bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in CB1 and CB2 receptors in the post‐mortem cerebellum of humans affected by spinocerebellar ataxias
Authors: Rodríguez‐Cueto Carmen , Benito Cristina , Fernández‐Ruiz Javier , Romero Julián , Hernández‐Gálvez Mariluz , Gómez‐Ruiz María 
Published: August 2013

Background and PurposeSpinocerebellar ataxias (SCAs) are a family of chronic progressive neurodegenerative diseases, clinically and genetically heterogeneous, characterized by loss of balance and motor coordination due to degeneration of the cerebellum and its afferent and efferent connections. Unlike other motor disorders, the possible role of changes in the endocannabinoid system in the pathogenesis of SCAs has not been investigated.Experimental ApproachThe status of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) receptors in the post‐mortem cerebellum of SCA patients and controls was investigated using immunohistochemical procedures.Key ResultsImmunoreactivity for the CB1 receptor, and also for the CB2 receptor, was found in the granular layer, Purkinje cells, neurons of the dentate nucleus and areas of white matter in the cerebellum of SCA patients at levels notably higher than controls. Double‐labelling procedures demonstrated co‐localization of CB1 and, in particular, CB2 receptors with calbindin, supporting the presence of these receptors in Purkinje neurons. Both receptors also co‐localized with Iba‐1 and glial fibrillary acidic protein in the granular layer and white matter areas, indicating that they are present in microglia and astrocytes respectively.Conclusions and ImplicationsOur results demonstrate that CB1 and CB2 receptor levels are significantly altered in the cerebellum of SCA patients. Their identification in Purkinje neurons, which are the main cells affected in SCAs, as well as the changes they experienced, suggest that alterations in endocannabinoid receptors may be related to the pathogenesis of SCAs. Therefore, the endocannabinoid system could provide potential therapeutic targets for the treatment of SCAs and its progression.Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐6
17‐β Oestradiol prevents cardiovascular dysfunction in post‐menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation
Authors: Bendale Dhaval Sharad , Karpe Pinakin Arun , Chhabra Richa , Shete Sachin Prabhakarrao , Shah Heta , Tikoo Kulbhushan 
Published: August 2013

Background and PurposeOestrogen therapy is known to induce cardioprotection in post‐menopausal metabolic syndrome (PMS). Hence, we investigated the effect of 17‐β oestradiol (E2) on functional responses to angiotensin II and cardiovascular dysfunction in a rat model of PMS.Experimental ApproachPMS was induced in ovariectomized rats by feeding a high‐fat diet for 10 weeks. Isometric tension responses of aortic rings to angiotensin II were recorded using an isometric force transducer. TUNEL assay and immunoblotting was performed to assess apoptosis and protein expression respectively in PMS.Key ResultsEndothelial dysfunction in PMS was characterized by enhanced angiotensin II‐induced contractile responses and impaired endothelial dependent vasodilatation. This was associated with an increased protein expression of AT1 receptors in the aorta and heart in PMS. PMS induced cardiac apoptosis by activating Bax and PARP protein expression. These changes were associated with a down‐regulation in the expression of silent information regulation 2 homologue (SIRT1)/P‐AMP‐activated PK (AMPK) and increased H3 acetylation in aorta and heart. E2 partially suppressed angiotensin II‐induced contractions, restored the protein expression of SIRT1/P‐AMPK and suppressed H3 acetylation. The role of SIRT1/AMPK was further highlighted by administration of sirtinol and compound C (ex vivo), which enhanced angiotensin II contractile responses and ablated the protective effect of E2 on PMS.Conclusion and ImplicationsOur results provide novel mechanisms for PMS‐induced cardiovascular dysfunction involving SIRT1/AMPK/ histone H3 acetylation, which was prevented by E2. The study suggests that therapies targeting SIRT1/AMPK/epigenetic modifications may be beneficial in reducing the risk of cardiovascular disorders.
Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3
Authors: Subramaniam Aruljothi , Shanmugam Muthu K , Ong Tina H , Li Feng , Perumal Ekambaram , Chen Luxi , Vali Shireen , Abbasi Taher , Kapoor Shweta , Ahn Kwang Seok , Kumar Alan Prem , Hui Kam M , Sethi Gautam 
Published: August 2013

