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Comparative results are presented on the effectiveness of rat-liver S9 or microsomal mix (M mix) in activating cyclophosphamide (CP) and its ability to induce a clastogenic effect in human lymphocytes in vitro. Structural chromosome changes were analysed exclusively in 1st division (M1) metaphases post-exposure. A high genotoxic response was observed for both metabolizing systems used. With an exposure of 2 h to different concentrations of S9 or M mix, the highest aberration yields were always found for the highest protein content. For CP treatment times of 1, 2 or 4 h together with S9 mix (protein content 10 mg/ml) or M mix (4 mg/ml), the latter was more efficient. With both systems, a lower clastogenic effect of CP was found at 4 h exposure than at 1 h or 2 h. Only a weak cytotoxic effect, reflected mainly by the reduction in the percentage of 3rd cycle cells (M3), and measured in terms of the proportion of M1, M2 and M3 cells, was induced by both systems. 相似文献
173.
Lena Lavie 《Chronobiology international》2013,30(1):115-128
There is evidence supporting an association between shift work and cardiovascular morbidity, but the underlying mechanisms are unknown. The present paper investigated the levels of cardiovascular biochemical risk factors in shift‐workers both with (n=26) and without (n=103) sleep complaints, and in day‐workers (n=173) working in the same plant. Blood samples were taken in the morning after an overnight fast and analyzed for homocysteine, C‐reactive protein, and lipid profile. Biochemical data were compared among groups after stratifying workers by age (i.e., <40 and ≥40 yrs). Shift‐workers who complained about sleep disturbances and who were ≥40 years of age had significantly higher levels of homocysteine than did their younger counterparts—shift‐workers who did not complain of sleep disturbances and day‐workers. There were no other between‐group differences in any of the biochemical variables. The results of this investigation demonstrate an association between sleep disturbances in older shift‐workers and mild hyperhomocysteinemia. The elevated homocysteine levels may play a role in the increased rates of cardiovascular morbidity in shift‐workers, and they may have practical implications regarding the nutrition of shift‐workers. 相似文献
174.
Nafizal Hossain Svetlana Ivanova Åsa Sjöholm Timén Jonas Bergare Tesfaledet Mussie Lena Bergström 《Bioorganic & medicinal chemistry letters》2013,23(14):4026-4030
A series of zwitterionic spirocyclic compounds were synthesised. In vitro data revealed that these compounds were potent CCR1 antagonists. In particular, 2, 4, 11 and 20 inhibited CCR1 mediated chemotaxis of THP-1 cells in a functional assay. 相似文献
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Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24–48 h inhibited voltage-gated Ca2+ channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable side effect of rosuvastatin treatment as it occurs through the same mechanisms as the lipid-lowering effects of the drug. 相似文献
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Wounding-Induced Stomatal Closure Requires Jasmonate-Mediated Activation of GORK K+ Channels by a Ca2+ Sensor-Kinase CBL1-CIPK5 Complex 总被引:1,自引:0,他引:1
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