bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A2Areceptor knockout mice
Authors: Castañé A , Wells L , Soria G , Hourani S , Ledent C , Kitchen I , Opacka‐Juffry J , Maldonado R , Valverde O 
Published: July 2008

Background and purpose:The purinergic system through the A2Aadenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A2Aadenosine receptors (A2ARs) in the behavioural and neurochemical responses to morphine associated with its motivational properties.Experimental approach:Mice lacking A2ARs (A2Aknockout (KO) mice) and wild‐type littermates were used to evaluate behavioural responses induced by morphine. Antinociception was assessed using the tail‐immersion and the hot‐plate tests. Place‐conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A2AKO mice after morphine administration.Key results:The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A2AKO mice. Also, naloxone did not induce place aversion in animals lacking the A2ARs.Conclusions and implications:Our findings demonstrate that the rewarding and aversive effects associated with morphine abstinence were abolished in A2AKO mice, supporting a differential role of the A2Aadenosine receptor in the somatic and motivational effects of morphine addiction. This study provides evidence for the role of A2ARs as general modulators of the motivational properties of drugs of abuse. Pharmacological manipulation of these receptors may represent a new target in the management of drug addiction.British Journal of Pharmacology(2008)155, 757–766; doi:10.1038/bjp.2008.299; published online 28 July 2008
Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: inhibition with iloprost and NONOate
Authors: Muzaffar S , Shukla N , Bond M , Sala‐Newby G B , Newby A C , Angelini G D , Jeremy J Y 
Published: July 2008

Background and purpose:To determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac1 and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs).Experimental approach:hVSMCs were incubated with xanthine–xanthine oxidase (X‐XO; a superoxide generating system) or the thromboxane A2 analogue, U46619 (±superoxide dismutase (SOD) or apocynin) for 16 h. The expression of PDE5 and NOX‐1 was assessed using Western blotting and superoxide measured. The role of Rac1 in superoxide generation was assessed by overexpressing either the dominant‐negative or constitutively active Rac isoforms. The effects of iloprost, DETA‐NONOate and the Rho‐kinase inhibitor, Y27632, on PDE5 and NOX‐1 expression were also studied.Key results:Following 16 h incubation, U46619 and X‐XO promoted the expression of PDE5 and NOX‐1, an effect blocked by SOD or apocynin when co‐incubated over the same time course. X‐XO and U46619 both promoted the formation of superoxide. Overexpression of dominant‐negative Rac1 or addition of iloprost, DETA‐NONOate or Y27632 completely blocked both superoxide release and PDE5 protein expression and activity.Conclusions and implications:These data demonstrate that superoxide derived from NOX upregulates the expression of PDE5 in human VSMCs. As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO.British Journal of Pharmacology (2008) 155, 847–856; doi:10.1038/bjp.2008.300; published online 28 July 2008
Increase in hemokinin‐1 mRNA in the spinal cord during the early phase of a neuropathic pain state
Authors: Matsumura T , Sakai A , Nagano M , Sawada M , Suzuki H , Umino M , Suzuki H 
Published: July 2008

Background and purpose:Substance P (SP), a representative member of the tachykinin family, is involved in nociception under physiological and pathological conditions. Recently, hemokinin‐1 (HK‐1) was identified as a new member of this family. Although HK‐1 acts on NK1 tachykinin receptors that are thought to be innate for SP, the roles of HK‐1 in neuropathic pain are still unknown.Experimental approach:Using rats that had been subjected to chronic constrictive injury (CCI) of the sciatic nerve as a neuropathic pain model, we examined the changes in expression of SP‐ and HK‐1‐encoding genes (TAC1 and TAC4, respectively) in the L4/L5 spinal cord and L4/L5 dorsal root ganglia (DRGs) in association with changes in pain‐related behaviours in this neuropathic pain state.Key results:The TAC4 mRNA level was increased on the ipsilateral side of the dorsal spinal cord, but not in DRGs, at day 3 after CCI. In contrast, the TAC1 mRNA level was significantly increased in the DRGs at day 3 after CCI without any changes in the dorsal spinal cord. Analysis of a cultured microglial cell line revealed the presence of TAC4 mRNA in microglial cells. Minocycline, an inhibitor of microglial activation, blocked the increased expression of TAC4 mRNA after CCI and inhibited the associated pain‐related behaviours and microglial activation in the spinal cord.Conclusions and implications:The present results suggest that HK‐1 expression is increased at least partly in activated microglial cells after nerve injury and is clearly involved in the early phase of neuropathic pain.British Journal of Pharmacology (2008) 155, 767–774; doi:10.1038/bjp.2008.301; published online 28 July 2008
Identification of regions of the P2X7receptor that contribute to human and rat species differences in antagonist effects
Authors: Michel A D , Clay W C , Ng S W , Roman S , Thompson K , Condreay J P , Hall M , Holbrook J , Livermore D , Senger S 
Published: July 2008

Background and purpose:Several P2X7receptor antagonists are allosteric inhibitors and exhibit species difference in potency. Furthermore,N2‐(3,4‐difluorophenyl)‐N1‐(2‐methyl‐5‐(1‐piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative allosteric effects at the human P2X7receptor but is a positive allosteric modulator of the rat P2X7receptor. In this study we have identified several regions of the P2X7receptor that contribute to the species differences in antagonist effects.Experimental approach:Chimeric human‐rat P2X7receptors were constructed with regions of the rat receptor being inserted into the human receptor. Antagonist effects at these receptors were measured in ethidium accumulation and radioligand binding studies.Key results:Exchanging regions of the P2X7receptor close to transmembrane domain 1 modified the effects of KN62, 4‐(4‐fluorophenyl)‐2‐(4‐methylsulphinylphenyl)‐5‐(4‐pyridyl)1H‐imidazole (SB203580) and GW791343. Further studies, in which single amino acids were exchanged, identified amino acid 95 as being primarily responsible for the differential allosteric effects of GW791343 and, to varying degrees, the species differences in potency of SB203580 and KN62. The species selectivity of pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid was affected by multiple regions of the receptor, with potency being particularly affected by the amino acid 126 but not by amino acid 95. A further region of the rat receptor (amino acids 154–183) was identified that, when inserted into the corresponding position in the human receptor, increased ATP potency 10‐fold.Conclusions:This study has identified several key residues responsible for the species differences in antagonist effects at the P2X7receptor and also identified a further region of the P2X7receptor that can significantly affect agonist potency at the P2X7receptor.British Journal of Pharmacology(2008)155, 738–751; doi:10.1038/bjp.2008.306; published online 28 July 2008
The insecticide fipronil and its metabolite fipronil sulphone inhibit the rat α1β2γ2L GABAAreceptor
Authors: Li P , Akk G 
Published: July 2008

Background and purpose:Fipronil is the active ingredient in a number of widely used insecticides. Human exposure to fipronil leads to symptoms (headache, nausea and seizures) typically associated with the antagonism of GABAAreceptors in the brain. In this study, we have examined the modulation of the common brain GABAAreceptor subtype by fipronil and its major metabolite, fipronil sulphone.Experimental approach:Whole‐cell and single‐channel recordings were made from HEK 293 cells transiently expressing rat α1β2γ2L GABAAreceptors.Key results:The major effect of fipronil was to increase the rate of current decay in macroscopic recordings. In single‐channel recordings, the presence of fipronil resulted in shorter cluster durations without affecting the intracluster open and closed time distributions or the single‐channel conductance. The α1V256S mutation, previously shown alleviate channel inhibition by inhibitory steroids and several insecticides, had a relatively small effect on channel block by fipronil. The mode of action of fipronil sulphone was similar to that of its parent compound but the metabolite was less potent at inhibiting the α1β2γ2L receptor.Conclusions and implications:We conclude that exposure to fipronil induces accumulation of receptors in a novel, long‐lived blocked state. This process proceeds in parallel with and independently of, channel desensitization. The lower potency of fipronil sulphone indicates that the conversion serves as a detoxifying process in mammalian brain.British Journal of Pharmacology(2008)155, 783–794; doi:10.1038/bjp.2008.309; published online 28 July 2008
Lives of Two Korean Mothers of Children With Schizophrenia:. An Interpretive Approach
Authors: Jung Min 
Published: July 2008

