Editorial Material
Clinical Neurology
Iris Noyman, Dana Ekstein, Firas Fahoum, Moshe Herskovitz, Ilan Linder, Bruria Ben Zeev, Sara Eyal
Summary: The recommendations suggest caution in using nirmatrelvir/ritonavir in patients with epilepsy who are on moderate-to-strong enzyme-inducing antiseizure medications (ASMs) and everolimus. It is advised to consider rectal diazepam as an alternative to buccal midazolam, adjust doses of ASMs that are cytochrome P450 (CYP3A4) substrates, and monitor drug efficacy and adverse drug reactions in patients treated with combinations of nirmatrelvir/ritonavir and ASMs that are CYP3A4 substrates or lamotrigine.
Article
Multidisciplinary Sciences
DengYong Zhang, GuanRu Zhao, Wanliang Sun, Dongdong Wang, Shuo Zhou, Zhong Liu, Zheng Lu
Summary: Analysis of bile in the microenvironment of perihilar cholangiocarcinoma (pCCA) using metabolomics and statistical methods can aid in clinical diagnosis. A study collected clinical information and bile samples from patients with pCCA and gallstones, analyzing the bile samples with untargeted metabolomics methods. Through multivariate and univariate analyses, potential differential metabolites were screened and changes in the pCCA pathway and therapeutic targets were explored. Significant differences were found in blood indicators between the two groups, and a significant correlation was observed between clinical parameters and certain metabolites in the metabolic group. The study suggests that bile untargeted metabolomics combined with statistical analysis techniques can be used for the diagnosis and treatment of pCCA.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Sarvesh Sabarathinam, Satish Kumar Rajappan Chandra, Vijayakumar Thangavel Mahalingam
Summary: The study found that the Maha yogaraja guggulu is a commonly used herbomineral polyherbal formulation that affects CYP3A4-mediated metabolism. Experimental results suggest that this formulation and its guggulsterone isomers may have drug interaction potential when used in combination with CYP3A4 substrates.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Clinical Neurology
Wyatt P. Bensken, Ivan Sanchez Fernandez
Summary: One in four people in the United States who take prescription drugs face difficulties affording them, including patients with epilepsy. Health plans often restrict coverage for newer antiseizure medications, leading to delays in treatment. Neurologists can address this issue by understanding the causes and finding actionable solutions.
Article
Food Science & Technology
Xiaocui Li, Yu Fu, Huawei Qiu, Xueyu Xu, Tingting Lin, Weiqing Hou, Weiying Chen, Rong Zhang, Zhongqiu Liu, Lijun Zhu
Summary: This study aimed to investigate the mechanism of yunaconitine (YAC) toxicity and its correlation with metabolic interactions. It was found that YAC could be metabolized into 20 different compounds by human liver microsomes, with CYP3A4 being the most important metabolic enzyme. Inhibition of CYP3A4 resulted in increased exposure and toxicity of YAC in mice. The kinetics of YAC metabolism by CYP3A4 followed a substrate inhibition model, with YAC acting as a moderately competitive inhibitor of CYP3A4. These findings suggest that clinical poisoning events involving YAC may be highly correlated with CYP3A4-mediated interactions.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Mingzong Li, Zenon Konteatis, Nelamangala Nagaraja, Yue Chen, Shubao Zhou, Guangning Ma, Stefan Gross, Katya Marjon, Marc L. Hyer, Everton Mandley, Max Lein, Anil K. Padyana, Lei Jin, Shuilong Tong, Rachel Peters, Joshua Murtie, Jeremy Travins, Matthew Medeiros, Peng Liu, Victoria Frank, Evan T. Judd, Scott A. Biller, Kevin M. Marks, Zhihua Sui, Samuel K. Reznik
Summary: This article presents the progress in the study of MAT2A inhibitors and reports the identification of two new MAT2A inhibitors with distinct properties. These inhibitors have the potential to be therapeutically effective and open up new opportunities for researching the therapeutic effects in the central nervous system.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mingzong Li, Zenon Konteatis, Nelamangala Nagaraja, Yue Chen, Shubao Zhou, Guangning Ma, Stefan Gross, Katya Marjon, Marc L. Hyer, Everton Mandley, Max Lein, Anil K. Padyana, Lei Jin, Shuilong Tong, Rachel Peters, Joshua Murtie, Jeremy Travins, Matthew Medeiros, Peng Liu, Victoria Frank, Evan T. Judd, Scott A. Biller, Kevin M. Marks, Zhihua Sui, Samuel K. Reznik
Summary: This study reports the identification of novel MAT2A inhibitors with distinct in vivo properties, and rapid generation of two brain-penetrant compounds. These findings create new opportunities to explore the potential therapeutic effects of SAM modulation in the central nervous system (CNS).
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Toxicology
Ryosuke Negoro, Naoki Yamada, Keita Watanabe, Yusuke Kono, Takuya Fujita
Summary: The small intestine plays a critical role in drug absorption and metabolism, highlighting the importance of developing a model to evaluate drug metabolism and toxicity in this organ for drug discovery. The study successfully generated cell models for pharmaceutical research which proved useful in examining the effects of drugs on specific genotypes.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Pathology
Victoria M. Pratt, Larisa H. Cavallari, Makenzie L. Fulmer, Andrea Gaedigk, Houda Hachad, Yuan Ji, Lisa Kalman, Reynold C. Ly, Ann M. Moyer, Stuart A. Scott, Ron H. N. van Schaik, Michelle Whirl-Carrillo, Karen E. Weck
Summary: The Association for Molecular Pathology PGx Working Group provides recommendations for defining key attributes of pharmacogenetic alleles and minimum variant sets for clinical testing. Their goal is to promote standardization of PGx gene/allele testing across clinical laboratories.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Article
Multidisciplinary Sciences
Elbatool G. G. Elalem, Musharraf Jelani, Alaa Khedr, Aftab Ahmad, Tareef Y. Y. Alaama, Mohamed Nabeel Alaama, Huda M. M. Al-Kreathy, Zoheir A. A. Damanhouri
Summary: This study investigated the association between CYP3A4 and CYP3A5 gene single nucleotide polymorphisms (SNPs) and the response to simvastatin treatment in hypercholesterolemia patients. The results showed that CYP3A4 and CYP3A5 gene mutations were associated with the patients' response to statins.
Editorial Material
Clinical Neurology
Julie Werenberg Dreier, Kimford J. J. Meador, Jakob Christensen
Summary: Antiseizure medications (ASMs) are commonly used by pregnant women for various conditions, but there is limited evidence on the cognitive risks of in utero exposure. Healthcare professionals and pregnant women face the challenge of balancing the risks and benefits of different treatments due to the lack of robust safety data. High-quality data on the safety of ASMs used in pregnancy are urgently needed, but randomized clinical trials are not possible in pregnant women. Therefore, evidence must be obtained from observational studies.
Article
Multidisciplinary Sciences
Moe Ichikawa, Hiroki Akamine, Michika Murata, Sumito Ito, Kazuo Takayama, Hiroyuki Mizuguchi
Summary: CYP3A4-expressing Caco-2 cells (CYP3A4-Caco-2) were generated in this study to establish a model for evaluating drug absorption and metabolism simultaneously. The overexpressed CYP3A4 in Caco-2 cells had comparable metabolizing activity to in vivo human small intestine tissue, and showed no negative effects on cell functions. This cell line could be a useful tool for pharmaceutical studies.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Alexandra L. Degraeve, Laure B. Bindels, Vincent Haufroid, Serge Moudio, Lidvine Boland, Kevin-Alexandre Delongie, Joseph P. Dewulf, Djamila Chaib Eddour, Michel Mourad, Laure Elens
Summary: This study explores the associations between gut microbiota composition and the pharmacokinetics of tacrolimus, an immunosuppressant used following transplantation. The results suggest that gut microbiota composition and diversity are linked to tacrolimus pharmacokinetic parameters. These findings support the relevance of studying the gut microbiota as an important contributor to tacrolimus pharmacokinetic variability.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Clinical Neurology
Roberta Roberti, Carmen De Caro, Luigi Francesco Iannone, Gaetano Zaccara, Simona Lattanzi, Emilio Russo
Summary: Cenobamate is a promising antiseizure medication for focal onset seizures in adults, with a unique mechanism of action and pharmacokinetic profile. Further clinical studies are needed to fully understand its clinical characteristics and potential interactions with other drugs.
