bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches to Barrett's oesophagus treatment—the role of proton pump inhibitors and other interventions
Authors: Jankowski J. , Sharma P. 
Published: January 2004

SummaryDespite implementation of screening and surveillance strategies, a significantly large number of patients with Barrett's oesophagus remain undiagnosed. In those who are identified, the management options include acid reduction therapies with proton pump inhibitors or anti‐reflux surgery. Endoscopic ablative therapies have also been attempted. In addition to having inherent procedure‐related risks with ablative therapies, these alternatives may be limited by high rates of failure, need for continued acid suppressive therapy, metaplasia persistence under otherwise normal appearing tissue, need for procedural expertise, and continued risk for adenocarcinoma development. Therefore, a widely applicable chemoprevention strategy that cost‐effectively reduces the rate of progression from oesophagitis to adenocarcinoma in high‐risk patients and perhaps those at lower rates of risk is highly desirable. The AspECT trial currently underway is seeking to determine the effects of high‐ and low‐dose proton pump inhibitor therapy with and without low‐dose aspirin as Barrett's oesophagus chemoprevention.
Appropriate use of proton pump inhibitors with traditional nonsteroidal anti‐inflammatory drugs and COX‐2 selective inhibitors
Authors: Kimmey M. B. , Lanas A. 
Published: January 2004

SummaryNonsteroidal anti‐inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications in the USA, annually accounting for over 100 million prescriptions. Gastrointestinal complications associated with NSAIDs are common, and result in a substantial amount of morbidity and mortality, despite the advent of the cyclooxygenase‐2 selective inhibitors or ‘coxibs’. Emerging clinical and economic data suggest that, depending on the baseline risk to patients, the use of a traditional NSAID alone or in combination with a proton pump inhibitor are effective and well tolerated alternatives to coxibs. The optimal therapeutic strategy for NSAID selection and use of co‐therapy should be guided by a consideration of each patient's risk of having an adverse event arising from the NSAID. Patients at the highest risk for gastrointestinal complications with traditional NSAIDs are those with a history of an ulcer or ulcer complication, those of advanced age (greater than 65 years), and those receiving concurrent aspirin, anticoagulants or corticosteroid therapy. Proton pump inhibitor co‐therapy is highly effective in reducing NSAID‐related dyspeptic symptoms, healing the injured mucosa even in those who continue to ingest NSAIDs, and preventing gastrointestinal complications. In addition to their selective use in patients who experience NSAID‐related dyspepsia and other symptoms, proton pump inhibitor co‐therapy should be considered in those at high risk (with coxib or traditional NSAID therapy) and is necessary in high‐risk patients receiving aspirin, with or without NSAID therapy.
Management of peptic ulcer bleeding—the roles of proton pump inhibitors and Helicobacter pylori eradication
Authors: Holtmann G. , Howden C. W. 
Published: January 2004

SummaryPeptic ulcer bleeding is associated with substantial morbidity and mortality. The goals of management are to control any active bleeding and prevent re‐bleeding and then to heal the ulcer and prevent its recurrence. Initial management strategies are guided by the patient's clinical condition and endoscopic findings. Thus, treatment may consist of endoscopic and medical therapy and, sometimes, surgery. Control of acid secretion, preferably with proton pump inhibitor therapy in the initial management continues to evolve; it has also been used as both an adjunct to endoscopic therapy and as primary treatment. These agents have been found to be effective in some trials in the reduction of re‐bleeding and the need for surgery, although there is no clear benefit demonstrated for overall mortality. Proton pump inhibitors have been administered either intravenously or orally in different trials. The long‐term management of patients with peptic ulcer, after the initial bleeding episode, should include patient stratification based upon risk factors for ulcer recurrence (i.e. Helicobacter pylori infection, use of aspirin or nonsteroidal anti‐inflammatory drugs). Elimination or modification of these risk factors reduces the risk of ulcer recurrence and, hence, of recurrent ulcer bleeding.
Balancing the ideal versus the practical—considerations of colorectal cancer prevention and screening
Authors: Lieberman D. A. , Atkin W. 
Published: January 2004

