Role of Inflammation in the Pathogenesis of Diabetic Nephropathy

Diabetic nephropathy is the major microvascular complication of diabetes mellitus and remains the leading cause of increased morbidity and mortality for diabetic patients. Recent evidence suggests that chronic subclinical inflammation is a key pathogenetic mechanism of the disease. Pro-inflammatory cytokines and particularly tumor necrosis factor and its receptors appear to play a major role in the process and are emerging novel biomarkers of the development and progression of diabetic nephopathy. Moreover, manipulation of the TNF superfamily system will hopefully provide a new therapeutic option for the disease

Ekspresija i obrada somatostatina u gušterači u razvoju i u duktalnom adenokarcinomu gušterače

Somatostatin is a gastrointestinal peptide hormone that inhibits growth of pancreatic cancer as reported by an increasing body of evidence. Yet this is not always the case. To clarify the controversy we aimed to identify the expression of somatostatin in developing human embryonic pancreatic tissue and pancreatic adenocarcinoma given that somatostatin positive cells were shown either into primitive pancreatic ductal epithelium or into pancreatic carcinoma. Tissue sections representing pancreatic fetal specimens (n=15) and ductal pancreatic adenocarcinoma specimens (n=15) were assessed using immunohistochemical methods for somatostatin expression. Normal primitive exocrine ductal epithelium and endocrine epithelium showed a definite, statistically significant, higher expression of somatostatin over neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (p1=0.021, p2=0.001, p3<0.0001and p4=0.003 respectively) during the 8th to the 10th week. No statistically significantly different expression of somatostatin in the mantle zone of the islets over neoplastic tissue of mixed (p5=0.16) and pureductal type (p6=0.65), from the 13th to the 24th week was demonstrated. Pancreatic cancer cells can express somatostatin in a model that reproduces the normal expression of the peptide by d-cells during embryonal organogenesis. Therapy aimed at pancreatic cancer must be targeted to somatostatin and analogues as a potential adjuvant novel option.Somatostatin je probavni peptidni hormon koji suzbija rast raka gušterače, za što postoji sve više dokaza. No to se ne događa uvijek. Cilj studije bio je utvrditi ekspresiju somatostatina u ljudskom embrijskom tkivu gušterače u razvoju i u adenokarcinomu gušterače, s tim da su na somatostatin pozitivne stanice dokazane ili u primitivnom duktalnom epitelu gušterače ili u karcinomu gušterače. Tkivni isječci koji su predstavljali uzorke fetalne gušterače (n=15) i uzorke adenokarcinoma gušterače (n=15) ispitani su pomoću imunohistokemijskih metoda za ekspresiju somatostatina. Normalan primitivni egzokrini duktalni epitel i endokrini epitel pokazao je konačnu, statistički značajno višu ekspresiju somatostatina iznad neoplastičnog tkiva gušterače miješanog (duktalno-endokrinog) i čistog duktalnog tipa (p1=0,021, P2=0,001, p3<0,0001 odnosno p4=0,003) tijekom 8. do 10. tjedna. Nije dokazana statistički značajno različita ekspresija somatostatina u ovojnom sloju (mantle zone, mantle layer) otočića iznadneoplastičnog tkiva miješanog (p5=0,16) i čistog duktalnog tipa (p6=0,65) od 13. do 24. tjedna. Dakle, stanice raka gušterače mogu izražavati somatostatin na naein koji ponavlja normalnu d-staničnu ekspresiju peptida za vrijeme embrijske organogeneze. Liječenje zbog raka gušterače usmjereno na somatostatin i njegove analoge moglo bi predstavljati novu mogućnosti adjuvantne terapije

Inductive Construction of 2-Connected Graphs for Calculating the Virial Coefficients

In this paper we give a method for constructing systematically all simple 2-connected graphs with n vertices from the set of simple 2-connected graphs with n-1 vertices, by means of two operations: subdivision of an edge and addition of a vertex. The motivation of our study comes from the theory of non-ideal gases and, more specifically, from the virial equation of state. It is a known result of Statistical Mechanics that the coefficients in the virial equation of state are sums over labelled 2-connected graphs. These graphs correspond to clusters of particles. Thus, theoretically, the virial coefficients of any order can be calculated by means of 2-connected graphs used in the virial coefficient of the previous order. Our main result gives a method for constructing inductively all simple 2-connected graphs, by induction on the number of vertices. Moreover, the two operations we are using maintain the correspondence between graphs and clusters of particles.Comment: 23 pages, 5 figures, 3 table

Application of Headspace Solid-Phase Microextraction for Determination of Chloro-Organic Compounds in Sewage Samples

Solid phase microextraction (SPME) has been optimized and applied to the determination of the volatile halogenated compounds (VHCs) and semi-volatile halogenated compounds (SVHCs). Three types of SPME fiber coated with different stationary phases (PDMS–100 μm, CAR/PDMS-75 μm, PDMS/DVB–65 μm) were used to examine their extraction efficiencies for the compounds tested. Experimental parameters such as the selection of SPME coatings, extraction time, and addition of salts were studied. The carboxen-polydimethylsiloxane (CAR/PDMS) fiber appears to be the most suitable for the determination of VHCs. Analytical parameters such as linearity, limit of detection, and precision were also evaluated. Application of ECD detector for the determination of VHCs and SVHCs allows their determination on the low concentration level, ranging from 0.005 to 0.8 μg/L−1. The HS-SPME-GC/ECD procedure gave good analytical precision expressed as relative standard deviation (RSD) (ranged from 5.08% to 8.07%) for a concentration level of 5 μg/L−1 and good linearity (r2 > 0.98) in a wide calibration range. The applied HS-SPME-GC/ECD method was found to be a quick and effective technique for the determination of microtrace amounts of volatile and semi-volatile halogenated compounds in samples containing high amounts of various organic compounds

Entertainment starts with an E: the ecstasy market in Greece

The purpose of this article is to provide an account of the social organisation of the ecstasy market in Greece. Concern about ecstasy production, distribution and use in Greece has risen since ecstasy appeared in the country in the early to mid-1990s, and continues to be fuelled by media reports which reinforce the perception that there are huge profits for traders. Moreover, the Greek authorities have adopted a 'war on drug' rhetoric when it comes to ecstasy trafficking. Thus, the fact that such mentalities are commonplace, while the knowledge deficit about the particular market remains gaping, makes it an imperative to examine the structure and dynamics of the ecstasy market in the country. We aim here to provide an account of the 'extent' and nature of the ecstasy market in Greece as well as a presentation of the 'actors' involved. We also explicitly focus on the issue of price of ecstasy tablets in the country, which we regard as key to the understanding of the logic of this particular market. Our investigation of various aspects of the market concludes with a number of more systematic observations regarding the particular business

Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice

<p>Abstract</p> <p>Background</p> <p>Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity.</p> <p>Methods</p> <p>Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ <it>in vitro</it>.</p> <p>Results</p> <p>OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression <it>in vivo</it>. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our <it>in vivo </it>findings.</p> <p>Conclusions</p> <p>Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice.</p

Making waves: collaboration in the time of SARS-CoV-2 - rapid development of an international co-operation and wastewater surveillance database to support public health decision-making

The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE "SARS-CoV-2 in sewage" database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

Background: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.Results: We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.Conclusion: This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system

The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC): let’s cooperate! [Commentary]

The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken