bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase
Authors: Stewart Victoria C. , Stone Rebecca , Gegg Matthew E. , Sharpe Martyn A. , Hurst Roger D. , Clark John B. , Heales Simon J. R. 
Published: March 2003

AbstractCultured rat and human astrocytes and rat neurones were shown to release reduced glutathione (GSH). In addition, GSH oxidation was retarded by the concomitant release of a factor from the cells. One possibility is that this factor is extracellular superoxide dismutase (SOD). In support of this, the factor was found to bind heparin, have a molecular mass estimated to be between 50 and 100 kDa, and CuZn‐type SOD protein and cyanide sensitive enzyme activity were demonstrated in the cell‐conditioned medium. In addition, supplementation of native medium with exogenous CuZn‐type SOD suppressed GSH oxidation. We propose that preservation of released GSH is essential to allow for maximal up‐regulation of GSH metabolism in neurones. Furthermore, cytokine stimulation of astrocytes increased release of the extracellular SOD, and enhanced stability of GSH. This may be a protective strategy occurring in vivo under conditions of oxidative stress, and suggests that SOD mimetics may be of therapeutic use.
Prostaglandin A1 inhibits rotenone‐induced apoptosis in SH‐SY5Y cells
Authors: Wang Xiaoxia , Qin Zheng‐Hong , Leng Yan , Wang Yumei , Jin Xiannu , Chase Thomas N. , Bennett M. Catherine 
Published: March 2003

AbstractThe degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor‐κB (NF‐κB) and caspase‐3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A1 (PGA1), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH‐SY5Y cells to the complex I inhibitor rotenone. Dose‐dependent apoptosis was preceded by the nuclear translocation of NF‐κB and then the activation of caspase‐3 over the ensuing 24 h. PGA1 increased the expression of HSP70 and HSP27 and protected against rotenone‐induced apoptosis, without increasing necrotic death. PGA1 blocked the rotenone‐induced nuclear translocation of NF‐κB and attenuated, but did not abolish, the caspase‐3 elevation. Unexpectedly, the caspase‐3 inhibitor, Ac‐DEVD.CHO (DEVD), at a concentration that completely prevented the caspase‐3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF‐κB nuclear translocation and caspase‐3 activation. PGA1 appears to protect against rotenone‐induced cell death by inducing HSPs and blocking nuclear translocation of NF‐κB in a process that attenuates caspase‐3 activation, but is not mediated by its inhibition.
Involvement of double‐stranded RNA‐dependent protein kinase and phosphorylation of eukaryotic initiation factor‐2α in neuronal degeneration
Authors: Chang Raymond Chuen‐Chung , Suen Ka‐Chun , Ma Chi‐Him , Elyaman Wassim , Ng Ho‐Keung , Hugon Jacques 
Published: March 2003

AbstractInhibition of protein translation plays an important role in apoptosis. While double‐stranded RNA‐dependent protein kinase (PKR) is named as it is activated by double‐stranded RNA produced by virus, its activation induces an inhibition of protein translation and apoptosis via the phosphorylation of the eukaryotic initiation factor 2α (eIF2α). PKR is also a stress kinase and its levels increase during ageing. Here we show that PKR activation and eIF2α phosphorylation play a significant role in apoptosis of neuroblastoma cells and primary neuronal cultures induced by the β‐amyloid (Aβ) peptides, the calcium ionophore A23187 and flavonoids. The phosphorylation of eIF2α and the number of apoptotic cells were enhanced in over‐expressed wild‐type PKR neuroblastoma cells exposed to Aβ peptide, while dominant‐negative PKR reduced eIF2α phosphorylation and apoptosis induced by Aβ peptide. Primary cultured neurons from PKR knockout mice were also less sensitive to Aβ peptide toxicity. Activation of PKR and eIF2α pathway by Aβ peptide are triggered by an increase in intracellular calcium because the intracellular calcium chelator BAPTA‐AM significantly reduced PKR phosphorylation. Taken together, these results reveal that PKR and eIF2α phosphorylation could be involved in the molecular signalling events leading to neuronal apoptosis and death and could be a new target in neuroprotection.
Effects on free radical generation by ligands of the peripheral benzodiazepine receptor in cultured neural cells
Authors: Jayakumar A. R. , Panickar K. S. , Norenberg M. D. 
Published: March 2003

AbstractThe effect of peripheral benzodiazepine receptor (PBR) ligands on free radical production was investigated in primary cultures of rat brain astrocytes and neurons as well as in BV‐2 microglial cell lines using the fluorescent dye dichlorofluorescein‐diacetate. Free radical production was measured at 2, 30, 60 and 120 min of treatment with the PBR ligands 1‐(2‐chlorophenyl‐N‐methylpropyl)‐3‐isoquinolinecarboxamide (PK11195), 7‐chloro‐5‐(4‐chlorophenyl)‐1,3‐dihydro‐1‐methyl‐2H‐1,4‐benzodiazepin‐2‐one (Ro5‐4864) and protoporphyrin IX (PpIX) (all at 10 nm). In astrocytes, all ligands showed a significant increase in free radical production at 2 min. The increase was short‐lived with PK11195, whereas with Ro5‐4864 it persisted for at least 2 h. PpIX caused an increase at 2 and 30 min, but not at 2 h. Similar results were observed in microglial cells. In neurons, PK11195 and PpIX showed an increase in free radical production only at 2 min; Ro5‐4864 had no effect. The central‐type benzodiazepine receptor ligand, clonazepam, was ineffective in eliciting free radical production in all cell types. As the PBR may be a component of the mitochondrial permeability transition (MPT) pore, and free radical production may occur following induction of the MPT, we further investigated whether cyclosporin A (CsA), an inhibitor of the MPT, could prevent free radical formation by PBR ligands. CsA (1 µm) completely blocked free radical production following treatment with PK11195 and Ro5‐4864 in all cell types. CsA was also effective in blocking free radical production in astrocytes following PpIX treatment, but it failed to do so in neurons and microglia. Our results indicate that exposure of neural cells to PBR ligands generates free radicals, and that the MPT may be involved in this process.
Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats
Authors: Höglinger Günter U. , Féger Jean , Prigent Annick , Michel Patrick P. , Parain Karine , Champy Pierre , Ruberg Merle , Oertel Wolfgang H. , Hirsch Etienne C. 
Published: March 2003

AbstractIn Parkinson's disease, nigral dopaminergic neurones degenerate, whereas post‐synaptic striatal target neurones are spared. In some atypical parkinsonian syndromes, both nigral and striatal neurones degenerate. Reduced activity of complex I of the mitochondrial respiratory chain has been implicated in both conditions, but it remains unclear if this affects the whole organism or only the degenerating brain structures. We therefore investigated the differential vulnerability of various brain structures to generalized complex I inhibition. Male Lewis rats infused with rotenone, a lipophilic complex I inhibitor [2.5 mg/kg/day intraveneously (i.v.) for 28 days], were compared with vehicle‐infused controls. They showed reduced locomotor activity and loss of striatal dopaminergic fibres (54%), nigral dopaminergic neurones (28.5%), striatal serotoninergic fibres (34%), striatal DARPP‐32‐positive projection neurones (26.5%), striatal cholinergic interneurones (22.1%), cholinergic neurones in the pedunculopontine tegmental nucleus (23.7%) and noradrenergic neurones in the locus ceruleus (26.4%). Silver impregnation revealed pronounced degeneration in basal ganglia and brain stem nuclei, whereas the hippocampus, cerebellum and cerebral cortex were less affected. These data suggest that a generalized mitochondrial failure may be implicated in atypical parkinsonian syndromes but do not support the hypothesis that a generalized complex I inhibition results in the rather selective nigral lesion observed in Parkinson's disease.
Level of haem oxygenase does not obligatorily reflect the sensitivity of PC12 cells to an oxidative shock induced by glutathione depletion
Authors: Leon Albertine , Le Foll Isabelle , Charriault‐Marlangue Christiane , Leprince Jérome , Vaudry Hubert , Gabriel Cécilia , Duval Dominique 
Published: March 2003

AbstractIn order to investigate the function of haem oxygenase in neuronal cell death or survival, we have determined in PC12 cells whether induction of haem oxygenase mRNA and protein or inhibition of haem oxygenase activity may be able to modulate the cell response to an oxidative stress. Inhibition of glutathione biosynthesis by buthionine sulfoximine (BSO) has indeed been demonstrated, in this cell line, to decrease the intracellular content of glutathione and to trigger a gradual and programmed cell death. Inhibition of haem oxygenase by zinc protoporphyrin IX, a potent inhibitor of this enzyme, or by a recently described peptidic inhibitor, induced a significant decrease in the toxicity of BSO. This protective action was not due to an alteration in the metabolism of glutathione and was still observed when the protecting agent was added several hours after BSO treatment. Induction of haem oxygenase‐1 mRNA and protein by either haemin or pyrrolidine dithiocarbamate was associated with no protection or a significant reduction in the toxicity of BSO respectively. Our results indicate that induction of haem oxygenase‐1 is not obligatorily associated with an improved resistance towards oxidative stress and suggest that a byproduct of haem degradation may also become detrimental.
Human substance P receptor lacking the C‐terminal domain remains competent to desensitize and internalize
Authors: Richardson Mark D. , Balius Anastasia M. , Yamaguchi Keisuke , Freilich Emily R. , Barak Larry S. , Kwatra Madan M. 
Published: March 2003

AbstractSubstance P receptor (SPR) and its naturally occurring splice‐variant, lacking the C‐terminal tail, are found in brain and spinal cord. Whether C‐terminally truncated SPR desensitizes like full‐length SPR is controversial. We used a multivaried approach to determine whether human SPR (hSPR) and a C‐terminally truncated mutant, hSPRΔ325, differ in their desensitization and internalization. In HEK‐293 cells expressing either hSPRΔ325 or hSPR, SP‐induced desensitization of the two receptors was similar when measured by inositol triphosphate accumulation or by transient translocation of coexpressed PKCβII‐GFP to the plasma membrane. Moreover, translocation of β‐arrestin 1 or 2‐GFP (βarr1‐GFP or βarr2‐GFP) to the plasma membrane, and receptor internalization were also similar. However, hSPR and hSPRΔ325 differ in their phosphorylation and in their ability to form β‐arrestin‐containing endocytic vesicles. Unlike hSPR, hSPRΔ325 is not phosphorylated to a detectable level in intact HEK293 cells, and whereas hSPR forms vesicles containing either βarr1‐GFP or βarr2‐GFP, hSPRΔ325 does not form any vesicles with βarr1‐GFP, and forms fewer vesicles with βarr2‐GFP. We conclude that truncated hSPR undergoes agonist‐dependent desensitization and internalization without detectable receptor phosphorylation.
Differentiation of human retinal pigment epithelial cells into neuronal phenotype by N‐(4‐hydroxyphenyl)retinamide
Authors: Chen Shanyi , Samuel William , Fariss Robert N. , Duncan Todd , Kutty R. Krishnan , Wiggert Barbara 
Published: March 2003

AbstractARPE‐19, a human retinal pigment epithelial (RPE) cell line, has been widely used in studies of RPE function as well as gene expression. Here, we report the novel finding that N‐(4‐hydroxyphenyl)retinamide (fenretinide), a synthetic retinoic acid derivative and a potential chemopreventive agent against cancer, induced the differentiation of ARPE‐19 cells into a neuronal phenotype. The treated cells lost their epithelial phenotype and exhibited a typical neuronal shape with long processes (four to five times longer than the cell body). The onset of fenretinide‐induced neuronal differentiation was dose and time dependent, started within 1–2 days, and lasted at least 4 weeks. Immunohistochemical studies indicated that the expression of neurofilament proteins (NF160 and NF200), calretinin and neural cell adhesion molecule was increased in these differentiated cells. Western blot analysis indicated that cellular retinaldehyde‐binding protein, which is normally expressed in RPE cells, was decreased in treated cells. Protein analysis on a two‐dimensional gel followed by matrix‐assisted laser desorption ionization–time of flight mass spectrometric analysis demonstrated that heat‐shock protein 70 was increased after fenretinide treatment. Thus, fenretinide, a synthetic retinoid, is able to induce neuronal differentiation of human RPE cells in culture.
The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures
Authors: Chen Yongmei , Swanson Raymond A. 
Published: March 2003

AbstractCysteine availability is normally the rate‐limiting factor in glutathione synthesis. How neurons obtain cysteine from extracellular space is not well established. Here we used mouse cortical neuron cultures to examine the role of the excitatory amino acid transporters (EAATs) in neuronal cysteine uptake. The cultured neurons expressed both EAAT2 and EAAT3. Cysteine uptake was predominately (> 85%) Na+‐dependent, with an apparent Km of 37 μm. Cysteine uptake was reduced by the EAAT substratesl‐glutamate andl‐aspartate and by synthetic EAAT inhibitors. The non‐selective EAAT inhibitor threo‐β‐hydroxyaspartate had a significantly greater maximal inhibitory effect than did the EAAT2‐selective inhibitor, dihydrokainate, indicating uptake by both EAAT2 and EAAT3. Serine, a substrate of ASC uptake system, had negligible effects on cysteine uptake at 10‐fold excess concentrations. To assess the functional importance of EAAT‐mediated cysteine uptake in neuronal glutathione synthesis, cultures were treated with diethylmaleate to deplete glutathione, then incubated with cysteine in the presence or absence of EAAT inhibitors. Threo‐β‐benzyloxyaspartate and the non‐transportable inhibitor threo‐β‐hydroxyaspartate both inhibited the cysteine‐dependent glutathione synthesis. The findings suggest that neuronal EAAT activity can be a rate‐limiting step for neuronal glutathione synthesis and that the primary function of EAATs expressed by neuronsin vivomay be to transport cysteine.
Cellular and behavioural effects of the adenosine A2a receptor antagonist KW‐6002 in a rat model of l‐DOPA‐induced dyskinesia
Authors: Lundblad M. , Vaudano E. , Cenci M. A. 
Published: March 2003

AbstractWe have examined the ability of KW‐6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of l‐DOPA in 6‐hydroxydopamine‐lesioned rats. In animals rendered dyskinetic by a previous course of l‐DOPA treatment, KW‐6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the severity of dyskinesia when coadministered with l‐DOPA. A second experiment was undertaken in order to study the effects of KW‐6002 in l‐DOPA‐naive rats. Thirty‐five animals were allotted to four groups to receive a 21‐day treatment with: (i) KW‐6002 (10 mg/kg/day); (ii) l‐DOPA (6 mg/kg/day) i.p.; (iii) KW‐6002 plus l‐DOPA (same doses as above) or (iv) vehicle. Chronic treatment with KW‐6002‐only produced a significant relief of motor disability in the rotarod test in the absence of any abnormal involuntary movements. Combined treatment with l‐DOPA and KW‐6002 improved rotarod performance to a significantly higher degree than did each of the two drugs alone. However, this combined treatment induced dyskinesia to about the same degree as did l‐DOPA alone. In situ hybridization histochemistry showed that KW‐6002 treatment alone caused an approximately 20% reduction in the striatal levels of preproenkephalin mRNA, whereas neither the coadministration of KW‐6002 and l‐DOPA nor l‐DOPA alone significantly altered the expression of this transcript in the dopamine‐denervated striatum. Either alone or in combination with l‐DOPA, KW‐6002 did not have any modulatory effect on prodynorphin mRNA expression or FosB/ΔFosB‐like immunoreactivity in the dopamine‐denervated striatum.These results show that monotreatment with an adenosine A2a receptor antagonist can relieve motor disability without inducing behavioural and cellular signs of dyskinesia in rats with 6‐hydroxydopamine lesions. Cotreatment with KW‐6002 and l‐DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug.
Well‐being, sense of coherence, and burnout in stroke victims and spouses during the first few months after stroke
Authors: Nilsson Imogene , Axelsson Karin , Gustafson Yngve , Lundman Berit , Norberg Astrid 
Published: March 2003

Well‐being, sense of coherence, and burnout in stroke victims and spouses during the first few months after stroke Ten stroke victims, who had recently suffered their first manifest stroke with lasting neurological symptoms, participated, together with their spouses, in a study aimed at elucidating the well‐being, sense of coherence (SOC), and burnout during the first few months after discharge.The stroke victims had no substantial speech disturbances, and showed no evidence of significant cognitive impairment, signifying they were mildly to moderately impaired by their stroke. All subjects were investigated at 1 and 3 months after homecoming. The methods used in this study were open‐ended interviews with all research participants, performed at two different appointments, and three self‐reporting questionnaires: the well‐being measure (WM), the SOC scale, and the burnout measure (BM). The instruments suit each other well, broaden the picture of living with stroke and give an attuned comprehensive understanding. The most striking finding was the substantial differences in the results, both regarding the stroke victims and their spouses, clearly indicating the limited value current generalizations have. The results also pointed to considerable distress both in stroke victims and spouses, although individuals with a weak SOC clearly displayed more difficulties in coping with the situation and risk of burnout, than did those with a strong SOC.
A comparison of patient needs as ranked by patients and nurses
Authors: Hallström Inger , Elander Gunnel 
Published: March 2003

A comparison of patient needs as ranked by patients and nurses A group of patients (n=69) were asked to arrange the three most important of 10 groups of needs, identified by patients in a previous study, in order of priority from one to three. A group of nurses (n=89) were asked to arrange same groups of needs in order of priority from one to three according to how they believed patients would rank them. No significant differences were found between patients cared for at medical and at surgical wards or between nurses working at different departments. However, differences were found between the rankings of patients and nurses.
The relationship between coping strategies and family burden among relatives of admitted psychiatric patients
Authors: Östman Margareta , Hansson Lars 
Published: March 2003

Relationship between coping strategies and family burden among relatives of admitted psychiatric patients Coping strategies as assessed by a projective coping instrument, showed only a weak relationship to perceived family burden and participation in care among 78 close relatives of voluntarily and compulsorily admitted psychiatric patients in this study conducted in two psychiatric services in Sweden in 1997. The results rather indicate that problem solving coping strategies are used when the relatives are in situations amenable to change and that emotion‐focused coping strategies are used in situations that are chronic and unchangeable. Furthermore, no differences in coping strategies were found between the relatives and a Swedish normative sample.No relationships were found between coping strategies and when the relative thought that the patient’s mental health had led to mental problems in the relative or if the relative experienced that the relationship with the patient had been negatively affected by the mental illness. The usefulness of coping instruments based on personality components in research on family burden is called into question, and a reconsideration of qualitative research methods is recommended.
The applicability of the Antonovsky Sense of Coherence Scale to a group of Pentecostalists
Authors: Langius  , Björvell  
Published: March 2003

The applicability of the Antonovsky Sense of Coherence Scale to a group of Pentecostalists A methodological issue concerning the Antonovsky of Sense of Coherence (SOC) scale was raised in an earlier study questioning the applicability of the scale in different populations, and among these the Pentecostalists. The question was raised when a group of Pentecostalists had had difficulties in filling in another scale intended to measure the SOC.Therefore, the aim of this study was to test the applicability of the 29‐item Antonovsky SOC scale in a group of people (n=37) belonging to a church of the Pentecostal Movement and to compare the results with those of a randomized group (n=145) from a general population. The Pentecostalists filled in the scale with no obvious difficulties. No significant differences were found between the Pentecostal group and the group of a general population regarding the total SOC scale scores (mean 152, SD 16 and mean 151, SD 18, respectively). The applicability difficulties found in the earlier study, however using an other SOC scale, could not be confirmed in the present study.To conclude, the Antonovsky SOC scale has so far not shown to have applicability weakness.
The baby was the focus of attention – first‐time parents’ experiences of their intimate relationship
Authors: Ahlborg Tone , Strandmark Margaretha 
Published: March 2003

The baby was the focus of attention – first‐time parents’ experience of their intimate relationship The purpose of this study was to describe the phenomenon of ‘first‐time parents’ intimate relationship’, to focus on their mental health, and the ability to support them professionally. Ten Swedish parents (five couples) were interviewed on two occasions, when the first baby was 6 and 18 months old, respectively. A descriptive phenomenological method was used. The findings show that the essence of the phenomenon is ‘The baby was the focus of attention’. This had different meanings for the couples, putting them in two categories. For the first category, the essence was that the baby was the focus of mutual concern, which implied a fostered relationship. The strain of parenthood in this category was mild. In the second category, the baby was focused on at the expense of the father, who felt rejected emotionally. This impaired the relationship and parenthood involved a severe strain. The way the spouses communicated differed between the two categories. This study shows that mental health can be affected, especially among first‐time fathers, and this could jeopardize the relationship and family health. An awareness of this fact is needed among the health professionals giving care to first‐time parents.