Morphine diesters. I. Synthesis and action on guinea pig ileum

3,6-Dipropanoylmorphine (DPM), 3,6-dibutanoylmorphine (DBM), and 3,6-dihexanoylmorphine (DHM) were prepared as prospective long-acting narcotic analgesics. The purity and structure of these compounds were authenticated by high pressure liquid chromatography and direct probe mass spectrometry. In aqueous solution the stability of the HCI salts of these compounds decreased with increasing alkyl chain length such that DHM underwent rapid hydrolysis to 6-monohexanoylmorphine (MHM). A comparison of DPM, DBM, and MHM with morphine (MO) and 3,6-diacetylmorphine (DAM, heroin) in the electrically stimulated guinea pig ileum myenteric plexus longitudinal muscle strip preparation (GUPIL) revealed similar potencies and efficacies for all compounds, but marked differences in the onset of drug action (MO greater than DAM greater than MHM greater than DPM greater than DBM, faster to slower). In a periodically washed GUPIL preparation DBM and MHM were five times longer acting than MO, DAM or DPM.     

Observations on induced carcinosis peritonei of the guinea pig

A diethylnitrosamine-induced hepatocellular carcinoma cell suspension (line-10), injected intraperitoneally in Sewall Wright strain-2 guinea pigs, causes ascites with implantation of malignant cells on the peritoneal surface. At these sites, swelling of the mesothelial cells and simultaneous proliferation of underlying fibroblasts and capillaries are seen. When there are about four layers of malignant cells and the mesothelial lining is disrupted, papillary projections of fibroblasts with capillaries, covered by malignant cells develop. These begin to behave as a "tissue". In these areas basement membrane destruction and lymphatic and blood vessel infiltration are demonstrable. These developments have been investigated by light microscopy, histochemistry, transmission- and scanning electron microscopy.     

Toxic action of influenza virus on lymphoid-macrophagal reactions in guinea pigs]

Influenza viruses with different degrees of virulence for the human being produced various reactions of the lymphoid-macrophagal elements in the peritoneal exudate of guinea pigs inoculated intraperitoneally. The higher the virulence of the strain for the human being -- the deeper the inhibition of the lymphoid and macrophagal cells of guinea pigs. Low virulent strains of influenza virus induced a considerable functional activity of macrophages, but were devoid of the lympholytic activity. Because of close corrleation between the virulence of the virus and the cellular content of the exudate the lymphocytic-macrophagal reaction in the animals resistant to influenza virus could serve for determination of the toxic activity of the viruses under study.     

Evaluation of the modulating action of Yersinia pestis adenylate cyclase on guinea pig peritoneal leukocytes using chemiluminescence

The biological action of Y. pestis adenylate cyclase on peritoneal leukocytes of guinea pigs has been studied by means of chemiluminescence. Y. pestis adenylate cyclase is supposed to contribute to the "oxidation" explosion of phagocytes in plague.     

Desulphation of heparin by mice and guinea pig leukocytes

Leukocytes from mice and guinea pigs were tested for their sulphate-splitting activity on heparin. Mouse macrophages showed the highest degrading activity while mouse neutrophils and lymphocytes were less active. In comparison, guinea pig spleen cells and leukocytes showed only a weak degrading activity. Mouse macrophages maintained in tissue culture were also found to degrade heparin, the amount of sulphate released increasing with time up to 96 h. Spleen extracts were found to neutralize the anticoagulatory activity of heparin.     

Biochemical properties of the bromodeoxyuridine-induced guinea pig virus.

The biophysical and biochemical properties of the virus particles released by guinea pig embryo cells treated with 5-bromo-2'-deoxyuridine (BUdR) have been compared to those of the B-type mouse mammary tumor virus (MMTV) and the C-type Rauscher murine leukemia virus. The high-molecular-weight (60 to 70S) RNA of the BUdR-induced guinea pig virus (GPV) has a molecular weight of 8 X 106 when measred by mixed agarose polyacylamide gel electrophoresis. The virus particles isolated from the tissue culture medium of BUdR-induced guniea pig cells have the following properties in common with MMTV: (i) a buoyant density of 1.18 g/ml in sucrose and 1.21 g/ml in CsCl, and (ii) a DNA polymerase that prefers Mg2+ over Mn2+ in an assay using the synthetic template poly(rC):oligo(dG). No nucleic acid sequence homology between GPV RNA and the viral RNAs of the MMTV, murine leukemia virus, hamster sarcoma virus, or Mason-Pfizer monkey virus could be observed in a competition hybridization assay using the radioactive-labeled GPV 60 to 70S RNA. By this same competition by hybridization assay the frequency of GPV proviral sequences was estimated to be at least 83 per haploid cellular genome of guniea pig cells. No nucleic acid sequences related to be GPV RNA were detected in the DNA of normal tissues of mice, rats, cats, dogs, baboons, or humans by direct RNA-DNA hybridization using radioactive GPV60 to 70S RNA.