bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice
Authors: Moriguchi Shigeki , Han Feng , Shioda Norifumi , Yamamoto Yui , Nakajima Takeharu , Nakagawasai Osamu , Tadano Takeshi , Yeh Jay Z. , Narahashi Toshio , Fukunaga Kohji 
Published: April 2009

AbstractAberrant behaviors related to learning and memory in olfactory bulbectomized (OBX) mice have been documented in the previous studies. We reported that the impairment of long‐term potentiation (LTP) of hippocampal CA1 regions from OBX mice was associated with down‐regulation of CaM kinase II (CaMKII) and protein kinase C (PKC) activities. We now demonstrated that the nootropic drug, nefiracetam, significantly improved spatial reference memory‐related behaviors as assessed by Y‐maze and novel object recognition task in OBX mice. Nefiracetam also restored hippocampal LTP injured in OBX mice. Nefiracetam treatment restored LTP‐induced PKCα (Ser657) and NR1 (Ser896) phosphorylation as well as increase in their basal phosphorylation in the hippocampal CA1 region of OBX mice. Likewise, nefiracetam improved LTP‐induced CaMKIIα (Thr286) autophosphorylation and GluR1 (Ser831) phosphorylation and increased their basal phosphorylation. The enhancement of PKCα (Ser657) and CaMKIIα (Thr286) autophosphorylation by nefiracetam was inhibited by treatment with (±)‐α‐Methyl‐(4‐carboxyphenyl)glycine and DL‐2‐Amino‐5‐phosphonovaleric acid, respectively. The enhancement of LTP induced by nefiracetam is inhibited by treatment with 2‐methyl‐6‐(phenylethynyl)‐pyridine, but not by treatment with LY367385, suggesting that metabotropic glutamate receptor 5 (mGluR5) but not mGluR1 is involved in the nefiracetam‐induced LTP enhancement. Taken together, nefiracetam ameliorates OBX‐induced deficits in memory‐related behaviors and impairment of LTP in the hippocampal CA1 region through activation of NMDAR and mGluR5, thereby leading to an increase in activities of CaMKIIα (Thr286) and PKCα (Ser657), respectively.
PrPc activation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin‐1 in the signal transduction pathway
Authors: Pantera Barbara , Bini Chiara , Cirri Paolo , Paoli Paolo , Camici Guido , Manao Giampaolo , Caselli Anna 
Published: April 2009

AbstractCellular prion protein (PrPc) is a ubiquitous glycoprotein, whose physiological role is poorly characterized. It has been suggested that PrPc participates in neuritogenesis, neuroprotection, copper metabolism, and signal transduction. In this study we detailed the intracellular events induced by PrPc antibody‐mediated cross‐linking in PC12 cells. We found a Fyn‐dependent activation of the Ras‐Raf pathway, which leads to a rapid and transient phosphorylation of extracellular regulated kinases. In addition, this activation cascade relies on the engagement of integrins, and involves focal adhesion kinase activation. We demonstrated the tyrosine phosphorylation of caveolin‐1 as a consequence of PrPc stimulation, and showed that phosphocaveolin‐1 scaffolds and coordinates protein complexes involved in PrPc‐dependent signaling. Moreover, we found that caveolin‐1 phosphorylation, is a mechanism for recruiting the C‐terminal Src kinase and inactivating Fyn, so as to terminate cell signaling. Furthermore our data support a significant role for PrPc as a response mediator in neuritogenesis and cell differentiation.
Mild cholesterol depletion reduces amyloid‐β production by impairing APP trafficking to the cell surface
Authors: Guardia‐Laguarta Cristina , Coma Mireia , Pera Marta , Clarimón Jordi , Sereno Lidia , Agulló José M. , Molina‐Porcel Laura , Gallardo Eduard , Deng Amy , Berezovska Oksana , Hyman Bradley T. , Blesa Rafael , Gómez‐Isla Teresa , Lleó Alberto 
Published: April 2009

AbstractIt has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and γ‐secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Aβ40 and Aβ42 in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol‐dependent decrease in the APP C‐terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)‐based technique to study APP–Presenilin 1 (PS1) interactions and lipid rafts in intact cells. Our data indicate that cholesterol depletion reduces association of APP into lipid rafts and disrupts APP–PS1 interaction. Taken together, our results suggest that mild membrane cholesterol reduction impacts the cleavage of APP upstream of γ‐secretase and appears to be mediated by changes in APP trafficking and partitioning into lipid rafts.
New light on the serotonergic paradox in the rat circadian system
Authors: Cuesta Marc , Clesse Daniel , Pévet Paul , Challet Etienne 
Published: April 2009

AbstractThe main mammalian circadian clock, localized in the suprachiasmatic nuclei can be synchronized not only with light, but also with serotonergic activation. Serotonergic agonists and serotonin reuptake inhibitors (e.g., fluoxetine) have a non‐photic influence (shifting effects during daytime and attenuation of photic resetting during nighttime) on hamsters’ and mice’ main clock. Surprisingly, in rats serotonergic modulation of the clock shows essentially photic‐like featuresin vivo(shifting effects during nighttime). To delineate this apparent paradox, we analyzed the effects of fluoxetine and serotonin agonists on rats’ clock. First, fluoxetine induced behavioral phase‐advances associated with down‐regulated expression of the clock genesPer1andRorβand up‐regulated expression ofRev‐erbαduring daytime. Moreover, fluoxetine produced an attenuation of light‐induced phase‐advances in association with altered expression ofPer1,Per2andRorβduring nighttime. Second, we showed that 5‐HT1Areceptors ‐maybe with co‐activation of 5‐HT7receptors‐ were implicated in non‐photic effects on the main clock. By contrast, 5‐HT3and 5‐HT2Creceptors were involved in photic‐like effects and, for 5‐HT2Csubtype only, in potentiation of photic resetting. Thus this study demonstrates that as for other nocturnal rodents, a global activation of the serotonergic system induces non‐photic effects in the rats’ clock during daytime and nighttime.
Medicines submitted to narcotics regulations in France, 1992–2007
Authors: Baumevieille Marie , Daveluy Amélie , Maurain Catherine , Bégaud Bernard , Haramburu Françoise 
Published: April 2009

AbstractThe objective was to study the current narcotics regulations which are the most restrictive regarding prescription and dispensation practice in France, and their evolution over the period 1992–2007. This is an example of regulation in a European member state regarding medicines with a risk of abuse or dependence. Narcotics regulations were studied in the French public health code. Status and indications of medicines concerned were found on the French medicine agency website, and the retrospective part of the study was conducted using the French public statute law website. Seventeen medicines were found. Three were psychotropics and fourteen narcotics. The prescription rules could be different for a given substance according to the route of administration or indication. In 2007, half of the narcotic opioids could be prescribed for 28 days, whereas in 1992, most of them could be prescribed for only 7 days. These results show the adaptation of French narcotics regulations, with the development of medicines indicated in acute or chronic pain treatment or opioid maintenance treatment.
Networks of Empire: Linkage and Reciprocity in Nineteenth‐Century Irish and Indian History
Authors: Crosbie Barry 
Published: April 2009

AbstractRecent debates surrounding Ireland's historical relationship with the British empire have focused almost exclusively upon its constitutional and political ties with Britain. The question of Ireland's colonial status continues to be heavily debated in Irish historiography and has been a contributing factor in obscuring our wider understanding of the complexity of Ireland's involvement in empire. For over 200 years, Ireland and India were joined together by an intricate series of networks that were borne out of direct Irish involvement in British imperialism overseas. Whether as migrants, soldiers, administrators, doctors, missionaries or educators, the Irish played an important role in administering, governing and populating vast areas of Britain's eastern empire. This article discusses new approaches to the study of Ireland's imperial past that allow us to move beyond the old ‘coloniser‐colonised’ debate, to address the key issue of whether Ireland or the varieties of Irishness of its imperial servants and settlers made a specific difference to the experience of empire. By highlighting the multiplicity of Irish connections within the context of the nineteenth‐century British empire in India, this article describes how imperial networks were used by contemporaries (settlers, migrants and indigenous agents) as mechanisms for the exchange of a whole set of ideas, practices and goods between Ireland and India during the colonial era.
The History of Medieval Theatre / Theatre of Medieval History: Dramatic Documents and the Performance of the Past
Authors: Symes Carol 
Published: April 2009

AbstractTheatre history has long been a sub‐discipline of literary criticism or, more recently, performance studies; it is usually not the province of trained historians. While potentially problematic for the study of any period, this trend has had a particularly limiting effect on the study of medieval drama and its larger historical contexts. This article explains why, offers a brief overview of medieval theatre's modern history and the current state of intellectual inquiry, and then suggests some historical uses of dramatic texts and of performance itself as an analytical category.
Botulinum Toxin A in the Treatment of Chronic Tension‐Type Headache With Cervical Myofascial Trigger Points: A Randomized, Double‐Blind, Placebo‐Controlled Pilot Study
Authors: Harden R. Norman , Cottrill Jerod , Gagnon Christine M. , Smitherman Todd A. , Weinland Stephan R. , Tann Beverley , Joseph Petra , Lee Thomas S. , Houle Timothy T. 
Published: April 2009

Objective.— To evaluate the efficacy of botulinum toxin A (BT‐A) as a prophylactic treatment for chronic tension‐type headache (CTTH) with myofascial trigger points (MTPs) producing referred head pain.Background.— Although BT‐A has received mixed support for the treatment of TTH, deliberate injection directly into the cervical MTPs very often found in this population has not been formally evaluated.Methods.— Patients with CTTH and specific MTPs producing referred head pain were assigned randomly to receive intramuscular injections of BT‐A or isotonic saline (placebo) in a double‐blind design. Daily headache diaries, pill counts, trigger point pressure algometry, range of motion assessment, and responses to standardized pain and psychological questionnaires were used as outcome measures; patients returned for follow‐up assessment at 2 weeks, 1 month, 2 months, and 3 months post injection. After 3 months, all patients were offered participation in an open‐label extension of the study. Effect sizes were calculated to index treatment effects among the intent‐to‐treat population; individual time series models were computed for average pain intensity.Results.— The 23 participants reported experiencing headache on a near‐daily basis (average of 27 days/month). Compared with placebo, patients in the BT‐A group reported greater reductions in headache frequency during the first part of the study (P = .013), but these effects dissipated by week 12. Reductions in headache intensity over time did not differ significantly between groups (P = .80; maximum d = 0.13), although a larger proportion of BT‐A patients showed evidence of statistically significant improvements in headache intensity in the time series analyses (62.5% for BT‐A vs 30% for placebo). There were no differences between the groups on any of the secondary outcome measures.Conclusions.— The evidence for BT‐A in headache is mixed, and even more so in CTTH. However, the putative technique of injecting BT‐A directly into the ubiquitous MTPs in CTTH is partially supported in this pilot study. Definitive trials with larger samples are needed to test this hypothesis further.
Migraine Treatment With Rizatriptan and Almotriptan: A Crossover Study
Authors: Ng‐Mak Daisy S. , Hu X. H. , Bigal Marcelo 
Published: April 2009

Background.— Rizatriptan and almotriptan are effective and well‐tolerated triptans that have not been compared directly.Objective.— To evaluate the effectiveness of rizatriptan 10 mg and almotriptan for the acute treatment of migraine, in a real‐world setting.Methods.— Of a large, multicenter, open‐label, crossover study, we conducted a substudy to contrast the effectiveness of rizatriptan 10 mg and almotriptan 12.5 mg for the acute treatment of 2 migraine attacks in a sequential, crossover manner. Time to outcome was assessed using stopwatches. Mean and median times to onset of pain relief (PR) and pain freedom (PF) for rizatriptan and almotriptan were compared. The effect of rizatriptan on times to onset of PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order, and use of rescue medication), was computed via a Cox proportional hazard model.Results.— Out of the 146 patients taking almotriptan as their usual care medication, 79 used stopwatch for both attacks. Significantly more patients taking rizatriptan achieved onset of PR within 2 hours after dosing than those taking almotriptan (88.6% vs 73.4%, P = .007). A higher proportion of patients taking rizatriptan achieved PF within 2 hours after dosing than those taking almotriptan (55.7% vs 45.6%, P = .10). Times to onset of PR and PF were significantly shorter with those patients taking rizatriptan than with those taking almotriptan (median time to PR: 45 vs 60 minutes, P = .002; median time to PF: 100 vs 135 minutes, P = .004). The adjusted proportional hazard ratios (rizatriptan vs almotriptan) for times to onset of PR and PF were 1.51 (95% confidence interval 1.20 to 1.88) and 1.42 (95% confidence interval 1.15 to 1.76), respectively. More patients were very satisfied when treating their attacks with rizatriptan than with almotriptan. Rizatriptan was preferred by most patients.Conclusions.— Times to achieve PR and PF were significantly shorter for patients using rizatriptan, as compared with those using almotriptan.
Electroconvulsive seizure thresholds and kindling acquisition rates are altered in mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions
Authors: Otto James F. , Singh Nanda A. , Dahle E. Jill , Leppert Mark F. , Pappas Chris M. , Pruess Timothy H. , Wilcox Karen S. , White H. Steve 
Published: April 2009

SummaryPurpose:  Benign familial neonatal convulsions (BFNC) is caused by mutations in the KCNQ2 and KCNQ3 genes, which encode subunits of the M‐type potassium channel. The purpose of this study was to examine the effects of orthologous BFNC‐causing mutations on seizure thresholds and the acquisition of corneal kindling in mice with heterozygous expression of the mutations.Methods:  The effects of the Kcnq2 gene A306T mutation and the Kcnq3 gene G311V mutation were determined for minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures. The rate of corneal kindling acquisition was also determined for Kcnq2 A306T and Kcnq3 G311V mice.Results:  Seizure thresholds were significantly altered relative to wild‐type animals in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Differences in seizure threshold were found to be dependent on the mutation expressed, the seizure testing paradigm, the genetic background strain, and the gender of the animal. Mutations in Kcnq2 and Kcnq3 were associated with an increased rate of corneal kindling. In the Kcnq2 A306T mice, an increased incidence of death occurred during and immediately following the conclusion of the kindling acquisition period.Conclusions:  These results suggest that genetic alterations in the subunits that underlie the M‐current and cause BFNC alter seizure susceptibility in a sex‐, mouse strain‐, and seizure‐test dependent manner. Although the heterozygous mice do not appear to have spontaneous seizures, the increased seizure susceptibility and incidence of death during and after kindling suggests that these mutations lead to altered excitability in these animals.
Runt‐related gene 2 is involved in the inhibition of matrix metalloproteinase‐13 expression by roxithromycin in human gingival epithelial cell cultures
Authors: Tabuchi Seiko , Sakuta Tetsuya , Oyama Tohru , Tokuda Masayuki , Tatsuyama Syouko , Kajihara Takehiro , Nagaoka Shigetaka , Beppu Mahiro , Sugihara Kazumasa , Ikebe Tetsuro , Shirasuna Kanemitsu , Torii Mitsuo 
Published: April 2009

Background and Objective:  Matrix metalloproteinase (MMP)‐13 has wide substrate specificity compared with other MMPs and appears to be involved in periodontitis. Previously, we reported that roxithromycin (RXM) inhibits vascular endothelial growth factor expression induced by tumour necrosis factor‐α in human periodontal ligament cells, but little is known about the effect of RXM on MMP‐13 expression in human gingival epithelial cells. We therefore examined the effect of RXM on MMP‐13 mRNA expression and production in cultured human gingival epithelial cells.Material and Methods:  Human epithelial cell lines (Ca9‐22, TU4, SCCTF and HSC‐3) were plated in tissue culture dishes. Then, the culture supernatants and sediments were collected and the production of MMP‐13 was analysed using enzyme‐linked immunosorbent assay; the expression of MMP‐13 mRNA and runt‐related gene 2 mRNA was assessed using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time RT‐PCR. We also studied the effect of Runx2 short interfering RNA (siRNA) on the induction of MMP‐13.Results:  Roxithromycin downregulated the induction of MMP‐13 in Ca9‐22 cells. Roxithromycin suppressed the expression of MMP‐13 mRNA not only in Ca9‐22 cells, but also in other human epithelial cell lines. Roxithromycin strongly inhibited the expression of Runx2 mRNA. Furthermore, Runx2 siRNA inhibited the induction of MMP‐13 in Ca9‐22 cells.Conclusion:  These results indicate that RXM suppresses MMP‐13 via the downregulation of Runx2 in human gingival epithelial cell cultures.
A review of EEG and ERP studies in bipolar disorder
Authors: Degabriele Racheal , Lagopoulos Jim 
Published: April 2009

Objective:The electroencephalogram (EEG) can be a useful tool in determining differences in general neural activity and specific waveforms in individuals with a number of psychiatric disorders. This paper aims to outline and discuss significant findings in EEG and event-related potential (ERP) research into bipolar disorder (BD).Methods:A literature review was performed through searches of MedLine, EMBASE, CINAHL and PsycInfo medical research databases for papers published from 1985 onwards. References of selected articles were also examined for other relevant studies.Results:Differences in general EEG data were found in subjects with BD, namely increased theta and delta and decreased alpha wave bands. Changes in EEG were also found in euthymic BD subjects and those undergoing medication programmes. ERP studies commonly report prolonged latencies and reduced amplitudes in the P300 component. Hyperfunctioning of the right hemisphere in BD was also reported in some studies, although further confirmation of this finding is required. Finally, the effects of medication and the role that genetics plays in EEG still remain unclear.Conclusions:The literature reviewed demonstrates supporting evidence for the presence of significant differences in EEG and ERP data in subjects with BD. However, methodological considerations such as varying mood states and medication status of the patients need to be followed more stringently for future research to bring about a robust model of the cognitive deficits of BD.
The Clitoral Complex: A Dynamic Sonographic Study
Authors: Foldes Pierre , Buisson Odile 
Published: April 2009

ABSTRACT

Introduction
The existence of the G-spot remains controversial partly because no appropriate structure and innervation have been clearly demonstrated in this pleasurable vaginal area. Using sonography, we wanted to visualize the movements of the clitoris and its anatomical relationship with the anterior wall of the vagina during voluntary perineal contraction and vaginal penetration without sexual stimulation.

Aim
The aim of this presentation is to provide a dynamic sonographic study of the clitoris and to describe the movements of the quiescent clitoral complex during a voluntary perineal contraction. We aim to visualize the mechanical consequences of the pressure of the anterior vaginal wall with women who claim to have a special sensitivity of the G-spot area and vaginal orgasm. Histology and immunohistochemistry of the G-spot and other female genital tissues are beyond the scope of this study and have not been discussed.

Method
The ultrasounds were performed in five healthy volunteers with the Voluson® General Electric® Sonography system (GE Healthcare, Zipf, Austria), with a 12-MHz flat probe, and with a vaginal probe. We used functional sonography of the quiescent clitoris with voluntary perineal contractions and with finger penetration without sexual stimulation.

Main Outcome Measures
We focused on the size of the clitoris (raphe, glans, and clitoral bodies) and of the length of the movements of the clitoris during voluntary perineal contractions.

Results
The coronal planes during perineal contraction and finger penetration demonstrated a close relationship between the root of the clitoris and the anterior vaginal wall.

Conclusions
We suggest that the special sensitivity of the lower anterior vaginal wall could be explained by pressure and movement of clitoris’ root during a vaginal penetration and subsequent perineal contraction. The G-spot could be explained by the richly innervated clitoris.
Malleable Implant Substitution for the Management of Penile Prosthesis Pump Erosion: A Pilot Study
Authors: Köhler Tobias S. , Modder Joshua K. , Dupree James M. , Bush Nicol C. , McVary Kevin T. 
Published: April 2009

ABSTRACT

Introduction
Managing isolated scrotal pump erosion or infection in patients with inflatable penile prosthesis (IPP) is a challenging problem. We describe our malleable implant substitution technique to address this problem.

Aim
The aim of this study was to describe and assess the outcomes of the malleable implant substitution technique.

Methods
In this retrospective case series, six patients underwent removal of the infected and/or eroded scrotal pump, and replacement of the entire IPP with a malleable prosthesis. This procedure was only performed in men in the absence of penile pain on palpation or overwhelming sepsis. The procedure utilized components of the Mulcahy washout protocol with loose scrotal wound approximation and drains as necessary.

Main Outcome Measures
The main outcome is a recurrent infection rate and prosthesis functionality of the malleable implant substitution technique.

Results
All six men who underwent the procedure have done well and remain infection-free. Two men have undergone conversion from a malleable prosthesis back to IPP. Three are considering conversion to an IPP as they are satisfied with their current malleable prosthesis function. One man had a distal erosion of the malleable prosthesis that necessitated complete removal.

Conclusions
We believe the malleable implant substitution technique provides an excellent option for management of isolated scrotal pump erosion or infection and prevents the problems associated with the other common management strategies.