Background and PurposeAberrant activation of STAT3 is frequently encountered and promotes proliferation, survival, metastasis and angiogenesis in hepatocellular carcinoma (HCC). Here, we have investigated whether emodin mediates its effect through interference with the STAT3 activation pathway in HCC.Experimental ApproachThe effect of emodin on STAT3 activation, associated protein kinases and apoptosis was investigated using various HCC cell lines. Additionally, we also used a predictive tumour technology to analyse the effects of emodin . The in vivo effects of emodin were assessed in an orthotopic mouse model of HCC.Key ResultsEmodin suppressed STAT3 activation in a dose‐ and time‐dependent manner in HCC cells, mediated by the modulation of activation of upstream kinases c‐Src, JAK1 and JAK2. Vanadate treatment reversed emodin‐induced down‐regulation of STAT3, suggesting the involvement of a tyrosine phosphatase and emodin induced the expression of the tyrosine phosphatase SHP‐1 that correlated with the down‐regulation of constitutive STAT3 activation. Interestingly, silencing of the SHP‐1 gene by siRNA abolished the ability of emodin to inhibit STAT3 activation. Finally, when administered i.p., emodin inhibited the growth of human HCC orthotopic tumours in male athymic nu/nu mice and STAT3 activation in tumour tissues.Conclusions and ImplicationsEmodin mediated its effects predominantly through inhibition of the STAT3 signalling cascade and thus has a particular potential for the treatment of cancers expressing constitutively activated STAT3.
Emerging therapeutic aspects in oncology
Authors: MacEwan David J 
Published: August 2013

Cancer remains a peculiarly stubborn disease to treat. Some forms of cancer have seen tremendous advances in the effectiveness of their treatments, whereas other forms have remained resistant to pharmacological control. This lack of hope for success is in part due to the types of drugs that are used in the clinic, and the targeted biological system being based purely on cellular growth rates. However, recent drugs designed to affect specific signalling pathways or proteins have been showing much success. Thanks to the ingenuity of pharmacologists in understanding and targeting these processes, there have been real improvements in treatment. Here we are presented with some of the research into such critical systems that have to be understood, so that they can be conquered. We will also look at the challenges facing cancer pharmacologists and what the field may present to us all in the future.Linked ArticlesThis article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue‐8
Antagonism of endogenous nociceptin/orphanin FQ inhibits infarction‐associated ventricular arrhythmias via PKC‐dependent mechanism in rats
Authors: Han Y , Guo Z , Wang L L , Zhang L Z , Yao T P 
Published: August 2013

Background and PurposeEvidence indicates nociceptin/orphanin FQ (N/OFQ) may participate in the pathology of cardiac arrhythmias associated with myocardial infarction. But the role of N/OFQ in the arrhythmogenesis in acute myocardial infarction is unclear. The aim of this study was to investigate the effects of endogenous N/OFQ on infarction‐associated arrhythmias.Experimental ApproachThe expression of N/OFQ, PKC activity and ventricular arrhythmias in presence and absence of UFP‐101, a specific antagonist of N/OFQ receptor, were examined following permanent coronary artery occlusion in anaesthetized rats. The effect of N/OFQ on action potential duration was examined in isolated rat cardiomyocytes.Key ResultsIt was observed that N/OFQ was increased by 41% in the myocardium after coronary artery occlusion (P < 0.01 vs. control). Pretreatment with UFP‐101 (10−7 mol·kg−1, i.v.) reduced the incidence of ventricular ectopic beats by 70% and ventricular tachycardia by 51% respectively (all P < 0.05 vs. control). Meanwhile, PKC activity was elevated in the rats treated with UFP‐101 (by 35%, P < 0.05 vs. control). A selective PKC inhibitor, calphostin C, completely abolished the anti‐arrhythmic effects of UFP‐101 (P < 0.01). N/OFQ (at 10−11, 10−9 and 1 × 10−7 mol·L−1) shortened the action potential duration by 3% (P > 0.05), 10% (P < 0.05) and 22% (P < 0.01), respectively, via N/OFQ receptor.Conclusions and ImplicationsAntagonism of endogenous N/OFQ produces anti‐arrhythmic effects on ventricular arrhythmias in acute myocardial infarction, possibly via modulating PKC activity and action potential of myocytes.
Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9‐tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats
Authors: Rock Erin M , Sticht Martin A , Duncan Marnie , Stott Colin , Parker Linda A 
Published: August 2013

Background and PurposeThe cannabinoid 1 (CB1) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin‐induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ9‐tetrahydrocannabivarin (THCV), for their ability to produce these behavioural effect characteristics of CB1 receptor inverse agonism in rats.Experimental ApproachIn experiment 1, we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea‐induced behaviour) in the same manner as SR and AM251. In experiment 2, we investigated the potential of THCV and CBDV to enhance conditioned gaping produced by a toxin in the same manner as CB1 receptor inverse agonists.Key ResultsSR (10 and 20 mg·kg−1) and AM251 (10 mg·kg−1) produced conditioned gaping; however, THCV (10 or 20 mg·kg−1) and CBDV (10 or 200 mg·kg−1) did not. At a subthreshold dose for producing nausea, SR (2.5 mg·kg−1) enhanced lithium chloride (LiCl)‐induced conditioned gaping, whereas Δ9‐tetrahydrocannabinol (THC, 2.5 and 10 mg·kg−1), THCV (2.5 or 10 mg·kg−1) and CBDV (2.5 or 200 mg·kg−1) did not; in fact, THC (2.5 and 10 mg·kg−1), THCV (10 mg·kg−1) and CBDV (200 mg·kg−1) suppressed LiCl‐induced conditioned gaping, suggesting anti‐nausea potential.Conclusions and ImplicationsThe pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists. As well, these compounds may have therapeutic potential in reducing nausea.
Angiotensin II type 1a receptor signalling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy
Authors: Yasuno Shinji , Kuwahara Koichiro , Kinoshita Hideyuki , Yamada Chinatsu , Nakagawa Yasuaki , Usami Satoru , Kuwabara Yoshihiro , Ueshima Kenji , Harada Masaki , Nishikimi Toshio , Nakao Kazuwa 
Published: August 2013

Background and PurposeAngiotensin II has been implicated in the development of various cardiovascular ailments, including cardiac hypertrophy and heart failure. The fact that inhibiting its signalling reduced the incidences of both sudden cardiac death and heart failure in several large‐scale clinical trials suggests that angiotensin II is involved in increased cardiac arrhythmogenicity during the development of heart failure. However, because angiotensin II also promotes structural remodelling, including cardiomyocyte hypertrophy and cardiac fibrosis, it has been difficult to assess its direct contribution to cardiac arrhythmogenicity independently of the structural effects.Experimental ApproachWe induced cardiac hypertrophy in wild‐type (WT) and angiotensin II type 1a receptor knockout (AT1aR‐KO) mice by transverse aortic constriction (TAC). The susceptibility to ventricular tachycardia (VT) assessed in an in vivo electrophysiological study was compared in the two genotypes. The effect of acute pharmacological blockade of AT1R on the incidences of arrhythmias was also assessed.Key ResultsAs described previously, WT and AT1aR‐KO mice with TAC developed cardiac hypertrophy to the same degree, but the incidence of VT was much lower in the latter. Moreover, although TAC induced an increase in tyrosine phosphorylation of connexin 43, a critical component of gap junctional channels, and a reduction in ventricular levels of connexin 43 protein in both genotypes, the effect was significantly ameliorated in AT1aR‐KO mice. Acute pharmacological blockade of AT1R also reduced the incidence of arrhythmias.Conclusions and ImplicationsOur findings demonstrate that AT1aR‐mediated signalling makes a direct contribution to the increase in arrhythmogenicity in hypertrophied hearts independently of structural remodelling.
Southwest Barents Sea rift basin evolution: comparing results from backstripping and time‐forward modelling
Authors: Clark S. A. , Glorstad‐Clark E. , Faleide J. I. , Schmid D. , Hartz E. H. , Fjeldskaar W. 
Published: August 2013

AbstractWe present tectonic models of progressive basin formation in the south‐west Barents Sea derived as part of the PETROBAR project (Petroleum‐related studies of the Barents Sea region). The basin architecture developed as a multi‐stage rift preceding the creation of the sheared/transtensional margin conjugate to NE Greenland. N‐ to NNE‐striking basins, with sediment thicknesses in places exceeding 15 km, are separated by basement highs. We use two basin analysis approaches, BMT™ backstripping and TecMod™time‐forward modelling, to determine stretching factors through time along the profile PETROBAR‐07. This 550 km‐long profile derived from wide‐angle reflection/refraction seismic data acquired in 2007, coincident with deep multichannel seismic reflection data. Detailed stratigraphic analysis of the reflection profile, in concert with a dense grid of 2D profiles tied to wells, provides timing and water depth constraint for the models. Velocity analysis of the wide‐angle data provides constraint on the cumulative crustal stretching. The north‐west trending cross‐section extends from continental craton, at the Varanger Peninsula, to within 16 km of the interpreted continent–ocean boundary. Rifting along the profile was episodic, with four distinct phases of basin formation during the Carboniferous, the Late Permian–Triassic, the Late Jurassic–Early Cretaceous and the Late Cretaceous–Eocene. Collectively, the basins exhibit a general trend of younging, narrowing, and deepening oceanward, suggesting a gradual focusing of rifting prior to final breakup. Cumulative stretching factors derived from BMT and TecMod correlate well with observed crustal thinning, and the two models provide uncertainty bounds for stretching factors for the separate rift phases. In contrast to orthogonally rifted margins, stretching is relatively minor immediately prior to transform breakup, with greater stretching occurring during earlier rift phases.
From Ethnicity to Race in the Canadian Review of Sociology, 1964 to 2010
Authors: Ramos Howard 
Published: August 2013

La Revue canadienne de sociologie a été un forum important pour la recherche sur l'ethnicité et la race. Grâce à une analyse des publications publiés dans la revue entre 1964 et 2010 nous constatons que l'ethnicité a reçu plus d'attention que la race, et que la majorité des publications se sert d'une approche d’économie politique et des méthodes quantitatives. Au fil du temps, nous relevons l'abandon du concept d'ethnicité et la montée de la race et nous relevons moins d’études quantitatives. Ces changements ont lieu en parallèle avec des changements politiques et démographiques au Canada et sont en réponse aux iniquités raciales.The Canadian Review of Sociology has been an important venue for scholarship on ethnicity and race. Through an analysis of publications dealing with both terms in the journal, between 1964 and 2010, the paper finds that publications have focused more on ethnicity than race, using a political economy approach, and quantitative methods. Over time, significant changes have occurred, including a move away from ethnicity to race and a move away from quantitative methods. Many of these changes have occurred in conjunction with policy and demographic changes in Canada and as a response to ongoing racial inequities.
The Boss: Conspicuous Invisibility in Ho Chi Minh City
Authors: HARMS ERIK 
Published: August 2013

AbstractThis article introduces the figure of the Vietnamese boss, (ông chủ), in this case, the Chairman of the Board of Directors of a Ho Chi Minh City securities trading company. The boss's body techniques, lifestyle choices, and movement through different spaces in the city offer a view into the “everyday presentation of wealth” among business leaders who drive much of the economic transformation in contemporary Vietnam. In order to illuminate how the figure speaks to a particular moment in Vietnam's great urban transformation, the essay describes practices of “conspicuous invisibility” through which the boss manages what can and cannot be seen about his wealth. As a figure, the boss stands out against the background of economic privatization, the emergence of a stock market, rapid urbanization, and the changing moral valuation of those who accumulate wealth. The article also suggests that conspicuous invisibility both produces and is produced by new kinds of urban spaces. [Vietnam, Ho Chi Minh City, Saigon, New Urban Zones, elites].
Multicenter study on endoscopic ultrasound‐guided expandable biliary metal stent placement: Choice of access route, direction of stent insertion, and drainage route
Authors: Dhir Vinay , Artifon Everson L. A. , Gupta Kapil , Vila Juan J. , Maselli Roberta , Frazao Mariana , Maydeo Amit 
Published: August 2013

Background and AimEndoscopic ultrasonography‐guided biliary drainage (EUS‐BD) using expandable biliary metal stents has emerged as an acceptable alternative in patients with failed endoscopic retrograde cholangiopancreatography for malignant biliary obstruction. However, there is no consensus over the preferred access route (transhepatic or extrahepatic), direction of stent insertion (antegrade or retrograde) or drainage route (transluminal or transpapillary) in patients potentially suitable for multiple methods. The present study compares success and complication rates in patients undergoing EUS‐BD via different methods.MethodsThis was a multicenter retrospective analysis. Records of patients who underwent EUS‐BD for malignant obstructive jaundice at four centers were entered in a standard database. Success and complications were compared for different techniques.ResultsSixty‐eight patients were analyzed. EUS‐BD was successful in 65 patients (95.6%). There was no significant difference in the success rates of different techniques. Complications wereseen in 14 patients (20.6%) and mortality in three patients (4.4%). Complications were significantly higher for the transhepatic route compared to the transduodenal route (30.5% vs 9.3%, P = 0.03). There was no significant difference in complication rates among transluminal and transpapillary stent placements, or direct and rendezvous stenting. Logistic regression analysis showed transhepatic access to be the only independent risk factor for complications (P = 0.031, t = 2.2).ConclusionEUS‐BD can be carried out with high success rates regardless of the choice of access route, stent direction or drainage route. However, complications are significantly higher with transhepatic access. The transduodenal route should be chosen for EUS‐guided and rendezvous stent placements, when both routes are available.
Limbic encephalitis: a clinical‐radiological comparison between herpetic and autoimmune etiologies
Authors: Oyanguren B. , Sánchez V. , González F. J. , de Felipe A. , Esteban L. , López‐Sendón J. L. , Garcia‐Barragán N. , Martínez‐San Millán J. , Masjuán J. , Corral I. 
Published: August 2013

BackgroundHerpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical‐radiological pattern.Materials and methodsAll cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV‐1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings.ResultsTwelve patients with positive polymerase chain reaction for HSV‐1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1).ConclusionsThere are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.
A commercial foot pump for emergency ventilation of horses, proof‐of‐principle during equine field anaesthesia
Authors: von Ritgen S. , Auer U. , Schramel J. , Moens Y. 
Published: August 2013

SummaryAt present there is no alternative to the use of a demand valve and pressurised oxygen for emergency ventilation in large animal field anaesthesia, therefore we aimed at providing a proof‐of‐principle of a small (2.5 l) commercial foot pump to provide emergency intermittent positive pressure ventilation (IPPV) in large animals. The study was performed during elective field anaesthesia for castration of 5 Haflinger stallions. Horses were premedicated with acepromazine i.m. after catheterisation of the jugular vein, further sedation was obtained with detomidine and butorphanol i.v. Anaesthesia was induced with ketamine and midazolam i.v. and maintained with a constant rate infusion of midazolam, ketamine and xylazine. After endotracheal intubation the foot pump, modified with a manually operated expiratory valve, was connected to the endotracheal tube and oxygen (6 l/min) was supplied. Anaesthesia was monitored using spirometry, respiratory gas analysis, pulse oximetry and arterial blood gas analysis. When arterial partial pressure of carbon dioxide (PaCO2) exceeded 6.65 kPa, IPPV was provided by 2–4 consecutive compressions of the pump aiming at a tidal volume of 10 ml/kg bwt. The PaCO2 was maintained at 6.18 ± 3.06 kPa (mean ± s.d.) with a respiratory rate of 4–10 breaths/min. The tidal volume was 2678–8300 ml with a peak inspiratory pressure of 24 ± 6.6 cmH2O and a mean minute volume of 68.5 ± 13 l/min. Inspired oxygen concentration ranged from 26–46% (36 ± 7%) and arterial partial pressure of oxygen from 8.38–11.03 kPa (10.1 ± 0.93 kPa). The modified foot pump enables the practitioner to provide IPPV to large animals in emergency situations.