bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease
Authors: DAPERNO M. , SOSTEGNI R. , CANAPARO R. , SERPE L. , LAVAGNA A. , CROCELLÀ L. , CASTAGNO F. , VERNETTO A. , RIGAZIO C. , ERCOLE E. , D’ANTICO S. , PERA A. , ZARA G. , ROCCA R. 
Published: July 2009

Aliment Pharmacol Ther 30, 843–853SummaryBackground  Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5‐aminosalicylic acid, 5‐ASA) were described.Aim  To explore potential interactions between thiopurines and concomitant medications.Methods  A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S‐methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments.Results  Based on TPMT genetics, 95% IBD patients were wild‐type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7–29.5). No difference in TPMT activity was noted according to 5‐ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose‐effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co‐treated with 5‐ASA. In patients on active thiopurines also, 6‐TGN and 6‐MMP levels were evaluated and no significant difference was observed based on co‐medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016).Conclusions  Our data suggest the absence of significant interactions between thiopurines and 5‐ASA.
The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I study
Authors: BEAUMONT H. , SMOUT A. , AANEN M. , RYDHOLM H. , LEI A. , LEHMANN A. , RUTH M. , BOECKXSTAENS G. 
Published: July 2009

SummaryBackground  Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro‐oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required.Aim  To study the effect of AZD9343, a new selective GABAB receptor agonist, in healthy volunteers.Methods  A total of 27 subjects participated in a placebo‐controlled, randomized, two‐centre phase I study. Subjects underwent oesophageal manometry and pH‐metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days.Results  Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short‐lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate.Conclusions  Like baclofen, AZD9343 dose‐dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABAB agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted.
Postoperative development of aspirin resistance following coronary artery bypass
Authors: Kempfert J. , Anger K. , Rastan A. , Krabbes S. , Lehmann S. , Garbade J. , Sauer M. , Walther T. , Dhein S. , Mohr F. W. 
Published: July 2009

AbstractBackground  Aspirin therapy is known to substantially reduce mortality and the rate of ischaemic complications after coronary artery bypass grafting (CABG). Rates of perioperative aspirin resistance cited in the literature are up to 50% and could be influenced by extracorporeal circulation. Thus, aspirin resistance after CABG may have a significant clinical relevance.Materials and methods  In 59 patients undergoing CABG (on‐pump, off‐pump and combined procedures) aspirin resistance was investigated by arachidonic acid induced platelet aggregometry. Clinical relevance was assessed with 12‐month follow up.Results  Two types of resistance were observed: A preoperative resistance (despite oral aspirin or in vitro addition) was present in 29% and a postoperative developing type was seen in 49% resulting in only 22% of patients with a ‘normal’ reaction to aspirin. If patients were already on oral aspirin at admission, the rate of resistance was significantly reduced. Off‐pump surgery or pump‐times exceeding 120 min had no significant impact on resistance. During the 12‐month follow up (98·3%), there were three deaths (one stroke, one intestinal ischaemia, one mediastinitis after postoperative delirium) in patients with the perioperative resistance and none in other patients (P = 0·345). In none of those patients who presented with perioperative aspirin resistance, could this aspirin resistance be demonstrated when tested again after 12 months?Conclusions  Aspirin resistance is a transient phenomenon present in the majority of patients undergoing CABG. The three deaths in the resistant group may – although not statistically significant – indicate the possibility of a worse outcome for patients with aspirin resistance.
Recording and controlling the 4D light field in a microscope using microlens arrays
Authors: LEVOY M. , ZHANG Z. , MCDOWALL I. 
Published: July 2009