BACKGROUND: Although many persons with schizophrenia live at home and rely on family members for support, few studies have looked at the experience from the perspective of the family member as a caregiver. OBJECTIVE: The goal of this study was to understand the experiences of Korean mothers who are taking care of children with schizophrenia. DESIGN: The study method was Heideggerian hermeneutic phenomenology. This method enabled the researcher to seek out, from two Korean mothers' stories, their meanings of life in the framework of their sociocultural context. RESULTS: The mothers' caring experiences played an important part in their life. Their caring experiences led to despair or to the creation of a new way of life, depending on bow free the mothers were from the ideology of "super mother"; how they perceived their past before their child became il and whether they thought of caring as a burden or as a new challenge in their lives. CONCLUSIONS: This study showed the importance of the interpretive approach in gaining a full understanding of caregivers' lives. It also highlights the needs for nurses to carefully assess and intervene when working with families of mentally il persons, especially when the culture of the client is unfamiliar.
An Investigation on the Polymer Composite Medical Device - External Fixator
Authors: Baidya K. P. , Ramakrishna S. , Rahman M. , Ritchie A. , Huang Zheng-Ming 
Published: July 2008

Primary impetus for the development of composite materials for medical usage came from orthopedic implant application. In case of metal alloys stiffness mismatch causes stress shielding in applications such as bone plates, total hip replacement, and total knee replacement. Moreover, the metal alloys and ceramics are radio opaque, and in some cases they result in undesirable artifacts in X-ray radiography. In the case of polymer composite materials the radio transparency can be adjusted by adding contrast medium to the polymer. More over the polymer composite materials are fully compatible with the modern diagnostic methods such as computed tomography (CT) and magnetic resonance imaging (MRI) as they are non-magnetic. The current study reports the development of a radiolucent fiber reinforced polymer composite material for a biomedical device, Ilizarov external fixator. Material fabrication and characterization are described. Quantitative X-ray radiographic analysis was carried out to choose the best from the probable materials. The Finite Element Method (FEM) was employed to determine the worst possible in service loading condition, and the ring dimensions were modified accordingly. Half ring prototypes were produced using two types of composite materials: knitted aramid fiber fabric reinforced epoxy and random short carbon (RSC) fiber reinforced epoxy. The in-plane compressive strength and axial stiffness of the complete frame were measured according to ASTM specifications. The performance was evaluated and compared to an existing system in simulated in-service conditions.
125I-Labeled PLA/PEO Block Copolymer: Biodistribution Studies in Rats
Authors: Novakova K. , Laznicek M. , Rypacek F. , Machova L. 
Published: July 2008

Block copolymers have a potential utility as drug carriers. In order to study their in vivo fate, the biodegradable block copolymer poly(D,L- lactide ethylene oxide) (PLA/PEO) (Mw 5000/5000) with a p-methoxyphenyl moiety was radio labeled with 125I. The copolymer was [125I] iodinated in the organic medium by a chloramine T method. The labeling efficiency was about 5%, and the agent was freed from [125I] iodide by dialysis. The tissue distribution of radioactivity was determined at 5 min, 1, 2 and 24 hrs after intravenous injection of male rats with 125I-labeled copolymer in the dose 4.5–5.5 mg/kg. After administration of the labeled copolymer, a high concentration of radioactivity in the liver during the initial time intervals was found. At the subsequent intervals after dosing, an increase in 125I activity in the bowels was determined. The distribution of radioactivity into inflamed areas was evaluated as well. The inflammatory-to-non-inflammatory muscle tissue ratios increased with time from 2.18 (5 min), 3.63 (1 h) to 3.68 (2 hrs); after 24 hrs, this ratio was significantly lower (1.70). The PLA/PEO copolymer exhibits along residence time in the blood stream and, therefore, it could be employed as a drug delivery system for inflammatory and cancer treatment.
Impedance Control of a Single Shaft-Type Clutch Using Homogeneous Electrorheological Fluid
Authors: Nakamura Taro , Saga Norihiko , Nakazawa Masaru 
Published: July 2008

