bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications
Authors: Miyatake Shin , Ichiyama Hiroki , Kondo Eiji , Yasuda Kazunori 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Efficacy of oral administration of nonsteroidal anti‐inflammatory drugs (NSAIDs) on the synovial and muscle tissues has been established.• However, efficacy of percutaneous administration of NSAIDs has not sufficiently been established because of lack of scientific data. WHAT THIS STUDY ADDS • The diclofenac concentration in the muscle and fat at 12 h after topical application with a pair of tapes containing a total of 30 mg diclofenac sodium was significantly higher than that after oral application of a capsule containing 37.5 mg diclofenac sodium, whereas there was no significant difference in the plasma diclofenac level between the two applications.• The concentration in the synovial membrane and fluid was significantly lower after topical application than after oral application.AIMSTo compare tissue concentrations of diclofenac resulting from topical and oral applications of diclofenac according to clinically recommended prescriptions.METHODSDiclofenac sodium was applied to 14 subjects (four male and 10 female), who were scheduled to undergo knee arthroplasty due to osteoarthritis, according to the oral or topical prescription (a capsule containing 37.5 mg diclofenac sodium or two tapes containing a total of 30 mg diclofenac sodium). At 12 h after prescription, the diclofenac concentration in the fat, muscle and synovial tissues was measured with liquid chromatography and mass analysis.RESULTSThe diclofenac concentration in the muscle was significantly higher (P = 0.0196) after topical application (average 9.29 ng ml−1) than after oral application (0.66 ng ml−1), whereas there was no significant difference in the plasma diclofenac level (4.70 and 6.63 ng ml−1) between the two applications. The concentration in the synovial membrane was significantly (P = 0.0181) lower in the topical application (4.99 ng ml−1) than in the oral application (15.07 ng ml−1).CONCLUSIONSWhereas plasma levels resulting from topical and oral applications of diclofenac according to clinically recommended prescriptions were comparable, concentration levels in the muscle and synovial tissues were different.
Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia
Authors: Paulsson Kajsa , An Qian , Moorman Anthony V. , Parker Helen , Molloy Gael , Davies Teresa , Griffiths Mike , Ross Fiona M. , Irving Julie , Harrison Christine J. , Young Bryan D. , Strefford Jon C. 
Published: December 2008

SummaryPromoter methylation is a common phenomenon in tumours, including haematological malignancies. In the present study, we investigated 36 cases of high hyperdiploid (>50 chromosomes) acute lymphoblastic leukaemia (ALL) with methylation‐specific multiplex ligase‐dependent probe amplification to determine the extent of aberrant methylation in this subgroup. The analysis, which comprised the promoters of 35 known tumour suppressor genes, showed that 16 genes displayed abnormal methylation in at least one case each. The highest number of methylated gene promoters seen in a single case was thirteen, with all but one case displaying methylation for at least one gene. The most common targets were ESR1 (29/36 cases; 81%), CADM1 (IGSF4, TSLC1; 25/36 cases; 69%), FHIT (24/36 cases; 67%) and RARB (22/36 cases; 61%). Interestingly, quantitative reverse transcription‐polymerase chain reaction showed that although methylation of the CADM1 and RARB promoters resulted in the expected pattern of downregulation of the respective genes, no difference could be detected in FHIT expression between methylation‐positive and ‐negative cases. Furthermore, TIMP3 was not expressed regardless of methylation status, showing that aberrant methylation does not always lead to gene expression changes. Taken together, our findings suggest that aberrant methylation of tumour suppressor gene promoters is a common phenomenon in high hyperdiploid ALL.
Bone mineral density and bone turnover in Romanian children and young adults with classical 21‐hydroxylase deficiency are influenced by glucocorticoid replacement therapy
Authors: Zimmermann Anca , Sido Paula Grigorescu , Schulze Egbert , Al Khzouz Camelia , Lazea Cecilia , Coldea Cristina , Weber Matthias M. 
Published: December 2008

SummaryObjective  It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21‐hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients.Design  Cross‐sectional study.Measurements  Twenty‐eight Caucasian patients with classical 21‐hydroxylase deficiency (5–39 years). Clinical parameters, hormonal status, osteocalcin (OC), C‐terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z‐scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were calculated for the entire treatment period.Results  Patients with severely reduced BMD Z‐scores (≤–2·5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P = 0·003/P = 0·026) and normal Z‐scores (> –1 SD) (P = 0·005/P = 0·011). Mean hydrocortisone equivalent doses > 20 mg/m2/day led to significantly lower lumbar BMD Z‐scores (–2·16 ± 1·4 SD) vs. doses ≤ 20 mg/m2/day (–0·59 ± 1·25 SD) (P = 0·008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86·45 ± 37·45 ng/ml) and CTX (1·45 ± 0·43 ng/ml) were significantly increased compared to an age‐ and sex‐matched control group in patients with active growth; only CTX was slightly increased in patients who completed growth.Conclusions  High cumulative and mean glucocorticoid doses negatively impact on BMD in children and young adults with classical 21‐hydroxylase deficiency. Substitution therapy should be adapted particularly at this life period to prevent bone loss.
Coadministration of active phthalates results in disruption of foetal testicular function in rats
Authors: Martino‐Andrade Anderson J. , Morais Rosana N. , Botelho Giuliana G. K. , Muller Graziela , Grande Simone W. , Carpentieri Giovanna B. , Leão Gabriel M. C. , Dalsenter Paulo R. 
Published: December 2008

SummaryThe reproductive effects of the coadministration of di‐2‐(ethylhexyl) phthalate (DEHP) and di‐butyl phthalate (DBP) were studied in both foetal and adult male rat offspring exposed in utero. Pregnant Wistar rats were treated by oral gavage from gestation day 13 to 21 with vehicle control, 150 mg DEHP/kg body weight (bw)/day, 100 mg DBP/kg bw/ or a combination of the two compounds (DEHP 150 + DBP 100 mg/kg bw/day). An additional group of dams received 500 mg DBP/kg bw/day. A significant decrease in foetal testicular testosterone levels was observed in animals exposed to 500 mg DBP/kg/day or the phthalate mixture. Similarly, histological analysis of the foetal testis revealed that the coadministration of DEHP and DBP was able to increase the diameter of seminiferous cords and induce gonocyte multinucleation at doses that individually had no significant effects on these variables. However, in the phthalate mixture group, no significant changes were observed in anogenital distance and nipple retention, variables that are used to indicate possible anti‐androgenic effects. Also, the adult endpoints investigated, that included reproductive organ weights and the number of spermatids per testis, were unaffected by any treatment regimen. Overall, coadministration of DEHP and DBP in utero significantly reduced testicular testosterone levels and resulted in misshapen seminiferous cords and gonocyte multinucleation in rat foetal testis. Our results also confirm that these foetal endpoints seem to be the most sensitive markers of prenatal phthalate exposure.
The spatial distribution of vegetation types in the Serengeti ecosystem: the influence of rainfall and topographic relief on vegetation patch characteristics
Authors: Reed D. N. , Anderson T. M. , Dempewolf J. , Metzger K. , Serneels S. 
Published: December 2008

