Increase In Lactate Concentration Research Articles

The Influence of Pedaling Frequency on Blood Lactate Accumulation in Cycling Sprints.

Anaerobic performance diagnostics in athletes relies on accurate measurements of blood lactate concentration and the calculation of blood lactate accumulation resulting from glycolytic processes. In this study, we investigated the impact of pedaling frequency on blood lactate accumulation during 10-second maximal isokinetic cycling sprints. Thirteen trained males completed five 10-second maximal isokinetic cycling sprints on a bicycle ergometer at different pedaling frequencies (90 rpm, 110 rpm, 130 rpm, 150 rpm, 170 rpm) with continuous power and frequency measurement. Capillary blood samples were taken pre-exercise and up to 30 minutes post-exercise to determine the maximum blood lactate concentration.Blood lactate accumulation was calculated as the difference between maximal post-exercise and pre-start blood lactate concentration. Repeated measurement ANOVA with Bonferroni-adjusted post hoc t-tests revealed significant progressive increases in maximal blood lactate concentration and accumulation with higher pedaling frequencies (p<0.001; η2+>+0.782).The findings demonstrate a significant influence of pedaling frequency on lactate accumulation, emphasizing its relevance in anaerobic diagnostics. Optimal assessment of maximal lactate formation rate is suggested to require a pedaling frequency of at least 130 rpm or higher, while determining metabolic thresholds using the maximal lactate formation rate may benefit from a slightly lower pedaling frequency.

Role of GPR81 in regulating intramuscular triglyceride storage during aerobic exercise in rats.

Lactate, a metabolite of exercise, plays a crucial role in the body. In these studies, we aimed to investigate the role of G protein-coupled receptor 81 (GPR81), a specific receptor for lactate, in regulating lipid storage in the gastrocnemius muscle of rats. To achieve this, we measured the impact of sodium 3-hydroxybutyrate (3-OBA) concentration and time on the cAMP-PKA signaling pathway in the gastrocnemius muscles ofrats. Our investigation involved determining the effects of administering 3-OBA at a concentration of 3 mmol L-1 just 15 min before exercise. As expected, exercise led to a notable increase in intramuscular lactate concentration in rats. However, injecting 3-OBA prior to exercise yielded intriguing results. It not only further augmented the cAMP-PKA signaling pathway but also boosted the expression of lipolysis-related proteins such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Simultaneously, it decreased the expression of fat-synthesizing proteins, including acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS), while increasing the protein expression of cytochrome c oxidase subunit Ⅳ(COX Ⅳ) and the activity of citrate synthetase (CS). Unfortunately, there was no significant change observed in intramuscular triglyceride (IMTG) content. In summary, our findings shed light on the role of lactate in partially regulating intramuscular triglycerides during exercise.

A57 LONG-TERM EXPOSURE TO ANTICANCER TREATMENTS INCREASES AUTOPHAGY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background The most common type of esophageal cancer, esophageal squamous cell carcinoma (ESCC), has a 5-year survival rate of only 15%. This low survival rate is to some extent attributed to a high relapse rate, which is, in part, linked to the presence of cancer stem cells (CSC). CSC are a subpopulation of tumor cells that show reduced sensitivity to conventional anticancer therapies, increased potency and self-renewal capacities. With that in mind, ESCC cell lines were exposed in a prolonged manner to anticancer treatments (radiotherapy, 5-FU chemotherapy, and combined therapy) in our laboratory. As expected, an increase in the proportion of CSC (CD44highCD24high) was observed by flow cytometry following the treatments. In pursuit of innovative therapeutic approaches, we conducted an in-depth investigation of the proteomic profiles of these cell lines by mass spectrometry (MS), seeking to unveil novel biological mechanisms. Interestingly, many proteins associated with metabolism and autophagy were modulated. Several alterations were observed by a metabolomic approach as well, namely an increase in intracellular lactate concentration. Recently, a novel role for lactate has been described: lactylation, which is a post-translational modification. Lactylome of those cell lines revealed alteration in proteins related to autophagy and those results led to my research project. Aims Investigate the role of lactylation in autophagy of ESCC. Methods Human ESCC cell lines (including the cell lines exposed to anticancer treatments) will be used as cell culture models. Cell and organoid cultures, mass spectrometry, qPCR, WB, and proliferation assay were used. Results MS analysis of proteins related to autophagy (i.e. RAB1B, CK2, SNX6 et GABARAP) suggests differential regulation of autophagy in cell lines exposed to prolonged treatments. A strong contribution of the 5-FU treatment to the autophagic modification is observable in the double-treated cells. Thus, we confirmed an increase in the LC3BII/I ratio by WB in the cell lines exposed to anticancer treatments. LC3BII/I WB used in combination with Bafilomycin A1 treatment for inhibition of autophagosome and lysosome fusion is a commonly used read-out for autophagic flux. To further study the link between lactylation, autophagy and CSC, we screened 10 human ESCC cell lines for their LC3BII/I ratio. Four cell lines were selected: TE1, TE2, HCE4 and TE5. Using Bafilomycin A1, we confirmed that the autophagic flux in those cell lines was not blocked. Those cell lines will now be used to perform lactylome analysis of sorted CSC cells. Conclusions In brief, our results showed that the autophagic flux is increased in cells exposed to prolonged treatments. This suggests that autophagy could play a role in ESCC response to treatment. Funding Agencies CIHRTRIANGLE, Chaires de recherche du Canada, CRCHUS, Université de Sherbrooke

