Pyrazine-Fused Triterpenoids Block the TRPA1 Ion Channel in Vitro and Inhibit TRPA1-Mediated Acute Inflammation in Vivo

TRPA1 is a nonselective cation channel, most famously expressed in nonmyelinated nociceptors. In addition to being an important chemical and mechanical pain sensor, TRPA1 has more recently appeared to have a role also in inflammation. Triterpenoids are natural products with anti-inflammatory and anticancer effects in experimental models. In this paper, 13 novel triterpenoids were created by synthetically modifying betulin, an abundant triterpenoid of the genus Betula L., and their TRPA1-modulating properties were examined. The Fluo 3-AM protocol was used in the initial screening, in which six of the 14 tested triterpenoids inhibited TRPA1 in a statistically significant manner. In subsequent whole-cell patch clamp recordings, the two most effective compounds (pyrazine-fused triterpenoids 8 and 9) displayed a reversible and dose- and voltage-dependent effect to block the TRPA1 ion channel at submicromolar concentrations. Interestingly, the TRPA1 blocking action was also evident in vivo, as compounds 8 and 9 both alleviated TRPA1 agonist-induced acute paw inflammation in mice. The results introduce betulin-derived pyrazine-fused triterpenoids as promising novel antagonists of TRPA1 that are potentially useful in treating diseases with a TRPA1-mediated adverse component

Physical and chemical consequences of artificially deepened thermocline in a small humic lake - a paired whole-lake climate change experiment

Peer reviewe

TRPA1 Mediates Contact Hypersensitivity Induced by 2,4-Dinitrochlorobenzene

publishedVersionNon peer reviewe

Standardization of physical measurements in European health examination surveys-experiences from the site visits.

BACKGROUND: Health examination surveys (HESs) provide valuable data on health and its determinants at the population level. Comparison of HES results within and between countries and over time requires measurements which are free of bias due to differences in or adherence to measurement procedures and/or measurement devices. METHODS: In the European HES (EHES) Pilot Project, 12 countries conducted a pilot HES in 2010-11 using standardized measurement protocols and centralized training. External evaluation visits (site visits) were performed by the EHES Reference Centre staff to evaluate the success of standardization and quality of data collection. RESULTS: In general, standardized EHES protocols were followed adequately in all the pilot surveys. Small deviations were observed in the posture of participants during the blood pressure and height measurement; in the use of a tourniquet when drawing blood samples; and in the calibration of measurement devices. Occasionally, problems with disturbing noise from outside or people coming into the room during the measurements were observed. In countries with an ongoing national HES or a long tradition of conducting national HESs at regular intervals, it was more difficult to modify national protocols to fulfil EHES requirements. CONCLUSIONS: The EHES protocols to standardize HES measurements and procedures for collection of blood samples are feasible in cross-country settings. The prerequisite for successful standardization is adequate training. External and internal evaluation activities during the survey fieldwork are also needed to monitor compliance to standards

Equivalence of Conventionally-Derived and Parthenote-Derived Human Embryonic Stem Cells

As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited. The objective of this work was to determine points of equivalence and differences between conventionally-derived hESC and parthenote-derived hESC lines (phESC) in the undifferentiated state and during neural differentiation.hESC and phESC were exposed to the same expansion conditions and subsequent neural and retinal pigmented epithelium (RPE) differentiation protocols. Growth rates and gross morphology were recorded during expansion. RTPCR for developmentally relevant genes and global DNA methylation profiling were used to compare gene expression and epigenetic characteristics. Parthenote lines proliferated more slowly than conventional hESC lines and yielded lower quantities of less mature differentiated cells in a neural progenitor cell (NPC) differentiation protocol. However, the cell lines performed similarly in a RPE differentiation protocol. The DNA methylation analysis showed similar general profiles, but the two cell types differed in methylation of imprinted genes. There were no major differences in gene expression between the lines before differentiation, but when differentiated into NPCs, the two cell types differed in expression of extracellular matrix (ECM) genes.These data show that hESC and phESC are similar in the undifferentiated state, and both cell types are capable of differentiation along neural lineages. The differences between the cell types, in proliferation and extent of differentiation, may be linked, in part, to the observed differences in ECM synthesis and methylation of imprinted genes