Search PubMed⌕ Search

Biomedical subjects

I Landau

Publications and source records attributed to I Landau.

At least 91 records · Page 5Linked to original sources

[Trypanosomes of Estrildidae birds. II. Biological studies].

Studies on the biology of 4 Trypanosomes of Estrildidae birds described in a previous paper (Chandenier et al., 1988) are related. In Culicoides nubeculosus, the complete development is achieved in 7 days. After a phase of intense multiplication of amastigotes in the gut, infective trypomastigotes appear. In cultures, infective stages are obtained in 13 days. Transmission to clean birds was attempted: in two out of 8 attempts, a satisfactory level of parasitaemia is obtained. Surprisingly Trypanosomes infecting the new birds are unable to develop further in cultures or in Culicoides. The most likely hypothesis is the lack of a factor allowing the Trypanosomes to mature.

Animals↗

Iron chelators: in vitro inhibitory effect on the liver stage of rodent and human malaria.

The activity of desferrioxamine (Desferal) and desferrithiocin (a newly developed oral iron chelator) was evaluated against the liver stage of Plasmodium yoelii and P. falciparum in the rodent and the human hepatocyte in vitro culture system. The two iron chelators were found to inhibit the liver schizogony of both the rodent and the human Plasmodium species at concentrations achievable in vivo. P. falciparum proved to be more sensitive (ic 95% below 20 micromol/l than P. yoelii (ic 95% 50-100 micromol/l). As assessed by electron microscopy, drug administration was associated with focal clarification of the cytoplasm thought to be reversible. As desferrioxamine and desferrithiocin are known to be equally active on the blood stage of rodent and human plasmodia, iron chelators are deserving of further investigation as potential alternative candidates to existing drugs for radical cure of malaria.

Animals↗

Experimental modifications of the circadian rythm of Plasmodium vinckei petteri following cryopreservation; probable resistance of the merozoïte to thawing.

Plasmodium vinckei petteri, in white mice, is a particularly useful strain for studies on the circadian rythm of Plasmodium. An experimental model was set up: it showed that the rythm of asexual schizogony in the blood varies with the time and the mode of inoculation (cryopreserved blood or syringe passage). When frozen blood is injected, the time of schizogony depends on the time of injection; on the contrary, when the passage is by syringe from mouse to mouse, the rythm of schizogony is the same in the donor and the receptor mouse, regardless of the time of injection. The only possible explanation is that all intracellular parasites are destroyed by the thawing of blood and the free merozoïte is the only resistant stage.

Animals↗

Observations on early and late post-sporozoite tissue stages in primate malaria. V. The effect of pyrimethamine and proguanil upon tissue hypnozoites and schizonts of Plasmodium cynomolgi bastianellii.

Two rhesus monkeys were each infected with 2.1 x 10(6) sporozoites of Plasmodium cynomolgi bastianellii; one was treated with 1.0 mg of pyrimethamine base per kg body weight for 5 d after sporozoite inoculation. A further 2 monkeys were each infected with 9.75 x 10(6) sporozoites of the same parasite; one was treated with 10 mg of proguanil per kg body weight for 4 out of 5 d after inoculation. The treated monkeys showed a delayed primary parasitaemia and relapses. In sections of liver biopsies taken 7.5 d after sporozoite inoculation, all monkeys showed numerous hypnozoites. However, there were no full grown schizonts and only rare retarded schizonts in the treated monkeys, in contrast to the untreated monkeys which had many mature or nearly mature schizonts. Later biopsies confirmed the continued presence of hypnozoites in all monkeys.

Animals↗

Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures.

We have studied the effect of natural and recombinant human interferons (HuIFN-alpha, -beta, and -gamma), and interleukin 1 (IL-1) on development of sporozoites of Plasmodium falciparum in cultures of functional hepatocytes. HuIFN-gamma inhibits hepatic schizogony of P. falciparum at very low concentrations (0.1 to 10 international units/ml), the target being the hepatocyte. Application after sporozoite inoculation is effective, suggesting an intracellular mechanism. There is also an 84% inhibition after application from 4 to 6 days following inoculation so that by day 6, there was a disappearance of a significant number of schizonts previously present at day 4, indicating more than a parasitostatic effect, and probably a postassembly action. HuIFN-alpha and -beta were effective, but only at 1000-fold higher concentrations than HuIFN-gamma. IL-1 (5 U/ml) also inhibited hepatic development of P. falciparum sporozoites; however, IL-1 treatment was effective only when applied before sporozoite inoculation.

Animals↗

Photooxidation products of primaquine. Structure, antimalarial activity and hemolytic effects.

Photooxidation of primaquine (1) and 5-hydroxyprimaquine (5) afforded a blue dye for which o-quinone structure 4 was elaborated. Similar oxidation of N-ethoxyacetylprimaquine (10) afforded o-quinone 11. Tissue schizontocidal activity of 4 and 11, and bisquinolylmethine 3 prepared earlier, showed that none of them had noteworthy antimalarial activity, but all three produced methemoglobin.

Animals↗

Antimalarial activity and inhibition of monoamine oxidases A and B by exo-erythrocytic antimalarials. Optical isomers of primaquine, N-acylated congeners, primaquine metabolites and 5-phenoxy-substituted analogues.

When the terminal amino group in the side chain of primaquine was blocked with an ethoxyacetyl group shown in 2, or eliminated by oxidative deamination to carboxylic acid 3, the antimalarial effect was markedly reduced in a screening assay which measures tissue schizonticidal activity. The optical isomers 1A and 1B of primaquine had similar antimalarial potency to the racemic mixture but 1B appeared less toxic. The 5-phenoxy-substituted analogue 4, belonging to a new class of antimalarials, showed similar potency in the assays to either 1A or 1B but seemed less cytotoxic than (+/-)-primaquine. Compounds 1A and 1B were found to be competitive inhibitors of human monoamine oxidase (MAO) A and B (Ki range 103-225 microM), but 4 showed 10-30-fold greater competitive inhibition of MAO A (Ki = 6.8 microM) and 40-90-fold greater non-competitive inhibition of MAO B (Ki = 2.3 microM).

Animals↗

[Inhibition of the infectivity of Plasmodium gametocytes by the serum of the parasite host. Perfecting an experimental model].

In the course of experimental malarial infections the infectivity of the gametocytes falls abruptly and at an early stage of the infection. This phenomenon is independent of the production of circulating antibodies. With Plasmodium yoelii nigeriensis infecting the white mouse, the maximum infectivity of gametocytes for Anopheles stephensi occurs on day 2, and on day 5 no more oocysts develop in the mosquito. The behaviour of the plasmodial strain in the mouse and particularly the "crisis" phenomenon were studied in detail in standardized experimental conditions. The decrease of the infectivity for the Anopheles begins just before the peak of parasitaemia, and a concomitant increase in the number of circulating gametocytes is observed. These events are very shortly followed by the crisis. The more severe is the crisis and virulent the infection, the earlier and more abrupt is the loss of infectivity. Previous studies having shown that this inhibition of the gametocytes infectivity was linked to a serum factor, our research aimed at setting up an experimental model allowing the identification of this factor. The intravenous injection of 5th day serum to mice harbouring infective gametocytes did not determine any loss of the gametocytes infectivity in the receiving mice. In order to study in vitro the effect of the 5th day serum, this one was added to blood from mice with highly infective gametocytes, and mosquitoes were fed on this through a membrane. As a result, a significant decrease of the infectivity of gametocytes was observed. This inhibition is immediate and does not appear to be "dose-dependent". Inversely, serum from mice still infective to the mosquito did not reduce the infectivity of the gametocytes. The experimental model set up thus comprises: a) mouse blood containing P. y. nigeriensis infective gametocytes to which is added the serum to be tested; b) Anopheles stephensi fed through a membrane; this allows quantifying the infectivity of the gametocytes in the presence of normal serum (control) or inhibitory serum. This model proved to be reliable; it should promote the study of any factor likely to modify the infectivity of Plasmodium gametocytes to the mosquito.

Animals↗

Fractionation of mouse malarious blood according to parasite developmental stage, using a Percoll-sorbitol gradient.

Asexual intraerythrocytic malarial parasites permeabilize the membrane of their host cell to small monelectrolytes and anions. Since permeabilization increases with parasite maturation, this property has been used previously to fractionate blood infected with Plasmodium falciparum and P. knowlesi according to the developmental stage of the parasite, using Percoll-sorbitol density gradients. We have extended this method to fractionate mouse blood infected with four species of rodent malaria: P. chahaudi, P. vinckei, P. voelii and P. berghei. While the method works in principle in this case, the polyparasitism which characterizes these species prevented explicit separation according to developmental stage. Hence, erythrocytes harbouring several ring-stage parasites appeared in the same fraction which contained cells hosting a single trophozoite, and polyparasitized trophozoites were associated with singly-infected schizont. This observation implies that permeabilization of the host cell membrane results from the integrated metabolic activity of the parasite(s) and is not related to a specific phase of parasite development.

