Annual ryegrass toxicity research update

Annual ryegrass toxicity (ARGT) is a complex disease that kills sheep and cattle grazing pastures which contain infected ryegrass. The disease results when a nematode (Anguina agrostis) and a batcerium (Corynebacterium sp.) invade annual ryegrass and cause the seed heads to become toxic as the grass dries off. The bacterium produces a complex toxin of 18 glycolipid compounds or corynetoxins which have been found to be virtually identical to the antibiotic tunicamycin

Annual ryegrass toxicity research update

Annual ryegrass toxicity (ARGT) is a complex disease that kills sheep and cattle grazing pastures which contain infected ryegrass. The disease results when a nematode (Anguina agrostis) and a batcerium (Corynebacterium sp.) invade annual ryegrass and cause the seed heads to become toxic as the grass dries off. The bacterium produces a complex toxin of 18 glycolipid compounds or corynetoxins which have been found to be virtually identical to the antibiotic tunicamycin

Potential for optimising Deep Brain stimulation through tremor quantification

Introduction: Deep Brain Stimulation (DBS) can be used to minimise tremor when pharmaceutical therapies fail. DBS devices emit a bi-phasic pulse train with variable: » Amplitude » Pulse Duration » Frequency. These parameters are set based on clinical observation of tremor and side-effects. Aims: Develop an objective measure of tremor severity. Determine the influence of each stimulus parameter on measured tremor. Method: 6 adults with DBS implants in the Posterior Subthalamic Area to alleviate tremor were recruited. Tremor was recorded using a sensitive motion tracking system with sensors placed on the elbows and wrists. Stimulus amplitude, pulse-duration & frequency were systematically adjusted. Patients were asked to hold their arms out and complete finger-nose exercises during measurements. Following objective measures of tremor were calculated: » RMS Amplitude » Velocity » Power Spectral Density » Frequency » C90 volume. C90 Volume is the volume of an ellipsoid that covers 90% of the data when plotted on a x, y, z plane. Pearson’s Correlations were calculated between: » Each objective measure » Angular & translational measures » Clinical ratings & objective measures. Results: As expected all measures except frequency were significantly (p < 0.05) inter-correlated. Correlations between angular and translational data were marginal. Clinical ratings were correlated (p < 0.05) to angular RMS in all patients. Best correlations with clinical ratings were seen with C90 volume in 3 patients (p < 0.01). Conclusion: The proposed objective measures can be used to quantify tremor severity. Further investigation is required to determine the best objective measure. Real-time implementation might lead to automated stimulus optimisation

Action potential afterdepolarization mediated by a Ca2+-activated cation conductance in myenteric AH neurons

Abstract2We investigated the nature of afterdepolarizing potentials in AH neurons from the guinea-pig duodenum using whole-cell patch-clamp recordings in intact myenteric ganglia. Afterdepolarizing potentials were minimally activated following action-potential ¢ring under normal conditions, but after application of charybdotoxin (40 nM) or tetraethyl ammonium (TEA; 10^20 mM) to the bathing solution, prominent afterdepolarizing potentials followed action potentials. The whole-cell current underlying afterdepolarizing potentials (IADP) in the presence of TEA (10^20 mM) reversed at 338 mV and was not voltage-dependent. Reduction of NaCl in the bathing (Krebs) solution to 58 mM shifted the reversal potential of the IADP to 358 mV, suggesting that the current underlying the afterdepolarizing potential was carried by a mixture of cations. The relative contributions of Naþ and Kþ to this current were estimated to be about 1:5. Substitution of external Naþ with N-methyl D-glucamine blocked the current while replacement of internal Cl3 with gluconate did not block the IADP. The IADP was also inhibited when CsCl-¢lled patch pipettes were used. The IADP was blocked or substantially decreased in amplitude in the presence of N-type Ca2þ channel antagonists, g-conotoxin GVIA and g-conotoxin MVIIC, respectively, and was eliminated by external Cd2þ, indicating that it was dependent on Ca2þ entry. The IADP was also inhibited by ryanodine (10^20 WM), indicating that Ca2þ-induced Ca2þ release was involved in its activation. Ni£umic acid consistently inhibited the IADP with an IC50 of 63 WM. Using antibodies against the poreforming subunits of L-, N- and P/Q-type voltage-gated Ca2þ channels, we have demonstrated that myenteric AH neurons express N- and P/Q, but not L-type voltage-gated Ca2þ channels. We conclude that the ADP in myenteric AH neurons, in the presence of an L-type Ca2þ-channel blocker, is generated by the opening of Ca2þ-activated non-selective cation channels following action potential-mediated Ca2þ entry mainly through N-type Ca2þ channels. Ca2þ release from ryanodine-sensitive stores triggered by Ca2þ entry contributes signi¢cantly to the activation of this current. F 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved