SYNTHESIS OF OXYTOCIN USING IODINE FOR OXIDATIVE CYCLIZATION AND SILICA GEL ADSORPTION CHROMATOGRAPHY FOR PURIFICATION

Oxytocin (OT) was synthesized employing the solid phase method. Resins made of copolymers of polystyrene-1%-crosslinked with divinylbenzene gave better yields (73–95%) of Z-Cys(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH₂ (I) than 2%-crosslinked resins (10–56%). Reduction of I with Na-liq. NH₃ and oxidation with I₂-MeOH at –40° minimized dimer and polymer formation, and resulted in good yields (49–54%) of OT. The large volumes of MeOH required when several grams of I are reduced and then oxidized were rapidly evaporated in vacuo, and the residue was desalted by dissolving the peptide in a small volume of glacial acetic acid and filtering to remove the salt. OT was purified by adsorption chromatography on a silica gel column with combinations of MeOH-CHCl₃ of graded polarity. Oxytocin elutes with 33% MeOH-CHCl₃. After two purification steps by adsorption chromatography, the resulting OT was found to be homogeneous. The hormone was characterized chemically and found to be active biologically.     

TRANSIENT UNCROSSED CORTICOSPINAL FIBRES IN THE NEWBORN RAT

A small number of uncrossed corticospinal fibres were demonstrated in a 1-day-old rat by injection of horseradish peroxidase into one hemisphere of the cerebral cortex. These fibres were not demonstrable after the age of 7 days.     

Influence of a Bacterial Lipopolysaccharide on the Pharmacokinetics of Tobramycin in Rats

Abstract— The effects of Klebsiella pneumoniae O3 lipopolysaccharide on the renal handling and distribution characteristics of the aminoglycoside tobramycin were investigated in rats. Tobramycin (2 mg kg^?1) and inulin (100 mg kg^?1) were administered intravenously 2 h after administration of 50,250 or 500 μg kg^?1 lipopolysaccharide. Lipopolysaccharide delayed the disappearance of tobramycin from plasma in a dose-dependent manner. A dose-dependent decrease in systemic clearance of tobramycin was observed, although the elimination rate constant and fraction of urinary recovery of unchanged drug were not significantly different in any group. Lipopolysaccharide significantly decreased the central compartment volume of distribution of tobramycin, but did not influence the steady-state volume of distribution. A dose-related increase in the ratio of the rate constant of transfer to the peripheral compartment to the rate constant of transfer from peripheral compartment to central compartment was observed. The glomerular filtration rate was significantly decreased by pretreatment with 250 μg kg^?1 lipopolysaccharide and the clearance ratio was decreased by 20%, indicating that lipopolysaccharide increases the tubular reabsorption of tobramycin. Our findings suggest that K. pneumoniae O3 lipopolysaccharide modifies the glomerular filtration rate and tubular reabsorption without change in the terminal half-life and that drug distribution characteristics from the rapidly-distributing compartment to the peripheral compartment were altered without expansion of the extracellular fluid volume.