Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.

Ascorbic acid and glutathione (GSH) are antioxidants and free radical scavengers that provide the first line of defense against oxidative damage in the CNS. Using HPLC with electrochemical detection, we determined tissue contents of these antioxidants in brain and spinal cord in species with varying abilities to tolerate anoxia, including anoxia‐tolerant pond and box turtles, moderately tolerant garter snakes, anoxia‐intolerant clawed frogs (Xenopus laevis), and intolerant Long‐Evans hooded rats. These data were compared with ascorbate and GSH levels in selected regions of guinea pig CNS, human cortex, and values from the literature. Ascorbate levels in turtles were typically 100% higher than those in rat. Cortex, olfactory bulb, and dorsal ventricular ridge had the highest content in turtle, 5–6 µmol g−1 of tissue wet weight, which was twice that in rat cortex (2.82 ± 0.05 µmol g−1) and threefold greater than in guinea pig cortex (1.71 ± 0.03 µmol g−1). Regionally distinct levels (2–4 µmol g−1) were found in turtle cerebellum, optic lobe, brainstem, and spinal cord, with a decreasing anterior‐to‐posterior gradient. Ascorbate was lowest in white matter (optic nerve) in each species. Snake cortex and brainstem had significantly higher ascorbate levels than in rat or guinea pig, although other regions had comparable or lower levels. Frog ascorbate was generally in an intermediate range between that in rat and guinea pig. In contrast to ascorbate, GSH levels in anoxia‐tolerant turtles, 2–3 µmol g−1 of tissue wet weight, were similar to those in mammalian or amphibian brain, with no consistent pattern associated with anoxia tolerance. GSH levels in pond turtle CNS were significantly higher (by 10–20%) than in rat for several regions but were generally lower than in guinea pig or frog. GSH in box turtle and snake CNS were the same or lower than in rat or guinea pig. The distribution GSH in the CNS also had a decreasing anterior‐to‐posterior gradient but with less variability than ascorbate; levels were similar in optic nerve, brainstem, and spinal cord. The paradoxically high levels of ascorbate in turtle brain, which has a lower rate of oxidative metabolism than mammalian, suggest that ascorbate is an essential cerebral antioxidant. High levels may have evolved to protect cells from oxidative damage when aerobic metabolism resumes after a hypoxic dive.

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The aim of the present experiments was to study the characteristics and mechanisms of the rhythm induced by overdrive ('overdrive excitation', ODE) in the sinoatrial node (SAN) superfused in high [K(+)](o) (8-14 mM). It was found that: (1) overdrive may induce excitation in quiescent SAN and during a slow drive; (2) in spontaneously active SAN, overdrive may accelerate the spontaneous discharge; (3) immediately after the end of overdrive, a pause generally precedes the onset of the induced rhythm; (4) during the pause, an oscillatory potential (V(os)) may be superimposed on the early diastolic depolarization (DD); (5) during the subsequent late DD, a different kind of oscillatory potential appears near the threshold for the upstroke (ThV(os)) which is responsible for the initiation of spontaneous activity; (6) once started, the induced rhythm is fastest soon after overdrive; (7) faster drives induce longer and faster spontaneous rhythms; (8) the induced action potentials are slow responses followed by DD with a superimposed V(os), but ThV(os) is responsible for ODE; (9) the induced rhythm subsides when ThV(os) miss the threshold and gradually decay; (10) low [Ca(2+)](o) abolishes ODE; (11) in quiescent SAN, high [Ca(2+)](o) induces spontaneous discharge through ThV(os) and increases its rate by enhancing V(os) and shifting the threshold to more negative values, and (12) tetrodotoxin abolishes ODE as welll as the spontaneous discharge induced by high [Ca(2+)](o). In conclusion, in K(+)-depolarized SAN, ODE may be present in the apparent absence of calcium overload, is Ca(2+)- and Na(+)-dependent and is mediated by ThV(os) and not by V(os). Copyright 1997 S. Karger AG, Basel