Article
Biochemistry & Molecular Biology
Blessy George, Xia Wen, Edgar A. Jaimes, Melanie S. Joy, Lauren M. Aleksunes
Summary: Research indicates that among five 5-HT3 antagonist drugs, ondansetron shows the strongest inhibitory effect on the OCT2 and MATE1 transporters, significantly impacting the transport of ASP(+) in cell experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Fabian Mueller, Kathrin Hohl, Sascha Keller, Sven Schmidt-Gerets, Birgit Deutsch, Annette Schuler-Metz, Martin F. Fromm, Peter Stopfer, Arne Gessner
Summary: N-1-methylnicotinamide (NMN) is proposed as an endogenous biomarker for drug-drug interactions in the renal proximal tubule. NMN kinetics were analyzed in plasma and urine samples from two clinical trials involving a probe drug cocktail. The results showed that NMN clearance was specifically and sensitively affected by the inhibition of renal MATEs, indicating that NMNCLR can be used as a marker for MATE-mediated renal drug-drug interactions.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Cell Biology
Shu Yang, Han Wu, Yanchun Li, Lixin Li, Jiaqing Xiang, Lin Kang, Guangyan Yang, Zhen Liang
Summary: Phosphofructokinase 1 (PFK) and its platelet isoform (PFKP) play a significant role in the progression of kidney interstitial fibrosis by regulating glycolysis in proximal tubular epithelial cells (PTECs). Overexpression of PFKP promotes fibrosis and glycolysis, while knockdown of PFKP inhibits these processes. TGF-beta 1 recruits the SMAD3-SP1 complex to enhance PFKP expression, and treatment with isorhamnetin improves glycolysis and kidney fibrosis.
CELL DEATH & DISEASE
(2023)
Article
Environmental Sciences
Jionghan Zhuang, Gaohui Nie, Ruiming Hu, Chang Wang, Chenghong Xing, Guyue Li, Guoliang Hu, Fan Yang, Caiying Zhang
Summary: The study found that excessive molybdenum exposure induces autophagy in duck renal tubular epithelial cells, and inhibition of autophagy exacerbates molybdenum-induced mitochondrial dysfunction.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Jia He, Shuang Xu, Mingzhu Jiang, Ting Wang, Yue Zhang, Zhanjun Jia, Mi Bai, Aihua Zhang
Summary: Fibrosis is a common pathological phenomenon in progressive kidney disease. The upregulation of CDC20 in renal tubular cells and fibroblasts promotes renal fibrosis by activating beta-catenin. Inhibition of CDC20 may serve as a promising strategy for the prevention and treatment of renal fibrosis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Pathology
Yaqin Li, Congwei Luo, Yiqun Zeng, Zerong Zheng, Danping Tao, Qiao Liu, Yiyu Hong, Shuo Wang, Haibo Long, Zhaozhong Xu
Summary: This study suggests that IL-11 is critically involved in renal fibrosis by promoting tubular EMT. Inhibition of IL-11 can alleviate renal fibrosis induced by UUO. Micheliolide competitively inhibits the binding of IL-11 to IL-11Ra1, thus suppressing tubular EMT and interstitial fibrosis. These findings indicate IL-11 as a promising therapeutic target for renal fibrosis.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Medicine, Research & Experimental
Yohan Bignon, Leonore Wigger, Camille Ansermet, Benjamin D. Weger, Sylviane Lagarrigue, Gabriel Centeno, Fanny Durussel, Lou Gotz, Mark Ibberson, Sylvain Pradervand, Manfredo Quadroni, Meltem Weger, Francesca Amati, Frederic Gachon, Dmitri Firsov
Summary: Rhythmic adaptations in renal metabolism are suggested by circadian rhythmicity in renal function. By studying diurnal changes in renal metabolic pathways, we found that a significant number of RNAs, proteins, and metabolites in the kidneys of control mice display rhythmicity. Disruptions in key metabolic pathways were observed in the kidneys of mice with an inducible deletion of the circadian clock regulator Bmal1, resulting in impaired mitochondrial activity. The reabsorption of carnitine from primary urine was particularly affected, leading to decreased plasma and tissue carnitine levels.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Haoyu Shi, Hao Qi, Dongdong Xie, Jiayi Zhuang, Huiyue Qi, Yingbo Dai, Jiaqing Wu
Summary: Acute kidney injury (AKI) is a common clinical condition caused by sepsis and ischemia reperfusion (IR) injury. Impairment of function in renal tubular cells leads to renal tubular structural changes and ultimately AKI. In this study, we identified Acyl-CoA Synthetase Family Member 2 (ACSF2) as a target gene for its high specific expression in renal tubular cells and location in mitochondria. Silencing ACSF2 enhanced mitophagy, restored mitochondrial function, and protected against IR-induced AKI, suggesting ACSF2 as a potential therapeutic target.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Jialu Li, Chao Yu, Fengchen Shen, Binbin Cui, Na Liu, Shougang Zhuang
Summary: This study found that the inhibition of class IIa HDACs can improve renal function and reduce tubular cell injury and apoptosis in acute kidney injury (AKI), while promoting cellular autophagy and renal tubular cell proliferation. It also targets multiple signaling pathways associated with AKI pathogenesis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Shu Yang, Guangyan Yang, Xinyu Wang, Jiaqing Xiang, Lin Kang, Zhen Liang
Summary: This study demonstrates the anti-fibrotic role of SIRT2 in renal tubules and hepatocytes. SIRT2 inhibits fibrotic gene expression by reducing the activation of the TGF-beta signaling pathway. It interacts with and deacetylates SMAD2 and SMAD3 to promote their degradation and decrease the activation of SMAD3.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Theodoros Eleftheriadis, Georgios Pissas, Spyridon Golfinopoulos, Maria Efthymiadi, Vassilios Liakopoulos, Ioannis Stefanidis
Summary: Inhibition of malate dehydrogenase-2 (MDH-2) protects renal cells from death or senescence caused by ischemia-reperfusion injury. MDH-2 inhibition reduces oxidative stress and inflammation, and maintains cell proliferation capacity.
Article
Pharmacology & Pharmacy
Yan Liang, Zhenjie Liu, Lingyun Qu, Yingzi Wang, Yali Zhou, Lulu Liang, Yanhong Guo, Lin Tang
Summary: The study revealed an interaction between the IRE1/JNK pathway and ferroptosis in ischemia-reperfusion or hypoxia-reoxygenation induced acute kidney injury. Inhibiting the IRE1/JNK pathway has a protective effect on reducing I/R renal injury or AKI, and may serve as a therapeutic target for treating AKI.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Takashi Okuda, Yuki Nomura, Asami Konishi, Hidemi Misawa
Summary: The study found that tetrahydropyrimidine anthelmintics act as competitive inhibitors of CHT1, effectively inhibiting choline uptake and acetylcholine synthesis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Wei Chen, Bing Wang, Shanshan Liang, Meng Wang, Lingna Zheng, Si Xu, Jiali Wang, Hao Fang, Pu Yang, Weiyue Feng
Summary: This study reveals that graphene oxide nanosheets are excreted in urine through the kidneys, but the lateral size of the nanosheets affects their distribution in the kidneys and kidney injury. Small nanosheets are mainly excreted via glomerular filtration, while large nanosheets are predominantly excreted via proximal tubular secretion. During renal elimination, high-dose nanosheet treatment can induce different kidney injuries, with small nanosheets causing glomerular damage and large nanosheets causing tubular damage.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Endocrinology & Metabolism
Jun-Qing Zhang, Ying-Ying Li, Xue-Yan Zhang, Zeng-Hui Tian, Cheng Liu, Shi-Tao Wang, Fa-Rong Zhang
Summary: Renal fibrosis is a common pathological manifestation of chronic kidney diseases and a major cause of end-stage renal disease, but its pathogenesis remains unclear. Renal tubular epithelial cell senescence has been found to accelerate the progression of renal fibrosis. Oxidative stress, telomere attrition, and DNA damage are the major causes of renal tubular epithelial cell senescence. Interventions and therapeutic strategies targeting cellular senescence, such as calorie restriction, exercise, Klotho, senolytics, and senostatics, show potential for the treatment of renal fibrosis.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Health Care Sciences & Services
Bianca J. Levkovich, Judit Orosz, Gordon Bingham, D. James Cooper, Michael Dooley, Carl Kirkpatrick, Daryl A. Jones
Summary: Medication-related activations accounted for one-fourth of emergency team activations, often occurring early in a patient's admission. One-third of these medication-related activations were potentially preventable, with the most common causes being omission of beta-blockers and clinically inappropriate use of antihypertensive drugs.
BMJ QUALITY & SAFETY
(2023)
Review
Pharmacology & Pharmacy
George S. Q. Tan, Erica K. Sloan, Pete Lambert, Carl M. J. Kirkpatrick, Jenni Ilomaki
Summary: The use of real-world data in drug repurposing is advantageous for supplementing de novo drug discovery and incorporating real-world evidence in regulatory approvals. A scoping review analyzed 250 studies, including hypothesis generation, hypothesis validation, and safety assessment. Challenges include isolated data sources, false-positive signals, bias and confounding in hypothesis validation, and the lack of regulatory guidance.
DRUG DISCOVERY TODAY
(2023)
Article
Public, Environmental & Occupational Health
Holly Foot, Carl Kirkpatrick, Grant Russell, Nancy Sturman, Amelia Cossart, Christopher Freeman
Summary: The study investigates the attitudes of GPs, patients, and practice pharmacists towards the practice pharmacist model of care in the Australian primary care setting. The results show that the model is well accepted by all stakeholders and has promising evidence for broader implementation in the healthcare setting.
RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY
(2023)
Article
Microbiology
Guohua An, C. Buddy Creech, Nan Wu, Roger L. Nation, Kenan Gu, Demet Nalbant, Natalia Jimenez-Truque, William Fissell, Stephanie Rolsma, Pratish C. Patel, Amy Watanabe, Nicholas Fishbane, Carl M. J. Kirkpatrick, Cornelia B. Landersdorfer, Patricia Winokur
Summary: The population pharmacokinetic (PK) analysis of meropenem in 114 critically ill patients showed that the drug's clearance is affected by creatinine clearance and continuous renal replacement therapy, while volume of distribution is influenced by total bodyweight. The developed model serves as a valuable addition to the existing meropenem population PK models and is particularly useful for therapeutic drug monitoring programs with Bayesian forecasting. Monte Carlo simulations demonstrated that the dosing regimens of 2 g every 8 h with 3-h prolonged infusion (PI) and 4 g/day by continuous infusion (CI) are superior in terms of target attainment and potential toxicity when renal function information is unavailable.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Marion Hemmersbach-Miller, Stephen J. Balevic, Patricia L. Winokur, Cornelia B. Landersdorfer, Kenan Gu, Austin W. Chan, Michael Cohen-Wolkowiez, Thomas Conrad, Guohua An, Carl M. J. Kirkpatrick, Geeta K. Swamy, Emmanuel B. Walter, Kenneth E. Schmader
Summary: This study evaluated the pharmacokinetics of piperacillin/tazobactam and its changes in older adults. The estimated creatinine clearance had the most significant impact on the elimination clearance of piperacillin and tazobactam. Frailty did not have a remaining impact on their pharmacokinetics after accounting for renal function and body size.
CLINICAL PHARMACOKINETICS
(2023)
Article
Pharmacology & Pharmacy
Sam Mostafa, Thomas M. M. Polasek, Chad Bousman, Amin Rostami-Hodjegan, Leslie J. J. Sheffield, Ian Everall, Christos Pantelis, Carl M. J. Kirkpatrick
Summary: Studies that focus on individual covariates and ignore their interactions may not be adequate for model-informed precision dosing (MIPD). This study aimed to construct virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to determine the impact of these interacting covariates on predicted clozapine plasma concentrations. The results showed that increasing covariate virtualization improved the accuracy and reliability of the prediction models.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Microbiology
Silvia Lopez-Argueello, Maria Montaner, Alaa R. M. Sayed, Antonio Oliver, Jurgen B. Bulitta, Bartolome Moya
Summary: Beta-lactam antibiotics have been effective against susceptible Pseudomonas aeruginosa, but their penetration ability and binding to penicillin-binding proteins (PBPs) in intact bacteria have not been well studied. This research investigated the time course of PBP binding and target site penetration of 15 compounds in P. aeruginosa PAO1. The results showed that PBPs 1-4 were considerably bound in lysed bacteria, but the binding was attenuated in intact bacteria for slow penetrating beta-lactams. Imipenem showed the highest killing effect, while other drugs had lower killing rates. The study also found a correlation between PBP5/6 binding and the rate of net influx and PBP access.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Carlo Matera, Michael Kauk, Davide Cirillo, Marco Maspero, Claudio Papotto, Daniela Volpato, Ulrike Holzgrabe, Marco De Amici, Carsten Hoffmann, Clelia Dallanoce
Summary: In recent years, fluorescence resonance energy transfer (FRET) receptor sensors have played a significant role in studying GPCR ligand binding and activation. Researchers have synthesized two series of bitopic ligands, known as 12-Cn and 13-Cn, and examined their pharmacological effects on M-1, M-2, M-4, and M-5 FRET-based receptor sensors. The results showed selective activation of M-1 mAChRs with tertiary amine compounds 12-C5, 12-C7, and 12-C9, while methyl tetrahydropyridinium salts 13-C5, 13-C7, and 13-C9 exhibited some selectivity for M-1 and M-4 mAChRs. These findings provide insights into ligand-receptor interactions at a molecular level and offer new tools for studying them.
Article
Chemistry, Medicinal
Rasmus Walther, Jovana Krmar, Adrian Leistner, Bojana Svrkota, Biljana Otasevic, Andjelija Malenovic, Ulrike Holzgrabe, Ana Protic
Summary: A robust liquid chromatography method with charged aerosol detection was proposed as an alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs). The method utilized a gradient method with a Hypersil Gold C-18 column and acetonitrile as organic modifier to analyze polysorbate 80 (PS80) and magnesium stearate. Risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR), with critical method parameters (CMPs) including formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate.
