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Paraelectric thin films by nanoscale engineering of epitaxy and planar anisotropy for microwave phase shifter applications.

Epitaxial and (110) oriented paraelectric thin films of Ba0.60Sro.40TiO3 were grown on (100) oriented NdGaO3 orthorhombic substrates, and the nonlinear dielectric properties were studied at 10 GHz along selected in-plane crystallographic directions in the film thickness range of 25-1200 nm. The measured dielectric properties show strong residual strain and in-plane directional dependence. For instance, the in-plane relative permittivity is found to vary from as much as 500 to 150 along [110] and [001], respectively, in the 600 nm film. Tunability was found to vary from as much as 54% to 20% in all films and directions. In a given film, the best tunability is observed along the compressed axis in a mixed strain state, 54% along [110] in the 600 nm film. It is shown that, by nanoscale manipulation of epitaxy and planar anisotropy, the return loss and phase shift in a paraelectric can be tuned over a rather wide range. The approach presented herein opens avenues for obtaining various degrees of phase shift on the same film, enabling one with an additional degree of freedom in device design and fabrication as well as multifunctionality.

Anisotropy↗

The effect of an intermediate layer of flowable composite resin on microleakage in packable composite restorations.

OBJECTIVES: The aim of the present study was to evaluate the effect of a thin layer of flowable composite on microleakage in Class II direct packable composite resin restorations on young permanent teeth in vitro. METHODS: Twenty sound human premolars and molars extracted for orthodontic reasons were selected for this study. The teeth were randomly assigned into two groups of 10 teeth each (groups A and B). Class II cavities were prepared as uniformly as possible in the mesial and distal aspects of each tooth. The gingival margin extended apically approximately 0.5 mm beyond the cemento-enamel junction, in the dentin. Cavities in group A were restored with packable composite and Alert/Flow-it flowable composite, while groups B cavities were restored with Pyramid/Aeliteflo. The control cavities in groups A1 and B1 were restored with only packable composite. The teeth were immersed in 2% methylene blue solution for 24 h to allow dye penetration into possible existing gaps between the tooth substance and the restorative material. All teeth were subjected to thermocycling. RESULTS: The dye penetration ranged between 6.6 and 7.2 mm. No significant difference was found between the control and the experimental groups. CONCLUSION: The use of flowable composite resin as intermediate material does not reduce microleakage.

Adolescent↗

Characterization of inorganic fillers in visible-light-cured dental composite resins.

Inorganic fillers in seven visible-light (VL)-cured dental composite resins were examined for their size, composition, phase and content, employing the following analytical instruments. SEM observations indicated that five samples could be classified into the hybrid type while the remaining two belonged to micro-filled and sub-micron types. EDX analyses revealed that five samples contained BaO while others lacked BaO. XRD analyses showed that three were in vitreous phase, two were in the crystalline phase and two were mixtures of both. DTG thermal analyses indicated that the hybrid type composites had the higher inorganic filler content (wt%) than the composites of two other types. In conclusion, wide varieties exist in the inorganic fillers in VL-cured dental composite resins currently utilized.

Aluminum Oxide↗

Role of the basement membrane in the regeneration of skeletal muscle.

In many experimental models of skeletal muscle damage and in human muscle disease, empty basement membrane tubes remain following the destruction of muscle fibres. In the present study we test the hypothesis that the empty basement membrane tubes play an essential role in the orientation of regenerating muscle fibres. Two groups of 15 Wistar rats were used. In one group, aqueous barium chloride (BaCl2) solution was injected into the right quadriceps muscle; in the other group, freshly prepared 2% trypsin solution was similarly injected. The different stages of muscle cell necrosis and regeneration were observed by histology, by immunofluorescence using an anti-basement membrane antibody, and by transmission (TEM) and scanning electron microscopy (SEM) in animals killed 1-77 days following injection. Although there was muscle fibre necrosis at sites of BaCl2 injection, empty basement membrane tubes were well preserved. Myoblasts grew along the empty basement membrane tubes and by 77 days, the regenerated muscle fibres at the site of the injection were well oriented. Trypsin not only destroyed muscle fibres but also destroyed the basement membrane tubes; in the early stages of regeneration the myoblasts were disorientated but by 77 days, regeneration was comparable to that seen in the barium chloride injected muscle. The results of this study suggest that preservation of empty basement membrane tubes is not essential for the orientation of regenerating myoblasts in skeletal muscle.

Animals↗

Acute barium nitrate intoxication treated by hemodialysis.

A 22-year-old male was admitted to hospital with diarrhea and vomiting, cardiac arrhythmias, severe hypokalemia and gradual onset of muscular weakness. A potassium infusion was started, but for several hours serum potassium remained low. Evidence of toxic ingestion was initially lacking. When it became clear -- after a considerable delay -- that the patient had ingested barium nitrate, hemodialysis was started. This resulted in rapid clinical improvement with correction of hypokalemia and restored muscular function. Intoxication with barium causes hypokalemia, arrhythmias, muscular weakness and paralysis, often requiring respiratory support. This patient presented with symptoms typical of severe barium intoxication, non-responsive to potassium supplementation. There are few published reports on the use of hemodialysis in barium poisoning. This case confirms the possible benefit of hemodialysis in severe cases, where potassium supplementation alone is insufficient.

Adult↗

Comparison of the effects of endrallazine, hydrallazine and verapamil on human isolated arteries and veins.

1. The antagonist effects of endrallazine (BQ 22-708), hydrallazine and verapamil have been studied on the contractile responses produced by various agonists on human digital arteries and metacarpal veins obtained post mortem. 2. Endrallazine and hydrallazine antagonized the contractile responses to noradrenaline and serotonin in arteries by shifting the concentration-effect curves to the right and by reducing the maximum responses to both agonists. Neither drug had any effect on responses to BaCl2 in either tissue. 3. The same concentrations of endrallazine and hydrallazine which antagonized responses to noradrenaline and serotonin in arteries, had no effect on concentration-effect curves to those agonists in veins. 4. Hydrallazine was significantly more potent than endrallazine in reducing the maximum response to noradrenaline in arteries, and was less potent than endrallazine in reducing the maximum response to serotonin. 5. Verapamil antagonized the vasoconstrictor effect of all agonists tested in both arteries and veins. 6. It is concluded that in a similar manner to hydrallazine, endrallazine has a direct effect on human vascular smooth muscle at concentrations which are probably similar to those occurring in vivo. Both hydrallazine and endrallazine may produce selective arterio-dilatation by preventing the release of bound calcium from intracellular storage sites, an effect which is different to that of verapamil.

Arteries↗

Extracellular ATP directly gates a cation-selective channel in rabbit airway ciliated epithelial cells.

1. A membrane conductance activated by extracellular ATP was identified and characterized in freshly dissociated rabbit airway ciliated cells using the whole-cell and outside-out patch configurations of the patch-clamp technique. 2. In solutions designed to maximize currents through voltage-gated calcium channels, there were no indications of voltage-gated Ba2+ currents. 3. Extracellular ATP (but not UTP or ADP) activated a membrane conductance which remained activated for several minutes in the presence of ATP. The conductance was permeable to monovalent and divalent cations with approximate relative permeabilities (P) for PBa : PCs : PTEA of 4 : 1 : 0.1. Permeability to Cl- was negligible. 4. Including GDP-beta-S in the intracellular solution did not inhibit the effects of ATP, nor did GTP-gamma-S irreversibly activate the conductance. 5. In outside-out membrane patches, with GDP-beta-S in the pipette solution, ATP activated ion channels which had a chord conductance of approximately 6 pS in symmetrical 150 mM CsCl solutions at -120 mV. 6. Suramin (100 microM) inhibited the whole-cell currents activated by ATP (200 microM) by 93 +/- 3 %. Similar effects of suramin were observed on ATP-activated channels in outside-out membrane patches. 7. Extracellular ATP had a priming action on the response to subsequent exposure to ATP. At -40 mV, the time to half-maximal current activation (t1/2) was 46 +/- 9 s during the first exposure to 200 microM ATP and decreased to 5 +/- 3 s during a second exposure to the same concentration of ATP. The priming action of ATP was not inhibited by including GDP-beta-S in the intracellular solution. 8. The initial rate of activation increased with the concentration of ATP, and was voltage sensitive. During the first exposure to 200 microM ATP, t1/2 at +40 mV was 4-fold longer than t1/2 at -40 mV. 9. Half-maximal activation of the conductance shifted from 210 +/- 30 to 14 +/- 4 microM added ATP when CaCl2 in the extracellular solution was reduced from 1.58 to 0. 01 mM. The Hill coefficient for ATP was 1.2 in both solutions.10. These observations suggest that a form of ATP uncomplexed with divalent cations directly gates an ion channel (P2X receptor) in rabbit airway ciliated cells, which serves as a pathway for Ca2+ influx. This purinoceptor may contribute to sustained ciliary activation during prolonged exposures to ATP.

Adenosine Diphosphate↗

Calcium current activated by potassium ions in voltage-clamped rat hippocampal pyramidal neurones.

1. Neuronal activity results in local elevation of extracellular K+ concentration ([K+]o). 2. Using the patch-clamp technique in the whole-cell configuration, we investigated whether extracellular K+ activates non-voltage-operated Ca2+ channels in pyramidal cells cultured from rat embryonic hippocampi. 3. K+ (12 mM) reversibly activated a sustained inward current at a holding potential of -100 mV. Membrane conductance and variance of noise were significantly increased by K+. This current could be observed at membrane potentials negative to +60 mV. 4. Inhibitors of inward rectifier K+ channels and hyperpolarization-induced cation current reduced the current only at potentials negative to -50 mV. 5. The K+-induced current was activated in Na+-free but not in Ca2+-free medium, did not depend on cytosolic [Cl-], and was blocked by Cd2+ but not by organic channel inhibitors. 6. Half-maximal activation of the current (at -100 mV) was attained at [K+]o approximately 20 mM. 7. The current is similar to Igl, a K+-induced Ca2+ current described in glomerulosa cells. It was also present in pyramidal cells from prefrontal cortex but not in hippocampal bipolar and glial cells. 8. Activation of K+-induced Ca2+ current may elevate cytoplasmic [Ca2+] at [K+]o levels which are insufficent to activate voltage-dependent Ca2+ channels.

2-Amino-5-phosphonovalerate↗

T-tubule localization of the inward-rectifier K(+) channel in mouse ventricular myocytes: a role in K(+) accumulation.

1. The properties of the slow inward 'tail currents' (I(tail)) that followed depolarizing steps in voltage-clamped, isolated mouse ventricular myocytes were examined. Depolarizing steps that produced large outward K(+) currents in these myocytes were followed by a slowly decaying inward I(tail) on repolarization to the holding potential. These currents were produced only by depolarizations: inwardly rectifying K(+) currents, I(K1), produced by steps to potentials negative to the holding potential, were not followed by I(tail). 2. For depolarizations of equal duration, the magnitude of I(tail) increased as the magnitude of outward current at the end of the depolarizing step increased. The apparent reversal potential of I(tail) was dependent upon the duration of the depolarizing step, and the reversal potential shifted to more depolarized potentials as the duration of the depolarization was increased. 3. Removal of external Na(+) and Ca(2+) had no significant effect on the magnitude or time course of I(tail). BaCl(2) (0.25 mM), which had no effect on the magnitude of outward currents, abolished I(tail) and I(K1) simultaneously. 4. Accordingly, I(tail) in mouse ventricular myocytes probably results from K(+) accumulation in a restricted extracellular space such as the transverse tubule system (t-tubules). The efflux of K(+) into the t-tubules during outward currents produced by depolarization shifts the K(+) Nernst potential (E(K)) from its 'resting' value (close to -80 mV) to more depolarized potentials. This suggests that I(tail) is produced by I(K1) in the t-tubules and is inward because of the transiently elevated K(+) concentration and depolarized value of E(K) in the t-tubules. 5. Additional evidence for the localization of I(K1) channels in the t-tubules was provided by confocal microscopy using a specific antibody against Kir2.1 in mouse ventricular myocytes.

Animals↗

Direct and continuous detection of ATP secretion from primary monolayer cultures of bovine adrenal chromaffin cells.

A method was developed for direct and continuous detection of secretion of ATP from primary monolayer cultures of bovine adrenal chromaffin cells. ATP, which is costored with catecholamines within adrenal chromaffin cells, was released into the incubation medium, where it reacted with firefly luciferin-luciferase producing light detected by a photomultiplier located directly below the culture well. Acetylcholine, nicotine, the Ca2+ ionophore A23187, BaCl2, and KCl induced release of ATP. Induction of release of ATP by acetylcholine was dose dependent, with a threshold at 10(-7) M and a maximum at 10(-4) M. The dose-response curve for nicotine was bell shaped, with a threshold at 10(-7) M, a maximum at 10(-5) M, and diminished release at higher concentrations, an observation indicative of desensitization. Investigation of the initial rates of ATP secretion revealed that 10(-4) M nicotine actually induced release of ATP at a faster rate than 10(-5) M nicotine. However, the rate of ATP release evoked by 10(-4) M nicotine began to decline by 6 s, a result indicating the onset of receptor desensitization, whereas release induced by 10(-5) M nicotine continued unabated. Induction of release of ATP by acetylcholine or nicotine was biphasic, with a rapid, initial phase of release followed by a plateau at 0.5-1.5 min and a second phase of release beginning at 1.5-2 min, reaching a maximum by 2-3 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Time-dependent inhibition of stimulated adrenal catecholamine release by staurosporine.

Staurosporine, a potent inhibitor of protein kinases, is used to study the involvement of protein kinases in cellular processes. In the present studies, the effect of prolonged staurosporine treatment on catecholamine secretion in cultured bovine adrenal chromaffin cells was examined. Staurosporine inhibits catecholamine release stimulated by 10 microM nicotine, depolarizing concentrations of potassium (56 mM KCl), and 2 mM BaCl2. The effects of staurosporine on KCl-stimulated release are time dependent, with a half-time of approximately 50 min and a maximal inhibition at 2 h. Our results indicate that activation of a staurosporine-sensitive protein kinase is not directly involved in the stimulus-secretion coupling process. This does not rule out the possibility that Ca2+/phospholipid-dependent protein kinase or other protein kinases may acutely modulate release. However, these results suggest that a protein(s), which is phosphorylated by a staurosporine-sensitive protein kinase(s), is required to maintain the integrity of the stimulus-secretion coupling process.

Adrenal Glands↗

Developmental change in the calcium sensor for synaptic vesicle endocytosis in central nerve terminals.

Synaptic vesicle endocytosis is stimulated by calcium influx in mature central nerve terminals via activation of the calcium-dependent protein phosphatase, calcineurin. However, in different neuronal preparations calcineurin activity is either inhibitory, stimulatory or irrelevant to the process. We addressed this inconsistency by investigating the requirement for calcineurin activity in synaptic vesicle endocytosis during development, using vesicle recycling assays in isolated nerve terminals. We show that endocytosis occurs independently of calcineurin activity in immature nerve terminals, and that a calcineurin requirement develops 2-4 weeks after birth. Calcineurin-independent endocytosis is not due to the absence of calcineurin activity, since calcineurin is present in immature nerve terminals and its substrate, dynamin I, is dephosphorylated on depolarization. Calcineurin-independent endocytosis is calcium-dependent, since substitution of the divalent cation, barium, inhibits the process. Finally, we demonstrated that in primary neuronal cultures derived from neonatal rats, endocytosis that was initially calcineurin-independent developed a calcineurin requirement on maturation in culture. Our data account for the apparent inconsistencies regarding the role of calcineurin in synaptic vesicle endocytosis, and we propose that an unidentified calcium sensor exists to couple calcium influx to endocytosis in immature nerve terminals.

Age Factors↗

Experimental study of antidiarrheal activity of Salicairine.

Experimental antidiarrheal activity of a traditionally used medication, Salicairine, was demonstrated in comparison to loperamide by significant inhibition of castor oil-induced diarrhea in mice (increases in hard faeces/total faeces ratio of 38 and 54 and 5 and 54% with respect to controls, at 0.5 and 1 mL/kg and 1 and 2 mg/kg, respectively) and bisacodyl-induced increase in large intestine transit in rats (125 and 280 and 210% with respect to controls, at 0.4 and 2 mL/kg Salicairine and 5 mg/kg loperamide, respectively). Salicairine was able to reduce contractions of isolated rat duodenum induced by barium chloride and acetylcholine, although not completely (that is about 60%) as seen with loperamide. Also, it did not change normal gastrointestinal transit in mice at doses of 0.5 to 1 mL/kg, conversely to loperamide which had a significant effect (decrease of 50%) at 2 mg/kg. Finally, Salicairine at 0.01 mL/mL, like loperamide at 0.2 mg/mL, significantly increased net fluid absorption in rat colon, either in basal conditions (30 and 64% respectively) or after a prostaglandin E1-induced increase in net fluid secretion (41 and 35%, respectively). The antidiarrheal activity of Salicairine is possibly related, at least in part, to an increase in colon net fluid absorption or a decrease in net fluid secretion.

Acetylcholine↗

Effect of temperature reduction on the vas deferens hyperresponsiveness of sensitized mice.

1. The present study was designed to investigate the effect of active sensitization on the responsiveness of mouse vas deferens before and after moderate cooling. Contractile responses to noradrenaline (NA) were isometrically recorded in the vas deferens of control and ovalbumen-sensitized mice at 37 degrees C and 22 degrees C. 2. Enhancement of the vas deferens reactivity to NA was observed in the sensitized vs control mice at 37 degrees C and 22 degrees C (P < 0.01). In sensitized mice, maximal contraction was significantly increased compared with controls, and sensitization-induced hyperresponsiveness was greater at 22 degrees C compared with 37 degrees C. At 37 degrees C, contractile responses to barium chloride were significantly enhanced in the sensitized mice compared with controls, whereas the reduction of the temperature to 22 degrees C produced a marked inhibition of vas deferens contractions in both groups. Caffeine-induced contractions of the vas deferens were similar in control and sensitized mice at 37 degrees C. After moderate cooling to 22 degrees C, vas deferens from sensitized mice became hyperresponsive compared with controls. 3. Ouabain (0.1 mM) produced an increase of NA-induced contraction in control and sensitized vas deferens at 37 degrees C (P < 0.01). It had no significant effect in the control at 22 degrees C but produced a marked inhibition of NA-induced contraction in the sensitized vas deferens at 22 degrees C. Contractions to NA in the presence of vanadate (1 mM) were depressed in control and sensitized mice at both temperatures. 4. These results suggest that sensitization-induced hyperresponsiveness of the mouse vas deferens is mediated by an increased mobilization of intracellular calcium. The involvement of an unknown ouabain-sensitive pathway in sensitization-induced alterations is also discussed.

Analysis of Variance↗

Effect of verapamil and diltiazem on calcium-dependent electrical activity in cardiac Purkinje fibres.

The effects of verapamil and diltiazem on normal action potentials, abnormal automaticity at depolarized membrane potential and oscillatory afterpotentials were compared in sheep cardiac Purkinje fibres. Concentrations of verapamil and diltiazem exerting the same action on abnormal automaticity due to slow action potentials, caused different effects on action potential characteristics and on oscillatory afterpotentials. Diltiazem significantly shortened action potential duration whereas verapamil slightly lengthened it (NS). Diltiazem appeared to be more effective than verapamil in preventing the development of oscillatory afterpotentials induced by barium or by strophanthidin. In 50% of barium-treated preparations, verapamil caused the appearance of spontaneous activity due to enhanced normal diastolic depolarization, while diltiazem had no such effect. The observed differences were explained in terms of the different effects of the two drugs on currents other than the slow inward current, since diltiazem was more potent than verapamil in depressing Vmax.

Action Potentials↗

Effects of pinaverium bromide and verapamil on the motility of the rat isolated colon.

Pinaverium bromide was 30 times less potent than verapamil in inhibiting intraluminal pressure responses of in vitro rat colonic segments to barium chloride, acetylcholine, FK 33-824 or field stimulation. The inhibitory effects of both verapamil and pinaverium bromide on the pressure responses to field stimulation were antagonized similarly by exogenous calcium administration. These results support the concept that pinaverium bromide acts on calcium channels in the smooth muscle cell membrane.

Acetylcholine↗

Simultaneous measurement of contractile effects in the circular and longitudinal smooth muscle of the rat vas deferens by drugs perfused externally or via the lumen.

The effects of noradrenaline and barium chloride were studied in the rat isolated vas deferens by perfusion of drugs either externally or through the lumen of the organ. Two effects were recorded simultaneously in the same preparation: (a) isometric contractions, due to the tension elicited by drugs on the external (longitudinal) smooth muscle layer and (b) pressure of internal perfusion, due to contractions of the internal (circular) smooth muscle layer. It was found with the longitudinal muscle that: (a) the potency, expressed as pD2 values, and the maximum response to noradrenaline were lower if the drug was perfused internally rather than externally; (b) the differences in maximum effects were pronounced on the prostatic half but were not observed on the epididymal half; (c) the maximum response obtained by internal perfusion could be increased by simultaneously adding the same dose of drug externally; (d) when barium chloride was used instead of noradrenaline no significant differences were observed on pD2 values, but differences on maximal responses were similar to that observed for noradrenaline; (e) it was possible to block completely the effect of internal or external noradrenaline on the longitudinal muscle, by perfusing external phenoxybenzamine. In these conditions the responses of the circular muscle to the agonist were only partly blocked. With the circular muscle, the differences related to internal and external perfusion were less marked than in the longitudinal muscle. However, unlike the latter, the circular layer was slightly more sensitive to drugs applied internally, in relation to pD2 values. It is suggested that the difference in pD2 values may be due to the removal of noradrenaline by the neuronal uptake process, whereas the difference in maximal effect is due to the inaccessibility of part of the receptor population when drugs are added through the lumen.

Animals↗