mouse-kidney-transplantation-models-of-allograft-rejection

Mouse Kidney Transplantation: Models of Allograft Rejection

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

The University of Edinburgh

Vascular expression of the B1 kinin receptor is markedly upregulated with left ventricular dysfunction and angiotensin-converting enzyme (ACE) inhibition, but its function remains unclear. Inhibitors of ACE potentiate bradykinin-mediated B2 receptor-dependent vasodilatation and tissue plasminogen activator (tissue-type plasminogen activator [t-PA]) release. We investigated the contribution of the B1 receptor to the maintenance of vascular tone and t-PA release in patients with heart failure.

B1 kinin receptor does not contribute to vascular tone or tissue plasminogen activator release in the peripheral circulation of patients with heart failure.

Olanzapine is a second-generation atypical antipsychotic that is increasingly used in preference to older antipsychotic agents. Limited data is available concerning the toxic effects of olanzapine after deliberate overdose. Two patients presented to our institution after massive olanzapine ingestion, and required prolonged ventilatory support due to the development of coma and respiratory depression. Serum olanzapine concentrations were orders of magnitude higher than those associated with therapeutic doses, and remained elevated for several days after ingestion. Both patients made a full recovery with only supportive care, despite having initial serum drug concentrations > 2500 microg/l. These reports indicate the potential for olanzapine ingestion to cause coma that may persist for several days after overdose.

Prolonged toxicity after massive olanzapine overdose: two cases with confirmatory laboratory data.

Animal models suggest a vasomotor role for the B1 kinin receptor in cardiovascular disease states. In patients with heart failure treated with angiotensin-converting enzyme inhibition (ACEi), or combined B1/B2 receptor antagonism, but not B2 receptor antagonism alone, causes vasoconstriction. However, B1 agonism has no effect on vasomotor or fibrinolytic function. Findings from transgenic animals lacking the B2 receptor suggest that these conflicting data may be explained by cross-talk between B1 and B2 receptors. We hypothesized that B1 stimulation causes vasodilatation and tissue plasminogen activator release in the human forearm when B2 receptor signaling is inhibited. Forearm blood flow was measured in 16 patients with heart failure receiving ACEi. In double-blinded crossover studies, intrabrachial Lys-[Leu8]-des-Arg9-bradykinin (B1 antagonist), lys-des-Arg9-bradykinin (B1 agonist), bradykinin (B2 agonist), and sodium nitroprusside (endothelium-independent vasodilator) were infused alone or with HOE-140 (B2 antagonist). HOE-140 did not affect basal vascular tone or t-PA release, but it abolished bradykinin-induced vasodilatation and t-PA release (P < 0.0001). Blood flow and t-PA release were unaffected by B1 agonism or antagonism in the presence and absence HOE-140. Our findings do not support a role for crosstalk between the B1 and B2 kinin receptors in the human peripheral circulation.

Vascular B1 kinin receptors in patients with congestive heart failure.

The application of shockwave lithotripsy (SWL) in patients with arterial aneurysm remains controversial, and several case reports exist in the world literature that describe both safe use and rupture. In addition, other vascular complications have been reported. The potential for hemorrhage is affected by coagulation status and antiplatelet therapy, yet little evidence exists on their interaction with SWL. We aim to review the vascular complications after SWL.

Shockwave lithotripsy: arterial aneurysms and vascular complications.

Immunohistochemistry continues to be a powerful tool for the detection of antigens. There are several commercially available software packages that allow image analysis; however, these can be complex, require relatively high level of computer skills, and can be expensive. We compared 2 commonly available software packages, Adobe Photoshop CS6 and ImageJ, in their ability to quantify percentage positive area after picrosirius red (PSR) staining and 3,3'-diaminobenzidine (DAB) staining. On analysis of DAB-stained B cells in the mouse spleen, with a biotinylated primary rat anti-mouse-B220 antibody, there was no significant difference on converting images from brightfield microscopy to binary images to measure black and white pixels using ImageJ compared with measuring a range of brown pixels with Photoshop (Student t test, P=0.243, correlation r=0.985). When analyzing mouse kidney allografts stained with PSR, Photoshop achieved a greater interquartile range while maintaining a lower 10th percentile value compared with analysis with ImageJ. A lower 10% percentile reflects that Photoshop analysis is better at analyzing tissues with low levels of positive pixels; particularly relevant for control tissues or negative controls, whereas after ImageJ analysis the same images would result in spuriously high levels of positivity. Furthermore comparing the 2 methods by Bland-Altman plot revealed that these 2 methodologies did not agree when measuring images with a higher percentage of positive staining and correlation was poor (r=0.804). We conclude that for computer-assisted analysis of images of DAB-stained tissue there is no difference between using Photoshop or ImageJ. However, for analysis of color images where differentiation into a binary pattern is not easy, such as with PSR, Photoshop is superior at identifying higher levels of positivity while maintaining differentiation of low levels of positive staining.

A comparative study of 2 computer-assisted methods of quantifying brightfield microscopy images.

In this issue of Transplantation, Ma et al. describe the protective effect of administering the c-fms kinase inhibitor upon cellular rejection, suggesting an important pathogenic role for macrophages. In contrast, no effect upon the development of humerol rejection was evident. The role of macrophages in rejection is discussed.

Article	Year
B1 kinin receptor does not contribute to vascular tone or tissue plasminogen activator release in the peripheral circulation of patients with heart failure. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 15681300	2005
Prolonged toxicity after massive olanzapine overdose: two cases with confirmatory laboratory data. The Journal of toxicological sciences\| PubMed ID: 18670167	2008
Vascular B1 kinin receptors in patients with congestive heart failure. Journal of cardiovascular pharmacology\| PubMed ID: 19033823	2008
Shockwave lithotripsy: arterial aneurysms and vascular complications. Journal of endourology / Endourological Society\| PubMed ID: 21235424	2011
A comparative study of 2 computer-assisted methods of quantifying brightfield microscopy images. Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry\| PubMed ID: 23343954	2013
Macrophages and transplant rejection: a novel future target? Transplantation\| PubMed ID: 24092375	2013

George H. Tse

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