Trypanosoma cruzi: Possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs
About 200 clinically used amphiphilic cationic drugs have been shown to be active in vitro against Trypanosoma cruzi at concentrations of ⩽ 1 m M. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine,...
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| Veröffentlicht in: | Experimental parasitology 1985-01, Vol.60 (1), p.32-42 |
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| creator | Hammond, David J. Hogg, Janet Gutteridge, Winston E. |
| description | About 200 clinically used amphiphilic cationic drugs have been shown to be active
in vitro against
Trypanosoma cruzi at concentrations of ⩽ 1 m
M. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum ⩾ 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 m
M. These drugs have a possible role in the prevention of Chagas' disease by blood transfusion. |
| doi_str_mv | 10.1016/S0014-4894(85)80020-5 |
| format | Article |
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in vitro against
Trypanosoma cruzi at concentrations of ⩽ 1 m
M. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum ⩾ 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 m
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in vitro against
Trypanosoma cruzi at concentrations of ⩽ 1 m
M. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum ⩾ 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 m
M. These drugs have a possible role in the prevention of Chagas' disease by blood transfusion.</description><subject>Aminoacridines - metabolism</subject><subject>Aminoacridines - pharmacology</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Antiprotozoal Agents - metabolism</subject><subject>Antiprotozoal Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cations - metabolism</subject><subject>Cations - pharmacology</subject><subject>Chagas Disease - prevention & control</subject><subject>Chagas Disease - transmission</subject><subject>Cytoplasm - drug effects</subject><subject>Energy Metabolism - drug effects</subject><subject>Erythrocytes - drug effects</subject><subject>Erythrocytes - metabolism</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred A</subject><subject>Microscopy, Fluorescence</subject><subject>Parasitic diseases</subject><subject>Pharmacology. Drug treatments</subject><subject>Protozoal diseases</subject><subject>Time Factors</subject><subject>Transfusion Reaction</subject><subject>Tropical medicine</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><subject>Trypanosoma cruzi - metabolism</subject><subject>Trypanosoma cruzi - ultrastructure</subject><subject>Trypanosomiasis</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdtKHTEUhkOp2F3bRxByUYq9mLpympn0RkTUFgQF7XXIaWzKzGSazBS2T2_2gX0rhCSs9a0D_4_QKYHvBEh9_ghAeMVbyc9a8a0FoFCJd2hFQEJFOZfv0eqAfEAfc_4LAC2h_BgdM0lrwWCF0lNaT3qMOQ4a27S8hB_4IeYcTO-xjeOcYo9jhyeddA6zx3PSYx5CIeKIzRqbPka3i3bLNlju8RnrYfoTyumDxVbPJVE-Li3P-RM66nSf_ef9e4J-31w_Xf2s7u5vf11d3lWWU5grKpvGGCCic8y7jnfGNYbw2jWc6KamXjRGcsZKoK4LrK3kpIggvaC6NY6doK-7vlOK_xafZ1XWtr7v9ejjklXpQYTk4k2QcA5MACug2IE2FYmS79SUwqDTWhFQG1PU1hS1UVy1Qm1NUZsBp_sBixm8O1TtXSj5L_u8zlb3XRHThnzAWs4kYbRgFzvMF9X-B59UtsGP1ruQvJ2Vi-GNRV4BHyuqhQ</recordid><startdate>19850101</startdate><enddate>19850101</enddate><creator>Hammond, David J.</creator><creator>Hogg, Janet</creator><creator>Gutteridge, Winston E.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>19850101</creationdate><title>Trypanosoma cruzi: Possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs</title><author>Hammond, David J. ; Hogg, Janet ; Gutteridge, Winston E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-2977bb015fd3edf4fbd7b146d741a762e57b94336d766297ac9410209e52a8bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Aminoacridines - metabolism</topic><topic>Aminoacridines - pharmacology</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Antiprotozoal Agents - metabolism</topic><topic>Antiprotozoal Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cations - metabolism</topic><topic>Cations - pharmacology</topic><topic>Chagas Disease - prevention & control</topic><topic>Chagas Disease - transmission</topic><topic>Cytoplasm - drug effects</topic><topic>Energy Metabolism - drug effects</topic><topic>Erythrocytes - drug effects</topic><topic>Erythrocytes - metabolism</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred A</topic><topic>Microscopy, Fluorescence</topic><topic>Parasitic diseases</topic><topic>Pharmacology. Drug treatments</topic><topic>Protozoal diseases</topic><topic>Time Factors</topic><topic>Transfusion Reaction</topic><topic>Tropical medicine</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - drug effects</topic><topic>Trypanosoma cruzi - metabolism</topic><topic>Trypanosoma cruzi - ultrastructure</topic><topic>Trypanosomiasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hammond, David J.</creatorcontrib><creatorcontrib>Hogg, Janet</creatorcontrib><creatorcontrib>Gutteridge, Winston E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hammond, David J.</au><au>Hogg, Janet</au><au>Gutteridge, Winston E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypanosoma cruzi: Possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>1985-01-01</date><risdate>1985</risdate><volume>60</volume><issue>1</issue><spage>32</spage><epage>42</epage><pages>32-42</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>About 200 clinically used amphiphilic cationic drugs have been shown to be active
in vitro against
Trypanosoma cruzi at concentrations of ⩽ 1 m
M. Activity against epimastigote and trypomastigote forms was similar, and in both cases the most potent drugs were litracene, maprotiline, thioproperazine, and the acridines: acranil, aminacrine, and mepacrine. Fluorescence microscopy demonstrated that epimastigotes rapidly accumulate acridines initially in discrete subcellular organelles. The amount of drug incorporated during 15 min of incubation was sufficient to produce subsequent lysis of both trypomastigotes and epimastigotes within 24 hr at 4 C. Trypanocidal activity was dependent on the extracellular pH (optimum ⩾ 8) and drug exposure time, but was independent of red blood cell density, serum dilution, and temperature (4 to 37 C). Despite their trypanocidal activity, amphiphilic cationic drugs appear to have no significant effect on the energy state of red blood cells at a concentration of 1 m
M. These drugs have a possible role in the prevention of Chagas' disease by blood transfusion.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>3926530</pmid><doi>10.1016/S0014-4894(85)80020-5</doi><tpages>11</tpages></addata></record> |
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| subjects | Aminoacridines - metabolism Aminoacridines - pharmacology Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Antiprotozoal Agents - metabolism Antiprotozoal Agents - pharmacology Biological and medical sciences Cations - metabolism Cations - pharmacology Chagas Disease - prevention & control Chagas Disease - transmission Cytoplasm - drug effects Energy Metabolism - drug effects Erythrocytes - drug effects Erythrocytes - metabolism Human protozoal diseases Humans Infectious diseases Medical sciences Mice Mice, Inbred A Microscopy, Fluorescence Parasitic diseases Pharmacology. Drug treatments Protozoal diseases Time Factors Transfusion Reaction Tropical medicine Trypanosoma cruzi Trypanosoma cruzi - drug effects Trypanosoma cruzi - metabolism Trypanosoma cruzi - ultrastructure Trypanosomiasis |
| title | Trypanosoma cruzi: Possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs |
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