Summary
What is known and objective
A series of studies have indicated that valproic acid (VPA) plasma concentration decreased rapidly when used concomitantly with carbapenem antibiotics, including ...meropenem (MEPM), imipenem and panipenem, which may increase the risk of seizure breakthrough. However, the cause for the change in VPA pharmacokinetics is unclear. A retrospective analysis of VPA therapeutic drug monitoring (TDM) records was performed to investigate this VPA pharmacokinetics drug–drug interaction.
Methods
Three hundred and eighty one VPA TDM records from the Department of Neurosurgery of Xiangya Hospital from January 2012 to December 2014 were collected. The VPA TDM records were categorized by VPA and MEPM daily dosages in grams/day (g/day). A comparison of VPA plasma levels among different groups was performed to investigate the change in VPA level in this drug interaction.
Results and discussion
Remarkable decreases in VPA plasma level were observed when the drug was used concomitantly with MEPM in both 1.2 g/d and 1.6 g/d VPA groups (67·3 ± 4·6 μg/mL, n = 21 vs. 15·3 ± 1·9 μg/mL, n = 15, P < 0·001; 67·6 ± 1·2 μg/mL vs. 18·1 ± 2·6 μg/mL, n = 38, P < 0·001). No significant difference in VPA plasma concentrations was observed between the 1·2 g/day VPA + MEPM, 1·6 g/day VPA + MEPM and 2·0 g/day VPA + MEPM groups (15·3 ± 1·9 μg/mL, n = 15 vs. 18·1 ± 2·6 μg/mL, n = 38 vs. 9·0 ± 3·0 μg/mL, n = 7; P = 0·252). The decrease in VPA concentration was independent of MEPM daily dose (14·0 ± 5·1 μg/mL, n = 4 for high MEPM daily dose vs. 16·5 ± 1·9 μg/mL, n = 56 for low MEPM daily dose; P = 0·729). After discontinuation of MEPM for more than 7 days, VPA plasma concentration recovered to a value comparable to that before MPEM initiation (69·7 ± 4·2 μg/mL, n = 21 vs. 51·2 ± 8·1 μg/mL, n = 9; P = 0·48).
What is new and conclusion
This is the first study using a large number of VPA TDM records to investigate the change in VPA levels caused by concomitant use of MEPM. Our results imply that the decrease in drug concentration cannot be reversed by increasing VPA dose. Moreover, MEPM daily dose did not influence the drop in VPA plasma level. At least 7 days are required for the recovery of VPA plasma concentration after discontinuation of MEPM.
The magnitude of decrease in VPA plasma concentration was independent of VPA and MEPM daily dose in this drug‐drug interaction.
Nasopharyngeal aspirates were collected from 813 children <14 years old with acute lower respiratory tract infections in Lanzhou, China, from December 2006 to November 2009. PCR or RT-PCR was used to ...screen for the presence of 10 respiratory viruses. Viral agents were identified in 73.92% (601/813) of specimens, including RSV in 40.71%, hMPV in 6.15%, IFVA in 7.13%, IFVB in 0.98%, PIV1-3 in 7.87%, HCoV-HKU1 in 2.21%, HCoV-NL63 in 3.81%, HRV in 19.93%, AdV in 7.50% and HBoV in 11.56%. Two or more viruses were detected in 34.44% (280/813) of cases. The newly identified respiratory viruses, HBoV, hMPV, HCoV-HKU1 and HCoV-NL63, accounted for 22.01% of the detected viral pathogens. RSV and HRV were frequently detected in patients with bronchiolitis, and hMPV was frequently associated with pneumonia. HCoV-NL63 was found to be one of the causative agents of acute respiratory wheezing in young children. No seasonal variation was found in the incidence of detection of HCoV-HKU1, HCoV-NL63 or HBoV. This 3-year study demonstrated that viral pathogens play an important role in children with ALRTIs, and more attention should be paid to these newly identified viral agents.
Cypermethrin contamination was a potential threat to soil organisms. In the present work, reproductive damage in earthworms (Amynthas corticis) exposed to cypermethrin was investigated. It was found ...that earthworms could absorb and accumulate residual cypermethrin in soil, and also earthworm activities helped accelerate the degradation of cypermethrin in soil. The accumulation of cypermethrin in earthworms induced sperm damage, and cypermethrin not only caused the imbalance of calcium homeostasis in earthworm sperm cells by inhibiting earthworm sperm Ca2+-ATP and Ca2+-Mg2+-ATP enzyme activities but also caused barriers in acrosome reaction. It also affected sperm energy supply of earthworms by inhibiting the activity of Na+-K+-ATPase and Mg2+-ATPase of earthworm sperm. Meanwhile, the inhibition of acrosome enzyme activity of earthworm sperm by cypermethrin led to hinder fertilization and reduced cocoon production of earthworms, and the damage of cypermethrin to sperm of earthworm was a significant cause of its reproductive toxicity. The results of the evaluation of IBR index showed that reproductive toxicity of cypermethrin to earthworms reduced with the increasing time. The decreased reproductive toxicity of cypermethrin to earthworms at the later stage of exposure (42–56 d) might be due to a combination of reduced absorption of cypermethrin in soil by earthworms, decreased accumulation of cypermethrin in the body, and improved sperm capacitation.
•Earthworms could absorb and accumulate residual cypermethrin in soil.•Earthworm activities helped accelerate the degradation of cypermethrin in soil.•Damage to earthworm spermatozoa by cypermethrin was a significant cause of its reproductive toxicity.•Changes in sperm viability, acrosome enzyme activity and Ca2+-ATPase activity of earthworms indicated reproductive damage in earthworms.
Based on 4.4 fb -1 of e + e - annihilation data collected at the center-of-mass energies between 4.60 and 4.70 GeV with the BESIII detector at the BEPCII collider, the pure W-boson-exchange decay Λ c ...+ → Ξ 0 K + is studied with a full angular analysis. The corresponding decay asymmetry is measured for the first time to be α Ξ 0 K + = 0.01 ± 0.16(stat) ± 0.03(syst). This result reflects the noninterference effect between the S- and P-wave amplitudes. The phase shift between S- and P-wave amplitudes has two solutions, which are δ p - δ s = -1.55 ± 0.25(stat) ± 0.05(syst) rad or 1.59 ± 0.25(stat) ± 0.05(syst) rad.
Using a data sample of (10087 ± 44) x 10 6 J/ψ events collected by the BESIII detector in 2009, 2012, 2018 and 2019, the electromagnetic Dalitz process J/ψ → e + e - η(1405) is observed via the decay ...η(1405) → π 0 f 0 (980), f 0 (980) → π + π - , with a significance of about 9.8σ. The branching fraction of this decay is measured to be B(J/ψ → e + e − η(1405) → e + e − π 0 f 0 (980) → J/ψ→ e + e - η(1405) → e + e - π 0 f 0 (980) → e + e - π 0 π + π - ) = (2.04 ± 0.20(stat) ± 0.08(syst)) x 10 -7 . The branching fraction ratio B(J/ψ → e + e - η(1405))/B(J/ψ → γη(1405)) is determined to be (1.36 ± 0.17(stat) ± 0.06(syst)) x 10 -2 . Furthermore, an e + e - invariant mass dependent transition form factor of J/ψ → e + e - η(1405) is presented for the first time. The obtained result provides input for different theoretical models and is valuable for the improved understanding the intrinsic structure of the η(1405) meson.
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