bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso
Authors: Mandi Germain , Witte Steffen , Meissner Peter , Coulibaly Boubacar , Mansmann Ulrich , Rengelshausen Jens , Schiek Wolfgang , Jahn Albrecht , Sanon Mamadou , Wüst Kirsten , Walter‐Sack Ingeborg , Mikus Gerd , Burhenne Jürgen , Riedel Klaus‐Dieter , Schirmer Heiner , Kouyaté Bocar , Müller Olaf 
Published: January 2005

SummaryNew drug combinations against falciparum malaria which are both effective and affordable for Sub‐Saharan African populations are urgently needed. The combination of the well‐known drugs chloroquine (CQ) and methylene blue (MB) is such a promising new regimen. However, there is some concern that MB could cause development of haemolysis in patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, a condition which is prevalent in malaria‐endemic regions. Against this background, 74 G6PD‐deficient but otherwise healthy adult men were given a 3‐day oral regimen of a total of 1500 mg CQ and 780 mg MB in the District Hospital of Nouna in north‐western Burkina Faso. Haemolysis did not occur, haemoglobin levels remained stable or even rose in the study participants, and the drug regimen was well tolerated. Therefore, standard dosages of MB appear to be safe in G6PD‐deficient African populations with predominantly class III G6PD deficiency.
Follow up of the regression of the placenta left in situ in an advanced abdominal pregnancy using the Cavalieri method
Authors: Cetinkaya Mehmet B. , Kokcu Arif , Alper Tayfun 
Published: January 2005

AbstractIn this abdominal pregnancy, the dead fetus was delivered through an abdominal incision at the 36th gestational week. The placenta invaded the small intestine and the omentum was left in situ. The placental degeneration was monitored using serial serum β‐human chorionic gonadotropin values. In certain periods, the follow up of the placental regression was carried out using the Cavalieri method with abdominal ultrasound. It was seen that the placental volume had decreased by 83% at the end of 1 year. To the best of our knowledge, this is the first time this method has been used for this purpose.
Heterozygous hemophilia developed during pregnancy
Authors: Fukada Yukihito , Shima Takashi , Kawashima Shigeki , Hirata Shuji , Hoshi Kazuhiko 
Published: January 2005

AbstractIn rare cases, patients with heterozygous hemophilia show bleeding tendency due to a low factor VIII activity of <20%. Here we describe a case of heterozygous hemophilia that developed during pregnancy. The patient was a 33‐year‐old Japanese woman whose father and brother both showed elevated nasal bleeding tendencies. However, they had received no medication for this condition. At 26 weeks’ gestation she experienced heavy nasal bleeding. The prothrombin time and platelet count were normal, but the activated partial thromboplastin time was prolonged. Premature rupture of the membrane occurred, and an emergency cesarean section was carried out at 28 weeks’ gestation. A diagnosis of heterozygous hemophilia was made after the cesarean section. Hemophilia crisis and heterozygous hemophilia require special obstetric care, with close liaison with a hematologist. Guidelines for the management of such cases should be available and observed.
Tourniquet technique prevents profuse blood loss in placenta accreta cesarean section
Authors: Ikeda Tomoaki , Sameshima Hiroshi , Kawaguchi Hideki , Yamauchi Noriyuki , Ikenoue Tsuyomu 
Published: January 2005

AbstractAim: Profuse bleeding in placenta accreta is life‐threatening even under well‐prepared cesarean sections.Methods: We used a tourniquet technique to temporally shut off blood flow through the uterine and ovarian vessels at the level of the uterine cervix. The tourniquet consisted of manual compression followed by a rubber tube.Results: Total blood loss in cesarean section and hysterectomy in the two cases in which we applied this technique was significantly reduced compared with that in the two cases without it.Conclusion: This technique not only prevented massive bleeding from the accreted placentation, but also allowed physicians time to consider the necessity of subsequent hysterectomy.
The actin‐binding protein profilin I is localized at synaptic sites in an activity‐regulated manner
Authors: Neuhoff Henrike , Sassoè‐Pognetto Marco , Panzanelli Patrizia , Maas Christoph , Witke Walter , Kneussel Matthias 
Published: January 2005

AbstractMorphological changes at synaptic specializations have been implicated in regulating synaptic strength. Actin turnover at dendritic spines is regulated by neuronal activity and contributes to spine size, shape and motility. The reorganization of actin filaments requires profilins, which stimulate actin polymerization. Neurons express two independent gene products − profilin I and profilin II. A role for profilin II in activity‐dependent mechanisms at spine synapses has recently been described. Although profilin I interacts with synaptic proteins, little is known about its cellular and subcellular localization in neurons. Here, we investigated the subcellular distribution of this protein in brain neurons as well as in hippocampal cultures. Our results indicate that the expression of profilin I varies in different brain regions. Thus, in cerebral cortex and hippocampus profilin I immunostaining was associated predominantly with dendrites and was present in a subset of dendritic spines. In contrast, profilin I in cerebellum was associated primarily with presynaptic structures. Profilin I immunoreactivity was partially colocalized with the synaptic molecules synaptophysin, PSD‐95 and gephyrin in cultured hippocampal neurons, indicating that profilin I is present in only a subset of synapses. At dendritic spine structures, profilin I was found primarily in protrusions, which were in apposition to presynaptic terminal boutons. Remarkably, depolarization with KCl caused a moderate but significant increase in the number of synapses containing profilin I. These results show that profilin I can be present at both pre‐ and postsynaptic sites and suggest a role for this actin‐binding protein in activity‐dependent remodelling of synaptic structure.
Inhibitory avoidance learning altered ensemble activity of amygdaloid neurons in rats
Authors: Chang Chun‐Hui , Liang Keng‐Chen , Yen Chen‐Tung 
Published: January 2005

AbstractIn this study, we examined single‐unit activity in the amygdala before and after a rat had acquired an inhibitory avoidance task. Long‐Evans rats with microwires chronically implanted into the central nucleus (CeA) or basolateral complex (BLC) of the amygdala were acclimatized to the apparatus of a step‐through inhibitory avoidance task for three sessions. On the fourth session, rats in the experimental group received an inescapable footshock (3 mA, 1 s) as they stepped from the lit side into the dark side of the task apparatus, whereas rats in the control group received the same amount of shock on a different apparatus. All rats were tested for retention in the task apparatus 1 day after shock training. The experimental rats showed better retention than the controls as they stayed longer in the lit side. Ensemble unit activities were recorded in the amygdala nuclei from the indwelling wire bundles during the acclimation and test sessions. The data collected from well‐isolated amygdala units showed that neuronal discharge habituated from the first to the third acclimation session. In the test session, the experimental group, but not the control group, showed elevated firing rates in the CeA or BLC neurons located on either side of the brain. These findings provide the first piece of evidence showing that learning of an inhibitory avoidance task leads to an increase in amygdala neuronal discharges during a retention test.
Activation of group II mGlu receptors blocks the enhanced drug taking induced by previous exposure to amphetamine
Authors: Kim Jeong‐Hoon , Austin Jennifer D. , Tanabe Lauren , Creekmore Elizabeth , Vezina Paul 
Published: January 2005

AbstractRepeated exposure to amphetamine (AMPH) leads to the development of behavioural sensitization that can be demonstrated in rats as enhanced locomotor responding to and self‐administration of the drug. Glutamate systems are known to participate in the induction and expression of sensitization by psychostimulants. Group II metabotropic glutamate receptors (mGluRs), because they negatively regulate both vesicular and nonvesicular glutamate release, are thus well positioned to gate its expression. Here we report that the expression of locomotor sensitization by AMPH is completely prevented by a systemic injection of the selective group II mGluR agonist LY379268 at a dose that produced no effects when administered alone. The activation of group II mGluRs in AMPH‐sensitized rats also reduced the enhanced overflow of both dopamine and glutamate normally observed in the nucleus accumbens, a brain region critical for the generation of locomotor and drug self‐administration behaviours. To directly determine the effect of group II mGluR activation on enhanced drug self‐administration, AMPH‐sensitized rats were allowed to self‐administer a mixture of LY379268 and AMPH. These rats continued to self‐administer but did not exhibit the enhanced work output and drug intake observed in AMPH‐sensitized rats self‐administering AMPH alone. Thus, activating group II mGluRs prevents the expression of different manifestations of AMPH sensitization including enhanced self‐administration of the drug. These receptors may represent a potentially important target for therapeutic intervention directed at drugs of abuse.
Caspase‐independent retinal ganglion cell death after target ablation in the neonatal rat
Authors: Spalding Kirsty L. , Dharmarajan Arun M. , Harvey Alan R. 
Published: January 2005

AbstractIn neonatal rats, superior colliculus (SC) ablation results in a massive and rapid increase in retinal ganglion cell (RGC) death that peaks about 24 h post‐lesion (PL). Naturally occurring cell death during normal development, and RGC death after axonal injury in neonatal and adult rats, has primarily been ascribed to apoptosis. Given that normal developmental cell death is reported to involve caspase 3 activation, and blocking caspase activity in adults reduces axotomy‐induced death, we examined whether blocking caspases in vivo reduces RGC death after neonatal SC lesions. Neither general nor specific caspase inhibitors increased neonatal RGC survival 6 and 24 h PL. These inhibitors were, however, effective in blocking caspases in another well‐defined in vitro apoptosis model, the corpus luteum. Caspase 3 protein and mRNA levels in retinas from normal and SC‐lesioned neonatal rats were assessed 3, 6 and 24 h after SC removal using immunohistochemistry, western and northern blots and quantitative real‐time polymerase chain reaction. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) was used to independently monitor retinal cell death. The polymerase chain reaction data showed a small but insignificant increase in caspase 3 mRNA in retinas 24 h PL. Western blot analysis did not reveal a significant shift to cleaved (activated) caspase 3 protein. There was a small increase in the number of cleaved caspase 3 immunolabelled cells in the ganglion cell layer 24 h PL but this represented only a fraction of the death revealed by TUNEL. Together, these data indicate that, unlike the situation in adults, most lesion‐induced RGC death in neonatal rats occurs independently of caspase activation.
Expression of the repressor element‐1 silencing transcription factor (REST) is influenced by insulin‐like growth factor‐I in differentiating human neuroblastoma cells
Authors: Di Toro Rosanna , Baiula Monica , Spampinato Santi 
Published: January 2005

AbstractThe repressor element‐1 (RE‐1) silencing transcription factor (REST) interacts with an RE‐1 cis element and represses the transcription of neuron‐specific genes in neuronal progenitors but is down‐regulated in post‐mitotic neurons. We report that REST expression is modified, in a time‐dependent manner, in SH‐SY5Y neuroblastoma cells exposed to insulin‐like growth factor I (IGF‐I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF‐I for 2 days and then declines in 5‐day‐treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF‐I, we employed an antisense oligonucleotide (AS‐ODN) complementary to REST mRNA. In AS‐ODN‐treated cells, the effects elicited by IGF‐I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and βIII‐tubulin gene promoters contain an RE‐1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF‐I for 5 days and further elevated by AS‐ODN treatment. A parallel increase of growth cone‐associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF‐I and could contribute to down‐regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.
Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6‐hydroxydopamine lesioned rat without sensitizing motor behaviours
Authors: Lane E. L. , Cheetham S. C. , Jenner P. 
Published: January 2005

AbstractBTS 74 398 (1‐[1‐(3,4‐dichlorophenyl)cyclobutyl]−2‐(3‐diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP‐treated (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6‐hydroxydopamine (6‐OHDA)‐lesioned rats for the production of abnormal motor behaviours and the induction of striatal ΔFosB were determined in comparison with l‐3,4‐dihydroxyphenylalanine methyl ester (l‐dopa). Acute administration of BTS 74 398 induced a dose‐dependent ipsilateral circling response in unilaterally 6‐OHDA‐lesioned rats whereas l‐dopa produced dose‐dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, l‐dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both l‐dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In l‐dopa‐treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6‐OHDA‐lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal ΔFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by l‐dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.
Differential progression of proprioceptive and visual information processing deficits in Parkinson's disease
Authors: Keijsers N. L. W. , Admiraal M. A. , Cools A. R. , Bloem B. R. , Gielen C. C. A. M. 
Published: January 2005

