Delving into the Latest Updates on Louisiana State University Health Shreveport with Synapse

作者: Mychaskiw, George ; Ahmadzadeh, Shahab ; Everett, Erin S ; Kaye, Alan D ; Shekoohi, Sahar ; Baptiste, Carlo Jean ; Lehuquet, Arianna M ; Maitski, Rebecca ; Barrie, Sonnah ; Varrassi, Giustino ; Mason, Joseph W ; Plessala, Michael J

PURPOSE OF REVIEWDespite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.RECENT FINDINGSHowever, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

2024-11-01·Biochemical and Biophysical Research Communications

Possible regulation of the immune modulator tetraspanin CD81 by alpha-synuclein in melanoma

Article

作者: Aloy, Nirjhar M ; Graner, Michael W. ; Aloy, Nirjhar M. ; Witt, Stephan N. ; Graner, Michael W ; Witt, Stephan N ; Coughlan, Christina

We probed the mechanism by which the Parkinson's disease-associated protein α-synuclein (α-syn)/SNCA promotes the pathogenesis and progression of melanoma. We found that the human melanoma cell line SK-MEL-28 in which SNCA is knocked out (SNCA-KO) has low levels of tetraspanin CD81, which is a cell-surface protein that promotes invasion, migration, and immune suppression. Analyzing data from the Cancer Genome Atlas, we show that SNCA and CD81 mRNA levels are positively correlated in melanoma; melanoma survival is inversely related to the levels of SNCA and CD81; and SNCA/CD81 are inversely related to the expression of key cytokine genes (IL12A, IL12B, IFN, IFNG, PRF1 and GZMB) for immune activation and immune cell-mediated killing of melanoma cells. We propose that high levels of α-syn and CD81 in melanoma and in immune cells drive invasion and migration and in parallel cause an immunosuppressive microenvironment; these contributing factors lead to aggressive melanomas.

2024-11-01·Advances in Therapy

Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review

Review

作者: Kaye, Alan D ; Cooley, Jada F. ; Green, Abigail M ; Daniel, Charles P ; Daniel, Charles P. ; Rieger, Ross ; Claude, Joseph Tremblay ; Cooley, Jada F ; Green, Abigail M. ; Sala, Kelly R. ; Sala, Kelly R ; Potharaju, Pooja ; Ahmadzadeh, Shahab ; Patil, Shilpadevi ; Shekoohi, Sahar ; Kaye, Alan D.

BACKGROUNDThis analysis is a systematic literature review assessing efficacy and adverse effects of three alpha-2 agonists for the symptomatic management of autism spectrum disorder (ASD).METHODSThe present investigation involved an extensive systematic search for eligible studies in PubMed, Embase, Cochrane Library, and Google Scholar. Nine studies, collectively incorporating 226 patients, were assessed.RESULTSThe results demonstrated promising indications for use of alpha-2 agonists in the symptomatic management of autism spectrum disorders, including improvement of hyperactivity, impulsivity, attention deficit symptoms, irritability, and stereotypies in many of the participants studied.CONCLUSIONThe present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations.

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