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Increased myofibroblast contractile sensitivity in paraquat pretreated rat lung tissue.

In numerous tissues, contractility to certain characteristic agents is associated with cells other than muscle, e.g. actin-containing so-called myofibroblasts. Such cells are present in pulmonary interstitium of several mammalian species but their contractility has only been demonstrated from the proliferation of myofibroblasts in fibrotic lung tissues. This study has been done to evaluate such responses in normal tissues in contrast with fibrotic lungs and it was necessary to take account also of smooth muscle reactivity. Distinctive agonists: mepyramine and sodium tungstate characterised myofibroblast mediated contractility, in contrast with acetylcholine and barium chloride as specific smooth muscle stimulants. Histology and immunohistochemistry were used to evaluate the pharmacological results more precisely.

Acetylcholine↗

Functional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.

Human TASK-3 (hTASK-3) is a recently identified member of the two-pore domain potassium channel (2PDKC) family which in man is predominantly expressed in the cerebellum. Previous preliminary examination of this channel indicates that when expressed in Xenopus oocytes, it produces a K(+) selective background conductance and consequent shift in resting membrane potential, thus mimicking other 2PDKC. Here we describe some additional functional and pharmacological aspects of hTASK-3-mediated conductances expressed in both Xenopus oocytes and HEK293 cells. hTASK-3 expression produces steady-state currents that approximate Goldman--Hodgkin--Katz behaviour with respect to membrane potential. Despite this, voltage steps from -80 mV to potentials > approximately -20 mV induce currents that exhibit a clear time-dependent increase in current amplitude. Kinetically, this increase in current was well fit by a single exponential, the time constant of which was approximately 10 ms and appeared independent of test potential, between -20 and +80 mV. In HEK293 cells hTASK-3 currents were inhibited by extracellular acidosis with a mid-point for inhibition of pH 6.4. Furthermore, the activity of TASK-3 was potentiated by the volatile anaesthetic halothane but inhibited by the local anaesthetic bupivacaine.

1-Methyl-3-isobutylxanthine↗

Serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons.

The anti-epileptiform effect of serotonin was characterized in cellular models of epilepsy using electrophysiological recording techniques. In the bicuculline model, both serotonin (20 microM) and its 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 microM) completely blocked the epileptiform discharge and caused membrane hyperpolarization and reduction in input resistance. These effects were completely antagonized by the 5-HT1A receptor antagonist N-t-butyl-3(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenyl-propanamid e(WAY 100135) (10 microM). Epileptiform discharge induced by positive current injection was also blocked by serotonin. The presence of WAY 100135 renders serotonin ineffective in the same model. In the bicuculline model, epileptiform discharge blocked by serotonin reappeared and was also intensified when BaCl2 was added to the medium. To rule out the possibility of serotonin-induced hyperpolarization strengthening the inhibitory effect of endogenous Mg2+ on glutamate N-methyl-D-aspartic acid (NMDA) receptor we studied the antiepileptic effect of serotonin in the 0 Mg2+ model. Spontaneous activity and evoked bursts seen with the 0 Mg2+ model were completely blocked by serotonin. WAY 100135 completely antagonized serotonin effects in this model as well. This study provides evidence suggesting that in rat CA1 pyramidal neurons, serotonin can inhibit epileptiform activity in a variety of accepted epilepsy cellular models and that inhibition of epileptiform bursts by serotonin may be mediated by activation of the 5-HT1A receptor subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Dry deposition of sulfate-containing particulate at the highway intersection, coastal and suburban areas.

Sulfate-containing aerosol (SCA) dry deposition at the highway intersection, coastal location, and suburban area in Taiwan were analyzed and compared. Sampling was accomplished with a surrogate surface technique. Samples particles were coated with barium chloride (BaCl(2)) in a vacuum evaporator and then exposed to a relative humidity of 85% for 2 h to form distinctive products of SCAs. Treated samples were examined by a scanning electron microscopy. SCA dry deposition fluxes were 10.2, 4.1, 3.4 microgm(-2)s(-1) and nonsulfate-containing aerosol (NSCA) dry deposition fluxes were 23.3, 8.2, 13.5 microgm(-2)s(-1) at the highway intersection, coastal, and suburban areas. At the highway intersection, both SCA and NSCA dry deposition fluxes were much higher than those at the other two sites. The dry deposition of particles was also analyzed with a traditional technique. The number median diameters (NMDs) of SCA were 0.41, 0.82, and 1.2 mum at the highway intersection, coastal, and suburban sites, respectively. The highway intersection site had a small NMD, which showed that most sulfate-containing deposited aerosols existed in fine diameter range. The mass median diameters (MMDs) of SCA were 8.8, 19.5, and 14.9 mum at the highway intersection, coastal, and suburban sites, which were much higher than NMDs. Average numbers of SCAs in total particulate were 33%, 33%, and 22% at the highway intersection, coastal and suburban areas Most deposited particulates were nonsulfate-containing at the three sampling sites. SCAs less than 10 mum contributed 29%, 8%, and 7% to the total dry deposition at the highway intersection, coastal, and suburban areas, respectively. The contribution of fine particulate was significantly higher at the highway intersection site.

Air Pollutants↗

Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.

A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Continuously infused calcium hydroxide: its influence on hard tissue repair.

To study the ability of calcium hydroxide to promote hard tissue repair, Alza Alzet Osmotic Pumps, implanted in Sprague-Dawley rats, were used to deliver either calcium hydroxide and glycerol, barium hydroxide and glycerol, tetracycline and glycerol, or glycerol only to a standardized round bur defect in a rat femur. The pumps infused one of the reagents into the defects continuously over a 4-wk experimental period. The effects of each reagent on the healing of the bony defects were compared by histological evaluation. The Alza Osmotic Pump proved to be an effective method to deliver an agent to an experimental site. Our preliminary findings from a limited sample size indicated that calcium hydroxide contributed to a more complete osseous repair than either barium hydroxide or tetracycline. Barium hydroxide with a sustained pH equivalent to calcium hydroxide showed no greater healing than the controls. Tetracycline results were also similar to controls.

Animals↗

Dynamic mechanical analysis of storage modulus development in light-activated polymer matrix composites.

OBJECTIVES: The goal of this study was to evaluate the potential for using dynamic mechanical analysis of tubular geometry in a three-point flexure fixture for monitoring the storage modulus development of a light-activated polymer matrix composite. METHODS: Composite samples were inserted into PTFE tubes and tested in a three-point bend fixture in a dynamic mechanical analyzer (DMA) at 200 Hz with 20 microm amplitude. Samples were light activated for 60s (385 mW/cm(2) at the composite surface) and storage modulus (E') was measured continuously for the seven light-activated composites studied (one microfill, four hybrids and two unfilled resins). Cores of composite were removed from the PTFE sheath after 13.5 min and evaluated with the same parameters in the DMA. A finite element model of the test configuration was created and used to estimate operating parameters for the DMA. Degree of conversion (DC) was measured using micro-Fourier Transform Infrared (FTIR) spectroscopy for the microfilled composite samples and one hybrid 13.5 and 60 min after light activation. RESULTS: The E' for a generic hybrid and microfilled composite was 13,400+/-1100 and 5900+/-200 MPa, respectively, when cured within the tube and then removed and tested in the DMA. DC was 54.6% for the hybrid and 60.6% for the microfill. A linear regression of E' for the sheath and core vs core alone (r(2)=0.986) indicated a linear scaling of the sheath and core values for E' enabling a correction for estimated E' values of the composite core. SIGNIFICANCE: This method estimates the storage modulus growth during light-activated polymerization of highly filled dimethacrylates. Although the approach is phenomenological in that quantitative measurements of E' are not made directly from the DMA, estimates of early polymerization kinetics appear to be validated by three different approaches.

Barium Compounds↗

Rheologic properties of flowable, conventional hybrid, and condensable composite resins.

OBJECTIVES: This research was undertaken to investigate the viscoelastic properties related to handling characteristics of five commercial flowable, two conventional hybrid and two condensable composite resins and to investigate the effect on the viscosity of filler volume fraction of composites. METHODS: A dynamic oscillatory shear test was used to evaluate the storage shear modulus (G'), loss shear modulus (G"), loss tangent (tan delta) and complex viscosity (eta(*)) of the composite resins as a function of frequency (omega)-dynamic frequency sweep test from 0.01 to 100 rad/s at 25 degrees C-using an Advanced Rheometric Expansion System. To investigate the effect on the viscosity of the composites of the filler volume fraction, the filler weight% and filler volume% were measured by the Archimedes' principle using a pyknometer. RESULTS: The complex viscosity eta(*) of flowable composites was lower than that of the hybrid composites and significant differences were observed between brands. The complex viscosity eta(*) of condensable composites was higher than that of hybrid composites. The order of complex viscosity eta(*) at omega=10 rad/s in order of decreasing viscosity was as follows, Synergy compact, P-60, Z-250, Z-100, Aeliteflo, Tetric flow, Compoglass flow, Flow it and Revolution. The complex viscosity of flowable composites, normalized with respect to Z-100, was 0.04-0.56 but Synergy compact was 2.158 times higher than that of Z-100. The patterns of the change of loss tangent (tan delta) of the composite resins with increasing frequency were significantly different between brands. Phase angles delta ranged from 30.9 to 78.1 degrees at omega=10 rad/s. All composite resins exhibit pseudoplastic behavior with increasing shear rate. The relationships between the complex shear modulus G(*), the phase angle delta, and the shear rate omega were represented by the frequency domain phasor form, G(*)(omega)=G(*)e(i delta)=G(*) 90 degree angle delta. Only a weak relationship was found between filler volume% and the viscosity of the composite resins. SIGNIFICANCE: This investigation shows that the viscoelasticity of composites in the same class is significantly different between brands. This rheologic property of composite resins influences the handling characteristics of the materials. The locus of frequency domain phasor plots in a complex plane is a valuable method of representing the viscoelastic properties of composite resins.

Barium Compounds↗

In vitro contact wear of dental composites.

OBJECTIVE: The aim of this study is to determine the in vitro two-body contact wear mechanisms of three medium filled composites and compare these with a highly filled composite previously investigated. MATERIALS AND METHODS: Three commercial dental composites with filler mass fraction loading of 75-76% were evaluated. Two of the composites contained Ba-B-Al-silicate glass fillers and fumed silica with different particle sizes and distributions. One of these composites contained a fairly uniform distribution of filler particles ranging in size from 1 to 5 microm, whereas the particle size distribution in the second composite was bimodal consisting of small (less than 1 microm) and large (about 10 microm) particles. The third composite contained Ba-Al-silicate glass and silica with a filler particle size of approximately 1 microm. The composite disks were tested for wear against harder alumina counterfaces. Wear tests were conducted in distilled water using a pin-on-disk tribometer under conditions that represented typical oral conditions (sliding speed of 2.5 mm/s and contact loads ranging from 1 to 20 N). The wear tracks were analyzed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy to elucidate the wear mechanisms. The chemical composition of the water solution collected after the tests was determined using an inductively coupled plasma-mass spectrometer (ICP-MS) to detect possible chemical changes, e.g. dissolution of trace elements due to submersion or wear. The wear results were compared with those reported in an earlier study on a highly filled composite containing predominately alumino-silicate glass fillers and alumina at a filler loading of 92%. RESULTS: The differences in two-body wear rates between the three medium filled composites were not statistically significant (p<0.05) indicating that the variations in filler particle size and slight differences in chemical composition of the glass fillers do not affect the in vitro wear rates of these composites. Wear rates of these medium filled composites, however, were significantly lower than the highly filled composite (p<0.05). SEM, FTIR and ICP-MS analyses suggested that wear in the medium filled composites occurs by a complex set of processes involving tribochemical reactions between filler particles and water, formation of surface films containing a mixture of filler fragments and reaction products, and film delamination, as well as dissolution of the reaction products. SIGNIFICANCE: This study reveals that subtle changes in the filler particle size and small differences in filler composition do not significantly affect the two-body wear behavior of medium filled composites. However, the chemistry of filler particles plays an important role in altering the wear performance of composites when significant changes are made in the chemical composition of the fillers and when the filler loading is increased.

Aluminum Oxide↗

Laser-induced acoustic emissions in experimental dental composites.

A laser thermoacoustic technique was innovated to evaluate laser-induced acoustic emissions (AEs) in experimental dental composites aged with 75% ethanol solution. Experimental composite systems of 75/25 BisGMA/TEGDMA resin filled with 0, 12.6, 30.0, and 56.5 vol% of 8-microm silanized and unsilanized BaSiO6 were analyzed. The sample size was 4.65 mm (diameter) x 0.5 mm (thick). Aging effects of immersing in 75% ethanol for up to 14 h on AEs were then evaluated. A continuous-wave CO2 laser was used to heat the samples. Acoustic emissions were collected as a function of filler fraction, laser power, silanization, and immersion time. Onset of burst-pattern acoustic signals characteristic of fracturing occurred at different laser powers for different tested groups. Acoustic emissions generally increased with laser power, in which lower laser powers produced low-amplitude (45-50 dB) signals; the amplitude distribution (50-85 dB) became more extensive as laser powers increased. After immersion, the lower laser powers could produce the same phenomenon. The higher the filler fraction, the fewer AEs generated. A large percentage AE reduction due to silanization was noted as a function of filler fraction. Unsilanized specimens showed more thermal damages than did silanized ones.

Acoustics↗

Growth of calcium phosphate on poling treated ferroelectric BaTiO3 ceramics.

Barium titanate (BaTiO3; BTO) is ferroelectric and piezoelectric after poling treatment. In this study, the bioactivity of BTO was investigated after a poling treatment by examining the formation of crystal growth on specimen surfaces in vitro. Negatively charged BTO surfaces showed calcium phosphate (Ca-P) crystal growth, while deposition of sodium chloride was observed on the positively charged BTO surfaces. After 30 days immersion in Eagle's MEM, the thickness of Ca-P crystal on negatively charged BTO surfaces increased to 0.8-0.9 microm. These data indicate that incorporating selectively polarized BTO on implant surfaces is a promising means for improving the bioactivity of implant materials.

Barium Compounds↗

Fabrication of homogeneously cross-linked, functional alginate microcapsules validated by NMR-, CLSM- and AFM-imaging.

Cross-linked alginate microcapsules of sufficient mechanical strength can immunoisolate cells for the long-term treatment of hormone and other deficiency diseases in human beings. However, gelation of alginate by external Ba(2+) (or other divalent cations) produces non-homogeneous cross-linking of the polymeric mannuronic (M) and guluronic (G) acid chains. The stability of such microcapsules is rather limited. Here, we show that homogeneous cross-linking can be achieved by injecting BaCl(2) crystals into alginate droplets before they come into contact with external BaCl(2). The high effectiveness of this crystal gun method is demonstrated by confocal laser scanning microscopy and by advanced nuclear magnetic resonance imaging. Both techniques gave clear-cut evidence that homogeneous cross-linkage throughout the microcapsule is only obtained with simultaneous internal and external gelation. Atomic force microscopy showed a very smooth surface topography for microcapsules made by the crystal gun method, provided that excess Ba(2+) ions were removed immediately after gelation. In vitro experiments showed greatly suppressed swelling for crystal gun microcapsules. Even alginate extracted from Lessonia nigrescens (highly biocompatible) yielded microcapsules with long-term mechanical stability not hitherto possible. Encapsulation of rat islets, human monoclonal antibodies secreting hybridoma cells and murine mesenchymal stem cells transfected with cDNA encoding for bone morphogenetic protein (BMP-4) revealed that injection of BaCl(2) crystals has no adverse side effects on cell viability and function. However, the release of low-molecular weight factors (such as insulin) may be delayed when using alginate concentrations in the usual range.

Alginates↗

Finite element analysis of thermo-debonding mechanism in dental composites.

Finite element method (FEM) has been extensively used for evaluating interfacial status inside biomaterials. This study using FEM was designed to evaluate the thermal stress behavior of a filler-matrix interface. The results were then compared to those of a previous study obtained by a laser thermoacoustic technique (LTAT). The experimental systems (75/25 Bis-GMA/TEGDMA resin reinforced with 0, 25, 50, and 75 wt% 8-microm silanized/unsilanized BaSiO6) as used in the previous study were modeled in this study. The established finite element models were based on coefficient of thermal expansion (CTE) Mismatch Phenomenon. The mechanical properties of the silane coupling agent, such as elastic modulus and thermal expansion coefficient used in the silanized model, were assumed to have optimal heat flux transfer. A third (imaginary) material was proposed to block the transfer of thermal stress between the filler and matrix in the unsilanized model. The thermal load simulation was based on steady-state thermal analysis. The results showed that: (1) The strain energy and interfacial shearing stress calculated from FEM validate the results from the previous LTAT study. (2) Comparing the stress distribution of silanized and unsilanized FEM models, the acoustic signals in LTAT study are mainly derived from debonding of the filler-matrix interface of silanized specimens, and from the matrix area of unsilanized specimens. Based on results to date, we conclude that the finite element method may be a powerful tool for exploring thermoacoustic mechanisms of dental composites.

Acoustics↗

Characterization of ion transport mechanisms involved in bombesin-stimulated biliary secretion in rat cholangiocytes.

BACKGROUND/AIMS: Bombesin is a neuropeptide which stimulates fluid and bicarbonate secretion from cholangiocytes by stimulating Cl-/HCO3- exchange. However, the underlying regulation and interactions of ion transporters and channels mediating this bombesin-stimulated biliary secretion are not well characterized. The aim of the study was to characterize the ion transport processes involved in bombesin-stimulated secretion in polarized cholangiocytes in comparison with those of secretin. METHODS: Isolated bile duct units (IBDU) were prepared from normal rat liver. Biliary secretion induced by bombesin was measured by quantitative video-microscopy in the presence and absence of inhibitors. RESULTS: Bombesin-stimulated secretion was inhibited by H2-DIDS, NPPB, BaCl2, TEA, and acetazolamide. However, in contrast to secretin, bombesin-stimulated secretion was not inhibited by disruption of microtubules. CONCLUSIONS: Bombesin-stimulated biliary secretion is dependent on anion exchangers, Cl- and K+ channels, and carbonic anhydrase but not on microtubules. Bombesin regulates secretion in cholangiocytes by different mechanisms from those established for secretin.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