2,4-Disubstituted quinolines with additional substituents in positions 5-8 have been found to have anthelmintic properties. A number of 2,4-dimethoxy-6- or 8-arylquinolines have potent activity against the sheep nematode Haemonchus contortus, with LD99 values of the same order of magnitude as levamisole. These arylquinolines maintain their activity against levamisole-, ivermectin- and thiabendazole-resistant strains of H. contortus.

Introduction Acute metabolic acidosis of non-renal origin is usually a result of either lactic or ketoacidosis, both of which are associated with a high anion gap. There is increasing recognition, however, of a group of acidotic patients who have a large anion gap that is not explained by either keto-or lactic acidosis nor, in most cases, is inappropriate fluid resuscitation or ingestion of exogenous agents the cause.

Acidosis is a major factor that determines the upper limit of exercise endurance. We have previously shown that anions usually associated with intermediary metabolism are elevated in critically ill patients with metabolic acidosis and contribute significantly to acidosis generation. This study was to determine whether volunteers with normal metabolism would exhibit similar elevations in anions associated with intermediate metabolism when exposed to a short-term physiological stress leading to a brief lactic acidosis. Physiological stress was induced on five healthy male subjects by means of a ramped exercise protocol. Blood was obtained immediately prior to and post-exercise, plasma ultrafiltrate was prepared and analysed immediately both by enzyme assay and liquid chromatography coupled to electrospray-mass spectrometry (LC/ESI-MS). Metabolic acidosis concomitant with a significant increase in blood lactate occurred in each subject, but in addition, anions normally associated with intermediate metabolism were significantly elevated after exercise. The contribution of these anions to generating an acidosis, and thus potentially limiting the extent of exercise, has never been acknowledged.

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