PubMed · 7740674
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S S Slesarenko, Iu N Lopatinskiĭ, D A Tsurtsumiia. [Postoperative eventrations].. https://pubmed.ncbi.nlm.nih.gov/7740674/
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A collagen tissue polymer composite manufactured in sheep and prepared in two different forms (wet and dry) was compared to polypropylene mesh and to a control group for effectiveness in the repair of an abdominal wall defect in a rabbit model. The wet and dry patches were shown to differ significantly in their pore size. The wet material was shown to retain its natural porosity and promoted neovascularization, tissue integration, cellular infiltration, and neomatrix formation compared to the dry collagen-polymer patch. This material was superior to the polypropylene mesh implant, which was associated with significant adhesions. The appearance of type VI collagen was the earliest sign of new cell infiltration and neomatrix formation within the implant. New deposition of type VI collagen was apparent throughout the thickness of the implant within 4 weeks, followed by type III collagen accumulation. Decreased porosity of the collagen component in the dry patches resulted in a totally nonintegrated implant. This induced a foreign-body capsule with minimal cellular tissue infiltration and no deposition of collagen types VI and III within the implant.
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A series of 3,8-diazabicyclo[3.2.1]octanes substituted either at the 3 position (compounds 1) or at the 8 position (compounds 2) by a chlorinated heteroaryl ring were synthesized, as potential analogues of the potent natural analgesic epibatidine. When tested in the hot plate assay, the majority of the compounds showed significant effects, the most interesting being the 3-(6-chloro-3-pyridazinyl)-3,8-diazabicyclo[3.2.1]octane (1a). At a subcutaneous dose of 1 mg/kg, 1a induced a significant increase in the pain threshold, its action lasting for about 45 min. 1a also demonstrated good protection at a dose of 5 mg/kg in the mouse abdominal constriction test, while at 20 mg/kg it completely prevented the constrictions in the animals. Administration of naloxone (1 mg/kg i.p.) did not antagonize its antinociception while mecamylamine (2 mg/kg i.p.) did, thus suggesting the involvement of the nicotinic system in its action. Binding studies confirmed high affinity for the alpha 4 beta 2 nAChR subtype (Ki = 4.1 +/- 0.21 nM). nAChR functional activity studies on three different cell lines showed that 1a was devoid of any activity at the neuromuscular junction. Finally, due to the analogy in their pharmacological profile with that of epibatidine, compounds were compared from a structural and conformational point of view through theoretical calculations and high-field 1H NMR spectroscopy. Results indicate that all of them present one conformation similar to that of epibatidine.