bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabotropic glutamate receptor 5 localized in the limbic forebrain is critical for the development of morphine‐induced rewarding effect in mice
Authors: Aoki Takeshi , Narita Minoru , Shibasaki Masahiro , Suzuki Tsutomu
Published: September 2004

The aim of the present study was to clarify the role of the metabotropic glutamate 5 (mGlu5) receptor subtype in the development of rewarding effect induced by a prototypical µ‐opioid receptor agonist morphine in the mouse. In the conditioned place preference paradigm, intracerebroventricular (i.c.v.) administration of a selective mGlu5 receptor antagonist, 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP), attenuated the morphine‐induced rewarding effects. Using immunoblot analysis, we confirmed that the increased level of protein kinase Cγ (PKCγ) isoform was observed in the limbic forebrain of ICR mice conditioned with morphine. Here we found for the first time that the treatment with MPEP significantly inhibited the up‐regulation of PKCγ isoform in the limbic forebrain of mice showing the significant place preference. Furthermore, it should be mentioned that the protein level of mGlu5 was significantly increased in membrane preparations of the limbic forebrain obtained from morphine‐conditioned mice compared to those from saline‐conditioned mice. As well as the result from the immunoblot analysis, we demonstrated using the receptor binding assay that the number of mGlu5 receptors in the mouse limbic forebrain was significantly increased by morphine conditioning. The present data provide direct evidence that the activation of mGlu5 receptor linked to the increased PKCγ isoform in the mouse limbic forebrain is implicated in the development of rewarding effect of morphine.
3β‐20β‐dihydroxy‐5α‐pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone
Authors: Turkmen Sahruh , Lundgren Per , Birzniece Vita , Zingmark Elisabeth , Backstrom Torbjorn , Johansson Inga‐Maj
Published: September 2004

Allopregnanolone is a progesterone metabolite and GABA‐A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3β‐hydroxypregnane steroids antagonize allopregnanolone‐induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3β‐20β‐dihydroxy‐5α‐pregnane (UC1011) as a blocker of allopregnanolone‐induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2‐hydroxypropyl‐β‐cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone‐injected group on day 6. Day 3–6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone‐injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3–6), compared to the allopregnanolone‐injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 µm GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA‐A receptor reduce the negative allopregnanolone effect on learning in the water maze.
Mutation of the feh‐1 gene, the Caenorhabditis elegans orthologue of mammalian Fe65, decreases the expression of two acetylcholinesterase genes
Authors: Bimonte Marida , Gianni Davide , Allegra Danilo , Russo Tommaso , Zambrano Nicola
Published: September 2004

The molecular adaptor Fe65 is one of the cytosolic ligands of the Alzheimer's β‐amyloid precursor protein (APP), and this complex is believed to play important roles in mammalian cells. Upon cleavage of APP by specific processing activities, the complex between Fe65 and the APP intracellular domain (AICD) translocates to the nucleus. Experimental evidence suggests that the Fe65‐AICD complex regulates gene transcription. In Caenorhabditis elegans the orthologue of the Fe65 gene, feh‐1, regulates pharyngeal activity. In fact, the rate of pharyngeal contraction is increased following transient or stable suppression of the feh‐1 gene expression. Here we show that the increased contraction rate of the pharynx in feh‐1 mutant worms is associated to decreased acetylcholinesterase activity. The decreased activity is accompanied by reduced expression of ace‐1 and ace‐2 transcripts, coding for the two major acetylcholinesterase activities in the nematode. These results indicate a target of the regulatory mechanisms based on the Fe65‐APP complex that could be relevant for the pathogenesis of Alzheimer's disease.
The induction of behavioural sensitization is associated with cocaine‐induced structural plasticity in the core (but not shell) of the nucleus accumbens
Authors: Li Yilin , Acerbo Martin J. , Robinson Terry E.
Published: September 2004

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.
Cysteinyl‐leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys‐LT1 receptors and mitogen‐activated protein kinase pathway
Authors: Ciccarelli Renata , D'Alimonte Iolanda , Santavenere Clara , D'Auro Mariagrazia , Ballerini Patrizia , Nargi Eleonora , Buccella Silvana , Nicosia Folco Simonetta, Giancarlo , Caciagli Francesco , Di Iorio Patrizia
Published: September 2004

Cysteinyl‐leukotrienes (cys‐LTs), potent mediators in inflammatory diseases, are produced by nervous tissue, but their cellular source and role in the brain are not very well known. In this report we have demonstrated that rat cultured astrocytes express the enzymes (5′‐lipoxygenase and LTC4 synthase) required for cys‐LT production, and release cys‐LTs in resting condition and, to a greater extent, in response to calcium ionophore A23187, 1 h combined oxygen–glucose deprivation or 2‐methyl‐thioATP, a selective P2Y1/ATP receptor agonist. MK‐886, a LT synthesis inhibitor, prevented basal and evoked cys‐LT release. In addition, 2‐methyl‐thioATP‐induced cys‐LT release was abolished by suramin, a P2 receptor antagonist, or by inhibitors of ATP binding cassette proteins involved in cys‐LT release. We also showed that astrocytes express cys‐LT1 and not cys‐LT2 receptors. The stimulation of these receptors by LTD4 activated the mitogen‐activated protein kinase (MAPK) pathway. This effect was: (i) insensitive to inhibitors of receptor‐coupled Gi protein (pertussis toxin) or tyrosine kinase receptors (genistein); (ii) abolished by MK‐571, a cys‐LT1 selective receptor antagonist, or PD98059, a MAPK inhibitor; (iii) reduced by inhibitors of calcium/calmodulin‐dependent kinase II (KN‐93), Ca2+‐dependent and ‐independent (GF102903X) or Ca2+‐dependent (Gö6976) protein kinase C isoforms. LTD4 also increased astrocyte proliferation and glial fibrillary acidic protein content, which are considered hallmarks of reactive astrogliosis. Both effects were counteracted by cell pretreatment with MK‐571 or PD98059. Thus, cys‐LTs released from astrocytes might play an autocrine role in the induction of reactive astrogliosis that, in brain injuries, contributes to the formation of a reparative glial scar.
Rapid assessment of in vivo cholinergic transmission by amperometric detection of changes in extracellular choline levels
Authors: Parikh Vinay , Pomerleau Francois , Huettl Peter , Gerhardt Greg A. , Sarter Martin , Bruno John P.
Published: September 2004

Conventional microdialysis methods for measuring acetylcholine (ACh) efflux do not provide sufficient temporal resolution to relate cholinergic transmission to individual stimuli or behavioral responses, or sufficient spatial resolution to investigate heterogeneities in such regulation within a brain region. In an effort to overcome these constraints, we investigated a ceramic‐based microelectrode array designed to measure amperometrically rapid changes in extracellular choline as a marker for cholinergic transmission in the frontoparietal cortex of anesthetized rats. These microelectrodes exhibited detection limits of 300 nm for choline and selectivity (> 100 : 1) of choline over interferents such as ascorbic acid. Intracortical pressure ejections of choline (20 mm, 66–400 nL) and ACh (10 and 100 mm, 200 nL) dose‐dependently increased choline‐related signals that were cleared to background levels within 10 s. ACh, but not choline‐induced signals, were significantly attenuated by co‐ejection of the acetylcholinesterase inhibitor neostigmine (Neo; 100 mm). Pressure ejections of drugs known to increase cortical ACh efflux, potassium (KCl; 70 mm, 66, 200 nL) and scopolamine (Scop; 10 mm, 200 nL), also markedly increased extracellular choline signals, which again were inhibited by Neo. Scop‐induced choline signals were also found to be tetrodotoxin‐sensitive. Collectively, these findings suggest that drug‐induced increases in current measured with these microelectrode arrays reflect the oxidation of choline that is neuronally derived from the release and subsequent hydrolysis of ACh. Choline signals assessed using enzyme‐selective microelectrode arrays may represent a rapid, sensitive and spatially discrete measure of cholinergic transmission.
Associative somatodendritic interaction in layer V pyramidal neurons is not affected by the antiepileptic drug lamotrigine
Authors: Berger Thomas , Lüscher Hans‐R.
Published: September 2004

The antiepileptic drug lamotrigine was described to exert its effects on neuronal excitability via voltage‐gated sodium and calcium, as well as hyperpolarization‐activated conductances. In order to define the effects of lamotrigine on the excitability of layer V pyramidal cells of the rat somatosensory cortex we performed patch‐clamp recordings from the soma and dendrite of this major cortical output cell type in acute slices. Voltage‐clamp experiments revealed the blockade of the persistent sodium current by 50–100 µm lamotrigine as well as by 50 µm of the anticonvulsant drug phenytoin. In somatic current‐clamp studies lamotrigine, in a therapeutic concentration range, depolarizes the membrane potential reflecting the activation of the hyperpolarization‐activated current. This depolarization reduces the rheobase and increases the spiking frequency at the onset of the spike train. For long depolarizing current pulses under lamotrigine, however, a use‐dependent block of sodium channels reduces spiking frequency and spike amplitude. The depolarization due to 50–100 µm lamotrigine reduces additionally the critical frequency of back‐propagating spikes necessary to elicit a dendritic calcium action potential. Ten to thirty micromolar lamotrigine, in contrast, did not change the critical frequency. Lamotrigine blocks long‐lasting, high frequent spiking activity due to its use‐dependent sodium channel block, while burst activity is not impaired due to a depolarizing shift of the membrane potential. This drug therefore dampens epileptic activity while leaving the somatodendritic association in layer V pyramidal cells intact.
Cocaine increases medial prefrontal cortical glutamate overflow in cocaine‐sensitized rats: a time course study
Authors: Williams Jason M. , Steketee Jeffery D.
Published: September 2004

Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague–Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day × 4 days, i.p.) or cocaine (15 mg/kg/day × 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine‐induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine‐induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine‐induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine.
Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice
Authors: Kurrikoff Kaido , Kõks Sulev , Matsui Toshimitsu , Bourin Michel , Arend Andres , Aunapuu Marina , Vasar Eero
Published: September 2004

Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK2 receptor deficient (CCK2 −/−) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK2 −/− mice displayed mechanical hyposensitivity, which was reversed to the level of wild‐type animals after administration of naloxone (0.1–10 mg/kg). On the other hand, injection of L‐365260 (0.01–1 mg/kg), an antagonist of CCK2 receptors, decreased dose‐dependently, mechanical sensitivity in wild‐type mice. The mechanism of reduced mechanical sensitivity in CCK2 −/− mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK2 −/− mice natively expressed higher levels of lumbar CCK1, opioid δ and κ receptors. Next, we found that CCK2 −/− mice did not develop mechanical hyperalgesia in the Bennett's neuropathic pain model. Induction of neuropathy resulted in decrease of lumbar pro‐opiomelanocortin (POMC) gene expression in wild‐type mice, but increase of POMC expression in CCK2 −/− mice. In addition, induction of neuropathy resulted in further increase of opioid δ receptor in CCK2 −/− mice. Gene expression results indicate up‐regulation of opioid system in CCK2 −/− mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.
Binding partners L1 cell adhesion molecule and the ezrin‐radixin‐moesin (ERM) proteins are involved in development and the regenerative response to injury of hippocampal and cortical neurons
Authors: Haas Matilda A. , Vickers James C. , Dickson Tracey C.
Published: September 2004

Regeneration of the adult central nervous system may require recapitulation of developmental events and therefore involve the re‐expression of developmentally significant proteins. We have investigated whether the L1 cell adhesion molecule, and its binding partner, the ezrin‐radixin‐moesin (ERM) proteins are involved in the neuronal regenerative response to injury. Hippocampal and cortical neurons were cultured in vitro on either an L1 substrate or poly‐L‐lysine, and ERM and other neuronal proteins were localized immunocytochemically both developmentally and following neurite transection of neurons maintained in long‐term culture. Activated ERM was localized to growth cones up to 7 days in vitro but relatively mature cultures (21 days in vitro) were devoid of active ERM proteins. However, ERM proteins were localized to the growth cones of sprouting neuronal processes that formed several hours after neurite transection. In addition, the L1 substrate, relative to poly‐L‐lysine, resulted in significantly longer regenerative neurites, as well as larger growth cones with more filopodia. Furthermore, neurons derived from the cortex formed significantly longer post‐injury neurite sprouts at 6 h post‐injury than hippocampal derived neurons grown on both substrates. We have demonstrated that L1 and the ERM proteins are involved in the neuronal response to injury, and that neurons derived from the hippocampus and cortex may have different post‐injury regenerative neurite sprouting abilities.
Angiotensin II increases differentiation of dopaminergic neurons from mesencephalic precursors via angiotensin type 2 receptors
Authors: Rodriguez‐Pallares J. , Quiroz C. R. , Parga J. A. , Guerra M. J. , Labandeira‐Garcia J. L.
Published: September 2004

In addition to the well‐known actions of the humoral renin–angiotensin system, all components of this system are present in many tissues, including the brain, and may play a major role in brain development and differentiation. We investigated the possible effects of angiotensin II on the generation of dopaminergic phenotype neurons from proliferating neurospheres of mesencephalic precursors. We observed immunoreactivity for both angiotensin type 1 and type 2 (AT1 and AT2) receptors in the cell aggregates. Double immunolabeling studies revealed that both receptor types are located in neurons and astrocytes. Interestingly, neurons with a dopaminergic phenotype (i.e. tyrosine hydroxylase activity) showed double labeling for AT1 and AT2 receptors although the labeling for AT2 was more intense. Treatment of the neurospheres with angiotensin II (100 nm) during the differentiation period induced a marked increase (about 400%) in the generation of dopaminergic neurons. This was not affected by treatment with the AT1 antagonist ZD 7155 but was blocked by treatment with the AT2 antagonist PD 123319. This suggests that AT2 receptors mediate the stimulatory effect of angiotensin II on the generation of dopaminergic neurons. Apoptotic cell death studies and bromodeoxyuridine immunohistochemistry indicated that the increase in generation of dopaminergic neurons is not due to increased survival or proliferation of dopaminergic cells during treatment with angiotensin and suggested that angiotensin induces increased differentiation of mesencephalic precursors towards the dopaminergic phenotype. Manipulation of the renin–angiotensin system may be useful for increasing production of dopaminergic neurons for transplantation in Parkinson's disease.
Striatal dopamine D2/D3 receptor availability correlates with individual response characteristics to pain
Authors: Pertovaara Antti , Martikainen Ilkka K. , Hagelberg Nora , Mansikka Heikki , Någren Kjell , Hietala Jarmo , Scheinin Harry
Published: September 2004

We studied in healthy humans the contribution of cerebral dopamine D2/D3 receptors to individual differences in response characteristics to painful stimulation. Positron emission tomography was used to measure the dopamine D2/D3 binding potential (D2/D3 BP) with [11C]raclopride in the striatum (n = 8) and with [11C]FLB 457 in the extrastriatal regions (n = 11). Sensitivity to cutaneous heat pain was assessed by a traditional threshold method and by an analysis based on the signal detection theory which allows the separation of an individual subject's discriminative capacity from the response criterion, i.e. the area under the receiver operating characteristic curve provides a measure of the sensory discriminability (sensory factor) and the response criterion gives an estimate of the subject's response bias or attitude (nonsensory factor). The pain threshold and response criterion were inversely correlated with the D2/D3 BP in the right putamen, whereas the discriminative capacity was not significantly correlated with the D2/D3 BP in any brain region. The correlation of the D2/D3 BP in the putamen with the pain threshold and the subject's response criterion may rather be explained by a dopaminergic effect on nonsensory factors determining the subject's attitude towards pain than by a dopaminergic effect on the subject's discriminative capacity. Alternatively, striatal dopamine D2/D3 receptors could control a modulatory pathway producing a parallel shift in the stimulus–response function for sensory signals, mimicking a change in the subject's response criterion.
Specific and nonspecific effects of transcranial magnetic stimulation on picture–word verification
Authors: Dräger Bianca , Breitenstein Caterina , Helmke Ulf , Kamping Sandra , Knecht Stefan
Published: September 2004

Repetitive transcranial magnetic stimulation (rTMS) can temporarily impair or improve performance, including language processing. It remains unclear, however, (i) which scalp sites are most appropriate to achieve the desired effects and (ii) which experimental setups produce facilitation or inhibition of language functions. We assessed the effects of TMS at different stimulation sites on picture–word verification in healthy volunteers. Twenty healthy volunteers with left language lateralization, as determined by functional transcranial Dopplersonography, performed picture–word verification prior to and after rTMS (1 Hz for 600 s at 110% of subjects' resting motor thresholds). Stimulation sites were the classical language areas (Broca's and Wernicke's), their homolog brain regions of the right hemisphere, and the occipital cortex. Additionally, sham stimulation over Broca's area was applied in a subsample of 11 subjects. As a control task, 10 volunteers performed a colour–tone matching task under the same experimental conditions. There was a general nonspecific arousal effect for both verum and sham TMS for both the picture–word verification and for the control task. However, superimposed there were opposite effects on picture–word verification for stimulation of Wernicke's area and Broca's area, namely a relative inhibition in the case of Wernicke's area and a relative facilitation in the case of Broca's area. These results demonstrate that low frequency rTMS has both general arousing effects and domain‐specific effects.
Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro
Authors: Cunningham Mark O. , Woodhall Gavin L. , Thompson Sarah E. , Dooley David J. , Jones Roland S. G.
Published: September 2004

We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using whole‐cell patch‐clamp recordings of excitatory postsynaptic currents (EPSCs) in layer V neurons in slices of rat entorhinal cortex. Both drugs reduced the amplitude and increased the paired‐pulse ratio of EPSCs evoked by electrical stimulation of afferent inputs, suggesting a presynaptic effect to reduce glutamate release. The frequency of spontaneous EPSCs (sEPSCs) was concurrently reduced by GBP, further supporting a presynaptic action. There was no significant change in amplitude although a slight reduction was seen, particularly with gabapentin, which may reflect a reduction in the number of larger amplitude sEPSCs. When activity‐independent miniature EPSCs were recorded in the presence of tetrodotoxin, both drugs continued to reduce the frequency of events with no change in amplitude. The reduction in frequency induced by gabapentin or pregabalin was blocked by application of the l‐amino acid transporter substrate l‐isoleucine. The results show that gabapentin and pregabalin, like other anticonvulsants, reduce glutamate release at cortical synapses. It is possible that this reduction is a combination of two effects: a reduction of activity‐dependent release possibly via interaction with P/Q‐type voltage‐gated Ca channels, and a second action, as yet unidentified, occurring downstream of Ca influx into the presynaptic terminals.
The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals
Authors: Koh Seong‐Ho , Park Younjoo , Song Chi Won , Kim Jun Gyou , Kim Kisok , Kim Juhan , Kim Myung‐Ho , Lee Seung Ro , Kim Dong Won , Yu Hyun‐Jeung , Chang Dae‐il , Hwang Se Jin , Kim Seung Hyun
Published: September 2004

Poly(ADP‐ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3‐aminobenzamide (3‐AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3‐AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague–Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague–Dawley rats were used for sham operation. 3‐AB was administered to 85 rats 10 min before the occlusion [3‐AB group (n = 85) vs. control group without 3‐AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick end‐labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP‐ribose) polymer (PAR), cleaved caspase‐3, CD11b, intercellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), phospho‐Akt (pAkt) and phospho‐glycogen synthase kinase‐3 (pGSK‐3) were compared in the peri‐infarcted region of the 3‐AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3‐AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL‐positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase‐3, CD11b, ICAM‐1 and COX‐2 were significantly reduced, while the IRs of pAkt and pGSK‐3 were increased. These results suggest that 3‐AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.
Trajectories in public administration reforms in European Continental countries
Authors: Torres Lourdes
Published: September 2004

The aim of this article is to study key New Public Management (NPM) transformations undertaken at central level in the European Union public administrations of Germanic, Nordic and Southern European countries. Our study shows that there is no global tendency towards the same NPM model, although, within public administration models, there are strong similarities. Although some NPM initiatives have been taken as steps towards implementing these reforms, in other contexts they could have been adopted in order to ward off deeper reforms.
Trade Policy and Access to Retail Distribution
Authors: Richardson Martin
Published: September 2004

The paper develops a model in which foreign and domestic manufacturers producing differentiated goods sell through spatially differentiated retailers. There is free entry into retailing but access to the retail distribution network (by manufacturers) may be controlled. The author considers a domestic vertical control mechanism in which domestic retailers carry only domestic brands (termed “domestic dealing”) and compares the use of tariffs on imports and the enforcement of domestic dealing restrictions as means of increasing domestic welfare. It is shown that domestic dealing will always be prohibited when tariffs can be used. When trade policy is not available, however, domestic dealing may be desirable.
A Parameterized Representation of Uncertain Conceptual Spaces
Authors: Ahlqvist Ola
Published: September 2004

Most conceptual modeling in geographic information science to date has used a symbolic approach with little or no recognition of the semantic uncertainty often found in geographic concepts. This work describes a concept model based on parameterized concept descriptions that uses a spatial metaphor, the conceptual space, as an organizing structure (Gärdenfors 2000). This cognitive theory of conceptual spaces is combined with a formal representation of semantic uncertainty based on rough fuzzy sets. The conceptual space then represents each concept as a collection of rough fuzzy property definitions with associated salience weights, where a property itself can be treated as a special case of a concept. Instead of explicitly defining concept hierarchies, we can allow different conceptual structures to emerge through measures of concept inclusion and similarity. A land use/land cover example demonstrates how the model represents concepts, concept similarity, hierarchical structures and the context dependence of concepts. The final section of the paper points to the need for further studies of context effects, concept similarity measures, and uncertainty representation using the proposed model.
Weak Identification of Forward‐looking Models in Monetary Economics*
Authors: Mavroeidis Sophocles
Published: September 2004

Recently, single‐equation estimation by the generalized method of moments (GMM) has become popular in the monetary economics literature, for estimating forward‐looking models with rational expectations. We discuss a method for analysing the empirical identification of such models that exploits their dynamic structure and the assumption of rational expectations. This allows us to judge the reliability of the resulting GMM estimation and inference and reveals the potential sources of weak identification. With reference to the New Keynesian Phillips curve of Galí and Gertler [Journal of Monetary Economics (1999) Vol. 44, 195] and the forward‐looking Taylor rules of Clarida, Galí and Gertler [Quarterly Journal of Economics (2000) Vol. 115, 147], we demonstrate that the usual ‘weak instruments’ problem can arise naturally, when the predictable variation in inflation is small relative to unpredictable future shocks (news). Hence, we conclude that those models are less reliably estimated over periods when inflation has been under effective policy control.
Econometric Evaluation of the New Keynesian Phillips Curve*
Authors: Bårdsen Gunnar , Jansen Eilev S. , Nymoen Ragnar
Published: September 2004

We give an appraisal of the New Keynesian Phillips curve (NPCM) as an empirical model of European inflation. The favourable evidence for NPCMs on euro‐area data reported in earlier studies is shown to depend on specific choices made about estimation methodology. The NPCM can be re‐interpreted as a highly restricted equilibrium correction model. We also report the outcome of tests based on variable addition and encompassing of existing models. The results show that economists should not accept the NPCM too readily.
Beyond toleration: privacy, citizenship and sexual minorities in England and Wales
Authors: McGhee Derek
Published: September 2004

This paper examines two significant moments in sexual minority citizenship in England and Wales in relation to one of the Marshallian sets of rights, namely, civil or legal rights, focusing specifically on the Sex Offences legislation and policing practices. The first moment that will be examined here is the process whereby homosexual acts were decriminalized in the 1950s and 1960s; here special attention will be paid to the recommendations made by the Wolfenden Committee. The second moment is one we are currently experiencing, which is associated with the inclusive policing of sexual minority communities (especially lesbian, gay, bisexual and transgender communities) under the provisions of the Crime and Disorder Act 1998 and in the review of Sex Offences, especially in the consultation paper (Home Office 2000) and White Paper (Home Office 2002) associated with this review. Privacy and toleration dominate the first moment, at the same time it shall be demonstrated that privacy is also central to the British Sexual Citizenship literatures that have emerged in sociology in the post‐Wolfenden context. However, as the title suggests, the second moment under examination points to the emergence of a rather more extensive sexual minority citizenship beyond the boundaries of ‘homosexual privacy’ (which British Sexual Citizenship Studies is not currently engaging with) and perhaps even beyond the boundaries of toleration through ever more ‘inclusive’ policing strategies and through the review of sex offences in which many discriminatory laws are being ‘de‐homosexualized’.
Ethical issues in participatory action research
Authors: Löfman Päivi , Pelkonen Marjaana , Pietilä Anna‐Maija
Published: September 2004

The purpose of this article is to describe the ethical issues arising out of participatory action research (PAR), on the basis of both an empirical study and the research literature, and to discuss how to deal with these issues. The data consist of the experiences and results of three phases of PAR relating to orthopaedic patients with rheumatoid arthritis (RA) and the analysis of 20 articles on the ethics of action research. As a result, the following ethical issues and the ways to treat them were discussed: informed consent, confidentiality and anonymity, protecting an individual from harm, the role of the researcher, the location of ‘power’ in PAR, and the ownership of the research. The flexibility of PAR in use and its main features are also related to the decisions made and actions taken in response to ethical issues. It is particularly important in PAR to proceed according to the participants, and to involve them from the beginning of the process, in order to insure the equal balance of power between participants and researcher.
Prevalence of patients subjected to constraint in Norwegian nursing homes
Authors: Kirkevold Øyvind , Engedal Knut
Published: September 2004

Background:  A recent questionnaire showed that different kinds of constraint such as physical restraint, electronic surveillance, use of force or pressure in medical treatment and in activities of daily living (ADL) are frequently used in Norwegian nursing homes. The study did not include information at patient level, and except for studies about physical restraints, we have not found any studies reporting the prevalence of various forms of constraint.

Aim:  To describe the prevalence of various types of constraint in Norwegian nursing homes.

Materials and method:  A structured interview was carried out with the primary carers of a random sample of 1501 patients from 222 nursing‐home wards in 54 municipalities representing all five health regions in Norway. Data were collected from regular units (RUs) and special care units (SCUs) for persons with dementia. Episodes of constraint during 1 week were recorded. Five main groups of constraint were aggregated, mechanical restraint, nonmechanical restraint, electronic surveillance, force or pressure in medical examination or treatment and force or pressure in ADL.

