Antidepressants stimulate population growth in the harpacticoid copepod Nitocra spinipes

Like many pharmaceuticals, antidepressants are designed in such a way that they do not degrade easily. Due to their limited breakdown capabilities, they often enter sewage systems in their active form and may even end up in the environment. Significant concentrations of the commonly prescribed antidepressant citalopram have been measured in freshwater systems in the past. Moreover, recent experiments in our laboratory revealed effects on the life history of the harpacticoid copepod Nitocra spinipes caused by exposure to citalopram at concentrations of 100 ng/L and upward. It is, however, unclear how these effects on individuals propagate to the population level. In this study, freshly initialized populations of N. spinipes were exposed to citalopram hydrobromide at concentrations of 0 (control), 100, 1000 μg/L (18 populations per treatment). After 1, 3, 5, 6, 7, and 8 weeks, 3 replicate populations per treatment were permanently removed from the setup and preserved in 70% ethanol. All samples were first counted manually under a light microscope (excluding the larval stages which were too small) and subsequently photo-documented using a FlowCam. Manual counts showed no effects on the population abundance at 100 μg/L. At 1000 μg/L, population abundances were slightly reduced, at first, but strongly exceeded the control at weeks 7 and 8. This supposed stimulation effect may be attributed to an increased reproduction rate which had been observed earlier in individual females exposed to citalopram. At the time of abstract submission, the FlowCam pictures are still being processed. They are, however, expected to allow for a more thorough evaluation of the population dynamics, including high-resolution size-distributions of each sample, over time. The results of this study indicate no immediate threat of citalopram to N. spinipes at concentrations found in the environment (< 1 μg/L). However, they provide valuable insights into the form and timing of stressor-induced population-level effects on N. spinipes

Harpacticoid copepods in a DEB framework : investigating pharmaceutical effects on Nitocra spinipes

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Two dynamic energy budget models for the harpacticoid copepod Nitocra spinipes

The harpacticoid copepod Nitocra spinipes is a commonly used test species in ecotoxicological studies and subject of multiple international testing guidelines. While we strive for a better understanding of toxicant-induced effects in this species, physiological models rooted in the Dynamic Energy Budget (DEB) theory can help to explain such effects on the level of energy allocations within the organism. In previous works that aimed to capture the copepod life history in a DEB model, diverging assumptions on the growth pattern of copepods were made. While some authors presumed von Bertalanffy growth, others presumed an upcurving in length versus time due to metabolic acceleration. In this study we parametrized the two typified DEB models "abp" (metabolic acceleration from birth to puberty) and "sbp" (standard von Bertalanffy growth from birth to puberty) on life history data of N. spinipes. Besides using data from literature, we also measured additional length-at-time data to aid the parameter estimation. As the body proportions of N. spinipes changed continuously throughout its development, we used the square root of the top view area as a length measure to scale with the cube root of structural volume in length-to-volume conversions. Experimental data were predicted well with both models according to goodness of fit criteria. Despite a slightly better data fit in abp, we cannot rule out sbp as implausible. Overall, we expect both models to perform equally well in future applications. More detailed data on N. spinipes and closely related species are needed to support or reject the presumption of metabolic acceleration in the life history of copepods

Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: Anin vitroStudy

Background: Bacterial and fungal infections are common and often contribute to death in patients undergoing extracorporeal membrane oxygenation (ECMO). Drug disposition is altered during ECMO, and adsorption in the circuit is an established causative factor. Vancomycin and voriconazole are widely used, despite the lack of evidence-based prescription guidelines. Objective: The objective of this study was to determine the extraction of voriconazole and vancomycin by the Xenios/Novalung ECMO circuits. Methods: We have set up nine closed-loop ECMO circuits, consisting of four different iLAActivve® kits for neonatal, pediatric, and adult support: three iLA-ActivveMiniLung® petite kits, two iLA-ActivveMiniLung® kits, two iLA-ActivveiLA® kits, and two iLA-Activve X-lung® kits. The circuits were primed with whole blood and maintained at physiologic conditions for 24 h. Voriconazole and vancomycin were injected as a single-bolus age-related dose into the circuits. Pre-membrane (P2) blood samples were obtained at baseline and after drug injection at 2, 10, 30, 180, 360 min, and 24 h. A control sample at 2 min was collected for spontaneous drug degradation testing at 24 h. Results: Seventy-two samples were analyzed in triplicate. The mean percentage of drug recovery at 24 h was 20% for voriconazole and 62% for vancomycin. Conclusions: The extraction of voriconazole and vancomycin by contemporary ECMO circuits is clinically relevant across all age-related circuit sizes and may result in reduced drug exposure in vivo

Pregnancy related pharmacokinetics and antimicrobial prophylaxis during fetal surgery, cefazolin and clindamycin as examples

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis