Evaluating student understanding of core pharmacokinetic concepts.

Both educators and graduates have expressed concern about a perceived pharmacology knowledge gap that includes difficulty applying fundamental principles to clinical and research problems. Consequently, we sought to determine the extent to which current students can explain the meaning of, and appropriately apply, a subset of core concepts, and to identify any misconceptions arising from the responses. Of the twenty-four pharmacology core concepts arising from the recent international collaboration, four pharmacokinetic concepts were chosen, namely drug bioavailability, drug clearance, volume of distribution, and steady-state concentration.

Evaluating student understanding of pharmacodynamics core concepts.

Pharmacodynamics is an essential subdiscipline of pharmacology that underpins safe and effective prescribing and therapeutic decision-making, as well as drug discovery and development. The exponential increase in the number of therapeutic drugs has prompted members of the pharmacology educator community to question existing pharmacology curricula focused on individual drugs and move toward a curriculum focused on conceptual understanding. A first step towards conceptual understanding is to establish what students currently know about pharmacodynamic core concepts.

Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time-Resolved Limited Proteolysis Mass Spectrometry.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer-protein interaction. We deployed limited proteolysis mass spectrometry (LiP-MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon-α2a (IFN). Target conjugates were digested with the specific protease trypsin and a "heavy" N-IFN wild type (IFN-WT) for time-resolved quantification of the cleavage dynamics.

1-[(2-Chloro-phen-yl)di-phenyl-meth-yl]-1-pyrazole.

The title compound CHClN, also named as TRAM-34, crystallizes in the monoclinic space group 2/n. The dihedral angles between the pyrazole ring and the three six-membered rings are 62.28 (9), 69.

Fostering moral reflectivity in community pharmacists through moral case deliberation using the dilemma method.

Background: Moral case deliberation has been successfully implemented in multidisciplinary groups of secondary care professionals to support ethical decision making. It has not yet been reported for community pharmacists.

Aim: This study investigated whether moral case deliberation fosters moral reflectivity in community pharmacists.

Impact of surface chemistry of upconversion nanoparticles on time-dependent cytotoxicity in non-cancerous epithelial cells.

The application of upconversion nanoparticles (UCNPs) for cell and tissue analysis requires a comprehensive understanding of their interactions with biological entities to prevent toxicity or harmful effects. Whereas most studies focus on cancer cells, this work addresses non-cancerous cells with their regular in vitro physiology. Since it is generally accepted that surface chemistry largely determines biocompatibility in general and uptake of nanomaterials in particular, two bilayer surface coatings with different surface shielding properties have been studied: (i) a phospholipid bilayer membrane (PLM) and (ii) an amphiphilic polymer (AP).

New Inhibitors of β-1,4-Galactosyltransferase I Discovered by Virtual Screening.

Seven different enzymes comprise the galactosyltransferases family, of which β-1,4-galactosyltransferase I (β-1,4-GALT1) is the major contributor to galactosylation activity in cells. Since abnormalities in galactosylation are associated with many pathophysiological conditions, β-1,4-GALT1 is an interesting new target for drug discovery and molecular probe design. There are several known β-1,4-GALT1 inhibitors, but most of them suffer from low cell permeability and thus low in vivo activity.

IL-1β stimulates a novel axis within the NFκB pathway in endothelial cells regulated by IKKα and TAK-1.

In this study we examined the activation of the non-canonical NFκB signalling pathway in endothelial cells. In HUVECs, LIGHT stimulated a delayed induction of serine 866/870 p100 phosphorylation linked to p52 NFκB formation. Surprisingly, the canonical ligand, IL-1β, stimulated a rapid phosphorylation or p100 which was not associated with p52 formation.

Feasibility of a Pharmabuddy Care Service for patients with Parkinson's disease.

Background: Pharmaceutical care for patients with Parkinson's disease (PD) is complex. Specialized pharmaceutical care provided by a dedicated pharmacy team member (pharmabuddy) for these patients may reduce medication-related problems. The feasibility of this service for PD patients is unknown.

Probing the interplay between drug saturation, processing temperature and microstructure of amorphous solid dispersions with synchrotron X-ray phase-contrast tomography.

The impact of drug saturation and processing regime on the microstructure of amorphous solid dispersions (ASDs) produced by hot-melt extrusion (HME) has been investigated. By exploring various combinations of drug loadings and processing temperatures, a range of drug saturation points were obtained by HME. The process was monitored with an in-line low-frequency Raman probe to construct the respective solubility phase diagram (i.

Structure Elucidation of the Daptomycin Products Generated upon Heterologous Expression of the Daptomycin Resistance Gene Cluster .

Recently, a high-level daptomycin (DAP)-resistant strain (TS92) was identified, which mediates a 33% decline of DAP when incubated in Mueller-Hinton (MH) medium. The genetic background of the DAP resistance in TS92 is a newly discovered two-gene operon, named whose expression was reported to impair the structural integrity of DAP, eventually leading to its inactivation. Here, we set out to elucidate the chemical nature of -mediated DAP modification by applying a general unknown comparative screening (GUCS) approach in high-resolution mass spectrometry.

Pharmacists' perspectives on potential pharmacist prescribing: a nationwide survey in the Netherlands.

Background: Pharmacist prescribing legislation aims to enhance healthcare quality and accessibility. However, in many countries, like the Netherlands, it has not yet been legally established.

Aim: To investigate pharmacists' perspectives on potential pharmacist prescribing in the Netherlands.

Relevance of therapeutic prescription modifications in Dutch community pharmacies.

Objectives: Community pharmacists modify prescriptions to solve or prevent drug-related problems. To assess the relevance of prescription modifications, they are usually judged on clinical outcomes only, overlooking their humanistic and economic impact. This study aims to evaluate therapeutic prescription modifications performed by Dutch community pharmacists in terms of clinical outcome, along with the humanistic aspect "usability" and economic aspect "efficiency.

Early silicone oil opacification in the absence of emulsification is caused by an increased level of silicone dioxide.

Purpose: In October 2023, other cases with early silicone oil opacification within hours after intraocular implantation in the absence of emulsification occurred. While multiple, small series of this phenomenon are now documented during the last decade, the cause was never unmasked. In this study, we analyzed explanted patient samples, unused samples of the affected, and a control batch of the same silicone oil.

Advancing skin model development: A focus on a self-assembled, induced pluripotent stem cell-derived, xeno-free approach.

The demand for skin models as alternatives to animal testing has grown due to ethical concerns and the need for accurate substance evaluation. These alternatives, known as New Approach Methodologies (NAMs), are increasingly used for regulatory decisions. Current skin models from primary human cells often rely on bovine collagen, raising ethical issues.

Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier.

Background: The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet.

In-Depth Mass Spectrometry Study of Vanadium(IV) Complexes with Model Peptides.

Investigating the speciation of vanadium complexes in the presence of potential biomolecular targets under physiological conditions remains challenging, and further experimental techniques are needed to better understand the mechanism of action of potential metallodrugs. The interaction of two model peptides (angiotensin I and angiotensin II) with three well-known oxidovanadium(IV) compounds with antidiabetic and/or anticancer activity, [VO(pic)(HO)], [VO(ma)], and [VO(dhp)] (where pic, ma, and dhp are picolinate, maltolate, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate anions, respectively), was investigated by ESI-MS/MS (electrospray ionization tandem mass spectrometry) and complemented by EPR (electron paramagnetic resonance) spectroscopy measurements and theoretical calculations at the DFT (density functional theory) level. The results demonstrated that vanadium-peptide bonds are preserved after HCD (higher energy collisional dissociation) fragmentation, allowing for the identification of binding sites through a detailed analysis of the fragmentation spectra.

Transglutaminase-catalyzed covalent anti-myostatin peptide depots.

Nature realizes protein and peptide depots by catalyzing covalent bonds with the extracellular matrix (ECM) of tissues. We are translating this natural blueprint for the sustained delivery of a myostatin-inhibiting peptide (Anti-Myo), resulting in an enzyme depot established from injectable solutions. For that, we fused Anti-Myo to the D-domain of insulin-like growth factor I, a transglutaminase (TG) substrate.

In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies.

Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear.

Feasibility Study for the Use of Gene Electrotransfer and Cell Electrofusion as a Single-Step Technique for the Generation of Activated Cancer Cell Vaccines.

Cell-based therapies hold great potential for cancer immunotherapy. This approach is based on manipulation of dendritic cells to activate immune system against specific cancer antigens. For the development of an effective cell vaccine platform, gene transfer, and cell fusion have been used for modification of dendritic or tumor cells to express immune (co)stimulatory signals and to load dendritic cells with tumor antigens.