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A B S T R A C T When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V0, was concurrent with the observations that (a) a high resistance outer barrier Ro accounting for approximately 75% or more of the transcellular resistance of control skins had been penetrated and that (b) 10 -5 M amiloride and reduced [Na] outside caused the values of V o to increase towards mean values near -130 mV while the values of %Ro increased to >90%. It was of interest to observe that the values of E1 observed in studies of the current-voltage relationships were the same as the values of E~ defined as the values of voltage at the inner barrier when the Vo of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of El, --130 mV, represent the E Na of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of Vo to low negative values in approximately 10-15 min. For all values of transepithelial voltage

Tacrolimus is a marketed immunosuppressant used in liver and kidney transplantation. It is subject to extensive metabolism by CYP3A4 and is a substrate for P-glycoprotein-mediated transport. A pharmacokinetic interaction with rifampin, an antituberculosis agent and potent inducer of CYP3A4 and P-glycoprotein, and tacrolimus was evaluated in six healthy male volunteers. Tacrolimus was administered at doses of 0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected over 96 hours, after single oral and intravenous administration prior to and during an 18-day concomitant rifampin dosing phase. Coadministration of rifampin significantly increased tacrolimus clearance (36.0 +/- 8.1 ml/hr/kg vs. 52.8 +/- 9.6 ml/hr/kg; p = 0.03) and decreased tacrolimus bioavailability (14.4% +/- 5.7% vs. 7.0% +/- 2.7%; p = 0.03). Rifampin appears to induce both intestinal and hepatic metabolism of tacrolimus, most likely through induction of CYP3A and P-glycoprotein in the liver and small bowel.

Our study shows that police officers trained in naloxone administration can correctly recognize symptoms of opioid overdose, and can appropriately administer naloxone without significant adverse effects or outcomes. Furthermore, the administration of police naloxone does not result in a significant incidence of combativeness or need for scene escalations such as immediate detention. Further research is needed to investigate the impact of police naloxone; specifically, comparing outcomes of police delivery to EMS alone, as well as the impact on rural opioid overdoses.

A B s T a A C T Studies were done with isolated frog skin to determine the effects of 10 -4 M ouabain on the electrophysiological parameters of outer and inner barriers of the Na-transporting cells. Microelectrodes were used to impale the skins from the outer surface to determine the intracellular voltages (V~o) under conditions of short-circuiting and under conditions where a voltage clamp was used to vary the transepithelial voltage, V T. From this, the electrical resistances of outer (RS0) and inner (R 0 barriers were estimated. In addition, the driving force for active transepithelial Na transport (Esa = E't) was estimated from the values ofV T when the V o --0 mV (Helman and Fisher. 1977. J. Gen. Physid. 69: 571-604). Studies were done with skins bathed with the usual 2.4 meq/liter [K], in the inner solution as well as with reduced [K]t of 0.5 and 0 meq/liter. Characteristically, the responses to ouabain could be described by an inidal rapid phase (5-10 rain) during which time the R, was increased markedly and the E' 1 was decreased from control values. Thereafter, during the slow phases of the response, the resistances of both outer and inner barriers increased continuously and markedly with time leading ultimately to essentially complete inhibition of the short-circuit current. Similar studies were done with skins exposed to 10 -4 M amiIoride in the outer solution. Although estimates ofR ~ couM not be obtained under these conditions, the effects on the Imo and E't were similar to those observed for the Na-transporting skins. However, the magnitudes of the effects were less and relatively slower than observed for the Na-transporting skins. The results of these studies were analyzed within the context of a proposed electrical model that takes into account the observation that the magnitude of the voltage at the inner barrier appears to exceed the equilibrium potential for K especially when transepithelial Na transport is inhibited at the apical barrier of the cells.