Article
Health Policy & Services
John K. Jackson, Shane L. Scahill, Michael Mintrom, Carl M. Kirkpatrick
Summary: Since 1990, the Community Pharmacy Agreements (Agreements) between the Australian Federal government and the Pharmacy Guild of Australia (PGA) have had a significant impact on Australian community pharmacy. The Agreements primarily focus on dispensing remuneration and restrictions on the establishment of new pharmacies. Criticisms include the self-interest of pharmacy owners, lack of transparency, and impact on competition.
JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE
(2023)
Article
Microbiology
Jessica R. R. Tait, Marina Harper, Sara Cortes-Lara, Kate E. E. Rogers, Carla Lopez-Causape, Thomas R. R. Smallman, Yinzhi Lang, Wee Leng Lee, Jieqiang Zhou, Jurgen B. Bulitta, Roger L. L. Nation, John D. D. Boyce, Antonio Oliver, Cornelia B. B. Landersdorfer
Summary: The study evaluated the efficacy of ceftolozane-tazobactam against multidrug-resistant hypermutable P. aeruginosa isolates in cystic fibrosis (CF) using the hollow-fiber infection model. Results showed that isolates CW41 and CW44 harbored preexisting resistant subpopulations while CW35 did not. This emphasizes the importance of using ceftolozane-tazobactam in combination with another antibiotic in CF patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Victoria L. Oliver, Sarah Siederer, Anthony Cahn, Katarzyna Gajewska-Knapik, Rachel A. Gibson, Cleo Goodall, Carl Kirkpatrick, Jack Murray, Tri-Hung Nguyen, Ian Schneider, Pete Lambert, Michelle P. Mcintosh, Simon Parry
Summary: This study examines the role of ex vivo oxytocin metabolism and stability in late-stage pregnancy blood. The findings suggest that collecting blood into tubes containing EDTA effectively stabilizes oxytocin and inhibits oxytocinase activity. The measured concentrations of oxytocin vary between different analytical methods.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Hematology
John Coutsouvelis, Carl M. Kirkpatrick, Michael Dooley, Andrew Spencer, Glen Kennedy, Maggie Chau, Gillian Huang, Richard Doocey, Tandy-Sue Copeland, Louis Do, Peter Bardy, Ian Kerridge, Theresa Cole, Chris Fraser, Travis Perera, Stephen R. Larsen, Kate Mason, Tracey A. O'Brien, Peter J. Shaw, Lochie Teague, Andrew Butler, Anne-Marie Watson, Shanti Ramachandran, Jodie Marsh, Zulekha Khan, Nada Hamad
Summary: This study aimed to describe the incidence of SOS/VOD and patterns of defibrotide use from 2016 to 2020 based on data from the Australasian Bone Marrow Transplant Recipient Registry. The incidence of SOS/VOD was 4.1% in adult centers and 11.5% in pediatric centers. Defibrotide was administered to 74.8% of adult patients and 97.3% of pediatric patients with SOS/VOD. The 100-day survival rate was 51.8% for adults and 90.4% for pediatric patients.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Surgery
Steven Ivulich, Miranda Paraskeva, Eldho Paul, Carl Kirkpatrick, Michael Dooley, Gregory Snell
Summary: Everolimus in lung transplant recipients does not increase the risk of death or accelerate the progression to chronic lung allograft dysfunction compared to calcineurin inhibitor-based immunosuppression. The emergence of chronic lung allograft dysfunction, obstructive or restrictive phenotypes, and death rates showed no significant difference between the two groups. There is a lack of long-term evidence for survival and progression to chronic lung allograft dysfunction with Everolimus-based immunosuppression.
TRANSPLANT INTERNATIONAL
(2023)
Article
Surgery
Steven Ivulich, Eldho Paul, Carl Kirkpatrick, Michael Dooley, Greg Snell
Summary: Everolimus (EVE) is an alternative immunosuppressive agent for lung transplant recipients (LTR) who cannot tolerate conventional immunosuppression. It can be used as part of a calcineurin inhibitor (CNI) minimization or elimination strategy. This study compared the safety and efficacy outcomes of EVE in LTR receiving either a CNI minimization or elimination regimen. The results showed that LTR receiving EVE as part of the CNI elimination strategy had poorer survival outcomes, while the utilization of EVE for renal preservation was associated with improved survival. The study highlighted the importance of retaining a low dose CNI in immunosuppressive regimens for superior survival outcomes.
TRANSPLANT INTERNATIONAL
(2023)