Active management of the target P2Y12 reaction unit range in patients undergoing stent-assisted coil embolization for unruptured cerebral aneurysms

BackgroundPlatelet function tests have been increasingly adopted to measure patient responses to antiplatelet drugs, and to predict complications. However, no established optimal antiplatelet management for stent-assisted coil embolization (SAC) have been established. The purpose of the present study was to investigate the efficacy and feasibility of clopidogrel dose adjustment for active target P2Y12 reaction unit (PRU).MethodsA total of 202 consecutive patients undergoing SAC to treat unruptured intracranial aneurysms were prospectively recruited. All patients were given two antiplatelet agents starting 7 days prior to the procedure, and platelet function was measured with the VerifyNow test. Clopidogrel hyper-responsive patients received reduced dosing according to the values of follow-up PRUs before and 7, 14, 30, and 90 days after the procedure. Patients were divided into three groups according to clopidogrel responsiveness before treatment, and clinical outcomes and time in target PRU ranges (TTR) were analyzed.ResultsNo delayed ischemic or hemorrhagic events occurred that were associated with out-of-range PRU. PRU values in the hypo-responsive and hyper-responsive groups significantly improved 7 days after treatment with active target PRU management (p=0.05,<0.001, respectively). PRU values were controlled within the target PRU range with drug adjustment (p=0.034), and the time in TTR for all patients was 97% (4.8%–100%), which showed the feasibility of optimal control of PRU values with the protocol.ConclusionActive target PRU management can achieve control of optimal PRU values and may decrease perioperative ischemic and hemorrhagic events among patients undergoing SAC.

A review on community scale stationary and mobile production of biodiesel

Biodiesel has been commercially produced on a large scale, but its application is still limited primarily due to its production cost, which is relatively more expensive than that of fossil fuel. Recently, there has been an ongoing parallel development whereby biodiesel production is carried out on a community scale, including a mobile production unit of biodiesel with local input and demand. The produced biodiesel is often intended for use by the concerned local community, which greatly reduces logistics and transportation cost. Unlike typical biodiesel production plants, a mobile biodiesel unit consists of a biodiesel production facility placed inside a standard cargo container and mounted on a truck, so that it can be transported to a region near the location of the raw materials. In this paper, we review existing concepts and units for the development of community-scale and mobile production of biodiesel. These include the main reactor technology for biodiesel production, as well as the pre-treatment prior to conveyance to the reaction unit and post-treatment. The pre-treatment includes oil extraction from oilseeds by an oil-expeller unit, as well as quality control of the oil before it enters the reaction unit. The post-treatment includes refining and purification of the biodiesel to meet the product specification set by the biodiesel industry. This paper also discusses the production cost of biodiesel on a community scale, particularly when using a mobile biodiesel unit. The production cost varies from $0.76-1.12/l. This range is still not yet competitive to the current average price of approximately $0.98/l of diesel around the world. The production cost may be reduced by applying a biorefinery concept that may translate into an economically alluring and environmentally attractive business model.

Effect of Cesium and Phosphate Addition to Mo/V/W Mixed Oxide Catalysts for the Gas Phase Oxidation of Methacrolein to Methacrylic Acid

The present study investigates modified Mo/V/W mixed oxides as a possible alternative for state of the art heteropoly acid catalysts (HPA) in the partial oxidation of methacrolein (MAC) to methacrylic acid (MAA). Even though HPAs show an excellent activity and MAA selectivity, their long-term stability is unsatisfying, rendering the catalyst inoperable after runtimes of roughly 6 months. Mo/V/W mixed oxides consisting of M1 and a hexagonal (Mo,V,W)Ox-phase (h-phase) in varying proportions were modified by impregnation with aqueous solutions containing cesium and phosphate ions. All samples were characterized with respect to specific surface area, crystallinity, elemental and phase composition. The catalytic performance in the oxidation of MAC to MAA was investigated using a continuously operated reaction unit with tubular fixed bed reactor. Impregnation with cesium and phosphate ions and subsequent heating triggers the transformation of the mixed oxide into a Keggin-type HPA, whereby the h-phase is more reactive than M1. The transformation into HPA is accompanied by a change in the catalytic properties, i.e., the selectivity to MAA is considerably improved. Compared to HPA synthesized directly, however, the HPA samples obtained by transformation of mixed oxides exhibit no advantages, be it with respect to activity, MAA selectivity or stability.

The specifics of mathematical modeling complex multicomponent chemical processes

A critical analysis of the problem of identifying raw materials for hydrotreating diesel fuel by organosulphuric components and quantifying the value of the rate constant of the hydrodesulphurization reaction is presented. It is proposed to describe the raw material as a set of narrow fractions, in each of which the content of various organosulphuric components is considered as a single pseudo-component. The prospects of separate hydrotreatment of diesel fuel pre - fractionated into wide easily and hardly hydrogenated fractions are confirmed, which allows reducing the loading of the catalyst into the reaction unit of the plant by 1.4-1.7 times compared to the traditional process scheme.. It is proposed to use the concept of kinetic coefficient for mathematical modeling of the hydrotreating process instead of the incorrect reaction rate constant in this case. The dependence of the gross conversion rate constant of the raw material on the time of fixing the depth of its hydrodesulfurization is proved by the example of modeling the hydrotreatment of diesel fuel for a number of raw material variants.

Study of the Feasibility of Biodiesel Production, from Vegetable Oils and Catalysts of Seafood Residues, in a Batch Hydrogenation Reaction Unit, Assisted by Microwave and Conventional Heating

In this work, it was proposed to study the feasibility of biodiesel production, from residues of vegetable oils used in domestic activities, employing (CaCO3) shells prepared like calcium oxide (CaO) as catalysts, in a batch reaction unit, on bench scale, installed at IPEN-CNEN/SP. This unit is capable of operating with high pressure hydrogen gas (up to 200bar) and high temperature (up to 500°C, using microwave - MW (2.450MHz, with up to 2kW continuous and 8kW pulsed) and conventional heating – (electric) MC. In the tests, the oil load (mL), type and mass of catalyst, with or without hydrogen gas pressure (bar), temperature (°C), reaction time (h), microwave power (W), the speed of the load (rpm) agitation and the conventional heating were evaluated. The analytical determinations of the samples were carried out by means of density, gas chromatography (GC) and X-ray fluorescence. Data were collected in order to be compared with other methodologies, already used in the literature. The purpose of this work was to analyze the efficiency of the use of these types of catalysts and oils in the production of biodiesel, as an alternative technology. The Ca and CaO contents found in the pink shell, before and after the calcination, were 36.2% and 98.8%, respectively. The best result obtained for the density was 0.875182g/cm3, for the test with 4g of calcined shell catalyst and reaction of 1h. As to the methyl ester content, the highest result was 95.33%, in a test with 4g of catalyst and reaction of 3h. In the non-calcined shell test (22.5g), although the amount of mass used was much larger (5% of the oil mass), the ester content was very low, 2.11%.

Antiaggregation effect of clopidogrel in coronary heart disease patients using omeprazole

BackgroundAntiplatelet agents used in coronary heart disease (CHD) cause gastrointestinal side effects. Omeprazole can prevent and cure these antiplatelet side effects. Clopidogrel combined with aspirin increases the risk of gastrointestinal tract ulcers and bleeding. This research studied the effect of omeprazole on the antiplatelet effect of clopidogrel.MethodsCHD patients using clopidogrel and aspirin receive omeprazole 20 mg in a single dose for 10 days. Platelet antiaggregation point for clopidogrel was measured using VerifyNow P2Y12. The cutoff points used were: low on treatment platelet reactivity (LPR) <85 P2Y12 reaction unit (PRU), normal on treatment platelet reactivity (NPR) 85–208 PRU, and high on treatment platelet reactivity (HPR) >208 PRU.ResultsUsing the paired t-test PRU points pre- and post-omeprazole were 154 ± 85.89 PRU and 169.4 ± 56.15 PRU, respectively. The PRU points were consistent or decreased from the previous PRU points below the HPR cutoff (p: 0.215; >0.05). Before omeprazole use, five patients were categorized as NPR, two patients as LPR, and three patients as HPR. After omeprazole use, two patients, each from HPR and NPR category had a PRU point >208; the rest showed results below the HPR point.ConclusionsIn this study the PRU points of clopidogrel after omeprazole use showed a PRU <208. The hypothesis that omeprazole may reduce the antiaggregation effect of clopidogrel as shown by the increase in PRU above the cutoff points >208 PRU (HPR) was not proven.

Comparison of Shear Stress–Induced Thrombotic and Thrombolytic Effects Among 3 Different Antithrombotic Regimens in Patients With Acute Coronary Syndrome

Shear stress (SS)-induced platelet activation is suggested as an essential mechanism of the acute coronary syndrome (ACS). We aimed to compare SS-induced thrombotic and thrombolytic activities among 3 treatment regimens in patients with ACS who underwent percutaneous coronary intervention (PCI). Patients were nonrandomly enrolled and treated with one of 3 regimens (TICA: ticagrelor 180 mg/d; RIVA: clopidogrel 75 mg/d and rivaroxaban 5 mg/d; CLP: clopidogrel 75 mg/d), administered in addition to aspirin (100 mg/d) for 30 days. The global thrombosis test was applied to measure SS-induced thrombotic (occlusion time [OT]) and thrombolytic activity (lysis time [LT]) at day 2 and 30. Aspirin reaction unit (ARU) and P2Y12 reaction unit (PRU) were simultaneously measured using VerifyNow. Group differences in the OT, LT, ARU, and PRU were evaluated. Seventy-five patients (25 patients in each group) finished 30 days of follow-up. Clinical and angiographic characteristics did not differ among the 3 groups, except ACS subtype and pre-PCI coronary flow. No major adverse cardiovascular events occurred in any group during follow-up. The OT and LT did not differ among the 3 groups at day 30 (OT: TICA, 447.2 ± 87.1 vs RIVA, 458.5 ± 70.3, vs CLP, 471.9 ± 90.7, LT: 1522.3 ± 426.5 vs 1734.6 ± 454.3 vs 1510.2 ± 593.9) despite significant differences in the PRU among the 3 groups. Shear stress–induced thrombotic and thrombolytic activities did not differ among the 3 investigated antithrombotic treatments.

A 70-Year-Old Female with Unexpected Platelet Function Testing Results

A 70-year-old female with a history of hypertension and left A2 segment aneurysm was scheduled for pipeline embolization device (PED) placement. Preinterventional antiplatelet prophylaxis included aspirin and ticagrelor. Unexpectedly, after 13 days of treatment, VerifyNow showed a P2Y12 reaction unit (PRU) value of 216, approximately &gt;5 times the mean PRU of other patients on aspirin and ticagrelor. We confirmed platelet reactivity and ticagrelor resistance with light transmission aggregometry. Antiplatelet therapy was switched to prasugrel, and aspirin was continued. Eight days later, the P2Y12 reaction value (PRU) was 164. PED was placed without complications. Unlike clopidogrel, ticagrelor is a direct P2Y12 inhibitor that does not require metabolism to an active metabolite. Ticagrelor resistance is very rarely reported. To the best of our knowledge, there has been no case of ticagrelor resistance reported in the context of pre-PED placement prophylaxis.

Optimization of Reaction Selectivity Using CFD-Based Compartmental Modeling and Surrogate-Based Optimization

Mixing is considered as a critical process parameter (CPP) during process development due to its significant influence on reaction selectivity and process safety. Nevertheless, mixing issues are difficult to identify and solve owing to their complexity and dependence on knowledge of kinetics and hydrodynamics. In this paper, we proposed an optimization methodology using Computational Fluid Dynamics (CFD) based compartmental modelling to improve mixing and reaction selectivity. More importantly, we have demonstrated that through the implementation of surrogate-based optimization, the proposed methodology can be used as a computationally non-intensive way for rapid process development of reaction unit operations. For illustration purpose, reaction selectivity of a process with Bourne competitive reaction network is discussed. Results demonstrate that we can improve reaction selectivity by dynamically controlling rates and locations of feeding in the reactor. The proposed methodology incorporates mechanistic understanding of the reaction kinetics together with an efficient optimization algorithm to determine the optimal process operation and thus can serve as a tool for quality-by-design (QbD) during product development stage.

Optimization of Reaction Selectivity Using CFD-Based Compartmental Modeling and Surrogate-Based Optimization

Mixing is considered as a critical process parameter (CPP) during process development due to its significant influence on reaction selectivity and process safety. Nevertheless, mixing issues are difficult to identify and solve owing to their complexity and dependence on knowledge of kinetics and hydrodynamics. In this paper, we proposed an optimization methodology using Computational Fluid Dynamics (CFD) based compartmental modelling to improve mixing and reaction selectivity. More importantly, we have demonstrated that through the implementation of surrogate-based optimization, the proposed methodology can be used as a computationally non-intensive way for rapid process development of reaction unit operations. For illustration purpose, reaction selectivity of a process with Bourne competitive reaction network is discussed. Results demonstrate that we can improve reaction selectivity by dynamically controlling rates and locations of feeding in the reactor. The proposed methodology incorporates mechanistic understanding of the reaction kinetics together with an efficient optimization algorithm to determine the optimal process operation and thus can serve as a tool for quality-by-design (QbD) during product development stage.