Redox regulation of vascular prostanoid synthesis by the nitric oxide-superoxide system

Oxygen is involved in cell signaling through oxygenases and oxidases and this applies especially for the vascular system. Nitric oxide (*NO) and epoxyarachidonic acids are P450-dependent monooxygenase products and prostacyclin is formed via cyclooxygenase and a heme-thiolate isomerase. The corresponding vasorelaxant mechanisms are counteracted by superoxide which not only traps *NO but through the resulting peroxynitrite blocks prostacyclin synthase by nitration of an active site tyrosine residue. In a model of septic shock, this leads to vessel constriction by activation of the thromboxane A2-prostaglandin endoperoxide H2 receptor. This sequence of events is part of endothelial dysfunction in which the activated vascular smooth muscle counteracts and regenerates vessel tone by cyclooxygenase-2-dependent prostacyclin synthesis. Peroxynitrite was found to activate cyclooxygenases by providing the peroxide tone at nanomolar concentrations. Such new insights into the control of vascular function have allowed us to postulate a concept of redox regulation in which a progressive increase of superoxide production by NADPH-oxidase, mitochondria, xanthine oxidase, and even uncoupled NO-synthase triggers a network of signals originating from an interaction of *NO with superoxide.     

The effect of vitamins A, E and K on experimentally induced histomoniasis in turkeys

Vitamins A, E and K were incorporated into turkey starter rations at normal (1 x ), 5 x and 50 x the National Research Council recommended vitamin levels and evaluated for their effect on histomoniasis in turkeys. Infected as well as comparable unifected poults were included in all trials. Each vitamin was also evaluated at normal and 50 x the NRC level in combination with ipronidazole, a low-level antihistomonal agent. In addition to performance parameters, glutamate oxaloacetate transaminase (GOT) and lactate dehydrogenase (LDH) plasma enzyme levels were used to evaluate the vitamin effect. None of the vitamins tested alone were found to be effective in terms of reducing mortality and morbidity following a severe Histomonas meleagridis challenge, regardless of the vitamin dose. A significant improvement in performance was demonstrated with the vitamin E (50 X)--ipronidazole combination and a numerical improvement with the vitamin A (50 X)--ipronidazole combination over ipronidazole alone or the poults fed NRC recommended vitamin levels. The GOT and LDH plasma enzyme levels correlated well with the progressive pathological changes associated with the disease. At 11 days post-infection both enzymes were consistently and significantly elevated above those of the uninfected controls, irrespective of the vitamin levels provided. The presence of low ipronidazole in most instances delayed the onset of clinical symptoms and was associated with a delay in enzyme elevation, indicating the excellent correlation and sensitivity of the enzyme method in assessing liver damage.