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Biomedical subjects

F G Collins

Publications and source records attributed to F G Collins.

At least 19 recordsLinked to original sources
PubMed1983

Effect of palmitate or lipid emulsion on nitrogen metabolism during hyperthermic perfusion of rat liver.

Livers of fasted rats were perfused for one hour at 37 degrees or 42 degrees. Endogenous hepatic ureogenesis was increased twofold at 42 degrees and the release of endogenous ninhydrin-reactive amino nitrogen was not changed by hyperthermia. Exogenous amino acids at 10 times the normal plasma concentration stimulated hepatic ureogenesis sevenfold at 37 degrees and over twofold at 42 degrees. Exogenous amino acids stimulated hepatic amino acid uptake at 37 degrees. Uptake of the exogenous amino acids at 42 degrees was about 40% of that observed at 37 degrees. However, exogenous amino acid uptake in the presence of 1 mM palmitate was not altered at 42 degrees. Ureogenesis in the presence of supplemental amino acids and palmitate was significantly reduced at 37 degrees and moderately reduced at 42 degrees, suggesting decreased amino acid catabolism. Ten percent Intralipid, a clinically available lipid emulsion primarily consisting of triglycerides in a physical form similar to chylomicrons at a perfusate concentration of 1 ml/100 ml, did not markedly alter hepatic ureogenesis or amino acid dynamics at 37 degrees or 42 degrees in the presence or absence of amino acids. It is concluded that palmitate blocks the adverse effect of hyperthermia on hepatic amino acid uptake.

Amino Acids↗
PubMed1983

Altered hepatic functions and microsomal activity in perfused rat liver by hyperthermia combined with alkylating agents.

Livers of fasted rats were perfused for one hour in the presence of cyclophosphamide (CP), mechlorethamine (HN2), or melphalan (L-PAM) at 37 degrees and 42 degrees C. Hepatic biosynthetic function was assessed by determining gluconeogenesis from lactate, ureogenesis from NH4Cl, and O2 consumption. Antipyrine (AP) metabolism was employed to assess microsomal mixed function oxygenase enzyme activity at elevated temperatures. The t 1/2 of AP increased 2.8-fold in a temperature-dependent manner between 37 degrees and 43 degrees C. In the presence of biosynthetic substrates, the t 1/2 of AP increased 1.8-fold between 37 degrees and 43 degrees C. CP activation was suppressed (27% at 125 micrograms/ml, 49% at 500 micrograms/ml) at 42 degrees C. The presence of biosynthetic substrates significantly attenuated the suppression of CP activation by hyperthermia. A dose-dependent decrease in biosynthetic function occurred in the presence of CP at 37 degrees and 42 degrees C suggesting hepatotoxicity and/or competition for biochemical intermediates. The t 1/2 of HN2 at 50 micrograms/ml was slightly decreased by 11% at 42 degrees C (19.6 min vs. 17.4 min). The half-lives of 10 micrograms/ml HN2 and 5 micrograms/ml L-PAM were not altered at 42 degrees C (17.1 min vs. 16.4 min and 44.6 min vs. 44.1 min, respectively). The adverse effects of HN2 and L-PAM on hepatic biosynthetic functions were minimal suggesting that alkylating agents not requiring metabolism by the liver would be most useful for hepatic thermochemotherapy. The data indicate that hyperthermia depresses hepatic microsomal drug metabolizing enzyme function and alters the perfusate pharmacokinetics of alkylating agents. Moreover, manipulation of the hepatic biochemical environment may modify the adverse effects of hyperthermia on microsomal activity.

Alkylating Agents↗
PubMed1980

Effect of palmitate on hepatic biosynthetic functions at hyperthermic temperatures.

Livers of fasted rats were perfused for 80 min at 37 degrees-43 degrees C, supplemented with lactate, NH4Cl, and ornithine in the presence or absence of palmitate. Hepatic functional integrity was maintained from 37 degrees to 42 degrees C as assessed by gluconeogenesis, ureogenesis, and O2 consumption. Between 42 degrees and 43 degrees C a sharp decline in biosynthetic function occurred. The sharp decline in biosynthetic function occurred. The ratio of lactate disappearance to glucose formation increased progressively with increasing temperature when compared with the ratio obtained at 37 degrees C. Exogenous palmitate significantly decreased the ratio of lactate disappearance to glucose formation at 43 degrees C. Furthermore, palmitate attenuated the detrimental effects of hyperthermia on gluconeogenesis, ureogenesis, and O2 consumption found in the absence of palmitate. The 3-hydroxybutyrate/acetoacetate ratio progressively decreased as the liver temperature was increased in the presence or absence of palmitate, indicating a more oxidized mitochondrial redox state. Palmitate significantly increased the 3-hydroxybutyrate/acetoacetate ratio in the presence of gluconeogenic and ureogenic substrates at all temperatures examined. The data suggest that provision of fatty acid has a protective effect in thermally stressed liver. Moreover, palmitate may substitute for the increased energy requirements of the hyperthermic state.

Ammonium Chloride↗
PubMed1980

Modification of the 4-(p-nitrobenzyl) pyridine assay for measurement of melphalan and mechlorethamine in plasma.

A sensitive, reproducible spectrophotometric assay for mechlorethamine and melphalan was developed through modifications in the use of 4-(p-nitrobenzyl) pyridine as the chromogenic reagent. Key factors that led to enhanced color development and consistency of results were: (1) protein precipitation with 4 degrees C perchloric acid; (2) control of the pH of the reaction with acetate buffer; (3) precise timing of color development in alkali; and (4) sample reading at the appropriate wavelength. The modifications allowed measurement of mechlorethamine and melphalan levels in perfusate samples obtained from isolated rat liver perfusions. Half-lives calculated from perfusate decay curves after addition of mechlorethamine at 50 microgram/ml and 10 microgram/ml were 15.9 min and 15.0 min respectively. The perfusate half-life after addition of melphalan at 5 microgram/ml was 44.2 min. Plasma levels of mechlorethamine were not detectable by this assay after intrapleural administration of 15 mg to one patient but were detectable after intravenous administration of 20 mg to a second patient.

Animals↗
PubMed1980

Inhibition of hepatic macromolecular processes in normal and regenerating liver by hyperthermia.

Incorporation of radioactive precursors into DNA, RNA and protein fractions isolated from perfused normal and 22 h regenerating rat livers were measured at temperatures between 37 and 43 degrees C. Compared to the 37 degrees C control levels of precursor incorporation, significant inhibition of precursor incorporation into nucleic acids and protein from slowly and rapidly proliferating livers occurred from 41 degrees to 43 degrees C. The time course of release of newly labeled protein into the perfusate was determined during 1.5 h of perfusion at supranormal temperatures in normal and regenerating liver. Release of radioactive labeled protein into the perfusate was significantly suppressed between 41 degrees and 43 degrees C in a time- and temperature-dependent manner. In both experimental models, the sharpest drop in the rates of precursor incorporation was found between 42 degrees C and 43 degrees C. It is concluded that hyperthermic perfusion (41 degrees to 43 degrees C) significantly suppresses precursor incorporation into hepatic DNA, RNA and protein in normal and regenerating liver. Moreover, the data indicate that macromolecular processes in regenerating liver are no more sensitive to the stress of hyperthermia than those found in normal liver.

Animals↗