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D C Warhurst

Publications and source records attributed to D C Warhurst.

At least 55 records · Page 3Linked to original sources
PubMed1996

Activity of pyronaridine and mepacrine against twelve strains of Plasmodium falciparum in vitro.

Pyronaridine, an acridine derivative, has been found effective in China for the treatment of drug-resistant falciparum malaria. The activities of pyronaridine and mepacrine were compared with those of standard antimalarial drugs in vitro against chloroquine-sensitive (CS) and chloroquine-resistant (CR) Plasmodium falciparum isolates to investigate cross resistance. The 50% inhibitory concentrations (IC(50)) against the resistant isolates were 2.8-fold higher than the sensitive isolates for pyronaridine (CS = 7.3 nM; CR = 20.5 nM) and 3.2-fold higher for mepacrine (CS = 13.3 nM; CR = 42.6 nM). These same isolates showed an 11-fold difference in sensitivity to chloroquine with mean IC(50) values of 21 nM for sensitive and 239 nM for resistant parasites. A significant correlation was observed between parasite sensitivity (IC(50)) to pyronaridine and the drugs, mepacrine, amodiaquine and chloroquine. However, the high level of activity seen with pyronaridine, even against the CR isolates, should encourage further field trials with this drug.

Amodiaquine↗
PubMed1995

Crithidia fasciculata as feeder cells for malaria parasites.

Crithidia fasciculata was used to replace murine peritoneal wash cells as feeder cells for the adaptation of Plasmodium falciparum isolates to continuous culture in vitro, thus avoiding the need to sacrifice animals. Fourteen of 17 malaria parasite isolates in one study, and 12 of 12 isolates in a second study, were successfully adapted to continuous culture in the presence of C. fasciculata, while only 5 of 17 parallel control isolates in the first study, and 2 of 12 isolates in the second study, were adapted in the absence of any feeder cells. Biochemical assays were performed to investigate various hypotheses put forward to explain the mode of action of feeder cells. No effect of C. fasciculata feeder cells was observed on lactate removal, osmotic pressure, or glucose or amino acid content of the malaria culture media. This feeder cell system was shown to reduce the pH of the malaria culture medium. Neither this feeder system nor another system, murine peritoneal macrophages, had any effect on the cysteine content of the culture medium. C. fasciculata was shown to reduce the redox potential of the culture medium, as were other malaria growth enhancers including cysteine and glutathione. This effect on the redox potential of the culture medium is proposed to be a possible mode of action for the feeder cell systems studied.

Animals↗
PubMed1994

In vitro assessment of susceptibility of Acanthamoeba polyphaga to drugs using combined methods of dye-binding assay and uptake of radiolabelled adenosine.

A technique based on binding of eosin dye to cell was applied to quantitate Acanthamoeba trophozoites in culture. Using this technique in combination with the uptake of radiolabelled adenosine, we assessed the activities of triazole (saperconazole), imidazole (ketoconazole, miconazole) and diamidine (berenil, pentamidine, dibromopropamidine) compounds against A. polyphaga trophozoites. The quantity of dye bound to the trophozoites correlated (r = 0.99) with the number of organisms per well. When inhibition of the growth of Acanthamoeba was the only parameter used to measure the effectiveness of these drugs, saperconazole was found to be most active with IC50 (concentration of drug that inhibited by 50%, the growth of A. polyphaga trophozoites incubated at 28 degrees C for 48 h) of 0.95 microM. The IC50s of the other drugs ranged from > or = 1500 microM for micronazole, the least active, to 3.0 microM for berenil. However, when efficacy was assessed by combining inhibition of growth with the uptake of [14C-8]adenosine by the drug treated organism, the diamidines, particularly berenil and pentamidine were considered most potent.

Acanthamoeba↗
PubMed1994

Detection and species identification of Cryptosporidium oocysts using a system based on PCR and endonuclease restriction.

The polymerase chain reaction (PCR) was used to produce a 556 bp nucleotide stretch, employing primers based on the published sequence of the 18S rRNA genes in Cryptosporidium parvum and C. muris. This sequence was found to contain 3 Mae I endonuclease restriction sites, 1 of which was present only in C. parvum. Mae I restriction of PCR products from 2 C. parvum isolates (one of human origin and the other of bovine origin), 1 C. muris isolate, and 1 C. baileyi isolate, showed a specific and reproducible profile for C. parvum that was different from the one obtained for both C. muris and C. baileyi. From these data, new Mae I restriction maps were proposed for the three species. The system was then used to screen 6 C. parvum isolates (from human and bovine hosts), and the C. parvum-specific profile was obtained for all isolates examined. It should be possible to adapt this protocol to detect small numbers of C. parvum oocysts in environmental samples (e.g. in water supplies).

Animals↗
PubMed1994

In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids.

Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents.

Alkaloids↗
PubMed1994

Diagnosis of amebic dysentery by detection of Entamoeba histolytica fecal antigen by an invasive strain-specific, monoclonal antibody-based enzyme-linked immunosorbent assay.

An invasive strain-specific monoclonal antibody against Entamoeba histolytica has been used in a capture enzyme-linked immunosorbent assay (ELISA) for the detection of invasive E. histolytica fecal antigen in clinical specimens and for the diagnosis of amebic dysentery in patients from Bangladesh. The fecal antigen capture ELISA (FAC-ELISA) did not cross-react with other parasite species in the clinical specimens or with noninvasive E. histolytica present in those specimens and in experimentally seeded stools. The limit of detection of the assay for invasive E. histolytica crude antigen diluted in phosphate-buffered saline or in stools was 0.58 and 3.9 micrograms/ml, respectively, which is the equivalent of approximately 72 and 487 E. histolytica trophozoites per well, respectively. The sensitivity, specificity, and efficiency of the FAC-ELISA were 87, 100, and 98%, respectively, for the detection of invasive E. histolytica antigens and 100, 100, and 100%, respectively, for the diagnosis of amebic dysentery. The FAC-ELISA is a potential alternative for the field diagnosis of amebic dysentery and for epidemiological studies to define the distribution of invasive E. histolytica.

Animals↗
PubMed1994

Value of microscopy in the diagnosis of dysentery associated with invasive Entamoeba histolytica.

AIMS: To assess the reliability of the detection of erythrophagocytic amoebic trophozoites in stool samples in the diagnosis of dysentery associated with invasive Entamoeba histolytica. METHODS: Amoebic culture was carried out on single stool samples collected from patients from Mexico, Colombia, and Bangladesh. The stools had been examined by light microscopy. Amoebic dysentery was diagnosed when erythrophagocytic E histolytica trophozoites were observed in a case of bloody diarrhoea. E histolytica isolates were characterised by isoenzyme electrophoresis and results correlated with microscopical findings in stools. Statistical analysis was performed using the chi 2 test. RESULTS: Where erythrophagocytic amoebae had been observed in dysenteric stool specimens the E histolytica phenotype was invariably invasive (p < 0.0001). Observation of erythrophagocytic amoebae in dysentery is 100% specific and predictive of infection with invasive E histolytica. When amoebic culture-positive cases only are considered it is 96% sensitive. In this study E histolytica of zymodeme XIV was more commonly associated with amoebic dysentery than zymodeme II. There was no significant difference between the carriage rate of invasive and non-invasive E histolytica in non-dysenteric diarrhoea. Asymptomatic subjects carried non-invasive E histolytica more frequently than invasive E histolytica. Patients with non-amoebic dysentery, when shown to be infected with E histolytica, carried non-invasive strains (12%). CONCLUSIONS: Sensitivity and specificity of microscopical examination of a single stool specimen for diagnosing amoebic dysentery is very high; intestinal carriage of invasive E histolytica detected by culture is not necessarily an indication of active disease as patients with diarrhoea and asymptomatic subjects shed invasive and non-invasive E histolytica. There are possibly two subpopulations of invasive E histolytica with different pathogenic potential which can be differentiated by zymodeme analysis.

Animals↗
PubMed1994

Accuracy of routine laboratory diagnosis of malaria in the United Kingdom.

AIMS: To study the accuracy of routine laboratory diagnosis of malaria with the aim of improving accuracy in diagnosis in the future. METHODS: A comparative study was made of all blood films submitted to two laboratories in London providing a slide-diagnostic service for malaria. RESULTS: There were 17 Plasmodium ovale infections, and of these only five (29.4%) were correctly diagnosed by the submitting laboratory; whereas of 210 other single species infections, 162 (77.1%) were correctly diagnosed (chi 2 = 18.4, p < 0.0001). There were six patients with mixed infections; only one (16.7%) was correctly diagnosed, whereas of 227 single species infections, 167 (73.6%) were correctly diagnosed (p = 0.007, using Fisher's exact test). There was no significant association between the presence of technical faults or numerous platelets and incorrect diagnosis. CONCLUSIONS: Plasmodium ovale and mixed infections were diagnosed incorrectly significantly more often than other species. The presence of technical faults or numerous platelets had no significant effect on whether or not submitting laboratories correctly diagnosed malaria.

Animals↗
PubMed1993

Malaria imported into the United Kingdom during 1991.

Two thousand, three hundred and thirty-two cases of human malaria were imported into the United Kingdom in 1991. There were twelve deaths; eleven of which were due to Plasmodium falciparum infection contracted in Kenya or West Africa. The annual total of cases of P. falciparum infection has increased throughout the last decade, reaching 1268 cases in 1991: over 90% of these were contracted in sub-Saharan Africa, whereas over 80% of P. vivax cases were contracted in South Asia. The largest category of infected travellers consisted of settled immigrants visiting friends and relatives in their country of origin.

Adolescent↗
PubMed1993

Alstonia species: are they effective in malaria treatment?

A review of the literature on Alstonia species indicates that evidence in support of their effectiveness in the treatment of malaria is controversial. The antiprotozoal activity of the major alkaloid present in Alstonia species, echitamine, was assessed in vitro against Plasmodium falciparum and Giardia intestinalis. Echitamine displayed little antiplasmodial activity, but two quinoline alkaloids from A. coriacea (corialstonine and corialstonidine) were found to have some activity against P. falciparum although this was approximately 10 times less than that of quinine. None of the three Alstonia alkaloids was active against G. intestinalis. These results are discussed in the context of previously published data.

Alkaloids↗
PubMed1993

Antimalarial activity from 'Mhekara' (Uapaca nitida Müll-Arg.), a Tanzanian tree.

An aqueous decoction of the root bark of Uapaca nitida Müll-Arg. is currently used locally at the Benedictine Mission at Peramiho in Tanzania to treat malaria. We have now demonstrated that extracts of root bark and leaves of this tree are active against the multidrug-resistant K1 strain of Plasmodium falciparum in vitro. An ethanolic extract of root bark showed activity against P. berghei in mice but at a dose which also showed toxic effects. The use of this plant in treating malaria appears to be novel and further studies would be of value.

Animals↗