Effect of processing induced particle alignment on the fracture toughness and fracture behavior of multiphase dental ceramics

Objective. To investigate the processing induced particle alignment on fracture behavior of four multiphase dental ceramics (one porcelain, two glass-ceramics and a glass-infiltrated-alumina composite). Methods. Disks (empty set12mm x 1.1 mm-thick) and bars (3 mm x 4 mm x 20 mm) of each material were processed according to manufacturer instructions, machined and polished. Fracture toughness (K(IC)) was determined by the indentation strength method using 3-point bending and biaxial flexure fixtures for the fracture of bars and disks, respectively. Microstructural and fractographic analyses were performed with scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Results. The isotropic microstructure of the porcelain and the leucite-based glass-ceramic resulted in similar fracture toughness values regardless of the specimen geometry. On the other hand, materials containing second-phase particles with high aspect ratio (lithium disilicate glass-ceramic and glass-infiltrated-alumina composite) showed lower fracture toughness for disk specimens compared to bars. For the lithium disilicate glass-ceramic disks, it was demonstrated that the occurrence of particle alignment during the heat-pressing procedure resulted in an unfavorable pattern that created weak microstructural paths during the biaxial test. For the glass-infiltrated-alumina composite, the microstructural analysis showed that the large alumina platelets tended to align their large surfaces perpendicularly to the direction of particle deposition during slip casting of green preforms. Significance. The fracture toughness of dental ceramics with anisotropic microstructure should be determined by means of biaxial testing, since it results in lower values. (C) 2009 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Biological monitoring of a xenomaterial for grafting: an evaluation in critical-size calvarial defects

Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiographed and histologically prepared for analysis. The data obtained from histological analysis reported that the particles of MBB did not promote an intense immunological response, evidencing its biocompatibility in rats. Our results clearly showed the interesting evidence that MBB was not completely reabsorbed at 9 months while a small amount of newly formed bone was deposited by osteoprogenitor cells bordering the defect. However, this discrete bone-forming stimulation was unable to regenerate the bone defect. Overall, our results suggest that the properties of MBB are not suitable for stimulating intense bone regeneration in critical bone defects in rats.

Functional mapping of the periaqueductal gray matter involved in organizing tonic immobility behavior in guinea pigs

Tonic immobility behavior (TI) is an innate response characterized by profound motor inhibition that is exhibited by prey when physical contact with a predator is prolonged and the situation inescapable. The periaqueductal gray matter (PAG) is intimately associated with the somatic and autonomic components of defensive reactions. This study investigated whether the TI response was able to recruit specific functional columns of the PAG by examining c-fos immunolocalization in guinea pigs. In the TI group, the innate response was invoked in animals through inversion and physical contention for at least 15 min. In the control group, the animals were physically manipulated only. Our results demonstrate that the defensive behavior of TI is capable of promoting the expression of Fos protein in different areas of the PAG, with higher levels of staining in the ventrolateral (vI) and lateral (I) columns. In addition, our results demonstrate increased Fos immunoreactivity (FOS-IR) in the dorsal raphe nucleus, the Edinger-Westphal nucleus, the cuneiform nucleus and the superior colliculus. In contrast, there were no significant alterations in the number of FOS-IR cells in the inferior colliculus or the oculomotor nucleus. Analysis of the results suggests that neuronal activation after the TI response differs by functional column of the PAG. (C) 2010 Elsevier B.V. All rights reserved.

GABAergic antagonist blocks the reduction of tonic immobility behavior induced by activation of 5-HT(2) receptors in the basolateral nucleus of the amygdala in guinea pigs

Tonic immobility (TI) is a temporary state of profound motor inhibition induced by situations that generate intense fear, with the objective of protecting an animal from attacks by predators. A preliminary study by our group demonstrated that microinjection into the basolateral nucleus of the amygdala (BLA) of an agonist to 5-HT(1A) and 5-HT(2) receptors promoted a decrease in TI duration. In the current study, the effects of GABAergic stimulation of the BLA and the possible interaction between GABA(A) and 5-HT(2) receptors on TI modulation were investigated. Observation revealed that GABAergic agonist muscimol (0.26 nmol) reduced the duration of TI episodes, while microinjection of the GABAergic antagonist bicuculline (1 nmol) increased TI duration. Additionally, microinjection of 5-HT(2) agonist receptors (alpha-methyl-5-HT, 0.32 nmol) into the BLA decreased TI duration, an effect reversed by pretreatment with bicuculline (at the dose that had no effect per se, 0.2 nmol). Moreover, the activation of GABA(A) and 5-HT(2) receptors in the BLA did not alter the spontaneous motor activity in the open field test. These experiments demonstrated that the activation of GABA(A) and 5-HT(2) receptors of the BLA possibly produce a reduction in unconditioned fear that decreases the TI duration in guinea pigs, but this is not due to increased spontaneous motor activity, which could affect a TI episode nonspecifically. Furthermore, these results suggest an interaction between GABAergic and serotoninergic mechanisms mediated by GABA(A) and 5-HT(2) receptors. In addition, the GABAergic circuit of the BLA presents a tonic inhibitory influence on TI duration. (C) 2009 Elsevier Inc. All rights reserved.

The effect of resource aggregation at different scales: Optimal foraging behavior of Cotesia rubecula

Resources can be aggregated both within and between patches. In this article, we examine how aggregation at these different scales influences the behavior and performance of foragers. We developed an optimal foraging model of the foraging behavior of the parasitoid wasp Cotesia rubecula parasitizing the larvae of the cabbage butterfly Pieris rapae. The optimal behavior was found using stochastic dynamic programming. The most interesting and novel result is that the effect of resource aggregation within and between patches depends on the degree of aggregation both within and between patches as well as on the local host density in the occupied patch, but lifetime reproductive success depends only on aggregation within patches. Our findings have profound implications for the way in which we measure heterogeneity at different scales and model the response of organisms to spatial heterogeneity.

Thermal characterization of copolymers obtained by radiation grafting of styrene onto poly(tetrafluoroethyleneperfluoropropylvinylether) substrates: thermal decomposition, melting behavior and low-temperature transitions

Differential scanning calorimetric (DSC) and thermogravimetric analysis (TGA) have been used to study the thermal decomposition, the melting behavior and low-temperature transitions of copolymers obtained by radiation-induced grafting of styrene onto poly (tetrafluoroethylene- perfluoropropylvinylether) (PFA) substrates. PFA with different contents of perfluoropropylvinylether (PPVE) as a comonomer have been investigated. A two step degradation pattern was observed from TGA thermograms of all the grafted copolymers, which was attributed to degradation of PSTY followed by the degradation of the PFA backbone at higher temperature. One broad melting peak can be identified for all copolymers, which has two components in the samples with higher PPVE content. The melting peak, crystal-crystal transition and the degree of crystallinity of the grafted copolymers increases with radiation grafting up to 50 kGy, followed by a decrease at higher doses. No such decrease was observed in the ungrafted PFA samples after irradiation. This indicated that the changes in the heats of transitions and crystallinity at low doses are due to the radiation effects on the microstructure of PFA (chain scission), whereas at higher doses the grafted PSTY is the driving force behind these changes. (C) 2001 Elsevier Science Ltd. All rights reserved.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis

This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events, We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population, The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization. responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.