SummaryBy inserting a microlens array at the intermediate image plane of an optical microscope, one can record four‐dimensional light fields of biological specimens in a single snapshot. Unlike a conventional photograph, light fields permit manipulation of viewpoint and focus after the snapshot has been taken, subject to the resolution of the camera and the diffraction limit of the optical system. By inserting a second microlens array and video projector into the microscope's illumination path, one can control the incident light field falling on the specimen in a similar way. In this paper, we describe a prototype system we have built that implements these ideas, and we demonstrate two applications for it: simulating exotic microscope illumination modalities and correcting for optical aberrations digitally.
Overlapping nuclei segmentation based on Bayesian networks and stepwise merging strategy
Authors: JEONG M.‐R. , KO B.C. , NAM J.‐Y. 
Published: July 2009

SummaryThis paper presents a new approach to the segmentation of fluorescencein situhybridization images. First, to segment the cell nuclei from the background, a threshold is estimated using a Gaussian mixture model and maximizing the likelihood function of the grey values for the cell images. After the nuclei segmentation, the overlapping and isolated nuclei are classified to facilitate a more accurate nuclei analysis. To do this, the morphological features of the nuclei, such their compactness, smoothness and moments, are extracted from training data to generate three probability distribution functions that are then applied to a Bayesian network as evidence. Following the nuclei classification, the overlapping nuclei are segmented into isolated nuclei using an intensity gradient transform and watershed algorithm. A new stepwise merging strategy is also proposed to merge fragments into a major nucleus. Experimental results using fluorescencein situhybridization images confirm that the proposed system produced better segmentation results when compared to previous methods, because of the nuclei classification before separating the overlapping nuclei.
Imaging of endodontic biofilms by combined microscopy (FISH/cLSM – SEM)
Authors: SCHAUDINN C. , CARR G. , GORUR A. , JARAMILLO D. , COSTERTON J.W. , WEBSTER P. 
Published: July 2009

SummaryScanning electron microscopy is a useful imaging approach for the visualization of bacterial biofilms in their natural environments including their medical and dental habitats, because it allows for the exploration of large surfaces with excellent resolution of topographic features. Most biofilms in nature, however, are embedded in a thick layer of extracellular matrix that prevents a clear identification of individual bacteria by scanning electron microscopy. The use of confocal laser scanning microscopy on the other hand in combination with fluorescence in situ hybridization enables the visualization of matrix embedded bacteria in multi‐layered biofilms. In our study, fluorescence in situ hybridization/confocal laser scanning microscopy and scanning electron microscopy were applied to visualize bacterial biofilm in endodontic root canals. The resulting fluorescence in situ hybridization /confocal laser scanning microscopy and scanning electron microscopy and pictures were subsequently combined into one single image to provide high‐resolution information on the location of hidden bacteria. The combined use of scanning electron microscopy and fluorescence in situ hybridization / confocal laser scanning microscopy has the potential to overcome the limits of each single technique.
BRIEF REPORT: Association between MTHFR 677C‐T polymorphism and alcohol dependence according to Lesch and Babor typology
Authors: Benyamina Amine , Saffroy Raphaël , Blecha Lisa , Pham Patrick , Karila Laurent , Debuire Brigitte , Lemoine Antoinette , Reynaud Michel 
Published: July 2009

ABSTRACTPrior studies have associated 677C‐T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C‐T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C‐T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management.
CLC– a novel susceptibility gene for allergic rhinitis?
Authors: Bryborn M. , Halldén C. , Säll T. , Cardell L. O. 
Published: July 2009

To cite this article:Bryborn M, Halldén C, Säll T, Cardell LO.CLC– a novel susceptibility gene for allergic rhinitis?.Allergy2010;65: 220–228.AbstractBackground: Studies of the nasal lavage fluid proteome have previously identified proteins differently expressed in patients with symptomatic allergic rhinitis, e.g. S100A7, prolactin‐inducible protein (PIP), wingless‐type MMTV integration site family, member 2B (WNT2B), Charcot‐Leyden crystal protein (CLC) and palate lung nasal epithelial clone (PLUNC). The aim of the present study was to investigate if genetic variation associated with allergic rhinitis can be found in these genes.Methods: Peripheral blood was collected from 251 patients with birch and/or grass pollen‐induced allergic rhinitis and 386 nonatopic healthy controls. A total of 39 single nucleotide polymorphisms (SNPs) distributed over the genesPIP,WNT2B,CLCandPLUNCwere selected from dbSNP, genotyped and investigated for associations with allergic rhinitis. Twelve additional SNPs were subsequently analysed forCLC.Results: All 22 investigated SNPs inCLCwere polymorphic. Ten SNPs yielded significant differences between cases and controls with respect to genotype frequencies. Homozygotes for the minor allele were more common in allergic individuals compared to healthy controls. The minor alleles of these SNPs were all located on the same haplotype. Furthermore, homozygotes for the minor allele of two of the promoter SNPs had higher average scores for birch in skin prick test. In contrast, for seven SNPs within the gene, heterozygotes and homozygotes for the major allele had higher average scores for grass. None of the other three genes showed association.Conclusion: Genetic variation inCLCwas found to be associated with allergic rhinitis. The pattern of variation is compatible with a recessive inheritance model and the previously observed altered protein levels detected in patients with allergic rhinitis.
Iloprost inhalation redistributes pulmonary perfusion and decreases arterial oxygenation in healthy volunteers
Authors: RIMEIKA D. , SANCHEZ‐CRESPO A. , NYREN S. , LINDAHL S. G. E. , WIKLUND C. U. 
Published: July 2009

Background: Previous studies have shown that ventilation–perfusion matching is improved in the prone as compared with that in the supine position. Regional differences in the regulation of vascular tone may explain this. We have recently demonstrated higher production of nitric oxide in dorsal compared with ventral human lung tissue. The purpose of the present study was to investigate regional differences in actions by another vasoactive mediator, namely prostacyclin. The effects on gas exchange and regional pulmonary perfusion in different body positions were investigated at increased prostacyclin levels by inhalation of a synthetic prostacyclin analogue and decreased prostacyclin levels by unselective cyclooxygenase (COX) inhibition.Methods: In 19 volunteers, regional pulmonary perfusion in the prone and supine position was assessed by single photon emission computed tomography using 99mTc macro‐aggregated albumin before and after inhalation of iloprost, a stable prostacyclin analogue, or an intravenous infusion of a non‐selective COX inhibitor, diclofenac. In addition, gas distribution was assessed in seven subjects using 99mTc‐labelled ultra‐fine carbon particles before and after iloprost inhalation in the supine position.Results: Iloprost inhalation decreased arterial PaO2 in both prone (from 14.2±0.5 to 11.7±1.7 kPa, P<0.01) and supine (from 13.7±1.4 to 10.9±2.1 kPa, P<0.01) positions.Iloprost inhalation redistributed lung perfusion from non‐dependent to dependent lung regions in both prone and supine positions, while ventilation in the supine position was distributed in the opposite direction. No significant effects of non‐selective COX inhibition were found in this study.Conclusions: Iloprost inhalation decreases arterial oxygenation and results in a more gravity‐dependent pulmonary perfusion in both supine and prone positions in healthy humans.
Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms
Authors: BAINS R. , MOE M. C. , VINJE M. L. , BERG‐JOHNSEN J. 
Published: July 2009

Background and objectives: The mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca2+ concentration [Ca2+]i and the mitochondrial membrane potential (ΔΨm) was therefore compared in rat and human synaptosomes, and the changes were related to interventions in the electron transport chain.Methods: Synaptosomes from rat and human cerebral cortex were loaded with the fluorescent probes fura‐2 ([Ca2+]i) and JC‐1 (ΔΨm) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 μM. The effect on the electron transport chain was investigated by blocking complex V.Results: Sevoflurane and propofol decreased ΔΨm in rat synaptosomes in a dose‐dependent manner, and to the same extent by equipotent doses. Inhibition of complex V enhanced the depolarizing effect of sevoflurane 2 MAC, but not of propofol 100 μM. Neither sevoflurane nor propofol affected [Ca2+]i significantly. Sevoflurane and propofol decreased ΔΨm in human synaptosomes to the same extent as in the rat experiments.Conclusions: Sevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Ψm was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.
Relationship between stroke volume, cardiac output and filling of the heart during tilt
Authors: BUNDGAARD‐NIELSEN M. , SØRENSEN H. , DALSGAARD M. , RASMUSSEN P. , SECHER N. H. 
Published: July 2009

