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Hemozoin formation, disposition and ...

The Johns Hopkins University.

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Hemozoin formation, disposition and detection in Plasmodium species.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Hemozoin formation, disposition and detection in Plasmodium species./
Author:	Pisciotta, John Matthew.
Description:	279 p.
Notes:	Adviser: David Sullivan.
Contained By:	Dissertation Abstracts International68-04B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3262488

Hemozoin formation, disposition and detection in Plasmodium species.
Pisciotta, John Matthew.

Hemozoin formation, disposition and detection in Plasmodium species. - 279 p.

Adviser: David Sullivan.

Thesis (Ph.D.)--The Johns Hopkins University, 2007.

Malaria remains a major public health problem throughout much of the world. The intraerythrocytic stage Plasmodium parasite is responsible for malaria pathology. Erythrocyte hemoglobin is catabolized in the parasite's digestive vacuole which releases soluble and toxic free heme. The Plasmodium parasite biomineralizes heme into an insoluble and relatively inert heme crystal called hemozoin. The in vivo mechanism of hemozoin formation, the process targeted by the medically important quinolines, has not been established. This research identifies neutral lipid nanospheres (NLNs) in the parasite digestive vacuole as the in vivo site of hemozoin formation and shifts the long held conception that heme crystallization occurs in an aqueous, polar environment to a non-polar, hydrophobic microenvironment. Quinoline drug resistance in malaria parasites is increasing and the identification of new drugs that selectively target hemozoin formation, yet are not subject to quinoline cross-resistance, is a priority. From over one thousand safe, FDA approved compounds five promising drugs were identified using an in vitro NLN-based method. These drugs also showed direct activity against parasites in culture. Accurate diagnosis is needed for effective malaria treatment. Laser desorption mass spectrometry (LDMS) was found to be a sensitive diagnostic technique for identification of malaria hemozoin in human blood. As confirmed by PCR, LDMS successfully detected Plasmodium hemozoin in the blood of pregnant Zambian women negative by optical microscopy alone. LDMS successfully identified all four species responsible for human malaria in human clinical blood samples. Potential protein evidence of P. falciparum was identified in 800 year old human remains. Hemozoin is formed in NLNs in Plasmodium and is a useful biomarker of blood stage malaria infection by LDMS.Subjects--Topical Terms:

1017734
Biology, Microbiology.

Hemozoin formation, disposition and detection in Plasmodium species.
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008 110520s2007 ||||||||||||||||| ||eng d
035 $a (UMI)AAI3262488
035 $a AAI3262488
040 $a UMI $c UMI
100 1 $a Pisciotta, John Matthew. $3 1267703
245 1 0 $a Hemozoin formation, disposition and detection in Plasmodium species.
300 $a 279 p.
500 $a Adviser: David Sullivan.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2065.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2007.
520 $a Malaria remains a major public health problem throughout much of the world. The intraerythrocytic stage Plasmodium parasite is responsible for malaria pathology. Erythrocyte hemoglobin is catabolized in the parasite's digestive vacuole which releases soluble and toxic free heme. The Plasmodium parasite biomineralizes heme into an insoluble and relatively inert heme crystal called hemozoin. The in vivo mechanism of hemozoin formation, the process targeted by the medically important quinolines, has not been established. This research identifies neutral lipid nanospheres (NLNs) in the parasite digestive vacuole as the in vivo site of hemozoin formation and shifts the long held conception that heme crystallization occurs in an aqueous, polar environment to a non-polar, hydrophobic microenvironment. Quinoline drug resistance in malaria parasites is increasing and the identification of new drugs that selectively target hemozoin formation, yet are not subject to quinoline cross-resistance, is a priority. From over one thousand safe, FDA approved compounds five promising drugs were identified using an in vitro NLN-based method. These drugs also showed direct activity against parasites in culture. Accurate diagnosis is needed for effective malaria treatment. Laser desorption mass spectrometry (LDMS) was found to be a sensitive diagnostic technique for identification of malaria hemozoin in human blood. As confirmed by PCR, LDMS successfully detected Plasmodium hemozoin in the blood of pregnant Zambian women negative by optical microscopy alone. LDMS successfully identified all four species responsible for human malaria in human clinical blood samples. Potential protein evidence of P. falciparum was identified in 800 year old human remains. Hemozoin is formed in NLNs in Plasmodium and is a useful biomarker of blood stage malaria infection by LDMS.
590 $a School code: 0098.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Biology, Parasitology. $3 1028974
690 $a 0410
690 $a 0718
710 2 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 68-04B.
790 $a 0098
790 1 0 $a Sullivan, David, $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3262488