AbstractIndirect evidence suggests that patients with Parkinson's disease (PD) have deficits not only in motor performance, but also in the processing of sensory information. We investigated the role of sensory information processing in PD patients with a broad range of disease severities and in a group of age‐matched controls. Subjects were tested in two conditions: pointing to a remembered visual target in complete darkness (DARK) and in the presence of an illuminated frame with a light attached to the index finger (FRAME). Differences in pointing errors in these two conditions reflect the effect of visual feedback on pointing. PD patients showed significantly larger constant and variable errors than controls in the DARK and FRAME condition. The difference of the variable error in the FRAME and DARK condition decreased as a function of the severity of PD. This indicates that any deficits in the processing of proprioceptive information occur already at very mild symptoms of PD, and that deficits in the use of visual feedback develop progressively in later stages of the disease. These results provide a tool for early diagnosis of PD and shed new light on the functional role of the brain structures that are affected in PD.
Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor‐mediated inhibition
Authors: Hentschke Harald , Schwarz Cornelius , Antkowiak Bernd 
Published: January 2005

AbstractGeneral anaesthetics cause sedation, amnesia and hypnosis. Although these clinically desired actions are indicative of an impairment of neocortical information processing, it is widely held that they are to a large part mediated by subcortical neural networks. Anaesthetic action on brain stem, basal forebrain and thalamus, all of which are known to modulate cortical excitability, would thus ultimately converge on neocortex, perturbing and reducing action potential activity therein. However, as neocortex harbours molecular targets of anaesthetics in high densities, notably GABAA receptors, neocortex itself should be very sensitive to anaesthetics. Here, we performed experiments to reveal the extent to which neocortex proper is a relevant target of the low concentrations of volatile anaesthetics causing sedation and hypnosis. We compared the effects of isoflurane, enflurane and halothane on spontaneous action potential activity of rat neocortical neurons in vivo and in isolated cortical networks in vitro, i.e. in the presence and absence of subcortical arousal systems. We observed that the anaesthetics decreased spontaneous firing of neurons via intracortical mechanisms; concentrations inducing hypnosis in humans reduced discharge rates both in vivo and in vitro to the same extent, approximately 50%. This decrease in neuronal activity was paralleled by a significant enhancement of neocortical GABAA receptor‐mediated inhibition. These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABAA receptors, mediate the sedative and hypnotic properties of volatile anaesthetics.
Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory
Authors: Radyushkin Konstantin , Anokhin Konstantin , Meyer Barbara I. , Jiang Qiuhong , Alvarez‐Bolado Gonzalo , Gruss Peter 
Published: January 2005

AbstractMammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal‐dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.
Dynamic reorganization of the astrocyte actin cytoskeleton elicited by cAMP and PACAP: a role for phosphatidylInositol 3‐kinase inhibition
Authors: Perez Virgili , Bouschet Tristan , Fernandez Céline , Bockaert Joël , Journot Laurent 
Published: January 2005

AbstractCyclic AMP (cAMP)‐raising agents induce astrocytes grown in vitro to adopt a stellate morphology resembling their in vivo appearance, through the depolymerization of actomyosin stress fibres. The signalling pathways responsible for cAMP‐induced astrocyte stellation have thus far remained largely elusive. We showed in this study that the neurotrophic peptide PACAP (pituitary adenylate cyclase‐activating polypeptide) mimicked the effect of forskolin, a direct activator of adenylate cyclase, on the actin cytoskeleton of primary rat astrocytes. The depolymerization of stress fibres induced by PACAP or forskolin was prevented by the expression of a constitutively active mutant of RhoA, but not by a protein kinase A (PKA) blocker, indicating that cAMP‐raising agents act upstream of RhoA, in a PKA‐independent manner. In addition, PACAP and forskolin inhibited basal Akt phosphorylation, and basal and epidermal growth factor (EGF)‐stimulated phosphatidylinositol 3‐kinase (PI 3‐K) activities. Incubation with a PI 3‐K blocker resulted in the depolymerization of stress fibres. This effect was blocked by the expression of a constitutively active mutant of RhoA, indicating that PI 3‐K inhibition acted upstream of RhoA. Together, these data demonstrate for the first time that depolymerization of stress fibres, and the resulting astrocyte stellation, induced by stimulation of cAMP production involves the inhibition of the PI 3‐K–RhoA pathway.