Life Sciences Commons^™

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin

Physiology Faculty Publications

Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.

Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.

Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …