bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roscovitine, a cyclin‐dependent kinase inhibitor, affects several gating mechanisms to inhibit cardiac L‐type (Ca(V)1.2) calcium channels
Authors: Yarotskyy V , Elmslie K S 
Published: August 2007

Background and purpose:L‐type calcium channels (Ca
(V)1.2) play an important role in cardiac contraction. Roscovitine, a cyclin‐dependent kinase inhibitor and promising anticancer drug, has been shown to affect Ca
(V)1.2 by inhibiting current amplitude and slowing activation. This research investigates the mechanism by which roscovitine inhibits Ca
(V)1.2 channels.Experimental approach:Ca
(V)1.2 channels were transfected into HEK 293 cells, using the calcium phosphate precipitation method, and currents were measured using the whole‐cell patch clamp technique.Key results:Roscovitine slows activation at all voltages, which precludes one previously proposed mechanism. In addition, roscovitine enhances voltage‐dependent, but not calcium‐dependent inactivation. This enhancement resulted from both an acceleration of inactivation and a slowing of the recovery from inactivation. Internally applied roscovitine failed to affect Ca
(V)1.2 currents, which supports a kinase‐independent mechanism and extracellular binding site. Unlike the dihydropyridines, closed state inactivation was not affected by roscovitine. Inactivation was enhanced in a dose‐dependent manner with an IC50=29.5±12 μM, which is close to that for slow activation and inhibition.Conclusions and implications:We conclude that roscovitine binds to an extracellular site on Ca
(V)1.2 channels to inhibit current by both slowing activation and enhancing inactivation. Purine‐based drugs could become a new option for treatment of diseases that benefit from L‐channel inhibition such as cardiac arrhythmias and hypertension.British Journal of Pharmacology (2007) 152, 386–395; doi:10.1038/sj.bjp.0707414; published online 13 August 2007
Agonist potency at P2X7 receptors is modulated by structurally diverse lipids
Authors: Michel A D , Fonfria E 
Published: August 2007

Background and purpose:The P2X7 receptor exhibits a high degree of plasticity with agonist potency increasing after prolonged receptor activation. In this study we investigated the ability of lipids to modulate agonist potency at P2X7 receptors.Experimental approach:A variety of lipids, including lysophosphatidylcholine, sphingosylphosphorylcholine and hexadecylphosphorylcholine were studied for their effect on P2X7 receptor‐stimulated ethidium bromide accumulation in cells expressing human recombinant P2X7 receptors and on P2X7 receptor‐stimulated interleukin‐1β (IL1β) release from THP‐1 cells. The effects of the lipids were also assessed in radioligand binding studies on human P2X7 receptors.Key results:At concentrations (3‐30 μM) below the threshold to cause cell lysis, the lipids increased agonist potency and/or maximal effects at P2X7 receptors in both ethidium accumulation and IL1β release studies. There was little structure activity relationship (SAR) for this effect and sub‐lytic concentrations of Triton X‐100 partially mimicked the effects of the lipids. The lipids caused cell lysis and increased intracellular calcium at higher concentrations (30‐100 μM) which complicated interpretation of their effects in functional studies. However, the lipids (3‐100 μM) also increased agonist potency 30‐100 fold in radioligand binding studies.Conclusions and implications:This study demonstrates that a diverse range of lipids increase agonist potency at the P2X7 receptor in functional and binding studies. The broad SAR, including the effect of Triton X‐100, suggests this may reflect changes in membrane properties rather than a direct effect on the P2X7 receptor. Since many of the lipids studied accumulate in disease states they may enhance P2X7 receptor function under pathophysiological conditions.British Journal of Pharmacology (2007) 152, 523–537; doi:10.1038/sj.bjp.0707417; published online 13 August 2007
The inhibition of monoacylglycerol lipase by URB602 showed an anti‐inflammatory and anti‐nociceptive effect in a murine model of acute inflammation
Authors: Comelli F , Giagnoni G , Bettoni I , Colleoni M , Costa B 
Published: August 2007

Background and purpose:2‐arachidonoylglycerol (2‐AG) is an endocannabinoid whose hydrolysis is predominantly catalysed by the enzyme monoacylglycerol lipase (MAGL). The development of MAGL inhibitors could offer an opportunity to investigate the anti‐inflammatory and anti‐nociceptive role of 2‐AG, which have not yet been elucidated. On these bases, URB602, a MAGL inhibitor, was tested in a murine model of inflammation/inflammatory pain.Experimental approach:Acute inflammation was induced by intraplantar injection of λ‐carrageenan into mice. The highest dose to be employed has been selected performing the tetrad assays for cannabimimetic activity in mice. URB602 anti‐inflammatory and anti‐nociceptive efficacy (assessed by plethysmometer and plantar test, respectively) was evaluated both in a preventive regimen (drug administered 30 min before carrageenan) and in a therapeutic regimen (URB602 administered 30 min after carrageenan). To elucidate the cannabinoid receptor involvement, rimonabant and SR144528, CB1and CB2selective antagonists, respectively, were given 15 min before URB602.Key results:Systemic administration of URB602 elicited a dose‐dependent anti‐oedemigen and anti‐nociceptive effect that was reversed exclusively by the CB2receptor antagonist. The efficacy of URB602 persisted also when the compound was administered in a therapeutic regimen, suggesting the ability of URB602 to improve established disease.Conclusions and implications:The present report highlighted the ability of the selective MAGL inhibitor, URB602, to prevent and treat an acute inflammatory disease without producing adverse psychoactive effects. The data presented herein also contributed to clarify the physiological role of 2‐AG in respect to inflammatory reactions, suggesting its protective role in the body.British Journal of Pharmacology(2007)152, 787–794; doi:10.1038/sj.bjp.0707425; published online 13 August 2007
Characterization of atypical antipsychotic drugs by a late decrease of striatal alpha1 spectral power in the electropharmacogram of freely moving rats
Authors: Dimpfel W 
Published: August 2007

Background and purpose:Drug administration modifies the balance of neurotransmitter‐controlled ion channel activity and consequently the firing pattern of local neuronal populations and intracerebral field potentials. Fast Fourier Transformation of these field potentials provides an electropharmacogram depicting drug‐induced changes within defined frequency ranges. The present investigation was undertaken to investigate the difference between atypical and typical antipsychotic drugs.Experimental approach:Adult Fisher rats were implanted with 4 bipolar concentric steel electrodes using a stereotactic surgical procedure. Field potentials from four selected brain areas in freely moving rats were used to analyse the frequency content of the electropharmacogram after administration of 4 clinically used atypical antipsychotic drugs.Key results:Atypical antipsychotics exerted effects similar to those reported for typical antipsychotics, on the electropharmacogram during the first hour after administration, whereas clear differences emerged during the second and third hour after dosing. During the latter period, only atypical antipsychotic drugs produced a statistically significant decrease in alpha1 and beta1 spectral power, especially within the striatum, somewhat less in the cortex.Conclusions and implications:Previous studies have attributed alpha1 frequency changes to the influence of 5‐hydroxytryptamine (5‐HT) and the present data are consistent with additional binding of atypical drugs to 5‐HT receptors. This implies that a change in the balance between dopaminergic and 5‐hydroxytryptaminergic neurotransmission (activation of both) is likely to underlie the relative lack of extrapyramidal side effects characteristic of atypical antipsychotics and also for their higher efficacy in the treatment of mood and cognition deficits in schizophrenics.British Journal of Pharmacology (2007) 152, 538–548; doi:10.1038/sj.bjp.0707427; published online 13 August 2007
Central nervous tissue: an excitable medium. A study using the retinal spreading depression as a tool
Authors: Hanke Wolfgang , de Lima Vera Maura Fernandes 
Published: August 2007

According to its physicochemical properties, neuronal tissue, including the central nervous system (CNS) and thus the human brain, is an excitable medium, which consequently exhibits, among other things, self-organization, pattern formation and propagating waves. Furthermore, such systems can be controlled by weak external forces. The spreading depression (SD), a propagating wave of excitation–depression, is such an event, which is additionally linked to a variety of medically important situations, classical migraine being just one example. Especially in retinal tissue, a true part of the CNS, the SD can be observed very easily with the naked eye and by video imaging techniques due to its big intrinsic optical signal.
We have investigated the retinal SD and its control by external physical parameters such as gravity and temperature. Beyond this, especially due to its medical relevance, the control of CNS excitability by pharmacological tools is of specific interest, and we have studied this question in detail using the retinal SD as an experimental tool to collect information about the control of CNS tissue excitability.
DNA based cladograms augment the discovery of a new Ips species from China (Coleoptera: Curculionidae: Scolytinae)
Authors: Cognato Anthony I. , Sun Jiang Hua 
Published: August 2007

AbstractThe implementation of DNA in taxonomic study is in its infancy because the association of the amount and type of nucleotide change with species boundaries has not been fully examined for most taxa. Mitochondrial cytochrome c oxidase I (COI) nucleotide data is currently the most popular molecular marker for delimiting species boundaries and a standard pair‐wise nucleotide divergence between groups of individuals has been suggested for the recognition of new species. It is unlikely that such a standard would be applicable across animal species, but the association of the amount and type of nucleotide change with species boundaries could help with the establishment of a taxon‐specific DNA taxonomy.This study utilizes DNA data from nuclear and mitochondrial genes to improve the taxonomy of an important forest beetle pest, Ips. Amount and type of nucleotide difference are associated with monophyletic species based on a cladistic analysis of these data. As a result, a new species from China is described for a clade of beetles whose nucleotide differences exceeded the amount of evolutionary change observed within currently recognized species. The COI data are analyzed independently with an expanded taxon data set, including pair‐wise nucleotide differences between recognized sister species. The wide range of average intraspecific pair‐wise nucleotide difference (0–10.0%) suggests limitations to the application of a standard percent nucleotide difference as a means to identify species boundaries. At most, average COI nucleotide intraspecific difference provides an informal guide to identify potential clades that may warrant further systematic investigation.© The Willi Hennig Society 2007.
Self‐Reported Cannabis Use in Great Britain in 1981
Authors: Mott Joy 
Published: August 2007

SummaryThe 1982 British Crime Survey collected information on self‐reported offending including cannabis use from a large representative sample of the population of Great Britain aged 16 and older. Five per cent of the sample said they had ever used cannabis compared with two per cent of a representative sample of people aged 16–19 in England and Wales interviewed in 1969. While there are some differnces between the present national samples in the proportions saying they had ever used cannabis, more of the 20–34 year olds of both sexes, particularly those who said they had completed their education after the age of 17, than of other sub‐groups in the sample said they had ever used done so. The limitations of national surveys of self‐reported drug use are discussed.
Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction
Authors: Mortimer Kevin J. , Tattersfield Anne E. , Tang Yufei , Wu Kai , Lewis Sarah , Hochhaus Gunther , Harrison Tim W. 
Published: August 2007

What is already known about this subject • All inhaled corticosteroids are absorbed into the systemic circulation and hence have the potential to cause adverse systemic effects.• Plasma drug concentrations following inhalation of 1000 µg fluticasone are considerably lower in people with airflow obstruction than in healthy volunteers but this is not the case for budesonide. What this study adds • This is the first study to determine whether changes in airflow obstruction within an individual affect the systemic absorption of inhaled fluticasone and budesonide;• Plasma concentrations of fluticasone and, to a lesser extent, those of budesonide were lower when the drugs were inhaled following induced bronchoconstriction;• The lower plasma concentrations of corticosteroids seen when the drugs were inhaled following induced bronchoconstriction is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.AimsTo determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation.MethodsTwenty people with mild asthma inhaled 1000 µg fluticasone (Accuhaler®) plus 800 µg budesonide (Turbohaler®) on two visits. On one occasion, prior to drug inhalation, FEV1 was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration‐time curve (AUC(0,5 h)) compared between visits.ResultsThe mean difference in FEV1 prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36–75) and 29% (IQR 2–44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007.ConclusionsThe lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.
Activation of protease‐activated receptor‐2 reduces airways inflammation in experimental allergic asthma
Authors: D'Agostino B. , Roviezzo F. , De Palma R. , Terracciano S. , De Nardo M. , Gallelli L. , Abbate G. F. , D'Aiuto E. , Russo M. , Cirino G. , Rossi F. 
Published: August 2007

