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[3-Benzyl-1,2-benzoisothiazoles: spasmolytic properties of the aminoalkyl derivatives].

The synthesis and chemical and pharmacological properties of 3-benzyl-1,2-benzisothiazoleaminoalkyl derivatives are reported. These compounds were studied because 4-dimethyl-2-phenyl-2-(1,2-benzisotiazol-3-yl)-butyramide and N,N-dimethyl-3-phenyl-3-(1,2-benzisothiazol-3-yl)propylamine were recently found to have antispasmodic properties. Most of the compounds studied aspecifically inhibited the contracturant effects of acetylcholine, histamine and BaCl2. Three of them showed mixed antagonism (competitive and non-competitive) versus acetylcholine and histamine, showing both antimuscarinic and antihistaminic properties. However the antimuscarinic action prevailed over the others, as shown by pA2 and pD'2 calculated values. On the basis of the results obtained, the structure-activity relationships is discussed.

Acetylcholine↗

[Compared efficacies of somes antispasmodic drugs on the digestive tract and the bladder of the anesthetized dog (author's transl)].

The antispasmodic activity of tiemonium, mebeverine, pitofenone + fenpiverinium association and N-butyl scopolammonium was compared in the anesthetized dog. Strain gauges were fixed on the gastric antro-fundic border, on the pylorus, on the descending duodenum and on the terminal colon. Pressure transducers were connected with water filled small balloons inserted into the gall bladder and the bladder. Five minutes after the intra-venous injection of the drugs, contraction of the smooth musculature was induced by 3 intra-venous injections of BaCl2 (1 mg.kg(-1)) at 3 minutes intervals. The results were expressed as ED50 values (mg.kg(-1)). 2. Tiemonium was the most potent of the 4 antispasmodic drugs. Its ED50 values were very similar for the different organs, ranging from 0.13 +/- 0.022 for the duodenum to 0.31 +/- 0.03 for the bladder. Mebeverine and pitofenone + fenpiverinium association were equipotent but for colon contraction, where mebeverine was more active (ED50 = 0.68 +/- 0.06). Other ED50 relatives to these 2 compounds were ranging from 0.40 +/- 0.02 (duodenum) to 1.32 +/- 0.14 (gall bladder). N-butyl scopolammonium was found to be the weakest antispasmodic drug on this model. Its activity was very weak on colon (ED50 = 5.21 +/- 0.037), gall bladder (ED50 = 5.40 +/- 0.074) and bladder (ED50 = 5.02 +/- 0.059). 3. The strong antispasmodic activity demonstrated on this model with tiemonium seems to be due to its potent inhibition of membrane Ca++ ions, added to its moderate anticholinergic activity.

Anesthesia↗

Inhibitory effect of xanthomicrol and 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14Z-dehydrocativic acid from Brickellia paniculata on the contractility of guinea-pig ileum.

Chemical fractionation of Brickellia paniculata methanolic extract by monitoring its inhibitory effect on K(+)-induced contraction in guinea-pig ileum in vitro led to the isolation of 5,4'-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol) and the labdane-diterpene 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14 Z-dehydrocativic acid (AAHDD). Both compounds inhibited the tonic contraction the effect being highly potent when a mixture in a proportion of 3 : 1 (xanthomicrol/AAHDD) was assayed. The phasic component of the contractile response with K(+) was also reduced by the compounds. Xanthomicrol depressed the spasms induced with ACh, Hist, and BaCl(2) and its effect on Ca (2+) concentration-response curve showed a type of non-surmountable calcium blocking action; unlike the flavonoid, AAHDD produced a parallel rightward shift of the concentration-response curve to calcium, suggesting a competitive antagonism with an estimated pA(2) of 4.66. Obtained results support, in part, the popular use of B. paniculata as a spasmolytic remedy.

Acetylcholine↗

[Experimental study on the action mechanism of a new bronchodilator agent, BB-1502].

The action mechanism of the bronchodilator activity of BB-1502 was studied in comparison with aminophylline. Orally administered BB-1502 did not inhibit passive cutaneous anaphylaxis in rats, an immediate allergic reaction of Type I, but strongly protected the same antigen-mediated anaphylactic asthma by the intraduodenal route, the activity being approximately 13 times more potent than that of aminophylline. BB-1502 also inhibited IgG-mediated anaphylactic asthma in guinea pigs by the oral route. Both IgE- and IgG-mediated histamine releases from rat lung were similarly inhibited by BB-1502, the potency being 2--3 times that of aminophylline. Disodium cromoglycate showed specific inhibition of the IgE-mediated reaction. BB-1502 and aminophylline showed nonspecific inhibition of the spasms of guinea pig ileum elicited by histamine, acetylcholine and BaCl2. Both compounds inhibited cyclic AMP and cyclic GMP phosphodiesterases (PDEs) derived from guinea pig organs. BB-1502 specifically inhibited the cyclic AMP PDE of lung and brain origins, while aminophylline showed no such specificity. The results of the present study suggested that the bronchodilator and anti-asthmatic actions of BB-1502 might, at least in part, be due to the regulation of cyclic nucleotide PDEs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Reactions of 2-mercaptobenzoic acid with divalent alkaline earth metal ions: synthesis, spectral studies, and single-crystal X-ray structures of calcium, strontium, and barium complexes of 2,2'-dithiobis(benzoic acid).

The treatment of MCl(2).nH(2)O (M = Ca, Sr, or Ba) with 2-mercaptobenzoic acid (H-2-MBA) in a 1:2 ratio in an EtOH/H(2)O/NH(3) mixture leads to the formation of extended polymeric solids [[Ca(OOCC(6)H(4)SSC(6)H(4)COO)(H(2)O)(2)].0.5(C(2)H(5)OH)](n)(1), [[Sr(OOCC(6)H(4)SSC(6)H(4)COO)(H(2)O)(2)].0.5(C(2)H(5)OH)](n)(2), and [[Ba(2)(OOCC(6)H(4)SSC(6)H(4)COO)(2)(H(2)O)(2)].0.5H(2)O](n)(3), respectively. In all of the cases, under the reaction conditions employed, the H-2-MBA ligand undergoes thiol oxidation to form 2,2'-dithiobis(benzoic acid) (H(2)-DTBB). While the DTBB forms a 1:1 complex with heavier alkaline earth metals (1-3), only an ammonium salt, [(HOOCC(6)H(4)SSC(6)H(4)COOH)(HOOCC(6)H(4)SSC(6)H(4)COONH(4))] (4), was obtained as the final product in the reaction of H-2-MBA with MgCl(2).6H(2)O. Compounds 1-4 have been characterized with the aid of elemental analysis, thermal analysis, and infrared spectroscopic studies. All of the products are found to be thermally stable and do not melt on heating to 250 degrees C. Thermogravimetry on complexes 1-3 indicates the loss of coordinated and lattice water/solvent molecules below 200 degrees C (for complex 2) or 350 degrees C (for complexes 1 and 3). The solid-state structures of all of the derivatives 1-4 have been established by single-crystal X-ray diffraction studies. The calcium and strontium coordination polymers 1 and 2 are isomorphous. The DTBB ligands in 1 and 2 are hexadentate, and the compounds have a channel structure in which solvent ethanol molecules are included. In compound 3, barium ion forms a complex 3-dimensional coordination polymer where both the carboxylate and the sulfur centers of the DTBB ligands (which are hepta- and octadentate) coordinate to the metal.

Journal Article↗

Solid-phase extraction with strong anion-exchange columns for selective isolation and concentration of urinary organic acids.

This is a new method for isolating and concentrating urinary organic acids before gas chromatography--mass spectrometry. Sulfate and phosphate anions are removed by precipitation with Ba(OH)2, and the urine pH is adjusted to 8-8.5. The sample is then applied onto small, disposable, strong-anion-exchange columns. Neutral and basic compounds are washed out with water, which is then removed by centrifugation and by rinsing the columns with methanol and diethyl ether. The organic acids are eluted with a 4/1 (by vol) mixture of an organic solvent--either n-butanol or ethyl acetate--and formic acid containing HSO4- (0.1 mol/L) as a highly selective counter-ion, and finally with methanol alone. Sulfate ions are retained, and the eluate is evaporated before trimethylsilyl derivatization. Analytical recoveries (about 100%) of organic acids compare favorably with those obtained with solvent extraction. This convenient procedure is selective and reproducible and is a suitable alternative to the more cumbersome diethylaminoethyl-Sephadex extraction method.

Acetates↗

Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition, antihistaminic and antispasmodic activities of Aller-7, a novel botanical formulation for allergic rhinitis.

Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a major challenge to health professionals. A large number of the world's population, including approximately 40 million Americans, suffers from allergic rhinitis. A novel, botanical formulation (Aller-7) has been developed for the treatment of allergic rhinitis using a combination of extracts from seven medicinal plants, including Phyllanthus emblica, Terminalia chebula, T. bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum, which have a proven history of efficacy and health benefits. The clinical manifestations of allergy are due to a number of mediators that are released from mast cells. The effect of Aller-7 on rat mesenteric mast cell degranulation was studied by incubating different concentrations of Aller-7 and challenging them with a degranulating agent, compound 48/80. The inhibitory activity of Aller-7 was determined against lipoxygenase and hyaluronidase, the key enzymes involved in the initiation and maintenance of inflammatory responses. Furthermore, most of these manifestations are due to histamine, which causes vasodilatation, increasing capillary permeability and leading to bronchoconstriction. Hence, the antihistaminic activity of Aller-7 was determined is isolated guinea pig ileum substrate using cetirizine as a positive control. The antispasmodic effect of Aller-7 on contractions of guinea pig tracheal chain was determined using papaverine and cetirizine as controls. Aller-7 exhibited potent activity in all these in vitro models tested, thus demonstrating the novel anti-allergic potential of Aller-7.

Animals↗

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↗

Anti-Stokes Yb3+ emission--valuable structure information in spectra of rare earth compounds measured with FT-Raman spectrometers.

Raman spectroscopy is a powerful and simple method which proved to be very useful in studies of solids. The most widely used Raman spectrometers are FT-Raman instruments with YAG:Nd(3+) laser as an excitation source. However, in the case of samples containing rare earth elements, the quality of FT-Raman spectra is often low due to strong fluorescence effects. We show that, in such cases, anti-Stokes part of the Raman spectra often contains strong, well resolved bands identified as multiphonon-assisted emission bands of Yb(3+) present as an impurity. We show on several examples that analysis of these bands may provide useful structure information, similar to that obtained by "Eu structure probe" method in optical spectroscopy. The Yb(3+) emission can be also measured using standard luminescence detection systems. However, the application of FT-Raman system allows one to obtain good quality spectra in a much cheaper, easier and faster way (in times as short as a few seconds). Moreover, high-sensitivity of FT-Raman spectrometers allows to detect even very small amounts of Yb(3+) impurity.

Barium Compounds↗

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↗

Morgagni hernia: an unexpected cause of respiratory complaints and a chest mass.

Morgagni hernia (MH) is the least common type of congenital diaphragmatic hernias. Although its course is often asymptomatic, it may be associated with various respiratory and gastrointestinal symptoms. We describe 7 children with MH during a 5-year period in three pediatric centers in Turkey. All children had acute or chronic respiratory symptoms; cough was the most frequent. The diagnosis was made by posterior-anterior (PA) and lateral chest X-rays. The PA chest X-rays showed a homogenous mass in 2 and a gas-filled cystic image in 3 children in the right cardiophrenic angle. A retrocardiac homogeneous density in one child, and bilateral consolidation in lower lung areas in another child were also seen. All lateral chest X-rays showed gas-filled bowel loops above the diaphragm. The diagnosis was confirmed by barium-contrast radiograph. Four patients had five additional anomalies, i.e., ventricular septal defect, right inguinal hernia, congenital hip dislocation, pectus carinatum, and obstruction of the uretero-pelvic junction. All of the hernias were repaired by an abdominal approach. There were no complications or recurrences during follow-up. In conclusion, MH should be considered in the differential diagnosis of cases of long-standing respiratory symptoms and/or when an unexplained radiological image, especially on the right cardiophrenic area, is present.

Barium Compounds↗

Antispasmodic activity of the fruits of Helicteres isora Linn.

Fruits of Helicteres isora Linn., commonly called Murudsheng in India, are usually prescribed in the Indian traditional systems of medicine, especially in Ayurveda, for a variety of intestinal complaints. The antispasmodic activity was checked in vitro on guinea-pig ileum against three spasmogens, acetylcholine, histamine and barium chloride. The IC(50) for each was determined. The activity was compared with standard antispasmodic agents, atropine and diphenhydramine hydrochloride. The activity was also studied in vivo by observing the gastrointestinal motility in mice using the marker technique and the ED(50) was calculated. Acute toxicity studies were conducted on mice using the method of Weil and the LD(50) was determined. The results indicated that the fruits possess very good antispasmodic activity.

Acetylcholine↗

Poisoning as a result of barium styphnate explosion.

BACKGROUND: Acute barium poisoning is most often the result of accidental or suicidal ingestion of the rodenticide, barium carbonate. We describe a trauma patient whose condition was complicated by severe acute barium toxicity from an explosion of the propellant, barium styphnate. In addition to critical injuries, the patient manifested classic signs of barium toxicity including repeated profound hypokalemia, cardiac arrhythmias, respiratory failure, prolonged gastrointestinal dysfunction, paralysis, myoclonus, hypertension, and profound lactic acidosis. METHODS: The patient required lidocaine for ventricular bigeminy, massive infusions of potassium, prolonged ventilatory support, and parenteral nutrition to manage the effects of barium toxicity. RESULTS: He is the first reported case to demonstrate recurrent profound hypokalemia as an effect of blood transfusions. CONCLUSIONS: Considering the paucity of information concerning management of this life-threatening problem, the pathophysiology of barium toxicity, including the transfusion related hypokalemia, and its management is reviewed.

Accidents, Occupational↗

Colorectal carcinoma screening procedure use among primary care patients.

BACKGROUND: Despite evidence-based recommendations for colorectal carcinoma screening, population-based surveys report low screening rates. To the authors' knowledge, the extent to which screening procedures are used by patients seen in primary care is not as clear. The authors estimated the annual and 5-year colorectal carcinoma screening procedure use among a cohort of primary care patients and evaluated the correlation between patient characteristics and the use of screening procedures. METHODS: The authors identified a cohort of patients (n = 21,833 patients) ages 55-70 years who had a primary care visit in 2003 and who were enrolled in a health plan for the 5-year period ending December 31, 2003. Using automated data for the 5-year period ending December 31, 2003, information on patient sociodemographic characteristics, primary care and health maintenance examination (HME) visits, comorbid diagnoses, income, and screening receipt was compiled. The latter included barium enema, colonoscopy, fecal occult blood testing (FOBT), and flexible sigmoidoscopy use. RESULTS: Approximately one-half of insured, primary care patients (54%) received recommended colorectal carcinoma screening procedures over the 5-year observation period. Among individuals who received screening, colonoscopy was used most frequently (39.9%), followed by flexible sigmoidoscopy testing alone (28.3%) or in combination with FOBT (4.3%). Annual screening rates increased by 3.1% between 1999 and 2003. Among individuals who did not receive recommended colorectal carcinoma screening, 64% had at least 3 HME visits, and 41% received at least 1 FOBT. Increasing HME visits and other primary care visit frequency, along with increasing age, income, male gender, and African-American race, were associated with screening receipt. CONCLUSIONS: Significant opportunities exist to increase colorectal carcinoma screening among primary care patients.

Adenocarcinoma↗

Subunit composition of G(o) proteins functionally coupling galanin receptors to voltage-gated calcium channels.

The neuropeptide galanin is widely expressed in the central nervous system and other tissues and induces different cellular reactions, e.g. hormone release from pituitary and inhibition of insulin release from pancreatic B cells. By microinjection of antisense oligonucleotides we studied the question as to which G proteins mediate the galanin-induced inhibition of voltage-gated Ca2+ channels in the rat pancreatic B-cell line RINm5F and in the rat pituitary cell line GH3. Injection of antisense oligonucleotides directed against alpha 01, beta 2, beta 3, gamma 2 and gamma 4 G protein subunits reduced the inhibition of Ca2+ channel current which was induced by galanin, whereas no change was seen after injection of cells with antisense oligonucleotides directed against alpha i, alpha q, alpha 11, alpha 14, alpha 15, beta 1, beta 4, gamma 1, gamma 3, gamma 5, or gamma 7 G protein subunits or with sense control oligonucleotides. In view of these data and of previous results, we conclude that the galanin receptors in GH3 and in RINm5F cells couple mainly to the G(0) protein consisting of alpha 01 beta 2 gamma 2 to inhibit Ca2+ channels and use alpha 01beta 3 gamma 4 less efficiently. The latter G protein composition was previously shown to be used by muscarinic M4 receptors to inhibit Ca2+ channels.

Amino Acid Sequence↗