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  1. Article ; Online: Differential Effects of Endocannabinoids on Amyloid-Beta Aggregation and Toxicity.

    Khavandi, Marzie / Rao, Praveen P N / Beazely, Michael A

    International journal of molecular sciences

    2023  Volume 24, Issue 2

    Abstract: The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) -induced cell ...

    Abstract The regulation and metabolism of the endocannabinoid system has received extensive attention for their potential neuroprotective effect in neurodegenerative diseases such as Alzheimer's disease (AD), which is characterized by amyloid β (Aβ) -induced cell toxicity, inflammation, and oxidative stress. Using in vitro techniques and two cell lines, the mouse hippocampus-derived HT22 cells and Chinese hamster ovary (CHO) cells expressing human cannabinoid receptor type 1 (CB1), we investigated the ability of endocannabinoids to inhibit Aβ aggregation and protect cells against Aβ toxicity. The present study provides evidence that endocannabinoids N-arachidonoyl ethanol amide (AEA), noladin and O-arachidonoyl ethanolamine (OAE) inhibit Aβ42 aggregation. They were able to provide protection against Aβ42 induced cytotoxicity via receptor-mediated and non-receptor-mediated mechanisms in CB1-CHO and HT22 cells, respectively. The aggregation kinetic experiments demonstrate the anti-Aβ aggregation activity of some endocannabinoids (AEA, noladin). These data demonstrate the potential role and application of endocannabinoids in AD pathology and treatment.
    MeSH term(s) Mice ; Animals ; Cricetinae ; Humans ; Endocannabinoids/pharmacology ; Endocannabinoids/metabolism ; Amyloid beta-Peptides/toxicity ; CHO Cells ; Cricetulus ; Alzheimer Disease/metabolism
    Chemical Substances Endocannabinoids ; Amyloid beta-Peptides
    Language English
    Publishing date 2023-01-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24020911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The opioid crisis: Naloxone and pharmacists to the rescue.

    Beazely, Michael A / Tsuyuki, Ross T

    Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC

    2021  Volume 154, Issue 5, Page(s) 289–290

    Language English
    Publishing date 2021-08-12
    Publishing country United States
    Document type Editorial
    ZDB-ID 2200008-2
    ISSN 1913-701X ; 1715-1635
    ISSN (online) 1913-701X
    ISSN 1715-1635
    DOI 10.1177/17151635211035127
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  3. Article ; Online: Search for lithium isotope effects in neuronal HT22 cells.

    Livingstone, James D / Gingras, Michel J P / Leonenko, Zoya / Beazely, Michael A

    Biochemistry and biophysics reports

    2023  Volume 34, Page(s) 101461

    Abstract: Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes ( ...

    Abstract Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes (
    Language English
    Publishing date 2023-03-31
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2831046-9
    ISSN 2405-5808 ; 2405-5808
    ISSN (online) 2405-5808
    ISSN 2405-5808
    DOI 10.1016/j.bbrep.2023.101461
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  4. Article ; Online: The Interplay Between Cholesterol and Amyloid-β on HT22 Cell Viability, Morphology, and Receptor Tyrosine Kinase Signaling.

    Robinson, Morgan J / Newbury, Sean / Singh, Kartar / Leonenko, Zoya / Beazely, Michael A

    Journal of Alzheimer's disease : JAD

    2023  Volume 96, Issue 4, Page(s) 1663–1683

    Abstract: Background: There is a lack of understanding in the molecular and cellular mechanisms of Alzheimer's disease that has hindered progress on therapeutic development. The focus has been on targeting toxic amyloid-β (Aβ) pathology, but these therapeutics ... ...

    Abstract Background: There is a lack of understanding in the molecular and cellular mechanisms of Alzheimer's disease that has hindered progress on therapeutic development. The focus has been on targeting toxic amyloid-β (Aβ) pathology, but these therapeutics have generally failed in clinical trials. Aβ is an aggregation-prone protein that has been shown to disrupt cell membrane structure in molecular biophysics studies and interfere with membrane receptor signaling in cell and animal studies. Whether the lipid membrane or specific receptors are the primary target of attack has not been determined.
    Objective: This work elucidates some of the interplay between membrane cholesterol and Aβ42 on HT22 neuronal cell viability, morphology, and platelet-derived growth factor (PDGF) signaling pathways.
    Methods: The effects of cholesterol depletion by methyl-β-cyclodextrin followed by treatment with Aβ and/or PDGF-AA were assessed by MTT cell viability assays, western blot, optical and AFM microscopy.
    Results: Cell viability studies show that cholesterol depletion was mildly protective against Aβ toxicity. Together cholesterol reduction and Aβ42 treatment compounded the disruption of the PDGFα receptor activation. Phase contrast optical microscopy and live cell atomic force microscopy imaging revealed that cytotoxic levels of Aβ42 caused morphological changes including cell membrane damage, cytoskeletal disruption, and impaired cell adhesion; cell damage was ameliorated by cellular cholesterol depletion.
    Conclusions: Cholesterol depletion impacted the effects of Aβ42 on HT22 cell viability, morphology, and receptor tyrosine kinase signaling.
    MeSH term(s) Animals ; Cell Survival ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/metabolism ; Cholesterol/metabolism ; Protein-Tyrosine Kinases ; Peptide Fragments/metabolism
    Chemical Substances Amyloid beta-Peptides ; Cholesterol (97C5T2UQ7J) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Peptide Fragments
    Language English
    Publishing date 2023-12-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-230753
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  5. Article ; Online: What Is Known about Community Pharmacy-Based Take-Home Naloxone Programs and Program Interventions? A Scoping Review.

    Cid, Ashley / Daskalakis, George / Grindrod, Kelly / Beazely, Michael A

    Pharmacy (Basel, Switzerland)

    2021  Volume 9, Issue 1

    Abstract: A variety of new sources describing community pharmacy-based take-home naloxone (THN) programs have emerged recently in the literature. There is a need to define the types of take-home naloxone programs being offered to support future research designs in ...

    Abstract A variety of new sources describing community pharmacy-based take-home naloxone (THN) programs have emerged recently in the literature. There is a need to define the types of take-home naloxone programs being offered to support future research designs in implementing and evaluating standardized programs that fill pharmacist and patient knowledge gaps and lift current barriers for optimal community pharmacy naloxone provision. The objective of this paper is to summarize the literature on community pharmacy-based THN programs, including specific program interventions used to increase naloxone dispensing, naloxone availability and dispensing patterns, facilitators and barriers for the THN programs, and knowledge gaps. Online databases such as PubMed, EMBASE, Scopus, and International Pharmaceutical Abstracts (IPA) and a search of the grey literature were used to identify eligible sources. Sources were screened by two reviewers for eligibility in COVIDENCE software. Both reviewers compared screening results and resolved conflicts through discussion. A data extraction form for all identified full texts was completed by both reviewers and results were compiled through reviewer discussion. Fifty-two sources met the eligibility criteria. The top three barriers identified were: cost/coverage of naloxone, stigma, and education/training for pharmacists. THN program interventions included screening tools, checklists, pocket cards, patient brochures, and utilizing the pharmacy management system to flag eligible patients. Patient knowledge gaps included naloxone misinformation and lack of awareness, while pharmacists demonstrated administrative, clinical, and counselling knowledge gaps. Naloxone availability was found to be highly variable, where independent and rural pharmacies were less likely to stock or dispense naloxone. Further, pharmacies located in districts with higher rates of opioid overdose deaths and lower household income were also less likely to have naloxone available. This review identified multiple new programs, showcasing that the implementation and evaluation of THN programs are an expanding area of research. Future research should focus on implementing and evaluating a THN program through a randomized controlled trial design that incorporates solutions for the barriers and knowledge gaps identified in this study.
    Language English
    Publishing date 2021-02-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737194-3
    ISSN 2226-4787 ; 2226-4787
    ISSN (online) 2226-4787
    ISSN 2226-4787
    DOI 10.3390/pharmacy9010030
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  6. Article ; Online: Investigating Community Pharmacy Take Home Naloxone Dispensing during COVID-19: The Impact of One Public Health Crisis on Another.

    Daskalakis, George / Cid, Ashley / Grindrod, Kelly / Beazely, Michael A

    Pharmacy (Basel, Switzerland)

    2021  Volume 9, Issue 3

    Abstract: A recent report found that the number of opioid-related deaths in Ontario in the first 15 weeks of the COVID-19 pandemic was 38.2% higher than in the 15 weeks before the pandemic. Our study sought to determine if pharmacy professionals self-reported an ... ...

    Abstract A recent report found that the number of opioid-related deaths in Ontario in the first 15 weeks of the COVID-19 pandemic was 38.2% higher than in the 15 weeks before the pandemic. Our study sought to determine if pharmacy professionals self-reported an increase or decrease in naloxone provision due to the pandemic and to identify adjustments made by pharmacy professionals to dispense naloxone during the pandemic. A total of 231 Ontario community pharmacy professionals completed an online survey. Pharmacy professionals' barriers, facilitators, and comfort level with dispensing naloxone before and during the pandemic were identified. The sample consisted of mostly pharmacists (99.1%). Over half (51.1%) reported no change in naloxone dispensing, while 22.9% of respondents reported an increase and 24.7% a decrease. The most common adjustments made during the pandemic were training patients how to administer naloxone over video or phone, delivering naloxone kits, and pharmacy technicians offering naloxone at prescription intake. Over half (55%) of participants said the top barrier for dispensing was that patients did not request naloxone. Naloxone distribution through pharmacies could be further optimized to address the increased incidence of overdose deaths during the pandemic. Future research should investigate the reasons for changes in naloxone dispensing.
    Language English
    Publishing date 2021-07-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737194-3
    ISSN 2226-4787 ; 2226-4787
    ISSN (online) 2226-4787
    ISSN 2226-4787
    DOI 10.3390/pharmacy9030129
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  7. Article: Frequently asked questions about naloxone: Part 2.

    Cid, Ashley / Patten, Alec / Grindrod, Kelly / Beazely, Michael A

    Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC

    2021  Volume 154, Issue 6, Page(s) 385–387

    Language English
    Publishing date 2021-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2200008-2
    ISSN 1913-701X ; 1715-1635
    ISSN (online) 1913-701X
    ISSN 1715-1635
    DOI 10.1177/17151635211045966
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  8. Article: Frequently asked questions about naloxone: Part 1.

    Cid, Ashley / Patten, Alec / Grindrod, Kelly / Beazely, Michael A

    Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC

    2021  Volume 154, Issue 5, Page(s) 301–304

    Language English
    Publishing date 2021-08-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2200008-2
    ISSN 1913-701X ; 1715-1635
    ISSN (online) 1913-701X
    ISSN 1715-1635
    DOI 10.1177/17151635211034528
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  9. Article: Frequently asked questions about naloxone: Part 3.

    Cid, Ashley / Patten, Alec / Grindrod, Kelly / Beazely, Michael A

    Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC

    2021  Volume 155, Issue 1, Page(s) 9–11

    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2200008-2
    ISSN 1913-701X ; 1715-1635
    ISSN (online) 1913-701X
    ISSN 1715-1635
    DOI 10.1177/17151635211056571
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  10. Article ; Online: Drug-Drug Interaction of the Sodium Glucose Co-Transporter 2 Inhibitors with Statins and Myopathy: A Disproportionality Analysis Using Adverse Events Reporting Data.

    Alkabbani, Wajd / Pelletier, Ryan / Beazely, Michael A / Labib, Youssef / Quan, Breanna / Gamble, John-Michael

    Drug safety

    2022  Volume 45, Issue 3, Page(s) 287–295

    Abstract: Introduction: An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports.: Objective: We aimed to assess if ... ...

    Abstract Introduction: An increased risk of myopathy due to a potential interaction between sodium glucose co-transporter-2 inhibitors (SGLT-2i) and HMG-CoA reductase inhibitors (statins) has been suggested by case reports.
    Objective: We aimed to assess if the reporting of myopathy is disproportionally higher among people using both SGLT-2i and statins compared to using either SGLT-2i or statins alone.
    Methods: We conducted a disproportionality analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS). We included reports with at least one antihyperglycemic agent. We compared the proportion of myopathy cases to non-cases between those not using SGLT-2i or statins, using SGLT-2i only, statins only, or both. We calculated the reporting odds ratio and 95% confidence interval. We further stratified by individual SGLT-2i and selected statins (rosuvastatin or atorvastatin).
    Results: We included 688,388 reports with at least one antihyperglycemic agent recorded, of which 9.80% had at least one SGLT-2i agent. Among all included reports, there were a total of 2202 myopathy cases with the majority, 61.26%, occurring among those using statins alone and only 2.72% of myopathy cases were among those using both SGLT-2i and statins together. Reporting of myopathy was not disproportionally higher among those reporting the use of SGLT-2i with statins (reporting odds ratio 2.95, 95% confidence interval 2.27-3.85) compared to statins alone (reporting odds ratio 6.41, 95% confidence interval 5.86-7.02).
    Conclusions: Reports of myopathy were not disproportionally higher among those using SGLT-2i with statins compared to SGLT-2i or statins alone at the class level. Further observational studies may be needed to better assess this interaction at the agent level.
    MeSH term(s) Diabetes Mellitus, Type 2/chemically induced ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Drug Interactions ; Glucose ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Hypoglycemic Agents ; Muscular Diseases/chemically induced ; Muscular Diseases/epidemiology ; Sodium ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Symporters
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors ; Symporters ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-03-05
    Publishing country New Zealand
    Document type Journal Article ; Comment
    ZDB-ID 1018059-x
    ISSN 1179-1942 ; 0114-5916
    ISSN (online) 1179-1942
    ISSN 0114-5916
    DOI 10.1007/s40264-022-01166-3
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