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1.
Loy S. F.; Conlee R. K.; Winder W. W.; Nelson A. G.; Arnall D. A.; Fisher A. G. 《Journal of applied physiology》1986,61(2):654-659
Ten competitive cyclists were exercised to exhaustion to test the potential of a 24-h fast for increasing endurance. One group (n = 4) was tested at an initial intensity of 86% maximum O2 uptake (VO2max) (HI) and a second group (n = 6) at 79% VO2max (MI). Both groups repeated test rides in fasted and normal-diet conditions. Time to fatigue was designated at two points: fatigue 1 occurred when pedal frequency could not be maintained at the initial percent VO2max; fatigue 2 occurred when pedal frequency could not be maintained at a workload of approximately 65% VO2max. In both HI and MI the 24-h fast had no effect on resting muscle glycogen stores but significantly increased plasma free fatty acid (FFA) levels. Despite the increased FFA availability, time to fatigue was reduced in the fasted groups. Fatigue 1 and 2 times (mean +/- SE) for HI-fasted were 42.0 +/- 6.2 and 170.0 +/- 20.4 min, respectively, compared with those of the HI-normal diet of 115.3 +/- 25.6 and 201.0 +/- 14.8 min. Fatigue 1 and 2 times for MI-fasted were 142.0 +/- 19.6 and 167.5 +/- 10.5 min compared with those of the MI-normal diet of 191.3 +/- 25.0 and 214.3 +/- 18.9 min. The cause of fatigue at fatigue 1 was not readily apparent. Fatigue 2 in all groups seemed to be related to hypoglycemia as well as muscle glycogen depletion. 相似文献
2.
The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds. 相似文献
3.
Hrushikesh S. Chaudhari Omkar S. Palkar KM Abha Mishra Kalyan K. Sethi 《Journal of biochemical and molecular toxicology》2023,37(9):e23417
During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B ( 1 ) and isavuconazole ( 2 ) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole ( 3 ) and deferasirox ( 4 ) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 ( 5 ) and APX001A ( 6 ), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis. 相似文献
4.
Cytochrome P-448 (mol wt 55,000 Daltons) from rabbit liver was purified to a specific content of 16.6 nmol/mg. Mice were immunised with this preparation, their spleens removed and dissociated lymphocytes hybridised with myeloma cells. Four monoclonal antibodies against cytochrome P-448 were raised and partially characterised. All four antibodies interacted with cytochrome P-448 in intact microsomal fractions and selectively immunoadsorbed cytochrome P-448 from solubilised microsomal preparations. One of the antibodies inhibited benzo[a] pyrene hydroxylase activity in a reconstituted system, one had no effect on activity and two increased activity. The possible applications of such antibodies are discussed. 相似文献
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V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
7.
Haffner CD McDougald DL Reister SM Thompson BD Conlee C Fang J Bass J Lenhard JM Croom D Secosky-Chang MB Tomaszek T McConn D Wells-Knecht K Johnson PR 《Bioorganic & medicinal chemistry letters》2005,15(23):5257-5261
We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. 相似文献
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10.
R K Conlee C M Tipton 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1975,149(2):473-475
This study was undertaken because of uncertainties regarding the influence of hormones on myocardial glycogen metabolism of fed and fasted rats. The results indicate that adrenal hormones exert a stabilizing effect on myocardial glycogen levels in fed animals but are not necessary for synthesis to occur. Hypophysectomy eliminates the glycogen increase that occurs from fasting in normal animals while insulin deficiency leads to elevated glycogen stores in both fed and fasted conditions. These findings suggest that changes in myocardial glycogen metabolism are the results of a synergetic relationship between a variety of hormonal and nutritional factors. 相似文献