Pigment Formation in Schistosoma mansoni Infections in the White Mouse *

Kloetzel, Kurt; Lewert, Robert M.

doi:10.4269/ajtmh.1966.15.28

Cited by 44 publications

(16 citation statements)

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“…That leaves the protonephridial system, which ramifies through internal tissues but is poorly understood, or the tegument, where aquaporin is very abundant in the surface membranes. As lactate is expelled via aquaporin pores [65], excess water may travel the same route, and the Na/K pump in the tegument membranes is also likely involved. The 8-fold disparity in plasma fluid intake means that the female has a much greater task than the male, and this must represent a significant metabolic burden.…”

Section: Resultsmentioning

confidence: 99%

“…It is unclear whether Hz can be selectively eliminated during regurgitation, while important cathepsins, peptidases, saposins, and a variety of carrier protein homologs are retained [11], [63], [64]. However, the Hz expelled into the bloodstream of infected animals [65], [66] has been proposed to exert an immunomodulatory effect on the host [67].…”

Section: Waste Disposalmentioning

confidence: 99%

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Schistosome Feeding and Regurgitation

et al. 2014

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Schistosomes are parasitic flatworms that infect >200 million people worldwide, causing the chronic, debilitating disease schistosomiasis. Unusual among parasitic helminths, the long-lived adult worms, continuously bathed in blood, take up nutrients directly across the body surface and also by ingestion of blood into the gut. Recent proteomic analyses of the body surface revealed the presence of hydrolytic enzymes, solute, and ion transporters, thus emphasising its metabolic credentials. Furthermore, definition of the molecular mechanisms for the uptake of selected metabolites (glucose, certain amino acids, and water) establishes it as a vital site of nutrient acquisition. Nevertheless, the amount of blood ingested into the gut per day is considerable: for males ∼100 nl; for the more actively feeding females ∼900 nl, >4 times body volume. Ingested erythrocytes are lysed as they pass through the specialized esophagus, while leucocytes become tethered and disabled there. Proteomics and transcriptomics have revealed, in addition to gut proteases, an amino acid transporter in gut tissue and other hydrolases, ion, and lipid transporters in the lumen, implicating the gut as the site for acquisition of essential lipids and inorganic ions. The surface is the principal entry route for glucose, whereas the gut dominates amino acid acquisition, especially in females. Heme, a potentially toxic hemoglobin degradation product, accumulates in the gut and, since schistosomes lack an anus, must be expelled by the poorly understood process of regurgitation. Here we place the new observations on the proteome of body surface and gut, and the entry of different nutrient classes into schistosomes, into the context of older studies on worm composition and metabolism. We suggest that the balance between surface and gut in nutrition is determined by the constraints of solute diffusion imposed by differences in male and female worm morphology. Our conclusions have major implications for worm survival under immunological or pharmacological pressure.

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Section: Resultsmentioning

confidence: 99%

Section: Waste Disposalmentioning

confidence: 99%

Schistosome Feeding and Regurgitation

et al. 2014

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“…Similar to Plasmodium spp., schistosomes feed on ingested erythrocytes, which is essential for parasite development, growth, and reproduction. Cathepsin D plays an important role in the digestion of hemoglobin, released from the erythrocytes into proteins, amino acids, and pigment (Kloetzel and Lewert 1966;Lawrence 1973;Brindley et al 2001, Morales et al 2008). It has been speculated that an interference with hemoglobin digestion is involved in the mechanisms of action of mefloquine against Plasmodium Tilley 1997, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice

et al. 2009

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It has been recently documented that the antimalarial drug mefloquine shows in vivo activity against schistosomes. In the present study, we assessed the effect of mefloquine on the morphology of adult Schistosoma japonicum worms. Mice were infected with S. japonicum cercariae for 35 days and then treated with a single 400-mg/kg oral dose of mefloquine. Groups of mice were killed between 24 h and 14 days post-treatment and worms were recovered from the liver and mesenteric veins, fixed in 70% alcohol, stained with acid carmine, and examined under a light microscope. Worms obtained from nontreated mice served as controls. S. japonicum recovered from mice 24 h post-treatment had severely dilated guts and the entire worm body was swollen. Meanwhile, reproductive glands, including the testis, ovary, and vitelline gland, showed signs of degeneration. Damage further progressed, particularly among vitelline glands, which resulted in disturbance of ova formation and cessation of oviposition 3 days post-treatment. Three to 7 days after mefloquine administration, adherence of host leukocytes on the damaged tegument was observed. Our results confirm that mefloquine possesses antischistosomal properties, exhibiting a rapid onset of action and causing extensive morphologic damage to adult S. japonicum.

