The effect of oxytocin on contractility of the equine oesophagus: a potential treatment for oesophageal obstruction.

This study was performed to determine the effect of administration of i.v. oxytocin on the contractility of the musculature associated with the equine oesophagus. Nine clinically normal horses were fitted with a nasogastric tube modified with inflatable latex cuffs. These cuffs were connected to piezoelectric pressure recording devices. Oxytocin in 3 different doses or saline controls were administered i.v. in a randomised block pattern. Systolic blood pressure, ECG, heart rate and nasogastric tube cuff pressures were then measured for 60 min. Administration of oxytocin i.v. at 0.11 and 0.22 iu/kg bwt, resulted in a short-term statistically significant relaxation of the musculature of the equine oesophagus. When oxytocin was administered at 0.11, 0.22 and 0.44 iu/kg bwt, no clinically significant cardiovascular changes were seen. In approximately 5% of the oxytocin administrations, signs of mild short-term abdominal discomfort were observed. In clinical cases of noncomplicated oesophageal obstruction, it is suggested that reduction in tone of oesophageal musculature may result in passage of oesophageal obstructions with reduced risk of oesophageal injury when compared to other traditional treatments.

Disposition and metabolism of codorphone in the rat, dog, and man.

The disposition and metabolism of codorphone, 17-cyclopropyl-methyl-4,5 alpha-8 beta-ethyl-3-methoxymorphinan-6-one (I), a new narcotic antagonist, analgesic agent, have been studied in the rat, dog, and man. Rats and dogs were given single 100- and 50-mg/kg po doses, respectively, of I-3H; human volunteers received single 10- to 30-mg doses of unlabeled I po. The compound appeared to be well absorbed in the three species. In rats the highest levels of radioactivity were in liver, adrenals, kidneys, spleen, and lungs. Excretion was primarily fecal in rats and dogs. In man about 50% of the dose appeared in the 24-hr urine. I was about 95% metabolized by each species. The major metabolites in rats resulted from 3- and/or 17-dealkylation. Metabolism in dogs was characterized primarily by 17-dealkylation. The major pathways of I metabolism in man were 17-dealkylation and 6-reduction. In the three species significant glucuronic acid conjugation of metabolites occurred.

Methodology for the identification of the urinary metabolites of the analgesic-narcotic antagonist, codorphone, by gas chromatography mass spectrometry.

Methodology is presented for the identification of codorphone and its metabolites in urine samples using gas chromatography mass spectrometry. The procedure focuses on the clean-up of biological samples and a derivatization technique suitable for these samples. Sep-Pak C-18 cartridges were employed in the clean-up procedure permitting the biological sample to be derivatized in a relatively small volume of reagents. The derivatization procedure incorporated a one-step trimethylsilyloxime reaction to prevent enol formation while simultaneously derivatizing free hydroxyl groups with the excess trimethylsilylimidazole present in the reaction mixture. This was followed by the addition of BSTFA directly to this reaction mixture to complete derivatization of any metabolites possessing dealkylation of the nitrogen. Using this derivatization scheme, synthetic metabolites were analyzed by gas chromatography mass spectrometry, and their mass spectra were characterized emphasizing the diagnostic fragment ions observed in the spectra. To illustrate the usefulness of this methodology, a urine sample obtained from a dog that had been dosed with codorphone was analyzed by gas chromatography mass spectrometry, and the metabolites were identified by comparison to the mass spectra of the synthetic derivatives.

Rates of release of subcutaneously injected antigens in the rat. Comparison of an aqueous preparation with two alum-precipated preparations.

Release of antigen E-125 I from the site of subcutaneous injection in male rats was delayed significantly when either of two alum-precipitated preparations containing 1.0-1.2 mg of Al/ml was administered rather than an aqueous preparation. The rates of 125I excretion were similarly influenced being statistically slower through the first week after single doses of the alum-precipitated preparations. The results of these studies strongly support the view that alum-precipitated vaccines offer more protection from system reactions than aqueous vaccines.

Improved colorimetric determination of aspirin and salicylic acid concentrations in human plasma.

An improvement in a previously described method for the determination of plasma salicylic acid and aspirin levels in humans is described. The procedure was simplified by employing only one plasma sample for both salicylates. More accurate estimation of salicylates, particularly aspirin, was achieved by using two different calibration curves. Salicylic acid was estimated by reaction with an aqueous solution of the Folin-Ciocalteu phenol reagent. Absorbance of the blue-colored complex, which formed on addition of sodium hydroxide, was measured at 670 nm. The influence of alkalinity in the formation of the colored complex is discussed. The average recovery of aspirin added to plasma was 94.61%; it was 214.72% by the previous method.