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The neuroprotective properties of palmitoylethanolamine against oxidative stress in a neuronal cell line
R Scott Duncan, Kent D Chapman, Peter Koulen
Molecular Neurodegeneration , 2009, DOI: 10.1186/1750-1326-4-50

Abstract: Indeed PEA protected HT22 cells from oxidative stress in part by mediating an increase in phosphorylated Akt (pAkt) and ERK1/2 immunoreactivity as well as pAkt nuclear translocation. These changes take place within a time frame consistent with neuroprotection. Furthermore, we determined that changes in pAkt immunoreactivity elicited by PEA were not mediated by activation of cannabinoid receptor type 2 (CB2), thus indicating a novel mechanism of action. These results establish a role for PEA as a neuroprotectant against oxidative stress, which occurs in a variety of neurodegenerative diseases.The results from this study reveal that PEA protects HT22 cells from oxidative stress and alters the localization and expression levels of kinases known to be involved in neuroprotection by a novel mechanism. Overall, these results identify PEA as a neuroprotectant with potential as a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.N-Acylethanolamines (NAEs) are endogenous lipids involved in cell signaling and they are synthesized in response to cellular injury [1,2]. The NAE, arachidonylethanolamide (AEA), is a cannabinoid exhibiting cytoprotective properties against a wide variety of pathological insults including excitotoxicity, oxidative stress and hypoxia [3-10]. Cannabinoids activate the G-protein-coupled cannabinoid receptors (CB1 and CB2) leading to downregulation of PKA and activation of the ERK MAPK pathway, a neuroprotective signaling pathway [11-18]. Furthermore, the activation of Akt by cannabinoids further supports their role as neuroprotectants [16]. Interestingly, concentrations of AEA in various tissues including the brain are relatively low compared to other NAE species such as the non-cannabinoid NAE, palmitoylethanolamine (PEA) [19,20].Some saturated and monounsaturated NAEs have been shown to activate ERK1/2 phosphorylation pathway through a CB1-independent mechanism [21]. Interestingly, the yeast Saccharomyces cerevisiae,

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Overexpression of Fatty Acid Amide Hydrolase Induces Early Flowering in Arabidopsis thaliana
Neal D. Teaster,Jantana Keereetaweep,Aruna Kilaru,Yuh-Shuh Wang,Christopher N.-Q. Tran,Brian G. Ayre,Kent D. Chapman,Elison B. Blancaflor
Frontiers in Plant Science , 2012, DOI: 10.3389/fpls.2012.00032

Abstract: N-acylethanolamines (NAEs) are bioactive lipids derived from the hydrolysis of the membrane phospholipid N-acylphosphatidylethanolamine (NAPE). In animal systems this reaction is part of the “endocannabinoid” signaling pathway, which regulates a variety of physiological processes. The signaling function of NAE is terminated by fatty acid amide hydrolase (FAAH), which hydrolyzes NAE to ethanolamine and free fatty acid. Our previous work in Arabidopsis thaliana showed that overexpression of AtFAAH (At5g64440) lowered endogenous levels of NAEs in seeds, consistent with its role in NAE signal termination. Reduced NAE levels were accompanied by an accelerated growth phenotype, increased sensitivity to abscisic acid (ABA), enhanced susceptibility to bacterial pathogens, and early flowering. Here we investigated the nature of the early flowering phenotype of AtFAAH overexpression. AtFAAH overexpressors flowered several days earlier than wild type and AtFAAH knockouts under both non-inductive short day (SD) and inductive long day (LD) conditions. Microarray analysis revealed that the FLOWERING LOCUS T (FT) gene, which plays a major role in regulating flowering time, and one target MADS box transcription factor, SEPATALLA3 (SEP3), were elevated in AtFAAH overexpressors. Furthermore, AtFAAH overexpressors, with the early flowering phenotype had lower endogenous NAE levels in leaves compared to wild type prior to flowering. Exogenous application of NAE 12:0, which was reduced by up to 30% in AtFAAH overexpressors, delayed the onset of flowering in wild type plants. We conclude that the early flowering phenotype of AtFAAH overexpressors is, in part, explained by elevated FT gene expression resulting from the enhanced NAE hydrolase activity of AtFAAH, suggesting that NAE metabolism may participate in floral signaling pathways.

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Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide
Julio D Duarte, Issam Zineh, Ben Burkley, Yan Gong, Taimour Y Langaee, Stephen T Turner, Arlene B Chapman, Eric Boerwinkle, John G Gums, Rhonda M Cooper-DeHoff, Amber L Beitelshees, Kent R Bailey, Roger B Fillingim, Bruce C Kone, Julie A Johnson
Journal of Translational Medicine , 2012, DOI: 10.1186/1479-5876-10-56

Abstract: We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant.In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed.Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.Hydrochlorothiazide (HCTZ) is one of the most commonly prescribed antihypertensive drug in the US, with approximately 118 million prescriptions dispensed in 2010, either alone or combined with another antihypertensive [1,2]. HCTZ and other thiazide diuretics are recommended by current hypertension treatment guidelin

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Neurological adverse events following regional anesthesia administration
Christopher D Kent, Laurent Bollag
Local and Regional Anesthesia , 2010, DOI: http://dx.doi.org/10.2147/LRA.S8177

Abstract: rological adverse events following regional anesthesia administration Review (3787) Total Article Views Authors: Christopher D Kent, Laurent Bollag Published Date October 2010 Volume 2010:3 Pages 115 - 123 DOI: http://dx.doi.org/10.2147/LRA.S8177 Christopher D Kent, Laurent Bollag Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, USA Abstract: Regional anesthesia and analgesia have been associated with improved analgesia, decreased postoperative nausea and vomiting, and increased patient satisfaction for many types of surgical procedures. In obstetric anesthesia care, it has also been associated with improved maternal mortality and major morbidity. The majority of neurological adverse events following regional anesthesia administration result in temporary sensory symptoms; long-term or permanent disabling motor and sensory problems are very rare. Infection and hemorrhagic complications, particularly with neuraxial blocks, can cause neurological adverse events. More commonly, however, there are no associated secondary factors and some combination of needle trauma, intraneural injection, and/or local anesthetic toxicity may be associated, but their individual contributions to any event are difficult to define.

