bluuebunny/crossref_metadata_2025_split huggingface dataset:
AVE 0991, a non‐peptide mimic of angiotensin‐(1–7) effects, attenuates pulmonary remodelling in a model of chronic asthma
Authors: Rodrigues‐Machado M G , Magalhães G S , Cardoso J A , Kangussu L M , Murari A , Caliari M V , Oliveira M L , Cara D C , Noviello M L M , Marques F D , Pereira J M , Lautner R Q , Santos R A S , Campagnole‐Santos M J 
Published: August 2013

Background and PurposeAVE 0991 (AVE) is a non‐peptide compound, mimic of the angiotensin (Ang)‐(1–7) actions in many tissues and pathophysiological states. Here, we have investigated the effect of AVE on pulmonary remodelling in a murine model of ovalbumin (OVA)‐induced chronic allergic lung inflammation.Experimental ApproachWe used BALB/c mice (6–8 weeks old) and induced chronic allergic lung inflammation by OVA sensitization (20 μg·mouse−1, i.p., four times, 14 days apart) and OVA challenge (1%, nebulised during 30 min, three times per·week, for 4 weeks). Control and AVE groups were given saline i.p and challenged with saline. AVE treatment (1 mg·kg−1·per day, s.c.) or saline (100 μL·kg−1·per day, s.c.) was given during the challenge period. Mice were anaesthetized 72 h after the last challenge and blood and lungs collected. In some animals, primary bronchi were isolated to test contractile responses. Cytokines were evaluated in bronchoalveolar lavage (BAL) and lung homogenates.Key ResultsTreatment with AVE of OVA sensitised and challenged mice attenuated the altered contractile response to carbachol in bronchial rings and reversed the increased airway wall and pulmonary vasculature thickness and right ventricular hypertrophy. Furthermore, AVE reduced IL‐5 and increased IL‐10 levels in the BAL, accompanied by decreased Ang II levels in lungs.Conclusions and ImplicationsAVE treatment prevented pulmonary remodelling, inflammation and right ventricular hypertrophy in OVA mice, suggesting that Ang‐(1–7) receptor agonists are a new possibility for the treatment of pulmonary remodelling induced by chronic asthma.
Cannabidivarin‐rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor‐independent mechanism
Authors: Hill T D M , Cascio M‐G , Romano B , Duncan M , Pertwee R G , Williams C M , Whalley B J , Hill A J 
Published: August 2013

Background and PurposeEpilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis‐derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors.Experimental ApproachThe anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg−1) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using static beam and grip strength assays. Binding of CBDV BDSs to cannabinoid CB1 receptors was evaluated using displacement binding assays.Key ResultsCBDV BDSs exerted significant anticonvulsant effects in the pentylenetetrazole (≥100 mg·kg−1) and audiogenic seizure models (≥87 mg·kg−1), and suppressed pilocarpine‐induced convulsions (≥100 mg·kg−1). The isobolographic study revealed that the anticonvulsant effects of purified CBDV and CBD were linearly additive when co‐administered. Some motor effects of CBDV BDSs were observed on static beam performance; no effects on grip strength were found. The Δ9‐tetrahydrocannabinol and Δ9‐tetrahydrocannabivarin content of CBDV BDS accounted for its greater affinity for CB1 cannabinoid receptors than purified CBDV.Conclusions and ImplicationsCBDV BDSs exerted significant anticonvulsant effects in three models of seizure that were not mediated by the CB1 cannabinoid receptor and were of comparable efficacy with purified CBDV. These findings strongly support the further clinical development of CBDV BDSs for the treatment of epilepsy.
Inhibitory effects of marine‐derived DNA‐binding anti‐tumour tetrahydroisoquinolines on the Fanconi anaemia pathway
Authors: Martínez Sandra , Pérez Laura , Galmarini Carlos M , Aracil Miguel , Tercero Juan C , Gago Federico , Albella Beatriz , Bueren Juan A 
Published: August 2013

Background and PurposeWe have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA‐binding anti‐cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter‐strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells.Experimental ApproachInitially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated.Key ResultsWhile untransformed FA‐deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA‐deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA‐competent counterparts, even though these FA‐deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC.Conclusions and ImplicationsOur data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti‐tumour drugs.
Headache and pituitary disease: a systematic review
Authors: Kreitschmann‐Andermahr I. , Siegel S. , Weber Carneiro R. , Maubach J. M. , Harbeck B. , Brabant G. 
Published: August 2013

SummaryHeadache is very common in pituitary disease and is reported to be present in more than a third of all patients with pituitary adenomas. Tumour size, cavernous sinus invasion, traction or displacement of intracranial pain‐sensitive structures such as blood vessels, cranial nerves and dura mater, and hormonal hypersecretion are implicated causes. The present review attempts to systematically review the literature for any combination of headache and pituitary or hormone overproduction or deficiency. Most data available are retrospective and/or not based on the International Headache Society (IHS) classification. Whereas in pituitary apoplexy a mechanical component explains the almost universal association of the condition with headaches, this correlation is less clear in other forms of pituitary disease and a positive impact of surgery on headaches is not guaranteed. Similarly, invasion into the cavernous sinus or local inflammatory changes have been linked to headaches without convincing evidence. Some studies suggest that oversecretion of GH and prolactin may be important for the development of headaches, and treatment, particularly with somatostatin analogues, has been shown to improve symptoms in these patients. Otherwise, treatment rests on general treatment options for headaches based on an accurate clinical history and a precise classification which includes assessment of the patient's psychosocial risk factors.
Patients' preferences when comparing analogue implant impressions using a polyether impression material versus digital impressions (Intraoral Scan) of dental implants
Authors: Wismeijer Daniel , Mans Ronny , van Genuchten Michiel , Reijers Hajo A. 
Published: August 2013

AbstractObjectivesThe primary objective of this clinical study was to assess the patients' perception of the difference between an analogue impression approach on the one hand and an intra‐oral scan (IO scan) on the other when restoring implants in the non‐aesthetic zone. A second objective was to analyse the difference in time needed to perform these two procedures.Materials and methodsThirty consecutive patients who had received 41 implants (Straumann tissue level) in the non‐aesthetic zone in an implant‐based referral practice setting in the Netherlands. As they were to receive crown and or bridge work on the implants, in one session, the final impressions were taken with both an analogue technique and with an intraoral scan. Patients were also asked if, directly after the treatment was carried out, they would be prepared to fill out a questionnaire on their perception of both techniques. The time involved following these two procedures was also recorded.ResultsThe preparatory activities of the treatment, the taste of the impression material and the overall preference of the patients were significantly in favour of the IO scan. The bite registration, the scan head and gag reflex positively tended to the IO scan, but none of these effects were significant. The overall time involved with the IO scan was more negatively perceived than the analogue impression. Overall less time was involved when following the analogue impression technique than with the IO scan.ConclusionsThe overall preference of the patients in our sample is significantly in favour of the approach using the IO scan. This preference relates mainly to the differences between the compared approaches with respect to taste effects and their preparatory activities. The patients did perceive the duration of IO scan more negatively than the analogue impression approach.
‘Voluntary’ Poverty Alleviation Resettlement in China
Authors: Xue Longyi , Wang Mark Y. , Xue Tao 
Published: August 2013

ABSTRACTCurrent conceptualizations of resettlement in China as either voluntary or involuntary are too rigid. New guidelines and policies, particularly around Poverty Alleviation Resettlement (PAR), are emphasizing the importance of voluntarism. Little is known, however, about how the principle of voluntary relocation of villagers has actually been implemented. This study explores this process by examining local implementation and experiences of PAR in Linfen Prefecture, Shanxi. It introduces China's nationwide PAR programme, and then identifies the spatial and temporal characteristics of PAR in Linfen from 1997 to 2010, highlighting the factors that contribute to widespread voluntary resettlement.
Transcutaneous monitoring of partial pressure of carbon dioxide during endoscopic retrograde cholangiopancreatography using a double‐balloon endoscope with carbon dioxide insufflation under conscious sedation
Authors: Miyoshi Hideaki , Shimatani Masaaki , Kato Kota , Sumimoto Kimi , Kurishima Akiko , Kusuda Takeo , Fukata Norimasa , Ikeura Tsukasa , Takaoka Makoto , Okazaki Kazuichi 
Published: August 2013

