ABSTRACT
We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ 2) receptor ligands. Two ligands with high σ 2 receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [18F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ 2 receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [18F]9 to σ 2 receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [18F]9 in the brain that is consistent with the distribution pattern of σ 2 receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [18F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [18F]9 as the first highly specific and promising imaging agent for σ 2 receptors in the brain.
ABSTRACT
Objective:To investigate the diagnostic value of micro RNA (miR)-21, miR-29a and D-dimer in myocardial ischemia-reperfusion.Methods:The clinical data of 80 patients with myocardial ischemia-reperfusion (ischemia-reperfusion group) and 80 patients without coronary artery stenosis (control group) in Yueqing People′s Hospital, Zhejiang Province from May 2017 to October 2018 were retrospectively analyzed. The patients in ischemia-reperfusion group were treated with percutaneous coronary intervention (PCI). The levels of miR-21, miR-29a, D-dimer, cardiac troponin (cTN), high sensitive C-reactive protein (hs-CRP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured in the ischemia-reperfusion group before operation, 1 and 5 d after operation, and the indexes in control group were measured on the day of admission.Results:In control group, the miR-21, miR-29a, D-dimer, cTn, hs-CRP and NT-proBNP were 0.14 ± 0.03, 0.19 ± 0.07, (123.2 ± 23.1) μg/L, (0.02 ± 0.01) μg/L, (0.65 ± 0.23) mg/L and (160 ± 78) ng/L. In ischemia-reperfusion group, the indexes before operation were 0.36 ± 0.08, 0.30 ± 0.05, (812.2 ± 95.7) μg/L, (0.48 ± 0.07) μg/L, (5.36 ± 2.67) mg/L and (853 ± 462) ng/L; the indexes 1 d after operation were 0.31 ± 0.07, 0.26 ± 0.04, (685.0 ± 29.3) μg/L, (0.41 ± 0.09) μg/L, (4.28 ± 1.59) mg/L and (560 ± 256) ng/L; the indexes 5 d after operation were 0.22 ± 0.03, 0.20 ± 0.04, (216.0 ± 27.6) μg/L, (0.30 ± 0.06) μg/L, (2.36 ± 0.78) mg/L and (382 ± 136) ng/L. The miR-21, miR-29a, D-dimer, cTn, hs-CRP and NT-proBNP before operation and 1, 5 d after operation in ischemia-reperfusion group were significantly higher than those in control group, and there were statistical differences ( P<0.05). In ischemia-reperfusion group, the indexes 1 and 5 d after operation were significantly lower than those before operation, the indexes 5 d after operation were significantly lower than those 1 d after operation, and there were statistical differences ( P<0.05). Conclusions:miR-21, miR-29a, D-dimer, cTn, hs-CRP and NT-proBNP are closely related to the clinical myocardial ischemia-reperfusion state.
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<p><b>OBJECTIVE</b>To explore the pathologic features and prognosis of early and late onset severe preeclampsia.</p><p><b>METHODS</b>An observational study was conducted in 178 cases of severe preeclampsia collected during January 2010 to December 2014 from Haidian Maternal and Child Health Hospital.The cases were divided into two groups according to the onset of gestational age of the severe preeclampsia, with 54 cases of namely early onset (onset ≤ 34 weeks) and 124 cases of late onset (onset >34 weeks). Clinical characteristics of the patients, perinatal outcome and the pathologic characteristics of the placentas in each group were evaluated.</p><p><b>RESULTS</b>Decidual vascular disease, placental infarction, abruptio placentae and placental villi dysplasia were seen in both groups. The incidence of placental villi dysplasia was the highest, followed by placental infarction. Incidence of severe decidual vascular disease of early and late onset severe decidual vascular disease were 16.7% (9/54) and 5.6% (7/124), respectively.Incidence of placental infarction of early and late onset severe preeclampsia were 48.1% (26/54) and 61.3% (76/124). Incidence of placental villi dysplasia of early and late onset severe preeclampsia were 79.6% (43/54) and 50.8% (63/124). Incidence of Severe decidual vascular disease, placental infarction and placental villi dysplasia were significantly different between early and late onset severe preeclampsia cases (P<0.05), while there was no difference in decidual vascular disease and placenta thrombi (P>0.05). Fetal survival rate of every group was 81.5% (44/54) and 93.5% (116/124). Incidence of fetal growth retardation was 55.6% (30/54) and 38.7% (48/124). The fetal survival rate and incidence of fetal growth retardation were different between two groups (P<0.05).</p><p><b>CONCLUSIONS</b>The incidence of decidual vascular disease and placental villi dysplasia in early onset severe preeclampsia is higher than those in late onset severe preeclampsia. Neonatal outcome and prognosis in early onset severe preeclampsia are worse than those in late onset severe preeclampsia.</p>