bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimum Taxation of Each Year's Income
Authors: GAUBE THOMAS 
Published: February 2007

AbstractIn this paper, a two‐type, two‐period model of optimum income taxation is investigated. I assume full commitment and that current income determines the agents' tax burden in each period. It is shown that such a tax system does not allow one to implement the optimal long‐term tax contract and that it implies positive marginal tax rates at the upper end of the income distribution.
Unemployment Insurance under Moral Hazard and Limited Commitment: Public versus Private Provision
Authors: THOMAS JONATHAN P. , WORRALL TIM 
Published: February 2007

AbstractThis paper analyzes a model of private unemployment insurance under limited commitment and a model of public unemployment insurance subject to moral hazard in an economy with a continuum of agents and an infinite time horizon. The dynamic and steady‐state properties of the optimum private unemployment insurance scheme are established. The interaction between public and private unemployment insurance schemes is examined. Examples are constructed to show that for some parameter values increased public insurance can reduce welfare by crowding out private insurance more than one‐to‐one and that for other parameter values a mix of both public and private insurance can be welfare maximizing.
Evidence for Association of Polymorphisms inCYP2J2and Susceptibility to Essential Hypertension
Authors: Wu Sheng‐Nan , Zhang Yi , Gardner Charles O. , Chen Qi , Li Yan , Wang Gu‐Liang , Gao Ping‐Jin , Zhu Ding‐Liang 
Published: February 2007

SummaryObjectiveEvidence from animal models and human studies suggests that CYP2J2 plays a mechanistic role in the development of hypertension. The present study aims to investigate the potential genetic contribution of theCYP2J2gene to the etiology of essential hypertension (EH) and individual blood pressure.MethodsWe selected eight polymorphisms in/or around theCYP2J2gene and performed a case‐control association study involving 841 Han Chinese subjects, including 415 unrelated hypertensives and 426 age‐, gender‐ and area‐matched normotensives.ResultsThree functionally identified variants (CYP2J2 *2, *7 andCYP2J2 *8) and SNP rs11572182 represented rare polymorphisms in Han Chinese. However, the difference in rs1155002 genotype distribution between hypertensive and healthy subjects was close to significance (P = 0.06) in the whole sample. Interestingly, significant evidence for an association with rs1155002 was found in females when stratified by gender. In females, theTThomozygote of rs1155002 seems to be a risk factor for hypertension (p = 0.014). In addition, ANOVA analysis suggestedTTcarriers had significantly higher systolic blood pressure (p = 0.016). The genotype frequencies for rs10493270, rs1180273 and rs1324491 revealed no statistically significant differences. Likewise, four‐marker haplotype frequencies showed no significant differences between cases and controls.ConclusionOur data provide strong evidence that theCYP2J2gene is a susceptibility factor for essential hypertension, especially in females, and influences individual systolic blood pressure in the Chinese Han population.
Serotonin and neuronal growth factors – a convergence of signaling pathways
Authors: Cowen Daniel S. 
Published: February 2007

AbstractMonoamines, including serotonin (5‐HT), have traditionally been associated with short‐term signaling pathways in neurons, such as the modulation of cAMP and Ca2+levels. In contrast, neuronal growth factors, such as neurotrophins, have been traditionally associated with signaling pathways, such as those for activation of extracellular‐regulated kinase (ERK) and Akt (protein kinase B), which are known to induce long‐term protective changes. It has therefore been unclear how antidepressants that increase serotonin (5‐HT), induce such changes as hippocampal neuroprotection and neurogenesis. It has been hypothesized, that the actions of 5‐HT may be mediated indirectly through increased synthesis of peptide growth factors. However, there is increasing evidence that some subtypes of 5‐HT receptors can directly couple to activation of the ERK and Akt pathways. Such coupling suggests a more direct potential role for 5‐HT in mediating the long‐term actions induced by antidepressants.
CB1 receptors diminish both Ca2+ influx and glutamate release through two different mechanisms active in distinct populations of cerebrocortical nerve terminals
Authors: Godino María del Carmen , Torres Magdalena , Sánchez‐Prieto José 
Published: February 2007

