Pharmacokinetic aspects of Tert-Butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethyl disulfide was performed after administration of two different single doses (35 and 300 mg/kg) of either the cold or labelled drug. Plasma or blood samples were treated with dithiothreitol, perchloric acid, and, after filtration, submitted to further purification with anionic resein. In the final step, the drug was retained on a cationic resin column, eluted with NaCl 1M and detected according to the method of Ellman (1958). Alternatively, radioactive drug was detected by liquid scintillation counting. The results corresponding to the smaller dose of total drug suggested a pharmacokinetic behavior related to a one open compartment model with the following parameters: area under the intravenous curve (AUC i.v.):671 ± 14; AUC oral: 150 ± 40 µg.min. ml [raised to the power of -1]; elimination rate constant: 0.071 min [raised to the power of -1]; biological half life: 9.8 min; distribution volume: 0.74 ml/g. For the higher dose, the results seemed to obey a more complex undertermined model. Combining the results, the occurence of a dose-dependent pharmacokinetic behavior is suggested, the drug being rapidly absorbed and rapidly eliminated; the elimination process being related mainly to metabolization. The drug seems to be more toxic when administered I.V. because by this route it escapes first pass metabolism, while being quickly distributed to tissues. The maximum tolerated blood level seems to be around 16 µg/ml.

On the association between HLA-A1 and B5 and clinical forms of schistosomiasis mansoni

The association between both HLA-A1 and B5 antigens and chronic forms of human schistosomiasis was studied in 64 patients and 26 normal controls from a southern Brazilian hospital. No apparent correlation between the chronic forms of the disease and the expression of those antigens was detected. However, the analysis of these date together with those observed on an Egyptian sample suggests that the presence of either of the antigens and the hepatomegalic forms of schistosomiasis is significant, without heterogeneity. Converseley, the association of histocompatibility antigens with splenogegaly is consistent and significant only for HLA-B5, but not HLA-A1

The efficiency of Lutz, Kato-Katz and Baermann-Moraes (adapted) techniques association to the diagnosis of intestinal helmints

The association of Lutz/Kato-Katz and Lutz/Bermann-Moraes (adapted techniques was used to improve better results that ranged from 0.4 to 11 times in the search of eggs of Ascaris lumbricoides, Schistosoma mansoni, Trichiuris trichiura, Taenia sp. and larvae of Strongyloides stercoralis.

Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil and its relevance to the treatment and control of malaria

With the use of a simple formulary, field by health agents was ewstablished a monitoring programme for responses of P. falciparum to the antimalarial drugs. This monitoring programme is emphasized for knowledge of the epidemiology of the drug resistance and the control of malaria falciparum in Amazonan Basin where occurs more than 95% of Brazilian malaria cases every year. It was demonstrated that still now 4-aminoquinolines have a great importance for the mortality control in areas where just SUCAM (National Health Foundation - Health Ministry) agenst are present without any medical assistance. The results obtained permitted the simplification of malaria treatment in Brazil Important conclusions were established in the field of malaria drug resistance.

Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquire, and praziquantel) were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50%) values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to praziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni of three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs.

Use of a selective medium with potassium tellurite to follow intestinal colonization of hospitalized patients by drug-resistant Enterobacteriaceae

Nosocomial infections are a relevant factor in complicating the recovery of patients interned for even minor causes. In attempt to determine their origin it is crucial to consider that their origin is of an endogenous nature. Looking for an acessible expression of intestinal colonization we analyzed fecal samples from 3 separate groups of hospital patients collected after different lenghts of time. For practical reasons one group was studied prospectively and two other groups (patients hospitalized for up to 7 days and patients hospitalized for more than 7 days) were compared to one another. We looked for the emergence of tellurite resistance among Enterobacteriaceae using a selective medium. MacConkey potassium tellurite (MCPT). The frequence of prospectively studied patients with tellurite resistant strains was significantly greater after 7 days of hospitalization. For the two other groups, patients with more than 7 days of hospitalization showed a significant increase of bacterial species and of strains with new antimicrobial resistance markers. High molecular weigth plasmids were detected in some of these strains. These data show that the MCPT medium is a useful tool for the investigation of bowel colonization in hospitalized patients by drug-resistant Enterobacteriaceae.

An experimental and clinical assay with ketoconazole in the treatment of Chagas disease

Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.