bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation
Authors: Benfield Mark R. , Tejani Amir , Harmon William E. , McDonald Ruth , Stablein Donald M. , McIntosh Matthew , Rose Stephen ,   The CCTPT study group
Published: May 2005

Abstract:  Acute rejection leading to renal graft failure is more frequent among children. In patients treated with T cell antibody induction, retrospective data from the pediatric registry show a 22% reduction in the risk of graft failure. We conducted a randomized trial (n = 287) using OKT3 mAbs in one (OKT3) arm and intravenous cyclosporine in the other arm (CYS). Maintenance therapy consisted of randomized, double blind Sandimmune® or Neoral® together with prednisone and either azathioprine (AZA) or mycophenolate mofetil (MMF). Morbidity, mortality, rejection rates and adverse reactions in the two study arms were similar. Through 4 yr, graft failure was 27% in OKT3 and 19% in CYS (p = 0.15). One‐year graft survival was 89.1% in OKT3 and 89.2% in CYS (p = .19). In multivariate analysis, OKT3 had a numerically inferior graft survival (RR = 1.4, CI 0.8–2.2, p = 0.22). In OKT3 graft survival was inferior for children aged 6 yr or younger. Our trial demonstrates that the incidence of acute rejection or graft failure in pediatric patients is not improved by OKT3 induction therapy relative to cyclosporine induction.
Loss of antibodies to measles and varicella following solid organ transplantation in children
Authors: Warmington Lise , Lee Bonita E. , Robinson Joan L.
Published: May 2005

Abstract:  The objective of this study was to determine if loss of antibodies to measles and to varicella occurs in pediatric solid organ transplant recipients. Antibodies were measured in eight hepatic, four cardiac, and six renal transplant patients who had antibodies to measles prior to transplantation, and in six hepatic, five cardiac, and seven renal transplant patients who had antibodies to varicella prior to transplantation. Within 6 months of the transplant, loss of antibodies occurred in four of 18 patients who were seropositive for measles prior to transplantation (22.2%) and in two of 18 patients who were seropositive for varicella prior to transplantation (11.1%). In conclusion, serology for measles and varicella should be considered annually following solid organ transplantation so that appropriate advice can be given to patients who have seroreverted.
Recurrent urinary tract infection in the post‐transplant reflux nephropathy patient: Is reflux in the native ureter the culprit?
Authors: Casale Pasquale , Grady Richard W. , Mitchell Michael E. , Healey Patrick
Published: May 2005

Abstract:  We assessed the prevalence of symptomatic, refluxing systems as a cause of recurrent urinary tract infection (UTI) in patients who underwent renal transplantation as result of renal failure from reflux nephropathy. Eleven patients from the age of 8 to 19 yr underwent renal transplantation for renal failure because of reflux nephropathy, between 1992 and 2003. Culture documented UTI were investigated and correlated with pre‐ and postoperative infection rates, voiding dysfunction (VD), concomitant nephrectomy, or nephroureterectomy with refluxing native remnants, and pretransplant ureteral reimplantation. Four patients with nephroureterectomies and no VD were infection free post‐transplant. Two of three patients reimplanted pretransplant with a history of VD had one or more UTI per month. Patients with nephrectomies without partial ureterectomies with or without VD also had one or more UTI per month. Refluxing systems in the immunosuppressed transplant patient may play a role in UTI especially when associated with VD. Surgical intervention of native refluxing systems may be warranted.
Disrupting the melanin‐concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function
Authors: Adamantidis Antoine , Thomas Elizabeth , Foidart Agnès , Tyhon Amélie , Coumans Bernard , Minet Arlette , Tirelli Ezio , Seutin Vincent , Grisar Thierry , Lakaye Bernard
Published: May 2005

In order to investigate the physiological properties of the melanin‐concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1Neo/Neo mice). Complementary experimental approaches were used to investigate alterations in the learning and memory processes of our transgenic model. The ability of the knockout strain to carry out the inhibitory passive avoidance test was found to be considerably impaired although no significant differences were observed in anxiety levels. This impaired cognitive property prompted us to explore modifications in N‐methyl d‐aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from the MCHR1Neo/Neo mice revealed significantly decreased NMDA responses. Finally, using in situ hybridization we found a 15% reduction in NMDAR1 subunit in the CA1 region. These results show for the first time a possible role for MCH in the control of the function of the NMDA receptor.
Up‐regulation of β2 and α7 subunit containing nicotinic acetylcholine receptors in mouse striatum at cellular level
Authors: Pakkanen Jukka S. , Jokitalo Eija , Tuominen Raimo K.
Published: May 2005

Nicotine releases dopamine in the brain by activating neuronal nicotinic acetylcholine receptors (nAChRs). Chronic nicotine treatment increases the number of nAChRs, which represents plasticity of the brain. Together these phenomena have been suggested to have a role in the development of nicotine addiction. In the brain nAChRs can be localized synaptically, extrasynaptically or intracellularly. The purpose of these studies was to clarify the effects of chronic nicotine treatment on the localization of β2 and α7 nAChR subunits in brain areas involved in nicotine addiction. Nicotine was administered orally in drinking water to male NMRI mice for 7 weeks. At the end of chronic nicotine treatment the localization of the nAChR subunits was studied in the dorsal striatum and in the ventral tegmental area (VTA) by using electron microscopy. In the brain areas studied β2 and α7 subunits were localized presynaptically and postsynaptically in axon endings and in dendrites. In both areas the majority of the β2 and α7 subunits were localized at extrasynaptic sites. In response to chronic nicotine treatment the β2 and α7 nAChR subunit labelling was increased at synaptic and extrasynaptic sites as well as intracellularly. This suggests that the trafficking of nAChR subunits is increased as a result of chronic nicotine treatment and nAChRs in all parts of neurons could have functional roles in the formation of nicotine addiction.
Effects of exposure to a predator on behaviour and serotonergic neurotransmission in different brain regions of C57bl/6N mice
Authors: Beekman Marjolein , Flachskamm Cornelia , Linthorst Astrid C. E.
Published: May 2005

Clinical studies and animal models have provided evidence that stress and serotonin may play a role in the aetiology of psychiatric diseases such as depression and anxiety. In addition, reciprocal interactions between stress and serotonergic neurotransmission have been demonstrated. However, the relationships between stress, serotonin and behaviour are far from completely understood. In this integrative study, we aimed to elucidate the effect of the psychological stress model predator exposure on behaviour and serotonergic neurotransmission in mice. We used a high time‐resolution microdialysis method to measure extracellular levels of serotonin (5‐hydroxytryptamine, 5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in the hippocampus, prefrontal cortex, lateral septum and caudate putamen of C57bl/6N mice, before (08:30–10:30 h), during (10:30–11:00 h) and after exposure (11:00–14:00 h) to a rat. Detailed behavioural observations were also made. Rat exposure resulted in behavioural activation, with predominant risk‐assessment activities, and in increases in hippocampal, cortical, septal but not striatal 5‐HT and 5‐HIAA. When rat exposure was repeated on the consecutive day, small behavioural differences and reductions in 5‐HIAA levels, but no differences in the 5‐HT response, as compared with the first exposure were observed. As increases in 5‐HT often coincide with behavioural activation, it was particularly interesting to find that 5‐HT also increased in periods when mice only made minor movements such as sniffing, and that an effect of predator stress was absent in the caudate putamen. Our results indicate that the presence of the rat leads to differential activation of serotonergic neurotransmission in higher brain structures, probably involved in the coping response to this potentially life‐threatening situation.
Oxygen consumption and mitochondrial membrane potential indicate developmental adaptation in energy metabolism of rat cortical neurons
Authors: Schuchmann Sebastian , Buchheim Katharina , Heinemann Uwe , Hosten Norbert , Buttgereit Frank
Published: May 2005

Neuronal energy needs are mainly covered via mitochondrial oxidative phosphorylation. Even if the energy supply appears identical in immature and adult brain, nevertheless quantitative differences exist. The present study focuses on the adaptations in cellular energy metabolism caused by the neuronal maturation. As main parameters of oxidative phosphorylation, cellular oxygen consumption and mitochondrial membrane potential were measured in isolated rat cortical cells using a Clark‐type oxygen electrode and microfluorometric techniques. In four age groups (E18–P2, P8–P12, P16–P20, ≥ P28), unstimulated neurons showed a significant age‐dependent increase in basal oxygen consumption (6.1 up to 10.2 nm/min/107 cells). The excitatory neurotransmitter glutamate induced a further, but age‐ and concentration‐independent, elevation of oxygen consumption to a plateau ≥ 14 nm/min/107 cells and a complete depolarization of mitochondrial membrane in neurons ≥ P8. Stimulation using K+ (5–50 mm) effected a concentration‐ and age‐dependent increase in oxygen consumption, but a similar nearby complete depolarization of mitochondrial membrane in all tested age groups. Furthermore, uncoupling mitochondrial membrane function followed by a complete depolarization of mitochondrial membrane showed a maximal oxygen consumption (14–15 nm/min/107 cells) only in neurons ≥ P8. These data suggest that developing and adult cortical neurons cover their increased need of energy following stimulation by an efficiency improvement of mitochondrial oxidative phosphorylation. The age‐independent limited capacity of mitochondrial oxidative phosphorylation, however, causes a reduction in cellular energy disposal in mature neurons and therefore may play a critical role in the increased sensitivity of adult neurons against excitotoxicity and ischaemia.
ΔFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment
Authors: Perrotti Linda I. , Bolaños Carlos A. , Choi Kwang‐Ho , Russo Scott J. , Edwards Scott , Ulery Paula G. , Wallace Deanna L. , Self David W. , Nestler Eric J. , Barrot Michel
Published: May 2005

The transcription factor ΔFosB is induced in the nucleus accumbens and dorsal striatum by chronic exposure to several drugs of abuse, and increasing evidence supports the possibility that this induction is involved in the addiction process. However, to date there has been no report of ΔFosB induction by drugs of abuse in the ventral tegmental area (VTA), which is also a critical brain reward region. In the present study, we used immunohistochemistry to demonstrate that chronic forced administration of cocaine induces ΔFosB in the rat VTA. This induction occurs selectively in a γ‐aminobutyric acid (GABA) cell population within the posterior tail of the VTA. A similar effect is seen after chronic cocaine self‐administration. Induction of ΔFosB in the VTA occurs after psychostimulant treatment only: it is seen with both chronic cocaine and amphetamine, but not with chronic opiates or stress. The expression of ΔFosB appears to be mediated by dopamine systems, as repeated administration of a dopamine uptake inhibitor induced ΔFosB in the VTA, while administration of serotonin or norepinephrine uptake inhibitors failed to produce this effect. Time course analysis showed that, following 14 days of cocaine administration, ΔFosB persists in the VTA for almost 2 weeks after cocaine withdrawal. This accumulation and persistence may account for some of the long‐lasting changes in the brain associated with chronic drug use. These results provide the first evidence of ΔFosB induction in a discrete population of GABA cells in the VTA, which may regulate the functioning of the brain's reward mechanisms.
Fucoidan inhibits cellular and neurotoxic effects of β‐amyloid (Aβ) in rat cholinergic basal forebrain neurons
Authors: Jhamandas Jack H. , Wie Myung Bok , Harris Kim , MacTavish David , Kar S.
Published: May 2005

The deposition of β‐amyloid protein (Aβ), a 39–43 amino acid peptide, in the brain and a loss of cholinergic neurons in the basal forebrain are pathological hallmarks of Alzheimer's disease (AD). Seaweeds consumed in Asia contain Fucoidan, a sulfated polysaccharide. Fucoidan has been known to exhibit various biological actions, such as an anti‐inflammatory and antioxidant action. In this study, using whole‐cell patch clamp recordings we examined the effects of Fucoidan on Aβ‐induced whole‐cell currents in acutely dissociated rat basal forebrain neurons. We further investigated whether Fucoidan is capable of blocking Aβ neurotoxicity in primary neuronal cultures. In dissociated cells, bath application of Aβ25−35 (1 µm) caused a reduction of the whole‐cell currents by 16%. Fucoidan, in a dose‐dependent manner, blocks the Aβ25−35 reduction of whole‐cell currents. Exposure of Aβ25−35 (20 µm) or Aβ1−42 (20 µm) to rat cholinergic basal forebrain cultures for 48 h resulted in 40–60% neuronal death, which was significantly decreased by pretreatment of cultures with Fucoidan (0.1–1.0 µm). Fucoidan also attenuated Aβ‐induced down‐regulation of phosphorylated protein kinase C. Aβ1−42‐induced generation of reactive oxygen species was blocked by prior exposure of cultures to Fucoidan. Furthermore, Aβ activation of caspases 9 and 3, which are signaling pathways implicated in apoptotic cell death, is blocked by pretreatment of cultures with Fucoidan. These results show that Fucoidan is able to block Aβ‐induced reduction in whole‐cell currents in basal forebrain neurons and has neuroprotective effects against Aβ‐induced neurotoxicity in basal forebrain neuronal cultures.
Expression of collapsin response mediator proteins 1, 2 and 5 is differentially regulated in newly generated and mature neurons of the adult olfactory system
Authors: Veyrac Alexandra , Giannetti Nathalie , Charrier Emmanuelle , Reymond‐Marron Isabelle , Aguera Michèle , Rogemond Veronique , Honnorat Jérôme , Jourdan François
Published: May 2005

Collapsin‐response mediator proteins (CRMPs) are highly expressed in the developing brain where they take part in several aspects of neuronal differentiation. CRMPs are still present postnatally, but their function remains speculative in the adult brain. We studied the expression and localization of CRMP1, CRMP2 and CRMP5 in two areas of the nervous system with persistent neurogenesis in adult mice, the olfactory mucosa and the olfactory bulb. In the olfactory mucosa, we have established that CRMP expression is restricted to postmitotic cells of the olfactory neurons lineage. CRMP5 is coexpressed with growth associated protein of 43 kDa (GAP43) in immature olfactory neurons and is down‐regulated in olfactory marker protein‐positive mature neurons. In contrast, CRMP1 and CRMP2 persist at all stages of differentiation from immature GAP43‐positive to fully mature olfactory neurons. In the olfactory bulb, CRMP1, CRMP2 and CRMP5 are abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons. In both areas, the subcellular distribution of CRMP1 or CRMP2 is different in mature vs. immature neurons, suggesting that these proteins are sequentially involved in various cellular events during neuronal lifetime. The variations of CRMP expression following axotomy are consistent with their differential localization and functional involvement in immature vs. mature neurons of the olfactory system. Our data bring new insight to the putative functions of CRMPs within areas of the adult nervous system with permanent neurogenesis, some related to differentiation of newly generated neurons but others occurring in mature neurons with a limited lifespan.
Motor pattern selection by nitric oxide in the stomatogastric nervous system of the crab
Authors: Stein Wolfgang , Eberle Christina C. , Hedrich Ulrike B. S.
Published: May 2005

The gas nitric oxide (NO) serves a diversity of functions in the nervous system and plays an important role in the modulation of oscillatory networks. We investigated the actions of intrinsically produced NO on the rhythmically active gastric mill circuit within the stomatogastric ganglion (STG) of the crab, Cancer pagurus. Bath application of different NO blockers exclusively to the STG terminated spontaneously active gastric mill rhythms. Furthermore, a reduction in the activity levels of projection neurons that sustain the gastric mill rhythm was observed, suggesting that NO blockade influences feedback mechanisms that affect projection neuron activity. When STG feedback to these projection neurons was intact, their activity decreased strongly with NO blockers present exclusively in the STG. When either neuronal feedback was eliminated or projection neurons were tonically activated, NO blockade did not terminate the gastric mill rhythm, indicating an indirect ascending control of the projection neurons. Together, our results show that ascending feedback from a motor network is important in shaping network activity and that this feedback is state‐dependent and can be modulated to alter the output of the motor network.
Osteonectin is a Schwann cell‐secreted factor that promotes retinal ganglion cell survival and process outgrowth
Authors: Bampton Edward T. W. , Ma Chi Him , Tolkovsky Aviva M. , Taylor Jeremy S. H.
Published: May 2005

We have investigated the factors made by Schwann cells (SCs) that stimulate survival and neurite outgrowth from postnatal rat retinal ganglion cells (RGCs). These effects are preserved under K252a blockade of the Trk family of neurotrophin receptors and are not fully mimicked by the action of a number of known trophic factors. To identify novel factors responsible for this regenerative activity, we have used a radiolabelling assay. Proteins made by SCs were labelled radioactively and then fed to purified RGCs. The proteins taken up by the RGCs were then isolated and further characterized. Using this assay we have identified a major 40 kDa factor taken up by RGCs, which was microsequenced and shown to be the matricellular protein osteonectin (ON). Using an in vitro assay of purified RGCs we show that ON promotes both survival and neurite outgrowth. We conclude that ON has a potential new role in promoting CNS repair.
Cortical and subcortical contributions to saccade latency in the human brain
Authors: Neggers S. F. W. , Raemaekers M. A. H. , Lampmann E. E. L. , Postma A. , Ramsey N. F.
Published: May 2005

An important property of our motor system is the ability to either perform or inhibit an automatic goal‐directed reaction. Imagine, for example, how easily we can catch a ball, while at the same time we would never grasp a stinging insect approaching us. The oculomotor system provides a good model to study this ability. Monkey midbrain superior colliculus neurons are responsible for automatic visually evoked saccades, whereas the frontal eye fields can prevent reflexive glances. Little is known about human superior colliculus or the competition between the midbrain and frontal areas controlling saccades. In the present functional magnetic resonance study we used the gap paradigm, where a stimulus fixated with the eyes is removed 200 ms prior to saccade target onset. Subjects were required to either look at the target or prevent an eye movement. From what is known from non‐human primate neurophysiology, it is expected that the gap will result in enlarged neuronal activity in the human superior colliculus, disinhibiting the oculomotor system and enhancing automatic reactions. Importantly, we demonstrate that the human superior colliculus homologue is indeed activated by the removal of a fixation target, in either task. The frontal eye fields show a reverse pattern when saccades were suppressed. Furthermore, magnitude of responses in the superior colliculus correlated negatively with saccade latency, and in the frontal eye fields positively. These findings confirm for the first time that the human superior colliculus generates automatic goal‐directed saccades, whereas the frontal eye fields can exert volitional control over automatic orienting.
Calculated phase equilibria in K2O‐FeO‐MgO‐Al2O3‐SiO2‐H2O for silica‐undersaturated sapphirine‐bearing mineral assemblages
Authors: KELSEY D. E. , WHITE R. W. , POWELL R.
Published: May 2005

Silica‐undersaturated, sapphirine‐bearing granulites occur in a large number of localities worldwide. Such rocks have historically been under‐utilized for estimating P–T evolution histories because of limited experimental work, and a consequent poor understanding of the topology and P–T location of silica‐undersaturated mineral equilibria. Here, a calculated P–T projection for sapphirine‐bearing, silica‐undersaturated metapelitic rock compositions is constructed using THERMOCALC for the FeO‐MgO‐Al2O3‐SiO2 (FMAS) and KFMASH (+K2O + H2O) chemical systems, allowing quantitative analysis of silica‐undersaturated mineral assemblages. This study builds on that for KFMASH sapphirine + quartz equilibria [Kelsey et al. (2004) Journal of Metamorphic Geology, vol. 22, pp. 559–578]. FMAS equilibria are significantly displaced in P–T space from silicate melt‐bearing KFMASH equilibria. The large number of univariant silica‐undersaturated KFMASH equilibria result in a P–T projection that is topologically more complex than could be established on the basis of experiments and/or natural assemblages. Coexisting sapphirine and silicate melt (with or without corundum) occur down to c. 900 °C in KFMASH, some 100 °C lower than in silica‐saturated compositions, and from pressures of c.≤1 to ≥12 kbar. Mineral compositions and composition ranges for the calculated phases are consistent with natural examples. Bulk silica has a significant effect on the stability of sapphirine‐bearing assemblages at a given P–T, resulting in a wide variety of possible granulite facies assemblages in silica‐undersaturated metapelites. Calculated pseudosections are able to reproduce many naturally occurring silica‐undersaturated assemblages, either within a single assemblage field or as the product of a P–T trajectory crossing several fields. With an understanding of the importance of bulk composition on sapphirine stability and textural development, silica‐undersaturated assemblages may be utilized in a quantitative manner in the detailed metamorphic investigation of high‐grade terranes.
Bulk chemical control on metamorphic monazite growth in pelitic schists and implications for U–Pb age data
Authors: FITZSIMONS I. C. W. , KINNY P. D. , WETHERLEY S. , HOLLINGSWORTH D. A.
Published: May 2005