SummaryColorectal cancer is responsible for over 500 000 deaths annually world‐wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average‐ or high‐risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.
Disruption of self‐organized actions in monkeys with progressive MPTP‐induced parkinsonism. I. Effects of task complexity
Authors: Pessiglione Mathias , Guehl Dominique , Hirsch Etienne C. , Féger Jean , Tremblay Léon 
Published: January 2004

AbstractParkinson's disease (PD) is characterized by motor symptoms, usually accompanied by cognitive deficits. The question addressed in this study is whether complexity of routine actions can exacerbate parkinsonian disorders that are often considered to be motor symptoms. To examine this question, we trained four vervet monkeys (Cercopithecus aethiops) to perform three multiple‐choice retrieval tasks. In order of ascending complexity, rewards were freely available (task 1), covered with transparent sliding plaques (task 2), and covered with opaque sliding plaques cued by symbols (task 3). Thus, from task 1 to task 2 we added a motor difficulty – the recall of context‐adapted movement; and from task 2 to task 3 we added a cognitive difficulty: the recall of symbol–reward associations. The more complex the task, the longer it took to learn, but after extensive training the performance was stable in all tasks, with similar retrieval durations. The monkeys then received systemic 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) injections (0.3–0.4 mg/kg) every 4–7 days, until the first motor symptoms appeared. In the course of MPTP intoxication, the behavioural performance declined while the motor symptoms were absent or mild – the retrieval duration increased, and non‐initiated choices and hesitations between choices became frequent. Interestingly, this decline was in proportion to task complexity, and was particularly pronounced with the cognitive difficulty. Furthermore, freezing appeared only with the cognitive difficulty. We therefore suggest that everyday cognitive difficulties may exacerbate hypokinesia (lack of initiation, abnormal slowness) and executive disorders (hesitations, freezing) in the early stages of human PD.
Modulation of feeding behaviour by blocking purinergic receptors in the rat nucleus accumbens: a combined microdialysis, electroencephalographic and behavioural study
Authors: Kittner H. , Krügel U. , Hoffmann E. , Illes P. 
Published: January 2004

AbstractThe nonspecific P2 receptor antagonist pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), the nonspecific P1 receptor antagonist 8‐(p‐sulphophenyl)‐theophylline (8‐SPT) and the combination of both were applied by retrograde microdialysis into the nucleus accumbens (NAc) before and during feeding of 18‐h food‐deprived rats. In addition to the registration of behavioural parameters, such as the amount and duration of food intake, the feeding‐induced changes in dopamine (DA) concentration and the concomitant changes of neuronal activity in the NAc and the ventral tegmental area (VTA) were simultaneously determined. The perfusion with PPADS (20 µm) diminished the amount of food intake and the duration of feeding. Furthermore, the P2 receptor antagonist blocked the feeding‐induced DA release and prevented the feeding‐elicited changes of the electroencephalography (EEG) power distribution which was characterised by an increase in the power of the 8.0–13.0‐Hz frequency band in the NAc and the VTA. The effects of PPADS could be completely prevented by the concomitantly perfused adenosine receptor antagonist 8‐SPT (100 µm). When given alone, 8‐SPT increased the amount of food ingested, the duration of feeding and the EEG power of the higher frequency range, particularly between 19.0 and 30.0 Hz, in both the NAc and the VTA. The feeding‐elicited DA release was supplemented to the enhanced DA level caused by the perfusion with 8‐SPT in an additive manner. The P2 and P1 receptor antagonists interact antagonistically in the modulation of feeding behaviour and the feeding‐induced changes of EEG activity suggesting that both endogenous extracellular ATP and adenosine are involved in the regulation of the feeding‐associated mesolimbic neuronal activity in a functionally antagonistic manner.
The antiepileptic drug levetiracetam selectively modifies kindling‐induced alterations in gene expression in the temporal lobe of rats
Authors: Gu Jessie , Lynch Berkley A. , Anderson Dina , Klitgaard Henrik , Lu Sun , Elashoff Michael , Ebert Ulrich , Potschka Heidrun , Löscher Wolfgang 
Published: January 2004

AbstractGene expression profiling by microarrays is a powerful tool for identification of genes that may encode key proteins involved in molecular mechanisms underlying epileptogenesis. Using the Affymetrix oligonucleotide microarray, we have surveyed the expression levels of more than 26,000 genes and expressed sequence tags (ESTs) in the amygdala‐kindling model of temporal lobe epilepsy. Furthermore, the effect of the antiepileptic drug levetiracetam (LEV) on kindling‐induced alterations of gene expression was studied. Treatment of rats with LEV during kindling acquisition significantly suppressed kindling development. For gene expression profiling, six groups of rats were included in the present study: (i) and (ii) sham‐operated rats treated with saline or LEV; (iii) and (iv) electrode‐implanted but non‐kindled rats treated with saline or LEV; (v) and (vi) kindled rats treated with saline or LEV. Treatment was terminated after 11 or 12 daily amygdala stimulations, when all vehicle‐treated rats had reached kindling criterion, i.e. a stage 5 seizure. Twenty‐four hours later, the ipsilateral temporal lobe was dissected for mRNA preparation. Six temporal lobe preparations from each group were analysed for differential gene expression. In control (non‐kindled) rats, LEV treatment was devoid of any significant effect on gene expression. In saline‐treated kindled rats, a large number of genes were observed to display mRNA expression alterations compared with non‐kindled rats. LEV treatment induced marked effects on gene expression from kindled rats. Previously described epilepsy‐related genes, such as neuropeptide Y (NPY), thyrotropin‐releasing hormone (TRH) and glial fibrillary acidic protein (GFAP) were confirmed to be up‐regulated by kindling and partially normalized by LEV treatment. Real‐time quantitative polymerase chain reaction confirmed NPY, TRH and GFAP expression data from chip experiments. Furthermore, a number of novel genes were identified from the gene chip experiments. A subgroup of these genes demonstrated correlation between expression changes and kindled phenotype measurements. In summary, this study identified many genes with potentially important roles in epileptogenesis and highlighted several important issues in using the gene chip technology for the study of animal models of CNS disorders.
CNTF promotes survival of retinal ganglion cells after induction of ocular hypertension in rats: the possible involvement of STAT3 pathway
Authors: Ji Jian‐Zhong , Elyaman Wassim , Yip Henry K. , Lee Vincent W. H. , Yick Leung‐Wah , Hugon Jacques , So Kwok‐Fai 
Published: January 2004

AbstractWe examined the neuroprotective effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cells (RGCs) in a rat glaucoma model with increased intraocular pressure (IOP) and studied the CNTF‐mediated activation of Janus kinase/signal transducer and activator of transcription (JAK‐STAT) pathway. Elevated IOP was induced by laser photocoagulation of the episcleral and limbal veins. The survival of RGCs was studied using Fluoro‐Gold labelled in ocular hypertensive eyes with or without CNTF intravitreal injection. Immunochemical staining and immunoblot analysis for CNTF and phosphorylated STAT3 (pSTAT3) were performed. There was a significant and progressive loss of RGCs in the retinas following the induction of elevated IOP. A single intravitreal injection of 2 µg in 2 µL CNTF significantly protected RGCs up to 4 weeks. pSTAT3 was only transiently expressed in ocular hypertensive eyes. However, in eyes treated with CNTF, pSTAT3 was observed up to 2 weeks after the induction of elevated IOP. In ocular hypertensive eyes, CNTF‐positive cells were found in the inner nuclear layer (INL), and there was a transient increase in the pSTAT3 cells in the ganglion cell layer and INL. Immunoblots showed that STAT3 was transiently phosphorylated after IOP increase, but with an injection of CNTF, pSTAT3 protein was observed up to 2 weeks after hypertensive glaucoma induction. Laser‐induced chronic ocular hypertension in rats resulted in the death of RGCs and a transient activation of STAT3 in the retina. Intravitreal injection of CNTF showed a significant protection of RGCs, and the JAK‐STAT signalling could be one of the important pathways that underlie the mechanism of CNTF neuroprotection in this rat glaucoma model.
Suppressing calcium/calmodulin‐dependent protein kinase II activity in the ventral tegmental area enhances the acute behavioural response to cocaine but attenuates the initiation of cocaine‐induced behavioural sensitization in rats
Authors: Licata Stephanie C. , Schmidt Heath D. , Pierce R. Christopher 
Published: January 2004

AbstractIn the present experiments we administered an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor antagonist (CNQX), N‐methyl‐D‐aspartate (NMDA) receptor antagonist (AP‐5), or l‐type calcium channel blocker (diltiazem) directly into the ventral tegmental area (VTA) before each of four daily systemic cocaine injections in order to assess their influence on the initiation phase of behavioural sensitization. Results indicated that pretreatment with CNQX or AP‐5 impaired the initiation of cocaine‐induced behavioural sensitization. Intra‐VTA administration of diltiazem significantly increased the behavioural activation induced by an acute cocaine injection, but impaired the development of cocaine‐induced behavioural sensitization. Because AMPA and NMDA receptors, as well as l‐type calcium channels are calcium permeable, we also investigated the role of the calcium‐activated second messenger calcium/calmodulin‐dependent protein kinase II (CaM‐KII). Similar to the results obtained with diltiazem, administration of the CaM‐KII inhibitor KN‐93 into the VTA enhanced the acute behavioural response to cocaine but prevented the augmentation of cocaine‐induced behavioural hyperactivity following repeated injections. Consistent with this finding, the behavioural hyperactivity produced by cocaine was markedly enhanced among homozygous α‐CaM‐KII knockout mice but the initiation of behavioural sensitization to cocaine was attenuated relative to wild‐type mice. Separate experiments performed in rats demonstrated an increase in total protein levels of CaM‐KII in the VTA 24 h after the last of seven daily injections of cocaine. Taken together, these results indicate that blocking l‐type calcium channels or impairing CaM‐KII activity in the VTA augments the acute behavioural hyperactivity induced by cocaine. The present findings also suggest that increased calcium influx through AMPA receptors, NMDA receptors and l‐type calcium channels on dopaminergic neurons in the VTA contributes significantly to the initiation of behavioural sensitization by amplifying calcium signalling through CaM‐KII.
Stimulus locking and feature selectivity prevail in complementary frequency ranges of V1 local field potentials
Authors: Kayser Christoph , König Peter 
Published: January 2004

AbstractThe local field potential (LFP) is a population measure of neuronal activity complementary to spike trains. Whereas the response properties of the spiking activity in the visual cortex have been characterized extensively, the responses of the LFP have not been well explored. No coherent picture exists about which frequency ranges exhibit feature tuning or show stimulus locked activity. Addressing this, we recorded LFP in the primary visual cortex of alert cats and calculated the tuning indices for orientation, spatial and temporal frequency. Furthermore, we quantified the locking of the power in different LFP frequency bands to the velocity profile of artificial and natural stimuli. We found that the LFP in alert animals is well tuned with similar specificity to orientation, spatial frequency and temporal frequency. Tuning to these features is most prominent in two frequency bands (8–23 Hz and 39–109 Hz). In two complementary frequency bands (23–39 Hz and above 109 Hz) the dynamics of the LFP power is locked tightly to the temporal structure of the stimulus. This locking is furthermore independent of the spatial structure of the stimulus. Together these four frequency bands cover the whole frequency range investigated. In contrast to previous studies, which often reported correlates of visual processing only in a limited frequency range of the LFP, the present results suggest that the entire frequency range of the LFP can be assigned a role in visual processing.
Median raphe mediates estrogenic effects to the hippocampus in female rats
Authors: Prange‐Kiel Janine , Rune Gabriele M. , Leranth Csaba 
Published: January 2004

