Increase In Lactate Research Articles

Rationale for the prevention of mastitis in cows during the dry period and after calving

Testing cows for mastitis before starting and treating all milch cows with a long-acting antimicrobial agent is an important component of the preventive preparation of animals for the dry period. In addition, determining the sensitivity of pathogens isolated on the farm and rotating antimicrobials increases the effectiveness of therapy and reduces the risk of resistant strains of microorganisms. The purpose of this study was to determine the preventive and therapeutic effects of preparations based on povidone-iodine and cefquinome sulfate for cows with mastitis. The following methods were used in the study: calculation of the total number of somatic cells by flow cytometry; California test; sensitivity to antimicrobial agents by agar disks; clinical and physiological method; statistical method. During the examination of cows for mastitis, it was identified that in the control group the number of somatic cells averaged 450 thousand/cm3, the total number of microorganisms was 130 thousand. In cows of the experimental group, productivity was 23.6%, the number of somatic cells was 600 thousand/cm3, microorganisms – 550 thousand CFU/cm3. It was identified that the isolated microflora showed high sensitivity to the preparation based on povidone-iodine and cefquinome sulfate. Therefore, udder conservation for cows of the experimental group with signs of mastitis was conducted with a product based on povidone-iodine, which affected the increase in lactation and improvement of milk quality after calving. The criteria for milk in the experimental group at the end of the experiment corresponded to the grade extra – 30%, top – 60%, and first – 10%. As a result of the therapy, lactation improved in cows, and the quality of milk corresponded to the first grade. At the end of the study, the quality of milk in cows of the control group corresponded to the extra Grade – 10%, top – 40%, and first – 50%. The practical value of the study lies in the prevention of mastitis on the farm, improving the quality of the resulting products, reducing the cost of veterinary care and culling animals

Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients.

Industrial production of food for animals and humans needs increasing amounts of pesticides, especially of organophosphates, which are now easily available worldwide. More than 3 million cases of acute severe poisoning are estimated to occur worldwide every year, and even more cases remain unreported, while 200,000-350,000 incidentally or intentionally poisoned people die every year. Diagnostic and therapeutic procedures in organophosphate poisoning have, however, remained unchanged. In addition to several neurologic symptoms (miosis, fasciculations), hypersecretion of salivary, bronchial, and sweat glands, vomiting, diarrhea, and loss of urine rapidly induce dehydration, hypovolemia, loss of conscience and respiratory distress. Within hours, signs of acidosis due to systemic hypoxia can be observed at first laboratory investigation after hospitalization. While determination of serum-cholinesterase does not have any diagnostic value, it has been established that hypoalbuminemia alone or accompanied by an increase in creatinine, lactate, or C-reactive protein serum levels has negative prognostic value. Increased serum levels of C-reactive protein are a sign of systemic ischemia. Protective mechanical ventilation should be avoided, if possible. In fact, acute respiratory distress syndrome characterized by congestion and increased weight of the lung, accompanied by heart failure, may become the cause of death. As the excess of acetylcholine at the neuronal level can persist for weeks until enough newly, locally synthesized acetylcholinesterase becomes available (the value of oximes in reducing this time is still under debate), after atropine administration, intravenous albumin and fluid infusion should be the first therapeutic interventions to reestablish normal blood volume and normal tissue oxygenation, avoiding death by cardiac arrest.

ISSLS PRIZE in basic science 2023: Lactate in lumbar discs-metabolic waste or energy biofuel? Insights from in vivo MRS and T2r analysis following exercise and nimodipine in healthy volunteers.

To quantitatively assess the dynamic changes of Lactate in lumbar discs under different physiological conditions using MRS and T2r. In step1, MRS and T2r sequences were standardized in 10 volunteers. Step2, analysed effects of high cellular demand. 66 discs of 20 volunteers with no back pain were evaluated pre-exercise (EX-0), immediately after targeted short-time low back exercises (EX-1) and 60min after (EX-2). In Step 3, to study effects of high glucose and oxygen concentration, 50 lumbar discs in 10 volunteers were analysed before (D0) and after 10days intake of the calcium channel blocker, nimodipine (D1). Lactate showed a distinctly different response to exercise in that Grade 1 discs with a significant decrease in EX-1 and a trend for normalization in Ex-2. In contrast, Pfirrmann grade 2 and 3 and discs above 40years showed a higher lactate relative to proteoglycan in EX-0, an increase in lactate EX-1 and mild dip in Ex-2. Similarly, following nimodipine, grade 1 discs showed an increase in lactate which was absent in grade 2 and 3 discs. In contrast, exercise and Nimodipine had no significant change in T2r values and MRS spectrum of proteoglycan, N-acetyl aspartate, carbohydrate, choline, creatine, and glutathione across age groups and Pfirrmann grades. MRS documented changes in lactate response to cellular demand which suggested a 'Lactate Symbiotic metabolic Pathway'. The differences in lactate response preceded changes in Proteoglycan/hydration and thus could be a dynamic radiological biomarker of early degeneration.

Long recovery induced by short exercise-to-rest ratio and effort duration determine the influence of hypoxia during repeated cycling sprints to exhaustion

Introduction
 Repeated sprints exercise (RSE) performed in hypoxia (RSH) induce greater performance improvement than in normoxia (Brocherie et al., 2017). It has been previously argued that RSH efficiency depend on the oxidative-glycolytic balance which is influenced by sprint duration and exercise-to-rest-ratio (E:R). Indeed, we recently showed that long sprint duration (e.g. 20 s vs 10 s or 5 s) blunts the additional impact of hypoxia on RSH with a constant large E:R of 1:22. However, E:R also influence acute response to RSH. Therefore, this study aims to compare acute responses during RSE to exhaustion with a short E:R (1:6) in normoxia (RSN) and hypoxia (FiO2 = 0.13) and the same sprint durations (5, 10 or 20 s) previously used.
 Methods
 On separate visits, 10 active participants completed in random order three RSH and three RSN sessions to exhaustion on a cycle-ergometer (Excalibur Sport, Lode) with three sprint durations and a constant short E:R of 1:6 (5:30; 10:60 and 20:120). Vastus lateralis muscle de-reoxygenation (Oxymon, Artinis Medical Systems) and power output were continuously recorded. Lower limb and breathing discomfort, blood lactate, and ratings of perceived exertion were evaluated immediately after exhaustion.
 Results
 Number of sprints and peak power output were higher while blood lactate was lower (all p < 0.001) during 5:30 compared to 10:60 or 20:120. No condition or interaction effects were reported for blood lactate and exercise-related sensation. Blood lactate and muscle deoxyhemoglobin increase (p < 0.001) and total hemoglobin decrease (p = 0.002) during sprint were more pronounced when sprint duration increased (no hypoxia effect).
 Discussion
 Similar deoxygenation changes during recovery were reported in hypoxia compared to normoxia suggesting that 1:6 ratio and the associated long recovery period seemed to allow myoglobin O2 store restauration, even with a FiO2 = 13%. Sprint effort should be interspersed by incomplete recovery making impossible the full O2 reloading myoglobin and PCr resynthesis. The increase in blood lactate and the concomitant decrease in muscle oxygenation during sprint with longer duration confirmed a switch in the oxidative-glycolytic balance for energy supply. Since short exercise-to-rest ratio blunt hypoxic effect during RSH due to too long recovery period, hypoxia did not participate to the switch from oxidative to glycolytic energy supply.
 Conclusion
 During RSE to exhaustion, a short exercise-to-rest ratio (i.e., 1:6) blunts the specific psychophysiological responses induced by hypoxia, probably due to too long of recovery period. Manipulating effort duration rather than hypoxic exposure is preferable to alter both anaerobic energy system solicitation and power produced during repeated cycling sprints to exhaustion using a short exercise-to-rest ratio.
 References
 Brocherie, F., Girard, O., Faiss, R., & Millet, G. P. (2017). Effects of repeated-sprint training in hypoxia on sea-level performance: A meta-analysis. Sports Medicine, 47, 1651-1660. https://doi.org/10.1007/s40279-017-0685-3

Lactic acidosis associated with metformin in patients with diabetic kidney disease; a mini-review

Background: Diabetes mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of metformin for diabetic kidney disease (DKD) patients. Methods: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial

BackgroundDespite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels.MethodsIn this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality.Results142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes.ConclusionsIn diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function.Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008).Graphical

Abstract 102: Imaging Markers Of Energy Metabolism In The Post-stroke Mouse Brain

Introduction: Cerebral ischemia results in a lesion comprised of dying cells surrounded by a band of tissue containing cells at risk of dying, called the penumbra. Understanding the status of energy metabolism in the stroke is necessary to get a clearer picture of the formation of the lesion, and may provide insights into potential therapeutic targets. The detection and distribution of energy metabolism biomarkers, particularly in ischemic brain tissue, presents significant challenges for conventional laboratory techniques due to the labile nature of these markers and the lack of unique chemical or spectroscopic handles. Fourier Transform infrared (FTIR) spectroscopic imaging can be used to map the distribution of different biochemical parameters, such as lipids, proteins, aggregated proteins, glycogen, lactate, pyruvate, ATP/ADP, NADH and glutamate. Methods: We employed the photothrombotic stroke model in adult mice to produce a permanent focal stroke lesion. Brain tissue was collected at multiple time points (1h to 4 weeks post-stroke). FTIR imaging was employed to map the distribution of unique biochemical fingerprints for over a dozen key metabolic markers. Immunohistochemistry was also performed on adjacent tissues to correlate biomarkers revealed by FTIR with the distribution of astrocytes, myelin and macrophages. Results: During the first week poststroke, the lesion shows decreased lipid esters, protein, ATP/ADP, NADH content while showing an increase in glutamate, aggregated protein, lactate and pyruvate. Glycogen can be seen to accumulate in the penumbra starting at 1 day post-stroke until 1 week post-stroke, which correlates with the appearance of astrocytes around the border of the stroke lesion. From 1 week to 4 weeks post-stroke, we observe an increase in lipid esters in the lesion, as well as a decrease in glycogen, lactate and pyruvate, while an increase in ATP/ADP and NADH can be observed. Conclusion: We are showing for the first time novel images of multiple energy metabolism biomarkers across a range of post-stroke time points in a mammalian brain. This type of imaging will be important in studying post-stroke interventions, particularly drugs that are known to alter energy metabolism.

Effects of Creatine Supplementation after 20 Minutes of Recovery in a Bench Press Exercise Protocol in Moderately Physically Trained Men.

The aims of this study were to analyse the effect of creatine supplementation on the performance improvement in a bench pressing (BP) strength test of muscle failure and to evaluate muscle fatigue and metabolic stress 20 min after the exercise. Fifty young and healthy individuals were randomly assigned to a creatine group (n = 25) or a placebo group (n = 25). Three exercise sessions were carried out, with one week of rest between them. In the first week, a progressive load BP test was performed until the individuals reached the one repetition maximum (1RM) in order to for us obtain the load-to-velocity ratio of each participant. In the second week, the participants conducted a three-set BP exercise protocol against 70% 1RM, where they performed the maximum number of repetitions (MNR) until muscle failure occurred, with two minutes of rest between the sets. After one week, and following a supplementation period of 7 days, where half of the participants consumed 0.3 g·kg-1·day-1 of creatine monohydrate (CR) and the other half consumed 0.3 g·kg-1·day-1 of placebo (PLA, maltodextrin), the protocol from the second week was repeated. After each set, and up to 20 min after finishing the exercise, the blood lactate concentrations and mean propulsive velocity (MPV) at 1 m·s-1 were measured. The CR group performed a significantly higher number of repetitions in Set 1 (CR = 14.8 repetitions, PLA = 13.6 repetitions, p = 0.006) and Set 2 (CR = 8 repetitions, PLA = 6.7 repetitions, p = 0.006) after supplementation, whereas no significant differences were seen in Set 3 (CR = 5.3 repetitions, PLA = 4.7 repetitions, p = 0.176). However, there was a significant increase in blood lactate at minute 10 (p = 0.003), minute 15 (p = 0.020), and minute 20 (p = 0.015) after the exercise in the post-supplementation period. Similarly, a significant increase was observed in the MPV at 1 m·s-1 in the CR group with respect to the PLA group at 10, 15, and 20 min after the exercise. Although the creatine supplementation improved the performance in the strength test of muscle failure, the metabolic stress and muscle fatigue values were greater during the 20 min of recovery.

Blood lactate in mild and moderate ARDS secondary to SARS COV 2

Background and objectivesElevated blood lactate levels are associated with poor outcome in several critical conditions. Patients with SARS-CoV-2 rarely develop hyperlactatemia. The purpose of this study is to evaluate the trend of lactatemia in patients affected by mild/moderate SARS-Co V-2-ARDS and if it affected prognosis. MethodsWe analyzed blood lactate levels in thirty-eight patients with severe SARS-CoV-2 infection admitted to COVID Care Unit of Santa Maria delle Grazie Hospital, Pozzuoli. ResultsTwenty patients survived and were discharged at home and 18 patients died. Despite severe hypoxia that affected all patients enrolled, T0 lactate was within normal values. All survivors showed a significant increase in lactate concentration the day prior to clinical improvement. In not-survivors levels of lactate did not increase significantly. ConclusionIn our study, patients who survive SARS CoV-2 ARDS have a fleeting increase in lactate, which precedes clinical improvement by one day.

The Association of the Oral Microbiota with the Effects of Acid Stress Induced by an Increase of Brain Lactate in Schizophrenia Patients.

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood-brain barrier, leading to the brain acidity. This study aimed to examine the association of the oral microbiota with the effects of acid stress induced by an increase of brain lactate in schizophrenia patients. The study included patients with a diagnosis of acute polyphasic psychotic disorder meeting criteria for schizophrenia at 3-month follow-up. Results: Individuals with a significantly higher total score on the Positive and Negative Syndrome Scale had statistically significantly lower lactate concentrations compared to those with a lower total score and higher brain lactate. We observed a positive correlation between Actinomyces and lactate levels in the anterior cingulate cap and a negative correlation between bacteria associated with lactate metabolism and some clinical assessment scales. Conclusions: Shifts in the oral microbiota in favour of lactate-utilising bacterial genera may represent a compensatory mechanism in response to increased lactate production in the brain. Assessment of neuronal function mediated by ALA-LAC-dependent NMDA regulatory mechanisms may, thus, support new therapies for schizophrenia, for which acidosis has become a differentiating feature of individuals with schizophrenia endophenotypes.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24hours) hyperacute stroke groups. Cross-sectional cohort. A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. Patients were divided into hyperacute (0-24hours), acute (24hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F=14.321) and creatine (F= 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r=-0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r=-0.472; lactate: r=0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC]=0.90). High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. 1. Stage 2.

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma.

Tumors meet their energy, biosynthesis, and redox demands through metabolic reprogramming. This metabolic abnormality results in elevated levels of metabolites, particularly lactate, in the tumor microenvironment. Immune cell reprogramming and cellular plasticity mediated by lactate and lactylation increase immunosuppression in the tumor microenvironment and are emerging as key factors in regulating tumor development, metastasis, and the effectiveness of immunotherapies such as immune checkpoint inhibitors. Reprogramming of glucose metabolism and the "Warburg effect" in hepatocellular carcinoma (HCC) lead to the massive production and accumulation of lactate, so lactate modification in tumor tissue is likely to be abnormal as well. This article reviews the immune regulation of abnormal lactate metabolism and lactate modification in hepatocellular carcinoma and the therapeutic strategy of targeting lactate-immunotherapy, which will help to better guide the medication and treatment of patients with hepatocellular carcinoma.

PS-BPB08-4: IMPAIRED TCA CYCLE METABOLISM IN DIABETIC NEPHROPATHY IS LINKED TO ALBUMINURIA AND KIDNEY INJURY

Objective: Recent work has highlighted potential contributions of impaired renal energy metabolism, including mitochondrial dysfunction and altered fatty acid metabolism, in chronic kidney diseases including diabetic nephropathy (DN). However, causal connections between specific metabolic abnormalities and pathophysiology of DN have been difficult to establish. Here, we approach this question using a mouse model recapitulating characteristic features of human DN and a targeted metabolomics platform designed to assess key metabolic pathways involving amino acids, fatty acids, glycolysis and the TCA cycle. Design and method: We generated a mouse model of DN with underlying activation of the renin-angiotensin system (RAS) by a renin transgene (R) driven by the albumin promoter on the Akita background of type I diabetes (A). We have shown that on a susceptible 129/Sv background, Akita-ReninTg (AR) mice exhibit cardinal characteristics of human DN including high-grade albuminuria and glomerulosclerosis, whereas AR mice on a C57BL/6 background do not develop DN. To assess the impact of genetic background on energy metabolism in DN, kidneys from 24-week-old male AR mice on both backgrounds were evaluated by the targeted metabolome analysis. To further distinguish the impact of RAS activation on relevant pathways associated with kidney disease development, 12-week-old male 129/Sv AR mice were treated with the angiotensin receptor blocker (ARB) losartan 10 mg/kg/day for 12 weeks. 24-hour urine samples were collected in metabolic cages and urine albumin levels were measured by EIA. Kidneys from age-matched parental 129/Sv and C57BL/6 wild-type mice were analyzed as controls. Results: A distinct metabolic profile was observed in kidneys of DN-susceptible 129/Sv AR mice including reduced levels of C2 acetyl-carnitine that reflect a deficiency in acetyl-CoA, perturbations of TCA cycle intermediates and increased lactate levels. In addition, levels of phosphorylated-AMPK were reduced. These metabolic changes were absent in DN-resistant C57BL/6 AR mice. Treatment of 129/Sv AR mice with the ARB dramatically reduced albuminuria (906 ± 169 vs 193 ± 42 μg/day, p &lt; 0.01) and attenuated kidney pathology while restoring levels of C2 acetyl-carnitine, TCA intermediates, lactate and phosphorylated-AMPK toward normal. ARB treatment also increased kidney ATP content. In 129/Sv mice, there were statistically significant correlations between albuminuria and kidney levels of lactate, acetyl-carnitine, citrate and succinate. Conclusions: Thus, there is a distinct profile of impaired energy metabolism associated with DN susceptibility that is attenuated by RAS blockade. Impaired TCA cycle function and coincident increases in lactate are linked to albuminuria in mice with DN, and may contribute to kidney injury.

EFEITO REPARADOR DA CORRIDA MODERADA SOBRE A MUSCULATURA DOS MEMBROS INFERIORES

ABSTRACT Introduction: Jogging can be a great way to improve physical condition, boosting mind and body. Its method of movement is simple, and there are no sporting limitations as to age, gender, or training place. Jogging is believed to help repair muscle and joint injuries in the lower limbs. Objective: To explore the effects of running on recovering lower limb muscles. Methods: We surveyed 60 undergraduate students who took a 400-meter test at the same site. According to the test results, they were divided into low, medium, and high fitness levels. A questionnaire survey was also used with 20 undergraduate students from the Physical Education Department. Four groups of volunteers did some jogging exercises. Physiological, biochemical, and muscle strength measurements were performed after jogging. The data were statistically treated. Results: The magnitude of change in the sagittal angle of the knee and ankle joint did not increase significantly with increasing jogging rate. The changes in the sagittal angles of the hip, knee, and ankle joints were the same for the volunteers with different jogging rates. After 60 minutes of exercise, the low-fitness group showed faster breathing, an elevated heart rate, and a higher rate of lactate and creatinine in the blood. After 120 minutes of exercise training, all sedentary volunteers showed an increase in lactate, creatinine, respiratory rate, and heart rate (P&lt;0.05). The test performance started to decrease at 400 meters. Conclusion: The maximal activation of different parts of the locomotor system changed under different rates of movement. Brief, controlled jogging may be beneficial to lower limb muscles. Still, long-term jogging may cause even more damage to the body and deleterious changes to rehabilitation in blood and biochemical parameters. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

Arterial Lactate Concentration at the End of Liver Transplantation is Independently Associated With One-Year Mortality

Liver transplant patients who develop hyperlactatemia are at increased risk of postoperative morbidity and short-term mortality, but there are few data on longer-term outcomes. We therefore investigated if arterial lactate concentration obtained immediately after surgery, at the time of admission to the intensive care unit (ICU), was associated with 1-year mortality. In this retrospective cohort study, all patients who underwent liver transplant surgery from a deceased donor between September 2013 and December 2019 were screened for inclusion. Patients who underwent combined transplantation surgery and those with a history of previous liver transplantation (ie, redo surgery) were not included. Logistic regression modeling included univariate and multivariate analyses. Receiver operating characteristic curves and areas under the curves were calculated. Lactate thresholds and association with outcome were analyzed for specificity, sensitivity, and Youden's index. Of 226 patients included, 18.4% died within 1 year of liver transplantation. Immediate postoperative lactate concentration was independently associated with 1-year mortality with an adjusted odds ratio of 1.35 (95% CI 1.16-1.59; P < .001) per mmol/L increase in lactate and an area under the curve of 0.80 (95% CI 0.72-0.87; P < .001). A lactate concentration of 2.25 mmol/L (cutoff determined using Youden's index) was associated with increased 1-year mortality with a sensitivity of 0.71 and a specificity of 0.72. Increased arterial lactate concentration on admission to the intensive care unit immediately after orthotopic liver transplantation is independently associated with increased 1-year mortality.

Inoculation with heterofermentative strains &lt;i&gt;Lentilactobacillus buchneri&lt;/i&gt; CNCM 40788 and &lt;i&gt;Lentilactobacillus hilgardii&lt;/i&gt; CNCM I-4785 either alone or combined improves fermentation and aerobic stability of ensiled triticale (X-triticosecale)

&lt;abstract&gt; &lt;p&gt;Triticale, a small-grain forage, was harvested for an ensiling experiment evaluating different silage inoculants. Fresh material (mean dry matter 404.1 g kg&lt;sup&gt;−1&lt;/sup&gt;) was wilted, chopped, and assigned to one of four treatment groups including water only (Control), heterofermentative strains &lt;italic&gt;Lentilactobacillus buchneri&lt;/italic&gt; (LB), &lt;italic&gt;Lentilactobacillus hilgardii&lt;/italic&gt; (LH), or combination (Combo) of both. Inoculants were applied at 4.0 x 10&lt;sup&gt;5&lt;/sup&gt; CFU per g of fresh forage, and the Combo contained both strains at 2.0 x 10&lt;sup&gt;5&lt;/sup&gt; CFU per g. Treated forage was packed into 7.57 L mini-silos for openings after 15, 30, and 130 d. Samples were collected at each opening for microbial enumeration of lactic acid bacteria, enterobacteria, yeasts, and moulds. Additional samples were collected for analysis of fermentation profiles, and nutritional analysis following dry matter determination and grinding. Aerobic stability was also evaluated at each opening through a 10-d period. Fermentation profiles were notably affected, including increases in acetic acid (g/kg DM) in LB and Combo treated silage after 15 d which resulted in reduced pH. Aerobic stability was vastly improved through inoculation by prolonging the time to reach 2˚ C above ambient, which was likely a result of decreased yeast counts. Our research validates the use of combined heterofermentative lactic acid bacteria strains on an ensiled small-grain specie, and further agrees with previous findings of prolonged aerobic stability through increases in lactate and acetate in response to co-inoculation.&lt;/p&gt; &lt;/abstract&gt;

Increased brain 1H-MRS glutamate and lactate signals following maximal aerobic capacity exercise in young healthy males: an exploratory study.

Physical exercise involves increased neuronal activity of many brain structures, but 1H-MRS investigations on the effects of human brain glutamate (Glu) concentrations on acute exercise have been sparse. Previous studies consistently found increases in brain lactate (Lac) concentrations following graded exercise up to 85% of the predicted maximal heart rate. However, the reported effects on brain concentrations of glutamine and glutamate were not consistent. This study aimed to determine the effect of acute intense graded maximal exercise on 1H-MRS signals related to concentrations of Glu, glutamate+glutamine (Glx), and Lac. Young adult males were randomly divided into two groups and subjected to 1H-MRS when resting (NE) or shortly after cessation of the intense graded exercise intended to pass the anaerobic threshold (E). 1H-MRS spectra were acquired from the large voxel encompassing the occipito-parietal cortex only once. Estimates of Glu, Glx, and Lac concentrations were calculated in institutional units by normalizing to a spectroscopic signal originating from creatine-containing compounds (Cr). Concentrations of Glu, Glx, and Lac were respectively 11%, 12.6%, and 48.5% higher in E than in NE (p < 0.001). The increased brain Lac signal in the exercising group indicated that in our experiment, vigorous exercise resulted in passing the anaerobic threshold and lactate apparently entered the brain. Concomitantly glutamate-related resonance signals from the vicinity of the occipito-parietal cortex were significantly increased; physiological mechanisms underlying these phenomena require further study. Future studies should evaluate whether the normalization rate of these concentrations is a marker of general physical fitness.

Is moderate-intensity interval training more tolerable than high-intensity interval training in adults with obesity?

