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Introduction: Cytokines play a major role in the pathogenesis of periodontal disease and may be used as markers in diagnosis. We aimed to evaluate correlation between progression of periodontal disease and plasma expression of several interleukins. Material and method:A total of 88 subjects, 40 males and 48 females, divided into 4 groups: healthy group (HG), early generalized chronic periodontitis group (EGP), moderate generalized chronic periodontitis group (MGP) and advanced generalized chronic periodontitis group (AGP), were included in the study. Enzyme-linked immunosorbent assay (ELISA) test was used for quantification of interleukin (IL)-1β, IL-8, IL-10 and IL-13 in the blood samples. Clinical periodontal parameters were recorded and statistical analysis, using SPSS version 25.0, was performed.Results: Both IL-1β and IL-8 plasmatic levels were significantly higher in EGP, MGP and AGP groups compared to the control group. IL-10 and IL-13 plasma levels were significantly higher in the HG compared to chronic periodontitis groups. Significant correlations were found between IL-1β, IL-8, IL-10 and IL-13 in chronic periodontitis patients and between IL-10 and IL-13 in the control group. Conclusion:Our results suggest that interdependence between these interleukins is much more frequent in chronic periodontitis patients and that plasma concentration of each interleukin, seems to be closely associated with periodontal disease progression. A possible causal relationship between periodontal and systemic inflammation is evident.

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BackgroundAminoglycosides are administered to treat (suspected) neonatal sepsis. The pharmacokinetics (PK) of this antibiotic class are expected to be different in neonates with perinatal asphyxia (PA) treated with therapeutic hypothermia (TH). Effective exposure of the aminoglycoside amikacin in neonates is achieved using a prospectively validated population PK mod-el-derived dosing regimen.1 However, dosing adjust-ments in case of PA with TH are lacking. The aim of the current (AMICOOL) study was to further explore amikacin disposition in neonates by quantifying the impact of PA treated with TH on amikacin clearance and to provide dosing recommendations for this specific patient population.MethodsAmikacin therapeutic drug monitoring data were retrospectively collected from term neonates with PA treated with TH and admitted to the neonatal inten-sive care units of VUmc Amsterdam and the University Hospitals Leuven between 2010–2015. Data were added to the original published amikacin population PK dataset.2 A data-driven covariate analysis was performed to assess the impact of PA treated with TH on amikacin clearance. Monte Carlo simulations facilitated the comparison of simulated amikacin exposures using the current dosing guidelines.1 and proposed dosing adaptations for PA treated with TH. We hereby aimed to achieve optimal amikacin trough (<5 mg/L) and peak (>24 mg/L) levels. Stochastic simulations were used to investigate the differ-ences in exposure among typical neonates with PA and TH with varying birth weights (1965–4220 g).ResultsData of 55 neonates with PA treated with TH were added to the original amikacin population PK dataset of 930 neonates.2 A 40.6% (RSE 9%) decrease in amikacin clearance for neonates with PA with TH was documented. Based on Monte Carlo simulations, the current dosing guidelines resulted in 40%–57% of neonates with PA and TH displaying amikacin trough concentrations above the toxic trough level (>5 mg/L), while an additional increase of the dosing interval with 12 hours decreased this percentage to 14%. Stochastic simulations showed that among typical neonates the percentage of patients with trough concentrations>5 mg/L ranges 14% to 25%.ConclusionIn neonates with perinatal asphyxia treated with therapeutic hypothermia, amikacin clearance is reduced with 40.6%. Based on simulations, an additional prolongation of the dosing interval with 12 hours results in optimised amikacin exposure and reduces toxicity in this specific population. As a future perspective, the model-based dosing proposal needs prospective validation. Since amikacin can be used as a surrogate for glomerular filtration, clearance of other drugs using the same elimination route could also be reduced in case of perinatal asphyxia treated with therapeutic hypothermia and may require further dosing adaptations.