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  1. Article ; Online: Does metformin affect outcomes in COVID-19 patients with new or pre-existing diabetes mellitus? A systematic review and meta-analysis.

    Ganesh, Adithan / Randall, Michael D

    British journal of clinical pharmacology

    2022  Volume 88, Issue 6, Page(s) 2642–2656

    Abstract: Aims: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in ... ...

    Abstract Aims: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM.
    Methods: Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842.
    Results: In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I
    Conclusion: Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.
    MeSH term(s) Bias ; COVID-19/drug therapy ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/epidemiology ; Humans ; Metformin/therapeutic use ; Pandemics
    Chemical Substances Metformin (9100L32L2N)
    Language English
    Publishing date 2022-02-23
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Review ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15258
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  2. Book: Medical sciences at a glance

    Randall, Michael D

    (At a glance series)

    2014  

    Author's details edited by Michael D. Randall
    Series title At a glance series
    MeSH term(s) Medicine
    Language English
    Size 160 pages :, illustrations
    Document type Book
    Note Includes index.
    ISBN 9781118360927 ; 9781118360934 ; 9781118360941 ; 9781118360958 ; 9781118360965 ; 9781118360972 ; 1118360923 ; 1118360931 ; 111836094X ; 1118360958 ; 1118360966 ; 1118360974
    Database Catalogue of the US National Library of Medicine (NLM)

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  3. Article ; Online: Sex differences in the role of phospholipase A

    Ahmad, Abdulla A / Randall, Michael D / Roberts, Richard E

    The Journal of physiology

    2017  Volume 595, Issue 21, Page(s) 6623–6634

    Abstract: Key points: The fat surrounding blood vessels (perivascular adipose tissue or PVAT) releases vasoactive compounds that regulate vascular smooth muscle tone. There are sex differences in the regulation of vascular tone, but, to date, no study has ... ...

    Abstract Key points: The fat surrounding blood vessels (perivascular adipose tissue or PVAT) releases vasoactive compounds that regulate vascular smooth muscle tone. There are sex differences in the regulation of vascular tone, but, to date, no study has investigated whether there are sex differences in the regulation of blood vessel tone by PVAT. This study has identified that the cyclooxygenase products thromboxane and PGF
    Abstract: Previous studies have demonstrated that perivascular adipose tissue (PVAT) causes vasoconstriction. In this present study, we determined the role of cyclooxygenase-derived prostanoids in this contractile response and determined whether there were any sex differences in the regulation of vascular tone by PVAT. Contractions in isolated segments of coronary arteries were determined using isolated tissue baths and isometric tension recording. Segments were initially cleaned of PVAT, which was then re-added to the tissue bath and changes in tone measured over 1 h. Levels of PGF
    MeSH term(s) Adipose Tissue/metabolism ; Adipose Tissue/physiology ; Animals ; Arachidonic Acid/metabolism ; Coronary Vessels/physiology ; Dinoprost/metabolism ; Female ; Male ; Phospholipases A2/metabolism ; Receptors, Prostaglandin/agonists ; Receptors, Prostaglandin/genetics ; Receptors, Prostaglandin/metabolism ; Receptors, Thromboxane A2, Prostaglandin H2/agonists ; Receptors, Thromboxane A2, Prostaglandin H2/genetics ; Receptors, Thromboxane A2, Prostaglandin H2/metabolism ; Sex Factors ; Swine ; Thromboxane B2/metabolism ; Vasoconstriction
    Chemical Substances Receptors, Prostaglandin ; Receptors, Thromboxane A2, Prostaglandin H2 ; prostaglandin F2alpha receptor ; Arachidonic Acid (27YG812J1I) ; Thromboxane B2 (54397-85-2) ; Dinoprost (B7IN85G1HY) ; Phospholipases A2 (EC 3.1.1.4)
    Language English
    Publishing date 2017-09-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP274831
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  4. Article ; Online: Sex differences in the regulation of porcine coronary artery tone by perivascular adipose tissue: a role of adiponectin?

    Ahmad, Abdulla A / Randall, Michael D / Roberts, Richard E

    British journal of pharmacology

    2017  Volume 174, Issue 16, Page(s) 2773–2783

    Abstract: Background and purpose: As there is sexual dimorphism in the regulation of vascular tone, the aim of this present study was to determine whether there are sex differences in perivascular adipose tissue (PVAT)-mediated regulation of the porcine coronary ... ...

    Abstract Background and purpose: As there is sexual dimorphism in the regulation of vascular tone, the aim of this present study was to determine whether there are sex differences in perivascular adipose tissue (PVAT)-mediated regulation of the porcine coronary artery (PCA) tone.
    Experimental approach: Isometric tension recording system was used to record changes in tone in PCAs. Western blot analysis was performed to examine the expression of adiponectin in PVAT and adiponectin receptors and adiponectin binding protein (APPL1) in PCA. The level of adiponectin released from PVAT was measured using elisa.
    Key results: In the presence of adherent PVAT, contractions to the thromboxane mimetic U46619 and endothelin-1 were significantly reduced in PCAs from females, but not males. In PCAs pre-contracted with U46619, re-addition of PVAT caused relaxation in PCAs from females, but not males. This relaxant response in females was attenuated by combined inhibition of NOS (with L-NAME) and COX (with indomethacin). Pre-incubation with an anti-adiponectin antibody abolished the relaxant effects of PVAT. The adiponectin receptor agonist (adipoRon) produced a greater relaxation in PCAs from females compared with males. However, there was no difference in either the expression or release of adiponectin from PVAT between sexes. Similarly, there was no difference in the expression of adiponectin receptors or the adiponectin receptor adaptor protein APPL1 in PCAs.
    Conclusion and implications: These findings demonstrate a clear sex difference in the regulation of coronary arterial tone in response to adiponectin receptor stimulation, which may underlie the anticontractile effects of PVAT in females.
    MeSH term(s) 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Adiponectin/physiology ; Adipose Tissue/physiology ; Animals ; Coronary Vessels/drug effects ; Coronary Vessels/physiology ; Endothelin-1/pharmacology ; Female ; In Vitro Techniques ; Male ; Sex Characteristics ; Swine ; Vasoconstriction ; Vasoconstrictor Agents/pharmacology
    Chemical Substances Adiponectin ; Endothelin-1 ; Vasoconstrictor Agents ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (76898-47-0)
    Language English
    Publishing date 2017-07-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.13902
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  5. Book: Disease management

    Randall, Michael D / Neil, Karen E

    a guide to clinical pharmacology

    2016  

    Author's details Michael D Randall, Karen E Neil
    MeSH term(s) Drug Therapy ; Pharmaceutical Preparations ; Pharmacological Phenomena
    Language English
    Dates of publication 2016-2016
    Size xvii, 472 pages :, illustrations ;, 25 cm
    Edition Third edition.
    Document type Book
    ISBN 0857112090 ; 9780857112095
    Database Catalogue of the US National Library of Medicine (NLM)

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  6. Article: The cardiovascular actions of anandamide: more targets?

    Randall, Michael D

    British journal of pharmacology

    2005  Volume 145, Issue 5, Page(s) 565–566

    MeSH term(s) Animals ; Arachidonic Acids/pharmacology ; Blood Pressure/drug effects ; Calcium Channel Blockers/pharmacology ; Endocannabinoids ; Hemodynamics/drug effects ; Polyunsaturated Alkamides ; Rats ; Receptors, Cannabinoid/drug effects
    Chemical Substances Arachidonic Acids ; Calcium Channel Blockers ; Endocannabinoids ; Polyunsaturated Alkamides ; Receptors, Cannabinoid ; anandamide (UR5G69TJKH)
    Language English
    Publishing date 2005-07
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1038/sj.bjp.0706234
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  7. Article ; Online: Sex differences in the role of NADPH oxidases in endothelium-dependent vasorelaxation in porcine isolated coronary arteries.

    Wong, Pui San / Randall, Michael D / Roberts, Richard E

    Vascular pharmacology

    2015  Volume 72, Page(s) 83–92

    Abstract: The present study examined whether vascular function, expression and activity of NADPH oxidases differ between sexes in porcine isolated coronary arteries (PCAs) using selective Nox inhibitors, ML-171 and VAS2870. Vascular responses of distal PCAs were ... ...

    Abstract The present study examined whether vascular function, expression and activity of NADPH oxidases differ between sexes in porcine isolated coronary arteries (PCAs) using selective Nox inhibitors, ML-171 and VAS2870. Vascular responses of distal PCAs were examined under myographic conditions in the presence of a range of inhibitors. Nox activity in PCA homogenates was assessed using lucigenin-enhanced chemiluminescence. Protein expression of Nox1, Nox2 and Nox4 was compared using Western immunoblotting. The presence of ML-171 or DPI had no effect on the bradykinin-induced vasorelaxation in PCAs from females. In males, DPI shifted the EC50 2.8-fold to the right. In the presence of L-NAME and indomethacin, DPI and ML-171 had no effect in females, but enhanced the bradykinin-induced vasorelaxation in males. ML-171 had no effect on the forskolin-induced vasorelaxation but decreased the potency of U46619-induced tone in both sexes in the absence or presence of endothelium. VAS2870 had no effect on the bradykinin-induced vasorelaxation in both sexes but reduces the EDH-type response in males only. Nox activity was reduced by DPI and ML-171, but not VAS2870 in PCAs from both sexes. Protein expression of Nox1 and Nox2 in PCAs was higher in males compared to females whereas Nox4 was higher in females. Inhibition of Nox with ML-171 enhances while VAS2870 reduces the EDH-type response in PCAs from males but not females. This indicates that Nox-generated ROS play a role in the EDH-type response in males with differences attributed to the differential expression of Nox isoforms. This may underlie the greater oxidative stress observed in males.
    MeSH term(s) 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology ; Animals ; Benzoxazoles/pharmacology ; Bradykinin/pharmacology ; Coronary Vessels/drug effects ; Coronary Vessels/metabolism ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Female ; Indomethacin/pharmacology ; Male ; NADPH Oxidases/metabolism ; NG-Nitroarginine Methyl Ester/pharmacology ; Oxidation-Reduction ; Sex Characteristics ; Swine ; Triazoles/pharmacology ; Vasodilation/drug effects ; Vasodilation/physiology
    Chemical Substances 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine ; Benzoxazoles ; Triazoles ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (76898-47-0) ; NADPH Oxidases (EC 1.6.3.-) ; Bradykinin (S8TIM42R2W) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X) ; Indomethacin (XXE1CET956)
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2082846-9
    ISSN 1879-3649 ; 1537-1891 ; 1879-3649
    ISSN (online) 1879-3649 ; 1537-1891
    ISSN 1879-3649
    DOI 10.1016/j.vph.2015.04.001
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  8. Article ; Online: Hyperoxic gassing with Tiron enhances bradykinin-induced endothelium-dependent and EDH-type relaxation through generation of hydrogen peroxide.

    Wong, Pui San / Roberts, Richard E / Randall, Michael D

    Pharmacological research

    2015  Volume 91, Page(s) 29–35

    Abstract: Oxygenation with 95%O2 is routinely used in organ bath studies. However, hyperoxia may affect tissue responses, particularly in studies which involve reactive oxygen species (ROS). Here, the effects of the antioxidant, Tiron, were investigated under ... ...

    Abstract Oxygenation with 95%O2 is routinely used in organ bath studies. However, hyperoxia may affect tissue responses, particularly in studies which involve reactive oxygen species (ROS). Here, the effects of the antioxidant, Tiron, were investigated under different gassing conditions in the porcine isolated coronary artery (PCA). Distal PCAs from male and female pigs were mounted in a wire myograph gassed with either 95%O2/5%CO2 or 95% air/5%CO2 and pre-contracted with U46619. Concentration-response curves to bradykinin were constructed in the presence of Tiron (1mM), a cell permeable superoxide scavenger and catalase (1000Uml(-1)) to breakdown H2O2. The H2O2 level in Krebs'-Henseleit solution was detected using Amplex Red. Bradykinin produced concentration-dependent vasorelaxations in male and female PCAs when gassed with either 95%O2 or air, with no differences in the Rmax or EC50. Tiron increased the potency of bradykinin only when gassed with 95%O2 in PCAs from both sexes. At 95%O2, catalase prevented the leftward shift caused by Tiron in both sexes indicating that catalase prevented the formation of H2O2 by Tiron. In female PCAs, addition of catalase to Tiron significantly reduced the Rmax. In the EDH-type response (using L-NAME and indomethacin), Tiron enhanced the potency of the bradykinin-induced vasorelaxation when gassed with 95%O2 in PCAs from both sexes. Biochemical analysis using Amplex Red demonstrated that H2O2 was generated in Krebs'-Henseleit solution when gassed with 95%O2, but not with air. Therefore, hyperoxic gassing conditions could alter the environment generating superoxide within the Krebs'-Henseleit buffer, which may, in turn, influence the in vitro pharmacological responses.
    MeSH term(s) 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/pharmacology ; Animals ; Bradykinin ; Coronary Vessels/drug effects ; Coronary Vessels/physiology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/physiology ; Female ; Hydrogen Peroxide/metabolism ; Hyperoxia/metabolism ; Hyperoxia/physiopathology ; In Vitro Techniques ; Male ; Superoxides/metabolism ; Swine ; Vasodilation/drug effects
    Chemical Substances Superoxides (11062-77-4) ; 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt (4X87R5T106) ; Hydrogen Peroxide (BBX060AN9V) ; Bradykinin (S8TIM42R2W)
    Language English
    Publishing date 2015-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2014.11.001
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    Zs.A 721: Show issues Location:
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  9. Article ; Online: Sex differences in the role of transient receptor potential (TRP) channels in endothelium-dependent vasorelaxation in porcine isolated coronary arteries.

    Wong, Pui San / Roberts, Richard E / Randall, Michael D

    European journal of pharmacology

    2015  Volume 750, Page(s) 108–117

    Abstract: Endothelial and smooth muscle Transient Receptor Potential (TRP) channels contribute to regulation of vascular tone. We have previously reported sex differences in the endothelial function in porcine isolated coronary arteries (PCAs). The present study ... ...

    Abstract Endothelial and smooth muscle Transient Receptor Potential (TRP) channels contribute to regulation of vascular tone. We have previously reported sex differences in the endothelial function in porcine isolated coronary arteries (PCAs). The present study examined the role of TRP channels in endothelium-dependent and H2O2-induced vasorelaxations in male and female PCAs. Distal PCAs were mounted in a wire myograph and precontracted with U46619. Concentration-response curves to bradykinin, H2O2 and A23187 were constructed in the presence of TRP channel antagonists with or without L-NAME and indomethacin to inhibit NO synthase and cyclooxygenase respectively. 2-APB (TRPC & TRPM antagonist) inhibited the maximum relaxation (Rmax) of the bradykinin-induced vasorelaxation and abolished the EDH-type response in PCAs from both sexes. SKF96365 (TRPC antagonist) inhibited the Rmax of bradykinin-induced vasorelaxation in males, and inhibited Rmax of the EDH-type response in both sexes. Pyr3 (TRPC3 antagonist) inhibited both the NO and EDH components of the bradykinin-induced vasorelaxation in males, but not females. RN1734 (TRPV4 antagonist) reduced the potency of the NO component of the bradykinin-induced vasorelaxation in females only, but inhibited the Rmax of the EDH-type component in both sexes. 2-APB, SKF96365 and RN1734 all reduced the H2O2-induced vasorelaxation, whereas Pyr3 had no effect. No differences in expression level of TRPC3 and TRPV4 between sexes were detected using Western blot. Present study demonstrated a clear sex differences in the role TRP channels where TRPC3 play a role in the NO- and EDH-type response in males and TRPV4 play a role in the NO-mediated response in females.
    MeSH term(s) Animals ; Boron Compounds/pharmacology ; Bradykinin/pharmacology ; Calcimycin/pharmacology ; Coronary Vessels/drug effects ; Coronary Vessels/metabolism ; Coronary Vessels/physiology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Female ; Gene Expression Regulation/drug effects ; Hydrogen Peroxide/pharmacology ; Imidazoles/pharmacology ; Indomethacin/pharmacology ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Pyrazoles/pharmacology ; Sex Characteristics ; Sulfonamides/pharmacology ; Swine ; Transient Receptor Potential Channels/antagonists & inhibitors ; Transient Receptor Potential Channels/metabolism ; Vasodilation/drug effects
    Chemical Substances Boron Compounds ; Imidazoles ; Pyrazoles ; RN 1734 ; Sulfonamides ; Transient Receptor Potential Channels ; ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate ; Calcimycin (37H9VM9WZL) ; Hydrogen Peroxide (BBX060AN9V) ; 2-aminoethoxydiphenyl borate (E4ES684O93) ; 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole (I61V87164A) ; Bradykinin (S8TIM42R2W) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X) ; Indomethacin (XXE1CET956)
    Language English
    Publishing date 2015-03-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2015.01.022
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  10. Article: A new endothelial target for cannabinoids.

    Randall, Michael D

    Molecular pharmacology

    2003  Volume 63, Issue 3, Page(s) 469–470

    MeSH term(s) Animals ; Arachidonic Acids/pharmacology ; Biological Factors/metabolism ; Cannabinoid Receptor Modulators ; Endocannabinoids ; Endothelium, Vascular/metabolism ; Fatty Acids, Unsaturated/metabolism ; Humans ; Polyunsaturated Alkamides ; Receptors, Cannabinoid ; Receptors, Drug/metabolism
    Chemical Substances Arachidonic Acids ; Biological Factors ; Cannabinoid Receptor Modulators ; Endocannabinoids ; Fatty Acids, Unsaturated ; Polyunsaturated Alkamides ; Receptors, Cannabinoid ; Receptors, Drug ; endothelium-dependent hyperpolarization factor ; anandamide (UR5G69TJKH)
    Language English
    Publishing date 2003-02-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/mol.63.3.469
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