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Modulation of Late Cretaceous and Cenozoic climate by variable drawdown of atmospheric pCO2 from weathering of basaltic provinces on continents drifting through the equatorial humid belt
D. V. Kent,G. Muttoni
Climate of the Past (CP) & Discussions (CPD) , 2013,

Abstract: The small reservoir of carbon dioxide in the atmosphere (pCO2) that modulates climate through the greenhouse effect reflects a delicate balance between large fluxes of sources and sinks. The major long-term source of CO2 is global outgassing from sea-floor spreading, subduction, hotspot activity, and metamorphism; the ultimate sink is through weathering of continental silicates and deposition of carbonates. Most carbon cycle models are driven by changes in the source flux scaled to variable rates of ocean floor production, but ocean floor production may not be distinguishable from being steady since 180 Ma. We evaluate potential changes in sources and sinks of CO2 for the past 120 Ma in a paleogeographic context. Our new calculations show that decarbonation of pelagic sediments by Tethyan subduction contributed only modestly to generally high pCO2 levels from the Late Cretaceous until the early Eocene, and thus shutdown of this CO2 source with the collision of India and Asia at the early Eocene climate optimum at around 50 Ma was inadequate to account for the large and prolonged decrease in pCO2 that eventually allowed the growth of significant Antarctic ice sheets by around 34 Ma. Instead, variation in area of continental basalt terranes in the equatorial humid belt (5° S–5° N) seems to be a dominant factor controlling how much CO2 is retained in the atmosphere via the silicate weathering feedback. The arrival of the highly weatherable Deccan Traps in the equatorial humid belt at around 50 Ma was decisive in initiating the long-term slide to lower atmospheric pCO2, which was pushed further down by the emplacement of the 30 Ma Ethiopian Traps near the equator and the southerly tectonic extrusion of SE Asia, an arc terrane that presently is estimated to account for 1/4 of CO2 consumption from all basaltic provinces that account for ~1/3 of the total CO2 consumption by continental silicate weathering (Dessert et al., 2003). A negative climate-feedback mechanism that (usually) inhibits the complete collapse of atmospheric pCO2 is the accelerating formation of thick cation-deficient soils that retard chemical weathering of the underlying bedrock. Nevertheless, equatorial climate seems to be relatively insensitive to pCO2 greenhouse forcing and thus with availability of some rejuvenating relief as in arc terranes or thick basaltic provinces, silicate weathering in this venue is not subject to a strong negative feedback, providing an avenue for ice ages. The safety valve that prevents excessive atmospheric pCO2 levels is the triggering of silicate weathering of continental areas and basaltic provinces in the temperate humid belt. Excess organic carbon burial seems to have played a negligible role in atmospheric pCO2 over the Late Cretaceous and Cenozoic.

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The Nachbin compactification via convergence ordered spaces
D. C. Kent,Dongmei Liu
International Journal of Mathematics and Mathematical Sciences , 1993, DOI: 10.1155/s0161171293000791

Abstract: We construct the Nachbin compactification for a T3.5-ordered topological ordered space by tailing a quotient of an ordered convergence space compactification. A variation of this quotient construction leads to a compactification functor on the category of T3.5-ordered convergence ordered spaces.

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Probablistic convergence spaces and regularity
P. Brock,D. C. Kent
International Journal of Mathematics and Mathematical Sciences , 1997, DOI: 10.1155/s0161171297000896

Abstract: The usual definition of regularity for convergence spaces can be characterized by a diagonal axiom R due to Cook and Fischer. The generalization of R to the realm of probabilistic convergence spaces depends on a t-norm T, and the resulting axiom RT defines “T-regularity ”, which is the primary focus of this paper. We give several characterizations of T-regularity, both in general and for specific choices of T, and investigate some of its basic properties.

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Ordered Cauchy spaces
D. C. Kent,R. Vainio
International Journal of Mathematics and Mathematical Sciences , 1985, DOI: 10.1155/s0161171285000539

Abstract: This paper is concerned with the notion of “ordered Cauchy space ” which is given a simple internal characterization in Section 2. It gives a discription of the category of ordered Cauchy spaces which have ordered completions, and a construction of the “fine completion functor ” on this category. Sections 4 through 6 deals with certain classes of ordered Cauchy spaces which have ordered completions; examples are given which show that the fine completion does not preserve such properties as uniformizability, regularity, or total boundedness. From these results, it is evident that a further study of ordered Cauchy completions is needed.

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Order compatibility for Cauchy spaces and convergence spaces
D. C. Kent,Reino Vainio
International Journal of Mathematics and Mathematical Sciences , 1987, DOI: 10.1155/s0161171287000279

Abstract: A Cauchy structure and a preorder on the same set are said to be compatible if both arise from the same quasi-uniform convergence structure on X. Howover, there are two natural ways to derive the former structures from the latter, leading to “strong ” and “weak ” notions of order compatibility for Cauchy spaces. These in turn lead to characterizations of strong and weak order compatibility for convergence spaces.

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