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Biomedical subjects

A Martí

Publications and source records attributed to A Martí.

27 records · Page 2Linked to original sources

The influence of a new compound, PATP, on glucose transport in the isolated fat cell.

A newly synthesized compound, N-(4-pyridylcarbonyl amino) 1, 2, 3, 6 tetrahydropyridine (PATP) was earlier found to elevate the blood glucose level in rats. This suggested that the compound might be accomplishing this by blocking glucose transport into tissue cells. This hypothesis has now been examined in the isolated fat cell system using a modification of the method to improve the accuracy of measurements made. This study indicated that PATP is a competitive inhibitor of glucose transport and metabolism (KI = 0.89 mM) but could not unequivocally prove that the effect was on transporter action alone. That the compounds action was at this level, however was shown by its ability to inhibit the uptake of the transported but non-metabolized sugar, 3-0-methyl glucose (KI = 3 mM). PATP is a nonphenolic inhibitor of glucose transport unrelated in structure to the sugar or to another more potent inhibitor, phloretin.

Adipose Tissue↗

The small nuclear ribonucleoproteins that react with anti-Sm and anti-RNP antibodies.

We have examined the polypeptide pattern of small nuclear ribonucleoprotein particles that react with monoclonal anti-Sm antibodies or polyclonal anti-(U1)RNP antibodies. The fresh nuclear extracts analyzed were prepared from human cells that had been pulse-chased with a mixture of 15 3H-labeled amino acids. In contrast to previous reports in the literature, the apparent molecular weights of the major polypeptides that remained in the 1 M NaCl-washed ribonucleoprotein-antibody complexes were approximately 80000, 55000, 28000, 25000, 14000 and 9000, when probed with monoclonal anti-Sm antibodies, and about 69000, 58000 and 35000, when polyclonal anti-(U1)RNP antibodies were used.

Antibodies↗

Interaction of doxorubicin with lipid systems.

The action of doxorubicin, a cancer chemotherapeutic agent, on liposomes of dipalmitoylphosphatidylcholine obtained by extrusion, with or without cholesterol, and on monolayers of the same composition, was determined by photon correlation spectroscopy, penetration kinetics, and adsorption isotherms. Doxorubicin produced a wider vesicle distribution in both of liposomes, but liposomes containing cholesterol underwent an increase of mean diameter as well as polydispersity. In contrast, films containing cholesterol showed least interaction with the drug. Since both lipids are neutral, any interaction must be primarily hydrophobic.

1,2-Dipalmitoylphosphatidylcholine↗

Rapid confirmation/quantitation of ecgonine methyl ester, benzoylecgonine, and cocaine in urine using on-line extraction coupled with fast HPLC and tandem mass spectrometry.

A rapid, rugged, and highly specific assay for the quantitation of cocaine (COC) and especially its primary metabolites benzoylecgonine (BZE) and ecgonine methyl ester (EME) in human urine has been established. Here, we investigated the use of on-line sample extraction coupled to rapid chromatography systems for tandem mass analysis of COC, EME, and BZE in human urine. Using this method, sample preparation consisted of a sole centrifugation step. Combined extraction and chromatographic run times were < 3.5 min. The lower limits of detection were 0.5 ng/mL, 2.0 ng/mL, and 0.5 ng/mL for EME, BZE, and COC, respectively. Linear calibration curves ranging from 7.5 ng/mL to 1000 ng/mL were produced for the test analytes. Within-day and between-day precision and accuracy of the assay were determined using human urine quality-control specimens at 5, 10, or 15; 150; and 1000 ng/mL. The analyses were performed over the course of five days, rendering %CVs < 10% for EME, BZE, and COC. Percent mean accuracy for the three analytes of 97 to 113% were obtained. Our data suggest that on-line sample extraction coupled with rapid high-performance liquid chromatography-tandem mass spectrometry may be a viable alternative for EME, BZE, and COC analyses in human urine.

Chromatography, High Pressure Liquid↗

Encapsulation of doxorubicin in neutral liposomes by passive methods: evidence of drug-lipid interaction at neutral pH.

Doxorubicin, an antineoplastic agent, was encapsulated in liposomes of dipalmitoylphosphatidylcholine with or without cholesterol, by the extrusion procedure. Doxorubicin was added to the lipid before drying, or was present in the rehydration buffer, and the influence of the method of encapsulation on size and polydispersity was determined by photon correlation spectroscopy. Results showed an important interaction between doxorubicin and liposomes, although cholesterol-containing vesicles were those that underwent the strongest insertion of the drug. One important parameter, which determined the extension of such interaction, was the curvature of the vesicle bilayer. So, liposomes extruded through a 50 nm membrane filter suffered the highest relative size variation in comparison with empty liposomes. Doxorubicin also produced an increase in polydispersity of vesicle population; therefore its presence resulted in some fusion and/or aggregation processes. The stability of liposomes was dependent on lipid content, on the method of drug trapping and on the presence or absence of such drug. Encapsulation efficiency seemed to be inversely related to liposome stability. Maximal values, which never exceed 0.015 +/- 0.005 mumol of drug per mumol of lipid, were obtained when the drug was dried together with the lipids.

1,2-Dipalmitoylphosphatidylcholine↗

[Lipid metabolism and lipogenesis: application of stable isotopes].

Fat metabolism is regulated by several neuroendocrine and nutritional factors, which affect equilibrium between lipogenesis and lipolysis. Lipid utilization and fate in the organism can be assessed by in vivo and in vitro methods by measuring the rate of the different metabolic pathways (dynamic aspects), but also the net balance which may lead to fat accumulation or loss (static aspects). The quantitation of synthesis and breakdown reactions can be performed by using different tracers such as radioactive and stable isotopes. Fatty acid synthesis can be independently measured by the intravenous infusion of 13C acetate and application of the MIDA technique. In brief, this method uses probability analysis to measure the synthesis of biological polymers. It is based on the mathematical principle that the labeling pattern of a polymer synthesized from a stable-isotopically labeled precursor will conform to a predicted binomial or multinomial expansion. Thus, the isotopic enrichment of the precursor pool is calculated from measurements on the product alone. In the case of fatty acid synthesis, the proportions of excess (above natural background abundance) of single-labeled and double labeled (EM1 and EM2 species respectively) are a function of the probability (p) that the precursor subunits were isotopically labeled. Using this value of P for the isotopic enrichment of the acetylCoA pool, the theoretical 13C enrichment in the fatty acid if 100% were newly formed from this acetate pool is calculated. The actual isotopic enrichment is measured by gas chromatography-mass spectrometry (GCMS). This value divided by the theoretical maximum value equals the fraction of the fatty acid that is newly formed (f). The value for f represents dilution of de novo synthesized fatty acid by non-de novo sources. This method requires that newly synthesized (labeled) and preformed (unlabeled) mix in the liver and communicate with plasma VLDL over the period of the isotope infusion. It also assumes that the major de novo fatty acid is only a single fatty acid, with minor elongation and/or desaturation processes. Finally, the infused isotopic acetate should have no physiologically important effect. This methodology can be applied to assess lipogenesis in very different nutritional and physiopathological conditions such as diabetes, AIDS, obesity, etc.

Acetates↗

[Main drug interactions at a hospital emergency department. Analysis of 100 cases].

We prospectively reviewed clinical charts of 100 consecutive patients that were admitted during the first trimester 1991 to the Emergency Department of a general hospital in order to determine the more frequent prescribed drugs and their interactions using a computer program (Drug Interaction Program), emphasizing in those drugs used to treat peptic ulcers. Number of drugs prescribed to each patient was 4.20 +/- 1.39. Antacids (39%) and cimetidine (35%) occupied the third and fourth place. There were interactions in 79 patients and in 66 of them (84%) they were important. Antacid and cimetidine were similarly prescribed, but of 35 patients who received cimetidine only 3 (8.5%) had a primary indication for its use (Gastrointestinal bleeding). Significant clinical interactions of cimetidine with other medications are analyzed. Our results indicate that drug interactions are a permanent risk in our hospitals. We suggest to use a computer program on drug interactions or an updated chart of medications in the emergency rooms of our hospitals.

Adolescent↗

[Report about drug interactions in a hospital emergency department].

In 1991, we report drug interactions found through the review of 100 clinical charts of an Emergency Department. Two years later we evaluated again the medical indications done at the same Emergency. There were no differences related to sex, age and number of drug administrated by patient when compared with the former group. There was, however, a significant decrease in the percentage of interactions and those important ones. Also, in the average of interactions and those important ones by patient. Among more used drug, antacid occupied a a second place with 36% and Ranitidine the ninth place with 16%. Cimetidine disappeared among the first ten medications. In those cases where antacid or Ranitidine were indicated, there were interactions in 54% and 25%, respectively, but these interactions were not significant. The results of this new analysis point out a significant decrease of drug interactions, showing that continuing education allows indicate the most adequate therapy to each patient.

Adult↗