CYP17A1 Enzyme activity is linked to ambulatory blood pressure in a family-based population study.

BACKGROUND: Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS: In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS: Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS: Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES: The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND: Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS: Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS: Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS: This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Effects of continuous positive airway pressure treatment on coronary vasoreactivity measured by (82)Rb cardiac PET/CT in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSA) increases the risk of cardiovascular disease. We aimed at evaluating the effect of continuous positive airway pressure (CPAP) treatment on coronary endothelium-dependent vasoreactivity in OSA patients by quantifying myocardial blood flow (MBF) response to cold pressure testing (CPT). METHODS: In the morning after polysomnography (PSG), all participants underwent a dynamic (82)Rb cardiac positron emitting tomography/computed tomography (PET/CT) scan at rest, during CPT and adenosine stress. PSG and PET/CT were repeated at least 6 weeks after initiating CPAP treatment. OSA patients were compared to controls and according to response to CPAP. Patients' characteristics and PSG parameters were used to determine predictors of CPT-MBF. RESULTS: Thirty-two untreated OSA patients (age 58 ± 13 years, 27 men) and 9 controls (age 62 ± 5 years, 4 men) were enrolled. At baseline, compared to controls (apnea-hypopnea index (AHI) = 5.3 ± 2.6/h), untreated OSA patients (AHI = 48.6 ± 19.7/h) tend to have a lower CPT-MBF (1.1 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.09). After initiating CPAP, CPT-MBF was not different between well-treated patients (AHI <10/h) and controls (1.3 ± 0.3 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.83), but it was lower for insufficiently treated patients (AHI ≥10/h) (0.9 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.0045). CPT-MBF was also higher in well-treated than in insufficiently treated patients (1.3 ± 0.3 mL/min/g vs. 0.9 ± 0.2 mL/min/g, p = 0.001). Mean nocturnal oxygen saturation (β = -0.55, p = 0.02) and BMI (β = -0.58, p = 0.02) were independent predictors of CPT-MBF in OSA patients. CONCLUSIONS: Coronary endothelial vasoreactivity is impaired in insufficiently treated OSA patients compared to well-treated patients and controls, confirming the need for CPAP optimization.

Variable-stiffness composite panels: Defect tolerance under in-plane tensile loading

Automated Fiber Placement is being extensively used in the production of major composite components for the aircraft industry. This technology enables the production of tow-steered panels, which have been proven to greatly improve the structural efficiency of composites by means of in-plane stiffness variation and load redistribution. However, traditional straight-fiber architectures are still preferred. One of the reasons behind this is related to the uncertainties, as a result of process-induced defects, in the mechanical performance of the laminates. This experimental work investigates the effect of the fiber angle discontinuities between different tow courses in a ply on the un-notched and open-hole tensile strength of the laminate. The influence of several manufacturing parameters are studied in detail. The results reveal that 'ply staggering' and '0% gap coverage' is an effective combination in reducing the influence of defects in these laminates

Calcination of aluminum hydroxide over pressure and residence time

This work investigates the possible effect of pressure and residence time to the reaction of aluminum hydroxide into aluminum oxide. Various pressurized conditions are used as well as the help of various residence times. The aim is to increase the conversion of the reaction with the use of different pressures and residence times. The tests were performed with a laboratory scale fluidized bed reactor at the Outotec R&D Center in Frankfurt. Additional test work such as particle size analysis and differential thermal analysis were also carried out. Some calcined samples were also characterized with X-ray diffraction at the University of Auckland to obtain a reaction pathway when using pressurized conditions. All of the results are then compared with previous results.

Terutroban, A TP-receptor antagonist, reduces portal pressure in cirrhotic rats.

Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2 /prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride (CCl4 ) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction), and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4 -cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4 -cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (α-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway. CONCLUSION: Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis. This effect is due to decreased hepatic resistance, which in CCl4 -cirrhotic rats was linked to decreased hepatic fibrosis, but not in BDL rats, in which the main mediator appeared to be an enhanced eNOS-dependent vasodilatation, which was not liver-selective, as it was associated with decreased arterial pressure. The potential use of terutroban for portal hypertension requires further investigation.

Drug loading of mesoporous silicon particles

Porous silicon (PSi) is a promising material to be utilized in drug delivery formulations. The release rate of the drug compound can be controlled by changing the pore properties and surface chemistry of PSi. The loading of a poorly soluble drug into mesoporous silicon particles enhances its dissolution in the body. The drug loading is based on adsorption. The attainable maximum loaded amount depends on the properties of the drug compound and the PSi material, and on the process conditions. The loading solvent also essentially affects the adsorption process. The loading of indomethacin into PSi particles with varying surface modification was studied. Solvent mixtures were applied in the loading, and the loaded samples were analyzed with thermal analysis methods. The best degree of loading was obtained using a mixture of dichloromethane and methanol. The drug loads varied from 7.7 w-% to 26.8 w-%. A disturbing factor in the loading experiments was the tendency of indomethacin to form solvates with the solvents applied. In addition, the physical form and stability of indomethacin loaded in PSi and silica particles were studied using Raman spectroscopy. In the case of silica, the presence of crystalline drug as well as the polymorph form can be detected, but the method proved to be not applicable for PSi particles.

Catalytic Wet Oxidation of Paper Mill Debarking Water

The objective of the research was to study the influence of temperature, oxygen pressure, catalysts loading and initial COD concentration of debarking wastewater on the pollutants during the catalytic oxidation. More importantly, how the addition of catalyst affects the wet oxidation process. The whole work was divided into two main sections, theoretical and experimental parts. The theoretical part reviews the pulp and paper industry from wood processing to paper production as well as operations that generate wastes. Treatment methods applicable for industrial pulp and paper mill effluents were also discussed. Wet oxidation and catalytic wet oxidation processes including mechanism, reactions, kinetics and industrial applications were previewed. In the experimental part, catalytic wet oxidation process were studied at 120-180°C, 0-10 bar oxygen pressure, 0-1 g/L catalyst concentration and 1000-3000 mg/L initial COD concentration. Responses, such as Chemical oxygen demand (COD), Total organic carbon (TOC), colour, lignin/tannin, Biochemical oxygen demand (BOD) and pH were measured. In the experiment, the best conditions occurred at 180°C, 10 bar, l g/L catalyst concentration and 3000mg/L initial COD. At these conditions; 74% COD, 97% lignin/tannin, 54% TOC, 90% colour were removed from the wastewater. pH was greatly reduced from 7 to 4.6. Lignin/tannin was removed most. Lignin/tannin showed linear dependency with colour during oxidation. Temperature made the most impact in reducing contaminants in debarked wastewater.

Blood pressure levels and haematoma growth in patients with Intracerebral Haemorrhage (ICH) A retrospective observational study

Intracerebral haemorrhage (ICH) is a spontaneous extravasation of blood into brain parenchyma. Although ICH represents approximately only 15% of all strokes, it is one of the major causes of stroke-related death and disability. One of the causes of poor outcome is the haematoma growth. The association between elevated blood pressure (BP) and haematoma enlargement in acute ICH has not been clarified. Our objective is to try to identify this relationship that may suggest an immediate target for intervention to possibly improve outcomes in patients with spontaneous ICH and might settle the controversy surrounding the optimal management of blood pressure.We propose a retrospective revision using a sample present in our database of approximately 250 patients with primary ICH and less than 12h from symptoms onset. Systolic blood pressure levels (SBP) are assessed at baseline, at 6h, at 12h, at 24h and at 72h, being these last four the average levels of the different recordings during those time intervals. Haematoma growth will be defined as an increase in the volume of intraparenchymal haemorrhage of >33% as measured by image analysis on the 24-hour CT or 72-hour CT compared with the baseline CT scan. A qualified neuroradiologist not informed of the aim of the study, will review the CT images. The secondary objective will be to correlate the BP levels in the acute phase of ICH with clinical outcome. We will evaluate early neurologic deterioration at 72h by using the National Institutes of Health Stroke Scale (NIHSS); outcome at 90 days by using the modified Rankin scale and mortality at 72h and 90 days. The statistical analysis will be adjusted by possibly confounding variables

