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Biomedical subjects

I Landau

Publications and source records attributed to I Landau.

At least 37 records · Page 2Linked to original sources

Thinning of the papillomacular bundle in the glaucomatous eye and its influence on the reference plane of the Heidelberg retinal tomography.

PURPOSE: To measure the thickness of the papillomacular bundle in glaucomatous eyes with good visual acuity and to evaluate the influence of an adjusted reference plane on the Heidelberg retinal tomography result. METHODS: The thickness of the papillomacular bundle was measured with optical coherence tomography in both eyes of eight patients with asymmetric glaucoma. The eye with less glaucomatous damage with normal visual field served as the control. The difference in the thickness of the papillomacular bundle between the control eye and the glaucomatous eye was used to correct the reference plane of Heidelberg retinal tomography. RESULTS: The thickness of the papillomacular bundle in glaucomatous eyes was reduced (P = 0.00037) and was 33.9 +/- 16.5 microm thinner than control eyes. A corrected reference plane in Heidelberg retinal tomography caused an increased classification value (-0.683 +/- 0.164), implying that more glaucoma damage was detected after the correction. In one case the value was shifted from normal to glaucomatous after an adjustment of the reference plane. CONCLUSION: The thickness of the papillomacular bundle is decreased in glaucomatous eyes, though these eyes have good visual acuity. Evaluation of glaucoma with Heidelberg retinal tomography using the standard reference plane may underestimate the glaucoma damage.

Aged↗

The effects of subcurative doses of chloroquine on Plasmodium vinckei petteri gametocytes and on their infectivity to mosquitoes.

The effects of subcurative doses of chloroquine on rodent and human Plasmodium transmission to the mosquito have been studied by several authors who showed a short-term (12 h) enhancement of gametocyte infectivity by the drug, restricted to chloroquine-resistant strains, and a long term (4-6 days) enhancement of gametocytogenesis of chloroquine-sensitive strains of Plasmodium chabaudi. We investigated both short- and long-term effects of chloroquine on Plasmodium vinckei petteri, a chloroquine-sensitive rodent Plasmodium strain. Chloroquine treatment reduced the index of gametocytogenesis to 73% (5 mg/kg) and 55% (2.5 mg/kg) of controls, on day 6 post-infection (p.i.). The reduction was statistically significant with 5 mg/kg chloroquine. However, the reduction of gametocyte numbers did not affect the transmission capabilities of the strain. Our experiments showed that doses of 1 mg/kg chloroquine had no effect on the oocyst counts, 12 h post-administration to mice. A statistically non-significant 61% reduction of oocyst numbers was observed in mosquitoes fed on mice treated with 5 mg/kg chloroquine. The effect of 5 mg/kg chloroquine administration on the infectivity of gametocytes to mosquitoes fed 1 h post-treatment was also investigated. An overall 41% reduction of oocyst numbers was observed. This immediate effect was statistically significant in 73% of the mice. These results are consistent with the hypothesis that the short-term enhancing effect of chloroquine on transmission is restricted to the drug-resistant strains of Plasmodium.

Animals↗

The biology and epidemiology of Eimeria exigua, a parasite of wild rabbits invading the host cell nucleus.

Prevalence and intensity of infection with Eimeria exigua were studied by monthly sampling of caecal faeces of 254 wild rabbits (Oryctolagus cuniculus) from 5 localities in France (Arjuzanx, Versailles, Donzere-Mondragon, Massereau, Gerstheim) and by a single sampling in autumn in a small island off the coast of Britany (Beniguet). Intensity was heavier in young than in adult rabbits but usually remained low. It decreased from north to south, was at a maximum during autumn and winter, and declined in spring. Prevalences were relatively high and their rank (4th or 5th out of 10) was constant in all localities. Prevalences decreased from north-west to south-east; they increased progressively during autumn and winter, were at a maximum during spring and declined in summer. E. exigua developed in the ileum, at the top of the villi and inside the host-cell nucleus. It is distinguished from congeneric species by a number of features: micro-localisation, multiplication in autumn and winter rather than in summer, low intensity and high prevalence. These characteristics may be the consequence of a short schizogony phase and of strong resistance of oocysts.

Animals↗

Final stage of maturation of the erythrocytic schizonts of rodent Plasmodium in the lungs.

