UvA-DARE (Digital Academic Repository) Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine

General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Results MTEP attenuated the development of morphinebut not cocaine-induced CPP. In contrast, MTEP suppressed the development of cocaine-but not morphineinduced psychomotor sensitization. α-Flupenthixol blocked the development of both cocaine-and morphine-induced CPP but did not affect the development of sensitization to either drug. Conclusion Dopamine receptor stimulation mediates cocaine and morphine reward but not sensitization. In contrast, the role of mGlu5 receptors in reward and sensitization is drug-specific

Towards the Human Colorectal Cancer Microbiome

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions

The state of indoor air quality in Pakistan—a review

Background and purpose: In Pakistan, almost 70% of the population lives in rural areas. Ninety-four percent of households in rural areas and 58% in urban areas depend on biomass fuels (wood, dung, and agricultural waste). These solid fuels have poor combustion efficiency. Due to incomplete combustion of the biomass fuels, the resulting smoke contains a range of health-deteriorating substances that, at varying concentrations, can pose a serious threat to human health. Indoor air pollution accounts for 28,000 deaths a year and 40 million cases of acute respiratory illness. It places a significant economic burden on Pakistan with an annual cost of 1% of GDP. Despite the mounting evidence of an association between indoor air pollution and ill health, policy makers have paid little attention to it. This review analyzes the existing information on levels of indoor air pollution in Pakistan and suggests suitable intervention methods. Methods: This review is focused on studies of indoor air pollution, due to biomass fuels, in Pakistan published in both scientific journals and by the Government and international organizations. In addition, the importance of environmental tobacco smoke as an indoor pollutant is highlighted. Results: Unlike many other developing countries, there are no long-term studies on the levels of indoor air pollution. The limited studies that have been undertaken indicate that indoor air pollution should be a public health concern. High levels of particulate matter and carbon monoxide have been reported, and generally, women and children are subject to the maximum exposure. There have been a few interventions, with improved stoves, in some areas since 1990. However, the effectiveness of these interventions has not been fully evaluated. Conclusion: Indoor air pollution has a significant impact on the health of the population in Pakistan. The use of biomass fuel as an energy source is the biggest contributor to poor indoor air quality followed by smoking. In order to arrest the increasing levels of indoor pollution, there is a dire need to recognize it as a major health hazard and formulate a national policy to combat it. An integrated effort, with involvement of all stakeholders, could yield promising results. A countrywide public awareness campaign, on the association of indoor air pollution with ill health, followed by practical intervention would be an appropriate approach. Due to the current socioeconomic conditions in the country, development and adoption of improved cooking stoves for the population at large would be the most suitable choice. However, the potential of biogas as a fuel should be explored further, and modern fuels (natural gas and LPG) need to be accessible and economical. Smoking in closed public spaces should be banned, and knowledge of the effect of smoking on indoor air quality needs to be quantified. © 2010 Springer-Verlag

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/795

Identification of surface proteins in Enterococcus faecalis V583

<p>Abstract</p> <p>Background</p> <p>Surface proteins are a key to a deeper understanding of the behaviour of Gram-positive bacteria interacting with the human gastro-intestinal tract. Such proteins contribute to cell wall synthesis and maintenance and are important for interactions between the bacterial cell and the human host. Since they are exposed and may play roles in pathogenicity, surface proteins are interesting targets for drug design.</p> <p>Results</p> <p>Using methods based on proteolytic "shaving" of bacterial cells and subsequent mass spectrometry-based protein identification, we have identified surface-located proteins in <it>Enterococcus faecalis </it>V583. In total 69 unique proteins were identified, few of which have been identified and characterized previously. 33 of these proteins are predicted to be cytoplasmic, whereas the other 36 are predicted to have surface locations (31) or to be secreted (5). Lipid-anchored proteins were the most dominant among the identified surface proteins. The seemingly most abundant surface proteins included a membrane protein with a potentially shedded extracellular sulfatase domain that could act on the sulfate groups in mucin and a lipid-anchored fumarate reductase that could contribute to generation of reactive oxygen species.</p> <p>Conclusions</p> <p>The present proteome analysis gives an experimental impression of the protein landscape on the cell surface of the pathogenic bacterium <it>E. faecalis</it>. The 36 identified secreted (5) and surface (31) proteins included several proteins involved in cell wall synthesis, pheromone-regulated processes, and transport of solutes, as well as proteins with unknown function. These proteins stand out as interesting targets for further investigation of the interaction between <it>E. faecalis </it>and its environment.</p

Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

Contains fulltext : 108207.pdf (publisher's version ) (Open Access)Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of >/=275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (p<0.0001). Proteomic profiling resulted in the identification of 12 differentially excreted proteins in urine of mice with acute liver injury (p<0.001), including superoxide dismutase 1 (SOD1), carbonic anhydrase 3 (CA3) and calmodulin (CaM), as novel biomarkers for APAP-induced liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT levels, but urinary CaM was already present in mice treated with high dose of APAP without elevated plasma ALT levels. Importantly, we showed in human urine after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001) in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury