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Biomedical subjects

A Tomas

Publications and source records attributed to A Tomas.

14 recordsLinked to original sources
PubMed2005

7-day rescue therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure.

BACKGROUND: Quadruple rescue therapy requires a complex scheme with four drugs. AIM: To evaluate the efficacy of ranitidine bismuth citrate-tetracycline-metronidazole rescue regimen, and to compare two different metronidazole dose schemes. METHODS: Prospective multicentre study including proton-pump inhibitor + clarithromycin + amoxicillin failures. Rescue regimen included two 7-day treatment: (i) ranitidine bismuth citrate (400 mg b.d.)-tetracycline (500 mg q.d.s.)-metronidazole (500 mg t.d.s.; RTM1); or (ii) the same regimen but with metronidazole 250 mg q.d.s. (RTM2). Eradication was confirmed with (13)C-urea breath test. RESULTS: A total of 150 patients were included (58 RTM1, 92 RTM2). All patients but two (one in each group) returned after treatment. About 86% in group RTM1 and 95% in RTM2 correctly took all the medications (P = 0.076). Per-protocol eradication rates with RTM1 and RTM2 were 74 (95% CI: 60-84) and 69% (59-78). The intention-to-treat eradication rates were 64 (51-75) and 70% (59-78; P > 0.05). The type of regimen was not associated with eradication in the multivariate analysis. Adverse effects were more frequent with RTM1 (41%) than with RTM2 (30%; P > 0.05). CONCLUSION: Seven-day triple rescue therapy with ranitidine bismuth citrate-tetracycline-metronidazole is effective for Helicobacter pylori eradication, and represents an encouraging alternative to quadruple therapy, with the advantage of simplicity. The administration of metronidazole every 6 h (together with tetracycline), and at a low dose (250 mg), achieves similar efficacy and is probably associated with a better compliance and a lower incidence of adverse effects.

Adult↗
PubMed2002

[Synthesis and crystalline structure of cis-monochloro(dimenthylsulfoxide)].

The synthesis of cis-monochloro(dimethylsulfoxide)(metforminuro) platine(II) was investigated. It crystallizes in the monoclinic system, space group P 2(1)/c with Z=4. The cell parameters are: a=9.173(2); b=11.286( 2); c=12.556( 3) (A); b=99.69(2) degrees. The structure of this compound was refined to R=0.031 and wR=0.038 using 1461 independent reflexions with I>3 s(I). The platinum coordination is square planar, built up from one Cl, one O from the dimethylsulfoxide, and one bidentate chelating ligand (metforminure anion) via the two imine nitrogen atoms in cis position. The negative charge of the metforminure ligand ensures the electric neutrality in the complex. The crystal packing is characterized by four hydrogen bonds, one of which is bifurcated (involving Cl atom (intramolecular bonding) and O(i) (intermolecular bonding; symmetry code i: x, 3/2-y; 1/2+z).

Catalysis↗
PubMed2001

Retrobiosynthetic nuclear magnetic resonance analysis of amino acid biosynthesis and intermediary metabolism. Metabolic flux in developing maize kernels.

Information on metabolic networks could provide the basis for the design of targets for metabolic engineering. To study metabolic flux in cereals, developing maize (Zea mays) kernels were grown in sterile culture on medium containing [U-(13)C(6)]glucose or [1,2-(13)C(2)]acetate. After growth, amino acids, lipids, and sitosterol were isolated from kernels as well as from the cobs, and their (13)C isotopomer compositions were determined by quantitative nuclear magnetic resonance spectroscopy. The highly specific labeling patterns were used to analyze the metabolic pathways leading to amino acids and the triterpene on a quantitative basis. The data show that serine is generated from phosphoglycerate, as well as from glycine. Lysine is formed entirely via the diaminopimelate pathway and sitosterol is synthesized entirely via the mevalonate route. The labeling data of amino acids and sitosterol were used to reconstruct the labeling patterns of key metabolic intermediates (e.g. acetyl-coenzyme A, pyruvate, phosphoenolpyruvate, erythrose 4-phosphate, and Rib 5-phosphate) that revealed quantitative information about carbon flux in the intermediary metabolism of developing maize kernels. Exogenous acetate served as an efficient precursor of sitosterol, as well as of amino acids of the aspartate and glutamate family; in comparison, metabolites formed in the plastidic compartments showed low acetate incorporation.

Amino Acids↗
PubMed2000

Enantioselective Michael reactions of chiral secondary enaminoesters with 2-substituted nitroethylenes. Syntheses of trans, trans-2,4-disubstituted pyrrolidine-3-carboxylates

The Michael reaction of chiral 3-substituted secondary enaminoesters with 2-substituted nitroethylenes leads to (Z)-adducts, with good to excellent diastereoselectivity. The nitro group of these adducts was catalytically reduced to give, after cyclization and chiral amine elimination, pyrrolines or pyrrolidines after further reduction. In particular, the syntheses of ethyl (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate are described.

Journal Article↗
PubMed2000

Auxin biosynthesis in maize kernels.

Auxin biosynthesis was analyzed in a maize (Zea mays) kernel culture system in which the seeds develop under physiological conditions similar to the in vivo situation. This system was modified for precursor feeding experiments. Tryptophan (Trp) is efficiently incorporated into indole-3-acetic acid (IAA) with retention of the 3, 3' bond. Conversion of Trp to IAA is not competed by indole. Labeling with the general precursors [U-(13)C(6)]glucose and [1, 2-(13)C(2)]acetate followed by retrobiosynthetic analysis strongly suggest that Trp-dependent IAA synthesis is the predominant route for auxin biosynthesis in the maize kernel. The synthesis of IAA from indole glycerol phosphate and IAA formation via condensation of indole with an acetyl-coenzyme A or phosphoenolpyruvate derived metabolite can be excluded.

Amino Acids↗
PubMed1999

Crystal structures of alpha-mercaptoacyldipeptides in the thermolysin active site: structural parameters for a Zn monodentation or bidentation in metalloendopeptidases.

Three alpha-mercaptoacyldipeptides differing essentially in the size of their C-terminal residues have been crystallized in the thermolysin active site. A new mode of binding was observed for 3 [HS-CH(CH(2)Ph)CO-Phe-Tyr] and 4 [HS-CH((CH(2))(4)CH(3))CO-Phe-Ala], in which the mercaptoacyl moieties act as bidentates with Zn-S and Zn-O distances of 2.3 and 2.4 A, respectively, the side chains fitting the S(1), S(1)', and S(2)' pockets. Moreover, a distance of 3.1 A between the sulfur atom and the OE1 of Glu(143) suggests that they are H-bonded and that one of these atoms is protonated. This H-bond network involving Glu(143), the mercaptoacyl group of the inhibitor, and the Zn ion could be considered a "modified" transition state mimic of the peptide bond hydrolysis. Due to the presence of the hindering (5-phenyl)proline, the inhibitor HS-CH(CH(2)Ph)CO-Gly-(5-Ph)Pro (2) interacts through the usual Zn monodentation via the thiol group and occupancy of S(1)' and S(2)' subsites by the aromatic moieties, the proline ring being outside the active site. The inhibitory potencies are consistent with these structural data, with higher affinities for 3 (4.2 x 10(-)(8) M) and 4 (4.8 x 10(-)(8) M) than for 2 (1.2 x 10(-)(6) M). The extension of the results, obtained with thermolysin being considered as the model of physiological zinc metallopeptidases, allows inhibitor-recognition modes for other peptidases, such as angiotensin converting enzyme and neutral endopeptidase, to be proposed and opens interesting possibilities for the design of new classes of inhibitors.

Crystallography, X-Ray↗
PubMed1999

In vitro and in vivo evaluation of a reusable double-channel sphincterotome.

BACKGROUND: To date, one reusable, double-channel sphincterotome has been approved by the Food and Drug Administration in the United States. Whether this device can be reprocessed easily and whether it is more durable than currently manufactured disposable sphincterotomes are uncertain. METHODS: Thirty double-channel, 20 mm, braided-wire sphincterotomes approved for multiple uses were studied in vitro/in vivo with regard to durability and sterilization. A cost analysis of reusable, disposable, and reprocessed disposable sphincterotomes was also carried out. RESULTS: Three of 10 sphincterotomes evaluated in vitro broke after 3, 4, and 8 uses. Electrical integrity was preserved after 10 uses in the remaining sphincterotomes. Nine sphincterotomes remained functional for at least 3 uses, five for 6 uses, and one for 10 uses. Culture results after inoculation demonstrated contamination with surviving organisms after manual cleaning and no growth after ethylene oxide sterilization. Sixty-one procedures were performed in vivo using 20 sphincterotomes (mean number of uses 3.1). No evidence of procedurally related infection occurred with reuse. Cost per use of this reusable sphincterotome was calculated to be $62.98; it became cost effective after 2.2 and 7.9 uses when compared with disposable and reprocessed, disposable sphincterotomes, respectively. CONCLUSIONS: This reusable sphincterotome proved to be safe, easily sterilized, and electrically intact after repeated use. In vivo, however, a progressive loss of function limited the mean number of uses to 3.1. In settings that preclude reuse of reprocessed disposable accessories, this reusable sphincterotome may provide a means to decrease costs associated with endoscopic retrograde cholangiopancreatography.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1998

Crystal structure of 11,18-oxidosteroids obtained by hypoiodination of cortisol acetonide.

The photochemical hypoiodination of cortisol acetonide, without neutralization of the excess of acidity during the work-up of the reaction, led to a mixture of 11 beta,18-oxido-17 alpha,21-dihydroxy-4-pregnen-3,20-dione and 11 beta,19-oxido-17 alpha,21-dihydroxy-4-pregnen-3,20-dione. Side chain cleavage of the former compound gave 11 beta,18-oxido-4-androsten-3,17-dione. The crystal structures of both of these 11 beta,18-oxidosteroids were determined by X-ray. The ring conformations are discussed and compared with those of aldosterone.

Crystallography, X-Ray↗
PubMed1997

NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801.

The ion channel of the N-methyl-D-aspartate (NMDA) receptor complex is subject to a voltage-dependent regulation by Mg2+ cations. Under physiological conditions, this channel is supposed to be blocked by a high concentration of magnesium in extracellular fluids. A single dose of magnesium organic salts (i.e., aspartate, pyroglutamate, and lactate) given orally to normal mice rapidly increases the plasma Mg2+ level and reveals a significant dose-dependent antagonist effect of magnesium on the latency of NMDA-induced convulsions; this effect is similar to that seen after administration of the dizocilpine (MK-801) channel blocker. An anticonvulsant effect of Mg2+ treatment is also observed with strychnine-induced convulsions but not with bicuculline-, picrotoxin-, or pentylenetetrazol-induced convulsions. In the forced swimming test, Mg2+ salts reduce the immobility time in a way similar to imipramine and thus resemble the antidepressant-like activity of MK-801. This activity is masked at high doses of magnesium by a myorelaxant effect that is comparable to MK-801-induced ataxia. Potentiation of yohimbine fatal toxicity is another test commonly used to evaluate putative antidepressant drugs. Administration of Mg2+ salts, like administration of imipramine strongly potentiates yohimbine lethality in contrast to MK-801, which is only poorly active in this test. Neither Mg2+ nor MK-801 treatment can prevent reserpine-induced hypothermia. These data demonstrate that oral administration of magnesium to normal animals can antagonize NMDA-mediated responses and lead to antidepressant-like effects that are comparable to those of MK-801. This important regulatory role of Mg2+ in the central nervous system needs further investigation to evaluate the potential therapeutic advantages of magnesium supplementation in psychiatric disorders.

Adrenergic alpha-Agonists↗
PubMed1995

A simple synthesis of 11,19-oxidosteroids.

The photochemical hypoiodination of cortisol acetonide gave a mixture of 18-iodocortisol acetonide and of the 11 beta,19-oxidoderivative. The proportion of the two products was slightly modified by the reaction temperature. Deprotection of the acetonide group of the 11 beta,19-oxidoderivative gave 11 beta,19-oxido-17 alpha,21-dihydroxy-4-pregnen-3,20-dione which led to the formation of 11 beta,19-oxido-4-androsten-3,17-dione upon treatment with sodium bismutate.

Androstenedione↗
PubMed1993

Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia.

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.

Adult↗
PubMed1989

Different large deletions of T cell receptor V beta genes in natural populations of mice.

A panel of geographically separate Mus m. domesticus and Swiss mice from several sources was screened for deletions in the T cell receptor variable (V) beta locus. Four out of forty-three strains tested show a deletion identical to or larger than the deletion previously described in SJL mice. To our knowledge, this is the first time that such important V beta deletions are described in inbred or partially inbred wild-derived strains of mice. On the other hand there seems to be very little polymorphism between the remaining V beta genes. Expression of V beta genes in peripheral and intra-thymic T cells was tested using antibodies specific for different V beta polypeptide chains. Flow cytometry analysis revealed a high expression of V beta 6 and V beta 17 genes in the Copacabana Swiss-derived strain and an absence of V beta 17 expression in the WLA wild-derived strain. The three Mus m. domesticus strains (WLA, DDO and WBG) having deleted two to three additional V beta subfamilies compared to SJL present no apparent immune deficiencies or autoimmune disorders. We conclude that relatively few V beta genes may suffice for unimpaired survival of wild mice and that there is a selective pressure for the structural conservation of the remaining V beta genes.

Animals↗