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Biomedical subjects

P Gilbert

Publications and source records attributed to P Gilbert.

249 records · Page 14Linked to original sources

Effect of phenoxyethanol on the permeability of Escherichia coli NCTC 5933 to inorganic ions.

Concentrations of phenoxyethanol which retarded the growth rate of Escherichia coli NCTC 5933 in nutrient broth, stimulated the rates of respiration and total oxygen uptake of cell suspensions with glucose as carbon source, and were able to dissipate artificially induced membrane proton gradients. In cells with repressed oxidative phosphorylating activity, no stimulation of respiration was observed. These actions were characteristic of uncouples of oxidative phosphorylation. Similar concentrations of the drug caused additional increased permeability of the cytoplasmic membrane to K+ but not to Li+, Na+, Ca++, Mg++, NO-3, Cl-, So--4, or PO---4. Drug induced permeability of the membrane to protons and potassium ions were not found to be directly coupled.

Cell Membrane Permeability↗

Inhibition of some respiration and dehydrogenase enzyme systems in Escherichia coli NCTC 5933 by phenoxyethanol.

Low concentrations (less than 0.2% w/v) of phenoxyethanol stimulated both the rate of respiration and total oxygen uptakes of Escherichia coli NCTC 5933 suspensions with glucose and other substrates, whilst higher concentrations (0.2--0.6% w/v) although still below those showing significant bactericidal activity, produced progressive levels of inhibition. The degree of respiratory inhibition varied with different substrates in the order malate less than succinate less than pyruvate less than or equal to glucose less than lactate, and suggested appreciable inhibition at a point after malate in the tricarboxylic acid cycle. This suggestion was supported by the use of tetrazolium salts as alternative electron acceptors, and by cytochrome difference spectra, which together implicated malate dehydrogenase as the most likely site of action. Isolated dehydrogenase enzymes of the tricarboxylic acid cycle in cell-free preparations were unaffected by high concentrations of phenoxyethanol (0.8% w/v) with the exception of malate dehydrogenase which was inhibited in extracts to extents similar to those of malate oxidation by intact bacteria. Lineweaver-Burke plots for malate dehydrogenase activity in the presence of phenoxyethanol suggested a competitive inhibition of the oxaloacetic acid-limited reaction and a non-competitive inhibition of the NADH-limited reaction. Accordingly, Ki values were found to be low when the rate of reaction was limited by oxaloacetic acid concentration yet relatively high when NADH was rate limiting.

Carbohydrate Metabolism↗

The lethal action of 2-phenoxyethanol and its analogues upon Escherichia coli NCTC 5933.

Bactericidal activity has been assessed for a number of glycolmonophenyl ethers towards Escherichia coli NCTC 5933, and the action of one analogue, 2-phenoxyethanol, has been studied in greater detail. For this compound the onset of bactericidal activity towards Escherichia coli occurred at concentrations which also induced considerable increases in drug uptake, marked leakage of cytoplasmic constituents, the cellular penetration of N-tolyl-alpha-napthylamine-8-sulphonic acid, and morphological changes consistent with gross membrane damage. However, temperature coefficients of rates of cellular leakage of low molecular weight cytoplasmic constituents, and rates of kill, were markedly different and suggested that the two phenomena were not integrally related, but that each was a consequence of some other action of the drug. Drug levels considerably below those possessing lethal activity, however, promoted the ready efflux of potassium ions from cells and caused disorganisation of the outer lipopolysaccharide-rich regions of the cell envelope.

Anti-Infective Agents, Local↗

Alkaline inorganic pyrophosphatase activity of mammalian-cell alkaline phosphatase.

Alkaline phosphatase prepared from mammalian cell cultures was found to have alkaline inorganic pyrophosphatase activity. Both of these activities appear to be associated with a single protein, as demonstrated by: (1) concomitant purification of alkaline phosphatase and alkaline inorganic pyrophosphatase; (2) proportional precipitation of alkaline phosphatase and inorganic pyrophosphatase activities by titrating constant amounts of an enzyme preparation with increasing concentration of antibody; (3) immune electrophoresis, which showed that precipitin bands that have alkaline phosphatase activity also have pyrophosphatase activity; (4) inhibition of pyrophosphatase activity by cysteine, an inhibitor of alkaline phosphatase activity; (5) similar subcellular localization of the two enzyme activities as demonstrated by histochemical methods; (6) hormonal and substrate induction of alkaline phosphatase activity in mammalian cell cultures, which produced a nearly parallel rise in inorganic pyrophosphatase activity.

Alkaline Phosphatase↗

Consanguinity and genetic morbidity in a British primary care setting: a pilot study with trained linkworkers.

OBJECTIVES: To assess the feasibility of detecting consanguineous relationships and significant genetic morbidity through screening pedigrees administered by a primary care trained linkworker. SUBJECTS AND METHODS: A case-controlled crossover study with pedigree recording by both genetic nurse specialists and a primary care worker. From 1012 records of British Pakistani patients registered with an inner city practice, 14 women, identified as having increased genetic risk, were recruited (Group 1). A further 14 age- and parity-matched women, with no indication of genetic morbidity in their General Practice records (Group 2), were also recruited. RESULTS: Valuable genetic information, not recorded in General Practice records, were ascertained through the screening pedigrees, in four members of Group 1 (29%) and six members of Group 2 (43%). There was poor agreement between the coefficients of inbreeding recorded from pedigrees prepared by the primary care worker and genetic nurse specialists (Kappa = 0.157; 95% CI 0.028-0.286). CONCLUSION: Pedigrees can be utilized as a General Practice screening tool to detect relevant genetic morbidity, not ascertained in General Practice records. The process is enhanced when a primary care worker, from the same culture as the volunteers, collects information using the patients' mother tongue.

Adult↗

Improved Coumadin therapy using a continuous quality improvement process.

Through the Continuous Quality Improvement process, we determined that a significant number of patients were receiving too much Coumadin and having potentially serious side effects. The number of patients studied is limited, and there are only two time intervals reported postintervention. This makes it difficult to draw a definite relationship between the observed rates of Coumadin overdosing and the selected intervention. By educating the physicians on proper Coumadin dosing, we were able to reduce the number of patients experiencing hemorrhage or other complications. Our follow-up data review 1 year later showed that the gain had not been maintained as well as we would have hoped. This demonstrates that active review by Pharmacy and Laboratory on a regular basis and additional physician education would be beneficial. Through this process we gained valuable experience using the FOCUS PDCA method of continuous quality improvement.

Anticoagulants↗