Reduction In Lactate Concentration Research Articles

A Customized Biohybrid Presenting Cascade Responses to Tumor Microenvironment.

Intrinsic characteristics of microorganisms, including non-specific metabolism sites, toxic byproducts, and uncontrolled proliferation constrain their exploitation in medical applications such as tumor therapy. Here, the authors report an engineered biohybrid that can efficiently target cancerous sites through a pre-determined metabolic pathway to enable precise tumor ablation. In this system, DH5α Escherichia coli is engineered by the introduction of hypoxia-inducible promoters and lactate oxidase genes, and further surface-armored with iron-doped ZIF-8 nanoparticles. This bioengineered E. coli can produce and secrete lactate oxidase to reduce lactate concentration in response to hypoxic tumor microenvironment, as well as triggering immune activation. The peroxidase-like functionality of the nanoparticles extends the end product of the lactate metabolism, enabling the conversion of hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals. This, coupled with the transformation of tirapazamine loaded on nanoparticles to toxic benzotriazinyl, culminates in severe tumor cell ferroptosis. Intravenous injection of this biohybrid significantly inhibits tumor growth and metastasis.

Simulation of tumor density evolution upon chemotherapy alone or combined with a treatment to reduce lactate levels

<abstract><p>In this study, we introduced a mathematical model mimicking as much as possible the evolutions and interactions between glioma and lactate in the brain, in order to test different therapies and administration protocols. We simulated both glioma cell density evolution and lactate concentration, and considered two therapies: chemotherapy and a treatment targeting lactate production. Three different protocols for administrating the therapies were tested. We compared the efficiency of the combined therapies, depending on the administration protocols and the dosage of the drugs, in order to evaluate the importance of controlling lactate production. Results show that the use of an agent to reduce lactate concentration permits one to significantly reduce the dose of the chemotherapeutic drug.</p></abstract>

Vitamin D-VDR (vitamin D receptor) alleviates glucose metabolism reprogramming in lipopolysaccharide-induced acute kidney injury.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI. Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI. Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used. Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells. Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

Comparison of Blood Lactate Concentrations in Patients with Closed Traumatic Brain Injuries after Surgical and Conservative Interventions

Introduction: A major public health problem, brain injury can cause disability and death. Managing traumatic brain injury (TBI) can involve surgical interventions (e.g., evacuation and decompressive craniotomy) and/or conservative interventions without surgery (e.g., oxygenation, resuscitation, antibiotics, osmotherapy, and analgesics). Lactate, a biomarker that exerts physiological effects, is sensitive to the lack of oxygen and ischemia in organs such as the brain in both types of interventions. The aim of our study was thus to compare lactate concentrations in patients with closed brain injuries after conservative and surgical interventions.
 Methods: In a cohort study, lactate concentration between patients with TBI in the conservative versus surgical intervention groups were analyzed using the chi-square test, the independent t test, and Spearman’s correlation test.
 Results: Lactate concentrations in patients with closed brain injuries at the baseline, 24-hour, and 72-hour blood sampling time points did not significantly differ between conservative and surgical interventions (ρ > 0.05). However, reductions in lactate concentrations after 24 and 72 hours did significantly differ between the intervention groups, despite being more reduced in surgical interventions (ρ = 0.001) than in conservative ones (ρ = 0.002). Lactate concentrations were also significantly lower after 24 and 72 hours in the surgical intervention group for patients with epidural hematoma (EDH, p= 0.001) than ones without EDH (ρ < 0.001).
 Conclusion: Lactate concentration is a reliable prognostic predictor for assessing the severity of brain injury other than the GCS, another common clinical predictor.

O-066 CSCM-NXC media containing a low lactate concentration seems to benefit expansion grade compared to traditional continuous media

Abstract Study question Does lactate presence in the culture medium have an effect on embryo development, specifically during blastocyst formation? Is it an age related effect? Summary answer There is a statistical significative reduction of early blastocyst formation and a trend towards higher proportion of expanded and hatching blastocysts in lower lactate concentration. What is known already Embryos after embryonic genome activation start an active consumption of glucose to convert it into pyruvate and lactate for ATP production through the TCA cycle. Conversion from pyruvate to lactate to produce NADH through LDH (lactate dehydrogenase) can be counterbalanced by increased amounts of lactate, which then can alter the NAD+/NADH ratio resulting in a higher oxidative stress and reduced metabolic activity. Recently, a new commercial media formulation with a substantial reduction of lactate has come in to the market reporting increased efficiency of blastocyst formation and amount of euploid embryos compare to its version with a traditional lactate concentration. Study design, size, duration From September to November 2021 embryos were cultured in two different continuous media (SAGE 1-STEP and FUJIFILM IRVINE SCIENTIFIC CSCM-NXC). A total of 260 correctly fertilized embryos were allocated in both types of media (119 in 1-STEP and 141 in CSCM-NXC). Patients containing more than one zygote had their embryos allocated as equally as possible in both types of media. Participants/materials, setting, methods Age of participants ranged from 24-45 years. The embryos were cultured in embryoscope+ and their destination was assigned as Transfer, Vitrification or Discard (if by day 6 they did not reach a good quality blastocyst). Morphokinetic parameters were measured and Gardner's grading system for blastocyst quality annotated. For blastocyst quality comparison, only day 5 was considered. Variables studied were utilisation and blastocyst formation rates, expansion grade, ICM and TE quality, patient age, and pregnancy rates. Main results and the role of chance Incubation of embryos in reduced lactate concentration reduced significantly (p-value=0.013) the proportion of embryos with expansion grade 1 (14.3% 1STEP vs 3.4% CSCM-NXC), in contrast, a trend towards higher expansion grades, more importantly grade 5 (7.8% 1STEP vs 14.9% CSCM-NXC) was observed. A slight reduction in proportion of discarded embryos (47.52% CSCM-NXC vs 54.62% 1STEP) and increased proportion of vitrified embryos (34.75% CSCM-NXC vs 27.73% 1STEP) was also observed. Regarding ICM and TE qualities, in general there was also a trend in benefit of use of CSCM-NXC medium (55.3% CSCM-NXC vs 50.7% 1STEP for grade A in ICM; 36.8% CSCM-NXC vs 30.1% 1STEP for grade A in TE). Morphokinetic parameters were not different between groups, except T3 which showed to be significative (p-value=0.026) earlier in 1STEP than CSCM-NXC (37.13 h vs 38.71 h respectively). Age subgroups of patient showed no difference in utilisation rates for ages < 37 years old, however, for ages ≥37 there was a higher proportion of utilised embryos (56.3 CSCM-NXC vs 41.9% 1STEP for 37-40 years old; 60% CSCM-NXC vs 42.3% 1STEP for >40 years old). Finally, pregnancy rates were equal for those fresh transfers between both groups. Limitations, reasons for caution The study has a reduced sample size, so statistical power is reduced. Furthermore, it cannot be discarded that the effect is not a contribution to other differences in formulation of both media. Time to birth or cumulated pregnancy parameter would be more indicative of benefits. Wider implications of the findings Two main hypotheses that require further validation: First, excess of certain metabolites in culture can impair development of preimplantation embryos. Second, embryos may be more sensitive to certain medium composition depending on age, so medium designed according to this may be a near future direction to improve IVF outcomes. Trial registration number NA

Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements(PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Effect of Lactobacillus hilgardii, Lactobacillus buchneri, or their combination on the fermentation and nutritive value of sorghum silage and corn silage

The objective of this study was to determine the effect of inoculation with Lactobacillus hilgardii with or without Lactobacillus buchneri on the fermentation, chemical composition, and aerobic stability of sorghum and corn silage after 2 ensiling durations. Sorghum forage was harvested at 27% dry matter (DM; experiment 1), and different corn hybrids were harvested at late (43.8% DM; experiment 2) or normal maturity (34% DM; experiment 3). All harvested forages were chopped and ensiled in quadruplicate in vacuum-sealed nylon-polyethylene bags (40 × 61 cm) for 30 and 90 d after treatment with (1) deionized water (uninoculated) or (2) L. buchneri (1.5 × 105 cfu/g of fresh weight; LB); (3) L. hilgardii (1.5 × 105 cfu/g of fresh weight; LH); or (4) L. buchneri and L. hilgardii (1.5 × 105 cfu/g of fresh weight of each inoculant). Data for each experiment were analyzed separately accounting for the 2 × 2 × 2 factorial treatment arrangement. Inoculating sorghum forage with LB or LH separately increased acetate and 1,2 propanediol concentration, tended to increase DM loss, reduced lactate concentration and the lactate-to-acetate ratio, and increased aerobic stability after 90 but not after 30 d of ensiling. Inoculating late-harvested corn silage with LB or LH separately increased and decreased DM loss, respectively, increased 1,2 propanediol concentration, reduced lactate-to-acetate ratio and yeast counts but did not affect aerobic stability. Inoculating normal-harvested corn silage with LH reduced DM loss and increased 1,2 propanediol concentration and yeast counts; LB reduced lactate concentration, lactate-to-acetate ratio, and total acids. Either inoculant alone increased aerobic stability after 30 or 90 d. The main benefit of combining LB with LH was prevention of increases in DM losses by LH or LB separately. No improvement in aerobic stability resulted from applying LH instead of LB separately or from combining them. Application of LB or LH separately improved aerobic stability of sorghum silage after 90 d and normal-harvested corn silage after 30 or 90 d but did not affect that of late-harvested corn silage.

The Acute Effect of Hyperoxia on Onset of Blood Lactate Accumulation (OBLA) and Performance in Female Runners during the Maximal Treadmill Test.

The objective of this study was to analyze the acute effect of hyperoxia during the maximal treadmill test (MTT) of runners. Participants included 10 female street runners who performed the MTT under two different conditions: hyperoxia (HYPX), inhaling oxygen (60% O2) every 3 min; and normoxia (NORM), without additional oxygen inhalation. Both groups performed the MTT with increases in the slope of the run every 3 min until voluntary exhaustion. The variables of lactate concentration, the onset of blood lactate accumulation (OBLA), peripheral oxygen saturation (SpO2), heart rate (HR), and Borg scale were evaluated. It was verified after the comparison (HYPX vs. NORM) that stage 3 (p = 0.012, Cohen’s d = 1.76) and stage 4 (p < 0.001; Cohen’s d = 5.69) showed a reduction in lactate under the HYPX condition. OBLA under the HYPX condition was identified at a later stage than NORM. There were no differences in Borg scale, SpO2, and HR between the different conditions. It was concluded that the HYPX condition contributed to a reduction in lactate concentration and delayed OBLA in runners.

Meta-analysis of effects of inoculation with Lactobacillus buchneri, with or without other bacteria, on silage fermentation, aerobic stability, and performance of dairy cows

A meta-analysis of 158 peer-reviewed articles was conducted to examine effects of inoculation with Lactobacillus buchneri (LB)-based inoculants (LBB) that did or did not include homolactic or obligate heterolactic bacteria on silage fermentation and aerobic stability. A complementary meta-analysis of 12 articles examined LBB inoculation effects on dairy cow performance. Raw mean differences between inoculant and control treatment means weighted by inverse variance were compared with a hierarchical effects model that included robust variance estimation. Meta-regression and subgrouping analysis were used to identify effects of covariates including forage type, application rate (≤104, 105, 106, or ≥ 107 cfu/g as fed), bacteria type (LB vs. LB plus other bacteria), enzyme inclusion, ensiling duration, and silo type (laboratory or farm scale). Inoculation with LBB increased acetate (62%), 1, 2 propanediol (364%) and propionate (30%) concentration and aerobic stability (73.8%) and reduced lactate concentration (7.2%), yeast counts (7-fold) and mold counts (3-fold). Feeding inoculated silage did not affect milk yield, dry matter intake, and feed efficiency in lactating dairy cows. However, forage type, inoculant composition, and dose effects on silage quality measures were evident. Inoculation with LBB increased aerobic stability of all silages except tropical grasses. Adding obligate homolactic or facultative heterolactic bacteria to LB prevented the small increase in DM losses caused by LB alone. The 105 and 106 cfu/g rates were most effective at minimizing DM losses while aerobic stability was only increased with 105, 106, and ≥ 107 cfu/g rates. Inoculation with LBB increased acetate concentration, reduced yeast counts and improved aerobic stability but did not improve dairy cow performance.

Research Highlights

Research Highlights

Beta-Alanine Supplementation Improved 10-km Running Time Trial in Physically Active Adults.

The purpose of this study was to investigate the effects of β-alanine supplementation on a 10 km running time trial and lactate concentration in physically active adults. Sixteen healthy subjects were divided randomly into two groups: β-alanine (n = 8) and placebo group (n = 8). The experimental group ingested 5 g/day of β-alanine plus 1 g of resistant starch, and control group ingested 6 g of resistant starch, both for 23 days. Time to complete a 10-km running time trial and lactate concentration following the test were assessed at baseline and post 23 days. The running training program was performed three times per week on non-consecutive days (day 1: running 7 km; day 2: six sprints of 500 m at maximum speed with 2 min of recovery; day 3: running 12 km). The time to complete a 10-km running time trial decreased significantly only for the β-alanine group (Pre = 3441 ± 326.7, Post = 3209 ± 270.5 s, p < 0.05). When analyzing the delta (Time post minus Time at baseline value) there was a statistically significant difference between the β-alanine vs placebo group (-168.8 ± 156.6 vs. -53.60 ± 78.81 s, p = 0.007), respectively. In addition, the β-alanine group presented lower blood lactate concentration after the 10-km test (β-alanine: Pre = 8.45 ± 1.94 vs. Post = 6.95 ± 2.44 mmol/L; Placebo: Pre = 8.7 ± 3.0 vs. Post = 10.8 ± 2.5 mmol/L, p = 0.03). In conclusion, β-alanine supplementation improved the 10-km running time trial and reduced lactate concentration in physically active adults.

ЕФЕКТИВНІСТЬ ЛІКУВАННЯ СПОРТИВНИХ КОНЕЙ ЗА МІОКАРДІОДИСТРОФІЇ

Recent years are characterized by close attention to diseases, which are often a component of metabolic syndrome (MS). The pathogenetic multifacency of the MS and the clinical heterogeneity of the manifestations of the diseases give the problem of contemporary sound, provides formation of new perspectives on their course and the development of therapies. The promising direction of drug therapy is the use of metabolic drugs. Metabolic therapy has become one of the areas in the treatment of heart failure, therefore the compulsory component of treatment should be drugs that act to stabilize the myocardial metabolism, and the correction of hypoxia and its effects is important for the adaptation of tissues to work in conditions of reduced supply of oxygen. The basis of metabolic therapy is the protection of the myocardium from cardiotoxic action of catecholamines released during physical activity, as well as energy-saving correction of oxidation processes. The purpose of the work was to study the effectiveness of metabolic therapy in sport horses for myocardial dystrophy. In order to assess the influence of metabolic syndrome (MS) on myocardium and the analysis of the effectiveness of metabolic therapy, patients with myocardial dystrophy of horses were selected. According to the results of clinical studies and analysis of indicators of blood of sick horses was divided into two groups: the first included animals that were treated, the second - which were not treated. From the control group of horses of two animals at 8 and 9 days was excluded from research due to complications due to the development of metabolic syndrome. Metabolic therapy in sports horse patients with myocardial dystrophy contributed to the restoration of work capacity, normalization of the frequency of respiration and pulse, reduction of the incidence of cardiac arrhythmias, arrhythmias and valve regurgitation, restoration of hydration (reduction of total protein content) and renal function (reduction of urea and creatinine concentrations), normalization carbohydrate metabolism, restoration and stabilization of membranes of cardiomyocytes (reduction of lactate concentration and activity of AST, СK, СK-MB, LDH, LDH-1), and consequently jay complication and development of metabolic dysfunction. In animals of the control group, which were not treated, complications of myocardial dystrophy in the form of a metabolic syndrome developed, which were manifested by an increase in the percentage of animals with reduced capacity for work, tachypnea and tachycardia, an increase in the incidence of cardiac noise, arrhythmias and valve regurgitation, the development of dehydration (increase in total protein content), violation renal function (increased urea concentration and creatinine), development of cardiomyocyte cytolysis syndrome (increased lactate and ac activity of the AST, CК, СК-MB, LDH, LDH-1).

Effects of the citrus flavonoid extract Bioflavex or its pure components on rumen fermentation of intensively reared beef steers

Two experiments were performed to study the effects of the citrus flavonoid extract Bioflavex (BF; Interquim SA, FerrerHealthTech, Sant Cugat, Barcelona, Spain) or its components on the rumen fermentation of a high-concentrate diet. In an in vivo experiment, eight Friesian steers (398 ± 12.2 kg bodyweight) fitted with a rumen cannula were given a basal concentrate (CTR) or a CTR supplemented with BF (450 mg/kg dry matter, DM) in a 2 × 4 crossover design. No differences were observed in performance parameters of BF and CTR steers. Diet BF increased pH values and the molar proportion of propionate and reduced lactate concentration as a result of an increase in the relative abundance of lactate-consuming microorganism Selenomomas ruminantium (P &lt; 0.01) and Megaesphaera elsdenii (P = 0.06). In an in vitro experiment, the effect of BF and its pure flavonoid components added to the incubation medium was studied separately. Bioflavex and its main components naringine, neohesperidine (NH) and poncirine (PC) were added to the incubation medium at 500 µg/g DM, with the unsupplemented substrate also included as a control (CTR). After 12 h of incubation, flavonoid mixture and NH and PC reduced (P &lt; 0.01) the volume of gas produced and the molar proportion of acetate (P &lt; 0.01), and increased that of propionate (P &lt; 0.01). PC reduced the relative quantification of Streptococcus bovis, whereas NH and BF increased the relative quantification of M. elsdenii in relation to CTR (P &lt; 0.01). Bioflavex supplementation in steers in feedlot was effective in preventing a collapse in pH and it enhanced rumen fermentation efficiency through modifying the activity of lactate-consuming bacteria and a greater molar proportion of propionate and a reduction of that of acetate, suggesting its positive role in modulating the activity of rumen microbiota.

Modified acetate Ringer's solutions versus Ringer's lactate solutions in perioperative patients: a systematic review

Objective To systematically review published randomized controlled trials(RCTs) comparing perioperative administration of modified Ringer's acetate(PA) versus Ringer's lactate solutions (LR) in terms of effect on patient outcomes, so as to provide some evidence for volume expansion. Methods PubMed, EMBASE, Cochrane library, Web of Science, Chinese Science Citation Database(CSCD), Chinese Biomedical Literature Database (CBM) were searched to identify RCTs comparing PA and LR published between January 1996 and June 2015. Cochrane Risk of Bias Tool was applied to assess the quality of literature. The RCTs meeting the criterion of inclusion were selected for meta-analysis. Outcomes included mortality, organ failure, pH, base excess (BE), partial pressure of carbon dioxide(PaCO2), lactate concentration, and bicarbonate anion(HCO3-). Results 265 published papers were searched, from which 12 RCTs (with 664 patients) were eligible according to the inclusion criterion. Mata-analysis showed that there were no statistically significant differences between PA group and LR group in BE and HCO3; pH value in the PA group was higher than that in the LR group(P=0.04); PaCO2 was higher in the LR(P=0.013); blood lactate concentration was higher in the LR group(P=0.000). Conclusion This study showed that modified Ringer acetate solution may reduce blood lactate concentration compared with Ringer lactate solution. However, the studies included in this review were of poor quality. The evaluation and comparison of these solutions for volume expansion is subject to investigation with high-quality randomised controlled double-blind large trials. Key words: Intraoperative period; Ringer's lactate solution; Modified acetate Ringer's solutions

Regulation of EPS production in Lactobacillus casei LC2W through metabolic engineering

Lactobacillus casei LC2W is an exopolysaccharide(EPS)-producing strain with probiotic effects. The low efficiency and unclear regulation mechanism of EPS biosynthesis have become main constraints for its application in food industry. To investigate the major rate-limiting factors of EPS biosynthesis and to improve its yield, metabolic engineering was applied to this strain. Eight relevant genes related to central metabolism, sugar-nucleotides supply, glycosyltransferase and cofactor engineering were cloned and overexpressed. The results suggested that nox, pfk, rfbB and galT genes were the largest contributors to EPS biosynthesis in this study, which elevated EPS yield by 46·0, 20, 17·4 and 19·6% respectively. Notably, under aerobic condition which was not a suitable condition for lactobacilli to grow in, recombinant strain LC-nox achieved the highest EPS yield of 263·7 mg l(-1) , which was increased by 75% compared to that of the starting strain. The oxygen stress was excluded since the phenomenon was not observed in the control strain under the same condition. Therefore, it was probably that higher NADH oxidase activity led to a decreased NADH availability and reduced lactate concentration, which resulted in the elevation of EPS yield. This study contributed to the understanding of EPS biosynthesis in Lact. casei through metabolic engineering and provided a starting point for introducing cofactor engineering into this strain. Overexpression of NADH oxidase was found to have a most significant effect on the EPS production. It is the first report that EPS could be accumulated to such a high level under aerobic condition in lactobacilli. Our results provided a novel strategy for the improvement of EPS production in lactic acid bacteria.

Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.

BLOOD GAS, LACTATE, AND HEMATOLOGY EFFECTS OF VENIPUNCTURE TIMING AND LOCATION AFTER MIST-NET CAPTURE OF MOURNING DOVES (ZENAIDA MACROURA), BOAT-TAILED GRACKLES (QUISCALUS MAJOR), AND HOUSE SPARROWS (PASSER DOMESTICUS).

Venous blood gas partial pressures, pH, bicarbonate and lactate concentrations, packed cell volume, white blood cell differential counts, and heterophil/lymphocyte ratios were measured from Mourning Doves (Zenaida macroura), Boat-tailed Grackles (Quiscalus major), and House Sparrows (Passer domesticus). Birds were bled promptly after mist-net capture and banding or following a targeted delay of 45-60 min, in order to assess the impacts of a brief holding period commonly practiced in large-scale bird banding operations. Additionally, effects of venipuncture location (basilic [=ulnar] vein versus jugular vein) were evaluated in male Boat-tailed Grackles sampled promptly after capture and banding. All comparisons were with unpaired samples; no birds were subjected to more than one venipuncture. All three species exhibited moderate improvements in blood gas and acid-base status after the delay, with reductions in lactate concentrations with or without concurrent increases in pH and bicarbonate. Boat-tailed Grackles exhibited an increased proportion of heterophils in the differential white blood cell count following a delay in sampling, suggestive of a stress leukogram. There were no significant differences between basilic and jugular venipuncture results from male Boat-tailed Grackles. Most metabolic, respiratory, and acid-base alterations were minor, but a small number of birds exhibited values (e.g., temperature-corrected pH <7.3, lactate >10 mmol/L) that could be of concern if combined with other adverse conditions. For such birds, a short delay between capture and processing could benefit their blood gas and acid-base status, although loss of time foraging or feeding young and greater activation of the hypophyseal-pituitary-adrenal axis are additional considerations.

Functionality of the white shrimp glucose transporter 1: Expression in Xenopus oocytes and gene silencing during hypoxia

The functionality of the Glucose Transporter 1 (LvGLUT1) from the white shrimp Litopenaeus vannamei was evaluated by heterologous expression in Xenopus laevis oocytes and by gene silencing during hypoxia in the gills and hepatopancreas of the shrimp. The LvGLUT1 mRNA was expressed and translated in Xenopus oocytes. The GLUT-1 protein localized in the plasma membrane and transported glucose into the oocytes at a rate of 2.25±0.5nmol/oocyte/2h. The effects of hypoxia and glut1 silencing on glucose and lactate concentrations were measured after injection of Lvglut1 dsRNA followed by 3, 24 and 48h of hypoxia. Gene silencing with Lvglut1 dsRNA was effectively triggered in both tissues. Glucose and lactate concentrations increased (p<0.05) during hypoxia in the gills and hepatopancreas. In the gills the effect of the interaction between hypoxia and silencing is evident, with a reduction in lactate concentration after 3 and 24h of hypoxia (fold change= −5.1 and −4.9, respectively) in the dsRNA-injected group compared to the control. Glucose concentration was also lower in the gills after 24 and 48h (−1.6 and −2-fold, respectively) in the same group. Lactate concentration in plasma decreased at least 2-fold in all dsRNA-injected hypoxia treatments whereas glucose concentration remained constant. Altogether these results indicate that the protein product of the Lvglut1 gene is a functional glucose transporter and plays a major role importing glucose during hypoxia in the gills.

