scholarly journals Fluorescence analysis of the interaction of isometamidium with Trypanosoma congolense

1993 ◽  
Vol 292 (1) ◽  
pp. 31-35 ◽  
Author(s):  
D Zilberstein ◽  
J Wilkes ◽  
H Hirumi ◽  
A S Peregrine
Keyword(s):  
Time Course ◽  
Fluorescence Analysis ◽  
Trypanosoma Congolense ◽  
Sub Saharan Africa ◽  
Temperature Dependent ◽  
Intact Cells ◽  
Uptake Process ◽  
Sub Saharan

Isometamidium chloride (Samorin) is the only compound recommended for prophylaxis against bovine trypanosomiasis in sub-Saharan Africa. The fluorescence property of this compound was used to investigate the interaction of the molecule with in vitro-derived bloodstream forms of Trypanosoma congolense IL 1180. Incubation of isometamidium with trypanosomes at 37 degrees C for 180 min resulted in a gradual alteration of the lambda max. with time (from 600 to 584 nm) and an increase in the intensity of trypanosome-associated fluorescence of approx. 2-fold. The alteration in fluorescence was temperature-dependent and inhibited by the addition of N-ethylmaleimide. In contrast, with intact cells addition of digitonin caused a rapid increase in fluorescence intensity to approximately four times that observed with intact cells. Uptake of isometamidium was also determined using radiolabelled drug; the results indicated that the time course of the uptake process resembled the fluorescence profile and was temperature-dependent. The results therefore indicate that the alteration of fluorescence is due to interaction of isometamidium with an intracellular component(s) and that isometamidium is transported across the plasma membrane via a protein carrier. The data also indicate that the described fluorescence technique can be used to investigate the role of membrane transport in resistance to isometamidium.

scholarly journals In Vitro, Ex Vivo, and In Vivo Activities of Diamidines against Trypanosoma congolense and Trypanosoma vivax

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Kirsten Gillingwater ◽  
Christina Kunz ◽  
Christiane Braghiroli ◽  
David W. Boykin ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Lead Compounds ◽  
Single Bolus Dose ◽  
Sub Saharan

ABSTRACT African animal trypanosomosis (AAT) is caused by the tsetse fly-transmitted protozoans Trypanosoma congolense and T. vivax and leads to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat nagana in cattle (diminazene diaceturate, homidium chloride, and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat nagana. Dicationic compounds have been demonstrated to have excellent efficacy against different kinetoplastid parasites. This study therefore evaluated the activities of 37 diamidines, using in vitro and ex vivo drug sensitivity assays. The 50% inhibitory concentrations obtained ranged from 0.007 to 0.562 μg/ml for T. congolense and from 0.019 to 0.607 μg/ml for T. vivax. On the basis of these promising results, 33 of these diamidines were further examined using in vivo mouse models of infection. Minimal curative doses of 1.25 mg/kg of body weight for both T. congolense- and T. vivax-infected mice were seen when the diamidines were administered intraperitoneally (i.p.) over 4 consecutive days. From these observations, 15 of these 33 diamidines were then further tested in vivo, using a single bolus dose for administration. The total cure of mice infected with T. congolense and T. vivax was seen with single i.p. doses of 5 and 2.5 mg/kg, respectively. This study identified a selection of diamidines which could be considered lead compounds for the treatment of nagana.

scholarly journals Lipophilic Guanylhydrazone Analogues as Promising Trypanocidal Agents: An Extended SAR Study

2020 ◽  
Vol 26 (8) ◽  
pp. 838-866
Author(s):  
Vasiliki Pardali ◽  
Erofili Giannakopoulou ◽  
Dimitrios-Ilias Balourdas ◽  
Vassilios Myrianthopoulos ◽  
Martin C. Taylor ◽  
...  
Keyword(s):  
Low Income ◽  
Critical Role ◽  
Adamantane Derivative ◽  
Sub Saharan Africa ◽  
Low Income Countries ◽  
Sub Saharan ◽  
Sar Study ◽  
Sar Analysis

In this report, we extend the SAR analysis of a number of lipophilic guanylhydrazone analogues with respect to in vitro growth inhibition of Trypanosoma brucei and Trypanosoma cruzi. Sleeping sickness and Chagas disease, caused by the tropical parasites T. brucei and T. cruzi, constitute a significant socioeconomic burden in low-income countries of sub-Saharan Africa and Latin America, respectively. Drug development is underfunded. Moreover, current treatments are outdated and difficult to administer, while drug resistance is an emerging concern. The synthesis of adamantane-based compounds that have potential as antitrypanosomal agents is extensively reviewed. The critical role of the adamantane ring was further investigated by synthesizing and testing a number of novel lipophilic guanylhydrazones. The introduction of hydrophobic bulky substituents onto the adamantane ring generated the most active analogues, illustrating the synergistic effect of the lipophilic character of the C1 side chain and guanylhydrazone moiety on trypanocidal activity. The n-decyl C1-substituted compound G8 proved to be the most potent adamantane derivative against T. brucei with activity in the nanomolar range (EC50=90 nM). Molecular simulations were also performed to better understand the structure-activity relationships between the studied guanylhydrazone analogues and their potential enzyme target.

Financing Energy Access in Africa

2018 ◽  
Author(s):  
Peter Kayode Oniemola ◽  
Jane Ezirigwe
Keyword(s):  
Oil And Gas ◽  
Sub Saharan Africa ◽  
Capital Investments ◽  
Energy Access ◽  
African Countries ◽  
Sustainable Technologies ◽  
Energy Technologies ◽  
Sub Saharan ◽  
Diesel Motors

To achieve universal energy access will attract huge capital investments. If sub-Saharan Africa is to realize anything close to the ambitious goals set for its energy access, then new actors, innovative funding mechanisms and sustainable technologies will have to be attracted. Finance is needed for activities such as rural electrification, clean cooking facilities, diesel motors and generators, other renewable energy technologies, oil and gas infrastructures, etc. Finance is also needed in research and development of suitable technologies and funding options as well as investment in the capacity to formulate and implement sound energy policies. This chapter examines the varied financing options for energy access in sub-Saharan Africa. It argues that with appropriate laws in place and effective mechanism for implementation, African countries can significantly engage private sector financing, international financial institutions and foreign donors. The role of the law here will be in creating an enabling environment for financing.

Human Development Paradigm for South Asia

2018 ◽  
Keyword(s):  
South Asia ◽  
Human Development ◽  
Sub Saharan Africa ◽  
Health And Nutrition ◽  
The People ◽  
Sub Saharan ◽  
Development Paradigm

In the chapter, Haq gives a snapshot of the human progress of South Asia, comparing it with other regions. He was worried about the region beginning to lag behind all other regions, including Sub-Saharan Africa. He highlights the role of the two largest economies in the region, India and Pakistan, in financing the major investment in education, health and nutrition for the people. Haq advocates some fiscal and monetary reforms are suggested to invest in human development.

scholarly journals An increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nancy S. Matowo ◽  
Jackline Martin ◽  
Manisha A. Kulkarni ◽  
Jacklin F. Mosha ◽  
Eliud Lukole ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Anopheles Funestus ◽  
Sub Saharan Africa ◽  
North West ◽  
Vector Population ◽  
Lake Zone ◽  
Sub Saharan ◽  
Long Lasting Insecticidal Nets ◽  
Study District

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.

scholarly journals Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jakob Weglage ◽  
Friederike Wolters ◽  
Laura Hehr ◽  
Jakob Lichtenberger ◽  
Celina Wulz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Colorectal Carcinogenesis ◽  
Sub Saharan Africa ◽  
Interleukin 4 ◽  
Health Burden ◽  
Sub Saharan ◽  
Considerable Morbidity ◽  
First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

Adoption of improved cassava varieties in Nigeria: Insights from DNA fingerprinting versus self-reporting varietal identification approaches

2021 ◽  
pp. 003072702199003
Author(s):  
Patience Ifeyinwa Opata ◽  
Oguejiofor Joseph Okorie ◽  
Juliana Chinasa Iwuchukwu ◽  
Chukwuma Otum Ume ◽  
Oyakhilomen Oyinbo
Keyword(s):  
Measurement Errors ◽  
Empirical Studies ◽  
Sub Saharan Africa ◽  
Limited Attention ◽  
Adoption Studies ◽  
Hidden Hunger ◽  
Varietal Identification ◽  
Sub Saharan ◽  
Cassava Varieties

Much of the empirical studies on crop varietal adoption in Sub-Saharan Africa relied on self-reported adoption in farm-household surveys, which is prone to measurement errors. In addition, farmers’ perceptions of consumption-related varietal traits in adoption studies has received limited attention compared with production-related traits. Using DNA-based and self-reported adoption measures, we analyze the adoption of improved cassava varieties (ICVs) with a focus on the extent of varietal misidentification, the sensitivity of the drivers of adoption to varietal misidentification and the role of farmers’ perceptions of biofortification trait in adoption decisions. We find that the adoption rate of ICVs is relatively high using both DNA-based and self-reported adoption measures, but there is notable misclassification in varietal adoption. We find that the mismatch in DNA-based and self-reported adoption measures leads to some variation in the factors that influence the likelihood and intensity of adoption of ICVs. This suggests that appropriate varietal identification helps in better understanding of the drivers of adoption. In addition, we find that despite the observed varietal misclassification, farmers’ perceptions of biofortification trait is significantly correlated with the probability and intensity of adoption of ICVs using both DNA-based and self-reported varietal identification. This suggests that inclusion of biofortification trait in cassava matters for both the likelihood and extent of adoption of ICVs. The latter lends credence to the emerging policy interests in breeding programs for biofortified crops to address hidden hunger in Nigeria.

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