High pressure compression of filter cakes

The purpose of this thesis was to investigate the compression of filter cakes at high filtration pressures with five different test materials and to compare the energy consumption of high pressure compression with the energy consumption of thermal drying. The secondary target of this study was to investigate the particle deformation of test materials during filtration and compression. Literature part consists of basic theory of filtration and compression and of the basic parameters that influence the filtration process. There is also a brief description about all of the test materials including their properties and their industrial production and processing. Theoretical equations for calculating the energy consumptions of the filtrations at different conditions are also presented. At the beginning of the experiments at experimental part, the basic filtration tests were done with all the five test materials. Filtration tests were made at eight different pressures, from 6 bars up to 100 bars, by using piston press pressure filter. Filtration tests were then repeated by using a cylinder with smaller slurry volume than in the first series of filtration tests. Separate filtration tests were also done for investigating the deformation of solid particles during filtration and for finding the optimal curve for raising the filtration pressure. Energy consumption differences between high pressure filtration and ideal thermal drying process were done partly experimentally and partly by using theoretical calculation equations. By comparing these two water removal methods, the optimal ranges for their use were found considering their energy efficiency. The results of the measurements shows that the filtration rate increased and the moisture content of the filter cakes decreased as the filtration pressure was increased. Also the porosity of the filter cakes mainly decreased when the filtration pressure was increased. Particle deformation during the filtration was observed only with coal particles.

Gas collisions and pressure quenching of the photoluminescence of silicon nanopowder grown by plasma-enhanced chemical vapor deposition

The quenching of the photoluminescence of Si nanopowder grown by plasma-enhanced chemical vapor deposition due to pressure was measured for various gases ( H2, O2, N2, He, Ne, Ar, and Kr) and at different temperatures. The characteristic pressure, P0, of the general dependence I(P)=I0exp(-P/P0) is gas and temperature dependent. However, when the number of gas collisions is taken as the variable instead of pressure, then the quenching is the same within a gas family (mono- or diatomic) and it is temperature independent. So it is concluded that the effect depends on the number of gas collisions irrespective of the nature of the gas or its temperature

The influence of a certain volume of fluid in the lower tear meniscus on intraocular pressure measurements using the non-contact tonometer

Background: Intraocular pressure (IOP) is the pressure inside the eye that helps to maintain the integrity and the suitable form of the ocular globe. Precise and accurate measures of IOP are needed for the diagnosis as well as follow-up of glaucoma. In daily clinical practice, Goldmann applanation tonometer (GAT) and Non-contact tonometer (NCT) are the most common devices for measuring IOP. A close agreement between these methods has been showed, particularly in normotensive patients and a poor agreement, especially when IOP levels are above the normal range. Ophthalmologists have noticed a poor agreement between NCT and GAT, observing that by using NCT and after comparing with GAT, there is an overestimation of IOP readings, and particularly it occurs when the eyes are tearful. Previous studies investigate the effect of tears in Non-contact tonometer readings by the instillation of artificial tears, concluding in one of the studies that the variation was less than 1mmHg and not clinically significant, in contrast with another study which the increases were sadistically significant. Tear menisci are a thin strip of tear fluid located between the bulbar conjunctiva and the eyelid margins. We think that the overestimation of IOP readings using NCT could be due to the presence of a higher volume of tear in the lower tear meniscus which might cause an optical interference in the optoelectronic applanation monitoring system of this deviceObjectives: To research the influence of a certain volume of fluid in the lower tear meniscus on IOP measurements using the NCT in healthy eyes. Moreover, to investigate the agreement between IOP readings obtained by NCT and GAT in the presence and absence of this volume of fluidMethods: The study design will be transversal for diagnostic tests of repeated measures. We will study patients with no ocular pathology and IOP<21mmHg. It will consist in the measurement of IOP using NCT before and after the instillation of COLIRCUSÍ FLUOTEST, used as a volume of fluid in the lower tear meniscus, to observe if there will be differences using the paired t-test. Moreover, we will take IOP measures by GAT in order to know the agreement between these methods after and before the application of these eyedrops, using the ICC (intraclass correlation coefficient) and the Bland-Altmann method

Low metal loading catalysts used for the selective hydrogenation of styrene

A series of Group VIII metal catalysts was obtained for the semi-hydrogenation of styrene. Catalysts were characterized by Hydrogen Chemisorption, TPR and XPS. Palladium, rhodium and platinum low metal loading prepared catalysts presented high activity and selectivity (ca. 98%) during the semi-hydrogenation of styrene, being palladium the most active catalyst. The ruthenium catalyst also presented high selectivity (ca. 98%), but the lowest activity. For the palladium catalyst, the influence of the precursor salt and of the reduction temperature on the activity and selectivity were studied. The following activity series was obtained: PdN-423 > PdCl-673 > PdCl-373> PtCl-673 > RhCl-673 >> RuCl-673. As determined by XPS, differences in activity could be attributed, at least in part, to electronic effects.