Rationale, design and population baseline characteristics of the PERFORM Vascular Project: an ancillary study of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) trial

<p><b>Purpose</b></p> <p>PERFORM is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke or transient ischemic attacks (TIAs). The PERFORM Vascular Project will evaluate the effect of terutroban on progression of atherosclerosis, as assessed by change in carotid intima-media thickness (CIMT) in a subgroup of patients.</p> <p><b>Methods and results</b></p> <p>The Vascular Project includes structural (CIMT, carotid plaques) and functional (carotid stiffness) vascular studies in all patients showing at least one carotid plaque at entry. Expected mean follow-up is 36 months. Primary endpoint is rate of change of CIMT. Secondary endpoints include emergent plaques and assessment of carotid stiffness. 1,100 patients are required for 90% statistical power to detect treatment-related CIMT difference of 0.025 mm. The first patient was randomized in April 2006.</p> <p><b>Conclusions</b></p> <p>The PERFORM Vascular Project will investigate terutroban’s effect on vascular structure and function in patients with a history of ischemic stroke or TIAs.</p&gt

Inunditos como análogos de reservatórios: um exemplo nos depósitos gonduânicos triássicos do Gráben Arroio Moirão, RS

O estudo de reservatórios de óleo e gás de sistemas continentais tem enfatizado, na última década, arenitos associados a inunditos, provenientes de fluxos hiperpicnais. Contudo, há poucos estudos para entender sua arquitetura e heterogeneidade, resultando em dificuldades de reconhecimento e de exploração. O presente trabalho visa à análise de pacotes triássicos da Bacia do Paraná pertencentes à Formação Santa Maria, que ocorrem como fragmentos isolados sobre o Escudo Sul-Rio-Grandense na região do Gráben Arroio Moirão (RS). Para tanto, fez-se uso de mapeamento sistemático, análise de heterogeneidade de fácies e estratigrafia de sequências, que incluem levantamento de perfis colunares, identificação de associações e sucessões de fácies e superfícies-chave. Além disso, classificaram-se os arenitos e qualificou-se a porosidade com base na análise petrográfica. Foi possível delimitar os principais depósitos de arenitos, no quais predomina geometria tabular, grãos mal selecionados e matriz argilosa. Distinguiram-se cinco ciclos deposicionais granodecrescentes ascendentes, limitados na base e no topo por superfícies erosivas, que marcam heterogeneidades recorrentes. As fácies-reservatório foram classificadas como subarcósios, de matriz argilosa oxidada, com agregados de caulinita, e porosidade intergranular do tipo shrinkage. A integração dos dados resultou na elaboração de um modelo de variação lateral e vertical de fácies de depósitos de inunditos. Nele, identificaram-se fácies constituídas por arenitos grossos a conglomeráticos, com estratificações cruzada tangencial e plano-paralela, como potenciais modelos análogos de reservatórios. Esses resultados possibilitam prospectar outros depósitos arenosos dessa unidade estratigráfica da Bacia do Paraná, para fins de dimensionar regionalmente o análogo de reservatório.The study of oil and gas reservoirs in continental systems has emphasized, in the last decade, sandstones associated with inundites, coming from hyperpicnal flows. However, there are few studies to understand its architecture and heterogeneity, resulting in difficulties for exploration and exploitation. The current work aims at the analysis of Triassic strata from the Paraná Basin belonging to the Santa Maria Formation, which occur as isolated fragments on the Sul-rio-grandense Shield in Arroio Moirão Graben (RS). For this, systematic mapping, facies heterogeneity analysis and sequence stratigraphy were used, including columnar profiles, identification of associations and sequences of facies and key surfaces. In addition, the sandstones were classified and the porosity was qualified based on the petrographic analysis. It was possible to define the main deposits of sandstones, in which predominate tabular geometry, poorly selected grains and clayey matrix. Five ascending granodecrescent depositional cycles were distinguished, limited at the base and at the top by erosive surfaces, which marked recurrent heterogeneities. The reservoir facies were classified as subarcósios, of oxidized clay matrix, with aggregates of kaolinite, and intergranular porosity of the shrinkage type. The integration of the data resulted in the elaboration of a model of lateral and vertical variation inundites deposits facies. In it, facies composed of conglomeratic thick sandstones were identified, with tangential cross stratification and planar stratification, as potential analog models of reservoirs. These results allow the prospection of other sandy deposits from this stratigraphic unit of the Paraná Basin, in order to size the reservoir analogue regionally

Discovery of novel GPVI receptor antagonists by structure-based repurposing.

Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug 'resistance', underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing

Effects of Aspirin on Endothelial Function and Hypertension

PURPOSE OF REVIEW: Endothelial dysfunction is intimately related to the development of various cardiovascular diseases, including hypertension, and is often used as a target for pharmacological treatment. The scope of this review is to assess effects of aspirin on endothelial function and their clinical implication in arterial hypertension. RECENT FINDINGS: Emerging data indicate the role of platelets in the development of vascular inflammation due to the release of proinflammatory mediators, for example, triggered largely by thromboxane. Vascular inflammation further promotes oxidative stress, diminished synthesis of vasodilators, proaggregatory and procoagulant state. These changes translate into vasoconstriction, impaired circulation and thrombotic complications. Aspirin inhibits thromboxane synthesis, abolishes platelets activation and acetylates enzymes switching them to the synthesis of anti-inflammatory substances. SUMMARY: Aspirin pleiotropic effects have not been fully elucidated yet. In secondary prevention studies, the decrease in cardiovascular events with aspirin outweighs bleeding risks, but this is not the case in primary prevention settings. Ongoing trials will provide more evidence on whether to expand the use of aspirin or stay within current recommendations

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure