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Objectives: Mezlocillin is used in the treatment of neonatal infectious diseases. However, due to the absence of population pharmacokinetic studies in neonates and young infants, dosing regimens differ considerably in clinical practice. Hence, this study aimed to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin.Methods: A prospective, open-label pharmacokinetic study of mezlocillin was carried out in newborns. Blood samples were collected using an opportunistic sampling method. HPLC was used to measure the plasma drug concentrations. A population pharmacokinetic model was developed using NONMEM software.Results: Ninety-five blood samples from 48 neonates and young infants were included. The ranges of postmenstrual age and birth weight were 29-40 weeks and 1200-4000 g, respectively, including term and preterm infants. A two-compartment model with first-order elimination was developed to describe the population pharmacokinetics of mezlocillin. Postmenstrual age, current weight and serum creatinine concentration were the most important covariates. Monte Carlo simulation results indicated that the current dose of 50 mg/kg q12h resulted in 89.2% of patients achieving the therapeutic target, when the MIC of 4 mg/L was used as the breakpoint. When increasing the dosing frequency to q8h, a dose of 20 mg/kg resulted in 74.3% of patients achieving the therapeutic target.Conclusions: A population pharmacokinetic model of mezlocillin in neonates and young infants was established. Optimal dosing regimens based on this model were provided for use in neonatal infections. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-β, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE. [ABSTRACT FROM AUTHOR]

Highlights • Baicalein improves learning and memory in TLE rats. • Baicalein attenuates hippocampus damage and mossy fibre sprouting in TLE rats. • Baicalein reduces oxidative stress and inflammation in TLE rats. • Baicalein affects the glucocorticoid pathway in the brains of TLE rats. • Baicalein affects actin-associated protein in the brains of TLE rats. Abstract Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is a refractory disease. Baicalein possesses various pharmacological activities, including neuroprotection in neurodegenerative disease. However, whether baicalein is protective in the treatment of TLE is not determined. Therefore, the present study investigated the role of baicalein in the treatment of TLE. Baicalein was injected intraperitoneally to TLE rats for two weeks after the onset of spontaneous recurrent seizures (SRS). Rats were observed for the occurrence of SRS, and cognitive and hippocampus injuries were evaluated. Oxidative stress and inflammatory cytokines were measured. Corticosterone and its receptor, actin-associated protein F-actin and cofilin-1 were investigated in the brains of epileptic rats. Baicalein significantly improved cognition and reduced hippocampus damage and mossy fibre sprouting in TLE rats without obvious SRS suppression. Baicalein produced excellent anti-oxidative and anti-inflammatory effects in TLE rats. Baicalein restored the disruption of the glucocorticoid signal pathway and actin-associated protein in TLE rats. These results suggest that the neuroprotective effects of baicalein on cognition and the hippocampus are associated with the suppression of oxidative stress and inflammation and the regulation of the glucocorticoid pathway and actin-associated protein in TLE rats. This evidence supports the use of baicalein as an adjuvant agent for epilepsy treatment. [ABSTRACT FROM AUTHOR]