Correlation Between Behavioral Alteration to Chronic Cocaine Treatment and G-Protein ADP-Ribosylation in Mice.

The role of Gi-proteins on cataleptic responses induced by SCH23390, a dopamine D1 receptor antagonist, and haloperidol, a mainly dopamine D2 receptor antagonist, one day after chronic cocaine treatment in mice was examined by injecting intravenously (i.v.) pertussis toxin, which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. SCH23390- and haloperidol-induced catalepsy was potentiated 3-24 h after administration of a single dose (5 and 10mg/kgi.v.) of the toxin, but not at 1 mg/kg. It was apparent that the longer the time interval between pertussis toxin and dopamine antagonists treatments, snd the higher the dose of pertussis toxin, the greater were the cataleptic reponses. Mice given subcutaneous administration (s.c.) of cocaine (10mg/kg) once every other day for 15 days (a total of 8 injections) exhibited an attenuated SCH23390-induced catalepsy (SCH23390 catalepsy) and an enhanced haloperidol-induced catalepsy (haloperidol catalepsy9 one day after the last cocaine injection.The inhibitory effect of chronic cocaine treatment on SCH23390 catalepsy was enhancing effect of that on haloperidol catalepsy was fuether enhanced with same dose of toxin. These results suggest that there may be an interrelationship between Gi-protein ADP-ribosylation and D2 receptor subsensivity (enhanced haloperidol catalepsy) induced by chronic cocaine treatment, whereas an opposite relationship exists between D1 peceptor supersensitivity (attenuation of SCH23390 catalepsy) induced by chronic cocain treatment and the ribosylation. Accordingly, behavioral sensitization (reverse tolerance) seen one day after chronic cocaine treatment, which result in D1 ewcwptor supersensitivity and D2 receptor subsensitivity may not involve Gi protein ADP-rebosylation

Analysis of the relationship between prescribed dose and dosimetric advantage of real-time intraoperatively built custom-linked seeds in iodine-125 prostate brachytherapy

Abstract Background The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. Methods We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. Results The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. Conclusions Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone