CD8+ T lymphocytes infiltrate in mammary tumours chemically­induced in female rats: what is the influence of ketotifen administration?

Background: Mammary cancer is one of the most frequent cancers among women. Neoplasia are complex masses composed of both neoplastic and non-neoplastic cells, like vascular and lymphatic endothelial cells, adipocytes, mesenchymal cells, fibroblasts, myeloid and inflammatory cells (lymphocytes, neutrophils, eosinophils, macrophages, and mast cells). This work aimed to evaluate the effects of ketotifen on the infiltrate of CD8+ T lymphocytes in mammary tumours chemically-induced in female rats. Material and methods: All experiments were performed in accordance with the legislation on the protection of animals used for scientific purposes. The experiments were approved by the Portuguese Competent Authority (no.008961) and University Ethics Committee (CE_12-2013). Thirty-four female Sprague-Dawley rats were randomly assigned to five experimental groups. At seven weeks of age, mammary tumours’ development was induced in animals from groups I, II, III (n=10+10+10) by a single intraperitoneal injection of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from groups IV and V were injected with saline. Groups II and IV (n=2) were treated with ketotifen in drinking water (1 mg/kg/day, 7 days/week) immediately after MNU administration for 18 weeks, while animals from group III received the ketotifen only after the development of the first mammary tumour. Groups I and V (n=2) received only water. Animals were sacrificed at 25 weeks of age by an overdose of ketamine and xylazine, followed by an exsanguination by cardiac puncture. Mammary tumors were collected and immersed in 10% buffered formalin. The infiltrate of CD8+ T lymphocytes was assessed by immunohistochemistry using the antibody anti-CD8 (ab33786; Abcam), at a dilution of 1:250, overnight. The immunoexpression was evaluated manually, counting the number of positive cells in five random fields, at a magnification of 400x. Data was statistically analysed using Statistical Package for the Social Sciences (SPSS). Results: Animals from groups IV and V did not develop any mammary tumor. The iummunoexpression of anti-CD8 was evaluated in 56 tumours (19 from group I, 19 from group II and 18 from group III). The antibody presented a cytoplasmatic immunoexpression in all mammary tumours. The mean number of immunopositive cells was 21.75 ± 1.74 in group I, 21.75 ± 1.74 in group II and 22.75 ± 2.01 in group III. No differences were observed among groups (p>0.05). Conclusions: Apparently, the ketotifen administration did not modulate the infiltrate of CD8+ T lymphocytes in mammary tumours chemically-induced in female rats. Further studies addressing the effects of different concentrations of ketotifen are warranted

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Marked isotopic variability within and between the Amazon River and marine dissolved black carbon pools

Riverine dissolved organic carbon (DOC) contains charcoal byproducts, termed black carbon (BC). To determine the significance of BC as a sink of atmospheric CO2 and reconcile budgets, the sources and fate of this large, slow-cycling and elusive carbon pool must be constrained. The Amazon River is a significant part of global BC cycling because it exports an order of magnitude more DOC, and thus dissolved BC (DBC), than any other river. We report spatially resolved DBC quantity and radiocarbon (Δ14C) measurements, paired with molecular-level characterization of dissolved organic matter from the Amazon River and tributaries during low discharge. The proportion of BC-like polycyclic aromatic structures decreases downstream, but marked spatial variability in abundance and Δ14C values of DBC molecular markers imply dynamic sources and cycling in a manner that is incongruent with bulk DOC. We estimate a flux from the Amazon River of 1.9–2.7 Tg DBC yr−1 that is composed of predominately young DBC, suggesting that loss processes of modern DBC are important

Enhancement of PLA-PVA surface adhesion in bilayer assemblies by PLA aminolisation

Data Availability: The raw/processed data required to reproduce these findings cannot be shared at this time due to legal or ethical reasons.Poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) present complementary barrier properties, and their combination in multilayer assemblies (laminates) could provide materials with more effective barrier capacity for food packaging purposes. However, their low chemical affinity compromises adequate polymer adhesion. Surface free energy modification of thermo-processed PLA films through treatment with 1,6-hexanediamine was used to enhance adhesion with polar PVA aqueous solutions. Treatments of 1 and 3 min increased the polar component of the solid surface tension, while treatments above 10 min provoked a corrosive effect in the films structure. Extensibility analyses of PVA solutions loaded with carvacrol (15 wt.%) and different Tween 85 ratios on PLA-activated surfaces allowed the selection of the 1-min aminolysed surface for obtaining PLA-PVA bilayers, by casting PVA solutions on the PLA films. This study revealed that despite aminolisation enhancing the PLA surface affinity for aqueous PVA solutions, casting-obtained bilayers presented limited oxygen barrier effectiveness due to heterogeneous thickness of PVA layer in the laminates.The authors acknowledge the financial support provided by the Ministerio de Economia y Competitividad (MINECO) of Spain (project AGL2016-76699-R). The author A. Tampau thanks MINECO for the pre-doctoral research grant #BES-2014-068100.info:eu-repo/semantics/publishedVersio

The red seaweed Grateloupia turuturu prevents epidermal dysplasia in HPV16-transgenic mice

Abstract: The role of dietary profiles in promoting or reducing the risk of multiple types of cancer is increasingly clear, driving the search for balanced foods and nutraceuticals. The red seaweed Grateloupia turuturu has been used as human food showing a balanced nutritional profile. This study aims to test in vivo chemopreventive effects of G. turuturu against cutaneous pre-malignant lesions in transgenic mice for the human papillomavirus type 16 (HPV16). Forty-four female HPV+/− or HPV−/− mice received a standard diet or were supplemented with 10% G. turuturu for 22 consecutive days. Cutaneous lesions (ear and chest skin) were identified histologically. Complementarily, the weights and histology of internal organs as well as blood biochemical and DNA integrity parameters were also assessed. G. turuturu consistently reduced the incidence of epidermal dysplasia induced by HPV16 on both cutaneous sites. Moreover, biochemical, DNA integrity and histological analyses confirmed G. turuturu edibility as no signs of toxicity were found. Dietary supplementation with G. turuturu is an effective and safe chemopreventive strategy in this model

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

Background: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective: This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods: We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1-4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results: Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions:Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition