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Biomedical subjects

W Peters

Publications and source records attributed to W Peters.

At least 307 records · Page 17Linked to original sources
PubMed1975

The chemotherapy of rodent malaria, XXI. Action of quinine and WR 122 (a 9-phenanthrenemethanol) on the fine structure of Plasmodium berghei in mouse blood.

The effects of quinine and a 9-phenanthrenemethanol, WR 122,455 on the fine structure of Plasmodium berghei have been investigated. Changes consequent upon quinine treatment were noted in the outer membranes (including those that surround the "food vacuole") and the digestive vacuoles. These changes were followed by cytoplasmic degeneration and vacuolization. WR 122,455 caused morphological changes in at least three areas of the parasite, (1) the outer membranes, (2) the digestive vacuole and (3) the nucleus. The relationship of these changes to the mode of action of these compounds is discussed. It seems possible that they interfere primarily with limiting membrane-mitochondrial functions. The modifications of pigment formation are characteristic of these compounds and differ from those seen with chloroquine or primaquine.

Animals↗
PubMed1975

The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity.

Data are provided on the activity of a variety of antimalarial drugs against drug-sensitive and drug-resistant lines of Plasmodium berghei in albino mice. Parallel data for the response of the drug-sensitive parasites to these compounds in vitro indicate whether the drugs have a chloroquine-like or quinine-like type of action, or neither. The value of this test system for drug evaluation is debated. It is concluded that the in vivo tests do provide a valuable indication of the potential use of a compound against drug-resistant malaria parasites of man. The tests may also provide a good indication of the future value of new compounds against strains of parasites that are already resistant to chloroquine. Where necessary, steps should be taken to protect promising new compounds.

Animals↗
PubMed1975

The chemotherapy of rodent malaria, XXIII Causal prophylaxis, part II: Practical experience with Plasmodium yoelii nigeriensis in drug screening.

Data are presented on the causal prophylactic action of about 100 compounds of various types against Plasmodium yoelii nigeriensis N67 in mice. Examples are given to show how action against pre-erythrocytic schizonts may be differentiated from action on emerging erythrocytic stages. In a series of 35 8-aminoquinolines, all but 10 showed definite causal prophylactic activity at tolerated doses. The data permit the compounds to be ranked in order of activity, and many are shown to be more active in this test system than primaquine. Marked causal prophylactic activity is displayed by a variety of quinone structures, several of which show a significant residual action on blood stages. A high level of activity is found in dihydrofolate reductase inhibitors within several chemical classes. Rorguanil is more effective as a causal prophylactic than a blood schizontocide in the mouse as in man. Sulphonamides and sulphones are also effective in this system. The active levels are influenced by the content of PABA in the diet of the hosts. Causal prophylactic action has been detected in a number of experimental compounds including some antibiotics (such as tetracycline and clindamycin). The pyrocatechol RC 12 shows only slight activity at the maximum tolerated dose. Chloroquine, mepacrine, quinine, quinolinemethanols and phenanthrenemethanols are inactive as causal prophylactics. It is concluded that a rodent malaria-mouse model does provide a relatively simple model for the screening of drugs for causal prophylaxis, and the data so obtained are of relevance to the detection of causal prophylactics against human malaria.

Amidines↗
PubMed1975

The experimental chemotherapy of leishmaniasis. II. The activity in tissue culture of some antiparasitic and antimicrobial compounds in clinical use.

A variety of compounds used in the treatment of parasitic or bacterial infections in man, including leishmaniasis itself, were examined for their activity against three lines of Leishmania in tissue culture. The organisms used were L. mexicana mexicana, L. tropical major and L. donovani; they were grown in dog sarcoma and hamster peritoneal exudate cell lines. Leishmanicidal activity was observed in a number of compounds currently in clinical use for the treatment of one or other form of leishmaniasis. Cycloguanil, nifurtimox, amphotericin B and monomycin were effective but pentamidine showed poor activity. In each case marked differences were observed in the level of response in the different parasite lines. Organic antimonials were most active when anmastigotes were exposed to them prior to entry of the parasites into host cells. This suggests that such compounds may exert an effect on amastigotes during their brief extracellular transit from one host cell to another in vivo. A number of antimalarials showed good to moderate leishmanicidal action, particularly against L. mexicana and L.t. major. Several schistosomicidal agents also possessed leishmanicidal properties. The commonly used broad spectrum antibiotics showed little if any activity. In discusssion a comparison is drawn between data published on the action of some of these drugs against L.t. major in mice and our observations with the same strain and L. mexicana in tissue culture. A remarkably good agreement is found for most of the compounds examined. General agreement is also noted between these data and reports of clinical trials although it is not possible to draw too many conclusions because of the failure in most clinical studies to make an accurate identification of the causative Leishmania. It is concluded that, although the tissue culture model is not to be considered as ideal and can probably be improved, data obtained by its use do bear relevance to the action compounds in vivo, and the model may be use in the screening of drugs for leishmanicidal activity.

Aminoquinolines↗
PubMed1975

The experimental chemotherapy of leishmaniasis. I: Techniques for the study of drug action in tissue culture.

Three lines of Leishmania have been grown successfully in tissue culture. L. mexicana mexicana, L.tropica major and L. donovani develop readily as amastigotes in dog sarcoma cells, and in a hamster peritoneal exudate cell line. The procedures used for cultivating both host cells and parasites are described, as are the methods employed for studying the senitivity of the parasites and hosts to drugs. It is concluded that the use of a tissue culture system is a valid way of determining the baseline sensitivity of a Leishmania to chemotherapy and the limitations of the technique are discussed. Illustrative data are presented of the response of two Leishmania species to amphotericin B and to a quinine analogue. L. mexicana mexicana is highly sensitive to amphotericin B and the response is shown to be consistent in duplicate experiments. L. mexicana mexicana and L. donovani are shown to have a different innate sensitivity to the quinine analogue.

Amphotericin B↗
PubMed1975

Incidental ectopic pregnancy.

Three cases of incidental ectopic pregnancy are described in which the patients were found to have unsuspected ectopic pregnancy when operated for an elective gynecologic procedure.

Adult↗
PubMed1974

Prevention of drug resistance in rodent malaria by the use of drug mixtures.

Development of resistance to chloroquine in rodent malaria is inhibited by giving this compound together with a potentiating mixture of pyrimethamine and sulfadoxine but this does not prevent the development of resistance to the last two compounds. The use of drug mixtures should be explored as a means of "protecting" chloroquine or new blood schizontocides intended for mass chemotherapy against human malaria. However, no general rule can be laid down without testing specific drug mixtures in long-term experiments in a suitable model such as rodent malaria.

Animals↗