The effects on sleep of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor administered as a lipophilic lactone prodrug, and pravastatin, an inhibitor administered in its active, hydrophilic, open-acid form, were compared by polysomnographic sleep monitoring. Twenty-four men with primary hypercholesterolemia (low-density lipoprotein 4 to 7 mmol/liter) each received 2 of the following 3 treatments in a randomized, incomplete block, crossover design study: lovastatin (40 mg/day), pravastatin (40 mg/day), and placebo. Test drug was administered once daily for 4 weeks during each half of the crossover study. Subjective sleep assessments were obtained throughout each treatment period, and polysomnographic recordings were obtained at the end of the 4-week treatment periods. Treatment periods were separated by a 1-week washout. Lovastatin did not differ from placebo regarding any polysomnographic parameter except "number of entries to wake," for which it produced fewer entries (i.e., change was in the direction of improvement). Pravastatin did not differ from placebo regarding any polysomnographic measures, but was associated with worsening in relation to lovastatin in the following parameters: sleep efficiency, entries to wake, percent rapid eye movement sleep, wake time during sleep, and total wake time. For each of these 4 parameters, although neither drug showed marked differences from placebo, the mean change in the lovastatin group was in the direction of improved sleep, whereas the change in the pravastatin group was in the direction of disturbed sleep. Neither lovastatin nor pravastatin had any effect on subjective, qualitative sleep ratings.(ABSTRACT TRUNCATED AT 250 WORDS)
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Mol Cancer Ther
May 2024
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, California.
N Engl J Med
December 2023
From the Medical Research Institute of New Zealand, Wellington (T.E.H., S. McGuinness, A.M.T., C.J.M.), and Middlemore Hospital (T.E.H.), Te Toka Tumai Auckland City Hospital (T.E.H., S. McGuinness, R.L.P., C.J.M.), and the School of Nursing, University of Auckland (R.L.P.), Auckland - all in New Zealand; Berry Consultants, Austin, TX (E.L., L.R.B., M.A.D., M.F., A.M., C.T.S., R.J.L., S.M.B.); Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast (M. Shyamsundar, C.M.O., D.F.M.), the Department of Critical Care, Belfast Health and Social Care Trust (M. Shyamsundar, D.F.M.), and the Centre for Public Health, Queen's University Belfast, Belfast Health and Social Care Trust, and the Department of Health (I.S.Y.), Belfast, Imperial College London (F.A.-B., A.C.G.), the Intensive Care National Audit and Research Centre (C.A., D.A.H., L.L., A.J.M., P.R.M., K.M.R.), University College London Hospitals (R.H.), and Imperial College Healthcare NHS Trust (A.C.G.), London, the Institute for Regeneration and Repair (A. Beane) and the Centre for Inflammation Research (R.H., M.S.-H.), University of Edinburgh, Edinburgh, the Faculty of Health Sciences, University of Bristol, and Bristol Haematology and Oncology Centre, University Hospitals Bristol and Weston NHS Trust, Bristol (C.A.B.), and NHS Blood and Transplant, Oxford (L.J.E.) - all in the United Kingdom; Institut Hospitalo-Universitaire Prometheus, University Paris-Saclay, the Department of Intensive Care, Raymond Poincaré Hospital, Assistance Publique-Hôpitaux de Paris, University Versailles Saint Quentin-University Paris-Saclay, the Laboratory of Infection and Inflammation-Unité 173, School of Medicine Simone Veil, University Versailles Saint Quentin-University Paris-Saclay, INSERM, and Fédération Hospitalo-Universitaire SEPSIS (Saclay and Paris Seine Nord Endeavor to Personalize Interventions for Sepsis) - all in Garches, France (D. Annane); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.A.); Nepal Intensive Care Research Foundation, Kathmandu (D. Aryal); Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand (D. Aryal, A. Beane); Unity Health Toronto (Z.B., J.C.M., M. Santos), the Interdepartmental Division of Critical Care Medicine, University of Toronto, and Toronto General Hospital Research Institute (E.C.G.), Peter Munk Cardiac Centre at University Health Network (P.R.L.), and Keenan Centre for Biomedical Research (J.C.M.), Toronto, Université de Sherbrooke, Sherbrooke, QC (F.L.), McGill University Health Centre, Montreal (P.R.L.), the Faculty of Medicine, University of British Columbia, Vancouver (S. Murthy), the Population Health and Optimal Practices Research Unit, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, and the Department of Anesthesiology and Critical Care Medicine, Université Laval, Quebec City (A.F.T.), and the University of Manitoba and CancerCare Manitoba, Winnipeg (R.Z.) - all in Canada; Julius Center for Health Sciences and Primary Care (M. Bonten, L.P.G.D.) and the Intensive Care Center (L.P.G.D.), University Medical Center Utrecht, Utrecht University, and the European Clinical Research Alliance on Infectious Diseases (M. Bonten), Utrecht, and Radboud University Medical Center, Nijmegen (F.V.) - all in the Netherlands; the Department of Anesthesiology and Intensive Care Medicine (F.M.B., S.W.) and the Institute for Infection Disease and Infection Control (S.W.), Jena University Hospital, Friedrich-Schiller University, and Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (S.W.) - both in Jena, Germany; the School of Public Health and Preventive Medicine (A. Burrell, A.C.C., C.G., A.M.H., Z.K.M., A.D.N., J.C.P., C.J.M., S.A.W.) and the School of Clinical Sciences (A.C.C.), Monash University, Alfred Hospital (A. Burrell, A.D.N.), and Monash Health (A.C.C., Z.K.M.), Melbourne, VIC, the Faculty of Medicine, University of Queensland, and the Intensive Care Unit, Princess Alexandra Hospital, Brisbane (P.S.K.), and St. John of God Health Care, Perth, WA (S.A.W.) - all in Australia; the Global Coalition for Adaptive Research, Larkspur (M. Buxton), the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, and the Department of Anesthesia, University of California, San Francisco, San Francisco (C.S.C.), and Harbor-UCLA Medical Center, Torrance (R.J.L.) - all in California; the Department of Biomedical Sciences, Humanitas University, and IRCCS Humanitas Research Hospital, Milan (M.C.); National University Hospital Singapore, Singapore (M.E.C.); Dr. Kamakshi Memorial Hospital (D.J.) and Apollo Speciality Hospitals (E.R.) - both in Chennai, India; the University of Antwerp, Antwerp, Belgium (H.G.); National Intensive Care Surveillance-MORU, Colombo, Sri Lanka (R.H.); Ziauddin University, Karachi, Pakistan (M.H.); the University of Pittsburgh (D.T.H., B.J.M., M.D.N., C.W.S., D.C.A.) and the University of Pittsburgh Medical Center (D.T.H., B.J.M.) - both in Pittsburgh; Jikei University School of Medicine and the University of Tokyo, Tokyo (N.I.), and St. Marianna University School of Medicine, Yokohama Seibu Hospital, Yokohama (H.S.) - all in Japan; University College Dublin Clinical Research Centre, St. Vincent's University Hospital, Dublin (A.D.N.); Universidad de La Sabana and Clínica Universidad de La Sabana - both in Chia, Colombia (L.F.R.); the Division of Clinical and Translational Research, Division of Critical Care, Department of Anesthesiology, Washington University School of Medicine, St. Louis (P.S.); and the Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (B.T.T.).
Respir Med
March 2020
Pulmonary, Allergy and Critical Care Division, Department of Medicine, Perelman School of Medicine, Philadelphia, PA, USA. Electronic address:
Inroduction: The mechanistic target of rapamycin inhibitors (mTORi) sirolimus and everolimus stabilize lung function in patients with pulmonary lymphangioleiomyomatosis (LAM) but do not induce remission. Pre-clinical studies suggest that simvastatin in combination with sirolimus induces LAM cell death. The objective of this study was to assess the safety of simvastatin with either sirolimus or everolimus in LAM patients.
View Article and Find Full Text PDFEur J Pharmacol
November 2019
Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Center for Comparative Respiratory Biology and Medicine, Davis, CA, USA; Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada; Autophagy Research Center, Health Policy Research Centre, Shiraz University of Medical Science, Shiraz, Iran. Electronic address:
Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells.
View Article and Find Full Text PDFBr J Pharmacol
September 2019
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia.
Background And Purpose: We have shown that cholesterol is synthesized in the principal cells of renal cortical collecting ducts (CCD) and stimulates the epithelial sodium channels (ENaC). Here we have determined whether lovastatin, a cholesterol synthesis inhibitor, can antagonize the hypertension induced by activated ENaC, following deletion of the cholesterol transporter (ATP-binding cassette transporter A1; ABCA1).
Experimental Approach: We selectively deleted ABCA1 in the principal cells of mouse CCD and used the cell-attached patch-clamp technique to record ENaC activity.
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