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1.  Placental transfer of pyridostigmine in the rat 
British Journal of Pharmacology  1970;38(1):202-205.
1. Carbon-14 labelled pyridostigmine in single doses was given by intramuscular injection to pregnant rats, and maternal blood, foetal and placental homogenates were examined for total radioactive content, pyridostigmine and its metabolite, 3-hydroxy-N-methyl pyridinium.
2. The level of radioactivity in all tissues was highest at 15 min and fell to negligible amounts at 24 hr. The concentrations in placenta were similar to those in maternal blood, but there was some indication of retention of radioactive drug in the placenta. The concentrations in the foetus were substantially lower, but the subsequent slow decline in concentration suggests that cumulation of the drug could occur with repeated doses.
3. The percentage of metabolite in the foetus was considerably higher than in placenta and blood, and the possible reasons for this are discussed.
PMCID: PMC1702639  PMID: 5413286
5.  Development of Injection-site Sarcomata in Rats: A Study of the Early Reactive Changes Evoked by a Carcinogenic Nitrosoquinoline Compound 
British Journal of Cancer  1970;24(2):300-311.
The early changes induced by a carcinogenic nitrosoquinoline compound (NTDQ) have been studied in the subcutaneous tissues of 88 rats. An initial acute infiammatory response is quickly replaced by a distinctive granuloma which is established by 10 days and persists indefinitely—a sequence which takes place both in adult and in newborn animals. Its main components—histiocytes, multinucleate giant cells and granulation tissue—are described in detail and the formation of giant cells by fusion from adjacent histiocytes has been traced. Autoradiographic studies with tritiated thymidine show heavy nuclear labelling in the histiocytes and fibroblasts during the first 10 days; this later declines but raised levels of nuclear labelling persist up to the end of the experiment. No proliferative activity is seen in the giant cells and these cells show only feeble phagocytic activity, tested by their ability to take up carbon particles. The experiments in which colloidal carbon was injected locally also provided some information on the lymphatic vessels in the vicinity of NTDQ-induced granulomata. It appears that, initially, the lesions contain large dilated lymphatic vessels. Later, a dense connective tissue barrier develops and lymphatic connections with the surrounding dermis are progressively reduced.
The properties of granulomata induced by NTDQ are discussed and some possible relationships between the formation of granulomata and eventual tumour developed are considered. Particular emphasis is given to two related features: the sustained proliferative activity of the fibroblasts and the resulting semi-isolation of the injection site lesion by the formation of a dense connective tissue barrier.
PMCID: PMC2008592  PMID: 5451571

Results 1-6 (6)