Quantitative Maximum Shear-Wave Stiffness of Breast Masses as a Predictor of Histopathologic Severity.

PubMed

Berg, Wendie A; Mendelson, Ellen B; Cosgrove, David O; Doré, Caroline J; Gay, Joel; Henry, Jean-Pierre; Cohen-Bacrie, Claude

2015-08-01

The objective of our study was to compare quantitative maximum breast mass stiffness on shear-wave elastography (SWE) with histopathologic outcome. From September 2008 through September 2010, at 16 centers in the United States and Europe, 1647 women with a sonographically visible breast mass consented to undergo quantitative SWE in this prospective protocol; 1562 masses in 1562 women had an acceptable reference standard. The quantitative maximum stiffness (termed "Emax") on three acquisitions was recorded for each mass with the range set from 0 (very soft) to 180 kPa (very stiff). The median Emax and interquartile ranges (IQRs) were determined as a function of histopathologic diagnosis and were compared using the Mann-Whitney U test. We considered the impact of mass size on maximum stiffness by performing the same comparisons for masses 9 mm or smaller and those larger than 9 mm in diameter. The median patient age was 50 years (mean, 51.8 years; SD, 14.5 years; range, 21-94 years), and the median lesion diameter was 12 mm (mean, 14 mm; SD, 7.9 mm; range, 1-53 mm). The median Emax of the 1562 masses (32.1% malignant) was 71 kPa (mean, 90 kPa; SD, 65 kPa; IQR, 31-170 kPa). Of 502 malignancies, 23 (4.6%) ductal carcinoma in situ (DCIS) masses had a median Emax of 126 kPa (IQR, 71-180 kPa) and were less stiff than 468 invasive carcinomas (median Emax, 180 kPa [IQR, 138-180 kPa]; p = 0.002). Benign lesions were much softer than malignancies (median Emax, 43 kPa [IQR, 24-83 kPa] vs 180 kPa [IQR, 129-180 kPa]; p < 0.0001). Usual benign lesions were soft, including 62 cases of fibrocystic change (median Emax, 32 kPa; IQR, 24-94 kPa), 51 cases of fibrosis (median Emax, 36 kPa; IQR, 22-102 kPa), and 301 fibroadenomas (median Emax, 45 kPa; IQR, 30-79 kPa). Eight lipomas (median Emax, 14 kPa; IQR, 8-15 kPa), 154 cysts (median Emax, 29 kPa; IQR, 10-58 kPa), and seven lymph nodes (median Emax, 17 kPa; IQR, 9-40 kPa) were softer than usual benign lesions (p < 0.0001 for lipomas and cysts; p = 0.007 for lymph nodes). Risk lesions were slightly stiffer than usual benign lesions (p = 0.002) but tended to be softer than DCIS (p = 0.14). Fat necrosis and abscesses were relatively stiff. Conclusions were similar for both small and large masses. Despite overlap in Emax values, maximum stiffness measured by SWE is a highly effective predictor of the histopathologic severity of sonographically depicted breast masses.

[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.

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.

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...

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.

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

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.

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

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

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.

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.

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.

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.

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.

Assessment of the radionuclide angiographic left ventricular maximum time-varying elastance calculation in man.

PubMed

Starling, M R; Gross, M D; Walsh, R A; Dell'Italia, L J; Montgomery, D G; Squicciarini, S A; Blumhardt, R

1988-08-01

This investigation was designed to determine whether left ventricular (LV) maximum time-varying elastance (Emax) calculations obtained using equilibrium radionuclide angiography (RNA) were comparable to those obtained using biplane contrast cineangiography (CINE), and whether simple, indirect P-V relations might provide reasonable, alternative estimates of Emax. Accordingly, we studied 19 patients with simultaneous high-fidelity micromanometer LV and fluid brachial artery (Ba) pressure recordings, CINE, and RNA under control conditions and during methoxamine and nitroprusside infusions. Emax was defined for CINE and RNA as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. The indirect P-V relations were similarly obtained from Ba peak (P) pressure versus minimum RNA LV volume (BaP/minV) and Ba dicrotic notch (di) pressure versus minimum RNA LV volume (Badi/minV) data points. The mean heart rates and LV (+)dP/dtmax values were minimally altered during the three loading conditions. The isochronal Emax values ranged from 1.40 to 6.73 mmHg/ml (mean 4.13 +/- 1.99 s.d. mmHg/ml) for CINE and from 1.48 to 7.25 (mean 4.35 +/- 1.81 mmHg/ml) for RNA (p = N.S.). Similarly, the unstressed volumes ranged from -10 to 80 ml (mean 30 +/- 23 ml) for CINE and from -8 to 77 ml (29 +/- 21 ml) for RNA (p = N.S.). The individual, isochronal Emax values by RNA correlated with those by CINE (r = 0.86). In 14 of the 19 patients, the BaP/minV and Badi/minV relations correlated with the isochronal Emax values calculated by RNA (r = 0.83 and 0.82, respectively), and these relations also correlated with the Emax values calculated by CINE (r = 0.82 and 0.78, respectively). The slope and V0 values for the BaP/minV and Badi/minV relations underestimated those for Emax by RNA and CINE (p less than 0.01 and p less than 0.05, respectively, for both). Thus, the isochronal Emax values calculated using RNA are comparable to those obtained using CINE in man. Moreover, indirect P-V relations underestimate these Emax values, but they are linearly related with the isochronal Emax values calculated by RNA and CINE. Consequently, these indirect P-V relations may provide a more simple, alternative estimate of LV contractile function in man.

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.

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.

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

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.

Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

PubMed

Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Kobeiter, Hicham; Breil, Stephane; Rahmouni, Alain

2003-12-01

To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

PubMed

Rahmouni, Alain; Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Belhadj, Karim; Gaulard, Philippe; Bouanane, Mohamed; Golli, Mondher; Kobeiter, Hicham

2003-12-01

To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

Hydraulic limits on maximum plant transpiration and the emergence of the safety-efficiency trade-off.

PubMed

Manzoni, Stefano; Vico, Giulia; Katul, Gabriel; Palmroth, Sari; Jackson, Robert B; Porporato, Amilcare

2013-04-01

Soil and plant hydraulics constrain ecosystem productivity by setting physical limits to water transport and hence carbon uptake by leaves. While more negative xylem water potentials provide a larger driving force for water transport, they also cause cavitation that limits hydraulic conductivity. An optimum balance between driving force and cavitation occurs at intermediate water potentials, thus defining the maximum transpiration rate the xylem can sustain (denoted as E(max)). The presence of this maximum raises the question as to whether plants regulate transpiration through stomata to function near E(max). To address this question, we calculated E(max) across plant functional types and climates using a hydraulic model and a global database of plant hydraulic traits. The predicted E(max) compared well with measured peak transpiration across plant sizes and growth conditions (R = 0.86, P < 0.001) and was relatively conserved among plant types (for a given plant size), while increasing across climates following the atmospheric evaporative demand. The fact that E(max) was roughly conserved across plant types and scales with the product of xylem saturated conductivity and water potential at 50% cavitation was used here to explain the safety-efficiency trade-off in plant xylem. Stomatal conductance allows maximum transpiration rates despite partial cavitation in the xylem thereby suggesting coordination between stomatal regulation and xylem hydraulic characteristics. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Applying Emax model and bivariate thin plate splines to assess drug interactions

PubMed Central

Kong, Maiying; Lee, J. Jack

2014-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95% point-wise confidence interval as well as its 95% simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies. PMID:20036878

Applying Emax model and bivariate thin plate splines to assess drug interactions.

PubMed

Kong, Maiying; Lee, J Jack

2010-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95 per cent point-wise confidence interval as well as its 95 per cent simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies.

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.

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.

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.

Elastic Properties of Lithium Disilicate Versus Feldspathic Inlays: Effect on the Bonding by 3D Finite Element Analysis.

PubMed

Trindade, Flávia Zardo; Valandro, Luiz Felipe; de Jager, Niek; Bottino, Marco Antônio; Kleverlaan, Cornelis Johannes

2016-10-03

To determine the elastic properties of five ceramic systems with different compositions (lithium disilicate vs. feldspathic ceramics) and processing methods and compare the stress distribution in premolars in the interface with inlays made with these systems loaded with the maximum normal bite force (665 N) using 3D finite element analysis (FEA). The elastic properties of five ceramic restoration materials (IPS e.max Press, IPS e.max CAD, Vita PM9, Vita Mark II, Vita VM7) were obtained using the ultrasonic pulse-echo method. Three-dimensional FEA simplified models of maxillary premolars restored with these ceramic materials were created. The models were loaded with a load at the two nodes on the occlusal surface in the middle of the tooth, 2 mm from the outside of the tooth, simulating a loading ball with a radius of 6 mm. The means values of density (g/cm³), Young's modulus (GPa), and Poison's ratio was 2.6 ± 0.3, 82.3 ± 18.3, and 0.22 ± 0.01 for IPS e.max Press; 2.3 ± 0.1, 83.5 ± 15.0, and 0.21 ± 0.01 for IPS e.max CAD; 2.5 ± 0.1, 44.4 ± 11.5, and 0.26 ± 0.08 for PM9; 2.4 ± 0.1, 70.6 ± 4.9, and 0.22 ± 0.01 for Vitamark II; 2.4 ± 0.1, 63.3 ± 3.9, and 0.23 ± 0.01 for VM7, respectively. The 3D FEA showed the tensile stress at the interface between the tooth and the inlay was dependent on the elastic properties of the materials, since the Vita PM9 and IPS e.max CAD ceramics presented the lowest and the highest stress concentration in the interface, respectively. The elastic properties of ceramic materials were influenced by composition and processing methods, and these differences influenced the stress concentration at the bonding interface between tooth and restoration. The lower the elastic modulus of inlays, the lower is the stress concentration at the bonding interfaces. © 2016 by the American College of Prosthodontists.

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.

[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.

Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Crossover Study Evaluating the Abuse Potential of the Antiepileptic Drug Lacosamide in Healthy Recreational Drug Users.

PubMed

Schoedel, Kerri A; Andreas, Jens-Otto; Doty, Pamela; Eckhardt, Klaus; Sellers, Edward M

2017-12-01

This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide. After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments. Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001). These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.

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.

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.

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.

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

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...

Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects

PubMed Central

Moore, Kenneth Todd; Byra, William; Vaidyanathan, Seema; Natarajan, Jaya; Ariyawansa, Jay; Salih, Hiba; Turner, Kenneth C

2015-01-01

Aims The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives. Methods An open label, non-randomized, sequential two period study. In treatment period 1 (TP1), subjects received rivaroxaban 20 mg once daily (5 days), followed by co-administration with a warfarin loading dose regimen of 5 or 10 mg (for the 10 mg regimen, the dose could be uptitrated to attain target international normalized ratio [INR] ≥2.0) once daily (2–4 days). When trough INR values ≥2.0 were attained, rivaroxaban was discontinued and warfarin treatment continued as monotherapy (INR 2.0–3.0). During treatment period 2, subjects received the same warfarin regimen as in TP1, but without rivaroxaban. Results During co-administration, maximum INR and prothrombin time (PT) values were higher than with rivaroxaban or warfarin monotherapy. The mean maximum effect (Emax) for INR after co-administration was 2.79–4.15 (mean PT Emax 41.0–62.7 s), compared with 1.41–1.74 (mean PT Emax 20.1–25.2 s) for warfarin alone. However, rivaroxaban had the smallest effect on INR at trough rivaroxaban concentrations. Neither rivaroxaban nor warfarin significantly affected maximum plasma concentrations of the other drug. Conclusions The combined pharmacodynamic effects during co-administration of rivaroxaban and warfarin were greater than additive, but the pharmacokinetics of both drugs were unaffected. Co-administration was well tolerated. When transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban concentration to minimize the effect of rivaroxaban on INR. PMID:25475601

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.

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

Population pharmacokinetic/pharmacodynamic model of clozapine for characterizing the relationship between accumulated exposure and PANSS scores in patients with schizophrenia.

PubMed

Shang, De-Wei; Li, Li-Jun; Wang, Xi-Pei; Wen, Yu-Guan; Ren, Yu-Peng; Guo, Wei; Li, Wen-Biao; Li, Liang; Zhou, Tian-Yan; Lu, Wei; Wang, Chuan-Yue

2014-06-01

The aim of this study was to characterize the relationship between accumulated exposure of clozapine and changes in Positive and Negative Syndrome Scale (PANSS) score in Chinese patients with schizophrenia by pharmacokinetic/pharmacodynamic (PK/PD) modeling. Sparse clozapine PK data and PANSS scores were collected from 2 clinical studies of Chinese inpatients with schizophrenia. Two other rich PK data sets were included for more accurate assessment of clozapine PK characteristics. The relationship between clozapine-accumulated exposure and PANSS score was investigated using linear, log-linear, E(max), and sigmoid models, and each model was evaluated using visual predictive condition and normalized prediction distribution error methods. Simulations based on the final PK/PD model were preformed to investigate the effect of clozapine on PANSS scores under different dose regimens. A total of 1391 blood clozapine concentrations from 198 subjects (180 patients and 18 healthy volunteers) and 576 PANSS scores from 137 patients were included for PK and PK/PD analysis. A first-order 2-compartment PK model with covariates gender and smoking status influencing systemic clearance adequately described the PK profile of clozapine. The decrease in total PANSS score during treatment was best characterized using cumulated clozapine area under the curve (AUC) data in the E(max) model. The maximum decrease in PANSS during clozapine treatment (Emax) was 55.4%, and the cumulated AUC(50) (cAUC(50)) required to attain half of E(max) was 296 mg·L(-1)·h(-1)·d(-1). The simulations demonstrated that the accelerated dose titration and constant dose regimens achieved a similar maximum drug response but with a slower relief of symptoms in dose titration regimen. The PK/PD model can describe the clinical response as measured by decreasing PANSS score during treatment and may be useful for optimizing the dose regimen for individual patients.

Flower-like BiOI microsphere/Ni@C nanocapsule hybrid composites and their efficient microwave absorbing activity

NASA Astrophysics Data System (ADS)

Liu, Xianguo; Yu, Jieyi; Cui, Caiyun; Sun, Yuping; Li, Xiaolong; Li, Zhenxing

2018-07-01

At present, microwave absorbers are prepared by dispersing absorbing nanomaterials in a binder, which can lead to the aggregation of nanomaterials in the binder and further affect the optimization of the absorption performances. Hybrid micro/nano-scale structures are beneficial for buffering agglomeration phenomena and the construction of multiple interfaces. Here, Ni@C nanocapsules are conjugated onto flower-like BiOI microspheres, forming micro/nano-scale hybrid composites. The multiple interfaces between BiOI microspheres and Ni@C nanocapsules can bring enhanced dielectric loss and increased attenuation constant, resulting in the enhancement of absorption capacity (the optimal reflection loss reaches  ‑61.35 dB), increased width of the effective absorption band (the maximum effective bandwidth, f Emax , is 5.86 GHz) and the reduction of absorption thickness (the thickness corresponding to f Emax is 1.7 mm). This study highlights a simple idea for the optimization of electromagnetic absorbing performance, which is of great significance in the development of microwave absorbers.

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.

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.

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.

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

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

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.

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.

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

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.

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.

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

Movement Variability Increases With Shoulder Pain When Compensatory Strategies of the Upper Body Are Constrained.

PubMed

López-Pascual, Juan; Page, Álvaro; Serra-Añó, Pilar

2017-10-13

This cross-sectional study analyzed the influence of chronic shoulder pain (CSP) on movement variability/kinematics during humeral elevation, with the trunk and elbow motions constrained to avoid compensatory strategies. For this purpose, 37 volunteers with CSP as the injured group (IG) and 58 participants with asymptomatic shoulders as the control group (CG) participated in the study. Maximum humeral elevation (Emax), maximum angular velocity (Velmax), variability of the maximum angle (CVEmax), functional variability (Func_var), and approximate entropy (ApEn) were calculated from the kinematic data. Patients' pain was measured on the visual analogue scale (VAS). Compared with the CG, the IG presented lower Emax and Velmax and higher variability (i.e., CVEmax, Func_var, and ApEn). Moderate correlations were achieved for the VAS score and the kinematic variables Emax, Velmax and variability of curve analysis, Func_varm, and ApEn. No significant correlation was found for CVEmax. In conclusion, CSP results in a decrease of angle and velocity and an increased shoulder movement variability when the neuromuscular system cannot use compensatory strategies to avoid painful positions.

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

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.

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.

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

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.

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.

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

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

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

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.

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.

[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.

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

Regional involvement of an endothelium-derived contractile factor in the vasoactive actions of neuropeptide Y in bovine isolated retinal arteries.

PubMed Central

Prieto, D.; Simonsen, U.; Nyborg, N. C.

1995-01-01

1. In vitro experiments in a microvascular myograph were designed in order to investigate the effects of human neuropeptide Y (NPY), its receptor subtype and the mechanisms underlying NPY actions in bovine isolated retinal proximal (PRA) and distal (DRA) arteries. 2. A single concentration of NPY (10 nM) induced a prompt and reproducible contraction which reached a plateau within 1-4 min, after which the response returned to baseline over the next 2-10 min. Cumulative addition of NPY induced concentration-dependent contractions of bovine retinal arteries, with an EC50[M] of 1.7 nM and a maximal response equal to 54 +/- 8% of Emax (absolute maximal contractile levels of vessels) and not different from that obtained by a single addition of the peptide. There were no significant differences in either sensitivity or maximal response to NPY between PRA and DRA. 3. Porcine NPY and the selective Y1-receptor agonist, [Pro34]NPY, also induced concentration-dependent contractions of the retinal arteries with a potency and maximal response not significantly different from those of human NPY; in contrast, the selective Y2-receptor agonist, NPY(13-36), caused only a 5% contraction at the highest concentration used. 4. Removal of extracellular Ca2+ or pretreatment with the 1,4-dihydropyridine Ca(2+)-channel blocker, nifedipine (1 microM), reduced the contractile response of 10 nM NPY to 18.4 +/- 3.3% (n = 6) and 18.6 +/- 3.9% (n = 6); respectively, of the controls. 5. Mechanical removal of the endothelium depressed the maximal contraction elicited by NPY in PRA but did not affect either sensitivity or maximal response to the peptide in DRA. In endothelium-intact arteries, blockade of the cyclo-oxygenase pathway with 3 microM indomethacin increased resting tension in both PRA and DRA and significantly inhibited sensitivity and maximal contraction to NPY of PRA and DRA, respectively. The thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist, SQ30741, reduced both sensitivity and maximal contraction to NPY in PRA but not in DRA. 6. In endothelium-denuded PRA, indomethacin but not SQ30741 significantly reduced NPY maximal response and induced a marked increase in resting tension suggesting a basal release of a vasodilator prostanoid from smooth muscle cells. 7. Superoxide dismutase (SOD) (150 u ml-1) reduced the maximal contraction to NPY in PRA. Inhibition of the nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NOARG) (30 microM), enhanced sensitivity and maximal contraction to NPY in both PRA and DRA. In the presence of L-NOARG, SOD did not further inhibit NPY responses in PRA. 8. NPY (10 nM) induced a 2.9 fold leftwards shift of the noradrenaline concentration-response curves in PRA and increased maximal response by 50 +/- 16%. Neither 1 nor 10 nM NPY affected noradrenaline responses in DRA. [Pro34]NPY (10 nM), but not NPY(13-36), mimicked the potentiating effect of NPY on noradrenaline responses in PRA. 9. TXA2 analogue, U46619, at 10 nM elicited 3.6 fold leftwards shift of the noradrenaline concentration-responses curves in PRA and increased the maximal contraction by 32 +/- 3%, whereas in the presence of 1 microM SQ30741, 10 nM NPY did not potentiate noradrenaline responses. 10. The present results indicate that NPY may play a role in the regulation of retinal blood flow through both a direct contractile action, independent of the vessel size and a potentiation of the responses induced by noradrenaline in the proximal part of the retinal circulation, both effects being mediated by Y1 receptors. NPY promotes Ca2+ influx through voltage-dependent Ca2+ channels and stimulates the synthesis of contractile prostanoids in PRA and DRA, although only in PRA does the peptide trigger the release of an endothelium-derived contractile factor which facilitates the contraction and also seems to account for the potentiating effect of NPY. PMID:8590997

Antigen Potency and Maximal Efficacy Reveal a Mechanism of Efficient T Cell Activation

PubMed Central

Wheeler, Richard J.; Zhang, Hao; Cordoba, Shaun-Paul; Peng, Yan-Chun; Chen, Ji-Li; Cerundolo, Vincenzo; Dong, Tao; Coombs, Daniel; van der Merwe, P. Anton

2014-01-01

T cell activation, a critical event in adaptive immune responses, follows productive interactions between T cell receptors (TCRs) and antigens, in the form of peptide-bound major histocompatibility complexes (pMHCs) on the surfaces of antigen-presenting-cells. Upon activation, T cells can lyse infected cells, secrete cytokines, such as interferon-γ (IFN-γ), and perform other effector functions with various efficiencies that directly depend on the binding parameters of the TCR-pMHC complex. The mechanism that relates binding parameters to the efficiency of activation of the T cell remains controversial; some studies suggest that the dissociation constant (KD) determines the response (the “affinity model”), whereas others suggest that the off-rate (koff) is critical (the “productive hit rate model”). Here, we used mathematical modeling to show that antigen potency, as determined by the EC50, the functional correlate that is used to support KD-based models, could not be used to discriminate between the affinity and productive hit rate models. Our theoretical work showed that both models predicted a correlation between antigen potency and KD, but only the productive hit rate model predicted a correlation between maximal efficacy (Emax) and koff. We confirmed the predictions made by the productive hit rate model in experiments with cytotoxic T cell clones and a panel of pMHC variants. Therefore, we suggest that the activity of an antigen is determined by both its potency and maximal efficacy. We discuss the implications of our findings to the practical evaluation of T cell activation, for example in adoptive immunotherapies, and relate our work to the pharmacological theory of dose-response. PMID:21653229

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.

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.

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

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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

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.

Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia.

PubMed

Rodriguez, Rodolfo; Ventura-Martinez, Rosa; Santiago-Mejia, Jacinto; Avila-Costa, Maria R; Fortoul, Teresa I

2006-02-01

1. We evaluated changes in contractility of the guinea-pig isolated ileum, using intact segments and myenteric plexus-longitudinal muscle (MPLM) preparations, after several times (5-160 min) of ischemia in situ. 2. Intestinal ischemia was produced by clamping the superior mesenteric artery. Ischemic and nonischemic segments, obtained from the same guinea-pig, were mounted in organ baths containing Krebs-bicarbonate (K-B) solution, maintained at 37 degrees C and gassed with 95% O2/5% CO2. The preparations were allowed to equilibrate for 60 min under continuous superfusion of warm K-B solution and then electrically stimulated at 40 V (0.3 Hz, 3.0 ms). Thereafter, complete noncumulative concentration-response curves were constructed for acetylcholine (ACh), histamine (HIS), potassium chloride (KCl), and barium chloride (BaCl2). Mean Emax (maximal response) values were calculated for each drug. 3. Our study shows that alterations of chemically and electrically evoked contractions are dependent on ischemic periods. It also demonstrates that contractile responses of ischemic tissues to neurogenic stimulation decreases earlier and to a significantly greater extent than the non-nerve mediated responses of the intestinal smooth muscle. Contractile responses to smooth muscle stimulants were all similarly affected by ischemia. Electron microscopy images indicated necrotic neuronal death. The decrease in reactivity of ischemic tissues to electrical stimulation was ameliorated by dexrazoxane, an antioxidant agent. 4. We consider the guinea-pig isolated ileum as a useful model system to study the processes involved in neuronal ischemia, and we propose that the reduction in maximal responses to electrical stimulation is a useful parameter to study neuroprotection.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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...

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.

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.

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.

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.

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.

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.

Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury.

PubMed

López-Pascual, Juan; Page, Álvaro; Serra-Añó, Pilar

2017-01-01

Obtaining kinematic patterns that depend on the shoulder injury may be important when planning rehabilitation. The main goal of this study is to explore whether the kinematic patterns of continuous and repetitive shoulder elevation motions are different according to the type of shoulder injury in question, specifically tendinopathy or rotator cuff tear, and to analyze the influence of the load handled during its assessment. For this purpose, 19 individuals with tendinopathy and 9 with rotator cuff tear performed a repetitive scaption movement that was assessed with stereophotogrammetry. Furthermore, static range of motion (ROM) and isometric strength were evaluated with a goniometer and a dynamometer, respectively. Dynamic measurements of maximum elevation (Emax), variablility of the maximum angle (VMA), maximum angular velocity (Velmax), and time to maximum velocity (tmaxvel) were found to be significantly different between the tendinopathy group (TG) and the rotator cuff tear group (RTCG). No differences were found in the ROM assessed with goniometry and the isometric strength. The effect of increasing the load placed in the hand during the scaption movement led to significant differences in Emax, VMA, tmaxvel and repeatability. Therefore, only the dynamic variables showed sufficient capability of detecting differences in functional performance associated with structural shoulder injury. The differences observed in the kinematic variables between patients with tendinopathy and rotator cuff tear seem to be related to alterations in thoracohumeral rhythm and neuromuscular control. Kinematic analysis may contribute to a better understanding of the functional impact of shoulder injuries, which would help in the assessment and treatment of shoulder pain.

Dynamic thoracohumeral kinematics are dependent upon the etiology of the shoulder injury

PubMed Central

López-Pascual, Juan; Page, Álvaro; Serra-Añó, Pilar

2017-01-01

Obtaining kinematic patterns that depend on the shoulder injury may be important when planning rehabilitation. The main goal of this study is to explore whether the kinematic patterns of continuous and repetitive shoulder elevation motions are different according to the type of shoulder injury in question, specifically tendinopathy or rotator cuff tear, and to analyze the influence of the load handled during its assessment. For this purpose, 19 individuals with tendinopathy and 9 with rotator cuff tear performed a repetitive scaption movement that was assessed with stereophotogrammetry. Furthermore, static range of motion (ROM) and isometric strength were evaluated with a goniometer and a dynamometer, respectively. Dynamic measurements of maximum elevation (Emax), variablility of the maximum angle (VMA), maximum angular velocity (Velmax), and time to maximum velocity (tmaxvel) were found to be significantly different between the tendinopathy group (TG) and the rotator cuff tear group (RTCG). No differences were found in the ROM assessed with goniometry and the isometric strength. The effect of increasing the load placed in the hand during the scaption movement led to significant differences in Emax, VMA, tmaxvel and repeatability. Therefore, only the dynamic variables showed sufficient capability of detecting differences in functional performance associated with structural shoulder injury. The differences observed in the kinematic variables between patients with tendinopathy and rotator cuff tear seem to be related to alterations in thoracohumeral rhythm and neuromuscular control. Kinematic analysis may contribute to a better understanding of the functional impact of shoulder injuries, which would help in the assessment and treatment of shoulder pain. PMID:28841697

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).

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.

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

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.

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).

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'

[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.

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.

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

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.

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.

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

Role of shear wave sonoelastography in differentiation between focal breast lesions.

PubMed

Dobruch-Sobczak, Katarzyna; Nowicki, Andrzej

2015-02-01

Our goal in this study was to evaluate the relevance of shear wave sonoelastography (SWE) in the differential diagnosis of masses in the breast with respect to ultrasound (US). US and SWE were performed (Aixplorer System, SuperSonic Imagine, Aix en Provence, France) in 76 women (aged 24 to 85) with 84 lesions (43 malignant, 41 benign). The study included BI-RADS-US (Breast Imaging Reporting and Data System for Ultrsound) category 3-5 lesions. In elastograms, the following values were calculated: mean elasticity in lesions (E(av.l)) and in fat tissue (E(av.f.)) and maximal (E(max.adj.)) and mean (E(av.adj.)) elasticity in lesions and adjacent tissues. The sensitivity and specificity of the BI-RADS category 4a/4b cutoff value were 97.7% and 90.2%. For an E(av.adj.) of 68.5 kPa, the cutoff sensitivity was 86.1% and the specificity was 87.8%, and for an E(max.adj.) of 124.1 kPa, 74.4% and 92.7%, respectively. For BI-RADS-US category 3 lesions, E(av.l), E(max.adj.) and E(av.adj.) were below cutoff levels. On the basis of our findings, E(av.adj.) had lower sensitivity and specificity compared with US. Emax.adj. improved the specificity of breast US with loss of sensitivity. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

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

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

Cross-bridge elasticity in single smooth muscle cells

PubMed Central

1983-01-01

In smooth muscle, a cross-bridge mechanism is believed to be responsible for active force generation and fiber shortening. In the present studies, the viscoelastic and kinetic properties of the cross- bridge were probed by eliciting tension transients in response to small, rapid, step length changes (delta L = 0.3-1.0% Lcell in 2 ms). Tension transients were obtained in a single smooth muscle cell isolated from the toad (Bufo marinus) stomach muscularis, which was tied between a force transducer and a displacement device. To record the transients, which were of extremely small magnitude (0.1 microN), a high-frequency (400 Hz), ultrasensitive force transducer (18 mV/microN) was designed and built. The transients obtained during maximal force generation (Fmax = 2.26 microN) were characterized by a linear elastic response (Emax = 1.26 X 10(4) mN/mm2) coincident with the length step, which was followed by a biphasic tension recovery made up of two exponentials (tau fast = 5-20 ms, tau slow = 50-300 ms). During the development of force upon activation, transients were elicited. The relationship between stiffness and force was linear, which suggests that the transients originate within the cross-bridge and reflect the cross-bridge's viscoelastic and kinetic properties. The observed fiber elasticity suggests that the smooth muscle cross-bridge is considerably more compliant than in fast striated muscle. A thermodynamic model is presented that allows for an analysis of the factors contributing to the increased compliance of the smooth muscle cross-bridge. PMID:6413640

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.

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.

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.

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

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

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.

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.

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.

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 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.

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus

PubMed Central

2011-01-01

Background The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. Methods 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 106 and 108 cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. Results 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 106 cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 108 cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log10 CFU/ml for agr functional vs. 2.41 log10 CFU/ml for agr dysfunctional MRSA (p = 0.0007). Conclusions Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections. PMID:21599878

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus.

PubMed

Tsuji, Brian T; MacLean, Robert D; Dresser, Linda D; McGavin, Martin J; Simor, Andrew E

2011-05-20

The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10(6) and 10(8) cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10(6) cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 10(8) cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log(10) CFU/ml for agr functional vs. 2.41 log(10) CFU/ml for agr dysfunctional MRSA (p = 0.0007). Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.

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.

Salinity effect on the maximal growth temperature of some bacteria isolated from marine enviroments.

PubMed

Stanley, S O; Morita, R Y

1968-01-01

Salinity of the growth medium was found to have a marked effect on the maximal growth temperature of four bacteria isolated from marine sources. Vibrio marinus MP-1 had a maximal growth temperature of 21.2 C at a salinity of 35% and a maximal growth temperature of 10.5 C at a salinity of 7%, the lowest salinity at which it would grow. This effect was shown to be due to the presence of various cations in the medium. The order of effectiveness of cations in restoring the normal maximal growth temperature, when added to dilute seawater, was Na(+) > Li(+) > Mg(++) > K(+) > Rb(+) > NH(4) (+). The anions tested, with the exception of SO(4)=, had no marked effect on the maximal growth temperature response. In a completely defined medium, the highest maximal growth temperature was 20.0 C at 0.40 m NaCl. A decrease in the maximal growth temperature was observed at both low and high concentrations of NaCl.

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

Skin temperature modifies the impact of hypohydration on aerobic performance.

PubMed

Kenefick, R W; Cheuvront, S N; Palombo, L J; Ely, B R; Sawka, M N

2010-07-01

This study determined the effects of hypohydration on aerobic performance in compensable [evaporative cooling requirement (E(req)) < maximal evaporative cooling (E(max))] conditions of 10 degrees C [7 degrees C wet bulb globe temperature (WBGT)], 20 degrees C (16 degrees C WBGT), 30 degrees C (22 degrees C WBGT), and 40 degrees C (27 degrees C WBGT) ambient temperature (T(a)). Our hypothesis was that 4% hypohydration would impair aerobic performance to a greater extent with increasing heat stress. Thirty-two men [22 +/- 4 yr old, 45 +/- 8 ml.kg(-1).min(-1) peak O(2) uptake (Vo(2 peak))] were divided into four matched cohorts (n = 8) and tested at one of four T(a) in euhydrated (EU) and hypohydrated (HYPO, -4% body mass) conditions. Subjects completed 30 min of preload exercise (cycle ergometer, 50% Vo(2 peak)) followed by a 15 min self-paced time trial. Time-trial performance (total work, change from EU) was -3% (P = 0.1), -5% (P = 0.06), -12% (P < 0.05), and -23% (P < 0.05) in 10 degrees C, 20 degrees C, 30 degrees C, and 40 degrees C T(a), respectively. During preload exercise, skin temperature (T(sk)) increased by approximately 4 degrees C per 10 degrees C T(a), while core (rectal) temperature (T(re)) values were similar within EU and HYPO conditions across all T(a). A significant relationship (P < 0.05, r = 0.61) was found between T(sk) and the percent decrement in time-trial performance. During preload exercise, hypohydration generally blunted the increases in cardiac output and blood pressure while reducing blood volume over time in 30 degrees C and 40 degrees C T(a). Our conclusions are as follows: 1) hypohydration degrades aerobic performance to a greater extent with increasing heat stress; 2) when T(sk) is >29 degrees C, 4% hypohydration degrades aerobic performance by approximately 1.6% for each additional 1 degrees C T(sk); and 3) cardiovascular strain from high skin blood flow requirements combined with blood volume reductions induced by hypohydration is an important contributor to impaired performance.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A New Look at the Impact of Maximizing on Unhappiness: Two Competing Mediating Effects

PubMed Central

Peng, Jiaxi; Zhang, Jiaxi; Zhang, Yan; Gong, Pinjia; Han, Bing; Sun, Hao; Cao, Fei; Miao, Danmin

2018-01-01

The current study aims to explore how the decision-making style of maximizing affects subjective well-being (SWB), which mainly focuses on the confirmation of the mediator role of regret and suppressing role of achievement motivation. A total of 402 Chinese undergraduate students participated in this study, in which they responded to the maximization, regret, and achievement motivation scales and SWB measures. Results suggested that maximizing significantly predicted SWB. Moreover, regret and achievement motivation (hope for success dimension) could completely mediate and suppress this effect. That is, two competing indirect pathways exist between maximizing and SWB. One pathway is through regret. Maximizing typically leads one to regret, which could negatively predict SWB. Alternatively, maximizing could lead to high levels of hope for success, which were positively correlated with SWB. Findings offered a complex method of thinking about the relationship between maximizing and SWB. PMID:29467694

3 CFR - Maximizing the Effectiveness of Federal Programs and Functions Supporting Trade and Investment

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Maximizing the Effectiveness of Federal Programs and Functions Supporting Trade and Investment Presidential Documents Other Presidential Documents Memorandum of February 17, 2012 Maximizing the Effectiveness of Federal Programs and Functions Supporting Trade and Investment Memorandum for the Heads of...

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.

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

Effects of spine flexion and erector spinae maximal force on vertical squat jump height: a computational simulation study.

PubMed

Blache, Yoann; Monteil, Karine

2015-03-01

The purpose of this study was to evaluate the single and combined effects of initial spine flexion and maximal isometric force of the erector spinae on maximal vertical jump height during maximal squat jumping. Seven initial flexions of the 'thorax-head-arm' segment (between 20.1° and 71.6°) and five maximal isometric forces of the erector spinae (between 5600 and 8600 N) were tested. Thus, 35 squat jumps were simulated using a 2D simulation model of the musculoskeletal system. Vertical jump height varied at most about 0.094 and 0.021 m when the initial flexion of the 'thorax-head-arm' segment and the maximal force of the erector spinae were, respectively, maximal. These results were explained for the most part by the variation of total muscle work. The latter was mainly influenced by the work produced by the erector spinae which increased at most about 57 and 110 J when the initial flexion of the 'thorax-head-arm' segment and the maximal force of the erector spinae were, respectively, maximal. It was concluded that the increase in the initial flexion of the 'thorax-head-arm' segment and in the maximal isometric force of the erector spinae enables an increase in maximal vertical jump height during maximal squat jumping.

Effects of Movement Velocity and Maximal Concentric and Eccentric Actions on the Bilateral Deficit

ERIC Educational Resources Information Center

Dickin, D. Clark; Too, Danny

2006-01-01

This study was performed to examine the effects of movement velocity and maximal concentric and eccentric actions on the bilateral deficit. Eighteen female participants performed maximal unilateral and bilateral knee extensions concentrically and eccentrically across six movement velocities (30, 60, 90, 120, 150, and 180[degrees]/s). Repeated…

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.

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.

Effect of Semirecumbent and Upright Body Position on Maximal and Submaximal Exercise Testing

ERIC Educational Resources Information Center

Scott, Alexander; Antonishen, Kevin; Johnston, Chris; Pearce, Terri; Ryan, Michael; Sheel, A. William; McKenzie, Don C.

2006-01-01

The study was designed to determine the effect of upright-posture (UP) versus semirecumbent (SR) cycling on commonly used measures of maximal and submaximal exercise capacity. Nine healthy, untrained men (M age = 27 years, SD = 4.8 years) underwent steady-state submaximal aerobic testing followed by a ramped test to determine maximal oxygen…

Effect of Age and Other Factors on Maximal Heart Rate.

ERIC Educational Resources Information Center

Londeree, Ben R.; Moeschberger, Melvin L.

1982-01-01

To reduce confusion regarding reported effects of age on maximal exercise heart rate, a comprehensive review of the relevant English literature was conducted. Data on maximal heart rate after exercising with a bicycle, a treadmill, and after swimming were analyzed with regard to physical fitness and to age, sex, and racial differences. (Authors/PP)

Phenomenology of maximal and near-maximal lepton mixing

NASA Astrophysics Data System (ADS)

Gonzalez-Garcia, M. C.; Peña-Garay, Carlos; Nir, Yosef; Smirnov, Alexei Yu.

2001-01-01

The possible existence of maximal or near-maximal lepton mixing constitutes an intriguing challenge for fundamental theories of flavor. We study the phenomenological consequences of maximal and near-maximal mixing of the electron neutrino with other (x=tau and/or muon) neutrinos. We describe the deviations from maximal mixing in terms of a parameter ɛ≡1-2 sin2 θex and quantify the present experimental status for \\|ɛ\\|<0.3. We show that both probabilities and observables depend on ɛ quadratically when effects are due to vacuum oscillations and they depend on ɛ linearly if matter effects dominate. The most important information on νe mixing comes from solar neutrino experiments. We find that the global analysis of solar neutrino data allows maximal mixing with confidence level better than 99% for 10-8 eV2<~Δm2<~2×10-7 eV2. In the mass ranges Δm2>~1.5×10-5 eV2 and 4×10-10 eV2<~Δm2<~2×10-7 eV2 the full interval \\|ɛ\\|<0.3 is allowed within ~4σ (99.995% CL) We suggest ways to measure ɛ in future experiments. The observable that is most sensitive to ɛ is the rate [NC]/[CC] in combination with the day-night asymmetry in the SNO detector. With theoretical and statistical uncertainties, the expected accuracy after 5 years is Δɛ~0.07. We also discuss the effects of maximal and near-maximal νe mixing in atmospheric neutrinos, supernova neutrinos, and neutrinoless double beta decay.

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.

Cardiorespiratory deconditioning with static and dynamic leg exercise during bed rest

NASA Technical Reports Server (NTRS)

Stremel, R. W.; Convertino, V. A.; Bernauer, E. M.; Greenleaf, J. E.

1976-01-01

Results are presented for an experimental study designed to compare the effects of heavy static and dynamic exercise training during 14 days of bed rest on the cardiorespiratory responses to submaximal and maximal exercise performed by seven healthy men aged 19-22 yr. The parameters measured were submaximal and maximal oxygen uptake, minute ventilation, heart rate, and plasma volume. The results indicate that exercise alone during bed rest reduces but does not eliminate the reduction in maximal oxygen uptake. An additional positive hydrostatic effect is therefore necessary to restore maximal oxygen uptake to ambulatory control levels. The greater protective effect of static exercise on maximal oxygen uptake is probably due to a greater hydrostatic component from the isometric muscular contraction. Neither the static nor the dynamic exercise training regimes are found to minimize the changes in all the variables studied, thereby suggesting a combination of static and dynamic exercises.

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.

Emotional Control and Instructional Effectiveness: Maximizing a Timeout

ERIC Educational Resources Information Center

Andrews, Staci R.

2015-01-01

This article provides recommendations for best practices for basketball coaches to maximize the instructional effectiveness of a timeout during competition. Practical applications are derived from research findings linking emotional intelligence to effective coaching behaviors. Additionally, recommendations are based on the implications of the…

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.

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.

Influence of simulated weightlessness on maximal oxygen uptake of untrained rats

NASA Technical Reports Server (NTRS)

Overton, J. Michael; Tipton, Charles M.

1987-01-01

The purpose of this study was to determine the effect of hindlimb suspension on maximal oxygen uptake of rodents. Male Sprague-Dawley rats were assigned to head-down (HD) suspension, horizontal (HOZ) suspension, or cage (C) control for 6-9 days. Rats were tested for maximal oxygen uptake before and after surgical instrumentation (Doppler flow probes, carotid and jugular cannulae), and after suspension. Body weight was significantly decreased after suspension in both HD and HOZ groups, but was significantly increased in the C group. Absolute maximal O2 uptake (ml/min) was not different in the C group. However, because of their increased weight, relative maximal O2 uptake (ml/min per kg) was significantly reduced. In contrast, both relative and absolute maximal O2 uptake were significantly lower, following suspension, for the HD and HOZ groups. These preliminary results support the use of hindlimb suspension as an effective model to study the mechanism(s) of cardiovascular deconditioning.

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

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.

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.

Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise.

PubMed

Demura, Shinichi; Morishita, Koji; Yamada, Takayoshi; Yamaji, Shunsuke; Komatsu, Miho

2011-11-01

L-Ornithine plays an important role in ammonia metabolism via the urea cycle. This study aimed to examine the effect of L-ornithine hydrochloride ingestion on ammonia metabolism and performance after intermittent maximal anaerobic cycle ergometer exercise. Ten healthy young adults (age, 23.8 ± 3.9 year; height, 172.3 ± 5.5 cm; body mass, 67.7 ± 6.1 kg) with regular training experience ingested L-ornithine hydrochloride (0.1 g/kg, body mass) or placebo after 30 s of maximal cycling exercise. Five sets of the same maximal cycling exercise were conducted 60 min after ingestion, and maximal cycling exercise was conducted after a 15 min rest. The intensity of cycling exercise was based on each subject's body mass (0.74 N kg(-1)). Work volume (watt), peak rpm (rpm) before and after intermittent maximal ergometer exercise and the following serum parameters were measured before ingestion, immediately after exercise and 15 min after exercise: ornithine, ammonia, urea, lactic acid and glutamate. Peak rpm was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion. Serum ornithine level was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion immediately and 15 min after intermittent maximal cycle ergometer exercise. In conclusion, although maximal anaerobic performance may be improved by L-ornithine hydrochloride ingestion before intermittent maximal anaerobic cycle ergometer exercise, the above may not depend on increase of ammonia metabolism with L-ornithine hydrochloride.

The effects of Poynting-Robertson drag on solar sails

NASA Astrophysics Data System (ADS)

Abd El-Salam, F. A.

2018-06-01

In the present work, the concept of solar sailing and its developing spacecraft are presented. The effects of Poynting-Robertson drag on solar sails are considered. Some analytical control laws with some mentioned input constraints for optimizing solar sails dynamics in heliocentric orbit using Lagrange's planetary equations are obtained. Optimum force vector in a required direction is maximized by deriving optimal sail cone angle. New control laws that maximize thrust to obtain certain required maximization in some particular orbital element are obtained.

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.

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.

Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation

USDA-ARS?s Scientific Manuscript database

Recent studies show that statin therapy, while effective at lowering the risk of cardiovascular disease (CVD), may be associated with an increased risk of diabetes. To test the effects of maximal dosages of rosuvastatin and atorvastatin (80mg/day and 40mg/day, respectively) we obtained frozen serum ...

Effect of resistance training regimens on treadmill running and neuromuscular performance in recreational endurance runners.

PubMed

Mikkola, Jussi; Vesterinen, Ville; Taipale, Ritva; Capostagno, Benoit; Häkkinen, Keijo; Nummela, Ari

2011-10-01

The purpose of this study was to assess the effects of heavy resistance, explosive resistance, and muscle endurance training on neuromuscular, endurance, and high-intensity running performance in recreational endurance runners. Twenty-seven male runners were divided into one of three groups: heavy resistance, explosive resistance or muscle endurance training. After 6 weeks of preparatory training, the groups underwent an 8-week resistance training programme as a supplement to endurance training. Before and after the 8-week training period, maximal strength (one-repetition maximum), electromyographic activity of the leg extensors, countermovement jump height, maximal speed in the maximal anaerobic running test, maximal endurance performance, maximal oxygen uptake ([V·]O(₂max)), and running economy were assessed. Maximal strength improved in the heavy (P = 0.034, effect size ES = 0.38) and explosive resistance training groups (P = 0.003, ES = 0.67) with increases in leg muscle activation (heavy: P = 0.032, ES = 0.38; explosive: P = 0.002, ES = 0.77). Only the heavy resistance training group improved maximal running speed in the maximal anaerobic running test (P = 0.012, ES = 0.52) and jump height (P = 0.006, ES = 0.59). Maximal endurance running performance was improved in all groups (heavy: P = 0.005, ES = 0.56; explosive: P = 0.034, ES = 0.39; muscle endurance: P = 0.001, ES = 0.94), with small though not statistically significant improvements in [V·]O(₂max) (heavy: ES = 0.08; explosive: ES = 0.29; muscle endurance: ES = 0.65) and running economy (ES in all groups < 0.08). All three modes of strength training used concurrently with endurance training were effective in improving treadmill running endurance performance. However, both heavy and explosive strength training were beneficial in improving neuromuscular characteristics, and heavy resistance training in particular contributed to improvements in high-intensity running characteristics. Thus, endurance runners should include heavy resistance training in their training programmes to enhance endurance performance, such as improving sprinting ability at the end of a race.

Maximal yields from multispecies fisheries systems: rules for systems with multiple trophic levels.

PubMed

Matsuda, Hiroyuki; Abrams, Peter A

2006-02-01

Increasing centralization of the control of fisheries combined with increased knowledge of food-web relationships is likely to lead to attempts to maximize economic yield from entire food webs. With the exception of predator-prey systems, we lack any analysis of the nature of such yield-maximizing strategies. We use simple food-web models to investigate the nature of yield- or profit-maximizing exploitation of communities including two types of three-species food webs and a variety of six-species systems with as many as five trophic levels. These models show that, for most webs, relatively few species are harvested at equilibrium and that a significant fraction of the species is lost from the web. These extinctions occur for two reasons: (1) indirect effects due to harvesting of species that had positive effects on the extinct species, and (2) intentional eradication of species that are not themselves valuable, but have negative effects on more valuable species. In most cases, the yield-maximizing harvest involves taking only species from one trophic level. In no case was an unharvested top predator part of the yield-maximizing strategy. Analyses reveal that the existence of direct density dependence in consumers has a large effect on the nature of the optimal harvest policy, typically resulting in harvest of a larger number of species. A constraint that all species must be retained in the system (a "constraint of biodiversity conservation") usually increases the number of species and trophic levels harvested at the yield-maximizing policy. The reduction in total yield caused by such a constraint is modest for most food webs but can be over 90% in some cases. Independent harvesting of species within the web can also cause extinctions but is less likely to do so.

Effect of constitutive inactivation of the myostatin gene on the gain in muscle strength during postnatal growth in two murine models.

PubMed

Stantzou, Amalia; Ueberschlag-Pitiot, Vanessa; Thomasson, Remi; Furling, Denis; Bonnieu, Anne; Amthor, Helge; Ferry, Arnaud

2017-02-01

The effect of constitutive inactivation of the gene encoding myostatin on the gain in muscle performance during postnatal growth has not been well characterized. We analyzed 2 murine myostatin knockout (KO) models, (i) the Lee model (KO Lee ) and (ii) the Grobet model (KO Grobet ), and measured the contraction of tibialis anterior muscle in situ. Absolute maximal isometric force was increased in 6-month-old KO Lee and KO Grobet mice, as compared to wild-type mice. Similarly, absolute maximal power was increased in 6-month-old KO Lee mice. In contrast, specific maximal force (relative maximal force per unit of muscle mass was decreased in all 6-month-old male and female KO mice, except in 6-month-old female KO Grobet mice, whereas specific maximal power was reduced only in male KO Lee mice. Genetic inactivation of myostatin increases maximal force and power, but in return it reduces muscle quality, particularly in male mice. Muscle Nerve 55: 254-261, 2017. © 2016 Wiley Periodicals, Inc.

The Immediate Effect of Neuromuscular Joint Facilitation (NJF) Treatment on Hip Muscle Strength.

PubMed

Wang, Hongdan; Huo, Ming; Huang, Qiuchen; Li, Desheng; Maruyama, Hitoshi

2013-11-01

[Purpose] This study investigated the change in hip muscle strength of younger persons after neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 45 healthy young people, who were divided into two groups: a NJF group and a proprioceptive neuromuscular facilitation (PNF) group. The NJF group consisted of 21 subjects (11 males, 10 females), and the PNF group consisted of 24 subjects (11 males, 13 females). [Methods] Participants in the NJF group received NJF treatment. We measured the maximal flexor strength and the maximal extensor strength during isokinetic movement of the hip joint before and after intervention in both groups. The angular velocities used were 60°/sec and 180°/sec. [Results] The NJF group showed significant increases in the maximal flexor strength and the maximal extensor strength after the intervention at each angular velocity. In the PNF group, the maximal flexor strength of 60°/sec and the maximal extensor strength of 180°/sec were significant increases. [Conclusion] These results suggest that there is an immediate effect of NJF intervention on hip muscle strength.

Effect of insulin-like factors on glucose transport activity in unweighted rat skeletal muscle

NASA Technical Reports Server (NTRS)

Henriksen, Erik J.; Ritter, Leslie S.

1993-01-01

The effect of 3 or 6 days of unweighting on glucose transport activity, as assessed by 2-deoxyglucose uptake, in soleus strips stimulated by maximally effective concentrations of insulin, IGF-I, vanadate, or phospholipase C (PLC) is examined. Progressively increased responses to maximally effective doses of insulin or insulin-like growth factor were observed after 3 and 6 days of unweighting compared with weight matched control strips. Enhanced maximal responses to vanadate (6 days only) and PLC (3 and 6 days) were also observed. The data provide support for the existance of postreceptor binding mechanisms for the increased action of insulin on the glucose transport system in unweighted rat skeletal muscle.

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 Neuromuscular Training on Children and Young Adults with Down Syndrome: Systematic Review and Meta-Analysis.

PubMed

Sugimoto, Dai; Bowen, Samantha L; Meehan, William P; Stracciolini, Andrea

2016-08-01

To synthesize existing research evidence and examine effects of neuromuscular training on general strength, maximal strength, and functional mobility tasks in children and young adults with Down syndrome. PubMed and EBSCO were used as a data source. To attain the aim of this study, literature search was performed under following inclusion criteria: (1) included participants with Down syndrome, (2) implemented a neuromuscular training intervention and measured outcome variables of general strength, maximal strength, and functional mobility tasks, (3) had a group of participants whose mean ages were under 30 years old, (4) employed a prospective controlled design, and (5) used mean and standard deviations to express the outcome variables. Effect size was calculated from each study based on pre- and post-testing value differences in general strength, maximal strength, and functional mobility tasks between control and intervention groups. The effect size was further classified in to one of the following categories: small, moderate, and large effects. Seven studies met inclusion criteria. Analysis indicated large to moderate effects on general strength, moderate to small effects on maximal strength, and small effect on functional mobility tasks by neuromuscular training. Although there were limited studies, the results showed that neuromuscular training could be used as an effective intervention in children and young adults with Down syndrome. Synthesis of seven reviewed studies indicated that neuromuscular training could be beneficial to optimize general and maximal muscular strength development in children and young adults with Down syndrome. Copyright © 2016 Elsevier 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.

AUC-Maximizing Ensembles through Metalearning.

PubMed

LeDell, Erin; van der Laan, Mark J; Petersen, Maya

2016-05-01

Area Under the ROC Curve (AUC) is often used to measure the performance of an estimator in binary classification problems. An AUC-maximizing classifier can have significant advantages in cases where ranking correctness is valued or if the outcome is rare. In a Super Learner ensemble, maximization of the AUC can be achieved by the use of an AUC-maximining metalearning algorithm. We discuss an implementation of an AUC-maximization technique that is formulated as a nonlinear optimization problem. We also evaluate the effectiveness of a large number of different nonlinear optimization algorithms to maximize the cross-validated AUC of the ensemble fit. The results provide evidence that AUC-maximizing metalearners can, and often do, out-perform non-AUC-maximizing metalearning methods, with respect to ensemble AUC. The results also demonstrate that as the level of imbalance in the training data increases, the Super Learner ensemble outperforms the top base algorithm by a larger degree.

AUC-Maximizing Ensembles through Metalearning

PubMed Central

LeDell, Erin; van der Laan, Mark J.; Peterson, Maya

2016-01-01

Area Under the ROC Curve (AUC) is often used to measure the performance of an estimator in binary classification problems. An AUC-maximizing classifier can have significant advantages in cases where ranking correctness is valued or if the outcome is rare. In a Super Learner ensemble, maximization of the AUC can be achieved by the use of an AUC-maximining metalearning algorithm. We discuss an implementation of an AUC-maximization technique that is formulated as a nonlinear optimization problem. We also evaluate the effectiveness of a large number of different nonlinear optimization algorithms to maximize the cross-validated AUC of the ensemble fit. The results provide evidence that AUC-maximizing metalearners can, and often do, out-perform non-AUC-maximizing metalearning methods, with respect to ensemble AUC. The results also demonstrate that as the level of imbalance in the training data increases, the Super Learner ensemble outperforms the top base algorithm by a larger degree. PMID:27227721

Maximizing the Effective Use of Formative Assessments

ERIC Educational Resources Information Center

Riddell, Nancy B.

2016-01-01

In the current age of accountability, teachers must be able to produce tangible evidence of students' concept mastery. This article focuses on implementation of formative assessments before, during, and after instruction in order to maximize teachers' ability to effectively monitor student achievement. Suggested strategies are included to help…

Strategic Placement of Treatments (SPOTS): Maximizing the Effectiveness of Fuel and Vegetation Treatments on Problem Fire Behavior and Effects

Treesearch

Diane M. Gercke; Susan A. Stewart

2006-01-01

In 2005, eight U.S. Forest Service and Bureau of Land Management interdisciplinary teams participated in a test of strategic placement of treatments (SPOTS) techniques to maximize the effectiveness of fuel treatments in reducing problem fire behavior, adverse fire effects, and suppression costs. This interagency approach to standardizing the assessment of risks and...

Effect of fluid ingestion on neuromuscular function during prolonged cycling exercise.

PubMed

Vallier, J-M; Grego, F; Basset, F; Lepers, R; Bernard, T; Brisswalter, J

2005-04-01

To investigate the effects of fluid ingestion on neuromuscular function during prolonged cycling exercise. Eight well trained subjects exercised for 180 minutes in a moderate environment at a workload requiring approximately 60% maximal oxygen uptake. Two conditions, fluid (F) and no fluid (NF) ingestion, were investigated. During maximal voluntary isometric contraction (MVC), prolonged cycling exercise reduced (p<0.05) the maximal force generating capacity of quadriceps muscles (after three hours of cycling) and root mean square (RMS) values (after two hours of cycling) with no difference between the two conditions despite greater body weight loss (p<0.05) in NF. The mean power frequency (MPF) for vastus lateralis muscle was reduced (p<0.05) and the rate of force development (RFD) was increased (p<0.05) only during NF. During cycling exercise, integrated electromyographic activity and perceived exertion were increased in both conditions (p<0.05) with no significant effect of fluid ingestion. The results suggest that fluid ingestion did not prevent the previously reported decrease in maximal force with exercise duration, but seems to have a positive effect on some indicators of neuromuscular fatigue such as mean power frequency and rate of force development during maximal voluntary contraction. Further investigations are needed to assess the effect of change in hydration on neural mechanisms linked to the development of muscular fatigue during prolonged exercise.

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.

Alterations in Strength and Maximal Oxygen Uptake Consequent to Nautilus Circuit Weight Training.

ERIC Educational Resources Information Center

Messier, Stephen P.; Dill, Mary Elizabeth

1985-01-01

The study compared the effects on muscular strength and maximal oxygen uptake of a Nautilus circuit weight training program, a free weight strength training program, and a running program. Nautilus circuit weight training appears to be equally effective for a training period of short duration. (MT)

Teacher Praise: Maximizing the Motivational Impact. Teaching Strategies.

ERIC Educational Resources Information Center

McVey, Mary D.

2001-01-01

Recognizes the influence of praise on human behavior, and provides specific suggestions on how to maximize the positive effects of praise when intended as positive reinforcement. Examines contingency, specificity, and selectivity aspects of praise. Cautions teachers to avoid the controlling effects of praise and the possibility that praise may…

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

USDA-ARS?s Scientific Manuscript database

We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response...

Institutional Effects in a Simple Model of Educational Production

ERIC Educational Resources Information Center

Bishop, John H.; Wobmann, Ludger

2004-01-01

This paper presents a model of educational production that tries to make sense of recent evidence on effects of institutional arrangements on student performance. In a simple principal-agent framework, students choose their learning effort to maximize their net benefits, while the government chooses educational spending to maximize its net…

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.

Effects of stand and inter-specific stocking on maximizing standing tree carbon stocks in the eastern United States

Treesearch

Christopher W. Woodall; Anthony W. D' Amato; John B. Bradford; Andrew O. Finley

2011-01-01

There is expanding interest in management strategies that maximize forest carbon (C) storage to mitigate increased atmospheric carbon dioxide. The tremendous tree species diversity and range of stand stocking found across the eastern United States presents a challenge for determining optimal combinations for the maximization of standing tree C storage. Using a...

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.

On Adaptation, Maximization, and Reinforcement Learning among Cognitive Strategies

ERIC Educational Resources Information Center

Erev, Ido; Barron, Greg

2005-01-01

Analysis of binary choice behavior in iterated tasks with immediate feedback reveals robust deviations from maximization that can be described as indications of 3 effects: (a) a payoff variability effect, in which high payoff variability seems to move choice behavior toward random choice; (b) underweighting of rare events, in which alternatives…

A Brief Review of Effective Teaching Practices That Maximize Student Engagement

ERIC Educational Resources Information Center

Harbour, Kristin E.; Evanovich, Lauren L.; Sweigart, Chris A.; Hughes, Lindsay E.

2015-01-01

What teachers do and how students perform intersect, making teachers a critical factor for determining student success. When teachers use effective practices, they maximize the probability that students will be actively engaged in instruction. Student engagement is one of the most well-established predictors of achievement; when students are more…

Effects of a Non-Circular Chainring on Sprint Performance During a Cycle Ergometer Test

PubMed Central

Hintzy, Frédérique; Grappe, Frédéric; Belli, Alain

2016-01-01

Non-circular chainrings have been reported to alter the crank angular velocity profile over a pedal revolution so that more time is spent in the effective power phase. The purpose of this study was to determine whether sprint cycling performance could be improved using a non-circular chainring (Osymetric: ellipticity 1.25 and crank lever mounted nearly perpendicular to the major axis), in comparison with a circular chainring. Twenty sprint cyclists performed an 8 s sprint on a cycle ergometer against a 0.5 N/kg-1 friction force in four crossing conditions (non-circular or circular chainring with or without clipless pedal). Instantaneous force, velocity and power were continuously measured during each sprint. Three main characteristic pedal downstrokes were selected: maximal force (in the beginning of the sprint), maximal power (towards the middle), and maximal velocity (at the end of the sprint). Both average and instantaneous force, velocity and power were calculated during the three selected pedal downstrokes. The important finding of this study was that the maximal power output was significantly higher (+ 4.3%, p < 0.05) when using the non-circular chainring independent from the shoe-pedal linkage condition. This improvement is mainly explained by a significantly higher instantaneous external force that occurs during the downstroke. Non-circular chainring can have potential benefits on sprint cycling performance. Key points The Osymetric non-circular chainring significantly maximized crank power by 4.3% during sprint cycling, in comparison with a circular chainring. This maximal power output improvement was due to significant higher force developed when the crank was in the effective power phase. This maximal power output improvement was independent from the shoe-pedal linkage condition. Present benefits provided by the non-circular chainring on pedalling kinetics occurred only at high cadences. PMID:27274658

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.

Acute administration of high doses of taurine does not substantially improve high-intensity running performance and the effect on maximal accumulated oxygen deficit is unclear.

PubMed

Milioni, Fabio; Malta, Elvis de Souza; Rocha, Leandro George Spinola do Amaral; Mesquita, Camila Angélica Asahi; de Freitas, Ellen Cristini; Zagatto, Alessandro Moura

2016-05-01

The aim of the present study was to investigate the effects of acute administration of taurine overload on time to exhaustion (TTE) of high-intensity running performance and alternative maximal accumulated oxygen deficit (MAODALT). The study design was a randomized, placebo-controlled, crossover design. Seventeen healthy male volunteers (age: 25 ± 6 years; maximal oxygen uptake: 50.5 ± 7.6 mL·kg(-1)·min(-1)) performed an incremental treadmill-running test until voluntary exhaustion to determine maximal oxygen uptake and exercise intensity at maximal oxygen uptake. Subsequently, participants completed randomly 2 bouts of supramaximal treadmill-running at 110% exercise intensity at maximal oxygen uptake until exhaustion (placebo (6 g dextrose) or taurine (6 g) supplementation), separated by 1 week. MAODALT was determined using a single supramaximal effort by summating the contribution of the phosphagen and glycolytic pathways. When comparing the results of the supramaximal trials (i.e., placebo and taurine conditions) no differences were observed for high-intensity running TTE (237.70 ± 66.00 and 277.30 ± 40.64 s; p = 0.44) and MAODALT (55.77 ± 8.22 and 55.06 ± 7.89 mL·kg(-1); p = 0.61), which seem to indicate trivial and unclear differences using the magnitude-based inferences approach, respectively. In conclusion, acute 6 g taurine supplementation before exercise did not substantially improve high-intensity running performance and showed an unclear effect on MAODALT.

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.

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

Pharmacodynamic Evaluation of the Activity of Antibiotics against Hemin- and Menadione-Dependent Small-Colony Variants of Staphylococcus aureus in Models of Extracellular (Broth) and Intracellular (THP-1 Monocytes) Infections

PubMed Central

Garcia, L. G.; Lemaire, S.; Kahl, B. C.; Becker, K.; Proctor, R. A.; Denis, O.; Tulkens, P. M.

2012-01-01

Staphylococcus aureus small-colony variants (SCVs) persist intracellularly, which may contribute to persistence/recurrence of infections and antibiotic failure. We have studied the intracellular fate of menD and hemB mutants (corresponding to menadione- and hemin-dependent SCVs, respectively) of the COL methicillin-resistant S. aureus (MRSA) strain and the antibiotic pharmacodynamic profile against extracellular (broth) and intracellular (human THP-1 monocytes) bacteria. Compared to the parental strain, SCVs showed slower extracellular growth (restored upon medium supplementation with menadione or hemin), reduced phagocytosis, and, for the menD SCV, lower intracellular counts at 24 h postinfection. Against extracellular bacteria, daptomycin, gentamicin, rifampin, moxifloxacin, and oritavancin showed similar profiles of activity against all strains, with a static effect obtained at concentrations close to their MICs and complete eradication as maximal effect. In contrast, vancomycin was not bactericidal against SCVs. Against intracellular bacteria, concentration-effect curves fitted sigmoidal regressions for vancomycin, daptomycin, gentamicin, and rifampin (with maximal effects lower than a 2-log decrease in CFU) but biphasic regressions (with a maximal effect greater than a 3-log decrease in CFU) for moxifloxacin and oritavancin, suggesting a dual mode of action against intracellular bacteria. For all antibiotics, these curves were indistinguishable between the strains investigated, except for the menD mutant, which systematically showed a lower amplitude of the concentration-effect response, with markedly reduced minimal efficacy (due to slower growth) but no change in maximal efficacy. The data therefore show that the maximal efficacies of antibiotics are similar against normal-phenotype and menadione- and hemin-dependent strains despite their different intracellular fates, with oritavancin, and to some extent moxifloxacin, being the most effective. PMID:22564838

Pharmacodynamic evaluation of the activity of antibiotics against hemin- and menadione-dependent small-colony variants of Staphylococcus aureus in models of extracellular (broth) and intracellular (THP-1 monocytes) infections.

PubMed

Garcia, L G; Lemaire, S; Kahl, B C; Becker, K; Proctor, R A; Denis, O; Tulkens, P M; Van Bambeke, F

2012-07-01

Staphylococcus aureus small-colony variants (SCVs) persist intracellularly, which may contribute to persistence/recurrence of infections and antibiotic failure. We have studied the intracellular fate of menD and hemB mutants (corresponding to menadione- and hemin-dependent SCVs, respectively) of the COL methicillin-resistant S. aureus (MRSA) strain and the antibiotic pharmacodynamic profile against extracellular (broth) and intracellular (human THP-1 monocytes) bacteria. Compared to the parental strain, SCVs showed slower extracellular growth (restored upon medium supplementation with menadione or hemin), reduced phagocytosis, and, for the menD SCV, lower intracellular counts at 24 h postinfection. Against extracellular bacteria, daptomycin, gentamicin, rifampin, moxifloxacin, and oritavancin showed similar profiles of activity against all strains, with a static effect obtained at concentrations close to their MICs and complete eradication as maximal effect. In contrast, vancomycin was not bactericidal against SCVs. Against intracellular bacteria, concentration-effect curves fitted sigmoidal regressions for vancomycin, daptomycin, gentamicin, and rifampin (with maximal effects lower than a 2-log decrease in CFU) but biphasic regressions (with a maximal effect greater than a 3-log decrease in CFU) for moxifloxacin and oritavancin, suggesting a dual mode of action against intracellular bacteria. For all antibiotics, these curves were indistinguishable between the strains investigated, except for the menD mutant, which systematically showed a lower amplitude of the concentration-effect response, with markedly reduced minimal efficacy (due to slower growth) but no change in maximal efficacy. The data therefore show that the maximal efficacies of antibiotics are similar against normal-phenotype and menadione- and hemin-dependent strains despite their different intracellular fates, with oritavancin, and to some extent moxifloxacin, being the most effective.

Effective Educational Videos: Principles and Guidelines for Maximizing Student Learning from Video Content

ERIC Educational Resources Information Center

Brame, Cynthia J.

2016-01-01

Educational videos have become an important part of higher education, providing an important content-delivery tool in many flipped, blended, and online classes. Effective use of video as an educational tool is enhanced when instructors consider three elements: how to manage cognitive load of the video; how to maximize student engagement with the…

Prenatal and postnatal toxicity induced in guinea-pigs by nitrosomethylurea.

PubMed

Epstein, S S; Hasumi, K; Iobal, Z M

1976-01-01

Oral administration of NMU at maximally tolerated doses of guinea-pigs from day 34 to 58 of pregnancy induced embryotoxic effects, as evidenced by a high incidence of stillbirths and reduction in birth weight, and postnatal toxic effects, as evidenced by stunting, progressive mortality and extensive fatty degeneration of the liver in F1 progeny. Similar administration of NMUT at maximally tolerated doses did not induce such toxic effects.

Using return on investment to maximize conservation effectiveness in Argentine grasslands.

PubMed

Murdoch, William; Ranganathan, Jai; Polasky, Stephen; Regetz, James

2010-12-07

The rapid global loss of natural habitats and biodiversity, and limited resources, place a premium on maximizing the expected benefits of conservation actions. The scarcity of information on the fine-grained distribution of species of conservation concern, on risks of loss, and on costs of conservation actions, especially in developing countries, makes efficient conservation difficult. The distribution of ecosystem types (unique ecological communities) is typically better known than species and arguably better represents the entirety of biodiversity than do well-known taxa, so we use conserving the diversity of ecosystem types as our conservation goal. We define conservation benefit to include risk of conversion, spatial effects that reward clumping of habitat, and diminishing returns to investment in any one ecosystem type. Using Argentine grasslands as an example, we compare three strategies: protecting the cheapest land ("minimize cost"), maximizing conservation benefit regardless of cost ("maximize benefit"), and maximizing conservation benefit per dollar ("return on investment"). We first show that the widely endorsed goal of saving some percentage (typically 10%) of a country or habitat type, although it may inspire conservation, is a poor operational goal. It either leads to the accumulation of areas with low conservation benefit or requires infeasibly large sums of money, and it distracts from the real problem: maximizing conservation benefit given limited resources. Second, given realistic budgets, return on investment is superior to the other conservation strategies. Surprisingly, however, over a wide range of budgets, minimizing cost provides more conservation benefit than does the maximize-benefit strategy.

Examining the Impact of the Walking School Bus With an Agent-Based Model

PubMed Central

Diez-Roux, Ana; Evenson, Kelly R.; Colabianchi, Natalie

2014-01-01

We used an agent-based model to examine the impact of the walking school bus (WSB) on children’s active travel to school. We identified a synergistic effect of the WSB with other intervention components such as an educational campaign designed to improve attitudes toward active travel to school. Results suggest that to maximize active travel to school, children should arrive on time at “bus stops” to allow faster WSB walking speeds. We also illustrate how an agent-based model can be used to identify the location of routes maximizing the effects of the WSB on active travel. Agent-based models can be used to examine plausible effects of the WSB on active travel to school under various conditions and to identify ways of implementing the WSB that maximize its effectiveness. PMID:24832410

Studies of the effects of Vilon and Epithalon on gene expression in mouse heart using DNA-microarray technology.

PubMed

Anisimov, S V; Bokheler, K R; Khavinson, V Kh; Anisimov, V N

2002-03-01

Expression of 15,247 clones from a cDNA library in the heart of mice receiving Vilon and Epithalon was studied by DNA-microarray technology. We revealed 300 clones (1.94% of the total count), whose expression changed more than by 2 times. Vilon changed expression of 36 clones, while Epithalon modulated expression of 98 clones. Combined treatment with Vilon and Epithalon changed expression of 144 clones. Vilon alone or in combination with Epithalon activated expression of 157 clones (maximally by 6.13 times) and inhibited expression of 23 clones (maximally by 2.79 times). Epithalon alone or in combination with Vilon activated expression of 194 clones (maximally by 6.61 times) and inhibited expression of 48 clones (maximally by 2.71 times). Our results demonstrate the specific effects of Epithalon and Vilon on gene expression.

[Effects of a high intensity interval training on the aerobic capacity of adolescents].

PubMed

Huerta Ojeda, Álvaro; Galdames Maliqueo, Sergio; Cataldo Guerra, Marianela; Barahona Fuentes, Guillermo; Rozas Villanueva, Tania; Cáceres Serrano, Pablo

2017-08-01

If aerobic capacity is stimulated early in life, maximal oxygen consumption during adulthood is assured. To analyze the effects of a high intensity interval training (HIIT) in adolescents on the maximal oxygen consumption (VO2max) measured using the 20-m shuttle run test (20mSRT). Twenty eight teenagers aged 13 ± 0.6 years were divided in two groups of 14 subjects each. One group was to a 16 sessions of HIIT interval training based on their individual maximal aerobic speed and the other continued with their usual exercise done at school. At baseline and the end of the intervention VO2max was measured using the 20mSTR. At the end of the intervention, the trained teenagers significantly improved their VO2max and the time spent in the 20mSTR. A HIIT program based on the individual maximal aerobic speed improves VO2max in adolescents.

Effect of 29 days of simulated microgravity on maximal oxygen consumption and fat-free mass of rats

NASA Technical Reports Server (NTRS)

Woodman, Christopher R.; Stump, Craig S.; Stump, Jane A.; Rahman, Zia; Tipton, Charles M.

1991-01-01

Effects of a 29-days exposure to simulated microgravity on the values of maximal oxygen consumption and fat-free mass (FFM) and on the mechanical efficiency of running were investigated in rats randomly assigned to one of three regimens: head-down suspension (HDS) at 45 deg, horizontal suspension (HS), or cage control (CC). Before suspension and on days 7, 14, 21, and 28, five exercise performance tests were carried out, with measurements related to maximal oxygen consumption, treadmill run time, and mechanical efficiency. It was found that maximal oxygen consumption of both HDS and HS groups decreased significantly at day 7, after which the HDS rats remained decreased while the HS rats returned to presuspension values. Apparent mechanical efficiency in the HDS and HS groups decreased by 22-35 percent during the experimental period, and FFM decreased significantly.

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.

A Comparison of the Habitual Landing Strategies from Differing Drop Heights of Parkour Practitioners (Traceurs) and Recreationally Trained Individuals.

PubMed

Standing, Regan J; Maulder, Peter S

2015-12-01

Parkour is an activity that encompasses methods of jumping, climbing and vaulting. With landing being a pertinent part of this practise, Parkour participants (traceurs) have devised their own habitual landing strategies, which are suggested to be a safer and more effective style of landing. The purpose of this study was to compare the habitual landing strategies of traceurs and recreationally trained individuals from differing drop heights. Comparisons between landing sound and mechanical parameters were also assessed to gauge the level of landing safety. Ten recreationally trained participants and ten traceurs performed three landings from 25% and 50% body height using their own habitual landing strategies. Results at 25% showed significantly lower maximal vertical force (39.9%, p < 0.0013, ES = -1.88), longer times to maximal vertical force (68.6%, p < 0.0015, ES = 1.72) and lower loading rates (65.1%, p < 0.0002, ES = -2.22) in the traceur group. Maximal sound was also shown to be lower (3.6%), with an effect size of -0.63, however this was not statistically significant (p < 0.1612). At 50%, traceurs exhibited significantly different values within all variables including maximal sound (8.6%, p < 0.03, ES = -1.04), maximal vertical force (49.0%, p < 0.0002, ES = -2.38), time to maximal vertical force (65.9%, p < 0.0067, ES = 1.32) and loading rates (66.3%, p < 0.0002, ES = -2.00). Foot strike analysis revealed traceurs landed using forefoot or forefoot-midfoot strategies in 93.2% of trials; whereas recreationally trained participants used these styles in only 8.3% of these landings. To conclude, the habitual landings of traceurs are more effective at lowering the kinetic landing variables associated with a higher injury risk in comparison to recreationally trained individuals. Sound as a measure of landing effectiveness and safety holds potential significance; however requires further research to confirm. Key pointsHabitual traceur landings were observed to be safer landing techniques in comparison to those utilised by recreationally trained individuals, due to the lower maximal vertical forces, slower times to maximal vertical force, lesser loading rates and lower maximal sound.Traceurs predominantly landed with the forefoot only, whereas recreationally trained individuals habitually utilised a forefoot to heel landing strategy.The habitual landing techniques performed by traceurs may be beneficial for other landing sports to incorporate into training to reduce injury.

Power Converters Maximize Outputs Of Solar Cell Strings

NASA Technical Reports Server (NTRS)

Frederick, Martin E.; Jermakian, Joel B.

1993-01-01

Microprocessor-controlled dc-to-dc power converters devised to maximize power transferred from solar photovoltaic strings to storage batteries and other electrical loads. Converters help in utilizing large solar photovoltaic arrays most effectively with respect to cost, size, and weight. Main points of invention are: single controller used to control and optimize any number of "dumb" tracker units and strings independently; power maximized out of converters; and controller in system is microprocessor.

Improving Large Cetacean Implantable Satellite Tag Designs to Maximize Tag Robustness and Minimize Health Effects to Individual Animals

DTIC Science & Technology

2013-09-30

Designs to Maximize Tag Robustness and Minimize Health Effects to Individual Animals Alexandre N. Zerbini Cascadia Research Collective 218 ½ 4th...the blubber-muscle interface and minimize physical and physiological effects of body penetrating tags to individual animals . OBJECTIVES (1...integrity of designs created in Objective (1) during laboratory experiments and in cetacean carcasses ; (3) Examine structural tissue damage in the

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

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.

Effect of ageing on hypoxic exercise cardiorespiratory, muscle and cerebral oxygenation responses in healthy humans.

PubMed

Puthon, Lara; Bouzat, Pierre; Robach, Paul; Favre-Juvin, Anne; Doutreleau, Stéphane; Verges, Samuel

2017-04-01

What is the central question of this study? This study aimed to determine the effect of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia during maximal incremental exercise. What is the main finding and its importance? Older healthy subjects had preserved hypoxic cardiorespiratory and tissue oxygenation responses at rest and during moderate exercise. At maximal exercise, they had a reduced hypoxic ventilatory response but similar maximal power output reduction compared with young individuals. This study suggests that until moderate exercise, hypoxic responses are preserved until the age of 70 years and therefore that ageing is not a contraindication for high-altitude sojourn. This study assessed the effects of ageing on cardiorespiratory and tissue oxygenation responses to hypoxia both at rest and during incremental maximal exercise. Sixteen young (20-30 years old) and 15 older healthy subjects (60-70 years old) performed two maximal incremental cycling tests in normoxia and hypoxia (inspiratory oxygen fraction 12%). Cardiorespiratory responses, prefrontal cortex and quadriceps tissue oxygenation (near-infrared spectroscopy) were measured during exercise as well as during hypercapnia at rest. The hypoxic ventilatory response was similar in young compared with older individuals at rest and during moderate-intensity exercise (50% maximal power output: young 0.9 ± 0.2 versus older 1.1 ± 0.8 l min -1  % -1 ; P > 0.05) but larger in young subjects during high-intensity exercise (maximal power output: 2.2 ± 0.8 versus 1.8 ± 1.1 l min -1  % -1 ; P < 0.05). The hypoxic cardiac response did not differ between groups both at rest and during exercise. During exercise in hypoxia, young subjects showed greater deoxygenation than older subjects, at both the prefrontal cortex and quadriceps levels. The hypoxia-induced reduction in maximal power output (young -32 ± 5% versus older -30 ± 6%; P > 0.05) and the hypercapnic responses did not differ between groups. Older healthy and active individuals below the age of 70 years have cardiorespiratory and tissue oxygenation responses to hypoxia similar to young individuals both at rest and during moderate-intensity exercise. Despite a lower hypoxic ventilatory response at maximal exercise, older individuals have similar oxygen desaturation and maximal power output reduction compared with young subjects. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

The Effect of Long-Term Therapeutics, Prophylaxis and Screening Techniques on Aircrew Medical Standards.

DTIC Science & Technology

1981-03-01

percentage of fat , maximal aerobic power, serum concentrations of triglycerides, total cholesterol and HDL cholesterol. This information is obtained fr-m each...drinkinq and physical activity related to health parameters su-h as wei ,iht , body fat content, maximal aerobic T1ewer and serum concentrations of...subjects, and the body fat is estimated from the body density (4). 3. The maximal aerobic power is assessed indirectly according to the method of Astrand

The Role of Autocrine-Paracrine Cascades in Breast Tumor Metastasis

DTIC Science & Technology

1999-08-01

tested a large series of anti-oxidants at non- toxic doses. The only compounds that worked in this series were resveratrol and curcumin . The...resveratrol gave a 20-35% maximal inhibition while the curcumin gave a maximal response between 40 and 60% maximal inhibition. While the resveratrol inhibited...IL-8 expression in both -7- THIS REPORT CONTAINS PROPRIETARY AND/OR UNPUBLISHED DATA the MD-231 and MD-435s cells, the inhibitory effects of curcumin

Using return on investment to maximize conservation effectiveness in Argentine grasslands

PubMed Central

Murdoch, William; Ranganathan, Jai; Polasky, Stephen; Regetz, James

2010-01-01

The rapid global loss of natural habitats and biodiversity, and limited resources, place a premium on maximizing the expected benefits of conservation actions. The scarcity of information on the fine-grained distribution of species of conservation concern, on risks of loss, and on costs of conservation actions, especially in developing countries, makes efficient conservation difficult. The distribution of ecosystem types (unique ecological communities) is typically better known than species and arguably better represents the entirety of biodiversity than do well-known taxa, so we use conserving the diversity of ecosystem types as our conservation goal. We define conservation benefit to include risk of conversion, spatial effects that reward clumping of habitat, and diminishing returns to investment in any one ecosystem type. Using Argentine grasslands as an example, we compare three strategies: protecting the cheapest land (“minimize cost”), maximizing conservation benefit regardless of cost (“maximize benefit”), and maximizing conservation benefit per dollar (“return on investment”). We first show that the widely endorsed goal of saving some percentage (typically 10%) of a country or habitat type, although it may inspire conservation, is a poor operational goal. It either leads to the accumulation of areas with low conservation benefit or requires infeasibly large sums of money, and it distracts from the real problem: maximizing conservation benefit given limited resources. Second, given realistic budgets, return on investment is superior to the other conservation strategies. Surprisingly, however, over a wide range of budgets, minimizing cost provides more conservation benefit than does the maximize-benefit strategy. PMID:21098281

Effect of Exercise Training and +Gz Acceleration Training on Men

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Simonson, Shawn R.; Stocks, Jodie M.; Evans, Joyce; Knapp, Charles F.; Cowell, Stephenie A.; Pemberton, Kendra N.; Wilson, Heather W.; Vener, Jamie M.; Evetts, Simon N.

2001-01-01

Countermeasures for reduction in work capacity (maximal oxygen uptake and strength) during spaceflight and enhanced orthostatic intolerance during re-entry, landing and egress from the return vehicle are continuing problems. The purpose for this study was to test the hypothesis that passive-acceleration training; supine, interval, exercise plus acceleration training and exercise combined with acceleration training would improve orthostatic tolerance in ambulatory men; and that addition of the aerobic exercise conditioning would not alter this improved tolerance from that of passive-acceleration training. Seven men (24-38 yr) underwent "Passive" training on the Ames human-powered centrifuge (HPC) for 30 min, "Exercise" training on the cycle ergometer with constant +Gz acceleration; and "Combined" exercise training at 40% to 90% of the HPC +Gz(max) exercise level. Maximal supine exercise loads increased significant (P<0.05) by 8.3% (Passive), 12.6% (Exercise), and by 15.4% (Combined) after training, but their post-training maximal oxygen uptakes and maximal heart rates were unchanged. Maximal time to fatigue (endurance) was unchanged with Passive was increased (P<0.05) with Exercise and Combined training. Thus, the exercise in the Exercise and Combined training Phases resulted in greater maximal loads and endurance without effect on maximal oxygen uptake or heart rate. There was a 4% to 6% increase (P<0.05) in all four quadriceps muscle volumes (right and left) after post-Combined training. Resting pre-tilt heart rate was elevated by 12.9% (P<0.05) only after Passive training suggesting that the exercise training attenuated the HR response. Plasma volume (% Delta) was uniformly decreased by 8% to 14% (P<0.05) at tilt-tolerance pre- vs. post-training indicating essentially no effect of training on the level of hypovolemia. Post-training tilt-tolerance time and heart rate were increased (P<0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training appeared to attenuate the increased Passive tilt-tolerance.

Influence of simulated microgravity on the maximal oxygen consumption of nontrained and trained rats

NASA Technical Reports Server (NTRS)

Woodman, Christopher R.; Monnin, Kimberly A.; Sebastian, Lisa A.; Tipton, Charles M.

1993-01-01

The effects of microgravity and endurance training (TR) on maximal O2 consumption was investigated in trained and nontrained (NT) rats subjected to head-down suspension (HDS) by comparing maximal O2 consumption, treadmill run time (RT), and mechanical efficiency (ME) of treadmill running in HDS rats, both NT and TR, and in respective cage controls. It was found that HDS for 28 days was associated with significant reduction in absolute maximal O2 consumption in both TR and NT rats. Relative maximal O2 consumption, however, was significantly reduced in TR but not NT rats. Reductions in RT and ME occurring in both TR and NT rats after 28 days of HDS were similar. The TR rats exhibited greater diuretic, natriuretic, and kaliuretic responses to HDS than the NT rats.

Stanol esters as a component of maximal dietary therapy in the National Cholesterol Education Program Adult Treatment Panel III report.

PubMed

Grundy, Scott M

2005-07-04

Use of plant stanols/sterols in forms that are sufficiently bioavailable for therapeutic effect should be a key element of maximal dietary therapy. This principle was recognized by National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and has been amply confirmed by experimental studies in humans. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) cholesterol levels has received less attention. The time has come, however, to reassert the importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease.

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.

The effect of acute maximal exercise on postexercise hemodynamics and central arterial stiffness in obese and normal-weight individuals.

PubMed

Bunsawat, Kanokwan; Ranadive, Sushant M; Lane-Cordova, Abbi D; Yan, Huimin; Kappus, Rebecca M; Fernhall, Bo; Baynard, Tracy

2017-04-01

Central arterial stiffness is associated with incident hypertension and negative cardiovascular outcomes. Obese individuals have higher central blood pressure (BP) and central arterial stiffness than their normal-weight counterparts, but it is unclear whether obesity also affects hemodynamics and central arterial stiffness after maximal exercise. We evaluated central hemodynamics and arterial stiffness during recovery from acute maximal aerobic exercise in obese and normal-weight individuals. Forty-six normal-weight and twenty-one obese individuals underwent measurements of central BP and central arterial stiffness at rest and 15 and 30 min following acute maximal exercise. Central BP and normalized augmentation index (AIx@75) were derived from radial artery applanation tonometry, and central arterial stiffness was obtained via carotid-femoral pulse wave velocity (cPWV) and corrected for central mean arterial pressure (cPWV/cMAP). Central arterial stiffness increased in obese individuals but decreased in normal-weight individuals following acute maximal exercise, after adjusting for fitness. Obese individuals also exhibited an overall higher central BP ( P  <   0.05), with no exercise effect. The increase in heart rate was greater in obese versus normal-weight individuals following exercise ( P  <   0.05), but there was no group differences or exercise effect for AIx@75 In conclusion, obese (but not normal-weight) individuals increased central arterial stiffness following acute maximal exercise. An assessment of arterial stiffness response to acute exercise may serve as a useful detection tool for subclinical vascular dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Effects of synchronous versus asynchronous mode of propulsion on wheelchair basketball sprinting.

PubMed

Faupin, Arnaud; Borel, Benoit; Meyer, Christophe; Gorce, Philippe; Watelain, Eric

2013-11-01

This study aimed to first investigate synchronous (SYN) versus asynchronous (ASY) mode of propulsion and, second, investigate the wheel camber effects on sprinting performance as well as temporal parameters. Seven wheelchair basketball players performed four maximal eight-second sprints on a wheelchair ergometer. They repeated the test according to two modes of propulsion (SYN and ASY) and two wheel cambers (9° and 15°). The mean maximal velocity and push power output was greater in the synchronous mode compared to the asynchronous mode for both camber angles. However, the fluctuation in the velocity profile is inferior for ASY versus SYN mode for both camber angles. Greater push time/cycle time (Pt/Ct) and arm frequency (AF) for synchronous mode versus asynchronous mode and inversely, lesser Ct and rest time (Rt) values for the synchronous mode, for which greater velocity were observed. SYN mode leads to better performance than ASY mode in terms of maximal propulsion velocity. However, ASY propulsion allows greater continuity of the hand-rim force application, reducing fluctuations in the velocity profile. The camber angle had no effect on ASY and SYN mean maximal velocity and push power output. The study of wheelchair propulsion strategies is important for better understanding physiological and biomechanical impacts of wheelchair propulsion for individuals with disabilities. From a kinematical point of view, this study highlights synchronous mode of propulsion to be more efficient, with regards to mean maximal velocity reaching during maximal sprinting exercises. Even if this study focuses on well-trained wheelchair athletes, results from this study could complement the knowledge on the physiological and biomechanical adaptations to wheelchair propulsion and therefore, might be interesting for wheelchair modifications for purposes of rehabilitation.

Effect of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of classical antiepileptic drugs against maximal electroshock-induced seizures in mice.

PubMed

Zagaja, Miroslaw; Pyrka, Daniel; Skalicka-Wozniak, Krystyna; Glowniak, Kazimierz; Florek-Luszczki, Magdalena; Glensk, Michał; Luszczki, Jarogniew J

2015-09-01

The effects of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Results indicate that xanthotoxin (50 and 100 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal electroshock-induced seizures (P<0.05 and P<0.001, respectively). Similarly, xanthotoxin (100 mg/kg, i.p.) markedly enhanced the anticonvulsant action of valproate in the maximal electroshock seizure test (P<0.001). In contrast, xanthotoxin (100 mg/kg, i.p.) did not affect the protective action of phenobarbital and phenytoin against maximal electroshock-induced seizures in mice. Moreover, xanthotoxin (100 mg/kg, i.p.) significantly increased total brain concentrations of carbamazepine (P<0.001) and valproate (P<0.05), but not those of phenytoin and phenobarbital, indicating pharmacokinetic nature of interactions between drugs. In conclusion, the combinations of xanthotoxin with carbamazepine and valproate, despite their beneficial effects in terms of seizure suppression in mice, were probably due to a pharmacokinetic increase in total brain concentrations of these antiepileptic drugs in experimental animals. Copyright © 2015. Published by Elsevier B.V.

Influence of resistance load on neuromuscular response to vibration training.

PubMed

Luo, Jin; Clarke, Michael; McNamara, Brian; Moran, Kieran

2009-03-01

The purpose of this study was to examine the influence of resistance load on the acute and acute residual effects of vibration training, with vibration applied directly to the bicep tendon in a maximal-effort dynamic resistance exercise (3 sets of maximal-effort bicep curls). Eleven participants were exposed to 4 training conditions in random order: exercise with 1 of 2 different loads (40% 1-repetition maximum [RM] or 70% 1RM load) combined with 1 of 2 vibration conditions (vibration [1.2 mm, 65 Hz] or sham vibration). Five minutes before and after the exercise, a set of maximal-effort bicep curls with a load of either 40 or 70% 1RM was performed as the pre- and posttraining test. Concentric elbow joint angular velocity, moment and power, and bicep root mean square electromyography (EMGrms) were measured during training and in the pre- and posttraining tests. The results show that during training (acute effect) and at 5 minutes after training (acute residual effect), vibration did not induce a significant change in EMGrms, mean and peak angular velocities, moment and power, time to peak power, and initial power at 100 milliseconds after the start of the concentric phase for either resistance load. Therefore, in aiming to train neuromuscular output using maximal-effort dynamic contractions (40 and 70% 1RM), there is no benefit in employing direct vibration, at least with a 1.2-mm amplitude and 65-Hz frequency. However, the amplitude of 1.2 mm may be too high to effectively stimulate neuromuscular output in maximal-effort dynamic contractions per se.

The effect of whole-body vibration therapy on bone metabolism, motor function, and anthropometric parameters in women with postmenopausal osteoporosis.

PubMed

Luo, Xiaotian; Zhang, Jifeng; Zhang, Chi; He, Chengqi; Wang, Pu

2017-11-01

To review the research literature on the effectiveness of whole-body vibration (WBV) therapy in women with postmenopausal osteoporosis. A systematic review was conducted by two independent reviewers. Mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I 2 test. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Nine randomized controlled trials involving 625 patients met the inclusion criteria. No significant improvement was found in bone mineral density (BMD) (SMD = -0.06, 95%CI= -0.22-0.11, p = 0.50); bone turnover markers (MD = -0.25, 95%CI= -0.54-0.03, p = 0.08); anthropometric parameters, including muscle mass, fat mass, body mass index (BMI), and weight (SMD = 0.02, 95%CI= -0.16-0.21, p = 0.81); or maximal isotonic knee extensor strength (SMD = 0.16, 95%CI= -0.63-0.95, p = 0.69). However, maximal isometric knee extensor strength improved (SMD = 0.71, 95%CI = 0.34-1.08, p = 0.0002). WBV is beneficial for enhancing maximal isometric knee extensor strength, but it has no overall treatment effect on BMD, bone turnover markers, anthropometric parameters, or maximal isotonic knee extensor strength in women with postmenopausal osteoporosis. Implication of rehabilitation Osteoporosis is the leading underlying cause of fractures in postmenopausal women, whole body vibration (WBV) has received much attention as a potential intervention for the management of osteoporosis in recent years. Whole body vibration is beneficial for enhancing maximal isometric knee extensor strength in women with postmenopausal osteoporosis. Whole body vibration has no overall treatment effect on bone mineral density, bone turnover markers, anthropometric parameters and maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.

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.

Maximal and submaximal endurance performance in adults with severe haemophilia.

PubMed

Herbsleb, M; Hilberg, T

2009-01-01

Maximal exercise testing, including the determination of maximal performance and maximal oxygen uptake (VO(2max)), is considered the gold standard for assessing maximal endurance performance. The effectiveness of such testing is often reduced in haemophilic adults owing to musculoskeletal impairments or pain rather than because of cardiac exertion. The measurement of submaximal performance parameters overcomes many limitations of maximal exercise testing but a testing standard is still lacking. The aim of this study was to investigate maximal and particularly submaximal endurance performance of adult patients with severe haemophilia A and B. Eleven patients and 11 matched healthy controls were tested by spiroergometry with a specific treadmill test and the power was calculated in Watts. The haemophilic group achieved lower absolute (210 +/- 63 W) and weight-related (2.94 +/- 0.98 W kg(-1)) maximal endurance performance compared with the control group (287 +/- 50 W resp. 3.82 +/- 0.53 W kg(-1); P

Carnot cycle at finite power: attainability of maximal efficiency.

PubMed

Allahverdyan, Armen E; Hovhannisyan, Karen V; Melkikh, Alexey V; Gevorkian, Sasun G

2013-08-02

We want to understand whether and to what extent the maximal (Carnot) efficiency for heat engines can be reached at a finite power. To this end we generalize the Carnot cycle so that it is not restricted to slow processes. We show that for realistic (i.e., not purposefully designed) engine-bath interactions, the work-optimal engine performing the generalized cycle close to the maximal efficiency has a long cycle time and hence vanishing power. This aspect is shown to relate to the theory of computational complexity. A physical manifestation of the same effect is Levinthal's paradox in the protein folding problem. The resolution of this paradox for realistic proteins allows to construct engines that can extract at a finite power 40% of the maximally possible work reaching 90% of the maximal efficiency. For purposefully designed engine-bath interactions, the Carnot efficiency is achievable at a large power.

The effect of lactate concentration on the handgrip strength during judo bouts.

PubMed

Bonitch-Góngora, Juan G; Bonitch-Domínguez, Juan G; Padial, Paulino; Feriche, Belen

2012-07-01

Judo is a combat sport in which the athletes attempt to hold and control their adversary through gripping techniques (kumi-kata) to apply opportune throwing techniques (nage-waza). Twelve male judo athletes, representing national teams, were recruited to investigate the changes in the maximal isometric strength in both hands before (pre) and after (post) 4 judo bouts and its relationship with the maximal blood lactic acid concentration. The subjects performed a maximal isometric contraction with each hand immediately before and after each bout. A blood sample was taken at 1, 3, and 14 minutes after each bout, and the lactic acid concentration was determined. An overall effect of the successive bouts on the maximal isometric handgrip strength of prebouts was observed for both hands (p < 0.05) but not in that of postbouts (p > 0.05). The dominant hand showed an overall decrease in the maximal isometric strength because of the bout, with the decrease being significant for the first, third, and fourth bouts (p < 0.05). The nondominant hand only showed a significant decrease in the first prebout and postbout (p < 0.05). We observed an inverse relationship between the maximal isometric handgrip strength of postbouts and maximum lactic acid concentration (Lacmax), and between the maximal isometric handgrip strength of postbouts and the lactic acid concentration at minute 14 of the recovery period (Lac14) (p < 0.05). These results show that successive judo bouts significantly reduce the maximal isometric strength of both hands and may suggest that fatigue of each hand depends on different factors. An enhanced understanding of the behavior of the isometric handgrip strength, and the factors that affect grip fatigue during judo bouts in the dominant and nondominant hands, can aid coaches in developing optimal training and exercise interventions that are aimed at mitigating decreases in the capacity of judo athletes to perform a grip.

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.

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

Influence of feedstock particle size on lignocellulose conversion--a review.

PubMed

Vidal, Bernardo C; Dien, Bruce S; Ting, K C; Singh, Vijay

2011-08-01

Feedstock particle sizing can impact the economics of cellulosic ethanol commercialization through its effects on conversion yield and energy cost. Past studies demonstrated that particle size influences biomass enzyme digestibility to a limited extent. Physical size reduction was able to increase conversion rates to maximum of ≈ 50%, whereas chemical modification achieved conversions of >70% regardless of biomass particle size. This suggests that (1) mechanical pretreatment by itself is insufficient to attain economically feasible biomass conversion, and, therefore, (2) necessary particle sizing needs to be determined in the context of thermochemical pretreatment employed for lignocellulose conversion. Studies of thermochemical pretreatments that have taken into account particle size as a factor have exhibited a wide range of maximal sizes (i.e., particle sizes below which no increase in pretreatment effectiveness, measured in terms of the enzymatic conversion resulting from the pretreatment, were observed) from <0.15 to 50 mm. Maximal sizes as defined above were dependent on the pretreatment employed, with maximal size range decreasing as follows: steam explosion > liquid hot water > dilute acid and base pretreatments. Maximal sizes also appeared dependent on feedstock, with herbaceous or grassy biomass exhibiting lower maximal size range (<3 mm) than woody biomass (>3 mm). Such trends, considered alongside the intensive energy requirement of size reduction processes, warrant a more systematic study of particle size effects across different pretreatment technologies and feedstock, as a requisite for optimizing the feedstock supply system.

Taking the easy way out? Increasing implementation effort reduces probability maximizing under cognitive load.

PubMed

Schulze, Christin; Newell, Ben R

2016-07-01

Cognitive load has previously been found to have a positive effect on strategy selection in repeated risky choice. Specifically, whereas inferior probability matching often prevails under single-task conditions, optimal probability maximizing sometimes dominates when a concurrent task competes for cognitive resources. We examined the extent to which this seemingly beneficial effect of increased task demands hinges on the effort required to implement each of the choice strategies. Probability maximizing typically involves a simple repeated response to a single option, whereas probability matching requires choice proportions to be tracked carefully throughout a sequential choice task. Here, we flipped this pattern by introducing a manipulation that made the implementation of maximizing more taxing and, at the same time, allowed decision makers to probability match via a simple repeated response to a single option. The results from two experiments showed that increasing the implementation effort of probability maximizing resulted in decreased adoption rates of this strategy. This was the case both when decision makers simultaneously learned about the outcome probabilities and responded to a dual task (Exp. 1) and when these two aspects were procedurally separated in two distinct stages (Exp. 2). We conclude that the effort involved in implementing a choice strategy is a key factor in shaping repeated choice under uncertainty. Moreover, highlighting the importance of implementation effort casts new light on the sometimes surprising and inconsistent effects of cognitive load that have previously been reported in the literature.

Anxiety responses to maximal exercise testing.

PubMed Central

O'Connor, P J; Petruzzello, S J; Kubitz, K A; Robinson, T L

1995-01-01

The influence of maximal exercise testing on state anxiety was examined in three separate studies. Highly trained male distance runners (Study 1, n = 12) as well as college students with average (Study 2, n = 16) and below average (Study 3, n = 32) physical fitness levels completed graded maximal exercise tests. This last group was also randomly assigned to either a control or an 8 week training programme in order to determine the effect of increased fitness on the psychological responses to maximal exercise testing. Physical fitness was determined by the measurement of maximal oxygen uptake. State anxiety (State-Trait Anxiety Inventory) was assessed before and from 2-15 min following exercise. It was found that the state anxiety responses to maximal exercise testing were not influenced by re-testing or by 8 weeks of endurance training. Across the three study groups, the anxiety response was variable during the first 5 min following exercise testing; increases, decreases and no changes in anxiety were observed when compared to pre-exercise levels. The anxiety response to maximal exercise appeared to be dependent on the pre-exercise anxiety levels as well as the timing of the post-exercise assessments. It is concluded that maximal exercise testing can be associated with negative mood shifts during the first 5 min after exercise; however, this response is transitory and followed by positive mood shifts 10-15 min following such tests. PMID:7551769

Neuromuscular function during knee extension exercise after cold water immersion.

PubMed

Wakabayashi, Hitoshi; Wijayanto, Titis; Tochihara, Yutaka

2017-06-23

Human adaptability to cold environment has been focused on in the physiological anthropology and related research area. Concerning the human acclimatization process in the natural climate, it is necessary to conduct a research assessing comprehensive effect of cold environment and physical activities in cold. This study investigated the effect of cold water immersion on the exercise performance and neuromuscular function during maximal and submaximal isometric knee extension. Nine healthy males participated in this study. They performed maximal and submaximal (20, 40, and 60% maximal load) isometric knee extension pre- and post-immersion in 23, 26, and 34 °C water. The muscle activity of the rectus femoris (RF) and vastus lateralis (VL) was measured using surface electromyography (EMG). The percentages of the maximum voluntary contraction (%MVC) and mean power frequency (MPF) of EMG data were analyzed. The post-immersion maximal force was significantly lower in 23 °C than in 26 and 34 °C conditions (P < 0.05). The post-immersion %MVC of RF was significantly higher than pre-immersion during 60% maximal exercise in 23 and 26 °C conditions (P < 0.05). In the VL, the post-immersion %MVC was significantly higher than pre-immersion in 23 and 26 °C conditions during 20% maximal exercise and in 26 °C at 40 and 60% maximal intensities (P < 0.05). The post-immersion %MVC of VL was significantly higher in 26 °C than in 34 °C at 20 and 60% maximal load (P < 0.05). The post-immersion MPF of RF during 20% maximal intensity was significantly lower in 23 °C than in 26 and 34 °C conditions (P < 0.05), and significantly different between three water temperature conditions at 40 and 60% maximal intensities (P < 0.05). The post-immersion MPF of VL during three submaximal trials were significantly lower in 23 and 26 °C than in 34 °C conditions (P < 0.05). The lower shift of EMG frequency would be connected with the decrease in the nerve and muscle fibers conduction velocity. To compensate for the impairment of each muscle fibers function, more muscle fibers might be recruited to maintain the working load. This might result in the greater amplitude of EMG after the cold immersion.

Morphology, mechanical, cross-linking, thermal, and tribological properties of nitrile and hydrogenated nitrile rubber/multi-walled carbon nanotubes composites prepared by melt compounding: The effect of acrylonitrile content and hydrogenation

NASA Astrophysics Data System (ADS)

Likozar, Blaž; Major, Zoltan

2010-11-01

The purpose of this work was to prepare nanocomposites by mixing multi-walled carbon nanotubes (MWCNT) with nitrile and hydrogenated nitrile elastomers (NBR and HNBR). Utilization of transmission electronic microscopy (TEM), scanning electron microscopy (SEM), and small- and wide-angle X-ray scattering techniques (SAXS and WAXS) for advanced morphology observation of conducting filler-reinforced nitrile and hydrogenated nitrile rubber composites is reported. Principal results were increases in hardness (maximally 97 Shore, type A), elastic modulus (maximally 981 MPa), tensile strength (maximally 27.7 MPa), elongation at break (maximally 216%), cross-link density (maximally 7.94 × 1028 m-3), density (maximally 1.16 g cm-3), and tear strength (11.2 kN m-1), which were clearly visible at particular acrylonitrile contents both for unhydrogenated and hydrogenated polymers due to enhanced distribution of carbon nanotubes (CNT) and their aggregated particles in the applied rubber matrix. Conclusion was that multi-walled carbon nanotubes improved the performance of nitrile and hydrogenated nitrile rubber nanocomposites prepared by melt compounding.

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.

Prostanoid-induced expression of matrix metalloproteinase-1 messenger ribonucleic acid in rat osteosarcoma cells

NASA Technical Reports Server (NTRS)

Clohisy, J. C.; Connolly, T. J.; Bergman, K. D.; Quinn, C. O.; Partridge, N. C.

1994-01-01

Individual prostanoids have distinct potencies in activating intracellular signaling pathways and regulating gene expression in osteoblastic cells. The E-series prostaglandins (PGs) are known to stimulate matrix metalloproteinase-1 (MMP-1) synthesis and secretion in certain rodent and human osteoblastic cells, yet the intracellular events involved remain unclear. To further characterize this response and its signal transduction pathway(s), we examined prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01. Northern blot analysis demonstrated that prostaglandin E2 (PGE2) and PGE1 were very potent stimulators (40-fold) of MMP-1 transcript abundance, PGF2 alpha and prostacyclin were weak stimulators (4-fold), and thromboxane-B2 had no effect. The marked increase in MMP-1 transcript abundance after PGE2 treatment was first detected at 2 h, became maximal at 4 h, and persisted beyond 24 h. This response was dose dependent and elicited maximal and half-maximal effects with concentrations of 10(-6) and 0.6 x 10(-7) M, respectively. Cycloheximide, a protein synthesis inhibitor, completely blocked this effect of PGE2, suggesting that the expression of other genes is required. Nuclear run-on experiments demonstrated that PGE2 rapidly activates MMP-1 gene transcription, with a maximal increase at 2-4 h. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 messenger RNA (mRNA) levels, with a maximal effect quantitatively similar to that observed with PGE2. Thus, in UMR 106-01 cells, different prostanoids have distinct potencies in stimulating MMP-1 mRNA abundance. Our data suggest that PGE2 stimulation of MMP-1 synthesis is due to activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 mRNA abundance. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase-A activation.

Effects of volume-based overload plyometric training on maximal-intensity exercise adaptations in young basketball players.

PubMed

Asadi, Abbas; Ramirez-Campillo, Rodrigo; Meylan, Cesar; Nakamura, Fabio Y; Cañas-Jamett, Rodrigo; Izquierdo, Mikel

2017-12-01

The aim of the present study was to compare maximal-intensity exercise adaptations in young basketball players (who were strong individuals at baseline) participating in regular basketball training versus regular plus a volume-based plyometric training program in the pre-season period. Young basketball players were recruited and assigned either to a plyometric with regular basketball training group (experimental group [EG]; N.=8), or a basketball training only group (control group [CG]; N.=8). The athletes in EG performed periodized (i.e., from 117 to 183 jumps per session) plyometric training for eight weeks. Before and after the intervention, players were assessed in vertical and broad jump, change of direction, maximal strength and a 60-meter sprint test. No significant improvements were found in the CG, while the EG improved vertical jump (effect size [ES] 2.8), broad jump (ES=2.4), agility T test (ES=2.2), Illinois agility test (ES=1.4), maximal strength (ES=1.8), and 60-m sprint (ES=1.6) (P<0.05) after intervention, and the improvements were greater compared to the CG (P<0.05). Plyometric training in addition to regular basketball practice can lead to meaningful improvements in maximal-intensity exercise adaptations among young basketball players during the pre-season.

Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics.

PubMed

Santos, Gilberto Monteiro dos; Montrezol, Fábio Tanil; Pauli, Luciana Santos Souza; Sartori-Cintra, Angélica Rossi; Colantonio, Emilson; Gomes, Ricardo José; Marinho, Rodolfo; Moura, Leandro Pereira de; Pauli, José Rodrigo

2014-01-01

To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training's equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.

Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics

PubMed Central

dos Santos, Gilberto Monteiro; Montrezol, Fábio Tanil; Pauli, Luciana Santos Souza; Sartori-Cintra, Angélica Rossi; Colantonio, Emilson; Gomes, Ricardo José; Marinho, Rodolfo; de Moura, Leandro Pereira; Pauli, José Rodrigo

2014-01-01

Objective To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. Methods The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training’s equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. Results The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Conclusion Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals. PMID:25628192

A Model of College Tuition Maximization

ERIC Educational Resources Information Center

Bosshardt, Donald I.; Lichtenstein, Larry; Zaporowski, Mark P.

2009-01-01

This paper develops a series of models for optimal tuition pricing for private colleges and universities. The university is assumed to be a profit maximizing, price discriminating monopolist. The enrollment decision of student's is stochastic in nature. The university offers an effective tuition rate, comprised of stipulated tuition less financial…

Holistic Admissions after Affirmative Action: Does "Maximizing" the High School Curriculum Matter?

ERIC Educational Resources Information Center

Bastedo, Michael N.; Howard, Joseph E.; Flaster, Allyson

2016-01-01

Selective colleges and universities purport to consider students' achievement in the context of the academic opportunities available in their high schools. Thus, students who "maximize" their curricular opportunities should be more likely to gain admission. Using nationally representative data, we examine the effect of "maximizing…

Using Maximal Isometric Force to Determine the Optimal Load for Measuring Dynamic Muscle Power

NASA Technical Reports Server (NTRS)

Spiering, Barry A.; Lee, Stuart M. C.; Mulavara, Ajitkumar P.; Bentley, Jason R.; Nash, Roxanne E.; Sinka, Joseph; Bloomberg, Jacob J.

2009-01-01

Maximal power output occurs when subjects perform ballistic exercises using loads of 30-50% of one-repetition maximum (1-RM). However, performing 1-RM testing prior to power measurement requires considerable time, especially when testing involves multiple exercises. Maximal isometric force (MIF), which requires substantially less time to measure than 1-RM, might be an acceptable alternative for determining the optimal load for power testing. PURPOSE: To determine the optimal load based on MIF for maximizing dynamic power output during leg press and bench press exercises. METHODS: Twenty healthy volunteers (12 men and 8 women; mean +/- SD age: 31+/-6 y; body mass: 72 +/- 15 kg) performed isometric leg press and bench press movements, during which MIF was measured using force plates. Subsequently, subjects performed ballistic leg press and bench press exercises using loads corresponding to 20%, 30%, 40%, 50%, and 60% of MIF presented in randomized order. Maximal instantaneous power was calculated during the ballistic exercise tests using force plates and position transducers. Repeated-measures ANOVA and Fisher LSD post hoc tests were used to determine the load(s) that elicited maximal power output. RESULTS: For the leg press power test, six subjects were unable to be tested at 20% and 30% MIF because these loads were less than the lightest possible load (i.e., the weight of the unloaded leg press sled assembly [31.4 kg]). For the bench press power test, five subjects were unable to be tested at 20% MIF because these loads were less than the weight of the unloaded aluminum bar (i.e., 11.4 kg). Therefore, these loads were excluded from analysis. A trend (p = 0.07) for a main effect of load existed for the leg press exercise, indicating that the 40% MIF load tended to elicit greater power output than the 60% MIF load (effect size = 0.38). A significant (p . 0.05) main effect of load existed for the bench press exercise; post hoc analysis indicated that the effect of load on power output was: 30% > 40% > 50% = 60%. CONCLUSION: Loads of 40% and 30% of MIF elicit maximal power output during dynamic leg presses and bench presses, respectively. These findings are similar to those obtained when loading is based on 1-RM.

The jet-disk symbiosis without maximal jets: 1D hydrodynamical jets revisited

NASA Astrophysics Data System (ADS)

Crumley, Patrick; Ceccobello, Chiara; Connors, Riley M. T.; Cavecchi, Yuri

2017-05-01

In this work we discuss the recent criticism by Zdziarski (2016, A&A, 586, A18) of the maximal jet model derived in Falcke & Biermann (1995, A&A, 293, 665). We agree with Zdziarski that in general a jet's internal energy is not bounded by its rest-mass energy density. We describe the effects of the mistake on conclusions that have been made using the maximal jet model and show when a maximal jet is an appropriate assumption. The maximal jet model was used to derive a 1D hydrodynamical model of jets in agnjet, a model that does multiwavelength fitting of quiescent/hard state X-ray binaries and low-luminosity active galactic nuclei. We correct algebraic mistakes made in the derivation of the 1D Euler equation and relax the maximal jet assumption. We show that the corrections cause minor differences as long as the jet has a small opening angle and a small terminal Lorentz factor. We find that the major conclusion from the maximal jet model, the jet-disk symbiosis, can be generally applied to astrophysical jets. We also show that isothermal jets are required to match the flat radio spectra seen in low-luminosity X-ray binaries and active galactic nuclei, in agreement with other works.

The protective effect of superoxide dismutase on isolated human mammary arteries preincubated with triglyceride-rich remnant lipoproteins.

PubMed

Savoiu, Germaine; Drăgan, Simona; Cristescu, Carmen; Serban, Corină; Noveanu, Lavinia; Ionescu, Daniela; Nicola, T; Duicu, Oana; Răducan, Andreea; Voicu, Mirela

2009-01-01

The main changes of the plasma lipid profile in patients with endothelial dysfunction are the increased triglyceride content of the lipoprotein remnant particles, the presence of the small and dense LDL particles and the decreasing of the HDL-cholesterol level. Considering these observations, we performed "in vitro" experiments using human mammary artery rings, in order to examine the effect of the lipoprotein "remnants" on endothelium-dependent vasodilatation induced by cumulative doses (10(-9) M - 10(-4) M) of adenosine (ADP) and to study the effect on endothelial--independent vasodilatation induced by cumulative doses (10(-9) M-10(-4) M) of sodium-nitropruside (NSP), respectively. Our results showed that 1 hour pre-incubation with triglyceride--rich lipoprotein remnants diminished the endothelial-dependent vasodilator response to ADP, but it has not modified the endothelial-independent vasodilator response to NSP. Vascular response was expressed as maximal vasodilatation from the 10(-4)M phenilephrine (PE) induced pre-contraction, considered as reference. In the case of ADP, the maximal vasodilatation was ranged in 36.50% +/- 10.81% interval, comparing with the control group that presented a maximal vasodilatation of 66.15% +/- 19.41% (p < 0.005). In the case of NSP the maximal vasodilatation was ranged in 99.78% +/- 10.53% interval, comparing with the control that presented a maximal vasodilatation of 98.99% +/- 12.45% (p = 0.44). One hour co-incubation of the rings with a solution containing lipoprotein remnants (1% oxidized IDL (ox-IDL) and antioxidant factor (150 U/mL 10(-4) M Superoxid dismutase (SOD) significantly reduced the impairment of the vasodilatation response to ADP. Maximal vasodilatation of ox-IDL and SOD coincubated human mammary artery rings was 58.50% +/- 10.63% compared to the control, were the maximal vasodilatation was 66.15% +/- 19.41% (p < 0.01), but has not modified the vasodilatation response to NSP (99% +/- 0.53% vs control 98.99% +/- 12.45%, p = 0.56). The endothelial dysfunction induced by the triglyceride-rich lipoprotein "remnants", could contribute to the pathogenesis of atherosclerosis and the treatment with high doses of antioxidants could "protect" the endothelium against the pro-atherogenic action of the lipoprotein "remnants".

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.

Improving Large Cetacean Implantable Satellite Tag Designs to Maximize Tag Robustness and Minimize Health Effects to Individual Animals

DTIC Science & Technology

2015-09-30

Olympia, WA, 98501 & National Marine Mammal Laboratory Alaska Fisheries Science Center, NOAA Fisheries 7600 Sand Point Way NE Seattle, WA...to Maximize Tag Robustness and Minimize Health Effects to Individual Animals Alexandre N. Zerbini Cascadia Research Collective 218 ½ 4 th Ave W...available to the marine mammal community after the conclusion of the project. This study has been carried out by scientists and engineers from eight

Benchmarking B-Cell Epitope Prediction with Quantitative Dose-Response Data on Antipeptide Antibodies: Towards Novel Pharmaceutical Product Development

PubMed Central

Caoili, Salvador Eugenio C.

2014-01-01

B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data. PMID:24949474

High-intensity and resistance training and elite young athletes.

PubMed

Ratel, Sébastien

2011-01-01

Although in the past resistance and high-intensity exercise training among young children was the subject of numerous controversies, it is now well-documented that this training mode is a safe and effective means of developing maximal strength, maximal power output and athletic performance in youth, provided that exercises are performed with appropriate supervision and precautions. Muscular strength and power output values measured from vertical jump and Wingate anaerobic tests are higher in elite than in non-elite young athletes and normal children, and the specific training effects on maximal power output normalised for body size are clearly more distinct before puberty. At present, there is no scientific evidence to support the view that high-intensity and/or resistance training might hinder growth and maturation in young children. Pre-pubertal growth is not adversely affected by sport at a competitive level and anthropometric factors are of importance for choice of sport in children. However, coaches, teachers and parents should be aware that unsupervised high-intensity and resistance training programmes involving maximal loads or too frequently repeated resistance exercises increase the risk of injury. Resistance training alone is an effective additional means of developing athletic performance throughout planned youth sports training programmes. Strategies for enhancing the effectiveness and safety of youth resistance and high-intensity exercise training are discussed in this chapter. Copyright © 2011 S. Karger AG, Basel.

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.

Women’s Sexual Arousal: Effects of High Alcohol Dosages and Self-Control Instructions

PubMed Central

George, William H.; Davis, Kelly Cue; Heiman, Julia R.; Norris, Jeanette; Stoner, Susan A.; Schacht, Rebecca L.; Hendershot, Christian S.; Kajumulo, Kelly F.

2011-01-01

The basic relationship between alcohol and women’s sexual arousal – especially genital arousal –received little research attention for nearly 30 years (e.g. Wilson & Lawson, 1978) until very recently (e.g. George et al., 2009). To investigate hypotheses based on earlier findings and Alcohol Myopia Theory (AMT), two experiments evaluated the effects of high blood alcohol concentrations (BACs) and arousal instructional demands on indices of vaginal responding and self-reported sexual arousal. In Experiment 1, self-control instructions to maximize (versus suppress) arousal increased peak and average Vaginal Pulse Amplitude (VPA) change. Self-control also interacted with a target BAC of .08% (versus .00%) to influence latency to peak arousal onset: Intoxicated women instructed to maximize showed a shorter latency to peak arousal than did intoxicated women instructed to suppress; however, sober women showed the same pattern. Also, in Experiment 1, the target BAC of .08% had no effect on VPA or subjective arousal measures. In Experiment 2, a target BAC of .10% (versus .00%) attenuated peak change and average change in VPA, but this dosage had no effects on latency to peak achieved arousal, or on subjective arousal. Instructions to maximize arousal (versus no instruction) had no effect on any arousal measures. Overall, among young moderate drinking women, alcohol had attenuating effects but only at the higher dosage. Maximize versus suppress instructions about arousal had predicted effects on arousal and interactive effects on latency, but only at the lower dosage. The findings highlight the importance of dosage and contextual factors in alcohol’s impact on the variability of women’s sexual responding. PMID:21439287

Effect of TPA on ion fluxes and DNA synthesis in vascular smooth muscle cells

PubMed Central

1985-01-01

Previous reports have suggested that phorbol esters can decrease the affinity of epidermal growth factor (EGF) for its cellular receptors. Investigations of the consequences of the interaction between phorbol esters and EGF, however, have been limited to EGF-stimulated Na/H exchange in A431 cells (Whitely, B., D. Cassel, Y.-X. Zuang, and L. Glaser, 1984, J. Cell Biol., 99:1162-1166). In the present study, the effect of the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) on EGF-stimulated ion transport and DNA synthesis was determined in cultured vascular smooth muscle cells (A7r5). It was found that TPA stimulated Na/H exchange when added alone (half-maximal stimulatory concentration, 25 nM). However, when cells were pretreated with TPA and then challenged with EGF, TPA significantly inhibited EGF-stimulated Na/H exchange (78%; half-maximal inhibition [Ki] at 2.5 nM). Subsequently the effects of TPA on Na/K/Cl co-transport were measured. TPA was observed to inhibit Na/K/Cl co-transport (half-maximal inhibitory concentration, 50 nM) and also to inhibit EGF-stimulated Na/K/Cl co-transport (100%; Ki at 5 nM). Finally, the effects of TPA on DNA synthesis were assessed. TPA had a modest stimulatory effect on DNA synthesis (half-maximal stimulatory concentration, 6 nM), but had a significant inhibitory effect on EGF-stimulated DNA synthesis (56%; Ki at 5 nM). These findings suggest that the inhibitory effect of TPA on EGF-receptor functions goes beyond previously reported effects on Na/H exchange in A431 cells and extends to EGF-stimulation of Na/K/Cl co- transport and DNA synthesis in vascular smooth muscle cells. PMID:2410432

Partial agonists for α4β2 nicotinic receptors stimulate dopaminergic neuron firing with relatively enhanced maximal effects

PubMed Central

Chen, Ying; Broad, Lisa M; Phillips, Keith G; Zwart, Ruud

2012-01-01

BACKGROUND AND PURPOSE Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows weak receptor activation to induce maximum physiological effects. We assessed the extent of α4β2 partial agonist-induced increase of firing rate in dopaminergic neurons and evaluated the influence of receptor reserve. EXPERIMENTAL APPROACH The relative maximal effects and potencies of six nicotinic agonists were assessed on recombinant human α4β2 and α7 receptors expressed in mammalian cell lines by measuring calcium influx. Agonist-induced increase of the spontaneous firing rate of dopaminergic neurons was recorded using microelectrodes in the ventral tegmental area of rat brain slices. KEY RESULTS All α4β2 partial and full agonists increased the firing rate concentration-dependently. Their sensitivity to subtype-selective antagonists showed predominant activation of native α4β2* receptors. However, partial agonists with relative maximal effects as low as 33% on α4β2 receptors maximally increased the firing rate and induced additional depolarization block of firing, demonstrating that partial activation of receptors caused the maximum increase in firing rate in the presence of a receptor reserve. CONCLUSIONS AND IMPLICATIONS Partial α4β2 agonists induced relatively enhanced effects on the firing rate of dopaminergic neurons, and the effect was mainly attributed to the existence of native α4β2* receptor reserve. The results have implications in the understanding of physiological effects and therapeutic efficacies of α4β2 partial agonists. PMID:21838750

Do Nondomestic Undergraduates Choose a Major Field in Order to Maximize Grade Point Averages?

ERIC Educational Resources Information Center

Bergman, Matthew E.; Fass-Holmes, Barry

2016-01-01

The authors investigated whether undergraduates attending an American West Coast public university who were not U.S. citizens (nondomestic) maximized their grade point averages (GPA) through their choice of major field. Multiple regression hierarchical linear modeling analyses showed that major field's effect size was small for these…

Early effects of ageing on the mechanical performance of isolated locomotory (EDL) and respiratory (diaphragm) skeletal muscle using the work-loop technique.

PubMed

Tallis, Jason; James, Rob S; Little, Alexander G; Cox, Val M; Duncan, Michael J; Seebacher, Frank

2014-09-15

Previous isolated muscle studies examining the effects of ageing on contractility have used isometric protocols, which have been shown to have poor relevance to dynamic muscle performance in vivo. The present study uniquely uses the work-loop technique for a more realistic estimation of in vivo muscle function to examine changes in mammalian skeletal muscle mechanical properties with age. Measurements of maximal isometric stress, activation and relaxation time, maximal power output, and sustained power output during repetitive activation and recovery are compared in locomotory extensor digitorum longus (EDL) and core diaphragm muscle isolated from 3-, 10-, 30-, and 50-wk-old female mice to examine the early onset of ageing. A progressive age-related reduction in maximal isometric stress that was of greater magnitude than the decrease in maximal power output occurred in both muscles. Maximal force and power developed earlier in diaphragm than EDL muscle but demonstrated a greater age-related decline. The present study indicates that ability to sustain skeletal muscle power output through repetitive contraction is age- and muscle-dependent, which may help rationalize previously reported equivocal results from examination of the effect of age on muscular endurance. The age-related decline in EDL muscle performance is prevalent without a significant reduction in muscle mass, and biochemical analysis of key marker enzymes suggests that although there is some evidence of a more oxidative fiber type, this is not the primary contributor to the early age-related reduction in muscle contractility. Copyright © 2014 the American Physiological Society.

Why Contextual Preference Reversals Maximize Expected Value

PubMed Central

2016-01-01

Contextual preference reversals occur when a preference for one option over another is reversed by the addition of further options. It has been argued that the occurrence of preference reversals in human behavior shows that people violate the axioms of rational choice and that people are not, therefore, expected value maximizers. In contrast, we demonstrate that if a person is only able to make noisy calculations of expected value and noisy observations of the ordinal relations among option features, then the expected value maximizing choice is influenced by the addition of new options and does give rise to apparent preference reversals. We explore the implications of expected value maximizing choice, conditioned on noisy observations, for a range of contextual preference reversal types—including attraction, compromise, similarity, and phantom effects. These preference reversal types have played a key role in the development of models of human choice. We conclude that experiments demonstrating contextual preference reversals are not evidence for irrationality. They are, however, a consequence of expected value maximization given noisy observations. PMID:27337391

Effects of Strength Training on Postpubertal Adolescent Distance Runners.

PubMed

Blagrove, Richard C; Howe, Louis P; Cushion, Emily J; Spence, Adam; Howatson, Glyn; Pedlar, Charles R; Hayes, Philip R

2018-06-01

Strength training activities have consistently been shown to improve running economy (RE) and neuromuscular characteristics, such as force-producing ability and maximal speed, in adult distance runners. However, the effects on adolescent (<18 yr) runners remains elusive. This randomized control trial aimed to examine the effect of strength training on several important physiological and neuromuscular qualities associated with distance running performance. Participants (n = 25, 13 female, 17.2 ± 1.2 yr) were paired according to their sex and RE and randomly assigned to a 10-wk strength training group (STG) or a control group who continued their regular training. The STG performed twice weekly sessions of plyometric, sprint, and resistance training in addition to their normal running. Outcome measures included body mass, maximal oxygen uptake (V˙O2max), speed at V˙O2max, RE (quantified as energy cost), speed at fixed blood lactate concentrations, 20-m sprint, and maximal voluntary contraction during an isometric quarter-squat. Eighteen participants (STG: n = 9, 16.1 ± 1.1 yr; control group: n = 9, 17.6 ± 1.2 yr) completed the study. The STG displayed small improvements (3.2%-3.7%; effect size (ES), 0.31-0.51) in RE that were inferred as "possibly beneficial" for an average of three submaximal speeds. Trivial or small changes were observed for body composition variables, V˙O2max and speed at V˙O2max; however, the training period provided likely benefits to speed at fixed blood lactate concentrations in both groups. Strength training elicited a very likely benefit and a possible benefit to sprint time (ES, 0.32) and maximal voluntary contraction (ES, 0.86), respectively. Ten weeks of strength training added to the program of a postpubertal distance runner was highly likely to improve maximal speed and enhances RE by a small extent, without deleterious effects on body composition or other aerobic parameters.

Effects of upper-body sprint-interval training on strength and endurance capacities in female cross-country skiers

PubMed Central

Vandbakk, Kristine; Welde, Boye; Kruken, Andrea Hovstein; Baumgart, Julia; Ettema, Gertjan; Karlsen, Trine; Sandbakk, Øyvind

2017-01-01

This study compared the effects of adding upper-body sprint-intervals or continuous double poling endurance training to the normal training on maximal upper-body strength and endurance capacity in female cross-country skiers. In total, 17 female skiers (age: 18.1±0.8yr, body mass: 60±7 kg, maximal oxygen uptake (VO2max): 3.30±0.37 L.min-1) performed an 8-week training intervention. Here, either two weekly sessions of six to eight 30-s maximal upper-body double poling sprint-intervals (SIG, n = 8) or 45–75 min of continuous low-to-moderate intensity double poling on roller skis (CG, n = 9) were added to their training. Before and after the intervention, the participants were tested for physiological and kinematical responses during submaximal and maximal diagonal and double poling treadmill roller skiing. Additionally, we measured maximal upper-body strength (1RM) and average power at 40% 1RM in a poling-specific strength exercise. SIG improved absolute VO2max in diagonal skiing more than CG (8% vs 2%, p<0.05), and showed a tendency towards higher body-mass normalized VO2max (7% vs 2%, p = 0.07). Both groups had an overall improvement in double poling peak oxygen uptake (10% vs 6% for SIG and CG) (both p<0.01), but no group-difference was observed. SIG improved 1RM strength more than CG (18% vs 10%, p<0.05), while there was a tendency for difference in average power at 40% 1RM (20% vs 14%, p = 0.06). Oxygen cost and kinematics (cycle length and rate) in double poling and diagonal remained unchanged in both groups. In conclusion, our study demonstrates that adding upper-body sprint-interval training is more effective than continuous endurance training in improving upper-body maximal strength and VO2max. PMID:28241030

Effects of chronic nitric oxide synthase inhibition on V'O2max and exercise capacity in mice.

PubMed

Wojewoda, M; Przyborowski, K; Sitek, B; Zakrzewska, A; Mateuszuk, L; Zoladz, J A; Chlopicki, S

2017-03-01

Acute inhibition of NOS by L-NAME (N ω -nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V'O 2max ) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V'O 2max and exercise performance have not been studied so far. In this study, we analysed the effect of L-NAME treatment, (LN2 and LN12, respectively) on V'O 2max and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO 2 - ) and nitrate (NO 3 - )) and prostacyclin (PGI 2 ) production in C57BL6/J mice. Mice treated with L-NAME for 2 weeks (LN2) displayed higher V'O 2max and better running capacity than age-matched control mice. In LN2 mice, NO bioavailability was preserved, as evidenced by maintained NO 2 - plasma concentration. PGI 2 production was activated (increased 6-keto-PGF 1α plasma concentration) and the number of circulating erythrocytes (RBC) and haemoglobin concentration were increased. In mice treated with L-NAME for 12 weeks (LN12), NO bioavailability was decreased (lower NO 2 - plasma concentration), and 6-keto-PGF 1α plasma concentration and RBC number were not elevated compared to age-matched control mice. However, LN12 mice still performed better during the maximal incremental running test despite having lower V'O 2max . Interestingly, the LN12 mice showed poorer running capacity during the prolonged sub-maximal incremental running test. To conclude, short-term (2 weeks) but not long-term (12 weeks) treatment with L-NAME activated robust compensatory mechanisms involving preservation of NO2- plasma concentration, overproduction of PGI 2 and increased number of RBCs, which might explain the fully preserved exercise capacity despite the inhibition of NOS.

General form of a cooperative gradual maximal covering location problem

NASA Astrophysics Data System (ADS)

Bagherinejad, Jafar; Bashiri, Mahdi; Nikzad, Hamideh

2018-07-01

Cooperative and gradual covering are two new methods for developing covering location models. In this paper, a cooperative maximal covering location-allocation model is developed (CMCLAP). In addition, both cooperative and gradual covering concepts are applied to the maximal covering location simultaneously (CGMCLP). Then, we develop an integrated form of a cooperative gradual maximal covering location problem, which is called a general CGMCLP. By setting the model parameters, the proposed general model can easily be transformed into other existing models, facilitating general comparisons. The proposed models are developed without allocation for physical signals and with allocation for non-physical signals in discrete location space. Comparison of the previously introduced gradual maximal covering location problem (GMCLP) and cooperative maximal covering location problem (CMCLP) models with our proposed CGMCLP model in similar data sets shows that the proposed model can cover more demands and acts more efficiently. Sensitivity analyses are performed to show the effect of related parameters and the model's validity. Simulated annealing (SA) and a tabu search (TS) are proposed as solution algorithms for the developed models for large-sized instances. The results show that the proposed algorithms are efficient solution approaches, considering solution quality and running time.

Causal Attribution and Coping Maxims Differences between Immigrants and Non-Immigrants Suffering from Back Pain in Switzerland.

PubMed

Mantwill, Sarah; Schulz, Peter J

2016-01-01

This study aimed at investigating the relationship between causal attributions and coping maxims in people suffering from back pain. Further, it aimed at identifying in how far causal attributions and related coping maxims would defer between immigrants and non-immigrants in Switzerland. Data for this study came from a larger survey study that was conducted among immigrant populations in the German- and Italian-speaking part of Switzerland. Included in the analyses were native Swiss participants, as well as Albanian- and Serbian-speaking immigrants, who had indicated to have suffered from back pain within the last 12 months prior to the study. Data was analyzed for overall 495 participants. Items for causal attributions and coping maxims were subject to factor analyses. Cultural differences were assessed with ANOVA and regression analyses. Interaction terms were included to investigate whether the relationship between causal attributions and coping maxims would differ with cultural affiliation. For both immigrant groups the physician's influence on the course of their back pain was more important than for Swiss participants (p <.05). With regard to coping, both immigrant groups were more likely to agree with maxims that were related to the improvement of the back pain, as well as the acceptance of the current situation (p <.05). The only consistent interaction effect that was found indicated that being Albanian-speaking negatively moderated the relationship between physical activity as an attributed cause of back pain and all three identified coping maxims. The study shows that differences in causal attribution and coping maxims between immigrants and non-immigrants exist. Further, the results support the assumption of an association between causal attribution and coping maxims. However cultural affiliation did not considerably moderate this relationship.

Causal Attribution and Coping Maxims Differences between Immigrants and Non-Immigrants Suffering from Back Pain in Switzerland

PubMed Central

2016-01-01

Objectives This study aimed at investigating the relationship between causal attributions and coping maxims in people suffering from back pain. Further, it aimed at identifying in how far causal attributions and related coping maxims would defer between immigrants and non-immigrants in Switzerland. Methods Data for this study came from a larger survey study that was conducted among immigrant populations in the German- and Italian-speaking part of Switzerland. Included in the analyses were native Swiss participants, as well as Albanian- and Serbian-speaking immigrants, who had indicated to have suffered from back pain within the last 12 months prior to the study. Data was analyzed for overall 495 participants. Items for causal attributions and coping maxims were subject to factor analyses. Cultural differences were assessed with ANOVA and regression analyses. Interaction terms were included to investigate whether the relationship between causal attributions and coping maxims would differ with cultural affiliation. Results For both immigrant groups the physician’s influence on the course of their back pain was more important than for Swiss participants (p <.05). With regard to coping, both immigrant groups were more likely to agree with maxims that were related to the improvement of the back pain, as well as the acceptance of the current situation (p <.05). The only consistent interaction effect that was found indicated that being Albanian-speaking negatively moderated the relationship between physical activity as an attributed cause of back pain and all three identified coping maxims. Conclusion The study shows that differences in causal attribution and coping maxims between immigrants and non-immigrants exist. Further, the results support the assumption of an association between causal attribution and coping maxims. However cultural affiliation did not considerably moderate this relationship. PMID:27583445

A new augmentation based algorithm for extracting maximal chordal subgraphs

DOE PAGES

Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

2014-10-18

If every cycle of a graph is chordal length greater than three then it contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms’more » parallelizability. In our paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. Finally, we experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.« less

A New Augmentation Based Algorithm for Extracting Maximal Chordal Subgraphs.

PubMed

Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

2015-02-01

A graph is chordal if every cycle of length greater than three contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms' parallelizability. In this paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. We experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.

Optimization in the utility maximization framework for conservation planning: a comparison of solution procedures in a study of multifunctional agriculture

PubMed Central

Stoms, David M.; Davis, Frank W.

2014-01-01

Quantitative methods of spatial conservation prioritization have traditionally been applied to issues in conservation biology and reserve design, though their use in other types of natural resource management is growing. The utility maximization problem is one form of a covering problem where multiple criteria can represent the expected social benefits of conservation action. This approach allows flexibility with a problem formulation that is more general than typical reserve design problems, though the solution methods are very similar. However, few studies have addressed optimization in utility maximization problems for conservation planning, and the effect of solution procedure is largely unquantified. Therefore, this study mapped five criteria describing elements of multifunctional agriculture to determine a hypothetical conservation resource allocation plan for agricultural land conservation in the Central Valley of CA, USA. We compared solution procedures within the utility maximization framework to determine the difference between an open source integer programming approach and a greedy heuristic, and find gains from optimization of up to 12%. We also model land availability for conservation action as a stochastic process and determine the decline in total utility compared to the globally optimal set using both solution algorithms. Our results are comparable to other studies illustrating the benefits of optimization for different conservation planning problems, and highlight the importance of maximizing the effectiveness of limited funding for conservation and natural resource management. PMID:25538868

Optimization in the utility maximization framework for conservation planning: a comparison of solution procedures in a study of multifunctional agriculture

USGS Publications Warehouse

Kreitler, Jason R.; Stoms, David M.; Davis, Frank W.

2014-01-01

Quantitative methods of spatial conservation prioritization have traditionally been applied to issues in conservation biology and reserve design, though their use in other types of natural resource management is growing. The utility maximization problem is one form of a covering problem where multiple criteria can represent the expected social benefits of conservation action. This approach allows flexibility with a problem formulation that is more general than typical reserve design problems, though the solution methods are very similar. However, few studies have addressed optimization in utility maximization problems for conservation planning, and the effect of solution procedure is largely unquantified. Therefore, this study mapped five criteria describing elements of multifunctional agriculture to determine a hypothetical conservation resource allocation plan for agricultural land conservation in the Central Valley of CA, USA. We compared solution procedures within the utility maximization framework to determine the difference between an open source integer programming approach and a greedy heuristic, and find gains from optimization of up to 12%. We also model land availability for conservation action as a stochastic process and determine the decline in total utility compared to the globally optimal set using both solution algorithms. Our results are comparable to other studies illustrating the benefits of optimization for different conservation planning problems, and highlight the importance of maximizing the effectiveness of limited funding for conservation and natural resource management.

The anti-tumor effect and biological activities of the extract JMM6 from the stem-barks of the Chinese Juglans mandshurica Maxim on human hepatoma cell line BEL-7402.

PubMed

Zhang, Yongli; Cui, Yuqiang; Zhu, Jiayong; Li, Hongzhi; Mao, Jianwen; Jin, Xiaobao; Wang, Xiangsheng; Du, Yifan; Lu, Jiazheng

2013-01-01

Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the extracted compound JMM6 were studied in BEL-7402 cells by MTT, Cell cycle analysis, Hoechst 33342 staining, Annexin V-FITC/PI assay and Detection of mitochondrial membrane potential (ΔΨm). After treatment with the JMM6, the growth of BEL-7402 cells was inhibited and cells displayed typical morphological apoptotic characteristics. Further investigations revealed that treatment with JMM6 mainly caused G2/M cell cycle arrest and induced apoptosis in BEL-7402 cells. To evaluate the alteration of mitochondria in JMM6 induced apoptosis. The data showed that JMM6 decreased significantly the ΔΨm, causing the depolarization of the mitochondrial membrane. Our results show that the JMM6 will have a potential advantage of anti-tumor, less harmful to normal cells. This paper not only summarized the JMM6 pick-up technology from Juglans mandshurica Maxim and biological characteristic, but also may provide further evidence to exploit the potential medicine compounds from the stem-barks of the Chinese Juglans mandshurica Maxim.

Robust 2DPCA with non-greedy l1 -norm maximization for image analysis.

PubMed

Wang, Rong; Nie, Feiping; Yang, Xiaojun; Gao, Feifei; Yao, Minli

2015-05-01

2-D principal component analysis based on l1 -norm (2DPCA-L1) is a recently developed approach for robust dimensionality reduction and feature extraction in image domain. Normally, a greedy strategy is applied due to the difficulty of directly solving the l1 -norm maximization problem, which is, however, easy to get stuck in local solution. In this paper, we propose a robust 2DPCA with non-greedy l1 -norm maximization in which all projection directions are optimized simultaneously. Experimental results on face and other datasets confirm the effectiveness of the proposed approach.

Endurance Training and V˙O2max: Role of Maximal Cardiac Output and Oxygen Extraction.

PubMed

Montero, David; Diaz-Cañestro, Candela; Lundby, Carsten

2015-10-01

Although endurance training (ET) commonly augments maximal oxygen consumption (V˙O2max), it remains unclear whether such increase is associated with that of maximal cardiac output (Qmax) alone or along with arteriovenous oxygen difference (a-V˙O2diff). Herein, we sought to systematically review and determine the effects of ET on V˙O2max, Qmax, and a-V˙O2diff at maximal exercise, and on their associations, in healthy young subjects. We conducted a systematic search of MEDLINE, Scopus, and Web of Science (from their inception until September 2014) for articles assessing the effects of ET lasting ≥3 wk on V˙O2max and Qmax and/or a-V˙O2diff at maximal exercise in healthy young adults (mean age <40 yr). Meta-analyses were performed to determine standardized mean differences (SMD) in V˙O2max, Qmax, and a-V˙O2diff at maximal exercise between posttraining and pretraining measurements. Subgroup and meta-regression analyses were used to evaluate associations among SMD and potential moderating factors. Thirteen studies were included after systematic review, comprising a total of 130 untrained or moderately trained healthy young subjects (mean age, 22-28 yr). Duration of ET programs ranged from 5 to 12.9 wk. After data pooling, V˙O2max (SMD = 0.75, P < 0.0001) and Qmax (SMD = 0.64, P < 0.0001), but not a-V˙O2diff at maximal exercise (SMD = 0.21, P = 0.23), were increased after ET. No significant heterogeneity was detected. With meta-regression, the SMD in Qmax was positively associated with the SMD in V˙O2max (B = 0.91, P = 0.007). The SMD in a-V˙O2diff at maximal exercise was not associated with the SMD in V˙O2max (B = 0.20, P = 0.40). Based on a relatively small number of studies, improvement in V˙O2max following 5-13 wk of ET is associated with increase in Qmax, but not in a-V˙O2diff, in previously untrained to moderately trained healthy young individuals.

Maximal feeding with active prey-switching: A kill-the-winner functional response and its effect on global diversity and biogeography

NASA Astrophysics Data System (ADS)

Vallina, S. M.; Ward, B. A.; Dutkiewicz, S.; Follows, M. J.

2014-01-01

Predators' switching towards the most abundant prey is a mechanism that stabilizes population dynamics and helps overcome competitive exclusion of species in food webs. Current formulations of active prey-switching, however, display non-maximal feeding in which the predators' total ingestion decays exponentially with the number prey species (i.e. the diet breadth) even though the total prey biomass stays constant. We analyse three previously published multi-species functional responses which have either active switching or maximal feeding, but not both. We identify the cause of this apparent incompatibility and describe a kill-the-winner formulation that combines active switching with maximal feeding. Active switching is shown to be a community response in which some predators become prey-selective and the formulations with maximal or non-maximal feeding are implicitly assuming different food web configurations. Global simulations using a marine ecosystem model with 64 phytoplankton species belonging to 4 major functional groups show that the species richness and biogeography of phytoplankton are very sensitive to the choice of the functional response for grazing. The phytoplankton biogeography reflects the balance between the competitive abilities for nutrient uptake and the degree of apparent competition which occurs indirectly between species that share a common predator species. The phytoplankton diversity significantly increases when active switching is combined with maximal feeding through predator-mediated coexistence.

Influence of adipocyte size and adipose depot on the in vitro lipolytic activity and insulin sensitivity of adipose tissue in dairy cows at the end of the dry period.

PubMed

De Koster, J; Van den Broeck, W; Hulpio, L; Claeys, E; Van Eetvelde, M; Hermans, K; Hostens, M; Fievez, V; Opsomer, G

2016-03-01

The aim of the present research was to describe characteristics of adipose tissue lipolysis in dairy cows with a variable body condition score (BCS). Ten clinically healthy Holstein Friesian cows were selected based on BCS and euthanized 10 to 13 d before the expected parturition date. Immediately after euthanasia, adipose tissue samples were collected from subcutaneous and omental fat depots. In both depots, we observed an increase in adipocyte size with increasing BCS. Using an in vitro explant culture of subcutaneous and omental adipose tissue, we aimed to determine the influence of adipocyte size and localization of adipose depot on the lipolytic activity in basal conditions and after addition of isoproterenol (nonselective β-agonist) and insulin in different concentrations. Glycerol release in the medium was used as a measure for lipolytic activity. We observed that the basal lipolytic activity of subcutaneous and omental adipose tissue increased with adipocyte volume, meaning that larger fat cells have higher basal lipolytic activity independent of the location of the adipose depot. Dose-response curves were created between the concentration of isoproterenol or insulin and the amount of glycerol released. The shape of the dose-response curves is determined by the concentration of isoproterenol and insulin needed to elicit the half-maximal effect and the maximal amount of stimulated glycerol release or the maximal inhibitory effect of insulin. We observed that larger fat cells released more glycerol upon maximal stimulation with isoproterenol and this was more pronounced in subcutaneous adipose tissue. Additionally, larger fat cells had a higher sensitivity toward lipolytic signals. We observed a trend for larger adipocytes to be more resistant to the maximal antilipolytic effect of insulin. The insulin concentration needed to elicit the half-maximal inhibitory effect of insulin was within the physiological range of insulin and was not influenced by adipocyte size or adipose depot. We conclude that overconditioned cows have larger adipocytes and are predisposed to excessive mobilization of body fat due to a higher basal and stimulated lipolytic activity of large adipocytes while the antilipolytic effect of insulin is preserved. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

First-principles study on doping and temperature dependence of thermoelectric property of Bi{sub 2}S{sub 3} thermoelectric material

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

Guo, Donglin; Hu, Chenguo, E-mail: hucg@cqu.edu.cn; Zhang, Cuiling

2013-05-15

Graphical abstract: The direction-induced ZT is found. At ZZ direction and n = 1.47 × 10{sup 19} cm{sup −3}, the ZT can reach maximal value, 0.36, which is three times as much as maximal laboratorial value. This result matches well the analysis of electron effective mass. Highlights: ► Electrical transportations of Bi{sub 2}S{sub 3} depend on the concentration and temperature. ► The direction-induced ZT is found. ► At ZZ direction and n = 1.47 × 10{sup 19} cm{sup −3}, the ZT can reach maximal value, 0.36. ► The maximal ZT value is three times as much as maximal laboratorial value.more » ► By doping and temperature tuning, Bi{sub 2}S{sub 3} is a promising thermoelectric material. - Abstract: The electronic structure and thermoelectric property of Bi{sub 2}S{sub 3} are investigated. The electron and hole effective mass of Bi{sub 2}S{sub 3} is analyzed in detail, from which we find that the thermoelectric transportation varies in different directions in Bi{sub 2}S{sub 3} crystal. Along ac plane the higher figure of merit (ZT) could be achieved. For n-type doped Bi{sub 2}S{sub 3}, the optimal doping concentration is found in the range of (1.0–5.0) × 10{sup 19} cm{sup −3}, in which the maximal ZT reaches 0.21 at 900 K, but along ZZ direction, the maximal ZT reaches 0.36. These findings provide a new understanding of thermoelectricity-dependent structure factors and improving ZT ways. The donor concentration N increases as T increases at one bar of pressure under a suitable chemical potential μ, but above this chemical potential μ, the donor concentration N keeps a constant.« less

AN APPRAISAL OF INSTRUCTIONAL UNITS TO ENHANCE STUDENT UNDERSTANDING OF PROFIT-MAXIMIZING PRINCIPLES. RESEARCH SERIES IN AGRICULTURAL EDUCATION.

