scholarly journals In Vitro Activity of Statins against Naegleria fowleri

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Aitor Rizo-Liendo ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Olfa Chiboub ◽  
Rubén L. Rodríguez-Expósito ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Key Factors ◽  
Key Enzyme ◽  
Liver And Kidney ◽  
Nægleria Fowleri ◽  
Coa Reductase ◽  
Effective Drugs

Naegleria fowleri causes a deadly disease called primary amoebic meningoencephalitis (PAM). Even though PAM is still considered a rare disease, the number of reported cases worldwide has been increasing each year. Among the factors to be considered for this, awareness about this disease, and also global warming, as these amoebae thrive in warm water bodies, seem to be the key factors. Until present, no fully effective drugs have been developed to treat PAM, and the current options are amphotericin B and miltefosine, which present side effects such as liver and kidney toxicity. Statins are able to inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is a key enzyme for the synthesis of ergosterol of the cell membrane of these amoebae. Therefore, the in vitro activity of a group of statins was tested in this study against two types of strains of Naegleria fowleri. The obtained results showed that fluvastatin was the most effective statin tested in this study and was able to eliminate these amoebae at concentrations of 0.179 ± 0.078 to 1.682 ± 0.775 µM depending on the tested strain of N. fowleri. Therefore, fluvastatin could be a potential novel therapeutic agent against this emerging pathogen.

scholarly journals In vitro activity of selected Ghanaian medicinal plants against parasites: Giardia lamblia, Entamoeba histolytica and Naegleria fowleri

2017 ◽  
Vol 11 (23) ◽  
pp. 279-283 ◽  
Author(s):  
Kyere-Davies Gertrude ◽  
Agyare Christian ◽  
Duah Boakye Yaw ◽  
Bains Trpta ◽  
M. Suzuki Brian ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Entamoeba Histolytica ◽  
Giardia Lamblia ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri

scholarly journals Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

2003 ◽  
Vol 47 (2) ◽  
pp. 524-528 ◽  
Author(s):  
Shannon M. Goswick ◽  
George M. Brenner
Keyword(s):  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri ◽  
Free Living Ameba ◽  
Primary Amebic Meningoencephalitis ◽  
Observation Period

ABSTRACT Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 μM (10 μg/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 μM (0.1 μg/ml). Azithromycin protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.

Photosynthesis, carbon partitioning and metabolite content during drought stress in peach seedlings

1998 ◽  
Vol 25 (2) ◽  
pp. 197 ◽  
Author(s):  
A. J. Escobar-Gutiérrez ◽  
B. Zipperlin ◽  
F. Carbonne ◽  
A. Moing ◽  
J.P. Gaudillére
Keyword(s):  
Drought Stress ◽  
Osmotic Adjustment ◽  
Osmotic Potential ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Short Term ◽  
Phloem Sap ◽  
Mature Leaves ◽  
Key Enzyme

Photosynthesis, metabolic carbon partitioning and the contribution of sorbitol to the osmotic potential of mature peach (Prunus persica (L.) Batsch) leaves and phloem sap were examined in plants undergoing two levels of a short term drought stress. The relationship between osmotic potential at full turgor and water potential showed that neither mild nor severe drought stress induced a significant active osmotic adjustment in mature leaves. The osmotic potential of leaves at full turgor was -1.9 MPa; sorbitol was the major organic component (20%). Leaf sucrose and starch contents were significantly reduced by drought. The partitioning of newly-fixed carbon was also affected by stress. These changes appeared to originate from the inhibition of photosynthesis induced by drought stress. At low photosynthetic rates, the turnover of organic ions was low, and sorbitol synthesis was favoured over that of sucrose. Water stress did not affect the in vitro activity of sucrose phosphate synthase (EC 2.4.1.14), the key enzyme in sucrose synthesis. The in vitro activity of aldose-6-phosphate reductase (EC 1.1.1.200), the key enzyme in sorbitol synthesis, tended to increase linearly in response to drought stress. It is concluded that, contrary to some other polyol-synthesising species, peach did not seem to benefit from sorbitol synthesis during short term drought stress for active osmotic adjustment in mature leaves. However, in phloem sap, increases in sucrose and especially sorbitol concentration were observed in stressed plants.

scholarly journals Epigallocatechin-3-gallate potently inhibits the in vitro activity of hydroxy-3-methyl-glutaryl-CoA reductase

2011 ◽  
Vol 52 (5) ◽  
pp. 897-907 ◽  
Author(s):  
Massimiliano Cuccioloni ◽  
Matteo Mozzicafreddo ◽  
Michele Spina ◽  
Chi Nhan Tran ◽  
Maurizio Falconi ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Coa Reductase

scholarly journals In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 689
Author(s):  
Hye Jee Hahn ◽  
Anjan Debnath
Keyword(s):  
Amphotericin B ◽  
Mevalonate Pathway ◽  
Unmet Need ◽  
Drug Regimen ◽  
Naegleria Fowleri ◽  
Protein Farnesyltransferase ◽  
Nægleria Fowleri ◽  
Different Strains ◽  
Coa Reductase

Free-living amoeba Naegleria fowleri causes a rapidly fatal infection primary amebic meningoencephalitis (PAM) in children. The drug of choice in treating PAM is amphotericin B, but very few patients treated with amphotericin B have survived PAM. Therefore, development of efficient drugs is a critical unmet need. We identified that the FDA-approved pitavastatin, an inhibitor of HMG Co-A reductase involved in the mevalonate pathway, was equipotent to amphotericin B against N. fowleri trophozoites. The genome of N. fowleri contains a gene encoding protein farnesyltransferase (FT), the last common enzyme for products derived from the mevalonate pathway. Here, we show that a clinically advanced FT inhibitor lonafarnib is active against different strains of N. fowleri with EC50 ranging from 1.5 to 9.2 µM. A combination of lonafarnib and pitavastatin at different ratios led to 95% growth inhibition of trophozoites and the combination achieved a dose reduction of about 2- to 28-fold for lonafarnib and 5- to 30-fold for pitavastatin. No trophozoite with normal morphology was found when trophozoites were treated for 48 h with a combination of 1.7 µM each of lonafarnib and pitavastatin. Combination of lonafarnib and pitavastatin may contribute to the development of a new drug regimen for the treatment of PAM.

In Vitro Activity of Phytocannabinoids from High Potency Cannabis sativa

Planta Medica ◽  
2012 ◽  
Vol 78 (05) ◽  
Author(s):  
A Husni ◽  
S Ross ◽  
O Dale ◽  
C Gemelli ◽  
G Ma ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
High Potency
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