Background and AimA double‐balloon (DB) endoscope can be selectively inserted into the afferent loop to carry out endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy, allowing various types of endoscopic treatments for pancreaticobiliary diseases to be successfully carried out. In order to make such a lengthy procedure more comfortable and safe, sedatives and carbon dioxide (CO2) insufflation are widely used for gastrointestinal endoscopy. However, these techniques can increase the risk of CO2 retention. Recently, a new sensor for transcutaneous measurement of partial pressure of carbon dioxide (PCO2) has been introduced. The aim of the present study was to evaluate the changes in transcutaneous PCO2 (PtcCO2) during DB‐ERCP with CO2 insufflation under conscious sedation and assess any complications related to sedation and CO2 insufflation.MethodsA total of 312 patients underwent DB‐ERCP with CO2 insufflation at our hospital between March 2009 and December 2012. The patients were moderately sedated using midazolamwith or without pentazocine. PtcCO2 was measured by a non‐invasive sensor throughout DB‐ERCP in all patients.ResultsThe mean peak PtcCO2 during the procedure was significantly higher than the mean PtcCO2 value before and after DB‐ERCP. Body mass index, procedure time and dose of pentazocine were significantly higher in the CO2 retention group (peak PtcCO2 ≥ 50 mmHg). CO2 narcosis was observed in one case.ConclusionsDB‐ERCP with CO2 insufflation under conscious sedation might have the potential to increase the risk of CO2 retention. Hence, non‐invasive and continuous PtcCO2 measurement is useful for early detection of hypercapnia.
Cardiac hormones target nuclear oncogenes c‐Fos and c‐Jun in carcinoma cells
Authors: Manimala Neil J. , Frost Chelsea D. , Lane Meghan L. , Higuera Mariana , Beg Rana , Vesely David L. 
Published: August 2013

AbstractBackgroundc‐Fos is a cellular proto‐oncogene which dimerizes with c‐Jun proto‐oncogene to form AP‐1 transcription factor, which upregulates transcription of genes involved in proliferation and cancer formation. Four cardiac hormones, that is, long‐acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) with anticancer effects in vivo are potent inhibitors of the Ras‐MEK 1/2‐ERK 1/2 kinase cascade and signal transducer and activator of transcription‐3 (STAT‐3) that activate c‐Fos and c‐Jun. These four cardiac hormones were investigated for their effects on proto‐oncogenes c‐Fos and c‐Jun within the nucleus of cancer cells.Materials and methodsFour cardiac hormones were evaluated for their ability to decrease proto‐oncogenes c‐Fos and c‐Jun, measured by ELISA in extracted nuclei of three human cancer cell lines.ResultsVessel dilator, LANP, KP and ANP over a concentration range of 100 pM–10 μM, maximally decreased c‐Fos by 61%, 60%, 61% and 59% in human hepatocellular cancer cells, by 82%, 74%, 78% and 74% in small‐cell lung cancer cells, and by 82%, 73%, 78% and 74% in human renal adenocarcinoma cells. c‐Jun was maximally reduced by vessel dilator, LANP, KP and ANP by 43%, 31%, 61% and 35% in hepatocellular cancer cells, by 65%, 49%, 59% and 40% in small‐cell lung cancer cells, and by 47%, 43%, 57% and 49% in renal cancer cells.ConclusionFour cardiac hormones are potent inhibitors of c‐Fos and c‐Jun proto‐oncogenes within the nucleus of cancer cells.
Impaired slow axonal transport in diabetic peripheral nerve is independent of RAGE
Authors: Juranek Judyta K. , Geddis Matthew S. , Rosario Rosa , Schmidt Ann Marie 
Published: August 2013

AbstractDiabetic peripheral nerve dysfunction is a common complication occurring in 30–50% of long‐term diabetic patients. The pathogenesis of this dysfunction remains unclear but growing evidence suggests that it might be attributed, in part, to alteration in axonal transport. Our previous studies demonstrated that RAGE (Receptor for Advanced Glycation Endproducts) contributes to the pathogenesis of diabetic peripheral neuropathy and impairs nerve regeneration consequent to sciatic nerve crush, particularly in diabetes. We hypothesize that RAGE plays a role in axonal transport impairment via the interaction of its cytoplasmic domain with mammalian Diaphanous 1 (mDia1) – actin interacting molecule. Studies showed that mDia1–RAGE interaction is necessary for RAGE‐ligand‐dependent cellular migration, AKT phosphorylation, macrophage inflammatory response and smooth muscle migration. Here, we studied RAGE, mDia1 and markers of axonal transport rates in the peripheral nerves of wild‐type C57BL/6 and RAGE null control and streptozotocin‐injected diabetic mice at 1, 3 and 6 h after sciatic nerve crush. The results show that in both control and diabetic nerves, the amount of RAGE accumulated at the proximal and distal side of the crush area is similar, indicating that the recycling rate for RAGE is very high and that it is evenly transported from and towards the neuronal cell body. Furthermore, we show that slow axonal transport of proteins such as Neurofilament is affected by diabetes in a RAGE‐independent manner. Finally, our study demonstrates that mDia1 axonal transport is impaired in diabetes, suggesting that diabetes‐related changes affecting actin binding proteins occur early in the course of the disease.
Energy‐efficient encoding by shifting spikes in neocortical neurons
Authors: Malyshev Aleksey , Tchumatchenko Tatjana , Volgushev Stanislav , Volgushev Maxim 
Published: August 2013

AbstractThe speed of computations in neocortical networks critically depends on the ability of populations of spiking neurons to rapidly detect subtle changes in the input and translate them into firing rate changes. However, high sensitivity to perturbations may lead to explosion of noise and increased energy consumption. Can neuronal networks reconcile the requirements for high sensitivity, operation in a low‐noise regime, and constrained energy consumption? Using intracellular recordings in slices from the rat visual cortex, we show that layer 2/3 pyramidal neurons are highly sensitive to minor input perturbations. They can change their population firing rate in response to small artificial excitatory postsynaptic currents (aEPSCs) immersed in fluctuating noise very quickly, within 2–2.5 ms. These quick responses were mediated by the generation of new, additional action potentials (APs), but also by shifting spikes into the response peak. In that latter case, the spike count increase during the peak and the decrease after the peak cancelled each other, thus producing quick responses without increases in total spike count and associated energy costs. The contribution of spikes from one or the other source depended on the aEPSCs timing relative to the waves of depolarization produced by ongoing activity. Neurons responded by shifting spikes to aEPSCs arriving at the beginning of a depolarization wave, but generated additional spikes in response to aEPSCs arriving towards the end of a wave. We conclude that neuronal networks can combine high sensitivity to perturbations and operation in a low‐noise regime. Moreover, certain patterns of ongoing activity favor this combination and energy‐efficient computations.
Regional increase of cerebral cortex thickness in juvenile myoclonic epilepsy
Authors: Alhusaini Saud , Ronan Lisa , Scanlon Cathy , Whelan Christopher D. , Doherty Colin P. , Delanty Norman , Fitzsimons Mary 
Published: August 2013

SummaryThe goal of this study was to characterize cerebral cortex thickness patterns in juvenile myoclonic epilepsy (JME). Surface‐based morphometry (SBM) was applied to process brain magnetic resonance images acquired from 24 patients with JME and 40 healthy controls and quantify cerebral cortex thickness. Differences in cortical thickness between patients and controls were determined using generalized linear model (covariates: age and gender). In patients with JME, thickness increase was detected bilaterally within localized regions in the orbitofrontal and mesial frontal cortices. Such thickness patterns coexisted with significant bilateral reduction in thalamic volume. These findings confirm that the underlying mechanisms in JME are related to aberrant corticothalamic structure and indicate that frontal cortex abnormalities are possibly linked to regional increase in cerebral cortical thickness.
Diphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat
Authors: Chen Yu‐Wen , Tzeng Jann‐Inn , Chen Ting‐Yun , Wang Jhi‐Joung , Chen Yu‐Chung , Hung Ching‐Hsia 
Published: August 2013

AbstractAlthough diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long‐lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose‐dependent fashion. We showed that diphenhydramine, as well as bupivacaine displayed a dose‐dependent cutaneous analgesia in response to dorsal cutaneous noxious stimuli. The relative potency (50% effective dose) was bupivacaine (0.023 [0.013–0.035]%) > diphenhydramine (0.078 [0.068–0.091]%; P < 0.001). On an equipotent basis, diphenhydramine had a similar duration of action to bupivacaine. Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.
An investigation on rotatory bending fretting fatigue damage of railway axles
Authors: Song C. , Shen M. X. , Lin X. F. , Liu D. W. , Zhu M. H. 
Published: August 2013

ABSTRACTFretting damage failure analysis of a Chinese carbon railway axle RD2 was carried out. The wheel hub was in situ cut to expose the damaged surface of the wheel seat to avoid additional damage. A small‐scale axle test rig was developed, and simulation tests were performed at different rotator speeds of 1800 and 2100 rpm. The wear mechanism of fretting damage areas was a combination of abrasive wear, oxidative wear and delamination. The fracture surfaces exhibited characterization of multisource and step‐profile. The fretting fatigue crack initiated at the subsurface and propagated along an inclined angle at the first stage. The fretting damage at the higher speed was more severe compared with the lower speed, which lead to a relatively shorter fatigue life. The damage morphologies of the axle in the simulation tests were in good agreement with that observed in the failure analysis on real axle.
Creation of arteriovenous fistulae for hemodialysis in octogenarians
Authors: Watorek Ewa , Golebiowski Tomasz , Kusztal Mariusz , Letachowicz Krzysztof , Letachowicz Waldemar , Augustyniak Bartosik Hanna , Garcarek Jerzy , Madziarska Katarzyna , Weyde Wacław , Klinger Marian 
Published: August 2013

AbstractElderly patients, defined as octogenarians and nonagenarians, are an increasing population entering renal replacement therapy. Advanced age appears as an exclusive factor negatively influencing dialysis practice. Elderly patients are referred late for the initiation of hemodialysis and more likely are offered catheters rather than arteriovenous fistulae (AVF), which increase mortality and negatively affect quality of life. We present our approach to the creation of vascular access for hemodialysis in this demanding population. In 2006–2012, 39 patients aged 85.9 ± 2.05 with end‐stage renal disease, mainly resulting from ischemic nephropathy, were admitted to the Department of Nephrology to establish permanent vascular access for hemodialysis: preferably AVF. Temporary dialysis catheters were implanted in uremic emergency to bridge the time to fistula creation/maturation. AVF was attempted in 87.2% of the patients. Primary AVF function was achieved in 54% of the patients. Cumulative proportional survival of AVF at months 12 and 24 was 81.5%. Ninety‐four percent of AVF were localized on the forearm: 74% in the distal and 20% in the proximal part. Mean duration of hemodialysis therapy was 20.80 ± 19.45 months. The mean time of AVF use was 15.9 ± 20.2 months. Until present, 38% have been dialyzed using AVF for 31.0 ± 18.8 months. Five patients died with functioning fistula. Eight patients initiated hemodialysis therapy with fistula. During further observation, the use of AVF increased to 62%. Elderly patients should not be denied creation of AVF as a rule. The outcome of AVF benefits more from acknowledging individual vascular conditions rather than age of the patient.