Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers.

Background: Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.

Fluid shear stress-induced changes in megalin trafficking enhance endocytic capacity in proximal tubule cells.

Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multi ligand receptors megalin and cubilin play pivotal roles in the endocytic uptake of normally filtered proteins in PT cells but also contribute to the uptake of nephrotoxic drugs, including aminoglycosides. We previously demonstrated that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) are superior to cells cultured under static conditions in recapitulating essential functional properties of PT cells .

Community College Student Persistence During the COVID-19 Crisis of Spring 2020.

This quantitative study examines the impact of the COVID-19 pandemic on students' persistence at a minority-serving, open-access, public, urban community college in New York City. Specifically, the project looked at factors associated with mid-semester college withdrawals during spring 2020 when the college shifted to remote instruction due to the COVID-19 pandemic. Utilizing data from three spring semesters (spring 2018, 2019, and 2020), four logistic regression models tested the marginal effects of student background and college program factors on mid-semester withdrawal and the moderating effect of spring 2020, the COVID-19 outbreak semester.

Fluid Shear Stress-Induced Changes in Megalin Trafficking Enhance Endocytic Capacity in Proximal Tubule Cells.

Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multiligand receptors megalin and cubilin play pivotal roles in the endocytic uptake of normally filtered proteins in PT cells but also contribute to the uptake of nephrotoxic drugs, including aminoglycosides. We previously demonstrated that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) are superior to cells cultured under static conditions in recapitulating essential functional properties of PT cells To identify drivers of the high-capacity, efficient endocytic pathway in the PT, we compared FSS-cultured OK cells with less endocytically active static-cultured OK cells.

Integrated stress response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use Drosophila melanogaster as a model to establish the integrated stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor that instructs oogenesis.

Adjusting surface coverage of Pt nanocatalyst decoration for selectivity control in CMOS-integrated SnO thin film gas sensors.

Smart gas-sensor devices are of crucial importance for emerging consumer electronics and Internet-of-Things (IoT) applications, in particular for indoor and outdoor air quality monitoring (, CO levels) or for detecting pollutants harmful for human health. Chemoresistive nanosensors based on metal-oxide semiconductors are among the most promising technologies due to their high sensitivity and suitability for scalable low-cost fabrication of miniaturised devices. However, poor selectivity between different target analytes restrains this technology from broader applicability.

Integrated Stress Response signaling acts as a metabolic sensor in fat tissues to regulate oocyte maturation and ovulation.

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we use as a model to establish the Integrated Stress response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor which instructs oogenesis.

Comparison of ultrafiltration and microdialysis for ceftriaxone protein-binding determination.

Background: High protein binding (PB) of antibiotics has an impact on their antimicrobial activity. It has been questioned whether in vitro PB determination can capture the dynamic and concentration-dependent PB of highly bound antibiotics.

Objectives: This clinical study compared in vitro ultrafiltration (UF) and in vivo IV microdialysis (MD) methods to determine ceftriaxone PB.

Effect of the human endotoxin challenge on tedizolid tissue penetration.

The effects of the human endotoxin challenge on tissue pharmacokinetics are unknown. In the present study, we aimed to assess the effect of the endotoxin challenge on interstitial fluid pharmacokinetics of tedizolid in healthy volunteers using intramuscular microdialysis. Eight healthy male subjects were treated with 200 mg of tedizolid phosphate for 6 days.

Accelerator mass spectrometry for quantification of micro- and therapeutic-dose diclofenac in microdialysis samples.

Microdialysis sampling after drug microdosing may provide tissue pharmacokinetic data early in clinical drug development. However, low administered doses and small sample volumes pose an analytical challenge, particularly for highly protein-bound drugs. Carbon-14 [C]diclofenac was used as a model drug to assess the technical and analytical feasibility of microdialysis after microdose administration in an setup.

Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers.

Objectives: The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study investigated the interchangeability of generic drugs with their originators by comparing bioequivalence parameters and stability data of generic cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs.

Methods: In this open-label, randomized, crossover bioequivalence study, three groups of 12 healthy volunteers each received a single intravenous infusion of either 2 g of cefepime or 4.

Small extracellular vesicles from plasma of women with preeclampsia increase myogenic tone and decrease endothelium-dependent relaxation of mouse mesenteric arteries.

Preeclampsia (PE) is a common syndrome of pregnancy, characterized by new-onset hypertension and proteinuria after gestational week 20, or new onset of hypertension and significant end-organ dysfunction. In the worst cases, it can threaten the survival of both mother and baby. Extracellular vesicles (EVs) are lipid-bilayer nanoparticles released from cells.

Diclofenac in vitro microdialysis study comparing different experimental set-ups to improve quantitative recovery.

