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To characterize utility of atrioventricular block (AVB) dogs as atrial fibrillation (AF) model, we studied remodeling processes occurring in their atria in acute (<2 weeks) and chronic (>4 weeks) phases. Fifty beagle dogs were used. Holter electrocardiogram demonstrated that paroxysmal AF occurred immediately after the production of AVB, of which duration tended to be prolonged in chronic phase. Electrophysiological analysis showed that inter-atrial conduction time and duration of burst pacing-induced AF increased in the chronic phase compared with those in the acute phase, but that atrial effective refractory period was hardly altered. Echocardiographic study revealed that diameters of left atrium, right pulmonary vein and inferior vena cava increased similarly in the acute and chronic phases. Histological evaluation indicated that hypertrophy and fibrosis in atrial tissue increased in the chronic phase. Electropharmacological characterization showed that i.v. pilsicainide effectively suppressed burst pacing-induced AF with increasing atrial conduction time and refractoriness of AVB dogs in chronic phase, but that i.v. amiodarone did not exert such electrophysiological effects. Taken together, AVB dogs in chronic phase appear to possess such pathophysiology as developed in the atria of early-stage AF patients, and therefore they can be used to evaluate drug candidates against early-stage AF.
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http://dx.doi.org/10.1016/j.jphs.2024.06.004 | DOI Listing |
Adv Exp Med Biol
September 2025
Department of Stem Cells & Regenerative Medicine, Center for Interdisciplinary Research, D. Y. Patil Education Society (Deemed to be University), Kolhapur, Maharashtra, India.
Wound healing is a dynamic and complex process that consists of four interconnected phases: hemostasis, inflammation, proliferation, and remodeling. This complex process is based on the coordinated actions of growth factors, cytokines, and other cellular interactions. However, conditions such as diabetes and chronic illnesses can disrupt this process and lead to nonhealing wounds or chronic ulcers.
View Article and Find Full Text PDFDiabetes Obes Metab
September 2025
Phase I Clinical Trial Research Ward, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and its presence increases the risk of multi-system diseases. This study aimed to investigate the multimorbidity trajectories of chronic diseases in people living with MASLD.
Methods: We identified 137 859 MASLD patients in UK Biobank and used 'propensity score matching' to match an equal number of non-MASLD controls.
Blood Neoplasia
November 2025
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic neoplasm characterized by an expansion of CD123 monocytes and plasmacytoid dendritic cells (pDCs). pDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial for patients with CMML.
View Article and Find Full Text PDFBlood Neoplasia
November 2025
The University of Texas MD Anderson Cancer Center, Houston, TX.
IO-202 is a humanized immunoglobulin G1 monoclonal antibody with high affinity and specificity for leukocyte immunoglobulin-like receptor B4 (LILRB4; ILT3), which is predominantly expressed in monocytes and monocytic blasts. IO-202 induces antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro and in patients with leukemia. Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R chronic myelomonocytic leukemia (CMML), and the phase 1b dose expansion data of IO-202 combined with AZA for the treatment of hypomethylating agent (HMA)-naïve CMML.
View Article and Find Full Text PDFJHEP Rep
October 2025
Janssen Pharmaceutica NV, Beerse, Belgium.
Background & Aims: Previous studies showed that combination treatment with short interfering RNA JNJ-73763989 (JNJ-3989) ± capsid assembly modulator bersacapavir (JNJ-56136379) and nucleos(t)ide analogs (NAs) was well tolerated by patients with chronic HBV (CHB), with JNJ-3989 dose-dependent reductions in viral markers, including HBsAg. The open-label, single-arm phase IIa PENGUIN study (NCT04667104) evaluated this regimen plus pegylated interferon alpha-2a (PegIFN-α2a) in patients with virologically suppressed CHB.
Methods: Patients who were either HBeAg-positive or -negative virologically suppressed and taking NAs were included; all received JNJ-3989 ± bersacapavir for 24 weeks (some either did not start or discontinued bersacapavir as a result of protocol amendment) with PegIFN-α2a added during the final 12 weeks of treatment.