Nowadays, alternative methods have been developed to predict intestinal permeability values in human as in vitro, in situ or ex vivo methods. They were developed by the necessity to avoid the problems of the human permeability experiments. However, determination of human permeability is needed to properly validate the alternative methods. For this reason, recently, Dahlgren et al. published an indirect method based on a deconvolution technique to estimate the human permeability in different gastrointestinal segments (jejunum, ileum and colon). Therefore, the objective of this research was to demonstrate that Doluisio technique is a useful method to predict the human permeability in different gastrointestinal segments. To achieve this goal, the rat permeability in different segments, of the same drugs studied by Dahlgren et al. (atenolol, metoprolol and ketoprofen), have been compared with the human data obtained by the deconvolution method. The results obtained in this work show that the Doluisio method is a reliable tool to predict segmental human permeability. Consequently, the deconvolution method can be employed to build an extensive database of human permeability, overall from ileum and colon, because there is a lack of human permeability data of these distal segments. Once there are enough human data available, the Doluisio technique will be a valuable alternative method to predict the permeability of new molecules with therapeutic activity without the requirement of human experiments.
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http://dx.doi.org/10.1016/j.ejps.2017.06.033 | DOI Listing |
Mikrobiyol Bul
October 2024
İnönü University Faculty of Medicine, Deparment of Medical Microbiology, Malatya, Türkiye.
The increasing antibiotic resistance in Pseudomonas aeruginosa, responsible for both community-acquired and hospital-acquired infections, is of global significance. The primary mechanisms contributing to resistance development in P.aeruginosa include the increased activity of efflux pumps, decreased permeability of outer membrane porins and the production of carbapenemases.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, United States.
Receptor interacting protein kinase 1 (RIPK1) crucially upregulates necroptosis and is a key driver of inflammation. An effective PET radioligand for imaging brain RIPK1 would be useful for further exploring the role of this enzyme in neuroinflammation and for assisting drug discovery. Here, we report our progress on developing a PET radioligand for RIPK1 based on the phenyl-1-dihydropyrazole skeleton of a lead RIPK1 inhibitor, GSK'963.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Białystok, Poland.
Acne vulgaris (AV) is a chronic inflammatory condition of the pilosebaceous units characterized by multiple immunologic, metabolic, hormonal, genetic, psycho-emotional dysfunctions, and skin microbiota dysbiosis. The latter is manifested by a decreased population (phylotypes, i.e.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
Ferroptosis and sonodynamic therapy (SDT) are both promising therapeutic modalities, but their clinical application remains challenging due to the hypoxic tumor microenvironment and limited supply of polyunsaturated fatty acids. Developing an agent with oxygen-enhanced SDT and increased ferroptosis sensitivity is crucial for advancing tumor therapy. In this study, catalase (Cat) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) highly expressed 4T1 cells were constructed lentivirus transfection.
View Article and Find Full Text PDFInt J Med Sci
January 2025
Health Management Institute, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China.
Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis.
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