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“…Although artemether induced worm hepatic shift and extensive effects on carbohydrate, nucleic acid, protein metabolism, and antioxidant system of the adult schistosomes in vivo after artemether administration (Xiao et al 2000;Xiao 2005b), no apparent action on the adults in vitro at a higher concentration of 100 μg/mL was observed (Xiao and Catto 1989). Since blood cells are taken up by both malaria and schistosomes for nutrition and generation of pigment after metabolism (Kloetzel and Lewert 1966), it is similar to malaria (Meshnick et al 1996) that an interaction between artemether and hemin, or other iron compounds may occur in schistosomes which results in cleavage of endoperoxide bond of the artemisinin compound, followed by formation of free radical and series of biochemical reactions toxic to the worms (Xiao et al 2003). Further in vitro study indicated that when schistosomes exposed to lower concentration of artemether together with hemin resulted in a decrease in worm motor activity, followed by severe tegumental damage, dilatation of gut, cloudiness of the worm body, and death (Xiao et al 2001).…”

Section: Introductionmentioning

confidence: 95%

The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum

2009

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Mefloquine, an antimalarial drug, has been found to be effective against various stages of schistosomes in vivo. The purpose of the study is to explore the in vitro effect of mefloquine against adult and juvenile Schistosoma japonicum and to compare its efficacy with praziquantel. Three-hour-old schistosomula were prepared by penetrating the mouse skin with schistosome cercariae, while schistosomes 7-, 14-, and 35-day-old were collected from mice infected with S. japonicum cercariae for 7, 14, and 35 days by perfusion. Schistosomes were placed to each of 24 wells of a Falcon plate and maintained in Hanks' balanced salt solution-20% calf serum. Besides observation on the direct in vitro effect of mefloquine and praziquantel, adult worms exposed to mefloquine and praziquantel for 1 and 4 h were transferred to the medium without the drugs and incubated continuously for another 72 h. The reversible effect of mefloquine and praziquantel was assessed by the recovery of the worm motor activity and parasite survival. The minimal effective concentration of mefloquine against adult schistosomes in vitro was 10 microg/mL, which revealed that the worm motor activity was first stimulated, then decreased significantly, followed by bleb formation, focal swelling and elongation of the worm body, cessation of gut peristalsis, and death of 56.3% (18/32) worms within 24-72 h. Similar appearance was seen in the adult worms exposed to higher mefloquine concentration of 20 and 30 microg/mL, but all worms died within 4-24 h. The adult schistosomes exposed to praziquantel 1-30 microg/mL showed fast spasmodic contraction of the worm body, followed by bleb formation along the tegument, feeble movement of oral sucker, and death of a part of males and females 72 h after incubation. When male and female schistosomes exposed to mefloquine 10 and 20 microg/mL for 1 and 4 h were transferred to the medium without the drug, no apparent recovery of worm motor activity and survival was seen. In case of worms exposed to praziquantel at the same concentration for 1 and 4 h before replacement of drug-free medium, a well recovery of worm motor activity, looseness of worm body, and reduction or disappearance of blebs along the tegument were observed. Mefloquine also exhibited in vitro effect against 3-h-old and 7- and 14-day-old schistosomula which was similar to that seen in adult worms, but all or parts of worms showed decrease in motor activity or even death (3-h-old and 7-day-old schistosomula) at a lower mefloquine concentration of 5 microg/mL. In 14 day-old schistosomula exposed to praziquantel 1-30 microg/mL, spasmodic contraction and significant decrease in motor activity of the worm body with movement of oral and ventral suckers were observed, but no death of worm was seen during a 3-day incubation period. The results indicate that in vitro mefloquine exhibits a direct killing effect against adult and juvenile S. japonicum which is different from that of praziquantel. Meanwhile, the juvenile schistosomes are more susceptible to mefloquine than ...

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Pigment Formation in Schistosoma mansoni Infections in the White Mouse *

Cited by 44 publications

References 0 publications

Schistosome Feeding and Regurgitation

Schistosome Feeding and Regurgitation

Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice

The in vitro effect of mefloquine and praziquantel against juvenile and adult Schistosoma japonicum

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