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.

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.

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.

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.

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.

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.

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.

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.

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 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.

TAK1 is involved in sodium L-lactate-stimulated p38 signaling and promotes apoptosis.

In the present study, we found that the phosphorylation of p38 mitogen-activated protein kinase (p38) was significantly increased in L-lactate-treated HeLa cells, which is under concentration- and time-dependent manner. The protein level of Bcl-2 was significantly reduced and Bax and C-caspase3 were significantly increased in L-lactate-treated cells. qRT-PCR analysis suggested that the expression level of apoptosis-related genes Bax, C-myc, and FasL were significantly upregulated by L-lactate treatment. In addition, p38 inhibitor SB203580 blocked the L-lactate-stimulated phosphorylation of p38 (p-p38) and apoptosis, which suggested that L-lactate-stimulated apoptosis may be related to the activation of p38. Moreover, TAK1 inhibitor Takinib reduced L-lactate-triggered phosphorylation of p38 and also apoptosis; however, ASK1 inhibitor NQDI-1 did not. Cells transfected with siRNA of TAK1(siTAK1) showed similar results with Takinib inhibitor. These results suggested that the L-lactate treatment elevated activation of p38 and apoptosis was related to TAK1. In this study, we suggested that TAK1 plays an important role in L-lactate-stimulated activation of p38 affecting apoptosis in HeLa cells.

Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?

BACKGROUND: There has been growing interest in the use of hypertonic sodium lactate (HSL) solution following traumatic brain injury (TBI) in humans. However, little is known about the effects of HSL on functional deficits with respect to the hyperosmotic nature of HSL. METHODS: We have compared the effects of HSL solution and isotonic saline solution using sensorimotor and cognitive tests for 14 days post-trauma in animals. Thirty minutes after trauma (impact-acceleration model), anesthetized rats were randomly allocated to receive a 2-h infusion of isotonic saline solution (TBI-saline group) or HSL (TBI-HSL group) (n = 10 rats per group). In another series of experiments using a similar protocol, the effects of equiosmolar doses of HSL and hypertonic saline solution (HSS) were compared in TBI rats (n = 10 rats per group). Blood lactate and ion concentrations were measured during the 2-h infusions. RESULTS: Compared to the TBI-saline group, the TBI-HSL group had a reduced latency to complete the adhesive removal test: 6 s (5-9) (median [25-75th centiles]) versus 13 s (8-17) on day 7, and 5 s (5-9) versus 11 s (8-26) on day 14 (P < 0.05), respectively, and a shorter delay to complete the radial arm maze test on day 7: 99 s (73-134) versus 176 s (127-300), respectively (P < 0.05). However, no differences were found between the TBI-HSL and TBI-HSS groups in neurocognitive tests performance. Compared to the TBI-saline group, the HSL and HSS groups had higher serum osmolality: 318 mOsm/Kg (315-321) and 315 mOsm/Kg (313-316) versus 307 mOsm/Kg (305-309), respectively (P < 0.05), and the HSL group had a higher serum lactate concentration: 6.4 mmol/L (5.3-7.2) versus 1.5 mmol/L (1.1-1.9) and 1.6 mmol/L (1.5-1.7), respectively (P < 0.05). CONCLUSIONS: These results indicate that improvements in cognitive and sensorimotor tests with HSL infusion post-TBI could be related to elevation of serum osmolality, not to exogenous administration of lactate.

Homology- and cross-resistance of Lactobacillus plantarum to acid and osmotic stress and the influence of induction conditions on its proliferation by RNA-Seq.

In this study, homology- and cross-resistance of Lactobacillus plantarum L1 and Lactobacillus plantarum L2 to acid and osmotic stress were investigated. Meanwhile, its proliferation mechanism was demonstrated by transcriptomic analysis using RNA sequencing. We found that the homologous-resistance and cross-resistance of L. plantarum L1 and L. plantarum L2 increased after acid and osmotic induction treatment by lactic acid and sodium lactate solution in advance, and the survival rate of live bacteria was improved. In addition, the count of viable bacteria of L. plantarum L2 significantly increased cultivated at a pH 5.0 with a 15% sodium lactate sublethal treatment, compared with the control group. Further study revealed that genes related to membrane transport, amino acid metabolism, nucleotide metabolism, and cell growth were significantly upregulated. These findings will contribute to promote high-density cell culture of starter cultures production in the fermented food industry.

Comparison of half-molar sodium lactate and mannitol to treat brain edema in severe traumatic brain injury: A systematic review.

PURPOSE: Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP). METHODS: This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3. RESULTS: From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09). CONCLUSION: Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.

Sodium lactate promotes stemness of human mesenchymal stem cells through KDM6B mediated glycolytic metabolism.

Mesenchymal stem cells (MSCs) are an important cell source for tissue homeostasis and repair due to their stemness characteristic. Lots of intrinsic signaling pathways have been reported to regulate MSC stemness, but the extrinsic signals such as sodium lactate, particularly in physiological conditions, are poorly understood. Herein, we evaluated the effect of sodium lactate on human MSC stemness regulation by examining colony-forming ability, energy metabolism, multi-lineage differentiation ability, and pluripotent gene and protein expression. The underlying mechanism was further investigated with gene knockdown as well as small molecule interference and rescue experiments. We found that: (1) low concentration (1 mM) of sodium lactate promoted the stemness of human MSCs; (2) the upregulation of glycolysis was responsible for the MSC stemness promotion; (3) lysine demethylase 6B (KDM6B) was the key regulator which mediated sodium lactate-induced glycolysis and human MSC stemness enhancement. This study indicated that sodium lactate played an important role in human MSC stemness maintenance in physiological conditions, which could be related to KDM6B mediated metabolic regulation. It would provide new insight into stem cell biology, and contribute to cell transplantation and tissue regeneration strategies.

Hypertonic sodium lactate improves microcirculation, cardiac function, and inflammation in a rat model of sepsis.

BACKGROUND: Hypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)). METHODS: Three groups were analyzed (n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics (n = 7/group). RESULTS: HSL improved mesenteric microcirculation (CLP-HSL 736 [407-879] vs. CLP-NaCl 241 [209-391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28-0.43] vs. 0.14 [0.10-0.18] mL/min/g, p < 0.0001), and left ventricular fractional shortening (55 [46-73] vs. 39 [33-52] %, p = 0.009). HSL also raised dP/dtmax slope (6.3 [3.3-12.1] vs. 2.7 [2.0-3.9] 103 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1-2.3] vs. 3.0 [2.2-3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31-43] vs. 113 [63-142], p = 0.03), the lung (108 [82-174] vs. 273 [222-445], p = 0.006), and the liver (24 [14-37] vs. 70 [50-89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08-10.30] vs. 3.19 [2.42-5.11] mmol/L, p = 0.04; 400 [174-626] vs. 189 [130-301] µmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1ß, 172 [119-446] vs. 928 [245-1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5-50.3] vs. 53.9 [30.8-85.6] pg/mL, p = 0.005; IL-10, 352 [267-912] vs. 905 [723-1243] pg/mL) as well as plasma VEGF-A (198 [185-250] vs. 261 [250-269] pg/mL, p = 0.009). CONCLUSIONS: Hypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.

How we can improve the antimicrobial performances of lactic acid bacteria? A new strategy to control Listeria monocytogenes in Gorgonzola cheese.

This study was aimed to evaluate the effectiveness of two lactic acid bacteria (LAB) cultures (Lactococcus lactis FT27 and Carnobacteroim divergens SCA), lactic acid/sodium lactate (LASL - l-lactic acid 61% (w/w) and L-sodium lactate 21% (w/w)) and their combination against four Listeria monocytogenes biotypes isolated from Gorgonzola cheese. In vitro antilisterial activity showed that the sensitivity to antimicrobials was strain-dependent. Antimicrobial challenge testing was performed on Gorgonzola rinds simulating contamination occurring at the beginning (6 days) and at the end (55 days) of the ripening period, to assess the antilisterial activity of LAB strains and LASL during the subsequent 60 days at 4 °C. LASL showed a higher antilisterial activity than LAB, maintaining the pathogen content below the EC limit (<2.0 log10 CFU/g) for 60 days. A strong listericidal effect was observed combining LAB with LASL (2,8 µL/cm2) Lc. lactis in combination with LASL completely inhibited the two L. monocytogenes strains in the first 50 days, while LASL with C. divergens was more effective in the second part of ripening when the pH raised. Data obtained encourage the use of LASL along with antimicrobial LAB rotation schemes during cheese ripening for the prevention and/or control of the L. monocytogenes on cheese surface.

Diagnostic Utility of Sodium Lactate Infusion and CO2-35% Inhalation for Panic Disorder.

Laboratory measures have played an integral role in diagnosing pathology; however, compared to traditional medicine, psychiatric medicine has lagged behind in using such measures. A growing body of literature has begun to examine the viability and development of different laboratory measures in order to diagnose psychopathologies. The present review examines the current state of development of both sodium lactate infusion and CO2-35% inhalation as potential ancillary measures to diagnose panic disorder (PD). A previously established 3-step approach to identifying laboratory-based diagnostic tests was applied to available literature assessing the ability of both sodium lactate infusion or CO2-35% inhalation to induce panic attacks in PD patients, healthy controls, and individuals with other psychiatric conditions. Results suggest that across the literature reviewed, individuals with PD were more likely to exhibit panic attacks following administration of sodium lactate or CO2-35% compared to control participants. The majority of the studies examined only compared individuals with PD to healthy controls, suggesting that these ancillary measures are underdeveloped. In order to further determine the utility of these ancillary measures, research is needed to determine if panic attacks following administration of these chemical agents are unique to PD, or if individuals with related pathologies also respond, which may be indicative of transdiagnostic characteristics found across disorders.

Characterisation of aluminium release by the enFlow® fluid-warming system in crystalloids and blood products.

The use of uncoated aluminium-heated plates in an intravenous fluid-warming system has been shown to produce high levels of aluminium in Sterofundin 1/1E, a balanced crystalloid solution. However, the effect of this fluid-warming device on other balanced crystalloid solutions and blood products has not been studied. Using mass spectrometry we measured aluminium levels in Plasma-Lyte 148, compound sodium lactate solution, 4% human albumin solution, expired resuspended packed red cells and fresh frozen plasma that were pumped through an enFlow® fluid-warming system at 2 ml.min-1 . Samples were taken at baseline before heating and then at 10-min intervals up to 60 min with the system set to warm the fluids to 40 °C. High concentrations of aluminium were found for Plasma-Lyte 148 and compound sodium lactate solutions (mean (SD) 223 (0.6) µmol.l-1 and 163 (0.2) µmol.l-1 at 60 min, respectively); both concentrations were significantly greater than the United States Food and Drug Administration recommended maximum limit for aluminium in intravenous nutrition of 25 µg.l-1 (0.9 µmol.l-1 ). Lower aluminium levels were found in 4% human albumin solutions, expired resuspended red cells and fresh frozen plasma at 60 min (mean (SD) 5.7 (0.1) µmol.l-1 , 2.7 (0.0) µmol.l-1 and 2.3 (0.4) µmol.l-1 , respectively). The process allowing addition of aluminium to be added to Sterofundin 1/1E by the enFlow fluid warmer also occurs in Plasma-Lyte 148 and compound sodium lactate solutions and to a lesser degree in blood products. The exact mechanism facilitating this process and its clinical significance remain unclear.