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http://hdl.handle.net/11375/29303
Title: | STUDIES OF STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA ON THE HOST RESPONSE TO SEPSIS |
Authors: | Carlin, Sean |
Advisor: | Liaw, Patricia |
Department: | Medical Sciences (Blood and Cardiovascular) |
Publication Date: | Jun-2024 |
Abstract: | Within the clinical literature, there is a discourse around the impact of hyperglycemia during critical illness, particularly sepsis. Since patients with chronic (e.g., diabetes mellitus) or acute (e.g., stress hyperglycemia) forms of hyperglycemia are more prone to developing infections, they are a population who have a higher potential for developing sepsis. Additionally, there are acquired aberrations to the host immune and coagulation systems in both hyperglycemia and sepsis independently. Combining a lack of concrete clinical understanding, an increased risk of infection, and independent changes to the host, we aimed to understand the effects of hyperglycemia on the host's response to polymicrobial sepsis. C57BL/6 mice from both biological sexes were administered a series of intraperitoneal injections of streptozotocin (50 mg/kg) to induce hyperglycemia at 5 weeks of age. The STZ-treated and age- and sex-matched untreated control mice were administer the fecal slurry to induce inflammation of the lining of the peritoneal cavity (peritoneum) called peritonitis, that leads to the development of sepsis. By taking the cecal contents of Sprague Dawley rats, we created a polymicrobial fecal slurry (0.6 mg/kg) that upon administration would induce sepsis. The mice had either an 8-hour hyperacute or 48-hour acute duration of sepsis exposure; at the endpoint, plasma, and organs were collected from the mice. We utilized the plasma to measure interleukin-6 (IL-6), interleukin-10 (IL-10), thrombin-antithrombin complex (TAT), protein C (PC), advanced glycation end-products (AGEs), and cell-free DNA (cfDNA). Additionally, we fixed, and H&E stained the organs (lungs, liver, and kidney). Finally, a section of the lung was snap-frozen and used to measure myeloperoxidase (MPO) concentration in the lung. Using the 8-hour hyperacute FIP model of sepsis, we observed significant increases in IL-6, IL-10, PC, and TAT but no difference in cfDNA and MPO in both glycemic states compared to non-septic controls. We then extended sepsis exposure to the 48-hour acute duration and observed no difference in survival or sepsis severity. Despite both glycemic conditions having similar coagulation responses during the hyperacute duration, we observed that STZ-treated mice, regardless of survival status, did not have significantly lower PC levels during the acute duration, while untreated non-survivors still had significantly lower levels. These data suggest a phenotypic shift in the coagulation profile of STZ-treated mice between 8 and 48 hours of sepsis exposure. |
URI: | http://hdl.handle.net/11375/29303 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Carlin_Sean_2023November_MSc.pdf | 2.22 MB | Adobe PDF | View/Open |
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