Alumina nanoparticles (AlNP) have been shown to accumulate in organs and penetrate biological barriers which lead to toxic effects in many organ systems. However, it is not known whether AlNP exposure to female mice during pregnancy can affect the development of the central nervous system or induce neurodevelopmental toxicity in the offspring. The present study aims to examine the effect of AlNP on neurodevelopment and associated underlying mechanism. ICR strain adult female mice were randomly divided into four groups, which were treated with normal saline (control), 10 μm particle size of alumina (bulk-Al), and 50 and 13 nm AlNP during entire pregnancy period. Aluminum contents in the hippocampus of newborns were measured and neurodevelopmental behaviors were tracked in the offspring from birth to 1 month of age. Furthermore, oxidative stress and neurotransmitter levels were measured in the cerebral cortex of the adolescents. Our results showed that aluminum contents in the hippocampus of newborns in AlNP-treated groups were significantly higher than those in bulk-Al and controls. Moreover, the offspring delivered by AlNP-treated female mice displayed stunted neurodevelopmental behaviors. Finally, the offspring of AlNP-treated mice demonstrated significantly increased anxiety-like behavior with impaired learning and memory performance at 1 month of age. The underlying mechanism could be related to increased oxidative stress and decreased neurotransmitter levels in the cerebral cortex. We therefore conclude that AlNP exposure of female mice during pregnancy can induce neurodevelopmental toxicity in offspring.
The effects of intrahepatic cholestasis of pregnancy (ICP) on hepatic function, changes of inflammatory cytokines and fetal outcomes were studied. In total, 663 pregnant women admitted to Daqing Longnan Hospital from July 2016 to December 2017 were selected. There were, 40 cases with ICP enrolled in the observation group, and 40 normal pregnant women were recruited in the normal group. They were also grouped according to hepatic function and inflammatory cytokines, with 40 cases in each group. Neonatal Apgar scores were recorded. The correlations of serum cholylglycine (CG) in pregnant women with umbilical artery systolic-to-diastolic (S/D) ratio in the third trimester of pregnancy, the alanine aminotransferase level, the high-sensitivity C-reactive protein (hs-CRP) level, neonatal Apgar score and gestational week were analyzed. The birth weight in the observation group was lighter than that in the normal group (P<0.05); the gestational week at birth was earlier than that in the normal group (P<0.05); Apgar score at birth was lower than that in the normal group (P<0.05), and the levels of inflammatory cytokines were higher than those in the control group (P<0.05). Apgar scores of newborns at birth and at 1 and 5 min after birth in the normal hepatic function and normal inflammatory cytokine groups were higher than those in the abnormal hepatic function group (P<0.05). The serum CG level in pregnant women was positively correlated with umbilical artery S/D ratio, the alanine aminotransferase level and the hs-CRP level in the third trimester of pregnancy, but negatively correlated with neonatal Apgar score and gestational week. Among patients with ICP, the higher the GG level in the body is, the higher the alanine aminotransferase, inflammatory cytokine and umbilical artery S/D ratio will be, which may cause lower neonatal Apgar score, neonatal asphyxia and premature delivery.
We have shown that gamma vinyl-GABA (GVG, VigabatrinR), a selective suicide inhibitor of GABA-transaminase (GABA-T), inhibits the effects of cocaine, nicotine, heroin, alcohol and methamphetamine both biochemically (dopamine) and behaviorally in rodents and primates. These data strongly suggest that the, use of GVG may represent a new strategy for the treatment of substance abuse [l]. To better understand the mechanism associated with this inhibition and the pharmacokinetics, as well as the potential side effects of this drug, we carried 'out investigations on developing a radiosynthesis of ["CIGVG for PET studies (tll2 for C-11 = 20 min). Several synthetic routes for the preparation of GVG including radiolabeling with longlived I4C (t1n for C-14 = 5730 yr) have been published [2, 31; however, they are not suitable for C-11 radiosynthesis. For example, a procedure,to prepare the key 2oxopyrrolidine-5-carboxaldehyde precursor that would in principle allow the incorporation of C-1 1 by employing Wittig condensation with["C]methyltriphenylphosphonium iodide was not straightforward (Scheme 1) [4, 5 , Kihlberg, 1990 #6, 61, We experienced this in our initial trials and other researchers made similar observations. Difficulties encountered during the isolation of the aldehyde precursor, its instability for storage, +s well as the subsequent timeconsuming Wittig reaction prompted us to pursue another synthetic pathway. Scheme 1
Based on the pharmacokinetic model of conventional agents, through introduction of sustained-release effect factor, we build a pharmacokinetic model of sustained-release agents so as to provide a new model of agents for clinical application. We discuss the properties of the new model and make a comparison with the conventional ones. By theoretical analysis and clinical data validation of metformin conventional agents and sustainedrelease ones, the model we build in this paper accords with the properties of sustained-release agents and it has practical value for clinical applications.
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