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Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice
Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the developmen...
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| Published in: | Experimental parasitology 2008-12, Vol.120 (4), p.314-319 |
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| creator | Francisco, Amanda Fortes de Abreu Vieira, Paula Melo Arantes, Jerusa Marilda Pedrosa, Maria Lúcia Martins, Helen Rodrigues Silva, Maisa Veloso, Vanja Maria de Lana, Marta Bahia, Maria Terezinha Tafuri, Washington Luiz Carneiro, Cláudia Martins |
| description | Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the development of infection in mice inoculated with
Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy. |
| doi_str_mv | 10.1016/j.exppara.2008.08.002 |
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Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2008.08.002</identifier><identifier>PMID: 18789321</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Analysis of Variance ; Analysis of variance (ANOVA) ; Animals ; benznidazole (BZ) ; Biological and medical sciences ; Chagas Disease - drug therapy ; Chagas Disease - mortality ; Chagas’ disease (CD) ; Days post-infection (dpi) ; Deferoxamine - pharmacology ; Deferoxamine - therapeutic use ; Deoxyribonucleic acid (DNA) ; desferrioxamine (DFO) ; Disease Models, Animal ; Drug Therapy, Combination ; Ethylenediamine tetraacetic acid (EDTA) ; Fundamental and applied biological sciences. Psychology ; Hemoglobins - analysis ; Intraperitoneal (ip) ; Iron - analysis ; Iron - blood ; Iron - metabolism ; Life cycle. Host-agent relationship. Pathogenesis ; Liver - chemistry ; Liver - drug effects ; Liver infusion tryptose (LIT) ; Male ; Mice ; Nitroimidazoles - pharmacology ; Nitroimidazoles - therapeutic use ; Parasitemia - drug therapy ; Parasitemia - mortality ; Polymerase Chain Reaction ; Polymerase chain reaction (PCR) ; Protozoa ; Random Allocation ; Reactive oxygen species (ROS) ; Siderophores - pharmacology ; Siderophores - therapeutic use ; Trypanocidal Agents - pharmacology ; Trypanocidal Agents - therapeutic use ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects</subject><ispartof>Experimental parasitology, 2008-12, Vol.120 (4), p.314-319</ispartof><rights>2008 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-d36f26d7e9885aeb200fec8fbeb39512596956bc173690d2044497a26ce354f43</citedby><cites>FETCH-LOGICAL-c471t-d36f26d7e9885aeb200fec8fbeb39512596956bc173690d2044497a26ce354f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20874216$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18789321$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Francisco, Amanda Fortes</creatorcontrib><creatorcontrib>de Abreu Vieira, Paula Melo</creatorcontrib><creatorcontrib>Arantes, Jerusa Marilda</creatorcontrib><creatorcontrib>Pedrosa, Maria Lúcia</creatorcontrib><creatorcontrib>Martins, Helen Rodrigues</creatorcontrib><creatorcontrib>Silva, Maisa</creatorcontrib><creatorcontrib>Veloso, Vanja Maria</creatorcontrib><creatorcontrib>de Lana, Marta</creatorcontrib><creatorcontrib>Bahia, Maria Terezinha</creatorcontrib><creatorcontrib>Tafuri, Washington Luiz</creatorcontrib><creatorcontrib>Carneiro, Cláudia Martins</creatorcontrib><title>Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the development of infection in mice inoculated with
Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy.</description><subject>Analysis of Variance</subject><subject>Analysis of variance (ANOVA)</subject><subject>Animals</subject><subject>benznidazole (BZ)</subject><subject>Biological and medical sciences</subject><subject>Chagas Disease - drug therapy</subject><subject>Chagas Disease - mortality</subject><subject>Chagas’ disease (CD)</subject><subject>Days post-infection (dpi)</subject><subject>Deferoxamine - pharmacology</subject><subject>Deferoxamine - therapeutic use</subject><subject>Deoxyribonucleic acid (DNA)</subject><subject>desferrioxamine (DFO)</subject><subject>Disease Models, Animal</subject><subject>Drug Therapy, Combination</subject><subject>Ethylenediamine tetraacetic acid (EDTA)</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemoglobins - analysis</subject><subject>Intraperitoneal (ip)</subject><subject>Iron - analysis</subject><subject>Iron - blood</subject><subject>Iron - metabolism</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Liver - chemistry</subject><subject>Liver - drug effects</subject><subject>Liver infusion tryptose (LIT)</subject><subject>Male</subject><subject>Mice</subject><subject>Nitroimidazoles - pharmacology</subject><subject>Nitroimidazoles - therapeutic use</subject><subject>Parasitemia - drug therapy</subject><subject>Parasitemia - mortality</subject><subject>Polymerase Chain Reaction</subject><subject>Polymerase chain reaction (PCR)</subject><subject>Protozoa</subject><subject>Random Allocation</subject><subject>Reactive oxygen species (ROS)</subject><subject>Siderophores - pharmacology</subject><subject>Siderophores - therapeutic use</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanocidal Agents - therapeutic use</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqFkEFr3DAQhUVoSbZpf0KLLs3NW0mWbamXUkKaFgK9pGchSyNWiy25krfN7q-PzJr2GHggGL73RvMQek_JlhLaftpv4WmadNJbRojYLiLsAm0okaRinMtXaEMI5RUXkl-hNznvSQEp45foiopOyJrRDUqP6TjpEHMcNTbpcPKf8Z1zYGYcHe4hnIK3-hQHwPMOkp6O2MSx9wEs_uvn3TLFPsWAzQ4GPceELWQHKfn4pMfCYR-KlsRiGb2Bt-i100OGd-t7jX59u3u8_V49_Lz_cfv1oTK8o3Nl69ax1nYghWg09OXMEiJcD30tG8oa2cqm7Q3t6lYSywgvR3eatQbqhjteX6Obc-6U4u8D5FmNPhsYBh0gHrIqgVzUjBWwOYMmxZwTODUlP-p0VJSopWy1V2vZi0moRWTxfVgXHPoR7H_X2m4BPq6AzkYPLulgfP7HMSI6zmhbuC9nDkodfzwklY2HYMD6VHpTNvoXvvIMy1Khpw</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Francisco, Amanda Fortes</creator><creator>de Abreu Vieira, Paula Melo</creator><creator>Arantes, Jerusa Marilda</creator><creator>Pedrosa, Maria Lúcia</creator><creator>Martins, Helen Rodrigues</creator><creator>Silva, Maisa</creator><creator>Veloso, Vanja Maria</creator><creator>de Lana, Marta</creator><creator>Bahia, Maria Terezinha</creator><creator>Tafuri, Washington Luiz</creator><creator>Carneiro, Cláudia Martins</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></search><sort><creationdate>20081201</creationdate><title>Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice</title><author>Francisco, Amanda Fortes ; de Abreu Vieira, Paula Melo ; Arantes, Jerusa Marilda ; Pedrosa, Maria Lúcia ; Martins, Helen Rodrigues ; Silva, Maisa ; Veloso, Vanja Maria ; de Lana, Marta ; Bahia, Maria Terezinha ; Tafuri, Washington Luiz ; Carneiro, Cláudia Martins</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-d36f26d7e9885aeb200fec8fbeb39512596956bc173690d2044497a26ce354f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Analysis of Variance</topic><topic>Analysis of variance (ANOVA)</topic><topic>Animals</topic><topic>benznidazole (BZ)</topic><topic>Biological and medical sciences</topic><topic>Chagas Disease - drug therapy</topic><topic>Chagas Disease - mortality</topic><topic>Chagas’ disease (CD)</topic><topic>Days post-infection (dpi)</topic><topic>Deferoxamine - pharmacology</topic><topic>Deferoxamine - therapeutic use</topic><topic>Deoxyribonucleic acid (DNA)</topic><topic>desferrioxamine (DFO)</topic><topic>Disease Models, Animal</topic><topic>Drug Therapy, Combination</topic><topic>Ethylenediamine tetraacetic acid (EDTA)</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hemoglobins - analysis</topic><topic>Intraperitoneal (ip)</topic><topic>Iron - analysis</topic><topic>Iron - blood</topic><topic>Iron - metabolism</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Liver - chemistry</topic><topic>Liver - drug effects</topic><topic>Liver infusion tryptose (LIT)</topic><topic>Male</topic><topic>Mice</topic><topic>Nitroimidazoles - pharmacology</topic><topic>Nitroimidazoles - therapeutic use</topic><topic>Parasitemia - drug therapy</topic><topic>Parasitemia - mortality</topic><topic>Polymerase Chain Reaction</topic><topic>Polymerase chain reaction (PCR)</topic><topic>Protozoa</topic><topic>Random Allocation</topic><topic>Reactive oxygen species (ROS)</topic><topic>Siderophores - pharmacology</topic><topic>Siderophores - therapeutic use</topic><topic>Trypanocidal Agents - pharmacology</topic><topic>Trypanocidal Agents - therapeutic use</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Francisco, Amanda Fortes</creatorcontrib><creatorcontrib>de Abreu Vieira, Paula Melo</creatorcontrib><creatorcontrib>Arantes, Jerusa Marilda</creatorcontrib><creatorcontrib>Pedrosa, Maria Lúcia</creatorcontrib><creatorcontrib>Martins, Helen Rodrigues</creatorcontrib><creatorcontrib>Silva, Maisa</creatorcontrib><creatorcontrib>Veloso, Vanja Maria</creatorcontrib><creatorcontrib>de Lana, Marta</creatorcontrib><creatorcontrib>Bahia, Maria Terezinha</creatorcontrib><creatorcontrib>Tafuri, Washington Luiz</creatorcontrib><creatorcontrib>Carneiro, Cláudia Martins</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><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Francisco, Amanda Fortes</au><au>de Abreu Vieira, Paula Melo</au><au>Arantes, Jerusa Marilda</au><au>Pedrosa, Maria Lúcia</au><au>Martins, Helen Rodrigues</au><au>Silva, Maisa</au><au>Veloso, Vanja Maria</au><au>de Lana, Marta</au><au>Bahia, Maria Terezinha</au><au>Tafuri, Washington Luiz</au><au>Carneiro, Cláudia Martins</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>120</volume><issue>4</issue><spage>314</spage><epage>319</epage><pages>314-319</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Iron chelators have been employed in various studies aimed at evaluating the relationship between the iron status of the host and the development of infection. In the present study, the effects of benznidazole (BZ) therapy in combination with the iron chelator desferrioxamine (DFO) on the development of infection in mice inoculated with
Trypanosoma cruzi Y strain have been investigated. Infected mice treated with DFO presented lower levels of parasitemia compared with infected untreated animals. Therapy with BZ for 21 days, with or without DFO, led to decreased parasitemia and reduced mortality, but BZ in combination with DFO treatment for 35 days (BZ/DFO-35) gave 0% mortality. All infected groups presented lower levels of iron in the liver, but serum iron concentrations were greater in DFO-35 and BZ/DFO-35, whereas hemoglobin levels were higher in BZ/DFO-35 and lower in DFO-35 compared with other treated groups. The percentage cure, determined from negative hemoculture and PCR results in animals that had survived for 60 days post-infection, was 18% for BZ and BZ/DFO-35, 42% for BZ combined with DFO for 21 days, and 67% for DFO-35. The results demonstrate that modification in iron stores increases BZ efficacy.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>18789321</pmid><doi>10.1016/j.exppara.2008.08.002</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis of Variance Analysis of variance (ANOVA) Animals benznidazole (BZ) Biological and medical sciences Chagas Disease - drug therapy Chagas Disease - mortality Chagas’ disease (CD) Days post-infection (dpi) Deferoxamine - pharmacology Deferoxamine - therapeutic use Deoxyribonucleic acid (DNA) desferrioxamine (DFO) Disease Models, Animal Drug Therapy, Combination Ethylenediamine tetraacetic acid (EDTA) Fundamental and applied biological sciences. Psychology Hemoglobins - analysis Intraperitoneal (ip) Iron - analysis Iron - blood Iron - metabolism Life cycle. Host-agent relationship. Pathogenesis Liver - chemistry Liver - drug effects Liver infusion tryptose (LIT) Male Mice Nitroimidazoles - pharmacology Nitroimidazoles - therapeutic use Parasitemia - drug therapy Parasitemia - mortality Polymerase Chain Reaction Polymerase chain reaction (PCR) Protozoa Random Allocation Reactive oxygen species (ROS) Siderophores - pharmacology Siderophores - therapeutic use Trypanocidal Agents - pharmacology Trypanocidal Agents - therapeutic use Trypanosoma cruzi Trypanosoma cruzi - drug effects |
| title | Trypanosoma cruzi: Effect of benznidazole therapy combined with the iron chelator desferrioxamine in infected mice |
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