Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

BACKGROUND Acute pancreatitis(AP) is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols(PEGs) are nonimmunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings.AIM To evaluate the protective effect of a 35-k Da molecular weight PEG(PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro.METHODS Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein(50 μg/kg/bw), while the control animals received saline solution. PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42 J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α(TNFα), staurosporine or cerulein. The severity of AP wasdetermined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42 J-treated cells. Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage.RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue m RNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammationinduced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner.CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42 J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.     

Impact of heterogeneity and socioeconomic factors on individual behavior in decentralized sharing ecosystems

Tens of millions of individuals around the world use decentralized content distribution systems, a fact of growing social, economic, and technological importance. These sharing systems are poorly understood because, unlike in other technosocial systems, it is difficult to gather large-scale data about user behavior. Here, we investigate user activity patterns and the socioeconomic factors that could explain the behavior. Our analysis reveals that (i) the ecosystem is heterogeneous at several levels: content types are heterogeneous, users specialize in a few content types, and countries are heterogeneous in user profiles; and (ii) there is a strong correlation between socioeconomic indicators of a country and users behavior. Our findings open a research area on the dynamics of decentralized sharing ecosystems and the socioeconomic factors affecting them, and may have implications for the design of algorithms and for policymaking.Every month, ∼150 million users worldwide share files over the Internet using BitTorrent (1), the most widely used decentralized peer-to-peer (P2P) communication protocol. Eleven years after its inception, file sharing through BitTorrent is one of the top three major contributors to the overall Internet traffic, accounting for 9–27% of the total traffic, depending on the continent (2, 3).The expansion in scale and breadth of decentralized file-sharing has highlighted the conflicts between the interests of creators (musicians and writers, e.g.) and those of P2P users. Creators and creative industries argue that they are being deprived of fair compensation for their work (4), which is being widely distributed for free in violation of copyright laws. Users, however, argue that P2P can be (and is) used for sharing nonproprietary contents, and warn that widespread monitoring of online activity by corporations and law enforcement violates P2P users’ right to privacy. Proof of the complexity of the situation includes the rejection of the Anti-Counterfeiting Trade Agreement by the European Parliament and the controversy with the Stop Online Piracy Act in the United States.Despite the growing social, economic, and technological importance of BitTorrent (4), there is currently little understanding of how users behave in this complex technosocial (5, 6) ecosystem. Due to the decentralized structure of P2P ecosystems, it is very difficult to gather large-scale data about interactions and behavioral patterns of the users without their explicit consent; this is in contrast to other forms of online exchange where all of the information is stored in a central system, be it publicly accessible as in Wikipedia (7), partially accessible through a public interface as in Twitter (8, 9) or Google [through its search logs (10) or its public services (11, 12)], or restricted as in Facebook (13, 14) or in email communications within organizations (15–18).Because of the difficulty to collect complete user-level data of large and representative samples of users (3), studies of user behavior in P2P networks have so far been based on (i) small datasets; (ii) aggregate data collected from “trackers” or from individual Internet service providers (ISPs); and (iii) incomplete user data collected using a single crawler client connected to the network (19–23).Here, we investigate the complete activity patterns of a large and representative pool of BitTorrent users. Our analysis reveals that P2P sharing is highly heterogeneous, that users are specialized, giving rise to well-defined user profiles, and that the abundance of certain user profiles in a country is highly correlated with socioeconomic factors. Our findings open a research area on the dynamics of decentralized sharing ecosystems, and may have implications for the understanding and design of algorithms and for policymaking.     

Breast Density Analysis Using an Automatic Density Segmentation Algorithm

Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density.     

Immunological,chemical and clinical aspects of exposure to mixtures of contact allergens

Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.