Calculation of a conversion factor for estimating the glycolytic contribution in exercise from post-exercise blood lactate concentration.

Purpose: Often, the glycolytic contribution in a bout of heavy or severe intensity exercise is estimated by multiplying the increase in blood lactate concentration above resting levels that is engendered by the exercise (in mM) by 3.3 (or 3) mL·kg-1 per mM. Our purpose was to verify the value of this conversion factor, using methods that were completely different from those of the original studies. Methods: Six women (mean ± SD), age, 23 ± 1year; VO2max, 46 ± 4mL·kg-1·min-1) and three men (23 ± 0years; 54 ± 8mL·kg-1·min-1) completed 6min of heavy intensity exercise in conditions of normoxia and hypoxia (FIO2, ∼12%). VO2 was measured throughout the exercise and 7min of recovery. The increase in glycolytic contribution was estimated as the reduction in aerobic contribution in hypoxia, after correction for the effects of hypoxia on the oxygen demand and on the contribution from phosphocreatine. The peak post-exercise blood lactate concentration was measured in fingerstick blood samples. Results: The ratio between the increase in estimated glycolytic contribution (in mL·kg-1) in hypoxia and the increase in peak blood lactate concentration (in mM) yielded an oxygen equivalent of 3.4 ± 0.4mL·kg-1 per mM (range, 2.6mL·kg-1 per mM to 4.0mL·kg-1 per mM) for cycle ergometer exercise. Conclusion: These results generally support the use of a common conversion factor to calculate the glycolytic contribution from post-exercise blood lactate concentrations. However, there is some inter-individual variability in the conversion factor.

Amifostine ameliorates bleomycin-induced murine pulmonary fibrosis via NAD+/SIRT1/AMPK pathway-mediated effects on mitochondrial function and cellular metabolism

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy.ObjectiveWe investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis.MethodsC57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK).ResultsThree doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment.ConclusionAmifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Molecular mechanism of circHIPK3 in mitochondrial function in septic acute kidney injury.

Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit-8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC-1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid-Schiff staining, and SA-β-gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)-148b-3p/DNMT1/3a/Klotho axis. Inhibition of miR-148b-3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR-148b-3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI.

Recycled UHT Milk Carton Cellulose Substrate for Colorimetric and Electrochemical Sensor of Lactate

Recycled cellulose prepared from UHT milk carton waste was employed as a novel substrate for colorimetric and electrochemical lactate sensors to evaluate the milk quality. The cellulose is initially extracted by chemical method (alkali and bleach treatment) to prepare the dual-sensing substrate. For colorimetric sensor, an enzyme immobilization was performed on the recycled cellulose substrate prior to enhancing specificity for lactate detection. Subsequently, the recycled cellulose substrate was dipped in an aluminum solution extracted from aluminum foil from the packaging to create a conductive working electrode with improved surface roughness compared with recycled cellulose substrate, confirmed by atomic force microscopy. For the physical and chemical characterization, scanning electron micrograph demonstrated 3D fibrous network with the porous in between, and X-ray photoelectron spectroscopy presented the binding energy with the Al-O peak at 73.256 eV, verifying the existence of aluminum on the recycled cellulose substrate after surface modification. For the sensing performance, the colorimetric sensor provides the increasing purpleness intensity with the increment of lactate concentration, while the aluminum-modified recycled cellulose substrate exhibited the increased current response upon the increased lactate concentration. Furthermore, this dual-lactate sensor can offer a linearity of 0.125-2 M, covering a cut-off lactate level (1.0 M) for milk spoilage. Ultimately, this sensor is successfully utilized for lactate determination in real milk samples, showing its high efficiency as an alternative platform for milk quality evaluation.

BLAST INJURI. ANESTHESIA AND INTRAOPERATIVE INTENSIVE CARE AT THE EARLY HOSPITAL STAGE (ADVANCE NOTICE)

Summary. Explosive injury is a combat multifactorial injury that occurs as a result of the combined damaging effect on the human body of a shock wave, gas jets, fire, toxic products of explosion and combustion, ammunition casing fragments, secondary projectiles. The hostilities taking place in Ukraine present many questions to anesthesiologists regarding the provision of medical care to victims of blast injuries. This type of injury is often associated with damage to 2-4 anatomical sites and sometimes more. Moreover, most of the hospital care is provided in civilian hospitals located close to fighting.&#x0D; The aim of study. The choice of anesthesia technology and intraoperative intensive therapy in victims of explosive trauma depending on the severity of the explosive trauma and the condition of the patients.&#x0D; Material and method. During the period March-December 2022, 226 (195 men, 31 women) patients of explosive injuries were admitted to the Zaporizhzhya Regional Clinical Hospital and assessed according to the GKO scale (standardized system for assessing the severity of injuries and the condition of patients.&#x0D; The results. Before the operation, there was normotension and moderate tachycardia. However, in 25 patients, the systolic blood pressure was less than 90 mm Hg, which required the use of sympathomimetics and infusion therapy with crystalloids and colloids. During the operation, sympathomimetics continued to be used in 42 patients. Norepinephrine was used in 37 patients in a dose of 0.1 to 0.4 μg/kg/min. Phenylephrine – in 5 patients in bolus doses of 20-100 μg.&#x0D; The indicators of systolic, diastolic, pulse, mean arterial pressure and heart rate at the stage of completion of the operation did not differ significantly from the initial ones. Before the operation, the patients had subcompensated metabolic and respiratory acidosis, hyperoxemia, and increased lactate concentration. At the stage of the operation, the phenomenon of metabolic acidosis increased, as evidenced by a significant increase in the BE indicator. Respiratory acidosis and hyperoxemia persisted. The concentration of lactate in the blood decreased significantly, on average by 21 %, but on average was (4.1±0.1) mmol/l.&#x0D; Conclusion. Assessing the severity of the patients on the GKO scale allows you to choose the anesthesia technology considering the influence of the drugs used for anesthesia on hemodynamics. At the stages of treatment of the patients of the blast trauma, it was possible to maintain normotension. Mixed decompensated acidosis and increased lactate at the end of the operation indicate oxygen debt.

Low oxygen in inspired air causes severe cerebrocortical hypoxia and cell death in the cerebral cortex of awake rats

Type 1 respiratory failure (T1RF) is associated with secondary acute brain injury (sABI). The underlying mechanisms of sABI could include injury to brain cells mediated either by hypoxia or by lung injury-triggered inflammation. To elucidate to what extent T1RF causes hypoxia and a consequent hypoxic injury in the brain in the absence of lung injury, we exposed healthy, conscious Sprague-Dawley rats to 48 h long low partial pressure of O2 in inspired air (PiO2) (7.5–8 % O2 in N2, CO2 < 0.5 %, normal barometric pressure) and measured the partial pressure of oxygen in the premotor cortex (PtO2), cerebral blood flow (CBF), lactate concentrations, and cell death. Low PiO2 significantly affected PtO2, which was 52.3 (SD 2.1) mmHg when PiO2 was normal but declined to 6.4 (SD 3.8) mmHg when PiO2 was low for 1 h. This was accompanied by increased lactate concentrations in plasma, CSF, and premotor cortex. Low PiO2 elevated the number of dead cells in the cerebral cortex from 5.6 (SD 4.8) % (when PiO2 was normal) to 20.5 (SD 4.1) % and 32.37 (SD 6.5) % after 24 h and 48 h exposure to low PiO2, respectively. The Mann-Kendall test could not detect any monotonic increase or decrease in pial blood flow during the 48 h exposure to low PiO2. In summary, our findings suggest that exposure to low PiO2 caused a severe hypoxia in the cerebral cortex, which triggers a massive cell death. Since these conditions mimic T1RF, hypoxic injury could be an important underlying cause of T1RF-induced sABI.

Results after intraoperative open and endovascular revascularization of acute mesenteric ischemia requiring a laparotomy

BackgroundAcute mesenteric ischemia (AMI) is a dreaded condition with a difficult diagnosis and high mortality. Due to different baseline situations, the frequently performed comparison between endovascular and open surgical treatment is interfered with selection bias. The purpose of this study was to review outcomes in AMI treatment with an open or endovascular approach in association with laparotomy and to evaluate the endovascular-first strategy in similar clinical situations.MethodsThe clinical data of 74 patients treated for AMI from 2007 to 2021 were retrospectively reviewed and compared. In-hospital mortality was appointed as the primary study endpoint. Risk factors for mortality were identified by using univariate and multivariate analysis.ResultsIn total, 61 patients (82%) were treated open surgically (OT) and, 13 patients (18%) with an endovascular approach (ET) in combination with laparatomy. The etiology of AMI was 49% arteriosclerotic and 51% thromboembolic occlusions. The total in-hospital mortality manifested at 43% (n =32) (OT 41% vs. ET 53.8%; P=0.54). As independent risk factors for in-hospital mortality, pneumatosis intestinalis (P=0.01), increased lactate concentration (P=0.04), and ischemic intestinal sections (P=0.01) were identified. Additionally, on univariate analysis patient age, congestive heart failure (> NYHA II) and atrial fibrillation were related with higher mortality.ConclusionsMorbidity and mortality of AMI remains at a high level. Conventional open or intraoperative endovascular therapy achieved similar results in patients with indication for laparotomy. Advanced disease stage with ischemic intestinal sections at presentation and cardiovascular comorbidities were associated with adverse outcome.

Dibutyl phthalate disrupts energy metabolism and morphology in the gills and induces hepatotoxicity in zebrafish.

This study investigated the acute effects of dibutyl phthalate (DBP) exposure on energy metabolism and gill histology in zebrafish (Danio rerio). The in vitro incubation of gill tissue with 10 μM DBP for 60 min altered tissue energy supply, as shown by decreased lactate content and lactate dehydrogenase (LDH) activity. Higher concentrations of DBP (100 μM and 1 mM) increased lactate content and LDH activity; however, they blocked glucose uptake, depleted the glycogen content in cellular stores, and induced injury to the gills, as measured by LDH release to the extracellular medium. In addition, in vivo exposure of fish to 1 pM DBP for 12 h induced liver damage by increasing alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) activities. Gill histology indicated hyperemia, lamellar fusion, lamellar telangiectasis, and necrosis. Data indicate that acute exposure of zebrafish gills to the higher DBP concentrations studied induces anaerobic cellular activity and high lactate production, causing gill damage, diminishing cell viability, and incurring liver dysfunction.

Lambda-cyhalothrin-induced pancreatic toxicity in adult albino rats

Lambda-cyhalothrin (LCT) is one of the most frequently utilized pyrethroids. This study aimed to explore the toxic effects of subacute exposure to LCT on the pancreas and the hepatic glucose metabolism in adult male albino rats. 20 rats were equally grouped into; Control group and LCT group. The latter received LCT (61.2 mg/kg b.wt.), orally on a daily basis for 28 days. At the end of experiment, blood samples were collected for the determination of serum glucose and insulin levels. Pancreases were harvested and levels of malondialdehyde (MDA); catalase (CAT); superoxide dismutase (SOD); reduced glutathione (GSH); tumor necrosis factor-α (TNF-α); interleukin-6 (IL-6); nuclear factor erythroid 2–related factor 2 (Nrf2); heme oxygenase 1 (HO-1); and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were assessed. Also, liver samples were analyzed for the activity of glucose metabolism enzymes, glycogen content, and pyruvate and lactate concentrations. Histopathological and immunohistochemical examinations of pancreatic tissues were undertaken as well. Results revealed hyperglycemia, hypoinsulinemia, increased MDA, TNF-α, IL-6, and NF-κB levels, in association with reduced CAT, SOD, GSH, Nrf2, and HO-1 levels in LCT group. Liver analyses demonstrated a clear disturbance in the hepatic enzymes of glucose metabolism, diminished glycogen content, decreased pyruvate, and increased lactate concentrations. Besides, pancreatic islets displayed degenerative changes and β-cells loss. Immunohistochemistry revealed diminished area percentage (%) of insulin and Nrf2 and increased TNF-α immunoreaction. In conclusion, subacute exposure to LCT induces pancreatic toxicity, mostly via oxidative and inflammatory mechanisms, and dysregulates hepatic glucose metabolism in albino rats.

Rest reduces venous lactate levels significantly in patients in outpatient clinic

Lactate is produced in the human body during physical activity and elimination takes time with a half-life of approximately 18 min. We, therefore, investigated the potential impact of resting time (RT) duration on lactate concentration in our outpatient venipuncture clinic for all lactate requests during a 4½-year period. All samples drawn for venous lactate analysis during a 4½-year period in our hospital outpatient venipuncture clinics were included in this study. RT was reported electronically at each visit. Results from a total of 831 samples were obtained for further analysis. We found varying lactate concentrations across resting time <15min (median 1.6 mmol/L, IQR[1.2–2.1] mmol/L), between <15 min and >30 min (median 1.4 mmol/L, IQR[1.0–1.9] mmol/L) and for >30 min (median 1.3 mmol/L, IQR[1.0–1.7] mmol/L). There was a significant difference between <15 min versus 15–30 min (p = 0.015), which gives a 17.7% higher lactate from 15–30 min to <15 min. There was a significant 28.3% increase in mean lactate concentration from >30min to <15min (p < 0.0001) when corrected for age. We found that lactate concentration was dependent on RT in the outpatient clinic. The difference was clinically significant. Based on the results of this study, we, therefore, conclude that a 15 min waiting time before venipuncture for lactate sampling in an outpatient clinic is of clinical importance.

Bacterial and Metabolic Factors of Staphylococcal Planktonic and Biofilm Environments Differentially Regulate Macrophage Immune Activation

Biofilm formation is a leading cause for chronic implant-related bone infections as biofilms shield bacteria against the immune system and antibiotics. Additionally, biofilms generate a metabolic microenvironment that shifts the immune response towards tolerance. Here, we compared the impact of the metabolite profile of bacterial environments on macrophage immune activation using Staphylococcus aureus (SA) and epidermidis (SE) conditioned media (CM) of planktonic and biofilm cultures. The biofilm environment had reduced glucose and increased lactate concentrations. Moreover, the expression of typical immune activation markers on macrophages was reduced in the biofilm environment compared to the respective planktonic CM. However, all CM caused a predominantly pro-inflammatory macrophage cytokine response with a comparable induction of Tnfa expression. In biofilm CM, this was accompanied by higher levels of anti-inflammatory Il10. Planktonic CM, on the other hand, induced an IRF7 mediated Ifnb gene expression which was absent in the biofilm environments. For SA but not for SE planktonic CM, this was accompanied by IRF3 activation. Stimulation of macrophages with TLR-2/-9 ligands under varying metabolic conditions revealed that, like in the biofilm setting, low glucose concentration reduced the Tnfa to Il10 mRNA ratio. However, the addition of extracellular L-lactate but not D-lactate increased the Tnfa to Il10 mRNA ratio upon TLR-2/-9 stimulation. In summary, our data indicate that the mechanisms behind the activation of macrophages differ between planktonic and biofilm environments. These differences are independent of the metabolite profiles, suggesting that the production of different bacterial factors is ultimately more important than the concentrations of glucose and lactate in the environment.

