bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects
Authors: Abdul Mohi Iqbal Mohammed , Jiang Xuemin , Williams Kenneth M. , Day Richard O. , Roufogalis Basil D. , Liauw Winston S. , Xu Hongmei , Matthias Anita , Lehmann Reginald P. , McLachlan Andrew J. 
Published: January 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Echinacea and policosanol are commonly used herbal medicines which may be ingested by patients receiving warfarin. Echinacea has been implicated in interacting with drug metabolizing enzymes and policosanol has been shown to decrease platelet aggregation. The potential interaction of echinacea and policosanol with warfarin has not previously been investigated. WHAT THIS STUDY ADDS • Concomitant treatments with echinacea increased the apparent clearance of S‐warfarin but did not have a clinically significant effect on warfarin pharmacodynamics in healthy subjects. Policosanol did not significantly affect warfarin pharmacokinetics or pharmacodynamics.AIMS This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects.METHODS This was an open‐label, randomized, three‐treatment, cross‐over, clinical trial in healthy male subjects (n= 12) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre‐treatment with each herbal medicine at recommended doses. Pharmacodynamic (INR, platelet activity) and pharmacokinetic (warfarin enantiomer concentrations) end points were evaluated.RESULTS The apparent clearance of (S)‐warfarin (90% CI of ratio; 1.01, 1.18) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinically significant change in INR (90% CI of AUC of INR; 0.91, 1.31). Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response. Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre‐treatment with the respective herbal medicines.CONCLUSION Echinacea significantly reduced plasma concentrations of S‐warfarin. However, neither echinacea nor policosanol significantly affected warfarin pharmacodynamics, platelet aggregation or baseline clotting status in healthy subjects.
Activity of aclidinium bromide, a new long‐acting muscarinic antagonist: a phase I study
Authors: Schelfhout Vanessa J. , Ferrer Pau , Jansat Josep Maria , Peris Francesc , Gil Esther Garcia , Pauwels Romain A. , Joos Guy F. 
Published: January 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Long‐acting inhaled bronchodilators are central in the symptomatic treatment of patients with chronic obstructive pulmonary disease (COPD). Until now the only long‐acting inhaled anticholinergic drug available in the clinic is tiotropium bromide.WHAT THIS STUDY ADDS• Aclidinium bromide is a new anticholinergic drug. In normal volunteers inhalation of this compound induced a long‐lasting bronchodilation and offered protection against the bronchoconstrictor effect of inhaled methacholine. Aclidinium bromide is now being developed as a long‐acting anticholinergic for patients with COPD.AIMAclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine‐induced bronchoconstriction.METHODSThis double‐blind, partial‐crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 µg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine).RESULTSAclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean ± SD AUC (l kPa−1 h) for placebo 24.4 ± 4.37, for 50 µg 29.0 ± 7.08, for 300 µg 31.2 ± 6.68 and for 600 µg 32.7 ± 7.95) (P< 0.009), except 50 µg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 µg compared with placebo at all assessments (Raw mean ± SD AUC (kPa s−1 l−1 h) for placebo 7.7 ± 3.46, for 300 µg 5.8 ± 2.33, for 600 µg 6.3 ± 3.11) (P< 0.04) except 600 µg at 24 h. Differences between aclidinium 300 and 600 µgvs.placebo in PC35 doubling concentration were significant at all assessments (mean ± SD AUC (mg ml−1 h) for placebo 100.0 ± 30.27, for 50 µg 117.2 ± 33.33, for 300 µg 168.9 ± 28.66 and for 600 µg 179.1 ± 15.73 (P< 0.0001). For all endpoints, there was a significant difference between aclidinium 50 µg and the higher doses (P< 0.0001). Aclidinium was not detected in plasma and was well tolerated.CONCLUSIONAclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long‐acting efficacy and providing a rationale for future studies in patients with COPD.
Evolutionary divergence of field and laboratory populations of Manduca sexta in response to host‐plant quality
Authors: DIAMOND SARAH E. , HAWKINS SARAH DYER , NIJHOUT H. FREDERIK , KINGSOLVER JOEL G. 
Published: January 2010

1. The tobacco hornworm, Manduca sexta, has been an important model system in insect biology for more than 50 years. In nature, M. sexta successfully utilises a range of host plants that vary in quality. The consequences of laboratory domestication and rearing on artificial diet for fitness of phytophagous insects on natural host plants have not been explored.2. We examine the evolutionary divergence of two domesticated laboratory populations and a field population (separated for more than 40 years, or > 250 laboratory generations) of M. sexta with respect to performance and fitness on two natural host plants: a typical host plant, tobacco (Nicotiana tabacum) and a novel host plant, devil's claw (Proboscidea louisianica).3. For both field and laboratory populations, rearing on devil's claw resulted in animals with lower survival, smaller final size, longer development time, and reduced size‐corrected fecundity than animals reared on tobacco. Reductions in some fitness components (survival and fecundity) were greater for the laboratory population animals than the field population animals.4. When reared on tobacco, the laboratory population animals had similar or larger pupal masses and slightly shorter development times than when reared on artificial diet, suggesting that laboratory domestication on artificial diet has not greatly affected the ability of M. sexta to perform well on a typical natural host plant.5. Although field and laboratory populations exhibited qualitatively similar responses to host‐plant quality, i.e. reduced performance on devil‘s claw, the magnitude of this reduction differed across populations, with the domesticated laboratory populations having greater reductions in performance than the field population. The use of domesticated populations as models for responses of field populations may therefore be more appropriate for considering environmental conditions that are relatively benign or near‐optimal, than when exploring responses to extreme or stressful conditions.
Comparative life‐history traits in a fig wasp community: implications for community structure
Authors: GHARA MAHUA , BORGES RENEE M. 
Published: January 2010

1. Whether life‐history traits can determine community composition and structure is an important question that has been well explored theoretically, but has received scant empirical attention. Life‐history traits of a seven‐member community of galler and parasitoid fig wasp species (Chalcidoidea), developing within the inflorescences (syconia) ofFicus racemosa(Moraceae) in India, were determined and used to examine community structure and ecology.2. Gallers were pro‐ovigenic (all eggs are mature upon adult emergence) whereas parasitoids were synovigenic (eggs mature progressively during adult lifespan). Initial egg load was correlated with body size for some species, and there was a trade‐off between egg number and egg size across all species. Although all species completed their development and left the syconium concurrently, they differed in their adult and pre‐adult lifespans. Providing sucrose solutions increased parasitoid lifespan but had no effect on the longevity of some galler species. While feeding regimes and body size affected longevity in most species, an interaction effect between these variables was detected for only one species.3. Life‐history traits of wasp species exhibited a continuum in relation to their arrival sequence at syconia for oviposition during syconium development, and therefore reflected their ecology. The largest number of eggs, smallest egg sizes, and shortest longevities were characteristic of the earliest‐arriving galling wasps at the smallest, immature syconia; the converse characterised the later‐arriving parasitoids at the larger, already parasitised syconia. Thus life history is an important correlate of community resource partitioning and can be used to understand community structure.4. This is the first comprehensive study of life‐history traits in a fig wasp community. The comparative approach revealed constraints and flexibility in trait evolution.
Discriminating between organic matter in soil from grass and forest by near‐infrared spectroscopy
Authors: Ertlen D. , Schwartz D. , Trautmann M. , Webster R. , Brunet D. 
Published: January 2010

The absorbance of near‐infrared (NIR) radiation by plants depends on the overtones of vibration, bending and stretching of the chemical bonds within their organic components. The wide variety of these bonds gives rise to characteristic NIR spectra, or ‘fingerprints’, of plant materials. Do these fingerprints remain in the soil when the plants decompose and allow discrimination between soils that have supported different types of vegetation? We have compared the NIR spectra of grassland soil with those of soil under forest in the Vosges mountains in France. Near‐infrared reflectances, R, from 370 samples of soil were recorded as A = log10(1/R) at wavelengths between 1100 and 2500 nm and averaged over 10‐nm intervals to give spectra each with 140 values. A canonical variate analysis (CVA) of the raw spectra discriminated well, but not perfectly, between grassland and forest soil, with Mahalanobis distance, D, of 4.87. Standardization along the spectra to remove effects of varied mineral composition achieved complete separation between the two sources with D = 9.81. Canonical variate analysis of first and second derivatives of the spectra distinguished the two groups even better, with D = 12.27 and D = 16.65, respectively.The results show much promise for inferring past vegetative cover from NIR spectra deriving from the organic matter in the soil. The next step will be to extend these studies to see how well we can distinguish other types of vegetation from such spectra.
Waterlogging and canopy interact to control species recruitment in floodplains
Authors: Kotowski Wiktor , Beauchard Olivier , Opdekamp Wout , Meire Patrick , Van Diggelen Rudy 
Published: January 2010

Summary 1. The extent to which seedling recruitment contributes to local functional diversity depends on the environmental filters operating in a plant community. Classical community assembly models assume that habitat constraints and competition act like hierarchical filters with habitat filtering as the dominant one. Alternative models assume a synergic interaction since responses to environmental stress and competition may impose physiological trade‐offs in plants. 2. River floodplains are an ideal system to test the relationship between habitat and competition filtering in community (re)assembly, as flooding causes changes in both habitat stress (waterlogging, resulting in anoxia and toxicity) and competition (dieback of vegetation) on one hand and acts as an effective seed dispersal vector on the other hand. 3. We conducted a mesocosm experiment on early community assembly from a pool of 34 floodplain species covering a wetness gradient. Seed mixtures were sown in a full factorial design with water level, canopy and mowing as controlling factors. We measured the biomass of all species after one growing season and determined germination and seedling growth traits, both outside (response to waterlogging/no waterlogging) and in a growth‐chamber (response to light/darkness). 4. Species recruitment was analysed in relation to the controlling factors and measured functional traits using co‐inertia analysis. Furthermore we analysed the effects of the controlling factors on several aspects of functional diversity. 5. There was no establishment in grass sward, unless mowing was applied. Species‐rich communities only developed when germination and early establishment phases occurred on waterlogged bare soil. High water level did not suppress establishment but reduced the total biomass and lowered inter‐specific competition. The effect of mowing on species richness depended upon the interplay between waterlogging and canopy. 6. Establishment success under canopy required seedling strategies to tolerate shade. The elimination of typical wetland specialists from oxic mesocosms was clearly an effect of their poorer and/or slower germination and lower competitive abilities in comparison to non‐wetland plants, leading to their disappearance in this low‐stress environment. 7. Our results indicate that single stress factors can enhance species richness and functional diversity through limiting competition but a synergic interaction of different stresses can lead to reduced richness.
Undervirilization in XY newborns may hide a 5α‐reductase deficiency: report of three new SRD5A2 gene mutations
Authors: Maimoun L. , Philibert P. , Cammas B. , Audran F. , Pienkowski C. , Kurtz F. , Heinrich C. , Cartigny M. , Sultan C. 
Published: January 2010

SummaryThe observation of ambiguous genitalia in the newborn signals a medical, surgical and psychological emergency. The most crucial decision will be the choice of sex assignment. Rapid and precise diagnosis is thus essential. In XY newborns with normal/high plasma testosterone (T), partial androgen insensitivity syndrome (PAIS) is usually the first diagnosis evoked, which implies an androgen receptor (AR) defect. The diagnosis of steroid‐5‐alpha‐reductase deficiency is rarely considered by the paediatrician. We report three new SRD5A2 gene mutations in four newborns from France, Morocco and Turkey. The newborns presented with ambiguous genitalia and normal plasma T values and the initial diagnosis\PAIS. In all four cases, normal sequences of the complete AR gene excluded this diagnosis and raised the hypothesis of 5α‐reductase deficiency. The entire coding region (5 exons) of the SRD5A2 gene was assessed by PCR and direct sequencing analysis. For patient 1, we identified a new homozygous 2bp deletion in exon 1 (c.122_123delAG). Patient 2 had a known homozygous mutation, p.G115D, in exon 2. New compound heterozygous mutations in exon 4 (p.A215V) and exon 5 (p.X255Q) were found in patient 3. Patient 4 presented a new substitution in exon 1 (p.S14R) associated with a known polymorphism (p.V89L). Our data confirm our previous experience and clearly demonstrate that a 5‐α reductase defect should be considered in all XY newborns with ambiguous genitalia and normal plasma T secretion, whatever their geographic area or ethnic group; moreover, this defect was not linked to specific phenotype. Early molecular diagnosis is indispensable for the crucial decision of the newborn’s sex of rearing.
Macrophage activity in semen is significantly correlated with sperm quality in infertile men
Authors: Tremellen K. , Tunc O. 
Published: January 2010

SummaryThe presence of leucocytes within semen has the potential to impair sperm function. Neutrophils and macrophages make up 95% of seminal leucocytes, with both having the ability to damage sperm via the generation of reactive oxygen species, proteases and the induction of apoptosis. Existing cytological techniques for quantifying leucocyte activity within semen (peroxidase, CD45) are less than ideal as they merely count the number of leucocytes, rather than assess their activity. Seminal plasma elastase effectively determines neutrophil activity, yet gives no insight into macrophage activity. Neopterin, a molecule released from activated macrophages, may be a useful marker for macrophage activity in the male reproductive tract. To examine this possibility a total of 63 asymptomatic subjects with male factor infertility and 11 fertile controls provided semen samples for measurement of various inflammatory markers. We were able to confirm for the first time that seminal plasma does indeed contain neopterin and that the levels of this macrophage activity marker are threefold higher in infertile than fertile men. Furthermore, seminal plasma neopterin concentration was significantly correlated with sperm oxidative stress, DNA fragmentation (TUNEL) and apoptosis (Annexin V), making it a useful marker of sperm quality. By contrast, seminal plasma elastase showed no correlation with any marker of sperm quality.
Characterizing the spatial distribution of giant pandas (Ailuropoda melanoleuca) in fragmented forest landscapes
Authors: Wang Tiejun , Ye Xinping , Skidmore Andrew K. , Toxopeus Albertus G. 
Published: January 2010

