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

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

THE EFFECT OF B-HYDROXYBUTYRATE ON HUMAN MICROGLIA: IMPLICATIONS FOR THE KETOGENIC DIET IN NEURODEGENERATIVE DISORDERS [Meeting Abstract]

Kasselman, Lora J.; Chevalier, Christine; Zhen, Juan; Grossfeld, David; Pinkhasov, Aaron; Gomolin, Irving; Reiss, Allison B.
ISI:000428916200029
ISSN: 1081-5589
CID: 3049452

MICROGLIA IN A HYPERGLYCEMIC ENVIRONMENT PROMOTE ALZHEIMER'S DISEASE-LIKE PATHOLOGY THROUGH CHOLINGERGIC SYNAPTIC DYSFUNCTION AND INCREASED AMYLOID B PRODUCTION [Meeting Abstract]

Arain, Hirra A.; Renna, Heather A.; Kasselman, Lora J.; Pinkhasov, Aaron; Gomolin, Irving; Jacobson, Alan M.; DeLeon, Joshua; Fazzari, Melissa; Reiss, Allison B.
ISI:000428916200033
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

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
Inflammation is a common feature of Parkinson Disease and other neurodegenerative disorders. Hypochlorous acid (HOCl) is a reactive oxygen species formed by neutrophils and other myeloperoxidase-containing cells during inflammation. HOCl chlorinates the amine and catechol moieties of dopamine to produce chlorinated derivatives collectively termed chlorodopamine. Here, we report that chlorodopamine is toxic to dopaminergic neurons both in vivo and in vitro Intrastriatal administration of 90 nmol chlorodopamine to mice resulted in loss of dopaminergic neurons from the substantia nigra and decreased ambulation-results that were comparable to those produced by the same dose of the parkinsonian poison, 1-methyl-4-phenylpyridinium (MPP+). Chlorodopamine was also more toxic to differentiated SH SY5Y cells than HOCl. The basis of this selective toxicity is likely mediated by chlorodopamine uptake through the dopamine transporter, as expression of this transporter in COS-7 cells conferred sensitivity to chlorodopamine toxicity. Pharmacological blockade of the dopamine transporter also mitigated the deleterious effects of chlorodopamine in vivo The cellular actions of chlorodopamine included inactivation of the α-ketoglutarate dehydrogenase complex, as well as inhibition of mitochondrial respiration. The latter effect is consistent with inhibition of cytochrome c oxidase. Illumination at 670 nm, which stimulates cytochrome c oxidase, reversed the effects of chlorodopamine. The observed changes in mitochondrial biochemistry were also accompanied by the swelling of these organelles. Overall, our findings suggest that chlorination of dopamine by HOCl generates toxins that selectively kill dopaminergic neurons in the substantia nigra in a manner comparable to MPP+.
PMID: 27026709
ISSN: 1096-0929
CID: 3466352

Inflaming the diseased brain: a role for tainted melanins

Jeitner, T M; Kalogiannis, M; Patrick, P A; Gomolin, I; Palaia, T; Ragolia, L; Brand, D; Delikatny, E J
Inflammation plays a crucial role in neurodegenerative diseases, but the irritants responsible for this response remain largely unknown. This report addressed the hypothesis that hypochlorous acid reacts with dopamine to produce melanic precipitates that promote cerebral inflammation. Spectrophotometric studies demonstrated that nM amounts of HOCl and dopamine react within seconds. A second-order rate constant for the reaction of HOCl and dopamine of 2.5 × 10(4)M(-1)s(-1) was obtained by measuring loss of dopaminergic fluorescence due to HOCl. Gravimetric measurements, electron microscopy, elemental analysis, and a novel use of flow cytometry confirmed that the major product of this reaction is a precipitate with an average diameter of 1.5 μm. Flow cytometry was also used to demonstrate the preferential reaction of HOCl with dopamine rather than albumin. Engulfment of the chlorodopamine particulates by phagocytes in vitro caused these cells to release TNFα and die. Intrastriatal administration of 10(6) particles also increased the content of TNFα in the brain and led to a 50% loss of the dopaminergic neurons in the nigra. These studies indicate that HOCl and dopamine react quickly and preferentially with each other to produce particles that promote inflammation and neuronal death in the brain.
PMID: 25585261
ISSN: 0006-3002
CID: 3466322

Impact of computerized physician order entry alerts on prescribing in older patients

Lester, Paula E; Rios-Rojas, Liliana; Islam, Shahidul; Fazzari, Melissa J; Gomolin, Irving H
BACKGROUND:A computerized physician order entry (CPOE) system provides opportunity for real-time alerts to prescribers. Winthrop University Hospital began using CPOE in 2009. OBJECTIVE:We sought to improve prescribing among older hospitalized patients by adding alerts to the CPOE system for potentially inappropriate medications. METHODS:In January 2011, informational alerts were integrated into the CPOE system for selected high-risk medications: diphenhydramine, metoclopramide, and all antipsychotics. We evaluated the effect of these alerts on prescribing frequency by comparing the number of prescriptions during the second quarters of 2010 ("pre-alert") with the second quarters of 2011 through 2013 ("post-alert"). Prescribing patterns were evaluated through a pharmacy database of medication orders. Frequency of prescribing was adjusted for total discharges. A comparison was made to ages 18-64 years, and comparing "as needed" vs standing orders. RESULTS:In the 65 years of age and older group, there were significant reductions in prescription rates pre-alert vs post-alert for diphenhydramine (p < 0.001) and metoclopramide (p < 0.001). There was no decrease in prescription rates for antipsychotics in older patients (p = 0.80). In the younger comparison group, no decreases in prescription rates for those drugs were observed. Our analysis is based on numbers of written prescriptions and not actual doses administered; therefore, no conclusions concerning the effect of these alerts on communication or documentation of risk/benefits of these medications can be ascertained. CONCLUSION/CONCLUSIONS:The data suggest that prescribing rates for drugs with the least efficacy and potential for harm and with alternative agents (i.e., diphenhydramine and metoclopramide) can be modified by CPOE alerts for older patients.
PMID: 25752906
ISSN: 1179-1969
CID: 3466342

Memantine standard tablet and extended-release dosing considerations: a pharmacokinetic analysis [Letter]

Lam, Sum; Smith, Candace; Gomolin, Irving H
PMID: 25688611
ISSN: 1532-5415
CID: 3466332