The effects of N‐butylhyoscine bromide (Buscopan) were examined on responses of guinea‐pig isolated intestine to transmural stimulation and to peristalsis induced by raising the intraluminal pressure. The drug acted rapidly and in low concentration to abolish peristaltic activity and responses to transmural stimulation when applied to the serosal surface of the ileum, but from 100 to 1000 times the concentration was required when it was applied to the mucosal surface. The effects were more persistent after mucosal than after serosal application. N‐Butylhyoscine bromide was bound to mucus and mucosal material, the ratio of free to bound drug being 2:1. The drug passed through portions of the intestinal wall containing Peyer's patches more rapidly than through portions containing no macroscopically visible lymphoid tissue. The rate of passage through Peyer's patches, but not through other portions, increased with increasing hydrostatic pressure. These findings help to explain why enterally administered N‐butylhyoscine bromide exerts anti‐cholinergic effects on the gut without producing systemic actions.
Biocompatibility tests have been compared for their suitability as routine safety tests for urinary catheters. Latex catheters from five manufacturers were tested by each of the following four methods: (1) a cell culture cytotoxicity assay of catheter extracts, (2) intracutaneous injection of the extracts into rabbits, (3) intramuscular implant of catheter pieces into rabbits, (4) catheterization of sheep (mucous membrane irritation). The rabbit intracutaneous and intramuscular tests are both current pharmacopoeial methods for ascertaining the suitability of polymers for medical use. The four tests each showed a cell or tissue response ranging from no detectable change to severe damage, according to the catheter batch or brand, and they each identified the same samples as most toxic and least toxic. However, they differed in sensitivity. The sheep test and the cell culture assay discriminated between catheters of intermediate toxicity and ranked as toxic catheters not identified as such by the two pharmacopoeial tests. The sheep test most closely approximates clinical usage, but is impractical for routine use. The cell culture assay is a suitable alternative. It also has the advantages of a clearly defined endpoint, good sensitivity, reproducibility, speed, and reduced animal usage.
SummaryIn order to investigate the reported heterogeneity of commercial heparin injections, lung and mucous preparations were fractionated by gel chromatography according to molecular size. Eluent pools were characterized by measuring electrophoretic mobility, anticoagulant activity using a reactivation assay and an anti-Xa assay, lipolytic activity and the protamine neutralization value. The only biological activity to show a marked relationship with the molecular size of the heparin fraction was the anti-Xa activation activity. This effect was more pronounced with the mucous heparins than with the lung heparin preparation studied.
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