This study demonstrates the application of a precise and variable impedance control to the homogeneous electrorheological (ER) clutch. The viscous coefficient of a homogeneous ER fluid can be changed by the application of an electric field. However, the ER effect of the fluid is easily changed by shear rate variation or temperature variation. Therefore, some feedback compensations are necessary for these systems to maintain a more precise viscosity. In this paper, we apply a force-based impedance control to the homogeneous ER clutch in order to use ER fluid more effectively. First, we study the fundamental characteristics of the homogeneous ER clutch. Next, we apply the viscous control based on the force control in order to maintain a more precise viscosity. The results of our experiment clearly show that the viscosity of the clutch has been accurately and stably controlled by the proposed control method.
Damage Mechanisms in Unidirectional SiC/Ti Composites under Transverse Creep Loading: Experiments and Modeling
Authors: Carrère N. , Kruch S. , Vassel A. , Chaboche J.–L. 
Published: July 2008

The damage mechanisms under transverse creep of two unidirectionalmetal matrix composites are investigated. This paper is based on a two-scale approach, and on experimental and numerical studies. On the macroscopic scale, the global response of the composite subjected to aconstant transverse load is analyzed. On the microscopic scale, the influence of each component (matrix, fibre and interface) on the global behavior is investigated. In the experimental part of the study, creep tests have been performed at different temperatures under vacuum, and scanning electron microscope (SEM) observations have allowed the investigation of the damageevolution under different applied loads. In the numerical work, the creep tests were simulated on a representative unit cell using the finite element method and taking into account the various nonlinearities (matrix viscoplasticity coupled with interface damage). The experimental and numerical results show that the global behavior of the composite depends on the local interfacial behavior. Two domains are evidenced as a function of the applied stress, a critical stress being thus determined. Below the critical stress, the interfaces remain undamaged, leading to a low creep rate and a long duration test. Above the critical stress, the interfaces are totally debonded, thereby increasing the secondary creep rate and leading to a possible specimen failure.
Improved Surface Treatment of SMA Foils and Damage Suppression of SMA-Foil Embedded CFRP Laminates
Authors: Ogisu Toshimichi , Ando Norio , Takaki Junji , Okabe Tomonaga , Takeda Nobuo 
Published: July 2008

The authors have been conducting research and development studies on some applications of embedded SMA foil actuators in CFRP laminates for weight reduction and improvement of reliability for next generation aircraft. The goal of this research is to develop a method for the suppression of damage growth in CFRP laminates. It is certified that one of the key technologies is bonding properties between SMA foils and CFRP laminates. In this paper, improvement of bonding properties between SMA foils and CFRP and confirmation of suppression effects of damage growth are described. Some surface treatments (sol-gel method, anodic-oxidation method and spattering method) were performed on SMA foils. Then, peel resistance and single lap shear strength tests were performed using surface treated SMA foils. It was found that treatment by 10%NaOH is the most effective treatment for improvement of bonding properties. The treated surface was found porous and rough, which is supposed to provide anchoring effects of SMA/CFRP interfaces. Then, quasi-static load-unload tests were performed using the optimum treatment as mentioned above to investigate the damage behavior of quasi-isotropic CFRP laminates with embedded SMA foils. Micromechanisms of fracture behavior and the correlation between the crack density and the residual strain were discussed. The recovery stress of the SMA foil generated at over Af temperature showed capability of suppression for onset of transverse cracks in quasi-isotropic CFRP laminates with embedded SMA foils.
Mechanical Property of Metallic Closed Cellular Materials Containing Organic Material for Passive Damping and Energy-Absorbing Systems
Authors: Kishimoto S. , Shinya N. 
Published: July 2008

