Sustained Chronic Maternal Hyperoxygenation Increases Myocardial Deformation in Fetuses with a Small Aortic Isthmus at Risk for Coarctation.

BACKGROUND: We aimed to assess differences in myocardial deformation in fetuses at risk for coarctation (CoA) and the effects of maternal hyperoxygenation on deformation. METHODS: Fetal echocardiography and velocity vector imaging were performed prospectively and serially in 48 fetuses with a small aortic isthmus and 48 gestation age-matched normal fetuses. Fetuses with a small aortic isthmus were randomly divided into two groups: one group with and the other group without maternal supplemental oxygen administration. The strain (S) and strain rate (SR) in the left ventricle (LV) and right ventricle (RV) were measured and compared between the groups. Regression analyses were performed to identify potential factors associated with myocardial deformation. RESULTS: Compared with normal fetuses, fetuses with a small aortic isthmus exhibited a lower S and SR at baseline. A negative correlation was found between aortic isthmus velocity-time integrals and S and SR at baseline (P < .05). In the group that received supplemental oxygen therapy, the S and SR in both the LV and RV increased as a function of time, especially 4 weeks after the initiation of oxygen therapy (P < .05). The duration of oxygen therapy and increased combined cardiac index were associated with increased myocardial deformation (P < .05). CONCLUSIONS: Myocardial deformation appears abnormal in those at risk for CoA beginning in utero, and chronic oxygen therapy appears to increase deformation measures. These findings may improve patient counseling and perinatal management.

Near-infrared induced phase-shifted ICG/Fe3O4 loaded PLGA nanoparticles for photothermal tumor ablation.

Near-infrared (NIR) laser-induced photothermal therapy (PTT) uses a photothermal agent to convert optical energy into thermal energy and has great potential as an effective local, minimally invasive treatment modality for killing cancer cells. To improve the efficacy of PTT, we developed poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulating superparamagnetic iron oxide (Fe3O4), indocyanine green (ICG), and perfluoropentane (PFP) as synergistic agents for NIR laser-induced PTT. We fabricated a novel type of phase-shifting fluorescent magnetic NPs, Fe3O4/ICG@PLGA/PFP NPs, that effectively produce heat in response to NIR laser irradiation for an enhanced thermal ablation effect and a phase-shift thermoelastic expansion effect, and thus, can be used as a photothermal agent. After in vitro treatment of MCF-7 breast cancer cells with Fe3O4/ICG@PLGA/PFP NPs and NIR laser irradiation, histology and electron microscopy confirmed severe damage to the cells and the formation of many microbubbles with iron particles at the edge or outside of the microbubbles. In vivo experiments in mice with MCF-7 tumors demonstrated that Fe3O4/ICG@PLGA/PFP NPs could achieve tumor ablation upon NIR laser irradiation with minimal toxicity to non-irradiated tissues. Together, our results indicate that Fe3O4/ICG@PLGA/PFP NPs can be used as effective nanotheranostic agents for tumor ablation.

Sustained maternal hyperoxygenation improves aortic arch dimensions in fetuses with coarctation.

The aim was to investigate the impact of maternal hyperoxygenation (HO) on cardiac dimensions in fetuses with isolated Coarctation (CoA). Fetal echocardiography was performed serially in 48 fetuses with CoA and gestation age matched normal fetues. The Z-scores for the mitral valve (MV), tricuspid valve (TV), aortic valve (AV), ascending aorta (AAo), isthmus, pulmonary valve (PV), main pulmonary artery (MPA), and descending aorta (DAo) were measured and compared among normal fetuses, CoA fetuses with oxygen and CoA fetuses with air. In the group with oxygen, 6 L/min oxygen was administered to the mother using a face mask. Regression analyses were performed to identify potential factors for HO outcome. The left heart dimension Z-scores increased gradually during HO therapy periods, especially at 4 weeks after oxygen therapy (P < 0.05). As for the case group with air, the left heart dimension remained unchanged. The duration of HO was associated with aortic arch Z-scores (adjusted R2 = 0.199, 0.60 for AAO and isthmus, respectively). Sustained maternal middle-flow oxygenation can be safely used to improve left heart dimensions in fetuses with isolated CoA. The duration of HO were associated with treatment outcome. These findings may provide useful information for developing novel treatment strategies.

Azaindole hydroxamic acids are potent HIV-1 integrase inhibitors.

HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication. Recently, HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Herein, we report the discovery of azaindole carboxylic acids and azaindole hydroxamic acids as potent inhibitors of the HIV-1 IN enzyme and their structure-activity relationships. Several 4-fluorobenzyl substituted azaindole hydroxamic acids showed potent antiviral activities in cell-based assays and offered a structurally simple scaffold for the development of novel HIV-1 IN inhibitors.