Article
Pharmacology & Pharmacy
Shailly Mehrotra, Atul Bhattaram, Kevin Krudys, Michael Bewernitz, Ramana Uppoor, Mehul Mehta, Tao Liu, Philip Sheridan, Norman Hershkowitz, Nicholas Kozauer, Eric Bastings, Billy Dunn, Angela Yuxin Men
Summary: The US FDA has concluded that drugs approved for treating partial onset seizures in adults can be applied to pediatric patients aged one month and older, eliminating the need for independent efficacy trials. This study analyzes dosing, pharmacokinetic, exposure-response, and clinical data from eight approved drugs to support the extrapolation of efficacy in pediatric patients with partial onset seizures. The results show that based on disease similarity, response to treatment, and exposure-response relationships, the extrapolation of efficacy in pediatric patients aged one month and above is justified.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Psychiatry
Jason M. Nagata, Jennifer L. Carlson, Neville H. Golden, Stuart B. Murray, Jin Long, Mary B. Leonard, Rebecka Peebles
EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY
(2019)
Article
Geriatrics & Gerontology
Joshua F. Baker, Anne B. Newman, Alka Kanaya, Mary B. Leonard, Babette Zemel, Iva Miljkovic, Jin Long, David Weber, Tamara B. Harris
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2019)
Meeting Abstract
Cardiac & Cardiovascular Systems
Joshua D. Bundy, Xuan Cai, Rupal Mehta, Julia J. Scialla, Geoffrey A. Block, Harold I. Feldman, Ian H. de Boer, James P. Lash, Jing Chen, Chi-yuan Hsu, Mirela A. Dobre, Mary B. Leonard, Panduranga S. Rao, Alan S. Go, Raymond R. Townsend, Edward R. Smith, Andreas Pasch, Tamara Isakova
Article
Urology & Nephrology
Tamara Isakova, Xuan Cai, Jungwha Lee, Rupal Mehta, Xiaoming Zhang, Wei Yang, Lisa Nessel, Amanda Hyre Anderson, Joan Lo, Anna Porter, Julie Wright Nunes, Lavinia Negrea, Lee Hamm, Edward Horwitz, Jing Chen, Julia J. Scialla, Ian H. de Boer, Mary B. Leonard, Harold I. Feldman, Myles Wolf, Lawrence J. Appel, Alan S. Go, Jiang He, James P. Lash, Akinlolu Ojo, Mahboob Rahman, Raymond R. Townsend
AMERICAN JOURNAL OF KIDNEY DISEASES
(2020)
Article
Medicine, General & Internal
Tait D. Shanafelt, Maryam S. Makowski, Hanhan Wang, Bryan Bohman, Mary Leonard, Robert A. Harrington, Lloyd Minor, Mickey Trockel
Article
Medicine, General & Internal
Tait D. Shanafelt, Hanhan Wang, Mary Leonard, Mary Hawn, Quinn McKenna, Rick Majzun, Lloyd Minor, Mickey Trockel
Summary: The alignment of values between physicians and their organization is influenced by the leadership behaviors of immediate supervisors. Efforts to improve values alignment should focus on the development of first-line physician leaders.
Article
Education, Scientific Disciplines
Manisha Desai, Mary Boulos, Gina M. Pomann, Gary K. Steinberg, Frank M. Longo, Mary Leonard, Thomas Montine, Andra L. Blomkalns, Robert A. Harrington
Summary: The field of data science has great potential in academic medical centers, and the practice of data science should be recognized as an important intellectual contribution. The authors propose an innovative model for a data science collaboratory, emphasizing collaboration, funding commitment, career development, and education.
Article
Pediatrics
Sumeet S. Vaikunth, Mary B. Leonard, Kevin K. Whitehead, David J. Goldberg, Jack Rychik, Babette S. Zemel, Catherine M. Avitabile
Summary: Patients with Fontan physiology exhibit significant deficits in both cortical (hip, distal one-third radius) and trabecular (lumbar spine, femoral neck, ultradistal radius) bone mineral density (BMD). Lower leg lean mass is associated with lower BMD and may indicate inadequate skeletal muscle loading. Interventions to increase muscle mass may improve bone accrual.
JOURNAL OF PEDIATRICS
(2021)
Article
Geriatrics & Gerontology
Michelle Guo, Babette S. Zemel, Colin P. Hawkes, Jin Long, Andrea Kelly, Mary B. Leonard, Diego Jaramillo, Sogol Mostoufi-Moab
Summary: Survivors of high-risk neuroblastoma treated with cis-retinoic acid (cis-RA) do not show severe impacts on bone mineral density and adiposity, but significant sarcopenia persists even years after treatment. Future studies are needed to determine if muscle-specific interventions can improve sarcopenia in this population of cancer survivors.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Editorial Material
Pediatrics
Mary B. Leonard, DeWayne M. Pursley, Lisa A. Robinson, Steven H. Abman, Jonathan M. Davis
PEDIATRIC RESEARCH
(2022)
Article
Rheumatology
Joshua F. Baker, Jon T. Giles, David Weber, Michael D. George, Mary B. Leonard, Babette S. Zemel, Jin Long, Patricia Katz
Summary: This study determined the prevalence of sarcopenic obesity in patients with rheumatoid arthritis (RA) and its associations with physical functioning using multiple methods. The results showed that the prevalence of low lean mass and sarcopenic obesity was higher in RA patients compared to the general population, and the recently validated methods for categorization were more strongly associated with physical function.
Article
Endocrinology & Metabolism
Rosara M. Bass, Babette S. Zemel, Virginia A. Stallings, Mary B. Leonard, Jaime Tsao, Andrea Kelly
Summary: This one-year longitudinal study examined bone health in youth with cystic fibrosis (CF) and found that bone accrual was preserved on average in CF patients, with deficits in bone geometry and strength not worsening over time. Lower bone accrual was mainly seen in males with CF, and it was correlated with age and BMI. These findings can provide useful insights for targeted screening and interventions.
JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY
(2022)
Article
Pediatrics
Amy J. Kogon, Lance S. Ballester, Jarcy Zee, Natalie Walker, Joshua J. Zaritsky, Meredith A. Atkinson, Christine B. Sethna, Andrew N. Hoofnagle, Mary B. Leonard, Michelle R. Denburg
Summary: This study aimed to determine whether daily cholecalciferol supplementation can increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. The results showed that cholecalciferol supplementation can safely increase 25OHD concentrations, but the ideal dosing to fully replete 25OHD concentrations in this population remains unknown.
PEDIATRIC NEPHROLOGY
(2023)
Meeting Abstract
Endocrinology & Metabolism
Aaron Misakian, Jin Long, Kyla Kent, Mary B. Leonard, Tandy Aye
HORMONE RESEARCH IN PAEDIATRICS
(2023)
Meeting Abstract
Endocrinology & Metabolism
Kyla Kent, Ariana Strickland, Jessica Whalen, Andrew Burghardt, Mary Leonard, Jin Long
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)