An Australian experience of using work practices to establish an exposure model for shearers.

This is an example of a national regulatory approach in estimating worker exposure to pesticide residues in wool.

Electrophysiological properties of neurons in intact rat dorsal root ganglia classified by conduction velocity and action potential duration.

1. L4 and L5 dorsal root ganglia of rats aged 4-5 wk were isolated in vitro with their dorsal roots and sciatic nerves intact. With the use of intracellular microelectrodes, conduction velocity (CV) was determined along both peripheral and central axons and active and passive membrane properties were investigated with the use of a single-electrode switching clamp. 2. Neurons were classified into one of the three subgroups, A alpha/beta, A delta, and C, on the basis of a combination of axonal CV and action potential duration. Soma diameters overlapped between these groups. 3. Action potentials elicited by nerve stimulation in all cells and by a somatic current step in A alpha/beta-cells were always blocked by tetrodotoxin (TTX) 0.1-1 microM), whereas somatic action potentials in a proportion of A delta-cells and all C cells were TTX-resistant. 4. Passive electrical properties differed significantly between A alpha/beta-, A delta-, and C cells. The contribution of the additional membrane of the axons to the recorded electrical properties was analyzed with the use of a compartmental model of the neurons (see APPENDIX). 5. Most neurons discharged only a single action potential at the onset of a depolarizing current step, but 33% of A alpha/beta-cells fired repetitively throughout the step. This was associated with a lower threshold for action potential initiation by depolarizing current and a shorter afterhyperpolarization than in other A alpha/beta-cells. 6. Afterhyperpolarizations varied in size and duration between neurons and most were either not or only slightly affected by replacing Ca2+ in the bathing solution with Co2+ or Ba2+ or by adding tetraethylammonium (1 and 10 mM). Outward tail currents following an active response could be fitted with one fast exponential (time constant = 13 +/- 1 ms, mean +/- SE) and, in 65% of cells, one to three slower time course currents (to which exponentials with time constants of approximately 50, 300, or 1,500 ms could be fitted). A very slow late-onset current (detected in 33% of C cells) resembled a Ca(2+)-dependent K+ conductance described in several other neurons. 7. Voltage transients showed "sag" during maintained hyperpolarizing current steps in 90% of A alpha/beta-cells and 70% of A delta-cells but only 13% of C cells. Time-dependent inward currents were recorded when membrane potential was hyperpolarized. These currents had mean activation time constants of approximately 40 ms at -120 mV and were Cs+ sensitive and Ba2+ insensitive. 8. The proportion of neurons with a transient outward current, IA, increased as CV decreased (36% of A alpha/beta-cells, 56% of A delta-cells, 63% of C cells). Outward currents in cells of all subgroups had either one or two of three inactivation time constants (means approximately 22, 120, and 800 ms). 9. This study shows that many of the electrical characteristics of isolated dorsal root ganglion neurons can be demonstrated in intact ganglia in which the neurons can be better identified functionally. The currents underlying the afterhyperpolarization in these cells are diverse across all subgroups and require further investigation. The electrical effects of retaining the axonal projections of the cells and the use of microelectrodes filled with 0.5 M KC1 are discussed in relation to the differences from data recorded in dissociated neurons.

Noradrenaline effects on cultured rat sensory neurones exposed to morphine in utero or in vitro.

Dorsal root ganglion (DRG) neurones cultured from newborn rats were chronically exposed to 1 microM morphine. Untreated cells and in vitro morphine treated cells were cultured for 1 or 2 weeks from control offspring while in utero morphine treated cells were cultured for 1 week from offspring of morphine dependent rats. Noradrenaline (1 microM) was applied by pressure ejection. Intracellular recordings measured the change in action potential duration (APD). Noradrenaline significantly decreased the APD of 1-week-old untreated cells while the 2-week-old untreated cells and the groups of morphine treated cells showed no significant change of APD following the drug application. Thus, newborn rat DRG neurones demonstrated a different sensitivity to noradrenaline with the culture duration or with morphine exposure.

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

Orally administered salbutamol undergoes an extensive first-pass effect. This study investigated the roles of the intestine (INT), liver (HEP), and lung (LUN) in salbutamol extraction. Salbutamol was administered to five groups of anesthetized rabbits by the following routes: intraduodenal (ID) (800 micrograms/kg), intraportal (IP), (60 micrograms/kg), intrajugular (IV) (60 micrograms/kg), endotracheal (ET) (60 micrograms/kg), and intraarterial (IA) (60 micrograms/kg). Multiple blood samples were drawn and the areas under salbutamol plasma concentrations-time curves (AUCs) were calculated. Since IA salbutamol administration generated 100% bioavailability (F), AUCIA was used as a reference for comparison. Salbutamol F values for the ID, IP, IV, and ET routes were 0.013, 0.15, 0.53, and 0.53, respectively. The ratio of the AUC of salbutamol administered before the organ (ID, IP, IV, or ET) to the AUC estimated when given after the organ (IP, IV, and IA) allowed assessment of the extraction ratio (E) of INT, HEP, and LUN, respectively. EINT was 0.92, EHEP was 0.71, and ELUN was 0.47. The mean ratio of the AUC of the metabolite (AUCM) over the AUC of the parent compound was 704 +/- 77 for the ID, compared with 83 +/- 12 for the IP, 11 +/- 1 for the IV, 1.7 +/- 0.3 for the ET routes, and 4 +/- 1 for the IA routes. On the other hand, when the AUCM was normalized by the dose, this ratio was INT = HEP > LUN, suggesting that the ability of INT to conjugate salbutamol is not very important.(ABSTRACT TRUNCATED AT 250 WORDS)