AbstractWe have investigated the mechanisms by which activation of cannabinoid receptors reduces glutamate release from cerebrocortical nerve terminals. Glutamate release evoked by depolarization of nerve terminals with high KCl (30 mmol/L) involves N and P/Q type Ca2+channel activation. However, this release of glutamate is independent of Na+ or K+ channel activation as it was unaffected by blockers of these channels (tetrodotoxin ‐TTX‐ or tetraethylammonium TEA). Under these conditions in which only Ca2+ channels contribute to pre‐synaptic activity, the activation of cannabinoid receptors with WIN55,212‐2 moderately reduced glutamate release (26.4 ± 1.2%) by a mechanism that in this in vitro model is resistant to TTX and consistent with the inhibition of Ca2+ channels. However, when nerve terminals are stimulated with low KCl concentrations (5–10 mmol/L) glutamate release is affected by both Ca2+ antagonists and also by TTX and TEA, indicating the participation of Na+ and K+ channel firing in addition to Ca2+ channel activation. Interestingly, stimulation of nerve terminals with low KCl concentrations uncovered a mechanism that further inhibited glutamate release (81.78 ± 4.9%) and that was fully reversed by TEA. This additional mechanism is TTX‐sensitive and consistent with the activation of K+ channels. Furthermore, Ca2+ imaging of single boutons demonstrated that the two pre‐synaptic mechanisms by which cannabinoid receptors reduce glutamate release operate in distinct populations of nerve terminals.
Possible involvement of protease‐activated receptor‐1 in the regulation of morphine‐induced dopamine release and hyperlocomotion by the tissue plasminogen activator‐plasmin system
Authors: Ito Mina , Nagai Taku , Mizoguchi Hiroyuki , Fukakusa Ayumi , Nakanishi Yutaka , Kamei Hiroyuki , Nabeshima Toshitaka , Takuma Kazuhiro , Yamada Kiyofumi 
Published: February 2007

AbstractWe have previously demonstrated that tissue plasminogen activator (tPA)‐plasmin system participates in the rewarding effect of morphine, by regulating dopamine release in the nucleus accumbens (NAc). However, it is unclear how plasmin increases the morphine‐induced release of dopamine and hyperlocomotion. In the present study we investigated whether protease activated receptor‐1 (PAR‐1) is involved in the regulation of acute morphine‐induced dopamine release by the tPA‐plasmin system. Morphine significantly but transiently increased extracellular tPA activity in the NAc, which was completely blocked by naloxone. Microinjection of a PAR‐1 antagonist, (tyr−1)‐thrombin receptor activating peptide 7, into the NAc significantly reduced morphine‐induced dopamine release in the NAc and hyperlocomotion although the treatment had no effect on basal dopamine release and spontaneous locomotor activity. Furthermore, the PAR‐1 antagonist blocked the ameliorating effect of plasmin on the defect of morphine‐induced dopamine release in the NAc of tPA‐deficient mice. In contrast, intracerebroventricular injection of the PAR‐1 antagonist had no effect on the antinociceptive effects of morphine in mice. These results suggest that PAR‐1 is a target for the tPA‐plasmin system in the regulation of acute morphine‐induced dopamine release in the NAc.
Mechanisms involved in the formation of dopamine‐induced intracellular bodies within striatal neurons
Authors: Lazzeri Gloria , Lenzi Paola , Busceti Carla L. , Ferrucci Michela , Falleni Alessandra , Bruno Valeria , Paparelli Antonio , Fornai Francesco 
Published: February 2007

AbstractRecent studies demonstrated that methamphetamine (METH) produces intracellular bodies which are reminiscent of those occurring during degenerative disorders. In vivo studies demonstrate the occurrence of these morphological alterations both in the dopamine (DA) neurons of the substantia nigra and striatal cells. These consist of neuronal bodies staining for a variety of antigens belonging to the ubiquitin–proteasome pathway. The formation of these intracellular bodies both in the substantia nigra and PC12 cells depends on the presence of endogenous DA. In the present study, we analyze the mechanisms which lead to METH‐induced intracellular bodies within non‐dopaminergic striatal neurons. We found that METH is no longer able to produce inclusions in vivo, in striatal cells, when striatal DA is lost. Similarly, in vitro, in primary striatal cell cultures which do not possess DA, METH administration does not produce inclusions. On the other hand, administration of DA to striatal cell cultures produces neuronal inclusions and cell death, which are both related to the inhibition of the ubiquitin–proteasome system and activation of specific‐DA receptors. In line with this, we produced subcellular alterations by administering dopamine agonists.
Dopaminergic neurons intrinsic to the striatum
Authors: Huot Philippe , Parent André 
Published: February 2007

AbstractThe striatum – the largest integrative component of the basal ganglia – harbors a population of neurons that express the enzyme tyrosine hydroxylase (TH), a faithful marker of dopaminergic neurons. The dopaminergic nature of these neurons is further supported by the fact that they express the dopamine (DA) transporter (DAT) and the nuclear orphan receptor Nurr1, a transcription factor essential for the expression of the DA phenotype by midbrain neurons. The vast majority of these neurons are morphologically similar to the medium‐sized aspiny striatal interneurons and they all express the enzyme GAD65. The striatal TH‐positive neurons increase markedly in number in animal models of Parkinson’s disease (PD), where striatal DA concentrations are low, but this increase is abolished by L‐dopa treatment. Hence, local DA concentrations appear to regulate the numerical density of this ectopic neuronal population, a phenomenon that is more likely the result of a shift in the phenotype of preexistent striatal interneurons rather than the recruitment of newborn neurons that will develop a DA phenotype. Altogether, these findings suggest that striatal TH‐positive neurons act as a local source of DA and, as such, are part of a compensatory mechanism that could be artificially enhanced to alleviate or delay PD symptoms.
Melanocortin receptor 4 is induced in nerve‐injured motor and sensory neurons of mouse
Authors: Tanabe Katsuhisa , Gamo Kazushige , Aoki Shunsuke , Wada Keiji , Kiyama Hiroshi 
Published: February 2007

AbstractWe previously identified melanocortin receptor 4 (MC4R) in a search for genes associated with hypoglossal nerve regeneration. As melanocortins promote nerve regeneration after axonal injury, we investigated whether MC4R functions as a key receptor for peripheral nerve regeneration. In situ hybridization revealed that MC4R mRNA is induced in mouse hypoglossal motor neurons after axonal injury, whereas mRNAs for MC1R, MC2R, MC3R, and MC5R are not expressed either before or after nerve injury. This result was confirmed by RT‐PCR. The level of MC4R mRNA expression increased significantly from day 3 after axotomy, reached a peak on day 5, and decreased to the control level on day 14. Similar induction of MC4R was observed in axotomized mouse dorsal root ganglia (DRGs). MC4R mRNA expression was induced exclusively among the MCR family in the L4‐6 DRG after sciatic nerve injury. We further examined whether alpha‐melanocortin stimulating hormone (alpha‐MSH) promotes neurite elongation via MC4R. In mouse DRG neuron culture, alpha‐MSH significantly promoted neurite outgrowth at a concentration of 10−8 mol/L. This neurite‐elongation effect was entirely inhibited by the addition of a selective MC4R blocker, JKC‐363. Therefore, it is concluded that alpha‐MSH could stimulate neurite elongation via MC4R in DRG neurons. The present results suggest that induction of MC4R is crucial for motor and sensory neurons to regenerate after axonal injury.
Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius
Authors: Martin Caroline , Dubouchaud Hervé , Mosoni Laurent , Chardigny Jean‐Michel , Oudot Alexandra , Fontaine Eric , Vergely Catherine , Keriel Christiane , Rochette Luc , Leverve Xavier , Demaison Luc 
Published: February 2007

SummaryAging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substrate, were evaluated at different matrix calcium concentrations. Pyruvate dehydrogenase and respiratory complex activities as well as their contents measured by Western blotting analysis were determined. Furthermore, the fatty acid profile of mitochondrial phospholipids was also measured. At physiological calcium concentration, state III respiration rate was lowered by aging in pyruvate conditions (−22%), but not with glutamate. The reduction of pyruvate oxidation resulted from a calcium‐dependent inactivation of the pyruvate dehydrogenase system and could provide for the well‐known proteolysis encountered during sarcopenia. Matrix calcium loading and aging increased ROS production. They also reduced the oxidative phosphorylation. This was associated with lower calcium retention capacities, suggesting that sarcopenic fibers are more prone to programmed cell death. Aging was also associated with a reduced mitochondrial superoxide dismutase activity, which does not intervene in toxic ROS overproduction but could explain the lower calcium retention capacities. Despite a lower content, cytochrome c oxidase displayed an increased activity associated with an increased n−6/n−3 polyunsaturated fatty acid ratio of mitochondrial phospholipids. In conclusion, we propose that mitochondria obtained from aged muscle fibers display several functional abnormalities explaining the increased proteolysis, ROS overproduction and vulnerability to apoptosis exhibited by sarcopenic muscle. These changes appear to be related to modifications of the fatty acid profile of mitochondrial lipids.
Eunuchs in Historical Perspective
Authors: Ringrose Kathryn M. 
Published: February 2007

AbstractThis article examines the meaning of the terms ‘eunuch’ and ‘castration’ and situates these terms in an historical context. It divides castrated eunuchs into two groups, those who castrate themselves voluntarily for religious reasons and those who are castrated by others either as a punishment or in order to create an individual who is significantly different from a whole man. This second group is further divided based on the tasks for which the eunuch is prepared. These may be sexual or lie in the area of personal service. Three major court cultures are compared, Islam, Byzantium, and China, and several religious cults that encourage self‐castration are also discussed.
Altered Distribution of KCC2 in Cortical Dysplasia in Patients with Intractable Epilepsy
Authors: Munakata Mitsutoshi , Watanabe Mika , Otsuki Taisuke , Nakama Hideyuki , Arima Kunimasa , Itoh Masayuki , Nabekura Junichi , Iinuma Kazuie , Tsuchiya Shigeru 
Published: February 2007

Summary:  Purpose: To examine the distribution of KCC2, a neuron‐specific K+–Cl− cotransporter, in human cortical dysplasia (CD). Methods: The immunohistochemical expression of KCC2 was investigated in 18 CD specimens obtained during epilepsy surgery. The histopathologic diagnoses were focal CD (FCD) type I (eight cases), FCD type II (six cases), and hemimegalencephaly (HME; four cases). Tissue sections were immunostained for KCC2 and compared with control sections. Results: In the mature nondysplastic cortex, all the layers showed diffuse neuropil staining for KCC2. The somata were stained much less, although subcortical ectopic neurons displayed dense staining in the cytosol (intrasomatic staining). In FCD type I, the cortex showed neuropil staining for KCC2 with less‐stained somata. Aberrant giant pyramidal neurons were also less stained at the soma, whereas immature neurons showed intrasomatic staining. Increased numbers of ectopic neurons with intrasomatic staining were noted in the subcortical white matter. In FCD type II, dysmorphic neurons displayed dense intrasomatic staining with reduced staining of the neighboring neuropils. Balloon cells did not stain for KCC2. Dysmorphic neurons in HME also showed intrasomatic staining. Conclusions: Neurons in CD tissues expressed KCC2. However, the subcellular distribution of KCC2 was altered, which might have affected the ionic homeostasis of Cl− and K+ involved in epileptic activity within CD tissues.
Levetiracetam and Felbamate Interact Both Pharmacodynamically and Pharmacokinetically: An Isobolographic Analysis in the Mouse Maximal Electroshock Model
Authors: Luszczki Jarogniew J. , Andres‐Mach Marta M. , Ratnaraj Neville , Patsalos Philip N. , Czuczwar Stanislaw J. 
Published: February 2007

Summary: Purpose:Polytherapy with two or more antiepileptic drugs (AEDs) is generally required for approximately 30% of patients with epilepsy, who do not respond satisfactorily to monotherapy. The potential usefulness of AED combinations, producing synergistic anticonvulsant efficacy and minimal adverse effects, is therefore of significant importance. The present study sought to ascertain the potential usefulness of levetiracetam (LEV) and felbamate (FBM) in combination in the mouse maximal electroshock (MES)‐induced seizure model. Methods:The anticonvulsant interaction profile between LEV and FBM in the mouse MES‐induced seizure model was determined using type II isobolographic analysis. Acute adverse effects (motor performance) were ascertained by use of the chimney test. LEV and FBM brain concentrations were measured by HPLC in order to determine any pharmacokinetic contribution to the observed antiseizure effect.Results:LEV in combination with FBM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, were supraadditive, whereas at the fixed ratio of 1:4, additivity was observed in the mouse MES model. Furthermore, none of the investigated combinations altered motor performance in the chimney test. Brain FBM concentrations were unaffected by concomitant LEV administration. In contrast, FBM significantly increased LEV brain concentrations.Conclusions:LEV in combination with FBM was associated with pharmacodynamic supraadditivity in the MES test. However, this anticonvulsant supraadditivity was associated with a concurrent increase in brain LEV concentrations indicating a pharmacokinetic contribution to the observed pharmacodynamic interaction between LEV and FBM.
Mood, Personality, and Health‐related Quality of Life in Epileptic and Psychogenic Seizure Disorders
Authors: Testa S. Marc , Schefft Bruce K. , Szaflarski Jerzy P. , Yeh Hwa‐Shain , Privitera Michael D. 
Published: February 2007