Results:  Patients (36.7%) in RUs and 45.0% of the patients in SCUs were subjected to any constraint. Most frequent was use of mechanical restraint (23.3% in RUs; 12.8% in SCUs) and use of force or pressure in ADL (20.9% in SCUs; 16.6% in RUs). Use of force or pressure in medical examination or treatment was more frequent used in SCUs (19.1%) compared with RUs (13.5%). Nonmechanical restraint was less frequently used (8.3% in SCUs; 3.0% in RUs) and electronic surveillance was seldom used (7.2% in RUs; 0.9% in SCUs).

Conclusion:  The use of constraint is a problem in Norwegian nursing homes. Studies are needed to learn more about why constraint is used, and if there is patient or ward characteristics that can explain the use of constraint.
Migraine and chronic daily headache management: a qualitative study of patients’ perceptions
Authors: Peters Michele , Abu‐Saad Huda Huijer , Vydelingum Vasso , Dowson Andrew , Murphy Margaret
Published: September 2004

Aim:  The aim of the study was to gain insight into the patients’ perceptions of migraine and chronic daily headache (CDH) management.

Methods:  Thirteen, semi‐structured and individual interviews with seven migraine and five CDH patients were carried out and analysed in QSR NUD*IST5, using a grounded theory methodology.

Results:  The participants described using five areas of management: 1) health care use; 2) medication use; 3) alternative therapies; 4) social support; and 5) lifestyle and self‐help. The participants described their expectations, preferences, worries and (dis)satisfaction in relation to these five areas of management. The participants adapted headache management to suit their needs and preferences, making migraine and CDH management highly individual and giving the headache patient a central role within their own care.

Conclusion:  Health care is changing towards a greater involvement of the patients in their own care. Therefore, it is important to increase understanding of the patients’ perspective of chronic diseases, including migraine and CDH. The results from this study inform health care professionals of the range of their patients’ needs and preferences. This knowledge can be used to shape clinical practice, to develop patient education programmes and to further research efforts into issues that are important to the headache patient.
The progression of suffering implies alleviated suffering
Authors: Rehnsfeldt Arne , Eriksson Katie
Published: September 2004

There is a lack of research focusing directly on both patients’ suffering and alleviated suffering in relation to care. The aim of this paper was to investigate the progression of suffering in relation to the encounter between the suffering person and the caregiver from the perspective of an understanding of life. The progression of suffering is assumed to be an existential ‘sign’ of the development of understanding of life as an ontological or spiritual entity, which demands a meaning‐creating encounter between the patient and caregiver. The concept ‘existential caring encounter’ was used to describe how the encounter between patient and caregiver can create meaning in communion and thereby alleviate suffering by making it bearable. The study was carried out using an interpretive, hermeneutic approach. The study as a whole comprises three parts, and these include letter‐writing and interviews. The findings are described by the following main theses: (a) a darkness in life understanding is existentially experienced as unbearable suffering and requires an encounter involving attentive care and confrontation; (b) the turning point means that the struggle of suffering begins; and (c) the encounter involves being meaning‐creating in a communion in the struggle of suffering. An understanding of the patterns of unbearable and bearable suffering can be of help to the caregiver in caring for the patient by serving as a basis for meaning‐creation in communion. This may thereby be a way of alleviating the patient's suffering by making it bearable during the progression of suffering.
Electronic nursing documentation in primary health care
Authors: Törnvall Eva , Wilhelmsson Susan , Wahren Lis Karin
Published: September 2004

The aim of this study was to describe and analyse nursing documentation based on an electronic patient record (EPR) system in primary health care (PHC) with emphasis on the nurses’ opinions and what, according to the nursing process and the use of the keywords, the nurses documented. The study was performed in one county council in the south of Sweden and included 42 Primary Health Care Centres (PHCC). It consisted of a survey, an audit of nursing records with the Cat‐ch‐Ing instrument and calculation of frequencies of keywords used during a 1‐year period. For the survey, district nurses received a postal questionnaire. The results from the survey indicated an overall positive tendency concerning the district nurses’ opinions on documentation. Lack of in‐service training in nursing documentation was noted and requested from the district nurses. All three parts of the study showed that the keywords nursing interventions and status were frequently used while nursing diagnosis and goal were infrequent. From the audit, it was noted that medical status and interventions appeared more often than nursing status. The study demonstrated limitations in the nursing documentation that inhibited the possibility of using it to evaluate the care given. In order to develop the nursing documentation, there is a need for support and education to strengthen the district nurses’ professional identity. Involvement from the heads of the PHCC and the manufactures of the EPR system is necessary, in cooperation with the district nurses, to render the nursing documentation suitable for future use in the evaluation and development of care.
Dimensions of informal care and quality of life among elderly family caregivers
Authors: Ekwall Anna , Sivberg Bengt , Hallberg Ingalill Rahm
Published: September 2004

The aim was to investigate dimensions of caregiving activities among elderly (75+) caregivers based on Nolan's model and to study the dimensions in relation to health‐related quality of life (Short Form 12). Responses to a Swedish postal survey (n = 4278, response rate 75–79 years old: 60%; 80–84: 56%; 85–89: 48% and 90+: 42%) showed that 783 persons (18%) were helping another person due to that person's impaired health, 41.6% women, mean age for women 81.8 years (SD 4.96) and for men 81.7 years (SD 4.32). The postal questionnaire included SF‐12, demographic data and questions about caregiving activities derived from Nolan's model, social network and contacts with health care. Adapting their activities to be prepared if something happened (52%), having regular contact to prevent problems (35%), helping in contacts with the hospital (57%), helping with instrumental activities of daily living (49%), personal activities of daily living (14%), medical care (11%) and helping to improve functions (14%) were the activities reported. Adapting own activities, regular contact, weak economy and needing instrumental help with daily living oneself predicted low MCS12. The importance of early involvement on the part of the caregivers was emphasized.
Nurses’ personal statements about factors that influence their decisions about the time they spend with residents with long‐term mental illness living in psychiatric group dwellings
Authors: Hellzén Ove
Published: September 2004

One seldom‐discussed issue is the factors that influence nurses’ decisions about the time they spend with residents in psychiatric care. This study uses a qualitative naturalistic approach and consists of an analysis of focus‐group interviews with nurses, which aimed to identify factors affecting nurses’ decisions about being with or being nonattendant in their relationship with their residents. Two series of focus‐group interviews were conducted, interpreted and analysed through content analysis. The study included all the staff (n = 32) at two municipal psychiatric group dwellings housing residents mainly with a diagnosis of long‐term schizophrenia. This study revealed that the main factor that determined nurses’ nurse/resident time together or nonattendance time was whether they liked or disliked the individual resident. One possible explanation is the carers’ change from a perspective in which the nursing care was given on the basis of each resident's needs and rights, based on the individual nurse's professional judgement, to a consumer perspective, which leads to a change in responsibility from themselves to the individual residents.
Midwives’ attitudes to and knowledge about a newly introduced foetal screening method
Authors: Ekelin Maria , Crang‐Svalenius Elizabeth
Published: September 2004

A number of screening procedures are offered by midwives during pregnancy and the number is increasing rapidly. The measurement of nuchal translucency is a fairly new ultrasound method for antenatal screening, primarily for Down syndrome. The results give a better risk calculation than maternal age alone and can mean a decrease in the number of invasive procedures needed to identify this syndrome prenatally. The aim of this study was to gain insight into the midwives’ point of view concerning the introduction of the method in two different hospitals. In one hospital it had been introduced as part of a research project while in the other it had been integrated as an offer in the antenatal care programme. A questionnaire was sent to the 80 midwives working in the antenatal clinics serving these two hospitals. A total of 79% of the questionnaires were answered. The results indicate that in both districts, the similarities are greater than the differences with regard to the midwives’ education, knowledge and their own opinions of their ability to inform pregnant women about the method. Although most of the respondents were positive to it, a number of midwives felt that, in general, information about foetal diagnosis was a difficult part of their work, mentioning both ethical and practical aspects. This highlights the need for continuing education, standardized policy and an ongoing ethical debate.
The Swedish version of the PACU‐Behavioural Pain Rating Scale: a reliable method of assessing postoperative pain?
Authors: Persson Karin , Östman Margareta
Published: September 2004

One of the obstacles to effective pain management in the Post‐Anaesthesia Care Unit (PACU) is the lack of systematic and comprehensive methods for assessing and treating postoperative pain. Nurses’ intuitive knowledge of pain were verbalized and divided into four categories of pain behaviours in the PACU‐Behavioural Pain Rating Scale. The aim of the present study was to test the reliability of the Swedish version by performing test–retest and interrater reliability in clinical conditions. Materials for this study were gathered through patient observations. The results showed poor agreement in the item restless, fair agreements in both items tense muscles and frowning and grimacing, while patients’ sounds showed moderate agreement. Interrater reliability showed moderate agreement in the item restless, very good agreement in tense muscles and patient sounds, and good agreement in frowning and grimacing. A refined classification of the separate categories and a careful review of the category of behaviours is suggested. A more detailed manual for the categories needs to be developed to establish more acceptable reliability.