Interval training (IT) has been shown to be a time-effective alternative to traditional training programmes in the management of obesity. Nevertheless, studies comparing the effects of different IT intensities on inflammation, muscle and liver damage, and perceptual responses in people with obesity are relatively scarce. This study aimed to compare the acute effects of two different IT protocols matched by the mean load and duration on biochemical and perceptual responses in sedentary adults with obesity. Twenty-two volunteers (age = 33.40 ± 10.01 years, BMI = 38.29 ± 7.09 kg/m²) were randomized to perform two conditions: moderate-intensity IT (MIIT) 5 × 3 min (70% of peak power output (PPO))/2 min (45%PPO) and high-intensity IT (HIIT) 8 × 1 min (90%PPO)/2 min (45%PPO). Blood samples were drawn before and after exercise for biochemical and haematological measurements. Rating of perceived exertion (RPE) was assessed during and after exercise. Perceptual pain was evaluated before, throughout and after exercise. C-reactive protein, white blood cells and neutrophils increased only after HIIT (p < 0.001, for all). Aspartate aminotransferase, alanine aminotransferase, creatine kinase and lactate dehydrogenase increased in both HIIT and MIIT (p < 0.001, for all), without any difference between sessions. HIIT induced a greater increase of blood lactate compared to MIIT (p < 0.05). Pain and RPE scores were higher during HIIT vs. MIIT (p < 0.001 and p < 0.01, respectively). MIIT induced fewer immune system perturbations and less muscle pain and was perceived as more tolerable compared to HIIT session. Therefore, MIIT could be used as a first step to promote body adaptations before starting a HIIT programme in sedentary people with obesity.

The effect of antibiotic versus no treatment at dry-off on udder health and milk yield in subsequent lactation: A retrospective analysis of Austrian health recording data from dairy herds.

Bovine mastitis is the most commonly diagnosed disease of dairy cows worldwide and causes extensive economic losses to milk producers. Intramammary infection status before dry-off plays a decisive role with respect to udder health and milk yield in the subsequent lactation. The aim of this study was to compare the effect of antibiotic dry cow therapy (DCT) versus no treatment at dry-off on milk yield, somatic cell count (SCC), inflammation of the mammary gland (IMG), and the incidence of clinical mastitis in the subsequent lactation. Dairy herd data from 251 Austrian dairy farms were recorded over an observation period of 12 mo and subsequently analyzed. The data set included 5,018 dairy cows: 2,078 were treated with antibiotics (abDCT group) and 2,940 were not treated (noDCT group) at dry-off. The abDCT group was subdivided, based on the antimicrobial active substances used for drying off, into 4 different groups (penicillins, cloxacillin, cephalosporins, and rifaximin). Based on bacteriological culture results, infections were grouped into those caused by major, minor, and other pathogens. Additionally, the IMG was defined via SCC from milk recording data using a cutoff of 200,000 cells/mL before drying off and after calving. The incidence of clinical mastitis cases within 30 and 90 d in milk was calculated using veterinary diagnosis data. To investigate the effect of different dry cow therapies on the following parameters: milk yield, SCC, and diagnosed clinical mastitis cases, different linear mixed models were constructed. Overall, the abDCT group was determined to have a significantly higher milk yield over 305 d in milk in the subsequent lactation (increase of 6.18%), compared with the noDCT group (increase of 4.29%). Both groups (abDCT and noDCT) demonstrated a decrease in the first SCC after calving compared with the SCC before dry-off, although the treated cows had a significantly higher reduction. Regarding the different antibiotic groups, with exception of the rifaximin treated cows, all antibiotic groups showed a significant difference from not treated cows with respect to SCC. Additionally, we were able to demonstrate that cows with IMG before dry-off had a 2.073 times higher chance of an increased SCC (>200,000 cells/mL) after calving. With respect to the veterinary diagnosis data, neither the IMG before drying off nor the type of DCT had a significant influence on the probability of developing clinical mastitis within 30 or 90 d in milk. Only a small number of treatments was accompanied with a bacteriological examination before drying off. However, the existing data in this study indicates that the intramammary infection status before dry-off in combination with different dry cow treatments influences udder health and milk yield after calving. Nevertheless, further studies with larger data sets of bacteriological examinations are necessary to enable a more in-depth investigation into the effects of different antibiotic substances used for DCT.

Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export

BackgroundTumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. PurposeIn this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. MethodsColony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. 1H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. ResultsFC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca2+ overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. ConclusionFC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved.