Publications by authors named "Korzekwa K"

Despite the vast amount of water on Earth, only a small percent is suitable for consumption, and these resources are diminishing. Moreover, water resources are unevenly distributed, leading to significant disparities in access to drinking water between countries and populations. Increasing consumption and the expanding human population necessitate the development of novel wastewater treatment technologies and the use of water treatment byproducts in other areas, such as fertilisers.

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Multidrug-resistant bacteria represent a significant challenge in the treatment of bacterial infections, often leading to therapeutic failures. This issue underlines the need to develop strategies that improve the efficacy of conventional antibiotic therapies. In this study, we aimed to assess whether a plant-derived compound, α-mangostin, and photodynamic therapy (PDT) could enhance the antibacterial activity of ciprofloxacin against uropathogenic strains of and .

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Article Synopsis
  • Nalbuphine (NAL) is an opioid that acts as a mixed κ-agonist/μ-antagonist and undergoes significant first-pass metabolism, prompting a study to understand its pharmacokinetics in individuals with varying liver impairments.
  • The study found that while NAL exposure was similar in subjects with mild hepatic impairment compared to healthy individuals, those with moderate and severe impairment had exposure levels that were approximately three-fold and eight-fold higher, respectively.
  • A mechanistic pharmacokinetic model, known as PDE-EHR, was developed to accurately describe NAL's metabolism and absorption, which can enhance predictions regarding drug interactions and overall drug behavior.
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One-compartment (1C) and permeability-limited models were used to evaluate the ability of microsomal and hepatocyte intrinsic clearances to predict hepatic clearance. Well-stirred (WSM), parallel-tube (PTM), and dispersion (DM) models were evaluated within the liver as well as within whole-body physiologically based pharmacokinetic frameworks. It was shown that a linear combination of well-stirred and parallel-tube average liver blood concentrations accurately approximates dispersion model blood concentrations.

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Salmonellosis associated with reptiles is a well-researched topic, particularly in China and the United States, but it occurs less frequently in Europe. The growth of the human population and changes in the environment could potentially increase the interaction between humans and free-living reptiles, which are an unidentified source of Salmonella species. In this study, we sought to explore this issue by comparing the microbiota of free-living European grass snakes, scientifically known as Natrix natrix, with that of captive banded water snakes, or Nerodia fasciata.

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Nalbuphine (NAL) is a κ-agonist/μ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR).

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Inflammatory bowel disease (IBD) encompasses several debilitating chronic gastrointestinal (GI) inflammatory disorders, including Crohn's disease and ulcerative colitis. In both conditions, mucosal inflammation is a key clinical presentation associated with altered serotonin (5-hydroxytryptamine or 5-HT) signaling. This altered 5-HT signaling is also found across various animal models of colitis.

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The second law of thermodynamics imposes a fundamental asymmetry in the flow of events. The so-called thermodynamic arrow of time introduces an ordering that divides the system's state space into past, future, and incomparable regions. In this work, we analyze the structure of the resulting thermal cones, i.

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Clearances are important parameters in pharmacokinetic (PK) models. All clearances in PK models are either process clearances that include diffusion, transport, and metabolism clearances or system clearances that include organ and systemic clearance. Clearance and volume of distribution are two independent parameters that characterize drug disposition in both individual compartments and systems of compartments.

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Salmonella enterica as common pathogens of humans and animals are good model organisms to conduct research on bacterial biology. Because these bacteria can multiply in both the external environments and in the living hosts, they prove their wide adaptability. It has been previously demonstrated that prolonged exposition of Salmonella serotype O48 cells to normal human serum led to an increase in resistance to sera in connection with the synthesis of very long O-antigen.

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Oral drug absorption is known to be impacted by the physicochemical properties of drugs, properties of oral formulations, and physiological characteristics of the intestine. The goal of the present study was to develop a mathematical model to predict the impact of particle size, feeding time, and intestinal transporter activity on oral absorption. A previously published rat continuous intestine absorption model was extended for solid drug absorption.

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We present a rigorous approach, based on the concept of continuous thermomajorization, to algorithmically characterize the full set of energy occupations of a quantum system accessible from a given initial state through weak interactions with a heat bath. The algorithm can be deployed to solve complex optimization problems in out-of-equilibrium setups and it returns explicit elementary control sequences realizing optimal transformations. We illustrate this by finding optimal protocols in the context of cooling, work extraction, and catalysis.

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The fluctuation-dissipation theorem is a fundamental result in statistical physics that establishes a connection between the response of a system subject to a perturbation and the fluctuations associated with observables in equilibrium. Here we derive its version within a resource-theoretic framework, where one investigates optimal quantum state transitions under thermodynamic constraints. More precisely, we first characterize optimal thermodynamic distillation processes, and then we prove a relation between the amount of free energy dissipated in such processes and the free-energy fluctuations of the initial state of the system.

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To improve predictions of concentration-time (C-t) profiles of drugs, a new physiologically based pharmacokinetic modeling framework (termed 'PermQ') has been developed. This model includes permeability into and out of capillaries, cell membranes, and intracellular lipids. New modeling components include (i) lumping of tissues into compartments based on both blood flow and capillary permeability, and (ii) parameterizing clearances in and out of membranes with apparent permeability and membrane partitioning values.

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Partition analysis has been described previously by W.W. Cleland to derive net rate constants and simplify the derivation of enzyme kinetic equations.

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Intricacies in intestinal physiology, drug properties, and food effects should be incorporated into models to predict complex oral drug absorption. A previously published human continuous intestinal absorption model based on the convection-diffusion equation was modified specifically for the male Sprague-Dawley rat in this report. Species-specific physiologic conditions along intestinal length - experimental velocity and pH under fasted and fed conditions, were measured and incorporated into the intestinal absorption model.

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The aim of this study was to assess the beneficial inhibitory effect of silver nanoparticles immobilized on SiO or TiO on biofilm formation by -one of the most dangerous pathogens isolated from urine and bronchoalveolar lavage fluid of patients hospitalized in intensive care units. Pure and silver doped nanoparticles of SiO and TiO were prepared using a novel modified sol-gel method. Ten clinical strains of and the reference PAO1 strain were used.

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Three CYP3A4 substrates, midazolam, ticlopidine, and diazepam, display non-Michaelis-Menten kinetics, form multiple primary metabolites, and are sequentially metabolized to secondary metabolites. We generated saturation curves for these compounds and analyzed the resulting datasets using a number of single-substrate and multisubstrate binding models. These models were parameterized using rate equations and numerical solutions of the ordinary differential equations.

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Complexities in P450-mediated metabolism kinetics include multisubstrate binding, multiple-product formation, and sequential metabolism. Saturation curves and intrinsic clearances were simulated for single-substrate and multisubstrate models using derived velocity equations and numerical solutions of ordinary differential equations (ODEs). Multisubstrate models focused on sigmoidal kinetics because of their dramatic impact on clearance predictions.

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Predicting drug-drug interactions (DDIs) from in vitro data is made difficult by not knowing concentrations of substrate and inhibitor at the target site. For in vivo targets, this is understandable, since intracellular concentrations can differ from extracellular concentrations. More vexing is that the concentration of the drug at the target for some in vitro assays can also be unknown.

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The cytochrome P450 enzymes (CYPs) are the most important enzymes in the oxidative metabolism of hydrophobic drugs and other foreign compounds (xenobiotics). The versatility of these enzymes results in some unusual kinetic properties, stemming from the simultaneous interaction of multiple substrates with the CYP active site. Often, the CYPs display kinetics that deviate from standard hyperbolic saturation or inhibition kinetics.

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Differential equations are used to describe time-dependent changes in enzyme kinetics and pharmacokinetics. Analytical and numerical methods can be used to solve differential equations. This chapter describes the use of numerical methods in solving differential equations and its applications in characterizing the complexities observed in enzyme kinetics.

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We study work extraction processes mediated by finite-time interactions with an ambient bath-partial thermalizations-as continuous-time Markov processes for two-level systems. Such a stochastic process results in fluctuations in the amount of work that can be extracted and is characterized by the rate at which the system parameters are driven in addition to the rate of thermalization with the bath. We analyze the distribution of work for the case in which the energy gap of a two-level system is driven at a constant rate.

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The impact of the Gram-negative bacterium ( on the microbiomic and pathogenic phenomena occurring in humans and other warm-blooded animals is relatively well-recognized. At the same time, there are scant data concerning the role of strains in the health and disease of cold-blooded animals. It is presently known that reptiles are common asymptomatic carriers of another human pathogen, , which, when transferred to humans, may cause a disease referred to as reptile-associated salmonellosis (RAS).

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Article Synopsis
  • The study aimed to assess the safety and effectiveness of combining quinacrine with capecitabine in treating patients with metastatic colorectal cancer (mCRC) who had not responded to previous treatments.
  • The trial established a maximum tolerated dose of quinacrine as 100 mg twice daily, with manageable side effects, while also noting 5 patients showed stable disease outcomes.
  • Although the expansion phase was stopped early due to manufacturing issues, the treatment regimen indicated a median time to tumor progression of 2.12 months and median overall survival of 5.22 months, suggesting potential benefits for heavily treated mCRC patients.
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