bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats
Authors: Jolly L , March JE , Kemp PA , Bennett T , Gardiner SM 
Published: July 2009

Background and purpose: Intermedin (IMD) is a newly identified member of the calcitonin family of peptides that shares structural and functional homology with adrenomedullin (AM).In vivocardiovascular effects of AM have been described, but relatively little is known of thein vivoactions of IMD. The purpose of this study was to compare the regional haemodynamic effects of IMD with those of AM in conscious rats, and investigate possible underlying mechanisms.Experimental approach: Measurements of blood pressure, heart rate and renal, mesenteric and hindquarters haemodynamics were made in conscious, chronically‐instrumented rats.Key results: IMD caused tachycardia and vasodilatation in all three vascular beds, associated with modest hypotension. At an equimolar dose (1 nmol·kg−1), most of the cardiovascular effects of IMD were greater than those of AM. The AM receptor antagonist, AM22–52, was equally effective in attenuating the renal and mesenteric vasodilator effects of IMD (1 nmol·kg−1) and AM (3 nmol·kg−1), but inhibition of NO synthase was more effective at reducing the vasodilator effects of IMD than AM. Vascular KATPchannel blockade with U‐37883A did not inhibit the vasodilator effects of either peptide.Conclusions and implications: In vivo, the regional haemodynamic profile of IMD resembles that of AM, and some of the vasodilator effects of IMD are mediated by AM receptors and NO, but not by KATPchannels. The cardiovascular effects of AM have been implicated in various pathological conditions, but whether or not endogenous IMD fulfils a similar role remains to be determined.
Prevention of arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen
Authors: Chang Kuo‐Chu , Liang Jin‐Tung , Tsai Pei‐Shan , Wu Ming‐Shiou , Hsu Kwan‐Lih 
Published: July 2009

Background and purpose: Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.Experimental approach: Diabetes was induced in rats by a single tail vein injection with 55 mg·kg−1steptozotocin (STZ). After induction of hyperglycaemia, animals were treated for 8 weeks with pyridoxamine (1 g·L−1in drinking water) and compared with the age‐matched untreated diabetic controls. Pulse wave reflection along the vasculature was derived using the impulse response function of the filtered aortic input impedance spectra.Key results: Treatment of this experimental diabetes with pyridoxamine resulted in a significant increase in wave transit time and a decrease in wave reflection factor, indicating that pyridoxamine attenuates the diabetes‐induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, pyridoxamine therapy ameliorated the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Glycation‐derived modification of aortic collagen was also found to be attenuated by administration of pyridoxamine to the STZ‐induced diabetic rats.Conclusions and implications: Pyridoxamine imparts significant protection against the diabetes‐induced deterioration in pulsatile arterial load imposed on the heart, at least partly through inhibition of the formation of advanced glycation end products and their accumulation on aortic collagen of the STZ‐treated rats.
Endogenous cannabinoids induce fever through the activation of CB1 receptors
Authors: Fraga D , Zanoni CIS , Rae GA , Parada CA , Souza GEP 
Published: July 2009

Background and purpose:  The effects of centrally administered cannabinoids on body core temperature (Tc) and the contribution of endogenous cannabinoids to thermoregulation and fever induced by lipopolysaccharide (LPS) (Sigma Chem. Co., St. Louis, MO, USA) were investigated.Experimental approach:  Drug‐induced changes in Tc of male Wistar rats were recorded over 6 h using a thermistor probe (Yellow Springs Instruments 402, Dayton, OH, USA) inserted into the rectum.Key results:  Injection of anandamide [(arachidonoylethanolamide (AEA); Tocris, Ellisville, MO, USA], 0.01–1 µg i.c.v. or 0.1–100 ng intra‐hypothalamic (i.h.), induced graded increases in Tc (peaks 1.5 and 1.6°C at 4 h after 1 µg i.c.v. or 10 ng i.h.). The effect of AEA (1 µg, i.c.v.) was preceded by decreases in tail skin temperature and heat loss index (values at 1.5 h: vehicle 0.62, AEA 0.48). Bell‐shaped curves were obtained for the increase in Tc induced by the fatty acid amide hydrolase inhibitor [3‐(3‐carbamoylphenyl)phenyl] N‐cyclohexylcarbamate (Cayman Chemical Co., Ann Arbor, MI, USA) (0.001–1 ng i.c.v.; peak 1.9°C at 5 h after 0.1 ng) and arachidonyl‐2‐chloroethylamide (ACEA; Tocris) (selective CB1 agonist; 0.001–1 µg i.c.v.; peak 1.4°C 5 h after 0.01 µg), but (R,S)‐(+)‐(2‐Iodo‐5‐nitrobenzoyl)‐[1‐(1‐methyl‐piperidin‐2‐ylmethyl)‐1H‐indole‐3‐yl] methanone (Tocris) (selective CB2 agonist) had no effect on Tc. AEA‐induced fever was unaffected by i.c.v. pretreatment with 6‐Iodo‐2‐methyl‐1‐[2‐(4‐morpholinyl)ethyl]‐1H‐indole‐3‐yl](4‐methoxyphenyl) methanone (Tocris) (selective CB2 antagonist), but reduced by i.c.v. pretreatment with N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251; Tocris) (selective CB1 antagonist). AM251 also reduced the fever induced by ACEA or LPS.Conclusions and implications:  The endogenous cannabinoid AEA induces an integrated febrile response through activation of CB1 receptors. Endocannabinoids participate in the development of the febrile response to LPS constituting a target for antipyretic therapy.
Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic
Authors: Kurz CM , Baranowska U , Łupiński S , Göthert M , Malinowska B , Schlicker E 
Published: July 2009

Background and purpose: We examined whether cannabinoid CB1and histamine H3receptors resemble α2‐adrenoceptors in that their presynaptically mediated cardiovascular effects are less marked in urethane‐ than in pentobarbitone‐anaesthetized pithed rats.Experimental approach: Effects of the cannabinoid agonist CP‐55,940 and the H3receptor agonist imetit on electrically induced tachycardic and vasopressor responses, respectively, was compared in pithed rats anaesthetized with urethane or pentobarbitone. The affinity of urethane for the three receptors was measured by radioligand binding studies in rat brain cortex membranes and its potency assessed in superfused mouse tissues preincubated with3H‐noradrenaline.Key results: The neurogenic tachycardic response was less markedly inhibited by CP‐55,940 in urethane‐ than in pentobarbitone‐anaesthetized pithed rats. Imetit inhibited the neurogenic vasopressor response after pentobarbitone but not after urethane. The catecholamine‐induced tachycardic and vasopressor response did not differ between rats anaesthetized with either compound. Urethane 10 mM (plasma concentration reached under anaesthesia) did not affect binding to CB1or H3receptors and α2adrenoceptors, nor did it alter the inhibitory effect of agonists at the three receptors on electrically evoked3H‐noradrenaline release.Conclusions and implications: Urethane, but not pentobarbitone, abolished the H3receptor‐mediated vascular response in pithed rats and attenuated the CB1receptor‐mediated cardiac response much more than pentobarbitone. The weaker effects of CB1, H3and α2receptor agonists cannot be explained by antagonism by urethane at the three receptorsin vitro. Pentobarbitone, but not urethane, is suitable as an anaesthetic for investigations of inhibitory presynaptic receptor function in pithed and anaesthetized rats.
Bioavailability of diazepam after intramuscular injection of its water‐soluble prodrug alone or with atropine–pralidoxime in healthy volunteers
Authors: Abbara C , Rousseau JM , Turcant A , Lallement G , Comets E , Bardot I , Clair P , Diquet B 
Published: July 2009

Background and purpose:  The aim of this study was to assess the relative bioavailability of diazepam after administration of diazepam itself or as a water‐soluble prodrug, avizafone, in humans.Experimental approach:  The study was conducted in an open, randomized, single‐dose, three‐way, cross‐over design. Each subject received intramuscular injections of avizafone (20 mg), diazepam (11.3 mg) or avizafone (20 mg) combined with atropine (2 mg) and pralidoxime (350 mg) using a bi‐compartmental auto‐injector (AIBC). Plasma concentrations of diazepam were quantified using a validated LC/MS–MS assay, and were analysed by both a non‐compartmental approach and by compartmental modelling.Key results:  The maximum concentration (Cmax) of diazepam after avizafone injection was higher than that obtained after injection of diazepam itself (231 vs. 148 ng·mL−1), while area under the curve (AUC) values were equal. Diazepam concentrations reached their maximal value faster after injection of avizafone. Injection of avizafone with atropine–pralidoxime (AIBC) had no effect on diazepam Cmax and AUC, but the time to Cmax was increased, relative to avizafone injected alone. According to the Akaike criterion, the pharmacokinetics of diazepam after injection as a prodrug was best described as a two‐compartment with zero‐order absorption model. When atropine and pralidoxime were injected with avizafone, the best pharmacokinetic model was a two‐compartment with a first‐order absorption model.Conclusion and implications:  Diazepam had a faster entry to the general circulation and achieved higher Cmax after injection of prodrug than after the parent drug. Administration of avizafone in combination with atropine and pralidoxime by AIBC had no significant effect on diazepam AUC and Cmax.
Atypical rolandic epilepsy
Authors: Fejerman Natalio 
Published: July 2009

SummaryTypical benign rolandic epilepsy (BRE) is a frequent and well‐delineated epileptic syndrome in childhood. Mild cognitive and behavioral difficulties are increasingly recognized in the course of BRE and should not be considered as atypical features. Atypical features are recognized on electroclinical grounds. These features, particularly early age at onset and frequent spikes or spike‐wave discharges, seem to be risk factors for neuropsychological deficits but also for an atypical evolution of BRE. Atypical evolutions of BRE are defined by the appearance of severe neuropsychological impairments and continuous spike‐and‐waves during slow sleep (CSWSS). The clinical expressions of these situations correspond to the syndromes known as atypical benign focal epilepsy of childhood (ABFEC), status of BRE, Landau‐Kleffner syndrome (LKS), and CSWSS syndrome, which may be part of a continuum related to BRE.
CSWS‐related autistic regression versus autistic regression without CSWS
Authors: Tuchman Roberto 
Published: July 2009

SummaryContinuous spike‐waves during slow‐wave sleep (CSWS) and Landau‐Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.
From rolandic epilepsy to continuous spike‐and‐waves during sleep and Landau‐Kleffner syndromes: Insights into possible genetic factors
Authors: Rudolf Gabrielle , Valenti Maria P. , Hirsch Edouard , Szepetowski Pierre 
Published: July 2009

SummaryEpilepsy is a frequent neurologic disease in childhood, characterized by recurrent seizures and sometimes with major effects on social, behavioral, and cognitive development. Childhood focal epilepsies particularly are age‐related diseases mainly occurring during developmental critical periods. A complex interplay between brain development and maturation processes and susceptibility genes may contribute to the development of various childhood epileptic syndromes associated with language and cognitive deficits. Indeed, the Landau‐Kleffner syndrome (LKS), the continuous spike‐and‐waves during sleep syndrome (CSWS), and the benign childhood epilepsy with centrotemporal spikes (BCECTS) or benign rolandic epilepsy, are different entities that are considered as part of a single continuous spectrum of disorders. Genetic predisposition with simple to complex modes of inheritance has long been suspected for this wide group of childhood focal epilepsies. Recent reports on the involvement of the SRPX2 and ELP4 genes with possible roles in cell motility, migration, and adhesion have provided first insights into the complex molecular bases of childhood focal epilepsies.
Acquired cognitive dysfunction with focal sleep spiking activity
Authors: Paquier Philippe F. , Verheulpen Denis , De Tiège Xavier , Van Bogaert Patrick 
Published: July 2009

SummaryThe syndrome of continuous spike‐waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non‐REM sleep, and takes the form of continuous bilateral and diffuse slow spike‐waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F‐fluorodeoxyglucose (PET‐FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike‐waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET‐FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.
Neurophysiology of CSWS‐associated cognitive dysfunction
Authors: Seri Stefano , Thai Jade Ndoc , Brazzo Daniela , Pisani Francesco , Cerquiglini Antonella 
Published: July 2009

SummaryThe phenomenon of continuous spikes and waves during slow‐wave sleep (CSWS) is associated with a number of epileptic syndromes, which share a behavioral phenotype characterized by deterioration of cognitive, behavioral, or sensorimotor functions. Available evidence seems to suggest that spike‐wave activity is a result of a complex interaction between cortical and subcortical inhibitory networks and can “per se” produce a transient loss of underlying cortical functions. Syndromes like Landau‐Kleffner syndrome, CSWS, and phenomena such as negative myoclonus could share in common—at least at the neurophysiological level—some similarities. Differences in behavioral phenotypes could be explained in term of maturational and genetic differences, as well as by the functional specificity of the involved areas.
Some facts about sleep relevant for Landau‐Kleffner syndrome
Authors: Mascetti Laura , Foret Ariane , Bonjean Maxime , Matarazzo Luca , Dang‐Vu Thanh , Maquet Pierre 
Published: July 2009

SummaryOur understanding of the neural mechanisms of non–rapid eye movement sleep (NREM) is steadily increasing. Given the intriguing activation of paroxysmal activity during NREM sleep in patients with Landau‐Kleffner syndrome (LKS), a thorough characterization of commonalities and differences between the neural correlates of LKS paroxysms and normal sleep oscillations might provide useful information on the neural underpinning of this disorder. Especially, given the suspected role of sleep in brain plasticity, this type of information is needed to assess the link between cognitive deterioration and electroencephalography (EEG) paroxysms during sleep.
The surgical treatment of Landau‐Kleffner syndrome
Authors: Cross J. Helen , Neville Brian G. R. 
Published: July 2009

