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Biomedical subjects

W Peters

Publications and source records attributed to W Peters.

At least 235 records · Page 13Linked to original sources
PubMed1984

The isolation and isoenzyme characterization of Leishmania braziliensis subsp. from patients with cutaneous leishmaniasis acquired in Belize.

Leishmanial organisms were cultivated from cutaneous lesions of British military personnel returning from Belize. Isoenzyme profiles of the freshly isolated organisms and 'marker' strains of New World Leishmania spp. were compared using 10 enzymes (ALAT, ASAT, ME, GPI, MPI, PGM, SOD, 6-PGDH, G-6-PDH and MDH), by starch gel electrophoresis. 19 of the 22 new isolates from Belize were isoenzymically indistinguishable from Leishmania braziliensis braziliensis (10 out of 10 enzymes) and clearly differentiated from L. b. guyanensis and L. b. panamensis (different in 6 out of 10 enzymes) and from L. mexicana mexicana and L. m. amazonensis (9 out of 10 enzymes). Two isolates closely resembled L. m. mexicana and one could not be positively identified. This is the first report of autochthonous human leishmaniasis caused by L. braziliensis group organisms as far north as latitude 16 degrees N.

Belize↗
PubMed1984

The characterization by isoenzyme electrophoresis of Leishmania isolated in the People's Republic of China.

Seven isolates of Leishmania from mainland China were characterized on the basis of their isoenzyme profiles for 10 enzymes. Five isolates were from human visceral leishmaniasis patients, and four of these showed isoenzyme patterns similar to the marker strain of Leishmania infantum, while one was similar to L. donovani sensu lato. One isolate was from a presumed reservoir host of human visceral leishmaniasis, the racoon dog Nyctereutes procyanoides, and was isoenzymically indistinguishable from L. infantum. An isolate of L. gerbilli from the great gerbil Rhombomys opimus was readily distinguishable from Old World marker strains and other Chinese leishmanias. This is the first report of the biochemical characterization of Chinese isolates of Leishmania.

Animals↗
PubMed1984

Uptake of [3H] dihydroartemisinine by erythrocytes infected with Plasmodium falciparum in vitro.

Artemisinine ( qinghaosu ) was reduced and radio-labelled using tritiated borohydride. The tritiated dihydroartemisinine produced was differentially accumulated from low concentrations in culture medium into erythrocytes infected with Plasmodium falciparum. Uninfected erythrocytes concentrated the drug less than two-fold whereas infected erythrocytes achieved more than 300 times the medium concentration. The uptake process is reversible and saturable, with a dissociation constant (Kd) at the hypothetical receptor of 10.5 nmol.l-1. Competition studies indicate that the receptor is the same as that for artemether , another quinghaosu derivative. Chloroquine showed an interesting partial inhibition of uptake but was unable to release the bound radio-labelled drug from infected cells.

Anisomycin↗
PubMed1984

The chemotherapy of rodent malaria XXXV. Further studies on the retardation of drug resistance by the use of a triple combination of mefloquine, pyrimethamine and sulfadoxine in mice infected with P. berghei and 'P. berghei NS'.

In the face of an increasing prevalence of Plasmodium falciparum resistant to chloroquine and to pyrimethamine-sulphonamide or -sulphone mixtures, the need for a new, effective blood schizontocide for treatment of acute malaria is urgent. The only such compound that is almost ready for release is mefloquine (M) but there is already a danger that parasites may become resistant to this compound if it is used extensively alone. Earlier studies using a rodent model indicated that mefloquine could be 'protected' by administering it with a pyrimethamine-sulfadoxine (PS) mixture, but the experimental technique used was open to criticism. The present experiments, using a relapse technique to develop drug resistance, more closely parallel the way antimalarials are likely to be deployed in human communities. They confirm that the development of resistance to the individual components in the P. berghei N line is delayed by the triple combination, and more so in the slightly chloroquine-resistant 'P. berghei NS' line. The combination did not prevent the development of resistance in a line initially resistant to PS, but the level reached was much less than those seen when P. berghei N or 'P. berghei NS' were exposed to MPS or to M alone. It was concluded that the use of a triple combination of M, P and S against P. falciparum would be of value in 'protecting' these compounds, and thus gain time while new agents against malaria are being developed.

Animals↗
PubMed1984

Generation of leukotrienes from human granulocytes by alveolysin from Bacillus alvei.

We investigated the effect of alveolysin on human granulocytes. Alveolysin is an exoprotein produced by Bacillus alvei and belongs to the group of sulfhydryl-activated cytolysins. Other members of this group are streptolysin O and theta-toxin from Clostridium perfringens. It is demonstrated that alveolysin leads to leukotriene generation from human granulocytes, which exert chemotactic (leukotriene B4) and slow-reacting substance (leukotriene C4, D4, and E4) activity under sublytic concentrations.

Animals↗
PubMed1984

The chemotherapy of rodent malaria, XXXVIII. Studies on the activity of three new antimalarials (WR 194,965, WR 228,258 and WR 225,448) against rodent and human malaria parasites (Plasmodium berghei and P. falciparum).

In addition to their blood schizontocidal action on Plasmodium berghei in vivo, two Mannich bases WR 194,965 and 228,258 are also active against chloroquine-sensitive and chloroquine-resistant lines of P. falciparum in vitro. The response of the lines to each drug differs but shows no correlation in either case with response to chloroquine. The 8-aminoquinoline WR 225,448 is also active against P. falciparum in vitro but at much higher concentrations than the Mannich bases. Application of the 'chloroquine-induced pigment clumping (CIPC) test' and the study of ultrastructural changes induced in P. berghei in drug-treated mice indicate that WR 194,965 has a mode of action somewhat resembling that of quinine. WR 228,258 in vitro shows a chloroquine-like effect, but not in vivo, suggesting that its mode of action in vivo is different from that of chloroquine. WR 225,448 has no action in the CIPC in vitro and affects primarily mitochondria of the parasites in vivo. It probably acts through a metabolite. Both pre-erythrocytic and erythrocytic stages of rodent malaria parasites are affected by WR 225,448.

Aminoquinolines↗
PubMed1984

The chemotherapy of rodent malaria XXXVI. Part IV. The activity of a new 8-aminoquinoline, WR 225,448 against exo-erythrocytic schizonts of Plasmodium yoelii yoelii.

Light microscope and ultrastructural studies show that WR 225,448, an 8-aminoquinoline related to primaquine, causes substantial damage to developing pre-erythrocytic (EE) schizonts of Plasmodium yoelii yoelii in the liver of young rats. In addition to lesions of the mitochondria and nuclear membranes, secretory granules in the parasite fail to reach the surrounding host cell cytoplasm across the parasite membrane. The effective dose of WR 225,448 is much lower than that of primaquine. However, hepatic damage is also seen in treated animals. This may be the summation of damage produced by the experimental inoculation of a large quantity of infective salivary gland tissue from mosquitoes (which is also seen in untreated animals) plus toxic effects of the drug itself. Particular attention would have to be directed to this aspect in preclinical toxicity testing of the compound.

Aminoquinolines↗
PubMed1984

The chemotherapy of rodent malaria, XXXVII. The in vivo action of two Mannich bases, WR 194,965 and WR 228,258 and an 8-aminoquinoline WR 225,448.

Two new Mannich base antimalarials, WR 194,965 and 228,258 exhibit blood schizontocidal action against Plasmodium berghei in vivo. This action is retained also against the P. berghei NS line which has a low level of resistance to chloroquine. While WR 228,258 is also active against the highly chloroquine-resistant RC line, WR 194,965 is not. Both compounds show slightly reduced activity against the highly mefloquine-resistant N/1100 line. WR 225,448, an 8-aminoquinoline, is as active against blood stages of the NS, RC and N/1100 lines of P. berghei as against the N strain, and more so on a dose/weight basis than the first two compounds. It shows a low level of cross-resistance against the primaquine-resistant P line. WR 225,448 has a clear causal prophylactic effect on the pre-erythrocytic schizonts of P. yoelii nigeriensis. While WR 194,965 and 228,258 also appeared to act on these stages, the effect is most probably due to residual action on emerging erythrocytic merozoites since pre-erythrocytic schizonts in treated animals were morphologically indistinguishable from those of the untreated control.

Aminoquinolines↗
PubMed1983

Rapid action of Qinghaosu and related drugs on incorporation of [3H]isoleucine by Plasmodium falciparum in vitro.

Using the incorporation of [3H]isoleucine into acid-insoluble products as an index of protein-synthetic activity, it was shown that Qinghaosu and two related drugs had a rapid effect on this process in human erythrocytes infected with Plasmodium falciparum in vitro. Inhibition could be seen 1 hr or less after addition of the drugs at concentrations from 5 mumole/1. to 50 nmole/1. It is recommended that the effects of these drugs be studied in cell-free protein-synthetic systems.

Animals↗