Publications by authors named "H Van der Spek"
Article Synopsis
- Polymyxin B has been used since the 1950s, but research on its pharmacokinetics (PK) and pharmacodynamics (PD) has been limited, particularly regarding its effectiveness against certain bacterial strains.
- In a study involving neutropenic infected mice, researchers found that the pharmacokinetic profile of polymyxin B was non-linear, with the fAUC/MIC index being the most indicative of efficacy against Klebsiella pneumoniae, while E. coli showed better correlation with fCmax/MIC.
- The study concluded that polymyxin B's standard dosing regimen may not effectively treat serious infections due to low kill rates against most clinical isolates, suggesting it might not be reliable as a standalone treatment.
Article Synopsis
- Flucloxacillin has been a long-standing treatment for methicillin-susceptible Staphylococcus aureus (MSSA), yet its pharmacodynamics are not fully understood.
- The study measured minimum inhibitory concentrations (MICs) of 305 MSSA isolates to establish wild-type distribution and tested the drug's effectiveness using a neutropenic mouse infection model.
- The findings revealed that maintaining flucloxacillin concentrations above certain thresholds (specifically, a percentage of time the unbound concentration remains above MIC) correlates with treatment efficacy, suggesting ways to optimize human dosing regimens.
Caenorhabditis elegans is a highly versatile model system, intensively used for functional, genetic, cytometric, and integrative studies. Due to its simplicity and large muscle cell number, C. elegans has frequently been used to study mitochondrial deficiencies caused by disease or drug toxicity.
View Article and Find Full Text PDFUse of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs.
View Article and Find Full Text PDFToday HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial.
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