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Current Concepts in Fluid Resuscitation and Vasopressor Use in Cirrhosis.
Semin Liver Dis
January 2025
Hepatology, University of Pennsylvania, Philadelphia, United States.
Critically ill patients with cirrhosis and liver failure not uncommonly have hypotension due to multifactorial reasons, that include hyperdynamic state with increased cardiac index, low systemic vascular resistance due to portal hypertension, following the use of beta blocker or diuretic therapy, and severe sepsis. These changes are mediated by microvascular alterations in the liver, systemic inflammation, activation of renin angiotensin aldosterone system, and vasodilatation due to endothelial dysfunction. Hemodynamic assessment includes measuring inferior vena cava indices, cardiac output and systemic vascular resistance using point-of-care ultrasound (POCUS), in addition to arterial waveform analysis, or pulmonary artery pressures, and lactate clearance to guide fluid resuscitation.
View Article and Find Full Text PDFFine-Tuning the Physicochemical Properties of Poly(lactic Acid) Nanoparticles for the Controlled Release of the BET Inhibitor JQ1: Influence of PVA Concentration.
Polymers (Basel)
January 2025
Facultad de Farmacia-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Unidad nanoDrug, Departamento de Química Inorgánica, Orgánica y Bioquímica, Universidad de Castilla-La Mancha, 02071 Albacete, Albacete, Spain.
The compounds targeting the bromo and extra terminal domain proteins (BET), such as the JQ1, present potent anti-cancer activity in preclinical models, however, the application of JQ1 at the clinical level is limited by its short half-life, rapid clearance, and non-selective inhibition of BET family proteins, leading to off-target effects and resistance. To address these challenges, the optimization of JQ1 delivery has been accomplished through polylactide (PLA) nanoparticles. PLA derivatives with varying molecular weights were synthesized via ring-opening polymerization using a zinc-based initiator and characterized using thermogravimetric analysis, differential scanning calorimetry, and infrared spectroscopy.
View Article and Find Full Text PDFPLK2 disrupts autophagic flux to promote SNCA/α-synuclein pathology.
Autophagy
January 2025
Laboratory of Molecular Neuropathology, Department of Pharmacology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology of Parkinson disease (PD). PLK2 (polo like kinase 2) is an evolutionarily conserved serine/threonine kinase that is more abundant in the brains of all family members, is highly expressed in PD, and is linked to SNCA deposition. However, in addition to its role in phosphorylating SNCA, the role of PLK2 in PD and the mechanisms involved in triggering neurodegeneration remain unclear.
View Article and Find Full Text PDFEnhanced Ocular Bioavailability and Prolonged Duration via Hydrophilic Surface Nanocomposite Vesicles for Topical Drug Administration.
Pharmaceutics
November 2024
Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, No. 280 University Town Outer Ring East Road, Guangzhou 510006, China.
Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye's complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional eye drops suffer from low bioavailability primarily due to rapid clearance mechanisms.
View Article and Find Full Text PDFEffect of A1470T Polymorphism on Lactate and Potassium Concentrations After Caffeine Ingestion During Acute Resistance Exercise.
Nutrients
December 2024
Laboratory of Genetics of Aging and Longevity, Kazan State Medical University, 420012 Kazan, Russia.
Background: The monocarboxylate transporter 1 (MCT1) plays a crucial role in regulating lactate and pyruvate transport across cell membranes, which is essential for energy metabolism during exercise. The A1470T (rs1049434) polymorphism has been suggested to influence lactate transport, with the T (major) allele associated with greater transport efficiency. This study aimed to investigate the effect of the polymorphism on lactate and potassium (K) concentrations in response to resistance exercise (RE) following caffeine (CAF) ingestion.
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