Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level

<p>Abstract</p> <p>Background</p> <p>Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats.</p> <p>Methods</p> <p>One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured.</p> <p>Results</p> <p>Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea.</p> <p>Conclusion</p> <p>These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.</p

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss

This is the final version of the article. Available from American Society for Clinical Investigation via the DOI in this record.The current frontline symptomatic treatment for Alzheimer’s disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR–selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD.ABT, AC, and PMS received funding from a Wellcome Trust Collaborative Award (201529/Z/16/Z). ABT, SJB, AJB, and TMH were funded through a Medical Research Council programme leader grant provided by the MRC Toxicology Unit. CCF, LMB, AJM, and HES were funded by the Eli Lilly Company. JMB received funding through a Lilly Research Award Program (LRAP) grant (Eli Lilly). RP received funding from the Marie Curie grant “Extrabrain” (European Commission). AC is a senior principal research fellow and PMS a principal research fellow of the National Health and Medical Research Council of Australia. Tissue samples were from Randy Woltjer at the Oregon Alzheimer’s Disease Center. The Oregon Alzheimer’s Disease Center is supported by NIH grant P30AG008017

Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Behavioural adaptation to psychological stress is dependent on neuronal plasticity and dysfunction at this cellular level may underlie the pathogenesis of affective disorders such as depression and post-traumatic stress disorder. Taking advantage of genome-wide microarray assay, we performed detailed studies of stress-affected transcripts in the amygdala - an area which forms part of the innate fear circuit in mammals. Having previously demonstrated the role of lipocalin-2 (Lcn-2) in promoting stress-induced changes in dendritic spine morphology/function and neuronal excitability in the mouse hippocampus, we show here that the Lcn-2 gene is one of the most highly upregulated transcripts detected by microarray analysis in the amygdala after acute restraint-induced psychological stress. This is associated with increased Lcn-2 protein synthesis, which is found on immunohistochemistry to be predominantly localised to neurons. Stress-naïve Lcn-2(-/-) mice show a higher spine density in the basolateral amygdala and a 2-fold higher rate of neuronal firing rate compared to wild-type mice. Unlike their wild-type counterparts, Lcn-2(-/-) mice did not show an increase in dendritic spine density in response to stress but did show a distinct pattern of spine morphology. Thus, amygdala-specific neuronal responses to Lcn-2 may represent a mechanism for behavioural adaptation to psychological stress.Marie Curie Excellence Grant from the European Commission.Medical Research Council Project GrantCOST Action ECMNe

Enriching Business Process Models with Decision Rules

Making the right decisions in time is one of the key tasks in every business. In this context, decision theory fosters decision-making based on well-defined decision rules. The latter evaluate a given set of input parameters and utilize evidenced data in order to determine an optimal alternative out of a given set of choices. In particular, decision rules are relevant in the context business processes as well. Contemporary process modeling languages, however, have not incorporated decision theory yet, but mainly consider rather simple, guard-based decisions that refer to process-relevant data. To remedy this drawback, this paper introduces an approach that allows embedding decision problems in business process models and applying decision rules to deal with them. As a major benefit, it becomes possible to automatically determine optimal execution paths during run time

Optimization of wear loss in silicon nitride (Si3N4)–hexagonal boron nitride (hBN) composite using DoE–Taguchi method

Introduction The contacting surfaces subjected to progressive loss of material known as ‘wear,’ which is unavoidable between contacting surfaces. Similar kind of phenomenon observed in the human body in various joints where sliding/rolling contact takes place in contacting parts, leading to loss of material. This is a serious issue related to replaced joint or artificial joint. Case description Out of the various material combinations proposed for artificial joint or joint replacement Si3N4 against Al2O3 is one of in ceramic on ceramic category. Minimizing the wear loss of Si3N4 is a prime requirement to avoid aseptic loosening of artificial joint and extending life of joint. Discussion and evaluation In this paper, an attempt has been made to investigate the wear loss behavior of Si3N4–hBN composite and evaluate the effect of hBN addition in Si3N4 to minimize the wear loss. DoE–Taguchi technique is used to plan and analyze experiments. Conclusion Analysis of experimental results proposes 15 N load and 8 % of hBN addition in Si3N4 is optimum to minimize wear loss against alumina

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background: Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting. Methods: The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained. Results: Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased. Conclusions: In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damageBackground: Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting. Methods: The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained. Results: Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased. Conclusions: In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.