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Journal of Human Kinetics Dec 2018The aim of this study was to investigate the effect of ingesting sodium bicarbonate (SB) and sodium citrate (SC) on 400 m high-intensity swimming performance and blood...
The aim of this study was to investigate the effect of ingesting sodium bicarbonate (SB) and sodium citrate (SC) on 400 m high-intensity swimming performance and blood responses. Six nationally ranked male swimmers (20.7 ± 2.1 yrs; 184 ± 6 cm; 79.9 ± 3.9 kg; 10.6 ± 1% body fat) participated in a double blinded, placebo controlled crossover trial. Ninety minutes after consuming SB (0.3 g·kg), SC (0.3 g·kg) or a placebo (PL) participants completed a single 400-m freestyle maximal test on three consecutive days. The order of the supplementation was randomized. Capillary blood samples were collected on 4 occasions: at rest (baseline), 60 min post-ingestion, immediately post-trial and 15 min post-trial. Blood pH, HCO concentration and base excess (BE) were determined. Blood pH, HCO, BE were significantly elevated from before loading to the pre-test (60 min post-ingestion) (p < 0.05) after SB ingestion, but not after SC ingestion (p > 0.05). Performance times were improved by 0.6% (p > 0.05) after supplementation of SB over PL in 5 out of 6 participants (responders). In contrast, ingestion of SC decreased performance by 0.2% (p > 0.05). No side effects were observed in either trial. Delayed blood response was observed after SC ingestion compared to SB and this provided no or modest ergogenic effect, respectively, for single bout high-intensity swimming exercise. Monitoring the magnitude of the time-to-peak level rise in alkalosis may be recommended in order to individualize the loading time accordingly before commencement of exercise.
PubMed: 30687422
DOI: 10.2478/hukin-2018-0022 -
MSphere Oct 2023Mycobacteria can colonize environments where the availability of metal ions is limited. Biological or inorganic chelators play an important role in limiting metal...
Mycobacteria can colonize environments where the availability of metal ions is limited. Biological or inorganic chelators play an important role in limiting metal availability, and we developed a model to examine survival in the presence of the chelator sodium citrate. We observed that instead of restricting growth, concentrated sodium citrate killed . RNAseq analysis during sodium citrate treatment revealed transcriptional signatures of metal starvation and hyperosmotic stress. Notably, metal starvation and hyperosmotic stress, individually, do not kill under these conditions. A forward genetic transposon selection was conducted to examine why sodium citrate was lethal, and several sodium-citrate-tolerant mutants were isolated. Based on the identity of three tolerant mutants, , , and we propose a dual stress model of killing by sodium citrate, where sodium citrate chelate metals from the cell envelope and then osmotic stress in combination with a weakened cell envelope causes cell lysis. This sodium citrate tolerance screen identified mutants in several other genes with no known function, with most conserved in the pathogen . Therefore, this model will serve as a basis to define their functions, potentially in maintaining cell wall integrity, cation homeostasis, or osmotolerance. IMPORTANCE Bacteria require mechanisms to adapt to environments with differing metal availability. When is treated with high concentrations of the metal chelator sodium citrate, the bacteria are killed. To define the mechanisms underlying killing by sodium citrate, we conducted a genetic selection and observed tolerance to killing in mutants of the magnesium transporter. Further characterization studies support a model where killing by sodium citrate is driven by a weakened cell wall and osmotic stress, that in combination cause cell lysis.
Topics: Mycobacterium smegmatis; Sodium Citrate; Osmotic Pressure; Mycobacterium tuberculosis; Homeostasis; Cations; Chelating Agents
PubMed: 37681985
DOI: 10.1128/msphere.00358-23 -
Biochemical and Biophysical Research... Jun 2016Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition...
3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.
Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Citrates; Gastric Mucosa; Glycolysis; Humans; Mitochondria; Pyruvates; Sodium Citrate; Stomach; Stomach Neoplasms
PubMed: 27163639
DOI: 10.1016/j.bbrc.2016.04.151 -
Frontiers in Nutrition 2018Blood alkalosis, as indicated by an increased blood bicarbonate concentration and pH, has been shown to be beneficial for exercise performance. Sodium bicarbonate,... (Review)
Review
Blood alkalosis, as indicated by an increased blood bicarbonate concentration and pH, has been shown to be beneficial for exercise performance. Sodium bicarbonate, sodium citrate, and sodium or calcium lactate, can all result in increased circulating bicarbonate and have all independently been shown to improve exercise capacity and performance under various circumstances. Although there is considerable evidence demonstrating the efficacy of these supplements in several sports-specific situations, it is commonly acknowledged that their efficacy is equivocal, due to contrasting evidence. Herein, we discuss the physiological and environmental factors that may modify the effectiveness of these supplements including, (i) absolute changes in circulating bicarbonate; (ii) supplement timing, (iii) the exercise task performed, (iv) monocarboxylate transporter (MCT) activity; (v) training status, and (vi) associated side-effects. The aim of this narrative review is to highlight the factors which may modify the response to these supplements, so that individuals can use this information to attempt to optimize supplementation and allow the greatest possibility of an ergogenic effect.
PubMed: 29868599
DOI: 10.3389/fnut.2018.00035 -
International Journal of Molecular... Dec 2022The aim of this paper is to provide a simple and efficient photoassisted approach to synthesize silver nanoparticles, and to elucidate the role of the key factors...
The aim of this paper is to provide a simple and efficient photoassisted approach to synthesize silver nanoparticles, and to elucidate the role of the key factors (synthesis parameters, such as the concentration of TSC, irradiation time, and UV intensity) that play a major role in the photochemical synthesis of silver nanoparticles using TSC, both as a reducing and stabilizing agent. Concomitantly, we aim to provide an easy way to evaluate the particle size based on Mie theory. One of the key advantages of this method is that the synthesis can be "activated" whenever or wherever silver nanoparticles are needed, by premixing the reactants and irradiating the final solution with UV radiation. UV irradiance was determined by using Keitz's theory. This argument has been verified by premixing the reagents and deposited them in an enclosed space (away from sunlight) at 25 °C, then checking them for three days. Nothing happened, unless the sample was directly irradiated by UV light. Further, obtained materials were monitored for 390 days and characterized using scanning electron microscopy, UV-VIS, and transmission electron microscopy.
Topics: Metal Nanoparticles; Sodium Citrate; Silver; Microscopy, Electron, Transmission; Ultraviolet Rays
PubMed: 36613702
DOI: 10.3390/ijms24010255 -
Journal of Fungi (Basel, Switzerland) Mar 2023Methanol, which produced in large quantities from low-quality coal and the hydrogenation of CO, is a potentially renewable one-carbon (C1) feedstock for...
Methanol, which produced in large quantities from low-quality coal and the hydrogenation of CO, is a potentially renewable one-carbon (C1) feedstock for biomanufacturing. The methylotrophic yeast is an ideal host for methanol biotransformation given its natural capacity as a methanol assimilation system. However, the utilization efficiency of methanol for biochemical production is limited by the toxicity of formaldehyde. Therefore, reducing the toxicity of formaldehyde to cells remains a challenge to the engineering design of a methanol metabolism. Based on genome-scale metabolic models (GSMM) calculations, we speculated that reducing alcohol oxidase (AOX) activity would re-construct the carbon metabolic flow and promote balance between the assimilation and dissimilation of formaldehyde metabolism processes, thereby increasing the biomass formation of . According to experimental verification, we proved that the accumulation of intracellular formaldehyde can be decreased by reducing AOX activity. The reduced formaldehyde formation upregulated methanol dissimilation and assimilation and the central carbon metabolism, which provided more energy for the cells to grow, ultimately leading to an increased conversion of methanol to biomass, as evidenced by phenotypic and transcriptome analysis. Significantly, the methanol conversion rate of AOX-attenuated strain PC110-AOX1-464 reached 0.364 g DCW/g, representing a 14% increase compared to the control strain PC110. In addition, we also proved that adding a co-substrate of sodium citrate could further improve the conversion of methanol to biomass in the AOX-attenuated strain. It was found that the methanol conversion rate of the PC110-AOX1-464 strain with the addition of 6 g/L sodium citrate reached 0.442 g DCW/g, representing 20% and 39% increases compared to AOX-attenuated strain PC110-AOX1-464 and control strain PC110 without sodium citrate addition, respectively. The study described here provides insight into the molecular mechanism of efficient methanol utilization by regulating AOX. Reducing AOX activity and adding sodium citrate as a co-substrate are potential engineering strategies to regulate the production of chemicals from methanol in .
PubMed: 37108877
DOI: 10.3390/jof9040422 -
Scientific Reports Jul 2019Mitochondrial respiratory chain complexes II, III, and IV and cytochrome c contain haem, which is generated by the insertion of Fe into protoporphyrin IX....
Mitochondrial respiratory chain complexes II, III, and IV and cytochrome c contain haem, which is generated by the insertion of Fe into protoporphyrin IX. 5-Aminolevulinic acid (ALA) combined with sodium ferrous citrate (SFC) was reported to enhance haem production, leading to respiratory complex and haem oxygenase-1 (HO-1) upregulation. Here, we investigated the effects of different concentrations of ALA and SFC alone or in combination (ALA/SFC) on fibroblasts from 8 individuals with mitochondrial diseases and healthy controls. In normal fibroblasts, expression levels of oxidative phosphorylation (OXPHOS) complex subunits and corresponding genes were upregulated only by ALA/SFC. Additionally, the increased oxygen consumption rate (OCR) and ATP levels in normal fibroblasts were more obvious after treatment with ALA/SFC than after treatment with ALA or SFC. OXPHOS complex proteins were enhanced by ALA/SFC, whereas OCR and ATP levels were increased in 6 of the 8 patient-derived fibroblasts. Further, HO-1 protein and mRNA levels were enhanced by ALA/SFC in all fibroblasts. The relative mtDNA copy number was increased by ALA/SFC. Thus, our findings indicate that ALA/SFC is effective in elevating OXPHOS, HO-1 protein, and mtDNA copy number, resulting in an increase in OCR and ATP levels, which represents a promising therapeutic option for mitochondrial diseases.
Topics: Adenosine Triphosphate; Aminolevulinic Acid; Biosynthetic Pathways; Case-Control Studies; Citric Acid; DNA Copy Number Variations; DNA, Mitochondrial; Female; Ferrous Compounds; Fibroblasts; Heme; Heme Oxygenase-1; Humans; In Vitro Techniques; Infant; Infant, Newborn; Male; Mitochondrial Diseases; Oxidative Phosphorylation; Oxygen Consumption; RNA, Messenger; Sodium Citrate; Up-Regulation
PubMed: 31332208
DOI: 10.1038/s41598-019-46772-x -
Child Neurology Open 2020Mutations in the SLC13A5 gene, a sodium citrate cotransporter, cause a rare autosomal recessive epilepsy (EIEE25) that begins during the neonatal period and is...
Mutations in the SLC13A5 gene, a sodium citrate cotransporter, cause a rare autosomal recessive epilepsy (EIEE25) that begins during the neonatal period and is associated with motor and cognitive impairment. Patient's seizure burden, semiology, and electroencephalography (EEG) findings have not been well characterized. Data on 23 patients, 3 months to 29 years of age are reported. Seizures began during the neonatal period in 22 patients. Although seizures are quite severe in many patients later in life, seizure freedom was attainable in a minority of patients. Multiple patients' chronic seizure management included a few common medications, phenobarbital and valproic acid in particular. Patients EEGs had a relatively well-preserved background for age, even in the face of frequent seizures, little slowing and multiple normal EEGs and do not support an epileptic encephalopathy. Other causes for the motor and cognitive delay beyond epilepsy warrant further study.
PubMed: 32551328
DOI: 10.1177/2329048X20931361 -
Journal of Medical Biochemistry Jan 2020This study aimed to verify whether blood drawn into six different commercial coagulation tubes generated comparable results of thrombin generation.
BACKGROUND
This study aimed to verify whether blood drawn into six different commercial coagulation tubes generated comparable results of thrombin generation.
METHODS
Blood was sequentially collected from 20 healthy subjects into different brand and draw volume 3.2% sodium citrate tubes (4.3 mL Sarstedt, 3.0 mL Greiner, 2.7 mL Becton Dickinson, 2.0 mL Kima, 1.8 mL Sarstedt and 1.0 mL Greiner). Thrombin generation was measured in plasma with the fully-automated ST Genesia analyzer using the weakest trigger (STG-BleedScreen).
RESULTS
Different values of lag time (LT), time to reach thrombin peak (TP), thrombin peak height (PH) and endogenous thrombin potential (ETP) were commonly found in different tubes. Thrombin generation was the lowest in 4.3 mL Sarstedt tubes and the highest in 1.0 mL Greiner tubes. Other tubes displayed intermediate values. In multiple comparisons, LT was significantly different in 6/15 cases (40%), whilst PH, TP and ETP were significantly different in 14/15 (93%), 13/15 (87%) and 13/15 (87%) cases. The mean percent bias of LT, PH, TP and ETP ranged between -6% and +1%, -27% and +116%, -22% and +8%, and between -18% and +65%. The intra-assay imprecision of LT, PH, TP and ETP was exceeded in 0/15 (0%), 13/15 (87%), 6/15 (40%) and 13/15 (87%) comparisons. The correlation of LT, PH, TP and ETP values in different tubes ranged between 0.718-0.971, 0.570-0.966, 0.725-0.977 and 0.101-0.904.
CONCLUSIONS
Blood collection for thrombin generation assays requires local standardization using identical tubes for brand and draw volume, and reference ranges calculated according to type of tubes.
PubMed: 32549773
DOI: 10.2478/jomb-2019-0016 -
Nephrology, Dialysis, Transplantation :... Jul 2009Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of...
BACKGROUND
Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method.
METHODS
During 15 haemodialysis treatments with a calcium-free dialysis solution, citrate was infused pre-dialyser and calcium was substituted post-dialyser. Systemic and extracorporeal citrate and calcium concentrations were repeatedly measured to calculate citrate and calcium pharmacokinetics.
RESULTS
Removal by dialysis constituted the major elimination pathway of citrate (83 +/- 5%). Systemic citrate load and concentrations were low (17 +/- 7 mmol/4 h, 0.3 +/- 0.15 mmol/l). Combined use of calcium-free dialysate and citrate infusion increased diffusible calcium to 80% of total calcium and induced substantial dialytic loss of calcium (43 +/- 4 mmol/4 h). Since calcium was substituted, systemic calcium balances were positive (approximately +5 mmol) and concentrations stable. Calcium supplementation correlated with calcium dialytic losses, which in turn were dependent on total calcium and haematocrit.
CONCLUSIONS
When using calcium-free dialysate during citrate anticoagulation, hypocalcaemia is very likely unless calcium is re-infused, because large amounts of calcium are lost in the dialysate. However, an accumulation of citrate in the patient's systemic circulation is an unlikely cause of hypocalcaemia since most of the citrate is removed by dialysis. Calcium substitution and monitoring are the most important safety measures. We propose a rational approach based on haematocrit and total calcium for the choice of the starting calcium supplementation rate.
Topics: Aged; Anticoagulants; Calcium Chloride; Citrates; Female; Humans; Male; Middle Aged; Renal Dialysis; Sodium Citrate
PubMed: 19196824
DOI: 10.1093/ndt/gfp017