This study investigated the critical role of Glut1-mediated glucose metabolism in the inflammatory response of macrophages, which are energy-intensive cells within the innate immune system. Inflammation leads to increased Glut1 expression, ensuring sufficient glucose uptake to support macrophage functions. We demonstrated that using siRNA to knock down Glut1 reduces the expression of various pro-inflammatory cytokines and markers, such as IL-6, iNOS, MHC II/CD40, reactive oxygen species, and the hydrogen sulfide (H₂S)-producing enzyme cystathionine γ-lyase (CSE). Glut1 activates a pro-inflammatory profile through a nuclear factor (NF)-κB, while silencing Glut1 can prevent lipopolysaccharide (LPS)-induced IκB degradation, blocking NF-κB activation. Glut1’s role in autophagy, an essential process for macrophage functions such as antigen presentation, phagocytosis, and cytokine secretion, was also measured. The findings show that LPS stimulation decreases autophagosome formation, but Glut1 knockdown reverses this effect, increasing autophagy beyond control levels. The study highlights Glut1’s importance in macrophage immune responses and its regulation of apoptosis during LPS stimulation. Knocking down Glut1 negatively impacts cell viability and mitochondrial intrinsic pathway signaling. These findings collectively suggest that targeting macrophage glucose metabolism through Glut1 could potentially serve as a target for controlling inflammation.

The aim of this study was to assess the adsorption of selected antibiotics: vancomycin, gentamicin, ciprofloxacine and tigecycline in an experimental continuous veno-venous hemofiltration circuit with the use of both polyethyleneimine-treated polyacrylonitrile (PAN) and the polysulfone (PS) filter membranes. The crystalloid fluid dosed with one of antibiotic was pumped from a reservoir through a hemofiltration circuit (with PAN or PS membrane) and back to reservoir. All ultrafiltrate was also returned to the reservoir. During the procedures samples were collected from the post-hemofilter port at 5, 15, 30, 45, 60, 90, and 120 min. To determine spontaneous degradation of the antimicrobials, an additional bag with each study drug was prepared, which was not attached to the hemofiltration circuit. The samples from these bags were used as controls. In the case of vancomycin, gentamycin and tigecycline there was a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to the control for PAN membrane (P < 0.05,P < 0.001,P < 0.001, respectively). In the case of ciprofloxacine adsorption was reversible and the drug concentrations increase to achieve the initial level for both membranes. Our studies indicated that a large portion of the administered dose of antibiotics may be adsorbed on a PAN membrane. In the case of gentamicin and tigecycline this amount is sufficiently big (over 90% of the administered dose) to be of clinical importance. In turn, adsorption on PS membranes is clearly lower (up to 10%) and may be clinically unimportant.

The aim of this study was to assess the in vitro adsorption of antibiotics: vancomycin, gentamicin, ciprofloxacin and tigecycline on both polyethyleneimine-treated polyacrylonitrile membrane of AN69ST filter and polysulfone membrane of AV1000 filter using porcine blood as a model close to in vivo conditions. The porcine blood with antibiotic dissolved in it was pumped into hemofiltration circuit (with AN69ST or AV1000 filter), ultrafiltration fluid was continuously returned to the reservoir containing blood with antibiotic. Blood samples to determine antibiotic concentrations were taken at minutes 0, 5, 15, 30, 45, 60, 90 and 120 from the pre- blood pump of the hemofiltration circuit. To assess possible spontaneous degradation of the drug in the solution there was an additional reservoir prepared for each antibiotic, containing blood with the drug, which was not connected to the circuit. In the case of vancomycin, ciprofloxacine and tigecycline, a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to initial value as well as to the concentrations in the control blood was observed, both for polyacrylonitrile and plolysulfone membrane. In the case of gentamicin, significant adsorption was noted only on polyacrylonitrile membrane. Our studies demonstrated that in full blood adsorption of antibiotics may be big enough to be of clinical significance. In particular in the case of polyacrylonitrile membrane.

Background: The primary objective of this study was to develop a population pharmacokinetic model of meropenem, based on the population of critically ill adult patients undergoing CRRT. The secondary one was to examine the relationship between patient characteristics (covariates) and individual PK parameters. Finally, we aimed to perform Monte Carlo simulations to assess the probability of target attainment (PTA) of %T > MIC considering the uncertainty of PK parameters. Materials and methods: The study population included 19 adult critically ill patients on CRRT, receiving 1 g of meropenem in 1-h infusions every 8 h. Blood samples were collected prior to (time zero) and 15, 30, 45, 60, 75, 90, 120, 180, 240 and 480 min after the start of meropenem administration. Population nonlinear mixed-effects modeling was conducted using NONMEM software, Fortran, and Wings for NONMEM. Results: A two-compartment model was used to describe the available data. Typical values of the central and peripheral volume of distribution, and the CRRT and inter-compartmental clearance for a theoretical patient with 24.6 g/l albumin concertation were V₁ = 27.9 l, V₂ = 33.7 l, Cl_CRRT = 15.1 l/h, and Q = 21.1 l/h. A significant covariate relationship between V₁ and albumin concentration was observed in the data that was described by a power relationship with − 2.87 exponent. Subsequently performed Monte Carlo simulations of the model allowed us to assess the impact of albumin concentration on PTA. The 40%T > 2 mg/l target was reached in more than 90% of subjects after 1-h infusion of 1000 mg q8h and steady-state conditions. The more stringent 100%T > 2 mg/l target requires higher doses and/or longer infusion durations that depend on the albumin concentration. Conclusions: The population PK model was successfully developed to describe the time course of meropenem concentrations. The hypoalbuminemia was found to be associated with higher PTA in the CRRT patients after multiple short-term infusions.