AbstractAim  To examine the effects of forest fragmentation on the distribution of the entire wild giant panda (Ailuropoda melanoleuca) population, and to propose a modelling approach for monitoring the spatial distribution and habitat of pandas at the landscape scale using Moderate Resolution Imaging Spectro‐radiometer (MODIS) enhanced vegetation index (EVI) time‐series data.Location  Five mountain ranges in south‐western China (Qinling, Minshan, Qionglai, Xiangling and Liangshan).Methods  Giant panda pseudo‐absence data were generated from data on panda occurrences obtained from the third national giant panda survey. To quantify the fragmentation of forests, 26 fragmentation metrics were derived from 16‐day composite MODIS 250‐m EVI multi‐temporal data and eight of these metrics were selected following factor analysis. The differences between panda presence and panda absence were examined by applying significance testing. A forward stepwise logistic regression was then applied to explore the relationship between panda distribution and forest fragmentation.Results  Forest patch size, edge density and patch aggregation were found to have significant roles in determining the distribution of pandas. Patches of dense forest occupied by giant pandas were significantly larger, closer together and more contiguous than patches where giant pandas were not recorded. Forest fragmentation is least in the Qinling Mountains, while the Xiangling and Liangshan regions have most fragmentation. Using the selected landscape metrics, the logistic regression model predicted the distribution of giant pandas with an overall accuracy of 72.5% (κ = 0.45). However, when a knowledge‐based control for elevation and slope was applied to the regression, the overall accuracy of the model improved to 77.6% (κ = 0.55).Main conclusions  Giant pandas appear sensitive to patch size and isolation effects associated with fragmentation of dense forest, implying that the design of effective conservation areas for wild giant pandas must include large and dense forest patches that are adjacent to other similar patches. The approach developed here is applicable for analysing the spatial distribution of the giant panda from multi‐temporal MODIS 250‐m EVI data and landscape metrics at the landscape scale.
Rhinitis: a complication to asthma
Authors: Hansen J. W. , Thomsen S. F. , Nolte H. , Backer V. 
Published: January 2010

To cite this article: Hansen JW, Thomsen SF, Nolte H, Backer V. Rhinitis: a complication to asthma. Allergy 2010; 65: 883–888.AbstractBackground:  Asthma and rhinitis often co‐occur, and this potentially increases the disease severity and impacts negatively on the quality of life. We studied disease severity, airway responsiveness, atopy, quality of life and treatment in subjects with both asthma and rhinitis compared to patients with asthma or rhinitis alone.Methods:  We examined 878 patients: 182 with asthma, 362 with rhinitis and 334 with both asthma and rhinitis. All had a clinical interview concerning severity of symptoms, treatment, and quality of life, a skin prick test, a lung function test and a bronchial provocation with methacholine.Results:  Patients with both asthma and rhinitis had less severe asthma based on the frequency of respiratory symptoms compared to patients with asthma alone (55%vs 66%P = 0.01). On the contrary, they were more airway responsive (P < 0.05) and had more perennial allergy (P < 0.001). Asthmatics had poor perception of the general health, independent of rhinitis (P < 0.001). No differences were found in asthma‐specific quality of life, whereas rhinitis‐specific quality of life was worse in those with both asthma and rhinitis compared to those with rhinitis alone (P < 0.01). Subjects with both diseases were undertreated in 85% of the cases.Conclusion:  We encourage that these observations be used in the evaluation and treatment of patients with asthma and rhinitis and that they contribute to the understanding of asthma and rhinitis as a uniform airways disease.
Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma
Authors: Scichilone N. , Battaglia S. , Sorino C. , Paglino G. , Martino L. , Paternò A. , Santagata R. , Spatafora M. , Nicolini G. , Bellia V. 
Published: January 2010

To cite this article: Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paternò A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy 2010; 65: 897–902.AbstractBackground:  Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta‐2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways.Aim:  To evaluate whether treatment with an extra‐fine inhaled combination provides additional effects vs a nonextra‐fine combination on airway function.Methods:  After a 1‐ to 4‐week run‐in period, patients with asthma were randomized to a double blind, double dummy, 12‐week treatment with either extra‐fine beclomethasone/formoterol (BDP/F) 400/24 μg daily or fluticasone propionate/salmeterol (FP/S) 500/100 μg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed.Results:  Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV1) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV1 in both BDP/F and FP/S groups (0.37 ± 0.13 l and 0.36 ± 0.12 l, respectively). PD20FEV1 Mch improved significantly from 90.42 (±30.08) μg to 432.41 (±122.71) μg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN2 test parameters.Conclusion:  The findings of this pilot study suggest that an extra‐fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN2 tests.