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Anesthesiology. 2000 Oct;93(4):1034-44.
Effects of isoflurane, sevoflurane, and halothane on myofilament Ca2+ sensitivity and sarcoplasmic reticulum Ca2+ release in rat ventricular myocytes.

Davies LA, Gibson CN, Boyett MR, Hopkins PM, Harrison SM.

School of Biomedical Sciences and the Academic Unit of Anaesthesia, University of Leeds, Leeds, United Kingdom.

BACKGROUND: The aim of this study was to describe and compare the effects of isoflurane, sevoflurane, and halothane at selected concentrations (i.e., concentrations that led to equivalent depression of the electrically evoked Ca2+ transient) on myofilament Ca2+ sensitivity, sarcoplasmic reticulum (SR) Ca2+ content, and the fraction of SR Ca2+ released during electrical stimulation (fractional release) in rat ventricular myocytes. METHODS: Single rat ventricular myocytes loaded with fura-2 were electrically stimulated at 1 Hz, and the Ca2+ transients and contractions were recorded optically. Cells were exposed to each anesthetic for 1 min. Changes in myofilament Ca2+ sensitivity were assessed by comparing the changes in the Ca2+ transient and contraction during exposure to anesthetic and low Ca2+. SR Ca2+ content was assessed by exposure to 20 mm caffeine. RESULTS: Isoflurane and halothane caused a depression of myofilament Ca2+ sensitivity, unlike sevoflurane, which had no effect on myofilament Ca2+ sensitivity. All three anesthetics decreased the electrically stimulated Ca2+ transient. SR Ca2+ content was reduced by both isoflurane and halothane but was unchanged by sevoflurane. Fractional release was reduced by both isoflurane and sevoflurane, but was unchanged by halothane. CONCLUSIONS: Depressed myofilament Ca2+ sensitivity contributes to the negative inotropic effects of isoflurane and halothane but not sevoflurane. The decrease in the Ca2+ transient is either responsible for or contributory to the negative inotropic effects of all three anesthetics and is either primarily the result of a decrease in fractional release (isoflurane and sevoflurane) or primarily the result of a decrease in SR Ca2+ content (halothane).

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11020759&dopt=Abstract

Hum Factors. 2000 Summer;42(2):183-94.
The effects of signal salience and caffeine on performance, workload, and stress in an abbreviated vigilance task.

Temple JG, Warm JS, Dember WN, Jones KS, LaGrange CM, Matthews G.

University of Cincinnati, Ohio 45221-0376, USA.

In 2 experiments, a 12-min computerized vigilance task was demonstrated to reproduce the vigilance decrement, high workload (NASA-TLX), and stressful character (Dundee Stress State Questionnaire) of vigilance tasks lasting 30 min or more. In Experiment 1, the abbreviated task was also shown to duplicate the signal salience effect, a major finding associated with long-duration vigilance tasks. Moreover, Experiment 2 showed that performance on the abbreviated task can be enhanced by caffeine - a drug that benefits long-duration tasks. This enhancement effect was limited to performance, however, suggesting that caffeine influences factors that control signal detection but not those that control task-induced stress. The results parallel those obtained with long-duration tasks and support a resource-depletion model of the vigilance decrement. The abbreviated task might be useful in situations in which long-duration tasks are precluded (e.g., performance assessment batteries, neuropsychological testing, and brain imaging).

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11022879&dopt=Abstract

Nat Cell Biol. 2000 Oct;2(10):686-94.
Temporally coordinated assembly and disassembly of replication factories in the absence of DNA synthesis.

Dimitrova DS, Gilbert DM.

Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA.

Here we show that exposure of aphidicolin-arrested Chinese hamster ovary (CHO) cells to the protein-kinase inhibitors 2-aminopurine or caffeine results in initiation of replication at successively later-replicating chromosomal domains, loss of the capacity to synthesize DNA at earlier-replicating sites, release of Mcm2 proteins from chromatin, and redistribution of PCNA and RPA from early- to late-replicating domains in the absence of detectable elongation of replication forks. These results provide evidence that, under conditions of replicational stress, checkpoint controls not only prevent further initiation but may also be required to actively maintain the integrity of stalled replication complexes.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11025658&dopt=Abstract

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