Practical use of dabigatran etexilate for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, and is the most prevalent factor for cardioembolic stroke. Vitamin K antagonists (VKAs) have been the standard of care for stroke prevention in patients with AF since the early 1990s. They are very effective for the prevention of cardioembolic stroke, but are limited by factors such as drug-drug interactions, food interactions, slow onset and offset of action, haemorrhage and need for routine anticoagulation monitoring to maintain a therapeutic international normalised ratio (INR). Multiple new oral anticoagulants have been developed as potential replacements for VKAs for stroke prevention in AF. Most are small synthetic molecules that target thrombin (e.g. dabigatran etexilate) or factor Xa (e.g. rivaroxaban, apixaban, edoxaban, betrixaban, YM150). These drugs have predictable pharmacokinetics that allow fixed dosing without routine laboratory monitoring. Dabigatran etexilate, the first of these new oral anticoagulants to be approved by the United States Food and Drug Administration and the European Medicines Agency for stroke prevention in patients with non-valvular AF, represents an effective and safe alternative to VKAs. Under the auspices of the Regional Anticoagulation Working Group, a multidisciplinary group of experts in thrombosis and haemostasis from Central and Eastern Europe, an expert panel with expertise in AF convened to discuss practical, clinically important issues related to the long-term use of dabigatran for stroke prevention in non-valvular AF. The practical information reviewed in this article will help clinicians make appropriate use of this new therapeutic option in daily clinical practice

Interactions of Bacillus Mojavensis and Fusarium Verticillioides With a Benzoxazolinone (Boa) and Its Transformation Product, Apo

En:Journal of Chemical Ecology (2007, vol. 33, n. 10, p. 1885-1897)The benzoxazolinones, specifically benzoxazolin-2(3H)-one (BOA), are important transformation products of the benzoxazinones that can serve as allelochemicals providing resistance to maize from pathogenic bacteria, fungi, and insects. However, maize pathogens such as Fusarium verticillioides are capable of detoxifying the benzoxazolinones to 2-aminophenol (AP), which is converted to the less toxic N-(2-hydroxyphenyl) malonamic acid (HPMA) and 2-acetamidophenol (HPAA). As biocontrol strategies that utilize a species of endophytic bacterium, Bacillus mojavensis, are considered efficacious as a control of this Fusarium species, the in vitro transformation and effects of BOA on growth of this bacterium was examined relative to its interaction with strains of F. verticillioides. The results showed that a red pigment was produced and accumulated only on BOA-amended media when wild type and the progeny of genetic crosses of F. verticillioides are cultured in the presence of the bacterium. The pigment was identified as 2-amino-3H-phenoxazin-3-one (APO), which is a stable product. The results indicate that the bacterium interacts with the fungus preventing the usual transformation of AP to the nontoxic HPMA, resulting in the accumulation of higher amounts of APO than when the fungus is cultured alone. APO is highly toxic to F. verticillioides and other organisms. Thus, an enhanced biocontrol is suggested by this in vitro study. =580 $aEn:Journal of Chemical Ecolog

Genetic and cellular aspects of the establishment of histocompatible stem cells: information gained from an animal model

The establishment of patient-specific histocompatible stem cells may be an alternative for overcoming current limitations in stem cell engineering. We are developing an animal model to assist the establishment of histocompatible, autologous stem cells. In this process, we obtained valuable information on establishing and characterizing stem cells. As an initial step, we succeeded in establishing histocompatible stem cells using preantral follicle cultures and subsequent parthenogenetic activation. The gene expression profile of the established stem cells was similar to that of embryonic stem cells (ESCs) derived from normal fertilization. On the other hand, we propose a way to derive histocompatible, ESC-like cells by co-culturing ovarian stromal cells with feeder fibroblasts, which may allow the derivation of stem cells from somatic tissue. However, more progress regarding the establishment and elucidation on origination of established cell lines is necessary to use this genetic manipulation-free procedure. Nevertheless, relevant information on the process will help to stimulate preclinical research on cell transformation into differentiated, undifferentiated, and even cancerous cells, as well as clinical studies on the application of induced pluripotent cells

Identification of mosquito repellent odours from Ocimum forskolei

<p>Abstract</p> <p>Background</p> <p>Native mosquito repellent plants have a good potential for integrated mosquito control in local settings. <it>Ocimum forskolei</it>, Lamiaceae, is used in Eritrea as a spatial mosquito repellent inside houses, either through crushing fresh plants or burning dry plants. We verified whether active repellent compounds could be identified using gas-chromatography coupled electroantennogram recordings (GC-EAD) with headspace extracts of crushed plants.</p> <p>Results</p> <p>EAD active compounds included (R)-(-)-linalool, (S)-(+)-1-octen-3-ol, trans-caryophyllene, naphthalene, methyl salicylate, (R)-(-)-α-copaene, methyl cinnamate and (E)-ocimene. Of these compounds (R)-(-)-linalool, methyl cinnamate and methyl salicylate reduced landing of female <it>Aedes aegypti </it>on human skin-odor baited tubes. The latter two are novel mosquito repellent compounds.</p> <p>Conclusions</p> <p>The identification of mosquito repellent compounds contributes to deciphering the mechanisms underlying repulsion, supporting the rational design of novel repellents. The three mosquito repellent compounds identified in this study are structurally dissimilar, which may indicate involvement of different sensory neurons in repulsion. Repulsion may well be enhanced through combining different repellent plants (or their synthetic mimics), and can be a locally sustainable part in mosquito control efforts.</p

Assortative Mating between European Corn Borer Pheromone Races: Beyond Assortative Meeting

BACKGROUND: Sex pheromone communication systems may be a major force driving moth speciation by causing behavioral reproductive isolation via assortative meeting of conspecific individuals. The 'E' and 'Z' pheromone races of the European corn borer (ECB) are a textbook example in this respect. 'Z' females produce and 'Z' males preferentially respond to a 'Z' pheromone blend, while the 'E' race communicates via an 'E' blend. Both races do not freely hybridize in nature and their populations are genetically differentiated. A straightforward explanation would be that their reproductive isolation is a mere consequence of "assortative meeting" resulting from their different pheromones specifically attracting males towards same-race females at long range. However, previous laboratory experiments and those performed here show that even when moths are paired in a small box - i.e., when the meeting between sexual partners is forced - inter-race couples still have a lower mating success than intra-race ones. Hence, either the difference in attractivity of E vs. Z pheromones for males of either race still holds at short distance or the reproductive isolation between E and Z moths may not only be favoured by assortative meeting, but must also result from an additional mechanism ensuring significant assortative mating at close range. Here, we test whether this close-range mechanism is linked to the E/Z female sex pheromone communication system. METHODOLOGY/PRINCIPAL FINDINGS: Using crosses and backcrosses of E and Z strains, we found no difference in mating success between full-sisters emitting different sex pheromones. Conversely, the mating success of females with identical pheromone types but different coefficients of relatedness to the two parental strains was significantly different, and was higher when their genetic background was closer to that of their male partner's pheromone race. CONCLUSIONS/SIGNIFICANCE: We conclude that the close-range mechanism ensuring assortative mating between the E and Z ECB pheromone races is unrelated to the difference in female sex pheromone. Although the nature of this mechanism remains elusive, our results show that it is expressed in females, acts at close range, segregates independently of the autosome carrying Pher and of both sex chromosomes, and is widely distributed since it occurs both in France and in the US

Very small embryonic-like stem cells (VSELs) represent a real challenge in stem cell biology : recent pros and cons in the midst of a lively debate

The concept that adult tissue, including bone marrow (BM), contains early-development cells with broader differentiation potential has again been recently challenged. In response, we would like to review the accumulated evidence from several independent laboratories that adult tissues, including BM, harbor a population of very rare stem cells that may cross germ layers in their differentiation potential. Thus, the BM stem cell compartment hierarchy needs to be revisited. These dormant, early-development cells that our group described as very small embryonic-like stem cells (VSELs) most likely overlap with similar populations of stem cells that have been identified in adult tissues by other investigators as the result of various experimental strategies and have been given various names. As reported, murine VSELs have some pluripotent stem cell characteristics. Moreover, they display several epiblast/germline markers that suggest their embryonic origin and developmental deposition in adult BM. Moreover, at the molecular level, changes in expression of parentally imprinted genes (for example, Igf2–H19) and resistance to insulin/insulin-like growth factor signaling (IIS) regulates their quiescent state in adult tissues. In several emergency situations related to organ damage, VSELs can be activated and mobilized into peripheral blood, and in appropriate animal models they contribute to tissue organ/regeneration. Interestingly, their number correlates with lifespan in mice, and they may also be involved in some malignancies. VSELs have been successfully isolated in several laboratories; however, some investigators experience problems with their isolation

Insect Repellents: Modulators of Mosquito Odorant Receptor Activity

Background: DEET, 2-undecanone (2-U), IR3535 and Picaridin are widely used as insect repellents to prevent interactions between humans and many arthropods including mosquitoes. Their molecular action has only recently been studied, yielding seemingly contradictory theories including odorant-dependent inhibitory and odorant-independent excitatory activities on insect olfactory sensory neurons (OSNs) and odorant receptor proteins (ORs). Methodology/Principal Findings: Here we characterize the action of these repellents on two Aedes aegypti ORs, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes; these ORs are respectively activated by the odors indole (AaOR2) and (R)-(2)-1-octen3-ol (AaOR8), odorants used to locate oviposition sites and host animals. In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs. Conclusions/Significance: These data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models