Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

<p>Abstract</p> <p>Background</p> <p>AhR activates the transcription of several target genes including CYP1B1. Recently, we showed <it>CYP1B1 </it>as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels.</p> <p>Methods</p> <p>Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after <it>ex vivo </it>and/or <it>in vivo </it>exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ⁹-tetrahydrocannabinol (Δ⁹-THC).</p> <p>Results</p> <p>After <it>ex vivo </it>exposure to TCDD (a highly potent AhR ligand) for 3 h, <it>Cyp1b1 </it>expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased <it>Cyp1b1 </it>transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (<it>in vivo </it>and <it>ex vivo</it>) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic <it>in vivo </it>treatment with Δ⁹-THC once daily for 7 seven days had no effect on <it>Cyp1b1 </it>expression</p> <p>Conclusions</p> <p>Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.</p

Regulation and Rose of Heme Oxygenase-1 (HO-1) During Inflammation in Human Gingival Fibroblasts (HGF)

Periodontitis is the most common cause of adult tooth loss in the U.S., with an estimated 1 in 3 adults suffering from some form and 10-15% of adults developing severe forms. In addition to its direct impact, periodontitis also contributes to the development of several other diseases, including cardiovascular disease, pre-term low birth weight, and diabetes. Although the primary function of HO-1 is the breakdown of heme to carbon monoxide, iron and bilirubin, it has also been shown to play an important role in wound repair and the resolution of inflammation by mechanisms involving homeostatic regulation of the redox state of cells. A series of experiments has been designed to determine whether and to what extent the levels of HO-1 mRNA and protein are regulated by inflammatory cytokines in HGF isolated from individuals with or without periodontitis. Preliminary results show that HO-1 mRNA is expressed in HGF cultures derived from patients with periodontitis and that mRNA levels are inhibited over 60% by Interleukin-1 at 6 hours (10 ng/ml, p \u3c 0.001). Interestingly however, HO-1 protein levels as measured by ELISA are not decreased by IL-1. Experiments are currently underway to address this apparent paradox, as well as the potential role of HO-1 in the regulation of inflammatory mediators in HGF

On directed information theory and Granger causality graphs

Directed information theory deals with communication channels with feedback. When applied to networks, a natural extension based on causal conditioning is needed. We show here that measures built from directed information theory in networks can be used to assess Granger causality graphs of stochastic processes. We show that directed information theory includes measures such as the transfer entropy, and that it is the adequate information theoretic framework needed for neuroscience applications, such as connectivity inference problems.Comment: accepted for publications, Journal of Computational Neuroscienc

Accretions of Various Types of Dark Energies onto Morris-Thorne Wormhole

In this work, we have studied accretion of the dark energies onto Morris-Thorne wormhole. For quintessence like dark energy, the mass of the wormhole decreases and phantom like dark energy, the mass of wormhole increases. We have assumed two types of dark energy like variable modified Chaplygin gas (VMCG) and generalized cosmic Chaplygin gas (GCCG). We have found the expression of wormhole mass in both cases. We have found the mass of the wormhole at late universe and this is finite. For our choices the parameters and the function $B(a)$, these models generate only quintessence dark energy (not phantom) and so wormhole mass decreases during evolution of the universe. Next we have assumed 5 kinds of parametrizations of well known dark energy models. These models generate both quintessence and phantom scenarios. So if these dark energies accrete onto the wormhole, then for quintessence stage, wormhole mass decreases upto a certain value (finite value) and then again increases to infinite value for phantom stage during whole evolution of the universe. We also shown these results graphically.Comment: 9 pages, 7 figures. arXiv admin note: text overlap with arXiv:1112.615

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Cardiac evaluation after experimental intoxication by Amorimia rigida (Malpighiaceae) extracts in rabbits

Clinical and laboratory changes were evaluated in rabbits after intoxication by Amorimia rigida, a plant that causes sudden death. Nine New Zealand male rabbits, averaging 3.54 kg, were categorized into three groups (n = 3) and received, for eight consecutive days, the equivalent of 30 g/kg dry matter of A. rigida water-soluble (SG) and water-insoluble (IG) extracts via nasoesophageal route. The control group received water. There were no alterations in creatine kinase enzyme (CK), CK myocardial fraction (CKMB) or troponine I (cTnI). None of the animals had clinical or electrocardiographic (conventional and Holter) alterations. There were progressive decreases in the left ventricular ejection fraction and systolic fractional shortening. Doppler echocardiography alterations suggested a systolic dysfunction in the SG and IG groups and diastolic dysfunction in IG group. It was concluded that the soluble and insoluble extracts of A. rigida cause deficit of cardiac function

Accuracy and repeatability of wrist joint angles in boxing using an electromagnetic tracking system

© 2019, The Author(s). The hand-wrist region is reported as the most common injury site in boxing. Boxers are at risk due to the amount of wrist motions when impacting training equipment or their opponents, yet we know relatively little about these motions. This paper describes a new method for quantifying wrist motion in boxing using an electromagnetic tracking system. Surrogate testing procedure utilising a polyamide hand and forearm shape, and in vivo testing procedure utilising 29 elite boxers, were used to assess the accuracy and repeatability of the system. 2D kinematic analysis was used to calculate wrist angles using photogrammetry, whilst the data from the electromagnetic tracking system was processed with visual 3D software. The electromagnetic tracking system agreed with the video-based system (paired t tests) in both the surrogate ( 0.9). In the punch testing, for both repeated jab and hook shots, the electromagnetic tracking system showed good reliability (ICCs > 0.8) and substantial reliability (ICCs > 0.6) for flexion–extension and radial-ulnar deviation angles, respectively. The results indicate that wrist kinematics during punching activities can be measured using an electromagnetic tracking system