Assessment of Oral LISPRO Treatment in Ameliorating Amyloid and Tau Pathology in Transgenic Alzheimer’s Mice Model
Poster Jun 19, 2017
Ahsan Habib, Darrell Sawmiller, David Rongo, Yang Xiang, Jun Tian, Huayan Hou, Jin Zeng, Brian Giunta, Lukasz Wojtas, Adam Smith, Douglas R Shytle, Takashi Mori, Glenn Currier and Jun Tan
Lithium is used primarily as a mood stabilizer for bipolar disorder and has been used to treat mania, depression and suicidal thoughts for a long time. In addition, it has also been shown to prevent cognitive decline which indicated that lithium has a potential therapeutic effect in Alzheimer’s disease (AD). However, one of the main problems that exist in the currently FDA-approved lithium pharmaceutics (carbonate and citrate) is that it has narrow therapeutic index and lithium plasma level change drastically which can cause adverse side effects. Here we investigated the safety, pharmacokinetics and therapeutic efficacies of LISPRO (ionic co-crystals of lithium salicylate with organic l-proline), lithium salicylate, Li2CO3 (currently used) and placebo. We found that LISPRO attenuate β-amyloid plaques and phosphorylation of tau through modulation of inflammation and GSK3β inactivation. Cytokine profiles in the brain, plasma and splenocyte suggest that LISPRO (8-weeks) down-regulates pro-inflammatory, up-regulates anti-inflammatory and suppresses renal COX2 expression in Tg2576 mice. Plasma and brain pharmacokinetics of lithium indicated that LISPRO showed significantly higher brain and steady plasma lithium levels on C57BL/6J (2-weeks) and Tg2576 (8-weeks) mice. Interestingly, chronic (20-weeks) administration of LISPRO produces a slightly higher, but non-significant brain to plasma lithium levels and reduces β-amyloid plaques, and tau-phosphorylation through modulation of presynaptic (synaptophysin) and post-synaptic protein (PSD95) expression in 3xTg-AD mice.
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
Treatment Options for Chronic Parvovirus Viremia in Pediatric Heart Transplant Patients in a Tertiary Care CenterPoster
This abstract discusses three cases of pediatric heart transplant patients who suffered from parvovirus (B19) infection. Of these patients, two ( B & C) responded well to standard intravenous Ig therapy. Patient A however, did not respond to standard treatment and was begun on subcutaneous Ig, which effectively diminished his viral load. Thus, subcutaneous Ig infusions might serve as a second line treatment for transplant patients with parvovirus who do not respond well to the standard approach.READ MORE
T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphomaPoster
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE