The emission in the region E>0.1MeV during disk and limb faint solar flares

NASA Astrophysics Data System (ADS)

Irene, Arkhangelskaja; Andrew, Arkhangelskiy; Yury, Kotov; Alexandr, Glyanenko; Maria, Kolchina; Alexey, Kirichenko

2013-06-01

Hard X-ray and gamma-ray emission in energy band E>50 keV was first observed by AVS-F apparatus onboard CORONAS-F satellite (detector SONG-D) during some solar flares with classes B and C by GOES classification. Such component registered in flares with duration less than 30 min. However γ-emission up to several tens of MeV was observed during some classes B and C events, which temporal profiles were not corresponded to Neupert effect. For example, during class B2.3 limb solar flare January 7, 2005 maximum observed energy was Emax˜36 MeV and during class B4.6 disk solar event January 12, 2005 maximum observed energy was Emax˜7 MeV. Properties of temporal profiles and energy spectra of faint solar flares, during which emission in the energy band of E>0.1 MeV were registered are discussed in the presented work. There is not any strong correlation between presence or absence of hard X-ray and γ-ray emission and the intensity of soft X-ray emission during solar flares. The one of illustration of this fact is the absence of any observed statistically significant count rate exceed above background level during some class M flares in the energy band E>0.1 MeV. The typical example of such flares is event November 8, 2001 (class M4.2, lasts from 14:59 UT up to 16:00 UT, maximum of soft X-ray emission was at 15:35 UT on GOES data).

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

PubMed

Lemoine, Adrien; Mazoit, Jean X; Bonnet, Francis

2016-11-01

Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. Systematic review of clinical trials. Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

[Effect of the thickness of reinforced glass ceramics on the degree of conversion of dual-cure resin cements].

PubMed

Zhu, Lin-Lin; Qiu, Li-Hong; Liu, Li-Yang; Li, Xiao-Lin

2017-10-01

To determine the effect of the thickness of reinforced glass ceramics on the degree of conversion (DC) of three dual-cure resin cements (Multilink N, RelyX Ultimate and NX3-Nexus). Upcera reinforced glass ceramics and IPS e.max CAD test specimen were processed, with different thickness, transmittance was tested by ultraviolet and visible spectrometer. The DC was evaluated using Fourier transform infrared (FT-IR) spectrometer, then the degree of conversion of polymerization before and after curing was calculated. SPSS 21.0 software package was used for data analysis. Transmittance decreased along with the thickness of reinforced glass ceramics increased. At 2 mm -thickness transmittance of upcera lithium disilicate glass ceramics was superior to IPS e.max CAD. The DC of dual-cured resin cement was decreased with the increase of thickness. At the same 2 mm group, the DC of Multilink N and RelyX Ultimate under upcera lithium disilicate glass ceramics were superior to that under IPS e.max CAD groups. At 2 mm-thickness transmittance of upcera lithium disilicate glass ceramics was superior to IPS e.max CAD. At the same 2 mm group, the DC of Multilink N and RelyX Ultimate under upcera lithium disilicate glass ceramics were superior to that under IPS e.max CAD groups.

Effect of Finishing and Polishing on Roughness and Gloss of Lithium Disilicate and Lithium Silicate Zirconia Reinforced Glass Ceramic for CAD/CAM Systems.

PubMed

Vichi, A; Fonzar, R Fabian; Goracci, C; Carrabba, M; Ferrari, M

To assess the efficacy of dedicated finishing/polishing systems on roughness and gloss of VITA Suprinity and IPS e.max CAD. A total of 24 blocks of Suprinity and 24 of e.max were cut into a wedge shape using an InLab MC-XL milling unit. After crystallization, the 24 Suprinity wedges were divided into four subgroups: group A.1: Suprinity Polishing Set Clinical used for 30 seconds and group A.2: for 60 seconds; group A.3: VITA Akzent Plus Paste; and group A.4: spray. The 24 e.max wedges (group B) were divided into four subgroups according to the finishing procedure: group B.1: Optrafine Ceramic Polishing System for 30 seconds and group B.2: for 60 seconds; group B.3: IPS e.max CAD Crystall/Glaze paste; and group B.4: spray. After finishing/polishing, gloss was assessed with a glossmeter and roughness evaluated with a profilometer. Results were analyzed by applying a two-way analysis of variance for gloss and another for roughness (α=0.05). One specimen per each subgroup was observed with a scanning electron microscope. For roughness, materials and surface were significant factors ( p<0.001). Suprinity exhibited significantly lower roughness than e.max. Also the Material-Surface Treatment interaction was statistically significant ( p=0.026). For gloss, both material and surface treatment were significant factors ( p<0.001). VITA Suprinity showed significantly higher gloss than e.max. Also the Material-Surface Treatment interaction was statistically significant ( p<0.001). Manual finishing/polishing for 60 seconds and glazing paste are the most effective procedures in lowering the roughness of CAD/CAM silica-based glass ceramics. Manual finishing/polishing for 60 seconds allows milled silica-based glass ceramics to yield a higher gloss. VITA Suprinity displayed higher polishability than IPS e.max CAD.

Nonlinear lymphangion pressure-volume relationship minimizes edema

PubMed Central

Venugopal, Arun M.; Stewart, Randolph H.; Laine, Glen A.

2010-01-01

Lymphangions, the segments of lymphatic vessel between two valves, contract cyclically and actively pump, analogous to cardiac ventricles. Besides having a discernable systole and diastole, lymphangions have a relatively linear end-systolic pressure-volume relationship (with slope Emax) and a nonlinear end-diastolic pressure-volume relationship (with slope Emin). To counter increased microvascular filtration (causing increased lymphatic inlet pressure), lymphangions must respond to modest increases in transmural pressure by increasing pumping. To counter venous hypertension (causing increased lymphatic inlet and outlet pressures), lymphangions must respond to potentially large increases in transmural pressure by maintaining lymph flow. We therefore hypothesized that the nonlinear lymphangion pressure-volume relationship allows transition from a transmural pressure-dependent stroke volume to a transmural pressure-independent stroke volume as transmural pressure increases. To test this hypothesis, we applied a mathematical model based on the time-varying elastance concept typically applied to ventricles (the ratio of pressure to volume cycles periodically from a minimum, Emin, to a maximum, Emax). This model predicted that lymphangions increase stroke volume and stroke work with transmural pressure if Emin < Emax at low transmural pressures, but maintain stroke volume and stroke work if Emin= Emax at higher transmural pressures. Furthermore, at higher transmural pressures, stroke work is evenly distributed among a chain of lymphangions. Model predictions were tested by comparison to previously reported data. Model predictions were consistent with reported lymphangion properties and pressure-flow relationships of entire lymphatic systems. The nonlinear lymphangion pressure-volume relationship therefore minimizes edema resulting from both increased microvascular filtration and venous hypertension. PMID:20601461

The marginal fit of E.max Press and E.max CAD lithium disilicate restorations: A critical review.

PubMed

Mounajjed, Radek; M Layton, Danielle; Azar, Basel

2016-12-01

This critical review aimed to assess the vertical marginal gap that was present when E.max lithium disilicate-based restoration (Press and CAD) are fabricated in-vitro. Published articles reporting vertical marginal gap measurements of in-vitro restorations that had been fabricated from E.Max lithium disilicate were sought with an electronic search of MEDLINE (PubMed) and hand search of selected dental journals. The outcomes were reviewed qualitatively. The majority of studies that compared the marginal fit of E.max press and E.max CAD restorations, found that the E.max lithium disilicate restorations fabricated with the press technique had significantly smaller marginal gaps than those fabricated with CAD technique. This research indicates that E.max lithium disilicate restorations fabricated with the press technique have measurably smaller marginal gaps when compared with those fabricated with CAD techniques within in-vitro environments. The marginal gaps achieved by the restorations across all groups were within a clinically acceptable range.

Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.

PubMed

Zhang, Dong-mei; Wang, Kun; Zhao, Xia; Li, Yun-fei; Zheng, Qing-shan; Wang, Zi-ning; Cui, Yi-min

2012-11-01

To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects. Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches. The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V(1)), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V(2)) were 0.323 L·h(-1)·kg(-1), 0.086 L/kg, 0.0957 L·h(-1)·kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E(max) model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC(*)), had a significant effect on the EC(50) value. The typical PD population values of maximum effect (E(max)), EC(50), baseline ACT value (E(0)) and the coefficient of RBC(*) on EC(50) were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E(max), EC(50), and E(0) were 6.80%, 46.4%, and 4.10%, respectively. Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.

77 FR 20445 - eMax Worldwide, Inc.; Order of Suspension of Trading

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-04

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] eMax Worldwide, Inc.; Order of Suspension of... the protection of investors require a suspension of trading in the securities of eMax Worldwide, Inc.... eMax Worldwide, Inc. has failed to make periodic filings with the Commission and has more than 300...

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 11: Commissioning of a system for the measurement of electron stopping powers

DOE Office of Scientific and Technical Information (OSTI.GOV)

McEwen, Malcolm; Roy, Timothy; Tessier, Frederic

Purpose: To develop the techniques required to experimentally determine electron stopping powers for application in primary standards and dosimetry protocols. Method and Materials: A large-volume HPGe detector system (>80% efficiency) was commissioned for the measurement of high energy (5–35 MeV) electron beams. As a proof of principle the system was used with a Y-90/Sr-90 radioactive source. Thin plates of absorbing material (< 0.1 gcm-2) were then placed between the source and detector and the emerging electron spectrum was acquired. The full experimental geometry was modelled using the EGSnrc package to validate the detector design, optimize the experimental setup and comparemore » measured and calculated spectra. Results: The biggest challenge using a beta source was to identify a robust spectral parameter to determine for each measurement. An end-point-fitting routine was used to determine the maximum energy, Emax, of the beta spectrum for each absorber thickness t. The parameter dEmax/dt is related to the electron stopping power and the same routine was applied to both measured and simulated spectra. Although the standard uncertainty in dEmax/dt was of the order of 5 %, by taking the ratio of measured and Monte Carlo values for dEmax/dt the uncertainty of the fitting routine was eliminated and the uncertainty was reduced to less than 2 %. The agreement between measurement and simulation was within this uncertainty estimate. Conclusion: The investigation confirmed the experimental approach and demonstrated that EGSnrc could accurately determine correction factors that will be required for the final measurement setup in a linac beam.« less

Utility of shear wave elastography to detect papillary thyroid carcinoma in thyroid nodules: efficacy of the standard deviation elasticity.

PubMed

Kim, Hye Jeong; Kwak, Mi Kyung; Choi, In Ho; Jin, So-Young; Park, Hyeong Kyu; Byun, Dong Won; Suh, Kyoil; Yoo, Myung Hi

2018-02-23

The aim of this study was to address the role of the elasticity index as a possible predictive marker for detecting papillary thyroid carcinoma (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for differentiating PTC from benign thyroid nodules. One hundred and nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided fine needle aspiration and core needle biopsy were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. Among 105 nodules, 14 were PTC and 91 were benign. The EMean, EMin, and EMax values were significantly higher in PTCs than benign nodules (EMean 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; EMin 27.9 vs. 17.8, p = 0.034; EMax 46.7 vs. 31.5, p < 0.001). The EMean, EMin, and EMax were significantly associated with PTC with diagnostic odds ratios varying from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively), and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The ESD values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p < 0.001). ESD had the highest specificity (96.6%) when applied with a cut-off value of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds ratio of 28.50. The shear elasticity index of ESD, with higher likelihood ratios for PTC, will probably identify nodules that have a high potential for malignancy. It may help to identify and select malignant nodules, while reducing unnecessary fine needle aspiration and core needle biopsies of benign nodules.

Effect of Calcifications on Breast Ultrasound Shear Wave Elastography: An Investigational Study.

PubMed

Gregory, Adriana; Mehrmohammadi, Mohammad; Denis, Max; Bayat, Mahdi; Stan, Daniela L; Fatemi, Mostafa; Alizad, Azra

2015-01-01

To investigate the effects of macrocalcifications and clustered microcalcifications associated with benign breast masses on shear wave elastography (SWE). SuperSonic Imagine (SSI) and comb-push ultrasound shear elastography (CUSE) were performed on three sets of phantoms to investigate how calcifications of different sizes and distributions influence measured elasticity. To demonstrate the effect in vivo, three female patients with benign breast masses associated with mammographically-identified calcifications were evaluated by CUSE. Apparent maximum elasticity (Emax) estimates resulting from individual macrocalcifications (with diameters of 2mm, 3mm, 5mm, 6mm, 9mm, 11mm, and 15mm) showed values over 50 kPa for all cases, which represents more than 100% increase over background (~21kPa). We considered a 2cm-diameter circular region of interest for all phantom experiments. Mean elasticity (Emean) values varied from 26 kPa to 73 kPa, depending on the macrocalcification size. Highly dense clusters of microcalcifications showed higher Emax values than clusters of microcalcification with low concentrations, but the difference in Emean values was not significant. Our results demonstrate that the presence of large isolated macrocalcifications and highly concentrated clusters of microcalcifications can introduce areas with apparent high elasticity in SWE. Considering that benign breast masses normally have significantly lower elasticity values than malignant tumors, such areas with high elasticity appearing due to presence of calcification in benign breast masses may lead to misdiagnosis.

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

PubMed

Liu, Feng; Walters, Stephen J; Julious, Steven A

2017-10-02

It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log linear shape curve under fixed dose allocation, no adaptive allocation, half adaptive and adaptive scenarios. The bias though is significantly increased for the Emax model if the true dose response follows a U-shaped curve. In most cases the Bayesian Emax model works effectively and efficiently, with low bias and good probability of success in case of monotonic dose response. However, if there is a belief that the dose response could be non-monotonic then the NDLM is the superior model to assess the dose response.

Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. Maxima challenge infection.

PubMed

Jenkins, Mark C; Stevens, Laura; O'Brien, Celia; Parker, Carolyn; Miska, Katrzyna; Konjufca, Vjollca

2018-02-14

The purpose of this study was to determine if conjugating a recombinant Eimeria maxima protein, namely EmaxIMP1, into 20 nm polystyrene nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherichia coli as a poly-His fusion protein, purified by NiNTA chromatography, and conjugated to 20 nm polystyrene NP (NP-EmaxIMP1). NP-EMaxIMP1 or control non-recombinant (NP-NR) protein were delivered per os to newly-hatched broiler chicks with subsequent booster immunizations at 3 and 21 days of age. In battery cage studies (n = 4), chickens immunized with NP-EMaxIMP1 displayed complete protection as measured by weight gain (WG) against E. maxima challenge compared to chickens immunized with NP-NR. WG in the NP-EMaxIMP1-immunized groups was identical to WG in chickens that were not infected with E. maxima infected chickens. In floor pen studies (n = 2), chickens immunized with NP-EMaxIMP1 displayed partial protection as measured by WG against E. maxima challenge compared to chickens immunized with NP-NR. In order to understand the basis for immune stimulation, newly-hatched chicks were inoculated per os with NP-EMaxIMP1 or NP-NR protein, and the small intestine, bursa, and spleen, were examined for NP localization at 1 h and 6 h post-inoculation. Within 1 h, both NP-EMaxIMP1 and NP-NR were observed in all 3 tissues. An increase was observed in the level of NP-EmaxIMP1 and NP-NR in all tissues at 6 h post-inoculation. These data indicate that 20 nm NP-EmaxIMP1 or NP-NR reached deeper tissues within hours of oral inoculation and elicited complete to partial immunity against E. maxima challenge infection. Published by Elsevier Ltd.

Allosteric modulation of semicarbazide-sensitive amine oxidase activities in vitro by imidazoline receptor ligands

PubMed Central

Holt, Andrew; Wieland, Barbara; Baker, Glen B

2004-01-01

Evidence indicates that imidazoline I2 binding sites (I2BSs) are present on monoamine oxidase (MAO) and on soluble (plasma) semicarbazide-sensitive amine oxidase enzymes. The binding site on MAO has been described as a modulatory site, although no effects on activity are thought to have been observed as a result of ligands binding to these sites. We examined the effects in vitro of several imidazoline binding site ligands on activities of bovine plasma amine oxidase (BPAO) and porcine kidney diamine oxidase (PKDAO) in a spectrophotometric protocol. While both enzymes were inhibited at high concentrations of all ligands, clonidine, cirazoline and oxymetazoline were seen, at lower concentrations, to increase activity of BPAO versus benzylamine, but not of PKDAO versus putrescine. This effect was substrate dependent, with mixed or biphasic inhibition of spermidine, methylamine, p-tyramine and β-phenylethylamine oxidation observed at cirazoline concentrations that increased benzylamine oxidation. With benzylamine as substrate, clonidine decreased KM (EC50 8.82 μM, Emax 75.1% of control) and increased Vmax (EC50 164.6 μM, Emax 154.1% of control). Cirazoline decreased Vmax (EC50 2.15 μM, Emax 91.4% of control), then decreased KM (EC50 5.63 μM, Emax 42.6% of control) and increased Vmax (EC50 49.0 μM, Emax 114.4% of decreased Vmax value). Data for clonidine fitted a mathematical model for two-site nonessential activation plus linear intersecting noncompetitive inhibition. Data for cirazoline were consistent with involvement of a fourth site. These results reveal an ability of imidazoline ligands to modulate BPAO kinetics allosterically. The derived mechanism may have functional significance with respect to modulation of MAO by I2BS ligands. PMID:15451775

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Repair bond strength of resin composite to bilayer dental ceramics

PubMed Central

2018-01-01

PURPOSE The purpose of this study was to investigate the effect of various surface treatments (ST) on the shear bond strength of resin composite to three bilayer dental ceramics made by CAD/CAM and two veneering ceramics. MATERIALS AND METHODS Three different bilayer dental ceramics and two different veneering ceramics were used (Group A: IPS e.max CAD+IPS e.max Ceram; Group B: IPS e.max ZirCAD+IPS e.max Ceram, Group C: Vita Suprinity+Vita VM11; Group D: IPS e.max Ceram; Group E: Vita VM11). All groups were divided into eight subgroups according to the ST. Then, all test specimens were repaired with a nano hybrid resin composite. Half of the test specimens were subjected to thermocycling procedure and the other half was stored in distilled water at 37℃. Shear bond strength tests for all test specimens were carried out with a universal testing machine. RESULTS There were statistically significant differences among the tested surface treatments within the all tested fracture types (P<.005). HF etching showed higher bond strength values in Groups A, C, D, and E than the other tested ST. However, bonding durability of all the surface-treated groups were similar after thermocycling (P>.00125). CONCLUSION This study revealed that HF etching for glass ceramics and sandblasting for zirconia ceramics were adequate for repair of all ceramic restorations. The effect of ceramic type exposed on the fracture area was not significant on the repair bond strength of resin composites to different ceramic types. PMID:29713430

Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.

PubMed

Shen, Chenlin; Huang, Xiaohui; Li, Jun; Zhang, Ping; Li, Lin; Zhang, Wei; Hu, Tingting; Pappoe, Faustina; Huang, Jihan; Tang, Haiqin

2016-01-01

1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.

Effect of Calcifications on Breast Ultrasound Shear Wave Elastography: An Investigational Study

PubMed Central

Gregory, Adriana; Mehrmohammadi, Mohammad; Denis, Max; Bayat, Mahdi; Stan, Daniela L.; Fatemi, Mostafa; Alizad, Azra

2015-01-01

Purpose To investigate the effects of macrocalcifications and clustered microcalcifications associated with benign breast masses on shear wave elastography (SWE). Methods SuperSonic Imagine (SSI) and comb-push ultrasound shear elastography (CUSE) were performed on three sets of phantoms to investigate how calcifications of different sizes and distributions influence measured elasticity. To demonstrate the effect in vivo, three female patients with benign breast masses associated with mammographically-identified calcifications were evaluated by CUSE. Results Apparent maximum elasticity (Emax) estimates resulting from individual macrocalcifications (with diameters of 2mm, 3mm, 5mm, 6mm, 9mm, 11mm, and 15mm) showed values over 50 kPa for all cases, which represents more than 100% increase over background (~21kPa). We considered a 2cm-diameter circular region of interest for all phantom experiments. Mean elasticity (Emean) values varied from 26 kPa to 73 kPa, depending on the macrocalcification size. Highly dense clusters of microcalcifications showed higher Emax values than clusters of microcalcification with low concentrations, but the difference in Emean values was not significant. Conclusions Our results demonstrate that the presence of large isolated macrocalcifications and highly concentrated clusters of microcalcifications can introduce areas with apparent high elasticity in SWE. Considering that benign breast masses normally have significantly lower elasticity values than malignant tumors, such areas with high elasticity appearing due to presence of calcification in benign breast masses may lead to misdiagnosis. PMID:26368939

Ceramic Inlays: Effect of Mechanical Cycling and Ceramic Type on Restoration-dentin Bond Strength.

PubMed

Trindade, F Z; Kleverlaan, C J; da Silva, L H; Feilzer, A J; Cesar, P F; Bottino, M A; Valandro, L F

2016-01-01

This study aimed to evaluate the bond strength between dentin and five different ceramic inlays in permanent maxillary premolars, with and without mechanical cycling. One hundred permanent maxillary premolars were prepared and divided into 10 groups (n=10) according to the ceramic system (IPS e.Max Press; IPS e.Max CAD; Vita PM9; Vita Mark II; and Vita VM7) and the mechanical cycling factor (with and without [100 N, 2 Hz, 1.2×10(6) cycles]). The inlays were adhesively cemented, and all of the specimens were cut into microbars (1×1 mm, nontrimming method), which were tested under microtensile loading. The failure mode was classified and contact angle, roughness, and microtopographic analyses were performed on each ceramic surface. The mechanical cycling had a significant effect (p=0.0087) on the bond strength between dentin and IPS e.max Press. The Vita Mark II group had the highest bond strength values under both conditions, with mechanical cycling (9.7±1.8 MPa) and without (8.2±1.9 MPa), while IPS e.Max CAD had the lowest values (2.6±1.6 and 2.2±1.4, respectively). The adhesive failure mode at the ceramic/cement interface was the most frequent. Vita Mark II showed the highest value of average roughness. IPS e.max Press and Vita Mark II ceramics presented the lowest contact angles. In conclusion, the composition and manufacturing process of ceramics seem to have an influence on the ceramic surface and resin cement bond strength. Mechanical cycling did not cause significant degradation on the dentin and ceramic bond strength under the configuration used.

The effect of core material, veneering porcelain, and fabrication technique on the biaxial flexural strength and weibull analysis of selected dental ceramics.

PubMed

Lin, Wei-Shao; Ercoli, Carlo; Feng, Changyong; Morton, Dean

2012-07-01

The objective of this study was to compare the effect of veneering porcelain (monolithic or bilayer specimens) and core fabrication technique (heat-pressed or CAD/CAM) on the biaxial flexural strength and Weibull modulus of leucite-reinforced and lithium-disilicate glass ceramics. In addition, the effect of veneering technique (heat-pressed or powder/liquid layering) for zirconia ceramics on the biaxial flexural strength and Weibull modulus was studied. Five ceramic core materials (IPS Empress Esthetic, IPS Empress CAD, IPS e.max Press, IPS e.max CAD, IPS e.max ZirCAD) and three corresponding veneering porcelains (IPS Empress Esthetic Veneer, IPS e.max Ceram, IPS e.max ZirPress) were selected for this study. Each core material group contained three subgroups based on the core material thickness and the presence of corresponding veneering porcelain as follows: 1.5 mm core material only (subgroup 1.5C), 0.8 mm core material only (subgroup 0.8C), and 1.5 mm core/veneer group: 0.8 mm core with 0.7 mm corresponding veneering porcelain with a powder/liquid layering technique (subgroup 0.8C-0.7VL). The ZirCAD group had one additional 1.5 mm core/veneer subgroup with 0.7 mm heat-pressed veneering porcelain (subgroup 0.8C-0.7VP). The biaxial flexural strengths were compared for each subgroup (n = 10) according to ISO standard 6872:2008 with ANOVA and Tukey's post hoc multiple comparison test (p≤ 0.05). The reliability of strength was analyzed with the Weibull distribution. For all core materials, the 1.5 mm core/veneer subgroups (0.8C-0.7VL, 0.8C-0.7VP) had significantly lower mean biaxial flexural strengths (p < 0.0001) than the other two subgroups (subgroups 1.5C and 0.8C). For the ZirCAD group, the 0.8C-0.7VL subgroup had significantly lower flexural strength (p= 0.004) than subgroup 0.8C-0.7VP. Nonetheless, both veneered ZirCAD groups showed greater flexural strength than the monolithic Empress and e.max groups, regardless of core thickness and fabrication techniques. Comparing fabrication techniques, Empress Esthetic/CAD, e.max Press/CAD had similar biaxial flexural strength (p= 0.28 for Empress pair; p= 0.87 for e.max pair); however, e.max CAD/Press groups had significantly higher flexural strength (p < 0.0001) than Empress Esthetic/CAD groups. Monolithic core specimens presented with higher Weibull modulus with all selected core materials. For the ZirCAD group, although the bilayer 0.8C-0.7VL subgroup exhibited significantly lower flexural strength, it had highest Weibull modulus than the 0.8C-0.7VP subgroup. The present study suggests that veneering porcelain onto a ceramic core material diminishes the flexural strength and the reliability of the bilayer specimens. Leucite-reinforced glass-ceramic cores have lower flexural strength than lithium-disilicate ones, while fabrication techniques (heat-pressed or CAD/CAM) and specimen thicknesses do not affect the flexural strength of all glass ceramics. Compared with the heat-pressed veneering technique, the powder/liquid veneering technique exhibited lower flexural strength but increased reliability with a higher Weibull modulus for zirconia bilayer specimens. Zirconia-veneered ceramics exhibited greater flexural strength than monolithic leucite-reinforced and lithium-disilicate ceramics regardless of zirconia veneering techniques (heat-pressed or powder/liquid technique). © 2012 by the American College of Prosthodontists.

Activated Rho Kinase Mediates Diabetes-Induced Elevation of Vascular Arginase Activation and Contributes to Impaired Corpora Cavernosa Relaxation: Possible Involvement of p38 MAPK Activation

PubMed Central

Nunes, Kenia P.; Yao, Lin; Liao, James K.; Webb, R. Clinton; Caldwell, Ruth B.; Caldwell, R. William

2013-01-01

Introduction Activated RhoA/Rho kinase (ROCK) has been implicated in diabetes-induced erectile dysfunction. Earlier studies have demonstrated involvement of ROCK pathway in the activation of arginase in endothelial cells. However, signaling pathways activated by ROCK in the penis remain unclear. Aim We tested whether ROCK and p38 MAPK are involved in the elevation of arginase activity and subsequent impairment of corpora cavernosal (CC) relaxation in diabetes. Methods Eight weeks after streptozotocin-induced diabetes, vascular functional studies, arginase activity assay, and protein expression of RhoA, ROCK, phospho-p38 MAPK, p38 MAPK, phospho-MYPT-1Thr850, MYPT-1 and arginase levels were assessed in CC tissues from nondiabetic wild type (WT), diabetic (D) WT (WT + D), partial ROCK 2+/− knockout (KO), and ROCK 2+/− KO + D mice. Main Outcome Measures The expression of RhoA, ROCK 1 and 2, phosphorylation of MYPT-1Thr850 and p38 MAPK, arginase activity/expression, endothelial- and nitrergic-dependent relaxation of CC was assayed. Results Diabetes significantly reduced maximum relaxation (Emax) to both endothelium-dependent acetylcholine (WT + D: Emax; 61 ± 4% vs. WT: Emax; 75 ± 2%) and nitrergic nerve stimulation. These effects were associated with increased expression of active RhoA, ROCK 2, phospho-MYPT-1Thr850, phospho-p38 MAPK, arginase II, and activity of corporal arginase (1.6-fold) in WT diabetic CC. However, this impairment in CC of WT + D mice was absent in heterozygous ROCK 2+/− KO + D mice for acetylcholine (Emax: 80 ± 5%) and attenuated for nitrergic nerve-induced relaxation. CC of ROCK 2+/− KO + D mice showed much less ROCK activity, did not exhibit p38 MAPK activation, and had reduced arginase activity and arginase II expression. These findings indicate that ROCK 2 mediates diabetes-induced elevation of arginase activity. Additionally, pretreatment of WT diabetic CC with inhibitors of arginase (ABH) or p38 MAPK (SB203580) partially prevented impairment of ACh- and nitrergic nerve-induced relaxation and elevation of arginase activity. Conclusion ROCK 2, p38 MAPK and arginase play key roles in diabetes-induced impairment of CC relaxation. PMID:23566117

L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

PubMed

Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

2018-03-01

The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of dexmedetomidine by L-arginine depends on arginase activity and the production of urea and ornithine.

The effect of spark plasma sintering on lithium disilicate glass-ceramics.

PubMed

Al Mansour, Fatima; Karpukhina, Natalia; Grasso, Salvatore; Wilson, Rory M; Reece, Mike J; Cattell, Michael J

2015-10-01

To evaluate the effects of spark plasma sintering (SPS) on the microstructure of lithium disilicate glass-ceramics. IPS e.max CAD glass-ceramic samples were processed using spark plasma sintering (SPS) and conventionally sintered (CS) as a comparison. Specimens were sintered at varying temperatures (T1: 840°C, T2: 820°C, T3: 800°C), heating rates (HR1: 150°C/min, HR2: 300°C/min, HR3: 500°C/min) and pressures (P1: 15MPa, P2: 50MPa, P3: 70MPa). IPS e.max Press glass powder samples were densified at 750 and 800°C (50 or 200MPa pressure). Samples were characterized using XRD, HTXRD, and SEM and quantitative image analysis. There was a significant increase in median crystal size (MCS) between the CS and the SPS T1 groups. A statistical difference (p>0.05) in MCS between SPS T1 and SPS T2 groups was observed. The SPS HR3 sample produced a smaller MCS than the CS, SPS HR1 and HR2 groups (p<0.05). The SPS P3 sample had a reduction in MCS compared with the CS group (p<0.05). XRD of the SPS samples revealed major lithium disilicate/lithium metasilicate phases and minor lithium orthophosphate and cristobalite/quartz phases. Densified IPS e.max Press glass samples resulted in fine fibrils or graduated lithium disilicate crystals. The effects of SPS were used to refine the microstructure of IPS e.max CAD lithium disilicate glass-ceramics. Densification by SPS of IPS e.max Press glass resulted in textured and fine nano-crystalline microstructures. SPS generated glass-ceramic microstructures may have unique properties and could be useful in the production of CAD/CAM materials for dentistry. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.

PubMed

de Godoy, Márcio Augusto Fressatto; Accorsi-Mendonça, Daniela; de Oliveira, Ana Maria

2003-02-01

We have evaluated the interaction between angiotensin II (Ang II) and the cholinergic transmission in anococcygeus smooth muscles isolated from rats treated (sympathectomised group) or not (vehicle group) with reserpine and alpha-methyl-p-tyrosine. For this, we contracted the tissues with Ang II in the presence and absence of atropine and hexamethonium. Ang II induced concentration-dependent contractions, which did not undergo temporal changes in tissues isolated from both groups of rats. In the vehicle group, Ang II induced more potent contractions than in the sympathectomised group. In the sympathectomised rat group, atropine inhibited the contractions induced by Ang II in a concentration-dependent fashion with no decrease in E(max). Additionally, hexamethonium inhibited the contraction induced by Ang II in a concentration-dependent fashion with a decrease in E(max). Association of atropine and hexamethonium produced Ang II-induced curves with rightward shifts from the control curve with a decrease in E(max). Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) reversed the effects of atropine and hexamethonium association. Conversely, in the vehicle group of rats, atropine and hexamethonium did not produce any significant effect. However, in the presence of yohimbine, atropine shifted the Ang II-induced curves to the right of the control curve with no E(max) decrease. Results suggest that there is a positive interaction between Ang II and cholinergic transmission in the rat anococcygeus smooth muscle mediated by angiotensin receptors located on pre-ganglionic cells.

Potassium Sodium Niobate-Based Lead-Free Piezoelectric Multilayer Ceramics Co-Fired with Nickel Electrodes

PubMed Central

Kawada, Shinichiro; Hayashi, Hiroyuki; Ishii, Hideki; Kimura, Masahiko; Ando, Akira; Omiya, Suetake; Kubodera, Noriyuki

2015-01-01

Although lead-free piezoelectric ceramics have been extensively studied, many problems must still be overcome before they are suitable for practical use. One of the main problems is fabricating a multilayer structure, and one solution attracting growing interest is the use of lead-free multilayer piezoelectric ceramics. The paper reviews work that has been done by the authors on lead-free alkali niobate-based multilayer piezoelectric ceramics co-fired with nickel inner electrodes. Nickel inner electrodes have many advantages, such as high electromigration resistance, high interfacial strength with ceramics, and greater cost effectiveness than silver palladium inner electrodes. However, widely used lead zirconate titanate-based ceramics cannot be co-fired with nickel inner electrodes, and silver palladium inner electrodes are usually used for lead zirconate titanate-based piezoelectric ceramics. A possible alternative is lead-free ceramics co-fired with nickel inner electrodes. We have thus been developing lead-free alkali niobate-based multilayer ceramics co-fired with nickel inner electrodes. The normalized electric-field-induced thickness strain (Smax/Emax) of a representative alkali niobate-based multilayer ceramic structure with nickel inner electrodes was 360 pm/V, where Smax denotes the maximum strain and Emax denotes the maximum electric field. This value is about half that for the lead zirconate titanate-based ceramics that are widely used. However, a comparable value can be obtained by stacking more ceramic layers with smaller thicknesses. In the paper, the compositional design and process used to co-fire lead-free ceramics with nickel inner electrodes are introduced, and their piezoelectric properties and reliabilities are shown. Recent advances are introduced, and future development is discussed. PMID:28793646

Pharmacokinetic and pharmacodynamic assessment of bioavailability for two prodrugs of methylprednisolone

PubMed Central

Daley-Yates, P. T.; Gregory, A. J.; Brooks, C. D.

1997-01-01

Aims The aim of this study was to establish whether pharmacokinetic differences between two pro-drugs of methylprednisolone (MP) are likely to be of clinical significance. Methods This study was a single-blind, randomized, crossover design comparing the bioequivalence of MP released from the pro-drugs Promedrol (MP suleptanate) and Solu-Medrol (MP succinate) after a single 250 mg (MP equivalent) intramuscular injection to 20 healthy male volunteers. Bioequivalence was assessed by conventional pharmacokinetic analysis, by measuring pharmacodynamic responses plus a novel approach using pharmacokinetic/pharmacodynamic modeling. The main measure of pharmacodynamic response was whole blood histamine (WBH), a measure of basophil numbers. Results The MP Cmax was less for MP suleptanate due to a longer absorption half-life of the prodrug from the intramuscular injection site. The bioavailability of MP was equivalent when based on AUC with a MP suleptanate median 108% of the MP succinate value (90% CI: 102–114%). For Cmax the MP suleptanate median was 81% of the MP succinate value (90% CI: 75–88%). The tmax for MP from MP suleptanate was delayed relative to MP succinate. The median difference was 200% (90% non-parametric CI: 141–283%). The area under the WBH effect-time curve (AUEC) and the maximum response (Emax ) were found to be equivalent (90% CI: 98–113% and 93–109% respectively). The maximum changes in other white blood cell counts, blood glucose concentration and the parameters of the pharmacodynamic sigmoid Emax model (EC50, Emax and γ) were also not significantly different between prodrugs. Conclusions MP suleptanate is an acceptable pharmaceutical alternative to MP succinate. The use of both pharmacokinetic and pharmacodynamic response data together gives greater confidence in the conclusions compared with those based only on conventional pharmacokinetic bioequivalence analysis. PMID:9205819

Abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users: A Phase I randomized controlled trial.

PubMed

Levy-Cooperman, Naama; Schoedel, Kerri A; Chakraborty, Bijan; Blum, David; Cheng, Hailong

2016-08-01

Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥7days between each treatment: ESL (800mg, 1600mg, 2000mg, and 2400mg); ALP (1.5mg and 3.0mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine-Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task-Revised tests. Peak scores for Drug-Liking VAS (maximum effect [Emax]) were significantly higher for both ALP doses than for PBO (p<0.0001), thereby confirming study validity. Drug-Liking VAS Emax was significantly lower for all ESL doses than both ALP doses (p<0.0001). Drug-Liking VAS Emax for ESL 800mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p=0.19). At the three higher ESL doses (1600mg and the supratherapeutic doses of 2000mg and 2400mg), Drug-Liking VAS Emax was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3-13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p<0.05), the effect of ESL (all doses) was significantly less than that of ALP (both doses). On most secondary measures, the dose-response relationship was relatively flat or showed saturation at higher ESL doses. Although significant differences were observed for ESL compared with those for PBO for some specific CRT and DAT endpoints (i.e., reaction time, manual tracking, hit latency), ALP demonstrated significant and dose-dependent impairment on the majority of cognitive endpoints when compared with PBO and ESL. Mean plasma concentrations of the active metabolite of ESL, eslicarbazepine, increased with increasing ESL dose. Pharmacokinetic parameters estimated for eslicarbazepine were generally comparable with results from previous studies in healthy volunteers. This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-'liking' at higher doses, the magnitude of these effects was small. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Categorical QSAR models for skin sensitization based on local lymph node assay measures and both ground and excited state 4D-fingerprint descriptors

NASA Astrophysics Data System (ADS)

Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Santos-Filho, Osvaldo A.; Esposito, Emilio X.; Hopfinger, Anton J.; Tseng, Yufeng J.

2008-06-01

In previous studies we have developed categorical QSAR models for predicting skin-sensitization potency based on 4D-fingerprint (4D-FP) descriptors and in vivo murine local lymph node assay (LLNA) measures. Only 4D-FP derived from the ground state (GMAX) structures of the molecules were used to build the QSAR models. In this study we have generated 4D-FP descriptors from the first excited state (EMAX) structures of the molecules. The GMAX, EMAX and the combined ground and excited state 4D-FP descriptors (GEMAX) were employed in building categorical QSAR models. Logistic regression (LR) and partial least square coupled logistic regression (PLS-CLR), found to be effective model building for the LLNA skin-sensitization measures in our previous studies, were used again in this study. This also permitted comparison of the prior ground state models to those involving first excited state 4D-FP descriptors. Three types of categorical QSAR models were constructed for each of the GMAX, EMAX and GEMAX datasets: a binary model (2-state), an ordinal model (3-state) and a binary-binary model (two-2-state). No significant differences exist among the LR 2-state model constructed for each of the three datasets. However, the PLS-CLR 3-state and 2-state models based on the EMAX and GEMAX datasets have higher predictivity than those constructed using only the GMAX dataset. These EMAX and GMAX categorical models are also more significant and predictive than corresponding models built in our previous QSAR studies of LLNA skin-sensitization measures.

Effect of hydrofluoric acid surface treatments on micro-shear bond strength of CAD/CAM ceramics

PubMed Central

Mokhtarpour, Faraneh; Alaghehmand, Homayoon; Khafri, Soraya

2017-01-01

Introduction Dental ceramics are appreciated as highly esthetic restorative materials that can simulate the appearance of natural dentition better than other materials. The aim of this study was to evaluate the effect of hydrofluoric acid concentration and etching time on micro-shear bond strength (μSBS) to IPS e.max CAD and Vita Mark II of a dual cured resin cement (Panavia F2.0). Methods This study was an experimental in vitro study, performed in the dental material research center of Babol University of Medical Sciences in 2016. Two hydrofluoric acid concentrations (5% and 10%) and three different etching times (20, 60 and 120 seconds) were used to etch the specimens respectively. A silane coupling agent (Clearfil porcelain activator) and priming and bonding agent (Clearfil SE bond) were used on the etched surfaces in accordance to the manufacturer’s instructions of use. Then resin cement was applied on the prepared ceramic surfaces and light cured. μSBS between resin cement and the porcelains were measured with a universal testing machine. Mode of failure was observed with 40× magnification by means of a Stereo microscope. Data were analyzed with ANOVA and independent-samples t-test and Chi-square tests. Results In both e.max and Vita Mark II groups, μSBS were not significantly different when different etching times (one-way ANOVA) and HF acid concentrations (Independent-samples t-test) were used (p>0.05), but the highest μSBS was shown in e.max specimens etched 60 s with 5% HF and Vita Mark II specimens etched 20 s with 10% HF. μSBS of e.max was significantly higher than Vita Mark II (p=0.00). Conclusion Best surface treatment for e.max and Vita Mark II ceramics is 20 s etch using 5 % hydrofluoric acid. PMID:29238488

Comparison of Marginal and Internal Adaptation of CAD/CAM and Conventional Cement Retained Implant-Supported Single Crowns.

PubMed

Nejatidanesh, Farahnaz; Shakibamehr, Amir Hossein; Savabi, Omid

2016-02-01

To evaluate the accuracy of marginal and internal adaptation of 2 computer-aided design/computer-aided manufacturing (CAD/CAM) and 2 conventionally made cement retained implant-supported restorations. An abutment and its corresponding fixture analog (Astra Tech) were inserted in left central incisor area of a maxillary cast. Four types of implant-supported single restorations were fabricated on the abutment (n = 10): e.max CAD (Cerec AC system), zirconia-based (Cercon system), IPS e.max Press, and metal-ceramic restorations. The internal and marginal gaps of the studied groups were measured by replica method and stereomicroscope. Data were subjected to 1-way ANOVA and Scheffe post hoc tests (α = 0.05). Mean internal gaps of Cercon (59.48 ± 16.49 μm) and e.max Press (75.62 ± 26.92 μm) groups were significantly different from e.max CAD (120.29 ± 16.74 μm) group, but there was no significant difference between metal-ceramic restorations (89.65 ± 47.84 μm) and e.max CAD. The marginal gaps of e.max CAD (32.02 ± 10.38 μm) and Cercon restorations (34.26 ± 11.41 μm) were significantly superior from metal ceramics (59.19 ± 17.81 μm) and e.max press (74.99 ± 24.51 μm). Within the limitations of this study, it can be concluded that although the marginal and internal gaps of the studied implant-supported restorations were in the clinically acceptable range, single crowns made with CAD/CAM technology provide better marginal fit.

New Materials Developments for Military High Power Electronics and Capacitors

DTIC Science & Technology

2009-04-27

parameters, permittivity and breakdown field strength, and can be given by equation 1. (1) Where U - energy density (J/ cm3), ε - relative material... permittivity εo - permittivity of free space (8.85418782 × 10-12 m-3 kg-1 s4 A2) Emax (V/µm) - maximum field strength before material breakdown... Permittivity can be described as the ability of the material to polar- ize in response to an electric field through separation of ions, twist- ing permanent

Conflict between internal combustion engine and thermoelectric generator during waste heat recovery in cars

NASA Astrophysics Data System (ADS)

Korzhuev, M. A.

2011-02-01

It is shown that an internal combustion engine and a thermoelectric generator (TEG) arranged on the exhaust pipe of this engine come into the conflict of thermal machines that is related to using the same energy resource. The conflict grows with increasing useful electric power W e of the TEG, which leads to the limitation of both the maximum TEG output power ( W {e/max}) and the possibility of waste heat recovery in cars.

Two-dimensional shear wave elastography of breast lesions: Comparison of two different systems.

PubMed

Ren, Wei-Wei; Li, Xiao-Long; He, Ya-Ping; Li, Dan-Dan; Wang, Dan; Zhao, Chong-Ke; Bo, Xiao-Wan; Liu, Bo-Ji; Yue, Wen-Wen; Xu, Hui-Xiong

2017-01-01

To evaluate the diagnostic performance of two different shear wave elastography (SWE) techniques in distinguishing malignant breast lesions from benign ones. From March 2016 to May 2016, a total of 153 breast lesions (mean diameter, 16.8 mm±10.5; range 4.1-90.0 mm) in 153 patients (mean age, 46.4 years±15.1; age range 20-86 years) were separately performed by two different SWE techniques (i.e. T-SWE, Aplio500, Toshiba Medical System, Tochigi, Japan; and S-SWE, the Aixplorer US system, SuperSonic Imagine, Provence, France). The maximum (Emax), mean (Emean) and standard deviation (ESD) of elasticity modulus values in T-SWE and S-SWE were analyzed. All the lesions were confirmed by ultrasound (US)-guided core needle biopsy (n = 26), surgery (n = 122), or both (n = 5), with pathological results as the gold standard. The areas under the receiver operating characteristic curves (AUROCs) were calculated. Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV) were calculated to assess the diagnostic performance between T-SWE and S-SWE. Operator consistency was also evaluated. Among the 153 lesions, 41 (26.8%) were malignant and 112 (73.2%) were benign. Emax (T-SWE: 40.10±37.14 kPa vs. 118.78±34.41 kPa; S-SWE: 41.22±22.54 kPa vs. 134.77±60.51 kPa), Emean (T-SWE: 19.75±16.31 kPa vs. 52.93±25.75 kPa; S-SWE: 20.95±10.98 kPa vs. 55.95±22.42 kPa) and ESD (T-SWE: 9.00±8.55 kPa vs. 38.44±12.30 kPa; S-SWE: 8.17±6.14 kPa vs. 29.34±13.88 kPa) showed statistical differences in distinguishing malignant lesions from benign ones both in T-SWE and S-SWE (all p < 0.05). In T-SWE, the diagnostic performance of ESD was the highest (AUROC = 0.958), followed by Emax (AUROC = 0.909; p = 0.001 in comparison with ESD) and Emean (AUROC = 0.892; p < 0.001 in comparison with ESD), while in S-SWE, the diagnostic performance of Emax was the highest (AUROC = 0.967), followed by ESD (AUROC = 0.962, p > 0.05 in comparison with Emax) and Emean (AUROC = 0.930, p = 0.034 in comparison with Emax). AUROC-max (T-SWE: 0.909 vs. 0.967), AUROC-mean (T-SWE: 0.892 vs. 0.930) and AUROC-SD (T-SWE: 0.958 vs. 0.962) showed no significant difference between T-SWE and S-SWE (all p > 0.05). The intra-class correlation coefficients (ICC) of the intra-operator consistency and inter-operator consistency respectively were 0.961 and 0.898 in T-SWE, while 0.954 and 0.897 in S-SWE. T-SWE and S-SWE are equivalent for distinguishing the breast lesions. In T-SWE, ESD had the best diagnostic performance, while in S-SWE, Emax had the best diagnostic performance.

Vascular endothelial dysfunction in patients with mild obstructive sleep apnea syndrome.

PubMed

Duchna, Hans-Werner; Stoohs, Riccardo; Guilleminault, Christian; Christine Anspach, Marie; Schultze-Werninghaus, Gerhard; Orth, Maritta

2006-11-01

We investigated endothelial dysfunction, an early manifestation of atherosclerosis, in patients with mild obstructive sleep apnea syndrome (OSAS) (5/h < AHI < 15/h). Endothelium-dependent and -independent vasodilatory function was tested in 10 patients with mild OSAS, 12 healthy controls and 20 subjects with moderate to severe OSAS using the hand vein compliance technique. Maximum endothelium-dependent vasodilation to bradykinin (Emax) was significantly blunted in patients with mild OSAS (68.6 +/- 30.2 %) compared to healthy controls (94.8 +/- 9.5 %; p < 0.05; moderate to severe OSAS: 57.1 +/- 23.4 %; p = 0.33). Mean endothelium-independent venodilation was not altered. After 160.7 +/- 82.2 nights of CPAP therapy, mean Emax was significantly improved to 90.8 +/- 23.8 % (p < 0.01 vs. baseline; p = 0.7 vs. healthy controls) in 7 patients with mild OSAS. Systemic endothelium-dependent venodilation is markedly reduced in subjects with mild OSAS, which may imply adverse cardiovascular consequences. CPAP-treatment leads to a sustained restoration of endothelial dysfunction in these patients and is thus highly recommended.

Preliminary experience using dynamic MRI at 3.0 Tesla for evaluation of soft tissue tumors.

PubMed

Park, Michael Yong; Jee, Won-Hee; Kim, Sun Ki; Lee, So-Yeon; Jung, Joon-Yong

2013-01-01

We aimed to evaluate the use of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) at 3.0 T for differentiating the benign from malignant soft tissue tumors. Also we aimed to assess whether the shorter length of DCE-MRI protocols are adequate, and to evaluate the effect of temporal resolution. Dynamic contrast-enhanced magnetic resonance imaging, at 3.0 T with a 1 second temporal resolution in 13 patients with pathologically confirmed soft tissue tumors, was analyzed. Visual assessment of time-signal curves, subtraction images, maximal relative enhancement at the first (maximal peak enhancement [Emax]/1) and second (Emax/2) minutes, Emax, steepest slope calculated by using various time intervals (5, 30, 60 seconds), and the start of dynamic enhancement were analyzed. The 13 tumors were comprised of seven benign and six malignant soft tissue neoplasms. Washout on time-signal curves was seen on three (50%) malignant tumors and one (14%) benign one. The most discriminating DCE-MRI parameter was the steepest slope calculated, by using at 5-second intervals, followed by Emax/1 and Emax/2. All of the steepest slope values occurred within 2 minutes of the dynamic study. Start of dynamic enhancement did not show a significant difference, but no malignant tumor rendered a value greater than 14 seconds. The steepest slope and early relative enhancement have the potential for differentiating benign from malignant soft tissue tumors. Short-length rather than long-length DCE-MRI protocol may be adequate for our purpose. The steepest slope parameters require a short temporal resolution, while maximal peak enhancement parameter may be more optimal for a longer temporal resolution.

Shear wave elastography in medullary thyroid carcinoma diagnostics.

PubMed

Dobruch-Sobczak, Katarzyna; Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-12-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4-15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB.

Reliability and mode of failure of bonded monolithic and multilayer ceramics.

PubMed

Alessandretti, Rodrigo; Borba, Marcia; Benetti, Paula; Corazza, Pedro Henrique; Ribeiro, Raissa; Della Bona, Alvaro

2017-02-01

To evaluate the reliability of monolithic and multilayer ceramic structures used in the CAD-on technique (Ivoclar), and the mode of failure produced in ceramic structures bonded to a dentin analog material (NEMA-G10). Ceramic specimens were fabricated as follows (n=30): CAD-on- trilayer structure (IPS e.max ZirCAD/IPS e.max Crystall./Connect/IPS e.max CAD); YLD- bilayer structure (IPS e.max ZirCAD/IPS e.max Ceram); LDC- monolithic structure (IPS e.max CAD); and YZW- monolithic structure (Zenostar Zr Translucent). All ceramic specimens were bonded to G10 and subjected to compressive load in 37°C distilled water until the sound of the first crack, monitored acoustically. Failure load (L f ) values were recorded (N) and statistically analyzed using Weibull distribution, Kruskal-Wallis test, and Student-Newman-Keuls test (α=0.05). L f values of CAD-on and YZW structures were statistically similar (p=0.917), but higher than YLD and LDC (p<0.01). Weibull modulus (m) values were statistically similar for all experimental groups. Monolithic structures (LDC and YZW) failed from radial cracks. Failures in the CAD-on and YLD groups showed, predominantly, both radial and cone cracks. Monolithic zirconia (YZW) and CAD-on structures showed similar failure resistance and reliability, but a different fracture behavior. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Population Pharmacokinetics and Exposure-Response of a Fixed-Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With Stage 2 Hypertension.

PubMed

Tsai, Max C; Wu, Jingtao; Kupfer, Stuart; Vakilynejad, Majid

2016-08-01

Population pharmacokinetic and exposure-response models for azilsartan medoxomil (AZL-M) and chlorthalidone (CLD) were developed using data from an 8-week placebo-controlled phase 3, factorial study of 20, 40, and 80 mg AZL-M every day (QD) and 12.5 and 25 mg CLD QD in fixed-dose combination (FDC) in subjects with moderate to severe essential hypertension. A 2-compartment model with first-order absorption and elimination was developed to describe pharmacokinetics. An Emax model for exposure-response analysis evaluated AZL-M/CLD effects on ambulatory systolic blood pressure (SBP). Estimated oral clearance and apparent volume of distribution (central compartment) were 1.47 L/h and 3.98 L for AZL, and 4.13 L/h and 62.1 L for CLD. Age as a covariate had the largest effect on AZL and CLD exposure (±20% change). Predicted maximal SBP responses (Emax ) were -15.6 and -23.9 mm Hg for AZL and CLD. Subgroup analysis identified statistically significant Emax differences for black vs nonblack subjects, whereby the reduced AZL response in black subjects was offset by greater response to CLD. The estimated Emax for AZL and CLD was generally greater in subjects with higher baseline BP. In conclusion, no dose adjustments to AZL-M or CLD are warranted based on identified covariates, and antihypertensive efficacy of AZL-M/CLD combination therapy is comparable in black and nonblack subjects. © 2015, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Retrospective population pharmacokinetic/pharmacodynamic analysis of pyridostigmine, a cholinesterase inhibitor, in Chinese males.

PubMed

Seng, Kok-Yong; Loke, Weng-Keong; Moochhala, Shabbir; Zhao, Bin; Lee, Jon-Deoon Edmund

2009-09-01

We have characterised the population pharmacokinetics-pharmacodynamics of pyridostigmine given as pyridostigmine bromide. Over three days 50 healthy Chinese male subjects each received seven doses of 30 mg pyridostigmine bromide orally (3 x 10 mg every 8 h). Plasma concentrations of pyridostigmine and red blood cell acetylcholinesterase (AChE) activity were determined at various times within the eight hours after the first and the seventh doses. The resulting pharmacokinetic data were fitted to a single compartment open model with first-order absorption and elimination. The pharmacodynamics were modelled using an inhibitory E(max) model. The potential influence of demographic and biological covariates on the model parameters was investigated. Nonlinear mixed effects modelling was performed using NONMEM. The apparent clearance and volume of distribution as well as absorption rate constant of plasma pyridostigmine were estimated to be 136 l/h, 130 l and 0.68 1/h, respectively. The maximum red blood cell AChE activity decrease (E(max)) and plasma pyridostigmine concentration producing 50% of this reduction (EC50) were estimated to be 9.32 AChE units per gram haemoglobin and 51.9 ng/ml, respectively. None of the tested covariates were found to be correlated with any of the model parameters. Dosing simulations suggested that 30 mg repeated every six hours might be needed to achieve steady-state trough percentage inhibition above the recommended 10% in healthy Chinese males. The pharmacokinetics and the effects of pyridostigmine on red blood cell AChE activity were described using a mixed effects model. For Chinese males, the dosing interval may have been shorter than that recommended for the Caucasian population. Additional studies are needed to confirm these findings.

Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.

PubMed

Tatsumiya, Katsuhisa; Yamanishi, Tomonori; Watanabe, Miho; Masuda, Akinori; Mizuno, Tomoya; Kamai, Takao; Yoshida, Ken-Ichiro

2009-12-01

To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3-10 microM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. In detrusor without urothelium, maximum contraction (E(max)) decreased after administration of fasudil at 3 or 10 micromol/L (both P < 0.01), or 30 micromol/L (72.5 + or - 7.43%, 58.4 + or - 8.04% and 68.4 + or - 9.6%, respectively, of the first curve). In detrusor with urothelium, E(max) decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 micromol/L of fasudil (84.9 + or - 6.7%, 67.9 + or - 5.2% and 35.2 + or - 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 micromol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 micromol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 micromol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1-50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 micromol/L). Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.

Static vs. mobile sink: The influence of basic parameters on energy efficiency in wireless sensor networks.

PubMed

Khan, Majid I; Gansterer, Wilfried N; Haring, Guenter

2013-05-15

Over the last decade a large number of routing protocols has been designed for achieving energy efficiency in data collecting wireless sensor networks. The drawbacks of using a static sink are well known. It has been argued in the literature that a mobile sink may improve the energy dissipation compared to a static one. Some authors focus on minimizing Emax , the maximum energy dissipation of any single node in the network, while others aim at minimizing Ebar , the average energy dissipation over all nodes. In our paper we take a more holistic view, considering both Emax and Ebar . The main contribution of this paper is to provide a simulation-based analysis of the energy efficiency of WSNs with static and mobile sinks. The focus is on two important configuration parameters: mobility path of the sink and duty cycling value of the nodes. On the one hand, it is well known that in the case of a mobile sink with fixed trajectory the choice of the mobility path influences energy efficiency. On the other hand, in some types of applications sensor nodes spend a rather large fraction of their total lifetime in idle mode, and therefore higher energy efficiency can be achieved by using the concept of reduced duty cycles. In particular, we quantitatively analyze the influence of duty cycling and the mobility radius of the sink as well as their interrelationship in terms of energy consumption for a well-defined model scenario. The analysis starts from general load considerations and is refined into a geometrical model. This model is validated by simulations which are more realistic in terms of duty cycling than previous work. It is illustrated that over all possible configuration scenarios in terms of duty cycle and mobility radius of the sink the energy dissipation in the WSN can vary up to a factor of nine in terms of Emax and up to a factor of 17 in terms of Ebar. It turns out that in general the choice of the duty cycle value is more important for achieving energy efficiency than the choice of the mobility radius of the sink. Moreover, for small values of the duty cycle, a static sink turns out to be optimal in terms of both Emax and Ebar . For larger values of the duty cycle, a mobile sink has advantages over a static sink, especially in terms of Emax . These insights into the basic interrelationship between duty cycle value and mobility radius of a mobile sink are relevant for energy efficient operation of homogeneous WSNs beyond our model scenario.

Assessment of short/long term electric field strength measurements for a pilot district

NASA Astrophysics Data System (ADS)

Kurnaz, Cetin; Yildiz, Dogan; Karagol, Serap

2018-03-01

The level of electromagnetic radiation (EMR) exposure increases day by day as natural consequences of technological developments. In recent years, the increasing use of cellular systems has made it necessary to measure and evaluate EMR originating from base stations. In this study, broadband and band selective electric field strength (E) measurements were taken at four different times in order to evaluate the change of short term E in Atakum district of Samsun, Turkey. The measurements were collected from 46 different locations using a SRM 3006 and a PMM 8053 EMR meter in a band from 100 kHz to 3 GHz, and the maximum E (Emax) and the average E (Eavg) were recorded. The highest values have been noticed in these measurements at 9.45 V/m and 17.53 V/m for Eavg and Emax respectively. Apart from these measurements, 24 hour long term E measurements were taken at a location where the highest value was observed and analyzed, to observe the change of Es during a day. At the end of the study, a tentative mathematical model that helps in computing the total E of the medium with 95% accuracy, was obtained.

Stock Analysis of Metapenaeus affinis (H.Milne Edwards, 1837) on the North Coast of Central Java, Indonesia

NASA Astrophysics Data System (ADS)

Wijaya Saputra, Suradi; Solichin, Anhar; Teguh Taufani, Wiwiet

2018-02-01

This research aims at studying the length of first capture (Lc), length of sexual mature (Lm), and the stock analysis of Metapenaeus affinis in the North coast of Central Java, Indonesia. The field research activities were conducted from May 2016 to April 2017 using survey method and direct observations on the catch area of fishing units. The results showed that total length of the first capture for the male shrimp is 76,4 mm and 63 mm for females. The total length of first sexual mature is 116 mm. Y'/R result analysis on male shrimp shows 0,595 maximum exploitation rate (Emax), the rate of exploitation at E0,1 is 0,521 and the rate of exploitation at E0.5 is 0,352. While the female shrimp obtained is Emax = 0.637, E0.1 = 0.562 and E0.50 = 0,373. To increase the production and to preserve shrimp resources, it is ideal if Lc = Lm, i.e. at a total length of 116 mm. In conclusion, the increase in length of first captured will increase Y / R 'and B / R'

Efficacy of Interventions to Improve Respiratory Function After Stroke.

PubMed

Menezes, Kênia Kp; Nascimento, Lucas R; Avelino, Patrick R; Alvarenga, Maria Tereza Mota; Teixeira-Salmela, Luci F

2018-07-01

The aim of this study was to systematically review all current interventions that have been utilized to improve respiratory function and activity after stroke. Specific searches were conducted. The experimental intervention had to be planned, structured, repetitive, purposive, and delivered with the aim of improving respiratory function. Outcomes included respiratory strength (maximum inspiratory pressure [P Imax ], maximum expiratory pressure [P Emax ]) and endurance, lung function (FVC, FEV 1 , and peak expiratory flow [PEF]), dyspnea, and activity. The quality of the randomized trials was assessed by the PEDro scale using scores from the Physiotherapy Evidence Database (www.pedro.org.au), and risk of bias was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The 17 included trials had a mean PEDro score of 5.7 (range 4-8) and involved 616 participants. Meta-analyses showed that respiratory muscle training significantly improved all outcomes of interest: P Imax (weighted mean difference 11 cm H 2 O, 95% CI 7-15, I 2 = 0%), P Emax (8 cm H 2 O, 95% CI 2-15, I 2 = 65%), FVC (0.25 L, 95% CI 0.12-0.37, I 2 = 29%), FEV 1 (0.24 L, 95% CI 0.17-0.30, I 2 = 0%), PEF (0.51 L/s, 95% CI 0.10-0.92, I 2 = 0%), dyspnea (standardized mean difference -1.6 points, 95% CI -2.2 to -0.9; I 2 = 0%), and activity (standardized mean difference 0.78, 95% CI 0.22-1.35, I 2 = 0%). Meta-analyses found no significant results for the effects of breathing exercises on lung function. For the remaining interventions (ie, aerobic and postural exercises) and the addition of electrical stimulation, meta-analyses could not be performed. This systematic review reports 5 possible interventions used to improve respiratory function after stroke. Respiratory muscle training proved to be effective for improving inspiratory and expiratory strength, lung function, and dyspnea, and benefits were carried over to activity. However, there is still no evidence to accept or refute the efficacy of aerobic, breathing, and postural exercises, or the addition of electrical stimulation in respiratory function. Copyright © 2018 by Daedalus Enterprises.

Novae as Tevatrons: prospects for CTA and IceCube

NASA Astrophysics Data System (ADS)

Metzger, B. D.; Caprioli, D.; Vurm, I.; Beloborodov, A. M.; Bartos, I.; Vlasov, A.

2016-04-01

The discovery of novae as sources of ˜0.1-1 GeV gamma-rays highlights the key role of shocks and relativistic particle acceleration in these transient systems. Although there is evidence for a spectral cut-off above energies ˜1-100 GeV at particular epochs in some novae, the maximum particle energy achieved in these accelerators has remained an open question. The high densities of the nova ejecta (˜10 orders of magnitude larger than in supernova remnants) render the gas far upstream of the shock neutral and shielded from ionizing radiation. The amplification of the magnetic field needed for diffusive shock acceleration requires ionized gas, thus confining the acceleration process to a narrow photoionized layer immediately ahead of the shock. Based on the growth rate of the hybrid non-resonant cosmic ray current-driven instability (considering also ion-neutral damping), we quantify the maximum particle energy, Emax, across the range of shock velocities and upstream densities of interest. We find values of Emax ˜ 10 GeV-10 TeV, which are broadly consistent with the inferred spectral cut-offs, but which could also in principle lead to emission extending to ≳ 100 GeV accessible to atmosphere Cherenkov telescopes, such as the Cherenkov Telescope Array (CTA). Detecting TeV neutrinos with IceCube is more challenging, although the prospects are improved for a nearby event (≲ kpc) or if the shock power during the earliest, densest phases of the outburst is higher than implied by the GeV light curves, due to downscattering of the gamma-rays within the ejecta.

Modeling spatially explicit fire impact on gross primary production in interior Alaska using satellite images coupled with eddy covariance

USGS Publications Warehouse

Huang, Shengli; Liu, Heping; Dahal, Devendra; Jin, Suming; Welp, Lisa R.; Liu, Jinxun; Liu, Shuguang

2013-01-01

In interior Alaska, wildfires change gross primary production (GPP) after the initial disturbance. The impact of fires on GPP is spatially heterogeneous, which is difficult to evaluate by limited point-based comparisons or is insufficient to assess by satellite vegetation index. The direct prefire and postfire comparison is widely used, but the recovery identification may become biased due to interannual climate variability. The objective of this study is to propose a method to quantify the spatially explicit GPP change caused by fires and succession. We collected three Landsat images acquired on 13 July 2004, 5 August 2004, and 6 September 2004 to examine the GPP recovery of burned area from 1987 to 2004. A prefire Landsat image acquired in 1986 was used to reconstruct satellite images assuming that the fires of 1987–2004 had not occurred. We used a light-use efficiency model to estimate the GPP. This model was driven by maximum light-use efficiency (Emax) and fraction of photosynthetically active radiation absorbed by vegetation (FPAR). We applied this model to two scenarios (i.e., an actual postfire scenario and an assuming-no-fire scenario), where the changes in Emax and FPAR were taken into account. The changes in Emax were represented by the change in land cover of evergreen needleleaf forest, deciduous broadleaf forest, and shrub/grass mixed, whose Emax was determined from three fire chronosequence flux towers as 1.1556, 1.3336, and 0.5098 gC/MJ PAR. The changes in FPAR were inferred from NDVI change between the actual postfire NDVI and the reconstructed NDVI. After GPP quantification for July, August, and September 2004, we calculated the difference between the two scenarios in absolute and percent GPP changes. Our results showed rapid recovery of GPP post-fire with a 24% recovery immediately after burning and 43% one year later. For the fire scars with an age range of 2–17 years, the recovery rate ranged from 54% to 95%. In addition to the averaging, our approach further revealed the spatial heterogeneity of fire impact on GPP, allowing one to examine the spatially explicit GPP change caused by fires.

Shear wave elastography in medullary thyroid carcinoma diagnostics

PubMed Central

Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z.; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-01-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. Aim The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. Materials and methods A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4–15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. Results The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. Conclusions SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB. PMID:26807293

Impulse propagation in dissipative and disordered chains with power-law repulsive potentials

NASA Astrophysics Data System (ADS)

Manciu, Marian; Sen, Surajit; Hurd, Alan J.

2001-09-01

We report particle dynamics based studies of impulse propagation in a chain of elastic beads with dissipative contacts and with randomly distributed masses. The interaction between the beads is characterized by the potential V( δ)∼ δn, δ≥0 being grain overlap, n>2 and at zero external loading, i.e., under conditions of “sonic vacuum” in which sound cannot propagate through the chain [J. Appl. Mech. Technol. Phys. 5 (1983) 733]. In the earlier work, we have confirmed the studies of Nesterenko and coworkers and have reported that impulses propagate as solitary waves in the system of interest in the absence of dissipation and disorder [Physica A 268 (1999) 644]. In the present study, we first discuss the effects of restitution and velocity dependent friction on the propagation of the impulse. We next report that the maximum energyEmax of the solitary wave as it propagates from a chain of monodisperse grains of mass m to a chain with masses m(1+ r( z) ɛ), where -1≤ r( z)≤1 and ɛ=const. that measures the degree of randomness, decays with linear distance traveled z as exp(- αEz), αE∼ ɛ2+ f( n) , f( n) being some n dependent constant for 2< n<∞. In monodisperse chains, the velocity of the solitary wave c∼ Emax( n-2)/2 n. In polydisperse chains, we show that the propagation speed of a non-dispersive solitary wave decays with distance as exp(- αcz), where αc= αE( n-2)/2 n.

Effect of different dental ceramic systems on the wear of human enamel: An in vitro study.

PubMed

Zandparsa, Roya; El Huni, Rabie M; Hirayama, Hiroshi; Johnson, Marc I

2016-02-01

The wear of tooth structure opposing different advanced dental ceramic systems requires investigation. The purpose of this in vitro study was to compare the wear of advanced ceramic systems against human enamel antagonists. Four ceramic systems (IPS e.max Press, IPS e.max CAD, Noritake Super Porcelain EX-3, and LAVA Plus Zirconia) and 1 control group containing human enamel specimens were used in this study (n = 12). All specimens were fabricated as disks 11 mm in diameter and 3 mm thick. The mesiopalatal cusps of the maxillary third molars were prepared to serve as the enamel styluses. All specimens were embedded individually in 25 mm(3) autopolymerizing acrylic resin blocks. Wear was measured with a cyclic loading machine and a newly designed wear simulator. All enamel styluses (cusps) were scanned using the Activity 880 digital scanner (SmartOptics). Data from the base line and follow-up scans were collected and compared with Qualify 2012 3-dimensional (3D) and 2D digital inspection software (Geomagic), which aligned the models and detected the geometric changes and the wear caused by the antagonist specimen. One-way ANOVA was used to analyze the collected data. After 125,000 bidirectional loading cycles, the mean loss of opposing enamel volume for the enamel disks in the control group was 37.08 μm(3), the lowest mean value for IPS e.max Press system was 39.75 μm(3); 40.58 μm(3) for IPS e.max CAD; 45.08 μm(3) for Noritake Super Porcelain EX-3 system; and 48.66 μm(3) for the Lava Plus Zirconia system. No statically significant differences were found among the groups in opposing enamel volume loss (P=.225) or opposing enamel height loss (P=.149). In terms of opposing enamel height loss, Lava Plus Zirconia system showed the lowest mean value of 27.5 μm. The mean value for the IPS e.max CAD system was 27.91 μm; 29.08 μm for the control enamel; 33.25 μm for the IPS e.max Press system; and 34.75 μm for the Noritake Super Porcelain EX-3 system. Within the limitations of this in vitro study, no differences were found in the linear and volumetric reduction of enamel cusps abraded against enamel disks and all other ceramic specimens. All ceramic systems exhibited high durability and were wear-friendly to opposing enamel. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

The effect of chronic hyperthyroidism and restored euthyroid state by methimazole therapy in rat small mesenteric arteries.

PubMed

Khorshidi-Behzadi, Mahdi; Alimoradi, Houman; Haghjoo-Javanmard, Shaghayegh; Reza Sharifi, Mohammad; Rahimi, Nastaran; Dehpour, Ahmad Reza

2013-02-15

Not much has been reported about the effects of hyperthyroidism and its correction on resistance vessels, and just two inconsistent studies have investigated the impacts of restored euthyroidism on vascular reactivity. In this regard, we designed the current study to evaluate the vascular reactivity of the mesenteric arteries of hyperthyroid and restore euthyroid rats. Hyperthyroidism was induced by administration of triiodothyronine (T3; 300μg/kg, i.p., for 12 weeks in T3 group). Euthyroidism was restored by administration of T3 for 8 weeks and then T3+Methimazole (0.003% in drinking water) for 4 weeks (T3+MMI group). According to the McGregor method, vascular relaxation and contractility response were measured in response to acetylcholine or phenylephrine respectively. We found that maximal contractility response (Emax) to phenylephrine in the T3 group was significantly decreased (P<0.001), and Emax to acetylcholine was significantly increased compared with the saline group (P<0.05). When N(G)-nitro-L-arginine methyl ester (L-NAME, 3×10(-4)M) was used, Emax to acetylcholine in the T3 group was still higher than the saline group (P<0.05). However, decrease in maximal response of the T3 group was significantly greater than the saline group (P<0.01). We also showed that when euthyroidism is restored by methimazole therapy, enhanced acetylcholine-induced vasorelaxation and impaired contractility response to phenylephrine were normalized, as there was no significant difference in Emax of the T3+MMI group versus the saline group (P>0.05). In conclusion, synthesis of both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in mesenteric arteries significantly increased as a consequence of hyperthyroidism, and this abnormal vascular reactivity is corrected by methimazole therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of region of interest size and ultrasound lesion size on the performance of 2D shear wave elastography (SWE) in solid breast masses.

PubMed

Skerl, K; Vinnicombe, S; Giannotti, E; Thomson, K; Evans, A

2015-12-01

To evaluate the influence of the region of interest (ROI) size and lesion diameter on the diagnostic performance of 2D shear wave elastography (SWE) of solid breast lesions. A study group of 206 consecutive patients (age range 21-92 years) with 210 solid breast lesions (70 benign, 140 malignant) who underwent core biopsy or surgical excision was evaluated. Lesions were divided into small (diameter <15 mm, n=112) and large lesions (diameter ≥15 mm, n=98). An ROI with a diameter of 1, 2, and 3 mm was positioned over the stiffest part of the lesion. The maximum elasticity (Emax), mean elasticity (Emean) and standard deviation (SD) for each ROI size were compared to the pathological outcome. Statistical analysis was undertaken using the chi-square test and receiver operating characteristic (ROC) analysis. The ROI size used has a significant impact on the performance of Emean and SD but not on Emax. Youden's indices show a correlation with the ROI size and lesion size: generally, the benign/malignant threshold is lower with increasing ROI size but higher with increasing lesion size. No single SWE parameter has superior performance. Lesion size and ROI size influence diagnostic performance. Copyright © 2015. Published by Elsevier Ltd.

Impact of gastric acidic challenge on surface topography and optical properties of monolithic zirconia.

PubMed

Sulaiman, Taiseer A; Abdulmajeed, Aous A; Shahramian, Khalil; Hupa, Leena; Donovan, Terrence E; Vallittu, Pekka; Närhi, Timo O

2015-12-01

To evaluate the surface topography and optical properties of monolithic zirconia after immersion in simulated gastric acid. Four partially stabilized (PSZ) and one fully stabilized (FSZ) zirconia materials were selected for the study: Prettau (PRT, Zirkonzahn), Zenostar (ZEN, Ivoclar), Bruxzir (BRX, Glidewell), Katana (KAT, Noritake) and FSZ Prettau Anterior (PRTA, Zirkonzahn). IPS e.max (Ivoclar) was used as a control. The specimens (10×10×1.2mm, n=5 per material) were cut, sintered, polished and cleaned before immersed in 5ml of simulated gastric acid solution (Hydrochloric acid (HCl) 0.06M, 0.113% solution in deionized distal water, pH 1.2) for 96h in a 37°C incubator. Specimens were weighed and examined for morphological changes under scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX). Surface roughness was evaluated by a confocal microscope. Surface gloss and translucency parameter (TP) values were determined by a reflection spectrophotometer before and after acid immersion. The data was analyzed by one-way ANOVA followed by Tukey's HSD post hoc test (p<0.05). PRTA displayed the most weight loss (1.40%) among the zirconia specimens. IPS e.max showed about three times more weight loss (3.05%) than zirconia specimens as an average. SEM examination indicated areas of degradation, bead-like shapes and smoothening of the polishing scratches after acid immersion. EDX displayed ion interactions and possible ion leaching from all specimens. Sa and Sq values for PRTA, ZEN and IPS e.max were significantly lower (p<0.05) after acid immersion. TP values increased significantly for PRT, ZEN and IPS e.max (p<0.05), while the surface gloss of ZEN, PRTA and IPS e.max increased (p<0.05). Monolithic zirconia materials show some surface alterations in an acidic environment with minimum effect on their optical properties. Whether a smoother surface is in fact a sign of true corrosion resistance or is purely the result of an evenly progressive corrosive process is yet to be confirmed by further research. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The Effect of Water or Wax-based Binders on the Chemical and Morphological Characteristics of the Margin Ceramic-Framework Interface.

PubMed

Güler, Umut; de Queiroz, José Renato Cavalcanti; de Oliveira, Luiz Fernando Cappa; Canay, Senay; Ozcan, Mutlu

2015-09-01

This study evaluated the effect of binder choice in mixing ceramic powder on the chemical and morphological features between the margin ceramic-framework interfaces. Titanium and zirconia frameworks (15 x 5 x 0.5 mm3) were veneered with margin ceramics prepared with two different binders, namely a) water/conventional or b) wax-based. For each zirconia framework material, four different margin ceramics were used: a- Creation Zi (Creation Willi Geller International); b- GC Initial Zr (GC America); Triceram (Dentaurum); and d- IPS emax (voclar Vivadent). For the titanium framework, three different margin ceramics were used: a- Creation Ti (Creation Willi Geller International); b- Triceram (Dentaurum); and c- VITA Titaniumkeramik (Vita Zahnfabrik). The chemical composition of the framework-margin ceramic interface was analyzed using Energy Dispersive X-ray Spectroscopy (EDS) and porosity level was quantified within the margin ceramic using an image program (ImageJ) from four random areas (100 x 100 pixels) on each SEM image. EDS analysis showed the presence of Carbon at the margin ceramic-framework interface in the groups where wax-based binder technique was used with the concentration being the highest for the IPS emax ZirCAD group. While IPS system (IPS ZirCAD and IPS Emax) presented higher porosity concentration using wax binder, in the other groups wax-based binder reduced the porosity of margin ceramic, except for Titanium - Triceram combination.

Expanded prediction equations of human sweat loss and water needs.

PubMed

Gonzalez, R R; Cheuvront, S N; Montain, S J; Goodman, D A; Blanchard, L A; Berglund, L G; Sawka, M N

2009-08-01

The Institute of Medicine expressed a need for improved sweating rate (msw) prediction models that calculate hourly and daily water needs based on metabolic rate, clothing, and environment. More than 25 years ago, the original Shapiro prediction equation (OSE) was formulated as msw (g.m(-2).h(-1))=27.9.Ereq.(Emax)(-0.455), where Ereq is required evaporative heat loss and Emax is maximum evaporative power of the environment; OSE was developed for a limited set of environments, exposures times, and clothing systems. Recent evidence shows that OSE often overpredicts fluid needs. Our study developed a corrected OSE and a new msw prediction equation by using independent data sets from a wide range of environmental conditions, metabolic rates (rest to 500 observations) by using a variety of metabolic rates over a range of environmental conditions (ambient temperature, 15-46 degrees C; water vapor pressure, 0.27-4.45 kPa; wind speed, 0.4-2.5 m/s), clothing, and equipment combinations and durations (2-8 h). Data are expressed as grams per square meter per hour and were analyzed using fuzzy piecewise regression. OSE overpredicted sweating rates (P<0.003) compared with observed msw. Both the correction equation (OSEC), msw=147.exp (0.0012.OSE), and a new piecewise (PW) equation, msw=147+1.527.Ereq-0.87.Emax were derived, compared with OSE, and then cross-validated against independent data (21 males and 9 females; >200 observations). OSEC and PW were more accurate predictors of sweating rate (58 and 65% more accurate, P<0.01) and produced minimal error (standard error estimate<100 g.m(-2).h(-1)) for conditions both within and outside the original OSE domain of validity. The new equations provide for more accurate sweat predictions over a broader range of conditions with applications to public health, military, occupational, and sports medicine settings.

[Infinite optical thickness of dentine porcelain of IPS E.max A color series].

PubMed

Sun, Ting; Shao, Long-quan; Yi, Yuan-fu; Deng, Bin; Wen, Ning; Zhang, Wei-wei

2011-02-01

To determine the infinite optical thickness of dentine porcelain of IPS E.max A color series. Cylindrical dentine porcelain specimens of the IPS E.max A color series were prepared with a diameter of 13 mm and thickness of 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 mm. The chromatic value of all the specimens was determined with CM-5 spectrometer against standard black and white background. The chromatic aberration (deltaE) was calculated by regression equation. The infinite optical thickness of dentine porcelain of the IPS E.max A color series ranged from 2.341 to 3.333 mm for a deltaE of 1.0, and from 2.064 to 2.904 mm for a deltaE of 1.5. As the chromaticity or thickness increased, the influence by the background color decreased, and the color of specimens became gradually close to the intrinsic color. The thickness of the background dentine porcelain specimens must exceed its infinite optical thickness to represent the intrinsic color and avoid the influence by the extrinsic color.

Flexural resistance of heat-pressed and CAD-CAM lithium disilicate with different translucencies.

PubMed

Fabian Fonzar, Riccardo; Carrabba, Michele; Sedda, Maurizio; Ferrari, Marco; Goracci, Cecilia; Vichi, Alessandro

2017-01-01

To compare flexural strength of CAD-CAM and heat-pressed lithium disilicate. For Pressed specimens (Group A), acrylate polymer blocks were cut with a saw in bars shape. Sprueing, investing and preheating procedures were carried out following manufacturer's instructions. IPS e.max Press ingots (Ivoclar-Vivadent) were divided into subgroups (n=15) according to translucency: A.1=HT-A3; A.2=MT-A3; A.3=LT-A3; A.4=MO2. Ingots were then pressed following manufacturer's instructions. For CAD-CAM specimens (Group B) blocks of IPS e.max CAD (Ivoclar-Vivadent) were divided into subgroups: B.1=HT-A3; B.2=MT-A3; B.3=LT-A3; B.4=MO2. Specimens (n=15) were obtained by cutting the blocks with a saw. Final crystallization was performed following manufacturer's instructions. Both Press and CAD specimens were polished and finished with silica carbide papers of increasing grit. Final dimensions of the specimens were 4.0±0.2mm, 1.2±0.2mm, and 16.0±0.2mm. Specimens were tested using a three-point bending test. Flexural strength, Weibull modulus, and Weibull characteristic strength were calculated. Flexural strength data were statistically analyzed. The overall means of Press and CAD specimens did not differ significantly. Within the Press group different translucencies were found to have similar flexural strength. Within the CAD group, statistically significant differences emerged among the tested translucencies (p<0.001). Specifically, MT had significantly higher flexural strength than HT and MO. Also, LT exhibited significantly higher flexural strength than MO. The choice between IPS e.max Press and IPS e.max CAD formulations can be based on different criteria than flexural resistance. Within each formulation, for IPS e.max Press translucency does not affect the flexural strength while for IPS e.max CAD it is an influential factor. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Optical properties of current ceramics systems for laminate veneers.

PubMed

Bagis, Bora; Turgut, Sedanur

2013-08-01

Full-ceramic systems can be produced by different techniques (layering, heatpressing, CAD/CAM) and have various compositions with different crystalline contents that may affect the optical properties of laminate restorations. A total of 60 specimens were prepared from e.max Press, e.max CAD, Empress Esthetic, e.max Ceram, Inline, and ZirPress systems (A1 shade; diameter 10mm; thickness 0.5 ± 0.05mm). The L*, a*, and b* values, chroma and translucency (TP) of each system were recorded before and after ageing. The statistical analyses were performed by ANOVA, Tukey's tests and the paired sample t-test (p<0.05). The L* value of the shade guide was significantly different from those of the full-ceramic systems; however, there were no significant differences between the a* values of Ceram, Esthetic, Inline and Zirpress. There were significant differences between the b* values of the shade guide compared with the full-ceramics except for e.max Press. The L* values decreased, and the a* and b* values increased after the ageing process for all groups. There were no significant differences between the ΔE values of the ceramic systems (p>0.05). The TP values decreased, and the chroma value increased significantly after the ageing process (p>0.05). The chroma of the shade guide was found to be the highest. None of the full-ceramic systems was able to match the color of the shade guide. The chemical structures of the ceramic systems were more effective for determining the optical parameters than the fabrication techniques. Ageing caused full-ceramics to become more opaque, darker, reddish and yellowish. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmacodynamic Evaluation of the Intracellular Activity of Antibiotics towards Pseudomonas aeruginosa PAO1 in a Model of THP-1 Human Monocytes

PubMed Central

Buyck, Julien M.; Tulkens, Paul M.

2013-01-01

Pseudomonas aeruginosa invades epithelial and phagocytic cells, which may play an important role in the persistence of infection. We have developed a 24-h model of THP-1 monocyte infection with P. aeruginosa PAO1 in which bacteria are seen multiplying in vacuoles by electron microscopy. The model has been used to quantitatively assess antibiotic activity against intracellular and extracellular bacteria by using a pharmacodynamic approach (concentration-dependent experiments over a wide range of extracellular concentrations to calculate bacteriostatic concentrations [Cs] and maximal relative efficacies [Emax]; Hill-Langmuir equation). Using 16 antipseudomonal antibiotics (three aminoglycosides, nine β-lactams, three fluoroquinolones, and colistin), dose-response curves were found to be undistinguishable for antibiotics of the same pharmacological class if data were expressed as a function of the corresponding MICs. Extracellularly, all of the antibiotics reached a bacteriostatic effect at their MIC, and their Emax exceeded the limit of detection (−4.5 log10 CFU compared to the initial inoculum). Intracellularly, Cs values remained unchanged for β-lactams, fluoroquinolones, and colistin but were approximately 10 times higher for aminoglycosides, whereas Emax values were markedly reduced (less negative), reaching −3 log10 CFU for fluoroquinolones and only −1 to −1.5 log10 CFU for all other antibiotics. The decrease in intracellular aminoglycoside potency (higher Cs) can be ascribed to the acid pH to which bacteria are exposed in vacuoles. The decrease in the Emax may reflect a reversible alteration of bacterial responsiveness to antibiotics in the intracellular milieu. The model may prove useful for comparison of antipseudomonal antibiotics to reduce the risk of persistence or relapse of pseudomonal infections. PMID:23478951

Mechanism-based pharmacodynamic modeling of the interaction of midazolam, bretazenil, and zolpidem with ethanol.

PubMed

Tuk, Bert; van Gool, Toon; Danhof, Meindert

2002-06-01

The pharmacokinetic and pharmacodynamic interactions of ethanol with the full benzodiazepine agonist midazolam, the partial agonist bretazenil and the benzodiazepine BZ1 receptor subtype selective agonist zolpidem have been determined in the rat in vivo, using an integrated pharmacokinetic-pharmacodynamic approach. Ethanol was administered as a constant rate infusion resulting in constant plasma concentrations of 0.5 g/l. The pharmacokinetics and pharmacodynamics of midazolam, bretazenil, and zolpidem were determined following an intravenous infusion of 5.0, 2.5, and 18 mg/kg respectively. The amplitude in the 11.5-30 Hz frequency band of the EEG was used as measure of the pharmacological effect. For each of the benzodiazepines the concentration-EEG effect relationship could be described by the sigmoid Emax pharmacodynamic model. Significant differences in both EC50 and Emax were observed. The values of the EC50 were 76 +/- 11, 12 +/- 3, and 512 +/- 116 ng/ml for midazolam, bretazenil, and zolpidem respectively. The values of the Emax were 113 +/- 9, 44 +/- 3, and 175 +/- 10 microV/s. In the presence of ethanol the values of the EC50 of midazolam and zolpidem were reduced to approximately 50% of the original value. The values for Emax and Hill-factor were unchanged Due to a large interindividual variability no significant change in EC50 was observed for bretazenil. Analysis of the data on basis of a mechanism-based model showed only a decrease in the apparent affinity constant KPD for all three drugs, indicating that changes in EC50 can be explained entirely by a change in the apparent affinity constant KPD without concomitant changes in the efficacy parameter ePD and the stimulus-effect relationship. The findings of this study show that the pharmacodynamic interactions with a low dose of ethanol in vivo are qualitatively and quantitatively similar for benzodiazepine receptor full agonists, partial agonists, and benzodiazepine BZ1 receptor subtype selective agonists. This interaction can be explained entirely by a change in the affinity of the biological system for each benzodiazepine.

Fracture resistance of computer-aided design and computer-aided manufacturing ceramic crowns cemented on solid abutments.

PubMed

Stona, Deborah; Burnett, Luiz Henrique; Mota, Eduardo Gonçalves; Spohr, Ana Maria

2015-07-01

Because no information was found in the dental literature regarding the fracture resistance of all-ceramic crowns using CEREC (Sirona) computer-aided design and computer-aided manufacturing (CAD-CAM) system on solid abutments, the authors conducted a study. Sixty synOcta (Straumann) implant replicas and regular neck solid abutments were embedded in acrylic resin and randomly assigned (n = 20 per group). Three types of ceramics were used: feldspathic, CEREC VITABLOCS Mark II (VITA); leucite, IPS Empress CAD (Ivoclar Vivadent); and lithium disilicate, IPS e.max CAD (Ivoclar Vivadent). The crowns were fabricated by the CEREC CAD-CAM system. After receiving glaze, the crowns were cemented with RelyX U200 (3M ESPE) resin cement under load of 1 kilogram. For each ceramic, one-half of the specimens were subjected to the fracture resistance testing in a universal testing machine with a crosshead speed of 1 millimeter per minute, and the other half were subjected to the fractured resistance testing after 1,000,000 cyclic fatigue loading at 100 newtons. According to a 2-way analysis of variance, the interaction between the material and mechanical cycling was significant (P = .0001). According to a Tukey test (α = .05), the fracture resistance findings with or without cyclic fatigue loading were as follows, respectively: CEREC VITABLOCKS Mark II (405 N/454 N) was statistically lower than IPS Empress CAD (1169 N/1240 N) and IPS e.max CAD (1378 N/1025 N) (P < .05). The IPS Empress CAD and IPS e.max CAD did not differ statistically (P > .05). According to a t test, there was no statistical difference in the fracture resistance with and without cyclic fatigue loading for CEREC VITABLOCS Mark II and IPS Empress CAD (P > .05). For IPS e.max CAD, the fracture resistance without cyclic fatigue loading was statistically superior to that obtained with cyclic fatigue loading (P < .05). The IPS Empress CAD and IPS e.max CAD showed higher fracture resistance compared with CEREC VITABLOCS Mark II. The cyclic fatigue loading negatively influenced only IPS e.max CAD. The CEREC VITABLOCS Mark II, IPS Empress CAD, and IPS e.max CAD ceramic crowns cemented on solid abutments showed sufficient resistance to withstand normal chewing forces. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Antiresorptive effect of a cathepsin K inhibitor ONO-5334 and its relationship to BMD increase in a phase II trial for postmenopausal osteoporosis.

PubMed

Tanaka, Makoto; Hashimoto, Yoshitaka; Hasegawa, Chihiro; Deacon, Steve; Eastell, Richard

2017-06-19

ONO-5334 is a cathepsin K inhibitor that induced bone mineral density (BMD) gain in a phase II study in postmenopausal osteoporosis patients. Even though the antiresorptive effect could only be monitored in the morning during the study, simulation can allow the antiresorptive effect to be assessed over 24 h, with assessment of the relationship to BMD gain. Inhibition of the serum C-telopeptide of type I collagen (sCTX) level at doses of ONO-5334 of 100 mg once daily (QD), 300 mg QD, and 50 mg twice daily (BID) was simulated using plasma ONO-5334 pharmacokinetic (PK) data for repeated dose administration in a phase I study and corresponding sCTX inhibition from the PK-pharmacodynamic (PK/PD) relationship. sCTX was selected because it has a high signal-to-noise ratio compared to other telopeptides. A negative sigmoidal shape for the PK/PD relationship between plasma ONO-5334 and sCTX levels was obtained in our previous study. The simulated sCTX inhibition reached >99% of the maximal inhibitory effect (Emax) at 0.5 h in all treatment groups, and decreased to <80% Emax at 8 and 12 h at 50 mg BID and 100 mg QD, respectively. However, sCTX inhibition at 300 mg QD was maintained at ≥82% Emax over 24 h. The mean sCTX inhibition rates for 24 h at 100 mg QD, 300 mg QD and 50 mg BID were 63, 95 and 80% Emax, respectively. There was a positive linear relationship by treatment group between mean sCTX inhibition over 24 h and observed BMD gain in the phase II study. The dose response for BMD with ONO-5334 at 100 and 300 mg QD and higher BMD gain at 50 mg BID vs. 100 mg QD can be explained by sCTX inhibition over 24 h. The simulation gave the antiresorptive effect of ONO-5334 over 24 h and allowed prediction of BMD gain due to ONO-5334. The registration number in The European Union Clinical Trials Register is 2007-002417-39 . The date of registration was August 31, 2007.

In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors.

PubMed

Jordan, Shaun; Chen, Ruoyan; Koprivica, Vuk; Hamilton, Ronald; Whitehead, Richard E; Tottori, Katsura; Kikuchi, Tetsuro

2005-07-11

This study determined the in vitro functional profile of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate (OPC-14523) at rat and human serotonin (5-HT) 5-HT1A receptors and binding affinity of OPC-14523 at human frontocortical 5-HT1A receptors. OPC-14523 (1 microM) increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding to 5-HT1A receptor-containing regions of rat brain tissue sections (approximately 53% of the effect of 1 microM (+)8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT) that were blocked by the selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635). OPC-14523 also behaved as a partial agonist in its stimulation of [35S]GTPgammaS binding to membranes from rat hippocampus (pEC50=7.60+/-0.23, Emax=41.1% of the effect of 10 microM (+)8-OH-DPAT), human frontal cortex (pEC50=7.89+/-0.08; Emax=64% of the effect of 10 microM (+)8-OH-DPAT), and Chinese Hamster Ovary cells expressing cloned human 5-HT1A receptors (pEC50=8.0+/-0.11; Emax=85.5% of the effect of 10 microM 5-HT), and all of these effects of OPC-14523 were blocked by WAY-100635. Taken together, these data support the development of OPC-14523 as an antidepressant whose mechanism of action involves potent partial agonist activity at 5-HT1A receptors.

The effect of five kinds of surface treatment agents on the bond strength to various ceramics with thermocycle aging.

PubMed

Noda, Yukari; Nakajima, Masatoshi; Takahashi, Masahiro; Mamanee, Teerapong; Hosaka, Keiichi; Takagaki, Tomohiro; Ikeda, Masaomi; Foxton, Richard M; Tagami, Junji

2017-11-29

This study evaluated the effects of ceramic surface treatment agents on shear bond strengths to ceramic materials with and without thermocycling. Ceramic plates were prepared from feldspathic ceramic; AAA, lithium disilicate ceramic material; IPS e.max Press, zirconia ceramic; Lava. Ceramic surfaces were pretreated with one of five surface treatment agents (Clearfil PhotoBond mixed with Porcelainbond activator (PB), Clearfil SE One mixed with Porcelainbond activator (SO), Ceramic Primer (CP), Universal Primer (UP), Scotchbond Universal (SU)), and then a resin cement (Clapearl DC) was filled. After 0, 5,000, and 10,000 thermocycles, micro-shear bond strengths between ceramic-cement interfaces were determined. SU exhibited significantly lower initial bond strength to AAA and e.max than PB, SO, CP, and UP. For Lava, PB, SO, CP and SU exhibited higher initial bond strengths than UP. Thermocycles reduced bond strengths to all the ceramic materials with any surface treatment.

Identification and in Vivo Evaluation of Liver X Receptor β-Selective Agonists for the Potential Treatment of Alzheimer’s Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stachel, Shawn J.; Zerbinatti, Celina; Rudd, Michael T.

2016-04-14

Herein, we describe the development of a functionally selective liver X receptor β (LXRβ) agonist series optimized for Emax selectivity, solubility, and physical properties to allow efficacy and safety studies in vivo. Compound 9 showed central pharmacodynamic effects in rodent models, evidenced by statistically significant increases in apolipoprotein E (apoE) and ATP-binding cassette transporter levels in the brain, along with a greatly improved peripheral lipid safety profile when compared to those of full dual agonists. These findings were replicated by subchronic dosing studies in non-human primates, where cerebrospinal fluid levels of apoE and amyloid-β peptides were increased concomitantly with anmore » improved peripheral lipid profile relative to that of nonselective compounds. These results suggest that optimization of LXR agonists for Emax selectivity may have the potential to circumvent the adverse lipid-related effects of hepatic LXR activity.« less

First-order approximation for the pressure-flow relationship of spontaneously contracting lymphangions.

PubMed

Quick, Christopher M; Venugopal, Arun M; Dongaonkar, Ranjeet M; Laine, Glen A; Stewart, Randolph H

2008-05-01

To return lymph to the great veins of the neck, it must be actively pumped against a pressure gradient. Mean lymph flow in a portion of a lymphatic network has been characterized by an empirical relationship (P(in) - P(out) = -P(p) + R(L)Q(L)), where P(in) - P(out) is the axial pressure gradient and Q(L) is mean lymph flow. R(L) and P(p) are empirical parameters characterizing the effective lymphatic resistance and pump pressure, respectively. The relation of these global empirical parameters to the properties of lymphangions, the segments of a lymphatic vessel bounded by valves, has been problematic. Lymphangions have a structure like blood vessels but cyclically contract like cardiac ventricles; they are characterized by a contraction frequency (f) and the slopes of the end-diastolic pressure-volume relationship [minimum value of resulting elastance (E(min))] and end-systolic pressure-volume relationship [maximum value of resulting elastance (E(max))]. Poiseuille's law provides a first-order approximation relating the pressure-flow relationship to the fundamental properties of a blood vessel. No analogous formula exists for a pumping lymphangion. We therefore derived an algebraic formula predicting lymphangion flow from fundamental physical principles and known lymphangion properties. Quantitative analysis revealed that lymph inertia and resistance to lymph flow are negligible and that lymphangions act like a series of interconnected ventricles. For a single lymphangion, P(p) = P(in) (E(max) - E(min))/E(min) and R(L) = E(max)/f. The formula was tested against a validated, realistic mathematical model of a lymphangion and found to be accurate. Predicted flows were within the range of flows measured in vitro. The present work therefore provides a general solution that makes it possible to relate fundamental lymphangion properties to lymphatic system function.

Effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on contractile receptor function in airway smooth muscle.

PubMed

de Vries, B; Roffel, A F; Zaagsma, J; Meurs, H

2001-11-23

In the present study, we investigated the effect of fenoterol-induced constitutive beta(2)-adrenoceptor activity on muscarinic receptor agonist- and histamine-induced bovine tracheal smooth muscle contractions. Bovine tracheal smooth muscle strips were incubated with 10 microM fenoterol or vehicle for various periods of time (5, 30 min, 18 h) at 37 degrees C. After extensive washout (3 h, 37 degrees C), isometric contractions were measured to the full muscarinic receptor agonist methacholine, the partial muscarinic receptor agonist 4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium (McN-A-343) and histamine. Fenoterol treatment significantly reduced the sensitivity (pEC(50)) to methacholine in a time-dependent manner, without affecting maximal contraction (E(max)). Fenoterol treatment similarly reduced the pEC(50) of McN-A-343 and histamine; however, E(max) values were also reduced, to approximately 70% of control after 18-h treatment. The inverse agonist timolol, having no effect on control preparations, consistently restored the reduced pEC(50) and E(max) values of the contractile agonists. Remarkably, in the presence of timolol the pEC(50) values of McN-A-343 and histamine in fenoterol-treated airways were significantly enhanced compared to controls. In conclusion, fenoterol-induced constitutive beta(2)-adrenoceptor activity reduces muscarinic receptor agonist- and histamine-induced contractions of bovine tracheal smooth muscle, which can be reversed by the inverse agonist timolol. Moreover, after beta(2)-adrenoceptor agonist treatment, inverse agonism by beta-adrenoceptor antagonists may cause enhanced airway reactivity to contractile mediators.

Incorporation of a recombinant Eimeria maxima IMP1 antigen into nanoparticles confers protective immunity against E. maxima challenge infection

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to determine if incorporating a recombinant Eimeria maxima protein, namely rEmaxIMP1, into gold nanoparticles (NP) could improve the level of protective immunity against E. maxima challenge infection. Recombinant EmaxIMP1 was expressed in Escherchia coli as a poly-His f...

Ipamorelin, the first selective growth hormone secretagogue.

PubMed

Raun, K; Hansen, B S; Johansen, N L; Thøgersen, H; Madsen, K; Ankersen, M; Andersen, P H

1998-11-01

The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The specificity of ipamorelin makes this compound a very interesting candidate for future clinical development.

Measurement of J-integral in CAD/CAM dental ceramics and composite resin by digital image correlation.

PubMed

Jiang, Yanxia; Akkus, Anna; Roperto, Renato; Akkus, Ozan; Li, Bo; Lang, Lisa; Teich, Sorin

2016-09-01

Ceramic and composite resin blocks for CAD/CAM machining of dental restorations are becoming more common. The sample sizes affordable by these blocks are smaller than ideal for stress intensity factor (SIF) based tests. The J-integral measurement calls for full field strain measurement, making it challenging to conduct. Accordingly, the J-integral values of dental restoration materials used in CAD/CAM restorations have not been reported to date. Digital image correlation (DIC) provides full field strain maps, making it possible to calculate the J-integral value. The aim of this study was to measure the J-integral value for CAD/CAM restorative materials. Four types of materials (sintered IPS E-MAX CAD, non-sintered IPS E-MAX CAD, Vita Mark II and Paradigm MZ100) were used to prepare beam samples for three-point bending tests. J-integrals were calculated for different integral path size and locations with respect to the crack tip. J-integral at path 1 for each material was 1.26±0.31×10(-4)MPam for MZ 100, 0.59±0.28×10(-4)MPam for sintered E-MAX, 0.19±0.07×10(-4)MPam for VM II, and 0.21±0.05×10(-4)MPam for non-sintered E-MAX. There were no significant differences between different integral path size, except for the non-sintered E-MAX group. J-integral paths of non-sintered E-MAX located within 42% of the height of the sample provided consistent values whereas outside this range resulted in lower J-integral values. Moreover, no significant difference was found among different integral path locations. The critical SIF was calculated from J-integral (KJ) along with geometry derived SIF values (KI). KI values were comparable with KJ and geometry based SIF values obtained from literature. Therefore, DIC derived J-integral is a reliable way to assess the fracture toughness of small sized specimens for dental CAD/CAM restorative materials; however, with caution applied to the selection of J-integral path. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis and Evaluation of Parameters Determining Maximum Efficiency of Fish Protection

NASA Astrophysics Data System (ADS)

Khetsuriani, E. D.; Kostyukov, V. P.; Khetsuriani, T. E.

2017-11-01

The article is concerned with experimental research findings. The efficiency of fish fry protection from entering water inlets is the main criterion of any fish protection facility or device. The research was aimed to determine an adequate mathematical model E = f(PCT, Vp, α), where PCT, Vp and α are controlled factors influencing the process of fish fry protection. The result of the processing of experimental data was an adequate regression model. We determined the maximum of fish protection Emax=94,21 and the minimum of optimization function Emin=44,41. As a result of the statistical processing of experimental data we obtained adequate dependences for determining an optimal rotational speed of tip and fish protection efficiency. The analysis of fish protection efficiency dependence E% = f(PCT, Vp, α) allowed the authors to recommend the following optimized operating modes for it: the maximum fish protection efficiency is achieved at the process pressure PCT=3 atm, stream velocity Vp=0,42 m/s and nozzle inclination angle α=47°49’. The stream velocity Vp has the most critical influence on fish protection efficiency. The maximum efficiency of fish protection is obtained at the tip rotational speed of 70.92 rpm.

Shear wave elastography of breast cancer: Sensitivity according to histological type in a large cohort.

PubMed

Evans, Andrew; Sim, Yee Ting; Thomson, Kim; Jordan, Lee; Purdie, Colin; Vinnicombe, Sarah J

2016-04-01

To define the shear wave elastography (SWE) characteristics of breast cancer histological types by size in a large cohort. Consecutive patients with US visible masses underwent SWE. All those with confirmed invasive breast cancer were included in the study. Histologic type was ascertained from core biopsy and surgical resection specimens. For each type, mean and median values for Emean and Emax were ascertained. Commoner tumour types were further analysed by invasive size. The significance of differences was established using the Chi-square test. 1137 tumours constituted the study group. The proportion of tumours with Emean below 50 kPa was higher in tubular cancers (23%) compared to ductal carcinomas of no specific type (DNST) (6%) (p < 0.001). Emax below 80 kPa was seen in 34% of tubular cancers compared to 16% of DNST (p < 0.002). Emean and Emax for lobular, mucinous, papillary and metaplastic cancers were not different from those of DNST. There were no significant differences in Emean or Emax between tumour types once broken down according to invasive size. Most breast cancer histological types have similar SWE characteristics. The exception is tubular cancer which has significantly lower stiffness than other histologic types, accounted for largely by their small size. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trials

PubMed Central

Othman, Ahmed A; Nothaft, Wolfram; Awni, Walid M; Dutta, Sandeep

2013-01-01

Aim To characterize quantitatively the relationship between ABT-102, a potent and selective TRPV1 antagonist, exposure and its effects on body temperature in humans using a population pharmacokinetic/pharmacodynamic modelling approach. Methods Serial pharmacokinetic and body temperature (oral or core) measurements from three double-blind, randomized, placebo-controlled studies [single dose (2, 6, 18, 30 and 40 mg, solution formulation), multiple dose (2, 4 and 8 mg twice daily for 7 days, solution formulation) and multiple-dose (1, 2 and 4 mg twice daily for 7 days, solid dispersion formulation)] were analyzed. nonmem was used for model development and the model building steps were guided by pre-specified diagnostic and statistical criteria. The final model was qualified using non-parametric bootstrap and visual predictive check. Results The developed body temperature model included additive components of baseline, circadian rhythm (cosine function of time) and ABT-102 effect (Emax function of plasma concentration) with tolerance development (decrease in ABT-102 Emax over time). Type of body temperature measurement (oral vs. core) was included as a fixed effect on baseline, amplitude of circadian rhythm and residual error. The model estimates (95% bootstrap confidence interval) were: baseline oral body temperature, 36.3 (36.3, 36.4)°C; baseline core body temperature, 37.0 (37.0, 37.1)°C; oral circadian amplitude, 0.25 (0.22, 0.28)°C; core circadian amplitude, 0.31 (0.28, 0.34)°C; circadian phase shift, 7.6 (7.3, 7.9) h; ABT-102 Emax, 2.2 (1.9, 2.7)°C; ABT-102 EC50, 20 (15, 28) ng ml−1; tolerance T50, 28 (20, 43) h. Conclusions At exposures predicted to exert analgesic activity in humans, the effect of ABT-102 on body temperature is estimated to be 0.6 to 0.8°C. This effect attenuates within 2 to 3 days of dosing. PMID:22966986

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Smith, Michael D.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Abstract Objective. To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. Methods. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (Emax; primary endpoint) using drug liking visual analog scale (VAS) score, Emax using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Results. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking Emax was significantly lower (P < 0.0001) compared with IN morphine ER. Overall drug liking and TDA Emax values were significantly lower (P < 0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). Conclusions. All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. PMID:27651510

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) versus Extended-Release Morphine Administered Orally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Objective. To compare the relative human abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine sulfate ER tablets Methods. This randomized, double-blind, triple-dummy, active- and placebo-controlled, 4-way crossover, single-center study included adult volunteers who were experienced, nondependent, recreational opioid users. Participants were randomized 1:1:1:1 to placebo, morphine-ADER-IMT (60 mg, intact), morphine-ADER-IMT (60 mg, manipulated), and morphine ER (60 mg, manipulated) and received 1 dose of each oral agent in crossover fashion, separated by ≥5 days. Pharmacodynamic and pharmacokinetic endpoints were assessed, including the primary endpoint of peak effect of Drug Liking (Emax) via Drug Liking Visual Analog Scale (VAS) score and the secondary endpoints of time to Emax (TEmax) and mean abuse quotient (AQ; a pharmacokinetic parameter associated with drug liking). Results. Thirty-eight participants completed the study. Median Drug Liking VAS Emax was significantly lower after treatment with manipulated morphine-ADER-IMT (67) compared with manipulated morphine ER (74; P = 0.007). TEmax was significantly shorter after treatment with manipulated morphine ER compared with intact (P < 0.0001) or manipulated (P = 0.004) morphine-ADER-IMT. Mean AQ was lower after treatment with intact (5.7) or manipulated (16.4) morphine-ADER-IMT compared with manipulated morphine ER (45.9). Conclusions. Manipulated morphine-ADER-IMT demonstrated significantly lower Drug Liking Emax compared with manipulated morphine ER when administered orally. Morphine-ADER-IMT would be an important new AD, ER morphine product with lower potential for unintentional misuse by chewing or intentional manipulation for oral abuse than currently available non-AD morphine ER products. PMID:27633773

Muscarinic receptor subtypes involved in carbachol-induced contraction of mouse uterine smooth muscle.

PubMed

Kitazawa, Takio; Hirama, Ryuichi; Masunaga, Kozue; Nakamura, Tatsuro; Asakawa, Koichi; Cao, Jinshan; Teraoka, Hiroki; Unno, Toshihiro; Komori, Sei-ichi; Yamada, Masahisa; Wess, Jürgen; Taneike, Tetsuro

2008-06-01

Functional muscarinic acetylcholine receptors present in the mouse uterus were characterized by pharmacological and molecular biological studies using control (DDY and wild-type) mice, muscarinic M2 or M3 single receptor knockout (M2KO, M3KO), and M2 and M3 receptor double knockout mice (M2/M3KO). Carbachol (10 nM-100 microM) increased muscle tonus and phasic contractile activity of uterine strips of control mice in a concentration-dependent manner. The maximum carbachol-induced contractions (Emax) differed between cervical and ovarian regions of the uterus. The stage of the estrous cycle had no significant effect on carbachol concentration-response relationships. Tetrodotoxin did not decrease carbachol-induced contractions, but the muscarinic receptor antagonists (11-[[2-[(diethylaminomethyl)-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b[2,3-b][1,4]benzodiazepin6-one (AF-DX116), N-[2-[2-[(dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4] benzodiazepine-11-carboxamide (AF-DX384), 4-diphenylacetoxy-N-methyl-piperidine(4-DAMP), para-fluoro-hexa hydro-sila-diphenidol (p-F-HHSiD), himbacine, methoctramine, pirenzepine, and tropicamide) inhibited carbachol-induced contractions in a competitive fashion. The pKb values for these muscarinic receptor antagonists correlated well with the known pKi values of these antagonists for the M3 muscarinic receptor. In uterine strips isolated from mice treated with pertussis toxin (100 microg/kg, i.p. for 96 h), Emax values for carbachol were significantly decreased, but effective concentration that caused 50% of Emax values (EC50) remained unchanged. In uterine strips treated with 4-DAMP mustard (30 nM) and AF-DX116 (1 microM), followed by subsequent washout of AF-DX116, neither carbachol nor N,N,N,-trimethyl-4-(2-oxo-1-pyrolidinyl)-2-butyn-1-ammonium iodide (oxotremorine-M) caused any contractile responses. Both M2 and M3 muscarinic receptor messenger RNAs were detected in the mouse uterus via reverse transcription polymerase chain reaction. Carbachol also caused contraction of uterine strips isolated from M2KO mice, but the concentration-response curve was shifted to the right and downward compared with that for the corresponding wild-type mice. On the other hand, uterine strips isolated from M3KO and M2/M3 double KO mice were virtually insensitive to carbachol. In conclusion, although both M2 and M3 muscarinic receptors were expressed in the mouse uterus, carbachol-induced contractile responses were predominantly mediated by the M3 receptor. Activation of M2 receptors alone did not cause uterine contractions; however, M2 receptor activation enhanced M3 receptor-mediated contractions in the mouse uterus.

Laser treatment of dental ceramic/cement layers: transmitted energy, temperature effects and surface characterisation.

PubMed

Pich, Olena; Franzen, René; Gutknecht, Norbert; Wolfart, Stefan

2015-02-01

In the present paper, we investigate the behaviour of different dental materials under laser irradiation. We have used e.max Ceram, e.max ZirCAD, and e.max Press dental ceramics and glass ionomer cement Ketac Cem in the present study. The dental ceramics were prepared in the form of samples with thickness of 0.5-2 mm. We used two lasers [solid-state laser (Er:YAG, Fidelis III+, Fotona) and an 810- nm diode laser (FOX, A.R.C)] for the transillumination of ceramic samples. It has been shown that the laser energy transmitted through the ceramic material decreases to 30-40% of the original values along with an increase in the thickness of the irradiated sample. Pigmented ceramic samples show more laser energy loss compared to the samples containing no pigment. We investigated the temperature evolution in composite sandwiched ceramic/cement samples under laser treatment. The increase in the irradiation time and laser power led to a temperature increase of up to 80 °C. The surfaces of irradiated ceramic samples were examined with X-ray photoelectron spectroscopy to evaluate changes in chemical composition, such as a decrease in the C signal, accompanied by a strong increase in the Zr peak for the Er:YAG laser, while the 810-nm diode laser showed no change in the ratio of elements on the surface.

EFFECTS OF LASER RADIATION ON MATTER. LASER PLASMA: Temporal and thermodynamic characteristics of plasma formation

NASA Astrophysics Data System (ADS)

Ignatavichyus, M. V.; Kazakyavichyus, É.; Orshevski, G.; Danyunas, V.

1991-11-01

An investigation was made of plasma formation accompanying the interaction with aluminum, iron, and VK-6 alloy targets of nanosecond radiation from a YAG:Nd3+ laser (Emax = 50 mJ, τ = 3-8 ns). The duration of the plasma formation process depended weakly on the laser radiation parameters [the power density was varied in the range 1-3 GW/cm2, the pulse rise time in the range 2-8 ns, or the rate of rise of the power density in the range (1-8) × 108 W · cm - 2 · ns -1]. A study was made of the establishment of a local thermodynamic equilibrium in a plasma jet excited by radiation from nanosecond and picosecond (E = 30 mJ, τ = 40 ps) lasers. The maximum of the luminescence from an aluminum plasma excited by picosecond laser radiation was found to correspond to a local thermodynamic equilibrium. A local thermodynamic equilibrium could be absent in the case of excitation by nanosecond laser radiation.

Phytochemical characteristic and uterotonic effect of aqueous extract of Ficus deltoidea leaves in rats uterus.

PubMed

Amiera, Z Umi Romaizatul; Nihayah, M; Wahida, I Farah; Rajab, N F

2014-09-01

Ficus deltoidea is traditionally consumed by Malay woman to augment labour and hastening parturition. This study was to investigate the phytochemical present and uterotonic activity of F. deltoidea var. Deltoidea (FDD) and F. deltoidea var. Angustifolia (FDA) leaves aqueous extract. FDD and FDA were qualitatively analysed. In uterine contraction activity, adult female Sprague Dawley rats were pretreated with 0.2 mg kg(-1) diethylstilbestrol 24 h to induce oestrus phase. The rats then killed and uterine horns were taken out, cut into two centimetres length and put into organ bath that connected to Powerlab instrument. The uterus separately tested with cumulative concentrations of FDD (10-1280 μg mL(-1)), FDA (10-1280 μg mL(-1)), oxytocin (0.02-0.64 μg mL(-1)) and combination of oxytocin (0.08 μg mL(-1)) with FDD and FDA (10-1280 μg mL(-1)). FDD showed presence of flavonoid, saponin and tannin meanwhile FDA consist of flavonoid, tannin and terpenoid. Result showed FDD, FDA and oxytocin induced a dose-related increase in force of contraction of isolated rat uterus. The maximum uterine contraction (Emax) produced by FDD, FDA and oxytocin were at the concentration 640 μg mL(-1) (EC50, 5.903 ± 0.529 μg mL), 20 μg mL(-1) (EC50, 290.5 ± 0.158 μg mL(-1)) and 0.4 μg mL(-1) (EC50, 0.060 ± 0.011 μg mL(-1)) respectively. Combination effects of oxytocin with FDD and FDA produced Emax at the concentration 80 μg mL(-1) (EC50, 270.3 ± 0.643 μg mL(-1)) and 1280 μg mL(-1) (EC50, 26.83 ± 0.727 μg mL(-1)), respectively. Study indicated F. deltoidea possess contractile effect on uterine contraction. This plant has great potential to develop as natural uterotonic agent in inducing labour and treatment for post-partum haemorrhage.

Shear Bond Strength of Resin Buttons to Lithium Disilicate and Leucite Reinforced Feldspathic Restorations

DTIC Science & Technology

2016-05-01

Hydrofluoric acid, silane coupling agent, light cured composite and ceramic restoration specimens (10 of each IPS e.max and Empress). The surface treatment...cured composite and ceramic restoration specimens (10 of each IPS e.max and Empress). The surface treatment in group C was applied to all specimens...and light cured for 20 seconds. 4) Group D: 5% Hydrofluoric acid, silane coupling agent, light cured composite and ceramic restoration (10 of

Differentiation of benign from malignant solid breast masses: comparison of two-dimensional and three-dimensional shear-wave elastography.

PubMed

Lee, Su Hyun; Chang, Jung Min; Kim, Won Hwa; Bae, Min Sun; Cho, Nariya; Yi, Ann; Koo, Hye Ryoung; Kim, Seung Ja; Kim, Jin You; Moon, Woo Kyung

2013-04-01

To prospectively compare the diagnostic performances of two-dimensional (2D) and three-dimensional (3D) shear-wave elastography (SWE) for differentiating benign from malignant breast masses. B-mode ultrasound and SWE were performed for 134 consecutive women with 144 breast masses before biopsy. Quantitative elasticity values (maximum and mean elasticity in the stiffest portion of mass, Emax and Emean; lesion-to-fat elasticity ratio, Erat) were measured with both 2D and 3D SWE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity of B-mode, 2D, 3D SWE and combined data of B-mode and SWE were compared. Sixty-seven of the 144 breast masses (47 %) were malignant. Overall, higher elasticity values of 3D SWE than 2D SWE were noted for both benign and malignant masses. The AUC for 2D and 3D SWE were not significantly different: Emean, 0.938 vs 0.928; Emax, 0.939 vs 0.930; Erat, 0.907 vs 0.871. Either 2D or 3D SWE significantly improved the specificity of B-mode ultrasound from 29.9 % (23 of 77) up to 71.4 % (55 of 77) and 63.6 % (49 of 77) without a significant change in sensitivity. Two-dimensional and 3D SWE performed equally in distinguishing benign from malignant masses and both techniques improved the specificity of B-mode ultrasound.

Long-term Cerec 3D chairside bridges milled from IPS e.max CAD LT blocks.

PubMed

Schneider, Oliver

The experienced Cerec user can manufacture high-quality, esthetic anterior and posterior bridges from IPS e.max CAD in a manageable 3-hour chairside session. On the basis of over 8 years of experience, it can be said that these restorations are clinically very well proven, provided they are used within the range of recommended indications. Experimental retainer bridges with extensions can be seen as highly interesting alternatives, although more clinical data are required for further confirmation.

Bonding Effectiveness of Luting Composites to Different CAD/CAM Materials.

PubMed

Peumans, Marleen; Valjakova, Emilija Bajraktarova; De Munck, Jan; Mishevska, Cece Bajraktarova; Van Meerbeek, Bart

To evaluate the influence of different surface treatments of six novel CAD/CAM materials on the bonding effectiveness of two luting composites. Six different CAD/CAM materials were tested: four ceramics - Vita Mark II; IPS Empress CAD and IPS e.max CAD; Celtra Duo - one hybrid ceramic, Vita Enamic, and one composite CAD/CAM block, Lava Ultimate. A total of 60 blocks (10 per material) received various mechanical surface treatments: 1. 600-grit SiC paper; 2. sandblasting with 30-μm Al2O3; 3. tribochemical silica coating (CoJet). Subsequent chemical surface treatments involved either no further treatment (control), HF acid etching (HF), silanization (S, or HF acid etching followed by silanization (HF+S). Two specimens with the same surface treatment were bonded together using two dual-curing luting composites: Clearfil Esthetic Cement (self-etching) or Panavia SA Cement (self-adhesive). After 1 week of water storage, the microtensile bond strength of the sectioned microspecimens was measured and the failure mode was evaluated. The bonding performance of the six CAD/CAM materials was significantly influenced by surface treatment (linear mixed models, p < 0.05). The luting cement had a significant influence on bond strength for Celtra Duo and Lava Ultimate (linear mixed models, p < 0.05). Mechanical surface treatment significantly influenced the bond strength for Celtra Duo (p = 0.0117), IPS e.max CAD (p = 0.0115), and Lava Ultimate (p < 0.0001). Different chemical surface treatments resulted in the highest bond strengths for the six CAD/CAM materials: Vita Mark II and IPS Empress CAD: S, HF+S; Celtra Duo: HF, HF+S; IPS e.max CAD: HF+S; Vita Enamic: HF+S, S. For Lava Ultimate, the highest bond strengths were obtained with HF, S, HF+S. Failure analysis showed a relation between bond strength and failure type: more mixed failures were observed with higher bond strengths. Mainly adhesive failures were noticed if no further surface treatment was done. The percentage of adhesive failures was higher for CAD/CAM materials with higher flexural strength (Celtra Duo, IPS e.max CAD, and Lava Ultimate). The bond strength of luting composites to novel CAD/CAM materials is influenced by surface treatment. For each luting composite, an adhesive cementation protocol can be specified in order to obtain the highest bond to the individual CAD/CAM materials.

Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile Reactivity of Rat Ileum to KCl and Carbachol

PubMed Central

Araujo, Layanne C. da Cunha; de Souza, Iara L. L.; Vasconcelos, Luiz H. C.; Brito, Aline de Freitas; Queiroga, Fernando R.; Silva, Alexandre S.; da Silva, Patrícia M.; Cavalcante, Fabiana de Andrade; da Silva, Bagnólia A.

2016-01-01

Aerobic exercise promotes short-term physiological changes in the intestinal smooth muscle associated to the ischemia-reperfusion process; however, few studies have demonstrated its effect on the intestinal contractile function. Thus, this work describes our observations regarding the influence of acute aerobic swimming exercise in the contractile reactivity, oxidative stress, and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min of swimming exercise in intercalated days 1 week before exercise. Then they were submitted to forced swimming for 1 h with a metal of 3% of their body weight attached to their body. Animals were euthanized immediately after the exercise section and the ileum was suspended in organ baths for monitoring isotonic contractions. The analysis of lipid peroxidation was performed in order to determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and intestinal smooth muscle morphology by histological staining. Cumulative concentration-response curves to KCl were altered in the EX-AC with an increase in both its efficacy and potency (Emax = 153.2 ± 2.8%, EC50 = 1.3 ± 0.1 × 10−2 M) compared to the SED group (Emax = 100%, EC50 = 1.8 ± 0.1 × 10−2 M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (Emax = 67.1 ± 1.4%, EC50 = 9.8 ± 1.4 × 10−7 M) compared to the SED group (Emax = 100%, EC50 = 2.0 ± 0.2 × 10−7 M). The exercise did not alter the MDA levels in the ileum (5.4 ± 0.6 μ mol/mL) in the EX-AC compared to the SED group (8.4 ± 1.7 μ mol/mL). Moreover, neither the circular nor the longitudinal smooth muscle layers thickness were modified by the exercise (66.2 ± 6.0 and 40.2 ± 2.6 μm, respectively), compared to the SED group (61.6 ± 6.4 and 34.8 ± 3.7 μm, respectively). Therefore, the ileum sensitivity to contractile agents is differentially altered by the acute aerobic swimming exercise, without affecting the oxidative stress and the morphology of ileum smooth muscle. PMID:27047389

Flexural strength and reliability of monolithic and trilayer ceramic structures obtained by the CAD-on technique.

PubMed

Basso, G R; Moraes, R R; Borba, M; Griggs, J A; Della Bona, A

2015-12-01

To evaluate the flexural strength, Weibull modulus, fracture toughness, and failure behavior of ceramic structures obtained by the CAD-on technique, testing the null hypothesis that trilayer structures show similar properties to monolithic structures. Bar-shaped (1.8mm×4mm×16mm) monolithic specimens of zirconia (IPS e.max ZirCAD - Ivoclar Vivadent) and trilayer specimens of zirconia/fusion ceramic/lithium dissilicate (IPS e.max ZirCAD/IPS e.max CAD Crystall./Connect/IPS e.max CAD, Ivoclar Vivadent) were fabricated (n=30). Specimens were tested in flexure in 37°C deionized water using a universal testing machine at a crosshead speed of 0.5mm/min. Failure loads were recorded, and the flexural strength values were calculated. Fractography principles were used to examine the fracture surfaces under optical and scanning electron microscopy. Data were statistically analyzed using Student's t-test and Weibull statistics (α=0.05). Monolithic and trilayer specimens showed similar mean flexural strengths, characteristic strengths, and Weibull moduli. Trilayer structures showed greater mean critical flaw and fracture toughness values than monolithic specimens (p<0.001). Most critical flaws in the trilayer groups were located on the Y-TZP surface subjected to tension and propagated catastrophically. Trilayer structures showed no flaw deflection at the interface. Considering the CAD-on technique, the trilayer structures showed greater fracture toughness than the monolithic zirconia specimens. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats

PubMed Central

Vara-Gama, Nancy; Soria-Arteche, Olivia; Moreno-Rocha, Luis A.; López-Muñoz, Francisco J.

2018-01-01

The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in Cmax, AUC0-24, and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action. PMID:29373537

Premolar Axial Wall Height Effect on CAD/CAM Crown Retention

DTIC Science & Technology

2016-05-24

OC axial wall height was required in a study that involved zirconia copings cemented on stainless steel dies. The results of this study reinforced...surface area was determined using a digital measuring microscope (Hirox). Scanned preparations (CEREC) were fitted with e.max CAD crowns and cemented ...Figure 14. RelyX Unicem Cementation

Comparison of mechanical properties of three machinable ceramics with an experimental fluorophlogopite glass ceramic.

PubMed

Leung, Brian T W; Tsoi, James K H; Matinlinna, Jukka P; Pow, Edmond H N

2015-09-01

Fluorophlogopite glass ceramic (FGC) is a biocompatible, etchable, and millable ceramic with fluoride releasing property. However, its mechanical properties and reliability compared with other machinable ceramics remain undetermined. The purpose of this in vitro study was to compare the mechanical properties of 3 commercially available millable ceramic materials, IPS e.max CAD, Vitablocs Mark II, and Vita Enamic, with an experimental FGC. Each type of ceramic block was sectioned into beams (n=15) of standard dimensions of 2×2×15 mm. Before mechanical testing, specimens of the IPS e.max CAD group were further fired for final crystallization. Flexural strength was determined by the 3-point bend test with a universal loading machine at a cross head speed of 1 mm/min. Hardness was determined with a hardness tester with 5 Vickers hardness indentations (n=5) using a 1.96 N load and a dwell time of 15 seconds. Selected surfaces were examined by scanning electron microscopy and energy-dispersive x-ray spectroscopy. Data were analyzed by the 1-way ANOVA test and Weibull analysis (α=.05). Weibull parameters, including the Weibull modulus (m) as well as the characteristic strength at 63.2% (η) and 10.0% (B10), were obtained. A significant difference in flexural strength (P<.001) was found among groups, with IPS e.max CAD (341.88 ±40.25 MPa)>Vita Enamic (145.95 ±12.65 MPa)>Vitablocs Mark II (106.67 ±18.50 MPa), and FGC (117.61 ±7.62 MPa). The Weibull modulus ranged from 6.93 to 18.34, with FGC showing the highest Weibull modulus among the 4 materials. The Weibull plot revealed that IPS e.max CAD>Vita Enamic>FGC>Vitablocs Mark II for the characteristic strength at both 63.2% (η) and 10.0% (B10). Significant difference in Vickers hardness among groups (P<.001) was found with IPS e.max CAD (731.63 ±30.64 H(V))>Vitablocs Mark II (594.74 ±25.22 H(V))>Vita Enamic (372.29 ±51.23 H(V))>FGC (153.74 ±23.62 H(V)). The flexural strength and Vickers hardness of IPS e.max CAD were significantly higher than those of the 3 materials tested. The FGC's flexural strength was comparable with Vitablocs Mark II. The FGC's Weibull modulus was the highest, while its Vickers hardness was the lowest among the materials tested. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

The role of enzyme and substrate concentration in the evaluation of serum angiotensin converting enzyme (ACE) inhibition by enalaprilat in vitro.

PubMed

Weisser, K; Schloos, J

1991-10-09

The relationship between serum angiotensin converting enzyme (ACE) activity and concentration of the ACE inhibitor enalaprilat was determined in vitro in the presence of different concentrations (S = 4-200 mM) of the substrate Hip-Gly-Gly. From Henderson plots, a competitive tight-binding relationship between enalaprilat and serum ACE was found yielding a value of approximately 5 nM for serum ACE concentration (Et) and an inhibition constant (Ki) for enalaprilat of approximately 0.1 nM. A plot of reaction velocity (Vi) versus total inhibitor concentration (It) exhibited a non-parallel shift of the inhibition curve to the right with increasing S. This was reflected by apparent Hill coefficients greater than 1 when the commonly used inhibitory sigmoid concentration-effect model (Emax model) was applied to the data. Slopes greater than 1 were obviously due to discrepancies between the free inhibitor concentration (If) present in the assay and It plotted on the abscissa and could, therefore, be indicators of tight-binding conditions. Thus, the sigmoid Emax model leads to an overestimation of Ki. Therefore, a modification of the inhibitory sigmoid Emax model (called "Emax tight model") was applied, which accounts for the depletion of If by binding, refers to It and allows estimation of the parameters Et and IC50f (free concentration of inhibitor when 50% inhibition occurs) using non-linear regression analysis. This model could describe the non-symmetrical shape of the inhibition curves and the results for Ki and Et correlated very well with those derived from the Henderson plots. The latter findings confirm that the degree of ACE inhibition measured in vitro is, in fact, dependent on the concentration of substrate and enzyme present in the assay. This is of importance not only for the correct evaluation of Ki but also for the interpretation of the time course of serum ACE inhibition measured ex vivo. The non-linear model has some advantages over the linear Henderson equation: it is directly applicable without conversion of the data and avoids the stochastic dependency of the variables, allowing non-linear regression of all data points contributing with the same weight.

Synergistic interaction between fentanyl and the histamine H3 receptor agonist R-(alpha)-methylhistamine, on the inhibition of nociception and plasma extravasation in mice.

PubMed

Poveda, Raquel; Fernández-Dueñas, Víctor; Fernández, Alejandro; Sánchez, Sílvia; Puig, Margarita M; Planas, Eulàlia

2006-07-10

Here we report a synergistic interaction between fentanyl and the histamine H(3) receptor agonist R-(alpha)-methylhistamine on the inhibition of nociception and plasma extravasation in mice. Chronic inflammation was induced by subplantar injection of Complete Freund's Adjuvant into the right hind paw, and the effect of the drugs was evaluated 7 days later. Nociception and plasma extravasation were assessed by hot-plate and Evans blue tests respectively. Subcutaneous administration of fentanyl (0.01-0.1 mg/kg) induced dose-related anti-nociceptive and anti-extravasation effects (E(max)=100% and 62%, respectively). R-(alpha)-methylhistamine administration (0.3-3 mg/kg) showed a dose-related inhibitory effect on extravasation (E(max)=65%) but not on nociception. To analyze possible interaction between these two drugs, a dose-response curve to fentanyl plus a fixed dose of R-(alpha)-methylhistamine (0.5 mg/kg) was obtained. The dose-response curve for the combined treatment showed a shift to the left compared with that for fentanyl alone. Our results confirm that fentanyl and R-(alpha)-methylhistamine interact in a synergic way, inhibiting nociception and plasma extravasation.

Chairside CAD/CAM materials. Part 2: Flexural strength testing.

PubMed

Wendler, Michael; Belli, Renan; Petschelt, Anselm; Mevec, Daniel; Harrer, Walter; Lube, Tanja; Danzer, Robert; Lohbauer, Ulrich

2017-01-01

Strength is one of the preferred parameters used in dentistry for determining clinical indication of dental restoratives. However, small dimensions of CAD/CAM blocks limit reliable measurements with standardized uniaxial bending tests. The objective of this study was to introduce the ball-on-three-ball (B3B) biaxial strength test for dental for small CAD/CAM block in the context of the size effect on strength predicted by the Weibull theory. Eight representative chairside CAD/CAM materials ranging from polycrystalline zirconia (e.max ZirCAD, Ivoclar-Vivadent), reinforced glasses (Vitablocs Mark II, VITA; Empress CAD, Ivoclar-Vivadent) and glass-ceramics (e.max CAD, Ivoclar-Vivadent; Suprinity, VITA; Celtra Duo, Dentsply) to hybrid materials (Enamic, VITA; Lava Ultimate, 3M ESPE) have been selected. Specimens were prepared with highly polished surfaces in rectangular plate (12×12×1.2mm 3 ) or round disc (Ø=12mm, thickness=1.2mm) geometries. Specimens were tested using the B3B assembly and the biaxial strength was determined using calculations derived from finite element analyses of the respective stress fields. Size effects on strength were determined based on results from 4-point-bending specimens. A good agreement was found between the biaxial strength results for the different geometries (plates vs. discs) using the B3B test. Strength values ranged from 110.9MPa (Vitablocs Mark II) to 1303.21MPa (e.max ZirCAD). The strength dependency on specimen size was demonstrated through the calculated effective volume/surface. The B3B test has shown to be a reliable and simple method for determining the biaxial strength restorative materials supplied as small CAD/CAM blocks. A flexible solution was made available for the B3B test in the rectangular plate geometry. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition.

PubMed

Claudino, M A; Priviero, F B M; Camargo, E A; Teixeira, C E; De Nucci, G; Antunes, E; Zanesco, A

2007-01-01

The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min. L-NAME treatment (2 and 10 mg/rat/day) started after 4 weeks of prior physical conditioning and lasted 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil and BAY 41-2272. The effect of electrical field stimulation (EFS) on the relaxations responses of CC was evaluated. Run training prevented the arterial hypertension induced by L-NAME treatment (LN-SD: 135+/-2 and 141+/-2 mm Hg for both doses of L-NAME) compared to LN-SD groups (154+/-1 and 175+/-2 mm Hg, for 2 and 10 mg of L-NAME, respectively). Run training produced an increase in the maximal responses (E(max)) of CC for ACh (C-SD: 47+/-3; C-TR: 52+/-1; and LN-TR: 53+/-3%) and SNP (C-SD: 89+/-1; C-TR: 98+/-1; and LN-TR: 95+/-1%). Both potency and E(max) for ACh were reduced in a dose of 10 mg of L-NAME, and run training restored the reduction of E(max) for ACh. No changes were found for BAY 41-2271 and sildenafil. Relaxing responses to EFS was reduced by L-NAME treatment that was restored by prior physical conditioning. In conclusion, our study shows a beneficial effect of prior physical conditioning on the impaired CC relaxing responses in rats made hypertensive by chronic NO blockade.

Adrenocorticotropin reverses vascular dysfunction and protects against splanchnic artery occlusion shock

PubMed Central

Squadrito, Francesco; Guarini, Salvatore; Altavilla, Domenica; Squadrito, Giovanni; Campo, Giuseppe M; Arlotta, Mariarita; Quartarone, Cristina; Saitta, Antonino; Cucinotta, Domenico; Bazzani, Carla; Cainazzo, Maria M; Mioni, Chiara; Bertolini, Alfio; Caputi, Achille P

1999-01-01

Tumour necrosis factor (TNF-α) is involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. On the other hand, inhibition of TNF-α is an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock. We therefore investigated the effects of the melanocortin peptide ACTH-(1–24) (adrenocorticotropin fragment 1–24) on the vascular failure induced by SAO shock.SAO-shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham-shocked rats survived for more than 4 h), enhanced serum TNF-α concentrations (755±81 U ml−1), decreased mean arterial blood pressure, leukopenia, and increased ileal leukocyte accumulation, as revealed by means of myeloperoxidase activity (MPO=9.4±1 U g−1 tissue). Moreover, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM–10 μM) (Emax and ED50 in shocked rats=7.16 mN mg−1 tissue and 120 nM, respectively; Emax and ED50 in sham-shocked rats=16.31 mN mg−1 tissue and 100 nM, respectively), reduced responsiveness to acetylcholine (ACh, 10 nM-10 μM) (Emax and ED50 in shocked rats=30% relaxation and 520 nM, respectively; Emax and ED50 in sham-shocked rats=82% relaxation and 510 nM, respectively) and increased staining for intercellular adhesion molecule-1 (ICAM-1).ACTH-(1–24) [160 μg kg−1 intravenously (i.v.), 5 min after SAO] increased survival rate [SAO+ACTH-(1–24)=80% at 4 h of reperfusion], reversed hypotension, reduced serum TNF-α (55±13 U ml−1), ameliorated leukopenia, reduced ileal MPO (1.2±0.2 U g−1 tissue), restored the reactivity to PE, improved the responsiveness to ACh and blunted the enhanced immunostaining for ICAM-1 in the aorta.Adrenalectomy only in part–but not significantly–reduced the ACTH-induced shock reversal, the survival rate of SAO+ACTH-(1–24) adrenalectomized rats being 60% at 4 h of reperfusion; and methylprednisolone (80 mg−1 i.v., 5 min after SAO) had a non-significant effect (10% survival) at 4 h of reperfusion.The present data show that melanocortins are effective also in SAO shock, their effect being, at least in part, mediated by reduced production of TNF-α. Furthermore, they demonstrate, for the first time, that this inhibition is responsible for the adrenocorticotropin-induced reversal of vascular failure and leukocyte accumulation. PMID:10516667

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

PubMed

Geoffroy, L; Dewez, D; Vernet, G; Popovic, R

2003-11-01

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

Growth, structure, and properties of epitaxial thin films of first-principles predicted multiferroic Bi2FeCrO6

NASA Astrophysics Data System (ADS)

Nechache, Riad; Harnagea, Catalin; Pignolet, Alain; Normandin, François; Veres, Teodor; Carignan, Louis-Philippe; Ménard, David

2006-09-01

The authors report the structural and physical properties of epitaxial Bi2FeCrO6 thin films on epitaxial SrRuO3 grown on (100)-oriented SrTiO3 substrates by pulsed laser ablation. The 300nm thick films exhibit both ferroelectricity and magnetism at room temperature with a maximum dielectric polarization of 2.8μC /cm2 at Emax=82kV/cm and a saturated magnetization of 20emu/cm3 (corresponding to ˜0.26μB per rhombohedral unit cell), with coercive fields below 100Oe. The results confirm the predictions made using ab initio calculations about the existence of multiferroic properties in Bi2FeCrO6.

Doppler-derived myocardial systolic strain rate is a strong index of left ventricular contractility

NASA Technical Reports Server (NTRS)

Greenberg, Neil L.; Firstenberg, Michael S.; Castro, Peter L.; Main, Michael; Travaglini, Agnese; Odabashian, Jill A.; Drinko, Jeanne K.; Rodriguez, L. Leonardo; Thomas, James D.; Garcia, Mario J.

2002-01-01

BACKGROUND: Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone. METHODS AND RESULTS: TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance-high-fidelity pressure catheter. Peak elastance (Emax) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (Sm) and peak (epsilon'(p)) and mean (epsilon'(m)) strain rates obtained at the basal septum were compared against Emax by linear regression. Emax as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between Emax and epsilon'(p) (r=0.94, P<0.01, y=0.29x+0.46) and epsilon'(m) (r=0.88, P<0.01) than for Sm (r=0.75, P<0.01). CONCLUSIONS: TDE-derived epsilon'(p) and epsilon'(m) are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S(m), perhaps by eliminating translational artifact.

Molecular imaging of angiogenesis with SPECT

PubMed Central

Boerman, Otto C.

2010-01-01

Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: 99mTc (Emax 141 keV, T1/2 6.02 h), 123I (Emax 529 keV, T1/2 13.0 h) and 111In (Emax 245 keV, T1/2 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed. PMID:20617435

The Effect of Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence

DTIC Science & Technology

2006-05-01

CEREC e.max* CAD crowns on preparations with moderate total occlusal convergence (16 degrees). Methods: 60 recently-extracted maxillary third molars ...The Effect of Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence Wyeth L. Hoopes The Effect of Molar Axial Wall... Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence is appropria tely acknowledged and beyond brief excerpts, is with

3D and 2D marginal fit of pressed and CAD/CAM lithium disilicate crowns made from digital and conventional impressions.

PubMed

Anadioti, Evanthia; Aquilino, Steven A; Gratton, David G; Holloway, Julie A; Denry, Isabelle; Thomas, Geb W; Qian, Fang

2014-12-01

This in vitro study evaluated the 3D and 2D marginal fit of pressed and computer-aided-designed/computer-aided-manufactured (CAD/CAM) all-ceramic crowns made from digital and conventional impressions. A dentoform tooth (#30) was prepared for an all-ceramic crown (master die). Thirty type IV definitive casts were made from 30 polyvinyl siloxane (PVS) impressions. Thirty resin models were produced from thirty Lava Chairside Oral Scanner impressions. Thirty crowns were pressed in lithium disilicate (IPS e.max Press; 15/impression technique). Thirty crowns were milled from lithium disilicate blocks (IPS e.max CAD; 15/impression technique) using the E4D scanner and milling engine. The master die and the intaglio of the crowns were digitized using a 3D laser coordinate measurement machine with accuracy of ±0.00898 mm. For each specimen a separate data set was created for the Qualify 2012 software. The digital master die and the digital intaglio of each crown were merged using best-fitting alignment. An area above the margin with 0.75 mm occlusal-gingival width circumferentially was defined. The 3D marginal fit of each specimen was an average of all 3D gap values on that area. For the 2D measurements, the marginal gap was measured at two standardized points (on the margin and at 0.75 mm above the margin), from standardized facial-lingual and mesial-distal digitized sections. One-way ANOVA with post hoc Tukey's honestly significant difference and two-way ANOVA tests were used, separately, for statistical analysis of the 3D and 2D marginal data (alpha = 0.05). One-way ANOVA revealed that both 3D and 2D mean marginal gap for group A: PVS impression/IPS e.max Press (0.048 mm ± 0.009 and 0.040 mm ± 0.009) were significantly smaller than those obtained from the other three groups (p < 0.0001), while no significant differences were found among groups B: PVS impression/IPS e.max CAD (0.088 mm ± 0.024 and 0.076 mm ± 0.023), C: digital impression/IPS e.max Press (0.089 mm ± 0.020 and 0.075 mm ± 0.015) and D: digital impression/IPS e.max CAD (0.084 mm ± 0.021 and 0.074 mm ± 0.026). The results of two-way ANOVA revealed a significant interaction between impression techniques and crown fabrication methods for both 3D and 2D measurements. The combination of PVS impression method and press fabrication technique produced the most accurate 3D and 2D marginal fits. © 2014 by the American College of Prosthodontists.

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

PubMed

Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

1997-03-01

The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

Interfacial modulus mapping of layered dental ceramics using nanoindentation

PubMed Central

Bushby, Andrew J; P'ng, Ken MY; Wilson, Rory M

2016-01-01

PURPOSE The aim of this study was to test the modulus of elasticity (E) across the interfaces of yttria stabilized zirconia (YTZP) / veneer multilayers using nanoindentation. MATERIALS AND METHODS YTZP core material (KaVo-Everest, Germany) specimens were either coated with a liner (IPS e.max ZirLiner, Ivoclar-Vivadent) (Type-1) or left as-sintered (Type-2) and subsequently veneered with a pressable glass-ceramic (IPS e.max ZirPress, Ivoclar-Vivadent). A 5 µm (nominal tip diameter) spherical indenter was used with a UMIS CSIRO 2000 (ASI, Canberra, Australia) nanoindenter system to test E across the exposed and polished interfaces of both specimen types. The multiple point load – partial unload method was used for E determination. All materials used were characterized using Scanning Electron Microscopy (SEM) and X – ray powder diffraction (XRD). E mappings of the areas tested were produced from the nanoindentation data. RESULTS A significantly (P<.05) lower E value between Type-1 and Type-2 specimens at a distance of 40 µm in the veneer material was associated with the liner. XRD and SEM characterization of the zirconia sample showed a fine grained bulk tetragonal phase. IPS e-max ZirPress and IPS e-max ZirLiner materials were characterized as amorphous. CONCLUSION The liner between the YTZP core and the heat pressed veneer may act as a weak link in this dental multilayer due to its significantly (P<.05) lower E. The present study has shown nanoindentation using spherical indentation and the multiple point load - partial unload method to be reliable predictors of E and useful evaluation tools for layered dental ceramic interfaces. PMID:28018566

Wear, strength, modulus and hardness of CAD/CAM restorative materials.

PubMed

Lawson, Nathaniel C; Bansal, Ritika; Burgess, John O

2016-11-01

To measure the mechanical properties of several CAD/CAM materials, including lithium disilicate (e.max CAD), lithium silicate/zirconia (Celtra Duo), 3 resin composites (Cerasmart, Lava Ultimate, Paradigm MZ100), and a polymer infiltrated ceramic (Enamic). CAD/CAM blocks were sectioned into 2.5mm×2.5mm×16mm bars for flexural strength and elastic modulus testing and 4mm thick blocks for hardness and wear testing. E.max CAD and half the Celtra Duo specimens were treated in a furnace. Flexural strength specimens (n=10) were tested in a three-point bending fixture. Vickers microhardness (n=2, 5 readings per specimen) was measured with a 1kg load and 15s dwell time. The CAD/CAM materials as well as labial surfaces of human incisors were mounted in the UAB wear device. Cusps of human premolars were mounted as antagonists. Specimens were tested for 400,000 cycles at 20N force, 2mm sliding distance, 1Hz frequency, 24°C, and 33% glycerin lubrication. Volumetric wear and opposing enamel wear were measured with non-contact profilometry. Data were analyzed with 1-way ANOVA and Tukey post-hoc analysis (alpha=0.05). Specimens were observed with SEM. Properties were different for each material (p<0.01). E.max CAD and Celtra Duo were generally stronger, stiffer, and harder than the other materials. E.max CAD, Celtra Duo, Enamic, and enamel demonstrated signs of abrasive wear, whereas Cerasmart, Lava Ultimate, Paradigm MZ100 demonstrated signs of fatigue. Resin composite and resin infiltrated ceramic materials have demonstrated adequate wear resistance for load bearing restorations, however, they will require at least similar material thickness as lithium disilicate restorations due to their strength. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

[In vitro study on shear bond strength of veneering ceramics to zirconia].

PubMed

Hu, Xiaoping; Zhu, Hongshui; Zeng, Liwei

2012-12-01

To investigate the shear bond strength between veneering ceramic and zirconia core in different all-ceramic systems. Twenty disk-shaped specimens with 8 mm in diameter and 3 mm in height for each zirconia system (Lava, Cercon, IPS e.max ZirCAD, Procera) were fabricated respectively and divided into four groups: Lava group, Cercon group, IPS e.max ZirCAD group, Procera group. For each group, 10 specimens were sintered with 1 mm corresponding veneering ceramic, while the other were sintered with 2 mm corresponding veneering ceramic respectively. The shear bond strength and fracture mode of specimens were observed and determined. The values of shear bond strength for Lava, Cercon, IPS e.max ZirCAD and Procera were (13.82 +/- 3.71), (13.24 +/- 2.09), (6.37 +/- 4.15), (5.19 +/- 5.31) MPa in the group of 1 mm thicked veneering ceramics, respectively, while the values in the group of 2mm thicked veneering ceramics were (38.77 +/- 1.69), (21.67 +/- 3.34), (12.70 +/- 4.24), (9.94 +/- 6.67) MPa. The values of Lava and Cercon groups were significantly higher than that of IPS e.max ZirCAD and Procera groups (P < 0.05). And the values of 2 mm thicked veneering ceramic group were significantly higher than that in 1 mm thicked groups (P < 0.05). Adhesive fracture between core and veneering ceramics were observed in the fracture modes of most specimens. The shear bond strength of veneering ceramic to the zirconia framework are different from the zirconia system we chose, and the thickness of veneering ceramic has a great impact on its shear bond strength.

Characterization of noradrenaline release in the locus coeruleus of freely moving awake rats by in vivo microdialysis.

PubMed

Fernández-Pastor, Begoña; Mateo, Yolanda; Gómez-Urquijo, Sonia; Javier Meana, J

2005-07-01

The origin and regulation of noradrenaline (NA) in the locus coeruleus (LC) is unknown. The neurochemical features of NA overflow (nerve impulse dependence, neurotransmitter synthesis, vesicle storage, reuptake, alpha2-adrenoceptor-mediated regulation) were characterized in the LC. Brain microdialysis was performed in awake rats. Dialysates were analyzed for NA. NA in the LC decreased via local infusion of Ca2+-free medium (-42+/-5%) or the sodium channel blocker tetrodotoxine (TTX) (-47+/-8%) but increased (333+/-40%) via KCl-induced depolarization. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-p-tyrosine (250 mg kg(-1), i.p.) and the vesicle depletory drug reserpine (5 mg kg(-1), i.p.) decreased NA. Therefore, extracellular NA in the LC satisfies the criteria for an impulse flow-dependent vesicular exocytosis of neuronal origin. Local perfusion of the alpha2-adrenoceptor agonist clonidine (0.1-100 microM) decreased NA (E(max)=-79+/-5%) in the LC, whereas the opposite effect (E(max)=268+/-53%) was observed with the alpha2A-adrenoceptor antagonist BRL44408 (0.1-100 microM). This suggests a tonic modulation of NA release through local alpha2A-adrenoceptors. The selective NA reuptake inhibitor desipramine (DMI) (0.1-100 microM) administered into the LC increased NA in the LC (E(max)=223+/-40%) and simultaneously decreased NA in the cingulate cortex, confirming the modulation exerted by NA in the LC on firing activity of noradrenergic cells and on the subsequent NA release in noradrenergic terminals. Synaptic processes underlying NA release in the LC are similar to those in noradrenergic terminal areas. NA in the LC could represent local somatodendritic release, but also the presence of neurotransmitter release from collateral axon terminals.

Acute resistance exercise reduces blood pressure and vascular reactivity, and increases endothelium-dependent relaxation in spontaneously hypertensive rats.

PubMed

Faria, Thaís de Oliveira; Targueta, Gabriel Pelegrineti; Angeli, Jhuli Keli; Almeida, Edna Aparecida Silveira; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

2010-09-01

The aim of the present study was to assess the effects of acute dynamic resistance exercise on resting blood pressure (BP) and on endothelial function of vascular bed of spontaneously hypertensive rats. Hemodynamic measurements were performed before and after acute dynamic resistance exercise in conscious animals. After exercise, the tail artery was cannulated for mean perfusion pressure with constant flow measurement and for performing concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) and dose-response curves to phenylephrine (PHE). PHE protocol was also repeated with damaged endothelium and after L-NAME and indomethacin perfusion on the tail. The maximal response (E(max)) and sensitivity (pD(2)) were evaluated to these drugs. Exercise reduced resting systolic and diastolic BP (Delta -79 +/- 1.8; -23 +/- 2.3 mmHg, respectively; P < 0.05). ACh-induced relaxation increased in the exercise group (pD(2) = 9.8 +/- 0.06, P < 0.05) when compared with control rats (pD(2) = 8.7 +/- 0.1). The E(max) to PHE with intact endothelium decreased following exercise condition (439 +/- 18 mmHg, P < 0.05) when compared with control rats (276 +/- 22 mmHg). This response was abolished after L-NAME and indomethacin administration. After damage of the endothelium, PHE responses were not significantly different between the groups; however, E(max) and pD(2) increased when compared with responses obtained with intact endothelium. The results demonstrated that acute dynamic resistance exercise decreased resting BP and reactivity to PHE and increased endothelium-dependent relaxation. Nitric oxide and vasodilators prostanoids appear to be involved in post-exercise endothelial and pressor responses.

Characterization of the Eimeria maxima sporozoite surface protein IMP1.

PubMed

Jenkins, M C; Fetterer, R; Miska, K; Tuo, W; Kwok, O; Dubey, J P

2015-07-30

The purpose of this study was to characterize Eimeria maxima immune-mapped protein 1 (IMP1) that is hypothesized to play a role in eliciting protective immunity against E. maxima infection in chickens. RT-PCR analysis of RNA from unsporulated and sporulating E. maxima oocysts revealed highest transcription levels at 6-12h of sporulation with a considerable downregulation thereafter. Alignment of IMP1 coding sequence from Houghton, Weybridge, and APU-1 strains of E. maxima revealed single nucleotide polymorphisms that in some instances led to amino acid changes in the encoded protein sequence. The E. maxima (APU-1) IMP1 cDNA sequence was cloned and expressed in 2 different polyHis Escherichia coli expression vectors. Regardless of expression vector, recombinant E. maxima IMP1 (rEmaxIMP1) was fairly unstable in non-denaturing buffer, which is consistent with stability analysis of the primary amino acid sequence. Antisera specific for rEmaxIMP1 identified a single 72 kDa protein or a 61 kDa protein by non-reducing or reducing SDS-PAGE/immunoblotting. Immunofluorescence staining with anti-rEmaxIMP1, revealed intense surface staining of E. maxima sporozoites, with negligible staining of merozoite stages. Immuno-histochemical staining of E. maxima-infected chicken intestinal tissue revealed staining of E. maxima developmental stages in the lamnia propia and crypts at both 24 and 48 h post-infection, and negligible staining thereafter. The expression of IMP1 during early stages of in vivo development and its location on the sporozoite surface may explain in part the immunoprotective effect of this protein against E. maxima infection. Published by Elsevier B.V.

THE EXCEPTIONAL SETS ON THE RUN-LENGTH FUNCTION OF β-EXPANSIONS

NASA Astrophysics Data System (ADS)

Zheng, Lixuan; Wu, Min; Li, Bing

Let β > 1 and the run-length function rn(x,β) be the maximal length of consecutive zeros amongst the first n digits in the β-expansion of x ∈ [0, 1]. The exceptional set Emaxφ = x ∈ [0, 1] :liminf n→∞rn(x,β) φ(n) = 0,limsupn→∞rn(x,β) φ(n) = +∞ is investigated, where φ : ℕ → ℝ+ is a monotonically increasing function with limn→∞φ(n) = +∞. We prove that the set Emaxφ is either empty or of full Hausdorff dimension and residual in [0, 1] according to the increasing rate of φ.

A Step-by-Step Conservative Approach for CAD-CAM Laminate Veneers

PubMed Central

Henríquez Gutiérrez, Ismael; Guzmán Marusic, Álvaro; Báez Rosales, Abelardo; Tisi Lanchares, José Pablo

2017-01-01

The use of CAD/CAM technology has allowed the fabrication of ceramic restorations efficiently and with predictable results. Lithium disilicate is a type of glass ceramic material that can be used for the elaboration of laminate veneers, being monolithic restorations which require characterization through a covering ceramic in order to achieve acceptable esthetic results. The next case report shows a predictable clinical protocol for the rehabilitation of the anterior teeth through the preparation of CAD/CAM veneers (e.max CAD, Ivoclar Vivadent, Liechtenstein) which have been characterized by a nanofluorapatite ceramic (e.max Ceram, Ivoclar Vivadent, Liechtenstein) through the layering technique. PMID:28884029

Determination of the Elasticity of Breast Tissue during the Menstrual Cycle Using Real-Time Shear Wave Elastography.

PubMed

Li, Xiang; Wang, Jian-Nan; Fan, Zhi-Ying; Kang, Shu; Liu, Yan-Jun; Zhang, Yi-Xia; Wang, Xue-Mei

2015-12-01

We examined breast tissue elasticity during the menstrual cycle using real-time shear wave elastography (RT-SWE), a recent technique developed for soft tissue imaging. Written informed consent for RT-SWE was obtained from all eligible patients, who were healthy women aged between 19 and 52 y. Young's moduli of the breast tissue in the early follicular, late phase and luteal phase were compared. There were no significant differences in the mean, maximum and minimum elasticity values (Emean, Emax and Emin) and standard deviation (ESD). RT-SWE of glandular tissue revealed that ESD was increased in the early follicular phase compared with the luteal phase. Means ± SD of Emin, Emax and Emean in glandular tissue were 5.174 ± 2.138, 8.308 ± 3.166 and 6.593 ± 2.510, respectively, and in adipose tissue, 3.589 ± 2.083, 6.733 ± 3.522 and 4.857 ± 2.564, respectively. There were no significant differences in stiffness between glandular and adipose tissues throughout the menstrual cycle, but glandular tissue stiffness was lower in the luteal phase than in the early follicular phase. On the basis of these observations in normal healthy women, we believe we have obtained sufficient information to establish the baseline changes in human breast elasticity during the menstrual cycle. In the future, we intend to compare the elasticity values of healthy breast tissue with those of breast tissue affected by various pathologies. Our results reveal the significant potential of RT-SWE in the rapid and non-invasive clinical diagnosis of breast diseases, such as breast cancers. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Treatment of resistant tattoos using a new generation Q-switched Nd:YAG laser: influence of beam profile and spot size on clearance success.

PubMed

Karsai, Syrus; Pfirrmann, Gudrun; Hammes, Stefan; Raulin, Christian

2008-02-01

Multiple treatments of resistant tattoos often result in fibrosis and visible textural changes that lessen response to subsequent treatments. The aim of this study is to evaluate the influence of beam profile and spot size on clearance rates and side effects in the setting of resistant tattoos. Thirty-six professional, black tattoos (32 patients) were treated unsuccessfully with a Q-switched Nd:YAG laser (MedLite C3, HoyaConBio Inc., Fremont, CA). Because of therapy resistance all tattoos were re-treated using a new generation Nd:YAG laser (MedLite C6, HoyaConBio Inc.). Maximum energy fluence (E (max)), mean energy fluence, mean spot size, level of clearance, side effects and beam profile (irradiance distribution) of both laser systems were assessed and evaluated in a retrospective study. All tattoos were previously treated with the C3 laser at 1,064 nm using a mean E(max) of 5.8+/-0.8 J/cm(2) (range 3.8-7.5 J/cm(2)) as compared with a mean E(max) of 6.4+/-1.6 J/cm(2) (range 3.2-9.0 J/cm(2)) during the C6 treatment course. Corresponding spot sizes were larger during C6 treatments as compared with C3 (5.0+/-0.9 and 3.6+/-0.2 mm, respectively). The C6 laser had a "flat top" and homogenous profile regardless of the spot size. For the C3 laser the beam shape was "Gaussian," and the homogeneity was reduced by numerous micro-spikes and micro-nadirs. After the C6 treatment course 33.3% of the tattoos showed clearance of grade 1 (0-25%), 16.7% of grade 2 (26-50%), 16.7% of grade 3 (51-75%), 30.5% of grade 4 (76-95%), 2.8% of grade 5 (96-100%). The total rate of side effects due to C6 treatment was 8.3% in all tattoos (hyperpigmentation 5.6%, hypopigmentation 2.7%, textural changes/scars 0%). This clinical study documents for the first time the impact of a 1,064-nm Nd:YAG laser with a more homogenous beam profile and a larger spot size on the management of resistant tattoos. Only a few treatment sessions were necessary to achieve an additional clearance with a low rate of side effects.

Effect of Split-File Digital Workflow on Crown Margin Adaptation

DTIC Science & Technology

2017-03-30

you in your future publication/presentation efforts. LINDA STEEL -GOODWIN, Col, USAF, BSC Director, Clinical Investigations & Research Support...METHODS Multiple pilot studies were completed to define a working model with appropriate restoration settings ( cement gap 20 µm, extra cement gap 40...depressions for standardization. Right: Zirconia and e.max restorations had a cement gap (CG) = 20 µm ; extra cement gap (ECG) = 40 µm, and distance to

The Effect of Sintering Time on the Marginal Fit of Zirconia Copings.

PubMed

Khaledi, Amir Ali Reza; Vojdani, Mahroo; Farzin, Mitra; Pirouzi, Sudabeh; Orandi, Sepideh

2018-01-03

This study analyzed the effect of different sintering times on the marginal adaptation of zirconia ceramic copings. Thirty copings of pre-sintered 3Y-TZP blanks were milled and subsequently sintered in a special furnace for three different durations (n = 10 per group). The sintering time was 1 hour, 15 minutes for IPS e.max ZirCAD, 4 hours 20 minutes for Speed ZrO 2, and 7 hours 20 minutes for the conventional ZrO 2 group. The marginal gaps of specimens were measured at 18 spots on the master die by employing a digital microscope. One-way ANOVA test compared the mean differences among the 3 groups (α = 0.05). The mean values for the marginal gap of the IPS e.max ZirCAD, Speed ZrO 2 , and conventional ZrO 2 groups were 41.06 ± 14.03, 43.03 ± 11.67, and 39.88 ± 15.23 μm, respectively. There was no statistically significant difference among the groups regarding the marginal gap. Different sintering times did not alter the marginal fit of the zirconia copings. The mean values of the marginal gap were within the clinically acceptable level for all three groups. © 2018 by the American College of Prosthodontists.

Parallel Synthesis of photoluminescent π-conjugated polymers by polymer reactions of an organotitanium polymer with a titanacyclopentadiene unit.

PubMed

Matsumura, Yoshimasa; Fukuda, Katsura; Inagi, Shinsuke; Tomita, Ikuyoshi

2015-04-01

A regioregular organometallic polymer with titanacyclopentadiene unit, obtained by the reaction of a 2,7-diethynylfluorene derivative and a low-valent titanium complex, is subjected to the reaction with three kinds of electrophiles (i.e., sulfur monochloride, hydrochloric acid, and dichlorophenylphosphine) to give π-conjugated polymers possessing both fluorene and building blocks originated from the transformation of the titanacycles in the main chain. For example, a phosphole-containing polymer whose number-average molecular weight is estimated as 5000 is obtained in 50% yield. The obtained thiophene, butadiene, and phosphole-containing polymers exhibit efficient photoluminescence (PL) with emission colors of blue, green, and yellow, respectively. For example, the phosphole-containing polymer exhibits yellow PL with an emission maximum (Emax ) of 533 nm and a quantum yield (Φ) of 0.37. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence that tachykinin NK2 receptors modulate resting tone in the rat isolated small intestine.

PubMed Central

Maggi, C. A.; Giuliani, S.

1996-01-01

1. In the progress of experiments aimed at evaluating the role of tachykinins as enteric nonadrenergic noncholinergic (NANC) transmitters, we noted that certain tachykinin receptor antagonists produce a relaxation of circular muscle strips in the rat small intestine. This study aimed to assess the nature of this response and to determine the receptor type involved. The majority of the experiments were performed in capsaicin- (10 microM for 15 min) pretreated mucosa-free circular muscle strips from the rat small intestine, in the presence of atropine (1 microM), guanethidine (3 microM) and indomethacin (10 microM). 2. Under isometric recording of mechanical activity, the tachykinin NK1 receptor antagonist SR 140,333 (0.1 microM) had no effect on resting tone or spontaneous activity in duodenal or ileal circular muscle strips. The NK2 receptor antagonists, MEN 10,627 (0.1 microM) and GR 94,800 (0.1 microM) produced, after a delay of 10-15 min, a relaxation which averaged 61 +/- 3 and 57 +/- 6% (n = 6 and 4, respectively) of the maximal response (Emax) to isoprenaline (1 microM). The effect of maximal concentrations of MEN 10,627 and GR 94,800 when applied together was non-additive. The relaxant effect of MEN 10,627 (0.1 microM) was similar in the absence and presence of apamin (0.3 microM) and L-nitroarginine (100 microM). 3. Under isotonic recording of mechanical activity, MEN 10,627 (10 nM-1 microM) produced a concentration- and time-related relaxation of duodenal strips. The maximal relaxation averaged 72 +/- 4 and 69 +/- 4% (n = 5 each) of Emax to isoprenaline (1 microM) and was achieved 15-20 or 20-30 min after application of 1.0 or 0.1 microM MEN 10,627, respectively. 4. Duodenal strips were relaxed by other NK2 receptor selective antagonists (values in parentheses are % of Emax to isoprenaline at the given concentration of antagonist) GR 94,800 (69 +/- 3% at 1 microM, n = 4), SR 48,968 (60 +/- 3% at 1 microM, n = 4) and MDL 29,913 (66 +/- 4% at 1 microM, n = 4). SR 48,965 (1 microM), the inactive enantiomer of SR 48,968, was without effect. The NK1 receptor selective antagonists, SR 140,333 (0.1 microM), FK 888 (10 microM) RP 67,580 (1 microM) and GR 82,334 (10 microM) were also without effect (n = 4-5). 5. A cocktail of peptidase inhibitors, thiorphan, bestatin and captopril (1 microM each) had no significant effect on tone or spontaneous activity of duodenal strips. In the presence of peptidase inhibitors, MEN 10,627 (1 microM) produced a relaxation of duodenal strips (72 +/- 6% of Emax to isoprenaline, n = 5), whilst GR 82,334 (10 microM, n = 6) had no significant effect. 6. The relaxant response to MEN 10,627 was preserved in mucosa-free strips not pre-exposed to capsaicin. Tetrodotoxin (1 microM), saxitoxin (1 microM), hexamethonium (100 microM) and omega-conotoxin (0.1 microM) had no significant effect on the resting tone of duodenal strips nor did they affect the relaxation to MEN 10,627. L-Nitroarginine (100 microM) increased the tone of the strips but did not affect the response to MEN 10,627. Nifedipine (1 microM) relaxed the strips by 62 +/- 4% (n = 4), but in its presence a small relaxant effect to MEN 10,627 (26 +/- 5%, n = 4) was still evident. 7. Under isotonic recording of mechanical activity along the longitudinal axis, MEN 10,627 (1 microM) produced a slowly developing relaxation (39 +/- 3% of Emax to isoprenaline; n = 6) of whole segments of rat duodenum. When similar experiments were performed on whole segments of rat proximal colon MEN 10,627 had no effect. 8. The present findings document the observation that tachykinin NK2 receptors contribute to the maintenance of resting tone of the rat isolated small intestine. We found no evidence to suggest that this effect follows the blockade of the contractile effect of spontaneously released endogenous tachykinins. The present findings raise the possibility that constitutively active NK2 receptors account for the relaxant effect produced by NK2 receptor ant PMID:8818352

Evidence that tachykinin NK2 receptors modulate resting tone in the rat isolated small intestine.

PubMed

Maggi, C A; Giuliani, S

1996-07-01

1. In the progress of experiments aimed at evaluating the role of tachykinins as enteric nonadrenergic noncholinergic (NANC) transmitters, we noted that certain tachykinin receptor antagonists produce a relaxation of circular muscle strips in the rat small intestine. This study aimed to assess the nature of this response and to determine the receptor type involved. The majority of the experiments were performed in capsaicin- (10 microM for 15 min) pretreated mucosa-free circular muscle strips from the rat small intestine, in the presence of atropine (1 microM), guanethidine (3 microM) and indomethacin (10 microM). 2. Under isometric recording of mechanical activity, the tachykinin NK1 receptor antagonist SR 140,333 (0.1 microM) had no effect on resting tone or spontaneous activity in duodenal or ileal circular muscle strips. The NK2 receptor antagonists, MEN 10,627 (0.1 microM) and GR 94,800 (0.1 microM) produced, after a delay of 10-15 min, a relaxation which averaged 61 +/- 3 and 57 +/- 6% (n = 6 and 4, respectively) of the maximal response (Emax) to isoprenaline (1 microM). The effect of maximal concentrations of MEN 10,627 and GR 94,800 when applied together was non-additive. The relaxant effect of MEN 10,627 (0.1 microM) was similar in the absence and presence of apamin (0.3 microM) and L-nitroarginine (100 microM). 3. Under isotonic recording of mechanical activity, MEN 10,627 (10 nM-1 microM) produced a concentration- and time-related relaxation of duodenal strips. The maximal relaxation averaged 72 +/- 4 and 69 +/- 4% (n = 5 each) of Emax to isoprenaline (1 microM) and was achieved 15-20 or 20-30 min after application of 1.0 or 0.1 microM MEN 10,627, respectively. 4. Duodenal strips were relaxed by other NK2 receptor selective antagonists (values in parentheses are % of Emax to isoprenaline at the given concentration of antagonist) GR 94,800 (69 +/- 3% at 1 microM, n = 4), SR 48,968 (60 +/- 3% at 1 microM, n = 4) and MDL 29,913 (66 +/- 4% at 1 microM, n = 4). SR 48,965 (1 microM), the inactive enantiomer of SR 48,968, was without effect. The NK1 receptor selective antagonists, SR 140,333 (0.1 microM), FK 888 (10 microM) RP 67,580 (1 microM) and GR 82,334 (10 microM) were also without effect (n = 4-5). 5. A cocktail of peptidase inhibitors, thiorphan, bestatin and captopril (1 microM each) had no significant effect on tone or spontaneous activity of duodenal strips. In the presence of peptidase inhibitors, MEN 10,627 (1 microM) produced a relaxation of duodenal strips (72 +/- 6% of Emax to isoprenaline, n = 5), whilst GR 82,334 (10 microM, n = 6) had no significant effect. 6. The relaxant response to MEN 10,627 was preserved in mucosa-free strips not pre-exposed to capsaicin. Tetrodotoxin (1 microM), saxitoxin (1 microM), hexamethonium (100 microM) and omega-conotoxin (0.1 microM) had no significant effect on the resting tone of duodenal strips nor did they affect the relaxation to MEN 10,627. L-Nitroarginine (100 microM) increased the tone of the strips but did not affect the response to MEN 10,627. Nifedipine (1 microM) relaxed the strips by 62 +/- 4% (n = 4), but in its presence a small relaxant effect to MEN 10,627 (26 +/- 5%, n = 4) was still evident. 7. Under isotonic recording of mechanical activity along the longitudinal axis, MEN 10,627 (1 microM) produced a slowly developing relaxation (39 +/- 3% of Emax to isoprenaline; n = 6) of whole segments of rat duodenum. When similar experiments were performed on whole segments of rat proximal colon MEN 10,627 had no effect. 8. The present findings document the observation that tachykinin NK2 receptors contribute to the maintenance of resting tone of the rat isolated small intestine. We found no evidence to suggest that this effect follows the blockade of the contractile effect of spontaneously released endogenous tachykinins. The present findings raise the possibility that constitutively active NK2 receptors account for the relaxant effect produced by NK2 receptor ant

Modeling of Particle Acceleration at Multiple Shocks Via Diffusive Shock Acceleration: Preliminary Results

NASA Technical Reports Server (NTRS)

Parker, Linda Neergaard; Zank, Gary P.

2013-01-01

We present preliminary results from a model that diffusively accelerates particles at multiple shocks. Our basic approach is related to box models (Protheroe and Stanev, 1998; Moraal and Axford, 1983; Ball and Kirk, 1992; Drury et al., 1999) in which a distribution of particles is diffusively accelerated inside the box while simultaneously experiencing decompression through adiabatic expansion and losses from the convection and diffusion of particles outside the box (Melrose and Pope, 1993; Zank et al., 2000). We adiabatically decompress the accelerated particle distribution between each shock by either the method explored in Melrose and Pope (1993) and Pope and Melrose (1994) or by the approach set forth in Zank et al. (2000) where we solve the transport equation by a method analogous to operator splitting. The second method incorporates the additional loss terms of convection and diffusion and allows for the use of a variable time between shocks. We use a maximum injection energy (Emax) appropriate for quasi-parallel and quasi-perpendicular shocks (Zank et al., 2000, 2006; Dosch and Shalchi, 2010) and provide a preliminary application of the diffusive acceleration of particles by multiple shocks with frequencies appropriate for solar maximum (i.e., a non-Markovian process).

Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with non-valvular atrial fibrillation: results from ROCKET AF.

PubMed

Girgis, I G; Patel, M R; Peters, G R; Moore, K T; Mahaffey, K W; Nessel, C C; Halperin, J L; Califf, R M; Fox, K A A; Becker, R C

2014-08-01

Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF. © 2014, The American College of Clinical Pharmacology.

Mechanical fatigue degradation of ceramics versus resin composites for dental restorations.

PubMed

Belli, Renan; Geinzer, Eva; Muschweck, Anna; Petschelt, Anselm; Lohbauer, Ulrich

2014-04-01

For posterior partial restorations an overlap of indication exists where either ceramic or resin-based composite materials can be successfully applied. The aim of this study was to compare the fatigue resistance of modern dental ceramic materials versus dental resin composites in order to address such conflicts. Bar specimens of five ceramic materials and resin composites were produced according to ISO 4049 and stored for 14 days in distilled water at 37°C. The following ceramic materials were selected for testing: a high-strength zirconium dioxide (e.max ZirCAD, Ivoclar), a machinable lithium disilicate (e.max CAD, Ivoclar), a pressable lithium disilicate ceramic (e-max Press, Ivoclar), a fluorapatite-based glass-ceramic (e.max Ceram, Ivoclar), and a machinable color-graded feldspathic porcelain (Trilux Forte, Vita). The composite materials selected were: an indirect machinable composite (Lava Ultimate, 3M ESPE) and four direct composites with varying filler nature (Clearfil Majesty Posterior, Kuraray; GrandioSO, Voco; Tetric EvoCeram, Ivoclar-Vivadent; and CeramX Duo, Dentsply). Fifteen specimens were tested in water for initial strength (σin) in 4-point bending. Using the same test set-up, the residual flexural fatigue strength (σff) was determined using the staircase approach after 10(4) cycles at 0.5 Hz (n=25). Weibull parameters σ0 and m were calculated for the σin specimens, whereas the σff and strength loss in percentage were obtained from the fatigue experiment. The zirconium oxide ceramic showed the highest σin and σff (768 and 440 MPa, respectively). Although both lithium disilicate ceramics were similar in the static test, the pressable version showed a significantly higher fatigue resistance after cyclic loading. Both the fluorapatite-based and the feldspathic porcelain showed equivalent initial and cyclic fatigue properties. From the composites, the highest filled direct material Clearfil Majesty Posterior showed superior fatigue performance. From all materials, e.max Press and Clearfil Majesty Posterior showed the lowest strength loss (29.6% and 32%, respectively), whereas the other materials lost between 41% and 62% of their flexural strength after cyclic loading. Dental ceramics and resin composite materials show equivalent fatigue strength degradation at loads around 0.5σin values. Apart from the zirconium oxide and the lithium disilicate ceramics, resin composites generally showed better σff after 10,000 cycles than the fluorapatite glass-ceramic and the feldspathic porcelain. Resin composite restorations may be used as an equivalent alternative to glass-rich-ceramic inlays regarding mechanical performance. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Hybrid model analysis of intra-aortic balloon pump performance as a function of ventricular and circulatory parameters.

PubMed

Ferrari, Gianfranco; Khir, Ashraf W; Fresiello, Libera; Di Molfetta, Arianna; Kozarski, Maciej

2011-09-01

We investigated the effects of the intra-aortic balloon pump (IABP) on endocardial viability ratio (EVR), cardiac output (CO), end-systolic (V(es)) and end-diastolic (V(ed)) ventricular volumes, total coronary blood flow (TCBF), and ventricular energetics (external work [EW], pressure-volume area [PVA]) under different ventricular (E(max) and diastolic stiffness) and circulatory (arterial compliance) parameters. We derived a hybrid model from a computational model, which is based on merging computational and hydraulic submodels. The lumped parameter computational submodel consists of left and right hearts and systemic, pulmonary, and coronary circulations. The hydraulic submodel includes part of the systemic arterial circulation, essentially a silicone rubber tube representing the aorta, which contains a 40-mL IAB. EVR, CO, V(es), and V(ed), TCBF and ventricular energetics (EW, PVA) were analyzed against the ranges of left ventricular E(max) (0.3-0.5-1 mm Hg/cm(3)) and diastolic stiffness V(stiffness) (≈0.08 and ≈0.3 mm Hg/cm(3), obtained by changing diastolic stiffness constant) and systemic arterial compliance (1.8-2.5 cm(3)/mm Hg). All experiments were performed comparing the selected variables before and during IABP assistance. Increasing E(maxl) from 0.5 to 2 mm Hg/cm(3) resulted in IABP assistance producing lower percentage changes in the selected variables. The changes in ventricular diastolic stiffness strongly influence both absolute value of EVR and its variations during IABP (71 and 65% for lower and higher arterial compliance, respectively). V(ed) and V(es) changes are rather small but higher for lower E(max) and higher V(stiffness). Lower E(max) and higher V(stiffness) resulted in higher TCBF and CO during IABP assistance (∼35 and 10%, respectively). The use of this hybrid model allows for testing real devices in realistic, stable, and repeatable circulatory conditions. Specifically, the presented results show that IABP performance is dependent, at least in part, on left ventricular filling, ejection characteristics, and arterial compliance. It is possible in this way to simulate patient-specific conditions and predict the IABP performance at different values of the circulatory or ventricular parameters. Further work is required to study the conditions for heart recovery modeling, baroreceptor controls, and physiological feedbacks. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Contractile effects of bradykinin on the isolated human small bronchus.

PubMed

Molimard, M; Martin, C A; Naline, E; Hirsch, A; Advenier, C

1994-01-01

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.

Mechanical properties and internal fit of 4 CAD-CAM block materials.

PubMed

Goujat, Alexis; Abouelleil, Hazem; Colon, Pierre; Jeannin, Christophe; Pradelle, Nelly; Seux, Dominique; Grosgogeat, Brigitte

2018-03-01

Recent polymer-based computer-assisted design and computer-assisted manufacturing (CAD-CAM) materials have been commercialized for inlay restorations, a polymer-infiltrated ceramic-network (PICN) and composite resin nanoceramics. Little independent evidence regarding their mechanical properties exists. Internal adaptation is an important factor for the clinical success and longevity of a restoration, and data concerning this parameter for inlays made with these blocks are scarce. The purpose of this in vitro study was to evaluate and compare the mechanical properties (flexural strength, flexural modulus, Vickers hardness, fracture toughness) and the internal adaptation of these recent polymer-based blocks with a lithium disilicate glass-ceramic block. The materials tested in this study were a PICN material (Vita Enamic), 2 composite resin nanoceramics (Lava Ultimate; 3M ESPE and Cerasmart; GCDental Products), and a lithium disilicate glass-ceramic (IPS e.max CAD). Mechanical properties were evaluated according to ISO norm DIS 6872:2013. Bar-shaped specimens (18×3×3 mm) were prepared and submitted to a 3-point bend test using a universal testing machine at a cross-head speed of 0.5 mm/min. In addition, identical cavities were prepared in 60 human mandibular extracted molars (n=15) and optically scanned to receive mesioocclusodistal inlays milled with the 4 materials tested in a CEREC Inlab milling machine. The replica technique and a stereomicroscope (×20) were used to measure the internal fit of the inlays at 9 preselected locations. All data were statistically analyzed using 1-way ANOVA and the post hoc Tukey multiple comparison or Games-Howell test (α=.05). The mean flexural strength of the tested blocks ranged from 148.7 ±9.5 MPa (Vita Enamic) to 216.5 ±28.3 MPa (Cerasmart). The mean flexural modulus ranged from 23.3 ±6.4 GPa (Vita Enamic) to 52.8 ±10.5 GPa (IPS e.max CAD). The mean Vickers hardness ranged from 0.66 ±0.02 GPa (Cerasmart) to 5.98 ±0.69 GPa (IPS e.max CAD). The mean fracture toughness ranged from 1.2 ±0.17 MPa.m 1/2 (Cerasmart) to 1.8 ±0.29 MPa.m 1/2 (IPS e.max CAD). The values for internal discrepancy ranged from 119 ±55 μm to 234 ±51 μm. The mean internal discrepancy was significantly higher for Lava Ultimate (P<.05) than IPS e.max CAD and Cerasmart but not for Vita Enamic. The factor ''material'' was statistically significant in relation to the mechanical properties evaluated in this study (P<.05). The Pearson correlation was negative between the flexural strength results and the internal discrepancy of the materials tested (R 2 =0.941; P<.05). The mechanical properties of the CAD-CAM block materials tested were within the acceptable range for fabrication of single restorations according to the ISO standard for ceramics (ISO 6872:2008). IPS e.max CAD and Cerasmart were observed to have superior flexural strength and better internal fit. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

The effect of isoenzyme-selective PDE inhibitors on methacholine-induced contraction of guinea-pig and rat ileum.

PubMed Central

Tomkinson, A.; Raeburn, D.

1996-01-01

1. We have examined the effects of the isoenzyme-selective phosphodiesterase (PDE) inhibitors, vinpocetine (type 1), siguazodan (type 3), rolipram (type 4) and zaprinast (type 5) and the non-selective PDE inhibitor enprofylline on methacholine (MCh) contractile concentration-response curves on guinea-pig and rat isolated ileum. 2. In guinea-pig ileum, vinpocetine (10-300 microM), zaprinast (1-300 microM) and enprofylline (100-1000 microM) produced a concentration-dependent depression of the maximum response (Emax) to MCh only without effect on the MCh EC50 values (rank order of potency: zaprinast > vinpocetine > enprofylline). In contrast, siguazodan (10-300 microM) and rolipram (10-300 microM) produced a rightward displacement of the MCh concentration-response curve (increase in EC50: rank order; rolipram > siguazodan), with effects on the MCh maximum seen only at higher concentrations. 3. In the rat ileum, vinpocetine (10-300 microM), zaprinast (0.1-300 microM) and enprofylline (100-1000 microM) caused depression of the MCh maximum contraction (rank order: zaprinast > vinpocetine > enprofylline). Low concentrations of rolipram and siguazodan had no significant effect on the MCh maximum. In the presence of higher concentrations (> 100 microM) of rolipram and siguazodan, a maximum response was not achieved at the highest concentration of MCh tested. As in the guinea-pig ileum, only rolipram (10-300 microM) and siguazodan (10-300 microM) produced a significant, concentration-dependent, rightward displacement of the MCh concentration-response curve (increase in EC50: rank order: rolipram > siguazodan). 4. In the guinea-pig ileum, isoprenaline (0.1 microM) produced a rightward displacement (approximately 3 fold) of the MCh concentration-response curve, accompanied by a significant depression of the maximum response. Increasing the isoprenaline concentration (1 microM) had no further effect on either parameter. Sodium nitroprusside (SNP, > or = 10 microM) produced a concentration-dependent depression of the MCh maximum without an effect on the EC50. 5. In the rat ileum, isoprenaline (1 microM) produced a concentration-dependent rightward displacement (approximately 2.8 fold) of the MCh concentration-response curve with depression of the MCh maximum at higher (> or = 100 microM) concentrations. SNP produced depression of the MCh maximum at a concentration of 10 microM and above. Effects on the MCh EC50 were seen only at 100 and 300 microM. 6. In guinea-pig ileum, isoprenaline (0.1 microM) in combination with rolipram (10 microM) further increased the MCh EC50 and reduced the MCh maximum. The combination of SNP (10 microM) with zaprinast (0.1 microM) produced no further significant effect than SNP alone. 7. In rat ileum, isoprenaline (1 microM) in combination with rolipram (10 microM) further increased the EC50 and reduced the maximum. SNP (10 microM) had no significant effect on either the MCh maximum or EC50. A combination with zaprinast (1 microM) had no further effect. 8. In conclusion, all the PDE inhibitors tested produced a concentration-dependent inhibition of the MCh concentration-response curve, indicating a modulator role for the PDE isoenzymes in gastrointestinal smooth muscle contractility. The PDE inhibitors that elevate cyclic GMP produced a depression of the MCh maximum response only, whilst those that elevate cyclic AMP produced a rightward displacement of the MCh concentration-response curve. This was confirmed by the use of isoprenaline and SNP. This difference in the type of inhibition produced by these PDE isoenzyme inhibitors may reflect a different intracellular site/mechanism by which the cyclic AMP- and cyclic GMP-activated kinases act functionally to antagonize the contractile response. PMID:8864552

Influence of biophase distribution and P-glycoprotein interaction on pharmacokinetic-pharmacodynamic modelling of the effects of morphine on the EEG

PubMed Central

Groenendaal, D; Freijer, J; de Mik, D; Bouw, M R; Danhof, M; de Lange, E C M

2007-01-01

Background and purpose: The aim was to investigate the influence of biophase distribution including P-glycoprotein (Pgp) function on the pharmacokinetic-pharmacodynamic correlations of morphine's actions in rat brain. Experimental approach: Male rats received a 10-min infusion of morphine as 4 mg kg−1, combined with a continuous infusion of the Pgp inhibitor GF120918 or vehicle, 10 or 40 mg kg−1. EEG signals were recorded continuously and blood samples were collected. Key results: Profound hysteresis was observed between morphine blood concentrations and effects on the EEG. Only the termination of the EEG effect was influenced by GF120918. Biophase distribution was best described with an extended catenary biophase distribution model, with a sequential transfer and effect compartment. The rate constant for transport through the transfer compartment (k1e) was 0.038 min−1, being unaffected by GF120918. In contrast, the rate constant for the loss from the effect compartment (keo) decreased 60% after GF120918. The EEG effect was directly related to concentrations in the effect compartment using the sigmoidal Emax model. The values of the pharmacodynamic parameters E0, Emax, EC50 and Hill factor were 45.0 μV, 44.5 μV, 451 ng ml−1 and 2.3, respectively. Conclusions and implications: The effects of GF120918 on the distribution kinetics of morphine in the effect compartment were consistent with the distribution in brain extracellular fluid (ECF) as estimated by intracerebral microdialysis. However, the time-course of morphine concentrations at the site of action in the brain, as deduced from the biophase model, is distinctly different from the brain ECF concentrations. PMID:17471181

Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

PubMed Central

da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

2016-01-01

Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

Pharmacokinetic/pharmacodynamic modeling of psychomotor impairment induced by oral clonazepam in healthy volunteers.

PubMed

dos Santos, Fábio Monteiro; Gonçalves, José Carlos Saraiva; Caminha, Ricardo; da Silveira, Gabriel Estolano; Neves, Claúdia Silvana de Miranda; Gram, Karla Regina da Silva; Ferreira, Carla Teixeira; Jacqmin, Philippe; Noël, François

2009-10-01

This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 +/- 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.

Effects of fenoterol on beta-adrenoceptor and muscarinic M2 receptor function in bovine tracheal smooth muscle.

PubMed

De Vries, B; Roffel, A F; Kooistra, J M; Meurs, H; Zaagsma, J

2001-05-11

Prolonged (18 h) incubation of isolated bovine tracheal smooth muscle with the beta2-adrenoceptor agonist fenoterol (10 microM) induced desensitization of isoprenaline-induced adenylyl cyclase activity in bovine tracheal smooth muscle membranes, characterized by a 25% decrease in maximal effect (Emax) (P < 0.05), while the sensitivity to the agonist (pEC50) was unchanged. The Emax value of isoprenaline-induced smooth muscle relaxation of submaximal methacholine-induced contractile tones was similarly reduced by about 25% (P < 0.001), while the pEC50 value was diminished by 1.0 log unit (P < 0.001). As determined by 30 microM gallamine-induced muscarinic M2 receptor antagonism and pertussis toxin-induced inactivation of G(i alpha), muscarinic M2 receptor-mediated functional antagonism did not play a role in isoprenaline-induced relaxation of bovine tracheal smooth muscle contracted by methacholine, both in control and in 18-h fenoterol-treated tissue. In line with these observations, we found no enhanced muscarinic M2 receptor-mediated inhibition of 1 microM forskolin-stimulated adenylyl cyclase activity after 18-h fenoterol treatment. These data indicate that 18-h fenoterol treatment of bovine tracheal smooth muscle induces beta2-adrenoceptor desensitization and reduced functional antagonism of methacholine-induced contraction by beta-adrenoceptor agonists, without a change of muscarinic M2 receptor function.

Effect of Home Bleaching on the Translucency of CAD/CAM Systems.

PubMed

Karci, Muhammet; Demir, Necla

2017-11-10

To evaluate the effect of a home bleaching agent (Opalescence PF) on the translucency of CAD/CAM ceramic systems. The 28 sintered ceramic specimens (IPS Empress CAD and IPS e.max CAD; 15 mm long, 10 mm wide, 1 mm thick) were divided into two subgroups as control and bleaching groups (n = 7). Carbamide peroxide (CP), 16%, home bleaching agent was applied onto the surface of each specimen for 6 hours per day for 7 days. A spectrophotometer (VITA Easyshade Advance) was used to measure the CIE L * a * b * coordinates and the reflectance value (Y) of the specimens on white and black backgrounds. The translucency parameter (TP), contrast ratio (CR), and opalescence parameter (OP) of the specimens were calculated. The data were statistically analyzed using Kolmogorov-Smirnov, one-way ANOVA, Tukey's test, and Pearson's correlation. Statistically significant differences in the TP values after 16% CP bleaching treatment were observed (p ˂ 0.05); however, no significant differences were found in the OP and CR values after the surface treatment (p ˃ 0.05). According to our study, patients who have all-ceramic restorations in their mouths should be careful when using home bleaching agents, because whitening agents can affect the translucency of all-ceramic restorations such as e.max CAD and Empress CAD. © 2017 by the American College of Prosthodontists.

A Biomathematical Model of the Restoring Effects of Caffeine on Cognitive Performance During Sleep Deprivation

DTIC Science & Technology

2013-01-01

following inhibitory Emax model to formulate the PD effect: gPD tð Þ ¼ 1 gPK ðtÞ gPK50 þgPK ðtÞ , ð3Þ where gPK (t) denotes the concentration of caffeine...the maximal effect is observed when gPK is infinitely large, i.e., when gPD approaches zero. Also, the baseline effect, i.e., the effect in the absence... gPK (t) at discrete- time index t, with t¼1, 2, y, for an orally administered caffeine dose given at time index t0 can be expressed by the following

Pharmacokinetics, pharmacodynamics and the pharmacokinetic/ pharmacodynamic relationship of zolpidem in healthy subjects.

PubMed

de Haas, S L; Schoemaker, R C; van Gerven, J M A; Hoever, P; Cohen, A F; Dingemanse, J

2010-11-01

Zolpidem is one of the most frequently prescribed hypnotics, as it is a very short-acting compound with relatively few side effects. Zolpidem's short duration of action is partly related to its short elimination half-life, but the associations between plasma levels and pharmacodynamic (PD) effects are not precisely known. In this study, the concentration-effect relationships for zolpidem were modelled. Zolpidem (10 mg) was administered in a double-blind, randomised, placebo-controlled trial to determine PD and pharmacokinetics (PK) in 14 healthy volunteers. Zolpidem was absorbed and eliminated quickly, with a median T(max) of 0.78 h (range: 0.33-2.50) and t(1/2) of 2.2 h. Zolpidem reduced saccadic peak velocity (SPV), adaptive tracking performance, electroencephalogram (EEG) alpha power and visual analogue scale (VAS) alertness score and increased body sway, EEG beta power and VAS 'feeling high'. Short- and long-term memory was not affected. Central nervous system effects normalised more rapidly than the decrease of plasma concentrations. For most effects, zolpidem's short duration of action could be adequately described by both a sigmoid E(max) model and a transit tolerance model. For SPV and EEG alpha power, the tolerance model seemed less suitable. These PK/PD models have different implications for the mechanism underlying zolpidem's short duration of action. A sigmoid E(max) model (which is based on ligand binding theory) would imply a threshold value for the drug's effective concentrations. A transit tolerance model (in which a hypothetical factor builds up with time that antagonises the effects of the parent compound) is compatible with a rapid reversible desensitisation of GABAergic subunits.

Comparison of 3D and 2D shear-wave elastography for differentiating benign and malignant breast masses: focus on the diagnostic performance.

PubMed

Choi, H Y; Sohn, Y-M; Seo, M

2017-10-01

To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy. Histopathological findings were regarded as the reference standard. The diagnostic performance of each data set was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) analysis to compare sensitivity and specificity. Among 205 lesions, 105 (51.22%) were malignant and 100 (48.78%) were benign. Compared to benign masses, malignant masses had higher values of Emax and Emean on both 2D and 3D SWE, the differences of which were statistically significant (p<0.001). The AUCs of 2D, 3D axial, and sagittal SWE were significantly higher than that of 3D coronal SWE (p<0.05). In addition, the sensitivities of axial, sagittal, and coronal 3D SWE were all higher than that of 2D SWE for Emean (81.9%, 87.6%, and 89.5% versus 70.5%, respectively, p<0.05). Conversely, the specificity of 2D and 3D axial SWE was higher than that of 3D sagittal and coronal SWE (Emax, 84%, 83% versus 76%, 73%; Emean, 85%, 81% versus 68%, 50%, respectively, p<0.05). We also assessed changes in Breast Imaging-Reporting and Data System (BI-RADS) category 3 and category 4a lesions by adding each of the parameters for 2D and 3D SWE in B-mode US. The specificity, PPV, and accuracy of combined 2D or combined 3D SWE with B-mode US was statistically higher than that of B-mode US alone for differentiating benign and malignant lesions (p<0.05). Among SWE images, 2D SWE, and 3D SWE axial and sagittal images exhibited superior diagnostic performance compared to 3D coronal images. Addition of 3D SWE images to B-mode US improved the diagnostic performance for distinguishing benign from malignant masses. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

CHBPR: Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats: role of PDE1

PubMed Central

Giachini, Fernanda R.; Lima, Victor V.; Carneiro, Fernando S.; Tostes, Rita C.; Webb, R. Clinton

2011-01-01

Recent evidence suggests that angiotensin II (Ang II) upregulates phosphodiesterase (PDE)-1A expression. We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic cyclic guanosine 3', 5'-monophosphate (cGMP), contributing to increased vascular contractility. Male Sprague-Dawley rats received mini-osmotic pumps with Ang II (60 ng.min−1) or saline for 14 days. PE-induced contractions were increased in aorta (Emax168±8 vs. 136±4%) and small-mesenteric arteries [(SMA), Emax170±6 vs. 143±3%] from Ang II infused rats compared to control. PDE1 inhibition with vinpocetine (10µM) reduced PE-induced contraction in aortas from Ang II rats (Emax94±12%) but not in control (154±7%). Vinpocetine decreased the sensitivity to PE in SMA from Ang II rats compared to vehicle (pD2 5.1±0.1 vs. 5.9±0.06), but not in control (6.0±0.03 vs. 6.1±0.04). Sildenafil (10µM), a PDE5 inhibitor reduced PE-induced maximal contraction similarly in Ang II and control rats. Arteries were contracted with PE (1µM) and concentration-dependent relaxation to vinpocetine and sildenafil was evaluated. Aortas from Ang II rats displayed increased relaxation to vinpocetine compared to control (Emax82±12 vs. 44±5%). SMA from Ang II rats showed greater sensitivity during vinpocetine-induced relaxation, compared to control (pD2 6.1±0.3 vs. 5.3±0.1). No differences in sildenafil-induced relaxation were observed. PDE1A and PDE1C expressions in aorta and PDE1A expression in SMA were increased in Ang II rats. cGMP production, which is decreased in arteries from Ang II rats, was restored after PDE1 blockade. We conclude that PDE1 activation reduces cGMP bioavailability in arteries from ANG II, contributing to increased contractile responsiveness. PMID:21282562

Light curing through glass ceramics with a second- and a third-generation LED curing unit: effect of curing mode on the degree of conversion of dual-curing resin cements.

PubMed

Flury, Simon; Lussi, Adrian; Hickel, Reinhard; Ilie, Nicoleta

2013-12-01

The aim of this study was to measure the degree of conversion (DC) of five dual-curing resin cements after different curing modes with a second- and a third-generation light-emitting diode (LED) curing unit. Additionally, irradiance of both light curing units was measured at increasing distances and through discs of two glass ceramics for computer-aided design/manufacturing (CAD/CAM). Irradiance and spectra of the Elipar FreeLight 2 (Standard Mode (SM)) and of the VALO light curing unit (High Power Mode (HPM) and Xtra Power Mode (XPM)) were measured with a MARC radiometer. Irradiance was measured at increasing distances (control) and through discs (1.5 to 6 mm thickness) of IPS Empress CAD and IPS e.max CAD. DC of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA was measured with an attenuated total reflectance-Fourier transform infrared spectrometer when self-cured (negative control) or light cured in SM for 40 s, HPM for 32 s, or XPM for 18 s. Light curing was performed directly (positive control) or through discs of either 1.5- or 3-mm thickness of IPS Empress CAD or IPS e.max CAD. DC was analysed with Kruskal-Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). Maximum irradiances were 1,545 mW/cm(2) (SM), 2,179 mW/cm(2) (HPM), and 4,156 mW/cm(2) (XPM), and all irradiances decreased by >80 % through discs of 1.5 mm, ≥95 % through 3 mm, and up to >99 % through 6 mm. Generally, self-curing resulted in the lowest DC. For some cements, direct light curing did not result in higher DC compared to when light cured through ceramic discs. For other cements, light curing through ceramic discs of 3 mm generally reduced DC. Light curing was favourable for dual-curing cements. Some cements were more susceptible to variations in curing mode than others. When light curing a given cement, the higher irradiances of the third-generation LED curing unit resulted in similar DC compared to the second-generation one, though at shorter light curing times.

Tracheal relaxation of five medicinal plants used in Mexico for the treatment of several diseases.

PubMed

Sánchez-Recillas, Amanda; Mantecón-Reyes, Paul; Castillo-España, Patricia; Villalobos-Molina, Rafael; Ibarra-Barajas, Maximiliano; Estrada-Soto, Samuel

2014-03-01

To assess the relaxant effect of several organic extracts obtained from Agastache mexicana (A. mexicana), Cochlospermum vitifolium (C. vitifolium), Cordia morelosana (C. morelosana), Lepechinia caulescens (L. caulescens) and Talauma mexicana (T. mexicana) used in Mexican traditional medicine for the treatment of several diseases. Extracts were obtained by maceration at room temperature using hexane, dichloromethane and methanol for each plant material. The organic extracts were evaluated ex vivo to determine their relaxant activity on the contractions induced by carbachol (cholinergic receptor agonist, 1 μ mol/L) in isolated rat tracheal rings. A total of 15 extracts were evaluated (three for each species). All test samples showed significant relaxant effect, in a concentration-dependent manner, on the contractions induced by 1 μ mol/L carbachol, with exception of extracts from C. morelosana. Active extracts were less potent than theophylline [phosphodiesterase inhibitor, EC50: (28.79±0.82) μg/mL] that was used as positive control. Concentration-response curves revealed that the extracts with more significant effects were dichloromethanic extracts of T. mexicana [Emax: (103.03±3.32)% and EC50: (159.39±3.72) μg/mL) and C. vitifolium [Emax: (106.58±2.42)% and EC50: (219.54±7.61) μg/mL]. Finally, hexanic and dichloromethanic extracts from A. mexicana were fully effective but less potent than T. mexicana and C. vitifolium. Less polar extracts obtained from A. mexicana, T. mexicana and C. vitifolium exhibited greater relaxant effect on tracheal rat rings, which allows us to suggest them as sources for the isolation of bioactive molecules with potential therapeutic value in the treatment of asthma. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Stress distribution difference between Lava Ultimate full crowns and IPS e.max CAD full crowns on a natural tooth and on tooth-shaped implant abutments.

PubMed

Krejci, Ivo; Daher, René

2017-04-01

The goal of this short communication is to present finite element analysis comparison of the stress distribution between CAD/CAM full crowns made of Lava Ultimate and of IPS e.max CAD, adhesively luted to natural teeth and to implant abutments with the shape of natural teeth. Six 3D models were prepared using a 3D content-creating software, based on a micro-CT scan of a human mandibular molar. The geometry of the full crown and of the abutment was the same for all models representing Lava Ultimate full crowns (L) and IPS e.max CAD full crowns (E) on three different abutments: prepared natural tooth (n), titanium abutment (t) and zirconia abutment (z). A static load of 400 N was applied on the vestibular and lingual cusps, and fixtures were applied to the base of the models. After running the static linear analysis, the post-processing data we analyzed. The stress values at the interface between the crown and the abutment of the Lt and Lz groups were significantly higher than the stress values at the same interface of all the other models. The high stress concentration in the adhesive at the interface between the crown and the abutment of the Lava Ultimate group on implants might be one of the factors contributing to the reported debondings of crowns.

Masking properties of ceramics for veneer restorations.

PubMed

Skyllouriotis, Andreas L; Yamamoto, Hideo L; Nathanson, Dan

2017-10-01

The translucency and opacity of ceramics play a significant role in emulating the natural color of teeth, but studies of the masking properties and limitations of dental ceramics when used as monolayer restorations are lacking. The purpose of this in vitro study was to determine the translucency of 6 materials used for veneer restorations by assessing their translucency parameters (TPs), contrast ratios (CRs), and potential to mask dark tooth colors. Ten square- or disk-shaped specimens (0.5-mm thickness, shade A2) were fabricated from Vitablocks Mark II (VMII; Vita Zahnfabrik), IPS e.max CAD LT (EMXC LT; Ivoclar Vivadent AG), IPS e.max CAD HT (EMXC HT; Ivoclar Vivadent AG), IPS Empress CAD LT (EMP LT; Ivoclar Vivadent AG), IPS e.max Press LT (EMXP LT; Ivoclar Vivadent AG), and CZR (CZR; Kuraray Noritake Dental Inc). Their luminance (Y) values over black and over white tiles were measured, followed by their color (CIELab) over black tiles and white tiles and shaded A2 (control group), A3.5, A4, and B4 acrylic resin blocks. All measurements were performed using a spectrophotometer in 2 different areas on each specimen. Then CRs, TPs, and color differences (over shaded backgrounds) were determined. Data were subjected to 1-way and 2-way ANOVA (α=.05) for analysis. Mean CR values of EMXP LT were significantly higher than those of the other tested materials, whereas VMII and EMXC HT had the lowest values (P<.001). Mean TP values over black and over white backgrounds of VMII and EMXC HT were significantly higher than those of the other tested materials, while EMXP LT and EMXC LT revealed the lowest values (P<.001). Background shade A4 displayed the highest mean effect (expressed in ΔE* values) on the color of the ceramic materials, whereas shade B4 demonstrated the lowest mean background effect (P<.001). Significant differences in translucency among the tested ceramics were revealed (P<.001). The EMXC LT and EMXP LT groups were the least translucent under the conditions of this study (P<.001). All tested ceramics exhibited poor masking properties against the A4 background. The color differences of most tested ceramics were more acceptable when tested against the B4 background (ΔE*≤3.3). Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Changes in the response to excitatory antagonists, agonists, and spasmolytic agents in circular colonic smooth muscle strips from patients with diverticulosis.

PubMed

Alvarez-Berdugo, D; Espín, F; Arenas, C; López, I; Clavé, P; Gallego, D

2015-11-01

Colonic samples from asymptomatic diverticulosis (DS) patients presented enhanced electrical field stimulation (EFS)-contractions, in an earlier study of ours, suggesting increased endogenous responses. The aim of this study was to explore changes in excitatory neuromuscular transmission and to assess the pharmacodynamics of spasmolytic agents in DS. Circular muscle strips from sigmoid colon of DS patients (n = 30; 69.5 ± 14.8 years) and controls (n = 32; 64.7 ± 16.2 years) were studied using organ baths to evaluate the direct effect of excitatory agonists (carbachol, neurokinin A [NKA] and substance P [SP]), and the effect of antagonists (atropine and NK2 antagonist GR94800) and spasmolytic drugs (otilonium bromide [OB] and N-butyl-hyoscine) on the contractions induced by EFS-stimulation of excitatory motorneurons. qRT-PCR was also performed to compare mRNA expression of M2 , M3 , NK2 receptors and L-type calcium channels. Contractions to carbachol (Emax : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS; p < 0.0005) and NKA (Emax : 387.8 ± 35.6% vs 1102.0 ± 190.1%; p < 0.0005) were higher in DS group, without differences for SP. Higher potency for DS patients was observed in the concentration-response curves for atropine (pIC50  = 8.56 ± 0.15 control vs pIC50  = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR94800 (pIC50  = 7.21 ± 0.18 control vs pIC50  = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency (pIC50 ) was observed for spasmolytic drugs in DS, whereas no differences were found regarding the relative expression of the receptors evaluated between groups. The greater response to cholinergic and tachykinergic agonists and greater potency for muscarinic and NK2 antagonists observed in DS might play a role in the spasticity found in diverticular disease. © 2015 John Wiley & Sons Ltd.

Effect of metal opaquer on the final color of 3 ceramic crown types on 3 abutment configurations.

PubMed

Arif, Rabia; Yilmaz, Burak; Mortazavi, Aras; Ozcelik, Tuncer B; Johnston, William M

2018-04-30

The effect of a recently introduced metal opaquer when used to mask the color of a titanium abutment under ceramic crown systems is unknown. The purpose of this study was to compare the color coordinates of 3 ceramic crown types-characterized monolithic lithium disilicate (LDC) (IPS e.max; Ivoclar Vivadent AG), layered lithium disilicate (LDL) (IPS e.max; Ivoclar Vivadent AG), and layered zirconia (ZL) (H.C. Starck)-on 3 abutment configurations, nonopaqued titanium (Ti), resin opaqued titanium (Op), and zirconia (Zir). In addition, the color differences (CIEDE2000) were evaluated among the 3 crown types on 3 different abutment substrates. Ten Ti disks (10×1 mm) were fabricated with computer-aided design and computer-aided manufacturing (CAD-CAM) to represent the Ti abutments. Five Ti specimens were opaqued (Op) (whiteMetal Opaquer wMO; Blue Sky Bio), and 5 were not opaqued (Ti). Ten zirconia disks were fabricated with CAD-CAM and sintered (10×1.2 mm). Five disks were used as backings to represent Zir abutments, and 5 disks were layered with 1 mm of porcelain (B1, IPS e.Max Ceram; Ivoclar Vivadent AG) to represent layered zirconia crowns (ZL). Ten lithium disilicate plates (14×14×1.2 mm) were sectioned from CAD blocks (B1 IPS e.Max CAD; Ivoclar Vivadent AG). Five plates were layered with the same porcelain (B1, 1 mm), and 5 plates were surface characterized and glazed. An LDL crown on a Zir abutment configuration was used as the control. The 3 simulated crown types (n=5) were optically connected to each of the 3 abutment types, and the color of the 9 groups was measured using a spectroradiometer. Measured data were reported in CIELab coordinates. CIELab data were used to calculate color differences between the control and the 8 experimental groups. Color data were summarized for each group, and analyzed by repeated-measures ANOVA. For pairwise comparisons, a Bonferroni correction of t tests was used, and for interpretive analysis of resulting color difference data, a 1-way ANOVA and subsequent Tukey testing for pairwise comparisons were used. The statistical significance of the analysis of color coordinates was found to be P≤.002. Although 3-way interaction was not found to be significant (P=.335), all three 2-way interactions of the main effects were found to be significant (P≤.002). All crown types on the Zir abutment revealed color differences from the control group. The color differences of the crown types on the Op and Zir abutment configurations compared with the control (LDL/Zir) were not (P>.05) statistically different. Colors of tested crown systems on Ti backing were each unacceptably different from the control group. Colors of these systems on zirconia backing were not perceivably different. Use of opaquer on titanium backing resulted in a small color difference from the control group (P>.05) for each crown system, demonstrating that it may be used to prevent the unfavorable metal show-through that can influence the final color of all ceramic crown systems tested. Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

[Esthetic restoration for anterior teeth with the hot pressed porcelain laminate veneers].

PubMed

Xu, Shao-ping; Luo, Xiao-ping; Shi, Yu-juan

2012-10-01

To evaluate the esthetic effect of anterior porcelain veneers fabricated with the heat pressed glass ceramic. Thirty-two patients, who wanted to receive a aesthetic restorative treatment for 206 anterior teeth were selected. Among them, 20 were for dental fluorosis, 8 were for light tetracycline stained teeth, the other 4 were labial enamel hypoplasia or obvious crack on the surface of enamel. According to the color of adjacent teeth,skin and lips, heat pressed IPS e.max ingots of different color were chosen to mold the restorations. Afterwards, special straining technique was conducted on the marginal ridge and incisor ridge of the veneers after carefully trimmed in the mouth. Restorations were them bonded with Variolink II resin cement. After 7 years of follow-up, a modified USPHS criterion was used to evaluate the esthetic effect. The translucency of veneers was superior. Marginal integrity of the veneers was perfect and it docked well with the marginal terminate line of the abutment. There was no edge coloring after the veneers were used for 7 years, and the veneers produce an excellent chameleon effect by absorbing the color of adjacent teeth and gums, at the same time, veneers could produce a feature of surface morphology of natural enamel after careful carve. In the long-term clinical observation, 5 of the 206 veneers were fractured or fell off. This porcelain laminate veneers fabricated from the heat pressed IPS e.max Press ingots include the following advantages, such as simple operating procedure, high mechanical strength, very little dental tissue was ground off and nice aesthetic effect. Ultra-thin veneers are especially suitable for aesthetic practice to dental fluorosis, light tetracycline and natural worn teeth.

Arachidonic acid metabolites follow the preferential course of cyclooxygenase pathway for the basal tone in the internal anal sphincter.

PubMed

de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

2009-04-01

Present studies determined the roles of the cyclooxygenase (COX) versus the lipoxygenase (LO) pathways in the metabolic pathway of arachidonic acid (AA) in the internal anal sphincter (IAS) tone. Studies were performed in the rat IAS versus the nontonic rectal smooth muscle (RSM). Indomethacin, the dual COX inhibitor, but not nordihydroguaiaretic acid (NDGA), the LO inhibitor, produced a precipitous decrease in the IAS tone. However, when added in the background of indomethacin, NDGA caused significant reversal of the IAS tone. These inhibitors had no significant effect on the RSM. To follow the significance of COX versus LO pathways, we examined the effects of AA and its metabolites. In the IAS, AA caused an increase in the IAS tone (Emax=38.8+/-3.0% and pEC50=3.4+/-0.1). In the RSM, AA was significantly less efficacious and potent (Emax=11.3+/-3.5% and pEC50=2.2+/-0.3). The AA metabolites (via COXs) PGF2alpha and U-46619 (a stable analog of thromboxane A2) produced increases in the IAS tone and force in the RSM. Conversely, AA metabolites (via 5-LO) lipoxin A4, 5-HETE, and leukotriene C4 decreased the IAS tone. Finally, the contractile effects of AA in the IAS were selectively attenuated by the COX-1 but not the COX-2 inhibitor. Collectively, the specific effects of AA and the COX inhibitor, the Western blot and RT-PCR analyses showing specifically higher levels of COX-1, suggest a preferential role of the COX (specifically COX-1) pathway versus the LO in the regulation of the IAS tone.

Pharmacodynamics of Imipenem in Combination with β-Lactamase Inhibitor MK7655 in a Murine Thigh Model

PubMed Central

Mavridou, Eleftheria; Melchers, Ria J. B.; van Mil, Anita C. H. A. M.; Mangin, E.; Motyl, Mary R.

2014-01-01

MK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed against several beta-lactamase producing Pseudomonas aeruginosa and Klebsiella pneumoniae strains to determine its effect in vitro and in vivo. Neutropenic mice were infected in each thigh 2 h before treatment with an inoculum of approximately 5 × 106 CFU. They were treated with IMP/C alone (every 2 hours [q2h], various doses) or in combination with MK7655 in either a dose fractionation study or q2h for 24 h and sacrificed for CFU determinations. IMP/MK7655 decreased MICs regarding IMP MIC. The PK profiles of IMP/C and MK7655 were linear over the dosing range studied and comparable with volumes of distribution (V) of 0.434 and 0.544 liter/kg and half-lives (t1/2) of 0.24 and 0.25 h, respectively. Protein binding of MK7655 was 20%. A sigmoidal maximum effect (Emax) model was fit to the PK/PD index responses. The effect of the inhibitor was not related to the maximum concentration of drug in serum (Cmax)/MIC, and model fits for T>MIC and area under the concentration-time curve (AUC)/MIC were comparable (R2 of 0.7 and 0.75), but there appeared to be no significant relationship of effect with dose frequency. Escalating doses of MK7655 and IMP/C showed that the AUC of MK7655 required for a static effect was dependent on the dose of IMP/C and the MIC of the strain, with a mean area under the concentration-time curve for the free, unbound fraction of the drug (fAUC) of 26.0 mg · h/liter. MK7655 shows significant activity in vivo and results in efficacy of IMP/C in otherwise resistant strains. The exposure-response relationships found can serve as a basis for establishing dosing regimens in humans. PMID:25403667

The fracture load and failure types of veneered anterior zirconia crowns: an analysis of normal and Weibull distribution of complete and censored data.

PubMed

Stawarczyk, Bogna; Ozcan, Mutlu; Hämmerle, Christoph H F; Roos, Malgorzata

2012-05-01

The aim of this study was to compare the fracture load of veneered anterior zirconia crowns using normal and Weibull distribution of complete and censored data. Standardized zirconia frameworks for maxillary canines were milled using a CAD/CAM system and randomly divided into 3 groups (N=90, n=30 per group). They were veneered with three veneering ceramics, namely GC Initial ZR, Vita VM9, IPS e.max Ceram using layering technique. The crowns were cemented with glass ionomer cement on metal abutments. The specimens were then loaded to fracture (1 mm/min) in a Universal Testing Machine. The data were analyzed using classical method (normal data distribution (μ, σ); Levene test and one-way ANOVA) and according to the Weibull statistics (s, m). In addition, fracture load results were analyzed depending on complete and censored failure types (only chipping vs. total fracture together with chipping). When computed with complete data, significantly higher mean fracture loads (N) were observed for GC Initial ZR (μ=978, σ=157; s=1043, m=7.2) and VITA VM9 (μ=1074, σ=179; s=1139; m=7.8) than that of IPS e.max Ceram (μ=798, σ=174; s=859, m=5.8) (p<0.05) by classical and Weibull statistics, respectively. When the data were censored for only total fracture, IPS e.max Ceram presented the lowest fracture load for chipping with both classical distribution (μ=790, σ=160) and Weibull statistics (s=836, m=6.5). When total fracture with chipping (classical distribution) was considered as failure, IPS e.max Ceram did not show significant fracture load for total fracture (μ=1054, σ=110) compared to other groups (GC Initial ZR: μ=1039, σ=152, VITA VM9: μ=1170, σ=166). According to Weibull distributed data, VITA VM9 showed significantly higher fracture load (s=1228, m=9.4) than those of other groups. Both classical distribution and Weibull statistics for complete data yielded similar outcomes. Censored data analysis of all ceramic systems based on failure types is essential and brings additional information regarding the susceptibility to chipping or total fracture. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Fit of lithium disilicate crowns fabricated from conventional and digital impressions assessed with micro-CT.

PubMed

Kim, Jae-Hyun; Jeong, Ji-Hye; Lee, Jin-Han; Cho, Hye-Won

2016-10-01

Although the number of lithium disilicate crowns fabricated with computer-aided design and computer-aided manufacturing (CAD-CAM) technology has increased, the accuracy of the prostheses produced by using digital pathways remains unknown. The purpose of this in vitro study was to compare marginal and internal discrepancies of lithium disilicate crowns fabricated from digital and conventional impressions. A typodont mandibular first molar was prepared for a lithium disilicate crown, and 20 duplicate dies were fabricated by milling poly(methyl methacrylate) resin blocks from laboratory scans. Four groups of 5 lithium disilicate crowns each were created by using a CS3500 (Carestream Dental) intraoral digital impression; Trios (3shape) intraoral digital impression; Ceramill Map400 (Amann Girrbach) extraoral digital impression; and a heat-press technique as a control group. All of the IPS e.max CAD (Ivoclar Vivadent AG) crowns were produced using a 5-axis milling engine (Ceramill Motion2). The lithium disilicate crowns were cemented with zinc phosphate cement under finger pressure. Marginal and internal discrepancies were measured using micro-computed tomography (SkyScan1172). One-way ANOVAs with the Tukey honest significant differences test were used for statistical analysis of the data (α=.05). The mean marginal discrepancies of CS3500 lithium disilicate crowns were 129.6 μm, 200.9 μm for Ceramill Map400, and 207.8 μm 176.1 μm for the heat-press technique; and the internal discrepancy volumes for CS3500 were 25.3 mm 3 , 40.7 mm 3 for Trios, 29.1 mm 3 for Ceramill Map400, and 29.1 and 31.4 mm 3 for the heat-press technique. The CS3500 group showed a significantly better marginal discrepancy than the other 3 groups and a smaller internal discrepancy volume than the Trios group (P<.05). Significant differences were found between IPS e.max CAD crowns produced using 2 intraoral digital impressions, whereas no differences were found between IPS e.max CAD crowns produced from an extraoral digital impression and IPS e.max Press crowns produced using a heat-press technique. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes

PubMed Central

Guo, Chunna; Liao, Xiaoping; Wang, Mingru; Wang, Feng; Yan, Chaoqun; Xiao, Xia; Sun, Jiang

2015-01-01

Streptococcus suis serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as S. suis. This study evaluated the in vitro and in vivo antimicrobial activities of CEQ against four strains of S. suis serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (106 to 108 CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (Emax) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%ƒT>MIC) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (R2 = 91% and R2 = 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (P = 0.006) and a 2-fold exposure time (P = 0.01) were required for a 1-log kill using large inocula of 108 CFU/thigh. PMID:26666923

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

PubMed

de Souza, Bruno Palmieri; da Silva, Edilson Dantas; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito

2014-09-05

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and β-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling of Particle Acceleration at Multiple Shocks Via Diffusive Shock Acceleration: Preliminary Results

NASA Astrophysics Data System (ADS)

Parker, L. N.; Zank, G. P.

2013-12-01

Successful forecasting of energetic particle events in space weather models require algorithms for correctly predicting the spectrum of ions accelerated from a background population of charged particles. We present preliminary results from a model that diffusively accelerates particles at multiple shocks. Our basic approach is related to box models (Protheroe and Stanev, 1998; Moraal and Axford, 1983; Ball and Kirk, 1992; Drury et al., 1999) in which a distribution of particles is diffusively accelerated inside the box while simultaneously experiencing decompression through adiabatic expansion and losses from the convection and diffusion of particles outside the box (Melrose and Pope, 1993; Zank et al., 2000). We adiabatically decompress the accelerated particle distribution between each shock by either the method explored in Melrose and Pope (1993) and Pope and Melrose (1994) or by the approach set forth in Zank et al. (2000) where we solve the transport equation by a method analogous to operator splitting. The second method incorporates the additional loss terms of convection and diffusion and allows for the use of a variable time between shocks. We use a maximum injection energy (Emax) appropriate for quasi-parallel and quasi-perpendicular shocks (Zank et al., 2000, 2006; Dosch and Shalchi, 2010) and provide a preliminary application of the diffusive acceleration of particles by multiple shocks with frequencies appropriate for solar maximum (i.e., a non-Markovian process).

Selective inhibitory action of Biginelli-type dihydropyrimidines on depolarization-induced arterial smooth muscle contraction.

PubMed

Cernecka, Hana; Veizerova, Lucia; Mensikova, Lucia; Svetlik, Jan; Krenek, Peter

2012-05-01

Dihydropyridine calcium channel blockers have some disadvantages such as light sensitivity and relatively short plasma half-lives. Stability of dihydropyrimidines analogues could be of advantage, yet they remain less well characterized. We aimed to test four newly synthesized Biginelli-type dihydropyrimidines for their calcium channel blocking activity on rat isolated aorta. Dihydropyrimidines (compounds A-D) were prepared by the Biginelli-like three-component condensation of benzaldehydes with urea/thiourea and dimethyl or diethyl acetone-1,3-dicarboxylate, and their physicochemical properties and effects on depolarization-induced and noradrenaline-induced contractions of rat isolated aorta were evaluated. Dihydropyrimidines A and C blocked KCl-induced contraction only weakly (-log(IC50)=5.03 and 3.73, respectively), while dihydropyrimidine D (-log(IC50)=7.03) was almost as potent as nifedipine (-log(IC50)=8.14). Washout experiments revealed that dihydropyrimidine D may bind strongly to the L-type calcium channel or remains bound to membrane. All tested dihydropyrimidines only marginally inhibited noradrenaline-induced contractions of rat isolated aorta (20% reduction of noradrenaline E(max) ), indicating a more selective action on L-type calcium channel than nifedipine with 75% inhibition of noradrenaline E(max) at 10(-4) m nifedipine). Compounds A and, particularly, D are potent calcium channel blockers in vitro, with a better selectivity in inhibiting depolarization-induced arterial smooth muscle contraction than nifedipine. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Bactericidal Effect and Pharmacodynamics of Cethromycin (ABT-773) in a Murine Pneumococcal Pneumonia Model

PubMed Central

Kim, Myo-Kyoung; Zhou, Wen; Tessier, Pamela R.; Xuan, Dawei; Ye, Min; Nightingale, Charles H.; Nicolau, David P.

2002-01-01

Cethromycin (ABT-773), a new ketolide, possesses potent in vitro activity against Streptococcus pneumoniae. The objective of this study was to investigate the in vivo bactericidal activity of cethromycin against macrolide-susceptible and -resistant S. pneumoniae in a murine pneumonia model and to describe the pharmacodynamic (PD) profile of cethromycin. Eight (two macrolide susceptible, six macrolide resistant) clinical isolates of S. pneumoniae were investigated. Cyclophosphamide administration rendered ICR mice transiently neutropenic prior to intratracheal inoculation with 0.05 ml of an S. pneumoniae suspension containing 107 to 108 CFU/ml. Oral cethromycin was initiated 12 to 14 h postinoculation over a dosage range of 0.1 to 800 mg/kg of body weight/day. Lungs from seven to eight mice per treatment and control groups were collected at 0 and 24 h posttherapy to assess bacterial density. The cumulative mortality (n = 12 to 13) was assessed at 120 h (end of therapy) and at 192 h (3 days posttherapy). Recovery of pneumococci from the lungs of infected animals prior to the initiation of therapy ranged from 4.6 to 7.2 log10 CFU. Growth in untreated control animals over a 24-h study period increased 0.3 to 2.7 log10 CFU. Cethromycin demonstrated a substantial bactericidal effect, regardless of macrolide susceptibility. Correlation between changes in bacterial density (24 h) and survival over both 120 and 192 h were statistically significant. All three PD parameters demonstrated a significant correlation with changes in log10 CFU/lung (Spearman's correlation coefficient, P < 0.001); however, the goodness of fit as assessed with the maximum effect (Emax) model revealed that the maximum concentration of free drug in serum (Cmax free)/MIC and the area under the free drug concentration-time curve (AUCfree)/MIC best explained the relationship between drug exposure and reductions in viable bacterial counts. These data reveal that an approximate cethromycin AUCfree/MIC of 50 or Cmax free/MIC of 1 results in bacteriostatic effects, while higher values (twofold) maximize survival. PMID:12234843

Influences of multiple firings and aging on surface roughness, strength and hardness of veneering ceramics for zirconia frameworks.

PubMed

Tang, Xuehua; Luo, Huinan; Bai, Yang; Tang, Hui; Nakamura, Takashi; Yatani, Hirofumi

2015-09-01

To evaluate the effects of multiple firings and aging on surface roughness, strength, and hardness of veneering ceramics for zirconia frameworks. Five different veneering ceramics for zirconia frameworks were used: Vintage ZR (ZR), Cerabien ZR (CZR), VitaVM9 (VM9), Cercon ceram KISS (KISS), and IPS e.max ceram (e.max). Specimens were fired 2 or 10 times in order to accelerate aging. Surface roughness was evaluated using laser profilometry. Flexural strength and Vickers hardness were also measured. Surface topography was observed using scanning electron microscopy. After accelerated aging, the surface roughness of all specimens fired 10 times was significantly lower than that of the same specimens fired 2 times (P=0.000). Except for VM9, the flexural strength of all specimens fired 10 times was greater than that of the same specimens fired 2 times, and the differences were significant for ZR and CZR (P<0.01). The flexural strength of VM9 fired 10 times was significantly lower than that of VM9 fired 2 times (P=0.034). The Vickers hardness of ZR and VM9 fired 10 times was significantly higher than that of the same specimens fired 2 times (P<0.05), but that of KISS fired 10 times was significantly lower than that of KISS fired 2 times (P=0.000). Multiple firings had a positive effect on the surface roughness of all aged veneering ceramics used for zirconia restorations and on the strength and hardness of many aged veneering ceramics used for zirconia restorations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of moderate liver impairment on the pharmacokinetics of opicapone.

PubMed

Rocha, José Francisco; Santos, Ana; Falcão, Amílcar; Lopes, Nelson; Nunes, Teresa; Pinto, Roberto; Soares-da-Silva, Patrício

2014-03-01

Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. The purpose of this study was to evaluate the effect of moderate liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD; effect on COMT activity) of OPC. An open-label, parallel-group study in patients (n = 8) with moderate liver impairment (Child-Pugh category B, score of 7 to 9) and matched healthy subjects (n = 8, control) with normal liver function. All subjects received a single 50-mg oral dose of OPC, with plasma and urine concentrations of opicapone and its metabolites measured up to 72 h post-dose, including soluble COMT (S-COMT) activity. A one-way analysis of variance (ANOVA) was used to compare the main PK and PD parameters between groups. Point estimates (PE) of geometric mean ratios (GMR) and corresponding 90 % confidence intervals (90%CI) for the ratio hepatic/control subjects of each parameter were calculated and compared with the reference interval (80-125 %). Exposure to opicapone (AUC and Cmax) increased significantly in patients with moderate hepatic impairment (PE [90%CI]: AUC0-∞, 184 % [135-250 %]; Cmax, 189 % [144-249 %]). Although apparent total clearance (CL/F) of opicapone was decreased by ∼35 %, similar elimination half-life and unbound/bound fractions of opicapone were observed between the two groups. Both rate and extent of exposure to BIA 9-1103 were higher in the hepatically impaired group, but not statistically significant compared with the control group. Similar to the parent (opicapone), the observed increase in exposure to BIA 9-1106 was statistically significant in the hepatically impaired group over the control group. BIA 9-1106 was the only metabolite detected in urine and its urine PK parameters were in accordance with plasma data. Maximum S-COMT inhibition (Emax) occurred earlier for the hepatically impaired group with values of 100 % and 91.2 % for the hepatically impaired and control groups respectively. Both Emax and AUEC for the hepatically impaired group reached statistical significance over the control group. OPC was well tolerated in both hepatically impaired and control groups. The bioavailability of an orally administered single dose of 50 mg OPC was significantly higher in patients with moderate chronic hepatic impairment, perhaps by a reduced first-pass effect. As the tolerability profile of OPC was favourable under the conditions of this study and its exposure is completely purged from systemic circulation before the subsequent dose administration, no OPC dose adjustment is needed in patients with mild to moderate chronic hepatic impairment. However, as OPC is under clinical development for use as adjunctive therapy in levodopa-treated patients with Parkinson's disease, an adjustment of levodopa and/or OPC regimens in patients should be carefully considered based on a potentially enhanced levodopa dopaminergic response and the associated tolerability.

Modeling the onset and offset of dental pain relief by ibuprofen.

PubMed

Li, Hanbin; Mandema, Jaap; Wada, Russell; Jayawardena, Shyamalie; Desjardins, Paul; Doyle, Geraldine; Kellstein, David

2012-01-01

Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects

PubMed Central

Rocha, José Francisco; Almeida, Luis; Falcão, Amílcar; Palma, P Nuno; Loureiro, Ana I; Pinto, Roberto; Bonifácio, Maria João; Wright, Lyndon C; Nunes, Teresa; Soares-da-Silva, Patrício

2013-01-01

Aims The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. Methods This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. Results Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (Emax) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100 h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT–opicapone complex. Conclusion Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen. PMID:23336248

Biaxial flexural strength of CAD/CAM ceramics.

PubMed

Buso, L; Oliveira-Júnior, O B; Hiroshi Fujiy, F; Leão Lombardo, G H; Ramalho Sarmento, H; Campos, F; Assunção Souza, R O

2011-06-01

Aim of the study was to evaluate the biaxial flexural strength of ceramics processed using the Cerec inLab system. The hypothesis was that the flexural strength would be influenced by the type of ceramic. Ten samples (ISO 6872) of each ceramic (N.=50/n.=10) were made using Cerec inLab (software Cerec 3D) (Ø:15 mm, thickness: 1.2 mm). Three silica-based ceramics (Vita Mark II [VM], ProCad [PC] and e-max CAD ECAD]) and two yttria-stabilized tetragonal-zirconia-polycrystalline ceramics (Y-TZP) (e-max ZirCad [ZrCAD] and Vita In-Ceram 2000 YZ Cubes [VYZ]) were tested. The samples were finished with wet silicone carbide papers up to 1 200-grit and polished in a polishing machine with diamond paste (3 µm). The samples were then submitted to biaxial flexural strength testing in a universal testing machine (EMIC), 1 mm/min. The data (MPa) were analyzed using the Kruskal-Wallis and Dunn (5%) tests. Scanning electronic microscopy (SEM) was performed on a representative sample from each group. The values (median, mean±sd) obtained for the experimental groups were: VM (101.7, 102.1±13.65 MPa), PC (165.2, 160±34.7 MPa), ECAD (437.2, 416.1±50.1 MPa), ZrCAD (804.2, 800.8±64.47 MPa) and VYZ (792.7, 807±100.7 MPa). The type of ceramic influenced the flexural strength values (P=0.0001). The ceramics ECADa, e-max ZrCADa and VYZa presented similar flexural strength values which were significantly higher than the other groups (PCb and VM IIb), which were similar statistically between them (Dunn's test). The hypothesis was accepted. The polycrystalline ceramics (Y-TZP) should be material chosen for make FPDs because of their higher flexural strength values.

Biased ligand quantification in drug discovery: from theory to high throughput screening to identify new biased μ opioid receptor agonists

PubMed Central

Winpenny, David; Clark, Mellissa

2016-01-01

Background and Purpose Biased GPCR ligands are able to engage with their target receptor in a manner that preferentially activates distinct downstream signalling and offers potential for next generation therapeutics. However, accurate quantification of ligand bias in vitro is complex, and current best practice is not amenable for testing large numbers of compound. We have therefore sought to apply ligand bias theory to an industrial scale screening campaign for the identification of new biased μ receptor agonists. Experimental Approach μ receptor assays with appropriate dynamic range were developed for both Gαi‐dependent signalling and β‐arrestin2 recruitment. Δlog(Emax/EC50) analysis was validated as an alternative for the operational model of agonism in calculating pathway bias towards Gαi‐dependent signalling. The analysis was applied to a high throughput screen to characterize the prevalence and nature of pathway bias among a diverse set of compounds with μ receptor agonist activity. Key Results A high throughput screening campaign yielded 440 hits with greater than 10‐fold bias relative to DAMGO. To validate these results, we quantified pathway bias of a subset of hits using the operational model of agonism. The high degree of correlation across these biased hits confirmed that Δlog(Emax/EC50) was a suitable method for identifying genuine biased ligands within a large collection of diverse compounds. Conclusions and Implications This work demonstrates that using Δlog(Emax/EC50), drug discovery can apply the concept of biased ligand quantification on a large scale and accelerate the deliberate discovery of novel therapeutics acting via this complex pharmacology. PMID:26791140

Chairside CAD/CAM materials. Part 1: Measurement of elastic constants and microstructural characterization.

PubMed

Belli, Renan; Wendler, Michael; de Ligny, Dominique; Cicconi, Maria Rita; Petschelt, Anselm; Peterlik, Herwig; Lohbauer, Ulrich

2017-01-01

A deeper understanding of the mechanical behavior of dental restorative materials requires an insight into the materials elastic constants and microstructure. Here we aim to use complementary methodologies to thoroughly characterize chairside CAD/CAM materials and discuss the benefits and limitations of different analytical strategies. Eight commercial CAM/CAM materials, ranging from polycrystalline zirconia (e.max ZirCAD, Ivoclar-Vivadent), reinforced glasses (Vitablocs Mark II, VITA; Empress CAD, Ivoclar-Vivadent) and glass-ceramics (e.max CAD, Ivoclar-Vivadent; Suprinity, VITA; Celtra Duo, Dentsply) to hybrid materials (Enamic, VITA; Lava Ultimate, 3M ESPE) have been selected. Elastic constants were evaluated using three methods: Resonant Ultrasound Spectroscopy (RUS), Resonant Beam Technique (RBT) and Ultrasonic Pulse-Echo (PE). The microstructures were characterized using Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Raman Spectroscopy and X-ray Diffraction (XRD). Young's modulus (E), Shear modulus (G), Bulk modulus (B) and Poisson's ratio (ν) were obtained for each material. E and ν reached values ranging from 10.9 (Lava Ultimate) to 201.4 (e.max ZirCAD) and 0.173 (Empress CAD) to 0.47 (Lava Ultimate), respectively. RUS showed to be the most complex and reliable method, while the PE method the easiest to perform but most unreliable. All dynamic methods have shown limitations in measuring the elastic constants of materials showing high damping behavior (hybrid materials). SEM images, Raman spectra and XRD patterns were made available for each material, showing to be complementary tools in the characterization of their crystal phases. Here different methodologies are compared for the measurement of elastic constants and microstructural characterization of CAD/CAM restorative materials. The elastic properties and crystal phases of eight materials are herein fully characterized. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Three-year clinical evaluation of two ceramic crown systems: a preliminary study.

PubMed

Etman, Maged K; Woolford, M J

2010-02-01

The clinical performance and failure mechanisms of recently introduced ceramic crown systems used to restore posterior teeth have not been adequately examined. The purpose of this prospective clinical study was to evaluate and compare the clinical performance of 2 new ceramic crown systems with that of metal ceramic crowns using modified United States Public Health Services (USPHS) criteria. Ninety posterior teeth requiring crown restorations in 48 patients were randomized into 3 equal groups (n=30) for which different crown systems were used: an experimental hot-pressed glass ceramic based on a modified lithium disilicate ceramic (IPS e.max Press), an alumina-coping-based ceramic (Procera AllCeram), and a metal ceramic (Simidur S 2 veneered with IPS Classic Porcelain). The crowns were assessed over 3 years using the modified USPHS criteria. Crowns that developed visible cracks were sectioned and removed, and the surfaces were analyzed using a scanning electron microscope (SEM). The data were analyzed using the Kruskal-Wallis nonparametric statistical test, followed by the Mann-Whitney test with Bonferroni correction (alpha=.05). USPHS evaluation showed that the IPS e.max Press and metal ceramic crowns experienced fewer clinical changes than Procera AllCeram. Visible roughness, wear, and deformity were noticed in occlusal contact areas of Procera AllCeram crowns. SEM images showed well defined wear facets in both ceramic crown systems. Kruskal-Wallis tests showed a significant difference (P<.05) in Alpha scores among the 3 crown systems. Mann-Whitney tests showed significant differences among groups. IPS e.max Press crowns demonstrated clinical behavior comparable to Procera AllCeram and metal ceramic crowns, but the wear resistance of this crown type was superior to the Procera AllCeram crowns, according to modified USPHS criteria.

SU-E-T-89: Characterization of Dental Restoration Material for Cs-137 Radiation Dosimetry.

PubMed

Ratliff, S; Gustafson, B; Barry, K

2012-06-01

The purpose of this work is to characterize the radiation-induced thermoluminescence properties of a dental restoration material and to see if the material might be feasible for use in retrospective radiation dosimetry. Retrospective, or accidental, dosimetry is the study of using nearby materials to measure radiation received by individuals. In this project we obtained samples of Ivoclar Vivadent e.max CAD material, a glass-ceramic used for making dental restorations such as full or partial crowns. The samples were machined into square chips .32 cm × .32 cm × .089 cm and annealed in the same furnace used by the dentist. The samples were exposed to a Cs-137 source using a PMMA source holder and then read in a Harshaw 3500 TLD reader. The samples were read without nitrogen gas flux using heating rates of 5 degrees C/s or 10 degrees C/s up to a maximum temperature of 400 degrees Celsius. The glow curves were analyzed using Systat PeakFIT peak-fitting software and Microsoft Excel spreadsheets. The authors gratefully thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN for the dental restoration materials and the use of their dental furnace. A sample subjected to a radiation exposure of .04 C/kg exhibits a glow curve with a prominent peak at approximately 140 degrees Celsius, which is well-modeled by the first order glow curve deconvolution formula developed by Kitis, Gomez-Ros, and Tuyn. The activation energy corresponding to this peak is approximately 1 eV. The thermoluminescent signal fades with time after exposure. Ivoclar Vivadent e.max CAD dental restoration material has the potential to be used as a material for retrospective Cs-137 radiation dosimetry. Future work could look at its thermoluminescent dosimetry properties in more detail and also at other dental restoration materials. The authors would like to thank Dr. Aaron Imdieke and the staff of River City Dental, St. Cloud, MN, for the donation of scrap dental restoration materials and the use of their dental furnace. © 2012 American Association of Physicists in Medicine.

Electric Field and Current Density Performance Analysis of Sf6, C4f8 and CO2 Gases As An Insulation

NASA Astrophysics Data System (ADS)

Mazli, Ahmad Danial Ahmad; Jamail, Nor Akmal Mohd; Azlin Othman, Nordiana

2017-08-01

SF6 gases are not only widely used as an insulating component in electric power industry but also as an arc extinguishing performance in high voltage (HV) gas-insulated circuit breaker (GCB). SF6 gases is generally used in the production of semiconductor materials and devices. Though these gasses is widely used in many application, the presences of temperature hotspot in the insulations may affect the insulation characteristics particularly electric field and current density. Therefore, it is important to determine the relationship between electric field and current density of gasses used in the insulator in the presence of hotspot. In this paper, three types of gases in particular Sulphur Hexafluoride (SF6), Octafluorocylobutane (C4F8), and Carbon Dioxide (CO2) was used in the insulator for gas insulation with the presence of two hotspots. These two hotspost were detected by referring the rising temperature in the insulator which are 1000 and 2000 Kelvin temperature for hotspot 1 and hotspot 2, respectively. From the simulation results, it can be concluded that Sulphur Hexafluoride (SF6) is the best choice for gas insulation since it had the lowest current density and electric field compared to Octafluorocylobutane (C4F8), and Carbon Dioxide (CO2). It is observed that the maximum current density and electric field for SF6 during normal condition are 358.94 × 103 V/m and 0.643 × 109 A/m2, respectively. Meanwhile, during temperature rising at hotspot 1 and hotspot 2, SF6 also had lowest current density and electric field compared to the other gasses where the results for Emax and Jmax at hotspot 1 are 322.34 × 103 V/m and 1.934 × 109 A/m2, respectively; While, Emax and Jmax at hotspot 2 are 259.77× 103 V/m and 2.824 × 109 A/m2. The results of this analysis can be used to find the best choices of gas that can be used in the insulator.

Quantitative Lesion-to-Fat Elasticity Ratio Measured by Shear-Wave Elastography for Breast Mass: Which Area Should Be Selected as the Fat Reference?

PubMed

Youk, Ji Hyun; Son, Eun Ju; Gweon, Hye Mi; Han, Kyung Hwa; Kim, Jeong-Ah

2015-01-01

To investigate whether the diagnostic performance of lesion-to-fat elasticity ratio (Eratio) was affected by the location of the reference fat. For 257 breast masses in 250 women who underwent shear-wave elastography before biopsy or surgery, multiple Eratios were measured with a fixed region-of-interest (ROI) in the mass along with multiple ROIs over the surrounding fat in different locations. Logistic regression analysis was used to determine that Eratio was independently associated with malignancy adjusted for the location of fat ROI (depth, laterality, and distance from lesion or skin). Mean (Emean) and maximum (Emax) elasticity values of fat were divided into four groups according to their interquartile ranges. Diagnostic performance of each group was evaluated using the area under the ROC curve (AUC). False diagnoses of Eratio were reviewed for ROIs on areas showing artifactual high or low stiffness and analyzed by logistic regression analysis to determine variables (associated palpable abnormality, lesion size, the vertical distance from fat ROI to skin, and elasticity values of lesion or fat) independently associated with false results. Eratio was independently associated with malignancy adjusted for the location of fat ROI (P<0.0001). Among four groups of fat elasticity values, the AUC showed no significant difference (<25th percentile, 25th percentile~median, median~75th percentile, and ≥75th percentile; 0.973, 0.982, 0.967, and 0.954 for Emean; 0.977, 0.967, 0.966, and 0.957 for Emax). Fat elasticity values were independently associated with false results of Eratio with the cut-off of 3.18 from ROC curve (P<0.0001). ROIs were set on fat showing artifactual high stiffness in 90% of 10 false negatives and on lesion showing vertical striped artifact or fat showing artifactual low stiffness in 77.5% of 71 false positives. Eratio shows good diagnostic performance regardless of the location of reference fat, except when it is placed in areas of artifacts.

Quantitative Lesion-to-Fat Elasticity Ratio Measured by Shear-Wave Elastography for Breast Mass: Which Area Should Be Selected as the Fat Reference?

PubMed Central

Youk, Ji Hyun; Son, Eun Ju; Gweon, Hye Mi; Han, Kyung Hwa; Kim, Jeong-Ah

2015-01-01

Objectives To investigate whether the diagnostic performance of lesion-to-fat elasticity ratio (Eratio) was affected by the location of the reference fat. Methods For 257 breast masses in 250 women who underwent shear-wave elastography before biopsy or surgery, multiple Eratios were measured with a fixed region-of-interest (ROI) in the mass along with multiple ROIs over the surrounding fat in different locations. Logistic regression analysis was used to determine that Eratio was independently associated with malignancy adjusted for the location of fat ROI (depth, laterality, and distance from lesion or skin). Mean (Emean) and maximum (Emax) elasticity values of fat were divided into four groups according to their interquartile ranges. Diagnostic performance of each group was evaluated using the area under the ROC curve (AUC). False diagnoses of Eratio were reviewed for ROIs on areas showing artifactual high or low stiffness and analyzed by logistic regression analysis to determine variables (associated palpable abnormality, lesion size, the vertical distance from fat ROI to skin, and elasticity values of lesion or fat) independently associated with false results. Results Eratio was independently associated with malignancy adjusted for the location of fat ROI (P<0.0001). Among four groups of fat elasticity values, the AUC showed no significant difference (<25th percentile, 25th percentile~median, median~75th percentile, and ≥75th percentile; 0.973, 0.982, 0.967, and 0.954 for Emean; 0.977, 0.967, 0.966, and 0.957 for Emax). Fat elasticity values were independently associated with false results of Eratio with the cut-off of 3.18 from ROC curve (P<0.0001). ROIs were set on fat showing artifactual high stiffness in 90% of 10 false negatives and on lesion showing vertical striped artifact or fat showing artifactual low stiffness in 77.5% of 71 false positives. Conclusion Eratio shows good diagnostic performance regardless of the location of reference fat, except when it is placed in areas of artifacts. PMID:26368920

The biophysical and physiological basis for mitigated elevations in heart rate with electric fan use in extreme heat and humidity

NASA Astrophysics Data System (ADS)

Ravanelli, Nicholas M.; Gagnon, Daniel; Hodder, Simon G.; Havenith, George; Jay, Ollie

2017-02-01

Electric fan use in extreme heat wave conditions has been thought to be disadvantageous because it might accelerate heat gain to the body via convection. However, it has been recently shown that fan use delays increases in heart rate even at high temperatures (42 °C) in young adults. We here assess the biophysical and physiological mechanisms underlying the apparently beneficial effects of fan use. Eight males (24 ± 3 y; 80.7 ± 11.7 kg; 2.0 ± 0.1 m2) rested at either 36 °C or 42 °C, with (F) or without (NF) electric fan use (4.2 m/s) for 120 min while humidity increased every 7.5 min by 0.3 kPa from a baseline value of 1.6 kPa. Heart rate (HR), local sweat rate (LSR), cutaneous vascular conductance (CVC), core and mean skin temperatures, and the combined convective/radiative heat loss (C+R), evaporative heat balance requirements (Ereq) and maximum evaporative potential (Emax) were assessed. C+R was greater with fan use at 36 °C (F 8 ± 6, NF 2 ± 2 W/m2; P = 0.04) and more negative (greater dry heat gain) with fan use at 42 °C (F -78 ± 4, NF -27 ± 2 W/m2; P < 0.01). Consequently, Ereq was lower at 36 °C (F 38 ± 16, NF 45 ± 3 W/m2; P = 0.04) and greater at 42 °C (F 125 ± 1, NF 74 ± 3 W/m2; P < 0.01) with fan use. However, fan use resulted in a greater Emax at baseline humidity at both 36 °C (F 343 ± 10, NF 153 ± 5 W/m2; P < 0.01) and 42 °C (F 376 ± 13, NF 161 ± 4 W/m2; P < 0.01) and throughout the incremental increases in humidity. Within the humidity range that a rise in HR was prevented by fan use but not without a fan, LSR was higher in NF at both 36 °C ( P = 0.04) and 42 °C ( P = 0.05), and skin temperature was higher in NF at 42 °C ( P = 0.05), but no differences in CVC or core temperatures were observed (all P > 0.05). These results suggest that the delayed increase in heart rate with fan use during extreme heat and humidity is associated with improved evaporative efficiency.

Particle Acceleration at a Twin CME at 1 AU

NASA Astrophysics Data System (ADS)

Parker, L. N.; Li, G.

2017-12-01

We present results from both the Particle Acceleration and Transport in the Heliosphere (PATH) and Particle Acceleration at Multiple Shocks (PAMS) models for a twin CME scenario. The PATH model follows a CME using a numerical MHD module and solves the Parker transport equation at the shock yielding the accelerated particle spectrum, while PAMS solves the steady-state cosmic ray transport equation at an individual shock analytically to yield the diffusive shock acceleration (DSA) spectrum. We address the injection of an upstream particle distribution into the acceleration process for a two shock system at 1 AU. Only those particles that exceed a theoretically motivated prescribed injection energy, Einj, and up to a maximum injection energy (Emax) appropriate for quasi-parallel and quasi-perpendicular shocks (Zank et al., 2000, 2006; Dosch and Shalchi, 2010) are injected. Results from PAMS are then compared to observations at 1 AU from the Advanced Composition Explorer (ACE) spacecraft. In addition, we test the concept of electron acceleration at low injection energies for a single and multiple shock system using the same method as in Neergaard Parker and Zank, 2012 and Neergaard Parker et al., 2014.

The relationship between alloying elements and biologically produced ennoblement in natural waters.

PubMed

Eashwar, M; Lakshman Kumar, A; Hariharasuthan, R; Sreedhar, G

2015-01-01

A range of stainless steels, nickel-chromium and nickel-chromium-molybdenum alloys were exposed to coastal seawater from Mandapam (Indian Ocean) and freshwater from a perennial pond. Biofilms from both test waters produced an ennoblement of the open circuit potential (OCP) on all alloys as expected, which was slower but substantially larger in freshwater. In both waters an interesting relationship was perceived between the plateau OCP (Emax) and the mass percentage of the major alloying elements. In particular, iron exhibited strong positive correlations with Emax (r(2) ≥ 0.77; p < 0.0005), while the sum of chromium, nickel and molybdenum presented significant negative correlations (r(2) ≤ -0.81; p = 0.0002). Consistent with the regression analyses, Euclidean distance clustering yielded patterns where Inconel-600 and the nickel-chromium-molybdenum alloys had the smallest similarities of OCP with other alloys. The results emphatically reinforce a key role for surface passive films in the ennoblement phenomenon in natural waters.

Variable rainfall intensity and tillage effects on runoff, sediment, and carbon losses from a loamy sand under simulated rainfall.

PubMed

Truman, C C; Strickland, T C; Potter, T L; Franklin, D H; Bosch, D D; Bednarz, C W

2007-01-01

The low-carbon, intensively cropped Coastal Plain soils of Georgia are susceptible to runoff, soil loss, and drought. Reduced tillage systems offer the best management tool for sustained row crop production. Understanding runoff, sediment, and chemical losses from conventional and reduced tillage systems is expected to improve if the effect of a variable rainfall intensity storm was quantified. Our objective was to quantify and compare effects of a constant (Ic) intensity pattern and a more realistic, observed, variable (Iv) rainfall intensity pattern on runoff (R), sediment (E), and carbon losses (C) from a Tifton loamy sand cropped to conventional-till (CT) and strip-till (ST) cotton (Gossypium hirsutum L.). Four treatments were evaluated: CT-Ic, CT-Iv, ST-Ic, and ST-Iv, each replicated three times. Field plots (n=12), each 2 by 3 m, were established on each treatment. Each 6-m2 field plot received simulated rainfall at a constant (57 mm h(-1)) or variable rainfall intensity pattern for 70 min (12-run ave.=1402 mL; CV=3%). The Iv pattern represented the most frequent occurring intensity pattern for spring storms in the region. Compared with CT, ST decreased R by 2.5-fold, E by 3.5-fold, and C by 7-fold. Maximum runoff values for Iv events were 1.6-fold higher than those for Ic events and occurred 38 min earlier. Values for Etot and Ctot for Iv events were 19-36% and 1.5-fold higher than corresponding values for Ic events. Values for Emax and Cmax for Iv events were 3-fold and 4-fold higher than corresponding values for Ic events. Carbon enrichment ratios (CER) were or=1.0 for CT plots (except for first 20 min). Maximum CER for CT-Ic, CT-Iv, ST-Ic, and ST-Iv were 2.0, 2.2, 1.0, and 1.2, respectively. Transport of sediment, carbon, and agrichemicals would be better understood if variable rainfall intensity patterns derived from natural rainfall were used in rainfall simulations to evaluate their fate and transport from CT and ST systems.

In Vitro Comparison of Marginal and Internal Fit of Press-on-Metal Ceramic (PoM) Restorations with Zirconium-Supported and Conventional Metal Ceramic Fixed Partial Dentures Before and After Veneering.

PubMed

Varol, Seda; Kulak-Özkan, Yasemin

2015-07-01

To compare marginal and internal fit between 3- and 4-unit press-on-metal (PoM) ceramic, zirconia-supported, and conventional metal ceramic fixed partial dentures (FPDs) before and after veneering. Ten pieces for each 3- and 4-unit MC, IPS InLine PoM, and IPS e.max ZirCAD/Zir Press FPDs were produced. Cross-sections from silicone replicas were examined and measured with a light microscope. Occlusal, axial, intermarginal, and marginal mean adaptation scores of cross-sectioned replicas and means of measurements obtained from 4 sites were calculated independently. Mean values for molars were 78.44 ± 32.01 μm (MC), 89.84 ± 29.20 μm (PoM), and 85.17 ± 28.49 μm (Zir). Premolar values were 76.08 ± 27.92 μm (MC), 89.94 ± 23.49 μm (PoM), and 87.18 ± 28.25 μm (Zir). No difference existed between the means of 3- and 4-unit FPDs except the molar-intermarginal region. The mean value of 4-unit FPDs (93.88 ± 25.41 μm) was less than the 3-unit FPDs (103.68 ± 24.55 μm) at the molar-inter marginal region. A gap increase was observed in all sites except the molar-axio-occlusal region after veneering. According to the mean difference, gap increases at the molar-marginal, molar-intermarginal, and premolar-intermarginal regions were statistically significant. A statistical difference was found at the molar-marginal region for 4-unit MCR (p = 0.041) and 4-unit PoM FPDs (p = 0.042) before and after veneering. Gap increase after veneering of 4-unit metal ceramics at molar-intermarginal, premolar-marginal, and premolar-intermarginal regions (p = 0.020; p = 0.015; p = 0.004) was significant. The gap measurements of the IPS InLine PoM and IPS e.max ZirCAD/Zir Press groups were all clinically acceptable. No studies on marginal and internal fit in the IPS InLine PoM system have been published to date. This study should be supported with future studies. No significant increase was observed after press-veneering the IPS e.max ZirCAD frameworks with an IPS e.max ZirPress material; therefore, we recommend the use of this combination. © 2014 by the American College of Prosthodontists.

Comparison of three and four point bending evaluation of two adhesive bonding systems for glass-ceramic zirconia bi-layered ceramics.

PubMed

Gee, C; Weddell, J N; Swain, M V

2017-09-01

To quantify the adhesion of two bonding approaches of zirconia to more aesthetic glass-ceramic materials using the Schwickerath (ISO 9693-2:2016) three point bend (3PB) [1] test to determine the fracture initiation strength and strain energy release rate associated with stable crack extension with this test and the Charalamabides et al. (1989) [2] four point bend (4PB) test. Two glass-ceramic materials (VITABLOCS Triluxe forte, Vita Zahnfabrik, Germany and IPS.emax CAD, Ivoclar Vivadent, Liechtenstein) were bonded to sintered zirconia (VITA InCeram YZ). The former was resin bonded using a dual-cure composite resin (Panavia F 2.0, Kuraray Medical Inc., Osaka, Japan) following etching and silane conditioning, while the IPS.emax CAD was glass bonded (IPS e.max CAD Crystall/Connect) during crystallization of the IPS.emax CAD. Specimens (30) of the appropriate dimensions were fabricated for the Schwickerath 3PB and 4PB tests. Strength values were determined from crack initiation while strain energy release rate values were determined from the minima in the force-displacement curves with the 3PB test (Schneider and Swain, 2015) [3] and for 4PB test from the plateau region of stable crack extension. Strength values for the resin and glass bonded glass ceramics to zirconia were 22.20±6.72MPa and 27.02±3.49MPa respectively. The strain energy release rates for the two methods used were very similar and for the glass bonding, (4PB) 15.14±5.06N/m (or J/m 2 ) and (3PB) 16.83±3.91N/m and resin bonding (4PB) 8.34±1.93N/m and (3PB) 8.44±2.81N/m respectively. The differences in strength and strain energy release rate for the two bonding approaches were statistically significant (p<0.05). SEM observations showed fracture occurred adhesively for the resin bonding and cohesively for the glass bonding. The present results indicate 3PB and 4PB tests have very similar values for the strain energy release rate determination. However while strength tests reveal minimal differences between resin and glass bonding, strain energy release rates for the latter are superior for bonding CAD/CAM milled glass-ceramics to zirconia. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Transient and residual stresses in a pressable glass-ceramic before and after resin-cement coating determined using profilometry.

PubMed

Isgró, G; Addison, O; Fleming, G J P

2011-05-01

The effect of heat-pressing and subsequent pre-cementation (acid-etching) and resin-cementation operative techniques on the development of transient and residual stresses in different thicknesses of a lithium disilicate glass-ceramic were characterised using profilometry prior to biaxial flexure strength (BFS) determination. 60 IPS e.max Press discs were pressed and divested under controlled conditions. The discs were polished on one surface to thicknesses of 0.61±0.05, 0.84±0.08, and 1.06±0.07 mm (Groups A-C, respectively). The mean of the maximum deflection (acid-etching and resin-coating was determined using high resolution profilometery prior to BFS testing. Paired sample t-tests were performed (p<0.05) on the 20 individual samples in each group (Groups A-C) for each comparison. Differences between the baseline quantification and resin-cement coating deflection values and BFS values for Groups A-C were determined using a one-way ANOVA with post hoc Tukey tests (p<0.05). Baseline quantification for Groups A-C identified no significant differences between the group means of the maximum deflection values (p=0.341). Following HF acid-etching, a significant increase in deflection for all groups (p<0.001) was identified compared with the baseline quantification. Additionally, resin-cement coating significantly increased deflection for Group A (p<0.001), Group B (p<0.001) and Group C (p=0.001) specimens for the individual groups. The increased deflection from baseline quantification to resin-cement coating was significantly different (p<0.001) for the three specimen thicknesses, although the BFS values were not. The lower reported baseline quantification range of the mean of the maximum deflection for the IPS e.max(®) Press specimens was predominantly the result of specimen polishing regime inducing a tensile stress state across the surface defect integral which accounted for the observed surface convexity. Acid-etching and resin-cementation had a significant impact on the development and magnitude of the transient and residual stresses in the lithium disilicate glass-ceramic investigated. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of milling and postmilling procedures on the surface roughness of CAD/CAM materials.

PubMed

Mota, Eduardo Gonçalves; Smidt, Laura Nunes; Fracasso, Lisiane Martins; Burnett, Luiz Henrique; Spohr, Ana Maria

2017-11-12

The aim of this study was to evaluate the surface roughness and analyze the surface topography of five different CAD/CAM ceramics and one CAD/CAM composite resin for CEREC after milling and postmilling procedures. Blocks of the ceramics Mark II, IPS Empress CAD, IPS e.max CAD, Suprinity and Enamic, and blocks of the composite resin Lava Ultimate were milled at CEREC MCXL. Ten flat samples of each material were obtained. The surface roughness (Ra) test was performed before and after milling, crystallization, polishing, and glaze when indicated, followed by SEM and AFM analysis. Data were submitted to one-way ANOVA with repeated measures and the Tukey HSD test (α = 0.05). The milling step significantly increased the roughness of all the tested materials (P < .05). Lithium-based ceramics (IPS e.max CAD and Suprinity) were more suitable to roughness than the other tested materials (P < .05). The polishing methods were able to reduce roughness to baseline values, except for lithium-based ceramics. Glaze reduced significantly the roughness of lithium-based ceramics without a difference from the baseline. SEM and AFM images revealed that glazed surfaces are smoother than polished surfaces. All hard-milling CAD/CAM materials, that is, fully sintered, should be only hand polished. The glaze step can be suppressed resulting in time saving. However, the glaze step in soft-milling lithium disilicate is imperative. © 2017 Wiley Periodicals, Inc.

Analysis of molecular determinants of affinity and relative efficacy of a series of R- and S-2-(dipropylamino)tetralins at the 5-HT1A serotonin receptor

PubMed Central

Alder, J Tracy; Hacksell, Uli; Strange, Philip G

2003-01-01

Factors influencing agonist affinity and relative efficacy have been studied for the 5-HT1A serotonin receptor using membranes of CHO cells expressing the human form of the receptor and a series of R-and S-2-(dipropylamino)tetralins (nonhydroxylated and monohydroxylated (5-OH, 6-OH, 7-OH, 8-OH) species). Ligand binding studies were used to determine dissociation constants for agonist binding to the 5-HT1A receptor: Ki values for agonists were determined in competition versus the binding of the agonist [3H]-8-OH DPAT. Competition data were all fitted best by a one-binding site model.Ki values for agonists were also determined in competition versus the binding of the antagonist [3H]-NAD-199. Competition data were all fitted best by a two-binding site model, and agonist affinities for the higher (Kh) and lower affinity (Kl) sites were determined. The ability of the agonists to activate the 5-HT1A receptor was determined using stimulation of [35S]-GTPγS binding. Maximal effects of agonists (Emax) and their potencies (EC50) were determined from concentration/response curves for stimulation of [35S]-GTPγS binding. Kl/Kh determined from ligand binding assays correlated with the relative efficacy (relative Emax) of agonists determined in [35S]-GTPγS binding assays. There was also a correlation between Kl/Kh and Kl/EC50 for agonists determined from ligand binding and [35S]-GTPγS binding assays. Simulations of agonist binding and effect data were performed using the Ternary Complex Model in order to assess the use of Kl/Kh for predicting the relative efficacy of agonists. PMID:12684269

Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

PubMed

Nashawi, Houda; Masocha, Willias; Edafiogho, Ivan O; Kombian, Samuel B

The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system. One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. The paclitaxel-treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel-treated rats produced a significantly higher maximal response (Emax) than those from untreated rats (p < 0.001). Bath application of GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax in slices from untreated rats (p < 0.01) but not from paclitaxel-treated rats. In this study, there was a GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain (PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP. © 2016 S. Karger AG, Basel.

In Vivo Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Streptococcus suis Serotype 2 at Varied Initial Inoculum Sizes.

PubMed

Guo, Chunna; Liao, Xiaoping; Wang, Mingru; Wang, Feng; Yan, Chaoqun; Xiao, Xia; Sun, Jiang; Liu, Yahong

2016-02-01

Streptococcus suis serotype 2 is an emerging zoonotic pathogen and causes severe disease in both pigs and human beings. Cefquinome (CEQ), a fourth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria such as S. suis. This study evaluated the in vitro and in vivo antimicrobial activities of CEQ against four strains of S. suis serotype 2 in a murine neutropenic thigh infection model. We investigated the effect of varied inoculum sizes (10(6) to 10(8) CFU/thigh) on the pharmacokinetic (PK)/pharmacodynamic (PD) indices and magnitudes of a particular PK/PD index or dose required for efficacy. Dose fractionation studies included total CEQ doses ranging from 0.625 to 640 mg/kg/24 h. Data were analyzed via a maximum effect (Emax) model using nonlinear regression. The PK/PD studies demonstrated that the percentage of time that serum drug levels were above the MIC of free drug (%ƒT>MIC) in a 24-h dosing interval was the primary index driving the efficacy of both inoculum sizes (R(2) = 91% and R(2) = 63%). CEQ doses of 2.5 and 40 mg/kg body weight produced prolonged postantibiotic effects (PAEs) of 2.45 to 8.55 h. Inoculum sizes had a significant influence on CEQ efficacy. Compared to the CEQ exposure and dosages in tests using standard inocula, a 4-fold dose (P = 0.006) and a 2-fold exposure time (P = 0.01) were required for a 1-log kill using large inocula of 10(8) CFU/thigh. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

HYDROGEN PEROXIDE FORMATION FROM THE PHOTOOXIDATION OF FORMALDEHYDE AND ITS PRESENCE IN RAINWATER

EPA Science Inventory

The photooxidation of formaldehyde with sunlamps (E(max) = 3100 A) produces hydrogen peroxide (H2O2) at varying concentrations depending upon the amount of water vapor present. It is postulated that the variable production of H2O2 is a result of condensation on the reactor surfac...

Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

PubMed

De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

2016-06-01

In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of mechanical and optical behavior of current esthetic dental restorative CAD/CAM composites.

PubMed

Stawarczyk, Bogna; Liebermann, Anja; Eichberger, Marlis; Güth, Jan-Frederik

2015-03-01

To determine the mechanical and optical properties of CAD/CAM composites (LAVA Ultimate, Cerasmart, Shofu Block and two exp. CAD/CAM composites), a hybrid material (VITA Enamic), a leucite (IPS Empress CAD) and a lithium disilicate glass-ceramic (IPS e.max CAD). Three-point flexural strength (FS) was investigated according ISO 6872:2008 (N=240/n=30). Two-body wear (TBW) was analyzed in a chewing simulator (1,200,000 cycles, 50N, 5°/55°C) using human teeth as antagonists (N=120/n=15). Quantitative analysis of wear was carried out with a 3D-scanner and associated matching software. Discoloration rate (DR) after 14 days of storage in cress, curry, red wine, and distilled water (N=384/n=12), and translucency (T) (N=384/n=48) of CAD/CAM materials were measured in a spectrophotometer (400-700nm wavelength). Data were analyzed using two-/one-way ANOVA with Scheffé post-hoc test, Kruskal-Wallis-H test, and linear mixed models (α=0.05). IPS e.max CAD showed the highest FS (p<0.001), followed by LAVA Ultimate; however, not different from the remaining CAD/CAM composites (exception: Shofu Block). The lowest FS showed VITA Enamic and IPS Empress CAD (p<0.001). IPS Empress CAD, VITA Enamic, exp. CAD/CAM composite 2, followed by IPS e.max presented lower material TBW than the remaining CAD/CAM materials (p<0.001). The highest antagonist wear was observed for the tested glass-ceramics and the hybrid material (p<0.001). Storage medium (red wine>curry>cress>distilled water) exerted the highest influence on DR (p<0.001), closely followed by CAD/CAM material. Glass-ceramics showed lower DR than CAD/CAM composites (p<0.001). CAD/CAM composites presented moderate FS, high T and antagonist friendly behavior. Glass-ceramic demonstrated the most favorable DR and lowest TBW on the material side. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of five CAD/CAM materials by microstructural characterization and mechanical tests: a comparative in vitro study.

PubMed

Sonmez, Nesrin; Gultekin, Pinar; Turp, Volkan; Akgungor, Gokhan; Sen, Deniz; Mijiritsky, Eitan

2018-01-08

Polymer infiltrated ceramics and nano-ceramic resins are the new restorative materials which have been developed in order to enhance the adverse properties of glass-matrix ceramics and resin composites. The aim of the present in vitro study was to evaluate the characteristics of various CAD/CAM materials through mechanical, microstructural, and SEM analysis. Five test groups (n = 22) were formed by using the indicated CAD/CAM blocks: VITA Enamic (VITA Zahnfabrik), Lava Ultimate (3 M ESPE), IPS e.max CAD (Ivoclar Vivadent), IPS Empress CAD (Ivoclar Vivadent), and VITA Mark II (VITA Zahnfabrik). Two specimens from each test group were used for XRD and EDS analysis. Remaining samples were divided into two subgroups (n = 10). One subgroup specimens were thermocycled (5 °C to 55 °C, 30s, 10,000 cycles) whereas the other were not. All of the specimens were evaluated in terms of flexural strength, Vickers hardness, and fracture toughness. Results were statistically analyzed using two-way ANOVA, one-way ANOVA, Tukey's HSD, and Student's t tests (α = .05). Fractured specimens were evaluated using SEM. The highest Vickers microhardness value was found for VITA Mark II (p < .001), however flexural strength and fracture toughness results were lowest conversely (p < .05). IPS e.max CAD was found to have the highest flexural strength (p < .001). Fracture toughness of IPS e.max CAD was also higher than other tested block materials (p < .001). Lava Ultimate and VITA Enamic's mechanical properties were affected negatively from thermocycling (p < .05). Microhardness, flexural strength, and fracture toughness values of Lava Ultimate and VITA Enamic were found to be similar to VITA Mark II and IPS Empress CAD groups. It should be realised that simulated aging process seem to affect ceramic-polymer composite materials more significantly than glass ceramics.

Plastic damage induced fracture behaviors of dental ceramic layer structures subjected to monotonic load.

PubMed

Wang, Raorao; Lu, Chenglin; Arola, Dwayne; Zhang, Dongsheng

2013-08-01

The aim of this study was to compare failure modes and fracture strength of ceramic structures using a combination of experimental and numerical methods. Twelve specimens with flat layer structures were fabricated from two types of ceramic systems (IPS e.max ceram/e.max press-CP and Vita VM9/Lava zirconia-VZ) and subjected to monotonic load to fracture with a tungsten carbide sphere. Digital image correlation (DIC) and fractography technology were used to analyze fracture behaviors of specimens. Numerical simulation was also applied to analyze the stress distribution in these two types of dental ceramics. Quasi-plastic damage occurred beneath the indenter in porcelain in all cases. In general, the fracture strength of VZ specimens was greater than that of CP specimens. The crack initiation loads of VZ and CP were determined as 958 ± 50 N and 724 ± 36 N, respectively. Cracks were induced by plastic damage and were subsequently driven by tensile stress at the elastic/plastic boundary and extended downward toward to the veneer/core interface from the observation of DIC at the specimen surface. Cracks penetrated into e.max press core, which led to a serious bulk fracture in CP crowns, while in VZ specimens, cracks were deflected and extended along the porcelain/zirconia core interface without penetration into the zirconia core. The rupture loads for VZ and CP ceramics were determined as 1150 ± 170 N and 857 ± 66 N, respectively. Quasi-plastic deformation (damage) is responsible for crack initiation within porcelain in both types of crowns. Due to the intrinsic mechanical properties, the fracture behaviors of these two types of ceramics are different. The zirconia core with high strength and high elastic modulus has better resistance to fracture than the e.max core. © 2013 by the American College of Prosthodontists.

Machinability of CAD-CAM materials.

PubMed

Chavali, Ramakiran; Nejat, Amir H; Lawson, Nathaniel C

2017-08-01

Although new materials are available for computer-aided design and computer-aided manufacturing (CAD-CAM) fabrication, limited information is available regarding their machinability. The depth of penetration of a milling tool into a material during a timed milling cycle may indicate its machinability. The purpose of this in vitro study was to compare the tool penetration rate for 2 polymer-containing CAD-CAM materials (Lava Ultimate and Enamic) and 2 ceramic-based CAD-CAM materials (e.max CAD and Celtra Duo). The materials were sectioned into 4-mm-thick specimens (n=5/material) and polished with 320-grit SiC paper. Each specimen was loaded into a custom milling apparatus. The apparatus pushed the specimens against a milling tool (E4D Tapered 2016000) rotating at 40 000 RPM with a constant force of 0.98 N. After a 6-minute timed milling cycle, the length of each milling cut was measured with image analysis software under a digital light microscope. Representative specimens and milling tools were examined with scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy. The penetration rate of Lava Ultimate (3.21 ±0.46 mm/min) and Enamic (2.53 ±0.57 mm/min) was significantly greater than that of e.max CAD (1.12 ±0.32 mm/min) or Celtra Duo (0.80 ±0.21 mm/min) materials. SEM observations showed little tool damage, regardless of material type. Residual material was found on the tools used with polymer-containing materials, and wear of the embedding medium was seen on the tools used with the ceramic-based materials. Edge chipping was noted on cuts made in the ceramic-based materials. Lava Ultimate and Enamic have greater machinability and less edge chipping than e.max CAD and Celtra Duo. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

PubMed

Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

1991-02-01

1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

NASA Astrophysics Data System (ADS)

Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

Effect of Stress Corrosion and Cyclic Fatigue on Fluorapatite Glass-Ceramic

NASA Astrophysics Data System (ADS)

Joshi, Gaurav V.

2011-12-01

Objective: The objective of this study was to test the following hypotheses: 1. Both cyclic degradation and stress corrosion mechanisms result in subcritical crack growth in a fluorapatite glass-ceramic. 2. There is an interactive effect of stress corrosion and cyclic fatigue to cause subcritical crack growth (SCG) for this material. 3. The material that exhibits rising toughness curve (R-curve) behavior also exhibits a cyclic degradation mechanism. Materials and Methods: The material tested was a fluorapatite glass-ceramic (IPS e.max ZirPress, Ivoclar-Vivadent). Rectangular beam specimens with dimensions of 25 mm x 4 mm x 1.2 mm were fabricated using the press-on technique. Two groups of specimens (N=30) with polished (15 mum) or air abraded surface were tested under rapid monotonic loading. Additional polished specimens were subjected to cyclic loading at two frequencies, 2 Hz (N=44) and 10 Hz (N=36), and at different stress amplitudes. All tests were performed using a fully articulating four-point flexure fixture in deionized water at 37°C. The SCG parameters were determined by using a statistical approach by Munz and Fett (1999). The fatigue lifetime data were fit to a general log-linear model in ALTA PRO software (Reliasoft). Fractographic techniques were used to determine the critical flaw sizes to estimate fracture toughness. To determine the presence of R-curve behavior, non-linear regression was used. Results: Increasing the frequency of cycling did not cause a significant decrease in lifetime. The parameters of the general log-linear model showed that only stress corrosion has a significant effect on lifetime. The parameters are presented in the following table.* SCG parameters (n=19--21) were similar for both frequencies. The regression model showed that the fracture toughness was significantly dependent (p<0.05) on critical flaw size. Conclusions: 1. Cyclic fatigue does not have a significant effect on the SCG in the fluorapatite glass-ceramic IPS e.max ZirPress. 2. There was no interactive effect between cyclic degradation and stress corrosion for this material. 3. The material exhibited a low level of R-curve behavior. It did not exhibit cyclic degradation. *Please refer to dissertation for table.

Influence of various bonding techniques on the fracture strength of thin CAD/CAM-fabricated occlusal glass-ceramic veneers.

PubMed

Yazigi, Christine; Kern, Matthias; Chaar, Mohamed Sad

2017-11-01

To evaluate the efficiency of immediate dentin sealing and the effects of different bonding protocols on the fracture strength of CAD/CAM occlusal veneers bonded to exposed dentin. Ninety-six extracted maxillary premolars were initially divided into three main groups with 32 specimens each: without immediate dentin sealing, immediate dentin sealing/total etching and immediate dentin sealing/selective etching. Teeth were identically prepared in the dentin to receive occlusal veneers of 0.8mm thickness, milled from lithium disilicate ceramic blocks (IPS e.max CAD). Each main group was later subdivided, according to the pre-cementation surface etching protocol (total/selective), into two subgroups with 16 specimens each. All restorations were adhesively bonded using a resin cement (Variolink Esthetic). Half of the specimens of each subgroup were subjected to thermo-dynamic loading in a chewing simulator with 1,200,000 cycles at 10kg load. The other half and the surviving specimens were subjected to quasi-static loading until failure. Statistical analysis was performed using three-way ANOVA and Tukey's post-hoc tests. All specimens except one survived the artificial aging. A significantly higher fracture strength of restorations (p ≤ 0.001) was obtained when immediate dentin sealing was followed regardless of the etching method with values ranging from a minimum of 1122 ± 336N to a maximum of 1853 ± 333N. Neither the pre-cementation treatment nor the artificial aging had a statistical significant effect on the fracture strength. Immediate dentin sealing protocol is recommended whenever dentin is exposed during the preparation for thin glass-ceramic occlusal veneers. Copyright © 2017 Elsevier Ltd. All rights reserved.

LED and Halogen Light Transmission through a CAD/CAM Lithium Disilicate Glass-Ceramic.

PubMed

Pereira, Carolina Nemesio de Barros; De Magalhães, Cláudia Silami; Daleprane, Bruno; Peixoto, Rogéli Tibúrcio Ribeiro da Cunha; Ferreira, Raquel da Conceição; Cury, Luiz Alberto; Moreira, Allyson Nogueira

2015-01-01

The effect of thickness, shade and translucency of CAD/CAM lithium disilicate glass-ceramic on light transmission of light-emitting diode (LED) and quartz-tungsten-halogen units (QTH) were evaluated. Ceramic IPS e.max CAD shades A1, A2, A3, A3.5, high (HT) and low (LT) translucency were cut (1, 2, 3, 4 and 5 mm). Light sources emission spectra were determined. Light intensity incident and transmitted through each ceramic sample was measured to determine light transmission percentage (TP). Statistical analysis used a linear regression model. There was significant interaction between light source and ceramic translucency (p=0.008) and strong negative correlation (R=-0.845, p<0.001) between ceramic thickness and TP. Increasing one unit in thickness led to 3.17 reduction in TP. There was no significant difference in TP (p=0.124) between shades A1 (ß1=0) and A2 (ß1=-0.45) but significant reduction occurred for A3 (ß1=-0.83) and A3.5 (ß1=-2.18). The interaction QTH/HT provided higher TP (ß1=0) than LED/HT (ß1=-2.92), QTH/LT (ß1=-3.75) and LED/LT (ß1=-5.58). Light transmission was more effective using halogen source and high-translucency ceramics, decreased as the ceramic thickness increased and was higher for the lighter shades, A1 and A2. From the regression model (R2=0.85), an equation was obtained to estimate TP value using each variable ß1 found. A maximum TP of 25% for QTH and 20% for LED was found, suggesting that ceramic light attenuation could compromise light cured and dual cure resin cements polymerization.

Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN

PubMed Central

Bardgett, Megan E.; Chen, Qing-Hui; Guo, Qing; Calderon, Alfredo S.; Andrade, Mary Ann

2014-01-01

Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-d-aspartate (NMDA) receptors reduced (P < 0.01) renal SNA and MAP in urethane-chloralose-anesthetized dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P < 0.05) in DH rats. The latter was not explained by increased PVN expression of NMDA receptor NR1 subunit protein, increased PVN neuronal excitability, or decreased brain water content. Interestingly, PVN injection of the pan-specific excitatory amino acid transporter (EAAT) inhibitor dl-threo-β-benzyloxyaspartic acid produced smaller sympathoexcitatory and pressor responses in DH rats, which was associated with reduced glial expression of EAAT2 in PVN. Like chronic hypertension and heart failure, dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases. PMID:24671240

Wear characteristics of polished and glazed lithium disilicate ceramics opposed to three ceramic materials.

PubMed

Saiki, Osamu; Koizumi, Hiroyasu; Akazawa, Nobutaka; Kodaira, Akihisa; Okamura, Kentaro; Matsumura, Hideo

2016-01-01

This study compared the wear characteristics of a heat-pressed lithium disilicate ceramic material opposed to feldspathic porcelain, a lithium disilicate glass ceramic, and zirconia materials. Ceramic plate specimens were prepared from feldspathic porcelain (EX-3 nA1B), lithium disilicate glass ceramics (e.max CAD MO1/C14), and zirconia (Katana KT 10) and then ground or polished. Rounded rod specimens were fabricated from heat-pressed lithium disilicate glass ceramic (e.max press LT A3) and then glazed or polished. A sliding wear testing apparatus was used for wear testing. Wear of glazed rods was greater than that of polished rods when they were abraded with ground zirconia, ground porcelain, polished porcelain, or polished lithium disilicate ceramics. For both glazed and polished rods, wear was greater when the rods were abraded with ground plates. The findings indicate that application of a polished surface rather than a glazed surface is recommended for single restorations made of heat-pressed lithium disilicate material. In addition, care must be taken when polishing opposing materials, especially those used in occlusal contact areas. (J Oral Sci 58, 117-123, 2016).

[Preliminary study of bonding strength between diatomite-based dental ceramic and veneering porcelains].

PubMed

Lu, Xiao-li; Gao, Mei-qin; Cheng, Yu-ye; Zhang, Fei-min

2015-04-01

In order to choose the best veneering porcelain for diatomite-based dental ceramic substrate, the bonding strength between diatomite-based dental ceramics and veneering porcelains was measured, and the microstructure and elements distribution of interface were analyzed. The coefficient of thermal expansion (CTE) of diatomite-based dental ceramics was detected by dilatometry. Three veneering porcelain materials were selected with the best CTE matching including alumina veneering porcelain (group A), titanium porcelain veneering porcelain (group B), and E-max veneering porcelain (group C). Shear bonding strength was detected. SEM and EDS were used to observe the interface microstructure and element distribution. Statistical analysis was performed using SPSS 17.0 software package. The CTE of diatomite-based dental ceramics at 25-500 degrees centigrade was 8.85×10-6K-1. The diatomite-based substrate ceramics combined best with group C. Shear bonding strength between group A and C and group B and C both showed significant differences(P<0.05). SEM and EDS showed that the interface of group C sintered tightly and elements permeated on both sides of the interface. The diatomite-based substrate ceramics combines better with E-max porcelain veneer.

Pharmacokinetic-pharmacodynamic profile of systemic nitric oxide-synthase inhibition with L-NMMA in humans

PubMed Central

Mayer, Bernhard X; Mensik, Christa; Krishnaswami, Sriram; Derendorf, Hartmut; Eichler, Hans-Georg; Schmetterer, Leopold; Wolzt, Michael

1999-01-01

Aims It has been demonstrated that inhibition of endothelium derived nitric oxide with NG-monomethyl-l-arginine (l-NMMA) results in a different cardiac and peripheral vascular response. The purpose of this study was to investigate the pharmacokinetic-pharmacodynamic profile of l-NMMA and pharmacokinetic interactions with l-arginine in healthy subjects. Methods Plasma pharmacokinetics were analysed from two different studies: In study 1, 3 mg kg−1 l-NMMA was administered i.v. over 5 min and systemic haemodynamics, cardiac output (CO), fundus pulsation amplitude (FPA), and NO-exhalation (exhNO) were measured at baseline and 15, 65, 95, 155, and 305 min after start of drug administration (n=7). In study 2, 17 mg kg−1 min−1 of the physiologic substrate for nitric oxide synthase, l-arginine, was coinfused i.v. over 30 min with a primed constant infusion of 50 μg kg−1 min−1 l-NMMA (n=8). Results Bolus infusion of l-NMMA resulted in a maximum plasma concentration of 12.9±3.4 μg ml−1 (mean±s.d.) with elimination half-life of 63.5±14.5 min and clearance of 12.2±3.5 ml min−1 kg−1 and caused a small hypertensive response, decreased CO by 13%, FPA by 26%, exhNO by 46% and increased systemic vascular resistance by 16% (P<0.05 each) 15 min after start of drug administration. Although only limited data points were available in the l-NMMA plasma concentration range between 0 and 4 μg ml−1, drug effects over time were in good agreement with an Emax model (r2>0.98 each), which also suggested that concentrations producing half-maximum effects were higher for FPA than for CO and exhNO. The coinfusion with l-arginine caused a nearly two-fold increase in plasma l-NMMA levels, indicating a pharmacokinetic interaction. Conclusions In the absence of a systemic hypertensive response, l-NMMA significantly decreased CO, exhNO, and FPA. The concentration calculated to produce a half maximal effect was equivalent for exhNO and CO, but markedly higher for FPA. Furthermore, measurement of FPA is susceptible to changes in l-NMMA levels at small plasma concentrations. PMID:10336578

Ceramic materials for porcelain veneers: part II. Effect of material, shade, and thickness on translucency.

PubMed

Barizon, Karine T L; Bergeron, Cathia; Vargas, Marcos A; Qian, Fang; Cobb, Deborah S; Gratton, David G; Geraldeli, Saulo

2014-10-01

Information regarding the differences in translucency among new ceramic systems is lacking. The purpose of this study was to compare the relative translucency of the different types of ceramic systems indicated for porcelain veneers and to evaluate the effect of shade and thickness on translucency. Disk specimens 13 mm in diameter and 0.7-mm thick were fabricated for the following 9 materials (n=5): VITA VM9, IPS Empress Esthetic, VITA PM9, Vitablocks Mark II, Kavo Everest G-Blank, IPS Empress CAD, IPS e.max CAD, IPS e.maxPress, and Lava Zirconia. VITA VM9 served as the positive control and Lava as the negative control. The disks were fabricated with the shade that corresponds to A1. For IPS e.maxPress, additional disks were made with different shades (BL2, BL4, A1, B1, O1, O2, V1, V2, V3), thickness (0.3 mm), and translucencies (high translucency, low translucency). Color coordinates (CIE L∗ a∗ b∗) were measured with a tristimulus colorimeter. The translucency parameter was calculated from the color difference of the material on a black versus a white background. One-way ANOVA, the post hoc Tukey honestly significant difference, and the Ryan-Einot-Gabriel-Welsch multiple range tests were used to analyze the data (α=.05). Statistically significant differences in the translucency parameter were found among porcelains (P<.001) according to the following rank: VM9>PM9, Empress Esthetic>Empress CAD>Mark II, Everest, e.max CAD>e.max Press>Lava. Significant differences also were noted when different shades and thickness were compared (P<.001). Different ceramic systems designed for porcelain veneers present varying degrees of translucency. The thickness and shade of lithium disilicate ceramic affect its translucency. Shade affects translucency parameter less than thickness. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Adjusting dental ceramics: An in vitro evaluation of the ability of various ceramic polishing kits to mimic glazed dental ceramic surface.

PubMed

Steiner, René; Beier, Ulrike S; Heiss-Kisielewsky, Irene; Engelmeier, Robert; Dumfahrt, Herbert; Dhima, Matilda

2015-06-01

During the insertion appointment, the practitioner is often faced with the need to adjust ceramic surfaces to fit a restoration to the adjacent or opposing dentition and soft tissues. The purpose of this study was to assess the ceramic surface smoothness achieved with various commercially available ceramic polishing kits on different commonly used ceramic systems. The reliability of the cost of a polishing kit as an indicator of improved surface smoothness was assessed. A total of 350 ceramic surfaces representing 5 commonly available ceramic systems (IPS Empress Esthetic, IPS e.max Press, Cergo Kiss, Vita PM 9, Imagine PressX) were treated with 5 types of ceramic polishing systems (Cerapreshine, 94006C, Ceramiste, Optrafine, Zenostar) by following the manufacturers' guidelines. The surface roughness was measured with a profilometer (Taylor Hobson; Precision Taylor Hobson Ltd). The effects of ceramic systems and polishing kits of interest on surface roughness were analyzed by 2-way ANOVA, paired t test, and Bonferroni corrected significance level. The ceramic systems and polishing kits statistically affected surface roughness (P<.001).The polishing kit Zenostar on IPS e.max Press created the smoothest ceramic surface. No correlation could be established between the high cost of the polishing kit and low surface roughness. None of the commonly used ceramic polishing kits could create a surface smoother than that of glazed ceramic (P<.001). The inclusion of a diamond polishing paste step is recommended to improve surface smoothness (P<.001). The cost of ceramic polishing kits is not recommended as a reliable indicator of better performance of ceramic polishing kits (P>.30). Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

A novel bronchial ring bioassay for the evaluation of small airway smooth muscle function in mice.

PubMed

Liu, John Q; Yang, Dennis; Folz, Rodney J

2006-08-01

Advances in our understanding of murine airway physiology have been hindered by the lack of suitable, ex vivo, small airway bioassay systems. In this study, we introduce a novel small murine airway bioassay system that permits the physiological and pharmacological study of intrapulmonary bronchial smooth muscle via a bronchial ring (BR) preparation utilizing BR segments as small as 200 microm in diameter. Using this ex vivo BR bioassay, we characterized small airway smooth muscle contraction and relaxation in the presence and absence of bronchial epithelium. In control BRs, the application of mechanical stretch is followed by spontaneous bronchial smooth muscle relaxation. BRs pretreated with methacholine (MCh) partially attenuate this stretch-induced relaxation by as much as 42% compared with control. MCh elicited a dose-dependent bronchial constriction with a maximal tension (E(max)) of 8.7 +/- 0.2 mN at an EC(50) of 0.33 +/- 0.02 microM. In the presence of nifedipine, ryanodine, 2-aminoethoxydiphenyl borate, and SKF-96365, E(max) to MCh was significantly reduced. In epithelium-denuded BRs, MCh-induced contraction was significantly enhanced to 11.4 +/- 1.0 mN with an EC(50) of 0.16 +/- 0.04 microM (P < 0.01). Substance P relaxed MCh-precontracted BR by 62.1%; however, this bronchial relaxation effect was completely lost in epithelium-denuded BRs. Papaverine virtually abolished MCh-induced constriction in both epithelium-intact and epithelium-denuded bronchial smooth muscle. In conclusion, this study introduces a novel murine small airway BR bioassay that allows for the physiological study of smooth muscle airway contractile responses that may aid in our understanding of the pathophysiology of asthma.

Concentration-effect relationship of levodopa in patients with Parkinson's disease after oral administration of an immediate release and a controlled release formulation.

PubMed Central

Harder, S; Baas, H; Bergemann, N; Demisch, L; Rietbrock, S

1995-01-01

1. The relationship between plasma concentration of levodopa and motor-response was investigated in 12 patients with Parkinson's disease who showed marked response fluctuations, after a single oral dose of an immediate release (IR) formulation (100 mg levodopa/25 mg genserazide) and a controlled release (CR) formulation (300 mg levodopa/75 mg benserazide), using a double-blind, randomized, cross-over design. 2. The sum score of the Columbia University Rating Scale (CURS sigma) was used for pharmacodynamic assessment. A sigmoidal Emax-model was fitted to the data using a semiparametric pharmacokinetic/dynamic approach. 3. The dose-corrected AUC of levodopa after the IR-formulation was 27.5 (+/- 9.1 s.d.) ng ml-1 h per mg and 23.2 (+/- 4.6 s.d.) ng ml-1 h per mg after the CR-formulation. Cmax was 1714 (+/- 1027 s.d.) ng ml-1 after the IR-formulation and 1494 (+/- 383 s.d.) ng ml-1 after the CR-formulation. 4. With both preparations, the maximal response to levodopa (Emax) was a decrease in the CURS sigma rating of about 27 scores. Estimates of the EC50 of levodopa were 495 (+/- 144 s.d.) ng ml-1 (IR) and 1024 (+/- 502 s.d.) ng ml-1 (CR), respectively (95%-CI: 1.51-2.66, point estimator 1.95). The mean duration of the motor response was 1.9 (+/- 0.5 s.d.) h (IR) and 2.8 (+/- 0.7 s.d.) h (CR), respectively (95%-CI: 1.12-2.04, point estimator 1.53).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7756097

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

PubMed Central

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple Emax model with a fixed E0, which provided a common Emax and an approximate twofold difference in ED50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries. PMID:21151159

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients.

PubMed

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E(max) model with a fixed E(0), which provided a common E(max) and an approximate twofold difference in ED(50) for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.

Pharmacokinetics and Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone, After Intranasal Administration in Recreational Drug Users.

PubMed

Mickle, Travis C; Guenther, Sven M; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Dickerson, Daniel; Webster, Lynn R

2017-10-28

Developing an acetaminophen-free, immediate-release hydrocodone product remains an unmet medical need; however, new opioid analgesics should not introduce new abuse risks. Benzhydrocodone is a prodrug of hydrocodone that must be metabolized into hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. This study evaluated the intranasal pharmacokinetics and abuse potential of benzhydrocodone active pharmaceutical ingredient (API) compared with hydrocodone bitartrate (HB) API. Single-center, randomized, double-blind, crossover study. Clinical research site. Healthy adult, nondependent, recreational opioid users. Subjects (N = 51 Completers) were randomized to receive 13.34 mg of intranasal benzhydrocodone API and 15.0 mg of intranasal HB API (molar-equivalent doses of hydrocodone). Blood samples were taken, and Drug Liking scores (assessed on a bipolar visual analog scale) were obtained throughout each dosing interval. Nasal irritation and safety were assessed. Peak hydrocodone plasma concentration (Cmax) was 36.0% lower, and total hydrocodone exposures (AUClast and AUCinf) were 20.3% and 19.5% lower, respectively, for benzhydrocodone API compared with HB API (P < 0.0001). All partial AUC values were lower for benzhydrocodone API, with a ≥ 75% reduction in hydrocodone exposure at all time intervals up to one hour postdose (P < 0.0001). Median Tmax of hydrocodone following benzhydrocodone API was delayed by more than one hour compared with HB. Drug Liking score, as assessed by maximal liking (Emax), was significantly lower for benzhydrocodone API vs HB API (P = 0.004), with 45% of subjects showing a ≥ 30% reduction in Drug Liking Emax. Reductions in hydrocodone exposure and associated decreases in Drug Liking relative to HB suggest that the prodrug benzhydrocodone may deter intranasal abuse. © 2017 American Academy of Pain Medicine.

Bayesian design criteria: computation, comparison, and application to a pharmacokinetic and a pharmacodynamic model.

PubMed

Merlé, Y; Mentré, F

1995-02-01

In this paper 3 criteria to design experiments for Bayesian estimation of the parameters of nonlinear models with respect to their parameters, when a prior distribution is available, are presented: the determinant of the Bayesian information matrix, the determinant of the pre-posterior covariance matrix, and the expected information provided by an experiment. A procedure to simplify the computation of these criteria is proposed in the case of continuous prior distributions and is compared with the criterion obtained from a linearization of the model about the mean of the prior distribution for the parameters. This procedure is applied to two models commonly encountered in the area of pharmacokinetics and pharmacodynamics: the one-compartment open model with bolus intravenous single-dose injection and the Emax model. They both involve two parameters. Additive as well as multiplicative gaussian measurement errors are considered with normal prior distributions. Various combinations of the variances of the prior distribution and of the measurement error are studied. Our attention is restricted to designs with limited numbers of measurements (1 or 2 measurements). This situation often occurs in practice when Bayesian estimation is performed. The optimal Bayesian designs that result vary with the variances of the parameter distribution and with the measurement error. The two-point optimal designs sometimes differ from the D-optimal designs for the mean of the prior distribution and may consist of replicating measurements. For the studied cases, the determinant of the Bayesian information matrix and its linearized form lead to the same optimal designs. In some cases, the pre-posterior covariance matrix can be far from its lower bound, namely, the inverse of the Bayesian information matrix, especially for the Emax model and a multiplicative measurement error. The expected information provided by the experiment and the determinant of the pre-posterior covariance matrix generally lead to the same designs except for the Emax model and the multiplicative measurement error. Results show that these criteria can be easily computed and that they could be incorporated in modules for designing experiments.

A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.

PubMed

Simon, N; Viallet, F; Boulamery, A; Eusebio, A; Gayraud, D; Azulay, J-P

2016-04-01

Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia. Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study. They received a single dose of levodopa equal to 150 % of their usual daily dose. Blood samples, motor evaluations (UPDRS III scale) and peak-dose dyskinesia (Goetz scale) were examined after administration. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed using NONMEM software. Pharmacokinetic analysis identified a one-compartment model with the following parameter values [bootstrap 95 % CI]: absorption rate constant (KA) 1.86 1/h [1.08-3.25], clearance 36.6 L/h [31.3-42.8], and volume of distribution 42.9 L [34.3-52.3]. Between-subject variability was 122 % [71-183] and 38 % [26-47] for KA and clearance, respectively. Residual variability was 1120 μg/L [886-1290]. UPDRS III and dyskinesia were best described with an effect compartment and similar KE0 values of 1.37 1/h [1.01-1.77]. For UPDRS III, the E0, EC50, Emax, and Hill coefficient were 31.4 [28.4-35.3], 1410 μg/L [1200-1700], 0.72 [0.71-0.75], and 4.26 [3.20-5.58], respectively. For dyskinesia, the EC50 and Emax were 6280 μg/L [3420-37,900] and 17.9 [12.3-80.8], respectively. Residual variability was 3.15 [2.75-3.53] for UPDRS III and 2.66 [1.94-3.51] for dyskinesia. No covariates influenced the parameters. In patients treated with levodopa and suffering from dyskinesia, the motor response and dyskinesia have close onsets and duration effects. Maximal motor response tends to be inevitably associated with dyskinesia.

In vitro pharmacodynamics of gamithromycin against Mycoplasma mycoides subspecies mycoides Small Colony.

PubMed

Mitchell, John D; Goh, Shan; McKellar, Quintin A; McKeever, Declan J

2013-09-01

Mycoplasma mycoides mycoides Small Colony (MmmSC) is the causative agent of contagious bovine pleuropneumonia (CBPP), which is responsible for major economic losses in sub-Saharan Africa. Current control relies on live attenuated vaccines, which are of limited efficacy, and antimicrobials are now being assessed as an alternative or adjunct to vaccination. The objective of this study was to determine the in vitro effector kinetics of the macrolide antimicrobial, gamithromycin, against MmmSC in artificial medium and adult bovine serum. Furthermore, it was determined if any differences in gamithromycin activity between these two matrices were mirrored by the older macrolides, tylosin and tilmicosin. Minimum inhibitory concentrations (MICs) for gamithromycin, tylosin and tilmicosin against MmmSC strains B237 and Tan8 were determined in artificial medium and serum. Time-kill curves were constructed at concentrations corresponding to multiples of the MIC for all three macrolides in artificial medium and for gamithromycin in serum. Data were fitted to sigmoid Emax models. Post-antibiotic effects (PAE) were established by exposing strain B237 to antimicrobials at 10× MIC for 1h and monitoring mycoplasma growth thereafter. MICs for gamithromycin, tylosin and tilmicosin were 64-, 8- and 64-fold lower, respectively, in serum than in artificial medium at an inoculum size of 10(6)cfu/mL B237. A similar pattern emerged for Tan8. All three antimicrobials were mycoplasmastatic with maximum effects of -0.44, -0.32 and -0.49log10(cfu/mL) units for gamithromycin, tylosin and tilmicosin, respectively, against B237 in artificial medium. Tylosin and tilmicosin elicited longer PAEs than gamithromycin. In conclusion, gamithromycin, tylosin and tilmicosin all demonstrated in vitro efficacy against MmmSC and represent potential candidates for clinical studies to assess their therapeutic effect against CBPP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dose-response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes.

PubMed

Hayato, Seiichi; Hasegawa, Setsuo; Hojo, Seiichiro; Okawa, Hiroki; Abe, Hiroaki; Sugisaki, Nobuyuki; Munesue, Masahiro; Horai, Yukio; Ohnishi, Akihiro

2012-05-01

This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (-5.0% -21.0%), 28.7% (15.7% -41.6%), and 16.9% (3.9% -29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC(0-t)) and the pH 4 holding time could be described using a sigmoid maximum effect (E(max)) model. Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion.

Anti-Inflammatory Components from the Root of Solanum erianthum

PubMed Central

Chen, Yu-Chang; Lee, Hong-Zin; Chen, Hsin-Chun; Wen, Chi-Luan; Kuo, Yueh-Hsiung; Wang, Guei-Jane

2013-01-01

Two new norsesquiterpenoids, solanerianones A and B (1–2), together with nine known compounds, including four sesquiterpenoids, (−)-solavetivone (3), (+)-anhydro-β-rotunol (4), solafuranone (5), lycifuranone A (6); one alkaloid, N-trans-feruloyltyramine (7); one fatty acid, palmitic acid (8); one phenylalkanoid, acetovanillone (9), and two steroids, β-sitosterol (10) and stigmasterol (11) were isolated from the n-hexane-soluble part of the roots of Solanum erianthum. Their structures were elucidated on the basis of physical and spectroscopic data analyses. The anti-inflammatory activity of these isolates was monitored by nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells. The cytotoxicity towards human lung squamous carcinoma (CH27), human hepatocellular carcinoma (Hep 3B), human oral squamous carcinoma (HSC-3) and human melanoma (M21) cell lines was also screened by using an MTT assay. Of the compounds tested, 3 exhibited the strongest NO inhibition with the average maximum inhibition (Emax) at 100 μM and median inhibitory concentration (IC50) values of 98.23% ± 0.08% and 65.54 ± 0.18 μM, respectively. None of compounds (1–9) was found to possess cytotoxic activity against human cancer cell lines at concentrations up to 30 μM. PMID:23771024

Fracture strength testing of crowns made of CAD/CAM composite resins.

PubMed

Okada, Ryota; Asakura, Masaki; Ando, Akihiro; Kumano, Hirokazu; Ban, Seiji; Kawai, Tatsushi; Takebe, Jun

2018-03-28

The purpose of this study was to ascertain whether computer aided design/computer aided manufacturing (CAD/CAM) composite resin crowns have sufficient strength to withstand the bite force of the molar teeth. The null hypothesis was that the fracture strength of CAD/CAM composite resin crowns is lower than the average maximum bite force of the molar tooth. The crowns, which shape is the right maxillary first molar, were fabricated using four CAD/CAM blanks made of composite resins (Block HC: HC, KZR-CAD HR: HR, KZR-CAD HR2: HR2, Avencia Block: AVE) and one CAD/CAM blank made of lithium disilicate glass-ceramic (IPS e.max CAD: IPS), which was used as a control. Fracture strength of fabricated crowns bonded to metal abutment and biaxial flexural strength of the materials were evaluated. The results of fracture strength test and biaxial flexural strength test showed different tendencies. The fracture strength of CAD/CAM composite resin crowns except HC ranged from 3.3kN to 3.9kN, and was similar to that of IPS (3.3kN). In contrast, biaxial flexural strength of CAD/CAM composite resins ranged from 175MPa to 247MPa, and was significantly lower than that of IPS (360MPa). All CAD/CAM composite resin crowns studied presented about 3-4 times higher fracture strength than the average maximum bite force of the molar tooth (700-900N), which result leads to the conclusion that CAD/CAM composite resin crowns would have sufficient strength to withstand the bite force of the molar teeth. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Diagnostic performances of shear wave elastography: which parameter to use in differential diagnosis of solid breast masses?

PubMed

Lee, Eun Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Lee, Jong Tae; Yoon, Jung Hyun

2013-07-01

To evaluate which shear wave elastography (SWE) parameter proves most accurate in the differential diagnosis of solid breast masses. One hundred and fifty-six breast lesions in 139 consecutive women (mean age: 43.54 ± 9.94 years, range 21-88 years), who had been scheduled for ultrasound-guided breast biopsy, were included. Conventional ultrasound and SWE were performed in all women before biopsy procedures. Ultrasound BI-RADS final assessment and SWE parameters were recorded. Diagnostic performance of each SWE parameter was calculated and compared with those obtained when applying cut-off values of previously published data. Performance of conventional ultrasound and ultrasound combined with each parameter was also compared. Of the 156 breast masses, 120 (76.9 %) were benign and 36 (23.1 %) malignant. Maximum stiffness (Emax) with a cut-off of 82.3 kPa had the highest area under the receiver operating characteristics curve (Az) value compared with other SWE parameters, 0.860 (sensitivity 88.9 %, specificity 77.5 %, accuracy 80.1 %). Az values of conventional ultrasound combined with each SWE parameter showed lower (but not significantly) values than with conventional ultrasound alone. Maximum stiffness (82.3 kPa) provided the best diagnostic performance. However the overall diagnostic performance of ultrasound plus SWE was not significantly better than that of conventional ultrasound alone. • SWE offers new information over and above conventional breast ultrasound • Various SWE parameters were explored regarding distinction between benign and malignant lesions • An elasticity of 82.3 kPa appears optimal in differentiating solid breast masses • However, ultrasound plus SWE was not significantly better than conventional ultrasound alone.

78 FR 40506 - Certain Toner Cartridges and Components Thereof; Issuance of General Exclusion Order and Cease...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

..., China; Zhuhai Rich Imaging Technology Co., Ltd. of Guangdong, China; Standard Image Co., Ltd. (a/ k/a.... (d/b/a Huebon Co., Ltd., d/b/a Ink-Tank) of Guangdong, China; Standard Image USA, Inc. (d/b/a Imaging... ) of San Antonio, Texas; Do It Wiser LLC (d/b/a Image Toner) of Marietta, Georgia; E-Max Group, Inc. (d...

Crystal scintillators for use in check-light source for thermoluminescent systems

NASA Astrophysics Data System (ADS)

Nagpal, J. S.; Sabharwal, S. C.; Chougaonkar, M. P.; Godbole, S. V.

1999-08-01

Beta ( 63Ni, Emax 0.063 MeV) excited radioluminescence of indigenously grown crystal scintillators CsI(Tl), Bi 4Ge 3O 12 and CdWO 4 has been studied for its use in check-light source needed for thermoluminescence systems. Temperature coefficient of the light output over 298-323 K and the beta-induced TL of the scintillators over 298-553 K are reported.

A comparative study of sliding wear of nonmetallic dental restorative materials with emphasis on micromechanical wear mechanisms.

PubMed

Dupriez, Nataliya Deyneka; von Koeckritz, Ann-Kristin; Kunzelmann, Karl-Heinz

2015-05-01

The purpose of this study is to investigate the in vitro tribological behavior of modern nonmetallic restorative materials. Specimen prepared of IPS e.max Press lithium disilicate glass ceramic, IPS Empress Esthetic leucite-reinforced glass ceramic, Everest ZS Blanks yttria-stabilized zirconia and Lava Ultimate composite were subjected to wear using a wear machine designed to simulate occlusal loads. The wear of the investigated materials and antagonists were evaluated by a three-dimensional surface scanner. The quantitative wear test results were used to compare and rank the materials. Specimens were divided into two groups with steatite and alumina antagonists. For each antagonist material an analysis of variance was applied. As a post hoc test of the significant differences, Tukey's honest significant difference test was used. With steatite antagonist: wear of zirconia < wear of leucite-reinforced ceramic < wear of lithium disilicate ceramic < wear of Lava Ultimate composite. No significant wear difference was found for steatite antagonist. The wear of IPS e.max Press and Lava Ultimate against hard alumina was found to be twice lower as compared to their wear when opposing to steatite. The differences were associated with materials mechanical properties (hardness and fracture toughness) and with materials microstructure. Wear mechanisms are discussed. © 2014 Wiley Periodicals, Inc.

Integrating three-dimensional digital technologies for comprehensive implant dentistry.

PubMed

Patel, Neal

2010-06-01

The increase in the popularity of and the demand for the use of dental implants to replace teeth has encouraged advancement in clinical technology and materials to improve patients' acceptance and clinical outcomes. Recent advances such as three-dimensional dental radiography with cone-beam computed tomography (CBCT), precision dental implant planning software and clinical execution with guided surgery all play a role in the success of implant dentistry. The author illustrates the technique of comprehensive implant dentistry planning through integration of computer-aided design/computer-aided manufacturing (CAD/CAM) and CBCT data. The technique includes clinical treatment with guided surgery, including the creation of a final restoration with a high-strength ceramic (IPS e.max CAD, Ivoclar Vivadent, Amherst, N.Y.). The author also introduces a technique involving CAD/CAM for fabricating custom implant abutments. The release of software integrating CEREC Acquisition Center with Bluecam (Sirona Dental Systems, Charlotte, N.C.) chairside CAD/CAM and Galileos CBCT imaging (Sirona Dental Systems) allows dentists to plan implant placement, perform implant dentistry with increased precision and provide predictable restorative results by using chairside IPS e.max CAD. The precision of clinical treatment provided by the integration of CAD/CAM and CBCT allows dentists to plan for ideal surgical placement and the appropriate thickness of restorative modalities before placing implants.

Effects of intra-aortic balloon pump counterpulsation on left ventricular mechanoenergetics in a porcine model of acute ischemic heart failure.

PubMed

Malliaras, Konstantinos; Charitos, Efstratios; Diakos, Nikolaos; Pozios, Iraklis; Papalois, Apostolos; Terrovitis, John; Nanas, John

2014-12-01

We investigated the effects of intra-aortic balloon pump (IABP) counterpulsation on left ventricular (LV) contractility, relaxation, and energy consumption and probed the underlying physiologic mechanisms in 12 farm pigs, using an ischemia-reperfusion model of acute heart failure. During both ischemia and reperfusion, IABP support unloaded the LV, decreased LV energy consumption (pressure-volume area, stroke work), and concurrently improved LV mechanical performance (ejection fraction, stroke volume, cardiac output). During reperfusion exclusively, IABP also improved LV relaxation (tau) and contractility (Emax, PRSW). The beneficial effects of IABP support on LV relaxation and contractility correlated with IABP-induced augmentation of coronary blood flow. In conclusion, we find that during both ischemia and reperfusion, IABP support optimizes LV energetic performance (decreases energy consumption and concurrently improves mechanical performance) by LV unloading. During reperfusion exclusively, IABP support also improves LV contractility and active relaxation, possibly due to a synergistic effect of unloading and augmentation of coronary blood flow.

The effect of heat treatments applied to superstructure porcelain on the mechanical properties and microstructure of lithium disilicate glass ceramics.

PubMed

Özdemir, Hatice; Özdoğan, Alper

2018-01-30

The aim of this study was to investigate that heat treatments with different numbers applied to superstructure porcelain whether effects microstructure and mechanical properties of lithium disilicate ceramic (LDC). Eighty disc-shaped specimens were fabricated from IPS e.max Press. Specimens were fired at heating values of porcelain in different numbers and divided four groups (n=5). Initial Vickers hardness were measured and X-ray diffraction (XRD) analysis was performed. Different surface treatment were applied and then Vickers hardness, surface roughness and environmental scanning electron microscopy (ESEM) analysis were performed. Data were analyzed with Varyans analysis and Tukey HSD test (α=0.05). Initial hardness among groups was no significant different (p>0.05), but hardness and surface roughness after surface treatments were significant different (p<0.05). Lithium disilicate (LD) peaks decrease depended on firing numbers. ESEM observations showed that firing number and surface treatments effect microstructure of LDC. Increasing firing numbers and surface treatments effect the microstructure of LDC.

Stability criteria for wide binary stars harboring Oort Clouds

NASA Astrophysics Data System (ADS)

Calandra, M. F.; Correa-Otto, J. A.; Gil-Hutton, R. A.

2018-03-01

Context. In recent years, several numerical studies have been done in the field of the stability limit. Although, many of them included the analysis of asteroids or planets, is not possible to find in the literature any work on how the presence of a binary star could affect other possible configurations in a three-body problem. In order to develop this subject we consider other structures like Oort Clouds in wide binary systems. Regarding the existence of Oort Clouds in extrasolar systems there are recent works that do not reject its possible existence. Aim. The aim of this work is to obtain the stability limit for Oort Cloud objects considering different masses of the secondary star and zero and non-zero inclinations of the particles. We improve our numerical treatment getting a mathematical fit that allows us to find the limit and compare our results with other previous works in the field. Methods: We use a symplectic integrator to integrate binary systems where the primary star is m1 = 1 M⊙ and the secondary, m2, takes 0.25 M⊙ and 0.66 M⊙ in two sets of simulations S1 and S2. The orbital parameters of the secondary star were varied in order to study different scenarios. We also used two different integration times (one shorter than the other) and included the presence of 1000 to 10 000 massless particles in circular orbits to form the Oort Cloud. The particles were disposed in four different inclination planes to investigate how the presence of the binary companion could affect the stability limit. Results: Using the Maximum Eccentricity Method, emax, together with the critical semimajor axis acrit we found that the emax criteria could reduce the integration times to find the limit. For those cases where the particles were in inclined orbits we found that there are particle groups that survive the integration time with a high eccentricity. These particle groups are found for our two sets of simulations, meaning that they are independent of the secondary mass. We also find for the co-planar case that the numerical value of the stability limit for retrograde orbits is higher than those found for prograde orbits. These results are in agreement with several published studies. Finally, the results obtained in this work allow us to build a numerical expression depending of the mass ratio, e2 and ip to find acrit, which can be compared with other recent works in the field.

Dissociation of end systole from end ejection in patients with long-term mitral regurgitation.

PubMed

Brickner, M E; Starling, M R

1990-04-01

To determine whether left ventricular (LV) end systole and end ejection uncouple in patients with long-term mitral regurgitation, 59 patients (22 control patients with atypical chest pain, 21 patients with aortic regurgitation, and 16 patients with mitral regurgitation) were studied with micromanometer LV catheters and radionuclide angiograms. End systole was defined as the time of occurrence (Tmax) of the maximum time-varying elastance (Emax), and end ejection was defined as the time of occurrence of minimum ventricular volume (minV) and zero systolic flow as approximated by the aortic dicrotic notch (Aodi). The temporal relation between end systole and end ejection in the control patients was Tmax (331 +/- 42 [SD] msec), minV (336 +/- 36 msec), and then, zero systolic flow (355 +/- 23 msec). This temporal relation was maintained in the patients with aortic regurgitation. In contrast, in the patients with mitral regurgitation, the temporal relation was Tmax (266 +/- 49 msec), zero systolic flow (310 +/- 37 msec, p less than 0.01 vs. Tmax), and then, minV (355 +/- 37 msec, p less than 0.001 vs. Tmax and p less than 0.01 vs. Aodi). Additionally, the average Tmax occurred earlier in the patients with mitral regurgitation than in the control patients and patients with aortic regurgitation (p less than 0.01, for both), whereas the average time to minimum ventricular volume was similar in all three patient groups. Moreover, the average time to zero systolic flow also occurred earlier in the patients with mitral regurgitation than in the control patients (p less than 0.01) and patients with aortic regurgitation (p less than 0.05). Because of the dissociation of end systole from minimum ventricular volume in the patients with mitral regurgitation, the end-ejection pressure-volume relations calculated at minimum ventricular volume did not correlate (r = -0.09), whereas those calculated at zero systolic flow did correlate (r = 0.88) with the Emax slope values. We conclude that end ejection, defined as minimum ventricular volume, dissociates from end systole in patients with mitral regurgitation because of the shortened time to LV end systole in association with preservation of the time to LV end ejection due to the low impedance to ejection presented by the left atrium. Therefore, pressure-volume relations calculated at minimum ventricular volume might not be useful for assessing LV chamber performance in some patients with mitral regurgitation.

Ontology-driven data integration and visualization for exploring regional geologic time and paleontological information

NASA Astrophysics Data System (ADS)

Wang, Chengbin; Ma, Xiaogang; Chen, Jianguo

2018-06-01

Initiatives of open data promote the online publication and sharing of large amounts of geologic data. How to retrieve information and discover knowledge from the big data is an ongoing challenge. In this paper, we developed an ontology-driven data integration and visualization pilot system for exploring information of regional geologic time, paleontology, and fundamental geology. The pilot system (http://www2.cs.uidaho.edu/%7Emax/gts/)

Characterization of the Chemical Constitution and Profile of Pharmacological Activity of PGB(x).

DTIC Science & Technology

1982-02-26

ischemia. Fed. Proc. 40 , 692 (1980). 3. Burkman, A. M. and Phornchirasilp, S., Prostaglandin Bx enhances the inotropic efficacy (Emax) of...nitroketone 10 was then converted to the sodium salt of the corresponding nitronic acid on treatment with an equimolar amount of sodium metabolite in...bromide in chloroform-ethyl acetate to give unsaturated aldehyde 12 in 40 ’ yield. The reaction of compound 9 with dimethyl (2-oxoheptvl) phosphonate in

Fracture, roughness and phase transformation in CAD/CAM milling and subsequent surface treatments of lithium metasilicate/disilicate glass-ceramics.

PubMed

Alao, Abdur-Rasheed; Stoll, Richard; Song, Xiao-Fei; Abbott, John R; Zhang, Yu; Abduo, Jaafar; Yin, Ling

2017-10-01

This paper studied surface fracture, roughness and morphology, phase transformations, and material removal mechanisms of lithium metasilicate/disilicate glass ceramics (LMGC/LDGC) in CAD/CAM-milling and subsequent surface treatments. LMGC (IPS e.max CAD) blocks were milled using a chairside dental CAD/CAM milling unit and then treated in sintering, polishing and glazing processes. X-ray diffraction was performed on all processed surfaces. Scanning electron microscopy (SEM) was applied to analyse surface fracture and morphology. Surface roughness was quantitatively characterized by the arithmetic average surface roughness R a and the maximum roughness R z using desktop SEM-assisted morphology analytical software. The CAD/CAM milling induced extensive brittle cracks and crystal pulverization on LMGC surfaces, which indicate that the dominant removal mechanism was the fracture mode. Polishing and sintering of the milled LMGC lowered the surface roughness (ANOVA, p < 0.05), respectively, while sintering also fully transformed the weak LMGC to the strong LDGC. However, polishing and glazing of LDGC did not significantly improve the roughness (ANOVA, p > 0.05). In comparison of all applied fabrication process routes, it is found that CAD/CAM milling followed by polishing and sintering produced the smoothest surface with R a = 0.12 ± 0.08µm and R z = 0.89 ± 0.26µm. Thus , it is proposed as the optimized process route for LMGC/LDGC in dental restorations. This route enables to manufacture LMGC/LDGC restorations with cost effectiveness, time efficiency, and improved surface quality for better occlusal functions and reduced bacterial plaque accumulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Altered disposition and effect of lerisetron in rats with elevated alpha 1-acid glycoprotein levels.

PubMed

Jauregizar, N; Calvo, R; Suarez, E; Quintana, A; Raczka, E; Lukas, J C

2001-06-01

To examine the effect of changes in plasma alpha1-acid glycoprotein (AAG) levels on the pharmacokinetics (PK) and pharmacodynamics (PD) of lerisetron, a novel serotonin 5-HT3 receptor antagonist, in the rat. After subcutaneous administration of turpentine oil, AAG was significantly elevated compared with controls. The PK of unchanged lerisetron (UL; high-performance liquid chromatography with radioactivity monitoring) and total lerisetron (TL; unchanged + changed, scintillation counting) was characterized post intravenous (i.v.) 14C lerisetron (50 microg/kg) in control and turpentine oil pretreated rats. The PK (0-180 min) was described by a two-compartmental model. Protein binding of lerisetron in vitro was measured using an ultrafiltration technique. The effect of lerisetron (5 microg/kg, i.v.) over 180 min was measured in anesthetized rats (control and pretreated) with the Bezold-Jarisch reflex (inhibition of bradycardia after 16 microg/kg serotonin i.v.) as the endpoint. PD parameters were estimated by sigmoid Emax models. The unbound fraction was significantly diminished in pretreated rats (mean +/- SEM) (6.60 +/- 1.23% vs. control 14.4 +/- 1.40%, P < 0.05). Volume of distribution (V) and clearance for UL and TL were significantly decreased when compared to the controls (P < 0.0001 for UL and P < 0.05 for TL). Plasma clearance based on unbound concentration for UL did not differ between groups but the unbound V and steady-state unbound V remained decreased (P < 0.05 and P < 0.0001). Pretreated rats showed a significantly diminished drug effect: the area under the E-t curve over 180 min was (mean +/- SEM) 5,189 +/- 657.7 in control animals vs. 3,486 +/- 464.4 in the pretreated group (P < 0.05). The EC50 (concentration at half maximum effect) for UL and TL were increased in pretreated rats and were not compensated when the unbound concentration was used. An increase in AAG causes alterations in the PK and PD of lerisetron, and because this is not compensated with the unbound concentration, we suggest that mechanisms not linked to protein binding may be involved.

Bradycardia and Hypothermia Complicating Azithromycin Treatment.

PubMed

Benn, Kerri; Salman, Sam; Page-Sharp, Madhu; Davis, Timothy M E; Buttery, Jim P

2017-08-11

BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35.2°C) and bradycardia (65 beats/minute) after the second dose, which resolved over several days post-treatment, consistent with persistence of high tissue azithromycin concentrations relative to those in plasma. A sigmoid Emax pharmacokinetic/pharmacodynamic model suggested a maximal azithromycin-associated reduction in heart rate of 23 beats/minute. Monitoring for these potential adverse effects should facilitate appropriate supportive care in similar cases. CONCLUSIONS Recommended azithromycin doses can cause at least moderate bradycardia and hypothermia in vulnerable pediatric patients, adverse effects that should prompt appropriate monitoring and which may take many days to resolve.

Enhanced strain effect of aged acceptor-doped BaTiO3 ceramics with clamping domain structures

NASA Astrophysics Data System (ADS)

Wang, Lei; Zhou, Zhiyong; Zhao, Xiaobo; Liu, Zhen; Liang, Ruihong; Dong, Xianlin

2017-03-01

A clamping domain structure is proposed to improve the amount of non-180° domain switching in BaTiO3 based piezoelectric ceramics. Experimental results show a large unipolar strain of 0.23% at 5 kV/mm in aged 0.5 mol. % Mn doped BaTiO3 ceramics with clamping domain structures, and the normalized strain (d33*= Smax/Emax) reaches 600 pm/V at low electric fields of 2 or 3 kV/mm. In contrast, pure BaTiO3 ceramics with clamping domain structures exhibit no clear polarization constriction or strain enhancement at 3 kV/mm. Electron paramagnetic resonance spectra verify the existence of titanium vacancies, Mn2+ and Mn4+, in 0.5 mol. % Mn doped BaTiO3 ceramics. These results indicate that the enhanced strain effect can be attributed to the combined effect of the clamping domain structure and stabilization of defect dipoles. This method provides a general way to obtain large strain in ferroelectrics.

Large Electrocaloric Effect in Lead-Free (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3 Ceramics Prepared via Citrate Route

PubMed Central

Shi, Jing; Zhu, Rongfeng; Liu, Xing; Yuan, Ningyi; Ding, Jianning; Luo, Haosu

2017-01-01

The 1 wt % Li-doped (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3 (BCZT-Li) ceramics prepared by the citrate method exhibit improved phase purity, densification and electrical properties, which provide prospective possibility to develop high-performance electrocaloric materials. The electrocaloric effect was evaluated by phenomenological method, and the BCZT-Li ceramics present large electrocaloric temperature change ∆T, especially large electrocaloric responsibility ξ = ∆Tmax/∆Emax, which can be comparable to the largest values reported in the lead-free piezoelectric ceramics. The excellent electrocaloric effect is considered as correlating with the coexistence of polymorphic ferroelectric phases, which are detected by the Raman spectroscopy. The large ξ value accompanied by decreased Curie temperature (around 73 °C) of the BCZT-Li ceramics prepared by the citrate method presents potential applications as the next-generation solid-state cooling devices. PMID:28927004

Chairside CAD/CAM materials. Part 3: Cyclic fatigue parameters and lifetime predictions.

PubMed

Wendler, Michael; Belli, Renan; Valladares, Diana; Petschelt, Anselm; Lohbauer, Ulrich

2018-06-01

Chemical and mechanical degradation play a key role on the lifetime of dental restorative materials. Therefore, prediction of their long-term performance in the oral environment should base on fatigue, rather than inert strength data, as commonly observed in the dental material's field. The objective of the present study was to provide mechanistic fatigue parameters of current dental CAD/CAM materials under cyclic biaxial flexure and assess their suitability in predicting clinical fracture behaviors. Eight CAD/CAM materials, including polycrystalline zirconia (IPS e.max ZirCAD), reinforced glasses (Vitablocs Mark II, IPS Empress CAD), glass-ceramics (IPS e.max CAD, Suprinity PC, Celtra Duo), as well as hybrid materials (Enamic, Lava Ultimate) were evaluated. Rectangular plates (12×12×1.2mm 3 ) with highly polished surfaces were prepared and tested in biaxial cyclic fatigue in water until fracture using the Ball-on-Three-Balls (B3B) test. Cyclic fatigue parameters n and A* were obtained from the lifetime data for each material and further used to build SPT diagrams. The latter were used to compare in-vitro with in-vivo fracture distributions for IPS e.max CAD and IPS Empress CAD. Susceptibility to subcritical crack growth under cyclic loading was observed for all materials, being more severe (n≤20) in lithium-based glass-ceramics and Vitablocs Mark II. Strength degradations of 40% up to 60% were predicted after only 1 year of service. Threshold stress intensity factors (K th ) representing the onset of subcritical crack growth (SCG), were estimated to lie in the range of 0.37-0.44 of K Ic for the lithium-based glass-ceramics and Vitablocs Mark II and between 0.51-0.59 of K Ic for the other materials. Failure distributions associated with mechanistic estimations of strength degradation in-vitro showed to be useful in interpreting failure behavior in-vivo. The parameter K th stood out as a better predictor of clinical performance in detriment to the SCG n parameter. Fatigue parameters obtained from cyclic loading experiments are more reliable predictors of the mechanical performance of contemporary dental CAD/CAM restoratives than quasi-static mechanical properties. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Anticraving Effect of Baclofen in Alcohol-Dependent Patients.

PubMed

Imbert, Bruce; Alvarez, Jean-Claude; Simon, Nicolas

2015-09-01

Baclofen is a GABA-B receptor agonist currently used in the treatment of spasticity. In recent years, baclofen has been used to reduce craving, voluntary alcohol intake and withdrawal syndrome of alcoholic patients. To date, there are no data available to estimate the relationship between baclofen exposure and the variation of craving. The first objective of this study was to investigate the variation of craving as a function of exposure, and the second was to explore the possible existence of baclofen responders and nonresponders. Sixty-seven outpatients, 43 men/24 women (weight: 73 kg [42 to 128]; age: 49 years old [29 to 68]) followed in the addictology unit, were studied during 3 months after treatment initiation. Baclofen was administered by oral route. Therapeutic drug monitoring enabled the measurement of plasma concentrations. Craving level was assessed by the Obsessive-Compulsive Drinking Scale (OCDS). A population pharmacokinetic (PK)-pharmacodynamic analysis of the OCDS variation following baclofen administration was performed. Demographic data, biological data, and tobacco consumption were tested for their influence on the parameters. Data were modeled with a 1-compartment model with first-order absorption and elimination. PK analysis confirms the results of our previous study. An Emax model best-described the exposure-OCDS relationship. None of the covariates tested was able to improve the fit or decrease intersubject variability. However, 2 subpopulations were defined for the exposure corresponding to half the maximal effect (BE50). The proportion of patients being classified as responders was 38% (95% confidence interval [CI] 7 to 76), the maximal decrease in OCDS (Emax ) was 72% (95% CI 25 to 85), and the BE50 was 12.6 (95% CI 0.02 to 74.3) or 4,390 (95% CI 20.4 to 31,800) h mg/l for responders and nonresponders, respectively. We defined the relationship between baclofen exposure and craving in patients with alcohol use disorder. Baclofen treatment decreased craving in all patients. However, we drew up the hypothesis of 2 subpopulations of patients differentiated by their speed of response. A wide interindividual variability in response was depicted, making it currently impossible to predict which group a patient will belong to. Copyright © 2015 by the Research Society on Alcoholism.

Effect of Ti:sapphire laser on shear bond strength of orthodontic brackets to ceramic surfaces.

PubMed

Erdur, Emire Aybuke; Basciftci, Faruk Ayhan

2015-08-01

With increasing demand for orthodontic treatments in adults, orthodontists continue to debate the optimal way to prepare ceramic surfaces for bonding. This study evaluated the effects of a Ti:sapphire laser on the shear bond strength (SBS) of orthodontic brackets bonded to two ceramic surfaces (feldspathic and IPS Empress e-Max) and the results were compared with those using two other lasers (Er:YAG and Nd:YAG) and 'conventional' techniques, i.e., sandblasting (50 µm) and hydrofluoric (HF) acid. In total, 150 ceramic discs were prepared and divided into two groups. In each group, the following five subgroups were prepared: Ti:sapphire laser, Nd:YAG laser, Er:YAG laser, sandblasting, and HF acid. Mandibular incisor brackets were bonded using a light-cured adhesive. The samples were stored in distilled water for 24 hours at 37°C and then thermocycled. Extra samples were prepared and examined using scanning electron microscopy (SEM). SBS testing was performed and failure modes were classified. ANOVA and Tukey's HSD tests were used to compare SBS among the five subgroups (P < 0.05). Feldspathic and IPS Empress e-Max ceramics had similar SBS values. The Ti:sapphire femtosecond laser (16.76 ± 1.37 MPa) produced the highest mean bond strength, followed by sandblasting (12.79 ± 1.42 MPa) and HF acid (11.28 ± 1.26 MPa). The Er:YAG (5.43 ± 1.21 MPa) and Nd:YAG laser (5.36 ± 1.04 MPa) groups were similar and had the lowest SBS values. More homogeneous and regular surfaces were observed in the ablation pattern with the Ti:sapphire laser than with the other treatments by SEM analysis. Within the limitations of this in vitro study, Ti:sapphire laser- treated surfaces had the highest SBS values. Therefore, this technique may be useful for the pretreatment of ceramic surfaces as an alternative to 'conventional' techniques. © 2015 Wiley Periodicals, Inc.

Attention Span, Anxiety and Benzodiazepine Receptors

DTIC Science & Technology

1991-02-26

response experiments , membranes were washed five times prior to freezing, and various concentrations of GABA were added to the incubation medium immediately...Similar results are obtained in the experiments where the animals were treated with 4 mg/kg/day of Ro 15-1788 for 14 days (data not shown). The highest...vehicle-treated or Ro 1S-l788-treated ra:ts (4 mg/kg/day for 14 days in drinking water), sacrificed 72 hours after drug withdrawal. EXPERIMENT Emax

All ceramic table tops analyzed using swept source optical coherence tomography

NASA Astrophysics Data System (ADS)

Stoica, Eniko Tunde; Marcauteanu, Corina; Sinescu, Cosmin; Negrutiu, Meda Lavinia; Topala, Florin; Duma, Virgil Florin; Bradu, Adrian; Podoleanu, Adrian Gh.

2016-03-01

Erosion is the progressive loss of tooth substance by chemical processes that do not involve bacterial action. The affected teeth can be restored by using IPS e.max Press "table tops", which replace the occlusal surfaces. In this study we applied a fast in-house Swept Source Optical Coherence Tomography (SS OCT) system to analyze IPS e.max Press "table tops". 12 maxillary first premolars have been extracted and prepared for "table tops". These restorations were subjected to 3000 alternating cycles of thermo-cycling in a range from -10°C to +50°C mechanical occlusal loads of 200 N were also applied. Using SS OCT we analyze the marginal seal of these restorations, before and after applying the mechanical and thermal strain. The characteristics of the SS OCT system utilized are presented. Its depth resolution, measured in air is 10 μm. The system is able to acquire entire volumetric reconstructions in 2.5 s. From the dataset acquired high resolution en-face projections were also produced. Thus, the interfaces between all ceramic "table tops" and natural teeth were analyzed on the cross-sections (i.e., the B-scans) produced and also on the volumetric (tri-dimensional (3D)) reconstructions, several open interfaces being detected. The study therefore demonstrates the utility of SS OCT for the analysis of lithium disilicate glass ceramic "table tops".

Endothelium-specific insulin resistance leads to accelerated atherosclerosis in areas with disturbed flow patterns: a role for reactive oxygen species.

PubMed

Gage, Matthew C; Yuldasheva, Nadira Y; Viswambharan, Hema; Sukumar, Piruthivi; Cubbon, Richard M; Galloway, Stacey; Imrie, Helen; Skromna, Anna; Smith, Jessica; Jackson, Christopher L; Kearney, Mark T; Wheatcroft, Stephen B

2013-09-01

Systemic insulin resistance is associated with a portfolio of risk factors for atherosclerosis development. We sought to determine whether insulin resistance specifically at the level of the endothelium promotes atherosclerosis and to examine the potential involvement of reactive oxygen species. We cross-bred mice expressing a dominant negative mutant human insulin receptor specifically in the endothelium (ESMIRO) with ApoE(-/-) mice to examine the effect of endothelium-specific insulin resistance on atherosclerosis. ApoE(-/-)/ESMIRO mice had similar blood pressure, plasma lipids and whole-body glucose tolerance, but blunted endothelial insulin signalling, in comparison to ApoE(-/-) mice. Atherosclerosis was significantly increased in ApoE(-/-)/ESMIRO mice at the aortic sinus (226 ± 16 versus 149 ± 24 × 10(3) μm(2), P = 0.01) and lesser curvature of the aortic arch (12.4 ± 1.2% versus 9.4 ± 0.9%, P = 0.035). Relaxation to acetylcholine was blunted in aorta from ApoE(-/-)/ESMIRO mice (Emax 65 ± 41% versus 103 ± 6%, P = 0.02) and was restored by the superoxide dismutase mimetic MnTMPyP (Emax 112 ± 15% versus 65 ± 41%, P = 0.048). Basal generation of superoxide was increased 1.55 fold (P = 0.01) in endothelial cells from ApoE(-/-)/ESMIRO mice and was inhibited by the NADPH oxidase inhibitor gp91ds-tat (-12 ± 0.04%, P = 0.04), the NO synthase inhibitor L-NMMA (-8 ± 0.02%, P = 0.001) and the mitochondrial specific inhibitor rotenone (-23 ± 0.04%, P = 0.006). Insulin resistance specifically at the level of the endothelium leads to acceleration of atherosclerosis in areas with disturbed flow patterns such as the aortic sinus and the lesser curvature of the aorta. We have identified a potential role for increased generation of reactive oxygen species from multiple enzymatic sources in promoting atherosclerosis in this setting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chronic aerobic swimming exercise promotes functional and morphological changes in rat ileum

PubMed Central

da Cunha Araujo, Layanne Cabral; de Souza, Iara Leão Luna; Vasconcelos, Luiz Henrique César; de Freitas Brito, Aline; Queiroga, Fernando Ramos; Silva, Alexandre Sérgio; da Silva, Patrícia Mirella; de Andrade Cavalcante, Fabiana; da Silva, Bagnólia Araújo

2015-01-01

Several studies have reported the gastrointestinal (GI) effects promoted by the physical exercise. Thus, we aimed to evaluate the influence of swimming exercise on the contractile reactivity, lipid peroxidation and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and groups exercised for two (EX2), four (EX4), six (EX6) or eight (EX8) weeks, 5 days/week. Animals were killed; the ileum was removed and suspended in organ baths where the isotonic contractions were recorded. Lipid peroxidation was evaluated by MDA (malondialdehyde) measurement with TBARS (thiobarbituric acid reactive substances) assay and morphology by histological staining. Cumulative concentration-response curves to KCl were attenuated, as the Emax values were changed from 100% (SED) to 63.1±3.9 (EX2), 48.8±3.8 (EX4), 19.4±1.8 (EX6) and 59.4±2.8% (EX8). Similarly, cumulative concentration-response curves to carbamylcholine hydrochloride (CCh) were attenuated, as the Emax values were changed from 100% (SED) to 74.1±5.4 (EX2), 75.9±5.2 (EX4) and 62.9±4.6 (EX6), but not in the EX8 (89.7±3.4%). However, CCh potency was increased in this latter, as the EC50 was altered from 1.0±0.1×10−6 (SED) to 2.1±0.4×10−7 (EX8). MDA concentration was altered only in EX4 (44.3±4.4) compared with SED (20.6±3.6 μmol/l). Circular layer was reduced in SED when compared with the exercised groups. Conversely, longitudinal layer was increased. In conclusion, chronic swimming exercise reduces the ileum contraction, equilibrates the oxidative damage and promotes changes in tissue size to establish an adaptation to the exercise. PMID:26424698

The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication?

PubMed

Calmasini, Fabiano B; Candido, Tuany Z; Alexandre, Eduardo C; D'Ancona, Carlos A; Silva, Daniel; de Oliveira, Marco Antonio; De Nucci, Gilberto; Antunes, Edson; Mónica, Fabíola Z

2015-03-01

Alpha1 (α1)-blockers, 5-alpha reductase and phosphodiesterase type-5 inhibitors are pharmacological classes currently available for benign prostatic hyperplasia (BPH) treatment. Mirabegron, a beta-3 adrenoceptor (β3-AR) agonist has been approved for the therapy of overactive bladder and may constitute a new therapeutic option for BPH treatment. This study is aimed to evaluate the in vitro effects of mirabegron in human and rabbit prostatic smooth muscle. In rabbit prostate, electrical field stimulation (EFS)-induced contraction and concentration-response curve (CRC) to mirabegron in phenylephrine pre-contracted tissues were carried out. The potency (pEC50 ) and maximal response (Emax ) values were determined. In human prostate, CRC to phenylephrine was carried out in the absence and presence of mirabegron. Immunohistochemistry analysis for β3-AR was also carried out. In human prostate, immunohistochemistry analysis revealed the presence of β3-AR on the transition zone and mirabegron reduced by 42% the phenylephrine-induced contractions. In rabbit prostate, mirabegron produced concentration-dependent relaxations (pEC50 : 6.01 ± 0.12; Emax : 106 ± 3%), which were fully resistant to the blockade of β1-AR and β2-AR. The β3-AR blocker L748,337 caused a six-fold rightward shift in mirabegron-induced relaxations. Mirabegron (10 μM) reduced by 63% the EFS-induced contractions. Inhibitors of nitric oxide (L-NAME) and of soluble guanylate cyclase (ODQ) along with a cocktail of K+ channel blockers (apamin, charybdotoxin, glibenclamide, tetraethylammonium) all failed to significantly affect the mirabegron-induced rabbit relaxations. Mirabegron relaxes prostatic smooth muscle, providing an experimental support for the clinical investigation of its combination with an α1-blockers or PDE5 inhibitors in the treatment of BPH. Prostate 75:440-447, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Modelling the effect of essential oil of betel leaf (Piper betle L.) on germination, growth, and apparent lag time of Penicillium expansum on semi-synthetic media.

PubMed

Basak, Suradeep; Guha, Proshanta

2015-12-23

The current study aimed at characterizing the chemical components of betel leaf (Piper betle L. var. Tamluk Mitha) essential oil (BLEO) and modelling its effect on growth of Penicillium expansum on semi-synthetic medium. Gas chromatography-mass spectrophotometry (GC-MS) analysis of BLEO revealed the presence of different bioactive phenolic compounds in significant amounts. Among 46 different components identified, chavibetol (22.0%), estragole (15.8%), β-cubebene (13.6%), chavicol (11.8%), and caryophyllene (11.3%) were found to be the major compounds of BLEO. A disc diffusion and disc volatilization method were used to evaluate antifungal activity of the oil against a selected food spoilage mould. The logistic model was used to study the kinetics of spore germination. Prediction and validation of antifungal effect of BLEO was performed on semi-synthetic medium (apple juice agar) using predictive microbiological tools. The Baranyi and Roberts model was used to estimate maximum growth rate (μmax in mm/day) and apparent lag time (λ in days) of the mould. Secondary modelling was performed using a re-parameterized Monod-type equation based on cardinal values to study the effect of different BLEO concentration on estimated growth parameters. Emax (minimum concentration of oil at which mould growth was inhibited) and MIC (minimum inhibitory concentration of BLEO at which lag time is infinite) value of BLEO against P. expansum was estimated to be 0.56 and 0.74 μl/ml, respectively, which was found to be similar on potato dextrose agar (PDA) as well as apple juice agar (AJA) medium. The correlation between estimated growth parameters of the mould on both the media was obtained with satisfactory statistical indices (R(2) and RMSE). This study revealed inhibitory efficacy of BLEO on spore germination, mycelial growth and apparent lag time of P. expansum in a dose-dependent manner. Hence, BLEO has potential to be used as a natural food preservative. Copyright © 2015 Elsevier B.V. All rights reserved.

Case report: quantification of methadone-induced respiratory depression using toxicokinetic/toxicodynamic relationships.

PubMed

Mégarbane, Bruno; Declèves, Xavier; Bloch, Vanessa; Bardin, Christophe; Chast, François; Baud, Frédéric J

2007-01-01

Methadone, the most widely delivered maintenance therapy for heroin addicts, may be responsible for life-threatening poisonings with respiratory depression. The toxicokinetics and the toxicokinetic/toxicodynamic (TK/TD) relationships of methadone enantiomers have been poorly investigated in acute poisonings. The aim of this study was to describe the relationships between methadone-related respiratory effects and their corresponding concentrations. We report a 44-year-old methadone-maintained patient who ingested a 240-mg dose of methadone. He was found comatose with pinpoint pupils and respiratory depression. He was successfully treated with intravenous naloxone infusion over the course of 31 hours at a rate adapted to maintain normal consciousness and respiratory rate. We performed a TK/TD analysis of the naloxone infusion rate needed to maintain his respiratory rate at more than 12 breaths per minute (as toxicodynamics parameter) versus plasma R,S- and R-methadone concentrations (as toxicokinetics parameter), determined using an enantioselective high-performance liquid chromatography assay. Initial plasma R,S-methadone concentration was 1,204 ng/ml. Decrease in plasma R- and S-methadone concentrations was linear and demonstrated a first-order pharmacokinetics (maximal observed concentrations 566 and 637 ng/ml, half-lives 16.1 and 13.2 hours, respectively). TK/TD correlation between naloxone infusion rate and R,S- and R-methadone concentrations fitted well a sigmoidal Emax model (concentration associated with a half-maximum effect [EC50] 334 and 173 ng/ml, Hill coefficient 10.0 and 7.8, respectively). In our chronically treated patient, EC50 values were in the range of previously reported values regarding methadone analgesic effects, suggesting that plasma methadone concentrations to prevent withdrawal are lower than those associated with methadone analgesic effects. After the ingestion of a toxic dose of a racemic mixture, plasma R- and S-enantiomer concentrations decreased in parallel. Despite large inter-individual variability in methadone toxicokinetics and toxicodynamics, TK/TD relationships would be helpful for providing quantitative data regarding the respiratory response to methadone in poisonings. However, further confirmatory TK/TD data are needed.

Determinants of the development of mitral regurgitation in pacing-induced heart failure.

PubMed

Takagaki, Masami; McCarthy, Patrick M; Goormastic, Marlene; Ochiai, Yoshie; Doi, Kazuyoshi; Kopcak, Michael W; Tabata, Tomotsugu; Cardon, Lisa A; Thomas, James D; Fukamachi, Kiyotaka

2003-01-01

The pacing-induced heart failure model provides an opportunity to assess the structural and functional determinants of mitral regurgitation (MR) in dilated cardiomyopathy. This study aimed to evaluate MR to better understand the multitude of factors contributing to its development. Heart failure was induced by rapid ventricular pacing (230 beats/min) in 40 mongrel dogs. Left ventricular (LV) size and MR were evaluated echocardiographically. LV contractility was analyzed using a conductance catheter. MR increased to mild in 12 animals (regurgitant orifice area, 0.06+/-0.05 cm(2)), moderate in 15 (0.14+/-0.07 cm(2)), and severe in 13 (0.34+/-0.16 cm(2)). The grade of MR had an inverse relationships with E(max) (the slope of the end-systolic pressure-volume relationship, p<0.01) and dE/dt (the slope of the maximum rate of change of pressure-end-diastolic volume [V(ED)] relationship, p<0.01) and positive relationships with V(ED) and end-diastolic cross-sectional areas and lengths (p<0.05) by univariate analysis. The dE/dt had an independently significant (p<0.01) relationship by multivariable logistic regression. Many factors influence the development of MR and because of its similarity to the clinical situation, this model can be used to investigate MR and heart failure, as well as new surgical therapies.

Inside marginal adaptation of crowns by X-ray micro-computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dos Santos, T. M.; Lima, I.; Lopes, R. T.

The objective of this work was to access dental arcade by using X-ray micro-computed tomography. For this purpose high resolution system was used and three groups were studied: Zirkonzahn CAD-CAM system, IPS e.max Press, and metal ceramic. The three systems assessed in this study showed results of marginal and discrepancy gaps clinically accepted. The great result of 2D and 3D evaluations showed that the used technique is a powerful method to investigate quantitative characteristics of dental arcade. (authors)

Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

PubMed

Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

2008-05-01

Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity.

PubMed

Juarez, Esther; Tufiño, Cecilia; Querejeta, Enrique; Bracho-Valdes, Ismael; Bobadilla-Lugo, Rosa A

2017-11-01

To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α 1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD 2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p < 0.01 hypercaloric diet vs standard diet) in the presence of both prazosin and losartan but only in endothelium-intact vessels. Diet-induced obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p < 0.05 vs standard diet). Seven-week hypercaloric diet-induced obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

Inoculum Effects of Ceftobiprole, Daptomycin, Linezolid, and Vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at Inocula of 105 and 107 CFU Injected into Opposite Thighs of Neutropenic Mice

PubMed Central

Lee, Dong-Gun; Murakami, Yoichi; Andes, David R.

2013-01-01

Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 104.5 to 105.7 CFU/thigh (low inoculum [LI]) in one thigh and 106.4 to 107.2 CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (Emax) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls. PMID:23295932

Effect of overglazed and polished surface finishes on the compressive fracture strength of machinable ceramic materials.

PubMed

Asai, Tetsuya; Kazama, Ryunosuke; Fukushima, Masayoshi; Okiji, Takashi

2010-11-01

Controversy prevails over the effect of overglazing on the fracture strength of ceramic materials. Therefore, the effects of different surface finishes on the compressive fracture strength of machinable ceramic materials were investigated in this study. Plates prepared from four commercial brands of ceramic materials were either surface-polished or overglazed (n=10 per ceramic material for each surface finish), and bonded to flat surfaces of human dentin using a resin cement. Loads at failure were determined and statistically analyzed using two-way ANOVA and Bonferroni test. Although no statistical differences in load value were detected between polished and overglazed groups (p>0.05), the fracture load of Vita Mark II was significantly lower than those of ProCAD and IPS Empress CAD, whereas that of IPS e.max CAD was significantly higher than the latter two ceramic materials (p<0.05). It was concluded that overglazed and polished surfaces produced similar compressive fracture strengths irrespective of the machinable ceramic material tested, and that fracture strength was material-dependent.

Aortic relaxant activity of Crataegus gracilior Phipps and identification of some of its chemical constituents.

PubMed

Hernández-Pérez, Abigail; Bah, Moustapha; Ibarra-Alvarado, César; Rivero-Cruz, José Fausto; Rojas-Molina, Alejandra; Rojas-Molina, Juana Isela; Cabrera-Luna, José Alejandro

2014-12-15

This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior) on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC50 = 8.69 ± 4.34 µg/mL and an Emax = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+)-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species.

Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression.

PubMed

Pirat, Celine; Dacquet, Catherine; Leclerc, Veronique; Hennuyer, Nathalie; Beucher-Gaudin, Monique; Zanirato, Ghislaine; Géant, Anne; Staels, Bart; Ktorza, Alain; Farce, Amaury; Caignard, Daniel-Henri; Berthelot, Pascal; Lebegue, Nicolas

2017-09-08

A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC 50  = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Passive Multistatic Detection of Maritime Targets using Opportunistic Radars

DTIC Science & Technology

2014-03-01

coordinate position for aa =1:1:length(Err_time1) Err_Total1( aa ) = max(abs(Err_time1( aa )),abs(Err_L1( aa ))+abs(Err_thetaR1( aa ))); end for aa =1...1:length(Err_time1) Err_Total1( aa ) = max(abs(Err_Total1( aa )),abs(Err_thetaR1( aa ))); end 93 %%%%%%%%%%%%%%%%%%%%% Tx 2...Err_Total2=zeros(size(Err_time2)); % Find th emax of the three source of error and use that for that % coordinate position for aa =1:1:length

Pharmacokinetics (PK), Pharmacodynamics (PD), and PK-PD Integration of Danofloxacin in Sheep Biological Fluids

PubMed Central

Aliabadi, F. Shojaee; Landoni, M. F.; Lees, P.

2003-01-01

The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules. PMID:12543670

[All-ceramic resin bonded fixed partial denture made of IPS hot-pressed casting porcelain restore anterior missing teeth: a three years clinical observation].

PubMed

Zhou, Tuan feng; Wang, Xin zhi; Zhang, Gui rong

2011-02-18

To clinic observation of IPS Empress2 and IPS e.max all ceramic resin bonded fixed partial dentures used in one anterior teeth lost in upper jaw or less than two anterior tooth lost in lower jaw. 22 patients, 26 restorations had been made, which included 16 single-retainer all ceramic resin bonded fixed partial dentures and 10 two-retainers all ceramic resin bonded fixed partial dentures. Secondary caries of the abutments, shade in the margin of the retainers and the integrity of the restorations had been observed at 3 months, 6 months, 1 year, 2 years and 3 years after all ceramic resin bonded fixed partial dentures having been bonded. In the 3 years of clinic observation of the anterior all ceramic resin bonded fixed partial dentures, 1 two-retainers restoration lost bond after it had been made for 3 months, a retainer of one two-retainers restoration was broken after 6 months, but they are still used after modified as one-retainer all ceramic resin bonded fixed partial dentures, 1 two-retainers restoration lost bond two year later, It was integrity and re-bonded again that was still stable. No secondary carries and no shade in margin of the retainers had been found. Their color matches with the nature teeth excellently. The success rate was 88.5%. IPS Empress 2 and IPS e.max all ceramic resin bonded fixed partial dentures should be a good selection in one or two teeth lose in anterior jaws.

Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects

PubMed Central

Shin, Jae-Gook; Kang, Won-ku; Shon, Ji-Hong; Arefayene, Million; Yoon, Young-Ran; Kim, Kyung-Ah; Kim, Doo-Il; Kim, Dong-Soo; Cho, Kwang-Hyun; Woosley, Raymond L; Flockhart, David A

2007-01-01

Aims The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of quinidine-induced QT prolongation in healthy Caucasian and Korean subjects to investigate interethnic differences in susceptibility to drug-induced arrhythmia. Methods A randomized, double-blind crossover study was conducted in 24 (12 male and 12 female) Korean and 13 (seven male and six female) Caucasian subjects. After a 20 min infusion of quinidine (4 mg kg−1) or saline, the serum concentration of quinidine and the QT interval corrected by Bazett's formula (QTc) were monitored. The dynamic data were analyzed by means of a population modelling approach using NONMEM. Results There were no statistical differences in the pharmacokinetic profiles of quinidine between ethnic groups. The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in female subjects. According to an Emax model , the population modelling approach revealed that E0 (ms) was related to gender (408 + [34*(1 − Sex)]; 1 for male and 0 for female), ΔEmax (ms) was related to ethnicity ((136*fETHN) + Cfemale: fETHN = 1 for Koreans and 1.26 for Caucasians; Cfemale was 106 only for Caucasian females), and EC50 was estimated to be 3.13 µm. Conclusions These results suggest that Korean subjects were less sensitive to quinidine-induced QT prolongation than Caucasian subjects, and that this trend was particularly true for females. Further population-based studies are merited to characterize more completely the ethnic differences in drug-induced QT prolongation between Asians and other ethnic groups. PMID:17096683

Influence of low concentration acid treatment on lithium disilicate core/veneer ceramic bond strength

PubMed Central

Garcia, Rudan P.; Conti, Paulo CR.; Pereira, Jefferson R.; Valle, Accácio Ld.

2013-01-01

Objective: This study evaluated the influence of low concentration acid treatment on the shear bond strength between lithium disilicate (LD) infrastructure and veneering porcelain. The surface morphology characteristic after this acid treatment was also examined. Study Design: LD reinforced ceramic cylinders (n=10) (IPS e.max Press, Ivoclar-Vivadent, Schaan, Liechtenstein) were treated (LD-treated) with a low concentration acid solution (Invex Liquid – Ivoclar-Vivadent, Schaan, Liechtenstein) or not treated with the acid solution (LD-untreated). They were veneered with a glass ceramic (IPS e.max Ceram, Ivoclar-Vivadent, Schaan, Liechtenstein). A metal ceramic group (CoCr) was tested as control. Shear bond strength (SBS) was conducted using a universal testing machine at 0.5 mm/min. Surface morphology characteristics after acid treatment were analyzed using scanning electron microscopy. Results: The acid treatment at low concentrations did not influence the SBS of the LD/veneering porcelain interface. The CoCr group showed the significant higher SBS value (35.59 ± 5.97 MPa), followed by LD-untreated group (27.76 ± 3.59 MPa) and LD-treated (27.02 ± 4.79 MPa). The fracture modes were predominantly adhesive for CoCr group and cohesive within the infrastructure for DL groups. Scanning Electron Microscopy (SEM) analysis showed no morphological differences between treated and untreated LD surfaces. Conclusions: Low concentration acid treatment did not improved SBS of veneering ceramic to LD and did not cause morphological changes on the LD surface. Key words:Lithium disilicate, glass ceramics, acid etching, shear bond strength, scanning electron microscopy. PMID:24455073

Brittleness index of machinable dental materials and its relation to the marginal chipping factor.

PubMed

Tsitrou, Effrosyni A; Northeast, Simon E; van Noort, Richard

2007-12-01

The machinability of a material can be measured with the calculation of its brittleness index (BI). It is possible that different materials with different BI could produce restorations with varied marginal integrity. The degree of marginal chipping of a milled restoration can be estimated by the calculation of the marginal chipping factor (CF). The aim of this study is to investigate any possible correlation between the BI of machinable dental materials and the CF of the final restorations. The CEREC system was used to mill a wide range of materials used with that system; namely the Paradigm MZ100 (3M/ESPE), Vita Mark II (VITA), ProCAD (Ivoclar-Vivadent) and IPS e.max CAD (Ivoclar-Vivadent). A Vickers Hardness Tester was used for the calculation of BI, while for the calculation of CF the percentage of marginal chipping of crowns prepared with bevelled marginal angulations was estimated. The results of this study showed that Paradigm MZ100 had the lowest BI and CF, while IPS e.max CAD demonstrated the highest BI and CF. Vita Mark II and ProCAD had similar BI and CF and were lying between the above materials. Statistical analysis of the results showed that there is a perfect positive correlation between BI and CF for all the materials. The BI and CF could be both regarded as indicators of a material's machinability. Within the limitations of this study it was shown that as the BI increases so does the potential for marginal chipping, indicating that the BI of a material can be used as a predictor of the CF.

Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.

PubMed

Mustad, Vikkie A; Demichele, Stephen; Huang, Yung-Sheng; Mika, Amanda; Lubbers, Nathan; Berthiaume, Nathalie; Polakowski, Jim; Zinker, Brad

2006-10-01

Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood lipids and vascular function in an animal model of insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.

Transmitted irradiance through ceramics: effect on the mechanical properties of a luting resin cement.

PubMed

Ilie, Nicoleta

2017-05-01

The study aims to characterise the curing behaviour of a light-curing luting composite (Variolink® Aesthetic LC, Ivoclar Vivadent) polymerised at different exposure times (10 s, 20 s) through different ceramics (IPS Empress CAD and IPS e.max CAD, Ivoclar Vivadent) and ceramic thicknesses (no ceramic, 0.5, 1, 1.5 and 2 mm). Curing units' (Bluephase Style, Ivoclar Vivadent) variation in irradiance delivered up to 10-mm exposure distance as well as the incident and transmitted irradiance and radiant exposure up to 6-mm ceramic thickness were assessed on a laboratory-grade spectrometer. A total of 216 (18 groups, n = 12) thin and flat luting composite specimens of 500-μm thickness were prepared and stored after curing in a saturated vapour atmosphere for 24 h at 37 °C. Micro-mechanical properties (Vickers hardness, HV and indentation modulus, Y HU ) were determined by means of an automatic micro-hardness indenter. Within the study design, the radiant exposure received by the luting composite varied from 2.56 to 24.75 J/cm 2 , showing a high impact on the measured properties. Comparing the effect of the parameters exposure time, ceramic thickness and type, the highest influence on the micro-mechanical parameters was identified for exposure time, while this influence was stronger on HV (p < 0.001, η P 2  = 0.452) than on Y HU (p < 0.001, η P 2  = 0.178). The influence of ceramic type was significant but low (η P 2  = 0.161 on HV and 0.113 on Y HU ), while the influence of ceramic thickness was the lowest (η P 2  = 0.04 and 0.05, respectively). Slightly higher irradiance values were transmitted through Empress CAD up to a ceramic thickness of 3 mm (p < 0.001), while being comparable with e.max for thicker slices. Differences in translucency between ceramics were reflected in the micro-mechanical properties of the luting composite. The radiant exposure reaching the luting composite is determined by the incident irradiance, exposure time, ceramic type and ceramic thickness. At the analysed incident irradiance, exposure time was the most consistent parameter affecting the micro-mechanical properties of the luting composite, and this effect was strongly reflected in the more translucent ceramic Empress CAD. Within the curing conditions, an exposure time of 20 s is recommended.

Impact of Gastric Acid Induced Surface Changes on Mechanical Behavior and Optical Characteristics of Dental Ceramics.

PubMed

Kulkarni, Aditi; Rothrock, James; Thompson, Jeffery

2018-01-14

To test the impact of exposure to artificial gastric acid combined with toothbrush abrasion on the properties of dental ceramics. Earlier research has indicated that immersion in artificial gastric acid has caused increased surface roughness of dental ceramics; however, the combined effects of acid immersion and toothbrush abrasion and the impact of increased surface roughness on mechanical strength and optical properties have not been studied. Three commercially available ceramics were chosen for this study: feldspathic porcelain, lithium disilicate glass-ceramic, and monolithic zirconium oxide. The specimens (10 × 1 mm discs) were cut, thermally treated as required, and polished. Each material was divided into four groups (n = 8 per group): control (no exposure), acid only, brush only, acid + brush. The specimens were immersed in artificial gastric acid (50 ml of 0.2% [w/v] sodium chloride in 0.7% [v/v] hydrochloric acid mixed with 0.16 g of pepsin powder, pH = 2) for 2 minutes and rinsed with deionized water for 2 minutes. The procedure was repeated 6 times/day × 9 days, and specimens were stored in deionized water at 37°C. Toothbrush abrasion was performed using an ISO/ADA design brushing machine for 100 cycles/day × 9 days. The acid + brush group received both treatments. Specimens were examined under SEM and an optical microscope for morphological changes. Color and translucency were measured using spectrophotometer CIELAB coordinates (L*, a*, b*). Surface gloss was measured using a gloss meter. Surface roughness was measured using a stylus profilometer. Biaxial flexural strength was measured using a mechanical testing machine. The data were analyzed by one-way ANOVA followed by Tukey's HSD post hoc test (p < 0.05). Statistically significant changes were found for color, gloss, and surface roughness for porcelain and e.max specimens. No statistically significant changes were found for any properties of zirconia specimens. The acid treatment affected the surface roughness, color, and gloss of porcelain and e.max ceramics. The changes in translucency and mechanical strength for all materials were not statistically significant. Zirconia ceramic showed resistance to all treatments. © 2018 by the American College of Prosthodontists.

Origin and voltage dependence of asparagine-induced depolarization in intestinal cells of Xenopus embryo.

PubMed Central

Bergman, C; Bergman, J

1985-01-01

The kinetics and voltage dependence of asparagine (Asn)-induced depolarization in endoderm cells from Xenopus laevis embryos were analysed using current-clamp techniques. The depolarization is assumed to reflect the activation of an amino acid membrane carrier; it is accompanied by a slight increase in membrane resistance and cannot be explained by only the electrogenic character of the Asn carrier. It is proposed that the Asn depolarization arises, at least in part, from the decrease of the permeability ratio PK/PNa indirectly associated with the Na-coupled amino acid uptake. At room temperature (20-23 degrees C) the Asn response develops according to a single exponential function whose time constant is correlated with the final level of depolarization. Both amplitude and rise time of the depolarization are sensitive to variations of membrane potential and changes in Asn or Na external concentrations. Lowering the temperature decreases the amplitude of the Asn depolarization and increases its rise time with a Q10 factor of two; the kinetics remain of the Michaelis-Menten type, with a marked decrease in delta Emax and no change in Km. When the holding potential is altered by depolarizing and hyperpolarizing currents, the Asn response varies according to a bell-shaped characteristic presenting an optimum near the normal resting level. Membrane depolarizations induced by Na/K-pump inhibitors or high external K concentrations reduce the size of the Asn response; repolarizing the cell by current injection does not reverse the inhibitory effect of external K ions. Hyperpolarizing the membrane with a K-free Ringer solution increases the amplitude of the Asn response. In all these cases a decrease in delta Emax accounts for the apparent voltage sensitivity of the carrier mechanism. When induced by alterations of [K]o, an additional change in Km is observed, suggesting a K/Na-competitive inhibition of the Asn carrier. The results are discussed in terms of the amino acid carrier and passive membrane properties. It is suggested that the outward K-electrochemical gradient contributes an additional source of energy to the Na-dependent Asn uptake. PMID:4057089

Influence of Surface Conditioning Protocols on Reparability of CAD/CAM Zirconia-reinforced Lithium Silicate Ceramic.

PubMed

Al-Thagafi, Rana; Al-Zordk, Walid; Saker, Samah

2016-01-01

To test the effect of surface conditioning protocols on the reparability of CAD/CAM zirconia-reinforced lithium silicate ceramic compared to lithium-disilicate glass ceramic. Zirconia-reinforced lithium silicate ceramic (Vita Suprinity) and lithium disilicate glass-ceramic blocks (IPS e.max CAD) were categorized into four groups based on the surface conditioning protocol used. Group C: no treatment (control); group HF: 5% hydrofluoric acid etching for 60 s, silane (Monobond-S) application for 60 s, air drying; group HF-H: 5% HF acid etching for 60 s, application of silane for 60 s, air drying, application of Heliobond, light curing for 20 s; group CO: sandblasting with CoJet sand followed by silanization. Composite resin (Tetric EvoCeram) was built up into 4 x 6 x 3 mm blocks using teflon molds. All specimens were subjected to thermocycling (5000x, 5°C to 55°C). The microtensile bond strength test was employed at a crosshead speed of 1 mm/min. SEM was employed for evaluation of all the debonded microbars, the failure type was categorized as either adhesive (failure at adhesive layer), cohesive (failure at ceramic or composite resin), or mixed (failure between adhesive layer and substrate). Two-way ANOVA and the Tukey's HSD post-hoc test were applied to test for significant differences in bond strength values in relation to different materials and surface pretreatment (p < 0.05). The highest microtensile repair bond strength for Vita Suprinity was reported in group CO (33.1 ± 2.4 MPa) and the lowest in group HF (27.4 ± 4.4 MPa). Regarding IPS e.max CAD, group CO showed the highest (30.5 ± 4.9 MPa) and HF the lowest microtensile bond strength (22.4 ± 5.7 MPa). Groups HF, HF-H, and CO showed statistically significant differences in terms of all ceramic types used (p < 0.05). The control group showed exclusively adhesive failures, while in HF, HF-H, and CO groups, mixed failures were predominant. Repair bond strength to zirconia-reinforced lithium silicate ceramics and lithium-disilicate glass ceramic could be improved when ceramic surfaces are sandblasted with CoJet sand followed by silanization.

Characterization of silicon carbide and diamond detectors for neutron applications

NASA Astrophysics Data System (ADS)

Hodgson, M.; Lohstroh, A.; Sellin, P.; Thomas, D.

2017-10-01

The presence of carbon atoms in silicon carbide and diamond makes these materials ideal candidates for direct fast neutron detectors. Furthermore the low atomic number, strong covalent bonds, high displacement energies, wide bandgap and low intrinsic carrier concentrations make these semiconductor detectors potentially suitable for applications where rugged, high-temperature, low-gamma-sensitivity detectors are required, such as active interrogation, electronic personal neutron dosimetry and harsh environment detectors. A thorough direct performance comparison of the detection capabilities of semi-insulating silicon carbide (SiC-SI), single crystal diamond (D-SC), polycrystalline diamond (D-PC) and a self-biased epitaxial silicon carbide (SiC-EP) detector has been conducted and benchmarked against a commercial silicon PIN (Si-PIN) diode, in a wide range of alpha (Am-241), beta (Sr/Y-90), ionizing photon (65 keV to 1332 keV) and neutron radiation fields (including 1.2 MeV to 16.5 MeV mono-energetic neutrons, as well as neutrons from AmBe and Cf-252 sources). All detectors were shown to be able to directly detect and distinguish both the different radiation types and energies by using a simple energy threshold discrimination method. The SiC devices demonstrated the best neutron energy discrimination ratio (E\\max (n=5 MeV)/E\\max (n=1 MeV)  ≈5), whereas a superior neutron/photon cross-sensitivity ratio was observed in the D-PC detector (E\\max (AmBe)/E\\max (Co-60)  ≈16). Further work also demonstrated that the cross-sensitivity ratios can be improved through use of a simple proton-recoil conversion layer. Stability issues were also observed in the D-SC, D-PC and SiC-SI detectors while under irradiation, namely a change of energy peak position and/or count rate with time (often referred to as the polarization effect). This phenomenon within the detectors was non-debilitating over the time period tested (> 5 h) and, as such, stable operation was possible. Furthermore, the D-SC, self-biased SiC-EP and semi-insulating SiC detectors were shown to operate over the temperature range -60 °C to +100 °C.

Influence of implant abutment material and ceramic thickness on optical properties.

PubMed

Jirajariyavej, Bundhit; Wanapirom, Peeraphorn; Anunmana, Chuchai

2018-05-01

Anterior shade matching is an essential factor influencing the esthetics of a ceramic restoration. Dentists face a challenge when the color of an implant abutment creates an unsatisfactory match with the ceramic restoration or neighboring teeth. The purpose of this in vitro study was to evaluate the influence of abutment material and ceramic thickness on the final color of different ceramic systems. Four experimental and control ceramic specimens in shade A3 were cut from IPS e.max CAD, IPS Empress CAD, and VITA Suprinity PC blocks. These specimens had thicknesses of 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm, respectively, for the experimental groups, and 4 mm for the controls. Background abutment specimens were fabricated to yield 3 different shades: white zirconia, yellow zirconia, and titanium at a 3-mm thickness. All 3 ceramic specimens in each thickness were placed in succession on different abutment backgrounds with glycerin optical fluid in between, and the color was measured. A digital spectrophotometer was used to record the specimen color value in the Commission Internationale De L'éclairage (CIELab) color coordinates system and to calculate the color difference (ΔE) between the control and experimental groups. The Kruskal-Wallis test was used to analyze the effect of ceramic thickness on different abutments, and the pair-wise test was used to evaluate within the group (α=.05). The color differences between the test groups and the control decreased with increasing ceramic thickness for every background material. In every case, significant differences were found between 1.0- and 2.5-mm ceramic thicknesses. Only certain 2.5-mm e.max CAD, VITA Suprinity PC, and Empress CAD specimens on yellow-shade zirconia or VITA Suprinity PC on titanium were identified as clinically acceptable (ΔE<3). Increasing ceramic restoration thickness over the abutment background decreased the color mismatch. Increasing the thickness of ceramic on a yellow-shaded zirconia abutment rather than on titanium or white zirconia yielded a more esthetic color for the whole restoration. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Roughness, surface energy, and superficial damages of CAD/CAM materials after surface treatment.

PubMed

Strasser, Thomas; Preis, Verena; Behr, Michael; Rosentritt, Martin

2018-02-05

The aim of this study was to examine the effects of surface pre-treatment on CAD/CAM materials including ceramics, zirconia, resin-infiltrated ceramic, and resin-based composite. Specimens were made of ten CAD/CAM materials (Celtra Duo, Degudent, D; Vita Suprinity, Vita, D; E.max CAD, Ivoclar-Vivadent, FL; E.max ZirCAD, Ivoclar-Vivadent, FL; Vita Enamic, Vita, D; Cerasmart, GC, B; LAVA Ultimate, 3M, D; SHOFU Block HC, SHOFU, US; Grandio Blocs, VOCO, D; BRILLIANT Crios, Coltene, CH) and pretreated to represent clinical procedures (Hf 20 s/5%; phosphoric acid 20 s/37%; Monobond etch and prime (Ivoclar-Vivadent, FL); water-cooled diamond bur (80 μm; 4 μm); Al 2 O 3 -blasting (50 μm/1 bar, 50 μm/2 bar, 120 μm/1 bar, 120 μm/2 bar); untreated; manufacturer's instructions). SEM-analysis (Phenom, FEI, NL) of the surfaces was performed (magnifications ≤ 10,000×). Roughness values R a , R z (KJ 3D, Keyence, J), and surface energy SE (OCA15 plus, SCA20, DataPhysics, D) were determined (statistics: non-parametric Mann-Whitney U test/Kruskal-Wallis test for independent specimen, α = 0.05). Kruskal-Wallis revealed significant (p < 0.001) differences for all materials with different surface treatments. Roughness ranged from R a  = 0.05 μm (VS; D4)/R z  = 0.41 μm (VS; D4) to R a  = 1.82 μm (EMA; SB120/2)/R z  = 12.05 μm (CS; SB 120/2), SE from 22.7 mN/m (VE; M) to 52.8 mN/m (CD; M). SEM analysis showed material-dependent damages after pre-treatment. Different CAD/CAM materials require individual pre-treatment for optimized and protective surface activation. Cementation is a key factor for clinical success. Given the variety of available CAD/CAM materials, specific procedures are needed.

Role of oxidative stress in multiparity-induced endothelial dysfunction.

PubMed

Tawfik, Huda E; Cena, Jonathan; Schulz, Richard; Kaufman, Susan

2008-10-01

Multiparity is associated with increased risk of cardiovascular disease. We tested whether multiparity induces oxidative stress in rat vascular tissue. Coronary arteries and thoracic aorta were isolated from multiparous and age-matched virgin rats. Relaxation to ACh and sodium nitroprusside (SNP) was measured by wire myography. We also tested the effect of the superoxide dismutase mimetic MnTE2PyP (30 microM), the NADPH oxidase inhibitor apocynin (10 microM), and the peroxynitrite scavenger FeTPPs (10 microM) on ACh-mediated relaxation in coronary arteries. Vascular superoxide anion was measured using the luminol derivative L-012 and nitric oxide (NO) generation by the Griess reaction. Multiparity reduced maximal response and sensitivity to ACh in coronary arteries [maximal relaxation (E(max)): multiparous 49+/-3% vs. virgins 95%+/-3%; EC(50): multiparous 135+/-1 nM vs. virgins 60+/-1 nM], and in aortic rings (E(max): multiparous 38+/-3% vs. virgins 79+/-4%; EC(50): multiparous 160+/-2 nM vs. virgins 90+/-3 nM). Coronary arteries from the two groups relaxed similarly to SNP. Superoxide anions formation was significantly higher in both coronary arteries (2.8-fold increase) and aorta (4.1-fold increase) from multiparous rats compared with virgins. In multiparous rats, incubation with MnTE2PyP, apocynin, and FeTPPs improved maximal relaxation to ACh (MnTE2PyP: 74+/-5%; vehicle: 41+/-5%; apocynin: 73+/-3% vs. vehicle: 41+/-3%; FeTPPs: 72+/-3% vs. vehicle: 46+/-3%) and increased sensitivity (EC(50): MnTE2PyP: 61+/-0.5 nM vs. vehicle: 91+/-1 nM; apocynin: 45+/-3 nM vs. vehicle: 91+/-6 nM; FeTPP: 131 +/- 2 nM vs. vehicle: 185+/-1 nM). Multiparity also reduced total nitrate/nitrite levels (multiparous: 2.5+/-2 micromol/mg protein vs. virgins: 7+/-1 micromol/mg protein) and endothelial nitric oxide synthase protein levels (multiparous: 0.53+/-0.1 protein/actin vs. virgins: 1.0+/-0.14 protein/actin). These data suggest that multiparity induces endothelial dysfunction through decreased NO bioavailability and increased reactive oxygen species formation.

Evaluation of dynamic electromagnetic tracking deviation

NASA Astrophysics Data System (ADS)

Hummel, Johann; Figl, Michael; Bax, Michael; Shahidi, Ramin; Bergmann, Helmar; Birkfellner, Wolfgang

2009-02-01

Electromagnetic tracking systems (EMTS's) are widely used in clinical applications. Many reports have evaluated their static behavior and errors caused by metallic objects were examined. Although there exist some publications concerning the dynamic behavior of EMTS's the measurement protocols are either difficult to reproduce with respect of the movement path or only accomplished at high technical effort. Because dynamic behavior is of major interest with respect to clinical applications we established a simple but effective modal measurement easy to repeat at other laboratories. We built a simple pendulum where the sensor of our EMTS (Aurora, NDI, CA) could be mounted. The pendulum was mounted on a special bearing to guarantee that the pendulum path is planar. This assumption was tested before starting the measurements. All relevant parameters defining the pendulum motion such as rotation center and length are determined by static measurement at satisfactory accuracy. Then position and orientation data were gathered over a time period of 8 seconds and timestamps were recorded. Data analysis provided a positioning error and an overall error combining both position and orientation. All errors were calculated by means of the well know equations concerning pendulum movement. Additionally, latency - the elapsed time from input motion until the immediate consequences of that input are available - was calculated using well-known equations for mechanical pendulums for different velocities. We repeated the measurements with different metal objects (rods made of stainless steel type 303 and 416) between field generator and pendulum. We found a root mean square error (eRMS) of 1.02mm with respect to the distance of the sensor position to the fit plane (maximum error emax = 2.31mm, minimum error emin = -2.36mm). The eRMS for positional error amounted to 1.32mm while the overall error was 3.24 mm. The latency at a pendulum angle of 0° (vertical) was 7.8ms.

Hypotensive effect of aqueous extract of Averrhoa carambola L. (Oxalidaceae) in rats: an in vivo and in vitro approach.

PubMed

Soncini, Roseli; Santiago, Michael B; Orlandi, Lidiane; Moraes, Gabriel O I; Peloso, André Luiz M; dos Santos, Marcelo H; Alves-da-Silva, Geraldo; Paffaro, Valdemar A; Bento, Antonio C; Giusti-Paiva, Alexandre

2011-01-27

Averrhoa carambola L. (Oxalidaceae) leaves are used in Brazilian traditional medicine to treat hypertension. This study was conducted to evaluate the hypotensive effect of the aqueous extract of Averrhoa carambola (AEAc) and its underlying mechanisms in the isolated rat aorta. The effect of AEAc on the mean arterial pressure (MAP) was determined in vivo in anesthetized rats. In vitro, thoracic aortic rings were isolated and suspended in organ baths, and the effects of AEAc were studied by means of isometric tension recording experiments. In HPLC analysis, the fingerprint chromatogram of AEAc was established. In normotensive rats, AEAc (12.5-50.0 mg/kg, i.v.) induced dose-dependent hypotension. In vitro, AEAc caused a depression in the E(max) response to phenylephrine without a change in sensibility. Also, in a depolarized Ca(2+)-free medium, AEAc inhibited CaCl(2)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that AEAc inhibited the contractile mechanisms involving extracellular Ca(2+) influx. These results demonstrate the hypotensive effects of AEAc, and these effects may, in part, be due to the inhibition of Ca(2+), which supports previous claims of its traditional use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation

PubMed Central

Frey, N; Laveille, C; Paraire, M; Francillard, M; Holford, N H G; Jochemsen, Roeline

2003-01-01

Aims To study the relationship between the pharmacokinetics (PK) of gliclazide and its long-term pharmacodynamic (PD) effect in a large population of Type 2 diabetic patients and to identify factors predicting intersubject variability. Methods A PKPD database of 634 Type 2 diabetic patients with a total of 5258 fasting plasma glucose (FPG) samples was built up from the data collected during the clinical development of a modified release formulation of gliclazide (gliclazide MR). The PKPD analysis used a nonlinear mixed effect modelling approach. A mixture model was used to identify patients with a FPG response to treatment. In patients identified as responders, the decrease in FPG was related to gliclazide exposure (AUC) by an Emax relationship. An effect compartment was used to describe the link between PK and PD. A linear disease-progression model was used to assess the glycaemic deterioration observable over several months of treatment. Simulations were performed to evaluate the predictive performance of the PKPD model and to illustrate the time course of the antidiabetic effect of gliclazide MR. Results Disease state was found to be the main explanatory factor for intersubject variability in response to gliclazide. The percentage of responders to gliclazide, used as monotherapy, increased inversely to the number of classes of antidiabetic agents received prior to entry in the studies. In responders, the initial dose (30 mg) of the gliclazide MR dosing regimen induced half of the maximum hypoglycaemic effect. The equilibration half-life between the PK and PD steady states was 3 weeks (intersubject variability of 84%). The rate of disease progression was 0.84 mmol l−1 year−1 (intersubject variability 143%). The PKPD model adequately predicted the FPG profiles of 234 patients who received the current formulation of gliclazide. Simulation of a 1-year parallel dose ranging clinical trial illustrated the influence of dose, time and type of previous antidiabetic treatment on the percentage of patients with clinically significant improvement of blood glucose control. Conclusions This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state. These results underline the clinical interest of quickly increasing the dose of gliclazide MR according to the response to treatment in order to achieve effective blood glucose control. PMID:12580986

Bilateral Complete and Incomplete Fusion of Incisors and its Management.

PubMed

Da Costa, Godwin Clovis; Chalakkal, Paul; De Souza, Neil; Gavhane, Sanket

2017-01-01

This case report highlights the management of a case of bilateral complete and incomplete fusion of maxillary incisors in a 10-year-old child. A mock-up was done on the diagnostic cast. Pretreatment esthetic evaluation was done using bis-acryl composite temporaries which were transferred intraorally from the diagnostic cast using a putty index. An incisal overlap veneer preparation was done, following which, an IPS e-max veneer was cemented. A digital mock-up was carried out using the Adobe Photoshop and Corel Draw softwares to aid in laboratorial fabrication of the veneer.

The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors.

PubMed

Cunha, J F; Campestrini, F D; Calixto, J B; Scremin, A; Paulino, N

2001-03-01

We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC(50) values of 18 microM and E(max) of 100% (N = 10) or 20 microM and E(max) of 92% (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 +/- 7.0, 43 +/- 3.9 and 78 +/- 5.6%) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 microM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 microM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 +/- 12%. Glibenclamide (1 or 3 microM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K(+) channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 microM), a selective blocker of the large-conductance Ca(2+)-activated K(+) channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N(G)-nitroarginine (100 microM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 microM, while methylene blue (10 or 30 microM) or ODQ (1 microM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-(P)-Cl-Phe(6),Leu(17)[VIP] (0.1 microM), a VIP receptor antagonist, significantly inhibited (37 +/- 7%) relaxation induced by gentisic acid, whereas CGRP (8-37) (0.1 microM), a CGRP antagonist, only slightly enhanced the action of gentisic acid. Taken together, these results provide functional evidence for the direct activation of voltage and large-conductance Ca(+2)-activated K(+) channels, or indirect modulation of potassium channels induced by VIP receptors and accounts for the predominant relaxation response caused by gentisic acid in the guinea pig trachea.

Gloss and Stain Resistance of Ceramic-Polymer CAD/CAM Restorative Blocks.

PubMed

Lawson, Nathaniel C; Burgess, John O

2016-03-01

To evaluate the gloss and stain resistance of several new ceramic-polymer CAD/CAM blocks Specimens (4 mm) were sectioned from: Enamic (polymer-infused ceramic), LAVA Ultimate (nano-ceramic reinforced polymer), e.max (lithium disilicate), Paradigm C (porcelain), and Paradigm MZ100 (composite). Specimens were wet polished on a polishing wheel to either 320 grit silicon paper (un-polished, N = 8) or 2000 grit silicon carbide papers followed by a 0.05 μm alumina slurry (polished, N = 8). Initial gloss and color (L*a*b*) values were measured. Specimens were stored in a staining solution at 37°C in darkness for 12 days (simulating 1 year). After storage, L*a*b* values re-measured. Change in color was reported as ΔE00 based on the CIEDE2000 formula. Gloss and ΔE00 were analyzed by two-way analysis of variance (ANOVA) (alpha = .05). Separate one-way ANOVA and Tukey post-hoc analyses were performed for both polish conditions and all materials. Two-way ANOVA showed that factors material, polish and their interaction were significant for both gloss and ΔE00 (p < .01). Post-hoc analysis reveals that polished specimens had significantly less color change than un-polished specimens for Paradigm C and LAVA Ultimate. E.max had significantly higher gloss and less color change than all other materials. The composition and polish of CAD/CAM materials affects gloss and stain resistance. Ceramic-polymer hybrid materials can achieve the high gloss required for esthetic restorations. These materials should be polished in order to minimize staining. If polished, all of the tested materials exhibited clinically acceptable color changes at 1 year of simulated staining. (J Esthet Restor Dent 28:S40-S45, 2016). © 2015 Wiley Periodicals, Inc.

Validation of [(11) C]ORM-13070 as a PET tracer for alpha2c -adrenoceptors in the human brain.

PubMed

Lehto, Jussi; Hirvonen, Mika M; Johansson, Jarkko; Kemppainen, Jukka; Luoto, Pauliina; Naukkarinen, Tarja; Oikonen, Vesa; Arponen, Eveliina; Rouru, Juha; Sallinen, Jukka; Scheinin, Harry; Vuorilehto, Lauri; Finnema, Sjoerd J; Halldin, Christer; Rinne, Juha O; Scheinin, Mika

2015-03-01

This study explored the use of the α2C -adrenoceptor PET tracer [(11) C]ORM-13070 to monitor α2C -AR occupancy in the human brain. The subtype-nonselective α2 -AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency (Emax and EC50 ) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations of endogenous noradrenaline in the brain, in response to several pharmacological and sensory challenge conditions. We assessed occupancy from the bound-to-free ratio measured during 5-30 min post injection. Based on extrapolation of one-site binding, the maximal extent of inhibition of striatal [(11) C]ORM-13070 uptake (Emax ) achievable by atipamezole was 78% (95% CI 69-87%) in the caudate nucleus and 65% (53-77%) in the putamen. The EC50 estimates of atipamezole (1.6 and 2.5 ng/ml, respectively) were in agreement with the drug's affinity to α2C -ARs. These findings represent clear support for the use of [(11) C]ORM-13070 for monitoring drug occupancy of α2C -ARs in the living human brain. Three of the employed noradrenaline challenges were associated with small, approximately 10-16% average reductions in tracer uptake in the dorsal striatum (atomoxetine, ketamine, and the cold pressor test; P < 0.05 for all), but insulin-induced hypoglycemia did not affect tracer uptake. The tracer is suitable for studying central nervous system receptor occupancy by α2C -AR ligands in human subjects. [(11) C]ORM-13070 also holds potential as a tool for in vivo monitoring of synaptic concentrations of noradrenaline, but this remains to be further evaluated in future studies. © 2014 Wiley Periodicals, Inc.

Retrospective clinical evaluation of ceramic onlays placed by dental students.

PubMed

Archibald, Jennifer J; Santos, Gildo Coelho; Moraes Coelho Santos, Maria Jacinta

2017-09-16

Indirect restorations with partial or complete occlusal surface coverage have been recommended to restore teeth with weakened walls in order to prevent cusp fracture. The success of these restorations when performed by dental students is unknown. The purpose of this retrospective study was to evaluate the clinical performance of adhesively bonded ceramic onlay restorations placed by third- and fourth-year dental students. Sixty-five ceramic onlays were placed in patients between 2009 and 2015. The onlays were laboratory or chairside fabricated with a computer-aided design and computer-aided manufacturing (CAD-CAM) system, using either IPS e.max Press or IPS e.max CAD. An adhesive technique and luting composite resin agent were used to cement the restorations. Thirty-seven onlays were evaluated clinically using the modified United States Public Health Service (USPHS) criteria. Data were statistically analyzed using the Cox proportional hazards model to compare tooth type and failures and the Fisher exact and McNemar tests to compare the USPHS criteria for significant differences (α=.05). Survival probability was calculated using the Kaplan-Meier algorithm. Five onlays were considered to be failures and needed replacement. According to the Kaplan-Meier analysis, the estimated survival rate was 96.3% after 2 years and 91.5% at 4 years. All 5 of the failures occurred on molars (13.5%) and none on premolars (P=.025). A statistically significant difference was found for marginal discoloration between onlays placed within 0 to 3 years and 3 to 6 years (P<.05) but no differences between any other criteria. Ceramic onlays placed by dental students demonstrated acceptable long-term clinical performance. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

PubMed Central

Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric

2014-01-01

Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

PubMed

Borgarelli, M; Savarino, P; Crosara, S; Santilli, R A; Chiavegato, D; Poggi, M; Bellino, C; La Rosa, G; Zanatta, R; Haggstrom, J; Tarducci, A

2008-01-01

There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis.

PubMed

Acar, S; Millar, E; Mitkova, M; Mitkov, V

2016-11-01

The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. The following values of Young's modulus were found in subgroup A (adenomyosis): Emean - 72.7 (22.6-274.2) kPa (median, 5-95th percentiles), Emax - 94.8 (29.3-300.0) kPa, SD - 9.9 (2.6-26.3) kPa; in subgroup B (non adenomyosis) - 28.3 (12.7-59.5) kPa, 33.6 (16.0-80.8) kPa, 3.0 (1.4-15.6) kPa; in the control group - 24.4 (17.9-32.4) kPa, 29.8 (21.6-40.8) kPa, 2.3 (1.3-6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis.

CO2 and Nd:YAP laser interaction with lithium disilicate and Zirconia dental ceramics: A preliminary study

NASA Astrophysics Data System (ADS)

Rocca, Jean-Paul; Fornaini, Carlo; Brulat-Bouchard, Nathalie; Bassel Seif, Samy; Darque-Ceretti, Evelyne

2014-04-01

Lithium disilicate and Zirconia ceramics offer a high level of accuracy when used in prosthetic dentistry. Their bonding using different resins is highly dependent on micro-mechanical interlocking and adhesive chemical bonding. Investigation of the performances of high strength ceramics when their surface is modified for chemical and mechanical bonding is then required. The aim of this study is to investigate the possibility of using laser for surface treatment of different high strength CAD/CAM ceramics and thus to improve their mechanical and chemical properties. Thirty two CAD/CAM ceramic discs were divided into two different groups: lithium disilicate ceramics (IPS e.max CAD®, Ivoclar, Vivadent, Italy) and Zirconia ceramics (IPS e.max ZirCAD®, Ivoclar, Vivadent, Italy). The Laser surface treatment was performed by Carbon Dioxide laser (Dream Pulse Laser®, Daeshin Enterprise Corp., Korea) at 20 W, 25 W and 30 W CW and by Neodymium Yttrium Aluminum Perovskite laser (Nd:YAP Lokki®, Lobel Medical, France) at 10 W and 30 Hz. Physical modifications of the irradiated ceramic discs were observed by scanning electron microscopy (SEM) and chemically analyzed by Energy-Dispersive Spectroscopy (EDS). Surface wettability was tested using the water drop test and the crystalline structure was investigated using X-ray diffraction (XRD). The macroscopic observation showed a shinier structure in all the groups, while at the SEM observation only CO2 25 W and 30 W treated groups showed cracks and fissures. In the conditions of this study, CO2 laser and Nd:YAP laser with the parameters used create chemical and physical surface modifications of the ceramics, indicating the possibility of an improvement in adhesion of the tested ceramics.

A three-parameter two-state model of receptor function that incorporates affinity, efficacy, and signal amplification.

PubMed

Buchwald, Peter

2017-06-01

A generalized model of receptor function is proposed that relies on the essential assumptions of the minimal two-state receptor theory (i.e., ligand binding followed by receptor activation), but uses a different parametrization and allows nonlinear response (transduction) for possible signal amplification. For the most general case, three parameters are used: K d , the classic equilibrium dissociation constant to characterize binding affinity; ε , an intrinsic efficacy to characterize the ability of the bound ligand to activate the receptor (ranging from 0 for an antagonist to 1 for a full agonist); and γ , a gain (amplification) parameter to characterize the nonlinearity of postactivation signal transduction (ranging from 1 for no amplification to infinity). The obtained equation, E/Emax=εγLεγ+1-εL+Kd, resembles that of the operational (Black and Leff) or minimal two-state (del Castillo-Katz) models, E/Emax=τLτ+1L+Kd, with εγ playing a role somewhat similar to that of the τ efficacy parameter of those models, but has several advantages. Its parameters are more intuitive as they are conceptually clearly related to the different steps of binding, activation, and signal transduction (amplification), and they are also better suited for optimization by nonlinear regression. It allows fitting of complex data where receptor binding and response are measured separately and the fractional occupancy and response are mismatched. Unlike the previous models, it is a true generalized model as simplified forms can be reproduced with special cases of its parameters. Such simplified forms can be used on their own to characterize partial agonism, competing partial and full agonists, or signal amplification.

Pharmacokinetics and pharmacodynamics of rocuronium in young adult and elderly patients undergoing elective surgery.

PubMed

Varrique, Renan M; Lauretti, Gabriela R; Matsumoto, Julia A; Lanchote, Vera L; de Moraes, Natalia V

2016-11-01

To evaluate the impact of advanced age on rocuronium kinetic disposition in ASA I-III patients undergoing elective surgeries. Young adult (20-50 years, n = 15) and elderly patients (65-85 years, n = 14) submitted to surgery under general anaesthesia were investigated. All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol. Rocuronium-induced neuromuscular block was monitored by train of four stimulations of the adductor muscle of the thumb on the ulnar nerve. The pharmacokinetic parameters were calculated by non-compartmental analysis. The relationship between rocuronium plasma concentration and the neuromuscular blockade was described by a sigmoidal Emax model. Elderly patients presented decreased Cl (2.1 ml/kg per min vs 2.8 ml/kg per min; P = 0.0123); increased AUC/dose (507.8 μg min/ml (mg/kg) vs 392.2 μg min/ml/(mg/kg); P = 0.0168) and reduced volume of distribution (285.4 ml/kg vs 435.6 ml/kg, P = 0.0434) compared to young adults. The concentrations required to achieve 50% of maximum neuromuscular block (EC50) were similar for young adult (338.8 ng/ml) and elderly (462.7 ng/ml) patients (P > 0.05). Elderly patients showed increased AUC/D and reduced total Cl compared to young adult patients due to the age-related reduced renal function. Differences in the PK-PD properties of rocuronium in elderly population are due to changes in drug disposition rather than to alterations in the sensitivity to the drug. © 2016 Royal Pharmaceutical Society.

Three-dimensional shear wave elastography for differentiation of breast lesions: An initial study with quantitative analysis using three orthogonal planes.

PubMed

Wang, Qiao

2018-05-25

To prospectively evaluate the diagnostic performance of three-dimensional (3D) shear wave elastography (SWE) for breast lesions with quantitative stiffness information from transverse, sagittal and coronal planes. Conventional ultrasound (US), two-dimensional (2D)-SWE and 3D-SWE were performed for 122 consecutive patients with 122 breast lesions before biopsy or surgical excision. Maximum elasticity values of Young's modulus (Emax) were recorded on 2D-SWE and three planes of 3D-SWE. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, 2D-SWE and 3D-SWE were evaluated. Two combined sets (i.e., BI-RADS and 2D-SWE; BI-RADS and 3D-SWE) were compared in AUC. Observer consistency was also evaluated. On 3D-SWE, the AUC and sensitivity of sagittal plane were significantly higher than those of transverse and coronal planes (both P < 0.05). Compared with BI-RADS alone, both combined sets had significantly (P < 0.05) higher AUCs and specificities, whereas, the two combined sets showed no significant difference in AUC (P > 0.05). However, the combined set of BI-RADS and sagittal plane of 3D-SWE had significantly higher sensitivity than the combined set of BI-RADS and 2D-SWE. The sagittal plane shows the best diagnostic performance among 3D-SWE. The combination of BI-RADS and 3D-SWE is a useful tool for predicting breast malignant lesions in comparison with BI-RADS alone.

Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats.

PubMed

Bastos, Joana F A; Moreira, Italo J A; Ribeiro, Thaís P; Medeiros, Isac A; Antoniolli, Angelo R; De Sousa, Damião P; Santos, Márcio R V

2010-04-01

Citronellol is an essential oil constituent from the medicinal plants Cymbopogon citratus, Cymbopogon winterianus and Lippia alba which are thought to possess antihypertensive properties. Citronellol-induced cardiovascular effects were evaluated in this study. In rats, citronellol (1-20 mg/kg, i.v.) induced hypotension, which was not affected by pre-treatment with atropine, hexamethonium, N(omega)-nitro-L-arginine methyl ester hydrochloride or indomethacin, and tachycardia, which was only attenuated by pre-treatment with atropine and hexamethonium. These responses were less than those obtained for nifedipine, a reference drug. In intact rings of rat mesenteric artery pre-contracted with 10 microM phenylephrine, citronellol induced relaxations (pD(2) = 0.71 +/- 0.11; E(max) = 102 +/- 5%; n = 6) that were not affected by endothelium removal, after tetraethylamonium in rings without endothelium pre-contracted with KCl 80 mM. Citronellol strongly antagonized (maximal inhibition = 97 +/- 4%; n = 6) the contractions induced by CaCl(2) (10(-6) to 3 x 10(-3 )M) and did not induce additional effects on the maximal response of nifedipine (10 microM). Finally, citronellol inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. The present results suggest that citronellol lowers blood pressure by a direct effect on the vascular smooth muscle leading to vasodilation.

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers

PubMed Central

Ericsson, H; Fakt, C; Jolin-Mellgård, Å; Nordlander, M; Sohtell, L; Sunzel, M; Regårdh, C G

1999-01-01

Aims To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. Methods Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min−1 kg−1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. Results Clevidipine was administered up to a target dose rate of 48 nmol min−1 kg−1, where a pre-determined escape criterion was reached (HR>120 beats min−1) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min−1 kg−1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min−1 kg−1, and the volume of distribution at steady state was 0.56 l kg−1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min−1). Conclusions Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min−1 kg−1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine. PMID:10336577

Evaluation of the surface roughness of zirconia ceramics after different surface treatments.

PubMed

Kirmali, Omer; Akin, Hakan; Kapdan, Alper

2014-08-01

This study aimed to investigate the effects of different mechanical surface treatments of pre-sintered zirconium oxide (ZrO2) in an attempt to improve its bonding potential. One hundred and twenty IPS e-max ZirCAD (Ivoclar Vivadent) pre-sintered zirconia blocks (7 mm diameter, 3 mm height) received six different surface treatments (n = 20): Group C was untreated (control); Group E was Er:YAG laser irradiated; Group N was Nd:YAG laser irradiated; Group SB was sandblasted, Group SN was sandblasted and Nd:YAG laser irradiated; and Group SE was sandblasted and Er:YAG laser irradiated. After the surface treatments, the average surface roughness (Ra, µm) of each specimen was determined with a profilometer, then all the specimens were sintered. The surface roughness values were analysed through one-way ANOVA and Tukey's test. Changes in the morphological characteristics of ZrO2 were examined through scanning electron microscopy (SEM). Sintered sandblasted, Er:YAG laser treatment, sandblasted + Er:YAG laser and sandblasted + Nd:YAG laser irradiation resulted in a rougher surface than the other treatments. Nd:YAG laser irradiation alone was not effective in altering the zirconia surface morphology.

Light curing through glass ceramics: effect of curing mode on micromechanical properties of dual-curing resin cements.

PubMed

Flury, Simon; Lussi, Adrian; Hickel, Reinhard; Ilie, Nicoleta

2014-04-01

The aim of this study was to investigate micromechanical properties of five dual-curing resin cements after different curing modes including light curing through glass ceramic materials. Vickers hardness (VH) and indentation modulus (Y HU) of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA were measured after 1 week of storage (37 °C, 100 % humidity). The resin cements were tested following self-curing or light curing with the second-generation light-emitting diode (LED) curing unit Elipar FreeLight 2 in Standard Mode (1,545 mW/cm(2)) or with the third-generation LED curing unit VALO in High Power Mode (1,869 mW/cm(2)) or in XtraPower Mode (3,505 mW/cm(2)). Light curing was performed directly or through glass ceramic discs of 1.5 or 3 mm thickness of IPS Empress CAD or IPS e.max CAD. VH and Y HU were analysed with Kruskal-Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). RelyX Unicem 2 Automix resulted in the highest VH and Y HU followed by BeautiCem SA, BisCem, SpeedCEM, and finally Panavia F2.0. Self-curing of RelyX Unicem 2 Automix and SpeedCEM lowered VH and Y HU compared to light curing whereas self-curing of Panavia F2.0, BisCem, and BeautiCem SA led to similar or significantly higher VH and Y HU compared to light curing. Generally, direct light curing resulted in similar or lower VH and Y HU compared to light curing through 1.5-mm-thick ceramic discs. Light curing through 3-mm-thick discs of IPS e.max CAD generally reduced VH and Y HU for all resin cements except SpeedCEM, which was the least affected by light curing through ceramic discs. The resin cements responded heterogeneously to changes in curing mode. The applied irradiances and light curing times adequately cured the resin cements even through 1.5-mm-thick ceramic discs. When light curing resin cements through thick glass ceramic restorations, clinicians should consider to prolong the light curing times even with LED curing units providing high irradiances.

Influence of Etching Protocol and Silane Treatment with a Universal Adhesive on Lithium Disilicate Bond Strength.

PubMed

Kalavacharla, V K; Lawson, N C; Ramp, L C; Burgess, J O

2015-01-01

To measure the effects of hydrofluoric acid (HF) etching and silane prior to the application of a universal adhesive on the bond strength between lithium disilicate and a resin. Sixty blocks of lithium disilicate (e.max CAD, Ivoclar Vivadent) were sectioned into coupons and polished. Specimens were divided into six groups (n=10) based on surface pretreatments, as follows: 1) no treatment (control); 2) 5% HF etch for 20 seconds (5HF); 3) 9.5% HF etch for 60 seconds (9.5HF); 4) silane with no HF (S); 5) 5% HF for 20 seconds + silane (5HFS); and 6) 9.5% HF for 60 seconds + silane (9.5HFS). All etching was followed by rinsing, and all silane was applied in one coat for 20 seconds and then dried. The universal adhesive (Scotchbond Universal, 3M ESPE) was applied onto the pretreated ceramic surface, air thinned, and light cured for 10 seconds. A 1.5-mm-diameter plastic tube filled with Z100 composite (3M ESPE) was applied over the bonded ceramic surface and light cured for 20 seconds on all four sides. The specimens were thermocycled for 10,000 cycles (5°C-50°C/15 s dwell time). Specimens were loaded until failure using a universal testing machine at a crosshead speed of 1 mm/min. The peak failure load was used to calculate the shear bond strength. Scanning electron microscopy images were taken of representative e.max specimens from each group. A two-way analysis of variance (ANOVA) determined that there were significant differences between HF etching, silane treatment, and the interaction between HF and silane treatment (p<0.01). Silane treatment provided higher shear bond strength regardless of the use or concentration of the HF etchant. Individual one-way ANOVA and Tukey post hoc analyses were performed for each silane group. Shear bond strength values for each etch time were significantly different (p<0.01) and could be divided into significantly different groups based on silane treatment: no silane treatment: 0 HF < 5% HF < 9.5% HF; and RelyX silane treatment: 0 HF < 5% HF and 9.5% HF. Both HF and silane treatment significantly improved the bond strength between resin and lithium disilicate when used with a universal adhesive.

Effect of varying core thicknesses and artificial aging on the color difference of different all-ceramic materials.

PubMed

Dikicier, Sibel; Ayyildiz, Simel; Ozen, Julide; Sipahi, Cumhur

2014-11-01

Clinicians should reserve all-ceramics with high translucency for clinical applications in which high-level esthetics are required. Furthermore, it is unclear whether a correlation exists between core thickness and color change. The aim of this study was to examine the effects of different core thicknesses and artificial aging on the color stability of three all-ceramic systems. Ninety disc-shaped cores with different thicknesses (0.5 mm, 0.8 mm and 1.0 mm) were prepared from three all-ceramic systems, In-Ceram Alumina (IC), IPS e.max Press (EM) and Katana (K). The colors of the samples were measured with a spectrophotometer and the color parameters (L*, a*, b*, ΔE) were calculated according to the CIE L*a*b* (Commission Internationale de L'Eclairage) color system before and after aging. The effects of aging on color parameters were statistically significant (p < 0.001), regardless of core thickness. For all systems, the CIE a* values increased as the thickness of the core increased. Conversely, such increases in core porcelain thickness were correlated with decreasing CIE L* and b* values. Core thickness had a statistically significant effect on color change among the groups. Different core thicknesses (from 1.0-0.5 mm) and artificial aging affected color stability of the all-ceramic materials tested.

Diarylureas as allosteric modulators of the cannabinoid CB1 receptor: structure-activity relationship studies on 1-(4-chlorophenyl)-3-{3-[6-(pyrrolidin-1-yl)pyridin-2-yl]phenyl}urea (PSNCBAM-1).

PubMed

German, Nadezhda; Decker, Ann M; Gilmour, Brian P; Gay, Elaine A; Wiley, Jenny L; Thomas, Brian F; Zhang, Yanan

2014-09-25

The recent discovery of allosteric modulators of the CB1 receptor including PSNCBAM-1 (4) has generated significant interest in CB1 receptor allosteric modulation. Here in the first SAR study on 4, we have designed and synthesized a series of analogs focusing on modifications at two positions. Pharmacological evaluation in calcium mobilization and binding assays revealed the importance of alkyl substitution at the 2-aminopyridine moiety and electron deficient aromatic groups at the 4-chlorophenyl position for activity at the CB1 receptor, resulting in several analogs with comparable potency to 4. These compounds increased the specific binding of [(3)H]CP55,940, in agreement with previous reports. Importantly, 4 and two analogs dose-dependently reduced the Emax of the agonist curve in the CB1 calcium mobilization assays, confirming their negative allosteric modulator characteristics. Given the side effects associated with CB1 receptor orthosteric antagonists, negative allosteric modulators provide an alternative approach to modulate the pharmacologically important CB1 receptor.

Initial versus final fracture of metal-free crowns, analyzed via acoustic emission.

PubMed

Ereifej, Nadia; Silikas, Nick; Watts, David C

2008-09-01

To discriminate between initial and final fracture failure loads of four metal-free crown systems by the conjoint detection of acoustic emission signals during compressive loading. Teeth were prepared and used for crown construction with four crown systems; Vita Mark II (VM II) (Vita Zahnfabrik), IPS e.max Ceram/CAD (CAD) (Ivoclar-Vivadent), IPS e.max Ceram/ZirCAD (ZirCAD) (Ivoclar-Vivadent) and BelleGlass/EverStick (BGES) (Kerr/Stick Tech Ltd.). All samples were loaded in compression via a Co/Cr maxillary first molar tooth at 0.2mm/min and released acoustic signals were collected and analyzed. A minimum number of 15 crowns per group were loaded to final failure and values of loading at initial and final fracture were compared. Additional four samples per group were loaded till fracture initiation and were fractographically examined under the optical microscope. A lower threshold of 50dB was selected to exclude spurious background signals. Initial fracture forces were significantly lower than those of final fracture (p<0.05) in all groups and initial failure AE amplitudes were lower than those of final fracture. Mean initial fracture force of ZirCAD samples (1029.1N) was higher than those of VMII (744.4N), CAD (808.8 N) and BGES (979.7 N). Final fracture of ZirCAD also occurred at significantly higher force values (2091.7 N) than the rest of the groups; VMII (1120.9 N), CAD (1468.9 N) and BGES (1576.6 N). Significantly higher values of initial failure AE amplitude were found in VMII than CAD and BGES while those of final fracture were similar. All crowns observed under the microscope at initial fracture had signs of failure. Whereas the metal-free crowns examined showed significant variations in final failure loads, acoustic emission data showed that they all manifested initial failures at significantly lower load values.

RX-P873, a Novel Protein Synthesis Inhibitor, Accumulates in Human THP-1 Monocytes and Is Active against Intracellular Infections by Gram-Positive (Staphylococcus aureus) and Gram-Negative (Pseudomonas aeruginosa) Bacteria

PubMed Central

Buyck, Julien M.; Peyrusson, Frédéric

2015-01-01

The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by Staphylococcus aureus and Pseudomonas aeruginosa, using a pharmacodynamic approach allowing the determination of maximal relative efficacies (Emax values) and bacteriostatic concentrations (Cs values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter (S. aureus) and 2 to 8 mg/liter (P. aeruginosa), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains. Emax values (expressed as the decrease in the number of CFU from that in the initial inoculum) against S. aureus and P. aeruginosa reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h. Cs values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for S. aureus; ciprofloxacin and ceftazidime for P. aeruginosa). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against P. aeruginosa than against S. aureus. Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species. PMID:26014952

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis

PubMed Central

Millar, E; Mitkova, M; Mitkov, V

2016-01-01

Background The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. Methods One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. Results The following values of Young’s modulus were found in subgroup A (adenomyosis): Emean – 72.7 (22.6–274.2) kPa (median, 5–95th percentiles), Emax – 94.8 (29.3–300.0) kPa, SD – 9.9 (2.6–26.3) kPa; in subgroup B (non adenomyosis) – 28.3 (12.7–59.5) kPa, 33.6 (16.0–80.8) kPa, 3.0 (1.4–15.6) kPa; in the control group – 24.4 (17.9–32.4) kPa, 29.8 (21.6–40.8) kPa, 2.3 (1.3–6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). Conclusion This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis. PMID:27847535

Translucency of dental ceramics with different thicknesses.

PubMed

Wang, Fu; Takahashi, Hidekazu; Iwasaki, Naohiko

2013-07-01

The increased use of esthetic restorations requires an improved understanding of the translucent characteristics of ceramic materials. Ceramic translucency has been considered to be dependent on composition and thickness, but less information is available about the translucent characteristics of these materials, especially at different thicknesses. The purpose of this study was to investigate the relationship between translucency and the thickness of different dental ceramics. Six disk-shaped specimens of 8 glass ceramics (IPS e.max Press HO, MO, LT, HT, IPS e.max CAD LT, MO, AvanteZ Dentin, and Trans) and 5 specimens of 5 zirconia ceramics (Cercon Base, Zenotec Zr Bridge, Lava Standard, Lava Standard FS3, and Lava Plus High Translucency) were prepared following the manufacturers' instructions and ground to a predetermined thickness with a grinding machine. A spectrophotometer was used to measure the translucency parameters (TP) of the glass ceramics, which ranged from 2.0 to 0.6 mm, and of the zirconia ceramics, which ranged from 1.0 to 0.4 mm. The relationship between the thickness and TP of each material was evaluated using a regression analysis (α=.05). The TP values of the glass ceramics ranged from 2.2 to 25.3 and the zirconia ceramics from 5.5 to 15.1. There was an increase in the TP with a decrease in thickness, but the amount of change was material dependent. An exponential relationship with statistical significance (P<.05) between the TP and thickness was found for both glass ceramics and zirconia ceramics. The translucency of dental ceramics was significantly influenced by both material and thickness. The translucency of all materials increased exponentially as the thickness decreased. All of the zirconia ceramics evaluated in the present study showed some degree of translucency, which was less sensitive to thickness compared to that of the glass ceramics. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Wear properties of dental ceramics and porcelains compared with human enamel.

PubMed

D'Arcangelo, Camillo; Vanini, Lorenzo; Rondoni, Giuseppe D; De Angelis, Francesco

2016-03-01

Contemporary pressable and computer-aided design/manufacturing (CAD/CAM) ceramics exhibit good mechanical and esthetic properties. Their wear resistance compared with human enamel and traditional gold based alloys needs to be better investigated. The purpose of this in vitro study was to compare the 2-body wear resistance of human enamel, gold alloy, and 5 different dental ceramics, including a recently introduced zirconia-reinforced lithium silicate ceramic (Celtra Duo). Cylindrical specimens were fabricated from a Type III gold alloy (Aurocast8), 2 hot pressed ceramics (Imagine PressX, IPS e.max Press), 2 CAD/CAM ceramics (IPS e.max CAD, Celtra Duo), and a CAD/CAM feldspathic porcelain (Vitablocs Mark II) (n=10). Celtra Duo was tested both soon after grinding and after a subsequent glaze firing cycle. Ten flat human enamel specimens were used as the control group. All specimens were subjected to a 2-body wear test in a dual axis mastication simulator for 120000 loading cycles against yttria stabilized tetragonal zirconia polycrystal cusps. The wear resistance was analyzed by measuring the vertical substance loss (mm) and the volume loss (mm(3)). Antagonist wear (mm) was also recorded. Data were statistically analyzed with 1-way ANOVA tests (α=.05). The wear depth (0.223 mm) of gold alloy was the closest to that of human enamel (0.217 mm), with no significant difference (P>.05). The greatest wear was recorded on the milled Celtra Duo (wear depth=0.320 mm), which appeared significantly less wear resistant than gold alloy or human enamel (P<.05). The milled and not glazed Celtra Duo showed a small but significantly increased wear depth compared with Aurocast8 and human enamel. Wear depth and volumetric loss for the glaze-fired Celtra Duo and for the other tested ceramics did not statistically differ in comparison with the human enamel. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Adhoc Wireless Network Control: Energy Efficiency and Hidden Terminal Considerations

DTIC Science & Technology

2009-12-01

Pnl (t) +Bn(t), Emax ) , (57) Ynl(t+ 1) = [Ynl(t)−Rnl,in(t)] + + γnl(t), (58) Dn(t+ 1) = [Dn(t...1− δ)Bn(t)] + + ∑ l∈On Pnl (t), (59) subject to constraints Rnl,in(t) ≤ Vnl(t) +Anl(t) ∀n, l, t, P (t) ∈ PS(t), ∑ l∈On Pnl (t) ≤ min ( En(t), P̂ ) ∀n...γnl(t)] ∣ ∣ ∣ ∣ ∣ ∣ X(t)   − 2E   ∑ n,l [Unl(t)µnl (S(t),P (t))−Dn(t) Pnl (t)] ∣ ∣ ∣ ∣ ∣ ∣ X(t)  − 2E   ∑ n,l [ηYnl(t)−

Effect of nano-scale characteristics of graphene on electrochemical performance of activated carbon supercapacitor electrodes

NASA Astrophysics Data System (ADS)

Jasni, M. R. M.; Deraman, M.; Suleman, M.; Hamdan, E.; Sazali, N. E. S.; Nor, N. S. M.; Shamsudin, S. A.

2016-02-01

Graphene with its typical nano-scale characteristic properties has been widely used as an additive in activated carbon electrodes in order to enhance the performance of the electrodes for their use in high performance supercapacitors. Activated carbon monoliths (ACMs) electrodes have been prepared by carbonization and activation of green monoliths (GMs) of pre-carbonized fibers of oil palm empty fruit bunches or self-adhesive carbon grains (SACGs) and SACGs added with 6 wt% of KOH-treated multi-layer graphene. ACMs electrodes have been assembled in symmetrical supercapacitor cells that employed aqueous KOH electrolyte (6 M). The cells have been tested with cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge discharge methods to investigate the effect of graphene addition on the specific capacitance (Csp), specific energy (E), specific power (P), equivalent series resistance (ESR) and response time (τo) of the supercapacitor cells. The results show that the addition of graphene in the GMs change the values of Csp, Emax, Pmax, ESR and τo from (61-96) F/g, 2 Wh/kg, 104 W/kg, 2.6 Ω and 38 s, to the respective values of (110-124) F/g, 3 Wh/kg, 156 W/kg, 3.4 Ω and 63 s. This study demonstrates that the graphene addition in the GMs has a significant effect on the electrochemical behavior of the electrodes.

Analysis of flexural strength and contact pressure after simulated chairside adjustment of pressed lithium disilicate glass-ceramic.

PubMed

Ramadhan, Ali; Thompson, Geoffrey A; Maroulakos, Georgios; Berzins, David

2018-04-30

Research evaluating load-to-failure of pressed lithium disilicate glass-ceramic (LDGC) with a clinically validated test after adjustment and repair procedures is scarce. The purpose of this in vitro study was to investigate the effect of the simulated chairside adjustment of the intaglio surface of monolithic pressed LDGC and procedures intended to repair damage. A total of 423 IPS e.max Press (Ivoclar Vivadent AG) disks (15 mm diameter, 1 mm height) were used in the study. The material was tested by using an equibiaxial loading arrangement (n≥30/group) and a contact pressure test (n≥20/group). Specimens were assigned to 1 of 14 groups. One-half was assigned to the equibiaxial load test and the other half underwent contact pressure testing. Testing was performed in 2 parts, before glazing and after glazing. Before-glazing specimens were devested and entered in the test protocol, while after-glazing specimens were devested and glazed before entering the test protocol. Equibiaxial flexure test specimens were placed on a ring-on-ring apparatus and loaded until failure. Contact pressure specimens were cemented to epoxy resin blocks with a resin cement and loaded with a 50-mm diameter hemisphere until failure. Tests were performed on a universal testing machine with a crosshead speed of 0.5 mm/min. Weibull statistics and likelihood ratio contour plots determined intergroup differences (95% confidence bounds). Before glazing, the equibiaxial flexural strength test and the Weibull and likelihood ratio contour plots demonstrated a significantly higher failure strength for 1EC (188 MPa) than that of the damaged and/or repaired groups. Glazing following diamond-adjustment (1EGG) was the most beneficial post-damage procedure (176 MPa). Regarding the contact pressure test, the Weibull and likelihood ratio contour plots revealed no significant difference between the 1PC (98 MPa) and 1PGG (98 MPa) groups. Diamond-adjustment, without glazing (1EG and 1PG), resulted in the next-to-lowest equibiaxial flexure strength and the lowest contact pressure. After glazing, the strength of all the groups, when subjected to glazing following devesting, increased in comparison with corresponding groups in the before-glazing part of the study. A glazing treatment improved the mechanical properties of diamond-adjusted IPS e.max Press disks when evaluated by equibiaxial flexure and contact pressure tests. Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period.

PubMed

Dong, Min; Fukuda, Tsuyoshi; Cox, Shareen; de Vries, Marij T; Hooper, David K; Goebel, Jens; Vinks, Alexander A

2014-11-01

The purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK-PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post-transplant period. A total of 214 MPA plasma concentrations-time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK-PD modelling. The PK-PD model was developed using non-linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK-PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co-medication and clinical laboratory data. Non-parametric bootstrapping and prediction-corrected visual predictive checks were performed to evaluate the final models. A two compartment model with a transit compartment absorption best described MPA PK. A non-linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h(-1) 70 kg(-1) ; Vc /F, 45.4 (29.6, 55.6) l; Vp /F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h(-1) ; Ka , 2.5 (1.45, 4.93) h(-1) . Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK-PD parameter estimates (and their 95% confidence intervals) were: E0 , 3.45 (2.61, 4.56) nmol h(-1)  mg(-1) protein and EC50 , 1.73 (1.16, 3.01) mg l(-1) . Emax was fixed to 0. There were two African-American patients in our study cohorts and both had low IMPDH baseline activities (E0 ) compared with Caucasian patients (mean value 2.13 mg l(-1) vs. 3.86 mg l(-1) ). An integrated population PK-PD model of MPA has been developed in paediatric renal transplant recipients. The current model provides information that will facilitate future studies and may be implemented in a Bayesian algorithm to allow a PK-PD guided therapeutic drug monitoring strategy. © 2014 The British Pharmacological Society.

Pharmacological characterization of the diuretic effect of Hibiscus sabdariffa Linn (Malvaceae) extract.

PubMed

Alarcón-Alonso, Javier; Zamilpa, Alejandro; Aguilar, Francisco Alarcón; Herrera-Ruiz, Maribel; Tortoriello, Jaime; Jimenez-Ferrer, Enrique

2012-02-15

Hibiscus sabdariffa L. (Malvaceae) populary known in Mexico as "Jamaica", "flor de Jamaica", has widely used in Mexican Traditional Medicine as antihypertensive and diuretic, although the latter activity has been reported the present work show evidence about the diuretic, natriuretic and potassium-sparing effects. To evaluate the diuretic activity of Hibiscus sabdariffa aqueous extract on in vivo and in situ models. The Hibiscus sabdariffa aqueous extract was administrated in increasing doses and evaluated the diuresis produced and disposal of electrolytes. Moreover, in isolated kidney was determined the renal filtration rate with plant extract, furosemide and amiloride. The yield of Hibiscus sabdariffa aqueous extraction was 28.3% and the chemical standardization from 1 g of extract was: 56.5 mg delphinidin-3-O-sambubioside, 20.8 mg/g cyanidin-3-O-sambubioside, 3.2 mg/g quercetin, 2.1 mg/g rutin and 2.7 mg/g chlorogenic acid. The diuretic and natriuretic effect of Hibiscus sabdariffa aqueous extract showed a dose-dependent behavior. The pharmacological constants of natriuretic effect was ED50=86 mg/kg and Emax=0.9 mEq/100 g/5 h. In the model of kidney in situ was observed that renal filtration increased 48% with the aqueous extract of Hibiscus sabdariffa and an additive effect when was perfuse with furosemide. The compound presents in Hibiscus sabdariffa as quercetin had effect on the vascular endothelium causing oxide nitric release, increasing renal vasorelaxation by increasing kidney filtration. Therefore, the diuretic effect of Hibiscus sabdariffa may be mediated by nitric oxide release. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine in healthy volunteers.

PubMed

Yassen, Ashraf; Olofsen, Erik; Romberg, Raymonda; Sarton, Elise; Danhof, Meindert; Dahan, Albert

2006-06-01

The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers. Data on the time course of the antinociceptive effect after intravenous administration of 0.05-0.6 mg/70 kg buprenorphine in healthy volunteers was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis. A three-compartment pharmacokinetic model best described the concentration time course. Four structurally different pharmacokinetic-pharmacodynamic models were evaluated for their appropriateness to describe the time course of buprenorphine's antinociceptive effect: (1) E(max) model with an effect compartment model, (2) "power" model with an effect compartment model, (3) receptor association-dissociation model with a linear transduction function, and (4) combined biophase equilibration/receptor association-dissociation model with a linear transduction function. The latter pharmacokinetic-pharmacodynamic model described the time course of effect best and was used to explain time dependencies in buprenorphine's pharmacodynamics. The model converged, yielding precise estimation of the parameters characterizing hysteresis and the relation between relative receptor occupancy and antinociceptive effect. The rate constant describing biophase equilibration (k(eo)) was 0.00447 min(-1) (95% confidence interval, 0.00299-0.00595 min(-1)). The receptor dissociation rate constant (k(off)) was 0.0785 min(-1) (95% confidence interval, 0.0352-0.122 min(-1)), and k(on) was 0.0631 ml . ng(-1) . min(-1) (95% confidence interval, 0.0390-0.0872 ml . ng(-1) . min(-1)). This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect for antinociception.

Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics

PubMed Central

Hafner, Marc; Heiser, Laura M.; Williams, Elizabeth H.; Niepel, Mario; Wang, Nicholas J.; Korkola, James E.; Gray, Joe W.; Sorger, Peter K.

2017-01-01

Traditional means for scoring the effects of anti-cancer drugs on the growth and survival of cell lines is based on relative cell number in drug-treated and control samples and is seriously confounded by unequal division rates arising from natural biological variation and differences in culture conditions. This problem can be overcome by computing drug sensitivity on a per-division basis. The normalized growth rate inhibition (GR) approach yields per-division metrics for drug potency (GR50) and efficacy (GRmax) that are analogous to the more familiar IC50 and Emax values. In this work, we report GR-based, proliferation-corrected, drug sensitivity metrics for ~4,700 pairs of breast cancer cell lines and perturbagens. Such data are broadly useful in understanding the molecular basis of therapeutic response and resistance. Here, we use them to investigate the relationship between different measures of drug sensitivity and conclude that drug potency and efficacy exhibit high variation that is only weakly correlated. To facilitate further use of these data, computed GR curves and metrics can be browsed interactively at http://www.GRbrowser.org/. PMID:29112189

Targeted benefits of prolonged-infusion piperacillin-tazobactam in an in vitro infection model of Pseudomonas aeruginosa.

PubMed

Zelenitsky, S; Nash, J; Weber, Z; Iacovides, H; Ariano, R

2016-10-01

Given the inconsistent clinical findings, our goal was to characterize the pharmacodynamics (PDs) of prolonged-infusion piperacillin-tazobactam (TZP) in an in vitro pharmacodynamic model of Pseudomonas aeruginosa. Specifically, the study was designed to investigate the influence of MIC on the activity of prolonged-infusion TZP using pharmacokinetics (PKs) consistent with a non-critically ill patient population. There was no benefit with prolonged- compared with standard-infusion TZP against isolates with susceptible MICs of 8 or 16 mg/L. However, prolonged-infusion TZP produced more than two times the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L. The PDs of TZP were well described by a sigmoid Emax model (r(2) = 0.84) where %ƒT>MIC thresholds of 27 and 75% were associated with bacteriostatic and bactericidal effects, respectively. However, the well-established PD relationship with %ƒT>MIC was not observed with prolonged-infusion TZP. In conclusion, this study characterizes the targeted benefits of prolong-infusion TZP based on pathogen MIC, and supports the assertion that the benefits are selective and most likely observed in patients with less susceptible pathogens or altered PKs.

Modelling of pain intensity and informative dropout in a dental pain model after naproxcinod, naproxen and placebo administration

PubMed Central

Björnsson, Marcus A; Simonsson, Ulrika S H

2011-01-01

AIMS To describe pain intensity (PI) measured on a visual analogue scale (VAS) and dropout due to request for rescue medication after administration of naproxcinod, naproxen or placebo in 242 patients after wisdom tooth removal. METHODS Non-linear mixed effects modelling was used to describe the plasma concentrations of naproxen, either formed from naproxcinod or from naproxen itself, and their relationship to PI and dropout. Goodness of fit was assessed by simultaneous simulations of PI and dropout. RESULTS Baseline PI for the typical patient was 52.7 mm. The PI was influenced by placebo effects, using an exponential model, and by naproxen concentrations using a sigmoid Emax model. Typical maximal placebo effect was a decrease in PI by 20.2%, with an onset rate constant of 0.237 h−1. EC50 was 0.135 µmol l−1. A Weibull time-to-event model was used for the dropout, where the hazard was dependent on the predicted PI and by the PI at baseline. Since the dropout was not at random, it was necessary to include the simulated dropout in visual predictive checks (VPC) of PI. CONCLUSIONS This model describes the relationship between drug effects, PI and the likelihood of dropout after naproxcinod, naproxen and placebo administration. The model provides an opportunity to describe the effects of other doses or formulations, after dental extraction. VPC created by simultaneous simulations of PI and dropout provides a good way of assessing the goodness of fit when there is informative dropout. PMID:21272053

The synergetic effect of edaravone and borneol in the rat model of ischemic stroke.

PubMed

Wu, Hai-Yin; Tang, Ying; Gao, Li-Yan; Sun, Wei-Xiang; Hua, Yao; Yang, Shi-Bao; Zhang, Zheng-Ping; Liao, Gao-Yong; Zhou, Qi-Gang; Luo, Chun-Xia; Zhu, Dong-Ya

2014-10-05

Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two drugs in the rat model of transient cerebral ischemia. Edaravone scavenged OH, NO and ONOO─ concentration-dependently, and borneol inhibited ischemia/reperfusion-induced tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) expressions. In the rat model of transient cerebral ischemia and reperfusion, the combination of edaravone and borneol significantly ameliorated ischemic damage with an optimal proportion of 4:1. Emax (% inhibition) of edaravone, borneol and two drugs in combination was 55.7%, 65.8% and 74.3% respectively. ED50 of edaravone and borneol was 7.17 and 0.36 mg/kg respectively. When two drugs in combination, ED50 was 0.484 mg/kg, in which edaravone was 0.387 mg/kg (ineffective dose) and borneol was 0.097 mg/kg (ineffective dose). Combination index (CI)<1 among effects observed in experiments, suggesting a significant synergistic effect. Reduced levels of pro-inflammatory mediators and free radicals were probably associated with the synergistic effect of edaravone and borneol. The combination exhibited a therapeutic time window of 6h in ischemia/reperfusion model, and significantly ameliorated damages in permanent ischemia model. Moreover, two drugs in combination promoted long-term effect, including improved elemental vital signs, sensorimotor functions and spatial cognition. Our results suggest that the combination of edaravone and borneol have a synergistic effect for treating ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

Evidence for non-adrenergic non-cholinergic contractile responses in bovine and swine trachea.

PubMed

Matera, M G; Amorena, M; Marabese, I; Loffreda, A; D'Agostino, B; Lucisano, A; Rossi, F

1997-01-01

Non-adrenergic non-cholinergic (NANC) contraction of airway smooth muscle has been observed in some but not all animal species. The aim of this study was to investigate the NANC-contractile responses in bovine and swine trachea. Proximal and distal bovine and swine trachea were cut in strips and placed in 10 ml organ baths equilibrated in Krebs Henseleit (KH) solution and electrically stimulated (10 sec, 60 V, 2 ms, 4, 10 and 30 Hz). Contractile frequency response curves performed in the presence of the muscarinic antagonist, atropine (100 mM), the angiotensin converting enzyme inhibitor, captopril (1 microM) and the neutral endopeptidase inhibitor, thiorphan (1 microM), added 30 min prior to electrical field stimulation (EFS). In some tissues, incubated with atropine thiorphan and captopril, were also evaluated the effects of a pretreatment with capsaicin (10 microM) or a selective NK1 receptor antagonist, SR 14033 (100 nM) added to the baths 30 min prior to EFS. Bovine and swine proximal and distal tracheal preparations contracted in a frequency-dependent manner to EFS (4, 10 and 30 Hz). Some experiments were also performed with substance P (0.1 nM to 1 microM) in absence or in presence of SR 14033 (10 nM or 100 nM). At the maximum frequency tested (30 Hz), the contractile response elicited in bovine proximal and distal preparations was 194.5 +/- 17.1% and 229.7 +/- 24.1%, of ACh (100 microM), respectively. Similarly, the contractile response elicited by EFS (30 Hz) in swine proximal and distal preparations was 187.2 +/- 12.1% and 181.6 +/- 9.2% of ACh (100 microM), respectively. In tissues incubated with atropine, a significant decrease in smooth muscle sensitivity to EFS was observed (P < 0.05). When tissues were pretreated with captopril and thiorphan, a significant increase in the contractile response to EFS (30 Hz) was observed in all tested tissue preparations (bovine, proximal 210.1 +/- 14.4%, distal 264.3 +/- 16.2%; swine, proximal 199.3 +/- 14.9%, distal 206.3 +/- 16.2%, P < 0.05). In the presence of atropine, captopril and thiorphan a significant increase in the contractile response was observed in bovine and swine distal preparations compared with tissues incubated with atropine only (P < 0.05). These effects were antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. A pretreatment with capsaicin statistically (P < 0.05) enhanced EFS-induced contraction in all tested preparations respect to tissues incubated with atropine, thiorphan and captopril. Substance P induced a concentration dependent contraction of bovine and swine isolated tracheal preparations which was antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. No significant difference in the contractile potency (EC50) nor in maximum response (Emax) was observed to exogenously administered substance P between proximal and distal tracheal preparations. These data suggest that NANC contractile responses are present in bovine and swine trachea and are more evident in distal airways.

Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.

PubMed

Sheng, Yu-Cheng; Wang, Kun; He, Ying-Chun; Yang, Juan; Zheng, Qing-Shan

2010-11-01

To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach. Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition. The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease. The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.

Effect of silane pretreatment on the immediate bonding of universal adhesives to computer-aided design/computer-aided manufacturing lithium disilicate glass ceramics.

PubMed

Yao, Chenmin; Zhou, Liqun; Yang, Hongye; Wang, Yake; Sun, Hualing; Guo, Jingmei; Huang, Cui

2017-04-01

The aim of this study was to investigate the effect of silane pretreatment on the universal adhesive bonding between lithium disilicate glass ceramic and composite resin. IPS e.max ceramic blocks etched with hydrofluoric acid were randomly assigned to one of eight groups treated with one of four universal adhesives (two silane-free adhesives and two silane-containing adhesives), each with or without silane pretreatment. Bonded specimens were stored in water for 24 h. The shear bond strength (SBS) of the ceramic-resin interface was measured to evaluate bond strength, and the debonded interface after the SBS test was analysed using field-emission scanning electron microscopy to determine failure mode. Light microscopy was performed to analyse microleakage and marginal sealing ability. Silane pretreatment significantly and positively influenced SBS and marginal sealing ability. For all the universal adhesive groups, SBS increased and the percentage of microleakage decreased after the pretreatment. Without the pretreatment, SBS and the percentage of microleakage were not significantly different between the silane-containing universal adhesive groups and the silane-free groups. Cohesive failure was the main fracture pattern. The results suggest that additional silane pretreatment can effectively improve the bonding strength and marginal sealing of adhesives to lithium disilicate glass ceramics. The bonding performance of silane-containing universal adhesives without pretreatment is similar to that of silane-free adhesives. © 2017 Eur J Oral Sci.

Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat.

PubMed

Scollon, Edward J; Starr, James M; Crofton, Kevin M; Wolansky, Marcelo J; DeVito, Michael J; Hughes, Michael F

2011-11-28

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E(max) model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure. Published by Elsevier Ireland Ltd.

CAD/CAM machining Vs pre-sintering in-lab fabrication techniques of Y-TZP ceramic specimens: Effects on their mechanical fatigue behavior.

PubMed

Zucuni, C P; Guilardi, L F; Fraga, S; May, L G; Pereira, G K R; Valandro, L F

2017-07-01

This study evaluated the effects of different pre-sintering fabrication processing techniques of Y-TZP ceramic (CAD/CAM Vs. in-lab), considering surface characteristics and mechanical performance outcomes. Pre-sintered discs of Y-TZP ceramic (IPS e.max ZirCAD, Ivoclar Vivadent) were produced using different pre-sintering fabrication processing techniques: Machined- milling with a CAD/CAM system; Polished- fabrication using a cutting device followed by polishing (600 and 1200 SiC papers); Xfine- fabrication using a cutting machine followed by grinding with extra-fine diamond bur (grit size 30 μm); Fine- fabrication using a cutting machine followed by grinding with fine diamond bur (grit size 46 μm); SiC- fabrication using a cutting machine followed by grinding with 220 SiC paper. Afterwards, the discs were sintered and submitted to roughness (n=35), surface topography (n=2), phase transformation (n=2), biaxial flexural strength (n=20), and biaxial flexural fatigue strength (fatigue limit) (n=15) analyses. No monoclinic-phase content was observed in all processing techniques. It can be observed that obtaining a surface with similar characteristics to CAD/CAM milling is essential for the observation of similar mechanical performance. On this sense, grinding with fine diamond bur before sintering (Fine group) was the best mimic protocol in comparison to the CAD/CAM milling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via modeling and simulation analysis in a D2 receptor occupancy study.

PubMed

Lim, Hyeong-Seok; Kim, Su Jin; Noh, Yook-Hwan; Lee, Byung Chul; Jin, Seok-Joon; Park, Hyun Soo; Kim, Soohyeon; Jang, In-Jin; Kim, Sang Eun

2013-03-01

To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development. In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12, with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding potential to D(2) receptor in putamen and caudate nucleus over time were analyzed using NONMEM, and simulations for the profiles of D2RO over time on various regimens of haloperidol were conducted to find the optimal dosing regimens. One compartment model with a saturable binding compartment, and inhibitory E(max) model in the effect compartment best described the data. Plasma haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml, in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h is near the optimal dose. This study showed that sparse D2RO measurements in steady state pharmacodynamic design after multiple dosing could reveal the possibility of treatment effect of D(2) antagonist, and could identify the potential optimal doses for later clinical studies by modeling and simulation.

Translucency of zirconia copings made with different CAD/CAM systems.

PubMed

Baldissara, Paolo; Llukacej, Altin; Ciocca, Leonardo; Valandro, Felipe L; Scotti, Roberto

2010-07-01

Zirconia cores are reported to be less translucent than glass, lithium disilicate, or alumina cores. This could affect the esthetic appearance and the clinical choices made when using zirconia-based restorations. The purpose of this in vitro study was to evaluate the translucency of zirconia copings for single crowns fabricated using different CAD/CAM systems, using lithium disilicate glass ceramic as a control. Using impressions made from a stainless steel complete-crown master die, 9 stone cast replicas were fabricated, numbered, and distributed into 8 ceramic ZrO(2) CAD/CAM system groups (Lava Frame 0.3 and 0.5, IPS e.max ZirCAD, VITA YZ, Procera AllZircon, Digizon, DC Zircon, and Cercon Base) and to a lithium disilicate glass-ceramic control group (IPS e.max Press) using a simple computer-generated randomization method. From each die, the manufacturer's authorized milling centers supplied 5 copings per group without applying any dying technique to the ceramic base material. The copings were prepared to allow for a 40-mum cement layer and were of different thicknesses according to system specifications. Translucency was measured by the direct transmission method with a digital photoradiometer mounted in a dark chamber. The light source was a 150-W halogen lamp beam. Measurements were repeated 3 times for each specimen. Data obtained were analyzed using 1-way ANOVA and the Bonferroni multiple comparison test (alpha=.05). Among ZrO(2) copings, Lava (0.3 mm and 0.5 mm thick) showed the highest (P<.05) values of translucency measured as light flow units (3.572 + or - 018 x 10(3) lx and 3.181 + or - 0.13 x 10(3) lx, respectively). These values represent 71.7% and 63.9%, respectively, of the glass-ceramic control group (4.98 x 10(3) lx). All ZrO(2) copings demonstrated different levels of light transmission, with the 2 Lava specimens showing the highest values. Translucency of zirconia copings was significantly lower (P=.001) than that of the lithium disilicate glass-ceramic control. Copyright 2010 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras.

PubMed

de Paula Silveira, Alessandra C; Chaves, Sacha B; Hilgert, Leandro A; Ribeiro, Ana Paula D

2017-03-01

The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. The purpose of this in vitro study was to evaluate by microcomputed tomography (μCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with μCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; P<.008). In assessment of AIS by the 3D reconstruction, LB presented significantly lower values than the other groups (Tukey post hoc test; P<.05). Bluecam presented lower values of AIS than Omnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model.

PubMed

Lepak, Alexander J; Andes, David R

2016-08-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0-∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10 The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model

PubMed Central

Lepak, Alexander J.

2016-01-01

Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae. Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0–∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship observed with escalating doses of delafloxacin. Maximal organism reductions ranged from 2 log10 to more than 4 log10. The median free-drug AUC/MIC magnitude associated with net stasis for each species group was 1.45, 0.56, and 40.3 for S. aureus, S. pneumoniae, and K. pneumoniae, respectively. AUC/MIC targets for the 1-log kill endpoint were 2- to 5-fold higher. Delafloxacin demonstrated in vitro and in vivo potency against a diverse group of pathogens, including those with phenotypic drug resistance to other classes. These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints for delafloxacin for the treatment of lower respiratory tract infections involving these pathogens. PMID:27216072

Endocrown restorations: Influence of dental remnant and restorative material on stress distribution.

PubMed

Tribst, João Paulo Mendes; Dal Piva, Amanda Maria de Oliveira; Madruga, Camila Ferreira Leite; Valera, Marcia Carneiro; Borges, Alexandre Luiz Souto; Bresciani, Eduardo; de Melo, Renata Marques

2018-06-20

The goal of this study was to evaluate the stress distribution in a tooth/restoration system according to the factors "amount of dental remnant" (3 levels) and "restorative material" (2 levels). Three endodontically treated maxillary molars were modeled with CAD software for conducting non-linear finite element analysis (FEA), each with a determined amount of dental remnant of 1.5, 3, or 4.5mm. Models were duplicated, and half received restorations in lithium disilicate (IPS e.max CAD), while the other half received leucite ceramic restorations (IPS Empress CAD), both from Ivoclar Vivadent (Schaan, Liechtenstein). The solids were imported to analysis software (ANSYS 17.2, ANSYS Inc., Houston, TX, USA) in STEP format. All contacts involving the resin cement were considered no-separation, whereas between teeth and fixation cylinder, the contact was considered perfectly bonded. The mechanical properties of each structure were reported, and the materials were considered isotropic, linearly elastic, and homogeneous. An axial load (300N) was applied at the occlusal surface (triploidism area). Results were determined by colorimetric graphs of maximum principal stress (MPS) on tooth remnant, cement line, and restoration. MPS revealed that both factors influenced the stress distribution for all structures; the higher the material's elastic modulus, the higher the stress concentration on the restoration and the lower the stress concentration on the cement line. Moreover, the greater the dental crown remnant, the higher the stress concentration on the restoration. Thus, the remaining dental tissue should always be preserved. In situations in which few dental remnants are available, the thicker the restoration, the higher the concentration of stresses in its structure, protecting the adhesive interface from potential adhesive failures. Results are more promising when the endocrown is fabricated with lithium disilicate ceramic. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Grinding damage assessment for CAD-CAM restorative materials.

PubMed

Curran, Philippe; Cattani-Lorente, Maria; Anselm Wiskott, H W; Durual, Stéphane; Scherrer, Susanne S

2017-03-01

To assess surface/subsurface damage after grinding with diamond discs on five CAD-CAM restorative materials and to estimate potential losses in strength based on crack size measurements of the generated damage. The materials tested were: Lithium disilicate (LIT) glass-ceramic (e.max CAD), leucite glass-ceramic (LEU) (Empress CAD), feldspar ceramic (VM2) (Vita Mark II), feldspar ceramic-resin infiltrated (EN) (Enamic) and a composite reinforced with nano ceramics (LU) (Lava Ultimate). Specimens were cut from CAD-CAM blocs and pair-wise mirror polished for the bonded interface technique. Top surfaces were ground with diamond discs of respectively 75, 54 and 18μm. Chip damage was measured on the bonded interface using SEM. Fracture mechanics relationships were used to estimate fracture stresses based on average and maximum chip depths assuming these to represent strength limiting flaws subjected to tension and to calculate potential losses in strength compared to manufacturer's data. Grinding with a 75μm diamond disc induced on a bonded interface critical chips averaging 100μm with a potential strength loss estimated between 33% and 54% for all three glass-ceramics (LIT, LEU, VM2). The softer materials EN and LU were little damage susceptible with chips averaging respectively 26μm and 17μm with no loss in strength. Grinding with 18μm diamond discs was still quite detrimental for LIT with average chip sizes of 43μm and a potential strength loss of 42%. It is essential to understand that when grinding glass-ceramics or feldspar ceramics with diamond discs surface and subsurface damage are induced which have the potential of lowering the strength of the ceramic. Careful polishing steps should be carried out after grinding especially when dealing with glass-ceramics. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system.

PubMed

Sane, Ramola; Agarwal, Sagar; Mittapalli, Rajendar K; Elmquist, William F

2013-04-01

The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar. Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics. Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB. We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice. Initially, the mice were administered 2.5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined. The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0.82, as compared with 3.5 in Mdr1a/b(-/-) mice, 6.6 in Bcrp1(-/-) mice, and 15 in Mdr1a/b(-/-)Bcrp1(-/-) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar. The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined. The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes. However, the ED50 was lower for Mdr1a/b(-/-) mice compared with Bcrp1(-/-) mice. These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose. Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma.

Shear bond strength of porcelain laminate veneers to enamel, dentine and enamel-dentine complex bonded with different adhesive luting systems.

PubMed

Öztürk, Elif; Bolay, Şükran; Hickel, Reinhard; Ilie, Nicoleta

2013-02-01

The aim of this study was to evaluate the shear bond strength of porcelain laminate veneers to 3 different surfaces by means of enamel, dentine, and enamel-dentine complex. One hundred thirty-five extracted human maxillary central teeth were used, and the teeth were randomly divided into 9 groups (n=15). The teeth were prepared with 3 different levels for bonding surfaces of enamel (E), dentine (D), and enamel-dentine complex (E-D). Porcelain discs (IPS e.max Press, Ivoclar Vivadent) of 2mm in thickness and 4mm in diameter were luted to the tooth surfaces by using 2 light-curing (RelyX Veneer [RV], 3M ESPE; Variolink Veneer [VV], Ivoclar Vivadent) and a dual-curing (Variolink II [V2], Ivoclar Vivadent) adhesive systems according to the manufacturers' instructions. Shear bond strength test was performed in a universal testing machine at 0.5mm/min until bonding failure. Failure modes were determined under a stereomicroscope, and fracture surfaces were evaluated with a scanning electron microscope. The data were statistically analysed (SPSS 17.0) (p=0.05). Group RV-D exhibited the lowest bond strength value (5.42±6.6MPa). There was statistically no difference among RV-D, V2-D (13.78±8.8MPa) and VV-D (13.84±6.2MPa) groups (p>0.05). Group VV-E exhibited the highest bond strength value (24.76±8.8MPa). The type of tooth structure affected the shear bond strength of the porcelain laminate veneers to the 3 different types of tooth structures (enamel, dentine, and enamel-dentine complex). When dentine exposure is necessary during preparation, enough sound enamel must be protected as much as possible to maintain a good bonding; to obtain maximum bond strength, preparation margins should be on sound enamel. Copyright © 2012 Elsevier Ltd. All rights reserved.

Three-dimensional printing fiber reinforced hydrogel composites.

PubMed

Bakarich, Shannon E; Gorkin, Robert; in het Panhuis, Marc; Spinks, Geoffrey M

2014-09-24

An additive manufacturing process that combines digital modeling and 3D printing was used to prepare fiber reinforced hydrogels in a single-step process. The composite materials were fabricated by selectively pattering a combination of alginate/acrylamide gel precursor solution and an epoxy based UV-curable adhesive (Emax 904 Gel-SC) with an extrusion printer. UV irradiation was used to cure the two inks into a single composite material. Spatial control of fiber distribution within the digital models allowed for the fabrication of a series of materials with a spectrum of swelling behavior and mechanical properties with physical characteristics ranging from soft and wet to hard and dry. A comparison with the "rule of mixtures" was used to show that the swollen composite materials adhere to standard composite theory. A prototype meniscus cartilage was prepared to illustrate the potential application in bioengineering.

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

PubMed

Klein, N; Sacher, J; Geiss-Granadia, T; Attarbaschi, T; Mossaheb, N; Lanzenberger, R; Pötzi, C; Holik, A; Spindelegger, C; Asenbaum, S; Dudczak, R; Tauscher, J; Kasper, S

2006-10-01

Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

Spectral entropy as a measure of hypnosis and hypnotic drug effect of total intravenous anesthesia in children during slow induction and maintenance.

PubMed

Klockars, Jaakko G M; Hiller, Arja; Münte, Sinikka; van Gils, Mark J; Taivainen, Tomi

2012-02-01

We evaluated whether spectral entropy (SpE) can measure the depth of hypnosis and the hypnotic drug effect in children during total intravenous anesthesia. Sixty healthy children, aged 3-16 yr, were studied. Anesthesia was induced with an increasing target controlled infusion of propofol, and maintained by a stable remifentanil infusion and variable concentrations of target controlled infusion propofol. Depth of hypnosis was assessed according to the University of Michigan Sedation Scale (UMSS). Estimated plasma (C(p)) and pseudo effect site (C(eff)) propofol concentrations reflected the hypnotic drug effect. Patients were stratified to three age groups. The correlations between SpE versus UMSS, C(p), and C(eff) were analyzed by Prediction Probability (P(k)). The pharmacodynamic relationship between SpE and C(p), and the differences of SpE values between the age groups at the corresponding UMSS levels, were studied. Respective mean P(k) values for the youngest, middle, and oldest age groups were: 1) during induction: SpE versus UMSS 0.87, 0.87, and 0.93; SpE versus C(p) 0.92, 0.95, and 0.97; and SpE versus C(eff) 0.88, 0.94, and 0.95; 2) during maintenance: SpE versus C(eff) 0.86, 0.75, and 0.81. The pharmacodynamic analysis determined an association between SpE and C(p) that followed the E(max) model closely. There were significant differences in SpE values between age groups at corresponding UMSS sedation levels. SpE measures the level of hypnosis and hypnotic drug effect in children during total intravenous anesthesia. There is an age dependency associated with SpE. Anesthesia should not be steered solely on the basis of SpE.

Effect of etching with distinct hydrofluoric acid concentrations on the flexural strength of a lithium disilicate-based glass ceramic.

PubMed

Prochnow, Catina; Venturini, Andressa B; Grasel, Rafaella; Bottino, Marco C; Valandro, Luiz Felipe

2017-05-01

This study examined the effects of distinct hydrofluoric acid concentrations on the mechanical behavior of a lithium disilicate-based glass ceramic. Bar-shaped specimens were produced from ceramic blocks (e.max CAD, Ivoclar Vivadent). The specimens were polished, chamfered, and sonically cleaned in distilled water. The specimens were randomly divided into five groups (n = 23). The HF1, HF3, HF5, and HF10 specimens were etched for 20 s with acid concentrations of 1%, 3%, 5%, and 10%, respectively, while the SC (control) sample was untreated. The etched surfaces were evaluated using a scanning electron microscope and an atomic force microscope. Finally, the roughness was measured, and 3-point bending flexural tests were performed. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test (α = 0.05). The Weibull modulus and characteristic strength were also determined. No statistical difference in the roughness and flexural strength was determined among the groups. The structural reliabilities (Weilbull moduli) were similar for the tested groups; however, the characteristic strength of the HF1 specimen was greater than that of the HF10 specimen. Compared with the untreated ceramic, the surface roughness and flexural strength of the ceramic were unaffected upon etching, regardless of the acid concentration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 885-891, 2017. © 2016 Wiley Periodicals, Inc.

The effect of boric acid on acethylcholine, bethanechol and potasssium-evoked responses on ileum of rat.

PubMed

Ince, S; Turkmen, R; Yavuz, H

2011-01-01

1 The aim of this study was to clarify the effect of boric acid on contractions of rat isolated ileum. 2 Contractile responses expressed as Emax and pD2 for acetylcholine (10(-3)-10(-8) m, Ach), bethanechol (10(-3)-10(-8) m) and potassium (10-80 × 10(-3) m, KCl) were determined in the absence and presence of boric acid (10(-3); 5 × 10(-4); 10(-4) m). 3 The contractile response to Ach in the presence of verapamil (10(-6) or 10(-8) m) or in calcium-free Tyrode's solution was also determined in the absence and presence of boric acid. 4 Boric acid did not affect the contractile response to Ach, bethanechol or KCl. Single or cumulative treatment of boric acid did not affect ileum muscle contraction evoked by KCl. The atropine-resistant component of Ach-induced contraction and 4-diphenyl-acetoxy-N-methyl-piperidine methiodide-resistant component of bethanechol-induced contraction were not inhibited by boric acid (10(-3) m). The contractile response to Ach was reduced in calcium-free Tyrode's solution, and the contractile response was not affected by (10(-8) m). The addition of boric acid (10(-3) m) in combination with verapamil (10(-8) m) did not significantly affect the contractile response to Ach. 5 In conclusion, boric acid does not affect contractions induced by Ach, bethanechol or potassium in rat isolated ileum. © 2011 Blackwell Publishing Ltd.

Influence of different surface treatments on bond strength of novel CAD/CAM restorative materials to resin cement.

PubMed

Kömürcüoğlu, Meltem Bektaş; Sağırkaya, Elçin; Tulga, Ayça

2017-12-01

To evaluate the effects of different surface treatments on the bond strength of novel CAD/CAM restorative materials to resin cement by four point bending test. The CAD/CAM materials under investigation were e.max CAD, Mark II, Lava Ultimate, and Enamic. A total of 400 bar specimens (4×1.2×12 mm) (n=10) milled from the CAD/CAM blocks underwent various pretreatments (no pretreatment (C), hydrofluoric acid (A), hydrofluoric acid + universal adhesive (Scotchbond) (AS), sandblasting (Sb), and sandblasting + universal adhesive (SbS)). The bars were luted end-to-end on the prepared surfaces with a dual curing adhesive resin cement (Variolink N, Ivoclar Vivadent) on the custom-made stainless steel mold. Ten test specimens for each treatment and material combination were performed with four point bending test method. Data were analyzed using ANOVA and Tukey's test. The surface treatment and type of CAD/CAM restorative material showed a significant effect on the four point bending strength (FPBS) ( P <.001). For LDC, AS surface treatment showed the highest FPBS results (100.31 ± 10.7 MPa) and the lowest values were obtained in RNC (23.63 ± 9.0 MPa) for control group. SEM analyses showed that the surface topography of CAD/CAM restorative materials was modified after treatments. The surface treatment of sandblasting or HF acid etching in combination with a universal adhesive containing MDP can be suggested for the adhesive cementation of the novel CAD/CAM restorative materials.

Investigations on the effects of mouthrinses on the colour stability and surface roughness of different dental bioceramics

PubMed Central

Varol, Osman

2017-01-01

PURPOSE In this study, three bioceramic materials, [IPS Empress CAD (Ivoclar), IPS e.max CAD (Ivoclar), and Lava Ultimate CAD (3M ESPE)] were treated with three commercial mouthrinses [Listerine, Tantum Verde, and Klorhex]; and changes in colour reflectance and surface roughness values were then quantitatively assessed. MATERIALS AND METHODS One hundred and twenty ceramic samples, with dimensions of 2 × 12 × 14 mm, were prepared and divided into nine sample groups, except three control samples. The samples were immersed in the mouthrinse solutions for 120 hrs, and changes in colour reflectance and surface roughness values were measured by UV light spectrophotometry (Vita Easyshade; VITA Zahnfabrik) and by profilometer device (MitutoyoSurftest SJ-301), respectively. The change of surface roughness was inspected by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). RESULTS There was a positive correlation between the ΔE and increase in the surface roughness. Two of the ceramic materials, IPS Empress and Lava Ultimate, were affected significantly by the treatment of the mouthrinse solutions (P<.05). The most affecting solution was Tantum Verde and the most affected material was Lava Ultimate. As expected, the most resistant material to ΔE and chemical corrosion was IPS e max CAD among the materials used. CONCLUSION This work implied that mouthrinse with lower alcohol content had less deteriorating effect on colour and on the surface morphology of the bioceramic materials. PMID:28680552

Theory‐based pharmacokinetics and pharmacodynamics of S‐ and R‐warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients

PubMed Central

Xue, Ling; Holford, Nick; Ding, Xiao‐liang; Shen, Zhen‐ya; Huang, Chen‐rong; Zhang, Hua; Zhang, Jing‐jing; Guo, Zhe‐ning; Xie, Cheng; Zhou, Ling; Chen, Zhi‐yao; Liu, Lin‐sheng

2016-01-01

Aims The aims of this study are to apply a theory‐based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S‐ and R‐warfarin. Methods Clinical data were obtained from 264 patients. Total concentrations for S‐ and R‐warfarin were measured by ultra‐high performance liquid tandem mass spectrometry. Genotypes were measured using pyrosequencing. A sequential population PK parameter with data method was used to describe the international normalized ratio (INR) time course. Data were analyzed with NONMEM. Model evaluation was based on parameter plausibility and prediction‐corrected visual predictive checks. Results Warfarin PK was described using a one‐compartment model. CYP2C9 *1/*3 genotype had reduced clearance for S‐warfarin, but increased clearance for R‐warfarin. The in vitro parameters for the relationship between prothrombin complex activity (PCA) and INR were markedly different (A = 0.560, B = 0.386) from the theory‐based values (A = 1, B = 0). There was a small difference between healthy subjects and patients. A sigmoid Emax PD model inhibiting PCA synthesis as a function of S‐warfarin concentration predicted INR. Small R‐warfarin effects was described by competitive antagonism of S‐warfarin inhibition. Patients with VKORC1 AA and CYP4F2 CC or CT genotypes had lower C50 for S‐warfarin. Conclusion A theory‐based PKPD model describes warfarin concentrations and clinical response. Expected PK and PD genotype effects were confirmed. The role of predicted fat free mass with theory‐based allometric scaling of PK parameters was identified. R‐warfarin had a minor effect compared with S‐warfarin on PCA synthesis. INR is predictable from 1/PCA in vivo. PMID:27763679

Effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations: in vitro study of color masking ability.

PubMed

Oh, Seon-Hee; Kim, Seok-Gyu

2015-10-01

The aim of the study was to evaluate the effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations. Three different types of disk-shaped zirconia coping specimens (Lava, Cercon, Zirkonzahn: ø10 mm × 0.4 mm) were fabricated and veneered with IPS e.max Press Ceram (shade A2), for total thicknesses of 1 and 1.5 mm. A total of sixty zirconia restoration specimens were divided into six groups based on their coping types and thicknesses. The abutment specimens (ø10 mm × 7 mm) were prepared with gold alloy, base metal (nickel-chromium) alloy, and four different shades (A1, A2, A3, A4) of composite resins. The average L*, a*, b* values of the zirconia specimens on the six abutment specimens were measured with a dental colorimeter, and the statistical significance in the effects of three variables was analyzed by using repeated measures analysis of variance (α=.05).The average shade difference (ΔE) values of the zirconia specimens between the A2 composite resin abutment and other abutments were also evaluated. The effects of zirconia specimen thickness (P<.001), abutment shade (P<.001), and type of zirconia copings (P<.003) on the final shade of the zirconia restorations were significant. The average ΔE value of Lava specimens (1 mm) between the A2 composite resin and gold alloy abutments was higher (close to the acceptability threshold of 5.5 ΔE) than th ose between the A2 composite resin and other abutments. This in-vitro study demonstrated that abutment shade, ceramic thickness, and coping type affected the resulting shade of zirconia restorations.

Randomized controlled within-subject evaluation of digital and conventional workflows for the fabrication of lithium disilicate single crowns. Part II: CAD-CAM versus conventional laboratory procedures.

PubMed

Sailer, Irena; Benic, Goran I; Fehmer, Vincent; Hämmerle, Christoph H F; Mühlemann, Sven

2017-07-01

Clinical studies are needed to evaluate the entire digital and conventional workflows in prosthetic dentistry. The purpose of the second part of this clinical study was to compare the laboratory production time for tooth-supported single crowns made with 4 different digital workflows and 1 conventional workflow and to compare these crowns clinically. For each of 10 participants, a monolithic crown was fabricated in lithium disilicate-reinforced glass ceramic (IPS e.max CAD). The computer-aided design and computer-aided manufacturing (CAD-CAM) systems were Lava C.O.S. CAD software and centralized CAM (group L), Cares CAD software and centralized CAM (group iT), Cerec Connect CAD software and lab side CAM (group CiL), and Cerec Connect CAD software with centralized CAM (group CiD). The conventional fabrication (group K) included a wax pattern of the crown and heat pressing according to the lost-wax technique (IPS e.max Press). The time for the fabrication of the casts and the crowns was recorded. Subsequently, the crowns were clinically evaluated and the corresponding treatment times were recorded. The Paired Wilcoxon test with the Bonferroni correction was applied to detect differences among treatment groups (α=.05). The total mean (±standard deviation) active working time for the dental technician was 88 ±6 minutes in group L, 74 ±12 minutes in group iT, 74 ±5 minutes in group CiL, 92 ±8 minutes in group CiD, and 148 ±11 minutes in group K. The dental technician spent significantly more working time for the conventional workflow than for the digital workflows (P<.001). No statistically significant differences were found between group L and group CiD or between group iT and group CiL. No statistical differences in time for the clinical evaluation were found among groups, indicating similar outcomes (P>.05). Irrespective of the CAD-CAM system, the overall laboratory working time for a digital workflow was significantly shorter than for the conventional workflow, since the dental technician needed less active working time. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Marginal Adaptation and Quality of Interfaces in Lithium Disilicate Crowns - Influence of Manufacturing and Cementation Techniques.

PubMed

Melo Freire, C A; Borges, G A; Caldas, Dbm; Santos, R S; Ignácio, S A; Mazur, R F

To evaluate the cement line thickness and the interface quality in milled or injected lithium disilicate ceramic restorations and their influence on marginal adaptation using different cement types and different adhesive cementation techniques. Sixty-four bovine teeth were prepared for full crown restoration (7.0±0.5 mm in height, 8.0 mm in cervical diameter, and 4.2 mm in incisal diameter) and were divided into two groups: CAD/CAM automation technology, IPS e.max CAD (CAD), and isostatic injection by heat technology, IPS e.max Press (PRESS). RelyX ARC (ARC) and RelyX U200 resin cements were used as luting agents in two activation methods: initial self-activation and light pre-activation for one second (tack-cure). Next, the specimens were stored in distilled water at 23°C ± 2°C for 72 hours. The cement line thickness was measured in micrometers, and the interface quality received scores according to the characteristics and sealing aspects. The evaluations were performed with an optical microscope, and scanning electron microscope images were presented to demonstrate the various features found in the cement line. For the cement line thickness, data were analyzed with three-way analysis of variance (ANOVA) and the Games-Howell test (α=0.05). For the variable interface quality, the data were analyzed with the Mann-Whitney U-test, the Kruskal-Wallis test, and multiple comparisons nonparametric Dunn test (α=0.05). The ANOVA presented statistical differences among the ceramic restoration manufacturing methods as well as a significant interaction between the manufacturing methods and types of cement (p<0.05). The U200 presented lower cement line thickness values when compared to the ARC with both cementation techniques (p<0.05). With regard to the interface quality, the Mann-Whitney U-test and the Kruskal-Wallis test demonstrated statistical differences between the ceramic restoration manufacturing methods and cementation techniques. The PRESS ceramics obtained lower scores than did the CAD ceramics when using ARC cement (p<0.05). Milled restorations cemented with self-adhesive resin cement resulted in a thinner cement line that is statistically different from that of CAD or pressed ceramics cemented with resin cement with adhesive application. No difference between one-second tack-cure and self-activation was noted.

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

PubMed

Casciano, Julian; Krishnan, Jerry; Small, Mary Buatti; Li, Chenghui; Dotiwala, Zenobia; Martin, Bradley C

2017-01-01

Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients

PubMed Central

de Winter, Brenda C. M.; Masman, Anniek D.; van Dijk, Monique; Baar, Frans P. M.; Tibboel, Dick; Koch, Birgit C. P.; van Gelder, Teun; Mathot, Ron A. A.

2017-01-01

Aims Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response. Method A population PD analysis using nonlinear mixed effect models was performed with data from 43 terminally ill patients. PK profiles were predicted by a previously described PK model and depth of sedation was measured using the Ramsay sedation score. Patient and disease characteristics were evaluated as possible covariates. The final model was evaluated using a visual predictive check. Results The effect of midazolam on the sedation level was best described by a differential odds model including a baseline probability, Emax model and interindividual variability on the overall effect. The EC50 value was 68.7 μg l–1 for a Ramsay score of 3–5 and 117.1 μg l–1 for a Ramsay score of 6. Comedication with haloperidol was the only significant covariate. The visual predictive check of the final model showed good model predictability. Conclusion We were able to describe the clinical response to midazolam accurately. As expected, there was large variability in response to midazolam. The use of haloperidol was associated with a lower probability of sedation. This may be a result of confounding by indication, as haloperidol was used to treat delirium, and deliria has been linked to a more difficult sedation procedure. PMID:28960387

Fatigue loading and R-curve behavior of a dental glass-ceramic with multiple flaw distributions.

PubMed

Joshi, Gaurav V; Duan, Yuanyuan; Della Bona, Alvaro; Hill, Thomas J; St John, Kenneth; Griggs, Jason A

2013-11-01

To determine the effects of surface finish and mechanical loading on the rising toughness curve (R-curve) behavior of a fluorapatite glass-ceramic (IPS e.max ZirPress) and to determine a statistical model for fitting fatigue lifetime data with multiple flaw distributions. Rectangular beam specimens were fabricated by pressing. Two groups of specimens (n=30) with polished (15 μm) or air abraded surface were tested under rapid monotonic loading in oil. Additional polished specimens were subjected to cyclic loading at 2 Hz (n=44) and 10 Hz (n=36). All fatigue tests were performed using a fully articulated four-point flexure fixture in 37°C water. Fractography was used to determine the critical flaw size and estimate fracture toughness. To prove the presence of R-curve behavior, non-linear regression was used. Forward stepwise regression was performed to determine the effects on fracture toughness of different variables, such as initial flaw type, critical flaw size, critical flaw eccentricity, cycling frequency, peak load, and number of cycles. Fatigue lifetime data were fit to an exclusive flaw model. There was an increase in fracture toughness values with increasing critical flaw size for both loading methods (rapid monotonic loading and fatigue). The values for the fracture toughness ranged from 0.75 to 1.1 MPam(1/2) reaching a plateau at different critical flaw sizes based on loading method. Cyclic loading had a significant effect on the R-curve behavior. The fatigue lifetime distribution was dependent on the flaw distribution, and it fit well to an exclusive flaw model. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Fatigue loading and R-curve behavior of a dental glass-ceramic with multiple flaw distributions

PubMed Central

Joshi, Gaurav V.; Duan, Yuanyuan; Bona, Alvaro Della; Hill, Thomas J.; John, Kenneth St.; Griggs, Jason A.

2013-01-01

Objectives To determine the effects of surface finish and mechanical loading on the rising toughness curve (R-curve) behavior of a fluorapatite glass-ceramic (IPS e.max ZirPress) and to determine a statistical model for fitting fatigue lifetime data with multiple flaw distributions. Materials and Methods Rectangular beam specimens were fabricated by pressing. Two groups of specimens (n=30) with polished (15 μm) or air abraded surface were tested under rapid monotonic loading in oil. Additional polished specimens were subjected to cyclic loading at 2 Hz (n=44) and 10 Hz (n=36). All fatigue tests were performed using a fully articulated four-point flexure fixture in 37°C water. Fractography was used to determine the critical flaw size and estimate fracture toughness. To prove the presence of R-curve behavior, non-linear regression was used. Forward stepwise regression was performed to determine the effects on fracture toughness of different variables, such as initial flaw type, critical flaw size, critical flaw eccentricity, cycling frequency, peak load, and number of cycles. Fatigue lifetime data were fit to an exclusive flaw model. Results There was an increase in fracture toughness values with increasing critical flaw size for both loading methods (rapid monotonic loading and fatigue). The values for the fracture toughness ranged from 0.75 to 1.1 MPa·m1/2 reaching a plateau at different critical flaw sizes based on loading method. Significance Cyclic loading had a significant effect on the R-curve behavior. The fatigue lifetime distribution was dependent on the flaw distribution, and it fit well to an exclusive flaw model. PMID:24034441

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

PubMed Central

Lei, Zhixin; Liu, Qianying; Yang, Bing; Ahmed, Saeed; Cao, Jiyue; He, Qigai

2018-01-01

The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research. PMID:29416722

Relative Bioavailability, Intranasal Abuse Potential, and Safety of Benzhydrocodone/Acetaminophen Compared with Hydrocodone Bitartrate/Acetaminophen in Recreational Drug Abusers.

PubMed

Guenther, Sven M; Mickle, Travis C; Barrett, Andrew C; Roupe, Kathryn Ann; Zhou, Jing; Lam, Vincent

2018-05-01

Benzhydrocodone is a hydrocodone prodrug that has been combined with acetaminophen (APAP) in a novel immediate-release analgesic. This study evaluated the relative bioavailability, intranasal abuse potential, and safety of benzhydrocodone/APAP compared with commercially available hydrocodone bitartrate (HB)/APAP. Single-center, randomized, double-blind, double-dummy, two-part study comprising a Dose Selection (Part A) phase and a Main Study (Part B) phase. Clinical research site. Healthy adult, nondependent, recreational opioid users with a history of intranasal abuse. Subjects (N = 42) in Part B received five in-clinic treatments consisting of intranasal and oral benzhydrocodone/APAP (13.34/650 mg), intranasal and oral hydrocodone/APAP (15/650 mg), and placebo, with four or more days of washout between treatments. Pharmacodynamic assessments included subjective effects of Drug Liking, Overall Drug Liking, and Take Drug Again (assessed on visual analog scale [VAS]), as well as nasal irritation. Pharmacokinetics and safety were also assessed. Hydrocodone Cmax was 11% lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P = 0.0027). Early cumulative hydrocodone exposures for intranasal benzhydrocodone/APAP through 0.5, 1, and 2 hours were reduced by approximately 50%, 29%, and 15%, respectively (P ≤ 0.0024). Correspondingly, Drug Liking VAS values up to two hours postdose were significantly lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P ≤ 0.0079), although peak Drug Liking VAS (Emax) scores were not different (P = 0.2814). Adverse nasal effects were more frequent for intranasal benzhydrocodone/APAP vs intranasal HB/APAP. Reduced hydrocodone exposure and drug liking at early time intervals, coupled with adverse nasal effects, can be expected to provide a level of deterrence to the intranasal route of abuse for benzhydrocodone/APAP.

Reporting numeric values of complete crowns. Part 1: Clinical preparation parameters.

PubMed

Tiu, Janine; Al-Amleh, Basil; Waddell, J Neil; Duncan, Warwick J

2015-07-01

An implemented objective measuring system for measuring clinical tooth preparations does not exist. The purpose of this study was to compare clinically achieved tooth preparations for ceramic crowns by general dentists with the recommended values in the literature with an objective measuring method. Two hundred thirty-six stone dies prepared for anterior and posterior complete ceramic crown restorations (IPS e.max Press; Ivoclar Vivadent) were collected from dental laboratories. The dies were scanned and analyzed using the coordinate geometry method. Cross-sectioned images were captured, and the average total occlusal convergence angle, margin width, and abutment height for each preparation was measured and presented with associated 95% confidence intervals. The average total occlusal convergence angles for each tooth type was above the recommended values reported in the literature. The average margin widths (0.40 to 0.83 mm) were below the minimum recommended values (1 to 1.5 mm). The tallest preparations were maxillary canines (5.25 mm), while the shortest preparations were mandibular molars (1.87 mm). Complete crown preparations produced in general practice do not achieve the recommended values found in the literature. However, these recommended values are not based on clinical trials, and the effects of observed shortfalls on the clinical longevity of these restorations are not predictable. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion.

PubMed

Delbin, Maria Andréia; Moraes, Camila; Camargo, Enilton; Mussi, Ricardo K; Antunes, Edson; de Nucci, Gilberto; Zanesco, Angelina

2007-07-01

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses (E(max)) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR: 6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place.

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children

PubMed Central

2014-01-01

Introduction The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. Methods Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. Results Ep dosing infusions ranged from 0.01 to 0.23 μg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. Conclusions According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen. PMID:24456639

Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

PubMed

Yassen, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L; Danhof, M; Dahan, A

2007-01-01

The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62).

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

PubMed

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

Effect of ceramic thickness and cement shade on the final shade after bonding using the 3D master system: a laboratory study.

PubMed

Montero, Javier; Gómez-Polo, Cristina

2016-06-01

The final color of a ceramic restoration is influenced by both the ceramic thickness and the cement shade. This study aims to evaluate the color stability according to the 3D Master System of e.max ceramic discs after bonding with different shades of luting agents. A total of 120 e.max.Press 2M1 HT ceramic discs (60 discs of 1-mm thick and 60 discs of 0.5 mm thick) and three different values of Variolink Veneer cement were used (-3, 0, +3) for the cementation process. An Easyshade compact device was used to measure color shade tabs, according to the 3D Master System, on the discs both before and after the cementation protocols. Bivariate and multivariate analyses were carried out with the spss v.21. After bonding with the different luting agents, only 30% remained as 2M1: specifically, 22% of the thinner discs and 37.3% of the thicker discs. In general, the effect of bonding increased the value and the chroma of the shade to a significant extent. Regression analyses revealed that the most significant predictor for all color parameters was cement shade, the thinner disc group bonded with -3 cement being the most unstable subgroup. According to the 3D Master System, the shade of the luting agent was the main predictor of the final color. However, the final color seems to be somewhat unpredictable, at least according to the modulating factors evaluated in the present study.

The effect of storage conditions, contamination modes and cleaning procedures on the resin bond strength to lithium disilicate ceramic.

PubMed

Klosa, Karsten; Wolfart, Stefan; Lehmann, Frank; Wenz, Hans-Jürgen; Kern, Matthias

2009-04-01

The purpose of this in-vitro study was to evaluate the resin bond strength to pre-etched lithium disilicate ceramic using different cleaning methods after two contamination modes (saliva or saliva and silicone). Plexiglas tubes filled with composite resin (MultiCore Flow) were bonded to etched and silanized ceramic disks made of lithium disilicate ceramic (IPS e.max Press) using a luting resin (Multilink Automix). Either etched or unetched ceramic surfaces were contaminated with saliva or with saliva followed by a disclosing silicone. Groups of 16 specimens each were bonded after pretreatment using 4 surface cleaning agents (37% phosphoric acid, 5% hydrofluoric acid, 96% isopropanol, air polishing device with sodium bicarbonate) in different combinations. Before measuring tensile bond strength, specimens were stored for 3 or 150 days with thermocycling. After 150 days of storage, etching of saliva-contaminated surfaces with 5% hydrofluoric acid and/or 37% phosphoric acid provided statistically significantly higher bond strengths (37.9 to 49.5 MPa) than the other cleaning methods (1.7 to 15.5 MPa). After saliva and silicone contamination, etching with 5% hydrofluoric acid provided statistically significantly higher bond strengths (44.5 to 50.3 MPa) than all other cleaning methods (0.3 to 13.5 MPa). Ceramic cleaning methods after try-in procedures have a significant influence on the resin bond strength and are dependent on the type of contamination. Re-etching lithium disilicate ceramic with 5% hydrofluoric acid is most effective in removing contamination with saliva and/or a silicone disclosing medium.

Radiation-mediated Shocks in Gamma-Ray Bursts: Pair Creation

NASA Astrophysics Data System (ADS)

Lundman, Christoffer; Beloborodov, Andrei M.; Vurm, Indrek

2018-05-01

Relativistic sub-photospheric shocks are a possible mechanism for producing prompt gamma-ray burst (GRB) emission. Such shocks are mediated by scattering of radiation. We introduce a time-dependent, special relativistic code which dynamically couples Monte Carlo radiative transfer to the flow hydrodynamics. The code also self-consistently follows electron–positron pair production in photon–photon collisions. We use the code to simulate shocks with properties relevant to GRBs. We focus on plane-parallel solutions, which are accurate deep below the photosphere. The shock generates a power-law photon spectrum through the first-order Fermi mechanism, extending upward from the typical upstream photon energy. Strong (high Mach number) shocks produce rising νF ν spectra. We observe that in non-relativistic shocks the spectrum extends to {E}\\max ∼ {m}e{v}2, where v is the speed difference between the upstream and downstream. In relativistic shocks the spectrum extends to energies E> 0.1 {m}e{c}2 where its slope softens due to Klein–Nishina effects. Shocks with Lorentz factors γ > 1.5 are prolific producers of electron–positron pairs, yielding hundreds of pairs per proton. The main effect of pairs is to reduce the shock width by a factor of ∼ {Z}+/- -1. Most pairs annihilate far downstream of the shock, and the radiation spectrum relaxes to a Wien distribution, reaching equilibrium with the plasma at a temperature determined by the shock jump conditions and the photon number per proton. We discuss the implications of our results for observations of radiation generated by sub-photospheric shocks.

Influence of different surface treatments on bond strength of novel CAD/CAM restorative materials to resin cement

PubMed Central

Kömürcüoğlu, Meltem Bektaş; Sağırkaya, Elçin

2017-01-01

PURPOSE To evaluate the effects of different surface treatments on the bond strength of novel CAD/CAM restorative materials to resin cement by four point bending test. MATERIALS AND METHODS The CAD/CAM materials under investigation were e.max CAD, Mark II, Lava Ultimate, and Enamic. A total of 400 bar specimens (4×1.2×12 mm) (n=10) milled from the CAD/CAM blocks underwent various pretreatments (no pretreatment (C), hydrofluoric acid (A), hydrofluoric acid + universal adhesive (Scotchbond) (AS), sandblasting (Sb), and sandblasting + universal adhesive (SbS)). The bars were luted end-to-end on the prepared surfaces with a dual curing adhesive resin cement (Variolink N, Ivoclar Vivadent) on the custom-made stainless steel mold. Ten test specimens for each treatment and material combination were performed with four point bending test method. Data were analyzed using ANOVA and Tukey's test. RESULTS The surface treatment and type of CAD/CAM restorative material showed a significant effect on the four point bending strength (FPBS) (P<.001). For LDC, AS surface treatment showed the highest FPBS results (100.31 ± 10.7 MPa) and the lowest values were obtained in RNC (23.63 ± 9.0 MPa) for control group. SEM analyses showed that the surface topography of CAD/CAM restorative materials was modified after treatments. CONCLUSION The surface treatment of sandblasting or HF acid etching in combination with a universal adhesive containing MDP can be suggested for the adhesive cementation of the novel CAD/CAM restorative materials. PMID:29279763

Effect of surface preparation with Nd:YAG and Er,Cr:YSGG lasers on the repair bond strength of lithium disilicate glass ceramic to a silorane-based composite resin.

PubMed

Ebrahimi Chaharom, Mohammad Esmaeel; Pournaghi Azar, Fatemeh; Mohammadi, Narmin; Nasiri, Rezvan

2018-01-01

Background. This study was undertaken to evaluate the repair bond strength of lithium disilicate glass ceramic to a silorane-based composite resin after surface preparation with Nd:YAG and Er,Cr:YSGG lasers. Methods. A total of 102 lithium disilicate glass ceramic samples (IPS e.max Press), measuring 5 mm in diameter and 4 mm in thickness, were randomly assigned to 6 groups (n=17): group 1, no surface preparation (control); group 2, acid etching with 9.5% hydrofluoric acid (HF); group 3, surface preparation with 4.5-W Nd:YAG laser; group 4, surface preparation with 6-W Nd:YAG laser; group 5, surface preparation with 1.5-W Er,Cr:YSGG laser; and group 6, surface preparation with 6-W Er,Cr:YSGG laser. After preparation of surfaces and application of silane, all the samples were repaired with the use of a silorane-based composite resin, followed by storage in distilled water at a temperature of 37°C for 24 hours and thermocycling. Finally, the samples were subjected to a shearing bond strength test; the fracture modes were determined under a stereomi-croscope. Results. There were significant differences between the HF group and the other groups (P=0.000). Two-by-two comparisons of the other groups revealed no significant differences (P>0.05). Conclusion. Use of HF proved the most effective surface preparation technique to increase the repair bond strength between lithium disilicate glass ceramic and silorane-based composite resin; compared to the control group.

Saturable Active Efflux by P-Glycoprotein and Breast Cancer Resistance Protein at the Blood-Brain Barrier Leads to Nonlinear Distribution of Elacridar to the Central Nervous System

PubMed Central

Sane, Ramola; Agarwal, Sagar; Mittapalli, Rajendar K.

2013-01-01

The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar. Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics. Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB. We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b(−/−), Bcrp1(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice. Initially, the mice were administered 2.5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined. The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0.82, as compared with 3.5 in Mdr1a/b(−/−) mice, 6.6 in Bcrp1(−/−) mice, and 15 in Mdr1a/b(−/−)Bcrp1(−/−) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar. The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined. The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes. However, the ED50 was lower for Mdr1a/b(−/−) mice compared with Bcrp1(−/−) mice. These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose. Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma. PMID:23397054

Evaluation of Dental Shade Guide Variability Using Cross-Polarized Photography.

PubMed

Gurrea, Jon; Gurrea, Marta; Bruguera, August; Sampaio, Camila S; Janal, Malvin; Bonfante, Estevam; Coelho, Paulo G; Hirata, Ronaldo

2016-01-01

This study evaluated color variability in the A hue between the VITA Classical (VITA Zahnfabrik) shade guide and four other VITA-coded ceramic shade guides using a Canon EOS 60D camera and software (Photoshop CC, Adobe). A total of 125 photographs were taken, 5 per shade tab for each of 5 shades (A1 to A4) from the following shade guides: VITA Classical (control), IPS e.max Ceram (Ivoclar Vivadent), IPS d.SIGN (Ivoclar Vivadent), Initial ZI (GC), and Creation CC (Creation Willi Geller). Photos were processed with Adobe Photoshop CC to allow standardized evaluation of hue, chroma, and value between shade tabs. None of the VITA-coded shade tabs fully matched the VITA Classical shade tab for hue, chroma, or value. The VITA-coded shade guides evaluated herein showed an overall unmatched shade in all tabs when compared with the control, suggesting that shade selection should be made using the guide produced by the manufacturer of the ceramic intended for the final restoration.

Micro-CT evaluation of the marginal fit of CAD/CAM all ceramic crowns

NASA Astrophysics Data System (ADS)

Brenes, Christian

Objectives: Evaluate the marginal fit of CAD/CAM all ceramic crowns made from lithium disilicate and zirconia using two different fabrication protocols (model and model-less). METHODS: Forty anterior all ceramic restorations (20 lithium disilicate, 20 zirconia) were fabricated using a CEREC Bluecam scanner. Two different fabrication methods were used: a full digital approach and a printed model. Completed crowns were cemented and marginal gap was evaluated using Micro-CT. Each specimen was analyzed in sagittal and trans-axial orientations, allowing a 360° evaluation of the vertical and horizontal fit. RESULTS: Vertical measurements in the lingual, distal and mesial views had and estimated marginal gap from 101.9 to 133.9 microns for E-max crowns and 126.4 to 165.4 microns for zirconia. No significant differences were found between model and model-less techniques. CONCLUSION: Lithium disilicate restorations exhibited a more accurate and consistent marginal adaptation when compared to zirconia crowns. No statistically significant differences were observed when comparing model or model-less approaches.

Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants

PubMed Central

Emoto, C; Mizuno, T; Schniedewind, B; Christians, Uwe; Adams, DM; Vinks, AA

2016-01-01

Sirolimus is increasingly being used in neonates and infants, but the mechanistic basis of age‐dependent changes in sirolimus disposition has not been fully addressed yet. In order to characterize the age‐dependent changes, serial sirolimus clearance (CL) estimates in individual young pediatric patients were collected and analyzed by population modeling analysis. In addition, sirolimus metabolite formation was also investigated to further substantiate the corresponding age‐dependent change in CYP3A activity. The increasing pattern over time of allometrically size‐normalized sirolimus CL estimates vs. age was well described by a sigmoidal Emax model. This age‐dependent increase was also observed within each individual patient over a 4‐year study period. CYP3A‐dependent sirolimus metabolite formation changed in a similar fashion. This study clearly demonstrates the rapid increase of sirolimus CL over time in neonates and infants, indicating the developmental change. This developmental pattern can be explained by a parallel increase in CYP3A metabolic activity. PMID:27501453

Analysis of the actions of the novel dopamine receptor-directed compounds (S)-OSU6162 and ACR16 at the D2 dopamine receptor

PubMed Central

Kara, Elodie; Lin, Hong; Svensson, Kjell; Johansson, Anette M; Strange, Philip G

2010-01-01

BACKGROUND AND PURPOSE The two phenylpiperidines, OSU6162 and ACR16, have been proposed as novel drugs for the treatment of brain disorders, including schizophrenia and Huntington's disease, because of their putative dopamine stabilizing effects. Here we evaluated the activities of these compounds in a range of assays for the D2 dopamine receptor in vitro. EXPERIMENTAL APPROACH The affinities of these compounds for the D2 dopamine receptor were evaluated in competition with [3H]spiperone and [3H]NPA. Agonist activity of these compounds was evaluated in terms of their ability to stimulate [35S]GTPγS binding. KEY RESULTS Both compounds had low affinities for inhibition of [3H]spiperone binding (pKi vs. [3H]spiperone, ACR16: <5, OSU6162: 5.36). Neither compound was able to stimulate [35S]GTPγS binding when assayed in the presence of Na+ ions, but if the Na+ ions were removed, both compounds were low-affinity, partial agonists (Emax relative to dopamine: ACR16: 10.2%, OSU6162:54.3%). Schild analysis of the effects of OSU6162 to inhibit dopamine-stimulated [35S]GTPγS binding indicated Schild slopes of ∼0.9, suggesting little deviation from competitive inhibition. OSU6162 was, however, able to accelerate [3H]NPA dissociation from D2 dopamine receptors, indicating some allosteric effects of this compound. CONCLUSIONS AND IMPLICATIONS The two phenylpiperidines were low-affinity, low-efficacy partial agonists at the D2 dopamine receptor in vitro, possibly exhibiting some allosteric effects. Comparing their in vitro and in vivo effects, the in vitro affinities were a reasonable guide to potencies in vivo. However, the lack of in vitro–in vivo correlation for agonist efficacy needs to be further addressed. PMID:20804495

Simultaneous measurement and integrated analysis of analgesia and respiration after an intravenous morphine infusion.

PubMed

Dahan, Albert; Romberg, Raymonda; Teppema, Luc; Sarton, Elise; Bijl, Hans; Olofsen, Erik

2004-11-01

To study the influence of morphine on chemical control of breathing relative to the analgesic properties of morphine, the authors quantified morphine-induced analgesia and respiratory depression in a single group of healthy volunteers. Both respiratory and pain measurements were performed over single 24-h time spans. Eight subjects (four men, four women) received a 90-s intravenous morphine infusion; eight others (four men, four women) received a 90-s placebo infusion. At regular time intervals, respiratory variables (breathing at a fixed end-tidal partial pressure of carbon dioxide of 50 mmHg and the isocapnic acute hypoxic response), pain tolerance (derived from a transcutaneous electrical acute pain model), and arterial blood samples were obtained. Data acquisition continued for 24 h. Population pharmacokinetic (sigmoid Emax)-pharmacodynamic models were applied to the respiratory and pain data. The models are characterized by potency parameters, shape parameters (gamma), and blood-effect site equilibration half-lives. All collected data were analyzed simultaneously using the statistical program NONMEM. Placebo had no systematic effect on analgesic or respiratory variables. Morphine potency parameter and blood-effect site equilibration half-life did not differ significantly among the three measured effect parameters (P > 0.01). The integrated NONMEM analysis yielded a potency parameter of 32 +/- 1.4 nm (typical value +/- SE) and a blood-effect site equilibration half-life of 4.4 +/- 0.3 h. Parameter gamma was 1 for hypercapnic and hypoxic breathing but 2.4 +/- 0.7 for analgesia (P < 0.01). Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack of good pain relief, moderate to severe respiratory depression remains possible.

Effects of Rhododendron maximum L. on Acer rubrum L. Seedling Establishment

Treesearch

Barton D. Clinton; James M. Vose

1996-01-01

Rhododendron maximum L. restricts regeneration of overstory species; however, the mechanisms are poorly understood. Three treatments were used to examine the effects of R. maximum germination success and survival of Acer rubrum L. under a closed overstory canopy: (1) R. maximum understory, (2)...

Randomized, Controlled Clinical Trial of Bilayer Ceramic and Metal-Ceramic Crown Performance

PubMed Central

Esquivel-Upshaw, Josephine; Rose, William; Oliveira, Erica; Yang, Mark; Clark, Arthur E.; Anusavice, Kenneth

2013-01-01

Purpose Analyzing the clinical performance of restorative materials is important, as there is an expectation that these materials and procedures will restore teeth and do no harm. The objective of this research study was to characterize the clinical performance of metal-ceramic crowns, core ceramic crowns, and core ceramic/veneer ceramic crowns based on 11 clinical criteria. Materials and Methods An IRB-approved, randomized, controlled clinical trial was conducted as a single-blind pilot study. The following three types of full crowns were fabricated: (1) metal-ceramic crown (MC) made from a Pd-Au-Ag-Sn-In alloy (Argedent 62) and a glass-ceramic veneer (IPS d.SIGN veneer); (2) non-veneered (glazed) lithium disilicate glass-ceramic crown (LDC) (IPS e.max Press core and e.max Ceram Glaze); and (3) veneered lithia disilicate glass-ceramic crown (LDC/V) with glass-ceramic veneer (IPS Empress 2 core and IPS Eris). Single-unit crowns were randomly assigned. Patients were recalled for each of 3 years and were evaluated by two calibrated clinicians. Thirty-six crowns were placed in 31 patients. A total of 12 crowns of each of the three crown types were studied. Eleven criteria were evaluated: tissue health, marginal integrity, secondary caries, proximal contact, anatomic contour, occlusion, surface texture, cracks/chips (fractures), color match, tooth sensitivity, and wear (of crowns and opposing enamel). Numerical rankings ranged from 1 to 4, with 4 being excellent, and 1 indicating a need for immediate replacement. Statistical analysis of the numerical rankings was performed using a Fisher’s exact test. Results There was no statistically significant difference between performance of the core ceramic crowns and the two veneered crowns at year 1 and year 2 (p > 0.05). All crowns were rated either as excellent or good for each of the clinical criteria; however, between years 2 and 3, gradual roughening of the occlusal surface occurred in some of the ceramic-ceramic crowns, possibly caused by dissolution and wear of the glaze. Statistically significant differences in surface texture (p = 0.0013) and crown wear (p = 0.0078) were found at year 3 between the metal-ceramic crowns and the lithium-disilicate-based crowns. Conclusion Based on the 11 criteria, the clinical performance of ceramic-ceramic crowns was comparable to that of the metal-ceramic crowns after 2 years; however, gradual roughening occurred between years 2 and 3, which resulted in differences in surface texture and wear. PMID:22978697

Effectiveness of Resistance Circuit-Based Training for Maximum Oxygen Uptake and Upper-Body One-Repetition Maximum Improvements: A Systematic Review and Meta-Analysis.

PubMed

Muñoz-Martínez, Francisco Antonio; Rubio-Arias, Jacobo Á; Ramos-Campo, Domingo Jesús; Alcaraz, Pedro E

2017-12-01

It is well known that concurrent increases in both maximal strength and aerobic capacity are associated with improvements in sports performance as well as overall health. One of the most popular training methods used for achieving these objectives is resistance circuit-based training. The objective of the present systematic review with a meta-analysis was to evaluate published studies that have investigated the effects of resistance circuit-based training on maximum oxygen uptake and one-repetition maximum of the upper-body strength (bench press exercise) in healthy adults. The following electronic databases were searched from January to June 2016: PubMed, Web of Science and Cochrane. Studies were included if they met the following criteria: (1) examined healthy adults aged between 18 and 65 years; (2) met the characteristics of resistance circuit-based training; and (3) analysed the outcome variables of maximum oxygen uptake using a gas analyser and/or one-repetition maximum bench press. Of the 100 articles found from the database search and after all duplicates were removed, eight articles were analysed for maximum oxygen uptake. Of 118 healthy adults who performed resistance circuit-based training, maximum oxygen uptake was evaluated before and after the training programme. Additionally, from the 308 articles found for one-repetition maximum, eight articles were analysed. The bench press one-repetition maximum load, of 237 healthy adults who performed resistance circuit-based training, was evaluated before and after the training programme. Significant increases in maximum oxygen uptake and one-repetition maximum bench press were observed following resistance circuit-based training. Additionally, significant differences in maximum oxygen uptake and one-repetition maximum bench press were found between the resistance circuit-based training and control groups. The meta-analysis showed that resistance circuit-based training, independent of the protocol used in the studies, is effective in increasing maximum oxygen uptake and one-repetition maximum bench press in healthy adults. However, its effect appears to be larger depending on the population and training characteristics. For large effects in maximum oxygen uptake, the programme should include ~14-30 sessions for ~6-12 weeks, with each session lasting at least ~20-30 min, at intensities between ~60 and 90% one-repetition maximum. For large effects in one-repetition maximum bench press, the data indicate that intensity should be ~30-60% one-repetition maximum, with sessions lasting at least ~22.5-60 min. However, the lower participant's baseline fitness level may explain the lighter optimal loads used in the circuit training studies where greater strength gains were reported.

