Plasmodium

Investigations with dolphin tissue have indicated that in this aquatic organism the breakdown of glucose or glycogen is qualitatively similar to 

In addition, the parasitic helminth, Schistosomoas mansoni, the nematode, Neopkctana glaseri, oyster muscle, the rat tapeworm, Hymenolepsis diminuta, contain systems which appear to be very similar to those found in yeast and animal tissue. 

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Development of Resistance. One of the principal disadvantages of sulfonamide therapy is the emergence of dmg-resistant strains of bacteria. Resistance develops by several mechanisms overproduction of PABA (38) altered permeabiUty of the organisms to sulfonamides (39) and reduced affinity of dihydropteroate synthetase for sulfonamides while the affinity for PABA is retained (40). Sulfonamides also show cross-resistance to other sulfonamides but not to other antibacterials. In plasmodia, resistance may occur by means of a bypass mechanism in which the organisms can use preformed foHc acid (41). 

Ga.metocytocides. These annihilate the sexual forms of the plasmodia (gametocytes) and also destroy the stages of the parasites in the Anopheles mosquito. 

The second type of antifolates bind preferentially with, and thus selectively inhibit, the enzyme dihydrofolate reductase contained in the plasmodia. This interferes with the abiUty of the malaria parasites to convert dihydrofolate to tetrahydrofoUc acid. In the erythrocyte host, however, dihydrofolate... 

The production of the polymer depends on several factors such as the composition of the growth medium, the time of harvest, and the particular stage of the life-cycle of organism under consideration. Eor P. polycephalum only plasmodia are the producers of j8-poly(L-malate) neither amoebae nor spherules (specialized cell forms that can survive unfavorable environmental conditions)... 

Table 1 Purification of /3-Poly(L-Malic Acid) and Its Potassium Salt from the Culture Medium of Plasmodia of Physarum polycephalum...

Grow microplasmodia in 25 x indented 2 liter Erlenmeyer flasks, each inoculated with 10-g plasmodia (24 h old) of Physarum polycephalum strain M3CVII in 500 ml growth medium. ... 

Figure 1 )S-Poly(L-malate) released into the culture medium during plasmodial growth of P. polycephalum. (a) Effect of the nutrient (o-glucose) on the growth of plasmodia (— —), and the production of )S-poly(L-malate) (—O—). Growth conditions are otherwise as indicated in Table 1 footnote 2. (b) Content of )S-poly(L-malate) (— —) and l-malate (—O—) in the culture medium during growth of strain M3CVIII under conditions indicated in Table 1 footnote 2. Inoculation on day 0. Growth termination on day 4.

Evidence for a physiological function of /S-poly(L-ma-late) is available for plasmodia of P. polycephalum. The... 

Substantial amounts of polymalatase have been isolated from plasmodial extracts. This may refer to stored enzyme before secretion, because /3-poly(L-malate) is not degraded in plasmodia [24]. Several other fungi were found to secrete /3-poly(L-malate) degrading activities to L-malic acid (Ratberger, Molitoris and Holler, unpublished results). These enzymes have not yet been purified and characterized. 

Leishmania spp., Rickettsia, Parvovirus spp., plasmodia and Toxoplasma spp., and prions... 

Malaria is transmitted by the bites of the Anopheles mosquitoes which introduce into the bloodstream one of four species of sporozoites of the plasmodia (Plasmodium falciparum, P. ovale, P. vivax or P. malariae). Initial symptoms of malaria are nonspecific and may resemble influenza and include chills, headache, fatigue, muscle pain, rigors, and nausea. The onset of the symptoms is between 1 to 3 weeks following exposure. Fever may appear 2 to 3 days after initial symptoms and may follow a pattern and occur every 2 or 3 days (P. vivax, P. ovale and P. malariae). Fever with P. falciparum can be erratic and may not follow specific patterns. It is not unusual for patients to have concomitant infections with P. vivax and P. falciparum. Falciparum malaria must always be regarded as a life-threatening medical emergency. 

In an uncomplicated attack of malaria (for all plasmodia except chloroquine-resistant P. falciparum and P. vivax), the recommended regimen is chloroquine 600 mg (base) initially, followed by 300 mg (base) 6 hours later, and then 300 mg (base) daily for 2 days.3 In severe illness or falciparum malaria, patients should be admitted to an acute care unit and quinidine gluconate 10 mgsalt/kg... 

All of these compounds are inhibitors of dihydrofolate reductase in bacteria, plasmodia, and humans. Fortunately, they have a significantly higher affinity to bacterial and protozoal dihydrofolate reductase. Pyrimethamine, for example, inhibits dihydrofolate reductase in parasites in concentrations that are a several hundred times lower than that required to inhibit dihydrofolate reductase in humans. This is the basis of their selective toxicity. Selective toxicity can be elevated upon the host organism s production of folic acid, which parasites are not able to use. 

Drugs effective against the erythrocyte stage of plasmodia infection... 

Primaquine is the most effective and most toxic drug from the whole series of known 8-aminoquinolines. It is generally used for treating exoerythrocyte forms of malaria caused by P. vivax and P. ovale. It also acts on the sexual forms of the plasmodia, which die in the human body upon using this drug. 

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