AbstractAim The aim of this study is to introduce a structural vegetation map of the Serengeti ecosystem and, based on the map, to test the relative influences of landscape factors on the spatial heterogeneity of vegetation in the ecosystem.Location This study was conducted in the Serengeti–Maasai Mara ecosystem in northern Tanzania and southern Kenya, between 34° and 36° E longitude, and 1° and 2° S latitude.Methods The vegetation map was produced from satellite imagery using data from over 800 ground‐truthing points. Spatial characteristics of the vegetation were analysed in the resulting map using thefragstatssoftware package. Average patch area and nearest neighbour distance (NND) were determined for grassland, shrubland and woodland vegetation types. The heterogeneity of vegetation types was estimated with Simpson’s diversity index (D). Structural equation modelling (SEM) was used to explore the relationships between the spatial characteristics of vegetation and three predictor variables: annual rainfall, coefficient of variation (CV) in annual rainfall, and topographic moisture index (TMI).Results A vegetation map is presented along with a detailed summary of the distribution of land‐cover classes and spatial heterogeneity in the ecosystem. Significant relationships were found between vegetation diversity (D) and TMI, and also betweenDand average rainfall. The average area of grassland patches showed significant relationships with average rainfall, with rainfall CV and with TMI. Grassland NND was positively associated with average rainfall. Woodland patch area showed a unimodal response to average rainfall and a negative linear association with TMI. Woodland NND showed a U‐shaped association with annual rainfall and a weaker positive linear association with TMI. An acceptable model that explained variation in shrubland patch characteristics could not be identified.Main conclusions The vegetation map and analysis thereof resulted in three significant causal explanatory models that demonstrate that both rainfall and topography are important contributors to the distribution of woodlands and grasslands in the Serengeti. These findings further indicate that changes in patch characteristics have a complex interaction with rainfall and with topography. Our results are concordant with recent studies suggesting that percent woody cover in African savannas receiving less thanc.650 mm year−1is bounded by average annual rainfall.
Differential permeability of rivers to raccoon gene flow corresponds to rabies incidence in Ontario, Canada
Authors: CULLINGHAM CATHERINE I. , KYLE CHRISTOPHER J. , POND BRUCE A. , REES ERIN E. , WHITE BRADLEY N. 
Published: December 2008

AbstractThe correlation of landscape features with genetic discontinuities reveals barriers to dispersal that can contribute to understanding present and future spread of wildlife diseases. This knowledge can then be used for targeting control efforts. The impact of natural barriers on raccoon dispersal was assessed through genetic analysis of samples from two regions, Niagara (N = 666) and St. Lawrence (N = 802). These areas are transected by major rivers and are at the northern front of a raccoon rabies epizootic. Genetic clusters were identified in each region using Bayesian clustering algorithms. In the Niagara region, two clusters were identified corresponding to either side of the Niagara River. For the St. Lawrence region, spatially congruent clusters were not identified, despite the presence of the intervening St. Lawrence River. These genetic data are consistent with raccoon rabies incidence data where rabies has been detected across the St. Lawrence River in Ontario while no cases have been detected in Ontario across the Niagara River. This is despite expectations of rabies incidence in Niagara before the St. Lawrence based on the progression of rabies from New York. The results from the two regions suggest different permeabilities to raccoons between New York and Ontario that may be attributed to the rivers. However, other factors have also been explored that could contribute to this difference between these study sites including the shape of the landscape and resource distribution.
Y not introgress? Insights into the genetics of speciation in European rabbits
Authors: PAYSEUR BRET A. 
Published: December 2008

AbstractHybridization between genetically divergent populations is common in nature. By comparing the rate of gene flow throughout the genome, loci that impede genetic mixing, and therefore underlie reproductive isolation, can be identified, providing key insights into the process of speciation. In a previous issue of Molecular Ecology, Geraldes et al. (2008) report the geographical distribution of Y chromosome lineages in wild populations of rabbits from across the Iberian Peninsula and southern France. Y chromosomes showed a high level of differentiation between rabbit subspecies on either side of a hybrid zone, despite clear evidence for gene flow at other loci. This provocative result suggests a role for the Y chromosome in reproductive isolation, and adds to a growing list of nascent species with mosaic patterns of differentiation across their genomes.
Limestone pseudoconglomerates in the Late Cambrian Gushan and Chaomidian Formations (Shandong Province, China): soft‐sediment deformation induced by storm‐wave loading
Authors: CHEN JITAO , CHOUGH SUNG KWUN , CHUN SEUNG SOO , HAN ZUOZHEN 
Published: December 2008

