Characterization of reactions of antimoniate and meglumine antimoniate with a guanine ribonucleoside at different pH.

It has been shown previously that Sb(V) forms mono- and bis-adducts with adenine and guanine ribonucleosides, suggesting that ribonucleosides may be a target for pentavalent antimonial drugs in the treatment of leishmaniasis. In the present work, the reactions of antimoniate (KSb(OH)(6)) and meglumine antimoniate (MA) with guanosine 5'-monophosphate (GMP) have been characterized at 37 degrees C in aqueous solution and two different pH (5 and 6.5), using ESI(-)-MS and (1)H NMR. Acid and base species for both 1:1 and 1:2 Sb(V)-GMP complexes were identified by ESI(-)-MS. The (1)H NMR anomeric region was explored for determining the concentrations of mono- and bis-adducts. This allows for the determination of stability constants for these complexes (5,900 L mol(-1) for 1:1 complex and 370 L mol(-1) for 1:2 complex, at pD 5 and 37 degrees C). Kinetic studies at different pH indicated that formation and dissociation of both 1:1 and 1:2 Sb-GMP complexes are slow processes and favored at acidic pH (2,150 L mol(-1) h(-1) for the rate constant of 1:1 complex formation and 0.25 h(-1) for the rate constant of 1:1 complex dissociation, at pD 5 and 37 degrees C). When MA was used, instead of antimoniate, formation of 1:1 Sb-GMP complex occurred, but with a slower rate constant. Assuming that MA consists essentially of a 1:1 Sb-meglumine complex, a stability constant for MA could also be estimated (8,600 L mol(-1) at pD 5 and 37 degrees C). Thermodynamic and kinetic data are consistent with the formation of 1:1 Sb-ribonucleoside complexes in vertebrate hosts, following treatment with pentavalent antimonial drugs.

Microwave treatment of human milk to prevent transmission of Chagas disease.

It is recognized that breast feeding is an alternative means of transmission of Chagas disease. However, thermal treatment of milk can prevent this occurrence. As domestic microwave ovens are becoming commonplace, the efficacy of microwave thermal treatment in inactivating Trypanosoma cruzi trypomastigotes in human milk was tested. Human milk samples infected with T. cruzi trypomastigotes (Y strain) from laboratory-infected mice, were heated to 63 degrees C in a domestic microwave oven (2,450 MHz, 700 W). Microscopical and serological examinations demonstrated that none of the animals inoculated orally or intraperitoneally with infected milk which had been treated, got the infection, while those inoculated with untreated, infected milk, became infected. It was concluded that the simple treatment prescribed, which can easily be done at home, was effective in inactivating T. cruzi trypomastigotes contained in human milk.

Schistosomiasis mansoni in Bananal (State of São Paulo, Brazil): I. Efficiency of diagnostic and treatment procedures.

Bananal is an important focus of Schistosoma mansoni in the State of São Paulo. Accordingly, programmed active search for human cases, annual coproscopic surveys and treatment of infected cases were started in 1998, aiming at producing a sharp prevalence rate drop by the year 2000. S. mansoni eggs were searched for in two Kato-Katz slides per patient. Cases were followed up according to the routine of the local Family Health Program. In 1998, 130 samples out of 3,860 showed S. mansoni eggs; in 1999, 105 out of 3,550, and in 2000, 64 out of 3,528. Prevalence rates were 3.4%, 2.9%, and 1.8%, and average egg-counts 59, 64, and 79 eggs per gram of feces respectively. Prevalence rates decreased steadily after treatment, but persistently positive cases showed no significant decrease in parasite burdens. Egg count variation depended on sex and age bracket. Persistent residual cases admittedly preclude the eradication of this infection by only searching for and treating carriers. In addition, resistance to therapy and low sensitivity of fecal examinations, can not be ignored. Moderate to heavy worm burdens, frequently associated with hepatomegaly elsewhere, produced no serious cases in Bananal.