Kelli's Presentation

Temporin A alone and in combination with Imipenem reduces lethality in a mouse model of Staphylococcal Sepsis

S/S of septicemia include: fever, tachycardia (increased HR), tachypnea (increased RR), oliguria (decreased urine output), hypotension, hypoperfusion of tissues, lactic acidosis, altered mental status, edema, decreased cardiac contractility, microthrombi, fluid overload in interstitial spaces due to increased capillary permeability.

Gram + bacteria- PG and LTA
Binding of CD14 + TLR-4 causes activation of TNF, IL-1, IL-6, IL-8 and other leukocytes and macrophages.

S. Aureus have superantigenic properties

Modulation of mediator cascade
Anti-inflammatory agents- prevent binding of CD-14
Synthetic peptides- amphibian skin, g.i. trat, gastric mucosa all have ability to bind to LTA

Temporins-
A-H, K, L
Active against MRSA and VRE

Imipenem-Broad spectrum antibiotic
High affinity for penicillin binding proteins—this means that while Imipenem has the ability to release cell wall components, it also has the ability to convert bacteria into round cells that inhibit the release of LTA.

Methods-
Mice anesthetized and injected with live S. aureus or heat killed cells
Mice received control, TMP-A, IMP, TMP-A and IMP.

Live vs. heat killed cells-
Used to determine whether temporin A is effective strictly against the bacteria or effective in regulating the inflammatory response by inhibiting the release of TNF & IL-6.

Do not want TNF and IL-6 because it will increase cytokines and cause our system to shut down.

Anti-microbial peptide is cationic and amphipathic. However, S. aureus can decrease its outer membrane electric potential, but can never become completely resistant to anti-microbial peptides.

Macrophages used as cell line because they are good at releasing cytokines. They have more TLR’s, more MHC receptors which will more likely activate transcription of cytokines.

TNF alpha levels used Elisa as well as IL-6

charts show that by using combination therapy of temporin A with Imipenem or by temporin A alone, the levels of TNF & IL-6 were significantly lowered by testing the heat-killed staph. Also, remember the second charts (B's) starting at time "0" is actually starting treatment 6 hours after bacterial contamination.

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