bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiplatelet drug interactions
Authors: Mackenzie I. S. , Coughtrie M. W. H. , MacDonald T. M. , Wei L. 
Published: November 2010

Abstract.  Mackenzie IS, Coughtrie MWH, MacDonald TM, Wei L. (Medicines Monitoring Unit (MEMO); and Centre for Oncology & Molecular Medicine, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School; Dundee, UK). Antiplatelet drug interactions (Review‐Symposium). J Intern Med 2010; 268: 516–529.Both laboratory studies in healthy volunteers and clinical studies have suggested adverse interactions between antiplatelet drugs and other commonly used medications. Interactions described include those between aspirin and ibuprofen, aspirin and other nonsteroidal anti‐inflammatory drugs (NSAIDs), and the thienopyridine, clopidogrel, and drugs inhibiting CYP2C19, notably the proton pump inhibitors (PPI) omeprazole and esomeprazole. Other interactions between thienopyridines and CYP3A4/5 have also been reported for statins and calcium channel blockers. The ibuprofen/aspirin interaction is thought to be caused by ibuprofen blocking the access of aspirin to platelet cyclo‐oxygenase. The thienopyridine interactions are caused by inhibition of microsomal enzymes that metabolize these pro‐drugs to their active metabolites. We review the evidence for these interactions, assess their clinical importance and suggest strategies of how to deal with them in clinical practice. We conclude that ibuprofen is likely to interact with aspirin and reduce its anti‐platelet action particularly in those patients who take ibuprofen chronically. This interaction is of greater relevance to those patients at high cardiovascular risk. A sensible strategy is to advise users of aspirin to avoid chronic ibuprofen or to ingest aspirin at least 2 h prior to ibuprofen. Clearly the use of NSAIDs that do not interact in this way is preferred. For the clopidogrel CYP2C19 and CYP3A4/5 interactions, there is good evidence that these interactions occur. However, there is less good evidence to support the clinical importance of these interactions. Again, a reasonable strategy is to avoid the chronic use of drugs that inhibit CYP2C19, notably PPIs, in subjects taking clopidogrel and use high dose H2 antagonists instead. Finally, anti‐platelet agents probably interact with other drugs that affect platelet function such as selective serotonin reuptake inhibitors, and clinicians should probably judge patients taking such combination therapies as at high risk for bleeding.
Drug–drug interactions in the treatment of HIV infection: focus on pharmacokinetic enhancement through CYP3A inhibition
Authors: Josephson F. 
Published: November 2010

Abstract.  Josephson F. (Medical Products Agency, Uppsala, Sweden). Drug–drug interactions in the treatment of HIV infection: focus on pharmacokinetic enhancement through CYP3A inhibition (Review‐Symposium). J Intern Med 2010; 268: 530–539.The aim of this review is to discuss the effect of pharmacokinetic drug–drug interactions (DDIs) in the antiretroviral treatment of HIV infection. In particular, but not exclusively, DDIs due to the cytochrome P450 3A (CYP3A) inhibitor ritonavir, which is used to increase antiretroviral drug exposure – a technique known as pharmacokinetic enhancement or ‘ritonavir boosting’– will be reviewed. The emphasis here will be on the treatment of important co‐morbidities common in patients with HIV, including dyslipidaemia, hypertension, tuberculosis and opiate dependence, as well as on the potentially life‐threatening interaction between ritonavir and inhalational steroids, and on the effect of acid‐reducing agents on some antiretroviral drugs. Finally, further developments with regard to the use of CYP3A‐blocking agents to augment the efficacy of antiviral therapy will be discussed.
Contactless determination of nuclear compressibility using 3D image‐ and model‐based analysis of drug‐induced cellular deformation
Authors: GLADILIN E. , SCHULZ M. , KAPPEL C. , EILS R. 
Published: November 2010

SummaryMechanical properties of the chromatin‐bearing nucleus in normal and pathological cells are of general interest for epigenetics and medicine. Conventional techniques for quantitative measurements of material properties of cellular matter are based on application of controlled forces onto the cellular or nuclear boundary and do not allow probing intracellular structures that are not directly accessible for physical contact inside the living cell. In this work, we present a novel approach for contactless determination of the nuclear compressibility (i.e. the Poisson's ratio ν) in living cells by means of image‐ and model‐based analysis of drug‐induced cell deformation. The Poisson's ratio of the HeLa cell nucleus is determined from time‐series of 3D images as a parameter of constitutive model that minimizes the dissimilarity between the numerically predicted and experimentally observed images.
Transcriptomic response of red grouse to gastro‐intestinal nematode parasites and testosterone: implications for population dynamics
Authors: WEBSTER L. M. I. , PATERSON S. , MOUGEOT F. , MARTINEZ‐PADILLA J. , PIERTNEY S. B. 
Published: November 2010

AbstractA central issue in ecology is in understanding the relative influences of intrinsic and extrinsic effects on population regulation. Previous studies on the cyclic population dynamics of red grouse (Lagopus lagopus scoticus) have emphasized the destabilizing effects of either nematode parasites or territorial behaviour and aggression. The potential interacting effects of these processes, mediated through density‐dependent, environmentally induced alterations of host immunocompetence influencing susceptibility to parasites have not been considered. Male red grouse at high density are more aggressive, associated with increased testosterone, which potentially could lead to reduced immunocompetence at a stage when parasites are most prevalent. This could depress individual condition, breeding performance and survival and thus drive or contribute to overall reductions in population size. Here, we characterize the transcriptomic response of grouse to nematode parasite infection and investigate how this is subsequently affected by testosterone, using a microarray approach contrasting red grouse with high and low parasite load at both high and low testosterone titre. A suite of 52 transcripts showed a significant level of up‐regulation to either chronic parasite load or experimental parasite infection. Of these, 51 (98%) showed a reduced level of expression under conditions of high parasite load and high testosterone. The genes up‐regulated by parasites and then down‐regulated at high testosterone titre were not necessarily associated with immune response, as might be intuitively expected. The results are discussed in relation to the fitness and condition of individual red grouse and factors influencing the regulation of abundance in natural populations.
Dangerous weapons: a cautionary tale of CRISPR defence
Authors: Dyall‐Smith Mike 
Published: November 2010

SummaryThe Cas/CRISPR system of prokaryotes is a recently recognized defence system that protects cells from invasion by foreign nucleic acids, such as plasmids or bacteriophages. Using the archaeon Sulfolobus, Gudbergsdottir et al. have demonstrated that when foreign DNA is both a target of the CRISPR system and also carries a gene that is essential for cell growth, surviving cells display mutations in the CRISPR system that eliminate the target directed spacer. This simulates natural scenarios where the invading DNA cannot be readily destroyed, such as a temperate bacteriophage that manages to evade CRISPR attack and integrate into the genome, so becoming ‘self’. CRISPR deletions ranged from precise removal of a single spacer up to elimination of an entire CRISPR array but the mechanism involved is not understood. Another surprising feature was that from one to two base mutations in the same target protospacer did not affect recognition by the Sulfolobus CRISPR system, something unexpected from studies in bacteria where spacer and target protospacer must match exactly. This study shows that even though the CRISPR system is a powerful weapon it can also be a dangerous one for the cell that carries it.
Secretion of early and late substrates of the type III secretion system from Xanthomonas is controlled by HpaC and the C‐terminal domain of HrcU
Authors: Lorenz Christian , Büttner Daniela 
Published: November 2010

SummaryThe plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria utilizes a type III secretion (T3S) system to inject effector proteins into eukaryotic cells. T3S substrate specificity is controlled by HpaC, which promotes secretion of translocon and effector proteins but prevents efficient secretion of the early substrate HrpB2. HpaC and HrpB2 interact with the C‐terminal domain (HrcUC) of the FlhB/YscU homologue HrcU. Here, we provide experimental evidence that HrcU is proteolytically cleaved at the conserved NPTH motif, which is required for binding of both HpaC and HrpB2 to HrcUC. The results of mutant studies showed that cleavage of HrcU contributes to pathogenicity and secretion of late substrates but is dispensable for secretion of HrpB2, which is presumably secreted prior to HrcU cleavage. The introduction of a point mutation (Y318D) into HrcUC activated secretion of late substrates in the absence of HpaC and suppressed the hpaC mutant phenotype. However, secretion of HrpB2 was unaffected by HrcUY318D, suggesting that the export of early and late substrates is controlled by independent mechanisms that can be uncoupled. As HrcUY318D did not interact with HrpB2 and HpaC, we propose that the substrate specificity switch leads to the release of HrcUC‐bound HrpB2 and HpaC.
Making ends meet in mycobacteria
Authors: Warner Digby F. , Mizrahi Valerie 
Published: November 2010

SummaryGenotoxic agents from endogenous and exogenous sources cause double‐strand breaks (DSBs) in chromosomal DNA. Given the threat these lesions pose to viability, it is not surprising that multiple, conserved mechanisms exist for their detection, processing and repair. Previous studies have established both functional non‐homologous end‐joining (NHEJ) and homologous recombination (HR) systems in mycobacteria. However, relative pathway utilization in these organisms, which include the major human pathogen Mycobacterium tuberculosis, remains unclear. In this issue, Glickman and colleagues describe an elegant assay to distinguish DSB repair outcomes through simple phenotypic screening. By applying their novel reporter system to a panel of repair pathway mutants, they identify an unexpected role for single‐strand annealing (SSA) in the related non‐pathogen, Mycobacterium smegmatis. As such, these results expand the mycobacterial DSB repair pathway complement to three mechanisms that are distinguishable by their differential requirements for the DSB‐resecting, helicase–nuclease machines, AdnAB and RecBCD. Notably, in an unexpected departure from classical models, they establish that mycobacterial RecBCD is a dedicated SSA nuclease, while AdnAB is required for RecA‐dependent HR. Here, we consider the implications of their observations, which include the asymmetric cross‐regulation of pathway function, for the role of DSB repair in mycobacterial pathogenesis.
A dual function of the CRISPR–Cas system in bacterial antivirus immunity and DNA repair
Authors: Babu Mohan , Beloglazova Natalia , Flick Robert , Graham Chris , Skarina Tatiana , Nocek Boguslaw , Gagarinova Alla , Pogoutse Oxana , Brown Greg , Binkowski Andrew , Phanse Sadhna , Joachimiak Andrzej , Koonin Eugene V. , Savchenko Alexei , Emili Andrew , Greenblatt Jack , Edwards Aled M. , Yakunin Alexander F. 
Published: November 2010

SummaryClustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR‐associated protein that is common to all CRISPR‐containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single‐stranded and branched DNAs including Holliday junctions, replication forks and 5′‐flaps. The crystal structure of YgbT and site‐directed mutagenesis have revealed the potential active site. Genome‐wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR–Cas system have a function in DNA repair.
Deletion of the RluD pseudouridine synthase promotes SsrA peptide tagging of ribosomal protein S7
Authors: Schaub Ryan E. , Hayes Christopher S. 
Published: November 2010

SummaryRluD catalyses formation of three pseudouridine residues within helix 69 of the 50S ribosome subunit. Helix 69 makes important contacts with the decoding centre on the 30S subunit and deletion of rluD was recently shown to interfere with translation termination in Escherichia coli. Here, we show that deletion of rluD increases tmRNA activity on ribosomes undergoing release factor 2 (RF2)‐mediated termination at UGA stop codons. Strikingly, tmRNA‐mediated SsrA peptide tagging of two proteins, ribosomal protein S7 and LacI, was dramatically increased in ΔrluD cells. S7 tagging was due to a unique C‐terminal peptide extension found in E. coli K‐12 strains. Introduction of the rpsG gene (encoding S7) from an E. coli B strain abrogated S7 tagging in the ΔrluD background, and partially complemented the mutant's slow‐growth phenotype. Additionally, exchange of the K‐12 prfB gene (encoding RF2) with the B strain allele greatly reduced tagging in ΔrluD cells. In contrast to E. coli K‐12 cells, deletion of rluD in an E. coli B strain resulted in no growth phenotype. These findings indicate that the originally observed rluD phenotypes result from synthetic interactions with rpsG and prfB alleles found within E. coli K‐12 strains.
Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy
Authors: Khorsand N. , Veeger N. J. G. M. , Muller M. , Overdiek J. W. P. M. , Huisman W. , van Hest R. M. , Meijer K. 
Published: November 2010

