Blood Glucose and Risk of Incident and Fatal Cancer in the Metabolic Syndrome and Cancer Project (Me-Can): Analysis of Six Prospective Cohorts

Tanja Stocks and colleagues carry out an analysis of six European cohorts and confirm that abnormal glucose metabolism is linked with increased risk of cancer overall and at specific sites

CD4陽性T細胞に発現するA20(tnfaip3) はTh2型アレルギー性気道炎症を抑制する

研究科: 千葉大学大学院医学薬学府（先端医学薬学専攻）学位記番号: 千大院医薬博甲第医1412号博士（医学）千葉大学 = Chiba Universit

Social micro-siting : increasing acceptance through local adaption

The establishment of land-based wind-farms often requires large land areas affecting a number of contradictory interests including the individual interests of citizens. In Sweden consultation is statutory, prescribed by Swedish Environmental Code including all individuals affected by the project. Projectors often invite to consultative process in a stage where the project has made some progress and where a site-plan is more or less established. From the citizen perspective, wind farm projects affecting the local area might seem threatening. For instance, for people living in rural areas, the characteristics of the surrounding environment are closely connected to their way of life. Thereby, “threats” towards the local environment might pose a threat to their entire outlook on life. Often this leads to frustration and rage towards the projector. This presentation introduces the basic features of a consultative process more thoroughly involving and adjusting to citizens and their local community and the distinguishing characteristics of their local physical and social environment, Social Micro-Siting. Social Micro-Siting has the potential to create added value to the participating community and to the projector, increasing the general acceptance of wind-farm localization. As the process is based on ongoing dialogue with the local citizens, it might also provide solutions to complex local issues of a more practical character.Godkänd; 2012; 20121218 (andbra)</p

Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis.

Improvements have been made to the safety and efficacy of bumped kinase inhibitors, and they are advancing toward human and animal use for treatment of cryptosporidiosis. As the understanding of bumped kinase inhibitor pharmacodynamics for cryptosporidiosis therapy has increased, it has become clear that better compounds for efficacy do not necessarily require substantial systemic exposure. We now have a bumped kinase inhibitor with reduced systemic exposure, acceptable safety parameters, and efficacy in both the mouse and newborn calf models of cryptosporidiosis. Potential cardiotoxicity is the limiting safety parameter to monitor for this bumped kinase inhibitor. This compound is a promising pre-clinical lead for cryptosporidiosis therapy in animals and humans

Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned.

Bumped Kinase Inhibitors, targeting Calcium-dependent Protein Kinase 1 in apicomplexan parasites with a glycine gatekeeper, are promising new therapeutics for apicomplexan diseases. Here we will review advances, as well as challenges and lessons learned regarding efficacy, safety, and pharmacology that have shaped our selection of pre-clinical candidates

SAR Studies of 5‑Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of <i>Toxoplasma gondii</i> CDPK1

We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from <i>T. gondii</i>. The current work, through structure–activity relationship studies, led to the discovery of compounds (<b>34</b> and <b>35</b>) with improved characteristics over the starting inhibitor <b>1</b> in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds <b>34</b> and <b>35</b> were further demonstrated to be more effective than <b>1</b> in a mouse infection model and markedly reduced the amount of <i>T. gondii</i> in the brain, spleen, and peritoneal fluid, and <b>35</b> given at 20 mg/kg eliminated <i>T. gondii</i> from the peritoneal fluid

Development of an Orally Available and Central Nervous System (CNS) Penetrant <i>Toxoplasma gondii</i> Calcium-Dependent Protein Kinase 1 (<i>Tg</i>CDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of <i>Toxoplasmosis</i>

New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite <i>Toxoplasma gondii</i>. To this end, we previously developed a potent and selective inhibitor (compound <b>1</b>) of <i>Toxoplasma gondii</i> calcium-dependent protein kinase 1 (<i>Tg</i>CDPK1) that possesses antitoxoplasmosis activity in vitro and in vivo. Unfortunately, <b>1</b> has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q–T syndrome, and consequently presents a cardiotoxicity risk. Here, we describe the identification of an optimized <i>Tg</i>CDPK1 inhibitor <b>32</b>, which does not have a hERG liability and possesses a favorable pharmacokinetic profile in small and large animals. <b>32</b> is CNS-penetrant and highly effective in acute and latent mouse models of <i>T. gondii</i> infection, significantly reducing the amount of parasite in the brain, spleen, and peritoneal fluid and reducing brain cysts by >85%. These properties make <b>32</b> a promising lead for the development of a new antitoxoplasmosis therapy