Solid phase microextraction (SPME) is a technology where a small amount of an extracting phase dispersed on a solid support is exposed to the sample for a well-defined period of time. The open-bed geometry and biocompatibility of the materials used for manufacturing of the devices makes it very convenient tool for direct extraction from complex biological matrices. The flexibility of the formats permits tailoring the method according the needs of the particular application. Number of studies concerning monitoring of drugs and their metabolites, analysis of metabolome of volatile as well as non-volatile compounds, determination of ligand-protein binding, permeability and compound toxicity was already reported. All these applications were performed in different matrices including biological fluids and tissues, cell cultures, and in living animals. The low invasiveness of in vivo SPME, ability of using very small sample volumes and analysis of cell cultures permits to address the rule of 3R, which is currently acknowledged ethical standard in R&D labs. In the current review systematic evaluation of the applicability of SPME to studies required to be conduct at different stages of drug discovery and development and translational medicine is presented. The advantages and challenges are discussed based on the examples directly showing given experimental design or on the studies, which could be translated to the models routinely used in drug development process.
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http://dx.doi.org/10.1016/j.jpba.2016.05.012 | DOI Listing |
Hepatology
January 2025
Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients.
View Article and Find Full Text PDFJ Clin Oncol
January 2025
Institute of Cancer Research, London, United Kingdom.
Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging.
View Article and Find Full Text PDFNeurology
February 2025
Department of Neurology, Yale University School of Medicine, New Haven, CT.
Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.
Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.
J Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFACS Biomater Sci Eng
January 2025
Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3E3, Canada.
Restenosis remains a long-standing limitation to effectively maintain functional blood flow after percutaneous transluminal angioplasty (PTA). While the use of drug-coated balloons (DCBs) containing antiproliferative drugs has improved patient outcomes, limited tissue transfer and poor therapeutic targeting capabilities contribute to off-target cytotoxicity, precluding adequate endothelial repair. In this work, a DCB system was designed and tested to achieve defined arterial delivery of an antirestenosis therapeutic candidate, cadherin-2 (N-cadherin) mimetic peptides (NCad), shown to selectively inhibit smooth muscle cell migration and limit intimal thickening in early animal PTA models.
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