ERIC Educational Resources Information Center

BARKER, RICHARD L.; BENDER, RALPH E.

TWENTY-TWO SELECTED OHIO VOCATIONAL AGRICULTURE TEACHERS AND 262 JUNIOR AND SENIOR VOCATIONAL AGRICULTURE STUDENTS PARTICIPATED IN A STUDY TO MEASURE THE RELATIVE EFFECTIVENESS OF NEWLY DEVELOPED INSTRUCTIONAL UNITS DESIGNED TO ENHANCE STUDENT UNDERSTANDING OF PROFIT-MAXIMIZING PRINCIPLES IN FARM MANAGEMENT. FARM MANAGEMENT WAS TAUGHT IN THE…

AN APPRAISAL OF INSTRUCTIONAL UNITS TO ENHANCE STUDENT UNDERSTANDING OF PROFIT-MAXIMIZING PRINCIPLES. APPENDIX TO FINAL REPORT.

ERIC Educational Resources Information Center

BARKER, RICHARD L.

TWENTY-TWO OHIO HIGH SCHOOLS OFFERING VOCATIONAL AGRICULTURE TO 262 JUNIOR AND SENIOR STUDENTS PARTICIPATED IN A STUDY TO MEASURE THE RELATIVE EFFECTIVENESS OF FARM MANAGEMENT INSTRUCTIONAL UNITS DESIGNED TO ENHANCE STUDENT UNDERSTANDING OF BASIC PROFIT-MAXIMIZING PRINCIPLES WHEN USED IN TEACHING VOCATIONAL AGRICULTURE STUDENTS IN THE SCHOOL…

Slow-motion scattering and coalescence of maximally charged black holes

NASA Technical Reports Server (NTRS)

Ferrell, Robert C.; Eardley, Douglas M.

1987-01-01

Systems consisting of several maximally charged, nonrotating black holes ('Reissner-Nordstrom' black holes) interacting with one another are studied. An effective action for the system in the slow-motion, fully strong-field regime is presented. An exact calculation of black-hole-black-hole scattering and coalescence in the slow-motion (but strong-field) limit is given.

The impacts of the quantum-dot confining potential on the spin-orbit effect.

PubMed

Li, Rui; Liu, Zhi-Hai; Wu, Yidong; Liu, C S

2018-05-09

For a nanowire quantum dot with the confining potential modeled by both the infinite and the finite square wells, we obtain exactly the energy spectrum and the wave functions in the strong spin-orbit coupling regime. We find that regardless of how small the well height is, there are at least two bound states in the finite square well: one has the σ x [Formula: see text] = -1 symmetry and the other has the σ x [Formula: see text] = 1 symmetry. When the well height is slowly tuned from large to small, the position of the maximal probability density of the first excited state moves from the center to x ≠ 0, while the position of the maximal probability density of the ground state is always at the center. A strong enhancement of the spin-orbit effect is demonstrated by tuning the well height. In particular, there exists a critical height [Formula: see text], at which the spin-orbit effect is enhanced to maximal.

Effect of antiischemic therapy on coronary flow reserve and the pressure-maximal coronary flow relationship in anesthetized swine.

PubMed

McFalls, E O; Duncker, D J; Sassen, L M; Gho, B C; Verdouw, P D

1991-12-01

The effect of nifedipine (0.5, 1.0, and 2.0 micrograms/kg/min), metoprolol (0.1, 0.5, and 1.0 mg/kg), the beta 1-selective adrenoceptor partial agonist epanolol (10, 50, and 200 micrograms/kg), or equivalent volumes of isotonic saline (n = 6, in each group), on coronary blood flow capacity were studied in anesthetized swine. Intracoronary bolus injections of adenosine (20 micrograms/kg/0.2 ml) were administered without and during three levels of coronary stenosis, prior to and following each dose of drug, to obtain maximal coronary blood flows at different perfusion pressures in the autoregulatory range. Coronary perfusion pressures were varied by partial inflation of a balloon around the left anterior descending coronary artery. Special care was taken that the stenoses not lead to myocardial ischemia. Three indices of coronary blood flow capacity were used: absolute coronary flow reserve (ACFR, the ratio of maximal to resting coronary blood flow), the slope and the extrapolated pressure at zero flow (Pzf) of the pressure-maximal coronary flow (PMCF) relationship, and relative coronary flow reserve (RCFR, the ratio of maximal coronary blood flow with a stenosis to maximal coronary blood flow without a stenosis) at two of the three levels of stenosis. Nifedipine decreased ACFR from 4.5 +/- 1.9 to 1.9 +/- 0.3 (mean +/- SD; p less than 0.05), reflecting in part the increase in resting coronary blood flow. The nifedipine-induced changes in maximal coronary blood flow were not only due to a drop in perfusion pressure, as the slope of the PMCF relationship decreased from 2.27 +/- 0.49 ml/(min.mm Hg) to 1.54 +/- 0.51 ml/(min.mm Hg) (p less than 0.05), and Pzf decreased from 30 +/- 4 mm Hg to 20 +/- 7 mm Hg (p less than 0.05). Consequently, calculated maximal coronary blood flow was attenuated from 114 +/- 31 ml/min to 93 +/- 37 ml/min at 80 mm Hg, but was enhanced from 23 +/- 13 to 37 +/- 24 ml/min at 40 mm Hg coronary perfusion pressure. In concert with the change in the PMCF relationship, RCFR at equivalent severe stenosis increased from 0.33 +/- 0.06 to 0.47 +/- 0.10 (p less than 0.05). No changes were observed with metoprolol, epanolol, or saline. The effect of nifedipine on the PMCF relationship not only provides a mechanism for the drug's antiischemic action, but should also be considered in the interpretation of coronary flow reserve measurements in patients on nifedipine treatment.

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

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.

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.

Immediate effects of kinesiotaping on quadriceps muscle strength: a single-blind, placebo-controlled crossover trial.

PubMed

Vercelli, Stefano; Sartorio, Francesco; Foti, Calogero; Colletto, Lorenzo; Virton, Domenico; Ronconi, Gianpaolo; Ferriero, Giorgio

2012-07-01

To investigate the immediate effects on maximal muscle strength of kinesiotaping (KT) applied to the dominant quadriceps of healthy subjects. Single-blind, placebo-controlled crossover trial. "Salvatore Maugeri" Foundation. With ethical approval and informed consent, a convenience sample of 36 healthy volunteers were recruited. Two subjects did not complete the sessions and were excluded from the analysis. Subjects were tested across 3 different sessions, randomly receiving 2 experimental KT conditions applied with the aim of enhancing and inhibiting muscle strength and a sham KT application. Quadriceps muscle strength was measured by means of an isokinetic maximal test performed at 60 and 180 degrees per second. Two secondary outcome measures were performed: the single-leg triple hop for distance to measure limb performance and the Global Rating of Change Scale (GRCS) to calculate agreement between KT application and subjective perception of strength. Compared with baseline, none of the 3 taping conditions showed a significant change in muscle strength and performance (all P > 0.05). Effect size was very low under all conditions (≤0.08). Very few subjects showed an individual change greater than the minimal detectable change. Global Rating of Change Scale scores demonstrated low to moderate agreement with the type of KT applied, but some placebo effects were reported independently of condition. Our findings indicated no significant effect in the maximal quadriceps strength immediately after the application of inhibition, facilitation, or sham KT. These results do not support the use of KT applied in this way to change maximal muscle strength in healthy people.

Influence of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the anticonvulsant and acute side-effect potentials of clobazam, lacosamide, and pregabalin in the maximal electroshock-induced seizure model and chimney test in mice.

PubMed

Florek-Luszczki, Magdalena; Zagaja, Miroslaw; Luszczki, Jarogniew J

2015-08-01

The influence of arachidonyl-2'-chloroethylamide (ACEA - a selective cannabinoid CB1 receptor agonist) on the anticonvulsant potency and acute adverse-effect potentials of clobazam, lacosamide, and pregabalin was determined in the maximal electroshock-induced seizure model and chimney test in mice. ACEA (2.5 mg/kg, i.p.) significantly enhanced the anticonvulsant potency of pregabalin in the mouse maximal electroshock-induced seizure model by decreasing the median effective dose (ED50 ) of pregabalin from 125.39 to 78.06 mg/kg (P < 0.05). In contrast, ACEA (2.5 mg/kg) had no significant impact on the anticonvulsant potency of clobazam and lacosamide in the mouse maximal electroshock-induced seizure model. On the other hand, ACEA (2.5 mg/kg) did not affect acute adverse effects of clobazam, lacosamide or pregabalin, and the median toxic doses (TD50 ) for the studied anti-epileptic drugs in combination with ACEA did not differ from the TD50 values as determined for the drugs administered alone in the chimney test. In conclusion, ACEA ameliorates the pharmacological profile of pregabalin, when considering both the anticonvulsant and the acute adverse effects of the drug in preclinical study on animals. The combination of pregabalin with ACEA can be of pivotal importance for patients with epilepsy as a potentially advantageous combination if the results from this study translate into clinical settings. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Quantification of type I error probabilities for heterogeneity LOD scores.

PubMed

Abreu, Paula C; Hodge, Susan E; Greenberg, David A

2002-02-01

Locus heterogeneity is a major confounding factor in linkage analysis. When no prior knowledge of linkage exists, and one aims to detect linkage and heterogeneity simultaneously, classical distribution theory of log-likelihood ratios does not hold. Despite some theoretical work on this problem, no generally accepted practical guidelines exist. Nor has anyone rigorously examined the combined effect of testing for linkage and heterogeneity and simultaneously maximizing over two genetic models (dominant, recessive). The effect of linkage phase represents another uninvestigated issue. Using computer simulation, we investigated type I error (P value) of the "admixture" heterogeneity LOD (HLOD) score, i.e., the LOD score maximized over both recombination fraction theta and admixture parameter alpha and we compared this with the P values when one maximizes only with respect to theta (i.e., the standard LOD score). We generated datasets of phase-known and -unknown nuclear families, sizes k = 2, 4, and 6 children, under fully penetrant autosomal dominant inheritance. We analyzed these datasets (1) assuming a single genetic model, and maximizing the HLOD over theta and alpha; and (2) maximizing the HLOD additionally over two dominance models (dominant vs. recessive), then subtracting a 0.3 correction. For both (1) and (2), P values increased with family size k; rose less for phase-unknown families than for phase-known ones, with the former approaching the latter as k increased; and did not exceed the one-sided mixture distribution xi = (1/2) chi1(2) + (1/2) chi2(2). Thus, maximizing the HLOD over theta and alpha appears to add considerably less than an additional degree of freedom to the associated chi1(2) distribution. We conclude with practical guidelines for linkage investigators. Copyright 2002 Wiley-Liss, Inc.

The influence of sodium bicarbonate on maximal force and rates of force development in the triceps surae and brachii during fatiguing exercise.

PubMed

Siegler, Jason C; Mudie, Kurt; Marshall, Paul

2016-11-01

What is the central question of this study? Does metabolic alkalosis in humans, induced by sodium bicarbonate, affect rates of skeletal muscle fatigue differentially in muscle groups composed predominately of slow- and fast-twitch fibres? What is the main finding and its importance? Sodium bicarbonate exhibited no effect on the fatigue profile observed between triceps surae and brachii muscle groups during and after 2 min of tetanic stimulation. For the first time in exercising humans, we have profiled the effect of sodium bicarbonate on the voluntary and involuntary contractile characteristics of muscle groups representative of predominately slow- and fast-twitch fibres. The effect of metabolic alkalosis on fibre-specific maximal force production and rates of force development (RFD) has been investigated previously in animal models, with evidence suggesting an improved capacity to develop force rapidly in fast- compared with slow-twitch muscle. We have attempted to model in vivo the fatigue profile of voluntary and involuntary maximal force and RFD in the triceps surae and brachii after sodium bicarbonate (NaHCO 3 ) ingestion. In a double-blind, three-way repeated-measures design, participants (n = 10) ingested either 0.3 g kg -1 NaHCO 3 (ALK) or equivalent calcium carbonate (PLA) prior to 2 min of continuous (1 Hz) supramaximal stimulation (300 ms at 40 Hz) of the triceps surae or brachii, with maximal voluntary efforts (maximal voluntary torque) coupled with direct muscle stimulation also measured at baseline, 1 and 2 min. Metabolic alkalosis was achieved in both ALK trials but was not different between muscle groups. Regardless of the conditions, involuntary torque declined nearly 60% in the triceps brachii (P < 0.001) and ∼30% in the triceps surae (P < 0.001). In all trials, there was a significant decline in normalized involuntary RFD (P < 0.05). Maximal voluntary torque declined nearly 28% but was not different between conditions (P < 0.01), and although declining nearly 21% in voluntary RFD (P < 0.05) there was no difference between PLA and ALK in either muscle group (P = 0.93). Sodium bicarbonate exhibited no effect on the fatigue observed between representative fibre-type muscle groups on maximal voluntary and involuntary torque or rates of torque development during and after 2 min of tetanic stimulation. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

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.

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

The repeated bout effect of typical lower body strength training sessions on sub-maximal running performance and hormonal response.

PubMed

Doma, Kenji; Schumann, Moritz; Sinclair, Wade H; Leicht, Anthony S; Deakin, Glen B; Häkkinen, Keijo

2015-08-01

This study examined the effects of two typical strength training sessions performed 1 week apart (i.e. repeated bout effect) on sub-maximal running performance and hormonal. Fourteen resistance-untrained men (age 24.0 ± 3.9 years; height 1.83 ± 0.11 m; body mass 77.4 ± 14.0 kg; VOpeak 48.1 ± 6.1 M kg(-1) min(-1)) undertook two bouts of high-intensity strength training sessions (i.e. six-repetition maximum). Creatine kinase (CK), delayed-onset muscle soreness (DOMS), counter-movement jump (CMJ) as well as concentrations of serum testosterone, cortisol and testosterone/cortisol ratio (T/C) were examined prior to and immediately post, 24 (T24) and 48 (T48) h post each strength training bout. Sub-maximal running performance was also conducted at T24 and T48 of each bout. When measures were compared between bouts at T48, the degree of elevation in CK (-58.4 ± 55.6 %) and DOMS (-31.43 ± 42.9 %) and acute reduction in CMJ measures (4.1 ± 5.4 %) were attenuated (p < 0.05) following the second bout. Cortisol was increased until T24 (p < 0.05) although there were no differences between bouts and no differences were found for testosterone and T/C ratio (p > 0.05). Sub-maximal running performance was impaired until T24, although changes were not attenuated following the second bout. The initial bout appeared to provide protection against a number of muscle damage indicators suggesting a greater need for recovery following the initial session of typical lower body resistance exercises in resistance-untrained men although sub-maximal running should be avoided following the first two sessions.

Developing a conservation strategy to maximize persistence of an endangered freshwater mussel species while considering management effectiveness and cost

USGS Publications Warehouse

Smith, David R.; McRae, Sarah E.; Augspurger, Tom; Ratcliffe, Judith A.; Nichols, Robert B.; Eads, Chris B.; Savidge, Tim; Bogan, Arthur E.

2015-01-01

We used a structured decision-making process to develop conservation strategies to increase persistence of Dwarf Wedgemussel (Alasmidonta heterodon) in North Carolina, USA, while accounting for uncertainty in management effectiveness and considering costs. Alternative conservation strategies were portfolios of management actions that differed by location of management actions on the landscape. Objectives of the conservation strategy were to maximize species persistence, maintain genetic diversity, maximize public support, and minimize management costs. We compared 4 conservation strategies: 1) the ‘status quo’ strategy represented current management, 2) the ‘protect the best’ strategy focused on protecting the best populations in the Tar River basin, 3) the ‘expand the distribution’ strategy focused on management of extant populations and establishment of new populations in the Neuse River basin, and 4) the ‘hybrid’ strategy combined elements of each strategy to balance conservation in the Tar and Neuse River basins. A population model informed requirements for population management, and experts projected performance of alternative strategies over a 20-y period. The optimal strategy depended on the relative value placed on competing objectives, which can vary among stakeholders. The protect the best and hybrid strategies were optimal across a wide range of relative values with 2 exceptions: 1) if minimizing management cost was of overriding concern, then status quo was optimal, or 2) if maximizing population persistence in the Neuse River basin was emphasized, then expand the distribution strategy was optimal. The optimal strategy was robust to uncertainty in management effectiveness. Overall, the structured decision process can help identify the most promising strategies for endangered species conservation that maximize conservation benefit given the constraint of limited funding.

Effects of pre-cooling procedures on intermittent-sprint exercise performance in warm conditions.

PubMed

Duffield, Rob; Marino, Frank E

2007-08-01

The aim of this study was to determine whether pre-cooling procedures improve both maximal sprint and sub-maximal work during intermittent-sprint exercise. Nine male rugby players performed a familiarisation session and three testing sessions of a 2 x 30-min intermittent sprint protocol, which consisted of a 15-m sprint every min separated by free-paced hard-running, jogging and walking in 32 degrees C and 30% humidity. The three sessions included a control condition, Ice-vest condition and Ice-bath/Ice-vest condition, with respective cooling interventions imposed for 15-min pre-exercise and 10-min at half-time. Performance measures of sprint time and % decline and distance covered during sub-maximal exercise were recorded, while physiological measures of core temperature (T (core)), mean skin temperature (T (skin)), heart rate, heat storage, nude mass, rate of perceived exertion, rate of thermal comfort and capillary blood measures of lactate [La(-)], pH, Sodium (Na(+)) and Potassium (K(+)) were recorded. Results for exercise performance indicated no significant differences between conditions for the time or % decline in 15-m sprint efforts or the distance covered during sub-maximal work bouts; however, large effect size data indicated a greater distance covered during hard running following Ice-bath cooling. Further, lowered T (core), T (skin), heart rate, sweat loss and thermal comfort following Ice-bath cooling than Ice-vest or Control conditions were present, with no differences present in capillary blood measures of [La(-)], pH, K(+) or Na(+). As such, the ergogenic benefits of effective pre-cooling procedures in warm conditions for team-sports may be predominantly evident during sub-maximal bouts of exercise.

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients.

PubMed

Benda, Nathalie M M; Seeger, Joost P H; Stevens, Guus G C F; Hijmans-Kersten, Bregina T P; van Dijk, Arie P J; Bellersen, Louise; Lamfers, Evert J P; Hopman, Maria T E; Thijssen, Dick H J

2015-01-01

Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload-alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60-75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III. Nederlands Trial Register NTR3671.

Effects of dynamic hyperinflation on exercise capacity and quality of life in stable COPD patients.

PubMed

Zhao, Li; Peng, Liyue; Wu, Baomei; Bu, Xiaoning; Wang, Chen

2016-09-01

Dynamic hyperinflation (DH) is an important pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). There is increasing evidence that DH has negative effects on exercise performance and quality of life. The objective of this study was to explore effects of DH on exercise capacity and quality of life in stable COPD patients. Fifty-eight COPD patients and 20 matched healthy individuals underwent pulmonary function test, 6-min walk test and symptom-limited cardiopulmonary exercise test (CPET). End-expiratory lung volume/total lung capacity ratio (EELVmax/TLC) at peak exercise of CPET was evaluated, and EELVmax/TLC ≥ 75% was defined as 'severe dynamic hyperinflation (SDH)'. Of the 58 patients studied, 29 (50.0%) presented with SDH (SDH+ group, EELVmax/TLC 79.60 ± 3.60%), having worse maximal exercise capacity reflected by lower peakload, maximal oxygen uptake (VO2 max), maximal carbon dioxide output (VCO2 max) and maximal minute ventilation (VEmax) than did those without SDH (SDH- group, EELVmax/TLC 67.44 ± 6.53%). The EELVmax/TLC ratio at peak exercise had no association with variables of pulmonary function and 6-min walk distance (6MWD), but correlated inversely with peakload, VO2 max, VCO2 max and VEmax (r = -0.300~-0.351, P < 0.05). Although no significant differences were observed, patients with EELVmax/TLC ≥ 75% tended to have higher COPD assessment test score (15.07 ± 6.55 vs 13.28 ± 6.59, P = 0.303). DH develops variably during exercise and has a greater impact on maximal exercise capacity than 6MWD, even in those with the same extent of pulmonary function impairment at rest. © 2015 John Wiley & Sons Ltd.

Influence of training and a maximal exercise test in analytical variability of muscular, hepatic, and cardiovascular biochemical variables.

PubMed

Romagnoli, Marco; Alis, Rafael; Aloe, Rosalia; Salvagno, Gian Luca; Basterra, Javier; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Lippi, Giuseppe

2014-04-01

Short, middle, and long-term exercise, as well as the relative intensity of the physical effort, may influence a broad array of laboratory results, and it is thereby of pivotal importance to appropriately differentiate the 'physiologic' from the 'pathological' effects of exercise. Therefore, the values of some biomarkers in physically active subjects may be cautiously interpreted since the results may fall outside the conventional reference ranges. It has been demonstrated that middle and long-term endurance and/or strenuous exercise triggers transient elevations of muscular and cardiac biomarkers. However, no data have been published about the effect of short-term maximal exercise test on the most useful muscular, hepatic and cardiovascular biomarkers. The aim of the present study was to assess the baseline concentrations of muscular, hepatic, and cardiovascular makers between trained and untrained subjects, along with changes induced by maximal exercise test. We measured C reactive protein (CRP), procalcitonin (PCT), gamma glutamyltransferase (GGT), creatine kinase-MB isoenzyme (CK-MB), Hs-TnT, NT-proBNP, CK, LDH, AST, and ALT in serum samples of physically active (trained) and physically inactive (sedentary) male collected before, immediately after a maximal exercise test and after a 30-min recovery period. Trained subjects tend to have significantly raised base concentrations of CK, CK-MB, ALT, and LDH compared to sedentary individuals, and this can be clearly interpreted as a mild injury of skeletal muscle. A single maximal exercise was also effective to transiently increase the concentrations of NT-proBNP, but not those of Hs-TnT, thus suggesting that the cardiac involvement is mostly benign in nature.

Obesity and stress urinary incontinence in women: compromised continence mechanism or excess bladder pressure during cough?

PubMed

Swenson, Carolyn W; Kolenic, Giselle E; Trowbridge, Elisa R; Berger, Mitchell B; Lewicky-Gaupp, Christina; Margulies, Rebecca U; Morgan, Daniel M; Fenner, Dee E; DeLancey, John O

2017-09-01

We compared two hypotheses as to why obesity is associated with stress urinary incontinence (SUI): (1) obesity increases demand on the continence system (e.g. higher cough pressure) and (2) obesity compromises urethral function and urethrovaginal support. A secondary analysis was performed using data from a case-control study of SUI in women. Measurements of urethrovaginal support (POP-Q point Aa, urethral axis), urethral function (maximal urethral closure pressure, MUCP), and measures of continence system demand (intravesical pressures at rest and during maximal cough) were analyzed. Cases and controls were divided into three body mass index (BMI) groups: normal (18.5-24.9 kg/m 2 ); overweight (25.0-29.9 kg/m 2 ); and obese (≥30 kg/m 2 ). Logistic regression models where created to investigate variables related to SUI for each BMI group. Structural equation modeling was used to test the direct and indirect relationships among BMI, SUI, maximal cough pressure, MUCP, and POP-Q point Aa. The study included 108 continent controls and 103 women with SUI. MUCP was the factor most strongly associated with SUI in all BMI groups. Maximal cough pressure was significantly associated with SUI in obese women (OR 3.191, 95% CI 1.326, 7.683; p < 0.01), but not in normal weight or overweight women. Path model analysis showed a significant relationship between BMI and SUI through maximal cough pressure (indirect effect, p = 0.038), but not through MUCP (indirect effect, p = 0.243) or POP-Q point Aa (indirect effect, p = 0.410). Our results support the first hypothesis that obesity is associated with SUI because of increased intravesical pressure, which therefore increases demand on the continence mechanism.

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)

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).

Effects of Variable Resistance Training on Maximal Strength: A Meta-Analysis.

PubMed

Soria-Gila, Miguel A; Chirosa, Ignacio J; Bautista, Iker J; Baena, Salvador; Chirosa, Luis J

2015-11-01

Variable resistance training (VRT) methods improve the rate of force development, coordination between antagonist and synergist muscles, the recruitment of motor units, and reduce the drop in force produced in the sticking region. However, the beneficial effects of long-term VRT on maximal strength both in athletes and untrained individuals have been much disputed. The purpose of this study was to compare in a meta-analysis the effects of a long-term (≥7 weeks) VRT program using chains or elastic bands and a similar constant resistance program in both trained adults practicing different sports and untrained individuals. Intervention effect sizes were compared among investigations meeting our selection and inclusion criteria using a random-effects model. The published studies considered were those addressing VRT effects on the 1 repetition maximum. Seven studies involving 235 subjects fulfilled the selection and inclusion criteria. Variable resistance training led to a significantly greater mean strength gain (weighted mean difference: 5.03 kg; 95% confidence interval: 2.26-7.80 kg; Z = 3.55; p < 0.001) than the gain recorded in response to conventional weight training. Long-term VRT training using chains or elastic bands attached to the barbell emerged as an effective evidence-based method of improving maximal strength both in athletes with different sports backgrounds and untrained subjects.

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.

Gamma loop contributing to maximal voluntary contractions in man.

PubMed Central

Hagbarth, K E; Kunesch, E J; Nordin, M; Schmidt, R; Wallin, E U

1986-01-01

A local anaesthetic drug was injected around the peroneal nerve in healthy subjects in order to investigate whether the resulting loss in foot dorsiflexion power in part depended on a gamma-fibre block preventing 'internal' activation of spindle end-organs and thereby depriving the alpha-motoneurones of an excitatory spindle inflow during contraction. The motor outcome of maximal dorsiflexion efforts was assessed by measuring firing rates of individual motor units in the anterior tibial (t.a.) muscle, mean voltage e.m.g. from the pretibial muscles, dorsiflexion force and range of voluntary foot dorsiflexion movements. The tests were performed with and without peripheral conditioning stimuli, such as agonist or antagonist muscle vibration or imposed stretch of the contracting muscles. As compared to control values of t.a. motor unit firing rates in maximal isometric voluntary contractions, the firing rates were lower and more irregular during maximal dorsiflexion efforts performed during subtotal peroneal nerve blocks. During the development of paresis a gradual reduction of motor unit firing rates was observed before the units ceased responding to the voluntary commands. This change in motor unit behaviour was accompanied by a reduction of the mean voltage e.m.g. activity in the pretibial muscles. At a given stage of anaesthesia the e.m.g. responses to maximal voluntary efforts were more affected than the responses evoked by electric nerve stimuli delivered proximal to the block, indicating that impaired impulse transmission in alpha motor fibres was not the sole cause of the paresis. The inability to generate high and regular motor unit firing rates during peroneal nerve blocks was accentuated by vibration applied over the antagonistic calf muscles. By contrast, in eight out of ten experiments agonist stretch or vibration caused an enhancement of motor unit firing during the maximal force tasks. The reverse effects of agonist and antagonist vibration on the ability to activate the paretic muscles were evidenced also by alterations induced in mean voltage e.m.g. activity, dorsiflexion force and range of dorsiflexion movements. The autogenetic excitatory and the reciprocal inhibitory effects of muscle vibration rose in strength as the vibration frequency was raised from 90 to 165 Hz. Reflex effects on maximal voluntary contraction strength similar to those observed during partial nerve blocks were not seen under normal conditions when the nerve supply was intact.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3612576

Effective regurgitant orifice area by the color Doppler flow convergence method for evaluating the severity of chronic aortic regurgitation. An animal study.

PubMed

Shiota, T; Jones, M; Yamada, I; Heinrich, R S; Ishii, M; Sinclair, B; Holcomb, S; Yoganathan, A P; Sahn, D J

1996-02-01

The aim of the present study was to evaluate dynamic changes in aortic regurgitant (AR) orifice area with the use of calibrated electromagnetic (EM) flowmeters and to validate a color Doppler flow convergence (FC) method for evaluating effective AR orifice area and regurgitant volume. In 6 sheep, 8 to 20 weeks after surgically induced AR, 22 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary EM flowmeters balanced against each other. Instantaneous AR orifice areas were determined by dividing these actual AR flow rates by the corresponding continuous wave velocities (over 25 to 40 points during each diastole) matched for each steady state. Echo studies were performed to obtain maximal aliasing distances of the FC in a low range (0.20 to 0.32 m/s) and a high range (0.70 to 0.89 m/s) of aliasing velocities; the corresponding maximal AR flow rates were calculated using the hemispheric flow convergence assumption for the FC isovelocity surface. AR orifice areas were derived by dividing the maximal flow rates by the maximal continuous wave Doppler velocities. AR orifice sizes obtained with the use of EM flowmeters showed little change during diastole. Maximal and time-averaged AR orifice areas during diastole obtained by EM flowmeters ranged from 0.06 to 0.44 cm2 (mean, 0.24 +/- 0.11 cm2) and from 0.05 to 0.43 cm2 (mean, 0.21 +/- 0.06 cm2), respectively. Maximal AR orifice areas by FC using low aliasing velocities overestimated reference EM orifice areas; however, at high AV, FC predicted the reference areas more reliably (0.25 +/- 0.16 cm2, r = .82, difference = 0.04 +/- 0.07 cm2). The product of the maximal orifice area obtained by the FC method using high AV and the velocity time integral of the regurgitant orifice velocity showed good agreement with regurgitant volumes per beat (r = .81, difference = 0.9 +/- 7.9 mL/beat). This study, using strictly quantified AR volume, demonstrated little change in AR orifice size during diastole. When high aliasing velocities are chosen, the FC method can be useful for determining effective AR orifice size and regurgitant volume.

Reading Dilemmas in a Foreign Language Reduces Both Deontological and Utilitarian Response Tendencies

ERIC Educational Resources Information Center

Muda, Rafal; Niszczota, Pawel; Bialek, Michal; Conway, Paul

2018-01-01

Moral dilemmas entail deciding whether to cause harm to maximize overall outcomes, such as killing 1 person to save 5. Past work has demonstrated that people are more willing to accept causing such outcome-maximizing harm when they read dilemmas in a foreign language they speak rather than their native language. Presumably this effect is due to…

Potential biomass and logs from fire-hazard-reduction treatments in Southwest Oregon and Northern California

Treesearch

R. James Barbour; Jeremy Fried; Peter J. Daugherty; Glenn Christensen; Roger. Fight

2008-01-01

The FIA BioSum model was used to simulate three fire-hazard-reduction policies in an area comprising northern California, southwestern Oregon, and the east slopes of the Cascade Mountains in Oregon. The policy scenarios, all subject to a stand-scale fire-hazard-reduction effectiveness constraint, included maximize torching index improvement (Max TI), maximize net...

Effects of Age on Maximal Work Capacity in Women Aged 18-48 Years.

ERIC Educational Resources Information Center

Hartung, G. Harley; And Others

Fifty-six healthy nontrained women aged 18 to 48 were tested for maximal work capacity on a bicycle ergometer. The women were divided into three age groups. A continuous step-increment bicycle ergometer work test was administered with the workload starting at 150 kpm (kilometers per minute) and 50 pedal rpm (revolutions per minute). The workload…

2,3-Diphosphoglycerate is a nonselective inhibitor of inositol 1,4,5-trisphosphate action and metabolism.

PubMed

Guillemette, G; Favreau, I; Lamontagne, S; Boulay, G

1990-04-25

Inositol 1,4,5-trisphosphate (InsP3) is an important second messenger generated from the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C in response to Ca2(+)-mobilizing stimuli. InsP3 interacts with specific intracellular receptors and triggers the release of sequestered Ca2+ from an intracellular store. We have looked at the influence of 2,3-diphosphoglycerate on the action and metabolism of InsP3 in the bovine adrenal cortex. 2,3-Diphosphoglycerate blocked InsP3 binding to adrenal cortex microsomes with a half-maximal efficiency of 0.5 mM. Scatchard analyses revealed that 2,3-diphosphoglycerate did not change the maximal capacity of the microsomes, but decreased their binding affinity for InsP3. The Ca2(+)-releasing activity of InsP3 on the same microsomal preparation was monitored with the fluorescent indicator, Fura-2. 2,3-Diphosphoglycerate blocked this activity with a half-maximal efficiency of 2 mM. The effect of 2,3-diphosphoglycerate could be overcome by supramaximal doses of InsP3, indicating a competitive inhibitory effect. The activity of InsP3 phosphatase from bovine adrenal cortex microsomes was also studied. 2,3-Diphosphoglycerate inhibited the activity of the phosphatase with a half-maximal efficiency of 0.3 mM. Lineweaver-Burke plots revealed that this effect was competitive. Finally, 2,3-diphosphoglycerate was also able to inhibit the activity of a partially purified preparation of InsP3 kinase from bovine adrenal cortex cytosol. The half-maximal dose was around 10 mM and the Lineweaver-Burke plot showed that the inhibition was competitive. These results show that 2,3-diphosphoglycerate can be considered as a structural analog of InsP3. Its inhibitory effects, however, are not selective enough to use it as an InsP3 protective agent in Ca2(+)-mobilization studies.

Strength improvements through occlusal splints? The effects of different lower jaw positions on maximal isometric force production and performance in different jumping types

PubMed Central

Maurer, Christian; Heller, Sebastian; Sure, Jil-Julia; Fuchs, Daniel; Mickel, Christoph; Wanke, Eileen M.; Groneberg, David A.

2018-01-01

Objective The influence of the jaw position on postural control, body posture, walking and running pattern has been reported in the literature. All these movements have in common that a relatively small, but well controlled muscle activation is required. The induced effects on motor output through changed jaw positions have been small. Therefore, it has been questioned if it could still be observed in maximal muscle activation. Method Twenty-three healthy, mid age recreational runners (mean age = 34.0 ± 10.3 years) participated in this study. Three different jump tests (squat jump, counter movement jump, and drop jumps from four different heights) and three maximal strength tests (trunk flexion and extension, leg press of the right and left leg) were conducted. Four different dental occlusion conditions and an additional familiarization condition were tested. Subjects performed the tests on different days for which the four occlusion conditions were randomly changed. Results No familiarization effect was found. Occlusion conditions with a relaxation position and with a myocentric condylar position showed significantly higher values for several tests compared to the neutral condition and the maximal occlusion position. Significance was found in the squat jump, countermovement jump, the drop jump from 32cm and 40cm, trunk extension, leg press force and rate of force development. The effect due to the splint conditions is an improvement between 3% and 12% (min and max). No influence of the jaw position on symmetry or balance between extension and flexion muscle was found. Conclusion An influence of occlusion splints on rate of force development (RFD) and maximal strength tests could be confirmed. A small, but consistent increase in the performance parameters could be measured. The influence of the occlusion condition is most likely small compared to other influences as for example training status, age, gender and circadian rhythm. PMID:29474465

The effect of lifelong exercise dose on cardiovascular function during exercise

PubMed Central

Carrick-Ranson, Graeme; Hastings, Jeffrey L.; Bhella, Paul S.; Fujimoto, Naoki; Shibata, Shigeki; Palmer, M. Dean; Boyd, Kara; Livingston, Sheryl; Dijk, Erika

2014-01-01

An increased “dose” of endurance exercise training is associated with a greater maximal oxygen uptake (V̇o2max), a larger left ventricular (LV) mass, and improved heart rate and blood pressure control. However, the effect of lifelong exercise dose on metabolic and hemodynamic response during exercise has not been previously examined. We performed a cross-sectional study on 101 (69 men) seniors (60 yr and older) focusing on lifelong exercise frequency as an index of exercise dose. These included 27 who had performed ≤2 exercise sessions/wk (sedentary), 25 who performed 2–3 sessions/wk (casual), 24 who performed 4–5 sessions/wk (committed) and 25 who performed ≥6 sessions/wk plus regular competitions (Masters athletes) over at least the last 25 yr. Oxygen uptake and hemodynamics [cardiac output, stroke volume (SV)] were collected at rest, two levels of steady-state submaximal exercise, and maximal exercise. Doppler ultrasound measures of LV diastolic filling were assessed at rest and during LV loading (saline infusion) to simulate increased LV filling. Body composition, total blood volume, and heart rate recovery after maximal exercise were also examined. V̇o2max increased in a dose-dependent manner (P < 0.05). At maximal exercise, cardiac output and SV were largest in committed exercisers and Masters athletes (P < 0.05), while arteriovenous oxygen difference was greater in all trained groups (P < 0.05). At maximal exercise, effective arterial elastance, an index of ventricular-arterial coupling, was lower in committed exercisers and Masters athletes (P < 0.05). Doppler measures of LV filling were not enhanced at any condition, irrespective of lifelong exercise frequency. These data suggest that performing four or more weekly endurance exercise sessions over a lifetime results in significant gains in V̇o2max, SV, and heart rate regulation during exercise; however, improved SV regulation during exercise is not coupled with favorable effects on LV filling, even when the heart is fully loaded. PMID:24458750

Consumption of açai (Euterpe oleracea Mart.) functional beverage reduces muscle stress and improves effort tolerance in elite athletes: a randomized controlled intervention study.

PubMed

Carvalho-Peixoto, Jacqueline; Moura, Mirian Ribeiro Leite; Cunha, Felipe Amorim; Lollo, Pablo Christiano B; Monteiro, Walace David; Carvalho, Lucia Maria Jaeger de; Farinatti, Paulo de Tarso Veras

2015-07-01

The study analyzed the effect of an açai (Euterpe oleracea Mart.) functional beverage (AB) on muscle and oxidative stress markers, cardiorespiratory responses, perceived exertion, and time-to-exhaustion during maximal treadmill running. The beverage was developed as an ergogenic aid for athletes and contained 27.6 mg of anthocyanins per dose. Fourteen athletes performed 3 exercise tests: a ramp-incremental maximal exercise test and 2 maximal exercise bouts performed in 2 conditions (AB and without AB (control)) at 90% maximal oxygen uptake. Blood was collected at baseline and after maximal exercise in both conditions to determine biomarkers. AB increased time to exhaustion during short-term high-intensity exercise (mean difference: 69 s, 95% confidence interval = -296 s to 159 s, t = 2.2, p = 0.045), attenuating the metabolic stress induced by exercise (p < 0.05). AB also reduced perceived exertion and enhanced cardiorespiratory responses (p < 0.05). The AB may be a useful and practical ergogenic aid to enhance performance during high-intensity training.

Discriminant locality preserving projections based on L1-norm maximization.

PubMed

Zhong, Fujin; Zhang, Jiashu; Li, Defang

2014-11-01

Conventional discriminant locality preserving projection (DLPP) is a dimensionality reduction technique based on manifold learning, which has demonstrated good performance in pattern recognition. However, because its objective function is based on the distance criterion using L2-norm, conventional DLPP is not robust to outliers which are present in many applications. This paper proposes an effective and robust DLPP version based on L1-norm maximization, which learns a set of local optimal projection vectors by maximizing the ratio of the L1-norm-based locality preserving between-class dispersion and the L1-norm-based locality preserving within-class dispersion. The proposed method is proven to be feasible and also robust to outliers while overcoming the small sample size problem. The experimental results on artificial datasets, Binary Alphadigits dataset, FERET face dataset and PolyU palmprint dataset have demonstrated the effectiveness of the proposed method.

A comparison of alternative medicare reimbursement policies under optimal hospital pricing.

PubMed Central

Dittman, D A; Morey, R C

1983-01-01

This paper applies and extends the use of a nonlinear hospital pricing model, recently posited in the literature by Dittman and Morey [1]. That model applied a hospital profit-maximizing behavior and studied the effects of optimal pricing of hospital ancillary services on the incidence of payment by private insurance companies and the Medicare trust fund. Here, we examine variations of the above model where both hospital profit-maximizing and profit-satisficing postures are of interest. We apply the model to three types of Medicare reimbursement policies currently in use or under legislative mandate to implement. The policies differ according to hospital size and whether cross-subsidies are allowed. We are interested in determining the effects of profit-maximizing and -satisficing behaviors of these three reimbursement policies on the levels of profits received, and on the respective implications for private payors and the Medicare trust fund. PMID:6347973

The rate of lactate removal after maximal exercise: the effect of intensity during active recovery.

PubMed

Riganas, C S; Papadopoulou, Z; Psichas, N; Skoufas, D; Gissis, I; Sampanis, M; Paschalis, V; Vrabas, I S

2015-10-01

The aim of the present investigation was to determine the greater rate of lactate removal after a maximal rowing test using different intensities during active recovery. Thirty elite male rowers performed a simulated incremental exercise protocol on rowing ergometer to determine their maximal oxygen uptake and they divided into three equal sized group according to the type of the recovery that followed the assessment. The first group (N.=10) subjected to 20 min of passive recovery, while the second (N.=10) and the third (N.=10) groups performed 20 min of active recovery using the 25% and the 50% of each individual’s maximal power output, respectively. During the recovery period, every two min were performed measurements for the assessment of blood lactate, oxygen consumption and heart rate (HR). It was found that after 10 min of active recovery at 50% and 25% of maximal power output lactate concentration reduced by 43% and 15%, respectively, while during passive recovery lactate concentration found to be slightly elevated by 1%. It was also found that during recovery period, HR, oxygen consumption and pulmonary ventilation was significant elevated at higher exercise intensity compared to lower exercise intensity and passive recovery. It is concluded that in elite male rowers the active recovery provided higher rate of lactate removal compared to passive recovery. Moreover, active recovery at 50% of maximal power output had better results in lactate clearance compared to the active recovery of lower intensity (25% of maximal power output).

Muscle-spring dynamics in time-limited, elastic movements.

PubMed

Rosario, M V; Sutton, G P; Patek, S N; Sawicki, G S

2016-09-14

Muscle contractions that load in-series springs with slow speed over a long duration do maximal work and store the most elastic energy. However, time constraints, such as those experienced during escape and predation behaviours, may prevent animals from achieving maximal force capacity from their muscles during spring-loading. Here, we ask whether animals that have limited time for elastic energy storage operate with springs that are tuned to submaximal force production. To answer this question, we used a dynamic model of a muscle-spring system undergoing a fixed-end contraction, with parameters from a time-limited spring-loader (bullfrog: Lithobates catesbeiana) and a non-time-limited spring-loader (grasshopper: Schistocerca gregaria). We found that when muscles have less time to contract, stored elastic energy is maximized with lower spring stiffness (quantified as spring constant). The spring stiffness measured in bullfrog tendons permitted less elastic energy storage than was predicted by a modelled, maximal muscle contraction. However, when muscle contractions were modelled using biologically relevant loading times for bullfrog jumps (50 ms), tendon stiffness actually maximized elastic energy storage. In contrast, grasshoppers, which are not time limited, exhibited spring stiffness that maximized elastic energy storage when modelled with a maximal muscle contraction. These findings demonstrate the significance of evolutionary variation in tendon and apodeme properties to realistic jumping contexts as well as the importance of considering the effect of muscle dynamics and behavioural constraints on energy storage in muscle-spring systems. © 2016 The Author(s).

Effects of ethnicity on the relationship between vertical jump and maximal power on a cycle ergometer.

PubMed

Rouis, Majdi; Coudrat, Laure; Jaafar, Hamdi; Attiogbé, Elvis; Vandewalle, Henry; Driss, Tarak

2016-06-01

The aim of this study was to verify the impact of ethnicity on the maximal power-vertical jump relationship. Thirty-one healthy males, sixteen Caucasian (age: 26.3 ± 3.5 years; body height: 179.1 ± 5.5 cm; body mass: 78.1 ± 9.8 kg) and fifteen Afro-Caribbean (age: 24.4 ±2.6 years; body height: 178.9 ± 5.5 cm; body mass: 77.1 ± 10.3 kg) completed three sessions during which vertical jump height and maximal power of lower limbs were measured. The results showed that the values of vertical jump height and maximal power were higher for Afro-Caribbean participants (62.92 ± 6.7 cm and 14.70 ± 1.75 W∙kg-1) than for Caucasian ones (52.92 ± 4.4 cm and 12.75 ± 1.36 W∙kg-1). Moreover, very high reliability indices were obtained on vertical jump (e.g. 0.95 < ICC < 0.98) and maximal power performance (e.g. 0.75 < ICC < 0.97). However, multiple linear regression analysis showed that, for a given value of maximal power, the Afro-Caribbean participants jumped 8 cm higher than the Caucasians. Together, these results confirmed that ethnicity impacted the maximal power-vertical jump relationship over three sessions. In the current context of cultural diversity, the use of vertical jump performance as a predictor of muscular power should be considered with caution when dealing with populations of different ethnic origins.

Sprint interval training (SIT) substantially reduces depressive symptoms in major depressive disorder (MDD): A randomized controlled trial.

PubMed

Minghetti, Alice; Faude, Oliver; Hanssen, Henner; Zahner, Lukas; Gerber, Markus; Donath, Lars

2018-07-01

Continuous aerobic exercise training (CAT) is considered a complementary treatment option in patients with major depressive disorder (MDD). Intermittent exercise training protocols, such as sprint interval training (SIT) have gained increasing popularity, but no studies on depressive symptoms following SIT in patients with MDD are available. Fifty-nine in-patients with MDD were randomly assigned to a SIT or CAT group. Medication was counterbalanced in both intervention arms. Both intervention groups received 3 weekly training sessions for 4-weeks (12 sessions in total). SIT comprised 25 bouts of 30 seconds at 80% of maximal power, whereas CAT consisted of 20 minutes of physical activity at 60% of maximal power. The training protocols were isocalorically designed. Maximal bicycle ergometer exercise testing yielded maximal and submaximal physical fitness parameters. The Beck-Depression-Inventory-II (BDI-II) was filled out by the patients before and after the intervention period. BDI-II scores substantially decreased in both groups with an effect size pointing towards a large effect (p < 0.001, η p ² = 0.70) while submaximal (0.07 < d < 0.89) and maximal (0.05 < d < 0.85) fitness variables improved in both groups. Short-term SIT leads to similar results as CAT in patients with MDD and can be regarded as a time-efficient and promising exercise-based treatment strategy. Copyright © 2018 Elsevier B.V. All rights reserved.

A new numerical method for calculating extrema of received power for polarimetric SAR

USGS Publications Warehouse

Zhang, Y.; Zhang, Jiahua; Lu, Z.; Gong, W.

2009-01-01

A numerical method called cross-step iteration is proposed to calculate the maximal/minimal received power for polarized imagery based on a target's Kennaugh matrix. This method is much more efficient than the systematic method, which searches for the extrema of received power by varying the polarization ellipse angles of receiving and transmitting polarizations. It is also more advantageous than the Schuler method, which has been adopted by the PolSARPro package, because the cross-step iteration method requires less computation time and can derive both the maximal and minimal received powers, whereas the Schuler method is designed to work out only the maximal received power. The analytical model of received-power optimization indicates that the first eigenvalue of the Kennaugh matrix is the supremum of the maximal received power. The difference between these two parameters reflects the depolarization effect of the target's backscattering, which might be useful for target discrimination. ?? 2009 IEEE.

Opioid receptor mediated anticonvulsant effect of pentazocine.

PubMed

Khanna, N; Khosla, R; Kohli, J

1998-01-01

Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

Effect of Repeated Whole Blood Donations on Aerobic Capacity and Hemoglobin Mass in Moderately Trained Male Subjects: A Randomized Controlled Trial.

PubMed

Meurrens, Julie; Steiner, Thomas; Ponette, Jonathan; Janssen, Hans Antonius; Ramaekers, Monique; Wehrlin, Jon Peter; Vandekerckhove, Philippe; Deldicque, Louise

2016-12-01

The aims of the present study were to investigate the impact of three whole blood donations on endurance capacity and hematological parameters and to determine the duration to fully recover initial endurance capacity and hematological parameters after each donation. Twenty-four moderately trained subjects were randomly divided in a donation (n = 16) and a placebo (n = 8) group. Each of the three donations was interspersed by 3 months, and the recovery of endurance capacity and hematological parameters was monitored up to 1 month after donation. Maximal power output, peak oxygen consumption, and hemoglobin mass decreased (p < 0.001) up to 4 weeks after a single blood donation with a maximal decrease of 4, 10, and 7%, respectively. Hematocrit, hemoglobin concentration, ferritin, and red blood cell count (RBC), all key hematological parameters for oxygen transport, were lowered by a single donation (p < 0.001) and cumulatively further affected by the repetition of the donations (p < 0.001). The maximal decrease after a blood donation was 11% for hematocrit, 10% for hemoglobin concentration, 50% for ferritin, and 12% for RBC (p < 0.001). Maximal power output cumulatively increased in the placebo group as the maximal exercise tests were repeated (p < 0.001), which indicates positive training adaptations. This increase in maximal power output over the whole duration of the study was not observed in the donation group. Maximal, but not submaximal, endurance capacity was altered after blood donation in moderately trained people and the expected increase in capacity after multiple maximal exercise tests was not present when repeating whole blood donations.

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

Effect of Aerobic Exercise Training on Ventilatory Efficiency and Respiratory Drive in Obese Subjects.

PubMed

Chlif, Mehdi; Chaouachi, Anis; Ahmaidi, Said

2017-07-01

Obese patients show a decline in exercise capacity and diverse degrees of dyspnea in association with mechanical abnormalities, increased ventilatory requirements secondary to the increased metabolic load, and a greater work of breathing. Consequently, obese patients may be particularly predisposed to the development of respiratory muscle fatigue during exercise. The aim of this study was to assess inspiratory muscle performance during incremental exercise in 19 obese male subjects (body mass index 41 ± 6 kg/m 2 ) after aerobic exercise training using the noninvasive, inspiratory muscle tension-time index (T T0.1 ). Measurements performed included anthropometric parameters, lung function assessed by spirometry, rate of perceived breathlessness with the modified Borg dyspnea scale (0-10), breathing pattern, maximal exercise capacity, and inspiratory muscle performance with a breath-by-breath automated exercise metabolic system during an incremental exercise test. T T0.1 was calculated using the equation, T T0.1 = P 0.1 /P Imax × T I /T tot (where P 0.1 represents mouth occlusion pressure, P Imax is maximal inspiratory pressure, and T I /T tot is the duty cycle). At rest, there was no statistically significant difference for spirometric parameters and cardiorespiratory parameters between pre- and post-training. At maximal exercise, the minute ventilation, the rate of exchange ratio, the rate of perceived breathlessness, and the respiratory muscle performance parameters were not significantly different pre- and post-training; in contrast, tidal volume ( P = .037, effect size = 1.51), breathing frequency ( P = .049, effect size = 0.97), power output ( P = .048, effect size = 0.79), peak oxygen uptake ( P = .02, effect size = 0.92) were significantly higher after training. At comparable work load, training induces lower minute ventilation, mouth occlusion pressure, ratio of occlusion pressure to maximal inspiratory pressure, T T0.1 , and rate of perceived breathlessness. Aerobic exercise at ventilatory threshold can induce significant improvement in respiratory muscle strength, maximal exercise capacity, and inspiratory muscle performance and decreased dyspnea perception in obese subjects. Copyright © 2017 by Daedalus Enterprises.

Comparison of Periodized and Non-Periodized Resistance Training on Maximal Strength: A Meta-Analysis.

PubMed

Williams, Tyler D; Tolusso, Danilo V; Fedewa, Michael V; Esco, Michael R

2017-10-01

Periodization is a logical method of organizing training into sequential phases and cyclical time periods in order to increase the potential for achieving specific performance goals while minimizing the potential for overtraining. Periodized resistance training plans are proposed to be superior to non-periodized training plans for enhancing maximal strength. The primary aim of this study was to examine the previous literature comparing periodized resistance training plans to non-periodized resistance training plans and determine a quantitative estimate of effect on maximal strength. All studies included in the meta-analysis met the following inclusion criteria: (1) peer-reviewed publication; (2) published in English; (3) comparison of a periodized resistance training group to a non-periodized resistance training group; (4) maximal strength measured by 1-repetition maximum (1RM) squat, bench press, or leg press. Data were extracted and independently coded by two authors. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (CIs) and potential moderators. The cumulative results of 81 effects gathered from 18 studies published between 1988 and 2015 indicated that the magnitude of improvement in 1RM following periodized resistance training was greater than non-periodized resistance training (ES = 0.43, 95% CI 0.27-0.58; P < 0.001). Periodization model (β = 0.51; P = 0.0010), training status (β = -0.59; P = 0.0305), study length (β = 0.03; P = 0.0067), and training frequency (β = 0.46; P = 0.0123) were associated with a change in 1RM. These results indicate that undulating programs were more favorable for strength gains. Improvements in 1RM were greater among untrained participants. Additionally, higher training frequency and longer study length were associated with larger improvements in 1RM. These results suggest that periodized resistance training plans have a moderate effect on 1RM compared to non-periodized training plans. Variation in training stimuli appears to be vital for increasing maximal strength, and longer periods of higher training frequency may be preferred.

Pre- and postnatal toxicity induced in guinea pigs by N-nitrosomethylurea.

PubMed

Hasumi, K; Wilber, J H; Berkowitz, J; Wilber, R G; Epstein, S S

1975-10-01

Oral administration of N-nitrosomethylurea at maximally tolerated doses to guinea pigs on alternate days from days 34-58 of pregnancy induced prenatal toxicity, as evidenced by a high frequency of stillbirths and intrauterine growth retardation, and postnatal toxicity, as evidenced by stunting and progressive mortality. Similar administration of N-nitrosomethylurethane at maximally tolerated doses did not induce such toxic effects.

Effective Client Management: Maximizing The Influence of External Sponsors Over Affiliated Armed Groups

DTIC Science & Technology

2017-12-01

MANAGEMENT : MAXIMIZING THE INFLUENCE OF EXTERNAL SPONSORS OVER AFFILIATED ARMED GROUPS by Anders C. Hamlin December 2017 Thesis Co...burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information . Send comments regarding this

Effects of coil characteristics for femoral nerve magnetic stimulation.

PubMed

Tomazin, Katja; Verges, Samuel; Decorte, Nicolas; Oulerich, Alain; Millet, Guillaume Y

2010-03-01

The aim of this study was to compare the efficiency of two coils used for femoral nerve magnetic stimulation and to compare them with electrical stimulation in inducing maximal response of the quadriceps. The mechanical and electromyographic (EMG) responses were dependent on the coil used. The 45-mm double coil showed greater efficiency to elicit a maximal quadriceps response, which was similar to electrical stimulation.

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

PubMed Central

Schuchardt, Christiane; Kulkarni, Harshad R.; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P.; Beer, Ambros J.

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably. PMID:27611841

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides.

PubMed

Kletting, Peter; Schuchardt, Christiane; Kulkarni, Harshad R; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P; Beer, Ambros J

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25-29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1-3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.

Effects on muscle strength, maximal jump height, flexibility and postural sway after soccer and Zumba exercise among female hospital employees: a 9-month randomised controlled trial.

PubMed

Barene, Svein; Holtermann, Andreas; Oseland, Harald; Brekke, Ole-Lars; Krustrup, Peter

2016-10-01

This 9-month randomised controlled workplace physical activity trial investigated the effects of soccer and Zumba exercise, respectively, on muscle strength, maximal jump height, sit-and-reach flexibility and postural sway among female workers. A total of 107 female hospital employees aged 25-63 were cluster-randomised to a soccer group, a Zumba group or a control group. Training was conducted outside working hours as two to three 1-h weekly sessions the first 3 months and once a week the last 6 months. Tests were conducted at baseline, after 3 and 9 months. The soccer group improved maximal neck extension strength both after 3 (1.2 kg; P < 0.05) and 9 months (1.7 kg; P < 0.01) compared to the control group. The Zumba group improved maximal trunk extension strength (3.1 kg; P = 0.04) after 3 months, with improvements in postural sway velocity moment (-9.2 mm(2)/s; P < 0.05) and lower limb lean mass (0.4 kg; P < 0.05) after 9 months. No significant intervention effects were revealed in vertical jump height or sit-and-reach flexibility. The present study indicates that workplace-initiated soccer and Zumba exercise may be beneficial for improvement of the neck and trunk strength, which may have preventive effects with regard to future perceived muscle pain in the respective body regions. Furthermore, the Zumba group revealed positive effects on lower limb lean mass and postural sway compared to the control group.

Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine, oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures in mice.

PubMed

Luszczki, Jarogniew J; Wlaz, Aleksandra; Karwan, Slawomir; Florek-Luszczki, Magdalena; Czuczwar, Stanislaw J

2013-11-15

The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN - a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four second-generation antiepileptic drugs (lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), the step-through passive avoidance task (assessing long-term memory) and the grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by high-pressure liquid chromatography to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5mg/kg, i.p.) significantly enhanced the anticonvulsant action of lamotrigine (P<0.05), pregabalin (P<0.001) and topiramate (P<0.05), but not that of oxcarbazepine in the maximal electroshock-induced tonic seizure test in mice. Furthermore, none of the investigated combinations of WIN with antiepileptic drugs were associated with any concurrent adverse effects with regards to motor performance, long-term memory or muscular strength. Pharmacokinetic characterization revealed that WIN had no impact on total brain concentrations of lamotrigine, oxcarbazepine, pregabalin and topiramate in mice. These preclinical data would suggest that WIN in combination with lamotrigine, pregabalin and topiramate is associated with beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced tonic seizure test. © 2013 Published by Elsevier B.V.

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.

Reaction mechanism interplay in determining the biological effectiveness of neutrons as a function of energy.

PubMed

Baiocco, G; Alloni, D; Babini, G; Mariotti, L; Ottolenghi, A

2015-09-01

Neutron relative biological effectiveness (RBE) is found to be energy dependent, being maximal for energies ∼1 MeV. This is reflected in the choice of radiation weighting factors wR for radiation protection purposes. In order to trace back the physical origin of this behaviour, a detailed study of energy deposition processes with their full dependences is necessary. In this work, the Monte Carlo transport code PHITS was used to characterise main secondary products responsible for energy deposition in a 'human-sized' soft tissue spherical phantom, irradiated by monoenergetic neutrons with energies around the maximal RBE/wR. Thereafter, results on the microdosimetric characterisation of secondary protons were used as an input to track structure calculations performed with PARTRAC, thus evaluating the corresponding DNA damage induction. Within the proposed simplified approach, evidence is suggested for a relevant role of secondary protons in inducing the maximal biological effectiveness for 1 MeV neutrons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of overweight and leisure-time activities on aerobic fitness in urban and rural adolescents.

