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Biomedical subjects

J A Turton

Publications and source records attributed to J A Turton.

At least 37 records · Page 2Linked to original sources
PubMed1993

Reduction of liver taurine in rats by beta-alanine treatment increases carbon tetrachloride toxicity.

Treatment of rats with beta-alanine increases the urinary taurine levels and markedly reduces the concentration of taurine in the liver. Dosing with carbon tetrachloride (CCl4) during treatment with beta-alanine results in a marked decrease in urinary taurine concomitant with a decrease in food intake. Treatment of animals with beta-alanine increases the hepatotoxicity of single doses of CCl4 as determined histologically and by measurement of serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. Urinary creatine is also raised significantly after the administration of CCl4 in beta-alanine-treated animals. However, the accumulation of triglycerides (TRIG) in the liver caused by dosing with CCl4 was not influenced by beta-alanine treatment. The data suggest that liver taurine levels may be an important factor in determining the degree of CCl4-induced cellular necrosis but not hepatic triglyceride accumulation.

Alanine Transaminase↗
PubMed1993

Effect of various non-hepatotoxic compounds on urinary and liver taurine levels in rats.

Administration of compounds which alter protein synthesis or sulphur amino acid metabolism in rats results in changes in the excretion of urinary taurine. Treatment with diethylmaleate (DEM) or phorone, which will deplete glutathione (GSH), reduces taurine excretion, whereas treatment with buthionine sulphoximine (BSO), which will inhibit glutathione synthesis, increases taurine excretion. Treatment with cycloheximide, an inhibitor of protein synthesis, increases taurine excretion, whereas pretreatment with phenobarbital, which will increase protein synthesis, decreases taurine excretion. Administration of agents which damage organs other than the liver such as the kidney, heart and testes, does not increase urinary taurine.

Animals↗
PubMed1993

Investigations into the effects of various hepatotoxic compounds on urinary and liver taurine levels in rats.

The effect of various hepatotoxicants on urinary taurine and urinary creatine has been studied in the rat. Several hepatotoxic agents, carbon tetrachloride, thioacetamide, galactosamine and allyl alcohol which all caused hepatic necrosis (sometimes accompanied by steatosis), resulted in a rise in urinary taurine and in some cases creatine, when administered to rats. Ethionine and hydrazine also raised urinary taurine but caused only steatosis and did not raise urinary creatine. Therefore urinary taurine and possibly creatine may be useful markers of liver injury and dysfunction. Liver taurine levels were also affected by some of the hepatotoxicants but in those cases where there was a rise in urinary taurine this could not be accounted for by the loss in liver taurine. It is suggested that the increase in urinary taurine is partly due to changes in protein synthesis and hence in sulphur amino acid metabolism caused by hepatotoxic agents. However, bromobenzene did not increase urinary taurine and alpha-naphthylisothiocyanate and lithocholate caused reduced levels. It is suggested that this lack of increase in urinary taurine may be due to depletion of glutathione or interference with the biliary system.

1-Naphthylisothiocyanate↗
PubMed1992

Comparative teratogenicity of nine retinoids in the rat.

he comparative teratogenicity of nine retinoids in Wistar rats was investigated. The compounds studied and dose levels tested (mg/kg) were: all-trans-retinoic acid (TRA), 6.25, 12.5, 25, 50, 100; etretinate (ETR), 25, 50; acitretin (ACIT), 25, 50; 13-cis-retinoic acid (13CRA), 100, 200; and five retinamides, each at 300 and 600 mg/kg, N-(4-hydroxyphenyl)-retinamide (4HPR); N-tetrazol-5-ylretinamide (TZR); N-butylretinamide (NBR); N-ethylretinamide (NER); 13-cis-N-ethylretinamide (13CNER). Retinoids were administered by oral intubation on days 10 and 11 post coitum (p.c.). Dams were killed on day 22 p.c. and examinations carried out to assess teratogenic potential. TRA, ETR, ACIT, 13CRA and 4HPR increased the incidence of resorptions. The incidence of abnormal fetuses, irrespective of the specific abnormalities induced, was markedly increased (50-100%) by TRA, ETR, ACIT, 13CRA and 4HPR, whereas TZR and NBR caused moderate increases (20-50%), and NER and 13CNER induced mild increases (10-20%). The incidences of CNS, craniofacial and urinogenital defects were generally high with TRA, ETR, ACIT and 13CRA. Cardiac vessel defects were markedly increased by 4HPR. Using a number of criteria, a generalized ranking order of the toxicity of the compounds was drawn up: TRA > ETR > ACIT > 13CRA > 4HPR > TZR identical to NBR > NER identical to 13CNER. The ranked order of relative in-vivo teratogenicity for the nine retinoids is compared with a previously reported in-vitro assessment of the compounds using a rat whole embryo culture technique.

Abnormalities, Drug-Induced↗
PubMed1991

Taurine, a possible urinary marker of liver damage: a study of taurine excretion in carbon tetrachloride-treated rats.

Carbon tetrachloride (CCl4) caused a dose-dependent increase in urinary taurine which correlated with both the histological and biochemical assessment of liver damage. The peak elevation in urinary taurine occurred within the first 48 h after dosing but there was still significant taurinuria 72 and 96 h after the intermediate dose (1 ml.kg-1) and highest dose (2 ml.kg-1), respectively. Levels of taurine in serum were also elevated over the 24 h period following a hepatotoxic dose (2 ml.kg-1) of CCl4. In contrast, although initially elevated, levels of taurine in the liver declined over the 24 h period following dosing and were significantly lower 96 h after a hepatotoxic dose of CCl4 (2 ml.kg-1). Male rats showed a different urinary profile for taurine than female rats after dosing with CCl4. A reduction in food intake seemed to lower urinary taurine levels although these changes were not statistically significant. There was a significant correlation between the level of urinary taurine and the level of serum AST for individual animals given a hepatotoxic dose of CCl4 (2 ml.kg-1). The data presented suggest that: i) taurine is produced by the liver in response to a toxic insult and subsequent leakage from damaged cells leads to increased levels in the urine; ii) the urinary taurine level may be a useful non-invasive marker of liver damage.

Alanine Transaminase↗
PubMed1989

Age-related changes in the haematology of female F344 rats.

As little comprehensive baseline data are available on age-related haematological changes in genetically-defined rat strains, the haematology of female F344 rats is described in animals sampled at 2, 4, 8, 20, 66 and 121 weeks of age. Values for Hb, RBC and PCV increased from 2 weeks of age to reach adult levels at 8 weeks, whereas MCV, MCH and reticulocyte counts were high initially but decreased to reach the adult range at 8 weeks. Between 66 and 121 weeks, reticulocyte counts were significantly increased and values for MCHC significantly decreased. Lymphocytes were the predominant white cell type in each age group. The absolute numbers of neutrophils and lymphocytes showed slight variations between 2 and 66 weeks and both cell types increased significantly between 66 and 121 weeks. Platelet counts showed no overall age-related trends. Fibrinogen values increased from 2 weeks of age to reach the adult level at 8 weeks. One animal of the 14 sampled at 121 weeks showed changes in the blood, liver and spleen consistent with a diagnosis of lymphoid leukaemia.

Aging↗
PubMed1987

Regulation of accessory cell function by retinoids in murine immune responses.

This study examines the effects of in-vivo immune regulation by vitamin A acetate (VAA) and 13-cis-retinoic acid (13-CRA) on in-vitro accessory cell function. Mice were fed a control diet, or diet containing VAA or 13-CRA, and monitored by body weight gains and diet consumptions at weekly intervals. At 4, 7 and 12 weeks mice were killed, differential blood counts performed and accessory cells isolated from lymphomedullary tissues. Histology confirmed that the chief feature of the lymphomedullary organs of the VAA-fed animals was an expansion of the splenic marginal zone and the paracortical region of the lymph nodes. There was an increase in the number of accessory cells present, and this included both dendritic cells and macrophages. The accessory cell function of these cells was also increased, as evidenced by both alloproliferative and allocytotoxic responses in vitro. In 13-CRA-fed animals the effects were similar to those seen with VAA, but were less pronounced. We suggest that the primary effects of these compounds on in-vivo immunoregulation could be due to their promotion of accessory cell function.

Animals↗
PubMed1985

Modulation of carcinogenesis in the urinary bladder by retinoids.

Bladder cancer has a 70% recurrence rate within five years and a high associated mortality. It commonly occurs in one or both of two predominant growth/behaviour patterns: either well-differentiated, relatively benign exophytic papillary lesions, or flat, poorly differentiated invasive carcinoma usually arising from carcinoma-in-situ. We have used the F344 rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a model for the papillary disease, and the BBN-treated B6D2F1 mouse for flat, invasive bladder carcinoma. In the rat, carcinogenesis is a multistage process and several retinoids will delay or even halt the development of bladder cancer. Inhibition of carcinogenesis is not complete, but there is a consistent reduction in the time-related incidence of papillomas and carcinomas and a concomitant improvement in the overall differentiation of the urothelium. In the BBN/mouse model, retinoids also have anticarcinogenic activity but interpretation of the results is more complicated. Unlike the F344 rat, the B6D2F1 mouse has a non-uniform response to BBN; not all mice develop bladder cancer even after treatment with very high doses of BBN and in those that do, more than one mechanism of carcinogenesis may be involved. Individual retinoids differ markedly in their ability to modulate bladder carcinogenesis in rodents; the behaviour of one analogue cannot be predicted automatically from data obtained with another. Combined data from rodent trials in this and other laboratories have identified N-(4-hydroxyphenyl)retinamide (HPR) as the most anticarcinogenic retinoid tested so far for the rodent bladder. It is also less toxic in rodents and better tolerated in humans than either 13-cis-retinoic acid or etretinate, two retinoids currently used in dermatological practice. A prophylactic chemopreventive trial of HPR in bladder cancer patients starting in 1985 will be centered on the Middlesex Hospital, London.

Animals↗
PubMed1985

Retinoid toxicity.

The long-term effects of N-ethylretinamide (NER) on the haematology of the rat, and the dose-related effects of retinoids on lymphoid organs of the mouse and rat were investigated. Retinoid-induced long-bone changes were used to develop a method for quantifying skeletal effects. This technique was used to investigate the activity of five retinamides in inducing long-bone changes in the rat. The ability of non-steroidal anti-inflammatory compounds (NSAICs) to prevent retinoid-induced skeletal effects was examined, and preliminary investigations made into the mechanisms of retinoid-induced long-bone remodelling. NER-fed rats had reduced red blood cell counts and fibrinogen values. Retinoids caused dose-related proliferation of the spleen and lymph nodes in the mouse and to a lesser extent in the rat. They induced dose-related reductions in femoral diaphysis and medullary cavity diameters in both rats and mice. Aspirin prevented NER-induced changes of rat long bones, but subsequent studies indicated this effect may be closely dependent on the dose level of both the retinoid and NSAIC administered. Retinoids induce rapid long-bone remodelling in the rat which tends to revert on feeding a control diet, but remodelling processes are different in the young growing rat and the mature animal.

Animals↗
PubMed1984

Cystoscopic examination of male and female dogs.

The use of cystoscopy is advocated as an aid to the early differential diagnosis of disease of the canine bladder. Techniques are described for carrying out urethroscopy and cystoscopy in both male and female dogs using modern medical diagnostic instruments. Males were examined with flexible paediatric bronchofibrescopes, which permitted urethroscopy and cystoscopy, but to obtain extensive biopsies or undertake cauterisation of the bladder surface with rigid endoscopes, a simple perineal urethrostomy was necessary. The bladder of females, on the other hand, was examined by cystoscopy and biopsied using standard rigid cystoscopes and resectoscopes.

Animals↗
PubMed1984

Principal components analysis of haematological data from F344 rats with bladder cancer fed N-(ethyl)-all-trans-retinamide.