Summary:  Purpose: Patients with psychogenic nonepileptic seizures (PNES) rate their health‐related quality of life (HRQOL) more poorly than those with epileptic seizures (ES). This has been explained in part by mood state. We sought to investigate whether HRQOL differences between diagnostic groups (PNES vs. ES) can be explained by additional, perhaps chronic, aspects of mood and personality. An understanding of these relationships may inform treatment designed to improve HRQOL in ES or PNES. Methods: One‐hundred fourteen individuals (69 ES and 45 PNES) completed the quality of life in Epilepsy‐89. The profile of mood states (POMS) and the Minnesota Multiphasic Personality Inventory‐2 (MMPI‐2) were employed to measure current and chronic mood symptoms, respectively. Multiple regression analyses determined the contribution of chronic mood symptoms to HRQOL beyond the variance accounted for by current mood state and seizure diagnosis. Results: Similar to previous reports, individuals with PNES reported poorer HRQOL than those with ES. Current mood state was strongly related to HRQOL and appeared to moderate the relationship between seizure diagnosis and HRQOL. However, when more chronic psychological symptoms, such as somatization and emotional distress, were included in a model, the moderating role of mood state was not significant. Conclusion: Analyzed independently, mood state is related to HRQOL, but when chronic indicators of psychological symptoms are included in a model mood is related to HRQOL, but, the moderating effect of mood is no longer significant. Treatments designed to improve HRQOL among individuals with intractable seizures should also address chronic psychological distress and symptoms associated with high levels of somatization.
Ebselen Prevents Chronic Alcohol‐Induced Rat Hippocampal Stress and Functional Impairment
Authors: Johnsen‐Soriano Siv , Bosch‐Morell Francisco , Miranda María , Asensio Samuel , Barcia Jorge M. , Romá Joaquín , Monfort Pilar , Felipo Vicente , Romero Francisco J. 
Published: February 2007

Background: Most of the previously published data suggest a role for oxidative or nitrosative stress in ethanol‐induced nervous system damage. Moreover, ethanol is able to impair learning abilities in adult mammalian brain, a process suggested to be directly related to hippocampal neurogenesis. Ebselen, a synthetic compound with antioxidant properties, is able to prevent ethanol‐induced impairment of neurogenesis in adult rats. The aim of the present work was to further demonstrate the ability of ebselen to prevent biochemical alterations, and preserve long‐term potentiation (LTP) and learning abilities, in the hippocampus of chronic alcoholic adult rats.Methods: Biochemical markers of oxidative stress (glutathione and malondialdehyde) were assayed in hippocampi of control rats and animals fed a liquid alcoholic diet (Lieber‐De Carli) supplemented or not with ebselen. Long‐term potentiation and hippocampal‐dependent tests were studied in all animal groups.Results: The hippocampal concentrations of glutathione and malondialdehyde were decreased and increased, respectively, in alcohol‐treated animals, and did not differ from those of the control and the alcohol+ebselen groups. Long‐term potentiation in hippocampal slices from ethanol‐treated animals was prevented, when compared with controls, and occurred with a similar profile in control animals and in the alcohol+ebselen groups. Learning ability was tested with the Morris water maze test. Escape latencies were higher in ethanol‐treated rats than in control animals or the ones treated with ethanol+ebselen.Conclusions: The results herein strongly suggest that oxidative mechanisms may underlie the hippocampal effects of ethanol in adult rats, in view of the protective effect of ebselen.