PubMed

Albarwani, Sulayma; Al-Hashmi, Khamis; Al-Abri, Mohammed; Jaju, Deepali; Hassan, Mohammed O

2009-08-01

The aim of this research was to study the effects of overweight and leisure-time activities on maximal aerobic capacity (VO(2)max) in urban and rural Omani adolescents. A total of 529 (245 males, 284 females) adolescents, aged 15-16 years were randomly selected from segregated urban and rural schools. Maximal aerobic capacity was estimated using the multistage 20-meter shuttle-run test. The body mass index (BMI) of urban boys and girls was significantly higher than that of rural boys and girls. Urban boys and girls spent significantly less weekly hours on sports activities and significantly more weekly hours on TV/computer games than their rural counterpart. Urban boys and girls achieved significantly less VO(2)max than rural boys and girls (44.2 and 33.0 vs. 48.3 and 38.6 mL/kg/min, respectively). Maximal aerobic capacity was negatively correlated with BMI in urban boys. Overweight and inactivity had significant negative effects on cardiorespiratory fitness in urban boys and girls as compared to their rural counterparts. Weight gain in adolescence requires early intervention.

Effectiveness of global postural reeducation in the treatment of temporomandibular disorder: case report.

PubMed

Monteiro, Wagner; Francisco de Oliveira Dantas da Gama, Thomaz; dos Santos, Robiana Maria; Collange Grecco, Luanda André; Pasini Neto, Hugo; Oliveira, Claudia Santos

2013-01-01

The aim of the present study was to evaluate the effectiveness of global postural reeducation in the treatment of temporomandibular disorder through bilateral surface electromyographic (EMG) analysis of the masseter muscle in a 23-year-old volunteer. EMG values for the masseter were collected at rest (baseline) and during a maximal occlusion. There was a change in EMG activity both at rest and during maximal occlusion following the intervention, evidencing neuromuscular rebalancing between both sides after treatment as well as an increase in EMG activity during maximal occlusion, with direct improvement in the recruitment of motor units during contractile activity and a decrease in muscle tension between sides at rest. The improvement in postural patterns of the cervical spine provided an improvement in aspects of the EMG signal of the masseter muscle in this patient. However, a multidisciplinary study is needed in order to determine the effect of different forms of treatment on this condition and compare benefits between interventions. Therefore, this study can provide a direction regarding the application of this technique in patients with temporomandibular disorder. Copyright © 2012 Elsevier Ltd. All rights reserved.

Informing Public Perceptions About Climate Change: A 'Mental Models' Approach.

PubMed

Wong-Parodi, Gabrielle; Bruine de Bruin, Wändi

2017-10-01

As the specter of climate change looms on the horizon, people will face complex decisions about whether to support climate change policies and how to cope with climate change impacts on their lives. Without some grasp of the relevant science, they may find it hard to make informed decisions. Climate experts therefore face the ethical need to effectively communicate to non-expert audiences. Unfortunately, climate experts may inadvertently violate the maxims of effective communication, which require sharing communications that are truthful, brief, relevant, clear, and tested for effectiveness. Here, we discuss the 'mental models' approach towards developing communications, which aims to help experts to meet the maxims of effective communications, and to better inform the judgments and decisions of non-expert audiences.

Calcitonin gene-related peptide (CGRP) in the circular muscle of guinea-pig colon: role as inhibitory transmitter and mechanisms of relaxation.

PubMed

Maggi, C A; Giuliani, S; Zagorodnyuk, V

1996-01-16

In the presence of 1 microM tetrodotoxin (TTX), human alpha calcitonin gene-related peptide (CGRP) produced a concentration-dependent relaxation (EC50 1.1 nM; Emax 86% of the relaxation to 1 microM isoprenaline) of mucosa-free circular muscle strips from the guinea-pig proximal colon. In the presence of TTX, the C-terminal fragment CGRP(8-37) produced a concentration (0.3-3 microM)-dependent rightward shift of the curve to CGRP. The TTX-resistant, receptor-mediated, CGRP-induced relaxation was unaffected by apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), alone or in combination, as well as by glibenclamide (3 microM) or (S)-ketoprofen (10 microM). Tetraethylammonium (TEA, 1-10 mM) and cyclopiazonic acid (CPA, 3-10 microM) produced a concentration-dependent partial inhibition of the relaxant response to CGRP. The inhibitory effect of TEA on the maximal relaxation produced by CGRP was prevented by nifedipine (1 microM) which did not affect the CGRP-relaxation of its own. In the presence of atropine (1 microM), guanethidine (3 microM), SR 140,333 (0.3 microM), MEN 10,627 (1 microM), apamin (0.3 microM) and L-NOARG (100 microM), the application of 1 microM capsaicin produced a transient relaxation of the strips. This response was not reproduced upon a second application of capsaicin, 60 min later, indicating complete desensitization. CGRP(8-37) (0.3-1.0 microM) produced a partial inhibitory effect (about 50% inhibition) of the relaxant response to capsaicin. In the presence of atropine (1 microM), guanethidine (3 microM), SR 140,333 (0.3 microM), MEN 10,627 (1 microM), apamin (0.3 microM), L-NOARG (100 microM) and after capsaicin in vitro pretreatment (10 microM for 15 min), electrical field stimulation (EFS, 10 Hz for 5 s) produced a transient relaxation which was unchanged by CGRP(8-37) (1 microM) while being abolished by TTX. In sucrose gap, brief superfusion with 0.3 microM CGRP produced a TTX (1 microM)- resistant membrane hyperpolarization and relaxation: the hyperpolarization produced by CGRP was inhibited by about 50% by either TEA (10 mM) or CPA (10 microM), while being unaffected by glibenclamide (3 microM). The combined application of TEA and CPA was not more effective (65% inhibition) in inhibiting the CGRP-induced hyperpolarization than each drug alone. We conclude that CGRP produces a direct relaxation of the circular muscle of the guinea-pig proximal colon by activating receptors sensitive to blockade by CGRP(8-37). Activation of Ca-dependent potassium channels and Ca release/reuptake from internal store(s) appear both to be involved in the action of CGRP. Endogenous CGRP mediates part of the relaxant response evoked by stimulation of capsaicin-sensitive primary afferent nerves in the circular muscle of guinea-pig colon, while it is not involved in the apamin and L-NOARG-resistant nonadrenergic noncholinergic (NANC) relaxation produced by electrical field stimulation of intrinsic inhibitory nerves.

Effect of core stability training on throwing velocity in female handball players.

PubMed

Saeterbakken, Atle H; van den Tillaar, Roland; Seiler, Stephen

2011-03-01

The purpose was to study the effect of a sling exercise training (SET)-based core stability program on maximal throwing velocity among female handball players. Twenty-four female high-school handball players (16.6 ± 0.3 years, 63 ± 6 kg, and 169 ± 7 cm) participated and were initially divided into a SET training group (n = 14) and a control group (CON, n = 10). Both groups performed their regular handball training for 6 weeks. In addition, twice a week, the SET group performed a progressive core stability-training program consisting of 6 unstable closed kinetic chain exercises. Maximal throwing velocity was measured before and after the training period using photocells. Maximal throwing velocity significantly increased 4.9% from 17.9 ± 0.5 to 18.8 ± 0.4 m·s in the SET group after the training period (p < 0.01), but was unchanged in the control group (17.1 ± 0.4 vs. 16.9 ± 0.4 m·s). These results suggest that core stability training using unstable, closed kinetic chain movements can significantly improve maximal throwing velocity. A stronger and more stable lumbopelvic-hip complex may contribute to higher rotational velocity in multisegmental movements. Strength coaches can incorporate exercises exposing the joints for destabilization force during training in closed kinetic chain exercises. This may encourage an effective neuromuscular pattern and increase force production and can improve a highly specific performance task such as throwing.

Tradeoff between assessment and control of aquatic invasive species: A case study of sea lamprey management in the St. Marys River

USGS Publications Warehouse

Robinson, Jason M.; Wilberg, Michael J.; Adams, Jean V.; Jones, Michael L.

2016-01-01

Allocating resources between the gathering of information to guide management actions and implementing those actions presents an inherent tradeoff. This tradeoff is evident for control of the Sea Lamprey Petromyzon marinus in the St. Marys River, connecting Lakes Huron and Superior and a major source of parasitic Sea Lampreys to Lake Huron and northern Lake Michigan. Larval Sea Lampreys in the St. Marys River are controlled through the application of Bayluscide, which is applied to areas of high larval density. Bayluscide applications are guided with an annual deepwater electrofishing survey to estimate larval Sea Lamprey density at relatively fine spatial scales. We took a resampling approach to describe the effect of sampling intensity on the success of the larval Sea Lamprey management program and explicitly incorporated the economic tradeoff between assessment and control efforts to maximize numbers of larvae killed in the St. Marys River. When no tradeoff between assessment and control was incorporated, increasing assessment always led to more larvae killed for the same treatment budget. When the tradeoff was incorporated, the sampling intensity that maximized the number of larvae killed depended on the overall budget available. Increased sampling intensities maximized effectiveness under medium to large budgets (US \\$0.4 to \\$2.0 million), and intermediate sampling intensities maximized effectiveness under low budgets. Sea Lamprey control actions based on assessment information outperformed those that were implemented with no assessment under all budget scenarios.

Expectation maximization for hard X-ray count modulation profiles

NASA Astrophysics Data System (ADS)

Benvenuto, F.; Schwartz, R.; Piana, M.; Massone, A. M.

2013-07-01

Context. This paper is concerned with the image reconstruction problem when the measured data are solar hard X-ray modulation profiles obtained from the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) instrument. Aims: Our goal is to demonstrate that a statistical iterative method classically applied to the image deconvolution problem is very effective when utilized to analyze count modulation profiles in solar hard X-ray imaging based on rotating modulation collimators. Methods: The algorithm described in this paper solves the maximum likelihood problem iteratively and encodes a positivity constraint into the iterative optimization scheme. The result is therefore a classical expectation maximization method this time applied not to an image deconvolution problem but to image reconstruction from count modulation profiles. The technical reason that makes our implementation particularly effective in this application is the use of a very reliable stopping rule which is able to regularize the solution providing, at the same time, a very satisfactory Cash-statistic (C-statistic). Results: The method is applied to both reproduce synthetic flaring configurations and reconstruct images from experimental data corresponding to three real events. In this second case, the performance of expectation maximization, when compared to Pixon image reconstruction, shows a comparable accuracy and a notably reduced computational burden; when compared to CLEAN, shows a better fidelity with respect to the measurements with a comparable computational effectiveness. Conclusions: If optimally stopped, expectation maximization represents a very reliable method for image reconstruction in the RHESSI context when count modulation profiles are used as input data.

Orbital Evasive Target Tracking and Sensor Management

DTIC Science & Technology

2012-03-30

maximize the total information gain in the observer-to-target assignment. We compare the information based approach to the game theoretic criterion where...tracking with multiple space borne observers. The results indicate that the game theoretic approach is more effective than the information based approach in...sensor management is to maximize the total information gain in the observer-to-target assignment. We compare the information based approach to the game

Effective Educational Videos: Principles and Guidelines for Maximizing Student Learning from Video Content

PubMed Central

Brame, Cynthia J.

2016-01-01

Educational videos have become an important part of higher education, providing an important content-delivery tool in many flipped, blended, and online classes. Effective use of video as an educational tool is enhanced when instructors consider three elements: how to manage cognitive load of the video; how to maximize student engagement with the video; and how to promote active learning from the video. This essay reviews literature relevant to each of these principles and suggests practical ways instructors can use these principles when using video as an educational tool. PMID:27789532

Jump Training in Youth Soccer Players: Effects of Haltere Type Handheld Loading.

PubMed

Rosas, F; Ramirez-Campillo, R; Diaz, D; Abad-Colil, F; Martinez-Salazar, C; Caniuqueo, A; Cañas-Jamet, R; Loturco, I; Nakamura, F Y; McKenzie, C; Gonzalez-Rivera, J; Sanchez-Sanchez, J; Izquierdo, M

2016-12-01

The aim of this study was to compare the effects of a jump training program, with or without haltere type handheld loading, on maximal intensity exercise performance. Youth soccer players (12.1±2.2 y) were assigned to either a jump training group (JG, n=21), a jump training group plus haltere type handheld loading (LJG, n=21), or a control group following only soccer training (CG, n=21). Athletes were evaluated for maximal-intensity performance measures before and after 6 weeks of training, during an in-season training period. The CG achieved a significant change in maximal kicking velocity only (ES=0.11-0.20). Both jump training groups improved in right leg (ES=0.28-0.45) and left leg horizontal countermovement jump with arms (ES=0.32-0.47), horizontal countermovement jump with arms (ES=0.28-0.37), vertical countermovement jump with arms (ES=0.26), 20-cm drop jump reactive strength index (ES=0.20-0.37), and maximal kicking velocity (ES=0.27-0.34). Nevertheless, compared to the CG, only the LJG exhibited greater improvements in all performance tests. Therefore, haltere type handheld loading further enhances performance adaptations during jump training in youth soccer players. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of a 6-month exercise program pilot study on walking economy, peak physiological characteristics, and walking performance in patients with peripheral arterial disease.

PubMed

Crowther, Robert G; Leicht, Anthony S; Spinks, Warwick L; Sangla, Kunwarjit; Quigley, Frank; Golledge, Jonathan

2012-01-01

The purpose of this study was to examine the effects of a 6-month exercise program on submaximal walking economy in individuals with peripheral arterial disease and intermittent claudication (PAD-IC). Participants (n = 16) were randomly allocated to either a control PAD-IC group (CPAD-IC, n = 6) which received standard medical therapy, or a treatment PAD-IC group (TPAD-IC; n = 10) which took part in a supervised exercise program. During a graded treadmill test, physiological responses, including oxygen consumption, were assessed to calculate walking economy during submaximal and maximal walking performance. Differences between groups at baseline and post-intervention were analyzed via Kruskal-Wallis tests. At baseline, CPAD-IC and TPAD-IC groups demonstrated similar walking performance and physiological responses. Postintervention, TPAD-IC patients demonstrated significantly lower oxygen consumption during the graded exercise test, and greater maximal walking performance compared to CPAD-IC. These preliminary results indicate that 6 months of regular exercise improves both submaximal walking economy and maximal walking performance, without significant changes in maximal walking economy. Enhanced walking economy may contribute to physiological efficiency, which in turn may improve walking performance as demonstrated by PAD-IC patients following regular exercise programs.

pH-control modes in a 5-L stirred-tank bioreactor for cell biomass and exopolysaccharide production by Tremella fuciformis spore.

PubMed

Zhu, Hu; Cao, Chunxu; Zhang, Shuaishuai; Zhang, Yan; Zou, Weisheng

2011-10-01

The effect of pH-control modes on cell growth and exopolysaccharide production by Tremella fuciformis was evaluated in a 5-L bioreactor. The results show that the maximal dry cell weight (DCW) and exopolysaccharide production were 23.57 and 4.48 g L⁻¹ in pH-stat fermentation, where the maximal specific growth rate (μ(max)) and specific production rate of exopolysaccharide (P(P/X)) were 1.03 and 0.24 d⁻¹, respectively; under pH-shift cultivation, the maximal DCW and exopolysaccharide production were 30.57 and 3.90 g L⁻¹, where the μ(max) and P(P/X) were 1.21 and 0.06 d⁻¹. Unlike batch fermentation, maximal DCW and exopolysaccharide production merely reached 15.04 and 2.0 g L⁻¹, where the μ(max) and P(P/X) were 0.86 and 0.05 d⁻¹, respectively. These results suggest that a pH-stat strategy is a more efficient way of performing the fermentation process to increase exopolysaccharide production. Furthermore, this research has also proved that the three-stage pH-control mode is effective for cell growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

Addressing the Common Pathway Underlying Hypertension and Diabetes in People Who Are Obese by Maximizing Health: The Ultimate Knowledge Translation Gap

PubMed Central

Dean, Elizabeth; Lomi, Constantina; Bruno, Selma; Awad, Hamzeh; O'Donoghue, Grainne

2011-01-01

In accordance with the WHO definition of health, this article examines the alarming discord between the epidemiology of hypertension, type 2 diabetes mellitus (T2DM), and obesity and the low profile of noninvasive (nondrug) compared with invasive (drug) interventions with respect to their prevention, reversal and management. Herein lies the ultimate knowledge translation gap and challenge in 21st century health care. Although lifestyle modification has long appeared in guidelines for medically managing these conditions, this evidence-based strategy is seldom implemented as rigorously as drug prescription. Biomedicine focuses largely on reducing signs and symptoms; the effects of the problem rather than the problem. This article highlights the evidence-based rationale supporting prioritizing the underlying causes and contributing factors for hypertension and T2DM, and, in turn, obesity. We argue that a primary focus on maximizing health could eliminate all three conditions, at best, or, at worst, minimize their severity, complications, and medication needs. To enable such knowledge translation and maximizing health outcome, the health care community needs to practice as an integrated team, and address barriers to effecting maximal health in all patients. Addressing the ultimate knowledge translation gap, by aligning the health care paradigm to 21st century needs, would constitute a major advance. PMID:21423684

The effect of swinging the arms on muscle activation and production of leg force during ski skating at different skiing speeds.

PubMed

Göpfert, Caroline; Lindinger, Stefan J; Ohtonen, Olli; Rapp, Walter; Müller, Erich; Linnamo, Vesa

2016-06-01

The study investigated the effects of arm swing during leg push-off in V2-alternate/G4 skating on neuromuscular activation and force production by the leg muscles. Nine skilled cross-country skiers performed V2-alternate skating without poles at moderate, high, and maximal speeds, both with free (SWING) and restricted arm swing (NOSWING). Maximal speed was 5% greater in SWING (P<0.01), while neuromuscular activation and produced forces did not differ between techniques. At both moderate and high speed the maximal (2% and 5%, respectively) and average (both 5%) vertical force and associated impulse (10% and 14%) were greater with SWING (all P<0.05). At high speed range of motion and angular velocity of knee flexion were 24% greater with SWING (both P<0.05), while average EMG of m. biceps femoris was 31% lower (all P<0.05) in SWING. In a similar manner, the average EMG of m. vastus medialis and m. biceps femoris were lower (17% and 32%, P<0.05) during the following knee extension. Thus, swinging the arms while performing V2-alternate can enhance both maximal speed and skiing economy at moderate and, in particularly, high speeds. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of maximal dynamic exercise on exhaled ethane and carbon monoxide levels in human, equine, and canine athletes.

PubMed

Wyse, Cathy; Cathcart, Andy; Sutherland, Rona; Ward, Susan; McMillan, Lesley; Gibson, Graham; Padgett, Miles; Skeldon, Kenneth

2005-06-01

Exercise-induced oxidative stress (EIOS) refers to a condition where the balance of free radical production and antioxidant systems is disturbed during exercise in favour of pro-oxidant free radicals. Breath ethane is a product of free radical-mediated oxidation of cell membrane lipids and is considered to be a reliable marker of oxidative stress. The heatshock protein, haem oxygenase, is induced by oxidative stress and degrades haemoglobin to bilirubin, with concurrent production of carbon monoxide (CO). The aim of this study was to investigate the effect of maximal exercise on exhaled ethane and CO in human, canine, and equine athletes. Human athletes (n = 8) performed a maximal exercise test on a treadmill, and canine (n = 12) and equine (n = 11) athletes exercised at gallop on a sand racetrack. Breath samples were taken at regular intervals during exercise in the human athletes, and immediately before and after exercise in the canine and equine athletes. Breath samples were stored in gas-impermeable bags for analysis of ethane by laser spectroscopy, and CO was measured directly using an electrochemical CO monitor. Maximal exercise was associated with significant increases in exhaled ethane in the human, equine, and canine athletes. Decreased concentrations of exhaled CO were detected after maximal exercise in the human athletes, but CO was rarely detectable in the canine and equine athletes. The ethane breath test allows non-invasive and real-time detection of oxidative stress, and this method will facilitate further investigation of the processes mediating EIOS in human and animal athletes.

Comprehensive home-based care coordination for vulnerable elders with dementia: Maximizing Independence at Home-Plus-Study protocol.

PubMed

Samus, Quincy M; Davis, Karen; Willink, Amber; Black, Betty S; Reuland, Melissa; Leoutsakos, Jeannie; Roth, David L; Wolff, Jennifer; Gitlin, Laura N; Lyketsos, Constantine G; Johnston, Deirdre

2017-12-01

Despite availability of effective care strategies for dementia, most health care systems are not yet organized or equipped to provide comprehensive family-centered dementia care management. Maximizing Independence at Home-Plus is a promising new model of dementia care coordination being tested in the U.S. through a Health Care Innovation Award funded by the Centers for Medicare and Medicaid Services that may serve as a model to address these delivery gaps, improve outcomes, and lower costs. This report provides an overview of the Health Care Innovation Award aims, study design, and methodology. This is a prospective, quasi-experimental intervention study of 342 community-living Medicare-Medicaid dual eligibles and Medicare-only beneficiaries with dementia in Maryland. Primary analyses will assess the impact of Maximizing Independence at Home-Plus on risk of nursing home long-term care placement, hospitalization, and health care expenditures (Medicare, Medicaid) at 12, 18 (primary end point), and 24 months, compared to a propensity-matched comparison group. The goals of the Maximizing Independence at Home-Plus model are to improve care coordination, ability to remain at home, and life quality for participants and caregivers, while reducing total costs of care for this vulnerable population. This Health Care Innovation Award project will provide timely information on the impact of Maximizing Independence at Home-Plus care coordination model on a variety of outcomes including effects on Medicaid and Medicare expenditures and service utilization. Participant characteristic data, cost savings, and program delivery costs will be analyzed to develop a risk-adjusted payment model to encourage sustainability and facilitate spread.

Effects of exercise-induced muscle damage on resting metabolic rate, sub-maximal running and post-exercise oxygen consumption.

PubMed

Burt, Dean Gareth; Lamb, Kevin; Nicholas, Ceri; Twist, Craig

2014-01-01

Exercise-induced muscle damage (EIMD), described as the acute weakness of the musculature after unaccustomed eccentric exercise, increases oxidative metabolism at rest and during endurance exercise. However, it is not known whether oxygen uptake during recovery from endurance exercise is increased when experiencing symptoms of EIMD. Therefore, the purpose of this study was to investigate the effects of EIMD on physiological and metabolic responses before, during and after sub-maximal running. After a 12 h fast, eight healthy male participants completed baseline measurements comprising resting metabolic rate (RMR), indirect markers of EIMD, 10 min of sub-maximal running and 30 min of recovery to ascertain excess post-exercise oxygen consumption (EPOC). Measurements were then repeated at 24 and 48 h after 100 Smith-machine squats. Data analysis revealed significant (P<0.05) increases in muscle soreness and creatine kinase (CK) and decreases in peak knee extensor torque at 24 and 48 h after squatting exercise. Moreover, RMR, physiological, metabolic and perceptual responses during sub-maximal running and EPOC were increased in the two days after squatting exercise (P<0.05). It is suggested that the elevated RMR was a consequence of a raised energy requirement for the degradation and resynthesis of damaged muscle fibres. The increased oxygen demand during sub-maximal running after muscle damage was responsible for the increase in EPOC. Individuals engaging in unaccustomed resistance exercise that results in muscle damage should be mindful of the increases in resting energy expenditure and increased metabolic demand to exercise in the days that follow.

Effects of Maximal Sodium and Potassium Conductance on the Stability of Hodgkin-Huxley Model

PubMed Central

Wang, Kuanquan; Yuan, Yongfeng; Zhang, Henggui

2014-01-01

Hodgkin-Huxley (HH) equation is the first cell computing model in the world and pioneered the use of model to study electrophysiological problems. The model consists of four differential equations which are based on the experimental data of ion channels. Maximal conductance is an important characteristic of different channels. In this study, mathematical method is used to investigate the importance of maximal sodium conductance g-Na and maximal potassium conductance g-K. Applying stability theory, and taking g-Na and g-K as variables, we analyze the stability and bifurcations of the model. Bifurcations are found when the variables change, and bifurcation points and boundary are also calculated. There is only one bifurcation point when g-Na is the variable, while there are two points when g-K is variable. The (g-Na,  g-K) plane is partitioned into two regions and the upper bifurcation boundary is similar to a line when both g-Na and g-K are variables. Numerical simulations illustrate the validity of the analysis. The results obtained could be helpful in studying relevant diseases caused by maximal conductance anomaly. PMID:25104970

Influence of lumbar spine extension on vertical jump height during maximal squat jumping.

PubMed

Blache, Yoann; Monteil, Karine

2014-01-01

The purpose of this study was to determine the influence of lumbar spine extension and erector spinae muscle activation on vertical jump height during maximal squat jumping. Eight male athletes performed maximal squat jumps. Electromyograms of the erector spinae were recorded during these jumps. A simulation model of the musculoskeletal system was used to simulate maximal squat jumping with and without spine extension. The effect on vertical jump height of changing erector spinae strength was also tested through the simulated jumps. Concerning the participant jumps, the kinematics indicated a spine extension and erector spinae activation. Concerning the simulated jumps, vertical jump height was about 5.4 cm lower during squat jump without trunk extension compared to squat jump. These results were explained by greater total muscle work during squat jump, more especially by the erector spinae work (+119.5 J). The erector spinae may contribute to spine extension during maximal squat jumping. The simulated jumps confirmed this hypothesis showing that vertical jumping was decreased if this muscle was not taken into consideration in the model. Therefore it is concluded that the erector spinae should be considered as a trunk extensor, which enables to enhance total muscle work and consequently vertical jump height.

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.

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

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.

Alpha-ketoisocaproate is not a true substrate for ATP production by pancreatic beta-cell mitochondria.

PubMed

Lembert, N; Idahl, L A

1998-03-01

The ability of alpha-ketoisocaproate (KIC) to induce ATP production in isolated mitochondria from pancreatic beta-cells was examined with a bioluminometric method. There was no ATP production from KIC when tested alone or in combination with malate (1 mmol/l), nor did DL-beta-hydroxybutyrate induce mitochondrial ATP production, whereas palmitoyl-carnitine and pyruvate were efficient stimulators of mitochondrial ATP production in the presence of an equimolar concentration of malate. However, KIC stimulated the mitochondrial ATP production when tested in combination with glutamate (10 mmol/l). The concentration necessary to obtain half-maximal stimulation was approximately 50 micromol/l KIC, and maximal activity, comparable to that obtained with fatty acids, was reached at 1 mmol/l KIC. Higher KIC concentrations inhibited the mitochondrial ATP production, whereas a plateau was attained at 1 mmol/l KIC in the presence of glutamine. Ca2+ stimulated the maximal mitochondrial ATP production induced by KIC. Maximal stimulation was obtained with 300 nmol/l Ca2+ in the presence of 0.3 mmol/l KIC. Ca2+ reduced the concentration of KIC necessary for half-maximal stimulation to <30 micromol/l. Leucine stimulated the mitochondrial ATP production in the presence of glutamate to the same extent as KIC. Half-maximal stimulation was observed with 2 mmol/l leucine. There were no additive effects on mitochondrial ATP production when KIC and leucine were tested in combination. The results demonstrate that KIC by itself is not a mitochondrial substrate for ATP production. KIC must transaminate with glutamate or glutamine to yield alpha-ketoglutarate and leucine. Since leucine allosterically activates glutamate dehydrogenase, which also produces alpha-ketoglutarate, the insulinogenic effect of KIC may in part be due to the intramitochondrial generation of alpha-ketoglutarate. Since KIC-induced ATP production reaches a plateau already at micromolar concentrations (i.e., far below the concentrations at which KIC induces insulin release), it is proposed here that the catabolism of KIC may induce additional signals related to insulin release.

Comparison between Unilateral and Bilateral Plyometric Training on Single and Double Leg Jumping Performance and Strength.

PubMed

Bogdanis, Gregory C; Tsoukos, Athanasios; Kaloheri, Olga; Terzis, Gerasimos; Veligekas, Panagiotis; Brown, Lee E

2017-04-18

This study compared the effects of unilateral and bilateral plyometric training on single and double-leg jumping performance, maximal strength and rate of force development (RFD). Fifteen moderately trained subjects were randomly assigned to either a unilateral (U, n=7) or bilateral group (B, n=8). Both groups performed maximal effort plyometric leg exercises two times per week for 6 weeks. The B group performed all exercises with both legs, while the U group performed half the repetitions with each leg, so that total exercise volume was the same. Jumping performance was assessed by countermovement jumps (CMJ) and drop jumps (DJ), while maximal isometric leg press strength and RFD were measured before and after training for each leg separately and both legs together. CMJ improvement with both legs was not significantly different between U (12.1±7.2%) and B (11.0±5.5%) groups. However, the sum of right and left leg CMJ only improved in the U group (19.0±7.1%, p<0.001) and was unchanged in the B group (3.4±8.4%, p=0.80). Maximal isometric leg press force with both legs was increased similarly between groups (B: 20.1±6.5%, U: 19.9±6.2%). However, the sum of right and left leg maximal force increased more in U compared to B group (23.8±9.1% vs. 11.9±6.2%, p=0.009, respectively). Similarly, the sum of right and left leg RFD0-50 and RFD0-100 were improved only in the U group (34-36%, p<0.01). Unilateral plyometric training was more effective at increasing both single and double-leg jumping performance, isometric leg press maximal force and RFD when compared to bilateral training.

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