Differential mRNA profiles reveal the potential roles of genes involved in lactate stimulation in mouse macrophages.

Lactate is a glycolysis end product, and its levels are markedly associated with disease severity, morbidity, and mortality in sepsis. It modulates key functions of immune cells, including macrophages. In this investigation, transcriptomic analysis was performed using lactic acid, sodium lactate, and hydrochloric acid-stimulated mouse bone marrow-derived macrophages (iBMDM), respectively, to identify lactate-associated signaling pathways. After 24 h of stimulation, 896 differentially expressed genes (DEG) indicated were up-regulation, whereas 792 were down-regulated in the lactic acid group, in the sodium lactate group, 128 DEG were up-regulated, and 41 were down-regulated, and in the hydrochloric acid group, 499 DEG were up-regulated, and 285 were down-regulated. Subsequently, clinical samples were used to further verify the eight genes with significant differences, among which Tssk6, Ypel4, Elovl3, Trp53inp1, and Cfp were differentially expressed in patients with high lactic acid, indicating their possible involvement in lactic acid-induced inflammation and various physiological diseases caused by sepsis. However, elongation of very long chain fatty acids protein 3 (Elovl3) was negatively correlated with lactic acid content in patients. The results of this study provide a necessary reference for better understanding the transcriptomic changes caused by lactic acid and explain the potential role of high lactic acid in the regulation of macrophages in sepsis.

The synergism of cytosolic acidosis and reduced NAD+/NADH ratio is responsible for lactic acidosis-induced vascular smooth muscle cell impairment in sepsis.

BACKGROUND: During sepsis, serve vascular dysfunctions lead to life-threatening multiple organ failure, due to vascular smooth muscle cells (VSMC) impairments, resulting in vasoplegia, hypotension and hypoperfusion. In addition, septic patients have an altered cell metabolism that leads to lactic acidosis. Septic patients suffering from lactic acidosis have a high risk of mortality. In addition, septic survivors are at risk of secondary vascular disease. The underlying mechanisms of whether and how lactic acidosis leads to the changes in VSMCs is not well understood. The aim of this study was to comprehensively investigate the effect of lactic acidosis on VSMCs and additionally compare the effects with those induced by pure acidosis and sodium lactate. METHODS: Primary human aortic smooth muscle cells (HAoSMCs) were treated for 48 h with lactic acidosis (LA_pH 6.8), hydrochloric acid (HCl_pH 6.8), sodium lactate (Na+-lactate_pH 7.4) and the respective controls (ctrl._pH 7.4; hyperosmolarity control: mannitol_pH 7.4) and comparatively analyzed for changes in (i) transcriptome, (ii) energy metabolism, and (iii) phenotype. RESULTS: Both types of acidosis led to comparable and sustained intracellular acidification without affecting cell viability. RNA sequencing and detailed transcriptome analysis revealed more significant changes for lactic acidosis than for hydrochloric acidosis, with lactate being almost ineffective, suggesting qualitative and quantitative synergism of acidosis and lactate. Bioinformatic predictions in energy metabolism and phenotype were confirmed experimentally. Lactic acidosis resulted in strong inhibition of glycolysis, glutaminolysis, and altered mitochondrial respiration which reduced cellular ATP content, likely due to increased TXNIP expression and altered NAD+/NADH ratio. Hydrochloric acidosis induced significantly smaller effects without changing the NAD+/NADH ratio, with the ATP content remaining constant. These metabolic changes led to osteo-/chondrogenic/senescent transdifferentiation of VSMCs, with the effect being more pronounced in lactic acidosis than in pure acidosis. CONCLUSIONS: Overall, lactic acidosis exerted a much stronger effect on energy metabolism than pure acidosis, whereas lactate had almost no effect, reflecting the qualitative and quantitative synergism of acidosis and lactate. As a consequence, lactic acidosis may lead to acute functional impairments of VSMC, sustained perturbations of the transcriptome and cellular dedifferentiation. Moreover, these effects may contribute to the acute and prolonged vascular pathomechanisms in septic patients.

Use of a compound modifier to retard the quality deterioration of frozen dough and its steamed bread.

To retard the quality deterioration of the dough during frozen storage, the effects of a compound modifier (CM) comprised of sodium stearoyl lactate, VC, and ß-glucanase on the properties of the frozen dough, as well as the quality of the frozen dough steamed bread were investigated. The results revealed that CM restricted the migration of water in the dough and improved its rheological properties. Furthermore, CM minimized the deterioration of specific volume and textural properties, and prevented starch retrogradation in the frozen dough steamed bread. Moreover, the addition of CM strengthened the secondary structure of gluten protein and formed a more resilient gluten network. The microstructure of the frozen dough steamed bread showed that CM reduced the damage caused by ice crystals on the gluten network. Overall, the use of CM strengthened the gluten network and effectively delayed the quality deterioration of the frozen dough, thus is potential as an improver for frozen dough.

Potassium Chloride, Sodium Lactate and Sodium Citrate Impaired the Antimicrobial Resistance and Virulence of Pseudomonas aeruginosa NT06 Isolated from Fish.

Sodium chloride (NaCl) is a commonly used additive in minimally processed fish-based products. The addition of NaCl to fish products and packaging in a modified atmosphere is usually efficient with regard to limiting the occurrence of the aquatic environmental pathogen Pseudomonas aeruginosa. Given the negative effects of excess NaCl in the diet, there is a growing demand to reduce NaCl in food products with safer substituents, but the knowledge of their impact on antibiotic resistant P. aeruginosa is limited. This study aimed to evaluate the physiological and transcriptome characteristics of P. aeruginosa NT06 isolated from fish and to determine the effect of selected concentrations of alternative NaCl compounds (KCl/NaL/NaC) on the P. aeruginosa NT06 virulence phenotype and genotype. In the study, among the isolated microorganisms, P. aeruginosa NT06 showed the highest antibiotic resistance (to ampicillin, ceftriaxone, nalidixic acid, and norfloxacin) and the ability to grow at 4 °C. The Comprehensive Antibiotic Resistance Database (CARD) and the Virulence Factor Database (VFDB) revealed the presence of 24 and 134 gene products assigned to AMR and VF in the P. aeruginosa NT06 transcriptome, respectively. KCl, KCl/NaL and KCl/NaL/NaC inhibited pyocyanin biosynthesis, elastase activity, and protease activity from 40 to 77%. The above virulence phenotypic observations were confirmed via RT-qPCR analyses, which showed that all tested AMR and VF genes were the most downregulated due to KCl/NaL/NaC treatment. In conclusion, this study provides insight into the potential AMR and VF among foodborne P. aeruginosa and the possible impairment of those features by KCl, NaL, and NaC, which exert synergistic effects and can be used in minimally processed fish-based products.

Expansion of carbon source utilization range of Shewanella oneidensis for efficient azo dye wastewater treatment through co-culture with Lactobacillus plantarum.

Shewanella oneidensis has demonstrated excellent potential for azo dye decolorization and degradation. However, in anaerobic environments, S. oneidensis has a narrow carbon source spectrum, which requires additional electron donors, such as sodium lactate. This increases the practical application costs for wastewater treatment. Here, we aimed to expand the carbon source utilization range of S. oneidensis FJAT-2478 by co-culturing it with Lactobacillus plantarum FJAT-7926, leveraging their commensalism relationship to develop a metabolic chain. Results showed that a 1:2 initial ratio of L. plantarum FJAT-7926 to S. oneidensis FJAT-2478 achieved a 97.16% decolorization rate of methyl orange when glucose served as the sole carbon source. This co-culture system achieved a decolorization rate comparable to that obtained using sodium lactate as an electron donor and was significantly higher than that achieved by L. plantarum FJAT-7926 (7.88%) or S. oneidensis FJAT-2478 (6.89%) alone. After undergoing five cycles, the co-culture system continued to exhibit effective decolorization. It was demonstrated that the co-culture system could use common and inexpensive carbon sources, such as starch, molasses, sucrose, and maltose, to decolorize azo dyes. For instance, 100 mg/L methyl orange could be degraded by over 98.05% within 24 h. The results indicated that the degradation rates of methyl orange were higher when L. plantarum was inoculated first, followed by a subsequent inoculation of S. oneidensis after 2 h. The co-culturing of L. plantarum FJAT-7926 and S. oneidensis FJAT-2478 proved to be an effective strategy in treating azo dye wastewater, expanding the potential practical applications of S. oneidensis.

Effects of Sodium Lactate Infusion in Two Girls with Glucose Transporter 1 Deficiency Syndrome.

BACKGROUND: Glucose is an important fuel for the brain. In glucose transporter 1 deficiency syndrome (GLUT1DS), the transport of glucose across the blood-brain barrier is limited. Most individuals with GLUT1DS present with developmental problems, epilepsy, and (paroxysmal) movement disorders, and respond favorably to the ketogenic diet. Similar to ketones, lactate is an alternative energy source for the brain. The aim of this study is to investigate whether intravenous infusion of sodium lactate in children with GLUT1DS has beneficial effects on their epilepsy. METHODS: We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study. RESULTS: Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study. CONCLUSION: This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest.

INTRODUCTION: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA. METHODS: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C. RESULTS: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls. CONCLUSIONS: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

Enhanced extracorporeal carbon dioxide removal by acidification and metabolic control.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) promotes protective ventilation in patients with acute respiratory failure, but devices with high CO2 extraction capacity are required for clinically relevant impact. This study evaluates three novel low-flow techniques based on dialysate acidification, also combined with renal replacement therapy, and metabolic control. METHODS: Eight swine were connected to a low-flow (350 mL/min) extracorporeal circuit including a dialyzer with a closed-loop dialysate circuit, and two membrane lungs on blood (MLb) and dialysate (MLd), respectively. The following 2-hour steps were performed: 1) MLb-start (MLb ventilated); 2) MLbd-start (MLb and MLd ventilated); 3) HLac (lactic acid infusion before MLd); 4) HCl-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate); 5) HCl-ßHB-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate and sodium 3-hydroxybutyrate). Caloric and fluid inputs, temperature, blood glucose and arterial carbon dioxide pressure were kept constant. RESULTS: The total MLs CO2 removal in HLac (130±25 mL/min), HCl-NaLac (130±21 mL/min) and HCl-ßHB-NaLac (124±18 mL/min) were higher compared with MLbd-start (81±15 mL/min, P<0.05) and MLb-start (55±7 mL/min, P<0.05). Minute ventilation in HLac (4.3±0.9 L/min), HCl-NaLac (3.6±0.8 L/min) and HCl-ßHB-NaLac (3.6±0.8 L/min) were lower compared to MLb-start (6.2±1.1 L/min, P<0.05) and MLbd-start (5.8±2.1 L/min, P<0.05). Arterial pH was 7.40±0.03 at MLb-start and decreased only during HCl-ßHB-NaLac (7.35±0.03, P<0.05). No relevant changes in electrolyte concentrations, hemodynamics and significant adverse events were detected. CONCLUSIONS: The three techniques achieved a significant extracorporeal CO2 removal allowing a relevant reduction in minute ventilation with a sufficient safety profile.

Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells.

Introduction: CD8+ T cells infiltrate virtually every tissue to find and destroy infected or mutated cells. They often traverse varying oxygen levels and nutrient-deprived microenvironments. High glycolytic activity in local tissues can result in significant exposure of cytotoxic T cells to the lactate metabolite. Lactate has been known to act as an immunosuppressor, at least in part due to its association with tissue acidosis. Methods: To dissect the role of the lactate anion, independently of pH, we performed phenotypical and metabolic assays, high-throughput RNA sequencing, and mass spectrometry, on primary cultures of murine or human CD8+ T cells exposed to high doses of pH-neutral sodium lactate. Results: The lactate anion is well tolerated by CD8+ T cells in pH neutral conditions. We describe how lactate is taken up by activated CD8+ T cells and can displace glucose as a carbon source. Activation in the presence of sodium lactate significantly alters the CD8+ T cell transcriptome, including the expression key effector differentiation markers such as granzyme B and interferon-gamma. Discussion: Our studies reveal novel metabolic features of lactate utilization by activated CD8+ T cells, and highlight the importance of lactate in shaping the differentiation and activity of cytotoxic T cells.

Comparative Study on the Sensing Kinetics of Carbon and Nitrogen Nutrients in Cancer Tissues and Normal Tissues Based Electrochemical Biosensors.

In this study, an electrochemical sensor was developed by immobilizing colon cancer and the adjacent tissues (peripheral healthy tissues on both sides of the tumor) and was used to investigate the receptor sensing kinetics of glucose, sodium glutamate, disodium inosinate, and sodium lactate. The results showed that the electrical signal triggered by the ligand-receptor interaction presented hyperbolic kinetic characteristics similar to the interaction of an enzyme with its substrate. The results indicated that the activation constant values of the colon cancer tissue and adjacent tissues differed by two orders of magnitude for glucose and sodium glutamate and around one order of magnitude for disodium inosinate. The cancer tissues did not sense sodium lactate, whereas the adjacent tissues could sense sodium lactate. Compared with normal cells, cancer cells have significantly improved nutritional sensing ability, and the improvement of cancer cells' sensing ability mainly depends on the cascade amplification of intracellular signals. However, unlike tumor-adjacent tissues, colon cancer cells lose the ability to sense lactate. This provides key evidence for the Warburg effect of cancer cells. The methods and results in this study are expected to provide a new way for cancer research, treatment, the screening of anticancer drugs, and clinical diagnoses.

Changes in nutrient consumption patterns of Lactobacillus fermentum mediated by sodium lactate.

BACKGROUND: During high-cell-density culture of Lactobacillus fermentum, the optimal pH is often maintained by adding NaOH. During cultivation at controlled pH, L. fermentum experiences osmotic stress due to the continuous accumulation of sodium lactate as a neutralizer product, affecting its survival in subsequent processing. The purpose of this study was to evaluate the nutrient consumption patterns of L. fermentum ATCC 14931 under sodium lactate stress and to screen nutrients that help it resist osmotic stress. RESULTS: The consumption and consumption rates of amino acids, purines, pyrimidines, vitamins, and metal ions were analyzed in chemically defined media containing 0.13, 0.31, or 0.62 mm L-1 sodium lactate. The highest consumption rates were found for arginine, guanine, folic acid, and Mn2+ , and the most consumed nutrients were glutamate + glutamine, guanine, ascorbic acid, and Na+ . Arginine 2.58 mm L-1 , guanine 0.23 mm L-1 , and Mn2+ 0.25 mm L-1 were added to the medium at sodium lactate concentrations of 0.13 and 0.62 mm L-1 , and arginine 2.58 mm L-1 , guanine 0.26 mm L-1 , and Mn2+ 0.25 mm L-1 at a sodium lactate concentration of 0.31 mm L-1 . The viable cell counts of L. fermentum ATCC 14931 were approximately 1.02-fold (P < 0.05) of the counts observed in control medium at all three concentrations of sodium lactate. CONCLUSION: The present results suggest that certain nutrients accelerate the growth of L. fermentum under sodium lactate stress and enhance its resistance to this adverse condition. © 2022 Society of Chemical Industry.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Observation on the effectiveness and safety of sodium bicarbonate Ringer's solution in the early resuscitation of traumatic hemorrhagic shock: a clinical single-center prospective randomized controlled trial.

BACKGROUND: Traumatic hemorrhagic shock (THS) is the main cause of death in trauma patients with high mortality. Rapid control of the source of bleeding and early resuscitation are crucial to clinical treatment. Guidelines recommend isotonic crystal resuscitation when blood products are not immediately available. However, the selection of isotonic crystals has been controversial. Sodium bicarbonate Ringer solutions (BRS), containing sodium bicarbonate, electrolyte levels, and osmotic pressures closer to plasma, are ideal. Therefore, in this study, we will focus on the effects of BRS on the first 6 h of resuscitation, complications, and 7-day survival in patients with THS. METHODS: /design. This single-center, prospective, randomized controlled trial will focus on the efficacy and safety of BRS in early THS resuscitation. A total of 400 adults THS patients will be enrolled in this study. In addition to providing standard care, enrolled patients will be randomized in a 1:1 ratio to receive resuscitation with BRS (test group) or sodium lactate Ringer's solution (control group) until successful resuscitation from THS. Lactate clearance at different time points (0.5, 1, 1.5, 3, and 6 h) and shock duration after drug administration will be compared between the two groups as primary end points. Secondary end points will compare coagulation function, temperature, acidosis, inflammatory mediator levels, recurrence of shock, complications, medication use, and 7-day mortality between the two groups. Patients will be followed up until discharge or 7 days after discharge. DISCUSSION: At present, there are still great differences in the selection of resuscitation fluids, and there is a lack of systematic and detailed studies to compare and observe the effects of various resuscitation fluids on the effectiveness and safety of early resuscitation in THS patients. This trial will provide important clinical data for resuscitation fluid selection and exploration of safe dose of BRS in THS patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100045044. Registered on 4 April 2021.

Addition of carbon sources and nutrient salts can inhibit gangue acidification by changing microbial community structure.

Acidic pollution from gangue oxidation has become a primary environmental problem in coal mining areas in China. The use of microorganisms to remediate acidic pollution in coal gangue piles has been indicated to be effective, but environmental differences and carbon sources in different mining areas have become important factors restricting microbial activity. Instead of the addition of new functional bacteria to gangue piles, carbon sources and nutrient salts were added to recently discharged gangue to enhance the activity of beneficial bacteria in the indigenous microbial community. The changes in pH and electrical conductivity (EC) of the gangue leachate as well as the composition and abundance of the functional microbial community on the surface of the gangue were analyzed by leaching simulation experiments and 16S rRNA sequencing. The results showed that the addition of a carbon source maintained the pH of the gangue leachate at 6.31~6.65 in 14 d, which was significantly higher than that of the control group, but the pH of the leachate decreased significantly after the addition of the carbon source was stopped. The most effective treatment is adding a low concentration of nutrient salt (20% concentration) and sodium lactate (0.02 g/L) to the gangue first, and then adding sodium lactate (0.1 mg/L) every 7 days. The addition of carbon sources and nutrient salts changed the microbial community composition on the surface of the gangue, and the species diversity index decreased. The dominant genera in the experimental group were Listeria, Arthrobacter, and Enterococcus. The functional gene types in the experimental and control groups were almost the same, but their relative abundance changed. The abundance of functional genes related to the sulfur cycle increased substantially in the experimental group, and the abundance of genes involved in the nitrogen and carbon cycles also increased, albeit to different degrees.

Lactate infusion as therapeutical intervention: a scoping review.

Traditionally, clinicians consider lactate as a waste product of anaerobic glycolysis. Interestingly, research has shown that lactate may serve as an alternative fuel for the brain to protect it against harm. The increasing scientific awareness of the potential beneficial side of lactate, however, is entering the clinic rather slowly. Following this, and realizing that the application of potential novel therapeutic strategies in pediatric populations often lags behind the development in adults, this review summarizes the key data on therapeutic use of intravenous infusion of sodium lactate in humans. PubMed and clinicaltrial.gov were searched up until November 2021 focusing on interventional studies in humans. Thirty-four articles were included in this review, with protocols of lactate infusion in adults with diabetes mellitus, traumatic brain injury, Alzheimer's disease, and cardiac disease. One study on lactate infusion in children was also included. Results of our literature search show that sodium lactate can be safely administrated, without major side effects. Additionally, the present literature clearly shows the potential benefits of therapeutic lactate infusion under certain pathological circumstances, including rather common clinical conditions like traumatic brain injury. CONCLUSION: This review shows that lactate is a save, alternative energy source for the adult brain warranting studies on the potential therapeutic effects of sodium lactate infusion in children. WHAT IS KNOWN: • Lactate is generally considered a waste product of anaerobic glycolysis. However, lactate also is an alternative fuel for different organs, including the brain. • Lactate infusion is not incorporated in standard care for any patient population. WHAT IS NEW: • Thirty-four studies investigated the therapeutic use of intravenous sodium lactate in different patient populations, all with different study protocols. • Literature shows that lactate infusion may have beneficial effects in case of hypoglycemia, traumatic brain injury, and cardiac failure without the risk of major side effects.

Comparison of ready-to-eat "organic" antimicrobials, sodium bisulfate, and sodium lactate, on Listeria monocytogenes and the indigenous microbiome of organic uncured beef frankfurters stored under refrigeration for three weeks.

Listeria monocytogenes has been implicated in several ready-to-eat (RTE) foodborne outbreaks, due in part to its ability to survive under refrigerated conditions. Thus, the objective of this study was to evaluate the effects of sodium bisulfate (SBS), sodium lactate (SL), and their combination as short-duration antimicrobial dips (10-s) on L. monocytogenes and the microbiome of inoculated organic frankfurters (8 Log10 CFU/g). Frankfurters were treated with tap water (TW), SBS0.39%, SBS0.78%, SL0.78%, SL1.56%, SBS+SL0.39%, SBS+SL0.78%. In addition, frankfurters were treated with frankfurter solution water (HDW)+SBS0.78%, HDW+SL1.56%, and HDW+SBS+SL0.78%. After treatment, frankfurters were vacuum packaged and stored at 4°C. Bacterial enumeration and 16S rDNA sequencing occurred on d 0, 7, 14, 21. Counts were Log10 transformed and calculated as growth potential from d 0 to d 7, 14, and 21. Data were analyzed in R using mixed-effects model and One-Way ANOVA (by day) with differences separated using Tukey's HSD at P ≤ 0.05. The 16S rDNA was sequenced on an Illumina MiSeq and analyzed in Qiime2-2018.8 with significance at P ≤ 0.05 and Q ≤ 0.05 for main and pairwise effects. An interaction of treatment and time was observed among the microbiological plate data with all experimental treatments reducing the growth potential of Listeria across time (P < 0.0001). Efficacy of treatments was inconsistent across time; however, on d 21, SBS0.39% treated franks had the lowest growth potential compared to the control. Among diversity metrics, time had no effect on the microbiota (P > 0.05), but treatment did (P < 0.05). Thus, the treatments potentially promoted a stable microbiota across time. Using ANCOM, Listeria was the only significantly different taxa at the genus level (P < 0.05, W = 52). Therefore, the results suggest incorporating SBS over SL as an alternative antimicrobial for the control of L. monocytogenes in organic frankfurters without negatively impacting the microbiota. However, further research using multiple L. monocytogenes strains will need to be utilized in order to determine the scope of SBS use in the production of RTE meat.

Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis.

BACKGROUND: Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. METHODS: Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. RESULTS: Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48-40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88-14.21). CONCLUSION: The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.

Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study.

OBJECTIVES: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. DESIGN: Randomized blinded study (animal model). SETTING: University animal research facility. SUBJECTS: Twenty-four adult male "New Zealand White" rabbits. INTERVENTIONS: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. MEASUREMENTS AND MAIN RESULTS: Pupillary reactivity (primary outcome), levels of S100ß protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100ß protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis. CONCLUSIONS: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

Metabolically induced intracellular pH changes activate mitophagy, autophagy, and cell protection in familial forms of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder induced by the loss of dopaminergic neurons in midbrain. The mechanism of neurodegeneration is associated with aggregation of misfolded proteins, oxidative stress, and mitochondrial dysfunction. Considering this, the process of removal of unwanted organelles or proteins by autophagy is vitally important in neurons, and activation of these processes could be protective in PD. Short-time acidification of the cytosol can activate mitophagy and autophagy. Here, we used sodium pyruvate and sodium lactate to induce changes in intracellular pH in human fibroblasts with PD mutations (Pink1, Pink1/Park2, α-synuclein triplication, A53T). We have found that both lactate and pyruvate in millimolar concentrations can induce a short-time acidification of the cytosol in these cells. This induced activation of mitophagy and autophagy in control and PD fibroblasts and protected against cell death. Importantly, application of lactate to acute brain slices of WT and Pink1 KO mice also induced a reduction of pH in neurons and astrocytes that increased the level of mitophagy. Thus, acidification of the cytosol by compounds, which play an important role in cell metabolism, can also activate mitophagy and autophagy and protect cells in the familial form of PD.