Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product

Isolation And Testing The Cholesterol Reduction Ability (In-Vitro) Of Lactococcus Lactis From Fermented Smooth Pigweed (Amaranthus Hybridus) Leaves

Probiotics are live microbial feed supplements, which positively affect the host animal by improving its intestinal microbial balance. Studies have shown probiotic activities of Lactococci isolated from dairy foods, which include the ability to inhibit the growth of other bacteria and the reduction of cholesterol. However, there is limited documented work on the probiotic activity in Lactococci from plant materials. The present study isolated and tested cholesterol reduction ability (in-vitro) of Lactococcus lactis isolates from fermented smooth pigweed (Amaranthus hybridus) leaves. The specific objectives were to: isolate L. lactis bacteria from A. hybridus leaves harvested at maturity (30 days), determine cholesterol reduction ability of L. lactis isolated from the A. hybridus leaves and establish whether there were any differences in the amounts of cholesterol reduced from the growth media by L. lactis and Lactobacillus acidophilus ATCC 43121 (the positive control). It further aimed at determining whether fermentation affected protein, mineral and moisture content in amaranthus leaves and the acceptability of the fermented leaves as compared to fresh boiled leaves. To achieve this, A. hybridus was grown at Kenya Agricultural Research Institute in Njoro. The leaves were harvested at maturity and fermented for five days. After fermentation, L. lactis strains were isolated and their ability to remove cholesterol from the growth medium tested. This ability was compared with that of Lb. acidophilus ATCC 43121. Consumer acceptability of the fermented leaves was also compared to freshly boiled leaves. The Lactococcal strains isolated reduced cholesterol level by 52 µg/ml and Lb. acidophilus ATCC 43121 reduced by 56 µg/ml indicating a similar reduction capability (p < 0.05) to that of the standard Lb. acidophilus ATCC 43121 probiotic. After fermentation, protein decreased from 36.07 to 16.65%, ash increased from 19.76 to 36.21% and moisture content increased from 5.44 to 6.22%, respectively.There was no significant difference (p < 0.05) in consumer acceptability whereby, the consumers scored 6.90 points for fermented leaves compared to av6.83 points scored by consumers for fresh boiled leaves This study concluded that fermented amaranthus leaves dish is a potential source of probiotics as the level of cholesterol reduction by the isolated Lactococcal strains compares favourably with the reduction levels of the control Lb. acidophilus ATCC 43121 which is a known probiotic

EFFECT OF MAIZE DENSITY, BEAN CULTIVAR AND BEAN SPATIAL ARRANGEMENT ON INTERCROP PERFORMANCE

On-farm trials to determine the optimum combination of maize (Zea mays   L.) density, bean (Phaseolus vulgaris   L.) cultivar and bean spatial arrangement to produce high yields of the intercrop combination were conducted in Chinyika Resettlement Area (CRA) and at Domboshava Training Centre (DTC) during the 1996/97 and 1997/98 rainy seasons. The effects of maize at 37, 000 and 24, 000 plants ha-1, bean cultivars 'Natal Sugar' and 'Carioca', and bean arranged in one or two rows between rows of maize or bean planted in the same row as maize were evaluated in a completed factorial arrangement. Maize density, bean cultivar, bean spatial arrangement and their interactions significantly (P&lt;0.01) affected maize and bean grain yields at both locations for the two seasons. Changing the maize density from 90 x 45 cm (24000 plants ha-1) to 90 x 30 cm (37000 plants ha-1) increased maize yield by 28 and 39% and reduced bean yields by 11 and 18% in the respective seasons. Maize yield was 19% less when intercropped with Natal Sugar than with Carioca. Same row and one row bean cultivar arrangements produced similar maize yields. Land equivalent ratios (LER) were greater than one for all but one intercrop arrangements at CRA but less frequently at DTC. The maize density of 90 x 30 cm with Carioca in the same row as maize produced the highest LER value at all sites, 1.73 at Chinyudze, and 1.53 at Domboshava. The same treatment gave the highest gross return ofZ$12 649 ha-1 at CRA. Carioca planted in the same row as maize at the maize density of 37,000 plants ha-1 is the most ideal approach to dryland maize/bean intercropping since it achieved high yields and allows easy weeding

Isolation And Testing The Cholesterol Reduction Ability (in-vitro) Of Lactococcus lactis From Fermented Smooth Pigweed (Amaranthus hybridus) Leaves

Probiotics are live microbial feed supplements, which positively affect the host animal by improving its intestinal microbial balance. Studies have shown probiotic activities of Lactococci isolated from dairy foods, which include the ability to inhibit the growth of other bacteria and the reduction of cholesterol. However, there is limited documented work on the probiotic activity in Lactococci from plant materials. The present study isolated and tested cholesterol reduction ability (in-vitro) of Lactococcus lactis isolates from fermented smooth pigweed (Amaranthus hybridus) leaves. The specific objectives were to: isolate L. lactis bacteria from A. hybridus leaves harvested at maturity (30 days), determine cholesterol reduction ability of L. lactis isolated from the A. hybridus leaves and establish whether there were any differences in the amounts of cholesterol reduced from the growth media by L. lactis and Lactobacillus acidophilus ATCC 43121 (the positive control). It further aimed at determining whether fermentation affected protein, mineral and moisture content in amaranthus leaves and the acceptability of the fermented leaves as compared to fresh boiled leaves. To achieve this, A. hybridus was grown at Kenya Agricultural Research Institute in Njoro. The leaves were harvested at maturity and fermented for five days. After fermentation, L. lactis strains were isolated and their ability to remove cholesterol from the growth medium tested. This ability was compared with that of Lb. acidophilus ATCC 43121. Consumer acceptability of the fermented leaves was also compared to freshly boiled leaves. The Lactococcal strains isolated reduced cholesterol level by 52 µg/ml and Lb. acidophilus ATCC 43121 reduced by 56 µg/ml indicating a similar reduction capability (p < 0.05) to that of the standard Lb. acidophilus ATCC 43121 probiotic. After fermentation, protein decreased from 36.07 to 16.65%, ash increased from 19.76 to 36.21% and moisture content increased from 5.44 to 6.22%, respectively.There was no significant difference (p < 0.05) in consumer acceptability whereby, the consumers scored 6.90 points for fermented leaves compared to av6.83 points scored by consumers for fresh boiled leaves This study concluded that fermented amaranthus leaves dish is a potential source of probiotics as the level of cholesterol reduction by the isolated Lactococcal strains compares favourably with the reduction levels of the control Lb. acidophilus ATCC 43121 which is a known probiotic

The effect of 2,4-D, dicamba and hand weeding on witchweed density and maize yield

(African Crop Science Journal 1999 7(4): 455-464

Intercropping maize with grain legumes for Striga control in Zimbabwe

On-farm experiments were conducted in Chinyika Resettlement Area during the 1994/95 and 1995/96 rainy seasons at four sites to test the effectiveness of intercropping maize with cowpea, groundnut, field bean and bambara nut in suppressing Striga asiatica   (L.) Kuntze. During the 1994/95 rainy season maize/cowpea intercrop supported less Striga asiatica plant m-2 than sole maize, while other intercrops supported similar numbers of emerged Striga asiatica plants m-2 as sole maize. Combined analysis over sites showed that the numbers of emerged Striga asiatica plants in the intercrops were similar to those in sole maize during the 1995/96 season. However, during the same season the number of emerged Striga asiatica plants was significantly (P&lt;0.05) lower in the maize/groundnut intercrop at 8 weeks after crop emergence (WACE) at one site but similar at the remaining sites. Due to moisture stress and severe competition from the parasitic weed, no maize grain was harvested during the 1994/95 season. The maize/cowpea intercrop had the lowest maize stover yield, while the maize/field bean intercrop had the highest stover yield. Maize grain yields were not significantly different for all treatments during the 1995/96 season but the partial land equivalent ratios (PLERs) ranged from 0.8 to 1.70 indicating that intercropping maize with legumes had an advantage over planting sole maize in Striga asiatica infested fields

The effect of rate and time of application of Nitrogen on maize yield in Chinyika Resettlement area, Zimbabwe

No abstract availabl

Maize response to method and rate of manure application

(African Crop Science Journal 1999 7(4): 407-414

Synergism between Amodiaquine and Its Major Metabolite, Desethylamodiaquine, against Plasmodium falciparum In Vitro

The in vitro activity of the prodrug amodiaquine and its metabolite monodesethyl-amodiaquine has been studied for three strains of Plasmodium falciparum: LS-2, LS-3, and LS-1. Both compounds showed significant activity against all three strains; the activity of amodiaquine was slightly higher than that of the metabolite. By use of a checkerboard design, interaction studies with both compounds yielded evidence of significant synergism; means of the sums of the fractional inhibitory concentrations were 0.0392 to 0.0746 for strain LS-2, 0.1567 to 0.3102 for strain LS-3, and 0.025 to 0.3369 for strain LS-1. In further investigations, the interaction of amodiaquine with monodesethyl-amodiaquine was tested at clinically relevant concentrations of both compounds. In these studies, involving amodiaquine at picomolar and femtomolar concentrations, the compound was found to exert high potentiating activity on monodesethyl-amodiaquine. This interaction produced mean ratios of observed to expected activity of 0.0505 to 0.0642 for strain LS-2, 0.0882 to 0.3820 for strain LS-3, and 0.0752 to 0.2924 for strain LS-1. The synergistic activity was most marked at monodesethyl-amodiaquine/amodiaquine ratios up to 100,000:1 but was still evident at higher ratios