The Antibacterial Action of Anaesthetic Vapours

Horton, J. N.; Sussman, Marcy L.; Mushin, William W.

doi:10.1093/bja/42.6.483

Cited by 17 publications

(7 citation statements)

References 10 publications

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“…halothane; eukaryotic translation initiation factor 2␣ phosphorylation; mammalian target of rapamycin pathway ALTHOUGH VOLATILE ANESTHETICS revolutionized medical practice when introduced in 1846, the mechanisms of action responsible for the physiological effects of these drugs remain essentially unknown. In addition to affecting cells of the central nervous system, these drugs affect all cells, tissues, and organisms examined (4,26,36). Molecular genetic studies with the small, relatively simple eukaryote Saccharomyces cerevisiae (yeast) provide an opportunity for gaining insight regarding physiologically relevant effects of these drugs (28) and generating hypotheses that are testable in more complex eukaryotes.…”

mentioning

confidence: 99%

“…In addition to affecting cells of the central nervous system, these drugs affect all cells, tissues, and organisms examined (4,26,36). Molecular genetic studies with the small, relatively simple eukaryote Saccharomyces cerevisiae (yeast) provide an opportunity for gaining insight regarding physiologically relevant effects of these drugs (28) and generating hypotheses that are testable in more complex eukaryotes.…”

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confidence: 99%

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Inhibition of mammalian translation initiation by volatile anesthetics

Palmer¹,

Rannels²,

Kimball³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Volatile anesthetics are essential for modern medical practice, but sites and mechanisms of action for any of their numerous cellular effects remain largely unknown. Previous studies with yeast showed that volatile anesthetics induce nutrient-dependent inhibition of growth through mechanisms involving inhibition of mRNA translation. Studies herein show that the volatile anesthetic halothane inhibits protein synthesis in perfused rat liver at doses ranging from 2 to 6%. A marked disaggregation of polysomes occurs, indicating that inhibition of translation initiation plays a key role. Dose-and time-dependent alterations that decrease the function of a variety of translation initiation processes are observed. At 6% halothane, a rapid and persistent increase in phosphorylation of the ␣-subunit of eukaryotic translation initiation factor (eIF)2 occurs. This is accompanied by inhibition of activity of the guanine nucleotide exchange factor eIF2B that is responsible for GDP-GTP exchange on eIF2. At lower doses, neither eIF2␣ phosphorylation nor eIF2B activity is altered. After extended exposure to 6% halothane, alterations in two separate responses regulated by the target of rapamycin pathway occur: 1) redistribution of eIF4E from its translation-stimulatory association with eIF4G to its translation-inactive complex with eIF4E-binding protein-1; and 2) decreased phosphorylation of ribosomal protein S6 (rpS6) with a corresponding decrease in active forms of a kinase that phosphorylates rpS6 (p70 S6K1 ). Changes in the association of eIF4E and eIF4G are observed only after extended exposure to low anesthetic doses. Thus dose-and time-dependent alterations in multiple processes permit liver cells to adapt translation to variable degrees and duration of stress imposed by anesthetic exposure. halothane; eukaryotic translation initiation factor 2␣ phosphorylation; mammalian target of rapamycin pathway ALTHOUGH VOLATILE ANESTHETICS revolutionized medical practice when introduced in 1846, the mechanisms of action responsible for the physiological effects of these drugs remain essentially unknown. In addition to affecting cells of the central nervous system, these drugs affect all cells, tissues, and organisms examined (4,26,36). Molecular genetic studies with the small, relatively simple eukaryote Saccharomyces cerevisiae (yeast) provide an opportunity for gaining insight regarding physiologically relevant effects of these drugs (28) and generating hypotheses that are testable in more complex eukaryotes. Extensive similarities exist between the activity of these drugs in mammals and simpler eukaryotes, such as yeast, suggesting conservation of cellular mechanisms responsible for the responses (28,34,45). These similarities include rapid and reversible induction of responses, a sharp dose-response curve, correlation between the lipophilicity of various anesthetics and their potency for inducing responses (termed the Meyer-Overton relationship), additivity of doses of different anesthetics in producing effects, and lack of effec...

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confidence: 99%

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confidence: 99%

Inhibition of mammalian translation initiation by volatile anesthetics

Palmer¹,

Rannels²,

Kimball³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…This confirms the qualitative observations of Barry, Paiement and Dubeau (1964), who concluded that halothane and methoxyfiurane in the usual clinical concentrations had no antibacterial activity against S. aureus and E. coli. Horton, Sussman and Mushin (1970) showed a 55 per cent reduction in the count of E. coli deposited on cellulose acetate membranes when exposed to 3.1 per cent halothane. However, survival of bacteria in this state is precarious, and 3 hours exposure to air of high humidity resulted in a 17 per cent reduction of count; exposure to air of low humidity for the same time reduced the count almost to zero.…”

Section: Discussionmentioning

confidence: 93%

The Effect of Halothane on Bacterial Growth Rate

Wardley‐Smith¹,

Nunn²

1971

British Journal of Anaesthesia

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The growth rate of four species of non-pathogenic bacteria in broth was estimated spectrophotometrically. Exposure to halothane (1-10 per cent) vaporized in air produced a dose-dependent depression of growth rate, but for all species the effect was negligible at clinical concentrations of halothane. The ED M was within the range 7-8 per cent halothane for three species: 50 per cent inhibition was not obtained with 10 per cent halothane in the fourth species. Inhibition of division with 10 per cent halothane was delayed by 20-25 minutes which was close to the mean generation time. The effect was fully reversible although there was again a lag of about 20 minutes before division was resumed after withdrawal of halothane.

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“…Studies showed that cyclophosphamide can inhibit bacterial translocation of the gastrointestinal tract [43] and reduce the abundance of lactobacilli and enterococci [44] in mice. Des urane, en urane, iso urane, methoxy urane, and sevo urane are widely used volatile anesthetics [45,46], most of these anesthetics have demonstrated antibacterial properties in vitro [47][48][49][50]. An early in vitro experiment showed that methoxy urane and iso urane exhibited excellent antibacterial activity, while en urane had less effect on a few pathogens [48].…”

Section: Discussionmentioning

confidence: 99%

Screening of Antibacterial Compounds With Novel Structure From The FDA Approved Drugs Using Machine Learning Methods

Li¹,

Tong²,

Yang³

et al. 2021

Preprint

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Background: Due to the lack of new antibiotics in recent years, bacterial resistance has increasingly become a serious problem globally. The aim of this study is to construct an antibacterial compound predictor using machine learning methods to screen potential antibacterial drugs.Methods: Active and inactive antibacterial compounds were acquired from the ChEMBL and PubChem database, which were used to construct benchmark datasets. The antibacterial compound predictor is constructed using the support vector machine (SVM), random forest (RF), and multi-layer perception (MLP) methods. We predicted the antibacterial activity of the Food and Drug Administration (FDA) approved drugs in the DrugBank database and screened novel antibacterial drugs through structural similarity analysis.Results: In the initial screen process, the results suggested that the benchmark dataset based on FP2 molecular fingerprints, along with the SVM, RF, and MLP methods showed excellent prediction performance (mean AUC > 0.9 for all models). Using the combination of these three models, a total of 957 potential antibacterial drugs were predicted. Most of the predicted drugs showed low structural similarities compared with the FDA approved antibacterial drugs. We finally screened 9 predicted antibacterial drugs with novel structures including 2 anti-tumor drugs (cyclophosphamide and ifosfamide), 2 ophthalmic drugs (apraclonidine and echothiophate) and 5 anesthetics (desflurane, enflurane, isoflurane, methoxyflurane, and sevoflurane).Conclusions: This study provides a new insight for predicting antibacterial compounds with novel structures by using FDA approved drugs. The predicted compounds with novel structures are worthy of further experimental verification in the future.

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The Antibacterial Action of Anaesthetic Vapours

Cited by 17 publications

References 10 publications

Inhibition of mammalian translation initiation by volatile anesthetics

Inhibition of mammalian translation initiation by volatile anesthetics

The Effect of Halothane on Bacterial Growth Rate

Screening of Antibacterial Compounds With Novel Structure From The FDA Approved Drugs Using Machine Learning Methods

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