scholarly journals Antimalarial Activity of the Myxobacterial Macrolide Chlorotonil A

2014 ◽  
Vol 58 (11) ◽  
pp. 6378-6384 ◽  
Author(s):  
Jana Held ◽  
Tamirat Gebru ◽  
Markus Kalesse ◽  
Rolf Jansen ◽  
Klaus Gerth ◽  
...  
Keyword(s):  
Screening Program ◽  
Antimalarial Activity ◽  
Stage Iv ◽  
Short Exposure ◽  
Parasite Development ◽  
Content Type ◽  
Highly Active ◽  
New Antibiotics ◽  
Further Development ◽  
Antimalarial Action

ABSTRACTMyxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylumProteobacteria. They are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. In the course of a bioactivity screening program of secondary metabolites produced bySorangium cellulosumstrains, the macrolide chlorotonil A was found to exhibit promising antimalarial activity. Subsequently, we evaluated chlorotonil A againstPlasmodium falciparumlaboratory strains and clinical isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory concentration between 4 and 32 nM; additionally, no correlations between the activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho, −0.046) were observed.Per ostreatment ofPlasmodium berghei-infected mice with four doses of as little as 36 mg of chlorotonil A per kg of body weight led to the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A acts against all stages of intraerythrocytic parasite development, including ring-stage parasites and stage IV to V gametocytes, and it requires only a very short exposure to the parasite to exert its antimalarial action. Conclusively, chlorotonil A has an exceptional and unprecedented profile of action and represents an urgently required novel antimalarial chemical scaffold. Therefore, we propose it as a lead structure for further development as an antimalarial chemotherapeutic.

scholarly journals High-Yield Resveratrol Production in Engineered Escherichia coli

2011 ◽  
Vol 77 (10) ◽  
pp. 3451-3460 ◽  
Author(s):  
Chin Giaw Lim ◽  
Zachary L. Fowler ◽  
Thomas Hueller ◽  
Steffen Schaffer ◽  
Mattheos A. G. Koffas
Keyword(s):  
Escherichia Coli ◽  
High Yield ◽  
Plant Polyphenols ◽  
Content Type ◽  
Scientific Investigations ◽  
Highly Active ◽  
Structure Activity ◽  
Health Promoting ◽  
The Subject ◽  
Further Development

ABSTRACTPlant polyphenols have been the subject of several recent scientific investigations since many of the molecules in this class have been found to be highly active in the human body, with a plethora of health-promoting activities against a variety of diseases, including heart disease, diabetes, and cancer, and with even the potential to slow aging. Further development of these potent natural therapeutics hinges on the formation of robust industrial production platforms designed using specifically selected as well as engineered protein sources along with the construction of optimal expression platforms. In this work, we first report the investigation of various stilbene synthases from an array of plant species considering structure-activity relationships, their expression efficiency in microorganisms, and their ability to synthesize resveratrol. Second, we looked into the construct environment of recombinantly expressed stilbene synthases, including different promoters, construct designs, and host strains, to create anEscherichia colistrain capable of producing superior resveratrol titers sufficient for commercial usage. Further improvement of metabolic capabilities of the recombinant strain aimed at improving the intracellular malonyl-coenzyme A pool, a resveratrol precursor, resulted in a final improved titer of 2.3 g/liter resveratrol.

scholarly journals In vitro and in vivo inhibition of erythrocytic development of malarial parasites by docetaxel.

1996 ◽  
Vol 40 (2) ◽  
pp. 358-361 ◽  
Author(s):  
V Sinou ◽  
P Grellier ◽  
J Schrevel
Keyword(s):  
Antimalarial Activity ◽  
Single Injection ◽  
Short Exposure ◽  
Parasite Development ◽  
Schizont Stage ◽  
Drug Injection ◽  
Sensitive Stage ◽  
Plasmodium Vinckei

The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stage; an inhibition of more than 60% of parasite development was observed at 10 nM. At this drug concentration, the development of the younger ring and trophozoite forms was unaffected. The in vivo antimalarial activity of docetaxel against the development in blood of old trophozoites of a species that causes malaria in rodents, Plasmodium vinckei petteri, was evaluated in IOPS-OF1 mice. Two tests were performed: the 4-day suppressive test, as described by Peters (W. Peters, p. 145-273, in Chemotherapy, and Drug Resistance in Malaria, vol. 1, 1987), and the effects of a single injection of docetaxel after inoculation of the parasites. A single injection of docetaxel at 40 mg/kg of body weight was sufficient to reduce drastically the level of parasitemia; 90% inhibition of the development of parasites in blood was observed 5 days after drug injection. This program avoided the toxicity observed when mice were treated with four injections of docetaxel. The possibility of using a single bolus of taxoids to treat malaria infections is discussed.

scholarly journals Small-Molecule Inhibitor of FosA Expands Fosfomycin Activity to Multidrug-Resistant Gram-Negative Pathogens

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Adam D. Tomich ◽  
Erik H. Klontz ◽  
Daniel Deredge ◽  
John P. Barnard ◽  
Christi L. McElheny ◽  
...  
Keyword(s):  
Small Molecule ◽  
Multidrug Resistant ◽  
Public Health Issue ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Track Record ◽  
New Strategy ◽  
New Antibiotics ◽  
Resistant Strains

ABSTRACTThe spread of multidrug or extensively drug-resistant Gram-negative bacteria is a serious public health issue. There are too few new antibiotics in development to combat the threat of multidrug-resistant infections, and consequently the rate of increasing antibiotic resistance is outpacing the drug development process. This fundamentally threatens our ability to treat common infectious diseases. Fosfomycin (FOM) has an established track record of safety in humans and is highly active againstEscherichia coli, including multidrug-resistant strains. However, many other Gram-negative pathogens, including the “priority pathogens”Klebsiella pneumoniaeandPseudomonas aeruginosa, are inherently resistant to FOM due to the chromosomalfosAgene, which directs expression of a metal-dependent glutathioneS-transferase (FosA) that metabolizes FOM. In this study, we describe the discovery and biochemical and structural characterization of ANY1 (3-bromo-6-[3-(3-bromo-2-oxo-1H-pyrazolo[1,5-a]pyrimidin-6-yl)-4-nitro-1H-pyrazol-5-yl]-1H-pyrazolo[1,5-a]pyrimidin-2-one), a small-molecule active-site inhibitor of FosA. Importantly, ANY1 potentiates FOM activity in representative Gram-negative pathogens. Collectively, our study outlines a new strategy to expand FOM activity to a broader spectrum of Gram-negative pathogens, including multidrug-resistant strains.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

A comparison between economic and organic store brands

2017 ◽  
Vol 45 (12) ◽  
pp. 1298-1316 ◽  
Author(s):  
Magali Jara ◽  
Gérard Cliquet ◽  
Isabelle Robert
Keyword(s):  
Brand Equity ◽  
Perceived Quality ◽  
Purchase Intentions ◽  
Path Model ◽  
Added Value ◽  
Store Brand ◽  
Store Brands ◽  
Content Type ◽  
Further Development

Purpose The purpose of this paper is to tackle the issue of store brand equity by considering two store brand’s positioning strategies: those with high perceived added value (the organic store brands), as opposed to economic brands. It takes place in the current environmental considerations showing the important role played by the packaging in determining the store brand equity. Design/methodology/approach A PLS Path model divided into four sub-models enables the authors to make specific predictions about customers’ purchase intentions. It also provides a concise operational calculation of the brand equity of each studied store brand. Findings Results show that economic brands build their equity with reinforced packaging, and organic brands maximise their brand equity by using simple packaging. In general, reinforced packaging improves the perceived quality of economic store brands but destroys that of organic brands. The calculations of overall equity scores for each studied store brand reveal that economic brands could benefit from further development whilst organic brands already maximise their equity. Practical implications Results will enable large retailers to develop effective campaigns focussing on perceived quality and more specifically by designing packaging that are suitable for the positioning of their brands – a simple packaging for organic brands and a reinforced packaging for economic brands to maximise customers’ value. Originality/value This is one of the first studies to deepen the store brand equity, comparing two contrasting types of brands, by studying specifically variations of the levels of customers’ perceived quality depending of two types of packaging.

scholarly journals Multiple Antibiotics Exert Delayed Effects against the Plasmodium falciparum Apicoplast

2007 ◽  
Vol 51 (10) ◽  
pp. 3485-3490 ◽  
Author(s):  
Erica L. Dahl ◽  
Philip J. Rosenthal
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Division ◽  
Antimalarial Activity ◽  
Mechanisms Of Action ◽  
Malaria Parasites ◽  
Delayed Effects ◽  
Delayed Death ◽  
Antimalarial Action ◽  
Multiple Antibiotics

ABSTRACT Several classes of antibiotics exert antimalarial activity. The mechanisms of action of antibiotics against malaria parasites have been unclear, and prior studies have led to conflicting results, in part because they studied antibiotics at suprapharmacological concentrations. We examined the antimalarial effects of azithromycin, ciprofloxacin, clindamycin, doxycycline, and rifampin against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) Plasmodium falciparum strains. At clinically relevant concentrations, rifampin killed parasites quickly, preventing them from initiating cell division. In contrast, pharmacological concentrations of azithromycin, ciprofloxacin, clindamycin, and doxycycline were relatively inactive against parasites initially but exerted a delayed death effect, in which the progeny of treated parasites failed to complete erythrocytic development. The drugs that caused delayed death did not alter the distribution of apicoplasts into developing progeny. However, the apicoplasts inherited by the progeny of treated parasites were abnormal. The loss of apicoplast function became apparent as the progeny of antibiotic-treated parasites initiated cell division, with the failure of schizonts to fully mature or for erythrocyte rupture to take place. These findings explain the slow antimalarial action of multiple antibiotics.

Education for sustainable development at Chemnitz University of Technology

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Martin Albert ◽  
Maria Uhlig
Keyword(s):  
Sustainable Development ◽  
Education For Sustainable Development ◽  
Cognitive Domain ◽  
New Combination ◽  
General Direction ◽  
Content Type ◽  
University Of Technology ◽  
Study Results ◽  
Study Programs ◽  
Further Development

Purpose This paper aims to examine the current state of education for sustainable development (ESD) at Chemnitz University of Technology (CUT) and to propose a guide for analysing sustainability at higher education institutions (HEI) in terms of implementation of the sustainable development goals (SDGs) and sustainability dimensions in the cognitive domain of education. Design/methodology/approach This paper uses a new combination of two frameworks, the “Phase Model of Sustainability in MBA (Master of Business Administration) Education”, developed by Hart et al. (2017), to classify sustainability-focused topics and United Nations Educational, Scientific and Cultural Organization’s (UNESCO’s) learning objectives for ESD (UNESCO, 2017) to classify sustainability-related topics. This paper analysed CUT’s study programs and faculties, the websites of the study programs and the (junior) professorships, using documentary analysis with a new set of keywords relating to the topic of incorporating sustainability in curricula. Findings The faculties and study programs of CUT are at different stages of integrating ESD. However, topics such as sustainable energy and production, recycling, sustainable management and innovation are prominent in the educational offerings of CUT. As the university is a technical university, the focus on these topics reflects the general direction of the organisation. Based on this study results, this study gives recommendations for further development for ESD at CUT. Originality/value This paper presents the case of CUT and a new guide for analysing sustainability at HEI, including recommendations for further development in relation to ESD.

Effects of camel milk hydrolysate on blood pressure and biochemical parameters in fructose-induced hypertensive rats

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mohammad Alshuniaber ◽  
Omar Alhaj ◽  
Qasem Abdallah ◽  
Haitham Jahrami
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Antihypertensive Drugs ◽  
Camel Milk ◽  
Short Exposure ◽  
Antihypertensive Activity ◽  
Content Type ◽  
Insulin Levels ◽  
Ace Activity

Purpose This study aims to investigate the antihypertensive effect of camel milk hydrolysate in rats with fructose-induced hypertension. Design/methodology/approach The antihypertensive effect of fermented camel milk was determined using 6 groups comprising 36 Wistar male rats. Blood pressure of rats was altered via exposure to a 10% fructose (w/v) diet in drinking water for 3 weeks before conducting 21 days of treatment. The authors conducted the experiment for short and long term using different doses of 800 and 1,200 mg/kg body weight. Serum was used to assay total cholesterol (TC), triglyceride (TG), glucose and insulin levels using standard biochemical kits. Findings The group that received 1,200 mg hydrolysate camel milk (HM) has significantly (p = 0.003) reduced systolic and diastolic blood pressure after a short exposure time (4–8 h). These effects were significantly (p = 0.005) comparable to the nifedipine (NIF) drug group. Similar long-term (21 days) effects on blood pressure were observed in 1,200 mg HM and NIF groups. Angiotensin-converting enzyme (ACE) activity and levels were also reduced in a correlation with blood pressure reduction only in HM1200 and HM800 treated groups. The authors observed no significant effect on blood pressure in groups receiving the 800 mg HM or 1,200 mg unhydrolyzed camel milk (UM). Rats receiving the 10% fructose diet showed significant differences from control rats regarding their blood biochemistry, including TG, TC, blood glucose and insulin levels. Rats in groups NIF, HM1200 and HM800 showed a significant (p < 0.05) reduction in serum glucose, insulin, TG and TC levels toward the baseline level. Research limitations/implications Further mechanistic investigation on the HM antihypertensive activity is highly recommended before suggesting HM as a product to reduce blood pressure. While drug–food interaction between HM and antihypertensive drugs, especially ACE inhibitors, is probable, UM seems not to affect blood pressure or ACE activity and therefore is expected to have no or minimal effects on the activity of other antihypertensive drugs. Investigation of ACE expression from various organs including lungs and leukocytes is highly recommended in future works using sodium dodecyl-sulfate polyacrylamide gel electrophoresis and western blot analysis or reverse transcription polymerase chain reaction. Originality/value No previous studies have measured the antihypertensive activity of milk hydrolysate mediated by the reduction of ACE activity and levels in plasma. Mechanisms involved in attenuating the levels of ACE warrant further investigation.

scholarly journals Complete Genome Sequence of Pseudomonas aeruginosa K34-7, a Carbapenem-Resistant Isolate of the High-Risk Sequence Type 233

2018 ◽  
Vol 7 (4) ◽  
Author(s):  
George Taiaroa ◽  
Ørjan Samuelsen ◽  
Tom Kristensen ◽  
Ole Andreas Løchen Økstad ◽  
Adam Heikal
Keyword(s):  
Pseudomonas Aeruginosa ◽  
High Risk ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Sequence Type ◽  
Resistant Isolate ◽  
Content Type ◽  
Carbapenem Resistant ◽  
New Antibiotics

Carbapenem-resistant Pseudomonas aeruginosa is defined as a “critical” priority pathogen for the development of new antibiotics. Here we report the complete genome sequence of an extensively drug-resistant, Verona integron-encoded metallo-β-lactamase-expressing isolate belonging to the high-risk sequence type 233.

scholarly journals Effect of Fluorescent Dyes onIn Vitro-Differentiated, Late-Stage Plasmodium falciparum Gametocytes

2014 ◽  
Vol 58 (12) ◽  
pp. 7398-7404 ◽  
Author(s):  
Tamirat Gebru ◽  
Benjamin Mordmüller ◽  
Jana Held
Keyword(s):  
Plasmodium Falciparum ◽  
Late Stage ◽  
Fluorescent Dyes ◽  
Clinical Symptoms ◽  
Laboratory Strain ◽  
Clinical Isolates ◽  
Synthetic Dyes ◽  
Content Type ◽  
Highly Active

ABSTRACTPlasmodium falciparumgametocytes are not associated with clinical symptoms, but they are responsible for transmitting the pathogen to mosquitoes. Therefore, gametocytocidal interventions are important for malaria control and resistance containment. Currently available drugs and vaccines are not well suited for that purpose. Several dyes have potent antimicrobial activity, but their use against gametocytes has not been investigated systematically. The gametocytocidal activity of nine synthetic dyes and four control compounds was tested against stage V gametocytes of the laboratory strain 3D7 and three clinical isolates ofP. falciparumwith a bioluminescence assay. Five of the fluorescent dyes had submicromolar 50% inhibitory concentration (IC50) values against mature gametocytes. Three mitochondrial dyes, MitoRed, dihexyloxacarbocyanine iodide (DiOC6), and rhodamine B, were highly active (IC50s < 200 nM). MitoRed showed the highest activity against gametocytes, with IC50s of 70 nM against 3D7 and 120 to 210 nM against clinical isolates. All compounds were more active against the laboratory strain 3D7 than against clinical isolates. In particular, the endoperoxides artesunate and dihydroartemisinin showed a 10-fold higher activity against 3D7 than against clinical isolates. In contrast to all clinically used antimalarials, several fluorescent dyes had surprisingly highin vitroactivity against late-stage gametocytes. Since they also act against asexual blood stages, they shall be considered starting points for the development of new antimalarial lead compounds.

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