Protection of athymic (Nu/Nu) BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ +) BALB/c mice

Athymic BALB/c (Nu/Nu) mice died at 7-13 days after inoculation (DAI) of Plasmodium berghei NK65, whereas their heterozygous (Nu/+) littermates died at 7-8 DAI. Nude (Nu/Nu) mice, reconstituted with 2 x 10(7) splenocytes from uninfected heterozygous (Nu/+) littermates at 20 days before parasite inoculation (DBI), died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+) mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Strongyloses ratti and S. stercoralis: effects of cambendazole, thiabendazole and mebendazole in vitro

The effects of in vitro incubation of three henzimidazole anthelmintics, thiabendazole, mebendazole and cambendazole on Strongyloides were compared. No drug affected hatching of S. ratti eggs or the viability of infective larvae or parasitic adult worms, but all three inhibited moulting of S. ratti larvae. In addition, cambendazole, but not thiabendazole or mebendazole, impaired the viability of S. ratti first- and second-stage larvae. The three drugs had no effect on isolated S. stercorais free-living adult worms, but they all prevented development of S. stercoralis rhabditiform larvae. Thiabendazole and mebendazole had no effect on the infectivity of either S. ratti or S. stercoralis infective larvae, but infection with these worms was abrogated by prior incubation with cambendazole. These results indicate that cambendazole acts in a different manner to the other two drugs. Since it is active against larvae migrating through the tissues, it is potentially of much greater value than thiabendazole or mebendazole in the therapy of strongyloidiasis.

Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse

Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R), or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively). Sodium gluconate and antimonium (Triostib R) shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.

"In vitro" activity of gentian violet against asexual Plasmodium falciparum parasites

In order to investigate whether gentian violet exhibited "in vitro" inhibitory activity against Plasmodium falciparum, the Authors have carried out 20 sensitivity tests according to the microtechnique described by RIECK MANN et al.5. Results have shown inhibition of schizonts'maturation at the following concentration: 1/1000; 1/1500; 1/2000; 1/2500; 1/3000 and 1/4000, thus demonstrating inhibitory activity of the tested dye against asexual blood parasites. The present data suggest gentain violet may be possibly used in the prophylaxis of transfusion-acquired malaria.

Active immunization against hepatitis B virus (HBV) with low-doses of plasma-derived vaccine by intradermal route

Schedule for vaccination against HBV infection has usually been based on three separate injections of 20 meg of the vaccine by intramuscular route. One of the main shortcomings to its use in large scale programs has been its high cost. Ninety out of 300 health workers were submitted to three injections of 2 meg of plasma-derived vaccine (PDV) by intradermal (ID) route on days 0, 30, and 180. Anti-HBs was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third dose, a non-significant difference. However, levels above 10 times the cut-off were observed in 29 (32.2%) and 77 (85.5%), respectively (p < 0.001). The results showed that a low-dose schedule is effective when used in health workers and should be tried with other risk groups.

Screening the mutagenic activities of coomonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay

The mutagenic activities of 16 anti-parasite drugs were screened by the Simultest in both qualitative (spot test) and quantitative (plate incorporation) assays with a Salmonella typhimurium pool composed by the indicator strains TA97, TA 98, TA100 and TA102. Four anti Chagas' disease drugs (nifurtimox, benznidazole, CL 64,855, and MK 436) and two anti-amebae drugs (metronidazole and tinidazole) gave positive results in qualitative tests and incorporation of rat liver microsomes did not alter the results. Comparative dose response curves of the mutagenic activities of CL 64,855, metronidazole and benznidazole obtained by the simultest and by individual Salmonella indicator strains demonstrated that both approachs have similar sensitivities. The results corroborate the validity of the Simultest, as a simplified, fast and economic version of the Ames test in preliminary screening of potential mutagenic drugs.

Antibodies against Entamoeba histolytica in individuals with intestinal amoebiasis presenting cysts and/or trophozoites in the feces

Serum samples were obtained from 154 individuals infected with Entamoeba histolytica (78 symptomatic and 76 asymptomatic). Twelve had trophozoites in the feces whereas 142 had only cysts. The sera were used to test the existence of antibodies anti-Entamoeba histolytica employing the Indirect Hemagglutination (IHA), Indirect Immunofluoresccnce (IFAT), Complement Fixation Reaction (CFR) and Counterimmunoelectrophoresis (CIEP). For those individuals with trophozoites in their feces, 75.0 were positive by IHA and IFAT, 83.0 by CFR and 41.7 by CIEP. In individuals who had only cysts, positive results by the same tests were respectively, 5.6%, 12.0%, 19.0% and 5.6%. The difference in relation to the tilers of antibodies detected through IHA, IFAT, CFR and CIEP and in relation to the presence of trophozoites or cysts in the feces was significative for four immunological reactions when X², was employed (P < 0.05).

Immunization aganist hepatitis B in children from endemic zone: evaluation of the antibody response against the DNA recombinant vaccine (Engerix B-20 mcg)

A previous seroepidemiological study in the rural zone of Vargem Alta (ES) SouthEast of Brazil, showed a prevalence of up to 9% of hepatitis B surface antigen (HBsAg) in some areas. One hundred susceptible children aging 1 to 5 years old were selected and immunized with a recombinant DNA hepatitis B vaccine (Smith-Kline 20 mcg) using the 0-1-6 months vaccination schedule. Blood samples were collected at the time of the first vaccine dose (month 0) in order to confirm susceptible individuals and 1,3,6 and 8 months after the first dose , to evaluate the antibody response. Our results showed that two and five months after the second dose, 79% and 88% of children seroconverted respectively, reaching 97% after the third dose. The levels of anti-HBs were calculated in milli International Units/ml (mIU/ml) and demonstrated the markedly increase of protective levels of antibodies after the third dose. These data showed a good immunogenicity of the DNA recombinant hepatitis B vaccine when administered in children of endemic areas.

Antibodies against non-structural c100/3 and structural core antigen of hepatitis C virus (HCV) in hemodialysis patients

Two groups of patients undergoing hemodialysis (HD) maintenance were evaluated for their antibody response to non-structural c100/3 protein and structural core protein of hepatitis C virus (HCV). Forty-six patients (Group 1) never presented liver abnormalities during HD treatment, while 52 patients (Group 2) had either current or prior liver enzyme elevations. Prevalence rates of 32.6% and 41.3% were found for anti-c100/3 and anti-HCV core antibodies, respectively, in patients with silent infections (Group 1). The rate of anti-c100/3 in patients of Group 2 was 71.15% and reached 86.5% for anti-HCV core antibodies. The recognition of anti-c100/3 and anti-core antibodies was significantly higher in Group 2 than in Group 1. A line immunoassay composed of structural and non-structural peptides was used as a confirmation assay. HBV infection, measured by the presence of anti-HBc antibodies, was observed in 39.8% of the patients. Six were HBsAg chronic carriers and 13 had naturally acquired anti-HBs antibodies. The duration of HD treatment was correlated with anti-HCV positivity. A high prevalence of 96.7% (Group 2) was found in patients who underwent more than 5 years of treatment. Our results suggest that anti-HCV core ELISA is more accurate for detecting HCV infection than anti-c100/3. Although the risk associated with the duration of HD treatment and blood transfusion was high, additional factors such as a significant non-transfusional spread of HCV seems to play a role as well. The identification of infective patients by more sensitive methods for HCV genome detection should help to control the transmission of HCV in the unit under study.

Drugs in ads and news: educating people in the nineteenth century press

This research aims at finding out how scientific knowledge reached the common people in nineteenth century Portugal, using newspapers as the main source of information. Collecting news on science and technology is part of a larger research project focused on producing a History of the Popularization of Science and Technology in Portugal, following a model already developed in the UK and the USA (Bauer 2007). This source was probably the most widespread vehicle to divulge the latest scientific news at the time to an unspecialised audience. The following themes are approached: Drug advertisements in the nineteenth century. How did scientific knowledge on diseases and treatments reach the consumer? How did newspapers deal with epidemics? What were the prevention measures and the known treatments at the time? And what was the role of newspapers as educators? Ads show us the interest on divulging new products and the role of publicity as moulder of minds. All these questions introduce us to the role of the media on the subject of social perception of science and technology and the way scientific knowledge reached the common citizen.