Several petrographic studies have linked accessory monazite growth in pelitic schist to metamorphic reactions involving major rock‐forming minerals, but little attention has been paid to the control that bulk composition might have on these reactions. In this study we use chemographic projections and pseudosections to argue that discrepant monazite ages from the Mount Barren Group of the Albany–Fraser Orogen, Western Australia, reflect differing bulk compositions. A new Sensitive High‐mass Resolution Ion Microprobe (SHRIMP) U–Pb monazite age of 1027 ± 8 Ma for pelitic schist from the Mount Barren Group contrasts markedly with previously published SHRIMP U–Pb monazite and xenotime ages of c. 1200 Ma for the same area. All dated samples experienced identical metamorphic conditions, but preserve different mineral assemblages due to variable bulk composition. Monazite grains dated at c. 1200 Ma are from relatively magnesian rocks dominated by biotite, kyanite and/or staurolite, whilst c. 1027 Ma grains are from a ferroan rock dominated by garnet and staurolite. The latter monazite population is likely to have grown when staurolite was produced at the expense of garnet and chlorite, but this reaction was not intersected by more magnesian compositions, which are instead dominated by monazite that grew during an earlier, greenschist facies metamorphic event. These results imply that monazite ages from pelitic schist can vary depending on the bulk composition of the host rock. Samples containing both garnet and staurolite are the most likely to yield monazite ages that approximate the timing of peak metamorphism in amphibolite facies terranes. Samples too magnesian to ever grow garnet, or too iron‐rich to undergo garnet breakdown, are likely to yield older monazite, and the age difference can be significant in terranes with a polymetamorphic history.
A transitional period of Ca2+‐dependent spike afterdepolarization and bursting in developing rat CA1 pyramidal cells
Authors: Chen Shmuel , Yue Cuiyong , Yaari Yoel
Published: May 2005

During postnatal development neurones display discharge behaviours that are not present in the adult, yet they are essential for the normal maturation of the nervous system. Neonatal CA1 pyramidal cells, like their adult counterparts, fire regularly, but excitatory GABAergic transmission drives them to generate spontaneous high‐frequency bursts until postnatal day (P) 15. Using intracellular recordings in hippocampal slices from rats at P8 to P25, we show herein that as the network‐driven burst activity fades out, most CA1 pyramidal cells become intrinsically bursting neurones. The incidence of intrinsic bursters begins to rise at P11 and attains a peak of 74% by P18–P19, after which it decreases over the course of a week, disappearing almost entirely at P25. Analysis of the effects of different voltage‐gated Ca2+ and Na+ channel antagonists, applied focally to proximal and distal parts of developing neurones, revealed a complex burst mechanism. Intrinsic bursting in developing neurones results from ‘ping‐pong’ interplay between a back‐propagating spike that activates T/R‐ and L‐type voltage‐gated Ca2+ channels in the distal apical dendrites and persistent voltage‐gated Na+ channels in the somatic region. Thus, developing pyramidal neurones transitionally express not only distinctive synaptic properties, but also unique intrinsic firing patterns, that may contribute to the ongoing formation and refinement of synaptic connections.
Cell type‐specific action of seizure‐induced intracellular zinc accumulation in the rat hippocampus
Authors: Côté Amélie , Chiasson Marilou , Peralta Modesto R. , Lafortune Kathleen , Pellegrini Luca , Tóth Katalin
Published: May 2005

Increased levels of intracellular zinc have been implicated in neuronal cell death in ischaemia, epilepsy and traumatic brain damage. However, decreases in zinc levels also lead to increased neuronal death and lowered seizure threshold. In the present study we investigated the physiological role of zinc in neurodegeneration and protection following epileptic seizures. Cells located in the strata oriens and lucidum of the CA3 region accumulated high concentrations of zinc and died. A decrease in zinc level could prevent the death of these neurones after seizures. Most of these cells were GABAergic interneurones. In contrast, neurones in the CA3 pyramidal cell layer accumulated moderate amounts of zinc and survived. Zinc chelation led to an increase in the mortality rate of these cells. Furthermore, in these cells low concentrations of intracellular zinc activated Akt (protein kinase B), thus providing protection against neurodegeneration. These results demonstrate that intracellularly accumulated zinc can be neurotoxic or neuroprotective depending on its concentration. This dual action is cell type specific.
A functional glutamatergic neurone network in the medial septum and diagonal band area
Authors: Manseau F. , Danik M. , Williams S.
Published: May 2005

