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31.
本文采用小鼠精子试验和小鼠睾丸DNA合成抑制试验,检测了JX-1对雄性生殖细胞的致突变作用。实验结果表明JX-1对小鼠精子总数、精子活动率及精子畸形率均无统计学意义的增加,与小鼠睾丸DNA合成抑制试验阴性反应一致。作者认为JX-1对雄性生殖细胞为一种非诱变剂。 相似文献
32.
David K.H. Lee 《Drug development research》1986,9(4):305-311
The effect of acute and subchronic dosing with etodolac on the renal PGE2 and 6-keto-PGF1α concentrations in the normal rat were studied. Etodolac and other nonsteroidal antiinflammatory drugs (NSAIDs) were administered orally, at equieffective antiinflammatory doses, to normal rats either as a single dose or as seven daily doses. Whole kidney prostaglandin (PG) concentrations were measured. In the acute study, etodolac (3 mg/kg) did not significantly lower the PGE2 levels for up to 4 hr postdosing. In contrast, naproxen (3 mg/kg) and piroxicam (0.5 mg/kg) significantly decreased the PGE2 levels to about 20% and 60% of control, respectively. Similar reductions in 6-keto-PGF1α concentrations were observed. In the subchronic study, etodolac (3 mg/kg/day) did not lower either PGF2 or 6-keto-PGF1α concentrations whereas naproxen (3 mg/kg/day), piroxicam (0.5 mg/kg/day), indomethacin (1 mg/kg/day), and aspirin (300 mg/kg/day) significantlydecreased both PGs. In both studies, the effect of etodolac was significantly different from that of the NSAIDs. It is concluded that etodolac possesses only a very weak capacity to lower renal PGs, and therefore is unlikely to cause any renal complications related to PG biosynthesis inhibition. 相似文献
33.
Teresa W. Tam Rui Liu John T. Arnason Anthony Krantis William A. Staines Pierre S. Haddad Brian C. Foster 《Journal of ethnopharmacology》2009,126(1):119-126
Aim of the study
Cree traditional medicine is commonly used concomitantly with prescribed drugs to treat health problems related to type II diabetes (T2D) that is endemic in the Cree population. However, the safety of traditional Cree medicines with respect to drug metabolism is unknown.Materials and methods
Seventeen anti-diabetic plant extracts were screened for their potential inhibition of 11 isoforms of the drug-metabolizing cytochrome P450s (CYPs), and flavin-containing monooxygenase 3 (FMO3) in fluorometric plate reader assays. Comparative analyses were conducted to determine if particular extracts were more inhibitory, or if particular enzymes were more inhibited.Results
Many anti-diabetic plant extracts inhibited the CYPs, with CYP2C and 3A isoforms being most prone to inhibition. The order of inhibition for the enzymes by the Cree plant extracts was: 2C19 > 3A7 > 3A5 > 3A4 > 2C9 > 2C8 > FMO3 > 1A2 > 2E1 > 19 > 2D6 > 2B6. Extracts from Rhododendron groenlandicum, Sorbus decora, and Kalmia angustifolia were identified as having strong inhibition towards many CYP isoforms.Conclusion
These findings demonstrate that extracts from most plant species examined have the potential to affect CYP2C- and 3A4-mediated metabolism, and have the potential to affect the bioavailability and pharmacokinetics of conventional and traditional medicines during concomitant use. 相似文献34.
R. K. Vesalainen K. U. O. Tahvanainen T. J. Kaila I. M. Kantola T. A. Kuusela D. L. Eckberg 《Clinical physiology and functional imaging》1997,17(2):135-133
We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double-blind, placebo-controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat R–R interval and systolic, mean and diastolic pressures. R–R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R–R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R–R interval and its mid- (0·07–0·15 Hz) and high- (0·15–0·40 Hz) frequency band power in the standing position during controlled breathing at 0·25 Hz. In the supine position, scopolamine did not affect R–R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory–inspiratory R–R interval ratio. This study showed that low-dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects. 相似文献
35.
We attempted to find out the role of α2-adrenoceptors of the medullary lateral reticular nucleus (LRN) in antinociception in rats. Spinal antinociception was evaluated using the tail-flick test, and supraspinal antinociception using the hotplate test. Antinociceptive effects were determined following local electric stimulation of the LRN, and following microinjections of medetomidine (an α2-adrenoceptor agonist; 1–10 μg), atipamezole (an α2-adrenoceptor antagonist; 20 μg) or lidocaine (4%) into the LRN. The experiments were performed using intact and spinalized Hannover-Wistar rats with a unilateral chronic guide cannula. Electric stimulation of the LRN as well as of the periaqueductal gray produced a significant spinal antinociceptive effect in intact rats. Medetomidine (1–10 μg), when microinjected into the LRN, produced no significant antinociceptive effect in the tail-flick test in intact rats. However, following spinalization, medetomidine in the LRN (10 μg) produced a significant atipamezole-reversible antinociceptive effect in the tail-flick test in the hot-plate test, medetomidine (10 μg) in the LRN produced a significant atipamezole-reversible increase of the paw-lick latency in intact rats. Microinjection of atipamezole (20 μg) or lidocaine alone into the LRN produced no significant effects in the tail-flick test. The results are in line with the previous evidence indicating brat the LRN and the adjacent ventrolateral medulla is involved in descending inhibition of spinal nocifensive responses. However, α2-adrenoceptors in the LRN do not mediate spinal antinociception but, on the contrary, their activation counteracts antinociception at the spinal cord level. The spinal aninociceptive effect of supraspinally administered medetomidine in spinalized rats can be explained by a spread of the drug (e.g., via circulation) which then directly activates α2-adrenoceptors at the spinal cord level. 相似文献
36.
37.
Double-labelling and electron microscopy were used to assess the distribution of GABAergic synapses made onto the neurites of spiking local interneurones in the locust. The aims were to determine the sites of inputs mediating inhibition of the spiking local interneurones and to ascertain the relative abundance of such inputs. This information should allow us to understand better the integrative properties of these spiking local interneurones and the role of inhibition in shaping their receptive field properties or in fine tuning their spike-mediated outputs. Spiking interneurones in a midline population were labelled by intracellular injection of horseradish peroxidase after physiological characterisation. Colloidal gold immunocytochemistry was then used on ultrathin sections of these neurones with a polyclonal antibody raised against GABA. Most GABAergic (inhibitory) input synapses onto the interneurones are made on their ventral neurites, which also receive afferent (excitatory) inputs. These inhibitory inputs to the ventral neurites constitute 43% of the identifiable synapses. Relatively few GABAergic inputs were found onto the dorsal neurites, which are predominantly the sites of output synapses from these interneurones. These results suggest that much synaptic integration takes place in the ventral field of branches and that GABA-mediated presynaptic inhibitory control of spike-mediated outputs from the dorsal neurites is unlikely to occur. © 1993 Wiley-Liss, Inc. 相似文献
38.
Amphetamine-induced mesolimbic dopamine release has been reported to reduce prepulse inhibition of the acoustic startle response. In addition, it is well known that mesolimbic dopamine stimulation leads to hyperactivity. The present study was undertaken to explore the possibility that one or the other measure may be a more sensitive in vivo indicator of dopamine release in the nucleus accumbens by determining if the amphetamine dose-response curves for these two behavioral measures were different. The data indicate that the dose-response curves obtained for the different behavioral measures are identical. These data are consistent with the idea that the same dopamine terminal field supports both prepulse inhibition of the acoustic startle response and dopamine-stimulated hyperactivity. 相似文献
39.
Michael Davis Robert S. Mansbach Neal R. Swerdlow Serge Campeau David L. Braff Mark A. Geyer 《Psychopharmacology》1990,102(1):1-4
Separate experiments conducted in two different laboratories assessed the importance of the prepulse intensity in the ability of apomorphine to reduce prepulse inhibition of acoustic startle responses. Rats were presented with noise bursts alone or noise bursts 100 ms after presentation of prepulse stimuli ranging from 70 to 85 or 90 dB. Throughout testing, the background noise was maintained at 65 dB. In both laboratories, apomorphine markedly decreased the absolute magnitude of prepulse inhibition when the prepulse stimuli were no more than 10 dB above the background. With more intense prepulse stimuli, apomorphine had no significant effect on prepulse inhibition. Hence, apomorphine does not interfere with the inhibitory process which actually mediates prepulse inhibition, but appears to affect the detectability of the prepulse. 相似文献
40.
MP Costi D Tondi M Rinaldi D Barlocco G Cignarella DV Santi C Musiu I Pudu G Vacca P La Colla 《European journal of medicinal chemistry》1996,31(12):1011-1016
A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds. 相似文献