Safety and outcome of coronary interventions with special reference to anticoagulation and stent type

University of Turku, Faculty of Medicine, Department of Cardiology and Cardiovascular Medicine, Doctoral Programme of Clinical Investigation, Heart Center, Turku University Hospital, Turku, Finland Division of Internal Medicine, Department of Cardiology, Seinäjoki Central Hospital, Seinäjoki, Finland Heart Center, Satakunta Central Hospital, Pori, Finland Annales Universitatis Turkuensis Painosalama Oy, Turku, Finland 2015 Antithrombotic therapy during and after coronary procedures always entails the challenging establishment of a balance between bleeding and thrombotic complications. It has been generally recommended to patients on long-term warfarin therapy to discontinue warfarin a few days prior to elective coronary angiography or intervention to prevent bleeding complications. Bridging therapy with heparin is recommended for patients at an increased risk of thromboembolism who require the interruption of anticoagulation for elective surgery or an invasive procedure. In study I, consecutive patients on warfarin therapy referred for diagnostic coronary angiography were compared to control patients with a similar disease presentation without warfarin. The strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation appeared to be a relatively safe alternative to bridging therapy, if the international normalized ratio level was not on a supratherapeutic level. In-stent restenosis remains an important reason for failure of long-term success after a percutaneous coronary intervention (PCI). Drug-eluting stents (DES) reduce the problem of restenosis inherent to bare metal stents (BMS). However, a longer delay in arterial healing may extend the risk of stent thrombosis (ST) far beyond 30 days after the DES implantation. Early discontinuation of antiplatelet therapy has been the most important predisposing factor for ST. In study II, patients on long-term oral anticoagulant (OAC) underwent DES or BMS stenting with a median of 3.5 years’follow-up. The selective use of DESs with a short triple therapy seemed to be safe in OAC patients, since late STs were rare even without long clopidogrel treatment. Major bleeding and cardiac events were common in this patient group irrespective of stent type. In order to help to predict the bleeding risk in patients on OAC, several different bleeding risk scorings have been developed. Risk scoring systems have also been used also in the setting of patients undergoing a PCI. In study III, the predictive value of an outpatient bleeding risk index (OBRI) to identify patients at high risk of bleeding was analysed. The bleeding risk seemed not to modify periprocedural or long-term treatment choices in patients on OAC after a percutaneous coronary intervention. Patients with a high OBRI often had major bleeding episodes, and the OBRI may be suitable for risk evaluation in this patient group. Optical coherence tomography (OCT) is a novel technology for imaging intravascular coronary arteries. OCT is a light-based imaging modality that enables a 12–18 µm tissue axial resolution to visualize plaques in the vessel, possible dissections and thrombi as well as, stent strut appositions and coverage, and to measure the vessel lumen and lesions. In study IV, 30 days after titanium-nitride-oxide (TITANOX)-coated stent implantation, the binary stent strut coverage was satisfactory and the prevalence of malapposed struts was low as evaluated by OCT. Long-term clinical events in patients treated with (TITANOX)-coated bio-active stents (BAS) and paclitaxel-eluting stents (PES) in routine clinical practice were examined in study V. At the 3-year follow-up, BAS resulted in better long-term outcome when compared with PES with an infrequent need for target vessel revascularization. Keywords: anticoagulation, restenosis, thrombosis, bleeding, optical coherence tomography, titanium

Alternative splicing by hnRNP L as a new modulator of hematopoietic cell differentiation, survival and migration

Les modifications post-transcriptionnelles de l’ARN messager (ARNm), comme l’épissage alternatif, jouent un rôle important dans la régulation du développement embryonnaire, de la fonction cellulaire et de l’immunité. De nouvelles évidences révèlent que l’épissage alternatif serait également impliqué dans la régulation de la maturation et de l’activation des cellules du système hématopoïétique. Le facteur hnRNP L a été identifié comme étant le principal régulateur de l’épissage alternatif du gène codant pour le récepteur CD45 in vitro. Le récepteur CD45 est une tyrosine phosphatase exprimée par toutes les cellules du système hématopoïétique qui contrôle le développement et l’activation des lymphocytes T. Dans un premier temps, nous avons étudié la fonction du facteur hnRNP L dans le développement des lymphocytes T et dans l’épissage de l’ARNm de CD45 in vivo en utilisant des souris dont le gène de hnRNP L a été supprimé spécifiquement dans les cellules T. La délétion de hnRNP L dans les thymocytes résulte en une expression aberrante des différents isoformes de CD45 avec une prédominance de l'isoforme CD45RA qui est généralement absent dans le thymus. Une conséquence de la délétion de hnRNP L est une diminution de la cellularité du thymus causée par un blocage partiel du développement des cellules pré-T au stade DN4. Cette réduction du nombre de cellules dans le thymus n’est pas liée à une hausse de la mort cellulaire. Les thymocytes déficients pour hnRNP L démontrent plutôt une prolifération augmentée comparée aux thymocytes sauvages due à une hyper-activation des kinases Lck, Erk1/2 et Akt. De plus, la délétion de hnRNP L dans le thymus cause une perte des cellules T en périphérie. Les résultats des expériences in vitro suggèrent que cette perte est principalement due à un défaut de migration des thymocytes déficients pour hnRNP L du thymus vers la périphérie en réponse aux chimiokines. L’épissage alternatif de CD45 ne peut expliquer ce phénotype mais l’identification de cibles par RNA-Seq a révélé un rôle de hnRNP L dans la régulation de l’épissage alternatif de facteurs impliqués dans la polymérisation de l’actine. Dans un second temps, nous avons étudié le rôle de hnRNP L dans l’hématopoïèse en utilisant des souris dont la délétion de hnRNP L était spécifique aux cellules hématopoïétiques dans les foies fœtaux et la moelle osseuse. L’ablation de hnRNP L réduit le nombre de cellules progénitrices incluant les cellules progénitrices lymphocytaires (CLPs), myéloïdes (CMPs, GMPs) et mégakaryocytes-érythrocytaires (MEPs) et une perte des cellules hématopoïétiques matures. À l’opposé des cellules progénitrices multipotentes (MPPs) qui sont affectées en absence de hnRNP L, la population de cellules souches hématopoïétiques (HSCs) n’est pas réduite et prolifère plus que les cellules contrôles. Cependant, les HSCs n’exprimant pas hnRNP L sont positives pour l'Annexin V et expriment CD95 ce qui suggère une mort cellulaire prononcée. Comme pour les thymocytes, une analyse par RNA-Seq des foies fœtaux a révélé différents gènes cibles de hnRNP L appartenant aux catégories reliées à la mort cellulaire, la réponse aux dommages à l’ADN et à l’adhésion cellulaire qui peuvent tous expliquer le phénotype des cellules n’exprimant pas le gène hnRNP L. Ces résultats suggèrent que hnRNP L et l’épissage alternatif sont essentiels pour maintenir le potentiel de différenciation des cellules souches hématopoïétiques et leur intégrité fonctionnelle. HnRNP L est aussi crucial pour le développement des cellules T par la régulation de l’épissage de CD45 ainsi que pour leur migration.

Diagnosing Patients Combining Principal Components Analysis and Case Based Reasoning

This paper addresses the application of a PCA analysis on categorical data prior to diagnose a patients data set using a Case-Based Reasoning (CBR) system. The particularity is that the standard PCA techniques are designed to deal with numerical attributes, but our medical data set contains many categorical data and alternative methods as RS-PCA are required. Thus, we propose to hybridize RS-PCA (Regular Simplex PCA) and a simple CBR. Results show how the hybrid system produces similar results when diagnosing a medical data set, that the ones obtained when using the original attributes. These results are quite promising since they allow to diagnose with less computation effort and memory storage

A abordagem homeopática aplicada na prática clínica veterinária : um estudo retrospectivo

A homeopatia é uma forma holística de medicina, que visa um dos príncipios hipocráticos ‘Similia similibus curantur’, o semelhante cura o semelhante, isto é, a doença pode ser tratada através da administração de princípios activos que induzam, num animal saudável, sintomas semelhantes aos provocados pela doença. É possível prescrever em diversas situações clínicas, como única opcção ou complementar de diferentes terapêuticas, de forma a promover a saúde animal. A presente dissertação consta de um estudo retrospectivo baseado numa amostra com 68 gatos e 23 cães, observados durante 60 dias no decorrer do estágio curricular na Clínica Refúgio da Bicharada, na qual se procede à caracterização da aplicação da homeopatia na prática clínica. A aplicação de tratamento homeopático verifica-se em 75% dos animais da amostra, enquanto que o tratamento homeopático complementar em 25% da amostra. O tratamento homeopático exclusivo foi prescrito com maior frequência na área da etologia (100%; n=28), seguido de doenças do tracto respiratório (90%; n=18) e gastroenterologia (55%; n=6). As doenças em que mais foi prescrito o tratamento homeopático exclusivo foi em coriza (93%; n=14); agressividade em ninhadas (100%; n=14); apatia comportamental (100%; n=9); osteoartrose (57%; n=4); gengivo-estomatite e asma brônquica (75%; n=3); e obstipação (100%; n=3). Verifica-se que em várias circunstâncias se recorre a medicamentos homeopáticos como opção terapêutica, aplicando-os como tratamento único ou complementar na prática clínica de pequenos animais.

Auditory brainstem response with alternative transducers: implications for newborn hearing screening

This paper studies the efficacy of a bone-conducted transducer compared to a traditional air conduction transducer for auditory brainstem response screening of newborns.

Loudness discomfort levels: A retrospective study comparing data from Pascoe (1988) and Washington University School of Medicine

Loudess discomfort levels (LDLs) were gathered from three Washington University School of Medicine sites, for a total of 325 subjects (total ears=454). These levels were compared to mean LDLs reported by Pascoe (1988). The results revealed that the mean LDL measured at WUSM (ie., the IHAFF procedure) is significantly different that the LDL reported by Pascoe (1988).

Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products

Objectives: To investigate people's views about the efficacy and specific risks of herbal, over-the-counter (OTC) conventional, and prescribed conventional medicines, and their likelihood of taking a second (herbal or OTC conventional) product in addition to a prescribed medicine. Methods: Experiment 1 (1 factor within-participant design); Experiment 2 (1 factor between-participant design). Convenience samples of general population were given a hypothetical scenario and required to make a number of judgements. Results: People believed herbal remedies to be less effective, but less risky than OTC and prescribed conventional medicines. Herbal medicines were not seen as being safer simply because of their easier availability. Participants indicated that they would be more likely to take a herbal medicine than a conventional OTC medicine in addition to a prescribed medicine, and less likely to consult their doctor in advance. Conclusion: People believe that herbal medicines are natural and relatively safe and can be used with less caution. People need to be given clear information about the risks and benefits of herbal medicines if they are to use such products safety and effectively. (c) 2006 Elsevier Ltd. All rights reserved.

Molecular and phenotypic characterization of the alternative seasonal growth habit and flowering time in barley (Hordeum vulgare ssp. vulgare L.)

Barley can be classified into three major agronomic types, based on its seasonal growth habit (SGH): spring, winter and alternative. Winter varieties require exposure to vernalization to promote subsequent flowering and are autumn-sown. Spring varieties proceed to flowering in the absence of vernalization and are sown in the spring. The ‘alternative’ (also known as ‘facultative’) SGH is only loosely defined and can be sown in autumn or spring. Here, we investigate the molecular genetic basis of alternative barley. Analysis of the major barley vernalization (VRN-H1, VRN-H2) and photoperiod (PPD-H1, PPD-H2) response genes in a collection of 386 varieties found alternative SGH to be characterized by specific allelic combinations. Spring varieties possessed spring loci at one or both of the vernalization response loci, combined with long-day non-responsive ppd-H1 alleles and wild-type alleles at the short-day photoperiod response locus, PPD-H2. Winter varieties possessed winter alleles at both vernalization loci, in combination with the mutant ppd-H2 allele conferring delayed flowering under short-day photoperiods. In contrast, all alternative varieties investigated possessed a single spring allele (either at VRN-H1 or at VRN-H2) combined with mutant ppd-H2 alleles. This allelic combination is found only in alternative types and is diagnostic for alternative SGH in the collection studied. Analysis of flowering time under controlled environment found alternative varieties flowered later than spring control lines, with the difference most pronounced under short-day photoperiods. This work provides genetic characterization of the alternative SGH phenotype, allowing precise manipulation of SGH and flowering time within breeding programmes, and provides the molecular tools for classification of all three SGH categories within national variety registration processes.

Translational research and therapeutic applications of neural crest-derived stem cells in regenerative periodontology

Regeneration of periodontal tissues aims to utilize tissue engineering techniques to restore lost periodontal tissues including the cementum, periodontal ligament and alveolar bone. Regenerative dentistry and its special field regenerative periodontology represent relatively new and emerging branches of translational stem cell biology and regenerative medicine focusing on replacing and regenerating dental tissues to restore or re-establish their normal function lost during degenerative diseases or acute lesions. The regeneration itself can be achieved through transplantation of autologous or allogenic stem cells, or by improving the tissue self-repair mechanisms (e.g. by application of growth factors). In addition, a combination of stem cells or stem cell-containing tissue with bone implants can be used to improve tissue integration and the clinical outcome. As the oral cavity represents a complex system consisting of teeth, bone, soft tissues and sensory nerves, regenerative periodontology relies on the use of stem cells with relatively high developmental potential. Notably, the potential use of pluripotent stem cell types such as human embryonic stem cells or induced pluripotent stem cells is still aggravated by ethical and practical problems. Thus, other cellular sources such as those readily available in the postnatal craniofacial area and particularly in oral structures offer a much better and realistic alternative as cellular regenerative sources. In this review, we summarize current knowledge on the oral neural crest-derived stem cell populations (oNCSCs) and discuss their potential in regenerative periodontology.

Alternative splicing and genetic diversity: silencers are more frequently modified by SNVs associated with alternative exon/intron borders

With the availability of a large amount of genomic data it is expected that the influence of single nucleotide variations (SNVs) in many biological phenomena will be elucidated. Here, we approached the problem of how SNVs affect alternative splicing. First, we observed that SNVs and exonic splicing regulators (ESRs) independently show a biased distribution in alternative exons. More importantly, SNVs map more frequently in ESRs located in alternative exons than in ESRs located in constitutive exons. By looking at SNVs associated with alternative exon/intron borders (by their common presence in the same cDNA molecule), we observed that a specific type of ESR, the exonic splicing silencers (ESSs), are more frequently modified by SNVs. Our results establish a clear association between genetic diversity and alternative splicing involving ESSs.

Comparative Studies of the (Anti) Mutagenicity of Baccharis dracunculifolia and Artepillin C by the Bacterial Reverse Mutation Test

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alternative low doses and routes of administering a prostaglandin F2 alpha analogue to induce luteolysis in Nelore cows

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2 alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, I M (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone < 1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.

The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats

The Copaiba oil has been used as an auxiliary treatment of inflammations, skin disorders and stomach ulcers, however, in dentistry, this alternative medicine has not been investigated yet. The purpose of this study was to evaluate the influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction. Twenty-eight wistar male rats had their lower first molar teeth extracted. Subsequently, they were divided in four groups, according to the treatment performed: (a) alveolar socket irrigation with copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily gavage with copaiba oil or (d) daily gavage with physiological serum. After the sacrifice, the mandibles were removed and processed in order to obtain decalcified histological sections. The results demonstrated high level of epithelial migration, small number of inflammatory cells and vascular enhancement in the animals which received systemic administration of copaiba oil. The rats treated with topic administration of copaiba oil presented ulcerations and large number of inflammatory cells. An increased bone neoformation was observed in both groups treated with copaiba oil when compared with placebo group. It could be concluded that topic or systemic administration of copaiba oil leads to a better alveolar bone healing, however the topic application on connective tissue should be carefully considered, regarding the whole socket wound healing. © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488.

Fontes hidrominerais do Brasil: componentes biologicamente ativos (BAC) naturais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)