Several studies investigated diclofenac tissue concentrations using microdialysis (MD). However, thorough evaluations of the optimal MD set-up for diclofenac are unavailable. Thus, this in vitro MD study aimed to compare different set-ups to improve quantitative recovery of diclofenac.

Phase I Study to Assess Safety of Laser-Assisted Topical Administration of an Anti-TNF Biologic in Patients With Chronic Plaque-Type Psoriasis.

Ablative fractional laser treatment facilitates epidermal drug delivery, which might be an interesting option to increase the topical efficacy of biological drugs in a variety of dermatological diseases. This work aims at investigating safety and tolerability of this new treatment approach in patients with plaque-type psoriasis. Eight patients with plaque-type psoriasis were enrolled in this study.

Plasma and soft tissue pharmacokinetics of ceftolozane/tazobactam in healthy volunteers after single and multiple intravenous infusion: a microdialysis study.

Objectives: To investigate ceftolozane/tazobactam pharmacokinetics (PK) in plasma and interstitial space fluid (ISF) of muscle and subcutaneous tissue and establish a population PK model.

Methods: Eight healthy volunteers received four IV doses of 1000/500 mg ceftolozane/tazobactam q8h in a prospective, open-labelled PK study. ISF concentration-time profiles were determined via in vivo microdialysis up to 8 h post-dose and efficacy of unbound ceftolozane and tazobactam was estimated using the time above MIC (%ƒT>MIC) and time above threshold concentration (%T>CT), respectively.

Protein binding of clindamycin in vivo by means of intravascular microdialysis in healthy volunteers.

Objectives: The efficacy of an anti-infective drug is influenced by its protein binding (PB), since only the free fraction is active. We hypothesized that PB may vary in vitro and in vivo, and used clindamycin, a drug with high and concentration-dependent PB to investigate this hypothesis.

Methods: Six healthy volunteers received a single intravenous infusion of clindamycin 900 mg.

Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial.

Background: The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking.

High voriconazole target-site exposure after approved sequence dosing due to nonlinear pharmacokinetics assessed by long-term microdialysis.

Voriconazole, a broad-spectrum antifungal drug used to prevent and treat invasive fungal infections, shows complex pharmacokinetics and is primarily metabolised by various CYP enzymes. An adequate unbound antibiotic concentration-time profile at the target-site of an infection is crucial for effective prophylaxis or therapy success. Therefore, the aim was to evaluate the pharmacokinetics of voriconazole after the approved sequence dosing in healthy volunteers in interstitial space fluid, assessed by microdialysis, and in plasma.

Lack of dermal penetration of topically applied gentamicin as pharmacokinetic evidence indicating insufficient efficacy.

Background: Treatment of skin and superficial soft tissue infections with topically applied antibiotics is a controversial topic, because only few clinical studies exist and target site concentrations after topical treatment are widely unknown.

Objectives: This study aimed to investigate the target site concentration of topically applied gentamicin as a potential cause of therapeutic failure and to explore if microporation by laser might be used to improve penetration of gentamicin through the skin barrier.

Methods: Six healthy volunteers were included in this cross-over Phase 1 study.

Pharmacokinetics of doripenem in plasma and epithelial lining fluid (ELF): comparison of two dosage regimens.

Purpose: In 2014, FDA released a warning for prescription of doripenem for ventilator-associated bacterial pneumonia due to unsatisfactory clinical cure rates. The present study explores if the observed lack of efficacy might be explained by insufficient target site pharmacokinetics in intensive care patients after two different infusion schemes.

Methods: Plasma and bronchoalveolar lavage sampling was performed in 16 intubated patients with pneumonia receiving doripenem either as 1-h or as 4-h infusion.

Differences in Sulfotyrosine Binding amongst CXCR1 and CXCR2 Chemokine Ligands.

Tyrosine sulfation, a post-translational modification found on many chemokine receptors, typically increases receptor affinity for the chemokine ligand. A previous bioinformatics analysis suggested that a sulfotyrosine (sY)-binding site on the surface of the chemokine CXCL12 may be conserved throughout the chemokine family. However, the extent to which receptor tyrosine sulfation contributes to chemokine binding has been examined in only a few instances.

Colistin Reduces LPS-Triggered Inflammation in a Human Sepsis Model In Vivo: A Randomized Controlled Trial.

The previously described anti-endotoxin effect of colistin has not been investigated in humans yet. We performed a randomized, double-blind, placebo-controlled crossover trial to determine the degree of colistin-driven modulation of inflammatory response in blood of lipopolysaccharide (LPS)-challenged healthy volunteers in a human endotoxemia model. After a single intravenous dose of 2.