Background: Although prothrombin complex concentrate (PCC) is often used to counteract vitamin K antagonist (VKA) therapy, evidence regarding the optimal dose for this indication is lacking. In Dutch hospitals, either a variable dose, based on body weight, target INR (international normalised ratio) and initial INR, or a fixed dose is used. Aim/objectives: In this observational, pilot study, the efficacy and feasibility of the fixed dose strategy compared to the variable dosing regimen, is investigated. Materials and Methods: Consecutive patients receiving PCC (Cofact®, Sanquin, Amsterdam) for VKA reversal because of a major non‐cranial bleed or an invasive procedure were enrolled in two cohorts. Data were collected prospectively in the fixed dose group, cohort 1, and retrospectively in the variable dose regimen, cohort 2. Study endpoints were proportion of patients reaching target INR and successful clinical outcome. Results: Cohort 1 consisted of 35 and cohort 2 of 32 patients. Target INR was reached in 70% of patients in cohort 1 versus 81% in cohort 2 (P = 0·37). Successful clinical outcome was seen in 91% of patients in cohort 1 versus 94% in cohort 2 (P = 1·00). Median INR decreased from 4·7 to 1·8 with a median dosage of 1040 IU factor IX (F IX) in cohort 1 and from 4·7 to 1·6 with a median dosage of 1580 IU F IX in cohort 2. Conclusion: This study suggests that a fixed dose of 1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our patient population and provides a basis for future research.
Prevalence of intestinal parasites among school children in northern districts of West Bank‐ Palestine
Authors: Hussein Ayman S. 
Published: November 2010

SummaryObjectives  To assess the prevalence of intestinal parasite infections in northern districts of West Bank, Palestine and to determine associated sociodemographic factors.Methods  Random sampling of schoolchildren from rural and urban areas was carried out. Participants provided faecal samples and answered a questionnaire about their demographics and hygiene habits. Faecal samples underwent microscopy and PCR to screen for protozoan and helminths.Results  Seven hundred and thirty‐five samples were collected from children aged 9.5 years on average. The overall prevalence of parasitic infection was 22.2%. The rates of infections with amoeba, Giardia intestinalis, Entrobius vermicularis and Ascaris lumbricoides were 9.7%, 4.1%, 1.6% and 3.8%, respectively. Real‐time PCR was performed to differentiate between Entamoeba histolytica and Entamoeba dispar. Results showed that 14% of samples positive with microscopy for amoeba were positive for E. histolytica. There was no significant association between sex and rates of infections (P‐value > 0.05). There were, however, significant association between parasite infections and parents’ education, place of residence, washing hands habits (P‐value > 0.05). No significant association was found with number of family members or eating in school canteens (P‐value > 0.05).Conclusions  Intestinal parasite infections are endemic in West Bank. Interventions such as health education and sanitation are needed.
Characterizing the relationship between sesame, coconut, and nut allergy in children
Authors: Stutius Lisa M. , Sheehan William J. , Rangsithienchai Pitud , Bharmanee Apinya , Scott Jordan E. , Young Michael C. , Dioun Anahita F. , Schneider Lynda C. , Phipatanakul Wanda 
Published: November 2010

Stutius LM, Sheehan WJ, Rangsithienchai P, Bharmanee A, Scott JE, Young MC, Dioun AF, Schneider LC, Phipatanakul W. Characterizing the relationship between sesame, coconut, and nut allergy in children. Pediatr Allergy Immunol 2010: 21: 1114–1118. © 2010 John Wiley & Sons A/SSesame and coconut are emerging food allergens in the United States. We sought to examine whether children allergic to peanuts and tree nuts are at increased risk of having an allergy to sesame or coconut. We performed a retrospective chart review of children who underwent skin prick testing (SPT) to sesame and coconut and identified 191 children who underwent SPT to sesame and 40 to coconut. Sensitization to sesame was more likely in children with positive SPT to peanuts (odds ratio [OR] = 6.7, 95% confidence interval [CI] [2.7–16.8], p < 0.001) and tree nuts (OR = 10.5, 95% CI [4.0–27.7], p < 0.001). Children with histories of both peanut and tree nut reaction were more likely to have a history of sesame reaction (OR = 10.2, 95% CI [2.7–38.7], p < 0.001). Children with sensitization or allergy to peanuts or tree nuts were not more likely to be sensitized or allergic to coconut. In conclusion, children with peanut or tree nut sensitization were more likely to be sensitized to sesame but not coconut. Children with clinical histories of both peanut and tree nut allergy were more likely to be allergic to sesame.
Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy
Authors: Mösges Ralph , Graute Vera , Christ Hildegard , Sieber Hans‐Jochen , Wahn Ulrich , Niggemann Bodo 
Published: November 2010

Mösges R, Graute V, Christ H, Sieber H‐Jochen, Wahn U, Niggemann B. Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy. Pediatr Allergy Immunol 2010: 21: 1135–1138. © 2010 John Wiley & Sons A/SThe recommendation to use sublingual‐swallow immunotherapy (SLIT) in children and adults with allergic rhinitis has been established over the past decade. Recently, ultra‐rush titration of SLIT has become more and more common, raising concerns about its safety in children with asthma. Fifty‐four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen (birch and possibly alder and/or hazel) from 14 study centers in Germany participated in a randomized, double‐blind, and placebo‐controlled study. Twenty‐seven were randomized to receive SLIT with standardized birch pollen allergen extract and the other 27 to receive placebo. An ultra‐rush high‐dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity (IR) within 90 min (30–90–150–300 IR) was used. The difference in mean PFR changes during ultra‐rush titration between SLIT and placebo was not significant (p = 0.056). A 95% probability that SLIT does not decrease PFR during ultra‐rush titration was demonstrated. Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred. No serious adverse event assessed by the investigator as related to study drug treatment was reported.
A latitudinal gradient in seed nutrients of the forest herb Anemone nemorosa
Authors: De Frenne P. , Kolb A. , Graae B. J. , Decocq G. , Baltora S. , De Schrijver A. , Brunet J. , Chabrerie O. , Cousins S. A. O. , Dhondt R. , Diekmann M. , Gruwez R. , Heinken T. , Hermy M. , Liira J. , Saguez R. , Shevtsova A. , Baskin C. C. , Verheyen K. 
Published: November 2010

AbstractThe nutrient concentration in seeds determines many aspects of potential success of the sexual reproductive phase of plants, including the seed predation probability, efficiency of seed dispersal and seedling performance. Despite considerable research interest in latitudinal gradients of foliar nutrients, a similar gradient for seeds remains unexplored. We investigated a potential latitudinal gradient in seed nutrient concentrations within the widespread European understorey forest herb Anemone nemorosa L. We sampled seeds of A. nemorosa in 15 populations along a 1900‐km long latitudinal gradient at three to seven seed collection dates post‐anthesis and investigated the relative effects of growing degree‐hours >5 °C, soil characteristics and latitude on seed nutrient concentrations. Seed nitrogen, nitrogen:phosphorus ratio and calcium concentration decreased towards northern latitudes, while carbon:nitrogen ratios increased. When taking differences in growing degree‐hours and measured soil characteristics into account and only considering the most mature seeds, the latitudinal decline remained particularly significant for seed nitrogen concentration. We argue that the decline in seed nitrogen concentration can be attributed to northward decreasing seed provisioning due to lower soil nitrogen availability or greater investment in clonal reproduction. This pattern may have large implications for the reproductive performance of this forest herb as the degree of seed provisioning ultimately co‐determines seedling survival and reproductive success.