Schizonts of all rodent Plasmodium studied (Plasmodium yoelii, P. chabaudi, P. vinckei) show a characteristic morphology when they are completely mature: rounded or slightly elongate merozoites, completely detached from the pigment mass. At this stage, they are localized principally in the spleen and the lungs but, in impression smears of these organs they show two different aspects. In the spleen, schizonts are either inside the host erythrocyte or extraglobular but still close to a pigment mass; free merozoites are rare. In the lungs, on the contrary, merozoites are often free and dispersed; electron microscopy showed them to lie against the endothelium. Work by physiologists has shown the blood circulation in the alveoli to be much slowed down. Free merozoites, lined against the endothelium of relatively rigid capillaries, are in the best possible conditions to make contact with the intact red blood cells. Lungs appear to be the privileged site for the invasion of erythrocytes by the merozoites.

Animals↗

Development of irreversible lesions in the brain, heart and kidney following acute and chronic murine malaria infection.

Irreversible pathological lesions were noted in the organs of mice infected with 1 of 3 rodent malaria species: Plasmodium chabaudi chabaudi, P. vinckei petteri and P. yoelii nigeriensis at different times during the course of the primary parasitaemia and long after microscopical clearance of the parasites. Moreover, similar lesions were also obtained when parasite levels were kept below 1% by subcurative drug treatment. The frequency and severity of the lesions correlated with the duration of the infection. Accumulation of tissue damage during chronic low-grade malaria infections has implications for the design of control measures.

Acute Disease↗

Survival of rodent malaria merozoites in the lymphatic network: potential role in chronicity of the infection.

Experiments performed during the last few years, lead us to hypothesise the existence of latent asexual forms of murine Plasmodium. In the present report we examined the organs of infected animals and describe novel structures, which we call merophores, containing merozoites which have resisted lysis seen with other asexual stage parasites. We propose that these merozoites represent a latent form of the parasite. Merophores were also found in the lymphatic circulation, and were demonstrated by subinoculation to have retained their viability. Depending on the parasite species two types of merophores were observed. For P. yoelii nigeriensis merophore sacks, with the latent merozoites found inside vesicles, were usually observed. Merophore leucocytes, where latent merozoites dispersed in the cytoplasm of macrophages or neutrophils, were solely seen with P. vinckei petteri. Both structures were seen in P. chabaudi chabaudi infections. Merophores were found in lymph nodes of rodents after the asexual parasitaemia had apparently subsided. They were formed soon after schizogony, principally in the spleen, either by pitting or by macrophage phagocytosis. Merophore numbers appeared to be proportional to the number of maturing schizonts. We propose that merophore formation and their circulation in the lymphatics play an important role in the pattern of recrudescences and chronicity of rodent malaria infections. It is further suggested that the lymphatic network, a privileged pathway for many parasites, might play a similar role in human malaria infections.

Animals↗

An in vivo study of the chlorhexidine release profile of the PerioChip in the gingival crevicular fluid, plasma and urine.

The release profile of chlorhexidine from the PerioChip (Chip), a biodegradable local delivery system that contains 2.5 mg of chlorhexidine gluconate (CHX) in a cross-linked hydrolyzed gelatin matrix, into the gingival crevice, was evaluated in an in vivo, open label, single-center, 10-day pharmacokinetic study conducted on 19 volunteers with chronic adult periodontitis. Each volunteer had a single chip inserted into each of 4 selected pockets, with probing pocket depths of between 5-8 mm, at time 0. Gingival crevicular fluid (GCF) samples were collected using filter paper strips prior to Chip placement and at 2 h, 4 h, 24 h and 2, 3, 4, 5, 6, 8, and 9 days post-Chip placement. The GCF volume was measured using a calibrated Periotron 6000. Blood samples were collected at times 0, 1, 4, 8, 12 h and 5 days post-dosing. Urine was collected as a total 24-h specimen immediately post-dosing and 2 single samples at time 0, prior to dosing, and 5 days. The CHX was eluted from the paper strips and the CHX levels in GCF, blood and urine quantified using HPLC. The results indicate an initial peak concentration of CHX in the GCF at 2 h post-Chip insertion (2007 microg/ml) with slightly lower concentrations of between 1300-1900 microg/ml being maintained over the next 96 h. The CHX concentration then progressively decreased until study conclusion with significant CHX concentrations (mean=57 microg/ml) still being detectable at study termination. CHX was not detectable in any of the plasma or urine samples at any time point during the study. These results indicate that the PerioChip can maintain clinically effective levels of CHX in the GCF of periodontal pockets for over 1 week with no detectable systemic absorption.

Adult↗

Chronosexuality of Plasmodium species of Central African Muridae.

A host harbouring many parasite species of the same genus is a phenomenon frequently observed in numerous parasitic infections. This is the case for the Plasmodium parasites of Muridae in Central Africa, where three different parasite species are found in the same rodent host species. It is highly likely that these three Plasmodium species are transmitted simultaneously by the same vector. We and others have shown that the maturation periods of the various asexual and sexual stages in the rodent, differ amongst the three parasites. In this article we propose that these differences are the product of complex adaptations which result, for all three Plasmodium species, in a maximum peak of infectivity to the insect vector occurring around 3 a.m., the period of highest activity of the nocturnal host rodent.

Animals↗

Modifications in the rhythm of schizogony in Plasmodium chabaudi chabaudi associated with the selection of chloroquine resistance.

A high level of drug resistance was obtained with a line of Plasmodium chabaudi maintained under intense chloroquine selection pressure according to the protocols established for P. berghei. The main objective of this work was to verify if the characteristic asynchronous schizogonic rhythm of naturally resistant rodent malaria parasites was also found when the drug resistance was induced experimentally. The degree of resistance was evaluated through the use of the "2% delay test" (DT) and the schizogonic rhythm, by reference to the synchronicity index (SI). The strain had originally a DT of 4.26 and an SI of 0.52. Following the application of 80 mg/kg chloroquine at each passage, as early as at the 8th passage the parasites rapidly became resistant and asynchronous. At the 17th passage the DT was 3.32 and the SI, 0.20. In the drug-resistant line the original indices, both the DT and the SI, were restored after deep-freezing, sporogony, or passage through a Percoll gradient, or simply by repeated intravenous subinoculations of blood. The clear correlation between asynchronicity and drug resistance is easily explained by the action of chloroquine, which favours the schizogonic cycles initiated by latent merozoites.

Animals↗

The use of scintigraphy to provide "proof of concept" for novel polysaccharide preparations designed for colonic drug delivery.

PURPOSE: The aim of the present study was to provide "proof of concept" data in man for novel polysaccharide preparations designed for colonic drug delivery using gamma scintigraphy. METHODS: Two placebo calcium pectinate matrix tablet formulations were studied: one contained calcium pectinate and pectin (CaP/P) and was designed to rapidly disintegrate in the ascending colon, the other contained calcium pectinate and guar gum (CaP/GG) and was designed to disintegrate more slowly, releasing its contents throughout the ascending and transverse colon. Both formulations were enteric coated in order to protect them from the stomach. Ten healthy volunteers received either a CaP/P or CaP/GG tablet, in a randomised cross-over study. Transit and disintegration of the radiolabelled formulations was followed by gamma scintigraphy. Rat studies were conducted in order to verify that the expected colonic degradation of the polysaccharide formulations was as a consequence of bacterial enzyme attack. RESULTS: The in vivo clinical study confirmed the results obtained in the rat and bench in vitro fermentation models; complete tablet disintegration for Formulation CaP/GG appeared to be slower than that of Formulation CaP/P and the time and the location of complete tablet disintegration was more reproducible with Formulation CaP/P compared to Formulation CaP/GG. CONCLUSIONS: These results provide "proof of concept" data for the use of calcium pectinate preparations for drug delivery to the colon and highlight the value of scintigraphy in focusing the development strategy for colonic targeting preparations.

Adult↗

Role of macrophages as possible transporters of Plasmodium yoelii nigeriensis merozoites through the lymphatic system. Preliminary note.

Vesicles containing apparently healthy merozoites from mature schizonts were observed in the spleen and lymph nodes of mice parasitized by Plasmodium yoelii nigeriensis. They differed from all parasitic stages undergoing digestion by the macrophage and from mature schizonts of the blood. Up to 40 merozoites from three mature schizonts may be seen in the same compartment. They are thought to be accumulations of latent merozoites.

Animals↗

Preliminary evaluation of primaquine activity on rodent malaria model after transdermal administration.

The aim of this preliminary study was to investigate the potential use of the transdermal route for primaquine administration in the treatment of malaria. Thus the activity of this drug on asexual blood forms of two rodent malaria parasites (P. v. petteri and P. y. nigeriensis) was evaluated following a single TTS patch application. Sustained plasma concentration values were observed for about 60 hours. The results obtained from a prepatency test showed that primaquine was more active towards P. v. petteri than P. y. nigeriensis. This preliminary study showed that the transdermal route for primaquine administration may be a promising strategy for improving the treatment of malaria in both causal prophylactic and prevention of relapses infection.

Administration, Cutaneous↗

The chemotherapy of rodent malaria. LIII. 'Fenozan B07' (Fenozan-50F), a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane: comparison with some compounds of the artemisinin series.

Fenozan B07, a difluorinated 3,3'-spirocyclopentane, 1,2,4-trioxane, is a novel, second-generation antimalarial endoperoxide which is a potent blood schizontocide against strains of rodent malaria that are highly resistant to a wide spectrum of classical antimalarials. Like compounds of the artemisinin series, its action is limited to the intra-erythrocytic stages, both asexual and sexual, and it is devoid of causal prophylactic activity. Both Fenozan B07 and the artemisinins are potent gametocytocides. In contrast to arteether, in a model using synchronous infection with Plasmodium vinckei petteri, Fenozan B07 inhibits the development of all asexual stages except preschizonts, as well as gametocytes. The activity of the artemisinin series in rodent-malaria models is limited to the rings and young trophozoites. The combined effect of Fenozan B07 with artesunate against P. v. petteri was only additive. A slight degree of potentiation was found in mice infected with asynchronous, drug-sensitive P. berghei but the combination was only additive against CQ-resistant P. yoelli ssp. NS. On the other hand, a significant degree of synergism was observed when mice infected with the artemisinin-resistant ART line of P. yoelii ssp. NS received combinations of Fenozan B07 with artemisinin. The conclusion is drawn from these and other data that there are significant differences between the blood schizontocidal actions of Fenozan B07 and the artemisinins. The basis of these differences remains to be determined.

Animals↗

The erythrocytic schizogony of two synchronized strains of plasmodium berghei, NK65 and ANKA, in normocytes and reticulocytes.

By a modified Percoll-glucose centrifugation technique the rings and young trophozoites of two strains of Plasmodium berghei, NK65 and ANKA, were separated from the other erythrocytic stages and inoculated into mice. The subsequent infection was followed for ANKA in normal mice and for NK65 in normal mice and in mice with high-grade reticulocytosis induced by injections of phenylhydrazine. The duration of the erythrocytic schizogony of the NK65 strain was shown to be independent of the age of the host cell, and the hour of inoculation did not influence the cycle of the ANKA strain.

Animals↗

Recurrence of malignant melanoma after irradiation diagnosed by glucose-fructose enhanced magnetic resonance imaging.

Two patients who had been given ruthenium plaque treatment for uveal melanoma were MR examined due to suspected recurrence. Spin-echo sequences were applied using a 1.5 T equipment. The examinations were performed in both patients two times with a 2-h interval. Immediately after the first examination the patients were perorally given 20 g glucose and 10 g fructose. An increase of signal intensity (prolongation of the relaxation times) and size of the uveal lesions could be visualized by a subtraction technique in both patients after the carbohydrate loading. In agreement with our previous studies of malignant melanoma the changed metabolism in the uveal lesions indicated recurrence of the tumour. One eye was available for histological examination. The morphological difference between areas of recurring and degenerating tumour was clearly seen. Similar changes were not observed by ultrasound.

Brachytherapy↗

Enhanced gametocyte formation by Plasmodium chabaudi in immature erythrocytes: pattern of production, sequestration, and infectivity to mosquitoes.

The objective of this study was to investigate the chronobiology and infectivity of the gametocytes of Plasmodium chabaudi chabaudi. In order to increase the production of gametocytes, mice were treated with phenylhydrazine to induce a hyper-reticulocytosis. The authors observed an important stimulation of gametocytogenesis. Gametocytes were seen as soon as the second day postinoculation and were produced periodically at each schizogony, every 24 hr. The gametocytic developmental cycle lasted 60 hr and consisted of 4 successive stages: stage 0 at 36 hr, from merozoite invasion, stage I at 42 hr, stage II at 48 hr, and stage III at 54 hr. An important fraction of stage II was sequestered in small peripheral capillaries. The numbers of oocysts in the mosquitoes fed on phenylhydrazine-treated mice were larger than in controls. When mosquitoes were fed at different times of the day, circadian differences in the oocyst counts were not statistically significant. However, stage II was considered to be probably the most infective stage because, like the infective gametocyte stage of other species of murine malaria, it is sequestered in the peripheral capillaries. In contrast with Plasmodium vinckei, there is no peak of infectivity at the time of sequestration of the infective stage; this is probably due to the inhibitory effect of the schizogony occurring at this time.

Animals↗

The gametocytes of Plasmodium vinckei petteri, their morphological stages, periodicity and infectivity.

Gametocyte production by P. vinckei petteri was cyclic, occurring at each schizogony every 24 h. They matured in 27 h from merozoite to type 0 microgametocyte, in 3 h from type 0 to type I, 6 h from type I to type II and 3 h from type II to type III. Transmission experiments showed that the time of maximum infectivity was midday when mice were inoculated at midnight, and midnight when mice were inoculated at midday. In all instances, maximum infectivity coincided with a peak in intensity by type II microgametocytes, a relationship confirmed by multiple correspondence analysis. The proportion of type II microgametocytes was higher in the mosquitoes blood meal than in smears of tail blood of mice, suggesting a sequestration phenomenon with this stage.

Animals↗