Several multivariate statistical methods are available which can alleviate the problems of analysing the large volumes of data generated from toxicological experiments. One such technique, principal components analysis, provides a method for exploring the relationships between a number of variables (such as blood parameters) and for eliminating redundant data if strong correlations exist between the characters. It also provides a method for clustering individuals, which may reveal similarities between animals in a treatment group or highlight individual 'outliers'. The application of principal components analysis to a set of haematological data from a trial evaluating the efficacy of a synthetic retinoid against carcinogen-induced bladder cancer in the rat has clearly shown, in two bivariate plots, that while some animals in the carcinogen-treated groups were normal, others were anaemic and that animals fed the synthetic retinoid and killed at 1 year had a microcytic anaemia. A full exploration of the data using conventional univariate statistical analysis would have involved at least 28 graphic representations of the data, as well as the interpretation of more than 130 means and SDs. Principal components analysis provides a valuable additional tool for the statistical analysis and exploration of toxicological data, but it must be used in conjunction with univariate or other multivariate methods if hypothesis testing is required. The use of multivariate techniques in toxicology may best be assessed by their practical application to toxicological data, and this paper presents such an evaluation with the aim of encouraging further exploration of the usefulness of principal components analysis. The raw data on which most analyses have been carried out are given.

Analysis of Variance↗
PubMed1979

Eradication of the pinworm Syphacia obvelata from an animal unit by anthelmintic therapy.

Thiabendazole incorporated in the diet at a rate of 0.1%, fed to all animals over a period of 3 months, successfully eliminated the parasite from the colony. Samples taken 12 months after treatment were still negative for the parasite. During the period between the discovery of the organism and the preparation of the diet a course of piperazine citrate was administered at a rate of 2 g/litre in the drinking water in order to limit the spread of the infection.

Animals↗
PubMed1978

Bacterial and mycoplasma flora of a laboratory colony of the common marmoset (Callithrix jacchus).

A survey was carried out to characterise the bacterial and mycoplasma flora of a closed colony of marmosets, Callithrix jacchus. Bordetella bronchiseptica and Staphylococcus aureus were the only potential bacterial pathogens isolated from the colony; Candida albicans was also identified. S aureus and C albicans were the only organisms which were associated with macroscopic lesions or overt disease. Post mortem examination of the animals proved only reliable method of establishing the presence of some bacterial species in the colony, eg, B bronchiseptica and of obtaining a reliable estimate of the incidence of the various organisms within the colony. The marmosets were all infected with ureaplasmas in the upper respiratory tract. Mycoplasma salivarium was isolated from this site in several animals. There was no evidence to indicate that cross-infection had occurred between the animal technicians and the marmosets, except in one possible case of candidiasis.

Animals↗
PubMed1978

Antibody responses in self-infections with Necator americanus.

Antibody responses were measured in a volunteer infected four times with Necator americanus over a 27-month period. The main source of antigen was culture fluid in which living adult N. americanus had been maintained for several days. Antibodies to worm acetylcholinesterase and IgE antibodies were detected only with this material, but antibodies were identified by the enzyme-linked immunosorbent (ELISA) assay, with either adult worm secretions or extracts of third-stage infective larvae. The total serum IgE level fell after the first infection, but although it then increased during subsequent infections, it never rose above 600 U per ml. None of the antibody responses suppressed the rat of worm development to maturity, or reduced the fecundity of the parasites. However, it is suggested that the development of the immune response may be associated with the waning of the severe gastro-intestinal symptoms which were experienced in this infection, and which are frequently characteristic of hookworm infections.

Acetylcholinesterase↗
PubMed1978

Composition of the milk of the common marmoset (Callithrix jacchus) and milk substitutes used in hand-rearing programmes, with special reference to fatty acids.

Analyses of marmoset (Callithrix jacchus) milk were carried out to determine values for crude protein, lactose, total lipids, major minerals, and osmotic pressure. Mean values were (g/100 ml): protein, 3.6; lactose, 7.5; total lipids, 7.7; minerals (mg/100 ml): sodium, 21.4; potassium, 54.3; calcium, 92.2; phosphorus, 22.8; magnesium, 5.0; chloride, 52.2; osmotic pressure, 354 mosm/kg water. Similar analyses were conducted on 2 milk substitutes used in hand-rearing programmes. Fatty acid analyses were carried out on natural milk, the milk substitutes, and the marmoset diet. For hand-rearing C. jacchus it is recommended that a human milk substitute is modified by increasing the levels of protein, carbohydrate, and total lipids, and that a small amount of fish oil is added.

Animal Feed↗