The medial septum and diagonal band complex (MS/DB) is important for learning and memory and is known to contain cholinergic and GABAergic neurones. Glutamatergic neurones have also been recently described in this area but their function remains unknown. Here we show that local glutamatergic neurones can be activated using 4‐aminopyridine (4‐AP) and the GABAA receptor antagonist bicuculline in regular MS/DB slices, or mini‐MS/DB slices. The spontaneous glutamatergic responses were mediated by AMPA receptors and, to a lesser extend, NMDA receptors, and were characterized by large, sometimes repetitive activity that elicited bursts of action potentials postsynaptically. Similar repetitive AMPA receptor‐mediated bursts were generated by glutamatergic neurone activation within the MS/DB in disinhibited organotypic MS/DB slices, suggesting that the glutamatergic responses did not originate from extrinsic glutamatergic synapses. It is interesting that glutamatergic neurones were part of a synchronously active network as large repetitive AMPA receptor‐mediated bursts were generated concomitantly with extracellular field potentials in intact half‐septum preparations in vitro. Glutamatergic neurones appeared important to MS/DB activation as strong glutamatergic responses were present in electrophysiologically identified putative cholinergic, GABAergic and glutamatergic neurones. In agreement with this, we found immunohistochemical evidence that vesicular glutamate‐2 (VGLUT2)‐positive puncta were in proximity to choline acetyltransferase (ChAT)‐, glutamic acid decarboxylase 67 (GAD67)‐ and VGLUT2‐positive neurones. Finally, MS/DB glutamatergic neurones could be activated under more physiological conditions as a cholinergic agonist was found to elicit rhythmic AMPA receptor‐mediated EPSPs at a theta relevant frequency of 6–10 Hz. We propose that glutamatergic neurones within the MS/DB can excite cholinergic and GABAergic neurones, and that they are part of a connected excitatory network, which upon appropriate activation, may contribute to rhythm generation.
Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice
Authors: Kuczewski Nicola , Aztiria Eugenio , Gautam Dinesh , Wess Jürgen , Domenici Luciano
Published: May 2005

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the use of M1–M5 mAChR‐deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli.
Discovery of Pulsed OH Maser Emission Stimulated by a Pulsar
Authors: Weisberg Joel M. , Johnston Simon , Koribalski Bärbel , Stanimirović Snezana
Published: May 2005

Stimulated emission of radiation has not been directly observed in astrophysical situations up to this time. Here we demonstrate that photons from pulsar B1641–45 stimulate pulses of excess 1720-megahertz line emission in an interstellar hydroxyl (OH) cloud. As this stimulated emission is driven by the pulsar, it varies on a few-millisecond time scale, which is orders of magnitude shorter than the quickest OH maser variations previously detected. Our 1612-megahertz spectra are inverted copies of the 1720-megahertz spectra. This “conjugate line” phenomenon enables us to constrain the properties of the interstellar OH line–producing gas. We also show that pulsar signals undergo significantly deeper OH absorption than do other background sources, which confirms earlier tentative findings that OH clouds are clumpier on small scales than are neutral hydrogen clouds.
Multicentre trials review process by research ethics committees in Spain: where do they stand before implementing the new European regulation?
Authors: Dal-Ré R , Ortega R , Morejón E
Published: May 2005

Objectives:To review the performance of research ethics committees (RECs) in Spain in assessing multicentre clinical trial (MCT) drug protocols, and to evaluate if they would comply with the requirements of the new EU Directive to be implemented by May 2004.

Design and setting:Prospective study of applications of MCT submitted to RECs.

Main measurements:Protocol related features and evaluation process dynamics.

Results:187 applications (24 protocols, 18 study drugs) to be performed in 114 centres, were reviewed by 62 RECs. RECs had a median number of 14 members, of which three were lay members. All applications were approved except four which were however approved by the other RECs involved. The median times from submission to approval and from submission to reception at the sponsor’s offices were 48 and 62 days, respectively. In 55% (101/183) of all applications approved, 41 RECs raised 307 queries, 40% of these were protocol related issues, and 38% related to the patients’ information sheets. RECs charging an evaluation fee in advance and applications with no queries raised were statistically significantly associated with shorter evaluation times. However, there is a gap of at least 1.5 weeks between the date of the meeting and the reception of the approval letter in the sponsor’s office.

Conclusions:Evaluating MCT protocols by RECs is a time consuming process. Needing 1.5 weeks for communicating the decision taken by RECs to the sponsor suggests serious administrative shortcomings within most RECs. By significantly reducing the time for communication of their decisions, the majority of RECs would comply with the Directive requirement of a maximum 60 day period for the assessment of MCT.
Subtle ethical dilemmas in geriatric management and clinical research
Authors: Rosin A J , van Dijk Y
Published: May 2005

Routine management of geriatric problems often raises ethical problems, particularly regarding autonomy of the old person. The carers or children may be unaware of the sensitivity of role reversal in dealing with the financial affairs; the need for a residential carer may compromise the old person’s privacy. Attending a day centre confers much benefit, but one must understand the old person’s resistance to change in the proposal of a new daily regimen. Similarly his or her autonomy must be the priority in planning for admittance to an old age home, and not the assumption that the family knows best. A common dilemma is the assessment of an old person’s competency in decision making, either about management of his affairs, or regarding consent to treatment, or participation in research. Because cognitive capacity is not always identical with competency, meaningful tools have recently been developed in which the emphasis is on the specific situation to be investigated.
Human organs, scarcities, and sale: morality revisited
Authors: Kishore R R
Published: May 2005

Despite stringent and fine tuned laws most jurisdictions are not able to curb organ trafficking. Nor are they able to provide organs to the needy. There are reports of the kidnapping and murder of children and adults to “harvest” their organs. Millions of people are suffering, not because the organs are not available but because “morality” does not allow them to have access to the organs. Arguments against organ sale are grounded in two broad considerations: (1) sale is contrary to human dignity, and (2) sale violates equity. Both these objections are examined in this article and it is concluded that they reflect a state of moral paternalism rather than pragmatism. It is argued that a live human body constitutes a vital source of supply of organs and tissues and that the possibilities of its optimum utilisation should be explored. Commercialisation should be curbed not by depriving a needy person of his genuine requirements but by making the enforcement agencies efficient.
Role of parents and peers in influencing the smoking status of high school students in Taiwan
Authors: Wen C P , Tsai S P , Cheng T Y , Hsu C C , Chen T , Lin H S
Published: May 2005

Objectives:To assess parental influence on smoking behaviour by high school students in an Asian culture and to compare the relative importance of parental and peer influence.

Methods:A 5% nationally representative sample, including 44 976 high school students in 10th to 12th grade (aged 15–18 years) in Taiwan, were surveyed in 1995. Each completed a long self administered questionnaire. Parental influence was measured by examining both parental behaviour (smoking status) and attitudes (perceived “tender loving care” (TLC) by adolescents). Changes in smoking status were used to determine peer influence, defined as the increase in the likelihood of smoking from grade 10 to 12 in a steady state environment. Odds ratios (ORs) were calculated for parental and peer influence, using logistic regression.

Results:Adolescents of smoking parents with low TLC had the highest smoking rates and those of non-smoking parents with high TLC had the lowest. The difference was more than twofold in boys and more than fourfold in girls. When either parental smoking status or TLC alone was considered, parental influence was similar to peer influence in boys, but larger than peer influence in girls. However, when smoking status and TLC were considered jointly, it became larger than peer influence for both groups (OR 2.8v1.8 for boys and OR 3.9v1.3 for girls).

Conclusion:When parental influence is taken as parental behaviour and attitude together, it plays a more important role than peer influence in smoking among high school students in Taiwan. This study, characterising such relationships among Asian populations for the first time, implies that future prevention programmes should direct more efforts toward the parental smoking and parent–child relationships, and not aim exclusively at adolescents in schools.
The health benefits of smoking cessation for adult smokers and for pregnant women in Taiwan
Authors: Wen C P , Cheng T Y , Lin C-L , Wu H-N , Levy D T , Chen L-K , Hsu C-C , Eriksen M P , Yang H-J , Tsai S P
Published: May 2005

Objective:To assess the benefits of smoking cessation regarding mortality reduction after smokers quit, and regarding the health of newborns after smoking mothers quit.

Methods:Relative mortality risks (RR) for smokers aged 35 or older who quit years ago were calculated from the follow up of 71 361 civil servants and teachers recruited since 1989. Data from the Pregnancy Risk Assessment Monitoring System in Taipei City were used to calculate the odds ratios of body weights of newborns born to mothers of different smoking status.

Results:Mortality risk for ex-smokers was significantly lower than that of current smokers for all causes (18%), all cancer (22%), lung cancer (39%), and ischaemic heart disease (54%). These benefits were not distinguishable initially, up to five years, but by year 17 and thereafter, substantial benefits of cessation accrued. Two thirds of smoking women quit during the first trimester of pregnancy, and only 2.2% of mothers smoked throughout pregnancy. The newborns from smoking mothers were smaller than those from never smoking mothers, but, if these mothers quit early in the first trimester, birth weights were normal.

Conclusions:The health benefits of smoking cessation, rarely reported for Asian populations, have been largely ignored by smokers in Taiwan, where cessation activities have been extremely limited. Findings of this study that risks from smoking can be attenuated or reversed should be widely communicated to motivate smokers to quit. Smokers should quit early, including smoking mothers, and not wait till medical conditions surfaced, to have the maximal benefits of cessation.
Smoking behaviour in Taiwan, 2001
Authors: Wen C P , Levy D T , Cheng T Yuan , Hsu C-C , Tsai S P
Published: May 2005

Purpose:To examine smoking behaviours in Taiwan and compare those behaviours to those in the USA.

Methods:Using the National Health Interview Survey (NHIS) of Taiwan (2001), a survey of over 20 000 participants, frequencies were calculated for smoking, ex-smoking, quantity smoked, and exposure to environmental tobacco smoke (ETS). Breakdowns by age, sex, and socioeconomic status were also calculated.

Results:The ratio of male to female smoking rates was 10.9 to 1 among adults (46.8%/4.3%), but 3.6 to 1 among underage teenagers (14.3%/4.0%). The proportion of underage to adult smokers was three times higher for girls than for boys. Smoking prevalence substantially increased during and after high school years, and peaked in those aged 30–39 years. Smoking rates of high school age adolescents increased more than threefold if they did not attend school or if they finished their education after high school. Low income and less educated smokers smoked at nearly twice the rate of high income and better educated smokers. The smoker/ex-smoker ratio was close to 7. Male daily smokers smoked on average 17 cigarettes/day, and females, 11. Half of the total population, especially infants and women of childbearing age, were exposed to ETS at home.

Conclusions:Taiwan has particularly high male smoking prevalence and much lower female prevalence. The low female prevalence is likely to increase if the current sex ratio of smoking by underage youth continues. The low quit rate among males, the high ETS exposure of females and young children at home, and the sharp increase in smoking rates when students leave school, are of particular concern. These observations on smoking behaviour can provide valuable insights to assist policymakers and health educators in formulating strategies and allocating resources in tobacco control.
Impact of UK policy initiatives on use of medicines to aid smoking cessation
Authors: West R , DiMarino M E , Gitchell J , McNeill A
Published: May 2005

Context:Increasing the use of effective smoking cessation aids could in principle have a substantial public health impact. The UK government has undertaken several major policy initiatives to try to increase usage of smoking cessation medicines. It is important to evaluate what effect, if any, these have had to inform future policy in the UK and internationally.

Objective:This study used sales data to examine the impact of government initiatives to increase access to smoking cessation medicines.

Design:Information about prescription and non-prescription sales (1999–2002) was obtained. Estimates of utilisation were compared with findings from the Office of National Statistics (ONS) omnibus surveys. The effects of policy initiatives (making the medicines reimbursable and making them available on general sale outside pharmacies) were assessed by means of time series analysis. In addition a new nicotine replacement therapy (NRT) product (a nicotine lozenge) was launched and the effect of this on total utilisation was assessed.

Results:Making bupropion, and subsequently nicotine replacement therapy (NRT), reimbursable had a major impact in medication usage; the estimated increase in each case was more than 80 000 “treatment weeks” purchased per month. In addition, introduction of a nicotine lozenge increased total utilisation and did not detract from usage of other medicines. According to both the sales and the survey data, the proportion of smokers using medicines to aid smoking cessation more than doubled from 8–9% in 1999 to 17% in 2002. The ONS surveys showed no increase in the proportions of smokers making quit attempts and so the effects were solely on the proportions of quit attempts that were aided by medication.

Conclusions:In the UK, making smoking cessation medicines reimbursable led to a large increase in utilisation. While the effect on smoking prevalence would be too small to be detected in national surveys it could have a substantial public health impact.
The Virginia Slims identity crisis: an inside look at tobacco industry marketing to women
Authors: Toll B A , Ling P M
Published: May 2005

Objectives:Because no prior studies have comprehensively analysed previously secret tobacco industry documents describing marketing female brands, the Virginia Slims brand was studied to explore how Philip Morris and competitors develop and adapt promotional campaigns targeting women.

Methods:Analysis of previously secret tobacco industry documents. The majority of the documents used were from Philip Morris.

Results:The key to Virginia Slims advertising was creating an aspirational image which women associated with the brand. Virginia Slims co-opted women’s liberation slogans to build a modern female image from 1968 through to the 1980s, and its market share grew from 0.24% to 3.16% during that time period. Ironically, the feminist image that worked very well for the brand was also the reason for its subsequent problems. Philip Morris experienced unprecedented losses in market share in the early 1990s, with a decline in market share for four consecutive years from 3.16% to 2.26%; they attributed this decline to both the fact that the brand’s feminist image no longer appealed to young women aged 18–24 years, and increased competition from more contemporary and lower priced competitors. Throughout the 1990s, attempts to reacquire young women while retaining Virginia Slims loyal (now older) smokers were made using a “King Size” line extension, new slogans, and loyalty building promotions.

Conclusions:Tobacco advertisers initially created distinct female brands with aspirational images; continued appeal to young women was critical for long term growth. The need for established brands to evolve to maintain relevance to young women creates an opportunity for tobacco counter-marketing, which should undermine tobacco brand imagery and promote aspirational smoke-free lifestyle images. Young women age 18–24 are extremely valuable to the tobacco industry and should be a focus for tobacco control programmes.