Effects of decreased lactate accumulation after dichloroacetate administration on exercise training-induced mitochondrial adaptations in mouse skeletal muscle.

Recent studies suggested that lactate accumulation can be a signal for mitochondrial biogenesis in skeletal muscle. We investigated whether reductions in lactate concentrations in response to dichloroacetate (DCA), an activator of pyruvate dehydrogenase, attenuate mitochondrial adaptations after exercise training in mice. We first confirmed that DCA administration (200 mg/kg BW by i.p. injection) 10 min before exercise decreased muscle and blood lactate concentrations after high-intensity interval exercise (10 bouts of 1 min treadmill running at 40 m/min with a 1 min rest). At the same time, exercise-induced signal cascades did not change by pre-exercise DCA administration. These results suggested that DCA administration affected only lactate concentrations after exercise. We next examined the effects of acute DCA administration on mRNA expressions involved with mitochondrial biogenesis after same high-intensity interval exercise and the effects of chronic DCA administration on mitochondrial adaptations after high-intensity interval training (increasing intensity from 38 to 43 m/min by the end of training period). Acute DCA administration did not change most of the exercise-induced mRNA upregulation. These data suggest that lactate reductions by DCA administration did not affect transcriptional activation after high-intensity interval exercise. However, chronic DCA administration attenuated, in part, mitochondrial adaptations such as training-induced increasing rates of citrate synthase (P = 0.06), β-hydroxyacyl CoA dehydrogenase activity (P < 0.05), cytochrome c oxidase IV (P < 0.05) and a fatty acid transporter, fatty acid translocase/CD36 (P < 0.05), proteins after exercise training. These results suggest that lactate accumulation during high-intensity interval exercise may be associated with mitochondrial adaptations after chronic exercise training.

Influence of intravenous thiamine supplementation on blood lactate concentration prior to cardiac surgery: A double-blinded, randomised controlled pilot study.

Stress related to surgery and critical illness depletes thiamine, essential in energy metabolism, and might result in high blood lactate concentrations and higher mortality. We hypothesised that thiamine supplementation would increase blood concentration of thiamine and reduce blood lactate concentration postoperatively. Moreover, we aimed to identify the prevalence of, and risk factors for, high blood lactate concentrations. This was a double-blind, randomised controlled pilot study from February to July 2012 including 30 patients scheduled for cardiac surgery with cardiopulmonary bypass. Patients were assigned randomly to receive thiamine (300 mg in 0.9% Normal saline solution) or placebo (0.9% Normal saline) preoperatively. One arterial blood sample was taken preoperatively and another postoperatively to measure thiamine concentration, and multiple samples were taken during surgery and ICU stay to determine lactate concentrations. Twenty-four hour urine samples were collected to measure urinary thiamine concentration. Preoperatively, we assessed extracellular mass to body cell mass ratio (ECM/BCM). The mean (SD) age of the patients was 58 (12) years, 73% were overweight, 10% were malnourished and the prevalence of thiamine deficiency was 10%. Patients in the thiamine group had significantly higher blood thiamine concentrations 2 days postoperatively [805.2 ± 289.8 ng g(-1) haemoglobin (Hb)] than those in the placebo group (591.2 ± 100.7 ng g(-1) Hb, P < 0.01). The mean blood lactate concentration changed significantly over time, but did not differ significantly between the groups. Patients with ECM/BCM more than 1 had higher lactate concentrations on admission to ICU than those with ECM/BCM less than 1 (2.1 ± 0.7 vs. 1.7 ± 0.6, P = 0.09) and were at a significantly greater risk of having a higher lactate concentration on ICU admission [odds ratio (OR) 13.5, 95% confidence interval (95% CI) 1.0 to 179.4, P < 0.05]. On the basis of these results, a sample size calculation for a larger study has been facilitated. Thiamine supplementation caused normalisation of blood and urine concentrations postoperatively but without a significant reduction in lactate concentration or clinical outcome. Body composition played an important role in lactate formation. Further research focusing on preoperative screening and optimal treatment of high lactate concentrations in this specific population is warranted. Clinicaltrials.gov identifier: NCT01524315.