Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis

Background Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis.This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor （VEGF） and intercellular adhesion molecule 1 （ICAM-1） in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis.Methods Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group,the model group,the magnesium sulfate group and the anisodamine group.The rabbit model of infusion phlebitis,induced by intravenous administration,was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline.We evaluated expression by histopathology,immunohistochemistry,reverse transcription-polymerase chain reaction,and Western blotting assay.Results Pathohistological changes of the model group were observed,such as loss of venous endothelial cells,inflammatory cell infiltration,edema and thrombus.The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion,inflammatory cell infiltration,proliferation,swelling of endothelium and perivascular hemorrhage.The model group showed the highest expressions of VEGF and ICAM-1 of the four groups （P〈0.01）.On the contrary,anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group （P 〈0.01）.There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group （P 〉0.05）.Conclusion Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1,and shows significant protective effects

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.

Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF α (100 U/ml) or IL 1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM 1 and VCAM 1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up regulated by TNF α, IL 1β in a concentration and time dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM 1 and on VCAM 1 expression. Cytokines might directly induce the expression of ICAM 1 and VCAM 1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

EFFECT OF REPERFUSION THERAPY ON SOLUBLE CELL ADHESION MOLECULES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective To observe the changes of serum soluble intercellular adhesion moiecuie type-1(ICAM-1) and E-selectin in patients with acute myocardial inlarction (AMI) receiving reperfusiontherapy. Methods Peripheral venous blood samples were taken from 21 patients with AMI before and4,8,12,24,48,72h after thrombolytic treatment or direct percutaneous transluminal coronary angioplasty (PTCA).Blood samples from 16 control subjects were drawn for one time. Serum concentration of ICAM-1 and E-selectinwas determined by double antibodies sandwich enzyme-linked immunosorbent assay. Results Serum levels ofICAM-1 and E-selectin were higher in patients with AMI than those in controls. Sixteen patients with AMIand successful roperfusion therapy had signifcantly reduction in serum concentration of ICAM-1 and E-selectinat 24 and 48h, but had a peak at 4h. The remaining live patients who failed in mperfusion theropy didn’t show anysignificant changes in these values. Conclusion The serum concentration of ICAM-1 and E-selectin waselevated significantly in patients with AMI Successful reperfusion therapy can reduce the increased serumconcentration.

Effect of heparin on the expressions of serum intercellular adhesion molecule-1 and hippocampus S100β protein after cardiopulmonary resuscitation in rabbits

Objective: Use heparin during cardiac arrest(CA) in rabbits and observe the serum intercellular adhesion molecule-1(ICAM-1) and hippocampal S100β protein expressions after cardiopulmonary resuscitation(CPR). Methods: Thirty-two New Zealand rabbits were randomly divided into, Group Ⅰ,control group; Group Ⅱ, saline group; Group Ⅲ, heparin group. Each animal underwent continuous hemodynamic monitoring including mean arterial pressure(MBP), heart rate(HR), and the end-tidal carbon dioxide partial pressure(Pet CO2). Twenty-four hours after resuscitation, serum and hippocampal neurons were collected from all animals. Enzyme linked immunosorbent assay was used to detect serum ICAM-1 and immunohistochemistry to detect the S100β protein in hippocampal neurons.According to the rate of positive cells, each hippocampal specimen was categorized into four expression levels. Results: The differences in the serum ICAM-1 concentration in the three groups were statistically significant. The expression of S100β protein in the hippocampus showed eight cases in group Ⅰ at level 1 and none in groups Ⅱ and Ⅲ. There was 1 case in group Ⅱ and 7 cases in group Ⅲ at level 2; five cases in group Ⅱ and 2 cases in group Ⅲ at level 3; 2 cases in group Ⅱ and 1 case in group Ⅲ at level 4. The expression strength of S100β protein in the three groups differed significantly(P < 0.05). Conclusions: Heparin therapy can reduce the expression of serum ICAM-1 and S100βprotein in hippocampal neurons during CPR. It is possible that heparin can have a positive effect on brain protection during CPR.

Intercelular adhesion molecule-1 and accumulation of eosinophils in nasal polyp tissue

Objective To investigate the relationship between intercellular adhesion molecule 1 (ICAM 1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic inflammation.Methods The expression of ICAM 1 and its natural ligand, lymphocyte function associated antigen 1 (LFA 1), in normal nasal mucosa from 6 controls and in nasal polyp tissue from 19 patients with nasal polyposis were determined with immunohistochemistry. With dual immunohistochemistry and May Griünwald Giemsa stain (MGG), the expression of LFA 1 and infiltrating eosinophils in nasal polyp tissue was observed.Results The expression of ICAM 1 and LFA 1 was stronger in the nasal polyp tissue than in normal nasal mucosa. There was a positive relationship between the infiltration of eosinophils and the expression of LFA 1 on eosinophils.Conclusion Accumulation of eosinophils in nasal polyp tissue is associated with the counter effect between adhesion molecules and its ligand on eosinophils.

Effect of Methyl-CpG Binding Domain Protein 2(MBD2) on AMD-like Lesions in ApoE-Deficient Mice

Summary： The role of methyl-CpG binding domain protein 2 （MBD2） in an ApoE-deficient mouse model of age-related macular degeneration （AMD） was investigated. Eight-week-old Mbd2/ApoE double deficient （Mbd2^-/- ApoE^-/-） mice （n=12, 24 eyes, experimental group） and MBD2 （wt） ApoE^-/- mice （n=12, 24 eyes, control group） were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch＇s membrane （BM） of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 （ICAM-1） immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group （P〉0.05）. Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium （RPE） were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group （P〈0.05）. Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.

Orosomucoid-like protein 3,rhinovirus and asthma

The genetic variants of orosomucoid-like protein 3(ORMDL3)gene are associated with highly significant increases in the number of human rhinovirus(HRV)-induced wheezing episodes in children.Recent investigations have been focused on the mechanisms of ORMDL3 in rhinovirus infection for asthma and asthma exacerbations.ORMDL3 not only regulates major human rhinovirus receptor intercellular adhesion molecule 1 expression,but also plays pivotal roles in viral infection through metabolisms of ceramide and sphingosine-1-phosphate,endoplasmic reticulum(ER)stress,ER-Golgi interface and glycolysis.Research on the roles of ORMDL3 in HRV infection will lead us to identify new biomarkers and novel therapeutic targets in childhood asthma and viral induced asthma exacerbations.