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  1. Article: Maternal Serum Melatonin Increases During Pregnancy and Falls Immediately After Delivery Implicating the Placenta as a Major Source of Melatonin.

    Ejaz, Haroon / Figaro, Juliana K / Woolner, Andrea M F / Thottakam, Bensita M V / Galley, Helen F

    Frontiers in endocrinology

    2021  Volume 11, Page(s) 623038

    Abstract: ... decreased markedly 24 h after delivery (P = 0.0013). Similar results were seen for serum levels of 6-OHMS ...

    Abstract Melatonin is a neuroendocrine hormone which regulates circadian rhythm and is also an antioxidant. The role of melatonin in pregnancy is emerging. The enzymes needed for endogenous synthesis of melatonin have been identified in the placenta, although the contribution to circulating maternal melatonin in normal pregnancy is unclear. This work aimed to determine serum levels of melatonin and its major metabolite 6-hydroxymelatonin sulfate (6-OHMS) in normal pregnant women during each trimester of pregnancy, and immediately after delivery. Blood samples were obtained from a cohort of healthy pregnant women during each trimester of pregnancy (n = 26), from women scheduled for elective Cesarean section (CS) before and after delivery (n = 15), along with placental samples, and from healthy non-pregnant women as controls (n = 30). Melatonin and its major metabolite, 6-OHMS, were measured using enzyme immunoassay. Levels of serum melatonin were significantly higher during pregnancy than in non-pregnant women (P = 0.025) and increased throughout pregnancy (P < 0.0001). In women undergoing CS, serum melatonin decreased markedly 24 h after delivery (P = 0.0013). Similar results were seen for serum levels of 6-OHMS, and placental tissue 6-OHMS levels correlated with week of gestation at delivery (p = 0.018). In summary, maternal melatonin production is higher in pregnant than in non-pregnant women, increases significantly during pregnancy with highest levels in the third trimester, and decreases abruptly after delivery. These results suggest that the placenta is a major source of melatonin and supports a physiological role for melatonin in pregnancy.
    MeSH term(s) Adolescent ; Adult ; Biomarkers/blood ; Cesarean Section/trends ; Circadian Rhythm/physiology ; Delivery, Obstetric/trends ; Female ; Humans ; Melatonin/blood ; Placenta/metabolism ; Pregnancy/blood ; Pregnancy Trimesters/blood ; Prospective Studies ; Young Adult
    Chemical Substances Biomarkers ; Melatonin (JL5DK93RCL)
    Language English
    Publishing date 2021-02-18
    Publishing country Switzerland
    Document type Clinical Trial ; Journal Article
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2020.623038
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  2. Article ; Online: Oxidative stress and mitochondrial dysfunction in sepsis.

    Galley, H F

    British journal of anaesthesia

    2011  Volume 107, Issue 1, Page(s) 57–64

    Abstract: Sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit (ICU), despite advances in healthcare and science. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes ...

    Abstract Sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit (ICU), despite advances in healthcare and science. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes in mitochondrial function which may result in organ damage. Normally, a complex system of interacting antioxidant defences is able to combat oxidative stress and prevents damage to mitochondria. Despite the accepted role that oxidative stress-mediated injury plays in the development of organ failure, there is still little conclusive evidence of any beneficial effect of systemic antioxidant supplementation in patients with sepsis and organ dysfunction. It has been suggested, however, that antioxidant therapy delivered specifically to mitochondria may be useful.
    MeSH term(s) Antioxidants/pharmacology ; Antioxidants/physiology ; Drug Delivery Systems/methods ; Humans ; Mitochondria/drug effects ; Mitochondria/physiology ; Oxidative Stress/physiology ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; Sepsis/physiopathology
    Chemical Substances Antioxidants ; Reactive Nitrogen Species ; Reactive Oxygen Species
    Language English
    Publishing date 2011-05-19
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1093/bja/aer093
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  3. Article ; Online: Mice, men, and medicine.

    Galley, H F

    British journal of anaesthesia

    2010  Volume 105, Issue 4, Page(s) 396–400

    MeSH term(s) Anesthesiology/standards ; Animal Experimentation/standards ; Animal Welfare/standards ; Animals ; Humans ; Mice ; Periodicals as Topic/standards ; Practice Guidelines as Topic ; Publishing/standards
    Language English
    Publishing date 2010-10
    Publishing country England
    Document type Editorial
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1093/bja/aeq256
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  4. Article ; Online: Dose assessment of melatonin in sepsis (DAMSEL2) study: Pharmacokinetics of two doses of oral melatonin in patients with sepsis.

    Galley, Helen F / Allen, Lee / Colin, Pieter J / Galt, Sally P / Webster, Nigel R

    Journal of pineal research

    2022  Volume 73, Issue 4, Page(s) e12830

    Abstract: ... dose. Blood samples and clinical measures were analysed over the next 24 h. Melatonin was well ...

    Abstract Sepsis is defined as a dysregulated host response to infection, and high-dose melatonin has been proposed as a treatment due to its antioxidant and anti-inflammatory properties. However, there are no data describing the pharmacokinetics of high-dose oral melatonin in critically ill patients. We undertook an open-label trial to determine the tolerance of melatonin administration in these patients and pharmacokinetic analysis, to inform a planned randomised controlled trial. Two cohorts of critically ill patients with sepsis due to community-acquired pneumonia received either 20 or 50 mg oral melatonin liquid as a single dose. Blood samples and clinical measures were analysed over the next 24 h. Melatonin was well tolerated and there were no adverse events. Pharmacokinetic modelling showed that a semiphysiological model, which incorporates saturable first-pass hepatic extraction, was a good fit for our data. Maximum levels of melatonin were extremely high in patients receiving the 50 mg dose and levels of the major metabolite were much lower than expected and not different from those seen after 20 mg, suggesting saturation at the higher dose. We conclude that 20 mg seems a suitable dose of liquid melatonin in patients with sepsis.
    MeSH term(s) Humans ; Melatonin/therapeutic use ; Critical Illness ; Antioxidants/therapeutic use ; Sepsis/drug therapy
    Chemical Substances Melatonin (JL5DK93RCL) ; Antioxidants
    Language English
    Publishing date 2022-09-11
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 632697-3
    ISSN 1600-079X ; 0742-3098
    ISSN (online) 1600-079X
    ISSN 0742-3098
    DOI 10.1111/jpi.12830
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  5. Article ; Online: Women at the table: reply from authors to Dr. Ward.

    Galley, H F / Colvin, L

    British journal of anaesthesia

    2014  Volume 112, Issue 3, Page(s) 589

    MeSH term(s) Anesthesiology/manpower ; Female ; Humans ; Male ; Physicians, Women/statistics & numerical data ; Sexism/prevention & control
    Language English
    Publishing date 2014-03
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1093/bja/aeu045
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  6. Article ; Online: Perioperative medicine and UK plc.

    Ackland, G L / Galley, H F / Shelley, B / Lambert, D G

    British journal of anaesthesia

    2018  Volume 122, Issue 1, Page(s) 3–7

    MeSH term(s) Anesthesia/methods ; Anesthesia/trends ; Drug Discovery/methods ; Drug Discovery/trends ; Humans ; Multimorbidity/trends ; Perioperative Care/methods ; Perioperative Care/trends ; State Medicine/trends ; United Kingdom
    Language English
    Publishing date 2018-10-26
    Publishing country England
    Document type Editorial
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1016/j.bja.2018.09.023
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  7. Article ; Online: Next on the agenda: gender.

    Galley, H F / Colvin, L A

    British journal of anaesthesia

    2013  Volume 111, Issue 2, Page(s) 139–142

    MeSH term(s) Anesthesiology/manpower ; Editorial Policies ; Female ; Humans ; Male ; Periodicals as Topic ; Physicians, Women/statistics & numerical data ; Sexism/prevention & control ; Sexism/statistics & numerical data ; United Kingdom
    Language English
    Publishing date 2013-08
    Publishing country England
    Document type Editorial
    ZDB-ID 80074-0
    ISSN 1471-6771 ; 0007-0912
    ISSN (online) 1471-6771
    ISSN 0007-0912
    DOI 10.1093/bja/aet133
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  8. Article ; Online: Clostridioides difficile canonical L,D-transpeptidases catalyze a novel type of peptidoglycan cross-links and are not required for beta-lactam resistance.

    Galley, Nicola F / Greetham, Darren / Alamán-Zárate, Marcel G / Williamson, Mike P / Evans, Caroline A / Spittal, William D / Buddle, Jessica E / Freeman, Jane / Davis, Georgina L / Dickman, Mark J / Wilcox, Mark H / Lovering, Andrew L / Fagan, Robert P / Mesnage, Stéphane

    The Journal of biological chemistry

    2023  Volume 300, Issue 1, Page(s) 105529

    Abstract: Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, ... ...

    Abstract Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (Ldt
    MeSH term(s) Bacterial Proteins/chemistry ; beta-Lactam Resistance ; beta-Lactams/pharmacology ; Catalysis ; Clostridioides difficile/enzymology ; Clostridioides difficile/genetics ; Peptidoglycan/chemistry ; Peptidyl Transferases/chemistry ; Peptidyl Transferases/genetics
    Chemical Substances Bacterial Proteins ; beta-Lactams ; Peptidoglycan ; Peptidyl Transferases (EC 2.3.2.12)
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.105529
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  9. Article: Melatonin Is a Feasible, Safe, and Acceptable Intervention in Doctors and Nurses Working Nightshifts: The MIDNIGHT Trial.

    Thottakam, Bensita M V J / Webster, Nigel R / Allen, Lee / Columb, Malachy O / Galley, Helen F

    Frontiers in psychiatry

    2020  Volume 11, Page(s) 872

    Abstract: ... work several 12 h nightshifts in a row at about 1-3 month intervals. We investigated the feasibility ...

    Abstract Nightshift working is associated with sleep deprivation, fatigue and attention/concentration deficits which, in healthcare workers, may impact on patient safety. Clinical staff in the UK routinely work several 12 h nightshifts in a row at about 1-3 month intervals. We investigated the feasibility and acceptability of a crossover trial of melatonin administration in clinical staff working nightshifts with an exploration of effects on sleep measures and attention/concentration tasks. This was a pilot, double-blinded, randomized, placebo-controlled crossover feasibility trial in doctors and nurses working 3 consecutive nightshifts at a tertiary referral hospital in the UK. Twenty five male and female subjects were randomized to receive either 6mg Circadin™ slow release melatonin or placebo before sleep after each consecutive nightshift, followed by a washout period, before crossing over to the other experimental arm. We used actigraphy for objective assessment of sleep parameters. The trial design was feasible and acceptable to participants with negligible side effects, but elevated melatonin levels were prolonged during the active arm (P=0.016). Double digit addition testing, a concentration/attention task, improved with melatonin treatment (P<0.0001). Lapses of vigilance or judgement while doctors or nurses are working nightshifts could impact on patient safety and melatonin may be a useful intervention. This study supports the conclusion that a larger definitive trial of this design is both feasible and safe.
    Language English
    Publishing date 2020-08-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2020.00872
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  10. Article ; Online: Molecular basis for substrate recognition and septum cleavage by AtlA, the major N-acetylglucosaminidase of Enterococcus faecalis.

    Roig-Zamboni, Véronique / Barelier, Sarah / Dixon, Robert / Galley, Nicola F / Ghanem, Amani / Nguyen, Quoc Phong / Cahuzac, Héloize / Salamaga, Bartłomiej / Davis, Peter J / Bourne, Yves / Mesnage, Stéphane / Vincent, Florence

    The Journal of biological chemistry

    2022  Volume 298, Issue 5, Page(s) 101915

    Abstract: The cleavage of septal peptidoglycan at the end of cell division facilitates the separation of the two daughter cells. The hydrolases involved in this process (called autolysins) are potentially lethal enzymes that can cause cell death; their activity, ... ...

    Abstract The cleavage of septal peptidoglycan at the end of cell division facilitates the separation of the two daughter cells. The hydrolases involved in this process (called autolysins) are potentially lethal enzymes that can cause cell death; their activity, therefore, must be tightly controlled during cell growth. In Enterococcus faecalis, the N-acetylglucosaminidase AtlA plays a predominant role in cell separation. atlA mutants form long cell chains and are significantly less virulent in the zebrafish model of infection. The attenuated virulence of atlA mutants is underpinned by a limited dissemination of bacterial chains in the host organism and a more efficient uptake by phagocytes that clear the infection. AtlA has structural homologs in other important pathogens, such as Listeria monocytogenes and Salmonella typhimurium, and therefore represents an attractive model to design new inhibitors of bacterial pathogenesis. Here, we provide a 1.45 Å crystal structure of the E. faecalis AtlA catalytic domain that reveals a closed conformation of a conserved β-hairpin and a complex network of hydrogen bonds that bring two catalytic residues to the ideal distance for an inverting mechanism. Based on the model of the AtlA-substrate complex, we identify key residues critical for substrate recognition and septum cleavage during bacterial growth. We propose that this work will provide useful information for the rational design of specific inhibitors targeting this enterococcal virulence factor and its orthologs in other pathogens.
    MeSH term(s) Acetylglucosaminidase/chemistry ; Animals ; Bacterial Proteins/metabolism ; Enterococcus faecalis/enzymology ; Enterococcus faecalis/metabolism ; Peptidoglycan/metabolism ; Zebrafish/metabolism
    Chemical Substances Bacterial Proteins ; Peptidoglycan ; Acetylglucosaminidase (EC 3.2.1.52)
    Language English
    Publishing date 2022-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.101915
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