SummaryBackgroundProteinase‐activated receptors (PAR)‐2 are members of the family of G‐protein‐coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR‐2 may affect airway functions and play a role in human diseases.ObjectiveAssessment of the role of PAR‐2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen ofParietaria judaicapollen.MethodsEvaluation of antigen challenge in rabbits treated with PAR‐2‐activating peptide (PAR‐2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR.ResultsPAR‐2AP pre‐treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper‐responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA‐DR‐positive cells while RTLA‐positive cells were unchanged. IFN‐γ and IL‐2 production were inhibited, with a concomitant increase in IL‐10 of about 10‐fold over the control values.ConclusionsIn this experimental model, PAR‐2 modulates bronchoconstriction interfering with antigen challenge‐induced immune response in rabbits sensitized and challenged to Par j 1.
Recombinant human luteinizing hormone, lutropin alfa, for the induction of follicular development and pregnancy in profoundly gonadotrophin‐deficient women
Authors: Kaufmann Robert , Dunn Randall , Vaughn Thomas , Hughes Graeme , O’Brien Fanny , Hemsey George , Thomson Barbara , St. L. O'Dea Louis 
Published: August 2007

SummaryObjective  To provide evidence of efficacy and safety for use of lutropin alfa in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency.Design  An open‐label, noncomparative extension of a randomized, double‐blind, placebo‐controlled studyPatients  A total of 31 hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in 23 medical centres in four countries were studied.Interventions  Lutropin alfa 75 IU and follitropin alfa (75–225 IU), individually based on each patient's response as is consistent with usual medical practice.Measurements  Follicular development as defined by (i) at least one follicle ≥ 17 mm; (ii) preovulatory serum oestradiol level ≥ 109 pg/ml on the day of hCG administration; and (iii) midluteal phase P4 level ≥ 7·9 ng/ml. Pregnancy and over‐response leading to cycle cancellation were considered treatment successes. Pregnancy rates were assessed.Results  In a total of 54 cycles, 27 of 31 (87·1%) profoundly gonadotrophin‐deficient patients achieved follicular development within three cycles. Twenty of 27 patients (74·1%) who achieved follicular development and received hCG became pregnant; 16 (59·3%) continued to clinical pregnancy. One patient was hospitalized for severe ovarian hyperstimulation syndrome. Lutropin alfa was well tolerated.Conclusions  Coadministration of lutropin alfa 75 IU and follitropin alfa is safe and effective in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in a setting consistent with established medical practice.
Intrauterine growth standards in a developing country: a study of singleton livebirths at 28–42 weeks' gestation
Authors: Yunis Khalid A. , Khawaja Marwan , Beydoun Hind , Nassif Yolla , Khogali Mustafa , Tamim Hala ,   for the National Collaborative Perinatal Neonatal Network (NCPNN)
Published: August 2007

