The effects of zoledronate on monocyte-derived dendritic cells from melanoma patients differ depending on the clinical stage of the disease.

Zoledronic acid has shown indirect anticancer effects on angiogenesis, the tumor microenvironment and immune responses. Its immunological action is exerted, at least in part, via its modulating properties. The aim of this study was to investigate the in vitro effects of zoledronic acid on the dendritic cells of melanoma patients. Peripheral blood samples were collected from 26 patients with melanoma and 11 healthy donors. Dendritic cells were derived from purified monocytes, and zoledronic acid (ZA) was added on the first day of culture. The phenotype and function of the generated cells were evaluated by flow cytometry. The ZA-treated monocytes from patients with early-stage disease generated DCs characterized by reduced endocytic activity and increased allostimulatory capacity compared with the untreated samples, allowing restoration of the DC function observed in normal subjects. In contrast, the ZA-treated monocytes from patients at stage III generated cells with higher CD14 antigen expression and endocytosis than the untreated samples. Therefore, in melanoma patients, the in vitro ZA effects differ according to the progression of the disease. In addition, our preliminary results appear to suggest that ZA effects are also influenced by the expression of CD14 antigen, indicating that the DC phenotype together with clinical characteristics must be considered in the choice of patients to be treated with ZA. Our work focus on the effect of ZA on monocyte-derived DCs from melanoma patients, showing that the effects of therapeutic doses of this drug might be mediated at least in part by modulation of myeloid cell function

Circulating MicroRNAs in Cutaneous Melanoma Diagnosis and Prognosis

Cutaneous melanoma represents a challenge for pharmacologists and clinicians due to their high degree of genetic and phenotypic heterogeneity. The identification of new non-invasive and informative biomarkers would therefore represent a substantial step to adequately treat melanoma patients. MicroRNAs (miRNAs) are a class of small non-coding RNAs that play an important role as negative regulators of gene expression. Several studies have demonstrated their correlation with disease status in different types of cancer including melanoma. Extracellular miRNAs are released from both tumor cells and/or normal cells. MiRNAs do not circulate freely in biological fluids but they are incorporated into extracellular vesicles or form complexes with lipids and proteins. Circulating miRNAs may represent potential biomarkers of cutaneous melanoma diagnosis and patient prognosis. Longitudinal monitoring of cell-free miRNAs in biological fluids of melanoma patients could help clinicians to predict disease progression before the tumor becomes resistant to a given drug. However, to confirm their clinical utility it will be necessary to validate the best available technique for their detection and quantification and to test selected miRNAs in prospective clinical trials

Adsorption Capabilities of Fungoid Chitosan Toward Organic Acids in Model Solutions and White Wine

In oenology, fungoid chitosan (CH) can be used as an adjuvant for microbial control, haziness prevention, metal chelation, and ochratoxin removal. In acidic media (such as wine), CH can ionise and interact with charged compounds, giving rise to a series of adsorption and/or removal phenomena, some of which potentially impairing the overall quality of wines. In this context, it is worth noting that the interaction between CH and acidic components of wines has been poorly studied so far, and detailed information on this subject is still lacking. To study those interactions, different doses of chitosan (0.5; 1.0; 2.0 g/L) were dispersed in hydro-alcoholic solution (HS), synthetic wine solution (SW), and white wine (W). Results demonstrated that the remotion of tartaric acid and the change of pH were strongly affected by the matrix and dosage. In W and SW, chitosan was found to adsorb tartaric acid up to about 200 mg/g and 350 mg/g CH, respectively. Accordingly, pH values increased; however, the magnitude depended on the matrix as a consequence of different buffer capacities. Interestingly, even in the absence of tartaric acid (e.g. in HS samples) CH addition caused a pH increase (up to 1.2 units for 2 g/L CH addition) which demonstrated that pH variations may not only depend on the amount of organic acids adsorbed. The chitosan dispersed in W showed the highest average diameter D [3,2] (127.96 μm) compared to the ones dispersed in SW (120.81 μm) and in HS (116.26 μm), probably due to the presence of organic acids on the polymer surface. The minor removal of tartaric acid in W compared to SW could probably depend on the competitive adsorption onto chitosan of other families of compounds present in wine such as polyphenols. The data suggested that chitosan addition could affect the pH and organic acid concentration of all matrices, depending on the doses and composition of the solutions

EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound - Part 1: Examination Techniques and Normal Findings (Short version)

Abstract ▼ In October 2014 the European Federation of Societies for Ultrasound in Medicine and Biology formed a Gastrointestinal Ultrasound (GIUS) task force group to promote the use of GIUS in a clinical setting. One of the main objectives of the task force group was to develop clinical recommendations and guidelines for the use of GIUS under the auspices of EFSUMB. The first part, gives an overview of the examination techniques for GIUS recommended by experts in the field. It also presents the current evidence for the interpretation of normal sonoanatomical and physiological features as examined with different ultrasound modalities

EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound - Part 1: Examination Techniques and Normal Findings (Long version).

Abstract ▼ In October 2014 the European Federation of Societies for Ultrasound in Medicine and Biology formed a Gastrointestinal Ultrasound (GIUS) task force group to promote the use of GIUS in a clinical setting. One of the main objectives of the task force group was to develop clinical recommendations and guidelines for the use of GIUS under the auspices of EFSUMB. The first part, gives an overview of the examination techniques for GIUS recommended by experts in the field. It also presents the current evidence for the interpretation of normal sonoanatomical and physiological features as examined with different ultrasound modalities

Physico-chemical and sensory characterization of a fruit beer obtained with the addition of cv. Lambrusco grapes must

In 2015, Italian Grape Ale (IGA) beers have been included as a new provisional sub-category of special-type fruit beers by the Beer Judge Certification Program, including those products whose brewing process is carried out in presence of determined quantities of grape must. However, information on the effects of these additions on the composition of final beers are still scarce. This work is hence focused on the chromatic, volatile, phenolic and sensory characterization of IGA beers obtained with the addition of grape musts during brewing process. To this aim, different amounts of must (5, 10 and 20%) from cv. Lambrusco red grapes were added to a lager wort before primary fermentation. Beers were then characterized by HPLC-MS, GC-MS and sensory analysis in order to determine phenolic and aroma compounds along with their sensory attributes. Results confirmed the addition of must from cv. Lambrusco grapes capable to enrich beers in color, acids, phenolic (up to 7-folded increased) and volatile compounds, while giving complexity to beers. These results, which were confirmed by a trained sensory panel, are among the very first insights on the impact of red grape must in brewing, both from a compositional and sensory point of view

Adrenal response of male rats exposed to prenatal stress and early postnatal stimulation

Stress in pregnant rats caused by chronic immobilization alters the pattern of secretion of corticosterone and modifies the hypothalamic-pituitary-adrenal axis (HPA) of the fetus. Early postnatal handling, however, may reverse the effects of increased secretion of corticosterone. We investigated the effects of prenatal stress and postnatal handling on the activity of the HPA axis of male offspring of stressed female rats. Male 90-day-old rats from four groups were investigated: prenatally stressed animals without postnatal handling, prenatally stressed animals with postnatal handling, unstressed control animals with postnatal handling, and unstressed control animals without postnatal handling. After sacrifice, the adrenal glands were weighed to determine the adrenal-somatic index. Apoptosis was evaluated by TUNEL assay and active caspase-3 expression. We found that the adrenal gland cortex:medulla ratio increased in animals with prenatal stress and that eventually the stress caused apoptosis. Handling newborns to simulate maternal activity ameliorated some of the negative effects of prenatal stress.Fil: Liaudat, Ana Cecilia. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, N.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Chen, S.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Romanini, María Cristina. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vivas, A.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Rolando, A.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Gauna, H.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Mayer, N.. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; Argentin

First results from the OSQAR photon regeneration experiment: No light shining through a wall

A new method to amplify the photon-axion conversions in magnetic field is proposed using a buffer gas at a specific pressure. As a first result, new bounds for mass and coupling constant for purely laboratory experiments aiming to detect any hypothetical scalars and pseudo-scalars which can couple to photons were obtained at 95% confidence level, excluding the PVLAS result newly disclaimed.Comment: 4 pages, 5 figure

SKI-1 and Furin Generate Multiple RGMa Fragments that Regulate Axonal Growth

SummaryThe nervous system is enormously complex, yet the number of cues that control axonal growth is surprisingly meager. Posttranslational modifications amplify diversity, but the degree to which they are employed is unclear. Here, we show that Furin and SKI-1 combine with autocatalytic cleavage and a disulfide bridge to generate four membrane-bound and three soluble forms of the repulsive guidance molecule (RGMa). We provide in vivo evidence that these proprotein convertases are involved in axonal growth and that RGMa cleavage is essential for Neogenin-mediated outgrowth inhibition. Surprisingly, despite no sequence homology, N- and C-RGMa fragments bound the same Fibronectin-like domains in Neogenin and blocked outgrowth. This represents an example in which unrelated fragments from one molecule inhibit outgrowth through a single receptor domain. RGMa is a tethered membrane-bound molecule, and proteolytic processing amplifies RGMa diversity by creating soluble versions with long-range effects as well

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis