Kinetic analyses of alcohol-induced potentiation of the response of GABA(A) receptors composed of alpha(1) and beta(1) subunits.

To investigate the kinetics of both the potentiation and desensitization of the response of ionotropic GABA receptors (GABA(A) receptors) in the presence of various compounds, we expressed receptors composed of alpha(1) and beta(1) subunits by injecting cells with the cRNAs synthesized from cloned bovine GABA(A) receptor cDNAs and measured the electrical responses of the cells electrophysiologically with or without the compounds. The potentiation of the GABA(A) receptor-mediated response was quantitatively analyzed using a simple model with the assumption that the receptors have two identical binding sites for GABA molecules with a dissociation constant of K(1), and one potentiation site for the compound with a dissociation constant of K(p), and that the binding of the compound to the potentiation site only increases the affinity of the GABA binding sites, changing K(1) to K(1p). The estimated K(p) and K(1p) were dependent on the functional groups and the chain length of the compounds. These results could be satisfactorily analyzed using this simple model. The potentiation of the GABA(A) receptor-mediated response by the components of essential oils used for aromatherapy was also examined. These compounds accelerated the decay of the response, possibly due to desensitization of the receptors, which was also analyzed on the basis of the model.

The effect of soybean oil refuse powder used as vehicle on the absorption of oxolinic acid in chickens under fasting and nonfasting conditions and the correlation with in vitro dissolution.

The effect of soybean oil refuse powder (SOR) when used as a vehicle on the absorption of oxolinic acid (OXA) powder in chicken, the dissolution profile of OXA and the correlation between in vivo and in vitro study were examined. To examine in vivo bioavailability, chickens fed or fasted were studied using a 2 x 2 crossover design. The OXA was administered OXA or OXA-SOR (1 : 9) mixture 20 mg OXA/kg. In vitro dissolution rates for OXA and OXA-SOR were measured using the paddle (PD) and the rotatory dialysis cell dissolution (PTSW) methods. Maximum plasma concentration (Cmax) and area under the curve (AUC) were significantly increased by the addition of SOR to OXA. Differences between OXA and OXA-SOR were more remarkable under fasted as compared with fed condition. In vitro dissolution rates of OXA-SOR pH 1.2, 6.5 and 7.2 as determined by the PD and the PTSW methods were increased in the presence of SOR vehicle. Differences between OXA and OXA-SOR in vitro dissolution rates were greater than in vivo bioavailability. Correlation between in vitro release (%) and in vivo absorption (%) showed good linearity (gamma=0.8805-0.9999).

Scintigraphic study on the distribution of radiolabeled cis-diamminedichloroplatinum (II) in the tumor-bearing rabbit: a comparison between intra-arterial injection with lipiodol and intravenous injection.

To compare the distribution of cis-diamminedichloroplatinum (II) (CDDP) on scintigraphic images between intra-arterial injection with lipiodol and intravenous injection, we obtained serial scintigraphic images using radiolabeled CDDP (Pt-195m CDDP), which had a high specific activity (7.4 x 10(6) Bq [200 microCi]/mg-CDDP), in the rabbit VX-2 tumor system. A dose of 9.25 x 10(6) Bq (250 microCi) of Pt-195m CDDP was injected at one shot via an ear vein, while 7.4 x 10(6) Bq (200 microCi of Pt-195m CDDP mixed with 1 ml of lipiodol was injected at one shot via a saphenous artery. Mean pixel count, which was corrected for the total dose injected, in the arterially injected tumor always exceeded than that in the intravenously injected tumor. Pt-195m CDDP uptake by the rabbit tumor at 2 hr was 7.8% of the total injected dose with intravenous injection and 16.0% with intra-arterial injection. These data suggest that intra-arterial injection with lipiodol is a more useful method to increase CDDP uptake by tumors than intra-venous injection.

[Temperature distribution and geometry of the electrodes in RF interstitial hyperthermia using circular and interstitial electrodes].

To evaluate the feasibility of clinical application of a newly developed interstitial hyperthermia system, which consists of an 8 MHz radiofrequency generator, interstitial needle electrodes, and a superficial circular electrode, we conducted preclinical experiments using an agar phantom and VX-2 carcinoma in the rabbit. In the experiment with an agar phantom, four 4 cm needle electrodes were placed in a square array at intervals of 1.0, 1.5, and 2.0 cm. Thermography demonstrated homogeneous temperature distribution at electrode intervals of 1.0 and 1.5 cm, but hot spots around the electrodes at an interval of 2.0 cm. When electrode deviation was less than 8 degrees from the parallel plane, no temperature deviation was observed. Using two 2 cm electrodes and two 4 cm electrodes in square array, thermography demonstrated a homogeneous temperature distribution in the area surrounded by the electrodes. Even if the electrodes were located at the periphery of the agar phantom, a homogeneous temperature distribution was obtained in the area surrounded by the electrodes. Using four 4 cm electrodes at intervals of 1.5 cm in VX-2 carcinoma in the rabbit, ideal heating was obtained: 42 degrees C at the periphery of the tumor and 43 degrees C at the center. These data suggest that the newly developed interstitial hyperthermia apparatus provides homogeneous heat distribution at electrode intervals of 1.5 cm or less and can be used in a Phase I study for deep-seated or superficial tumors.