Life sciences
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C57BL/6J (B6) mice self-administer substantial quantities of morphine compared to DBA/2J (D2) mice, and most of the genetic component of this strain difference has been attributed to a locus on chromosome 10 in the vicinity of the mu opioid receptor gene. To compare binding characteristics of mu opioid receptor populations between the two strains, mice were given single daily injections of a long-acting preparation of morphine sulfate (80 mg/kg, s.c.) or saline for a period of seven days, and euthanatized six hours after the last injection. Brains were removed and dissected into specific regions. ⋯ After repeated morphine injection, B6 mice exhibited a decrease in striatal [3H]DAMGO binding, indicating a downregulation of receptor density by approximately 45% (p=.0003 vs saline-treated B6), a phenomenon not observed in D2 mice. In frontal cortex, no differences in [3H]DAMGO binding were observed between strains or treatment groups. These results demonstrate a significant difference between mu opioid receptor regulation in B6 and D2 mice, and may underlie well documented strain differences in specific opioid-related behaviors.
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Tachyphylaxis to peripheral neural blockade was determined with repeated injections of a constant dose of lidocaine in three experimental models: sciatic nerve block, produced by intraneural or extraneural injections, and infiltration anesthesia. A decrease in the duration of the subsequent blocks was used as the index of tachyphylaxis development. The anesthetic content in the nerve or skin was determined using radiolabeled lidocaine. ⋯ Accelerated decline in lidocaine content of nerve or skin was observed with repeated blocks. Our data show that tachyphylaxis rapidly develops with both sciatic nerve blocks and infiltration anesthesia. The data also suggest that the mechanism is largely pharmacokinetic in nature.
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Jasmine green tea is an excellent source of natural polyphenol antioxidants including mainly (-) epicatechin (EC), (-) epicatechin gallate (ECG), (-) epigallocatechin (EGC) and (-) epigallocatechin gallate (EGCG). The present study was to test our hypothesis that ingestion of jasmine tea would protect red blood cell (RBC) membrane from free radical-induced oxidation if jasmine tea epicatechin isomers could be absorbed and circulated in blood. When incubated with RBC suspension, all four epicatechin isomers purified from jasmine tea exhibited a strong protection for RBC membrane to hemolysis induced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride (AAPH), an azo free radical initiator. ⋯ Although the in vitro antioxidative activity of EGCG and ECG was more effective than EGC and EC, the latter two isomers were more important in vivo in scavenging free radicals. This was because only EGC and EC instead of EGCG and ECG were circulating in blood stream after a gavage-dose of 100 mg jasmine tea GTP mixture. In fact, ingestion of jasmine tea GTP extracts was associated with a significant decrease in susceptibility of RBC to hemolysis in rats.
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At this time little is know about local anesthesia of the skin, and the sensitivity of different cutaneous regions to local anesthetics. Studies were conducted in mice to test the hypothesis that cutaneous regions are differentially sensitive to bupivacaine, and to the ability of epinephrine (EPI) to prolong local anesthesia. Infiltration of 0.25% and 0.5% bupivacaine s.c. in the dorsal aspect of the mouse tail produced local anesthesia that lasted 15 and 45 min, respectively, against radiant heat nociception. ⋯ Bupivacaine (0.25% and 0.5%) infiltrated in the dorsal aspect of the hind-paw produced local anesthesia that lasted 5 and 30 min, respectively. EPI prolonged the local anesthetic effects of the 0.25% concentration by only 10 min, whereas EPI did not prolong anesthesia but appeared to increase the efficacy of the 0.5% concentration. These results provide evidence of regional differences in cutaneous sensitivity to local anesthetics, and the ability of EPI to extend the duration of anesthesia.
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We administered methylnaltrexone, a peripheral opioid receptor antagonist, to guinea pigs previously injected with morphine sulfate to determine whether the compound could block opioid-induced cough suppression without blocking antinociception. The effects of methylnaltrexone (2.0, 1.6, 0.8 mg/kg) and of naltrexone (0.32, 0.16, 0.02 and 0.01 mg/kg) were compared in animals who had been injected with morphine sulfate (8.1 mg/kg). ⋯ Our results suggested that methylnaltrexone possesses opioid antagonist activity in receptors peripheral to the blood-brain barrier. Its peripheral activity makes methylnaltrexone a clinically interesting agent for maintaining the cough reflex in those who must take opioids for analgosia.