SummaryThe medical management of Landau‐Kleffner syndrome is usually effective for seizure control and eventual seizure remission. However, the response for language and behavior is often poor. Surgery, in the form of multiple subpial transections (MSTs) to include Wernicke’s area has been suggested as a way forward if electrophysiologic lateralization can be demonstrated. Surgical series in the literature are few and outcome from surgery variable
Sign language in Landau‐Kleffner syndrome
Authors: Deonna Thierry , Prelaz‐Girod Anne‐Claude , Mayor‐Dubois Claire , Roulet‐Perez Eliane 
Published: July 2009

SummaryThis article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau‐Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.
TRANSPLANTATION AND CELLULAR ENGINEERING: Long‐term storage does not alter functionality of in vitro generated human erythroblasts: implications for ex vivo generated erythroid transfusion products
Authors: Migliaccio Giovanni , Sanchez Massimo , Leblanc Amanda , Masiello Francesca , Tirelli Valentina , Migliaccio Anna Rita , Najfeld Vesna , Whitsett Carolyn 
Published: July 2009

BACKGROUND: Cultured human erythroid cells derived in vitro may represent alternative transfusion products. It is unknown, however, if these ex vivo expanded erythroid cells remain functional or develop genetic abnormalities after storage.STUDY DESIGN AND METHODS: Using mononuclear cells from four adult blood donors, erythroblasts were generated ex vivo in expansion cultures supplemented with stem cell factor, interleukin‐3, erythropoietin (EPO), dexamethasone, and estradiol. The viability and in vitro function of freshly expanded or short (1‐2 months)‐ and long (8 years)‐term‐stored erythroblasts cryopreserved in dimethyl sulfoxide were compared. Erythroblast function was defined as ability to proliferate in expansion media and mature in response to EPO. Cell number was determined manually and expressed as fold increase. Viability was assessed by trypan blue and propidium iodide exclusion. Maturation was evaluated by morphologic analyses and CD36/CD235a expression profiling. Cytogenetic evaluation included karyotype and multicolor fluorescence in situ hybridization analyses.RESULTS: Equivalent numbers (>80%) of erythroblasts were viable after short‐ and long‐term storage. Freshly expanded and short‐ and long‐term‐stored erythroblasts equally doubled in number (fold increase, 2.4) retaining an immature phenotype (23% of the cells were CD36highCD235aneg) when cultured for 4 days under expansion conditions. The numbers of freshly expanded and short‐term‐stored erythroblasts that matured when exposed for 4 days to EPO were also similar (approx. 22% of the cells became CD36negCD235ahigh). In spite of the massive amplification, ex vivo generated erythroblasts demonstrated a normal (46,XY) karyotype with no obvious genomic rearrangements.CONCLUSION: Ex vivo expanded erythroblasts remain functional and genetically normal after long‐term storage.
IMMUNOHEMATOLOGY: Rapid screening of granulocyte antibodies with a novel assay: flow cytometric granulocyte immunofluorescence test
Authors: Nguyen Xuan Duc , Flesch Brigitte , Sachs Ulrich J. , Kroll Hartmut , Klüter Harald , Müller‐Steinhardt Michael 
Published: July 2009

BACKGROUND: White blood cell (WBC)‐associated antibodies can lead to severe pulmonary transfusion reactions (transfusion‐related acute lung injury [TRALI]). Investigation of a large number of blood donor samples using the standard granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) proved to be difficult to perform due to the time‐consuming process and the large quantity of test cells required. This study describes the novel flow cytometric GIFT (Flow‐GIFT) method for a rapid detection of granulocyte antibodies by flow cytometric analysis.STUDY DESIGN AND METHODS: A total of 141 sera were analyzed for the presence of granulocyte antibodies that were previously associated with suspected TRALI. As test cells whole blood samples from human neutrophil antigen (HNA)‐typed donors were isolated using cell sedimentation in a ficoll density gradient. WBCs were incubated with the respective serum and binding of antibodies to the test cells was detected using fluorescein isothiocyanate–conjugated anti‐human antibody. Standard GIFT and GAT were performed as reference methods.RESULTS: Seven sera containing anti‐HNA‐3a, CD16, and HLA Class I were negative in the standard GIFT and eight sera containing anti‐HNA‐2a, anti‐CD16, and anti‐HLA Class I were not detected in the GAT. The novel Flow‐GIFT was able to detect all granulocyte antibodies, which were only detectable in a combination of standard GIFT and GAT. In serial dilution tests, the Flow‐GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT.CONCLUSION: The Flow‐GIFT method permits rapid detection of granulocyte antibodies requiring fewer donor test cells. This method is ideal for automation and will potentially open the way for screening of granulocyte antibodies in a large donor population.