The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of FICs (ΣFICs) and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.
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http://dx.doi.org/10.1590/s0074-02762011000800022 | DOI Listing |
Clin Cardiol
January 2025
Tehran Heart Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Background: Hypertension, a leading global risk factor for mortality and disability, disproportionately affects racial and ethnic minorities. Our study investigates the association between the type of prior antihypertensive medication use and the likelihood of cardiovascular events (CVE) and assesses whether the patient's race influences this relationship.
Methods: A retrospective study of 14 836 hypertension cases aged ≥ 40 years was conducted using data from HCA Healthcare between 2017 and 2023.
FEBS J
January 2025
Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Italy.
The trimeric intracellular cation channel B (TRIC-B), encoded by TMEM38B, is a potassium (K) channel present in the endoplasmic reticulum membrane, where it counterbalances calcium (Ca) exit. Lack of TRIC-B activity causes a recessive form of the skeletal disease osteogenesis imperfecta (OI), namely OI type XIV, characterized by impaired intracellular Ca flux and defects in osteoblast (OB) differentiation and activity. Taking advantage of the OB-specific Tmem38b knockout mouse (Runx2Cre;Tmem38b; cKO), we investigated how the ion imbalance affects the osteogenetic process.
View Article and Find Full Text PDFBone Res
January 2025
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, China.
Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mechanical protein Polysyctin-1 (PC1, Pkd1) regulates CTSK lineage tendon-derived mesenchymal stem cell (TDMSC) fate and ECM organization, thus affecting HO progression.
View Article and Find Full Text PDFJ Adv Res
January 2025
Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China. Electronic address:
Introduction: Pyroptosis represents a mode of programmed necrotic cell death (PCD), mediated by members of gasdermin family (GSDMs), such as GSDME. It is emerging as a promising approach for combating cancer. Notably, GSDME is the key modulator for the switch between apoptosis and pyroptosis in cells.
View Article and Find Full Text PDFBlood Press Monit
November 2024
Department of Cardiovascular Medicine, Centre for Epidemiological Studies and Clinical Trials, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, National Research Centre for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objective: The objective of this study was to investigate the efficacy of the nitrendipine/atenolol combination in comparison with standard-dose nitrendipine or atenolol monotherapy in reducing blood pressure (BP) and blood pressure variability (BPV) as assessed by ambulatory BP monitoring.
Methods: In a randomized, crossover trial, 32 patients (30-65 years) with grade 1 hypertension and elevated daytime reading-to-reading BPV were randomly assigned to receive either the nitrendipine/atenolol combination (10/20 mg) or standard-dose nitrendipine (10 mg) or atenolol (25 mg) monotherapy for 6 weeks, followed by a crossover to another treatment for 6 weeks.
Results: The final analysis included 31 patients (mean [±SD] age, 49.
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