scholarly journals Metabolite Biomarkers of Leishmania Antimony Resistance

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1063
Author(s):  
Sneider Alexander Gutierrez Guarnizo ◽  
Zemfira N. Karamysheva ◽  
Elkin Galeano ◽  
Carlos E. Muskus
Keyword(s):  
Drug Resistance ◽  
Energy Metabolism ◽  
Neglected Tropical Diseases ◽  
Energy Requirement ◽  
High Energy ◽  
Time Saving ◽  
Metabolic Remodeling ◽  
Close Relationship ◽  
Antimony Resistance ◽  
Antioxidant Stress

Leishmania parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. Leishmania exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using L. tropica promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using 1H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite’s efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.

scholarly journals Green synthesis: Proposed mechanism and factors influencing the synthesis of platinum nanoparticles

2020 ◽  
Vol 9 (1) ◽  
pp. 386-398 ◽  
Author(s):  
Mahmood S. Jameel ◽  
Azlan Abdul Aziz ◽  
Mohammed Ali Dheyab
Keyword(s):  
Green Synthesis ◽  
Reaction Temperature ◽  
Platinum Nanoparticles ◽  
Energy Requirement ◽  
Average Particle Size ◽  
High Energy ◽  
Energy Utilization ◽  
Critical Parameters ◽  
Synthesis Process ◽  
Average Particle

AbstractPlatinum nanoparticles (Pt NPs) have attracted interest in catalysis and biomedical applications due to their unique structural, optical, and catalytic properties. However, the conventional synthesis of Pt NPs using the chemical and physical methods is constrained by the use of harmful and costly chemicals, intricate preparation requirement, and high energy utilization. Hence, this review emphasizes on the green synthesis of Pt NPs using plant extracts as an alternative approach due to its simplicity, convenience, inexpensiveness, easy scalability, low energy requirement, environmental friendliness, and minimum usage of hazardous materials and maximized efficiency of the synthesis process. The underlying complex processes that cover the green synthesis (biosynthesis) of Pt NPs were reviewed. This review affirms the effects of different critical parameters (pH, reaction temperature, reaction time, and biomass dosage) on the size and shape of the synthesized Pt NPs. For instance, the average particle size of Pt NPs was reported to decrease with increasing pH, reaction temperature, and concentration of plant extract.

Energy Intakes of Ultraendurance Cyclists During Competition, an Observational Study

2012 ◽  
Vol 22 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Katherine E. Black ◽  
Paula M.L. Skidmore ◽  
Rachel C. Brown
Keyword(s):  
Observational Study ◽  
Energy Intake ◽  
Energy Requirement ◽  
Negative Relationship ◽  
Computer Software ◽  
High Energy ◽  
Energy Deficit ◽  
Food Diary ◽  
Food And Drink ◽  
And Performance

Endurance events >10 hr are becoming increasingly popular but provide numerous physiological challenges, several of which can be attenuated with optimal nutritional intakes. Previous studies in ultraendurance races have reported large energy deficits during events. The authors therefore aimed to assess nutritional intakes in relation to performance among ultraendurance cyclists. This observational study included 18 cyclists in a 384-km cycle race. At race registration each cyclist’s support crew was provided with a food diary for their cyclist. On completion of the race, cyclists were asked to recall their race food and drink intakes. All food and fluids were analyzed using a computer software package. Mean (SD) time to complete the race was 16 hr 21 min (2 hr 2 min). Mean (SD) energy intake was 18.7 (8.6) MJ, compared with an estimated energy requirement for the race of 25.5 (7.4) MJ. There was a significant negative relationship between energy intake and time taken to complete the race (p = .023, r2 = −.283). Mean (SD) carbohydrate, fat, and protein intakes were 52 (27), 15.84 (56.43), and 2.94 (7.25) g/hr, respectively. Only carbohydrate (p = .015, r2 = −.563) and fat intake (p = .037, r2 = −.494) were associated with time taken to complete the race. This study demonstrates the difficulties in meeting the high energy demands of ultraendurance cycling. The relationship between energy intake and performance suggests that reducing the energy deficit may be advantageous. Given the high carbohydrate intakes of these athletes, increasing energy intake from fat should be investigated as a means of decreasing energy deficits.

scholarly journals Energy Metabolism of Human Leukemic Lymphocytes and Granulocytes

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 151-167 ◽  
Author(s):  
JOHN LASZLO ◽  
Clarence Ellis
Keyword(s):  
Energy Metabolism ◽  
Chronic Lymphocytic Leukemia ◽  
Glucose Concentration ◽  
Acute Lymphocytic Leukemia ◽  
Aerobic Glycolysis ◽  
High Energy ◽  
Lymphocytic Leukemia ◽  
Anaerobic Conditions ◽  
High Energy Phosphate

Abstract 1. Leukocytes taken from patients having acute lymphocytic leukemia and chronic lymphocytic leukemia are characterized by high respiratory rates and low to absent aerobic glycolysis. Leukemic granulocytes have low respiratory rates and high aerobic glycolysis. 2. Lymphocytes and granulocytes have the capacity for high glycolytic rates under anaerobic conditions. 3. Lymphocyte respiration is independent of glucose concentration in contrast to granulocyte respiration. 4. High energy phosphate levels of lymphocytes and granulocytes are unchanged if these cells are incubated aerobically, either with or without glucose, or anaerobically in the presence of glucose. 5. Aerobic glycolysis can be induced in lymphocytes by the addition of foreign plasma. Foreign plasma may also alter granulocyte metabolism.

DDRE-27. METABOLIC SWITCHING AS A MECHANISM OF DRUG RESISTANCE AGAINST NAMPT INHIBITION IN GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi80-vi80
Author(s):  
Pratibha Sharma ◽  
Vinay Puduvalli
Keyword(s):  
Drug Resistance ◽  
Energy Metabolism ◽  
Cross Reactivity ◽  
Alternative Methods ◽  
Cross Resistance ◽  
Significant Heterogeneity ◽  
Drug Resistant ◽  
High Accumulation ◽  
Metabolic Switch ◽  
Nicotinamide Phosphoribosyltransferase

Abstract BACKGROUND Gliomas exhibit significant heterogeneity in treatment response and characteristically deploy resistance mechanisms that render conventional therapies ineffective. Recently, novel agents have been developed that target regulators of differential energy pathways specifically utilized by gliomas. We previously reported on the targeting of Nicotinamide Phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway and its essential role in glioma cell energy metabolism. Here, we determined the mechanisms by which glioma cells bypass blockade of energy metabolism and develop resistance to NAMPT inhibitors. METHODS Using isogenic parental and drug-resistant patient-derived glioma stem-like cells (GSCs), we examined adaptive changes after NAMPT inhibition in glycolysis, mitochondrial function (oxidative state, basal respiration rate, spare respiratory capacity, maximum respiration capacity and proton leak) and metabolite levels using Agilent Seahorse assay and targeted metabolomics. Cross reactivity across various NAMPT inhibitors was measured using Cell Titer Glo assay. RESULTS GSCs exposed for an extended period to sub-lethal doses of FK866, a potent NAMPT inhibitor, acquired drug resistance to the agent which were also cross-resistant to other NAMPT inhibitors. Drug-resistant GSCs showed a decrease in extracellular acidification rate and oxygen consumption rate compared to isogenic parental lines. Further, metabolomic analysis showed a high accumulation of glutamate, creatine and histidine metabolites in these cells. These results indicate a shift in metabolism of drug-resistant GSCs from carbon metabolism to nitrogen metabolism. CONCLUSIONS GSCs resistant to the NAMPT inhibitor, FK866 showed cross resistance to other NAMPT inhibitors indicating specificity of this effect. The resistance mechanism involves a shift of preferential energy generation from glycolysis to amino acid metabolism which allows the cells to use alternative methods to generate NAD. Additional results from ongoing studies to delineate the mechanisms of metabolic switch in the drug resistance lines will be presented that will help develop strategies to combat resistance to NAMPT inhibitors.

scholarly journals Proof of concept of wastewater treatment via passive aeration SND using a novel zeolite amended biofilm reactor

2018 ◽  
Vol 78 (10) ◽  
pp. 2204-2213 ◽  
Author(s):  
Liang Cheng ◽  
Raphael Marie-Guillaume Flavigny ◽  
Md Iqbal Hossain ◽  
Wipa Charles ◽  
Ralf Cord-Ruwisch
Keyword(s):  
Oxygen Supply ◽  
Energy Requirement ◽  
Operation Mode ◽  
High Energy ◽  
Biofilm Reactor ◽  
Low Energy ◽  
Treated Wastewater ◽  
Synthetic Wastewater ◽  
Bulk Solution ◽  
Nutrient Removal Efficiency

Abstract The current paper describes a novel passive aeration simultaneous nitrification and denitrification (PASND) zeolite amended biofilm reactor that removes organic carbon and nitrogen from wastewater with low-energy consumption. Next to the ammonium oxidizing bacteria (AOB), this reactor contained naturally enriched glycogen accumulating organisms (GAOs) and zeolite powder to initially adsorb BOD (acetate) and ammonium (NH4+-N) from synthetic wastewater under anaerobic conditions. Draining of the treated wastewater exposed the biofilm directly to air enabling low-energy oxygen supply by passive aeration. This allowed the adsorbed ammonium to be oxidized by the AOB and the produced nitrite and nitrate to be reduced simultaneously by the GAOs using the adsorbed BOD (stored as PHAs) as carbon source. Overall, with an operation mode of 1 h anaerobic and 4 h aerobic phase, the nutrient removal efficiency after single treatment was about 94.3% for BOD and 72.2% for nitrogen (NH4+-N). As high-energy aeration of the bulk solution for oxygen supply is completely avoided, the energy requirement of the proposed PASND biofilm reactor can be theoretically cut down to more than 50% compared to the traditional activated sludge process.

Fatty acid, tricarboxylic acid cycle metabolites, and energy metabolism in vascular smooth muscle

1994 ◽  
Vol 267 (2) ◽  
pp. H764-H769 ◽  
Author(s):  
J. T. Barron ◽  
S. J. Kopp ◽  
J. Tow ◽  
J. E. Parrillo
Keyword(s):  
Smooth Muscle ◽  
Fatty Acid ◽  
Energy Metabolism ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Lactate Production ◽  
Tca Cycle ◽  
High Energy ◽  
Tricarboxylic Acid ◽  
O2 Consumption

The influence of octanoate on O2 consumption, tricarboxylic acid (TCA) cycle intermediates, and high-energy phosphates was examined in intact resting porcine carotid artery to investigate the role of fatty acid in energy metabolism and its integration with glucose metabolism in vascular smooth muscle. Incubation of resting arteries with octanoate (0.5 mM), which was previously shown to inhibit aerobic glycolysis (6), inhibited lactate production by 64% and increased O2 consumption by 30%. The increase in O2 consumption with octanoate was approximately equal to that calculated to account for the ATP production lost by inhibition of aerobic lactate production by octanoate. In glucose-free medium, the level of high-energy phosphate was reduced but was restored when octanoate was included in the incubation medium. This was associated with an increase in O2 consumption. These results suggest that the energy requirements of resting carotid artery can be largely met by the oxidative metabolism of fatty acid. Octanoate induced anaplerosis of the TCA cycle, as indicated by a 70% increase in the level of citrate. Extracellular glucose was necessary for octanoate-induced anaplerosis, probably by providing the extra carbon via pyruvate carboxylation, whereas a coupled transamination involving aspartate was a less important anaplerotic mechanism.

scholarly journals Genomic and phenotypic characterization of experimentally selected resistant Leishmania donovani reveals a role for dynamin-1 like protein in the mechanism of resistance to a novel anti-leishmanial compound

2021 ◽  
Author(s):  
Aya Hefnawy ◽  
Gabriel Negreira ◽  
Marlene Jara ◽  
James A. Cotton ◽  
Ilse Maes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Visceral Leishmaniasis ◽  
Infectious Diseases ◽  
Leishmania Donovani ◽  
Neglected Tropical Diseases ◽  
Arms Race ◽  
Etiological Agent ◽  
Phenotypic Characterization ◽  
Tropical Diseases

AbstractThe implementation of prospective drug resistance (DR) studies in the R&D pipelines is a common practice for many infectious diseases, but not for Neglected Tropical Diseases. Here, we explored and demonstrated the importance of this approach, using as paradigms Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL. We experimentally selected resistance to TCMDC-143345 in vitro and characterized resistant parasites at genomic and phenotypic levels. We found that it took more time to develop resistance to TCMDC-143345 than to other drugs in clinical use and that there was no cross resistance to these drugs, suggesting a new and unique mechanism. By whole genome sequencing, we found two mutations in the gene encoding the L. donovani dynamin-1-like protein (LdoDLP1) that were fixed at highest drug pressure. Through phylogenetic analysis, we identified LdoDLP1 as a family member of the dynamin-related proteins, a group of proteins that impacts the shapes of biological membranes by mediating fusion and fission events, with a putative role in mitochondrial fission. We found that L. donovani lines genetically engineered to harbor the two identified LdoDLP1 mutations were resistant to TCMDC-143345 and displayed altered mitochondrial properties. By homology modeling, we showed how the two LdoDLP1 mutations may influence protein structure and function. Taken together, our data reveal a clear involvement of LdoDLP1 in the adaptation/resistance of L. donovani to TCMDC-143345.ImportanceHumans and their pathogens are continuously locked in a molecular arms race during which the eventual emergence of pathogen drug resistance (DR) seems inevitable. For neglected tropical diseases (NTDs), DR is generally studied retrospectively, once it has already been established in clinical settings. We previously recommended to keep one step ahead in the host-pathogen arms race and implement prospective DR studies in the R&D pipeline, a common practice for many infectious diseases, but not for NTDs. Here, using Leishmania donovani, the etiological agent of Visceral Leishmaniasis (VL), and TCMDC-143345, a promising compound of the GSK ‘Leishbox’ to treat VL, as paradigms, we experimentally selected resistance to the compound and proceeded to genomic and phenotypic characterization of DR parasites. The results gathered in the present study suggest a new DR mechanism involving the L. donovani dynamin-1 like protein (LdoDLP1) and demonstrate the practical relevance of prospective DR studies.

scholarly journals Assessment of Physical, Microstructural, Thermal, Techno-Functional, And Rheological Characteristics of Apple (Malus Domestica) Seeds of Northern Himalayas

2021 ◽  
Author(s):  
Mehnaza Manzoor ◽  
Jagmohan Singh
Keyword(s):  
Energy Requirement ◽  
Geometric Mean ◽  
High Energy ◽  
Particle Size Analysis ◽  
Absorption Capacity ◽  
Size Analysis ◽  
Scanning Electron Micrographs ◽  
Seed Flour ◽  
Mean Diameter ◽  
Golden Delicious

Abstract The study examined the physical, morphological, thermal, techno-functional, and rheological properties of two apple seed cultivars viz: red delicious (RD) and golden delicious (GD). Physical properties showed that red delicious seeds were significantly (p≤0.05) different in width, geometric mean diameter, arithmetic mean diameter, volume, and surface area than golden delicious seeds. The proximate composition of RD seed flour showed a higher amount of crude protein and fat content than GD seed flour. RD seed flour was significantly different in L*, a*, b* values, bulk density, water/oil absorption capacity and the emulsifying ability than GD seed flour. From particle size analysis it was possible to found that GD was significantly (p≤0.05) lower than RD flour macromolecules. Scanning electron micrographs showed oval/spherical starch granules of small size embedded in a continuous protein matrix. Thermograph revealed exothermic transition enthalpy for both RD and GD seed flour, which indicates a high energy requirement for crystallite melting. The rheological assays revealed high elastic modulus (G′), of seed flours that will help in modifying the texture of foods. This study suggests the potential of apple seeds in the formulation of protein-enriched foods to combat malnutrition while contributing to the reduction in industrial wastage.

Reversal of mitochondrial swelling associated with fatty acid oxidation. II. Effects of cytochrome c and carnitine on contraction of fatty acid swollen mitochondria

1968 ◽  
Vol 46 (9) ◽  
pp. 1151-1160 ◽  
Author(s):  
Misako Nakatani ◽  
W. C. McMurray
Keyword(s):  
Fatty Acid ◽  
Cytochrome C ◽  
Energy Requirement ◽  
Liver Mitochondria ◽  
High Energy ◽  
Fatty Acyl ◽  
Water Soluble ◽  
Rat Liver Mitochondria ◽  
Acid Oxidation ◽  
Swelling Agent

Rat liver mitochondria undergo reversible swelling in the presence of a fatty acyl CoA generating system. Contraction of the swollen mitochondria was observed on the addition of either carnitine or cytochrome c. At low concentrations the two agents acted synergistically. At high concentrations cytochrome c completely replaced the requirement for carnitine.Cytochrome c also promoted the contraction of mitochondria swollen in the presence of fatty acid alone, provided that either ATP or ADP was added to initiate the contraction. The stimulation by cytochrome c was greater in the presence of ADP, and the contraction was more sensitive to respiratory inhibitors or dinitrophenol but was less sensitive to oligomycin than in the presence of ATP. Studies of the metabolism of 14C-labelled palmitate during cytochrome c induced contraction showed that decreases in mitochondrial-bound fatty acid and corresponding increases in water-soluble metabolites coincided with the reversal of swelling. The results indicated that the energy requirement for mitochondrial contraction in the presence of cytochrome c was provided by generation of high-energy intermediates coupled to oxidation of the fatty acid swelling agent.

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