Chronopharmacology of analgesic effect and tolerance induced by six narcotic analgesics in mice.

Narcotic analgesics, especially morphine, exert significantly different effects depending on the time within one day. The objective of this study was to observe whether the dosing time of 6 narcotic analgesics in mice affected their efficacy, pain tolerance and recovery of tolerance. The chronopharmacology of these 6 narcotics was evaluated using a hot-plate model. Maximum possible effect (MPE) of morphine showed a significant 24 h rhythm, which was higher during the dark phase and lower during the light phase (P<0.05). Conversely, MPEs of fentanyl and bucinnazine groups during the light phase exceeded those during the dark phase (P<0.05). Pain tolerance developed after drug administration at 9:00 am or 9:00 pm for 5 days, of which bucinnazine produced lower tolerance at 9:00 am. After a 2-day washout period, the mice rapidly recovered from tolerance at 3:00 pm for 5-day morphine dosing at 9:00 pm, and for fentanyl dosing at 9:00 am. Not all narcotic analgesics displayed significant circadian variations, and the dosing time-dependent effects also depended on the types of narcotics. Therefore, the time of administration is crucial in clinical pain treatment. Chronotherapy may be more effective to relieve pain while reducing side effects.

Effects of Panax ginseng extract on exercise-induced oxidative stress.

AIM: This study was designed to study the effects of Panax ginseng extract (PGE) on lipid peroxidation and scavenger enzymes induced by an acute exhaustive exercise in sedentary humans. METHODS: Seven healthy male subjects performed 2 exhaustive incremental exercises on the treadmill before and after 8 weeks' PGE ingestion (2 g each time, 3 times a day) as the control and PGE exercise, respectively. VO2, HR, and exercise duration during exercise were measured. Blood samples were collected at rest, and immediately, 10 and 30 min after each test and used to measure malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). RESULTS: PGE administration significantly increased exercise duration until exhaustion by 1.5 min (p<0.05). MDA was significantly elevated following both trials (p<0.01), however, it was attenuated after PGE administration (p<0.01). CAT and SOD activities following exercise were significantly elevated, but the activities following control exercise were much lower than those following PGE exercise. CONCLUSIONS: These results suggest that the elevation in CAT and SOD activities as scavenger enzymes after PGE administration result in decrease of MDA level as one of PGE action mechanisms and consequently, prolong exercise duration until exhaustion. These findings support scientific claims that ginseng has ergogenic properties in facilitating recovery from exhaustive exercise.

Protective effects of acetylbergenin against carbon tetrachloride-induced hepatotoxicity in rats.

The present study was undertaken to investigate whether or not the hepatoprotective activity of acetylbergenin was superior to bergenin in carbon tetrachloride (CCl4)-intoxicated rat. Acetylbergenin was synthesized by acetylating bergenin, which was isolated from Mallotus japonicus. The hepatoprotective effects of acetylbergenin were examined against CCl4-induced liver damage in rats by means of serum and liver biochemical indices. Acetylbergenin was administered orally once daily for 7 successive days, then a 0.5 ml/kg mixture of CCl4 in olive oil (1:1) was intraperitoneally injected at 12 h and 36 h after the final administration of acetylbergenin. Pretreatment with acetylbergenin reduced the elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content dose dependently in CCl4-intoxicated rats. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored to almost normal levels. The results of this study strongly suggest that acetylbergenin has potent hepatoprotective activity against CCl4-induced hepatic damage in rats by glutathione-mediated detoxification as well as having free radical scavenging activity. In addition, acetylbergenin doses of 50 mg/kg showed almost the same levels of hepatoprotective activity as 100 mg/kg of bergenin, indicating that lipophilic acetylbergenin is more active against the antihepatotoxic effects of CCl4 than those of the much less lipophilic bergenin.

Trimethoprim-sulfamethoxazole compared to ampicillin in the treatment of shigellosis.

Twenty hospitalized children between 1 and 11 years of age were enrolled in a comparative randomized evaluation of trimethoprim-sulfamethoxazole (TM-SM) and ampicillin for the treatment of shigellosis. Each drug was provided for five days. The group treated with ampicillin had significantly more stools per day (mean 21.25) compared to the TM-SM group (8.64). Treatment with TM-SM appeared to be associated with a more rapid reversion of stool cultures to normal, but these differences compared to ampicillin were not statistically significant. Review of all isolates of Shigella from our hospital revealed a marked decrease in sensitivity to ampicillin over the last six years. This pattern has been observed in other centers. TM-SM may be the best drug for the treatment of shigellosis in areas where multiple antibiotic-resistant organisms are common.