AbstractSubcortical regions such as the medial septum–diagonal band of Broca and supramammillary area have been shown to mediate indirect oestrogenic effects on hippocampal morphology and function. Here, the role of the median raphe (MR), a serotonergic subcortical structure, is studied. To this end, 17β‐estradiol‐filled 30‐gauge cannulae were implanted into the MR of female ovariectomized rats; cholesterol‐filled cannulae served as controls. After seven days, using unbiased electron microscopic stereological calculations and semiquantitative analysis, the spine synapse density and surface density of glial fibrillary acidic protein‐positive astrocyte processes, respectively, were determined in the stratum radiatum of the CA1 region of the hippocampus. Changes in the serotonergic innervation of the hippocampal CA1 region were determined by immunohistochemistry and subsequent morphometric analysis. In the stratum radiatum of the CA1 region, local estradiol application into the MR resulted in a 47% increase in spine synapse density. Simultaneously, the density of glial fibrillary acidic protein‐positive fibers decreased by 16%. The density of serotonin (5‐HT) innervation of the strata lacunosum moleculare and radiatum of the CA1 region of the hippocampus was reduced in response to estradiol, as shown by a decrease in the length of fibers (27.6 and 48.3% decrease, respectively) and the number of large varicosities (32.5 and 38.8% decrease, respectively). These observations suggest a major role of the MR in mediating oestrogenic effects on the hippocampus and an involvement of the serotonergic system.
Turning behaviour induced by stimulation of the 5‐HT receptors in the subthalamic nucleus
Authors: Belforte J. E. , Pazo J. H. 
Published: January 2004

AbstractThe basal ganglia, which receive a rich serotonergic innervation, have been implicated in hyperkinetic and hypokinetic disorders. Moreover, a decrease in subthalamic nucleus (STN) activity has been associated with motor hyperactivity. To address the role of subthalamic serotonergic innervation in its motor function, turning behaviour was studied in rats with stimulation of the subthalamic serotonin (5‐HT) receptors by intracerebral microinjections. The intrasubthalamic administration of 5‐HT induced dose‐dependent contralateral turning behaviour, with a maximal effect at a dose of 2.5 µg in 0.2 µL. Similar results were observed with microinjections of other 5‐HT receptor agonists: quipazine (a 5‐HT2B/C/3 agonist), MK‐212 (a 5‐HT2B/C agonist) and m‐chlorophenylbiguanidine (a 5‐HT3 agonist), while microinjections of 5‐HT into the zona incerta or in the previously lesioned STN were ineffective. The effect of 5‐HT was blocked by coadministration of the antagonist mianserin. Stimulation of subthalamic 5‐HT receptors in animals bearing a lesion of the nigrostriatal pathway did not modify the motor response, which indicates that the dopamine innervation of the nucleus is not involved in this effect. Kainic acid lesion of the substantia nigra pars reticulata (SNr) suppressed the contralateral rotations elicited by stimulation of 5‐HT2B/C/3 subthalamic receptors. This suggests a role of the subthalamic–nigral pathway in the turning activity. Furthermore, the partial blockade of glutamatergic receptors in the SNr by the antagonist DNQX increased the contralateral circling elicited by stimulation of 5‐HT receptors in the STN. We concluded that the activation of the 5‐HT2B/C and 5‐HT3 subthalamic receptors elicited contralateral turning behaviour, probably via the subthalamic–nigral pathway.