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Biomedical subjects

G O Evans

Publications and source records attributed to G O Evans.

At least 19 recordsLinked to original sources
PubMed1997

Structure-activity relationship for two lipoxygenase inhibitors and their potential for inducing nephrotic syndrome.

In a study of structure-activity relationship with drug-induced nephropathy two lipoxygenase inhibitors, the N-hydroxyurea derivative 70C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxyurea) and the N-hydroxamic acid analogue 360C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxamic acid), were administered to rats. 70C and 360C were dosed to female Wistar rats at 100 mg/kg po daily for 7 days. Another group of rats was given a single intravenous bolus dose of puromycin aminonucleoside (PAN) at 100 mg/kg. Urine samples were collected from all groups during the study and plasma samples were collected after 7 days. Kidneys were excised and fixed for examination by electron microscopy. 70C- and PAN-treated groups both showed early changes in the glomeruli, in which the visceral cells appeared enlarged and showed varying degrees of foot process loss. This foot process loss was associated with decreases in total plasma protein and albumin and increases in the plasma cholesterol, triglycerides, creatinine, and urea were recorded. Marked proteinuria was observed in both the 70C and PAN groups. The foot process loss together with increased proteinuria, hypoalbuminemia, hypercholesterolemia, and lipemia are all characteristic of the human condition, Minimal Change Nephrotic Syndrome. All the biochemical and morphological investigations showed that 360C-treated rats were similar to the control group, suggesting that the hydroxyurea moiety of 70C is responsible, either directly or indirectly, for the induction of the nephrotic syndrome seen in rats.

Administration, Oral↗
PubMed1995

Nephrotic syndrome associated with N-hydroxyureas, inhibitors of 5-lipoxygenase.

The N-hydroxyurea derivatives 70C ((E)-N-[3-[3- (4-fluorophenoxy)phenyl[-1-(R,S)-methylprop-2-enyl]-N-hydroxyurea) and its (R) 225C and (S) 404C enantiomers, which were being developed as 5-lipoxygenase inhibitors for the treatment of certain allergic and inflammatory conditions, were found to cause severe glomerulonephropathy in the rat. The lesion appeared to be of greater severity in female rats compared with male rats. In addition, 70C and 225C treated animals appeared more severely affected than 404C treated animals. Detailed examination of the lesion in animals dosed with 225C showed that there was a clear relationship between the onset of the lesion and the dose given, i.e. the higher the dose the sooner the lesion developed. The earliest changes detected in the kidney by transmission electron microscopy were noted in the glomeruli, in which the visceral cells appeared enlarged and showed varying degrees of foot process loss. In the more advanced lesion, the degree of foot process loss became more obvious and changes in the kidney tubules were seen by light microscopy. The morphological changes were mirrored by a dose-related increase in water consumption, an increased kidney to body weight ratio and gastrointestinal oedema, suggesting impaired renal function. Shortly after the onset of foot process loss, decreases in the total plasma protein and albumin and increases in the plasma cholesterol, triglycerides, urea and creatinine were recorded. These changes, particularly the foot-process loss, together with increased proteinuria, hypoalbuminaemia, hypercholesterolaemia and lipaemia, are all characteristic of "minimal change nephrotic syndrome". Because of the serious nature of the kidney lesion caused by these N-hydroxyureas in the rat, it was considered that it precluded their development as therapeutic agents for use in man.

Administration, Oral↗
PubMed1994

Reticulocyte counts in canine and rat blood made by flow cytometry.

Absolute and percentage reticulocyte counts for sequestrated blood samples from healthy Wistar rats (n = 132) and beagles (n = 64) were made by thiazole orange and flow cytometry. The flow cytometric method showed good agreement with a manual counting method for both species, and the precision data for both of these counting methods were similar.

Animals↗
PubMed1994

Cellular and soluble CD4 measurements in cynomolgus monkeys.

Anti-human CD4 monoclonal antibodies have been successfully used to label T-lymphocytes in Cynomolgus monkeys by two different methods. A magnetisable bead separation was used prior to immunogold labelling of lymphocytes in one of the methods. In addition, an assay for soluble CD4 has been applied to the sera of these monkeys.

Animals↗
PubMed1991

Biochemical assessment of cardiac function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association.

Species differences in metabolism, tissue localization, specificity and sensitivity for cardiac damage influence the choice of biochemical investigation used in the assessment of cardiotoxicity. The tests currently used in toxicological studies are broadly categorized herein as enzymes and other proteins, lipids and electrolytes; some limitations of these tests are also discussed.

Alanine Transaminase↗
PubMed1990

Effect of heat treatment on plasma creatinine measurement.

The effects of heat treatment on plasma creatinine values obtained by enzymatic and kinetic alkaline picrate methods were compared. No marked differences were found for plasma samples following heat treatment at 56 degrees C for 0.5 or 1 h, compared to nonheat treated samples.

Creatinine↗
PubMed1989

Species relationships for plasma angiotensin converting enzyme activity using a furanacryloyl tripeptide substrate.

Angiotensin converting enzyme (ACE; EC 3.4.15.1) activities were compared in plasma samples obtained from three species using a furanacryloyl tripeptide substrate. The enzyme activity observed in Wistar rat plasma was higher than the activities observed in the other two species. Using this substrate, human and canine plasma enzyme activities were similar-unlike published data where hippuryl-histidyl-leucine was used as substrate.

Animals↗
PubMed1988

A comparison of two dye-binding methods for the determination of dog, rat and human plasma albumins.

Plasma albumin was determined in human, rat and dog samples by bromocresol green and bromocresol purple dye-binding methods. The bromocresol purple method produced significantly lower values in dog and rat plasma samples, although the use of homologous standards reduced the differences between the two methods. These observations reflect differing affinities of the two dyes for albumins of different species.

Animals↗
PubMed1988

Hypomagnesaemia, hypoalbuminaemia and plasma lipid changes in rats following the oral administration of ciclosporin.

1. The effects of orally administered ciclosporin (40, 50 or 80 mg/kg body wt) on plasma magnesium, albumin, total cholesterol and triglycerides have been studied in male Wistar rats. 2. Plasma magnesium and albumin were significantly lower in rats dosed with ciclosporin (40, 50 or 80 mg/kg) after 14 days. 3. Variable changes of plasma cholesterol and triglycerides were observed. Some implications of the inter-relationships of magnesium, albumin and plasma lipids in ciclosporin treatment are discussed.

Administration, Oral↗