Science 24 October 1997:
Vol. 278. no. 5338, p. 581
DOI: 10.1126/science.278.5338.581d

Random Samples

The incidence of malaria is increasing due to several factors,
including resistance of the parasite to currently available
antimalarial drugs, and there is an urgent need to develop new drugs
for both the prophylaxis and treatment of malaria (11). Among the targets being explored for the development of new drugs are the proteases of Plasmodium, which play critical roles in the parasite's life cycle and can be targeted with specific inhibitors (reviewed in references 3, 20-22, and 36).

We
have recently found that the major surface protein of the sporozoite,
the circumsporozoite protein (CSP), is proteolytically processed by a
parasite cysteine protease during invasion and that E-64, a cysteine
protease inhibitor, inhibits CSP processing as well as sporozoite
infectivity in vitro and in vivo (6). Other groups studying the erythrocytic stages of Plasmodium have found that parasite cysteine proteases play critical roles in hemoglobin degradation (39, 40) and merozoite release from erythrocytes (37).
Taken together, these data suggest that cysteine protease inhibitors
may target both preerythrocytic and erythrocytic stages of Plasmodium and may therefore be good drug candidates for the prevention and treatment of malaria.

The
anti-infective properties of garlic have long been known to Chinese and
Indian civilizations and were first described in Europe by Louis
Pasteur (13).
Garlic has an unusually high concentration of sulfur-containing
compounds, and its antibacterial properties are largely due to one
particular class of sulfur-containing compounds, the thiosulfinates (18).
The thiosulfinate structure [S(=O)S] appears to be essential for the
bactericidal, antifungal, and antiprotozoal properties of garlic,
likely reacting with SH-containing enzymes of these pathogens (34, 45).
Allicin is the most abundant thiosulfinate found in garlic and is
generated when the enzyme alliinase reacts with its substrate alliin (18, 41).
Enzyme and substrate are located in different compartments of the
clove, so that allicin is generated only when the clove is crushed (18, 41). Many lines of evidence indicate that allicin is primarily responsible for garlic's anti-infective properties (1, 5, 15, 34, 38, 43),
although studies have also found that ajoene, a metabolite of allicin
found when garlic is crushed specifically in oil, also has some
antibacterial properties (27). In fact, one study found that ajoene has an inhibitory effect on the erythrocytic stages of Plasmodium (30).

The
precise mechanism of action of the thiosulfinates has, in many cases,
not been demonstrated. However, when used at low concentrations,
allicin appears to react specifically with the free sulfhydryl group
present in the active site of cysteine proteases (32). Experiments with the intestinal parasite Entamoeba histolytica have shown that pure allicin inhibits both the cytopathological effects associated with infection (2) and the growth of the parasite (23)
via its inhibitory effect on the parasite's cysteine proteases. Because
of allicin's inhibitory activity on cysteine proteases and Plasmodium'srequirement for cysteine protease activity during various life cycle
stages, we set out to test the effects of allicin on the
preerythrocytic and erythrocytic stages of Plasmodium.

• don't walk barefoot anywhere outside, 
  


• don't kiss your dog or allow you dog to lick your face (fact of life:  dogs lick their butts - so, when the dog licks you or you kiss the dog, you may as well just kiss your dog's trasera), 
  


• all fruits & vegetables must be either peeled or cooked or soaked in Microdyne (etc) for 15 minutes to avoid parasites and pathogenic bacteria =  restaurant food???
  


• no mystery ice.  Ice from professional companies is fine.