AbstractThis paper focuses on the formative processes of limestone pseudoconglomerates in the Gushan and Chaomidian Formations (Late Cambrian) of the North China Platform, Shandong Province, China. The Gushan and Chaomidian Formations consist mainly of limestone and shale (marlstone) interlayers, wackestone to packstone, grainstone and microbialite as well as numerous limestone conglomerates. Seventy‐three beds of limestone pseudoconglomerate in the Gushan and Chaomidian Formations were analysed based on clast and matrix compositions, internal fabric, sedimentary structures and bed geometry. These pseudoconglomerates are characterized by oligomictic to polymictic limestone clasts of various shapes (i.e. flat to undulatory disc, blade and sheet), marlstone and/or grainstone matrix and various internal fabrics (i.e. intact, thrusted, edgewise and disorganized), as well as transitional boundaries. Limestone pseudoconglomerates formed as a result of soft‐sediment deformation of carbonate and argillaceous interlayers at a shallow burial depth. Differential early cementation of carbonate and argillaceous sediments provided the requisite conditions for the formation of pseudoconglomerates. Initial deformation (i.e. burial fragmentation, liquefaction and injection) and subsequent mobilization and disruption of fragmented clasts are two important processes for the formation of pseudoconglomerates. Burial fragmentation resulted from mechanical rupture of cohesive carbonate mud, whereas subsequent mobilization of fragmented clasts was due to the injection of fluid materials (liquefied carbonate sand and water‐saturated argillaceous mud) under increased stress. Storm‐wave loading was the most probable deformation mechanism, as an external triggering force. Subsequent re‐orientation and rounding of clasts were probably prolonged under normal compactional stress. Eventually, disrupted clasts, along with matrix materials, were transformed into pseudoconglomerates by progressive lithification. Soft‐sediment deformation is prevalent in alternate layers of limestone and mud(marl)stone and/or grainstone, regardless of their depositional environments.
Aseismic controls on in situ soft‐sediment deformation processes and products in submarine slope deposits of the Karoo Basin, South Africa
Authors: OLIVEIRA CARLOS M. M. , HODGSON DAVID M. , FLINT STEPHEN S. 
Published: December 2008

AbstractIntervals of soft‐sediment deformation features, including vertical fluid escape and load structures, are common and well‐exposed in Permian lower slope deposits of the Tanqua Depocentre, Karoo Basin. The structures mainly comprise elongated flames and load structures associated with ruptured sandstones and structureless siltstones, observed over a range of scales. The presence of an upper structureless siltstone layer linked to the flames, interpreted as a product of the debouching of fine‐grained material transported through the flame onto the palaeo‐seabed, together with the drag and upward folding of lower sandstone layers is evidence that the flames were formed in situ by upward movement of sediment‐rich fluids. Flames are oriented parallel to the deep‐water palaeoslope in lateral splay deposits between two major slope channel complexes. Statistical correlation and regression analyses of 180 flame structures from seven stratigraphic intervals suggest a common mechanism for the deformation and indicate the importance of fluidization as a deformation mechanism. Importantly, deformation occurred in an instantaneous and synchronous manner. Liquefaction and fluidization were triggered by incremental movement of sediment over steeper local gradients that were generated by deposition of a lateral splay on an inherited local north‐west‐facing slope. Seismic activity is not invoked as a trigger mechanism because of the restricted spatial occurrence of these features and the lack of indications of earthquakes during the time of deposition of the deep‐water succession. The driving mechanisms that resulted in the final configuration of the soft‐sediment deformation structures involved a combination of vertical shear stress caused by fluidization, development of an inverse density gradient and a downslope component of force associated with the local slope. Ground‐penetrating radar profiles confirm the overall north‐east orientation of the flame structures and provide a basis for recognition of potential larger‐scale examples of flames in seismic reflection data sets.
Histamine N‐methyltransferase 939A>G polymorphism affects mRNA stability in patients with acetylsalicylic acid‐intolerant chronic urticaria
Authors: Kim S.‐H. , Kang Y.‐M. , Kim S.‐H. , Cho B.‐Y. , Ye Y.‐M. , Hur G.‐Y. , Park H.‐S. 
Published: December 2008

Background:  Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N‐methyltransferase (HNMT).Objective:  To investigate the functional variability of HNMT gene in relation to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU).Methods:  Two single‐nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3′‐untranslated region polymorphism (3′‐UTR) was assessed using the pEGFP‐HNMT 3′‐UTR reporter construct to examine mRNA stability and fluorescence‐tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC‐1) transfected with the pHNMT CDS‐3′‐UTR construct and in the patients’ red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined.Results:  The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC‐1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils.Conclusion:  The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.
Topical glucocorticoids downregulate COX‐1 positive cells in nasal polyps
Authors: Ebbens F. A. , Maldonado M. , De Groot E. J. J. , Alobid I. , Van Drunen C. M. , Picado C. , Fokkens W. J. , Mullol J. 
Published: December 2008

Background: Influx of inflammatory cells is one of the hallmarks of nasal polyposis. As glucocorticoids (GC) are known to exhibit strong anti‐inflammatory effects, these drugs are frequently used in the treatment of the disease. Part of the anti‐inflammatory effects of GC is attributed to their interference with prostanoid synthesis. As cyclooxygenases (COX) are key enzymes in the synthesis of both pro‐ (COX‐1, COX‐2) and anti‐inflammatory prostanoids (COX‐2), we investigated the role of topical GC on COX‐1, COX‐2 and inflammatory markers in nasal polyps (NP).Methods: Immunohistochemical analysis of inflammatory markers (CD68, CD117, MBP, elastase, IgE, BB‐1, IL‐4, IL‐5 and IL‐6), COX‐1 and COX‐2 was performed on normal nasal mucosa (NM) (n = 18), non‐GC treated NP (n = 27) and topical GC treated NP (n = 12). NP groups were matched for allergy, asthma and ASA intolerance.Results: Increased numbers of eosinophils, IL‐5+ cells and IgE+ cells and decreased numbers of mastcells are striking features of NP inflammation (P < 0.05). In addition, increased numbers of COX‐1+ cells are observed in NP epithelium compared to NM (P < 0.05).Conclusion: Topical GC significantly reduce the number of COX‐1+ NP cells (P < 0.05), but have no significant effect on COX‐2+ NP cells. No significant reduction in the number of eosinophils is observed for GC treated NP. The number of IL‐5+ cells is however increased significantly upon GC treatment (P < 0.05).
Reproductive Maturation in the Male Eurasian Lynx (Lynx lynx): A Study on 55 Reproductive Organs Collected from Carcasses During 2002–2005
Authors: Axnér E , Uhlhorn H , Ågren E , Mörner T 
Published: December 2008

ContentsData on reproductive physiology from the Eu rasian lynx (Lynx lynx) are still scarce. The lynx is protected under Swedish hunting legislation. All lynx that are found dead or that are culled at hunting are to be sent to the Swedish National Veterinary Institute. In this study, we examined reproductive organs from 55 male lynx collected during the years 2002–2005. Age, body weight, testicular weight and volume, production of spermatozoa, and sperm viability were evaluated. The majority of the animals (39) had been killed in February and March, which is during the hunting season. The ages varied between 6 months and 17 years, body weight between 3.6 and 25.5 kg, and mean testes weight between 0.16 and 3.16 g. The gonadosomatic index was low compared with other species (approximately 0.02% in mature males). Mean testes weight differed significantly between males <12 months of age and all other age groups but did not differ between males of 18–23 months and older males. Spermatozoa could be collected but had lost most of their viability. Seven of 10 males of 18–23 months were fertile, as defined by the production of spermatozoa while no males ≤15 months of age were fertile. Adherence of the prepuce to the penis and absence of penile spines were associated with immaturity. The results indicate that most males are fertile during the reproductive season of their second year.