SummaryThis study aimed to develop fetal growth charts for the population of Greater Beirut, Lebanon, and compare them with previously established references. A survey of consecutive singleton livebirths admitted to normal nurseries and neonatal intensive care units of major hospitals, through the database project of the National Collaborative Perinatal Neonatal Network was used as a design. The study was conducted in nine major healthcare institutions serving the population of Beirut and its suburbs. A total of 24 767 singleton livebirths delivered between 28 and 42 weeks' gestation, with known data on gender, gestational age and anthropometric characteristics were recorded between 1 April 1999 and 31 March 2002. Growth charts were developed by plotting birthweight, length and head circumference percentiles against gestational age for male and female infants separately.Overall, 1348 (5.4%) pregnancies were delivered before 37 weeks' gestation and 1227 (4.9%) were low birthweight. Male infants were delivered slightly earlier than their female counterparts and the mean birthweight, length and head circumference were consistently higher in males. A total of 2247 (9.1%) infants were small‐for‐gestational‐age, with a male‐to‐female sex ratio of 1.03. Using previously established growth references that overestimated small‐for‐gestational‐age prevalence resulted in a greater proportion of false positives. The opposite was true for growth references that underestimated small‐for‐gestational‐age prevalence.The current growth charts present useful tools for assessing the general health status of newborn infants delivered at sea level in the urban areas of Lebanon and other East Mediterranean countries.
Effect of smoking and alcohol use during pregnancy on the occurrence of low birthweight in a farming region in South Africa
Authors: Jackson Debra J. , Batiste Elize , Rendall‐Mkosi Kirstie 
Published: August 2007

SummaryThe aim of this case–control study was to determine the risk factors for low birthweight in a farming region in South Africa, with particular attention to maternal alcohol use and smoking, both independently and in combination. Data collection was via structured postpartum interviews and review of antenatal and delivery records. The study setting was a regional referral hospital in a farming region. The study subjects were 200 infants with birthweight <2500g (cases) and 200 unmatched control infants of normal weight born during the same period as the cases. The outcome measure was low birthweight, i.e. infant birthweight <2500 g.Results showed the contribution of term low birthweight (as a measure of intrauterine growth retardation) to the total low‐birthweight incidence was almost 50%, indicating a substantial intrauterine growth retardation component in this population. Sociodemographic factors were not as predictive of low birthweight in this predominantly low income population. Smoking (adjusted OR 2.67, [95% CI 1.69, 4.20]) was the strongest life style‐related predictor of low birthweight. The alcohol low‐birthweight relationship was not significant when adjusted for smoking status (crude OR 2.15, [95% CI 1.37, 3.39]; adjusted OR 1.32, [95% CI 0.80, 2.20]). However, there appeared to be an interaction with combined use of these two substances during pregnancy that increased the risk of low birthweight (adjusted OR increased to 4.24, [95% CI 1.01, 17.76]. It is clear that life style factors such as smoking and drinking are contributing to the occurrence of low birthweight in the target region. A comprehensive health promotion programme needs to be implemented as an integral part of antenatal and family planning services, to reduce smoking and drinking by women in this community.
Growth outcomes for Australian Aboriginal children aged 11 years who were born with intrauterine growth retardation at term gestation
Authors: Sayers Susan , Mackerras Dorothy , Halpin Stephen , Singh Gurmeet 
Published: August 2007

SummaryLong‐term poor growth outcomes are well documented for intrauterine growth‐retarded babies (IUGR) in developed populations but there is a paucity of IUGR studies from disadvantaged populations where the greatest burden of IUGR occurs. Using a Northern Territory, Aboriginal cohort recruited at birth and followed up at a mean age of 11.4 years, comparisons of body size were made between children born at term who had been IUGR (n = 121) and those non‐IUGR (n = 341), and between those IUGR babies who had an appropriate ponderal index at birth (n = 72) and those with a low ponderal index (n = 49).Compared with non‐IUGR children, at follow‐up the IUGR children were almost 2 cm shorter (P = 0.10), 4 kg lighter (P < 0.01) and their head circumferences were almost a 1 cm smaller (P < 0.01). For the 121 term IUGR children, there were no significant differences in growth outcomes according to ponderal index measures at birth. These findings from an Australian Aboriginal sample are consistent with other comparisons of IUGR and non‐IUGR children in developed populations and suggest there may be no additional effects of IUGR on growth in childhood for disadvantaged populations similar to the Aboriginal population in the Northern Territory.