scholarly journals Artemether and Praziquantel: Origin, Mode of Action, Impact, and Suggested Application for Effective Control of Human Schistosomiasis

2018 ◽  
Vol 3 (4) ◽  
pp. 125 ◽  
Author(s):  
Robert Bergquist ◽  
Hala Elmorshedy
Keyword(s):  
Egg Production ◽  
Large Scale ◽  
Artemisinin Resistance ◽  
Effective Control ◽  
Artemisinin Derivatives ◽  
Malaria Therapy ◽  
Molecular Approaches ◽  
Life Cycle Stages ◽  
Praziquantel Treatment ◽  
Large Scale Field

The stumbling block for the continued, single-drug use of praziquantel (PZQ) against schistosomiasis is less justified by the risk of drug resistance than by the fact that this drug is inactive against juvenal parasites, which will mature and start egg production after chemotherapy. Artemisinin derivatives, currently used against malaria in the form of artemisinin-based combination therapy (ACT), provide an opportunity as these drugs are not only active against malaria plasmodia, but surprisingly also against juvenile schistosomes. An artemisinin/PZQ combination would be complimentary, and potentially additive, as it would kill two schistosome life cycle stages and thus confer a transmission-blocking modality to current chemotherapy. We focus here on single versus combined regimens in endemic settings. Although the risk of artemisinin resistance, already emerging with respect to malaria therapy in Southeast Asia, prevents use in countries where ACT is needed for malaria care, an artemisinin-enforced praziquantel treatment (APT) should be acceptable in North Africa (including Egypt), the Middle East, China, and Brazil, as these countries are not endemic for malaria. Thanks to recent progress with respect to high-resolution diagnostics, based on circulating schistosome antigens in humans and molecular approaches for snail surveys, it should be possible to keep areas scheduled for schistosomiasis elimination under surveillance, bringing rapid response to bear on problems arising. The next steps would be to investigate where and for how long APT should be applied to make a lasting impact. A large-scale field trial in an area with modest transmission should tell how apt this approach is.

scholarly journals Reduced Dosage of Methyl Bromide for Controlling Verticillium Wilt of Potato in Experimental and Commercial Plots

Plant Disease ◽  
1997 ◽  
Vol 81 (5) ◽  
pp. 469-474 ◽  
Author(s):  
A. Gamliel ◽  
A. Grinstein ◽  
Y. Peretz ◽  
L. Klein ◽  
A. Nachmias ◽  
...  
Keyword(s):  
Verticillium Wilt ◽  
Methyl Bromide ◽  
Large Scale ◽  
Field Experiments ◽  
Tuber Yield ◽  
Total Yield ◽  
Effective Control ◽  
Large Scale Field ◽  
Commercial Applications

The use of gas-impermeable films to reduce the dosage of methyl bromide (MB) required to control Verticillium wilt in potatoes was examined in field experiments, conducted in soils naturally infested with Verticillium dahliae. The incidence and severity of Verticillium wilt were significantly reduced (by 74 to 94%) by fumigation with MB at 50 g/m2 under standard low density polyethylene (LDPE) or at 25 g/m2 under gas-impermeable films. Fumigation at 25 g/m2 under LDPE was less effective. Disease severity was inversely correlated (r2 = 0.89 to 0.91) with chlorophyll content in the leaves. Fumigation also reduced (by 89 to 100%) stem colonization by the pathogen. Potato yield in the fumigated plots was significantly higher (26 to 69%), than in their nonfumigated counterparts, and was inversely correlated with disease index (r2 = 0.69 to 0.9). The percentage of high-value tubers (above 45 g) was 52 to 56% of total yield in the fumigated plots as compared with 32 to 40% in the nonfumigated controls. Thus, fumigation also improved the commercial quality of tuber yield. Effective control of V. dahliae and yield increases following MB fumigation at the recommended dosage or at a reduced dosage with gas-impermeable films was also observed in a consecutive crop. These results were verified in a large-scale field experiment using commercial applications, further demonstrating the feasibility of reducing MB dosages under farm conditions, without reducing its effectiveness in terms of disease control and yield improvement.

scholarly journals The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Min Zhang ◽  
Chengqi Wang ◽  
Jenna Oberstaller ◽  
Phaedra Thomas ◽  
Thomas D. Otto ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Large Scale ◽  
Artemisinin Resistance ◽  
Free Living ◽  
Artemisinin Derivatives ◽  
Evolutionary Origins ◽  
Algal Endosymbiont ◽  
Phenotype Screen ◽  
Artemisinin Combination Therapies

AbstractThe emergence and spread of Plasmodium falciparum parasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. Here, we develop a large-scale phenotypic screening pipeline and use it to carry out a large-scale forward-genetic phenotype screen in P. falciparum to identify genes allowing parasites to survive febrile temperatures. Screening identifies more than 200 P. falciparum mutants with differential responses to increased temperature. These mutants are more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical for P. falciparum tolerance to febrile temperatures and artemisinin include highly essential, conserved pathways associated with protein-folding, heat shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the ancestral genome of the parasite’s algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general are upregulated in response to heat shock, as are other Plasmodium genes with orthologs in plant and algal genomes. Plasmodium falciparum parasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiont-derived genes in the parasite’s genome, suggesting a link to the evolutionary origins of Plasmodium parasites in free-living ancestors.

scholarly journals The endosymbiotic origins of the apicoplast link fever-survival and artemisinin-resistance in the malaria parasite

2020 ◽  
Author(s):  
Min Zhang ◽  
Chengqi Wang ◽  
Jenna Oberstaller ◽  
Phaedra Thomas ◽  
Thomas D. Otto ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Large Scale ◽  
Artemisinin Resistance ◽  
Free Living ◽  
Artemisinin Derivatives ◽  
Evolutionary Origins ◽  
Algal Endosymbiont ◽  
Phenotype Screen ◽  
Artemisinin Combination Therapies

ABSTRACTBackgroundThe emergence and spread of Plasmodium falciparum parasites resistant to front-line antimalarial artemisinin-combination therapies (ACT) threatens to erase the considerable gains against the disease of the last decade. We developed a new large-scale phenotypic screening pipeline and used it to carry out the first large-scale forward-genetic phenotype screen in P. falciparum to identify genes that allow parasites to survive febrile temperatures.ResultsScreening identified more than 200 P. falciparum mutants with differential responses to increased temperature. These mutants were more likely to be sensitive to artemisinin derivatives as well as to heightened oxidative stress. Major processes critical for P. falciparum tolerance to febrile temperatures and artemisinin included highly essential, conserved pathways associated with protein-folding, heat-shock and proteasome-mediated degradation, and unexpectedly, isoprenoid biosynthesis, which originated from the parasite’s algal endosymbiont-derived plastid, the apicoplast. Apicoplast-targeted genes in general were up-regulated in response to heat shock, as were other Plasmodium genes with orthologs in plant and algal genomes.ConclusionsPlasmodium falciparum parasites appear to exploit their innate febrile-response mechanisms to mediate resistance to artemisinin. Both responses depend on endosymbiotic cyanobacterium-related ancestral genes in the parasite’s genome, suggesting a link to the evolutionary origins of Plasmodium parasites in free-living ancestors.

Biodata response elaboration: A large-scale field experiment

2010 ◽  
Author(s):  
Julia Levashina ◽  
Frederick P. Morgeson ◽  
Michael A. Campion
Keyword(s):  
Field Experiment ◽  
Large Scale ◽  
Scale Field ◽  
Large Scale Field

Anti-Mycobacterial Peroxides: A New Class of Agents for Development Against Tuberculosis

2020 ◽  
Vol 16 (3) ◽  
pp. 392-402
Author(s):  
Christiaan W. van der Westhuyzen ◽  
Richard K. Haynes ◽  
Jenny-Lee Panayides ◽  
Ian Wiid ◽  
Christopher J. Parkinson
Keyword(s):  
Subsequent Development ◽  
Antitubercular Activity ◽  
Organic Peroxide ◽  
New Drugs ◽  
Skeletal Myoblast ◽  
Artemisinin Derivatives ◽  
Malaria Therapy ◽  
New Class ◽  
Alternative Approach

