scholarly journals Etiology of lactic acidosis in malaria

2021 ◽  
Vol 17 (1) ◽  
pp. e1009122
Author(s):  
Hendrik Possemiers ◽  
Leen Vandermosten ◽  
Philippe E. Van den Steen
Keyword(s):  
Kidney Disease ◽  
Lactic Acidosis ◽  
Immune Cells ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Lactate Clearance ◽  
Anaerobic Glycolysis ◽  
Metabolic Disturbances ◽  
Multiple Factors ◽  
Liver And Kidney

Lactic acidosis and hyperlactatemia are common metabolic disturbances in patients with severe malaria. Lactic acidosis causes physiological adverse effects, which can aggravate the outcome of malaria. Despite its clear association with mortality in malaria patients, the etiology of lactic acidosis is not completely understood. In this review, the possible contributors to lactic acidosis and hyperlactatemia in patients with malaria are discussed. Both increased lactate production and impaired lactate clearance may play a role in the pathogenesis of lactic acidosis. The increased lactate production is caused by several factors, including the metabolism of intraerythrocytic Plasmodium parasites, aerobic glycolysis by activated immune cells, and an increase in anaerobic glycolysis in hypoxic cells and tissues as a consequence of parasite sequestration and anemia. Impaired hepatic and renal lactate clearance, caused by underlying liver and kidney disease, might further aggravate hyperlactatemia. Multiple factors thus participate in the etiology of lactic acidosis in malaria, and further investigations are required to fully understand their relative contributions and the consequences of this major metabolic disturbance.

AEROBIC GLYCOLYSIS OF X-IRRADIATED THYMOCYTES

1963 ◽  
Vol 41 (1) ◽  
pp. 2157-2169 ◽  
Author(s):  
Kimiko Araki ◽  
D. K. Myers
Keyword(s):  
Lactic Acid ◽  
Cell Damage ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Metabolic Inhibitors ◽  
Anaerobic Glycolysis ◽  
Acid Accumulation ◽  
X Irradiation ◽  
Thymus Cells ◽  
Rate Of Accumulation

The aerobic lactate production of rat thymocyte suspensions incubated at 37 °C for 2 hours was doubled following exposure to approximately 70 r X-radiation. Lower doses down to 18 r also produced a significant increase in aerobic lactate production. Increased lactate accumulation following exposure to 1000 r was observed after incubation for as little as 30–60 minutes, though the rate of accumulation increased still further between 2 and 4 hours incubation. A decrease in pH or temperature during incubation of irradiated thymocyte suspensions minimized the lactic acid accumulation. A comparison of the effects of X-irradiation in different media and of the effects of several metabolic inhibitors suggested that the increase in aerobic lactate production was a sensitive indicator of cell damage associated with the loss of intracellular potassium ions.Respiration and anaerobic glycolysis of the thymus cells were both much less sensitive than aerobic glycolysis to the effects of X-irradiation. The "anaerobic" lactate production of rat thymocyte suspensions in the presence of dinitrophenol was reduced by 50% after exposure to 5000–6000 r of X-radiation.

scholarly journals Lactic acidosis in the practice of a resuscitator

2020 ◽  
Vol 17 (3) ◽  
pp. 95-100
Author(s):  
V. V. Skvortsov ◽  
E. M. Skvortsova ◽  
R. Yu. Bangarov
Keyword(s):  
Differential Diagnosis ◽  
Critical Care ◽  
Lactic Acidosis ◽  
Critically Ill ◽  
Care Setting ◽  
Lactate Production ◽  
Lactate Clearance ◽  
Current Review ◽  
Lactate Levels ◽  
Elevated Lactate

The objective: to analyze literature and to compile the most accurate and complete view of lactic acidosis and specific parameters of its treatment in anesthesiology and resuscitation practice. Result. Lactate levels are commonly evaluated in critically ill patients. Hyperlactatemia is defined as a lactate level >2 mmol/L and it is common in the critical care setting. Hyperlactatemia and lactic acidosis may develop due to increase in lactate production, a decrease in lactate clearance, or a combination of both. The current review provides an overview of pathophysiology of lactate elevation followed by analysis of different etiologies of hyperlactatemia in critically ill patients.Additionally, approach to differential diagnosis and treatment of elevated lactate levels in this category of patients is discussed.

AEROBIC GLYCOLYSIS OF X-IRRADIATED THYMOCYTES

1963 ◽  
Vol 41 (10) ◽  
pp. 2157-2169 ◽  
Author(s):  
Kimiko Araki ◽  
D. K. Myers
Keyword(s):  
Lactic Acid ◽  
Cell Damage ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Metabolic Inhibitors ◽  
Anaerobic Glycolysis ◽  
Acid Accumulation ◽  
X Irradiation ◽  
Thymus Cells ◽  
Rate Of Accumulation

The aerobic lactate production of rat thymocyte suspensions incubated at 37 °C for 2 hours was doubled following exposure to approximately 70 r X-radiation. Lower doses down to 18 r also produced a significant increase in aerobic lactate production. Increased lactate accumulation following exposure to 1000 r was observed after incubation for as little as 30–60 minutes, though the rate of accumulation increased still further between 2 and 4 hours incubation. A decrease in pH or temperature during incubation of irradiated thymocyte suspensions minimized the lactic acid accumulation. A comparison of the effects of X-irradiation in different media and of the effects of several metabolic inhibitors suggested that the increase in aerobic lactate production was a sensitive indicator of cell damage associated with the loss of intracellular potassium ions.Respiration and anaerobic glycolysis of the thymus cells were both much less sensitive than aerobic glycolysis to the effects of X-irradiation. The "anaerobic" lactate production of rat thymocyte suspensions in the presence of dinitrophenol was reduced by 50% after exposure to 5000–6000 r of X-radiation.

scholarly journals PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Mao ◽  
Xiaoweng Wu ◽  
Zhengpeng Gong ◽  
Ming Yu ◽  
Zhi Huang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Expression Pattern ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Control Group

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.

scholarly journals Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Jin ◽  
Eun-Yeong Kim ◽  
Tae-Wook Chung ◽  
Chang Woo Han ◽  
So Young Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cancer Drug ◽  
Potential Candidate ◽  
Mitochondrial Ros

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

scholarly journals Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3018
Author(s):  
Marek Samec ◽  
Alena Liskova ◽  
Lenka Koklesova ◽  
Kevin Zhai ◽  
Elizabeth Varghese ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Effective Prevention ◽  
Anti Cancer ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

scholarly journals Remodeling of Cancer-Specific Metabolism under Hypoxia with Lactate Calcium Salt in Human Colorectal Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1518
Author(s):  
Keun-Yeong Jeong ◽  
Jae-Jun Sim ◽  
Min Hee Park ◽  
Hwan Mook Kim
Keyword(s):  
Colorectal Cancer ◽  
Intracellular Calcium ◽  
Cancer Cells ◽  
Calcium Salt ◽  
Lactate Production ◽  
Tca Cycle ◽  
Anaerobic Glycolysis ◽  
Human Colorectal Cancer ◽  
Antitumor Effects ◽  
Enzymatic Activation

Hypoxic cancer cells meet their growing energy requirements by upregulating glycolysis, resulting in increased glucose consumption and lactate production. Herein, we used a unique approach to change in anaerobic glycolysis of cancer cells by lactate calcium salt (CaLac). Human colorectal cancer (CRC) cells were used for the study. Intracellular calcium and lactate influx was confirmed following 2.5 mM CaLac treatment. The enzymatic activation of lactate dehydrogenase B (LDHB) and pyruvate dehydrogenase (PDH) through substrate reaction of CaLac was investigated. Changes in the intermediates of the tricarboxylic acid (TCA) cycle were confirmed. The cell viability assay, tube formation, and wound-healing assay were performed as well as the confirmation of the expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). In vivo antitumor effects were evaluated using heterotopic and metastatic xenograft animal models with 20 mg/kg CaLac administration. Intracellular calcium and lactate levels were increased following CaLac treatment in CRC cells under hypoxia. Then, enzymatic activation of LDHB and PDH were increased. Upon PDH knockdown, α-ketoglutarate levels were similar between CaLac-treated and untreated cells, indicating that TCA cycle restoration was dependent on CaLac-mediated LDHB and PDH reactivation. CaLac-mediated remodeling of cancer-specific anaerobic glycolysis induced destabilization of HIF-1α and a decrease in VEGF expression, leading to the inhibition of the migration of CRC cells. The significant inhibition of CRC growth and liver metastasis by CaLac administration was confirmed. Our study highlights the potential utility of CaLac supplementation in CRC patients who display reduced therapeutic responses to conventional modes owing to the hypoxic tumor microenvironment.

Anaerobic Glycolysis in Normal Human Erythrocytes Incubated in Vitro with Sodium Salicylate

1975 ◽  
Vol 49 (5) ◽  
pp. 375-384
Author(s):  
N. Worathumrong ◽  
A. J. Grimes
Keyword(s):  
Sodium Salicylate ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Human Erythrocytes ◽  
Anaerobic Glycolysis ◽  
Initial Stimulus ◽  
Sodium Efflux ◽  
Normal Human ◽  
Concentration Changes

1. Some effects of sodium salicylate upon anaerobic glycolysis have been studied in normal human erythrocytes incubated for up to 6 h at 37°C in autologous sera. 2. Both glucose consumption and lactate production were stimulated by concentrations of salicylate up to 60 mmol/l but at the highest concentration used (90 mmol/l) an initial stimulus was followed by inhibition of glycolysis. 3. Losses occurred of adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP) and adenosine 5′-phosphate (AMP) at higher concentrations of salicylate and there was a concomitant increase of inorganic phosphate. 4. Other phosphate esters underwent concentration changes at higher concentrations of salicylate that reflected inadequate concentrations of ATP for glycolysis. 5. The rates of sodium efflux from, and potassium influx into, erythrocytes were unaffected by the presence of salicylate at concentrations sufficient to stimulate glycolysis.

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