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Exam 2 11-20

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Glutamine and gut health
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Fosters GI tract healing, primary source of energy for mucosal cells in the small intestines, reduces bacterial adhesion to enterocytes.
It can help heal leaky gut syndrome due to fueling of mucosal cells, low serum glutamine correlates with intestinal barrier disruption, inflammation, and diarrheal diseases amongst children.
1. COX 1 - important for bicarbonate production into unstirred layer, produces vasodilatory prostaglandins that help feed the mucosal cells for a healthier unstirred layer
COX 2 is an enzyme in cells initiates Ric Adonic acid pathway to produce inflammatory cytokines (Advil (Nonsteroidal anti-inflammatory drugs (NSAIDs) designed to inhibit COX 2 to prevent inflammation)
2. Ibuprofin can weaken the unstirred layer making the gut more vulnerable to GI bleeding / problems
3. Tart cherry juice can inhibit COX 2 w/o inhibiting COX 1
barrier defects: permit dietary antigens & bacterial products to cross the epithelium and enter the lamina propria.

T-helper activation: TNF or IFN-gamma which signal the epithelial cells to increase flux across the leak pathway; increased antigens & bacteria foster accelerated cycle of inflammation.
In contrast, if antigen presenting cells promote T regulator cells, which produce IL-10, MLCK is inhibited and tighten the barrier.
1) indigestible fragments of gluten induce enterocytes to release protein Zonulin, which loosens TJ
2) Gluten fragments (glandian) cross the intestinal lining in abundance and accumulate under epithelial cells (enterocytes)
3) The gluten induces enterocytes to secrete interleukin-15 which arouses immune cells (intracellular lymphocytes) against enterocytes.
4) Tissue transglutaminase (TTG - enzyme released by damaged cells) modifies the gluten
5) Antigen-presenting cells (APCs) of the immune system join the modified gluten to HLA molecules and display the resulting complexes to other immune cells: helper T lymphocytes
6) Helper T Cells secrete molecules that attract other immune cells and can directly damage enterocytes
7) Helper T cells spur killer T Cells to directly attack enterocytes
-intestinal barrier disruption leads to autoimmune disease such as T1DM
Celiac and gut inflammation weakens TJ barrier.
The inflammation activates zonulin which signals Protein kinase C cascade which causes phosphorylation of G-acin and F-actin.
Zonulin inhibitor larazotide has been found in rodents to stabilize the intestinal barrier and normalizing auto-antibodies insult to the pancreatic islets to prevent T1DM
High correlation between gluten gut reactions and T1DM.