Background: Cardiac function curves are widely accepted to apply to humans but are not established for the entire range of filling of the heart that can be elicited during head‐up (HUT) and head‐down tilt (HDT), taken to represent minimal and maximal physiological filling of the heart, respectively. With the supine resting position as a reference, we assessed stroke volume (SV), cardiac output (CO) and filling of the heart during graded tilt to evaluate whether SV and CO are maintained during an assumed maximal physiological filling of the heart elicited by 90° HDT in healthy resting humans.Methods: In 26 subjects, central blood volume was manipulated with graded tilt from 60° HUT to 90° HDT. We measured SV, CO (Finometer®) and cardiac filling by echocardiography of the left ventricular end‐diastolic volume (LVEDV; n=12).Results: From supine rest to 60° HUT, SV and CO decreased 23 ml [confidence intervals (CI): 16–30; P<0.001; 23%] and 0.9 l/min (0.4–1.4; P<0.0001; 14%), respectively, but neither SV nor CO changed during HDT up to 70°. However, during 90° HDT, SV decreased 12 ml (CI: 6–19; P<0.0001; 12%), with an increase of 21 ml (9–33; P=0.002; 16%) in LVEDV because HR increased 3 bpm and CO decreased 0.5 l/min (ns).Conclusion: This study confirmed that SV and CO are maximal in resting, supine, healthy humans and decrease during HUT. However, 90° HDT was associated with increased LVEDV and induced a reduction in SV.
Effects of Chloroformic Extracts from Washed and Unwashed Papaya Seeds (Carica papaya) on the Sperm Concentration of Dogs
Authors: Ortega‐Pacheco A , Jiménez‐Coello M , Gutiérrez‐Blanco E , Acosta‐Viana KY , Guzmán‐Marín E , Zavala‐Sánchez MA , Montalvo‐Beltrán NE , Pérez‐Gutiérrez MS 
Published: July 2009

ContentsPapaya seeds (Carica papaya Linn) have been found to have a significant effect on sperm characteristics in some mammals, including humans, but no studies have investigated the effects on dogs. In the present study, a significant decrease in sperm concentration was observed in a group of dogs treated with extracts from washed papaya seeds, but no decrease was observed in the group of dogs treated with non‐washed seeds. An important effect of extract components from washed seeds such as fatty acids is probably involved in the reduction of sperm production because of Sertoli cell damage, as has been suggested for langur monkeys. Dilution of the active components in the non‐washed papaya seeds or interference with some of the components may reduce the expected effect on spermatogenesis. This first report on the effects of a chloroformic extract of papaya seeds in dogs suggests that an increased dose is necessary to achieve azoospermia.
Diagnostic spectrum of congenital hypothyroidism in Turkish children
Authors: Tamam Müge , Adalet Isık , Bakır Barış , Türkmen Cüneyt , Darendeliler Feyza , Baş Firdevs , Sanlı Yasemin , Kuyumcu Serkan 
Published: July 2009

AbstractBackground:  Congenital hypothyroidism (CH) is classified as transient or permanent. Transient CH can be treated with short‐term thyroxine replacement therapy or followed up without therapy, whereas lifelong thyroxine replacement is needed in permanent CH. Determination of the underlying etiology is essential for determination of follow‐up strategy. The purpose of the present study was therefore to assess the role of color Doppler ultrasonography (CDU) in etiologic diagnosis of CH together with radionuclide method and grayscale ultrasonography (GSU).Methods:  A total of 182 patients (83 female, 99 male) were evaluated. To determine etiologic diagnosis, the patients underwent a free T4 (fT4), thyroid‐stimulating hormone (TSH) and urinary iodine level measurement, and thyroid scintigraphy, perchlorate discharge test, CDU, and GSU.Results:  Fifty‐four patients had transient and 97 had permanent CH. Isolated hyperthyrotropinemia was diagnosed in 31 patients. Transient CH was due to iodine deficiency in 22 and excess iodine in 13 patients. In 97 patients with permanent CH, ectopia was present in 32 patients and agenesis of the thyroid gland was found in 22 patients, while 43 were diagnosed with dyshormonogenesis. In the ectopia group, GSU failed to detect ectopic tissues in all cases, whereas CDU was successful in determining the presence of ectopic thyroid in 20 cases. The sensitivity of CDU was 80% in determining ectopic tissue.Conclusion:  To determine etiologic diagnosis, radionuclide methods and sonographic modalities should be assessed together. The gold standard in the diagnosis of ectopic thyroid tissue is thyroid scintigraphy. CDU may be a major supportive diagnostic tool in the evaluation of ectopic thyroid gland.
Parental rights and medical decisions
Authors: DARE TIM 
Published: July 2009

SummaryMost countries grant parents rebuttable legal rights to make treatment decisions on behalf of their young children, creating a presumption in favor of parental rights. This article identifies and provides a preliminary assessment of a perhaps surprising variety of arguments for the presumption in favor of this parental right. The arguments considered include those flowing from ideas that parents are motivated by their child’s best interests; that they have privileged insight into their child’s preferences and capacities; that parental support has clinical significance and may be contingent upon respect for the presumption; that parents and families typically bear the burden of treatment decisions; that parents’ views often have a religious basis; that it would be improper to override parents’ wishes other than in conditions of complete certainty; and that parents have ‘natural authority’ over their children. It is unlikely that this is an exhaustive list of the arguments that could be offered in favor of the presumption, and the treatment in the paper is brief. Nevertheless, it is hoped that enough is said to suggest that it is harder to defend the presumption than we might have supposed.
Serine 209 resides within a putative p38(MAPK) consensus motif and regulates monoamine oxidase‐A activity
Authors: Cao Xia , Rui Lewei , Pennington Paul R. , Chlan‐Fourney Jennifer , Jiang Zhongjian , Wei Zelan , Li Xin‐Min , Edmondson Dale E. , Mousseau Darrell D. 
Published: July 2009

AbstractThe p38 mitogen‐activated protein kinase (MAPK) cascade as well as the enzyme monoamine oxidase‐A (MAO‐A) have both been associated with oxidative stress. We observed that the specific inhibition of the p38(MAPK) protein [using either a chemical inhibitor or a dominant‐negative p38(MAPK) clone] selectively induces MAO‐A activity and MAO‐A‐sensitive toxicity in several neuronal cell lines, including primary cortical neurons. Over‐expression of a constitutively active p38(MAPK) results in the phosphorylation of the MAO‐A protein and inhibition of MAO‐A activity. The MAO‐A(Ser209Glu) phosphomimic – bearing a targeted substitution within a putative p38(MAPK) consensus motif – is neither active nor neurotoxic. In contrast, the MAO‐A(Ser209Ala) variant (mimics dephosphorylation) does not associate with p38(MAPK), and is both very active and very toxic. Substitution of the homologous serine in the MAO‐B isoform, i.e. Ser200, with either Glu or Ala does not affect the catalytic activity of the corresponding over‐expressed proteins. These combined in vitro data strongly suggest a direct p38(MAPK)‐dependent inhibition of MAO‐A function. Based on published observations, this endogenous means of selectively regulating MAO‐A function could provide for an adaptive response to oxidative stress associated with disorders as diverse as depression, reperfusion/ischemia, and the early stages of Alzheimer’s disease.