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Exposure to soluble barium compounds: an interventional study in arc welders.

Soluble barium (Ba) compounds are well-known toxicants. Intoxications are mainly known in an acute form from casual or suicidal oral ingestion. No scientifically based data are available on possible health effects of inhalative exposure to soluble Ba salts at the workplace. Therefore, we investigated 18 welders in an interventional study over 1 week. They performed welding of Ba-containing stick electrodes and self-shielded flux cored wires under conditions similar to real working conditions. The welding fumes contained 31%-37% Ba, more than 90% of which was soluble in acids. Without appropriate preventive measures, a high rate of measurements exceeded the TLV values for total welding fumes of 5 mg/m3 and for soluble Ba of 0.5 mg/m3. The median fume concentrations were 13.2 mg/m3 in stick electrode welding and 12.3 mg/m3 in flux cored wire welding. The median Ba concentrations were 4.4 and 2.0 mg/m3 respectively. An integrated exhaust system built into the gun proved to be efficient in flux cored wire welding. The internal exposure to Ba reached median urine levels up to 101.7 micrograms/l (normal: below 20 micrograms/l) and median plasma concentrations of up to 24.7 micrograms/l (normal: below 8 micrograms/l). No health impact on the welders could be proven, but hypokalemia may have occurred as a result of the Ba exposure.

Air Pollutants, Occupational

[Routine double-contrast radiographic examination of the esophagus].

The authors evaluate the opportunity of extending the double-contrast technique to the X-rays examination of the esophagus, with particular regard to physical and chemical features of barium compounds used at present for the X-rays study of digestive tract. The authors expose the results of this kind of X-rays examination in the most important fields of esophageal pathology. Personal experience actually demonstrate the opportuny of extending the double-contrast technique to routine practice, as a first approach to the double-contrast study of the upper digestive tract.

Air

Barium sulfate suspension as a negative oral MRI contrast agent: in vitro and human optimization studies.

In vitro proton spectroscopy with line-width measurements and MR imaging were performed on various concentrations of commercially available single contrast (SC), double contrast, oral and rectal barium sulfate suspensions, as well as potassium sulfate, barium chloride, barium hydroxide, and 97% pure barium sulfate suspensions. Approximately 500 ml of 20%, 40%, 60%, and 70% w/w suspensions of SC oral barium sulfate suspensions were administered to four normal volunteers, respectively, and MR images were obtained at both 1.5 T and 0.15 T. Subsequently, 500 ml of 60% w/w suspensions of SC oral barium sulfate suspensions were administered to five normal volunteers and imaged at 1.5 T. All of the inert suspensions produced line-width broadening but the SC oral barium sulfate suspension at 50% and 70% stayed in suspension even after hours of standing undisturbed. As much as 80% of the small bowel and the entire colon were well visualized using the combination of 60% or 70% w/w SC barium sulfate suspensions with SE 550/22 and FISP pulse sequences. The effect was less at 0.15 T and also with the SE 2000/45/90 pulse sequences. We conclude that barium sulfate suspensions are useful as oral MRI contrast agents.

Administration, Oral

[Sensitivity of the prosobranch mollusk Potamopyrgus jenkinsi Smith to the action of metallic chlorides (ZnCl2, BaCl2, CuCl2) and to the synthetic molluscacide N-tritylmorpholine].

The toxicity of 3 metal chlorides (ZnCl2, BaCl2, CuCl2), and of N-trityl-morpholine (Triphenmorph or frescon) has been studied on the gastropod mollusc Potamopyrgus jenkinsi, in eucalcic and oligocalcic waters. The results showed the following order in the efficiency of the toxic compounds: triphenmorph greater than copper greater than barium greater than zinc. In eucalcic water, the toxicity of barium and decreased whereas the efficiency of triphenmorph and increased. The toxicity of the substances, at middle term, rose in relation to the time of the experiment. An exposure of 2 h to the toxic agents was sufficient to induce high mortality in P jenkinsi. In oligocalcic water, the juvenile snails were more sensitive than the adults to the action of metal chlorides, but they showed higher tolerance to Triphenmorph; in addition, the winter generation was more resistant than the summer one, except for barium.

Animals

[The anti-H1-histaminic and antimuscarinic effect of 2- and 4-[benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds].

This paper reports the synthesis of 2- and 4- [benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds and the evaluation of their inhibitory properties against histamine (H1), acetylcholine and barium chloride, on guinea pig isolated ileum. 4-[p.Methoxybenzyl-(2-dimethylaminoethyl)amino]-2-methoxy-pyrimidine (VIII) is shown to possess H1 receptor antagonist activity, with a potency similar to that observed for Tonzylamine. By contrast, a specific, although weak, antimuscarinic effect is displayed by 4-[benzyl-(2-dimethylaminoethyl)amino]-2-methoxy-5-methylthio-pyrimidine (XII).

Acetylcholine

[Exposed lead dioxide candles analyzed by a volumetric method, carried out as laboratory and field tests in Innsbruck (author's transl)].

Working up a great number of "lead-Dioxide-Candles" it took much less time to determine sulphate by a method of volumetric analysis with Ba(ClO4)2 and thoron or methylsulfonazo III as indicators compared with the so far used gravimetric determination of sulphate. With some training everybody will be able to make out the exact endpoint of the titration using thoron as indicator. The limits of error and the results gained from field-trials are shown. The possibilities of making statements of hygienically regional planning are discussed.

Air Pollutants

A patch-clamp study: secretagogue-induced currents in rat peritoneal mast cells.

Ca2+ entry through plasma membrane has been considered to play a significant role in elevating cytosolic free Ca2+ concentrations during stimulus-secretion coupling in mast cells, but electrophysiological evidence of the Ca2+ channels is lacking. We examined the properties of secretagogue (compound 48/80)-induced currents in rat peritoneal mast cells, using the patch-clamp technique. In the whole cell recordings, the addition of compound 48/80 induced transient currents that were suppressed by Cd or reduced by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). In Ringer solution containing 2 mM Ca2+, the current-voltage relation was fairly linear from -100 to 50 mV and the reversal potential was 14 +/- 10.1 mV (n = 9). When the external Ca2+ was approximately 1 microM, the compound 48/80-induced currents were marginal, but readmission of Ca2+ or Ba2+ to the bath solution led to an appearance of the currents. In the cell-attached patches, the stimulation enhanced the activity of inward current mediated by Ba2+. The unitary inward Ba2+ current was characterized by the unitary conductance of 10.5 +/- 2.0 pS (n = 10) with isotonic BaCl2 pipette solution, the extrapolated reversal potential of 60.7 +/- 16.0 mV (n = 10) positive to the resting membrane potentials. The percent open time of the inward Ba2+ current channel was not appreciably changed by voltage. In some whole cell recordings, an increase in openings of the cation-selective channel (20-45 pS) was identified in the stimulated cells. When the external Na+ was completely replaced by choline+, the compound 48/80-induced currents had a fairly linear current-voltage relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Pharmacological alterations of the activity of afferent fibers innervating hair cells.

To determine whether some of the substances that may be present in hair-cell sensory organs could affect neural activity in afferent fibers, we examined 56 compounds for the ability to alter the discharge rate of afferent fibers innervating hair cells in the lateral line organ of Xenopus laevis, the African clawed frog. These compounds included amino acids, glutamyl dipeptides, standard neurotransmitter candidates, and other constituents of tissues and body fluids. Substances found to be excitatory included some neutral amino acids (alanine, serine, threonine, asparagine, glutamine, and proline), ATP, carnosine, histidine, and barium chloride. Compounds that suppressed discharge included the aromatic amino acids (phenylalanine, tryptophan, and tyrosine), serotonin, and gamma-glutamyl dipeptides. GABA and acidic amino acids (glutamate, aspartate, and cysteine sulfinate) produced a brief excitation followed by a suppression of discharge rate. Several of these substances were active at sufficiently low concentrations that their presence in body fluids may affect afferent fiber discharge rate under normal or pathological conditions.

Amino Acids

Cholinergic receptor mechanisms in amphibian vasoconstrictor responses.

The four choline esters, namely acetylcholine, carbachol, methacholine and bethanechol, produced constriction of frog's perfused systemic blood vessels, acetylcholine and carbachol being more potent than methacholine and bethanechol. Pentolinium and dihydroergotamine, in submaximal receptor-blocking doses, also produced a uniform partial inhibition of all choline esters and other agonists including the direct-acting barium chloride. On the other hand atropine markedly inhibited the responses of the four choline esters without affecting the adrenaline and barium responses. Compound AHR-602, a specific ganglionic muscarinic excitatory receptor stimulant, did not produce any effect in these experiments. Eserine in higher doses produced slight vasoconstriction and markedly potentiated acetylcholine responses, but it inhibited partially those of the other three choline esters without significantly affecting adrenaline and barium responses. The results provide strong evidence in favor of involvement of the postganglionic muscarinic receptors only in vasoconstriction after choline esters. There seems to be a considerable nonspecific inhibitory activity in ganglionic and alpha-adrenergic blockers in their submaximal receptor-blocking doses. It may be that in frog the adrenergic and nicotinic receptors are not as well differentiated as muscarinic receptors are. The ganglionic muscarinic receptors also seem to be absent in the frog.

Acetylcholine

Synthesis and pharmacological characterization of a series of leukotriene analogues with antagonist and agonist activities.

The synthesis and biological characterization of a series of novel leukotriene antagonists and agonists are reported. All of these compounds are derivatives of (5S,6R,7Z)-5-hydroxy-6-mercapto-9-phenyl-7-nonenoic acid. One of the more potent compounds is (5S,6R,7Z)-6-[[(4-carboxy-2-methoxyphenyl)methyl]thio]-5-hydroxy-9 -(4- heptylphenyl)-7-nonenoic acid (3f). In vitro evaluation of this compound on guinea pig trachea revealed that it is a competitive antagonist of LTD4 and LTE4 with pKB values of 6.4 and 5.8, respectively. On guinea pig ileum, the pKB values obtained for it with LTD4 and E4 were both 7.2. The selectivity of 3f was shown by its lack of effect on carbachol, histamine, and barium chloride concentration-response curves in guinea pig trachea.

Animals

Quantification of the degradation products of sevoflurane in two CO2 absorbants during low-flow anesthesia in surgical patients.

Sevoflurane, a new inhalational anesthetic agent has been shown to produce degradation products upon interaction with CO2 absorbants. Quantification of these sevoflurane degradation products during low-flow or closed circuit anesthesia in patients has not been well evaluated. The production of sevoflurane degradation products was evaluated using a low-flow anesthetic technique in patients receiving sevoflurane anesthesia in excess of 3 h. Sevoflurane anesthesia was administered to 16 patients using a circle absorption system with O2 flow of 500 ml/min and average N2O flow of 273 ml/min. Preoperative and postoperative hepatic and renal function studies were performed. Gas samples were obtained from the inhalation and exhalation limbs of the anesthetic circuit for degradation product analysis and analyzed by gas chromatography/mass spectrometry for four degradation products. The first eight patients received sevoflurane anesthesia using soda lime, and the following eight patients received anesthesia using baralyme as the CO2 absorbant. CO2 absorbant temperatures were measured during anesthesia. Of the degradation products analyzed, only one compound [fluoromethyl-2, 2-difluoro-1-(trifluoromethyl) vinyl ether], designated compound A, was detectable. Concentrations of compound A increased during the first 4 h of anesthesia with soda lime and baralyme and declined between 4 and 5 h when baralyme was used. Mean maximum inhalation concentration of compound A using baralyme was 20.28 +/- 8.6 ppm (mean +/- SEM) compared to 8.16 +/- 2.67 ppm obtained with soda lime, a difference that did not reach statistical significance. A single patient achieved a maximal concentration of 60.78 ppm during low-flow anesthesia with baralyme. Exhalation concentrations of compound A were less than inhalation concentrations, suggesting patient uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

Interaction of potassium channel openers and blockers in canine atrial muscle.

1. The possibility that the interaction between potassium channel openers, e.g. cromakalim, pinacidil and nicorandil, and some potassium channel blockers involves a common site was investigated in canine atrial muscle. 2. Cromakalim, pinacidil and nicorandil produced a negative inotropic effect, their pD2 (-log EC50) values being 6.11 +/- 0.07, 5.37 +/- 0.09 and 4.55 +/- 0.07, respectively. 3. The potassium channel blockers, tetraethylammonium (TEA), tetrabutylammonium (TBA), 3,4-diaminopyridine (DAP), CsCl and BaCl2 all produced a positive inotropic effect. 4. The concentration-effect curves for the negative inotropic actions of pinacidil were shifted in a parallel way to the right by low concentrations of TEA, TBA or BaCl2. Maximum responses to pinacidil were depressed by higher concentrations of the blockers. An analysis of the non-competitive antagonism by TEA yielded pKA (-log KA) values of 4.00-4.05 for pinacidil. 5. The concentration-effect curves for cromakalim and nicorandil were shifted by TEA similarly to those for pinacidil, and a similar analysis yielded pKA values of 4.47-4.68 for cromakalim and 3.47-3.74 for nicorandil. 6. The KA values of cromakalim, pinacidil and nicorandil were about 10-30 times greater than their EC50 values, indicating that there are non-linear stimulus-effect relationships between the binding of the three potassium channel openers to their binding sites at potassium channels and their negative inotropic effects. 7. The dissociation constants for TEA could also be estimated from pA2 and pKB values for antagonizing competitively and non-competitively the negative inotropic effects of the three potassium channel openers; they were 3.47-3.89, and did not differ between the potassium channel openers. 8. The concentration-effect curves for the three potassium channel openers were not affected by DAP or CsCl. 9. These results suggest the following: (i) quaternary ammonium compounds like TEA and TBA antagonize the negative inotropic effect of cromakalim, pinacidil and nicorandil by binding to potassium channels, thus preventing binding of the channel openers to the same sites or closely related sites in canine right atrial muscles.

Animals

Changes in duodenal contractility induced by "calcium antagonists" with different modes of action.

The inhibitory action of nifedipine, verapamil, diltiazem and trifluoperazine has been examined on isolated duodenum from rats and rabbits. On rabbit duodenum Ca2+ antagonists caused a reduction of the spontaneous motility in very low concentrations (10(-12)-10(-6)M). On rat duodenum Ca2+ antagonists inhibited the contractile response to BaCl2, CaCl2 and to field stimulation, nifedipine being the most potent compound (threshold concentration down to 10(-12)M). The above results indicated that Ca2+ antagonists can markedly alter the duodenal motility, both basal and drug-stimulated. The high potency of nifedipine and the selective antagonism by Bay K 8644 against nifedipine suggest the presence of a specific receptor for the dihydropyridines (DHP receptor) in the duodenum.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Absorption and degradation of sevoflurane and isoflurane in a conventional anesthetic circuit.

Soda lime and Baralyme degrade sevoflurane, the rate of degradation being a direct function of temperature. We tested whether this degradation would impede the development of an anesthetizing concentration of sevoflurane (compared with isoflurane, a compound that is not degraded) in a circle-absorption system having an increased temperature consequent to (a) carbon dioxide production (200 mL/min) and absorption; and (b) a low inflow rate (70 mL/min). We also measured the temperatures reached in various parts of the absorption system when used in clinical practice, finding that peak temperatures usually reached 37 degrees - 46 degrees C when low inflow rates (500 mL/min) were applied. The tests in the model system demonstrated that soda lime and Baralyme absorbed both sevoflurane and isoflurane, and that both absorbants degraded sevoflurane but not isoflurane. Baralyme produced a fourfold greater degradation of sevoflurane vapor than did soda lime (0.66 mL/min compared with 0.17 mL/min). However, except for a slight delay at the start of anesthesia, neither absorption nor degradation should noticeably affect the requirement for anesthetic delivery in clinical practice, even in low-flow systems.

Absorption

[Antiarrhythmic effects of kappa-seleno-carrageenan in experimental animals].

The effect of Kappa-seleno-carrageenan, an organic compound containing selenium, on aconitine, BaCl2 and ouabain-induced arrhythmias were studied. When rats were given ip 9 mg.kg-1.d-1 x 5 d or ig single dose of 35, 70, 140 mg.kg-1, the threshold dose of aconitine was elevated significantly to induce HA. The effect seems to resemble that of ip Na2SeO3 1 mg.kg-1 x d-1 x 5 d. With increasing ig dose, the threshold dose of aconitine was elevated for inducing VE, VT, VF. When ip 9 mg.kg-1 x d-1 x 5 d or ig 70 mg.kg-1 was given, the threshold doses of BaCl2 in inducing VF (in rats) and ouabain in inducing VE (in guinea-pig) were elevated. However, no influence was observed for ip Na2SeO3 1 mg.kg-1 x d-1 x 5 d.

Aconitine

Inhibition of a voltage-dependent Ca current by concanavalin A.

Incubation of the hypotrichous ciliate Stylonychia mytilus in fluorescein-labeled concanavalin A (Con A, 0.1-0.5 microgram/ml) produced a strong fluorescence of its membranelles, but comparatively weak fluorescence of the other compound cilia and of the somatic membrane. Compared to untreated cells, the frequency of spontaneous backward movements was reduced in the presence of 0.5 microgram/ml ConA. In electrophysiological experiments Con A altered the excitability of the cell membrane. The two-peak action potential lost its second component which is associated with voltage-dependent Ca channels in the membranelles. The corresponding Ca current (Ca current I) was inhibited by low concentrations of Con A (0.2-0.5 microgram/ml). A second voltage-dependent Ca current (Ca current II) was not affected. Reducing the K outward current by intracellular Cs and/or extracellular tetraethylammonium, or changing the holding potential, did not restore the Con A-sensitive Ca current I. Con A also inhibited this current when Ca was replaced by Ba. The inhibitory effect of Con A on the voltage-dependent Ca current I was prevented by 10-30 mM alpha-methyl-D-mannoside, and the lectin wheat germ agglutinin (20 micrograms/ml) did not affect the Ca currents, indicating that the Con A effect was mediated by binding to specific sugar residues on the excitable membrane. The succinylated dimeric derivative of Con A did not inhibit Ca current I up to concentrations of 5 micrograms/ml. It is concluded that the two voltage-dependent Ca currents in Stylonychia can be chemically isolated due to their different sensitivity to Con A, which appears to bind preferentially to sites near or at the Ca channel in the membranellar membrane.

Animals