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  • 1
    Abstract: Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.
    Type of Publication: Journal article published
    PubMed ID: 27099174
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  • 2
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : The amylase activity of twenty strains of Lactobacillus species isolated from intestinal contents of pigs was studied in vitro. Hydrolysis of starch was measured by following the disappearance of starch in a broth medium during the growth of all three strains. The amount of enzyme activity varied among strains. Three strains (A-4, L9 and L23) were selected for further study based on their high amylolytic activity in a broth containing soluble starch as the only carbohydrate source. Strains A-4 and L23 were identified as L. acidophilus and strain L9 was identified as L. fermentum. Among the three cultures, L. acidophilus L23 was selected as a potential candidate for use as a probiotic for improving digestion of starch in pigs based on its growth and hydrolysis of raw starch. The enzyme activity of L. acidophilus L23 was associated with the cell envelope and that of L. fermentum L9 was extracellular. The enzyme activity of L. acidophilus A4 was found in both locations. The enzyme activity of L. acidophilus L23 was inducible rather than constitutive.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    350 Main Street , Malden , MA 02148 , USA. , and 9600 Garsington Road , Oxford OX4 2DQ , England . : Blackwell Science Inc
    Journal of cardiac surgery 17 (2002), S. 0 
    ISSN: 1540-8191
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Introduction: Angiotensin II (Ang II) exerts its biological effects by binding to Ang II receptors. Two major subtypes of Ang II receptors, AT1R and AT2R, have been recognized by ligand binding studies. AT1R mediates most of the Ang II effects in the cardiovascular system. Usually, the AT2R only occurs in the growing animal but disappears in adults. The function of the AT2R so far has not been elucidated clearly. Recent studies have suggested that the AT2R is coupled to an antigrowth process that counteracts the growth-promoting program initiated by AT1R activation. We previously reported that gene expression of AT1R and AT2R were regulated differently in a time-dependent manner after myocardial infarction (MI). However, it is still not clear how the transcriptional levels of AT1R and AT2R are regulated as well as their localization after MI. Therefore, the present study is to investigate Ang II receptor expression in rat heart after using specific Ang II receptor antibodies. Materials and Methods: MI was surgically induced in Wistar rats weighing around 200g by permanent ligation of the left anterior descending coronary artery. After 3, 7, 14 and 21 days of surgery, these rats were sacrificed and rat heart was collected. H&E staining was used to evaluate the morphological changes and immunohistochemistry was used to investigate the receptor expression and localization of AT1R and AT2R. Results: H&E Staining: Degraded myocardium and fibrosis were seen in the infarcted area of left ventricle. Immunohistochemistry: Degraded myocytes of infarcted area in the left ventricle demonstrated the strongest AT1R staining. Positive immunostaining for AT1R was also detected in the endocardium, myocardium, and epicardium. Occasionally, positivity was also observed in the coronary vessels, mainly coronary vascular endothelium, but not smooth muscle cells. In the left ventricular wall, AT1R expression increased mainly on day 3 but decreased thereafter as a result of degrading myocytes. On the other hand, in the non-infarcted area, AT1R expression was detected but weaker than the infarcted area. On the contrary, AT2R positive immunostaining was less intense than AT1R. It was mainly expressed in the degraded myocardium of infarcted area. Some positive staining was also in the endocardium and epicardium though very weakly. Occasionally, the endothelium of large coronary arteries was positively stained but not in the small vascular endothelium or vascular smooth muscle. The expression of AT2R was increased over time. The strongest expression of AT2R was found on day 21, post-surgery. There was no AT2 expression detected in the non-infarct area. Conclusion: (1) Ang II expression was changed in the heart after MI. (2) Both AT1R and AT2R expressions are increased after remodeling. (3) Up and down-regulation of AT1R and AT2R respectively in the different time points suggested that there is some interaction between each other but its mechanism needs to be further elucidated.
    Type of Medium: Electronic Resource
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