Thermal ring-opening polymerization of an unsymmetrical silicon-bridged [1]ferrocenophane in coordination nanochannels

Thermal ring-opening polymerization of the unsymmetrically substituted [1]ferrocenophane was performed in one-dimensional nanochannels of porous coordination polymers (PCPs).</p

Inhibitory Effects of Antithrombin III on Interactions between Blood Cells and Endothelial Cells during Retinal Ischemia-Reperfusion Injury

PURPOSE. Infiltrating leukocytes have long been widely thought to be key mediators of ischemia-reperfusion injury. Recently, however, evidence suggests that platelets accumulating in postischemic tissues also contribute to ischemia-reperfusion injury because of their inflammatory properties and promotion of formation of thrombi. This study was designed to evaluate quantitatively the inhibitory effects of antithrombin (AT)-III on the interactions between blood cells and retinal endothelial cells in vivo after transient retinal ischemia. METHODS. Transient retinal ischemia was induced for 60 minutes in male Long-Evans rats by ligation of the optic nerve. AT III (250 U/kg) was administered intravenously just after induction of ischemia. Leukocyte and platelet behavior in the retina was evaluated in vivo with a scanning laser ophthalmoscope. Expression of P-selectin and intracellular adhesion molecule (ICAM)-1 in the postischemic retina was investigated by reverse transcription-polymerase chain reaction and immunohistochemistry. After 14 days of reperfusion, ischemia-induced retinal damage was evaluated histologically. RESULTS. Administration of AT III significantly inhibited leukocyte rolling along the major retinal veins and subsequent accumulation of leukocytes in the postischemic retina. Furthermore, the maximum number of rolling and adherent platelets was reduced by 76% (P Ͻ 0.01) and 48% (P Ͻ 0.01), respectively, at 12 hours after reperfusion. Immunohistochemical studies also revealed the suppressive effect of AT III on expression of P-selectin and ICAM-1. Finally, histologic examination demonstrated the protective effects of AT III against retinal damage after transient retinal ischemia. CONCLUSIONS. This study demonstrates the inhibitory effects of AT III on leukocyte and platelet recruitment to the postischemic retina, which may account for the neuroprotective properties of this ␣-2 globulin against retinal ischemia-reperfusion injury. (Invest Ophthalmol Vis Sci. 2003;44:332-341) DOI: 10.1167/iovs.02-0493 I nfiltrating leukocytes have long been acknowledged to be a feature of ischemia-reperfusion injury. 1-4 Recently, however, evidence suggests that platelets also play an important role in the pathogenesis of ischemia-reperfusion injury. 5,6 The importance of platelets is supported by many studies that have demonstrated the beneficial effects of platelet depletion against ischemia-reperfusion injury. 20,21 Thrombin, which is the terminal serine protease of the coagulation cascade, has the ability to activate platelets and fibrinogen. Recently, many investigators have focused on the role of thrombin in various pathologic conditions. It has been demonstrated that an increase in thrombin in postischemic tissues activates vascular endothelial cells. Such activated vascular endothelial cells express adhesion molecules, which contribute to the recruitment of leukocytes and platelets. We recently developed an in vivo method to quantitatively evaluate platelet-endothelium interactions in rat retina. 26 Using this method, we have found that platelets roll along and adhere to retinal venous endothelium during ischemia-reperfusion and that these interactions are mediated by endothelial Pselectin, not by platelet P-selectin. MATERIALS AND METHODS Animal Model Male pigmented Long-Evans rats (200 -250 g) were used in this study. Transient retinal ischemia was induced for 60 minutes in the right eye of each rat

Preparation of Porous Polysaccharides Templated by Coordination Polymer with Three-Dimensional Nanochannels

Polymerization of monosaccharide monomers usually suffers from the production of polysaccharides with ill-defined structures because of the uncontrolled random reactions among many reactive hydroxyl groups on saccharide monomers. In particular, rational synthesis of polysaccharides with porosity approximating molecular dimensions is still in its infancy, despite their usefulness as drug carriers. Here, we disclose an efficient synthetic methodology for the preparation of polysaccharides with controllable mesoporosity in the structure, utilizing [Cu₃(benzene-1,3,5-tricarboxylate)]_<i>n</i> (HKUST-1; <b>1</b>) as templates. Cationic ring-opening polymerization of 1,6-anhydro glucose was performed in nanochannels of <b>1</b>, followed by removal of the host frameworks, giving polysaccharide particles as replicas of the original molds. Nitrogen adsorption measurement revealed that the obtained polysaccharide particles contained high mesoporosity in the structure, which could be controlled systematically depending on the polymerization conditions. Because of the large specific surface area, tunable porosity and particle size, we could also demonstrate the capabilities of our polysaccharides for loading and releasing of a drug molecule and protein

Activation of Nrf2/Keap1 pathway by oral Dimethylfumarate administration alleviates oxidative stress and age-associated infertility might be delayed in the mouse ovary

Abstract Background Age-associated infertility is a problem worldwide, and management of oxidative stress is known to be essential. Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway works as an essential defense mechanism against oxidative stress, and an oral drug Dimethylfumarate (DMF) is known to activate the pathway. Methods We tested the hypothesis that oral DMF could alleviate oxidative stress in the ovary, resulting in salvation of age-associated infertility in a mouse model of reproductive age, and we examined the effects of DMF administration. 20 mg/kg DMF was administrated to female mice from 32 to 48 weeks, and Nrf2 levels, antioxidant levels, ovarian reserve, DNA damage, and oxidative stress were examined. Results DMF administration resulted in elevated mRNA and protein levels of Nrf2, antioxidants, and telomere, and serum levels of Nrf2 and anti-mullerian hormone were also elevated. Results of TUNEL assay and Immunohistochemistry of mice ovarian tissues showed that DNA damage and oxidative stress were decreased by DMF administration, and significantly more oocytes were collected along with preservation of 60% more primordial follicles. Conclusions Our data suggest that DMF administration activates the Nrf2/Keap1 pathway, elevate levels of antioxidants, and decrease DNA damage and oxidative stress, resulting in improved ovarian reserve in the mouse ovary