Search PubMed⌕ Search

Biomedical subjects

L E Martin

Publications and source records attributed to L E Martin.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effects of one year's treatment with ranitidine and of truncal vagotomy on gastric contents.

Fifteen patients with peptic ulcer underwent 24 hour studies of gastric contents: before and on completing six weeks' treatment with oral ranitidine 150 mg bd, twice on maintenance treatment for nine to 12 months and one month after stopping the drug. For comparison, 11 patients underwent identical 24 hour studies three to 38 months after truncal vagotomy for duodenal ulcer. During treatment with ranitidine median 24 hour intragastric pH, nitrate concentration, and counts of total and nitrate reducing bacteria increased significantly regardless of dietary nitrate content; there was no significant increase in the median day time concentration of N-nitroso compounds. Despite these changes, an acid tide at some point in each 24 hour study period prevented persistent bacterial colonisation of the stomach. There were no significant differences between the biochemical and microbiological changes recorded during one year of treatment with ranitidine, and the observations on patients after truncal vagotomy. One month after stopping one year's treatment with ranitidine all variables examined returned to pretreatment levels. Treatment with ranitidine or vagotomy was associated with significant positive correlations among pH, nitrate concentration and bacterial counts. Correlations between pH and N-nitroso compound concentration and between concentrations of nitrite and N-nitroso compounds were not significant.

Adult↗
PubMed1986

Late intraphagosomal hydrogen ion concentration favors the in vitro antimicrobial capacity of a 37-kilodalton cationic granule protein of human neutrophil granulocytes.

We described previously (W.M. Shafer, L.E. Martin, and J.K. Spitznagel, Infect. Immun. 45:29-35, 1984) the presence of a 37-kilodalton cationic antimicrobial protein (37K CAP) in extracts of granules prepared from human polymorphonuclear granulocytes (PMN). In this investigation, we prepared 37K CAP from PMN granule extracts by sequential ion-exchange and molecular-sieve chromatography and examined its antimicrobial activity against a number of gram-negative and gram-positive bacteria. At concentrations of 5 micrograms/ml or lower, 37K CAP exerted selective antimicrobial activity against gram-negative bacteria. These bacteria included Acinetobacter lwoffii, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Pseudomonas cepacia, Salmonella typhi, Salmonella typhimurium, and Shigella sonnei. However, at 5 micrograms of 37K CAP per ml, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens resisted this antimicrobial activity. The bactericidal activity of 37K CAP was greatest in acidic (pH 5.5) as opposed to alkaline (pH 7.5) media. The level of S. typhimurium resistance to 37K CAP correlated with the presence of O antigen in the lipopolysaccharide. In the absence of O antigen repeat units, resistance was proportional to the length of the core oligosaccharide. These results suggest that 37K CAP may contribute significantly to the ability of PMN to kill gram-negative bacteria by nonoxidative means, particularly as the maturing phagolysosome becomes acidified.

Anti-Bacterial Agents↗
PubMed1986

Antigonococcal activity of human neutrophil cathepsin G.

We have shown that lysosomal cathepsin G, prepared from acid extracts of granules derived from human polymorphonuclear granulocytes, exhibits potent in vitro antimicrobial activity against Neisseria gonorrhoeae. An isolated isozyme of cathepsin G was found to exhibit antigonococcal activity by a nonenzymatic mechanism in a time-dependent manner. Moreover, we observed that the antigonococcal activity of cathepsin G was relatively independent of pH and evident over a pH range resembling that invoked for maturing phagolysosomes. Using a number of isogenic strains, we determined that certain mutations known to alter cell envelope structure rendered gonococci more susceptible to cathepsin G. This suggests that the susceptibility of gonococci to cathepsin G, and possibly other antimicrobial proteins derived from PMN granules, is genetically determined and possibly related to the structure of the gonococcal cell envelope.

Antimicrobial Cationic Peptides↗
PubMed1985

Determination of salbutamol in human plasma and urine by high-performance thin-layer chromatography.

A rapid, accurate and sensitive method for the determination of salbutamol in plasma and urine is described. Salbutamol is extracted using solid-phase techniques and converted to an indoaniline dye by reaction with dimethyl-p-phenylenediamine. The indoaniline is separated using high-performance thin-layer chromatography and quantified by absorption microdensitometry at 650 nm. The method is sensitive down to 20 ng/ml in urine and to 1 ng/ml in plasma and provides data in good agreement with that obtained by gas chromatography--mass spectrometry. The method can be used for analysis of pharmacokinetic studies.

Albuterol↗
PubMed1985

Qualitative and quantitative analysis of ranitidine and its metabolites by high-performance liquid chromatography-mass spectrometry.

Reversed-phase high-performance liquid chromatography systems for the separation of ranitidine and its metabolites ranitidine-N-oxide, ranitidine-S-oxide, and desmethylranitidine have been developed for use in high-performance liquid chromatography-mass spectrometry. A direct liquid introduction-high-performance liquid chromatography-mass spectrometry system to analyse qualitatively and quantitatively solutions containing ranitidine and its metabolites by reversed-phase chromatography is described. A sample of urine collected from a subject given an oral dose of 75 mg of ranitidine and 75 mg of tris-deuterated ranitidine was analysed by this system. Ranitidine and its metabolites were identified by the ion doublets in the mass spectra which were 3 a.m.u. apart.

Biotransformation↗
PubMed1984

Ranitidine disposition and systemic availability in hepatic cirrhosis.

Single-dose ranitidine kinetics were studied in 10 patients with cirrhosis as proved by liver biopsy. All were clinically stable. After an overnight fast, ranitidine was given in a randomized crossover order as a bolus intravenous injection (50 mg) or was taken by mouth (150 mg). Terminal t1/2 was 2.7 +/- 0.4 hr after oral dosing and 2.9 +/- 0.4 hr after intravenous injection. Total plasma clearance was 470 +/- 170 ml/min and the steady-state volume of distribution was 1.2 +/- 0.2 l/kg. There was considerable intersubject variability in the ranitidine serum concentration-time profile after oral dosing. Systemic availability as assessed by AUC analysis was 58% +/- 11%. Not all of the dose could be recovered in the urine as unchanged ranitidine and its known metabolites after intravenous injection. At 0.5 microgram/ml the serum protein binding of ranitidine was 4.6% +/- 1.3%. It is concluded that disposition of ranitidine in these 10 stable subjects with cirrhosis was not significantly altered. The minor changes observed in some were as likely to be the result of secondary perturbations in physiologic status as to effects of cirrhosis on drug metabolism.

Administration, Oral↗
PubMed1984

Automated extraction of drugs from biological fluids.

An automated continuous flow liquid-liquid extraction procedure is described for the separation of the H2-antagonist loxtidine from plasma samples containing two metabolites which interfere in the radioimmunoassay of the drug. The extraction of the bronchodilator salbutamol was studied using the DuPont Prep I automated liquid solid extraction apparatus, with a 12 cartridge capacity, and a vacuum extraction box designed in this laboratory to hold 30 Sep-pak C-18 (Waters Associates) cartridges. Twenty-four plasma samples per hour can be automatically processed with the Prep I. Although the vacuum box is not fully automated 45 plasma samples per hour can be processed. The Prep I can only be used with DuPont XAD, strong cation and anion exchange cartridges. Cartridges containing alumina, silica, florisil, cation and anion exchange resins and reverse phase packings can all be used with the vacuum extraction box. The latter costs only a fraction of the Prep I and therefore each analyst can have his own unit.

Acetates↗
PubMed1984

Cationic antimicrobial proteins isolated from human neutrophil granulocytes in the presence of diisopropyl fluorophosphate.

Acid (0.2 M sodium acetate, pH 4.0) extracts of granules recovered from disrupted human polymorphonuclear granulocytes (PMNs) exhibited in vitro antimicrobial activity against Salmonella typhimurium. To minimize proteolytic destruction or modification of antimicrobial proteins derived from these granules, we pretreated the PMNs with the serine protease inhibitor diisopropyl fluorophosphate. Fractionation of such extracts by carboxymethyl Sephadex and Sephadex G-75 chromatography resulted in the recovery of at least two antimicrobial, cationic proteins. These proteins differed substantially in antimicrobial activity, amino acid composition, and molecular weight (Mr, 37,000 and 57,000). As we have shown before (Shafer et al., Infect. Immun. 43:834-858), with unfractionated proteins, these two proteins exhibited diminished activity against a polymyxin B-resistant (PBr) mutant of S. typhimurium compared with their activity against the isogenic parental polymyxin B-sensitive (PBs) strain. Expression of the relevant mutation (prmA) in the PBr mutant decreases the electronegativity of lipid A, owing to increased 4-amino-4-deoxy-L-arabinosylation at the 4' phosphate residue (Vaara et al., FEBS Lett. 129:145-149). The data suggest that at least two different cationic proteins account for the antimicrobial capacity of extracts from human PMN granules. Moreover, the availability of anionic charges in the outer membrane of S. typhimurium due to free lipid A phosphates apparently dictates phenotypic levels of resistance to both of the cationic proteins extracted from human PMN granules.

Amino Acids↗
PubMed1983

Differential distribution of distinct forms of myeloperoxidase in different azurophilic granule subpopulations from human neutrophils.

Myeloperoxidase (MPO), a characteristic enzyme of human polymorphonuclear neutrophils (PMN), is localized in specialized lysosomal or azurophilic granules, and can be resolved into three distinct forms (I, II, III) by ion-exchange chromatography. Granules were isolated from single donor PMN and fractionated with centrifugation into two different azurophilic subpopulations (high and low density) by banding in a continuous sucrose density gradient. Ion-exchange chromatography of granule extracts indicated that the lower density granules contained mainly MPO forms II and III while the higher density granules appeared to contain all three forms, but in much reduced amounts. Sodium dodecylsulfate polyacrylamide gel electrophoresis showed that, the mobilities of the heavy subunits of MPO appeared to be inversely related to the density of the granule population from which they were extracted. These observations suggest that the different forms of MPO may have distinct functional roles and/or are a possible reflection of maturational differences among the granule subpopulations.

Adult↗
PubMed1982

Use of high-performance liquid chromatography-mass spectrometry for the study of the metabolism of ranitidine in man.

High-performance liquid chromatography has been used for the qualitative analysis of metabolites and the quantitative analysis of ranitidine in the urine from subjects given oral and intravenous doses of ranitidine. Ranitidine, ranitidine-N-oxide, ranitidine-S-oxide and desmethylranitidine were identified in extracts of the urine obtained by the XAD-methanol procedure. A selected-ion monitoring technique, using [2H3]ranitidine as the internal standard, was used to determine ranitidine. A normal-phase system consisting of methanol-propan-2-ol-5 M ammonium acetate (50:50:1) was used, and because of this the volume of urine which could be injected on-column without deterioration of the chromatography was limited to 10 microliters. This limited the sensitivity of the method to 1.0 microgram of ranitidine per millilitre of urine.

Administration, Oral↗
PubMed1981

Determination of ranitidine and its metabolites in human urine by reversed-phase ion-pair high-performance liquid chromatography.

A method using ion-pair high-performance liquid chromatography is presented for determining ranitidine, ranitidine N-oxide, ranitidine S-oxide and desmethyl ranitidine in the urine from four volunteers, given on separate occasions an intravenous and oral dose of 100 mg ranitidine. This method has been used to study the metabolism and pharmacokinetics of ranitidine by man. It was found that the elimination half-life of ranitidine ranged from 110-246 min. The mean renal clearance of ranitidine in these four volunteers was 512 ml/min.

Chromatography, High Pressure Liquid↗
PubMed1981

The use of on-line high-performance liquid chromatography-mass spectrometry for the identification of ranitidine and its metabolites in urine.

1. Reverse and normal phase h.p.l.c. systems have been developed for separation ranitidine and three metabolites, desmethylranitidine, ranitidine-S-oxide and ranitidine-N-oxide. 2. These h.p.l.c. systems have been evaluated for characterization of ranitidine and metabolites using an h.p.l.c. coupled to a mass spectrometer with a moving belt interface. 3. Ranitidine and its metabolites were thermally degraded under the conditions required to evaporate the reverse phase eluent that contained 40% aq. 0.05 M ammonium acetate. 4. The normal phase eluent was evaporated in the interface at a lower temp. and satisfactory mass spectra were obtained from 1 microgram of ranitidine and each metabolite injected on to the h.p.l.c. column. 5. Normal phase h.p.l.c.-mass spectrometry has been used to identify ranitidine and three of its metabolites in rabbit and human urine obtained after oral administration of ranitidine.

Animals↗
PubMed1981

Applications of high-voltage paper electrophoresis for the characterization of drug metabolites.

1. The application of high-voltage paper electrophoresis (h.v.p.e.) to the identification of drug metabolites in urine and bile has been investigated. 2. The major urinary metabolite of [3H]salbutamol in man had an electrophoretic mobility indicative of a sulphate ester. 3. A metabolite of [14C]ranitidine present in rat bile was shown to contain an ionized group with a pKa corresponding to a carboxylic acid. 4. The electrophoretic mobility-pH profile of a metabolite of radiolabelled N"-cyano-N-[2-[5-(dimethylaminomethyl)-2-furanylmethylthio]ethyl]-N-methylguanidine (14C-AH 18801) excreted in dog urine suggested that oxidation of the tertiary amine group of the compound had occurred. 5. H.v.p.e. provided valuable information on the structure of both phases I and phase II metabolites at a stage when the material was insufficiently pure for identification by other techniques.

Albuterol↗