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Biomedical subjects

A D Dayan

Publications and source records attributed to A D Dayan.

At least 37 records · Page 2Linked to original sources

Urinary bladder hyperplasia in the rat: non-specific pathogenetic considerations using a beta-lactam antibiotic.

Eight of the known chemical substances associated with neoplasia in man are known to target the urinary bladder urothelium. Preneoplastic changes have been identified following exposure to each of these chemicals, and they have also been seen to occur in many species of lab animals. The most important such change is preneoplastic hyperplasia. Adaptive hyperplasia is the first form of hyperplasia to appear. It can be seen both in untreated controls and dosed animals. The distinguishing features are that in treated groups it does not progress with dose or time, and the process is reversible. Reparative hyperplasia involves disruption of homeostasis. Its severity increases with dose and time. It is not seen in controls but it is still reversible during the recovery segment after exposure to a toxic substance. When reparative hyperplasia continues beyond a certain threshold of time and dose, it progresses to preneoplastic hyperplasia, which further progresses with continued stimulation to frank neoplasia. The synthetic beta-lactam penem antibiotic FCE 22891 and its metabolite FCE 22101 caused adaptive urothelial hyperplasia of the urinary bladder only in rats and in no other species. Based on the pharmacokinetic profile of FCE 22891 and FCE 22101, it can be deduced that the morphologic finding of adaptive urothelial hyperplasia is caused by reduction of intravesicular urine pH. This effect has no relevance to therapeutic use in humans. Further, it is important to distinguish adaptive and reparative hyperplasia in preclinical toxicity studies.

Animals↗

Effect of animal age on the uptake of large particulates across the epithelium of the rat small intestine.

A quantitative investigation into the transfer of latex polystyrene particles across the epithelium of the small intestine has been carried out using male weanling, adult and aged Sprague-Dawley rats. Orally administered polystyrene particles, 2 microns in diameter, were transferred from the lumen of the small intestine into the gut associated lymphoid tissues (Peyer's patches). No significant difference in the number of particles transported across the gut epithelium was detected between animals of different age groups. The concentration of particles detected in Peyer's patches excised from the proximal and distal regions of the small intestine of particle-treated animals did not differ significantly, except in aged rats. Particle concentration was significantly higher in Peyer's patch tissue than in adjacent Peyer's patch-free tissues of the small intestine in treated animals of all age groups. The assay method described here may be used for quantitative investigation of the transepithelial transport of large particulates.

Aging↗

Allergy to antimicrobial residues in food: assessment of the risk to man.

Meat and other dietary products from food animals and farmed fish in the West may contain residues of many antibiotics and antibacterial agents, or haptenised macromolecules, e.g. penicilloylated proteins. General surveys have shown a low incidence of detectable residues in most products (up to 0.5-2%). A notable proportion of the general population has true allergic sensitivity to these substances (up to 7-10% to "penicillin") due to prior medical treatment. However, cases of proven allergy to such substances in food are extremely rare, based on clinical and laboratory proof of an immunological reaction, whereas there are less well substantiated reports blaming antibiotics in up to 50% of cases of chronic urticaria. Consideration of nature of haptenisation by antimicrobial substances, of the inefficiency of the oral route for immunisation, and of the transient and unrepeatable nature of most examples of food-related reactions all suggest that allergy to antimicrobial residues in the diet is exceedingly rare.

Animals↗

Carcinogenicity and drinking water.

Water is a powerful solvent that readily dissolves many natural and synthetic substances from the environment (e.g. inorganic salts, humic acids and pesticide residues). The processes of purification, disinfection and preparation and storage necessary to provide and distribute drinking water may introduce further chemicals, including some used for these purposes and others derived by interaction between them and the compounds of natural origin. The composition of drinking water, therefore, is complex and varies between sites and with the seasons. Modern technology is employed to minimise the amounts of many of these substances, but some may persist, including derivatives generated by halogenation and ozonation for disinfection. Some of the substances are genotoxic in the laboratory and a few are proven experimental carcinogens--all at much higher concentrations than those normally found in a drinking water supply. Many ecological and epidemiological surveys have been done to compare the occurrence of various types of tumour in man with exposure to different types of drinking, but no consistent or reliable association has been found. There are serious and probably irremediable methodological weaknesses in these attempts, because of the difficulty of defining the nature of the waters consumed over a major part of life, and the variable composition of waters. The surveys do not permit even a realistic assessment of the upper confidence limit of the exclusion of the risk. Thus, although there is some experimental indication of the possible presence of carcinogenic substances in most or all drinking waters, and of how they are formed, the concentrations are very low and there is no realistic evidence that they have caused harm to man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of a cholecystokinin receptor antagonist on rat exocrine pancreatic response to raw soya flour.

1 Raw soya flour (RSF) in the diet induces pancreatic hypertrophy and hyperplasia in the rat, changes ascribed to production of a high circulating level of cholecystokinin (CCK) due to inhibition of trypsin in the duodenum. Prolonged ingestion results in pancreatic adenomas and carcinomas. 2 L-364, 718, a potent, highly specific CCK antagonist was used to investigate the short-term role of CCK. 3 In rats fed 50% RSF and L-364, 718 5 mg kg-1 p.o. twice daily for 4 d, there was inhibition of pancreatic hypertrophy and hyperplasia, which is further evidence that peripherally-acting CCK plays a major role in the generation of RSF-mediated changes in the pancreas.

Animals↗

A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat.

The effect of hexachlorophene (HCP; 2,2'-methylenebis(3,4,6-trichlorophenol), cuprizone (CPZ; bicyclohexone oxaldihydrazone) and triethyl tin (TET; triethyl tin sulphate) in producing vacuoles in the brain of the Sprague-Dawley rat has been quantified by image analysis of the extent of the spongy change in the white matter. The state of the astrocytes was assessed by immunocytochemical staining for glial fibrillary acidic protein (GFAP). HCP and TET caused a dose-related spongiosis, but cuprizone had no significant effect on the brain. With chronic HCP treatment, the spongiosis was accompanied by astrocyte hypertrophy and proliferation, and the extent of the gliotic reaction was related to the dose of HCP. The results demonstrate that HCP can produce and maintain astrocyte proliferation in the rat brain. Such an agent was required for use in an investigation of a putative tumour promoter in the rat.

Animals↗

Death of the LD50.

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Animal Testing Alternatives↗

Strength of meaning--strong words and a certain message?

The ability to convey specific meanings is important to scientists in their writing. However, difficulties arise when the ideas to be portrayed are judgmental. While extreme terms expressing strength of meaning are readily understood, more subtle ones appear not to be.

Humans↗

Who needs toxicology?

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Education, Medical, Undergraduate↗

Histopathological classification of nonantral gastric endocrine growths in man.

Recently, the gastric endocrine system has been recognized as the origin of benign and malignant tumors in pernicious anemia. It has also been found that the gastric endocrine cells respond to permanent elevation of serum gastrin levels induced by changes in acid secretion in response to surgical procedures, drug therapy and age. Therefore, a definition of nonantral gastric endocrine hyperplasia (simple or diffuse, linear or chain-forming, micronodular, adenomatoid), dysplasia (enlarging or fusing micronodules, microinvasion, nodular growth) and neoplasia (intramucosal carcinoid, invasive carcinoid) is presented. The individual entities are illustrated, together with the literature discussed and the techniques for their identification presented.

Endocrine System Diseases↗