Population pharmacokinetics of gabapentin in healthy Korean subjects with influence of genetic polymorphisms of ABCB1.

PubMed

Tran, Phuong; Yoo, Hee-Doo; Ngo, Lien; Cho, Hea-Young; Lee, Yong-Bok

2017-12-01

The objective of this study was to perform population pharmacokinetic (PK) analysis of gabapentin in healthy Korean subjects and to investigate the possible effect of genetic polymorphisms (1236C > T, 2677G > T/A, and 3435C > T) of ABCB1 gene on PK parameters of gabapentin. Data were collected from bioequivalence studies, in which 173 subjects orally received three different doses of gabapentin (300, 400, and 800 mg). Only data from reference formulation were used. Population pharmacokinetics (PKs) of gabapentin was estimated using a nonlinear mixed-effects model (NONMEM). Gabapentin showed considerable inter-individual variability (from 5.2- to 8.7-fold) in PK parameters. Serum concentration of gabapentin was well fitted by a one-compartment model with first-order absorption and lag time. An inhibitory Emax model was applied to describe the effect of dose on bioavailability. The oral clearance was estimated to be 11.1 L/h. The volume of distribution was characterized as 81.0 L. The absorption rate constant was estimated at 0.860 h -1 , and the lag time was predicted at 0.311 h. Oral bioavailability was estimated to be 68.8% at dose of 300 mg, 62.7% at dose of 400 mg, and 47.1% at dose of 800 mg. The creatinine clearance significantly influenced on the oral clearance (P < 0.005) and ABCB1 2677G > T/A genotypes significantly influenced on the absorption rate constant (P < 0.05) of gabapentin. However, ABCB1 1236C > T and 3435C > T genotypes showed no significant effect on gabapentin PK parameters. The results of the present study indicate that the oral bioavailability of gabapentin is decreased when its dosage is increased. In addition, ABCB1 2677G > T/A polymorphism can explain the substantial inter-individual variability in the absorption of gabapentin.

Ex vivo pharmacokinetic/pharmacodynamic relationship of valnemulin against Clostridium perfringens in plasma, the small intestinal and caecal contents of rabbits.

PubMed

Zhou, Yu-Feng; Yu, Yang; Sun, Jian; Tao, Meng-Ting; Zhou, Wen-Jie; Li, Xiao; Liao, Xiao-Ping; Liu, Ya-Hong

2016-06-01

The pharmacokinetic (PK) and ex vivo pharmacodynamic (PD) of valnemulin against Clostridium perfringens were investigated in plasma, the small intestinal and caecal contents of rabbits following intravenous (IV) or oral administration at 3 mg/kg bodyweight (BW). The postantibiotic effect (PAE) and postantibiotic sub-MIC effect (PA-SME) of valnemulin against C. perfringens ATCC13124 were also determined. The time-kill curves were established in vitro and ex vivo to evaluate the antibacterial activity of valnemulin against C. perfringens. The elimination half-lives (T1/2λz) of valnemulin in the jejunal fluids (7.82 h) or caecal contents (14.8 h) of rabbits was significantly longer than that in plasma (2.94 h). The MIC values of valnemulin against C. perfringens ATCC13124 were both 0.063 μg/mL in the artificial medium and jejunal fluids. The PAEs of valnemulin against C. perfringens were 2.9 h (1 × MIC) and 5.03 h (4 × MIC), and the PA-SMEs ranged from 7.9 h to 11.1 h. Valnemulin exhibited rapid, time-dependent killing feature, and the ex vivo dose-response profile was closely fitted to sigmoid Emax model (r(2) = 0.9985). The surrogate index of AUC24 h/MIC ratios required to achieve the bactericidal and virtual bacterial elimination effects were 57.5 and 90.1 h, respectively. Accordingly, the calculated daily dosage regimens of valnemulin for the bactericidal activity (1.96 mg/kg) and bacterial elimination (3.08 mg/kg) would be therapeutically effective in rabbits against C. perfringens with MIC ≤0.5 μg/mL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations: in vitro study of color masking ability

PubMed Central

Oh, Seon-Hee

2015-01-01

PURPOSE The aim of the study was to evaluate the effect of abutment shade, ceramic thickness, and coping type on the final shade of zirconia all-ceramic restorations. MATERIALS AND METHODS Three different types of disk-shaped zirconia coping specimens (Lava, Cercon, Zirkonzahn: ø10 mm × 0.4 mm) were fabricated and veneered with IPS e.max Press Ceram (shade A2), for total thicknesses of 1 and 1.5 mm. A total of sixty zirconia restoration specimens were divided into six groups based on their coping types and thicknesses. The abutment specimens (ø10 mm × 7 mm) were prepared with gold alloy, base metal (nickel-chromium) alloy, and four different shades (A1, A2, A3, A4) of composite resins. The average L*, a*, b* values of the zirconia specimens on the six abutment specimens were measured with a dental colorimeter, and the statistical significance in the effects of three variables was analyzed by using repeated measures analysis of variance (α=.05).The average shade difference (ΔE) values of the zirconia specimens between the A2 composite resin abutment and other abutments were also evaluated. RESULTS The effects of zirconia specimen thickness (P<.001), abutment shade (P<.001), and type of zirconia copings (P<.003) on the final shade of the zirconia restorations were significant. The average ΔE value of Lava specimens (1 mm) between the A2 composite resin and gold alloy abutments was higher (close to the acceptability threshold of 5.5 ΔE) than th ose between the A2 composite resin and other abutments. CONCLUSION This in-vitro study demonstrated that abutment shade, ceramic thickness, and coping type affected the resulting shade of zirconia restorations. PMID:26576252

Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids.

PubMed

Starr, James M; Scollon, Edward J; Hughes, Michael F; Ross, David G; Graham, Stephen E; Crofton, Kevin M; Wolansky, Marcelo J; Devito, Michael J; Tornero-Velez, Rogelio

2012-12-01

Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal E(max) model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.

Bonding effectiveness to different chemically pre-treated dental zirconia.

PubMed

Inokoshi, Masanao; Poitevin, André; De Munck, Jan; Minakuchi, Shunsuke; Van Meerbeek, Bart

2014-09-01

The objective of this study was to evaluate the effect of different chemical pre-treatments on the bond durability to dental zirconia. Fully sintered IPS e.max ZirCAD (Ivoclar Vivadent) blocks were subjected to tribochemical silica sandblasting (CoJet, 3M ESPE). The zirconia samples were additionally pre-treated using one of four zirconia primers/adhesives (Clearfil Ceramic Primer, Kuraray Noritake; Monobond Plus, Ivoclar Vivadent; Scotchbond Universal, 3M ESPE; Z-PRIME Plus, Bisco). Finally, two identically pre-treated zirconia blocks were bonded together using composite cement (RelyX Ultimate, 3M ESPE). The specimens were trimmed at the interface to a cylindrical hourglass and stored in distilled water (7 days, 37 °C), after which they were randomly tested as is or subjected to mechanical ageing involving cyclic tensile stress (10 N, 10 Hz, 10,000 cycles). Subsequently, the micro-tensile bond strength was determined, and SEM fractographic analysis performed. Weibull analysis revealed the highest Weibull scale and shape parameters for the 'Clearfil Ceramic Primer/mechanical ageing' combination. Chemical pre-treatment of CoJet (3M ESPE) sandblasted zirconia using Clearfil Ceramic Primer (Kuraray Noritake) and Monobond Plus (Ivoclar Vivadent) revealed a significantly higher bond strength than when Scotchbond Universal (3M ESPE) and Z-PRIME Plus (Bisco) were used. After ageing, Clearfil Ceramic Primer (Kuraray Noritake) revealed the most stable bond durability. Combined mechanical/chemical pre-treatment, the latter with either Clearfil Ceramic Primer (Kuraray Noritake) or Monobond Plus (Ivoclar Vivadent), resulted in the most durable bond to zirconia. As a standard procedure to durably bond zirconia to tooth tissue, the application of a combined 10-methacryloyloxydecyl dihydrogen phosphate/silane ceramic primer to zirconia is clinically highly recommended.

Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long-chain triglyceride emulsion of propofol in beagle dogs

PubMed Central

Lee, S-H; Ghim, J-L; Song, M-H; Choi, H-G; Choi, B-M; Lee, H-M; Lee, E-K; Roh, Y-J; Noh, G-J

2009-01-01

Background and purpose: Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations. Experimental approach: The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg·kg−1·min−1) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling. Key results: Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUClast and AUCinf between both formulations were acceptable for bioequivalence, whereas that of Cmax was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E0 (baseline ApEn)–Emax (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V1 of both formulations and sex for k21 of microemulsion propofol. The blood-brain equilibration rate constants (ke0, min−1) were 0.476 and 0.696 for microemulsion and LCT propofol respectively. Conclusions and implications: Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges. PMID:19925493

Effect of resin shades on opacity of ceramic veneers and polymerization efficiency through ceramics.

PubMed

Öztürk, Elif; Chiang, Yu-Chih; Coşgun, Erdal; Bolay, Şükran; Hickel, Reinhard; Ilie, Nicoleta

2013-11-01

The aim of this study was to assess the effect of different resin cement shades on the opacity and color difference of ceramics and to determine the polymerization efficiency of the resin cement at different shades after curing through ceramics. Two different ceramics (IPS e.max Press and IPS Empress(®)CAD, Ivoclar Vivadent) were used for this study. A light-cured veneer luting resin (Variolink Veneer, Ivoclar Vivadent) in four different shades of HV+1, HV+3, LV-1, and LV-3 was used for the colorimetric measurements. The color and spectral reflectance of the ceramics were measured according to the CIELab color scale relative to the standard illuminant D65 on a reflection spectrophotometer (ColorEye7000A, USA). Color differences (ΔE values) and the contrast ratios (CR) of the different groups of samples were calculated. In order to analyse the polymerization efficiency of the resin cements, the micromechanical properties of the resins were measured with an automatic microhardness indenter (Fisherscope H100C, Germany). The results were analysed using one-way ANOVA and Tukey's HSD post hoc tests (SPSS 18.0). The one-way ANOVA test showed that the values of ΔE and CR of the different specimen groups were significantly different (p<0.05). Group 1 (20.7 ± 0.5) (IPS-CAD without resin cement) exhibited the highest and group 10 (14.8 ± 0.5) (e.max:HV+3) exhibited the lowest ΔE value. Significant differences in the micromechanical properties were identified among the tested resin cements in different shades (p<0.05). Resin cement shade is an important factor for the opacity of a restoration. Furthermore, the resin shade affects the micromechanical properties of the underlying resin cement. Copyright © 2013 Elsevier Ltd. All rights reserved.

Translucency of zirconia-based pressable ceramics with different core and veneer thicknesses.

PubMed

Jeong, Il-Do; Bae, So-Yeon; Kim, Dong-Yeon; Kim, Ji-Hwan; Kim, Woong-Chul

2016-06-01

Little information is available on the translucency of zirconia-based pressable ceramic restorations with a pressed ceramic veneer and zirconia core in various thickness combinations. The purpose of this in vitro study was to assess the translucency of 3 types of zirconia-based pressable ceramics for different core-veneer thickness combinations. A bilayered ceramic specimen was prepared with a pressable ceramic (IPS e.max Zirpress, Initial IQ, Rosetta UltraPress) veneer over a zirconia core (Zenostar Zr). Three groups of specimens (n=7) were formed with the following core+veneer thicknesses: 1 +0.5 mm, 0.7 +0.8 mm, and 0.5 +1 mm. To obtain consistent thickness and high translucency, all specimens were subjected to surface grinding with a grinding machine. To eliminate the effect of differences in roughness on the translucency, the surface roughness of the ground specimens was measured with a scanning profiler, and the consistency of these measured values was verified through statistical analysis. The luminous transmittance of the specimens was measured with a spectrophotometer. The effects of the pressable ceramic type and core-veneer thickness combination on transmittance were assessed using a 2-way ANOVA (α=.05). The consistency of the surface roughness among the tested specimens was confirmed using a 1-way ANOVA and the Tukey HSD post hoc test (P<.05). The luminous transmittance exhibited a statistically significant dependence on both the type of pressable ceramic and the core-veneer thickness combination (P<.05). The type of pressable ceramic and core-veneer thickness combination affected the translucency of the restoration. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Influence of ceramic thickness and ceramic materials on fracture resistance of posterior partial coverage restorations.

PubMed

Bakeman, E M; Rego, N; Chaiyabutr, Y; Kois, J C

2015-01-01

This study evaluated the influence of ceramic thickness and ceramic materials on fracture resistance of posterior partial coverage ceramic restorations. Forty extracted molars were allocated into four groups (n=10) to test for two variables: 1) the thickness of ceramic (1 mm or 2 mm) and 2) the ceramic materials (a lithium disilicate glass-ceramic [IPS e.max] or leucite-reinforced glass ceramic [IPS Empress]). All ceramic restorations were luted with resin cement (Variolink II) on the prepared teeth. These luted specimens were loaded to failure in a universal testing machine, in the compression mode, with a crosshead speed of 1.0 mm/min. The data were analyzed using two-way analysis of variance and the Tukey Honestly Significantly Different multiple comparison test (α =0.05). The fracture resistance revealed a significant effect for materials (p<0.001); however, the thickness of ceramic was not significant (p=0.074), and the interaction between the thickness of ceramic and the materials was not significant (p=0.406). Mean (standard deviation) fracture resistance values were as follows: a 2-mm thickness of a lithium disilicate bonded to tooth structure (2505 [401] N) revealed a significantly higher fracture resistance than did a 1-mm thickness of leucite-reinforced (1569 [452] N) and a 2-mm thickness of leucite-reinforced ceramic bonded to tooth structure (1716 [436] N) (p<0.05). There was no significant difference in fracture resistance values between a lithium disilicate ceramic at 1-mm thickness (2105 [567] N) and at 2-mm thickness. Using a lithium disilicate glass ceramic for partial coverage restoration significantly improved fracture resistance compared to using a leucite-reinforced glass ceramic. The thickness of ceramic had no significant effect on fracture resistance when the ceramics were bonded to the underlying tooth structure.

The effect of adhesive failure and defects on the stress distribution in all-ceramic crowns.

PubMed

Liu, Yonggang; Xu, Yuanzhi; Su, Bo; Arola, Dwayne; Zhang, Dongsheng

2018-05-29

To explore the effect of adhesive failure and defects between the crown and cement on the stress distribution within all-ceramic crowns and the corresponding risk of failure. An IPS e.max crown of lithium disilicate produced by CAD/CAM for a first mandibular molar was modeled using finite element analysis based on X-ray micro-CT scanned images. Predefined debonding states and interfacial defects between the crown and cement were simulated using the model. The first principal stress distribution of the crown and cement was analyzed under a vertical occlusal load of 600 N. A concept of failure risk was proposed to evaluate the crown. Stress concentrations in the crown were identified on the occlusal surface surrounding the region of loading, beneath the area of loading and at the margin of the interior surface. Stress concentrations in the cement were also evident at the boundary of the debonded areas. The lower surface of the crown is safe to sustain the 600 N vertical load, but the top surface of the cement would undergo cohesive failure. According to the evaluation of failure risk of the crown, the conditions of highest risk corresponded to the conditions with highest percentage of cement damage. The risk of failure is not only associated with debonding between the crown and cement, but also associated with its distribution. Debonding related defects and cementing defects are more deleterious to the interfacial stress than debonding itself. The axial wall plays a critical role in maintaining the principal tensile stress of the crown at an acceptable level. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cellular Accumulation and Pharmacodynamic Evaluation of the Intracellular Activity of CEM-101, a Novel Fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in Human THP-1 Macrophages ▿ †

PubMed Central

Lemaire, Sandrine; Van Bambeke, Françoise; Tulkens, Paul M.

2009-01-01

CEM-101 is a novel fluoroketolide with lower MICs than those of telithromycin and macrolides. Our aim was to assess the cellular accumulation and intracellular activity of CEM-101 using models developed for analyzing the pharmacokinetics and pharmacological properties of antibiotics against phagocytized bacteria. We used THP-1 macrophages and Staphylococcus aureus (ATCC 25923 [methicillin (meticillin) sensitive]), Listeria monocytogenes (strain EGD), and Legionella pneumophila (ATCC 33153). CEM-101 reached cellular-to-extracellular-concentration ratios of about 350 within 24 h (versus approximately 20, 30, and 160 for telithromycin, clarithromycin, and azithromycin, respectively). This intracellular accumulation was suppressed by incubation at a pH of ≤6 and by monensin (proton ionophore) and was unaffected by verapamil (P-glycoprotein inhibitor; twofold accumulation increase for azithromycin) or gemfibrozil. While keeping with the general properties of the macrolide antibiotics in terms of maximal efficacy (Emax; approximately 1-log10-CFU decrease compared to the postphagocytosis inoculum after a 24-h incubation), CEM-101 showed significantly greater potency against phagocytized S. aureus than telithromycin, clarithromycin, and azithromycin (for which the 50% effective concentration [EC50] and static concentrations were about 3-, 6-, and 15-fold lower, respectively). CEM-101 was also about 50-fold and 100-fold more potent than azithromycin against phagocytized L. monocytogenes and L. pneumophila, respectively. These differences in EC50s and static concentrations between drugs were minimized when data were expressed as multiples of the MIC, demonstrating the critical role of intrinsic drug activity (MIC) in eliciting the antibacterial intracellular effects, whereas accumulation per se was unimportant. CEM-101 should show enhanced in vivo potency if used at doses similar to those of the comparators tested here. PMID:19564365

Cellular accumulation and pharmacodynamic evaluation of the intracellular activity of CEM-101, a novel fluoroketolide, against Staphylococcus aureus, Listeria monocytogenes, and Legionella pneumophila in human THP-1 macrophages.

PubMed

Lemaire, Sandrine; Van Bambeke, Françoise; Tulkens, Paul M

2009-09-01

CEM-101 is a novel fluoroketolide with lower MICs than those of telithromycin and macrolides. Our aim was to assess the cellular accumulation and intracellular activity of CEM-101 using models developed for analyzing the pharmacokinetics and pharmacological properties of antibiotics against phagocytized bacteria. We used THP-1 macrophages and Staphylococcus aureus (ATCC 25923 [methicillin (meticillin) sensitive]), Listeria monocytogenes (strain EGD), and Legionella pneumophila (ATCC 33153). CEM-101 reached cellular-to-extracellular-concentration ratios of about 350 within 24 h (versus approximately 20, 30, and 160 for telithromycin, clarithromycin, and azithromycin, respectively). This intracellular accumulation was suppressed by incubation at a pH of < or = 6 and by monensin (proton ionophore) and was unaffected by verapamil (P-glycoprotein inhibitor; twofold accumulation increase for azithromycin) or gemfibrozil. While keeping with the general properties of the macrolide antibiotics in terms of maximal efficacy (Emax; approximately 1-log10-CFU decrease compared to the postphagocytosis inoculum after a 24-h incubation), CEM-101 showed significantly greater potency against phagocytized S. aureus than telithromycin, clarithromycin, and azithromycin (for which the 50% effective concentration [EC50] and static concentrations were about 3-, 6-, and 15-fold lower, respectively). CEM-101 was also about 50-fold and 100-fold more potent than azithromycin against phagocytized L. monocytogenes and L. pneumophila, respectively. These differences in EC50s and static concentrations between drugs were minimized when data were expressed as multiples of the MIC, demonstrating the critical role of intrinsic drug activity (MIC) in eliciting the antibacterial intracellular effects, whereas accumulation per se was unimportant. CEM-101 should show enhanced in vivo potency if used at doses similar to those of the comparators tested here.

Chronic Neuropathic Pain in Mice Reduces μ-Opioid Receptor-Mediated G-protein Activity in the Thalamus

PubMed Central

Hoot, Michelle R.; Sim-Selley, Laura J.; Selley, Dana E.; Scoggins, Krista L.; Dewey, William L.

2011-01-01

Neuropathic pain is a debilitating condition that is often difficult to treat using conventional pharmacological interventions and the exact mechanisms involved in the establishment and maintenance of this type of chronic pain have yet to be fully elucidated. The present studies examined the effect of chronic nerve injury on μ-opioid receptors and receptor-mediated G-protein activity within the supraspinal brain regions involved in pain processing of mice. Chronic constriction injury (CCI) reduced paw withdrawal latency, which was maximal at 10 days post-injury. [d-Ala2,(N-Me)Phe4, Gly5-OH] enkephalin (DAMGO)-stimulated [35S]GTPγS binding was then conducted at this time point in membranes prepared from the rostral ACC (rACC), thalamus and periaqueductal grey (PAG) of CCI and sham-operated mice. Results showed reduced DAMGO-stimulated [35S]GTPγS binding in the thalamus and PAG of CCI mice, with no change in the rACC. In thalamus, this reduction was due to decreased maximal stimulation by DAMGO, with no difference in EC50 values. In PAG, however, DAMGO Emax values did not significantly differ between groups, possibly due to the small magnitude of the main effect. [3H]Naloxone binding in membranes of the thalamus showed no significant differences in Bmax values between CCI and sham-operated mice, indicating that the difference in G-protein activation did not result from differences in μ-opioid receptor levels. These results suggest that CCI induced a region-specific adaptation of μ-opioid receptor-mediated G-protein activity, with apparent desensitization of the μ-opioid receptor in the thalamus and PAG and could have implications for treatment of neuropathic pain. PMID:21762883

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

PubMed

Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

2014-08-15

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

Pharmacodynamics of selective androgen receptor modulators.

PubMed

Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

2003-03-01

The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

Evaluation of Ultra High Pressure (UHP) Firefighting in a Room-and-Contents Fire

DTIC Science & Technology

2017-03-15

Burn Room and Hangar Temperature Prior to Ignition ............................................... 18 Figure 12. Effect of Temperature on Normalized...Figure 20. Maximum Average Temperature and Heat Flux ......................................................... 22 Figure 21. Effect of Maximum Average...Aspirated Ceiling Temperature .................................... 23 Figure 22. Effect of Maximum Average Floor Heat Flux on Extinguishment Quantity

Influence of core thickness and artificial aging on the biaxial flexural strength of different all-ceramic materials: An in-vitro study.

PubMed

Dikicier, Sibel; Ayyildiz, Simel; Ozen, Julide; Sipahi, Cumhur

2017-05-31

The purpose of this study was to investigate the flexural strength of all-ceramics with varying core thicknesses submitted to aging. In-Ceram Alumina (IC), IPS e.max Press (EM) and Katana (K) (n=40), were selected. Each group contained two core groups based on the core thickness as follows: IC/0.5, IC/0.8, EM/0.5, EM/0.8, K/0.5 and K/0.8 mm in thickness (n=20 each). Ten specimens from each group were subjected to aging and all specimens were tested for strength in a testing machine either with or without being subjected aging. The mean strength of the K were higher (873.05 MPa) than that of the IC (548.28 MPa) and EM (374.32 MPa) regardless of core thickness. Strength values increased with increasing core thickness for all IC, EM and K regardless of aging. Results of this study concluded that strength was not significantly affected by aging. Different core thicknesses affected strength of the all-ceramic materials tested (p<0.05).

Dental Shade Guide Variability for Hues B, C, and D Using Cross-Polarized Photography.

PubMed

Sampaio, Camila S; Gurrea, Jon; Gurrea, Marta; Bruguera, August; Atria, Pablo J; Janal, Malvin; Bonfante, Estevam A; Coelho, Paulo G; Hirata, Ronaldo

2018-04-20

This study evaluated the color variability of hues B, C, and D between the VITA Classical shade guide (Vita Zahnfabrik) and four other VITA-coded ceramic shade guides using a digital camera (Canon EOS 60D) and computer software (Adobe Photoshop CC). A cross-polarizing filter was used to standardize external light sources influencing color match. A total of 275 pictures were taken, 5 per shade tab, for 11 shades (B1, B2, B3, B4, C1, C2, C3, C4, D2, D3, and D4), from the following shade guides: VITA Classical (control); IPS e.max Ceram (Ivoclar Vivadent); IPS d.SIGN (Ivoclar Vivadent); Initial ZI (GC); and Creation CC (Creation Willi Geller). Pictures were evaluated using Adobe Photoshop CC for standardization of hue, chroma, and value between shade tabs. The VITA-coded shade guides evaluated here showed an overall unmatched shade in all their tabs when compared to the control, suggesting that shade selection should be made with the corresponding manufacturer guide of the ceramic intended for the final restoration.

OCT evaluation of single ceramic crowns: comparison between conventional and chair-side CAD/CAM technologies

NASA Astrophysics Data System (ADS)

Gabor, A.; Jivanescu, A.; Zaharia, C.; Hategan, S.; Topala, F. I.; Levai, C. M.; Negrutiu, M. L.; Sinescu, C.; Duma, V.-F.; Bradu, A.; Podoleanu, A. Gh.

2016-03-01

Digital impressions were introduced to overcome some of the obstacles due to traditional impression materials and techniques. The aim of this in vitro study is to compare the accuracy of all ceramic crowns obtained with digital impression and CAD-CAM technology with the accuracy of those obtained with conventional impression techniques. Two groups of 10 crowns each have been considered. The digital data obtained from Group 1 have been processed and the all-ceramic crowns were milled with a CAD/CAM technology (CEREC MCX, Sirona). The all ceramic crowns in Group 2 were obtained with the classical technique of pressing (emax, Ivoclar, Vivadent). The evaluation of the marginal adaptation was performed with Time Domain Optical Coherence Tomography (TD OCT), working at a wavelength of 1300 nm. Tri-dimensional (3D) reconstructions of the selected areas were obtained. Based on the findings in this study, one may conclude that the marginal accuracy of all ceramic crowns fabricated with digital impression and the CAD/CAM technique is superior to the conventional impression technique.

Evaluation of marginal fit of two all-ceramic copings with two finish lines

PubMed Central

Subasi, Gulce; Ozturk, Nilgun; Inan, Ozgur; Bozogullari, Nalan

2012-01-01

Objectives: This in-vitro study investigated the marginal fit of two all-ceramic copings with 2 finish line designs. Methods: Forty machined stainless steel molar die models with two different margin designs (chamfer and rounded shoulder) were prepared. A total of 40 standardized copings were fabricated and divided into 4 groups (n=10 for each finish line-coping material). Coping materials tested were IPS e.max Press and Zirkonzahn; luting agent was Variolink II. Marginal fit was evaluated after cementation with a stereomicroscope (Leica MZ16). Two-way analysis of variance and Tukey-HSD test were performed to assess the influence of each finish line design and ceramic type on the marginal fit of 2 all-ceramic copings (α =.05). Results: Two-way analysis of variance revealed no statistically significant differences for marginal fit relative to finish lines (P=.362) and ceramic types (P=.065). Conclusion: Within the limitations of this study, both types of all-ceramic copings demonstrated that the mean marginal fit was considered acceptable for clinical application (⩽120 μm). PMID:22509119

Contribution of different antiretroviral regimens containing zidovudine, lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy.

PubMed

Sripan, Patumrat; Le Coeur, Sophie; Ingsrisawang, Lily; Cressey, Tim R; Bouazza, Naïm; Foissac, Frantz; Ngo-Giang-Huong, Nicole; Traisathit, Patrinee; Srirompotong, Ussanee; Ayudhaya, Orada Patamasingh Na; Puangsombat, Achara; Jungpipun, Jantana; Jittayanun, Kanokwan; Tréluyer, Jean-Marc; Jourdain, Gonzague; Lallemant, Marc; Urien, Saïk

2016-01-01

Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.

Effects of Rhododendron maximum thickest on tree seed dispersal, seedling morphology, and survivorship

Treesearch

Thomas T. Lei; Shawn W. Semones; John F. Walker; Barton D. Clinton; Erik T. Nilsen

2002-01-01

In the southern Appalachian forests, the regeneration of canopy trees is severely inhibited by Rhododendron maximum L., an evergreen understory shrub producing dense rhickets. While light availability is a major cause, other factors may also contribute to the absence of tree seedlings under R. maximum. We examined the effects of...

Forbearance for fluoxetine: do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?

PubMed

Fitzgerald, Paul J

2014-07-01

It is of high clinical interest to better understand the timecourse through which psychiatric drugs produce their beneficial effects. While a rough estimate of the time lag between initiating monoaminergic antidepressant therapy and the onset of therapeutic effect in depressed subjects is two weeks, much less is known about when these drugs reach maximum effect. This paper briefly examines studies that directly address this question through long-term antidepressant administration to humans, while also putting forth a simple theoretical approach for estimating the time required for monoaminergic antidepressants to reach maximum therapeutic effect in humans. The theory invokes a comparison between speed of antidepressant drug response in humans and in rodents, focusing on the apparently greater speed in rodents. The principal argument is one of proportions, comparing earliest effects of these drugs in rodents and humans, versus their time to reach maximum effect in these organisms. If the proportionality hypothesis is even coarsely accurate, then applying these values or to some degree their ranges to the hypothesis, may suggest that monoaminergic antidepressants require a number of years to reach maximum effect in humans, at least in some individuals.

Influence of ageing on glass and resin bonding of dental glass-ceramic veneer adhesion to zirconia: A fracture mechanics analysis and interpretation.

PubMed

Swain, M V; Gee, C; Li, K C

2018-04-26

Adhesion plays a major role in the bonding of dental materials. In this study the adhesion of two glass-ceramic systems (IPS e.max and VITABLOCS) to a zirconia sintered substrate using a glass (for IPS e.max) and resin (VITABLOCS) before and after exposure to ageing for 14 days in distilled water at 37 °C are compared using two interfacial fracture mechanics tests, the 3 point bend Schwickerath (Kosyfaki and Swain, 2014; Schneider and Swain, 2015) and 4 point bend (Charalambides et al., 1989) approaches. Both tests result in stable crack extension from which the strain energy release rate (G, N/m or J/m 2 ) can be determined. In the case of the 3 PB test the Work of Fracture was also determined. In addition, the Schwickerath test enables determination of the critical stress for the onset of cracking to occur, which forms the basis of the ISO (ISO9693-2:2016) adhesion test for porcelain ceramic adhesion to zirconia. For the aged samples there was a significant reduction in the resin-bonded strengths (Schwickerath) and strain energy release rate (both 3 and 4 PB tests), which was not evident for the glass bonded specimens. Critical examination of the force-displacement curves showed that ageing of the resin resulted in a major change in the form of the curves, which may be interpreted in terms of a reduction in the critical stress to initiate cracking and also in the development of an R-curve. The extent of the reduction in strain energy release rate following ageing was greater for the Schwickerath test than the Charalambides test. The results are discussed in terms of; the basic mechanics of these two tests, the deterioration of the resin bonding following moisture exposure and the different dimensions of the specimens. These in-vitro results raise concerns regarding resin bonding to zirconia. The present study uses a novel approach to investigate the role of ageing or environmental degradation on the adhesive bonding of two dental ceramics to zirconia. This continues to be a major clinical problem but current approaches, till now, have relied upon a myriad of strength based tests to quantify the extent of environmental degradation with time. In this paper we use two fracture mechanics approaches, based upon simple 3 and 4 point bend testing procedures that enable stable debonding crack extension to occur. The paper provides a more critical approach to evaluate the role of environmental degradation of adhesion for dental materials. Copyright © 2018. Published by Elsevier Ltd.

A randomized controlled clinical trial of 3-unit posterior zirconia-ceramic fixed dental prostheses (FDP) with layered or pressed veneering ceramics: 3-year results.

PubMed

Naenni, Nadja; Bindl, Andreas; Sax, Caroline; Hämmerle, Christoph; Sailer, Irena

2015-11-01

The aim of the present pilot study was to test whether or not posterior zirconia-ceramic fixed dental prostheses (FDPs) with pressed veneering ceramic exhibit less chipping than FDPs with layered veneering ceramics. Forty patients (13 female, 27 male; mean age 54 years (range 26.1-80.7 years) in need of one maxillary or mandibular three-unit FDP in the second premolar or molar region were recruited and treated at two separate centers at the University of Zurich according to the same study protocol. The frameworks were made out of zirconia using a CAD/CAM system (Cerec Sirona, Bensheim, Germany). The patients were randomly assigned to either the test group (zirconia frameworks veneered with pressed ceramic; IPS e.max ZirPress, Ivoclar Vivadent AG, Schaan, Liechtenstein; n=20) or the control group (layered veneering ceramic; IPS e.max Ceram, Ivoclar Vivadent AG, Schaan, Liechtenstein; n=20). All FDPs were adhesively cemented and evaluated at baseline (i.e., cementation), at 6 months and at 1 and 3 years of clinical service. The survival of the reconstruction was recorded. The technical outcome was assessed using modified United States Public Health Services (USPHS) criteria. The biologic parameters analyzed at abutment teeth and analogous non-restored teeth included probing pocket depth (PPD), plaque control record (PCR), bleeding on probing (BOP), and tooth vitality (CO2). Data was descriptively analyzed and survival was calculated using Kaplan-Meier statistics. 36 patients (25 female, 11 male; mean age 52.3 years) with 18 test and 18 control FDPs were examined after a mean follow-up of 36 months (95% CI: 32.6-39.1 months). Comparison of groups was done by Crosstabulation showing even distribution of the respective restored teeth amidst the groups. Survival rate was 100% for both test and control FDPs. Chipping of the veneering ceramic tended to occur more frequently in test (n=8; 40%) than in control (n=4; 20%) FDPs, albeit not significantly (p=0.3). No further differences of the technical outcomes of test and control FDPs occurred.In both test and control group healthy conditions and no difference of the biologic parameters at the abutment and un-restored teeth was found. Zirconia FDPs with pressed and layered veneering ceramics exhibited similar outcomes at 3 years. A trend to more chipping of the pressed veneering ceramic, however, was observed. Posterior restorations with zirconia frameworks are a viable treatment method. When restoring posterior teeth with all-ceramic restorations, care providers should be aware of the higher rate of chipping compared to the published data on conventional metal-ceramic restorations. Copyright © 2015. Published by Elsevier Ltd.

Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

PubMed

Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

2003-09-01

This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G protein activation at postsynaptic 5-HT(1A) receptors in the hippocampus. These data support a role of postsynaptic 5-HT(1A) receptors in the functional profiles of certain antipsychotic agents.

Correlation between in vitro and in vivo concentration–effect relationships of naproxen in rats and healthy volunteers

PubMed Central

Huntjens, Dymphy R H; Spalding, David J M; Danhof, Meindert; Della Pasqua, Oscar E

2006-01-01

Understanding the mechanisms underlying the analgesic effect of new cyclooxygenase inhibitors is essential to identify dosing requirements in early stages of drug development. Accurate extrapolation to humans of in vitro and in vivo findings in preclinical species is needed to optimise dosing regimen in inflammatory conditions. The current investigation characterises the inhibition of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) by naproxen in vitro and in vivo in rat and human blood. The inhibition of PGE2 in the absence or presence of increasing concentrations of naproxen (10−8–10−1 M) was measured by ex vivo whole blood stimulation with LPS, whereas inhibition of TXB2 was measured in serum following blood clotting. In further experiments, inhibition of PGE2 and TXB2 levels was also assessed ex vivo in animals treated with naproxen (2.5, 10, 25 mg kg−1). Subsequently, pharmacokinetic (PK)/pharmacodynamics (PD) modelling of in vitro and in vivo data was performed using nonlinear mixed effects in NONMEM (V). Inhibition of PGE2 and TXB2 was characterised by a sigmoid Emax model. The exposure–response relationships in vitro and in vivo were of the same order of magnitude in both species. IC80 estimates obtained in vitro were similar for PGE2 inhibition (130.8±11 and 131.9±19 10−6 M, mean±s.d. for humans and rats, respectively), but slightly different for TXB2 inhibition (103.9±15 and 151.4±40 10−6 M, mean±s.d. for humans and rats, respectively, P< 0.05). These differences, however, may not be biologically relevant. The results confirm the value of exposure–effect relationships determined in vitro as a means to predict the pharmacological activity in vivo. This analysis also highlights the need to parameterise concentration–effect relationships in early drug development, as indicated by the estimates of IC80 for PGE2 and TXB2 inhibition. PMID:16682968

In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion

PubMed Central

Yu, Yang; Zhou, Yu-Feng; Chen, Mei-Ren; Li, Xiao; Qiao, Gui-Lin; Sun, Jian; Liao, Xiao-Ping; Liu, Ya-Hong

2016-01-01

Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml. PMID:27218674

In Vivo Pharmacokinetics/Pharmacodynamics of Cefquinome in an Experimental Mouse Model of Staphylococcus Aureus Mastitis following Intramammary Infusion.

PubMed

Yu, Yang; Zhou, Yu-Feng; Chen, Mei-Ren; Li, Xiao; Qiao, Gui-Lin; Sun, Jian; Liao, Xiao-Ping; Liu, Ya-Hong

2016-01-01

Staphylococcus aureus remains the major cause of morbidity of bovine mastitis worldwide leading to massive economic losses. Cefquinome is a fourth generation cephalosporin, which preserves susceptibility and antibacterial activity against S. aureus. This work aims to study the pharmacokinetic (PK) and pharmacodynamic (PD) modeling following intramammary administration of cefquinome against S. aureus mastitis. The mouse model of S. aureus mastitis was developed for the PK/PD experiments. The plasma PK characteristics after intramammary injection of cefquinome at various single doses of 25, 50, 100, 200, 400 μg per gland (both fourth pairs of glands: L4 and R4) were calculated using one-compartment and first-order absorption model. PD study was investigated based on twenty-one intermittent dosing regimens, of which total daily dose ranged from 25 to 4800 μg per mouse and dosage intervals included 8, 12 or 24 h. The sigmoid Emax model of inhibitory effect was employed for PK/PD modeling. The results of PK/PD integration of cefquinome against S. aureus suggested that the percentage of duration that drug concentration exceeded the minimal inhibitory concentration (%T>MIC) and the ratio of area under time-concentration curve over MIC (AUC/MIC) are important indexes to evaluate the antibacterial activity. The PK/PD parameters of %T>MIC and AUC0-24/MIC were 35.98% and 137.43 h to obtain a 1.8 logCFU/gland reduction of bacterial colony counts in vivo, against S. aureus strains with cefquinome MIC of 0.5μg/ml.

Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

PubMed

Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2017-10-01

Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

Effect of radiance-to-reflectance transformation and atmosphere removal on maximum likelihood classification accuracy of high-dimensional remote sensing data

NASA Technical Reports Server (NTRS)

Hoffbeck, Joseph P.; Landgrebe, David A.

1994-01-01

Many analysis algorithms for high-dimensional remote sensing data require that the remotely sensed radiance spectra be transformed to approximate reflectance to allow comparison with a library of laboratory reflectance spectra. In maximum likelihood classification, however, the remotely sensed spectra are compared to training samples, thus a transformation to reflectance may or may not be helpful. The effect of several radiance-to-reflectance transformations on maximum likelihood classification accuracy is investigated in this paper. We show that the empirical line approach, LOWTRAN7, flat-field correction, single spectrum method, and internal average reflectance are all non-singular affine transformations, and that non-singular affine transformations have no effect on discriminant analysis feature extraction and maximum likelihood classification accuracy. (An affine transformation is a linear transformation with an optional offset.) Since the Atmosphere Removal Program (ATREM) and the log residue method are not affine transformations, experiments with Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data were conducted to determine the effect of these transformations on maximum likelihood classification accuracy. The average classification accuracy of the data transformed by ATREM and the log residue method was slightly less than the accuracy of the original radiance data. Since the radiance-to-reflectance transformations allow direct comparison of remotely sensed spectra with laboratory reflectance spectra, they can be quite useful in labeling the training samples required by maximum likelihood classification, but these transformations have only a slight effect or no effect at all on discriminant analysis and maximum likelihood classification accuracy.

40 CFR 141.60 - Effective dates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS National Primary Drinking Water Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.60 Effective dates. (a) The effective dates for § 141...

Effects of fasting on maximum thermogenesis in temperature-acclimated rats

NASA Astrophysics Data System (ADS)

Wang, L. C. H.

1981-09-01

To further investigate the limiting effect of substrates on maximum thermogenesis in acute cold exposure, the present study examined the prevalence of this effect at different thermogenic capabilities consequent to cold- or warm-acclimation. Male Sprague-Dawley rats (n=11) were acclimated to 6, 16 and 26‡C, in succession, their thermogenic capabilities after each acclimation temperature were measured under helium-oxygen (21% oxygen, balance helium) at -10‡C after overnight fasting or feeding. Regardless of feeding conditions, both maximum and total heat production were significantly greater in 6>16>26‡C-acclimated conditions. In the fed state, the total heat production was significantly greater than that in the fasted state at all acclimating temperatures but the maximum thermogenesis was significant greater only in the 6 and 16‡C-acclimated states. The results indicate that the limiting effect of substrates on maximum and total thermogenesis is independent of the magnitude of thermogenic capability, suggesting a substrate-dependent component in restricting the effective expression of existing aerobic metabolic capability even under severe stress.

30 CFR 817.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... either the maximum peak-particle-velocity limits of paragraph (d)(2), the scaled-distance equation of... authority before the initiation of blasting. (2) Maximum peak-particle velocity. (i) The maximum ground... site, in feet Maximum allowable peak particle velocity (V max) for ground vibration, in inches/second 1...

30 CFR 817.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... either the maximum peak-particle-velocity limits of paragraph (d)(2), the scaled-distance equation of... authority before the initiation of blasting. (2) Maximum peak-particle velocity. (i) The maximum ground... site, in feet Maximum allowable peak particle velocity (V max) for ground vibration, in inches/second 1...

30 CFR 817.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... either the maximum peak-particle-velocity limits of paragraph (d)(2), the scaled-distance equation of... authority before the initiation of blasting. (2) Maximum peak-particle velocity. (i) The maximum ground... site, in feet Maximum allowable peak particle velocity (V max) for ground vibration, in inches/second 1...

30 CFR 817.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... either the maximum peak-particle-velocity limits of paragraph (d)(2), the scaled-distance equation of... authority before the initiation of blasting. (2) Maximum peak-particle velocity. (i) The maximum ground... site, in feet Maximum allowable peak particle velocity (V max) for ground vibration, in inches/second 1...

30 CFR 817.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... either the maximum peak-particle-velocity limits of paragraph (d)(2), the scaled-distance equation of... authority before the initiation of blasting. (2) Maximum peak-particle velocity. (i) The maximum ground... site, in feet Maximum allowable peak particle velocity (V max) for ground vibration, in inches/second 1...

Comment and some questions on "Puzzles and the maximum effective moment (MEM) criterion in structural Geology"

NASA Astrophysics Data System (ADS)

Tong, Hengmao

2012-03-01

Zheng et al (Zheng and Wang, 2004; Zheng et al., 2011) proposed a new mechanism for ductile formation which is related to effective moment instead of shear stress, and the deformation zone develops along plane of maximum effective moment. The mathematical expression of maximum effective moment (The criterion of maximum effective moment, simplified as MEM criterion, Zheng and Wang, 2004; Zheng et al., 2011) is that Meff = 0.5 (σ1 - σ3) L sin2αsinα, where σ1 - σ3 is the yield strength of a material or rock, L is the unit length (of cleavage) in the σ1 direction, and α is the angle between σ1 and a certain plane. The effective moment reaches its maximum value when α is ±54.7° and deformation zones tend to appear in pairs with a conjugate angle of 2α, 109.4° facing to σ1. There is no remarkable Meff drop from the maximum values within the range of 54.7°±10°, where is favorable for the formation of ductile deformation zone. As a result, the origin of low-angle normal faults, high-angle reverse faults and certain types of conjugate strike-slip faults, which are incompatible with Mohr-Coulomb criterion, can be reasonably explained with MEM criterion (Zheng et al., 2011). Further more, lots of natural and experimental cases were found or collected to support the criterion.

Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center study.

PubMed

Florio, Tullio; Barbieri, Federica; Spaziante, Renato; Zona, Gianluigi; Hofland, Leo J; van Koetsveld, Peter M; Feelders, Richard A; Stalla, Günter K; Theodoropoulou, Marily; Culler, Michael D; Dong, Jesse; Taylor, John E; Moreau, Jacques-Pierre; Saveanu, Alexandru; Gunz, Ginette; Dufour, Henry; Jaquet, Philippe

2008-06-01

Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [3H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC50=1.2 pM and Emax=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs.

Gauging the Nearness and Size of Cycle Maximum

NASA Technical Reports Server (NTRS)

Wilson, Robert M.; Hathaway, David H.

2003-01-01

A simple method for monitoring the nearness and size of conventional cycle maximum for an ongoing sunspot cycle is examined. The method uses the observed maximum daily value and the maximum monthly mean value of international sunspot number and the maximum value of the 2-mo moving average of monthly mean sunspot number to effect the estimation. For cycle 23, a maximum daily value of 246, a maximum monthly mean of 170.1, and a maximum 2-mo moving average of 148.9 were each observed in July 2000. Taken together, these values strongly suggest that conventional maximum amplitude for cycle 23 would be approx. 124.5, occurring near July 2002 +/-5 mo, very close to the now well-established conventional maximum amplitude and occurrence date for cycle 23-120.8 in April 2000.

Correlation between Reynolds number and eccentricity effect in stenosed artery models.

PubMed

Javadzadegan, Ashkan; Shimizu, Yasutomo; Behnia, Masud; Ohta, Makoto

2013-01-01

Flow recirculation and shear strain are physiological processes within coronary arteries which are associated with pathogenic biological pathways. Distinct Quite apart from coronary stenosis severity, lesion eccentricity can cause flow recirculation and affect shear strain levels within human coronary arteries. The aim of this study is to analyse the effect of lesion eccentricity on the transient flow behaviour in a model of a coronary artery and also to investigate the correlation between Reynolds number (Re) and the eccentricity effect on flow behaviour. A transient particle image velocimetry (PIV) experiment was implemented in two silicone based models with 70% diameter stenosis, one with eccentric stenosis and one with concentric stenosis. At different times throughout the flow cycle, the eccentric model was always associated with a greater recirculation zone length, maximum shear strain rate and maximum axial velocity; however, the highest and lowest impacts of eccentricity were on the recirculation zone length and maximum shear strain rate, respectively. Analysis of the results revealed a negative correlation between the Reynolds number (Re) and the eccentricity effect on maximum axial velocity, maximum shear strain rate and recirculation zone length. As Re number increases the eccentricity effect on the flow behavior becomes negligible.

Morphine sulfate and naltrexone hydrochloride extended-release capsules: naltrexone release, pharmacodynamics, and tolerability.

PubMed

Johnson, Franklin; Setnik, Beatrice

2011-01-01

Morphine sulfate and naltrexone hydrochloride extended-release capsules (EMBEDA, King Pharmaceuticals, Inc., Bristol, TN), indicated for management of chronic, moderate-to-severe pain, contain pellets of extended-release morphine sulfate with a sequestered naltrexone core (MS-sNT). Taken as directed, morphine provides analgesia while naltrexone remains sequestered; if tampered with by crushing, naltrexone is released to mitigate morphine-induced euphoric effects. While it is necessary to establish that formulations intended to reduce attractiveness for abuse are successful in doing so, it is also necessary to demonstrate that product therapeutic integrity is maintained for patients. Data were reviewed from 3 studies to determine: 1) the quantity of naltrexone released when MS-sNT pellets are crushed (MS-sNTC) for at least 2 minutes with mortar and pestle); 2) the extent to which the naltrexone released upon crushing mitigated morphine-induced subjective effects; and 3) whether sequestered naltrexone precipitates opioid withdrawal when MS-sNT is taken as directed. The naltrexone bioavailability study compared naltrexone release from MS-sNTC with that from whole intact MS-sNT capsules (MS-sNTW) and an equal naltrexone solution (NS) dose. Equivalent bioavailability was established if 90% confidence intervals (CIs) for geometric mean ratios (maximum plasma naltrexone concentration [Cmax] and area under the concentration-time curve extrapolated to infinity [AUC∞]) fell between 80% and 125%. The oral pharmacodynamic study assessed drug liking and euphoria and pharmacokinetic properties of MS-sNTC and MS-sNTW compared with morphine sulfate solution (MSS) and placebo. The 12-month, open-label (OL) safety study evaluated safety of MS-sNT administered orally as directed in patients with chronic, moderate-to-severe pain. Safety assessments included withdrawal symptoms based on the Clinical Opiate Withdrawal Scale (COWS). Naltrexone from MS-sNTC met criteria for equivalent bioavailability to NS. Although morphine relative bioavailability was similar for MS-sNTC and MSS, mean peak (Emax) visual analog scale (VAS) scores for drug liking and Cole/Addiction Research Center Inventory Stimulation-Euphoria were significantly reduced for MS-sNTC vs MSS (p < 0.001). In these 2 studies, a total of 6 participants had one measurement of plasma naltrexone after MS-sNTW that was above the lower limit of quantification. In the OL safety study, 72/93 participants (77%) had no quantifiable naltrexone concentrations. There was neither evidence of naltrexone accumulation for any participant nor any significant correlation with MS-sNT dose, age, or sex. Of 4 participants with the highest naltrexone concentrations, none had COWS scores consistent with moderate opioid withdrawal symptoms. Only 5 participants had COWS scores consistent with moderate opioid withdrawal; all 5 had not taken MS-sNT as directed. Study populations may not be fully representative of patients receiving opioid therapy for the management of chronic, moderate-to-severe pain and of opioid abusers. When MS-sNT capsules are crushed, all of the sequestered naltrexone (relative to oral NS) is released and immediately available to mitigate morphine-induced effects. When MS-sNT was crushed, the naltrexone released abated drug liking and euphoria relative to that from an equal dose of immediate-release morphine from MSS administration in a majority of participants. Naltrexone concentrations were low over a period of 12 months without evidence of accumulation, and there were no observable opioid withdrawal symptoms when MS-sNT was taken as directed.

76 FR 59764 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... Change Relating to the Maximum Number of Quoters (``MNQ'') Permitted To Be Assigned in Equity Options...''),\\4\\ by establishing a higher maximum number of quoting participants (``Maximum Number of Quoters'' or...

Influence of translucence/opacity and shade in the flexural strength of lithium disilicate ceramics

PubMed Central

Santos, Mila Oliveira; do Amaral, Flávia Lucisano Botelho; França, Fabiana Mantovani Gomes; Basting, Roberta Tarkany

2015-01-01

Background: Lithium disilicate ceramic system consists of glass ceramic ingots with different grades of translucence which may influence its flexural strength. Aims: To assess the three-point flexural strength of the different lithium disilicate-based ceramic ingots (IPS e.max Press/Ivoclar Vivadent) with different levels of translucence and shade. Materials and Methods: Six groups of ceramic ingots were selected to represent different levels of translucence and shade (HTA1, HTBL2, LTA2, LTB2, MO2, and HO). They measured 25 mm × 5 mm × 2 mm (n = 10), according to ISO 6872 specifications, and tested on a universal test machine (EMIC). Statistical Analysis Used: A one-way analysis of variance (ANOVA) was used (α = 0.05). Results: The results (in MPa) were: HTA1 = 392.98; HTBL2 = 390.74; LTA2 = 390.46; LTB2 = 389.92; MO2 = 390.43; HO = 391.96. ANOVA showed no significant difference among groups (P = 0.1528). Conclusions: Different levels of translucence, opacity and shade of ingots did not affect their mechanical strength, and the use of these ceramics should be guided by the esthetic demands of each clinical situation. PMID:26430304

Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry: a bridge to individualized medicine.

PubMed

Bennett, Teresa A; Montesinos, Pau; Moscardo, Federico; Martinez-Cuadron, David; Martinez, Joaquin; Sierra, Jorge; García, Raimundo; de Oteyza, Jaime Perez; Fernandez, Pascual; Serrano, Josefina; Fernandez, Angeles; Herrera, Pilar; Gonzalez, Ataulfo; Bethancourt, Concepcion; Rodriguez-Macias, Gabriela; Alonso, Arancha; Vera, Juan A; Navas, Begoña; Lavilla, Esperanza; Lopez, Juan A; Jimenez, Santiago; Simiele, Adriana; Vidriales, Belen; Gonzalez, Bernardo J; Burgaleta, Carmen; Hernandez Rivas, Jose A; Mascuñano, Raul Cordoba; Bautista, Guiomar; Perez Simon, Jose A; Fuente, Adolfo de la; Rayón, Consolación; Troconiz, Iñaki F; Janda, Alvaro; Bosanquet, Andrew G; Hernandez-Campo, Pilar; Primo, Daniel; Lopez, Rocio; Liebana, Belen; Rojas, Jose L; Gorrochategui, Julian; Sanz, Miguel A; Ballesteros, Joan

2014-08-01

We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models. Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells. The sensitivity of single drugs is assessed for standard efficacy (EMAX) and potency (EC50) variables, ranked as percentiles within the population. The sensitivity of drug-combination treatments is assessed for the synergism achieved in each patient sample. We found a large variability among patient samples in the dose-response curves to a single drug or combination treatment. We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

A Comparison of Marginal Gaps of All-Ceramic Crowns Constructed from Scanned Impressions and Models.

PubMed

Tabesh, Raena; Dudley, James

This study compared the marginal gaps of computer-aided design/computer-aided manufacture (CAD/CAM)-fabricated all-ceramic crowns constructed from scanned impressions and models and with two different occlusal reduction designs. Two typodont mandibular first molars were prepared to receive CAD/CAM-fabricated all-ceramic crowns. Both molars were prepared to ideal crown reduction, the first with anatomical occlusal reduction (AOR) and the second with completely flat occlusal reduction (FOR). Nine polyvinyl siloxane impressions (PVS) were taken, and nine stone replicas fabricated for each preparation. All impressions and stone models were scanned using a laser scanner (Planmeca Planscan, E4D technologies), and 36 lithium disilicate (IPS e.max CAD) crowns were milled. The marginal gap was measured in four locations using a light stereomicroscope. Crowns constructed from preparations with both occlusal reduction designs demonstrated similar marginal gaps (FOR = 97.98; AOR = 89.12; P = .739). However, all crowns constructed from scanned impressions presented significantly larger marginal gaps than the crowns fabricated from scanned models (impressions = 109.26; models = 77.84; P = .002). Scanning stone models produced all-ceramic crowns with significantly smaller marginal gaps than scanning impressions, irrespective of the occlusal reduction design.

Fabrication and Piezoelectric Properties of Textured (Bi1/2K1/2)TiO3 Ferroelectric Ceramics

NASA Astrophysics Data System (ADS)

Nagata, Hajime; Saitoh, Masahiro; Hiruma, Yuji; Takenaka, Tadashi

2010-09-01

Textured (Bi1/2K1/2)TiO3 (BKT) ceramics were prepared by a reactive templated grain growth (RTGG) method to improve their piezoelectric properties. Also, a hot-pressing (HP) method was modified on the basis of RTGG method to obtain dense ceramics and promote the grain orientation. The textured BKT ceramics prepared by the RTGG and HP methods exhibited a relatively high orientation factor F of 0.82 and a high density ratio of 95-99%. Scanning electron microscopy (SEM) micrographs of the textured HP-BKT indicated a textured and poreless microstructure. In addition, the resistivity of the textured HP-BKT was 1.73×1013 Ω·cm. The piezoelectric strain constant d33 determined by means of resonance and antiresonance method was 125 pC/N for the direction parallel to the sheet-stacking direction of the RTGG process. From the measurement of field-induced stain, the normalized d33* (=Smax/Emax) at 80 kV/cm were 127 and 238 pm/V on the randomly oriented and textured samples (F=0.82) for the (∥) direction, respectively.

Impact on Bacterial Resistance of Therapeutically Nonequivalent Generics: The Case of Piperacillin-Tazobactam

PubMed Central

Rodriguez, Carlos A.; Agudelo, Maria; Aguilar, Yudy A.; Zuluaga, Andres F.

2016-01-01

Previous studies have demonstrated that pharmaceutical equivalence and pharmacokinetic equivalence of generic antibiotics are necessary but not sufficient conditions to guarantee therapeutic equivalence (better called pharmacodynamic equivalence). In addition, there is scientific evidence suggesting a direct link between pharmacodynamic nonequivalence of generic vancomycin and promotion of resistance in Staphylococcus aureus. To find out if even subtle deviations from the expected pharmacodynamic behavior with respect to the innovator could favor resistance, we studied a generic product of piperacillin-tazobactam characterized by pharmaceutical and pharmacokinetic equivalence but a faulty fit of Hill’s Emax sigmoid model that could be interpreted as pharmacodynamic nonequivalence. We determined the impact in vivo of this generic product on the resistance of a mixed Escherichia coli population composed of ∼99% susceptible cells (ATCC 35218 strain) and a ∼1% isogenic resistant subpopulation that overproduces TEM-1 β-lactamase. After only 24 hours of treatment in the neutropenic murine thigh infection model, the generic amplified the resistant subpopulation up to 20-times compared with the innovator, following an inverted-U dose-response relationship. These findings highlight the critical role of therapeutic nonequivalence of generic antibiotics as a key factor contributing to the global problem of bacterial resistance. PMID:27191163

Influence of Different Ceramic Systems on Marginal Misfit.

PubMed

Vargas, S P; Neves, A C C; Vitti, R; Amaral, M; Henrique, M N; Silva-Concílio, L R

2017-09-01

the aim of this study was to evaluate the marginal misfit at the interface between a ceramic coping and its abutment. Twenty-four specimens were made with solid abutments. The specimens were divided into 3 groups according to the ceramic system (n = 8): Lava (zirconia), IPS e.max Press (lithium disilicate), and IPS Empress Esthetic (leucite). All copings were cemented with resin luting agent (RelyX U200) and the marginal misfit were evaluated at 3 different times: initial, after cementation, and after mechanical cycling using a linear measuring microscope (Measuring Microscope STM-Olympus) at a magnification of 40x. All specimens were subjected to mechanical cycling (1 million cycles) by an universal testing machine (Instron 8800). The results were statistically analyzed using Analysis of Variance and Student's t-test (α = 0.05). all groups showed an increase in the marginal misfit after cementation. The lithium disilicate group demonstrated the lowest interacial gap values at each evaluation (p = 0.001). The zirconia and leucite groups showed similar interfacial gap values (initial, p = 0.244; and post cementation, p = 0.751). the cementation increase the marginal misfit, but the mechanical cycling did not influence the marginal misfit of the ceramics systems evaluated. Copyright© 2017 Dennis Barber Ltd.

Combined Stereophotogrammetry and Laser-Sintered, Computer-Aided Milling Framework for an Implant-Supported Mandibular Prosthesis: A Case History Report.

PubMed

Suarez, Maria J; Paisal, Iria; Rodriguez-Alonso, Veronica; Lopez-Suarez, Carlos

This study compared the marginal gaps of computer-aided design/computer-aided manufacture (CAD/CAM)-fabricated all-ceramic crowns constructed from scanned impressions and models and with two different occlusal reduction designs. Two typodont mandibular first molars were prepared to receive CAD/CAM-fabricated all-ceramic crowns. Both molars were prepared to ideal crown reduction, the first with anatomical occlusal reduction (AOR) and the second with completely flat occlusal reduction (FOR). Nine polyvinyl siloxane impressions (PVS) were taken, and nine stone replicas fabricated for each preparation. All impressions and stone models were scanned using a laser scanner (Planmeca Planscan, E4D technologies), and 36 lithium disilicate (IPS e.max CAD) crowns were milled. The marginal gap was measured in four locations using a light stereomicroscope. Crowns constructed from preparations with both occlusal reduction designs demonstrated similar marginal gaps (FOR = 97.98; AOR = 89.12; P = .739). However, all crowns constructed from scanned impressions presented significantly larger marginal gaps than the crowns fabricated from scanned models (impressions = 109.26; models = 77.84; P = .002). Scanning stone models produced all-ceramic crowns with significantly smaller marginal gaps than scanning impressions, irrespective of the occlusal reduction design.

The Effects of a Maximal Power Training Cycle on the Strength, Maximum Power, Vertical Jump Height and Acceleration of High-Level 400-Meter Hurdlers

PubMed Central

Balsalobre-Fernández, Carlos; Tejero-González, Carlos Mª; del Campo-Vecino, Juan; Alonso-Curiel, Dionisio

2013-01-01

The aim of this study was to determine the effects of a power training cycle on maximum strength, maximum power, vertical jump height and acceleration in seven high-level 400-meter hurdlers subjected to a specific training program twice a week for 10 weeks. Each training session consisted of five sets of eight jump-squats with the load at which each athlete produced his maximum power. The repetition maximum in the half squat position (RM), maximum power in the jump-squat (W), a squat jump (SJ), countermovement jump (CSJ), and a 30-meter sprint from a standing position were measured before and after the training program using an accelerometer, an infra-red platform and photo-cells. The results indicated the following statistically significant improvements: a 7.9% increase in RM (Z=−2.03, p=0.021, δc=0.39), a 2.3% improvement in SJ (Z=−1.69, p=0.045, δc=0.29), a 1.43% decrease in the 30-meter sprint (Z=−1.70, p=0.044, δc=0.12), and, where maximum power was produced, a change in the RM percentage from 56 to 62% (Z=−1.75, p=0.039, δc=0.54). As such, it can be concluded that strength training with a maximum power load is an effective means of increasing strength and acceleration in high-level hurdlers. PMID:23717361

The effects of a maximal power training cycle on the strength, maximum power, vertical jump height and acceleration of high-level 400-meter hurdlers.

PubMed

Balsalobre-Fernández, Carlos; Tejero-González, Carlos M; Del Campo-Vecino, Juan; Alonso-Curiel, Dionisio

2013-03-01

The aim of this study was to determine the effects of a power training cycle on maximum strength, maximum power, vertical jump height and acceleration in seven high-level 400-meter hurdlers subjected to a specific training program twice a week for 10 weeks. Each training session consisted of five sets of eight jump-squats with the load at which each athlete produced his maximum power. The repetition maximum in the half squat position (RM), maximum power in the jump-squat (W), a squat jump (SJ), countermovement jump (CSJ), and a 30-meter sprint from a standing position were measured before and after the training program using an accelerometer, an infra-red platform and photo-cells. The results indicated the following statistically significant improvements: a 7.9% increase in RM (Z=-2.03, p=0.021, δc=0.39), a 2.3% improvement in SJ (Z=-1.69, p=0.045, δc=0.29), a 1.43% decrease in the 30-meter sprint (Z=-1.70, p=0.044, δc=0.12), and, where maximum power was produced, a change in the RM percentage from 56 to 62% (Z=-1.75, p=0.039, δc=0.54). As such, it can be concluded that strength training with a maximum power load is an effective means of increasing strength and acceleration in high-level hurdlers.

A METHOD FOR DETERMINING THE RADIALLY-AVERAGED EFFECTIVE IMPACT AREA FOR AN AIRCRAFT CRASH INTO A STRUCTURE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, William C.

This report presents a methodology for deriving the equations which can be used for calculating the radially-averaged effective impact area for a theoretical aircraft crash into a structure. Conventionally, a maximum effective impact area has been used in calculating the probability of an aircraft crash into a structure. Whereas the maximum effective impact area is specific to a single direction of flight, the radially-averaged effective impact area takes into consideration the real life random nature of the direction of flight with respect to a structure. Since the radially-averaged effective impact area is less than the maximum effective impact area, themore » resulting calculated probability of an aircraft crash into a structure is reduced.« less

The impact of hydrofluoric acid etching followed by unfilled resin on the biaxial strength of a glass-ceramic.

PubMed

Posritong, Sumana; Borges, Alexandre Luiz Souto; Chu, Tien-Min Gabriel; Eckert, George J; Bottino, Marco A; Bottino, Marco C

2013-11-01

To evaluate the null hypotheses that hydrofluoric (HF) acid etching time would neither decrease the biaxial flexural strength of a glass-based veneering ceramic nor enhance it after silane and unfilled resin (UR) applications. Disc-shaped IPS e.max ZirPress specimens were allocated into 12 groups: G1-control (no-etching), G2-30 s, G3-60 s, G4-90 s, G5-120 s, G6-60 s+60 s. Groups (G7-G12) were treated in the same fashion as G1-G6, but followed by silane and UR applications. Surface morphology and roughness (Ra and Rq) of the ceramics were assessed by means of scanning electron microscopy (SEM) and profilometry, respectively. Flexural strength was determined by biaxial testing. Data were analyzed by two-way ANOVA and the Sidak test (α=0.05). Weibull statistics were estimated and finite element analysis (FEA) was carried out to verify the stress concentration end areas of fracture. The interaction (etching time vs. surface treatment) was significant for Ra (p=0.008) and Rq (0.0075). Resin-treated groups presented significantly lower Ra and Rq than non-treated groups, except for the 60s group (p<0.005). SEM revealed that etching affected the ceramic microstructure and that the UR was able to penetrate into the irregularities. A significant effect of etching time (p=0.029) on flexural strength was seen. G7-G12 presented higher strength than G1-G6 (p<0.0001). None of experimental groups failed to show 95% confidence intervals of σ0 and m overlapped. FEA showed lower stress concentration after resin treatment. HF acid etching time did not show a damaging effect on the ceramic flexural strength. Moreover, the flexural strength could be enhanced after UR treatment. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation

PubMed Central

Bolognini, D; Rock, EM; Cluny, NL; Cascio, MG; Limebeer, CL; Duncan, M; Stott, CG; Javid, FA; Parker, LA; Pertwee, RG

2013-01-01

Background and Purpose To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT1A receptor activation in animal models. Experimental Approach We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT1A receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB1 receptor activation by CP55940, using [35S]GTPγS-binding assays. Key Results In shrews, CBDA (0.1 and/or 0.5 mg·kg−1 i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg−1 i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT1A receptor antagonist, WAY100635 (0.1 mg·kg−1 i.p.), and, at 0.01 mg·kg−1 i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg−1 i.p.). In vitro, CBDA (0.1–100 nM) increased the Emax of 8-OH-DPAT. Conclusions and Implications Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available. PMID:23121618

Characterization of kinin receptors modulating neurogenic contractions of the mouse isolated vas deferens.

PubMed Central

Maas, J; Rae, G A; Huidobro-Toro, J P; Calixto, J B

1995-01-01

1. This study analyses the receptors mediating the effects of bradykinin (BK) and analogues on neurogenic twitch contractions of the mouse isolated vas deferens evoked, in the presence of captopril (3 microM), by electrical field stimulation with trains of 4 rectangular 0.5 ms pulses of supramaximal strength, delivered at a frequency of 10 Hz every 20 s. 2. BK (0.1-300 nM) induced a graded potentiation of twitches, with an EC50 (geometric mean and 95% confidence limits) of 4.5 nM (1.7-11.6) and an Emax of 315 +/- 19 mg per 10 mg of wet tissue (n = 6). Similar results were obtained in tissues challenged with Lys-BK, [Hyp3]-BK, Met,Lys-BK and the selective B2 receptor agonist [Tyr(Me)8]-BK (0.1-300 nM). 3. The selective B2 receptor antagonists, Hoe 140 (1-10 nM) and NPC 17731 (3-30 nM), caused graded rightward shifts of the curve to BK-induced twitch potentiation, yielding apparent pA2 values of 9.65 +/- 0.09 and 9.08 +/- 0.13, respectively, and Schild plot slopes not different from 1. Both antagonists (100 nM) failed to modify similar twitch potentiations induced by substance P (3 nM) or endothelin-1 (1 nM). Preincubation with the selective B1 receptor antagonist, [Leu8,des-Arg9]-BK (1 microM), increased the potentiating effect of BK on twitches at 30-300 nM. 4. In contrast to BK, the selective B1 receptor agonist, [des-Arg9]-BK (0.3-1000 nM) reduced the amplitude of twitches in a graded fashion, with an IC50 of 13.7 nM (10.4-16.1) and an Imax of 175 +/- 11 mg (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7606350

Large conductance Ca(2+)-activated K(+) channel (BKCa) activating properties of a series of novel N-arylbenzamides: Channel subunit dependent effects.

PubMed

Kirby, R W; Martelli, A; Calderone, V; McKay, N G; Lawson, K

2013-07-15

Large conductance calcium activated potassium channels (BKCa) are fundamental in the control of cellular excitability. Thus, compounds that activate BKCa channels could provide potential therapies in the treatment of pathologies of the cardiovascular and central nervous system. A series of novel N-arylbenzamide compounds, and the reference compound NS1619, were evaluated for BKCa channel opener properties in Human Embryonic Kidney (HEK293) cells expressing the human BKCa channel α-subunit alone or α+β1-subunit complex. Channel activity was determined using a non-radioactive Rb(+) efflux assay to construct concentration effect curves for each compound. All N-arylbenzamide compounds and NS1619 evoked significant (p <0.05) concentration related increases in Rb(+) efflux both in cells expressing α-subunit alone or α+β1-subunits. Co-expression of the β1-subunit modified the Rb(+) efflux responses, relative to that obtained in cells expressing the α-subunit alone, for most of the N-arylbenzamide compounds, in contrast to NS1619. The EC40 values of NS1619, BKMe1 and BKOEt1 were not significantly affected by the co-expression of the BKCa channel α+β1-subunits. In contrast, 5 other N-arylbenzamides (BKPr2, BKPr3, BKPr4, BKH1 and BKVV) showed a significant (p <0.05) 2- to 10-fold increase in EC40 values when tested on the BKCa α+β1-subunit expressing cells compared to BKCa α-subunit expressing cells. Further, the Emax values for BKPr4, BKVV and BKH1 were lower in the BKCa channel α+β1-subunit expressing cells. In conclusion, the N-arylbenzamides studied, like NS1619, were able to activate BKCa channels formed of the α-subunit only. The co-expression of the β1-subunit, however, modified the ability of certain compounds to active the channel leading to differentiated pharmacodynamic profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Effect of ceramic thickness and resin cement shades on final color of heat-pressed ceramic veneers].

PubMed

Ren, D F; Zhan, K R; Chen, X D; Xing, W Z

2017-02-09

Objective: To analyze the effect of ceramic materials thickness and resin cement shades on the final color of ceramic veneers in the discolored teeth, and to investigate the color agreement of try-in pastes to the corresponding resin cements. Methods: Sixty artificial maxillary central incisor teeth (C2 shade) were used to simulate the natural discolored teeth and prepared according to veneer tooth preparation protocol. Veneers of different thickness in the body region (0.50 and 0.75 mm) were fabricated using ceramic materials (LT A2 shade, IPS e.max Press). The ceramic veneer specimens were bonded to the artificial teeth using the 6 shades of resin cements (Variolink Veneer: shades of LV-3, LV-2, HV+3; RelyX™ Veneer: shades of TR, A3, WO) ( n= 5). A clinical spectrophotometer was used to measure the color parameters of ceramic veneers at the cervical, body and incisal regions. Color changes of veneers before and after cementation were calculated and registered as ΔE1, and the changes between try-in paste and the corresponding resin cements were registered as ΔE2. Results: Three-way ANOVA indicated that ΔE1 and ΔE2 values were significantly affected by the ceramic thickness, resin cement shades and measuring regions ( P< 0.05). The ΔE1 values of six shades ranged from 0.59-8.27. The ΔE1 values were more than 2.72 when the ceramic veneers were cemented with resin cements in shades of HV+3 and WO. The ΔE2 values of six shades ranged from 0.60-2.56. The shades of HV+3, WO and A3 resin cements were more than 1.60. Conclusions: Different thickness of ceramic materials, resin cement shades and measuring regions could affect the final color of ceramic veneers. The color differences of some resin cements and corresponding try-in pastes might be observed in clinical practice.

20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

PubMed

Cooper, Philip R; Mesaros, A Clementina; Zhang, Jie; Christmas, Peter; Stark, Christopher M; Douaidy, Karim; Mittelman, Michael A; Soberman, Roy J; Blair, Ian A; Panettieri, Reynold A

2010-04-20

Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 microm thickness) containing an intrapulmonary airway ( approximately 0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.

Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

PubMed

Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

2007-11-26

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

Effect of Acidic Agents on Surface Roughness of Dental Ceramics

PubMed Central

Kukiattrakoon, Boonlert; Hengtrakool, Chanothai; Kedjarune-Leggat, Ureporn

2011-01-01

Background: An increase in surface roughness of ceramics may decrease strength and affect the clinical success of ceramic restorations. However, little is known about the effect of acidic agents on ceramic restorations. The aim of this study was to evaluate the surface roughness of dental ceramics after being immersed in acidic agents. Methods: Eighty-three ceramic disk specimens (12.0 mm in diameter and 2.0 mm in thickness) were made from four types of ceramics (VMK 95, Vitadur Alpha, IPS Empress Esthetic, and IPS e.max Ceram). Baseline data of surface roughness were recorded by profilometer. The specimens were then immersed in acidic agents (citrate buffer solution, pineapple juice and green mango juice) and deionized water (control) at 37°C for 168 hours. One group was immersed in 4% acetic acid at 80°C for 168 hours. After immersion, surface roughness was evaluated by a profilometer at intervals of 24, 96, and 168 hours. Surface characteristics of specimens were studied using scanning electron microscopy (SEM). Data were analyzed using two-way repeated ANOVA and Tukey's multiple comparisons (α = 0.05). Results: For all studied ceramics, all surface roughness parameters were significantly increased after 168 hours immersion in all acidic agents (P < 0.05). After 168 hours in 4% acetic acid, there were significant differences for all roughness parameters from other acidic agents of all evaluated ceramics. Among all studied ceramics, Vitadur Alpha showed significantly the greatest values of all surface roughness parameters after immersion in 4% acetic acid (P < 0.001). SEM photomicrographs also presented surface destruction of ceramics in varying degrees. Conclusion: Acidic agents used in this study negatively affected the surface of ceramic materials. This should be considered when restoring the eroded tooth with ceramic restorations in patients who have a high risk of erosive conditions. PMID:22132009

μ-Opioid receptor activation inhibits N- and P-type Ca2+ channel currents in magnocellular neurones of the rat supraoptic nucleus

PubMed Central

Soldo, Brandi L; Moises, Hylan C

1998-01-01

The whole-cell voltage-clamp technique was used to examine opioid regulation of Ba2+ currents (IBa) through voltage-sensitive Ca2+ channels in isolated magnocellular supraoptic neurones (MNCs). The effects of local application of μ-, δ- or κ-opioid receptor selective agonists were examined on specific components of high voltage-activated (HVA) IBa, pharmacologically isolated by use of Ca2+ channel-subtype selective antagonists. The μ-opioid receptor selective agonist, DAMGO, suppressed HVA IBa (in 64/71 neurones) in a naloxone-reversible and concentration-dependent manner (EC50 = 170 nm, Emax = 19.5 %). The DAMGO-induced inhibition was rapid in onset, associated with kinetic slowing and voltage dependent, being reversed by strong depolarizing prepulses. Low-voltage activated (LVA) IBa was not modulated by DAMGO. Administration of κ- (U69 593) or δ-selective (DPDPE) opioid receptor agonists did not affect IBa. However, immunostaining of permeabilized MNCs with an antibody specific for κ1-opioid receptors revealed the presence of this opioid receptor subtype in a large number of isolated somata. μ-Opioid-induced inhibition in IBa was largely abolished after blockade of N-type and P-type channel currents by ω-conotoxin GVIA (1 μm) and ω-agatoxin IVA (100 nm), respectively. Quantitation of antagonist effects on DAMGO-induced reductions in IBa revealed that N- and P-type channels contributed roughly equally to the μ-opioid sensitive portion of total IBa. These results indicate that μ-opioid receptors are negatively coupled to N- and P-type Ca2+ channels in the somatodendritic regions of MNCs, possibly via a membrane-delimited G-protein-dependent pathway. They also support a scheme in which opioids may act in part to modulate cellular activity and regulate neurosecretory function by their direct action on the neuroendocrine neurones of the hypothalamic supraoptic neucleus. PMID:9824718

Reactive oxygen species potentiate the negative inotropic effect of cardiac M2-muscarinic receptor stimulation.

PubMed

Peters, S L; Sand, C; Batinik, H D; Pfaffendorf, M; van Zwieten, P A

2001-08-01

The aim of the present study was to investigate the influence of reactive oxygen species (ROS) on the contractile responses of rat isolated left atria to muscarinic receptor stimulation. ROS were generated by means of electrolysis (30 mA, 75 s) of the organ bath fluid. Twenty minutes after the electrolysis period, the electrically paced atria (3 Hz) were stimulated with the adenylyl cyclase activator forskolin (1 microM). Subsequently, cumulative acetylcholine concentration-response curves were constructed (0.01 nM-10 microM). In addition, phosphoinositide turnover and adenylyl cyclase activity under basal and stimulated conditions were measured. For these biochemical experiments we used the stable acetylcholine analogue carbachol. The atria exposed to reactive oxygen species were influenced more potently (pD2 control: 6.2 vs. 7.1 for electrolysis-treated atria, P<0.05) and more effectively (Emax control: 40% vs. 90% reduction of the initial amplitude, P<0.05) by acetylcholine. In contrast, ROS exposure did not alter the responses to adenosine, whose receptor is also coupled via a Gi-protein to adenylyl cyclase. The basal (40% vs. control, P<0.05) as well as the carbachol-stimulated (-85% vs. control, P<0.05) inositol-phosphate formation was reduced in atria exposed to ROS. The forskolin-stimulated adenylyl cyclase activity was identical in both groups but carbachol stimulation induced a more pronounced reduction in adenylyl cyclase activity in the electrolysis-treated atria. Accordingly we may conclude that ROS enhance the negative inotropic response of isolated rat atria to acetylcholine by both a reduction of the positive (inositide turnover) and increase of the negative (adenylyl cyclase inhibition) inotropic components of cardiac muscarinic receptor stimulation. This phenomenon is most likely M2-receptor specific, since the negative inotropic response to adenosine is unaltered by ROS exposure.

Mutant prevention concentration, pharmacokinetic-pharmacodynamic integration, and modeling of enrofloxacin data established in diseased buffalo calves.

PubMed

Ramalingam, B; Sidhu, P K; Kaur, G; Venkatachalam, D; Rampal, S

2015-12-01

The pharmacokinetic-pharmacodynamic (PK/PD) modeling of enrofloxacin data using mutant prevention concentration (MPC) of enrofloxacin was conducted in febrile buffalo calves to optimize dosage regimen and to prevent the emergence of antimicrobial resistance. The serum peak concentration (Cmax ), terminal half-life (t1/2 K10) , apparent volume of distribution (Vd(area) /F), and mean residence time (MRT) of enrofloxacin were 1.40 ± 0.27 μg/mL, 7.96 ± 0.86 h, 7.74 ± 1.26 L/kg, and 11.57 ± 1.01 h, respectively, following drug administration at dosage 12 mg/kg by intramuscular route. The minimum inhibitory concentration (MIC), minimum bactericidal concentration, and MPC of enrofloxacin against Pasteurella multocida were 0.055, 0.060, and 1.45 μg/mL, respectively. Modeling of ex vivo growth inhibition data to the sigmoid Emax equation provided AUC24 h /MIC values to produce effects of bacteriostatic (33 h), bactericidal (39 h), and bacterial eradication (41 h). The estimated daily dosage of enrofloxacin in febrile buffalo calves was 3.5 and 8.4 mg/kg against P. multocida/pathogens having MIC90 ≤0.125 and 0.30 μg/mL, respectively, based on the determined AUC24 h /MIC values by modeling PK/PD data. The lipopolysaccharide-induced fever had no direct effect on the antibacterial activity of the enrofloxacin and alterations in PK of the drug, and its metabolite will be beneficial for its use to treat infectious diseases caused by sensitive pathogens in buffalo species. In addition, in vitro MPC data in conjunction with in vivo PK data indicated that clinically it would be easier to eradicate less susceptible strains of P. multocida in diseased calves. © 2015 John Wiley & Sons Ltd.

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

PubMed

Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E; Singh, Pratap

2013-01-01

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Cramer-Rao Bound, MUSIC, and Maximum Likelihood. Effects of Temporal Phase Difference

DTIC Science & Technology

1990-11-01

Technical Report 1373 November 1990 Cramer-Rao Bound, MUSIC , And Maximum Likelihood Effects of Temporal Phase o Difference C. V. TranI OTIC Approved... MUSIC , and Maximum Likelihood (ML) asymptotic variances corresponding to the two-source direction-of-arrival estimation where sources were modeled as...1pI = 1.00, SNR = 20 dB ..................................... 27 2. MUSIC for two equipowered signals impinging on a 5-element ULA (a) IpI = 0.50, SNR

Results from a 64-pixel PIN-diode detector system for low-energy beta-electrons

NASA Astrophysics Data System (ADS)

Wuestling, Sascha; Fraenkle, F.; Habermehl, F.; Renschler, P.; Steidl, M.

2010-12-01

The KATRIN neutrino mass experiment is based on a precise energy measurement (Δ E/ E=5×10 -5) of electrons emerging from tritium beta decay ( Emax=18.6 keV). This is done by a large electrostatic retarding spectrometer (MAC-E Filter), which is followed by an electron detector. Key requirements for this detector are a large sensitive area (˜80 cm 2), a certain energy resolution (Δ E=600 eV @ 18.6 keV) but also a certain spatial resolution (˜3 mm), which leads to a multi-pixel design. As a tentative design on the way to the final detector, but also for operational service on the so-called pre-spectrometer experiment, a detector system with a reduced size (16 cm 2) and a reduced pixel number (64), making use of a monolithic segmented silicon PIN diode, was designed and built. While the design and very first measurements have been presented in Wuestling et al. [6], this publication shows the operational performance of the detector system. The robust concept of the electronics allowed adaptation to mechanically different experimental setups. The spacial resolution of the detector system proved to be essential in examining Penning trap induced background and other effects in the pre-spectrometer experiment. The detector performance test runs include energy resolution and calibration, background rates, correlation between pixels (crosstalk), spatially resolved rate analysis, and a dead-layer measurement [7]. The detector allows for background searches with a sensitivity as low as 1.3×10 -3 cps/cm 2 in the energy range of 20 keV. This allows the pre-spectrometer to be characterized with e-gun illumination with a signal to background ratio of better than 10 5 and the search for ultra low Penning discharge emissions.

In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1.

PubMed

Simmler, Linda D; Buchy, Danièle; Chaboz, Sylvie; Hoener, Marius C; Liechti, Matthias E

2016-04-01

Trace amine-associated receptor 1 (TAAR1) has been implicated in the behavioral effects of amphetamine-type stimulant drugs in rodents. TAAR1 has also been suggested as a target for novel medications to treat psychostimulant addiction. We previously reported that binding affinities at TAAR1 can differ between structural analogs of psychostimulants, and species differences have been observed. In this study, we complement our previous findings with additional substances and the determination of functional activation potencies. In summary, we present here pharmacological in vitro profiles of 101 psychoactive substances at human, rat, and mouse TAAR1. p-Tyramine, β-phenylethylamine, and tryptamine were included as endogenous comparator compounds. Functional cAMP measurements and radioligand displacement assays were conducted with human embryonic kidney 293 cells that expressed human, rat, or mouse TAAR1. Most amphetamines, phenethylamine, and aminoindanes exhibited potentially physiologically relevant rat and mouse TAAR1 activation (EC50 < 5 µM) and showed full or partial (Emax < 80%) agonist properties. Cathinone derivatives, including mephedrone and methylenedioxypyrovalerone, exhibited weak (EC50 = 5-10 µM) to negligible (EC50 > 10 µM) binding properties at TAAR1. Pipradrols, including methylphenidate, exhibited no affinity for TAAR1. We found considerable species differences in activity at TAAR1 among the highly active ligands, with a rank order of rat > mouse > human. This characterization provides information about the pharmacological profile of psychoactive substances. The species differences emphasize the relevance of clinical studies to translationally complement rodent studies on the role of TAAR1 activity for psychoactive substances. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users

PubMed Central

Harris, Stephen C; Perrino, Peter J; Smith, Ira; Shram, Megan J; Colucci, Salvatore V; Bartlett, Cynthia; Sellers, Edward M

2014-01-01

The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1–2 hours) versus OC and Oxy API (0.5–1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion. PMID:24243216

Marginal fit of all-ceramic crowns fabricated using two extraoral CAD/CAM systems in comparison with the conventional technique.

PubMed

Alqahtani, Fawaz

2017-01-01

The purpose of this study was to determine the effect of two extraoral computer-aided design (CAD) and computer-aided manufacturing (CAM) systems, in comparison with conventional techniques, on the marginal fit of monolithic CAD/CAM lithium disilicate ceramic crowns. This is an in vitro interventional study. The study was carried out at the Department of Prosthodontics, School of Dentistry, Prince Sattam Bin Abdul-Aziz University, Saudi Arabia, from December 2015 to April 2016. A marginal gap of 60 lithium disilicate crowns was evaluated by scanning electron microscopy. In total, 20 pressable lithium disilicate (IPS e.max Press [Ivoclar Vivadent]) ceramic crowns were fabricated using the conventional lost-wax technique as a control group. The experimental all-ceramic crowns were produced based on a scan stone model and milled using two extraoral CAD/CAM systems: the Cerec group was fabricated using the Cerec CAD/CAM system, and the Trios group was fabricated using Trios CAD and milled using Wieland Zenotec CAM. One-way analysis of variance (ANOVA) and the Scheffe post hoc test were used for statistical comparison of the groups (α=0.05). The mean (±standard deviation) of the marginal gap of each group was as follows: the Control group was 91.15 (±15.35) µm, the Cerec group was 111.07 (±6.33) µm, and the Trios group was 60.17 (±11.09) µm. One-way ANOVA and the Scheffe post hoc test showed a statistically significant difference in the marginal gap between all groups. It can be concluded from the current study that all-ceramic crowns, fabricated using the CAD/CAM system, show a marginal accuracy that is acceptable in clinical environments. The Trios CAD group displayed the smallest marginal gap.

Self-etching ceramic primer versus hydrofluoric acid etching: Etching efficacy and bonding performance.

PubMed

El-Damanhoury, Hatem M; Gaintantzopoulou, Maria D

2018-01-01

This study assessed the effect of pretreatment of hybrid and glass ceramics using a self-etching primer on the shear bond strength (SBS) and surface topography, in comparison to pretreatment with hydrofluoric acid and silane. 40 rectangular discs from each ceramic material (IPS e.max CAD;EM, Vita Mark II;VM, Vita Enamic;VE), were equally divided (n=10) and assigned to one of four surface pretreatment methods; etching with 4.8% hydrofluoric acid followed by Monobond plus (HFMP), Monobond etch & prime (Ivoclar Vivadent) (MEP), No treatment (NT) as negative control and Monobond plus (Ivoclar Vivadent) with no etching (MP) as positive control. SBS of resin cement (Multilink-N, Ivoclar Vivadent) to ceramic surfaces was tested following a standard protocol. Surface roughness was evaluated using an Atomic force microscope (AFM). Surface topography and elemental analysis were analyzed using SEM/EDX. Data were analyzed with two-way analysis of variance (ANOVA) and post-hoc Bonferroni test at a significance level of α=0.05. Pretreatment with HFMP resulted in higher SBS and increased surface roughness in comparison to MEP and MP. Regardless the method of surface pretreatment, the mean SBS values of EM ceramic was significantly higher (p<0.05) than those recorded for VM and VE, except when VE was treated with MEP, where the difference was statistically insignificant. Traces of fluoride ion were detected when MEP was used with VE and VM. Under limited conditions, using MEP resulted in comparable SBS results to HFMP; meanwhile HFMP remains the gold standard for pretreatment of glass ceramics for resin-luting cementation. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin

PubMed Central

Broad, John; Sanger, Gareth J

2013-01-01

Background and Purpose The antibiotic azithromycin is a suggested alternative to erythromycin for treating patients with delayed gastric emptying. However, although hypothesized to activate motilin receptors, supportive evidence is unavailable. This was investigated using recombinant and naturally expressed motilin receptors in human stomach, comparing azithromycin with erythromycin. Experimental Approach [125I]-motilin binding and calcium flux experiments were conducted using human recombinant motilin receptors in CHO cells. Neuromuscular activities were studied using circular muscle of human gastric antrum, after electrical field stimulation (EFS) of intrinsic nerves. Key Results Azithromycin (1–100 μM) and erythromycin (3–30 μM) concentration-dependently displaced [125I]-motilin binding to the motilin receptor (52 ± 7 and 58 ± 18% displacement at 100 and 30 μM respectively). Azithromycin, erythromycin and motilin concentration-dependently caused short-lived increases in intracellular [Ca2+] in cells expressing the motilin receptor. EC50 values were, respectively, 2.9, 0.92 and 0.036 μM (n = 3 each); and maximal activities were similar. In human stomach, EFS evoked cholinergically mediated contractions, attenuated by simultaneous nitrergic activation. Azithromycin and erythromycin lactobionate (30–300 μM each) facilitated these contractions (apparent Emax values of 2007 ± 396 and 1924 ± 1375%, n = 3–4 each concentration, respectively). These actions were slow in onset and faded slowly. The higher concentrations also evoked short-lived muscle contraction. Contractions to a submaximally effective concentration of carbachol were unaffected by either drug. Conclusions and Implications Azithromcyin activates human recombinant motilin receptors in therapeutically relevant concentrations, similar to erythromycin. In humans, gastric antrum azithromycin caused long-lasting facilitation of cholinergic activity. These actions explain the gastric prokinetic activity of azithromycin. PMID:23190027

Influence of abutment material and luting cements color on the final color of all ceramics.

PubMed

Dede, Dogu Ömür; Armaganci, Arzu; Ceylan, Gözlem; Cankaya, Soner; Celik, Ersan

2013-11-01

The purpose of this study is to evaluate the effects of different abutment materials and luting cements color on the final color of implant-supported all-ceramic restorations. Ten A2 shade IPS e.max Press disc shape all-ceramic specimens were prepared (11 × 1.5 mm). Three different shades (translucent, universal and white opaque) of disc shape luting cement specimens were prepared (11 × 0.2 mm). Three different (zirconium, gold-palladium and titanium) implant abutments and one composite resin disc shape background specimen were prepared at 11 mm diameter and appropriate thicknesses. All ceramic specimens colors were measured with each background and luting cement samples on a teflon mold. A digital spectrophotometer used for measurements and data recorded as CIE L*a*b* color co-ordinates. An optical fluid applied on to the samples to provide a good optical connection and measurements on the composite resin background was saved as the control group. ΔE values were calculated from the ΔL, Δa and Δb values between control and test groups and data were analyzed with one-way variance analysis (ANOVA) and mean values were compared by the Tukey HSD test (α = 0.05). One-way ANOVA of ΔL, Δa, Δb and ΔE values of control and test groups revealed significant differences for backgrounds and seldom for cement color groups (p the 0.05). Only zirconium implant abutment groups and gold palladium abutment with universal shade cement group were found to be clinically acceptable (ΔE ≤ 3.0). Using titanium or gold-palladium abutments for implant supported all ceramics will be esthetically questionable and white opaque cement will be helpful to mask the dark color of titanium abutment.

Effect of opicapone multiple‐dose regimens on levodopa pharmacokinetics

PubMed Central

Rocha, José‐Francisco; Sicard, Éric; Fauchoux, Nicolas; Falcão, Amílcar; Santos, Ana; Loureiro, Ana I.; Pinto, Roberto; Bonifácio, Maria João; Nunes, Teresa; Almeida, Luís

2016-01-01

Aims To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. Methods Two randomized, double blind, sex‐balanced, placebo‐controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once‐daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LB was administered. Results All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose‐dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax) and extent (AUEC) of the catechol‐O‐methyltransferase activity in relation to placebo. The tolerability profile was favourable. Conclusion Opicapone, as once‐daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long‐lasting and sustained catechol‐O‐methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo. PMID:27763682

Functional assessment of recombinant human alpha(2)-adrenoceptor subtypes with cytosensor microphysiometry.

PubMed

Pihlavisto, M; Scheinin, M

1999-12-03

We applied the Cytosensor Microphysiometry system to study the three human alpha(2)-adrenoceptor subtypes, alpha(2A), alpha(2B) and alpha(2C), expressed in Chinese hamster ovary (CHO) cells, and assessed its potential in the quantitative monitoring of agonist activity. The natural full agonist, (-)-noradrenaline, was used to define agonist efficacy. The imidazole derivative dexmedetomidine was a potent full agonist of all three receptor subtypes. The imidazolines clonidine and UK 14,304 (5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) appeared to be partial agonists at alpha(2B)-adrenoceptors (E(max) approximately 60% of (-)-noradrenaline) but full agonists at alpha(2A)- and alpha(2C)-adrenoceptors. The responses mediated by all three alpha(2)-adrenoceptor subtypes were partly inhibited by the sodium-hydrogen (Na(+)/H(+)) exchange inhibitor, MIA (5-(N-methyl-N-isobutyl)-amiloride). The agonist responses were totally abolished by pretreatment with pertussis toxin in cells with alpha(2A)- and alpha(2C)-adrenoceptors, and partly abolished in cells with alpha(2B)-adrenoceptors. The residual signal in alpha(2B)-cells was sensitive to the intracellular Ca(2+)chelator, BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester). Cholera toxin (which acts on G(s)-proteins) had no effect on the agonist responses. The results suggest that the extracellular acidification responses mediated by all three human alpha(2)-adrenoceptor subtypes are dependent on Na(+)/H(+)exchange and G(i/o) pathways, and that alpha(2B)-adrenoceptors are capable of coupling to another, G(i/o)-independent and Ca(2+)-dependent signaling pathway.

Elucidation of the pharmacokinetic/pharmacodynamic determinants of fosfomycin activity against Pseudomonas aeruginosa using a dynamic in vitro model.

PubMed

Bilal, Hajira; Peleg, Anton Y; McIntosh, Michelle P; Styles, Ian K; Hirsch, Elizabeth B; Landersdorfer, Cornelia B; Bergen, Phillip J

2018-06-01

To identify the fosfomycin pharmacokinetic (PK)/pharmacodynamic (PD) index (fT>MIC, fAUC/MIC or fCmax/MIC) most closely correlated with activity against Pseudomonas aeruginosa and determine the PK/PD target associated with various extents of bacterial killing and the prevention of emergence of resistance. Dose fractionation was conducted over 24 h in a dynamic one-compartment in vitro PK/PD model utilizing P. aeruginosa ATCC 27853 and two MDR clinical isolates (CR 1005 and CW 7). In total, 35 different dosing regimens were examined across the three strains. Microbiological response was examined by log changes and population analysis profiles. A Hill-type Emax model was fitted to the killing effect data (expressed as the log10 ratio of the area under the cfu/mL curve for treated regimens versus controls). Bacterial killing of no more than ∼3 log10 cfu/mL was achieved irrespective of regimen. The fAUC/MIC was the PK/PD index most closely correlated with efficacy (R2 = 0.80). The fAUC/MIC targets required to achieve 1 and 2 log10 reductions in the area under the cfu/mL curve relative to growth control were 489 and 1024, respectively. No regimen was able to suppress the emergence of resistance, and near-complete replacement of susceptible with resistant subpopulations occurred with virtually all regimens. Bacterial killing for fosfomycin against P. aeruginosa was most closely associated with the fAUC/MIC. Suppression of fosfomycin-resistant subpopulations could not be achieved even with fosfomycin exposures well above those that can be safely achieved clinically.

Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100.

PubMed

Yu, Rosie Z; Lemonidis, Kristina M; Graham, Mark J; Matson, John E; Crooke, Rosanne M; Tribble, Diane L; Wedel, Mark K; Levin, Arthur A; Geary, Richard S

2009-03-01

The in vivo pharmacokinetics/pharmacodynamics of 2'-O-(2-methoxyethyl) (2'-MOE) modified antisense oligonucleotides (ASOs), targeting apolipoprotein B-100 (apoB-100), were characterized in multiple species. The species-specific apoB antisense inhibitors demonstrated target apoB mRNA reduction in a drug concentration and time-dependent fashion in mice, monkeys, and humans. Consistent with the concentration-dependent decreases in liver apoB mRNA, reductions in serum apoB, and LDL-C, and total cholesterol were concurrently observed in animal models and humans. Additionally, the long duration of effect after cessation of dosing correlated well with the elimination half-life of 2'-MOE modified apoB ASOs studied in mice (t(1/2) congruent with 20 days) and humans (t(1/2) congruent with 30 days) following parental administrations. The plasma concentrations of ISIS 301012, observed in the terminal elimination phase of both mice and monkeys were in equilibrium with liver. The partition ratios between liver and plasma were similar, approximately 6000:1, across species, and thus provide a surrogate for tissue exposure in humans. Using an inhibitory E(max) model, the ASO liver EC(50s) were 101+/-32, 119+/-15, and 300+/-191 microg/g of ASO in high-fat-fed (HF) mice, transgenic mice containing the human apoB transgene, and monkeys, respectively. The estimated liver EC(50) in man, extrapolated from trough plasma exposure, was 81+/-122 microg/g. Therefore, extraordinary consistency of the exposure-response relationship for the apoB antisense inhibitor was observed across species, including human. The cross-species PK/PD relationships provide confidence in the use of pharmacology animal models to predict human dosing for second-generation ASOs targeting the liver.

Effect of processing on nutrients and fatty acid composition of garden cress (Lepidium sativum) seeds.

PubMed

Jain, Tanu; Grover, Kiran; Kaur, Gurpreet

2016-12-15

Garden cress seeds were undergone for different processing methods and analyzed for its nutritional composition. Effect of processing on nutrient retention was evaluated to attain the best processed form of seeds with maximum amount of nutrients. Soaking improved protein and ash by 2.10 and 2.48 percent respectively. Boiling improved fat and fibre by 1.66 and 8.32 percent respectively. Maximum retention of iron and zinc was found with roasting. It also improved calcium by 3.18 percent. Percent ionizable iron and bioavailability was found maximum with boiling (13.59 and 6.88% respectively). In vitro starch and protein digestibility were found maximum on boiling (57.98 and 32.39% respectively) with a decrease of 9.65 and 14.13 percent in phytin phosphorus and oxalate respectively. Amino acids and fatty acids were decreased with heat treatment and maximum retention was found with soaking. Overall improvement in nutrient composition and maximum nutrient retention was found with boiling method. Copyright © 2016 Elsevier Ltd. All rights reserved.

Laboratory Study of Topographic Effects on the Near-surface Tornado Flow Field

NASA Astrophysics Data System (ADS)

Razavi, Alireza; Sarkar, Partha P.

2018-03-01

To study topographic effects on the near-surface tornado flow field, the Iowa State University tornado simulator was used to simulate a translating tornado passing over three different two-dimensional topographies: a ridge, an escarpment and a valley. The effect of the translation speed on maximum horizontal wind speeds is observed for translation speeds of 0.15 and 0.50 m s^{-1} , with the lower value resulting in a larger maximum horizontal wind speed. The tornado translation over the three topographies with respect to flat terrain is assessed for changes in: (a) the maximum horizontal wind speeds in terms of the flow-amplification factor; (b) the maximum aerodynamic drag in terms of the tornado speed-up ratio; (c) the maximum duration of exposure at any location to high wind speeds of a specific range in terms of the exposure amplification factor. Results show that both the maximum wind amplification factor of 14%, as well as the maximum speed-up ratio of 14%, occur on the ridge. For all topographies, the increase in aerodynamic drag is observed to be maximized for low-rise buildings, which illustrates the importance of the vertical profiles of the horizontal wind speed near the ground. The maximum exposure amplification factors, estimated for the range of wind speeds corresponding to the EF2 (50-60 m s^{-1} ) and EF3 (61-75 m s^{-1}) scales, are 86 and 110% for the ridge, 4 and 60% for the escarpment and - 6 and 47% for the valley, respectively.

47 CFR 73.525 - TV Channel 6 protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (4) The maximum permissible effective radiated power (ERP) and antenna height may be adjusted for..., the maximum permissible vertically polarized ERP will be the maximum horizontally polarized ERP... it does not. (ii) If the applicant chooses to use mixed polarity, the permissible ERP is as follows...

78 FR 49370 - Inflation Adjustment of Maximum Forfeiture Penalties

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... ``civil monetary penalties provided by law'' at least once every four years. DATES: Effective September 13... increases the maximum civil monetary forfeiture penalties available to the Commission under its rules... maximum civil penalties established in that section to account for inflation since the last adjustment to...

Assessment of macroseismic intensity in the Nile basin, Egypt

NASA Astrophysics Data System (ADS)

Fergany, Elsayed

2018-01-01

This work intends to assess deterministic seismic hazard and risk analysis in terms of the maximum expected intensity map of the Egyptian Nile basin sector. Seismic source zone model of Egypt was delineated based on updated compatible earthquake catalog in 2015, focal mechanisms, and the common tectonic elements. Four effective seismic source zones were identified along the Nile basin. The observed macroseismic intensity data along the basin was used to develop intensity prediction equation defined in terms of moment magnitude. Expected maximum intensity map was proven based on the developed intensity prediction equation, identified effective seismic source zones, and maximum expected magnitude for each zone along the basin. The earthquake hazard and risk analysis was discussed and analyzed in view of the maximum expected moment magnitude and the maximum expected intensity values for each effective source zone. Moderate expected magnitudes are expected to put high risk at Cairo and Aswan regions. The results of this study could be a recommendation for the planners in charge to mitigate the seismic risk at these strategic zones of Egypt.

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

Developing a diagnostic tool for measuring maximum effective temperature within high pressure electrodeless discharges

NASA Astrophysics Data System (ADS)

Whiting, Michael; Preston, Barry; Mucklejohn, Stuart; Santos, Monica; Lister, Graeme

2016-09-01

Here we present an investigation into the feasibility of creating a diagnostic tool for obtaining maximum arc temperature measurements within a high pressure electrodeless discharge; utilizing integrating sphere measurements of optically thin lines emitted from mercury atoms within commercially available high pressure mercury lamp arc tubes. The optically thin lines chosen were 577 nm and 1014 nm from a 250 W high pressure mercury lamp operated at various powers. The effective temperature could be calculated by considering the relative intensities of the two optically thin lines and comparison with the theoretical ratio of the temperature dependent power emitted from the lines derived from the atomic spectral data provided by NIST. The calculations gave effective arc temperatures of 5755, 5804 and 5820 K at 200, 225, 250 W respectively. This method was subsequently used as a basis for determining maximum effective arc temperature within microwave-driven electrodeless discharge capsules, with varying mercury content of 6.07, 9.4 and 12.95 mg within 1 × 10-6 m3 giving maximum effective temperatures of 5163, 4768 and 4715 K respectively at 240 W.

Effect of etching time and resin bond on the flexural strength of IPS e.max Press glass ceramic.

PubMed

Xiaoping, Luo; Dongfeng, Ren; Silikas, Nick

2014-12-01

To evaluate the effect of hydrofluoric acid (HFA) etching time and resin cement bond on the flexural strength of IPS e.max(®) Press glass ceramic. Two hundred and ten bars, 25mm×3mm×2mm, were made from IPS e.max(®) Press ingots through lost-wax, hot-pressed ceramic fabrication technology and randomly divided into five groups with forty-two per group after polishing. The ceramic surfaces of different groups were etched by 9.5% hydrofluoric acid gel for 0, 20, 40, 60 and 120s respectively. Two specimens of each group were selected randomly to examine the surface roughness and 3-dimensional topography with atomic force microscope (AFM), and microstructure was analyzed by the field emission scanning electron microscope (FE-SEM). Then each group were subdivided into two subgroups (n=20). One subgroup of this material was selected to receive a thin (approximately 0.1mm) layer of resin luting agent (Variolink N) whereas the other subgroup remained unaltered. Half of subgroup's specimens were thermocycled 10,000 times before a 3-point bending test in order to determine the flexural strength. Interface between resin cement and ceramic was examined with field emission scanning electronic microscope. Roughness values increased with increasing etching time. The mean flexural strength values of group 0s, 20s, 40s, 60s and 120s were 384±33, 347±43, 330±53, 327±67 and 317±41MPa respectively. Increasing HF etching times reduced the mean flexural strength (p<0.05). However, the mean flexural strength of each group, except group 0s, increased significantly to 420±31, 435±50, 400±39 and 412±58MPa after the application of dual-curing resin cement. In the present investigation, no significant differences after thermocycling on the flexural strengths were evident. Overtime HF etching could have a wakening effect on IPS e.max(®) Press glass ceramic, but resin cement bonding to appropriately etched surface would strengthen the dental ceramic. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Contributions of stress corrosion and cyclic fatigue to subcritical crack growth in a dental glass-ceramic.

PubMed

Joshi, Gaurav V; Duan, Yuanyuan; Della Bona, Alvaro; Hill, Thomas J; St John, Kenneth; Griggs, Jason A

2014-08-01

The objective of this study was to test the following hypotheses: (1) both cyclic degradation and stress-corrosion mechanisms result in subcritical crack growth (SCG) in a fluorapatite glass-ceramic (IPS e.max ZirPress, Ivoclar-Vivadent) and (2) there is an interactive effect of stress corrosion and cyclic fatigue to accelerate subcritical crack growth. Rectangular beam specimens were fabricated using the lost-wax process. Two groups of specimens (N=30/group) with polished (15μm) or air-abraded surface were tested under rapid monotonic loading. Additional polished specimens were subjected to cyclic loading at two frequencies, 2Hz (N=44) and 10Hz (N=36), and at various stress amplitudes. All tests were performed using a fully articulated four-point flexure fixture in deionized water at 37°C. The SCG parameters were determined using the ratio of inert strength Weibull modulus to lifetime Weibull modulus. A general log-linear model was fit to the fatigue lifetime data including time to failure, frequency, peak stress, and the product of frequency and logarithm of stress in ALTA PRO software. SCG parameters determined were n=21.7 and A=4.99×10(-5) for 2Hz, and n=19.1 and A=7.39×10(-6) for 10Hz. After fitting the general log-linear model to cyclic fatigue data, the coefficients of the frequency term (α1), the stress term (α2), and the interaction term (α3) had estimates and 95% confidence intervals of α1=-3.16 (-15.1, 6.30), α2=-21.2 (-34.9, -9.73), and α3=0.820 (-1.59, 4.02). Only α2 was significantly different from zero. (1) Cyclic fatigue does not have a significant effect on SCG in the fluorapatite glass-ceramic evaluated and (2) there was no interactive effect between cyclic degradation and stress corrosion for this material. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Environmentally relevant pyrethroid mixtures: A study on the correlation of blood and brain concentrations of a mixture of pyrethroid insecticides to motor activity in the rat.

PubMed

Hughes, Michael F; Ross, David G; Starr, James M; Scollon, Edward J; Wolansky, Marcelo J; Crofton, Kevin M; DeVito, Michael J

2016-06-01

Human exposure to multiple pyrethroid insecticides may occur because of their broad use on crops and for residential pest control. To address the potential health risk from co-exposure to pyrethroids, it is important to understand their disposition and toxicity in target organs such as the brain, and surrogates such as the blood when administered as a mixture. The objective of this study was to assess the correlation between blood and brain concentrations of pyrethroids and neurobehavioral effects in the rat following an acute oral administration of the pyrethroids as a mixture. Male Long-Evans rats were administered a mixture of β-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate and cis- and trans-permethrin in corn oil at seven dose levels. The pyrethroid with the highest percentage in the dosing solution was trans-permethrin (31% of total mixture dose) while deltamethrin and esfenvalerate had the lowest percentage (3%). Motor activity of the rats was then monitored for 1h. At 3.5h post-dosing, the animals were euthanized and blood and brain were collected. These tissues were extracted and analyzed for parent pyrethroid using HPLC-tandem mass spectrometry. Cypermethrin and cis-permethrin were the predominate pyrethroids detected in blood and brain, respectively, at all dosage levels. The relationship of total pyrethroid concentration between blood and brain was linear (r=0.93). The pyrethroids with the lowest fraction in blood were trans-permethrin and β-cyfluthrin and in brain were deltamethrin and esfenvalerate. The relationship between motor activity of the treated rats and summed pyrethroid blood and brain concentration was described using a sigmoidal Emax model with the Effective Concentration50 being more sensitive for brain than blood. The data suggests summed pyrethroid rat blood concentration could be used as a surrogate for brain concentration as an aid to study the neurotoxic effects of pyrethroids administered as a mixture under the conditions used in this study. Published by Elsevier Ireland Ltd.

Effects of the type and thickness of ceramic, substrate, and cement on the optical color of a lithium disilicate ceramic.

PubMed

Pires, Laís A; Novais, Pollyanna M R; Araújo, Vinícius D; Pegoraro, Luiz F

2017-01-01

Reproducing the characteristics of natural teeth in ceramic crowns remains a complex and difficult process. The purpose of this in vitro study was to evaluate the effect of the substrate, cement, type, and thickness of the ceramic on the resulting color of a lithium disilicate ceramic. Forty ceramic disks were prepared from IPS e.max Press LT (low translucency) and HO (high opacity) in 2 different thicknesses (1.5 and 2 mm). The LT groups were composed of monolithic ceramic disks, and the HO groups were composed of disks fabricated with a 0.5-mm thickness combined with a 1- or 1.5-mm veneering ceramic thickness. Disks made of composite resin (R) and alloy (A) were used as substrate structures. The resin cement used was Variolink II. Color was measured with a spectrophotometer and expressed in CIELAB coordinates. Color differences (ΔE) were calculated. The data were analyzed with ANOVA and the Tukey HSD test (α=.05). When the ΔE of ceramic disks with both substrates, with and without cement, were compared, the lowest value (3) was obtained for ceramic HO with a 2-mm thickness/alloy substrate/without cement; the highest value (10) was obtained for ceramic LT with a1.5-mm thickness/alloy substrate/with cement. This difference was statistically significant. When the effect of cement on the ΔE of ceramics in both substrates was compared, the lowest value (1.1) occurred with ceramic HO with a 1.5-mm thickness/resin substrate, and the highest was observed for ceramic LT with a 1.5-mm thickness/alloy substrate (6.4). This difference was statistically significant. The substrate color, type and thickness of ceramic, and presence of the cement significantly influenced the resulting optical color. The ΔE values of cemented HO ceramics were lower than that of the LT ceramic. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Neolignans from Aristolochia elegans as antagonists of the neurotropic effect of scorpion venom.

PubMed

Zamilpa, Alejandro; Abarca-Vargas, Rodolfo; Ventura-Zapata, Elsa; Osuna-Torres, Lidia; Zavala, Miguel A; Herrera-Ruiz, Maribel; Jiménez-Ferrer, Enrique; González-Cortazar, Manasés

2014-11-18

The high frequency of poisoning by sting or bite from venomous animals has begun to be a serious public health problem in Mexico where scorpion sting is the most common. Because of this, there is the need to seek active substances in plant species with an antagonistic effect against neurotropic activity of scorpion venom. The aim of this work was to demonstrate which of the compounds contained in the n-hexane extract from Aristolochia elegans roots display activity against scorpion venom. Antagonist activity displayed by extract, fractions and isolated compounds obtained from Aristolochia elegans was guided by the inhibition of smooth muscle contraction induced by scorpion venom (Centruroides limpidus limpidus) in a model of isolated guinea pig ileum. The neolignans obtained from this extract were isolated and analyzed by chromatographic methods including HPLC. The chemical characterization of these compounds was performed by the analysis of (1)H and (13)C NMR spectra. The bio-guided chromatographic fractionation allowed us to isolate 4 known neolignans: Eupomatenoid-7 (1), licarin A (2), licarin B (3), eupomatenoid-1 (4) and other new neolignan which was characterized as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo [b] furan (5). This compound was named as eleganal. Compounds 1 and 2 were purified from the most active fraction AeF3 (EC50 of 149.9μg/mL, Emax of 65.66%). A doses-response analysis of eupomatenoid-7(1) and licarin A(2) allowed us to establish EC50 values (65.96μg/mL and 51.96μg/mL) respectively. The antagonistic effect against Centuroides limpidus limpidus scorpion venom displayed by the n-hexane extract from Aristolochia elegans roots is due to the presence of neolignans 1-2 contained in the fraction AeF3. Chemical analysis of fraction AeF2 allowed the isolation of a new compound which was identified as 2-(3'-hydroxy-4'-methoxyphenyl)-3-methyl-5-[(E)-α-propen-γ-al]-7-methoxy-benzo[b]furan (5), denominated as eleganal. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

On the Importance of Cycle Minimum in Sunspot Cycle Prediction

NASA Technical Reports Server (NTRS)

Wilson, Robert M.; Hathaway, David H.; Reichmann, Edwin J.

1996-01-01

The characteristics of the minima between sunspot cycles are found to provide important information for predicting the amplitude and timing of the following cycle. For example, the time of the occurrence of sunspot minimum sets the length of the previous cycle, which is correlated by the amplitude-period effect to the amplitude of the next cycle, with cycles of shorter (longer) than average length usually being followed by cycles of larger (smaller) than average size (true for 16 of 21 sunspot cycles). Likewise, the size of the minimum at cycle onset is correlated with the size of the cycle's maximum amplitude, with cycles of larger (smaller) than average size minima usually being associated with larger (smaller) than average size maxima (true for 16 of 22 sunspot cycles). Also, it was found that the size of the previous cycle's minimum and maximum relates to the size of the following cycle's minimum and maximum with an even-odd cycle number dependency. The latter effect suggests that cycle 23 will have a minimum and maximum amplitude probably larger than average in size (in particular, minimum smoothed sunspot number Rm = 12.3 +/- 7.5 and maximum smoothed sunspot number RM = 198.8 +/- 36.5, at the 95-percent level of confidence), further suggesting (by the Waldmeier effect) that it will have a faster than average rise to maximum (fast-rising cycles have ascent durations of about 41 +/- 7 months). Thus, if, as expected, onset for cycle 23 will be December 1996 +/- 3 months, based on smoothed sunspot number, then the length of cycle 22 will be about 123 +/- 3 months, inferring that it is a short-period cycle and that cycle 23 maximum amplitude probably will be larger than average in size (from the amplitude-period effect), having an RM of about 133 +/- 39 (based on the usual +/- 30 percent spread that has been seen between observed and predicted values), with maximum amplitude occurrence likely sometime between July 1999 and October 2000.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

PubMed

Borrat, Xavier; Valencia, José Fernando; Magrans, Rudys; Gimenez-Mila, Marc; Mellado, Ricard; Sendino, Oriol; Perez, Maria; Nunez, Matilde; Jospin, Mathieu; Jensen, Erik Weber; Troconiz, Inaki; Gambus, Pedro L

2015-07-01

The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively. We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

PubMed

Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

2011-09-01

The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

40 CFR 35.2205 - Maximum allowable project cost.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

40 CFR 35.2205 - Maximum allowable project cost.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

40 CFR 35.2205 - Maximum allowable project cost.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

40 CFR 35.2205 - Maximum allowable project cost.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

Inhibition of seedling survival under Rhodendron maximum (Ericaceae): could allelopathy be a cause?

Treesearch

Erik T. Nilsen; John F. Walker; Orson K. Miller; Shawn W. Semones; Thomas T. Lei; Barton D. Clinton

1999-01-01

In the Southern Appalachian Mountains a subcanopy species, Rhododendron maximum, inhibits the establishment and survival of canopy tree seedlings. One of the mechanisms by which seedlings could be inhibited is an allelopathic effect of decomposing litter or leachate from the canopy of R. maximum (R.m.) on seed germination, root...

A Global Sensitivity Analysis Method on Maximum Tsunami Wave Heights to Potential Seismic Source Parameters

NASA Astrophysics Data System (ADS)

Ren, Luchuan

2015-04-01

A Global Sensitivity Analysis Method on Maximum Tsunami Wave Heights to Potential Seismic Source Parameters Luchuan Ren, Jianwei Tian, Mingli Hong Institute of Disaster Prevention, Sanhe, Heibei Province, 065201, P.R. China It is obvious that the uncertainties of the maximum tsunami wave heights in offshore area are partly from uncertainties of the potential seismic tsunami source parameters. A global sensitivity analysis method on the maximum tsunami wave heights to the potential seismic source parameters is put forward in this paper. The tsunami wave heights are calculated by COMCOT ( the Cornell Multi-grid Coupled Tsunami Model), on the assumption that an earthquake with magnitude MW8.0 occurred at the northern fault segment along the Manila Trench and triggered a tsunami in the South China Sea. We select the simulated results of maximum tsunami wave heights at specific sites in offshore area to verify the validity of the method proposed in this paper. For ranking importance order of the uncertainties of potential seismic source parameters (the earthquake's magnitude, the focal depth, the strike angle, dip angle and slip angle etc..) in generating uncertainties of the maximum tsunami wave heights, we chose Morris method to analyze the sensitivity of the maximum tsunami wave heights to the aforementioned parameters, and give several qualitative descriptions of nonlinear or linear effects of them on the maximum tsunami wave heights. We quantitatively analyze the sensitivity of the maximum tsunami wave heights to these parameters and the interaction effects among these parameters on the maximum tsunami wave heights by means of the extended FAST method afterward. The results shows that the maximum tsunami wave heights are very sensitive to the earthquake magnitude, followed successively by the epicenter location, the strike angle and dip angle, the interactions effect between the sensitive parameters are very obvious at specific site in offshore area, and there exist differences in importance order in generating uncertainties of the maximum tsunami wave heights for same group parameters at different specific sites in offshore area. These results are helpful to deeply understand the relationship between the tsunami wave heights and the seismic tsunami source parameters. Keywords: Global sensitivity analysis; Tsunami wave height; Potential seismic tsunami source parameter; Morris method; Extended FAST method

Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways

PubMed Central

Keshavarz, Maryam; Schwarz, Heike; Hartmann, Petra; Wiegand, Silke; Skill, Melanie; Althaus, Mike; Kummer, Wolfgang; Krasteva-Christ, Gabriela

2017-01-01

An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin) are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM) involve caveolae. We hypothesized that caveolin-1 (cav-1), a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra- and intrapulmonary bronchi in cav-1 deficient (cav-1−/−) and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD) treated and non-treated precision-cut lung slices (PCLS). The presence of caveolae was investigated by electron microscopy. Receptor subtypes driving 5-HT-responses were studied by RT-PCR and videomorphometry after pharmacological inhibition with ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a dose dependent contraction in all airway segments. A significantly higher Emax was observed in the caudal trachea. Although, caveolae abundancy was largely reduced in cav-1−/− mice, muscarine-induced airway contraction was maintained, albeit at diminished potency in the middle trachea, in the caudal trachea and in the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from cav-1−/− mice reduced cholinergic constriction by about 50%, indicating that cholesterol-rich plasma domains account for a substantial portion of the muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most prevalent subtypes in the airways. The 5-HT-induced-constriction in PCLS could be antagonized by ketanserin, a 5-HT2A receptor inhibitor. In conclusion, the role of cav-1, caveolae, and cholesterol-rich plasma domains in regulation of airway tone are highly agonist-specific and dependent on airway level. Cav-1 is indispensable for serotonergic contraction of extrapulmonary airways and modulates cholinergic constriction of the trachea and main bronchus. Thus, cav-1/caveolae shall be considered in settings such as bronchial hyperreactivity in common airway diseases and might provide an opportunity for modulation of the constrictor response. PMID:28555112

Effect of superficial harrowing on surface properties of sand with rubber and waxed-sand with fibre riding arena surfaces: a preliminary study.

PubMed

Tranquille, C A; Walker, V A; Hernlund, E; Egenvall, A; Roepstorff, L; Peterson, M L; Murray, R C

2015-01-01

A recent epidemiological study identified various aspects of arena surfaces and arena surface maintenance that were related to risk of injury in horses and that arena maintenance is important in reducing injury risk. However, there has been little research into how properties of arena surfaces change with harrowing. This study aimed to compare the properties of different arena surface types pre- and post-harrowing. The Orono Biomechanical Surface Tester fitted with accelerometers and a single- and a three-axis load cell was used to test 11 arenas with two different surfaces types, sand with rubber (SR) and waxed-sand with fibre (WSF). Three drop tests were carried out at 10 standardised locations on each arena. Mixed models were created to assess the effect of surface type, pre- or post-harrowing, and drop number on the properties of the surface, including maximum horizontal deceleration, maximum vertical deceleration, maximum vertical load and maximum horizontal load. Post-harrowing, none of the parameters were altered significantly on SR. On WSF, maximum vertical deceleration and maximum vertical load significantly decreased post-harrowing. The differences in the effects of superficial harrowing on SR and WSF could be attributed to the different compositions and sizes of the surface material. The results suggest that different maintenance techniques may be more suitable for different surface types and that the effects of superficial harrowing are short-lived due to the rapid re-compaction of the surface with repeated drops on WSF. Further work is required to determine the effects of other maintenance techniques, and on other surface types. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis and prediction of operating vehicle load effects on Highway bridges under the weight charge policy

NASA Astrophysics Data System (ADS)

Huang, Haiyun; Zhang, Junping; Li, Yonghe

2018-05-01

Under the weight charge policy, the weigh in motion data at a toll station on the Jing-Zhu Expressway were collected. The statistic analysis of vehicle load data was carried out. For calculating the operating vehicle load effects on bridges, by Monte Carlo method used to generate random traffic flow and influence line loading method, the maximum bending moment effect of simple supported beams were obtained. The extreme value I distribution and normal distribution were used to simulate the distribution of the maximum bending moment effect. By the extrapolation of Rice formula and the extreme value I distribution, the predicted values of the maximum load effects were obtained. By comparing with vehicle load effect according to current specification, some references were provided for the management of the operating vehicles and the revision of the bridge specifications.

Augmentative effect of pulsatility on the wall shear stress in tube flow.

PubMed

Nakata, M; Tatsumi, E; Tsukiya, T; Taenaka, Y; Nishimura, T; Nishinaka, T; Takano, H; Masuzawa, T; Ohba, K

1999-08-01

Wall shear stress (WSS) has been considered to play an important role in the physiological and metabolic functions of the vascular endothelial cells. We investigated the effects of the pulse rate and the maximum flow rate on the WSS to clarify the influence of pulsatility. Water was perfused in a 1/2 inch transparent straight cylinder with a nonpulsatile centrifugal pump and a pulsatile pneumatic ventricular assist device (VAD). In nonpulsatile flow (NF), the flow rate was changed 1 to 6 L/min by 1 L/min increments to obtain standard values of WSS at each flow rate. In pulsatile flow (PF), the pulse rate was controlled at 40, 60, and 80 bpm, and the maximum flow rate was varied from 3.3 to 12.0 L/min while the mean flow rate was kept at 3 L/min. The WSS was estimated from the velocity profile at measuring points using the laser illuminated fluorescence method. In NF, the WSS was 12.0 dyne/cm2 at 3 L/min and 33.0 dyne/cm2 at 6 L/min. In PF, the pulse rate change with the same mean, and the maximum flow rate did not affect WSS. On the other hand, the increase in the maximum flow rate at the constant mean flow rate of 3 L/min augmented the mean WSS from 13.1 to 32.9 dyne/cm2. We concluded that the maximum flow rate exerted a substantial augmentative effect on WSS, and the maximum flow rate was a dominant factor of pulsatility in this effect.

Quasi-Maximum Likelihood Estimation of Structural Equation Models with Multiple Interaction and Quadratic Effects

ERIC Educational Resources Information Center

Klein, Andreas G.; Muthen, Bengt O.

2007-01-01

In this article, a nonlinear structural equation model is introduced and a quasi-maximum likelihood method for simultaneous estimation and testing of multiple nonlinear effects is developed. The focus of the new methodology lies on efficiency, robustness, and computational practicability. Monte-Carlo studies indicate that the method is highly…

47 CFR 22.535 - Effective radiated power limits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... limits. The effective radiated power (ERP) of transmitters operating on the channels listed in § 22.531 must not exceed the limits in this section. (a) Maximum ERP. The ERP must not exceed the applicable limits in this paragraph under any circumstances. Frequency range (MHz) Maximum ERP (Watts) 35-36 600 43...

47 CFR 22.535 - Effective radiated power limits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... limits. The effective radiated power (ERP) of transmitters operating on the channels listed in § 22.531 must not exceed the limits in this section. (a) Maximum ERP. The ERP must not exceed the applicable limits in this paragraph under any circumstances. Frequency range (MHz) Maximum ERP (Watts) 35-36 600 43...

The Effect of Suspension-Line Length on Viking Parachute Inflation Loads

NASA Technical Reports Server (NTRS)

Talay, Theodore A.; Poole, Lamont R.; Whitlock, Charles H.

1971-01-01

Analytical calculations have considered the effect on maximum load of increasing the suspension-line length on the Viking parachute. Results indicate that unfurling time is increased to 1.85 seconds from 1.45 seconds, and that maximum loads are increased approximately 5 percent with an uncertainty of -4 percent to +3 percent.

Effects of Estimation Bias on Multiple-Category Classification with an IRT-Based Adaptive Classification Procedure

ERIC Educational Resources Information Center

Yang, Xiangdong; Poggio, John C.; Glasnapp, Douglas R.

2006-01-01

The effects of five ability estimators, that is, maximum likelihood estimator, weighted likelihood estimator, maximum a posteriori, expected a posteriori, and Owen's sequential estimator, on the performances of the item response theory-based adaptive classification procedure on multiple categories were studied via simulations. The following…

Effects of Smoking on Respiratory Capacity and Control

ERIC Educational Resources Information Center

Awan, Shaheen N.; Alphonso, Vania A.

2007-01-01

The purpose of this study was to provide information concerning the possible early effects of smoking on measures of respiratory capacity and control in young adult female smokers vs. nonsmokers. In particular, maximum performance test results (vital capacity and maximum phonation time) and measures of air pressures and airflows during voiceless,…

New applications of maximum likelihood and Bayesian statistics in macromolecular crystallography.

PubMed

McCoy, Airlie J

2002-10-01

Maximum likelihood methods are well known to macromolecular crystallographers as the methods of choice for isomorphous phasing and structure refinement. Recently, the use of maximum likelihood and Bayesian statistics has extended to the areas of molecular replacement and density modification, placing these methods on a stronger statistical foundation and making them more accurate and effective.

47 CFR 90.545 - TV/DTV interference protection criteria.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contour (41 dBµV/m) (88.5 kilometers or 55.0 miles) of the DTV station. (b) Maximum ERP and HAAT. The maximum effective radiated power (ERP) and the antenna height above average terrain (HAAT) of the proposed... determined using the methods described in this section. (1) Each base station is limited to a maximum ERP of...

Effects of EVA gloves on grip strength and fatigue under low temperature and low pressure.

PubMed

Tian, Yinsheng; Ding, Li; Liu, Heqing; Li, Yan; Li, Deyu; Wang, Li

2016-03-01

To study the effects of wearing extravehicular activity (EVA) gloves on grip strength and fatigue in low temperature, low pressure and mixing of two factors (low temperature and low pressure). The maximum grip strength and fatigue tests were performed with 10 healthy male subjects wearing gloves in a variety of simulated environments. The data was analysed using the normalization method. The results showed that wearing gloves significantly affected the maximum grip strength and fatigue. Pressure (29.6, 39.2 kPa) had more influence on the maximum grip compared with control group while low temperatures (-50, -90, -110 °C) had no influence on grip but affected fatigue dramatically. The results also showed that the maximum grip strength and fatigue were influenced significantly in a compound environment. Space environment remarkably reduced strength and endurance of the astronauts. However, the effects brought by the compound environment cannot be understood as the superimposition of low temperature and pressure effects. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

The Effect of Valve Cooling upon Maximum Permissible Engine Output as Limited by Knock

NASA Technical Reports Server (NTRS)

Munger, Maurice; Wilsted, H D; Mulcahy, B A

1942-01-01

A Wright GR-1820-G200 cylinder was tested over a wide range of fuel-air ratios at maximum permissible power output as limited by knock with three different degrees of valve cooling. The valves used were stock valves (solid inlet valve and hollow sodium-cooled exhaust valve), hollow valves with no coolant, and hollow valves with flowing water as a coolant. Curves showing the variation in maximum permissible values of inlet-air pressure, indicated mean effective pressure, cylinder charge, and indicated specific fuel consumption with change in fuel-air ratio and valve cooling are shown. The use of valves cooled by a stream of water passing through their hollow interiors permitted indicated mean effective pressures 10 percent higher than the mean effective pressures permissible with stock valves when the engine was operated with fuel-air ratios from 0.055 to 0.065. Operation of the engine with lean mixtures with uncooled hollow valves resulted in power output below the output obtained with the stock valves. The data show an increase in maximum permissible indicated mean effective pressure due to cooling the valves, which averages only 2.1 percent with fuel-air ratios from 0.075 to 0.105.

Prediction of effects of wing contour modifications on low-speed maximum lift and transonic performance for the EA-6B aircraft

NASA Technical Reports Server (NTRS)

Allison, Dennis O.; Waggoner, E. G.

1990-01-01

Computational predictions of the effects of wing contour modifications on maximum lift and transonic performance were made and verified against low speed and transonic wind tunnel data. This effort was part of a program to improve the maneuvering capability of the EA-6B electronics countermeasures aircraft, which evolved from the A-6 attack aircraft. The predictions were based on results from three computer codes which all include viscous effects: MCARF, a 2-D subsonic panel code; TAWFIVE, a transonic full potential code; and WBPPW, a transonic small disturbance potential flow code. The modifications were previously designed with the aid of these and other codes. The wing modifications consists of contour changes to the leading edge slats and trailing edge flaps and were designed for increased maximum lift with minimum effect on transonic performance. The prediction of the effects of the modifications are presented, with emphasis on verification through comparisons with wind tunnel data from the National Transonic Facility. Attention is focused on increments in low speed maximum lift and increments in transonic lift, pitching moment, and drag resulting from the contour modifications.

Ion-thruster propellant utilization

NASA Technical Reports Server (NTRS)

Kaufman, H. R.

1971-01-01

The evaluation and understanding of maximum propellant utilization, with mercury used as the propellant are presented. The primary-electron region in the ion chamber of a bombardment thruster is analyzed at maximum utilization. The results of this analysis, as well as experimental data from a range of ion-chamber configurations, show a nearly constant loss rate for unionized propellant at maximum utilization over a wide range of total propellant flow rate. The discharge loss level of 1000 eV/ion was used as a definition of maximum utilization, but the exact level of this definition has no effect on the qualitative results and little effect on the quantitative results. There are obvious design applications for the results of this investigation, but the results are particularly significant whenever efficient throttled operation is required.

Control strategy of grid-connected photovoltaic generation system based on GMPPT method

NASA Astrophysics Data System (ADS)

Wang, Zhongfeng; Zhang, Xuyang; Hu, Bo; Liu, Jun; Li, Ligang; Gu, Yongqiang; Zhou, Bowen

2018-02-01

There are multiple local maximum power points when photovoltaic (PV) array runs under partial shading condition (PSC).However, the traditional maximum power point tracking (MPPT) algorithm might be easily trapped in local maximum power points (MPPs) and cannot find the global maximum power point (GMPP). To solve such problem, a global maximum power point tracking method (GMPPT) is improved, combined with traditional MPPT method and particle swarm optimization (PSO) algorithm. Under different operating conditions of PV cells, different tracking algorithms are used. When the environment changes, the improved PSO algorithm is adopted to realize the global optimal search, and the variable step incremental conductance (INC) method is adopted to achieve MPPT in optimal local location. Based on the simulation model of the PV grid system built in Matlab/Simulink, comparative analysis of the tracking effect of MPPT by the proposed control algorithm and the traditional MPPT method under the uniform solar condition and PSC, validate the correctness, feasibility and effectiveness of the proposed control strategy.

A figure of merit for AMTEC electrodes

NASA Technical Reports Server (NTRS)

Underwood, M. L.; Williams, R. M.; Jeffries-Nakamura, B.; Ryan, M. A.

1991-01-01

As a method to compare the results of alkali metal thermoelectric converter (AMTEC) electrode performance measured under different conditions, an AMTEC figure of merit called ZA is proposed. This figure of merit is the ratio of the experimental maximum power for an electrode to a calculated maximum power density as determined from a recently published electrode performance model. The calculation of a maximum power density assumes that certain loss terms in the electrode can be reduced to essentially zero by improved cell design and construction, and that the electrochemical exchange current is determined from a standard value. Other losses in the electrode are considered inherent to the electrode performance. Thus, these terms remain in the determination of the calculated maximum power. A value of ZA near one, then, indicates an electrode performance near the maximum possible performance. The primary limitation of this calculation is that the small electrode effect cannot be included. This effect leads to anomalously high values of ZA. Thus, the electrode area should be reported along with the figure of merit.

Comparison of temperature change among different adhesive resin cement during polymerization process.

PubMed

Alkurt, Murat; Duymus, Zeynep Yesil; Gundogdu, Mustafa; Karadas, Muhammet

2017-01-01

The aim of this study was to assess the intra-pulpal temperature changes in adhesive resin cements during polymerization. Dentin surface was prepared with extracted human mandibular third molars. Adhesive resin cements (Panavia F 2.0, Panavia SA, and RelyX U200) were applied to the dentin surface and polymerized under IPS e.max Press restoration. K-type thermocouple wire was positioned in the pulpal chamber to measure temperature change ( n = 7). The temperature data were recorded (0.0001 sensible) and stored on a computer every 0.1 second for sixteen minutes. Differences between the baseline temperature and temperatures of various time points (2, 4, 6, 8, 10, 12, 14, and 16 minute) were determined and mean temperature changes were calculated. At various time intervals, the differences in temperature values among the adhesive resin cements were analyzed by two-way ANOVA and post-hoc Tukey honestly test (α = 0.05). Significant differences were found among the time points and resin cements ( P < 0.05). Temperature values of the Pan SA group were significantly higher than Pan F and RelyX ( P < 0.05). Result of the study on self-adhesive and self-etch adhesive resin cements exhibited a safety intra-pulpal temperature change.

Application of TDCR-Geant4 modeling to standardization of 63Ni.

PubMed

Thiam, C; Bobin, C; Chauvenet, B; Bouchard, J

2012-09-01

As an alternative to the classical TDCR model applied to liquid scintillation (LS) counting, a stochastic approach based on the Geant4 toolkit is presented for the simulation of light emission inside the dedicated three-photomultiplier detection system. To this end, the Geant4 modeling includes a comprehensive description of optical properties associated with each material constituting the optical chamber. The objective is to simulate the propagation of optical photons from their creation in the LS cocktail to the production of photoelectrons in the photomultipliers. First validated for the case of radionuclide standardization based on Cerenkov emission, the scintillation process has been added to a TDCR-Geant4 modeling using the Birks expression in order to account for the light-emission nonlinearity owing to ionization quenching. The scintillation yield of the commercial Ultima Gold LS cocktail has been determined from double-coincidence detection efficiencies obtained for (60)Co and (54)Mn with the 4π(LS)β-γ coincidence method. In this paper, the stochastic TDCR modeling is applied for the case of the standardization of (63)Ni (pure β(-)-emitter; E(max)=66.98 keV) and the activity concentration is compared with the result given by the classical model. Copyright © 2012 Elsevier Ltd. All rights reserved.

Compositionally driven giant strain and electrostrictive co-efficient in lead free NBT-BT-BFO system

NASA Astrophysics Data System (ADS)

Duraisamy, Dhayanithi; Venkatesan, Giridharan Nambi

2018-01-01

As lead free alternatives, bismuth based ferroelectric ceramics are currently under intense investigation. Here, the authors report on the development of a lead free (1-2x)Na0.5Bi0.5TiO3-xBaTiO3-xBiFeO3: NBT-BT-BFO [x = 0.01, 0.03, 0.05, 0.07, and 0.09] ceramic. Rietveld analysis of the powder diffraction data reveals the existence of compositionally driven single and two phase combinations. The compositions corresponding to x = 0.01 and 0.03 are found to be crystallized in a monoclinic (Cc) system, whereas the compositions corresponding to x =0.05, 0.07, and 0.09 are found to have the coexistence of [monoclinic (Cc) + Cubic (pm-3m)] and [Tetragonal (P4bm) + Cubic (pm-3m)] phases. A high electric field induced strain has been obtained for x = 0.07, which can be attributed to the polarization extension mechanism at the proximity of the phase boundary between polar and nonpolar phases. Further, the manufactured ceramic is characterized by Smax/Emax of 858 pm/V and an electrostrictive co-efficient (Q33) of 0.045 m4 C-2 much higher than the values of well-established Pb(Zr,Ti)O3 and other lead free ceramics.

Cellular uptake and anticancer activity of carboxylated gallium corroles.

PubMed

Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H; Gray, Harry B; Termini, John; Lim, Punnajit

2016-04-19

We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax= 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 > 3 > 2 > 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging.

Cellular uptake and anticancer activity of carboxylated gallium corroles

PubMed Central

Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H.; Gray, Harry B.; Termini, John; Lim, Punnajit

2016-01-01

We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50 values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50 values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax = 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 >> 3 > 2 >> 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging. PMID:27044076

Fracture Resistance of Ceramic Laminate Veneers Bonded to Teeth with Class V Composite Fillings after Cyclic Loading.

PubMed

Sadighpour, Leyla; Geramipanah, Farideh; Rasaei, Vanya; Kharazi Fard, Mohammad J

2018-01-01

Porcelain laminate veneers (PLVs) are sometimes required to be used for teeth with composite fillings. This study examined the fracture strength of PLVs bonded to the teeth restored with different sizes of class V composite fillings. Thirty-six maxillary central incisors were divided into three groups ( n =12): intact teeth (control) and teeth with class V composite fillings of one-third or two-thirds of the crown height (small or large group, resp.). PLVs were made by using IPS e.max and bonded with a resin cement (RelyX Unicem). Fracture resistance ( N ) was measured after cyclic loading (1 × 10 6 cycles, 1.2 Hz). For statistical analyses, one-way ANOVA and Tukey test were used ( α =0.05). There was a significant difference between the mean failure loads of the test groups ( P =0.004), with the Tukey-HSD test showing lower failure loads in the large-composite group compared to the control ( P =0.02) or small group ( P =0.05). The control and small-composite groups achieved comparable results ( P > 0.05). Failure loads of PLVs bonded to intact teeth and to teeth with small class V composite fillings were not significantly different. However, extensive composite fillings could compromise the bonding of PLVs.

Cracking of porcelain surfaces arising from abrasive grinding with a dental air turbine.

PubMed

Chang, Chee W; Waddell, J Neil; Lyons, Karl M; Swain, Michael V

2011-12-01

The purpose of this in vitro study was to evaluate porcelain cracking induced by abrasive grinding with a conventional dental air turbine and abrasive diamond burs. Four commercially available porcelains were examined-Wieland ALLUX, Wieland ZIROX, IPS e.max Ceram, and IPS Empress Esthetic Veneering porcelain. Sixty discs of each porcelain type were fabricated according to manufacturer instructions, followed by an auto-glaze cycle. Abrasive grinding using fine, extra-fine, and ultra-fine diamond burs was carried out, using a conventional dental air turbine. The grinding parameters were standardized with regard to the magnitude of the force applied, rotational speed of the diamond bur, and flow rate of the water coolant. A testing apparatus was used to control the magnitude of force applied during the grinding procedure. The ground surfaces were then examined under scanning electron microscope. Cracking was seen for all porcelain types when ground with the fine bur. Cracking was not seen for specimens ground with the extra-fine or the ultra-fine bur. Wet abrasive grinding with a conventional dental air turbine and fine grit diamond burs has the potential to cause cracking in the four porcelain types tested. Similar abrasive grinding with smaller grit size particles does not cause similar observable cracking. © 2011 by the American College of Prosthodontists.

Effect of daily environmental temperature on farrowing rate and total born in dam line sows.

PubMed

Bloemhof, S; Mathur, P K; Knol, E F; van der Waaij, E H

2013-06-01

Heat stress is known to adversely affect reproductive performance of sows. However, it is important to know on which days or periods during the reproduction cycle heat stress has the greatest effects for designing appropriate genetic or management strategies. Therefore, this study was conducted to identify days and periods that have greatest effects on farrowing rate and total born of sows using 5 different measures of heat stress. The data consisted of 22,750 records on 5024 Dutch Yorkshire dam line sows from 16 farms in Spain and Portugal. Heat stress on a given day was measured in terms of maximum temperature, diurnal temperature range and heat load. The heat load was estimated using 3 definitions considering different upper critical temperatures. Identification of days during the reproduction cycle that had maximum effect was based on the Pearson correlation between the heat stress variable and the reproduction trait, estimated for each day during the reproduction cycle. Polynomial functions were fitted to describe the trends of these correlations and the days with greatest negative correlation were considered as days with maximum effect. Correlations were greatest for maximum temperature, followed by those for heat load and diurnal temperature range. Correlations for both farrowing rate and total born were stronger in gilts than in sows. This implies that heat stress has a stronger effect on reproductive performance of gilts than of sows. Heat stress during the third week (21 to 14 d) before first insemination had largest effect on farrowing rate. Heat stress during the period between 7 d before successful insemination until 12 d after that had largest effect on total born. Correlations between temperatures on consecutive days during these periods were extremely high ( > 0.9). Therefore, for farrowing rate the maximum temperature on 21 d before first insemination and for total born the maximum temperature at day of successful insemination can be used as predictive measures of heat stress in commercial sow farms. Additionally, differences between daughter groups of sires were identified in response to high temperatures. This might indicate possibilities for genetic selection on heat tolerance.

Duration of sustained phonation in kindergarten children.

PubMed

Harden, J R; Looney, N A

1984-03-01

Maximum sustained phonations of the vowels [a], [u] and [i] were obtained from 160 kindergarten children with a mean age of approximately 6.2 years. Subjects were grouped by sex and by the presence or absence of a voice disorder. Stop watch measurements of each subject's maximum phonations were compared with graphic level recorder measurements of those phonations . The results indicated that (1) the factor of sex had no significant effect on maximum phonation times; (2) the factor of voice group (non-voice-disordered/voice-disordered) did result in a significant effect (P less than 0.01) with the voice-disordered group achieving shorter phonations than the non-voice-disordered group; (3) the phonation times obtained from the two measurement procedures correlate significantly (P less than 0.05). Results also suggest that the vowel effect on maximum phonation time was significant (P less than 0.05) for both groups. The vowel [i] was phonated significantly longer than either [a] or [u] for males and females in both groups.

Performance Analysis and Optimization of Concentrating Solar Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Lamba, Ravita; Manikandan, S.; Kaushik, S. C.

2018-06-01

A thermodynamic model for a concentrating solar thermoelectric generator considering the Thomson effect combined with Fourier heat conduction, Peltier, and Joule heating has been developed and optimized in MATLAB environment. The temperatures at the hot and cold junctions of the thermoelectric generator were evaluated by solving the energy balance equations at both junctions. The effects of the solar concentration ratio, input electrical current, number of thermocouples, and electrical load resistance ratio on the power output and energy and exergy efficiencies of the system were studied. Optimization studies were carried out for the STEG system, and the optimum number of thermocouples, concentration ratio, and resistance ratio determined. The results showed that the optimum values of these parameters are different for conditions of maximum power output and maximum energy and exergy efficiency. The optimum values of the concentration ratio and load resistance ratio for maximum energy efficiency of 5.85% and maximum exergy efficiency of 6.29% were found to be 180 and 1.3, respectively, with corresponding power output of 4.213 W. Furthermore, at higher concentration ratio (C = 600), the optimum number of thermocouples was found to be 101 for maximum power output of 13.75 W, maximum energy efficiency of 5.73%, and maximum exergy efficiency of 6.16%. Moreover, the optimum number of thermocouple was the same for conditions of maximum power output and energy and exergy efficiency. The results of this study may provide insight for design of actual concentrated solar thermoelectric generator systems.

12 CFR 221.108 - Effect of registration of stock subsequent to making of loan.

Code of Federal Regulations, 2010 CFR

2010-01-01

... than the maximum loan value for the collateral specified in this part. (c) If the stock should become... increase the amount of the loan balance unless there was provided additional collateral having a maximum... value of the loan collateral or because of a decrease by the Board in the maximum loan value of the loan...

To study the effect of orbital sling on post operative vision in cases of maxillary carcinoma undergoing total maxillectomy.

PubMed

Shukla, Anirudh; Dudeja, Vivek

2014-06-01

To study effect of orbital sling on post operative vision in cases of maxillary carcinoma undergoing total maxillectomy. All patients with the principal procedure of "total maxillectomy" for histopathologically proven cases of carcinoma maxilla in department of otorhinolaryngology and head-neck surgery, N.S.C.B. medical college, Jabalapur, Madhya Pradesh, India from July 2011 to October 2013 were included. Out of the 20 patients irrespective of whether orbital sling was created or not, maximum number of patients 8 (40 %) showed a 3 step improvement, and maximum improvement seen was up to five steps. Out of the 14 patients in which orbital sling was created maximum number of patients 7 (50 %) showed a 3 step improvement, and maximum improvement seen was up to five steps. Out of the 6 patients in whom orbital sling was not created maximum number of patients 3 (50 %) showed a 2 step improvement, and maximum improvement seen was up to three steps. Infraorbital repair with the help of sling results in better improvement of vision as compared to those in whom sling was not or could not be made with no significant difference on eye movements.

Effects of pH and temperature on growth and glycerol production kinetics of two indigenous wine strains of Saccharomyces cerevisiae from Turkey

PubMed Central

Yalcin, Seda Karasu; Yesim Ozbas, Z.

2008-01-01

The study was performed in a batch system in order to determine the effects of pH and temperature on growth and glycerol production kinetics of two indigenous wine yeast strains Saccharomyces cerevisiae Kalecik 1 and Narince 3. The highest values of dry mass and specific growth rate were obtained at pH 4.00 for both of the strains. Maximum specific glycerol production rates were obtained at pH 5.92 and 6.27 for the strains Kalecik 1 and Narince 3, respectively. Kalecik 1 strain produced maximum 8.8 gL−1 of glycerol at pH 6.46. Maximum glycerol concentration obtained by the strain Narince 3 was 9.1 gL−1 at pH 6.48. Both yeasts reached maximum specific growth rate at 30°C. Optimum temperature range for glycerol production was determined as 25-30°C for the strain Kalecik 1. The strain Narince 3 reached maximum specific glycerol production rate at 30°C. Maximum glycerol concentrations at 30°C were obtained as 8.5 and 7.6 gL−1 for Kalecik 1 and Narince 3, respectively. PMID:24031225

75 FR 7293 - Temporary Agricultural Employment of H-2A Workers in the United States: 2010 Adverse Effect Wage...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-18

... Workers' Meals, and Maximum Travel Subsistence Reimbursement AGENCY: Employment and Training... the new 2010 Adverse Effect Wage Rates (AEWRs) and the 2010 maximum allowable meal and travel..., and qualified and who will be available at the time and place needed to perform the labor or services...

Optimizing any-aged management of mixed-species stands: II. effects of decision criteria

Treesearch

Robert G. Haight; Robert A. Monserud

1990-01-01

The effects of maximum present value and maximum volume objectives on the efficiencies of alternative silvicultural systems are determined by solving any-aged management problems for mixed-conifer stands in the Northern Rocky Mountains. Any-aged management problems are formulated with periodic planting and harvesting controls and without constraints on the stand age or...

Effect of Training Frequency on Maximum Expiratory Pressure

ERIC Educational Resources Information Center

Anand, Supraja; El-Bashiti, Nour; Sapienza, Christine

2012-01-01

Purpose: To determine the effects of expiratory muscle strength training (EMST) frequency on maximum expiratory pressure (MEP). Method: We assigned 12 healthy participants to 2 groups of training frequency (3 days per week and 5 days per week). They completed a 4-week training program on an EMST trainer (Aspire Products, LLC). MEP was the primary…

Effect of Water-Alcohol Injection and Maximum Economy Spark Advance on Knock-Limited Performance and Fuel Economy of a Large Air-Cooled Cylinder

NASA Technical Reports Server (NTRS)

Heinicke, Orville H.; Vandeman, Jack E.

1945-01-01

An investigation was conducted to determine the effect of a coolant solution of 25 percent ethyl alcohol, 25 percent methyl alcohol, and 50 percent water by volume and maximum-economy spark advance on knock-limited performance and fuel economy of a large air-cooled cylinder. The knock-limited performance of the cylinder at engine speeds of 2100 and 2500 rpm was determined for coolant-fuel ratios of 0.0, 0.2, and 0.4. The effect of water-alcohol injection on fuel economy was determined in constant charge-air flow tests. The tests were conducted at a spark advance of 20 deg B.T.C. and maximum-economy spark advance.

An EMA analysis of the effect of increasing word length on consonant production in apraxia of speech: a case study.

PubMed

Bartle, Carly J; Goozée, Justine V; Murdoch, Bruce E

2007-03-01

The effect of increasing word length on the articulatory dynamics (i.e. duration, distance, maximum acceleration, maximum deceleration, and maximum velocity) of consonant production in acquired apraxia of speech was investigated using electromagnetic articulography (EMA). Tongue-tip and tongue-back movement of one apraxic patient was recorded using the AG-200 EMA system during word-initial consonant productions in one, two, and three syllable words. Significantly deviant articulatory parameters were recorded for each of the target consonants during one, two, and three syllables words. Word length effects were most evident during the release phase of target consonant productions. The results are discussed with respect to theories of speech motor control as they relate to AOS.

Mass mortality of the vermetid gastropod Ceraesignum maximum

NASA Astrophysics Data System (ADS)

Brown, A. L.; Frazer, T. K.; Shima, J. S.; Osenberg, C. W.

2016-09-01

Ceraesignum maximum (G.B. Sowerby I, 1825), formerly Dendropoma maximum, was subject to a sudden, massive die-off in the Society Islands, French Polynesia, in 2015. On Mo'orea, where we have detailed documentation of the die-off, these gastropods were previously found in densities up to 165 m-2. In July 2015, we surveyed shallow back reefs of Mo'orea before, during and after the die-off, documenting their swift decline. All censused populations incurred 100% mortality. Additional surveys and observations from Mo'orea, Tahiti, Bora Bora, and Huahine (but not Taha'a) suggested a similar, and approximately simultaneous, die-off. The cause(s) of this cataclysmic mass mortality are currently unknown. Given the previously documented negative effects of C. maximum on corals, we expect the die-off will have cascading effects on the reef community.

Influence of Distributed Dead Loads on Vehicle Position for Maximum Moment in Simply Supported Bridges

NASA Astrophysics Data System (ADS)

Gupta, Tanmay; Kumar, Manoj

2017-06-01

Usually, the design moments in the simply supported bridges are obtained as the sum of moments due to dead loads and live load where the live load moments are calculated using the rolling load concept neglecting the effect of dead loads. For the simply supported bridges, uniformly distributed dead load produces maximum moment at mid-span while the absolute maximum bending moment due to multi-axel vehicles occur under a wheel which usually do not lie at mid-span. Since, the location of absolute maximum bending moment due to multi-axel vehicle do not coincide with the location of maximum moment due to dead loads occurring at mid-span, the design moment may not be obtained by simply superimposing the effect of dead load and live load. Moreover, in case of Class-A and Class-70R wheeled vehicular live loads, which consists of several axels, the number of axels to be considered over the bridge of given span and their location is tedious to find out and needs several trials. The aim of the present study is to find the number of wheels for Class-A and Class-70R wheeled vehicles and their precise location to produce absolute maximum moment in the bridge considering the effect of dead loads and impact factor. Finally, in order to enable the designers, the design moments due to Class-70R wheeled and Class-A loading have been presented in tabular form for the spans from 10 to 50 m.

Fatigue History and in-situ Loading Studies of the overload Effect Using High Resolution X-ray Strain Profiling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croft,M.; Jisrawi, N.; Zhong, Z.

High-energy synchrotron X-ray diffraction experiments are used to perform local crack plane strain profiling of 4140 steel compact tension specimens fatigued at constant amplitude, subjected to a single overload cycle, then fatigued some more at constant amplitude. X-ray strain profiling results on a series of samples employing in-situ load cycling are correlated with the crack growth rate (da/dN) providing insight into the da/dN retardation known as the 'overload effect'. Immediately after the overload, the strain under maximum load is greatly reduced but the range of strain, between zero and maximum load, remains unchanged compared to the pre-overload values. At themore » point of maximum retardation, it is the strain range that is greatly reduced while the maximum-load strain has begun to recover to the pre-overload value. For a sample that has recovered to approximately half of the original da/dN value following the overload, the strain at maximum load is fully recovered while the strain range, though partially recovered, is still substantially reduced. The dominance of the strain range in the overload effect is clearly indicated. Subject to some assumptions, strong quantitative support for a crack growth rate driving force of the suggested form [(K{sub max}){sup -p}({Delta}K){sup p}]{sup {gamma}} is found. A dramatic nonlinear load dependence in the spatial distribution of the strain at maximum retardation is also demonstrated: at low load the response is dominantly at the overload position; whereas at high loads it is dominantly at the crack tip position. This transfer of load response away from the crack tip to the overload position appears fundamental to the overload effect for high R-ratio fatigue as studied here.« less

Proceedings of the SMRM Degradation Study Workshop

NASA Technical Reports Server (NTRS)

1985-01-01

The proceedings of the Solar Maximum Repair Mission Degradation Study Workshop, held at the Goddard Space Flight Center in Greenbelt, Maryland on May 9 to 10, 1985 are contained. The results of tests and studies of the returned Solar Maximum Mission hardware and materials are reported. Specifically, the workshop was concerned with the effects of four years' exposure to a low-Earth orbit environment. To provide a background for the reported findings, the summary includes a short description of the Solar Maximum Mission and the Solar Maximum Repair Mission.

Climate change mitigation effect of harvested wood products in regions of Japan.

PubMed

Kayo, Chihiro; Tsunetsugu, Yuko; Tonosaki, Mario

2015-12-01

Harvested wood products (HWPs) mitigate climate change through carbon storage, material substitution, and energy substitution. We construct a model to assess the overall climate change mitigation effect (comprising the carbon storage, material substitution, and energy substitution effects) resulting from HWPs in regions of Japan. The model allows for projections to 2050 based on future scenarios relating to the domestic forestry industry, HWP use, and energy use. Using the production approach, a nationwide maximum figure of 2.9 MtC year -1 for the HWP carbon storage effect is determined for 2030. The maximum nationwide material substitution effect is 2.9 MtC year -1 in 2050. For the energy substitution effect, a nationwide maximum projection of 4.3 MtC year -1 in 2050 is established, with at least 50 % of this figure derived from east and west Japan, where a large volume of logging residue is generated. For the overall climate change mitigation effect, a nationwide maximum projection of 8.4 MtC year -1 in 2050 is established, equivalent to 2.4 % of Japan's current carbon dioxide emissions. When domestic roundwood production and HWP usage is promoted, an overall climate change mitigation effect is consistently expected to be attributable to HWPs until 2050. A significant factor in obtaining the material substitution effect will be substituting non-wooden buildings with wooden ones. The policy of promoting the use of logging residue will have a significant impact on the energy substitution effect. An important future study is an integrated investigation of the climate change mitigation effect for both HWPs and forests.

Simplified cementation of lithium disilicate crowns: Retention with various adhesive resin cement combinations.

PubMed

Johnson, Glen H; Lepe, Xavier; Patterson, Amanda; Schäfer, Oliver

2017-09-27

A composite resin cement and matching self-etch adhesive was developed to simplify the dependable retention of lithium disilicate crowns. The efficacy of this new system is unknown. The purpose of this in vitro study was to determine whether lithium disilicate crowns cemented with a new composite resin and adhesive system and 2 other popular systems provide clinically acceptable crown retention after long-term aging with monthly thermocycling. Extracted human molars were prepared with a flat occlusal surface, 20-degree convergence, and 4 mm axial length. The axio-occlusal line angle was slightly rounded. The preparation surface area was determined by optical scanning and the analysis of the standard tessellation language (STL) files. The specimens were distributed into 3 cement groups (n=12) to obtain equal mean surface areas. Lithium disilicate crowns (IPS e.max Press) were fabricated for each preparation, etched with 9.5% hydrofluoric acid for 15 seconds, and cleaned. Cement systems were RelyX Ultimate with Scotch Bond Universal (3M Dental Products); Monobond S, Multilink Automix with Multilink Primer A and B (Ivoclar Vivadent AG); and NX3 Nexus with OptiBond XTR (Kerr Corp). Each adhesive provided self-etching of the dentin. Before cementation, the prepared specimens were stored in 35°C water. A force of 196 N was used to cement the crowns, and the specimens were polymerized in a 35°C oven at 100% humidity. After 24 hours of storage at 100% humidity, the cemented crowns were thermocycled (5°C to 55°C) for 5000 cycles each month for 6 months. The crowns were removed axially at 0.5 mm/min. The removal force was recorded and the dislodgement stress calculated using the preparation surface area. The type of cement failure was recorded, and the data were analyzed by 1-way ANOVA and the chi-square test (α=.05) after the equality of variances had been assessed with the Levene test. The Levene test was nonsignificant (P=.936). The ANOVA revealed the mean removal stresses, and forces did not differ for RelyX Ultimate with Scotchbond Universal (3.9 MPa; 522 N) and Multilink Automix with Multilink Primer (3.7 MPa; 511 N); both differed significantly (P=.022) from the mean for NX3 Nexus with OptiBond XTR (2.9 MPa; 387 N). For all 3 cements, the modes of failure showed cement principally on the crown intaglio, and the chi-square analysis was nonsignificant (P=.601). IPS e.max Press (lithium disilicate) crowns were well retained (2.9-3.9 MPa; 387-522 N) by the 3 cement-adhesive combinations after 6 months of aging with monthly thermocycling. These results can serve as a basis for cement selection for this type of crown because the values significantly exceeded those for zinc phosphate. Cements using their matched dentin bonding agent as the ceramic primer were as successful as cements with a separate silane coupling agent. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Model-based analysis of fatigued human knee extensors : Effects of isometrically induced fatigue on Hill-type model parameters and ballistic contractions.

PubMed

Penasso, Harald; Thaller, Sigrid

2018-05-05

This study investigated the effect of isometrically induced fatigue on Hill-type muscle model parameters and related task-dependent effects. Parameter identification methods were used to extract fatigue-related parameter trends from isometric and ballistic dynamic maximum voluntary knee extensions. Nine subjects, who completed ten fatiguing sets, each consisting of nine 3 s isometric maximum voluntary contractions with 3 s rest plus two ballistic contractions with different loads, were analyzed. Only at the isometric task, the identified optimized model parameter values of muscle activation rate and maximum force generating capacity of the contractile element decreased from [Formula: see text] to [Formula: see text] Hz and from [Formula: see text] to [Formula: see text] N, respectively. For all tasks, the maximum efficiency of the contractile element, mathematically related to the curvature of the force-velocity relation, increased from [Formula: see text] to [Formula: see text]. The model parameter maximum contraction velocity decreased from [Formula: see text] to [Formula: see text] m/s and the stiffness of the serial elastic element from [Formula: see text] to [Formula: see text] N/mm. Thus, models of fatigue should consider fatigue dependencies in active as well as in passive elements, and muscle activation dynamics should account for the task dependency of fatigue.

Levels of maximum end-expiratory carbon monoxide and certain cardiovascular parameters following hubble-bubble smoking.

PubMed

Shafagoj, Yanal A; Mohammed, Faisal I

2002-08-01

The physiological effects of cigarette smoking have been widely studied, however, little is known regarding the effects of smoking hubble-bubble. We examined the acute effects of hubble-bubble smoking on heart rate, systolic, diastolic, and mean arterial blood pressure and maximum end-expiratory carbon monoxide. This study was carried out in the student laboratory, School of Medicine, Department of Physiology, University of Jordan, Amman, Jordan, during the summer of 1999. In 18 healthy habitual hubble-bubble smokers, heart rate, blood pressure, and maximum end-expiratory carbon monoxide was measured before, during and post smoking of one hubble-bubble run (45 minutes). Compared to base line (time zero), at the end of smoking heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and maximum end-expiratory carbon monoxide were increased 16 2.4 beats per minute, 6.7 2.5 mm Hg, 4.4 1.6 mm Hg, 5.2 1.7 mm Hg, and 14.2 1.8 ppm, (mean standard error of mean, P<.05). Acute short-term active hubble-bubble smoking elicits a modest increase in heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and maximum end-expiratory carbon monoxide in healthy hubble-bubble smokers.