Zoe Cohen

Thrombin activity and platelet microparticle formation are increased in type 2 diabetic platelets: a potential correlation with caspase activation.

Diabetics suffer from many complications including a prothrombotic condition. Activated platelet membrane provides an anchor, phosphatidylserine, for the attachment of the prothrombinase complex, which allows increased thrombin formation. This study aimed to further elucidate the interrelationship between coagulation proteins and activated platelets in type 2 diabetic blood. We found that there was a significant increase (30 x) in thrombin activity in the type 2 diabetic (ZDF) blood as compared to age-matched (ZL) controls (p<0.001). There was also a significant increase in the number of platelet microparticles in the type 2 diabetic rat compared to the lean control (p<0.001). Further, there were significant increases in caspase-3, -6, and -8 activities in the type 2 diabetic rats as compared to the lean controls (p<0.05). The combination of increased thrombin activity, increased PMP formation and increased caspase activity may contribute to the hypercoagulability of the diabetic blood. These results give more insight into the mechanisms underlying the interrelationship between diabetic platelets and coagulation proteins causing a prothrombotic condition in this patient population at increased risk from thromboembolic events.

Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.

Please cite this paper as: Ritter, Davidson, Henry, Davis‐Gorman, Morrison, Frye, Cohen, Chandler, McDonagh and Funk (2011). Exaggerated Neutrophil‐Mediated Reperfusion Injury after Ischemic Stroke in a Rodent Model of Type 2 Diabetes. Microcirculation 18(7), 552–561.

How microRNAs influence both hereditary and inflammatory-mediated colon cancers

MicroRNAs have emerged as important post-translational regulators of gene expression and are involved in several physiological and pathological states including the pathogenesis of human colon cancers. In regards to tumor development, microRNAs can act as oncogenes or tumor suppressors. Two hereditary predispositions (i.e., Lynch syndrome and familial adenomatous polyposis) contribute to the development of colon cancer. In addition, individuals who suffer from inflammatory bowel diseases such as Crohns disease or ulcerative colitis have a higher risk of developing colon cancer. Here, we discuss the occurrence of the deregulated expression of microRNAs in colon cancer that arise as a result of hereditary predisposition and inflammatory bowel disease.

Whole blood aggregation, coagulation, and markers of platelet activation in diet-induced diabetic C57BL/6J mice

AIMS Type 2 diabetes in humans is associated with hypercoaguability; however, little is known about platelet function in mouse models of type 2 diabetes used to study this disorder. Therefore, the purpose of this study was to examine platelet aggregation, coagulation, and markers of platelet activation in a diet-induced mouse model of type 2 diabetes. METHODS Four week old, male, C57BL/6J mice were randomized to a standard chow or high fat (60% beef lard) diet for 4 months. To examine platelet function we measured ADP-induced whole blood aggregometry, whole blood coagulation by thromboelastography, tail bleeding times, platelet microparticle and platelet expression of p-selectin and platelet expression of CD61 by flow cytometry. RESULTS Diabetic mice exhibited less aggregation (p<0.05), less coagulation (p<0.01), prolonged tail bleeding times (n.s.), and lower agonist stimulated platelet CD61 expression (p<0.001) compared to non-diabetic mice. There was no difference in platelet microparticle and platelet p-selectin expression. CONCLUSIONS Diet-induced type 2 diabetic mouse do not demonstrate the hypercoagulability and platelet activation typically observed in humans with this disorder. More studies are warranted to further explore platelet function in this mouse model; to determine their applicability for studying these alterations in type 2 diabetes.

Caspase inhibition of platelet activation.

The role of caspases in platelet function is not well understood. When platelets are activated, they express phosphatidylserine on the outer plasma membrane, form platelet microparticles, and aggregate (Pag). The aims of this study were to determine if caspases play a role in the platelet activation seen in type 2 diabetes. Diabetic rats (Zucker diabetic fatty) were treated with a broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone, in vivo and platelets were evaluated for phosphatidylserine expression, platelet microparticle formation, and Pag. We found a decreased phosphatidylserine exposure in zVAD-Zucker diabetic fatty rats compared to Zucker diabetic fatty-phosphate-buffered saline when activated with 20 μmol/l ADP. Zucker diabetic fatty rats treated with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone decreased platelet microparticle numbers compared to phosphate-buffered saline control Zucker diabetic fatty rats. Further, treatment with benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone significantly decreased Pag. These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role of these proteases and perhaps the underlying mechanisms involved in the chronic platelet activation observed in type 2 diabetes.

Inflammablog: peer-to-peer online learning in immunology

Is it possible for students in different courses, at different academic levels, and at different universities to learn immunology together using the Internet? We teach a colloquium on inflammation for undergraduates at the University of Arizona and a lecture course on human immunology for graduate students and clinical and basic science fellows at the University of Colorado Anschutz Medical Campus. Students in these programs, being scattered about large campuses, have little time for student-directed discussion and peer interactions, and they never have the opportunity to meet students in the course in the other state. Instead of requiring the usual essays and term papers, we set up a blog (an online discussion group) for the two courses, and required all students to post, and comment on other posts, within and between the courses. Student writing is normally directed at a single reader, the instructor, which seems like a waste of talent; we encouraged peer exchanges. Furthermore, we were interested in observing the interactions between the Colorado students, who were older and sometimes experienced professionals, and the younger Arizonans. We used a blog because it is administratively impossible to enroll the students in two universities in a single courseware (learning management system) site. Blogging has offered insights into students’ comfort with this form of social medium, and into the potential for this approach in light of the rapid adoption of blended and massively open online courses.