Background: With few exceptions, existing tuberculosis drugs were developed many years ago and resistance profiles have emerged. This has created a need for new drugs with discrete modes of action. There is evidence that tuberculosis (like other bacteria) is susceptible to oxidative pressure and this has yet to be properly utilised as a therapeutic approach in a manner similar to that which has proven highly successful in malaria therapy. Objective: To develop an alternative approach to the incorporation of bacterial siderophores that results in the creation of antitubercular peroxidic leads for subsequent development as novel agents against tuberculosis. Methods: Eight novel peroxides were prepared and the antitubercular activity (H37Rv) was compared to existing artemisinin derivatives in vitro. The potential for toxicity was evaluated against the L6 rat skeletal myoblast and HeLa cervical cancer lines in vitro. Results: The addition of a pyrimidinyl residue to an artemisinin or, preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. Conclusion: The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be a useful approach for creating oxidative drugs to target tuberculosis.

Hybrid Combination of GIS,GPS,WSN and GPRS Technology in Modern Digital Agriculture Application

2010 ◽  
Vol 108-111 ◽  
pp. 1158-1163 ◽  
Author(s):  
Peng Cheng Nie ◽  
Di Wu ◽  
Weiong Zhang ◽  
Yan Yang ◽  
Yong He
Keyword(s):  
Large Scale ◽  
Field Application ◽  
Wireless Sensor ◽  
Information Collection ◽  
Scale Field ◽  
Large Scale Field ◽  
Field Information ◽  
Intelligent Management ◽  
Digital Agriculture ◽  
And Control

In order to improve the information management of the modern digital agriculture, combined several modern digital agriculture technologies, namely wireless sensor network (WSN), global positioning system (GPS), geographic information system (GIS) and general packet radio service (GPRS), and applied them to the information collection and intelligent control process of the modern digital agriculture. Combining the advantage of the local multi-channel information collection and the low-power wireless transmission of WSN, the stable and low cost long-distance communication and data transmission ability of GPRS, the high-precision positioning technology of the DGPS positioning and the large-scale field information layer-management technology of GIS, such a hybrid technology combination is applied to the large-scale field information and intelligent management. In this study, wireless sensor network routing nodes are disposed in the sub-area of field. These nodes have GPS receiver modules and the electric control mechanism, and are relative positioned by GPS. They can real-time monitor the field information and control the equipment for the field application. When the GPS position information and other collected field information are measured, the information can be remotely transmitted to PC by GPRS. Then PC can upload the information to the GIS management software. All the field information can be classified into different layers in GIS and shown on the GIS map based on their GPS position. Moreover, we have developed remote control software based on GIS. It can send the control commands through GPRS to the nodes which have control modules; and then we can real-time manage and control the field application. In conclusion, the unattended automatic wireless intelligent technology for the field information collection and control can effectively utilize hardware resources, improve the field information intelligent management and reduce the information and intelligent cost.

scholarly journals Inverse Infiltration Modeling of Dike Covers Made of Dredged Material Using PEST and AMALGAM

Geosciences ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 41
Author(s):  
Tim Jurisch ◽  
Stefan Cantré ◽  
Fokke Saathoff
Keyword(s):  
Large Scale ◽  
Measurement Data ◽  
Fine Grained ◽  
Dredged Materials ◽  
Measurement Results ◽  
Large Scale Field ◽  
Eigenvalue Ratio ◽  
Ill Posed ◽  
Materials Used ◽  
Installation Technology

A variety of studies recently proved the applicability of different dried, fine-grained dredged materials as replacement material for erosion-resistant sea dike covers. In Rostock, Germany, a large-scale field experiment was conducted, in which different dredged materials were tested with regard to installation technology, stability, turf development, infiltration, and erosion resistance. The infiltration experiments to study the development of a seepage line in the dike body showed unexpected measurement results. Due to the high complexity of the problem, standard geo-hydraulic models proved to be unable to analyze these results. Therefore, different methods of inverse infiltration modeling were applied, such as the parameter estimation tool (PEST) and the AMALGAM algorithm. In the paper, the two approaches are compared and discussed. A sensitivity analysis proved the presumption of a non-linear model behavior for the infiltration problem and the Eigenvalue ratio indicates that the dike infiltration is an ill-posed problem. Although this complicates the inverse modeling (e.g., termination in local minima), parameter sets close to an optimum were found with both the PEST and the AMALGAM algorithms. Together with the field measurement data, this information supports the rating of the effective material properties of the applied dredged materials used as dike cover material.

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