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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 307 records · Page 17Linked to original sources

Ultrastructural investigations on the effect of praziquantel on the tegument of five species of cestodes.

Adult Hymenolepis diminuta, H. microstoma, H. nana, Echinococcus multilocularis, and Taenia (Hydatigera) taeniaeformis have been exposed in vitro in media containing 0.1 to 100 micrograms praziquantel/ml. Already after 5 min characteristic tegumental lesions, that were restricted to the growth zone of the neck region, were recognized using both scanning and transmission electron microscopy. Within the tegument numerous vacuoles were formed that released their contents to the exterior and finally caused destruction of the tegument. Proglottides of the central or posterior strobilar portions were never damaged. Larvae of T. taeniaeformis (cysticerci) and E. multilocularis (alveolar cysts) were studied employing the same methods both after in vitro exposure to and after in vivo treatment of their hosts with praziquantel. Strobilocerci of T. taeniaeformis developed identical tegumental lesions after contact with praziquantel whether incubated in vitro or treated in vitro. The wall of the bladder containing the larva remained unaffected. Evaginated protoscolices of E. multilocularis were damaged by in vitro contact with praziquantel while invaginated protoscolices remained intact. After in vivo exposure there were some fully developed evaginated and damaged protoscolices whereas all invaginated protoscolices and the cyst wall with its germinative layer were unaffected.

Animals↗

Evasion of the oxidative microbicidal activity of human monocytes by trypomastigotes of Trypanosoma dionisii.

Trypomastigotes of Trypanosoma dionisii, a stercorarian trypanosome from bats, are effectively killed by neutrophils from human peripheral blood but are less sensitive to the cytotoxic action of human monocytes. The mechanism of killing appears to involve peroxidase and hydrogen peroxide. Trypomastigotes are as effective as epimastigotes in inducing the formation of hydrogen peroxide by effector cells. They are, however, less sensitive than epimastigotes to the cytotoxic effect of peroxidase and hydrogen peroxide. They are therefore susceptible to the high concentrations of peroxidase found in the phagosome of the neutrophil, but resist the lower levels encountered in monocytes.

Humans↗

Immunocytochemical demonstration of catechol methyltransferase in Candida tropicalis.

Catechol methyltransferase (S-adenosyl-L-methionine : catechol O-methyltransferase; EC 2.1.1.6) was localized immunocytochemically in the yeast Candida tropicalis by the unlabelled antibody enzyme method, involving soluble peroxidase-antiperoxidase complex. Immunoreactivity was detected by light and electron microscopy in the outer layer of the cell wall and at the plasma membrane. The possible function of the methyltransferase in C. tropicalis id discussed.

Candida↗

O-demethylation of scoparone and studies on the scoparone-induced spectral change of cytochrome P-450 in rat liver microsomes.

Scoparone (6,7-dimethoxycoumarin) is demethylated to scopoletin (7-hydroxy-6-methoxycoumarin) and isoscopoletin (6-hydroxy-7-methoxycoumarin) by the cytochrome P-450-dependent monooxygenase system of rat liver microsomes. Under the conditions used, the ratio of scopoletin to isoscopoletin was determined to 1:1.8 +/- 0.1 for microsomes from untreated rats. Based on this reaction, a direct fluorometric method for the microsomal O-demethylation activity for scoparone is described. The fluorescence of the scopoletin formed in the incubation mixture is recorded after the adjustment of the excitation and emission wavelengths to 398 and 460 nm, respectively. The fluorescence of scoparone and isoscopoletin does not interfere with the test. Pretreatment of rats with phenobarbital or polycyclic hydrocarbons (3-metylcholanthrene, benzo[a]pyrene) causes a change in the ratio of the demethylation products scopoletin to isoscopoletin which was determined to be 1:2.5 +/- 0.1 (benzo[a]pyrene or 3-methylccholanthrene) or 1:5.9 +/- 0.01 (phenobarbital) respectively, and a significant increase in the amount of microsomal O-demethylation activity. Thus the ratio of the two products varies significantly with the state of induction. The difference spectra of scoparone with liver microsomes obtained from benzo[a]pyrene- and 3-methylcholanthrene-pretreated rats show an absorption peak at 416 nm and a trough at 393 nm with an isosbestic point at 405 nm. This scoparone-induced modified Type II spectral change seems to indicate the interaction of the 6- or 7-methoxy group of scoparone with the heme ion of the 394-nm form and its conversion into a modified ferrihemochrome with a absorption peak at 416 nm. This is modified ferrihemochrome is not identical with the 418-nm form of the cytochrome P-450.

Animals↗

In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. A light and electron microscopic study.

The effects of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) on Schistosoma mansoni was studied in vivo and in vitro by means of electron microscopy. It was found that 1. worms were contracted and became dislodged to the liver; 2. intensive vacuolisation occurred at distinct sites of the tegument within 5 min; 3. the surface coat remained unaffected; 4. host cells of the defense system attached to the tegumental vacuoles and started to penetrate into the interior of the parasites about 4 h after treatment; 5. only oral treatment of mice with a curative dose was lethal for the parasites, whereas worms treated with a subcurative dose recovered from the phenomena described above; 6. worms were fixed by fibroblasts to the walls of blood vessels 17 h after treatment; 7. the interior of the parasites was destroyed by host cells - especially eosinophilic granulocytes - while their exterior structures remained unchanged for some time; 8. worms disintegrated completely in the centre of typical granulomas as seen on days 14 and 18 after treatment; at this time only residues of the parasites were still recognisable within necrotic zones.

Animals↗

Electron microscopic studies on microfilariae of Dipetalonema viteae and Litomosoides carinii: the occurrence of intracellular parasites after treatment with metrifonate or diethylcarbamazine.

Microfilariae of Dipetalonema viteae and Litomosoides carinii were studied by means of electron microscopy after oral treatment of their hosts with metrifonate (3 x 100 mg/kg) or diethylcarbamazine (3 x 250 mg/kg). These dosages led to the disappearance of microfilariae from the peripheral venous blood. However, in numerous organs blood capillaries or interstitial spaces contained degenerating microfilariae. In these cases the cytoplasm of the microfilarian cells was completely lysed, whereas the cuticle seemed to be unaffected, at least initially. Microfilariae of both species were also often found intracellularly especially in liver and muscle cells after application of both drugs. The intracellular microfilariae, however, had fewer or even no lesions, suggesting that they might escape the activity of the drug.

Animals↗

Ovalocytosis in Papua New Guinea -- dominantly inherited resistance to malaria.

Analysis of ovalocytosis in families has demonstrated dominant inheritance. This conclusion is based on finding ovalocytic children of ovalocytic Melanesian mothers and normocytic Caucasian fathers. Inheritance of resistance to thermal deformation and to crenation upon storage correlated with inheritance of ovalocytic erythrocyte morphology. The latter was associated with in vitro resistance to invasion by P. falciparum.

Elliptocytosis, Hereditary↗

Scanning and transmission electron microscope studies on the efficacy of praziquantel on Hymenolepis nana (Cestoda) in vitro.

The dwarf tapeworm, Hymenolepis nana, was studied by means of scanning and transmission electron microscopy after in vitro exposure to 1, 10, and 100 micrograms/ml of the anthelmintic praziquantel (Droncit) for 5, 15, 30, and 60 min. The resulting vacuolization of the tegument was exclusively confined to the neck region of the tapeworms and was already observed after treatment for 5 min with 1 microgram/ml. This vacuolization finally led to the disruption of the syncytial layer in the apical region of the tegument. The tegumental microtriches and the surface coat remained unaffected. Proglottids of the middle or posterior regions of the worms never showed destruction.

Animals↗

Light and electron microscopic studies on the effect of praziquantel on Schistosoma mansoni, Dicrocoelium dendriticum, and Fasciola hepatica (Trematoda) in vitro.

The fine structure of the tegument of three trematode species, Schistosoma mansoni, Dicrocoelium dendriticum, and Fasciola hepatica, was studied by means of light scanning (SEM) and transmission electron microscopy (TEM) after in vitro exposure to 0, 1, 10, and 100 micrograms/ml of the anthelmintic praziquantel for 5, 15, 30, and 60 min. In S. mansoni and D. dendriticum the resulting vacuolization of the tegument was confined to numerous small areas scattered all over the surface of the parasites and this finally led to the disruption of the apical tegumental layer. No changes were found in the tegument of F. hepatica after treatment with praziquantel.

Animals↗

The in vitro uptake of 14C-praziquantel by cestodes, trematodes, and a nematode.

14C-praziquantel was rapidly taken up by Schistosoma mansoni, Fasciola hepatica, Hymenolepis nana, and isolated strobilocerci of Taenia taeniaeformis. Schistosoma mansoni lost praziquantel rapidly to drug-free medium. Chromatography of extracts prepared after incubation of S. mansoni and H. nana yielded no indication that praziquantel was metabolized. Autoradiography revealed a uniform distribution of praziquantel throughout the tissues of S. mansoni and H. nana. Uptake was considerably slower in the nematode Heterakis spumosa and apparently via the oral route.

Animals↗

The efficacy of amidantel, a new anthelmintic, on hookworms and ascarids in dogs.

Amidantel is a new anthelmintic from a new chemical class with an interesting anthelmintic spectrum. In dogs amidantel is highly effective in a single oral dose of 25 mg/kg against both hookworm species, Ancylostoma caninum and Unicinaria stenocephala. In Toxascaris leonina infected dogs a complete cure rate was achieved with a single oral dose of 50 mg/kg. Similar results were obtained with 8 mg/kg administered three times per day. The most sensitive parasite to amidantel was found to be Toxocara canis with a 100 per cent cure rate after a single oral treatment with 10 mg/kg. In preliminary trials amidantel was also effective against hookworms and ascarids after subcutaneous administration. All hookworms and almost all of the ascarids were eliminated with the faeces within 2 days after treatment. Amidantel was tolerated in all dosages tested by all the dogs without any symptoms.

Ancylostoma↗

[A method to detect microfilariae of Dipetalonema witei in the peripheral blood of mastomys natalensis (author's transl)].

A new cheap and time saving procedure is described for the detection of microfilariae of Dipetalonema witei in the peripheral blood of Mastomys natalensis. A special apparatus delivering an ether-air mixture is used to anesthetize the experimental animals for a short period in a very careful way and without side effects. The ether wapour induces a rapid shift of microfilariae within one minute from the lung to the peripheral blood.

Anesthesia, Inhalation↗

The effect of praziquantel on Hymenolepis diminuta in vitro.

Qualitative observations were made on Hymenolepis diminuta, H. microstoma, H. nana and pre-adult Echinococcus multilocularis in vitro. A dose as low as 0.0001 microgram praziquantel/ml affects the tapeworms, while concentrations of 0.01 - 0.1 and 1-10 microgram/ml cause contraction and paralysis in the contracted state within 10 min and 10-30 s, respectively. The in vitro effects of praziquantel on Hymenolepis diminuta have been studied using anaerobic and aerobic incubations and media containing or lacking glucose. Praziquantel inhibits glucose up-take by half at a concentration of 0.1 microgram/ml, both under anaerobic and aerobic conditions. The stimulation of lactate release was most marked in the absence of glucose. A doubling of the amount of lactate released during anaerobic incubation in the presence of glucose was achieved in 0.1 microgram/ml, while 0.01 microgram/ml had the same effect in the absence of glucose. Under aerobic conditions and in the absence of glucose, 0.1 microgram/ml doubled the amount of lactate released while 3 and 10 microgram/ml were without effect in the presence of glucose. Praziquantel increases the total amount of excreted acidic metabolites only in the absence of glucose. The oxygen consumption of H. diminuta was unaffected by praziquantel at a concentration of 10 microgram/ml. Worms treated in their host and then incubated display the same changes as worms treated in vitro. Praziquantel causes an efflux of glucose and alpha-amino-N from the worm into the medium. This impairment of tegumental integrity and the inhibition of glucose up-take and the stimulation of lactate release are reversible after a 15 min incubation in praziquantel solution. Discussion of pharmacokinetic data indicates, that in the in vivo situation, effective concentrations of praziquantel prevail for much longer. Mechanisms that might explain the observed effects are discussed.

Aerobiosis↗

[Experimental infection of soft ticks with Dipetalonema witei (author's transl)].

The intermediate host of Dipetalonema witei, the soft tick Ornithodoros moubata, can be infected experimentally with microfilariae. Microfilariae isolated from the blood of infected donor animals were injected into the dorsal haemocoel of the ticks where they developed to infectious filariae within approx. 50 days. The rate of infection of ticks was 100% when more than 100 microfilariae were injected. An average of 23% was recovered as infectious filariae. Up to 450 ticks can be infected with 1000 microfilariae each from a single donor animal within one year, whereas donor animals can only be used for about 1 month if ticks are naturally infected. The method described has advantages compared to natural tick infections with respect to the rate of infection of ticks, the development of microfilariae, and the amount of infectious material produced.

Animals↗