A new material, which has a high energy-absorbing capacity and light weight, has been developed by cold isostatic pressing and sintering. Powder particles of a polymer coated with a nickel-phosphorus alloy layer using electroless plating were pressed into pellets and sintered in a vacuum at a high temperature. A metallic closed cellular material containing an organic material was then fabricated. The physical, mechanical and ultrasonic properties of this material were measured. The density of this material is about 1.3-2.7 g/cm3. The compressive tests showed that the Young’s modulus of this material is very low and the stress-strain curves of this material have a linear elastic part, a plateau part and a wavy part. These results indicate that this material has a high energy absorbing capacity. The Young’s modulus of this material increases with an increase in the sintering temperature and the thickness of the cell walls. Ultrasonic measurements showed that the attenuation coefficient of this material is very large. These results also indicate that this metallic closed cellular material can be used for the materials in passive damping and energy-absorbing systems.
Hepatic 11beta‐HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis
Authors: Konopelska Sarah , Kienitz Tina , Hughes Beverly , Pirlich Matthias , Bauditz Jürgen , Lochs Herbert , Strasburger Christian J. , Stewart Paul M. , Quinkler Marcus 
Published: July 2008

SummaryContext  Nonalcoholic fatty liver disease represents the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury. The pathophysiology that leads to NASH is not well understood.Objective  We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor.Design and patients  75 patients (28 men, 47 women) underwent liver biopsy for elevation in liver enzymes. Histological diagnosis identified normal liver in eight, fatty liver in 20, NASH grade 1 in 22, grade 2 in nine, grade 3 in three patients, and other forms of hepatitis or cirrhosis in 13 patients. We quantified hepatic 11β‐hydroxysteroid dehydrogenase type1 (11β‐HSD1) and hexose‐6‐phosphate‐dehydrogenase (H6PDH) mRNA expression by real‐time PCR. In addition, analysis of 24 h urinary excretion of cortisol metabolites using GCMS was performed and compared with healthy controls.Results  11β‐HSD1 mRNA expression correlated significantly (R2= 0·809; P < 0·001) with H6PDH mRNA expression, negatively with waist‐to‐hip ratio in women (R2= 0·394; P= 0·005), but not with urinary (THF + 5α‐THF)/THE ratio, total cortisol metabolite excretion, age, BMI, degree of fatty liver or NASH stages. Total cortisol metabolite excretion was increased in patients with fatty liver or NASH compared with healthy controls.Conclusions  Our data suggest that expression of hepatic 11β‐HSD1 and H6PDH are closely interlinked. 11β‐HSD1 gene expression does not seem to be involved in the pathogenesis of fatty liver or NASH. However, those patients showed an increased 5α‐ and 5β‐reduction of cortisol leading to an increased cortisol turnover rate and an activation of the HPA axis.
Impacts of cattle on amphibian larvae and the aquatic environment
Authors: SCHMUTZER A. CHANDLER , GRAY MATTHEW J. , BURTON ELIZABETH C. , MILLER DEBRA L. 
Published: July 2008

Summary

Agricultural practices such as cattle farming may have direct or indirect negative effects on larval amphibians by decreasing water quality through deposition of nitrogenous waste, causing eutrophication, and grazing shoreline vegetation that contributes to detrital cover and food.
We sampled amphibian larvae on the Cumberland Plateau, Tennessee, U.S.A., twice per week, water quality twice per month and algal and detrital biomass once per month at seven wetlands (three cattle‐access and four non‐access) from March to August 2005 and 2006.
In general, species richness and diversity of amphibian larvae were greater in wetlands without cattle. Mean relative abundance of green frog (Rana clamitans) and American bullfrog (Rana catesbeiana) tadpoles was greater in non‐access wetlands. Body size of some ranid larvae was larger in cattle‐access wetlands but this trend did not exist for juveniles or adults. Dissolved oxygen was lower, while specific conductivity and turbidity were higher in cattle‐access wetlands. Mean biomass of detritus was lower in cattle‐access wetlands compared to non‐access wetlands; no differences were detected in algal biomass.
Given the negative impacts of cattle on water quality, detrital biomass, larval amphibian species richness and relative abundance of some amphibian species, we recommend that farmers consider excluding these livestock from aquatic environments.