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Post-acute care nursing home deaths in the COVID era: Potential for attribution bias [Letter]

Gomolin, Irving H; Hartley, Douglas A; Polsky, Bruce
PMID: 33742697
ISSN: 1532-5415
CID: 4822002

Alzheimer Disease Clinical Trials Targeting Amyloid: Lessons Learned From Success in Mice and Failure in Humans

Reiss, Allison B; Montufar, Natalie; DeLeon, Joshua; Pinkhasov, Aaron; Gomolin, Irving H; Glass, Amy D; Arain, Hirra A; Stecker, Mark M
BACKGROUND:The goal of slowing or halting the development of Alzheimer disease (AD) has resulted in the huge allocation of resources by academic institutions and pharmaceutical companies to the development of new treatments. The etiology of AD is elusive, but the aggregation of amyloid-β and tau peptide and oxidative processes are considered critical pathologic mechanisms. The failure of drugs with multiple mechanisms to meet efficacy outcomes has caused several companies to decide not to pursue further AD studies and has left the field essentially where it has been for the past 15 years. Efforts are underway to develop biomarkers for detection and monitoring of AD using genetic, imaging, and biochemical technology, but this is of minimal use if no intervention can be offered. REVIEW SUMMARY/RESULTS:In this review, we consider the natural progression of AD and how it continues despite present attempts to modify the amyloid-related machinery to alter the disease trajectory. We describe the mechanisms and approaches to AD treatment targeting amyloid, including both passive and active immunotherapy as well as inhibitors of enzymes in the amyloidogenic pathway. CONCLUSION/CONCLUSIONS:Lessons learned from clinical trials of amyloid reduction strategies may prove crucial for the leap forward toward novel therapeutic targets to treat AD.
PMID: 33646990
ISSN: 2331-2637
CID: 4801212

Effect of oxytocin on lipid accumulation under inflammatory conditions in human macrophages

Karten, Ariel; Vernice, Nicholas A; Renna, Heather A; Carsons, Steven E; DeLeon, Joshua; Pinkhasov, Aaron; Gomolin, Irving H; Glass, Daniel S; Reiss, Allison B; Kasselman, Lora J
INTRODUCTION AND AIMS/OBJECTIVE:Oxytocin (OT) is a neuropeptide hormone secreted by the posterior pituitary gland. Deficits in OT action have been observed in patients with behavioral and mood disorders, some of which correlate with an increased risk of cardiovascular disease (CVD). Recent research has revealed a wider systemic role that OT plays in inflammatory modulation and development of atherosclerotic plaques. This study investigated the role that OT plays in cholesterol transport and foam cell formation in LPS-stimulated THP-1 human macrophages. METHODS:THP-1 differentiated macrophages were treated with media, LPS (100 ng/ml), LPS + OT (10 pM), or LPS + OT (100 pM). Changes in gene expression and protein levels of cholesterol transporters were analyzed by real time quantitative PCR (RT-qPCR) and Western blot, while ox-LDL uptake and cholesterol efflux capacity were evaluated with fluorometric assays. RESULTS:RT-qPCR analysis revealed a significant increase in ABCG1 gene expression upon OT + LPS treatment, compared to LPS alone (p = 0.0081), with Western blotting supporting the increase in expression of the ABCG1 protein. Analysis of ox-LDL uptake showed a significantly lower fluorescent value in LPS + OT (100pM) -treated cells when compared to LPS alone (p < 0.0001). While not statistically significant (p = 0.06), cholesterol efflux capacity increased with LPS + OT treatment. CONCLUSION/CONCLUSIONS:We demonstrate here that OT can attenuate LPS-mediated lipid accumulation in THP-1 macrophages. These findings support the hypothesis that OT could be used to reduce pro-inflammatory and potentially atherogenic changes observed in patients with heightened CVD risk. This study suggests further exploration of OT effects on monocyte and macrophage cholesterol handling in vivo.
PMID: 33434610
ISSN: 1096-0945
CID: 4746722

Alzheimer's disease: many failed trials, so where do we go from here?

Reiss, Allison Bethanne; Glass, Amy D; Wisniewski, Thomas; Wolozin, Benjamin; Gomolin, Irving H; Pinkhasov, Aaron; De Leon, Joshua; Stecker, Mark M
Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with relentlessly progressive cognitive impairment and memory loss. AD pathology proceeds for decades before cognitive deficits become clinically apparent, opening a window for preventative therapy. Imbalance of clearance and buildup of amyloid β and phosphorylated tau proteins in the central nervous system is believed to contribute to AD pathogenesis. However, multiple clinical trials of treatments aimed at averting accumulation of these proteins have yielded little success, and there is still no disease-modifying intervention. Here, we discuss current knowledge of AD pathology and treatment with an emphasis on emerging biomarkers and treatment strategies.
PMID: 32699179
ISSN: 1708-8267
CID: 4532512

When Asymptomatic Bacteriuria is not Asymptomatic or "Pseudo-Urinary Tract Infection" [Letter]

Gomolin, Irving H
PMID: 30289984
ISSN: 1532-5415
CID: 3466392


Kasselman, Lora J.; Chevalier, Christine; Zhen, Juan; Grossfeld, David; Pinkhasov, Aaron; Gomolin, Irving; Reiss, Allison B.
ISSN: 1081-5589
CID: 3049452


Arain, Hirra A.; Renna, Heather A.; Kasselman, Lora J.; Pinkhasov, Aaron; Gomolin, Irving; Jacobson, Alan M.; DeLeon, Joshua; Fazzari, Melissa; Reiss, Allison B.
ISSN: 1081-5589
CID: 3049442

COX-2-dependent and independent effects of COX-2 inhibitors and NSAIDs on proatherogenic changes in human monocytes/macrophages

Voloshyna, Iryna; Kasselman, Lora J; Carsons, Steven E; Littlefield, Michael J; Gomolin, Irving H; De Leon, Joshua; Reiss, Allison B
It is the second decade of controversy regarding the cardiovascular effects of cyclo-oxygenase-2 (COX-2) inhibitors. At this time, celecoxib is the only available COX-2-specific inhibitor for treatment of pain and inflammation. Therefore, the present study was designed primarily to determine the impact of celecoxib on cholesterol handling (uptake via scavenger receptors and efflux from the cells) and foam cell formation in human THP-1 macrophages, followed by comparison to rofecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs). THP-1 human macrophages and peripheral blood mononuclear cells were incubated with: celecoxib, rofecoxib, naproxen (at 5, 10, 25 microM) and acetaminophen (0.5 mM, 1 mM)+/-oxidized low-density lipoprotein (oxLDL, 25 microg/mL). Scavenger receptors: CD36, LOX-1, SR-A1, and CXCL16 and cholesterol efflux proteins: ATP-binding cassette transporter (ABC) A1 and G1, and 27-hydroxylase were detected. The adhesion of monocytes to cultured endothelial cells with/ without COX-2 inhibitors/NSAIDs was also analyzed. The presence of celecoxib and rofecoxib (at high concentrations) significantly decreased expression of 27-hydroxylase and ABCA1, interfering with normal cholesterol outflow from macrophages. Acetaminophen and the non-specific COX inhibitor naproxen had no significant effect on these proteins. Only celecoxib had a profound effect on the class B scavenger receptor CD36 and the class E receptor LOX1. We demonstrate that in contrast to celecoxib, rofecoxib and naproxen increased adhesive properties of monocytes to endothelial cells. This work might contribute to our understanding of multiple mechanisms underlying elevated cardiovascular risk upon the use of COX-2 inhibitors and uncover new possibilities to enhance the safety profile of existing COX-2 inhibitors.
PMID: 27940550
ISSN: 1708-8267
CID: 2491412

Memantine Plasma Concentrations Among Patients With Dementia [Letter]

Gomolin, Irving H; Papamichael, Michael J; Fazzari, Melissa J; Rieger, Robert
PMID: 28027115
ISSN: 1533-712x
CID: 3466382

Linking Inflammation and Parkinson Disease: Hypochlorous Acid Generates Parkinsonian Poisons

Jeitner, Thomas M; Kalogiannis, Mike; Krasnikov, Boris F; Gomolin, Irving; Peltier, Morgan R; Moran, Graham R
PMID: 27672164
ISSN: 1096-0929
CID: 3466372