Animals↗

[Ultrastructure of chronic reticuloendothelial forms of Isospora of sparrows].

Mononucleated reticulo-endothelial stages of Isospora from Sparrows were studied by T. E. M. during the winter period when the extra intestinal infection is chronic. Results show a very slow evolution from merozoite to trophozoite stage, a transformation of the parasite nucleus and a characteristic reaction of the host cell. These observations are discussed in relation to what is known of hypnozoite and chronic schizogony of Plasmodium.

Animals↗

Selenium-induced cataract--a correlation of dry mass content and light scattering.

Selenium-induced cataracts in young rats were used to compare light scattering and dry mass concentration along the lens axis. Selenium-treated rats and control rats were examined 1, 2, 4 and 6 days after subcutaneous injection of selenium or 0.9% NaCl. The development of nuclear cataract was followed with a Scheimpflug slit-lamp camera. Light-scattering was determined by densitometry of the negatives taken by the Scheimpflug camera. Dry mass concentration was determined by quantitative microradiography of the extracted lenses. Increasing light scatter was seen from day 2 to day 6. The dry mass concentration, however, was not changed until day 6. Two distinct zones were found surrounding the center of the nucleus, one with increased and one with decreased dry mass. The rapid changes in dry mass concentration were probably caused by shifts in water distribution within the lens. Similar zones of hydration have also been found in human senile nuclear cataract. Selenium-induced cataract in the rat is discussed in relation to human nuclear cataract.

Animals↗

The chemotherapy of rodent malaria XLI. Causal prophylaxis. Part V. Effect of mefloquine on exoerythrocytic schizogony in Plasmodium yoelii yoelii.

Previous studies using mefloquine in rodents have suggested that this compound has no effect on pre-erythrocytic schizogony. In the present study, direct observations on 46-hour-old pre-erythrocytic schizonts of P. yoelii in the liver of rats have shown that mefloquine does induce recognizable changes in the peripheral, enzyme-containing vesicles but that these are insufficient to hinder the maturation of the parasites, thus confirming that this compound has no causal prophylactic value.

Animals↗

Complete development of hepatic stages of Plasmodium falciparum in vitro.

An in vitro model was developed to study the hepatic phase of Plasmodium falciparum, the only malaria parasite lethal to man. Primary cultures of human hepatocytes were inoculated with sporozoites of Brazilian and African strains of P. falciparum. On days 1 through 7 after inoculation examination of fluorescence-labeled and Giemsa-stained preparations demonstrated the presence of many intracellular parasites. In three separate sets of experiments all cultures were found to be infected with as many as 650 liver schizonts measuring up to 40 micrometers. After the addition of red blood cells, intraerythrocytic forms of P. falciparum were detected on days 12 and 13 by an immunofluorescence assay, indicating that the hepatic cycle had been completed in vitro.

Animals↗

Comparative clinical evaluation of ceftizoxime with clindamycin and gentamicin and cefoxitin in the treatment of postcesarean endomyometritis.

New third generation cephalosporins have been recommended as single agent antibiotic therapy in the treatment of postoperative infections. This study compares the new third generation cephalosporin ceftizoxime with cefoxitin, clindamycin and gentamicin in the treatment of postcesarean section endomyometritis. The results indicate that the clindamycin and gentamicin regimen is more efficacious in the treatment of severe infection after cesarean section than either ceftizoxime or cefoxitin regimens. Therefore, the results of this study suggest caution in substituting single drug antibiotic therapy with cefoxitin or the third generation cephalosporins for the standard clindamycin and gentamicin regimen in the treatment of postcesarean section endomyometritis until more clinical data are available.

Adult↗

[Cultivation of exo-erythrocytic schizonts of rodent Plasmodium in hepatocytes: a new experimental model for chemotherapy of malaria].

An in vitro experimental model using primary cultures of laboratory bred Thamnomys gazellae's hepatocytes and Plasmodium yoelii yoelii' sporozoites was set up for chemotherapeutic studies. The surface of the culture was reduced (0.5 cm) and allowed the rapid performance and analysis of schizonticide activity tests, with a reduced biological material (Rodents, Anopheles, sporozoites). Fifteen compounds were tested. When activity of molecules is known in vivo, both results in vivo and in vitro are parallel.

Animals↗