Four randomized, placebo-controlled, crossover studies were conducted among 282 healthy subjects to investigate whether an interaction exists between clopidogrel (300-mg loading dose/75-mg/day maintenance dose) and the proton-pump inhibitor (PPI) omeprazole (80 mg) when they are administered simultaneously (study 1); whether the interaction, if any, can be mitigated by administering clopidogrel and omeprazole 12 h apart (study 2) or by increasing clopidogrel to 600-mg loading/150-mg/day maintenance dosing (study 3); and whether the interaction applies equally to the PPI pantoprazole (80 mg) (study 4). Relative to levels after administration of clopidogrel alone in studies 1,2,3, and 4, coadministration of PPI decreased the AUC(0-24) of the clopidogrel active metabolite H4 by 40, 47, 41, and 14% (P ≤ 0.002), respectively; increased maximal platelet aggregation (MPA) induced by 5 micromol/l adenosine diphosphate (ADP) by 8.
View Article and Find Full Text PDFMechanotransduction modulates cellular functions as diverse as migration, proliferation, differentiation, and apoptosis. It is crucial for organ development and homeostasis and leads to pathologies when defective. However, despite considerable efforts made in the past, the molecular basis of mechanotransduction remains poorly understood.
View Article and Find Full Text PDFStatistical copolymerization of ethylene and isoprene was achieved by using a borohydrido half-lanthanidocene complex. Under copolymerization conditions, activation of [(Cp*)(BH(4))(2)Nd(thf)(2)] (Cp*=η(5)-C(5)Me(5)) by an appropriate alkylating agent affords trans-1,4-poly-isoprene-co-ethylene. Analysis of the microstructure of the copolymer revealed the presence of successive short sequences of ethylene/ethylene, trans-1,4-isoprene/ethylene, and trans-1,4-isoprene/trans-1,4-isoprene.
View Article and Find Full Text PDFBackground: This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.
View Article and Find Full Text PDFBackground: The 17p13.3 deletion syndrome (or Miller-Dieker syndrome, MDS, MIM 247200) is characterized by lissencephaly, mental retardation and facial dysmorphism. The phenotype is attributed to haploinsufficiency of two genes present in the minimal critical region of MDS: PAFAH1B1 (formerly referred to as LIS1) and YWHAE.
View Article and Find Full Text PDFCharacterization methods with regard to nanopowder flammability and explosivity are presented and illustrated for few nanopowders. Analytical models are developed in order to explain the dependency of the combustion times on the particle diameter. Experimental evidence shows that there exists, for carbonaceous and metallic materials, mainly two combustion regimes that are either kinetically controlled, for small size particles, or diffusion controlled, for large size particles.
View Article and Find Full Text PDFCompounds [Cp*(2)M(2)O(5)] (M = Mo, 1; W, 2) are efficient pre-catalysts for cyclooctene (COE) epoxidation by aqueous H(2)O(2) in acetonitrile/toluene. The reaction is quantitative, selective and takes place approximately 50 times faster for the W system (k(obs) = 4.32(9)x10(-4) s(-1) at 55 degrees C and 3x10(-3) M concentration for the dinuclear complex, vs.
View Article and Find Full Text PDFCalculation of the free energy profile for 1,4 butadiene polymerisation catalyzed by [Cp*ScR](+) highlights the kinetic preference for cis-1,4 over trans-1,4 insertions. The main differences between cis and trans configuration rely on the thermodynamics and the geometry of the precursor diene adduct.
View Article and Find Full Text PDFCongenital absence of the left pericardium (allowing communication between pericardial and pleural cavities) is a rare developmental defect that results from faulty partitioning of the pleuropericardic cavity during the 5th week of development. It occurs sporadically in most instances, and may be associated with other malformations of the thoracic viscera. We report here two sibs born to consanguineous parents with absent left fibrous pericardium and developmental defects of the septum transversum: left posterolateral diaphragmatic hernia in one child, left diaphragmatic eventration in the other sib.
View Article and Find Full Text PDFNanofabrication by molecular self-assembly involves the design of molecules and self-assembly strategies so that shape and chemical complementarities drive the units to organize spontaneously into the desired structures. The power of self-assembly makes it the ubiquitous strategy of living organized matter and provides a powerful tool to chemists. However, a challenging issue in the self-assembly of complex supramolecular structures is to understand how kinetically efficient pathways emerge from the multitude of possible transition states and routes.
View Article and Find Full Text PDFUncommon features of rare genetic disorders are often poorly known, as the likelihood of having them reported is low. We describe a 7-year-old boy with clinical and radiological diagnosis of pycnodysostosis, and c.436G>C (p.
View Article and Find Full Text PDFThe epidemiology of myxoma virus was studied by serology and molecular analysis of restriction fragment length polymorphisms (RFLPs) in genomic DNA. 159 isolates of myxoma virus were made over a period of 5 spring/summer epidemics from 12 field sites in south-eastern Australia. Virus isolates were classified into 10 genetic types using RFLPs detected with a panel of nine restriction endonucleases.
View Article and Find Full Text PDFObjectives: To compare the clinical and laboratory features and the rate of echocardiographic coronary artery abnormalities in patients with complete and incomplete forms of Kawasaki disease (KD) and to determine which additional clinical criteria might support a suspicion of KD.
Methods: We retrospectively reviewed the medical records of patients with KD who were admitted to the general pediatrics department of the Kremlin Bicêtre Teaching Hospital, France, between January 1995 and May 2006. We compared patients with a fever and four or five of the principal criteria (complete KD) to the other patients (incomplete KD).
For the last 15 years the fly cardiovascular system has attracted developmental geneticists for its potential as a model system of organogenesis. Heart development in Drosophila indeed provides a remarkable system for elucidating the basic molecular and cellular mechanisms of morphogenesis and, more recently, for understanding the genetic control of cardiac physiology. The success of these studies can in part be attributed to multidisciplinary approaches, the multiplicity of existing genetic tools, and a detailed knowledge of the system.
View Article and Find Full Text PDFBackground: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced.
Results: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel.
Enzymes involved in the mammalian microsomal metabolism of drugs are, in numerous cases, inhibited by compounds bearing an imidazolyl scaffold. However, the inhibition potency is highly dependent upon the accessibility of the imidazolyl nitrogen lone pair. In order to highlight some structural parameters of inhibitors that control this phenomenon, a series of compounds containing a nitrogen unsubstituted imidazolyl moiety with varying degrees of nitrogen lone pair accessibility was tested on human and rat hepatic cytochromes P450 and microperoxidase 8, an enzymatically active peptide derived from cytochrome c.
View Article and Find Full Text PDFThe mechanism of the initiation step of styrene polymerization promoted by single-component ansa-lanthanidocene catalysts [{Cp'XMe(2)Flu'}Ln(R)(ether)(n)] (Cp' = C(5)H(4); Flu' = 9-C(13)H(8); X = C or Si; R = allyl = CH(2)CHCH(2) or alkyl = CH(2)SiMe(3); ether = THF or Et(2)O, n = 0,1) has been studied from a combined experimental/theoretical perspective. First, detailed (13)C NMR studies conducted on syndiotactic oligostyrenes prepared by chain-growth polymerization with [{C(5)H(4)CMe(2)Flu'}Nd(eta(3)-1,3-C(3)H(3)(SiMe(3))(2))]/Mg(nBu)(2) (1:50) have shown that the insertion of styrene in these lanthanidocene systems proceeds selectively in a secondary (2,1) fashion, both at the initiation and propagation steps. Next, DFT studies of styrene insertion have been carried out on three model compounds, [{Cp'CMe(2)Flu'}Eu(eta(3)-allyl)(thf)] (I), [{Cp'SiMe(2)Flu'}Eu(eta(3)-allyl)(thf)] (II), and [{Cp'CMe(2)Flu'}Eu(eta(1)-CH(2)SiMe(3))(thf)] (III), in order to rationalize the influence of the ansa bridge (CMe(2) vs.
View Article and Find Full Text PDFA functional organ is constituted of diverse cell types. Each one occupies a distinct position and is associated to specific morphological and physiological functions. The identification of the genetic programs controlling these elaborated and highly precise features of organogenesis is crucial to understand how a mature organ works under normal conditions, and how pathologies can develop.
View Article and Find Full Text PDFPurpose: To compare the disease-free survival (DFS) of patients with surgical stage 1, intermediate-risk endometrial adenocarcinoma (EAC) treated with primary surgery with or without adjuvant vaginal vault brachytherapy (VVBT).
Patients And Methods: A retrospective chart review identified 575 patients with stage 1B, 1C or 2A endometrial cancer who had surgery between 1990 and 2004. All patients were surgically staged and 259 patients received postoperative VVBT.
Phenylahistin is a fungal diketopiperazine derived from isoprenylated (Phe-DeltaHis) cyclodipeptide. The (-)-enantiomer is a cell cycle inhibitor, which can be potentially used as an antitumor agent. By contrast, the (+)-enantiomer exhibits no antimicrotubule activity.
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