Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE： To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 （IL-6） overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING： Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS： Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups： sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS： Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES： The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy （x200）. RESULTS： In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION： The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.

Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide,glutathione peroxidase,and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO （P 〈 0.01）. The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）, compared with the physiological saline group （P 〈 0.05-0.01）. Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）. Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group （P 〉 0.05）. CONCLUSION： In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level.

Fused-ring induced end-on orientation in conjugated molecular dyads toward efficient single-component organic solar cells

The molecular orientations of conjugated materials on the substrate mainly include edge-on,face-on,and end-on.Edge-on and face-on orientations have been widely observed,while end-on orientation has been rarely reported.Since in organic solar cells(OSCs)charge transport is along the vertical direction,end-on orientation with conjugated backbones perpendicular to the substrate is recognized as the ideal microstructure for OSCs.In this work,we for the first time obtained the preferential end-on orientation in a conjugated molecular dyad that contains a conjugated backbone as donor and perylene bisimide side units as acceptor.This was realized by introducing a fused-ring structure to replace linear terthiophenes with conjugated backbones,yielding F-MDPBI and L-MDPBI respectively.Surprisingly,a shifting trend of the molecular orientation from dominating edge-on in L-MDPBI to preferential end-on in F-MDPBI was observed.As a consequence,vertical charge carrier mobilities in F-MDPBI are one order of magnitude higher than those with preferential edge-on orientation,so single-component OSCs based on this molecular dyad as a single photoactive layer provided a power conversion efficiency of 4.89% compared to 1.70% based on L-MDPBI with preferential edge-on orientation.

A comparative study of the aromaticity in some typical conjugated six-membered rings by the method of localized molecular orbital

The localized molecular orbitals and energy levels for four typical conjugated six-membered ring systems C_6H_6, C_3N_3H_3, B_3N_3H_6, and (B_3O_6)^(3-) as well as a non-aromatic reference molecule N_3Cl_6 have been calculated by using Edmiston-Ruedenberg energy localization technique under the CNDO/2 approximation in order to investigate the nature of aromaticity or quasi-aromaticity of the six-membered ring systems studied. The contour maps for π-type localized MO's (LMO) have been plotted to illustrate the bonding characteristics of the five ring systems studied. These LMO calculations show that for all the conjugated six-membered ring systems considered there exists local delocalization of π-bonds or three-centered and occasionally four-centered two-electron π-bonds in our terminology, and the cooperative effect among these π-bonds leading to the formation of a closed continuous x-conjugation system around the ring, which is necessary for the creation of aromaticity in the systems studied. We have been able to discuss the properties of these three-centered π-bonds in terms of the constituent atoms and electrons and the relevant orbitals involved.