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Biomedical subjects

G Conybeare

Publications and source records attributed to G Conybeare.

7 recordsLinked to original sources
PubMed1995

The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning.

The 1200-rat Biosure Study had six interrelated aims: (1) To see whether dietary restriction (80% ad lib.) reduces the age-standardized incidence of fatal or potentially fatal neoplasia before the age of 30 months. (2) To see whether the beneficial effects of diet restriction can be achieved by (a) limiting the daily period of access to food to 6 hr, or by (b) limiting the energy value of the diet. (3) To see whether reduced calorie intake between weaning and age 4 months influences survival and/or incidence of non-neoplastic and neoplastic diseases. (4) To compare effects of food consumption, energy intake and protein intake on survival and disease. (5) To study the relationships between body weight at different ages with eventual survival and disease incidence. (6) To provide a database for studying relationships between various in-life measurements and eventual survival and disease incidence in individual animals. Twelve groups of SKF Wistar rats consisting of 50 animals of each sex were fed according to different dietary regimens from when they were weaned at the age of 3 wk until they died, or had to be killed because they were sick, or until the experiment was terminated at 30 months. For five of the 12 dietary regimens, satellite groups consisting of 30 animals per sex were maintained in parallel and used to supply information on the effect of diet on circulating hormone levels during the course of the study. During the 13 wk post weaning a Standard Breeder diet (SB) was provided either ad lib. (four groups), 80% ad lib. (three groups), or with access to food limited to 6 hr per day (one group). During this same period two other groups were fed a Low Nutrient Breeder diet (LB) ad lib. A further group was fed a Low Nutrient Maintenance (high fibre) diet (LM) ad lib. Finally, one group was fed the high protein Porton Rat diet (PR) ad lib.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1991

Risks of premature death and cancer predicted by body weight in early adult life.

In a study of 30 months duration, involving 600 male and 600 female Wistar rats fed on 12 different diets/dietary regimes, none of which involved deliberate exposure to any known genotoxic carcinogen, highly significant between-group differences were observed in survival and incidence of various neoplastic and non-neoplastic diseases. A full report of the findings is being prepared. Here we report that, irrespective of diet or dietary regime, there were highly significant correlations of body weight at 29 weeks of age with premature death (P less than 0.0001 in both males and females), with development of benign or malignant neoplasm of any site (P less than 0.0001 in males and P less than 0.01 in females) and with development of malignant neoplasm at any site (P less than 0.0001 for sexes combined). Numerous kinds of neoplasm contributed to these overall correlations. The most significant were pituitary tumour (P less than 0.0001), mammary gland tumour (P less than 0.0001), squamous or anaplastic carcinoma of the jaw (P less than 0.001), and subcutaneous mesodermal tumours (P less than 0.05). The 20% of rats that were heaviest at 29 weeks were more than twice as likely to die prematurely than the lightest 20% (2.56 times--males, and 2.11 times--females), and almost twice as likely to develop a malignant tumour (1.87 times for the sexes combined). These findings have important implications for the design and interpretation of carcinogenicity tests in rodents and of laboratory and human studies of relationships between diet, ageing-related degenerative diseases, and cancer.

Animals↗
PubMed1989

Relation between dopaminergic control of pituitary lactotroph function and deceleration of age-related changes in serum prolactin of diet-restricted rats.

Pituitary lactotroph function has been examined in diet-restricted (6 hr/day) male and female rats and compared with that in animals fed ad lib. After 12 months the age-related increase in serum prolactin concentration was significantly attenuated in diet-restricted female rats. Similar effects were not observed in male rats. Isolated superfused anterior pituitary glands removed from rats on both feeding regimens at 12 or 18 months and challenged with dopamine in vitro (5 microM) did not show differential prolactin secretion. No significant differences were observed in serum prolactin secretion in vivo after administration of bromocriptine (3 mg/kg body weight, sc) or haloperidol (1.75 mg/kg body weight, ip). These results do not support an altered dopamine receptor function in the anterior pituitary lactotrophs. In contrast, central dopamine receptor function in rats 12 months of age was altered by dietary restriction, since the frequency of cataleptic responses to haloperidol injection (2 mg/kg body weight, ip) was significantly depressed in the test animals.

Aging↗
PubMed1989

SK&F 93574, a histamine H2-receptor antagonist, releases histamine in the dog.

This study was designed to establish whether SK&F 93574 releases histamine in dogs. Three female beagle dogs each received single infusions (on separate days) of each of SK&F 93574 (2.5 mg kg-1), polyvinylpyrrolidone (PVP, 20 mg kg-1) and sterile saline. The treatments were given at 14 day intervals by rapid intravenous infusion at 0.5 mL kg-1 min-1 for 2 minutes. Dogs showed clinical signs of histamine release such as vasodilation, licking lips, head drooping and increased gut movement after treatment with the known histamine releaser PVP or the test compound SK&F 93574. These signs were of similar severity and duration for the two compounds. No such changes were observed when the dogs received vehicle alone. Treatment with PVP or SK&F 93574 also resulted in markedly elevated plasma histamine concentrations (greater than 10-fold increase over control). It is concluded that intravenous administration of SK&F 93574 to dogs is associated with histamine release.

Animals↗
PubMed1988

Improved oral dosing technique for rats.

In a department assessing the safety of potential medicines, it was found that gavage-related death in rats could be virtually eliminated by the use of a modified dosing cannula. It had previously been found with a series of potential therapeutic agents that a number of rodents died with dyspnea following administration by gavage. It was known that this was not due to technical error; gavage with water in control groups led to death with similar symptoms in only one case per 220 rat years, or one in 80,520 doses. Accidental aspiration of small volumes of the oral dose was considered to be responsible for the drug-related deaths. Hypertonic, acidic sodium chloride solutions, used as a control, tonicity- and pH-matched to a compound solution in a long-term study, had similar effects. It was shown in a small experiment that the intratracheal lethal dose was approximately 1/200 the published oral LD50 of NaCl. Cannulae of various diameters, lengths, and materials were tested in order to devise a safer dosing method, which would not cause trauma but would allow economical dosing speeds to be achieved. For adult rats, a steel cannula 70-mm-long, with a maximum tip diameter of 4 mm, was chosen. Lighter rats could be dosed using cannulae of smaller tip diameter according to body weight. The adoption of our method, developed using a few rats, could save many unnecessary deaths in laboratory rodents as well as many spurious "treatment-related" pulmonary symptoms.

Administration, Oral↗
PubMed1988

An improved simple technique for the collection of blood samples from rats and mice.

The technique of blood collection from the lateral caudal vein has been improved. The method requires only moderate skill and no anaesthesia is necessary. Collection of blood samples causes little trauma and can be repeated at frequent (8 h) intervals thus making the method particularly suitable for pharmacokinetic and hormonal studies. Blood samples are uncontaminated by tissue fluids. Large volumes can be obtained, in mice up to 1.5 ml and in Wistar rats over 4 ml.

Animals↗