FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2556825577> ?p ?o ?g. }

• W2556825577 abstract "Mefloquine hydrochloride is an antimalarial agent that has been used for the past 40 years. Numerous reports of neurological side effects have recently led the FDA to issue a strong warning regarding long-term neurological effects. This warning lead to the U.S. Army’s Special Forces and other components to discontinue its use in July of 2013. Despite reported adverse side effects, mefloquine remains in circulation and is recommended to travelers going to specific Asian countries. Mefloquine has been used as a treatment for those already infected with the malaria parasite (blood concentrations ranging from 2.1 to 23 µM), and as prophylaxis (blood concentrations averaging 3.8 µM) (Dow 2003). The purpose of this study was to quantify Mefloquine’s toxicity using spontaneously active nerve cell networks growing on microelectrode arrays in vitro and to identify compounds that alleviate or reduce toxic effects. The current literature on mefloquine toxicity is lacking electrophysiological data. These data will contribute to research on the mechanism of adverse side effects associated with mefloquine use. Sequential titration experiments were performed by adding increasing concentrations of mefloquine solution to cultured neurons. Network responses were quantified and reversibility was examined. In each network, activity decreases were normalized as a percent of reference activity yielding a mean IC50 value of 5.97 ± 0.44 (SD) µM (n=6). After total activity loss, no activity was recovered with two successive medium changes. To test for network response desensitization resulting from sequential applications over 5-6 hr periods, one-point titrations at varying concentrations were conducted with fresh networks. These experiments yielded a single concentration response curve with an IC50 value of 2.97 µM. This represents a statistically significant shift (p < 0.0001) to lower concentrations of mefloquine, demonstrating that sequential applications result in network desensitization. After mefloquine exposures, cells were evaluated for irreversible cytotoxic damage. Over a 12-hour period under 6 µM mefloquine, process beading and granulation of somal cytoplasm were observed. At 8 µM mefloquine cell stress was apparent after only 10 minutes with major glial damage and process beading at 120 minutes. In this study, quinolinic acid served as a neuroprotectant at 20 µM. There have been multiple studies on the endogenous concentrations of quinolinic acid and current literature is quite variable. Immunocompromised individuals have some of the highest blood levels of quinolinic acid (up to 20 µM). With 30 min pre-applications of quinolinic acid, the mefloquine IC50 value shifted from 5.97 ± 0.44 µM (n=6), to 9.28 ± 0.55 µM (n=3). This represents a statistically significant change to higher mefloquine concentrations and demonstrates neuroprotection." @default.
• W2556825577 created "2016-11-30" @default.
• W2556825577 creator A5039380536 @default.
• W2556825577 date "2015-05-01" @default.
• W2556825577 modified "2023-09-28" @default.
• W2556825577 title "Cytotoxicity and functional toxicity of mefloquine and the search for protective compounds" @default.
• W2556825577 hasPublicationYear "2015" @default.
• W2556825577 type Work @default.
• W2556825577 sameAs 2556825577 @default.
• W2556825577 citedByCount "0" @default.
• W2556825577 crossrefType "dissertation" @default.
• W2556825577 hasAuthorship W2556825577A5039380536 @default.
• W2556825577 hasConcept C116263406 @default.
• W2556825577 hasConcept C126322002 @default.
• W2556825577 hasConcept C197934379 @default.
• W2556825577 hasConcept C203014093 @default.
• W2556825577 hasConcept C2777199930 @default.
• W2556825577 hasConcept C2777425658 @default.
• W2556825577 hasConcept C2778048844 @default.
• W2556825577 hasConcept C29730261 @default.
• W2556825577 hasConcept C33070731 @default.
• W2556825577 hasConcept C71924100 @default.
• W2556825577 hasConcept C86803240 @default.
• W2556825577 hasConcept C98274493 @default.
• W2556825577 hasConceptScore W2556825577C116263406 @default.
• W2556825577 hasConceptScore W2556825577C126322002 @default.
• W2556825577 hasConceptScore W2556825577C197934379 @default.
• W2556825577 hasConceptScore W2556825577C203014093 @default.
• W2556825577 hasConceptScore W2556825577C2777199930 @default.
• W2556825577 hasConceptScore W2556825577C2777425658 @default.
• W2556825577 hasConceptScore W2556825577C2778048844 @default.
• W2556825577 hasConceptScore W2556825577C29730261 @default.
• W2556825577 hasConceptScore W2556825577C33070731 @default.
• W2556825577 hasConceptScore W2556825577C71924100 @default.
• W2556825577 hasConceptScore W2556825577C86803240 @default.
• W2556825577 hasConceptScore W2556825577C98274493 @default.
• W2556825577 hasLocation W25568255771 @default.
• W2556825577 hasOpenAccess W2556825577 @default.
• W2556825577 hasPrimaryLocation W25568255771 @default.
• W2556825577 hasRelatedWork W1965953653 @default.
• W2556825577 hasRelatedWork W2016977143 @default.
• W2556825577 hasRelatedWork W2040967461 @default.
• W2556825577 hasRelatedWork W2053592362 @default.
• W2556825577 hasRelatedWork W2064519093 @default.
• W2556825577 hasRelatedWork W2076029094 @default.
• W2556825577 hasRelatedWork W2083254649 @default.
• W2556825577 hasRelatedWork W2144614889 @default.
• W2556825577 hasRelatedWork W2264246004 @default.
• W2556825577 hasRelatedWork W2368072868 @default.
• W2556825577 hasRelatedWork W2600489833 @default.
• W2556825577 isParatext "false" @default.
• W2556825577 isRetracted "false" @default.
• W2556825577 magId "2556825577" @default.
• W2556825577 workType "dissertation" @default.