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Biomedical subjects

F A Fitzpatrick

Publications and source records attributed to F A Fitzpatrick.

At least 127 records · Page 7Linked to original sources
PubMed1978

Gas chromatography of the prostaglandins.

Gas chromatography is the most widely used chromatographic technique. Its strength lies in the fact that three distinct operations--separation, detection, and quantitation--can be performed on all the components of mixtures within a reasonable time, and that qualitative information about the compound identity is associated with its retention time. Despite a prominent position in other areas of biochemistry, its success in the prostaglandin field has been rather limited. The technique itself is not at fault since samples with reasonable levels of prostaglandins have been analyzed without overwhelming difficulty. However, many samples demand a sensitivity exceeding the limits of either electron capture or flame ionization detectors. Shifts in research problems have contributed to its decline, but it is fair to add that these shifts were associated with the appearance of more sensitive and accurate analytical methods. Let us not despair for gas chromatography because its competitors, radioimmunoassay and gas chromatography-mass spectroscopy, also have deficiencies. In this chapter we have described several traditional gas chromatographic methods for prostaglandin analysis and outlined their strengths and weaknesses. Hopefully, this will prevent the misapplication of a useful analytical tool and also serve as an incentive to provoke contributions to this somewhat neglected technology. In conclusion, it cannot be stressed enough that all instrumental methods are at the mercy of chemistry. Chemistry can be exploited to enhance the value of a technique, or it can be disregarded to discredit the technique. The rise of sophisticated instruments has falsely diminished the value of chemistry in analytical methods development. It is imperative that we remind ourselves of its place and use it properly.

Animals↗
PubMed1977

Electron capture gas chromatographic detection of thromboxane B2.

An electron capture gas chromatographic method is described for the detection of thromboxane B2. Thromboxane B2 is esterified with diazomethane, followed by treatment with pentafluorobenzylhydroxylamine hydrochloride and silylation with BSA. In pyridine, the free aldehyde form of the acetal ring is favored allowing rapid formation of a novel thromboxane B2 pentafluorobenzyloxime. The method has been applied to detect thromboxane B2 formation during aggregation of washed platelets. It must be emphasized that by ordinary analytical standards, the derivatization reproducibility from 50-375 nanograms is poor (+/- 11% - +/- 42%); however, the improved selectivity of the method and its ability to detect nanogram levels of thromboxane B2 make it a useful complement to commonly employed bioassay techniques.

Arachidonic Acids↗
PubMed1977

Platelet rich plasma transforms exogenous prostaglandin endoperoxide H2 into thromboxane A2.

Platelet rich plasma transforms exogenous prostaglandin endoperoxide H2 into thromboxane A2 immediately prior to the initiation of irreversible aggregation. Selective thromboxane synthetase inhibitors block thromboxane A2 formation and aggregation. Thromboxane A2 formation appears to be essential during arachidonate mediated aggregation. The results presented reconcile the previously accepted paradoxical behavior of thromboxane synthetase in platelet rich plasma toward the prostaglandin endoperoxide H2 substrate.

Arachidonic Acids↗
PubMed1977

Inhibition of human platelet thromboxane synthetase by 9,11-azoprosta-5,13-dienoic acid.

The synthetic prostaglandin analog 9,11-azoprosta-5,13-dienoic acid (azo analog I) has been found to be a potent inhibitor of human platelet thromboxane synthetase by three independent analytical methods: electron-capture gas chromatography, radioisotopic thin-layer chromatography, and radioimmunoassay. In the presence of azo analog I, human platelet aggregation induced by either the prostaglandin endoperoxide PGH2 or arachidonic acid was antagonized. The addition of azo analog I shifted the transformation of endoperoxides away from thromboxane synthesis and toward prostaglandin E2 synthesis. The specificity of azo analog I is demonstrated by its selective inhibition of the second wave of either ADP- or epinephrine-induced platelet aggregation. These data indicate that PGH2 must be converted to thromboxane A2 in order to induce human platelet aggregation.

Arachidonic Acids↗
PubMed1976

High-performance liquid chromatographic analysis of prostaglandins formed during in vitro incubations with prostaglandin 15-dehydrogenase.

Dinoprost, dinoprostone, and prostaglandin E1 were each separated from their major 15-keto metabolites by high-performance liquid chromatography on a microparticulate, bonded, reversed-phase column after conversion to their p-bromophenacyl esters. Detection and simultaneous quantitation of prostaglandins in 1.0 ml of a 5-muM solution is possible. The method was applied to monitor prostaglandins formed during in vitro incubations with prostaglandin 15-dehydrogenase from monkey lungs. The advantages of this technique for assessing enzyme purity and activity are discussed.

Alcohol Oxidoreductases↗
PubMed1976

In vivo suppression of prostaglandin biosynthesis by non-steroidal anti-inflammatory agents.

In vivo effects of orally administered inhibitors on prostaglandin and F levels were determined in seven organs of the rat. Ibuprofen showed suppression in most tissues three hours after dosing with a return to control values by twenty-four hours. Flurbiprofen and indomethacin showed potent suppression at both three and twenty-four hours after dosing. 3-Acetonitrile, 4,5-bis(p-methoxyphenyl)-2-phenyl-pyrrole showed moderate suppression only in the stomach and duodenum at three hours after dosing with a return to control values by twenty-four hours. Acetaminophen incorporated as a control showed statistically significant suppression only in the liver after twenty-four hours.

Acetaminophen↗
PubMedDate not supplied

Synthesis and structure of the platelet aggregation factor thromboxane A2.

In 1975, Hamberg et al. reported evidence for the existence of an unstable platelet-aggregating factor which they named thromboxane A2 (TXA2) and for which they proposed a novel bicyclic oxetane structure (1, below) based on the short half-life of the factor (t1/2 (37 degrees C) = 32 s at pH 7.4) and the isolation of degradation products related to thromboxane (TXB2) (2, below). As natural TXA2 has not yet been isolated and characterized as a pure compound, we have synthesized the proposed structure (1) from TXB2 and compared its biological properties with those of authentic, biologically generated material. Here we present evidence that synthetic material having structure (1) is indistinguishable from platelet-derived TXA2 in various biological assays and that the proposed structure (1) for TXA2 is correct.

Blood Platelets↗