected on appropriate temporal and spatial scales, and fish morphological indicators consistent with gross and histological pathologic terminology, should be used for reporting fish lesion observations and kills. Further, this outlook will help to avoid bias and may foster a broader perspective for examining the health of estuarine systems in general.

Experimental approaches to the study of the effects of nutrients and water on carbon assimilation by trees.

This paper outlines the experiemental approaches needed to provide detailed information about the effects of nutrients and water on carbon assimilation, and hence growth of trees. Data from a large multidisciplinary experiment being conducted in Australia illustrate important aspects of the approach advocated. The system model consists of a series of submodels describing the main physiological processes considered to govern the growth of trees. It is argued that field experiments designed to investigate physiological processes and their interactions should involve treatments that cause large differences in the growth rates of trees and in the condition of the trees at any time. The biomass of experimental stands should be defined. Measurements of stem and leaf growth, litterfall, leaf photosynthetic characteristics, plant water status and soil water content, plant nutrient status and nutrient mineralization rates in the soil provide the information needed to explain observed differences in growth and to refine the models underlying the research.

Posthatch age and developmental age as a baseline for determination of the sensitive period for imprinting.

Two experiments comparing developmental age and posthatch age were performed. In the first experiment 143 Peking ducklings of different posthatch ages were imprinted, and their following responses examined in a simultaneous choice test. A sensitive period was evident on the basis of posthatch age. In the second experiment 99 ducklings were separated in three clusters of different posthatch ages, which did not vary within the clusters relative to their probability to be imprinted. The ducklings of each cluster were imprinted at various developmental ages, and the results show the involvement of developmental age. Thus, both experiments considered together favor the concept of an interaction of developmental and posthatch age. Imprinting and the determination of the sensitive period are dependent on prehatch and posthatch learning, so both developmental age and posthatch age are involved in setting the limit of the sensitive period.

Myxosporean infections in cultured tilapias in Israel.

Five new species of myxosporean parasite are described from cultured tilapias in Israel. These are: Myxosoma sarigi, Myxosoma equatorialis, Myxobolus israelensis, Myxobolus agolus, and Myxobolus galilaeus. The first four were found in hybrids of Oreochromis aureus X Oreochromis niloticus while Myxobolus galilaeus was found in Sarotherodon galilaeus. In addition, M. sarigi, M. israelensis, and Myxobolus sp. were also found in S. galilaeus. In the light of the present study, the taxonomy of myxosporean infections in tilapias is modified. Mature spores may localize in the melano-macrophage centers of the spleen and kidney where they may eventually be destroyed. No cases of mortality have so far been associated with these parasites.

Intestinal infections by Eimeria (s. l.) vanasi n. sp. (Eimeriidae, Apicomplexa, Protozoa) in cichlid fish.

Eimeria (s. l.) vanasi n. sp. is described from the intestine of a variety of cichlids in Israel and South Africa. Merogony and gamogony stages are both intra- and epiepithelial, Sporogony is exogenous with young zygotes being released from the fish in the faeces. Fully developed sporocysts are ellipsoid and apparently lacking both a Stieda body (characteristic of Eimeria s. st. and Epieimeria species) and a suture line (characteristic of Goussia species). In view of the present controversial generic status of piscine coccidia, the species is tentatively designated as Eimeria (s. l.) vanasi n. sp. (Eimeriidae, Apicomplexa, Protozoa).