Type 1 respiratory failure-induced hypoxemia triggers complex signaling responses and apoptosis in the rat brain

Type 1 respiratory failure (T1RF)is caused by lung injury or low partial pressure of O 2 (PO 2 ) in air. It is associated with secondary acute brain injury (sABI), but the mechanisms behind it are not clear and could include primary hypoxic injury, increased intracranial pressure due to hypoxemia or due to mechanical ventilation, or could be mediated by lung injury-triggered inflammation. This study aimed to elucidate the effects of T1RF-induced hypoxemia on the brain in the absence of lung injury. SD rats were exposed to 8%O 2 in N 2 for up to 48h. We measured tissue PO 2 (Pt O2 ) and cerebral blood flow (CBF) in the cerebral cortex (CC) and estimated lactate concentrations and apoptosis in the CC, ependymal layer (EL) and choroid plexuses (CPs) during the time course of hypoxemia using the TUNEL assay. Cerebrospinal fluid (CSF) samples were collected during normoxia, after 24h and 48h hypoxemia. The concentrations of 32 signaling molecules were estimated in these samples by multiplex assays. Expressions of 84 signaling molecules and 5 housekeeping genes in the CC were explored by RT 2 Profiler TM PCR Array. Numerical values are presented as mean (SD). Data was compared with one-way ANOVA and the Kruskal-Wallis test. The Mann-Kendall test was used to assess whether CBF was increasing or decreasing during hypoxemia. Fold changes in the expressions of the tested mRNAs were estimated using GeneGlobe software. Statistical significance was set at p&lt;0.05. Hypoxemia exerted a significant effect on Pt O2 in the CC (p&lt;0.01), which was 49.5 (2.99) mmHg (n=10) during normoxia but declined to 6.4 (3.8) mmHg (n=5) after 1h hypoxemia (p&lt;0.01 vs. normoxia) and then slowly increased, reaching 18.5 (2.8) mmHg (n=6) after 43h hypoxemia (p&lt;0.01 vs. normoxia and 1h hypoxemia). This was accompanied by a significant increase in lactate concentrations in the CC and CSF (p&lt;0.01), but not in plasma (p=0.055). Hypoxemia exerted significant effect on the number of apoptotic cells in the CC (p&lt;0.01), EL (p&lt;0.01) and CPs (p&lt;0.01). In the CC the number of apoptotic cells was 5.63 (4.76) during normoxia, 20.48 (4.1) % after 24h hypoxemia (p&lt;0.01 vs. control) and 32.37 (6.5) % after 48h hypoxemia (p&lt;0.01 vs. control, p&lt;0.05 vs. 24h hypoxemia). Any monotonic increase or decrease in the CBF during hypoxemia could not be detected (p&gt;0.05). There was a significant effect of the duration of hypoxemia on the concentrations for the following cytokines in the CSF: IL-15, IL-17A, CXCL10, VEGF, Erythropoietin, FGF21, FSTL-1, GDF8/Myostatin, LIF and SPARC. When compared to normoxia, the expression of 11 mRNAs, most of them for pro-inflammatory cytokines, were 2-2.5 folds lower after 6h hypoxemia. Expression of mRNAs for angiogenic VEGF and pro-inflamatory IL7 were 2 folds and 2-5 folds higher after 24h and 48h hypoxemia, respectively. Our findings revealed a complex response by thebrain during T1RF-induced hypoxemiaand suggest an association between TIRF-induced hypoxemia, tissue hypoxia and sABI. This study was supported by the Kuwait University Research Sector Grants no YM 05/18 and MY 02/18. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Infrared spectroscopy and biochemical parameters of rat tissues under heavy metal poisoning conditions

The increasing level of anthropogenic environmental pollution and effective means to reduce the negative impact of xenobiotics on animal and human health is an urgent problem today. Considering this, the purpose of the study is to examine the effect of heavy metals on accumulation processes under poisoning conditions, and biochemical parameters in the body of rats. Analogue groups were formed of rats of the same age, gender, and body weight to conduct the study. Rats were poisoned with solutions of copper sulfate, zinc sulfate, cadmium sulfate, and lead nitrate for 14 days. Using the method of infrared spectroscopy, substantial differences in the spatial structure of protein components in intact and poisoned animals were established. The difference between the spectral characteristics of the examined tissues is clearly demonstrated by the statistical indicators of skewness and kurtosis. It was determined that poisoning of rats with copper, zinc, cadmium, and lead ions affects the course of glycolysis reactions and the tricarboxylic acid cycle, which leads to a likely increase in serum concentrations of lactate and pyruvate, oxaloacetate and α-ketoglutarate and a decrease in Malate content compared to intact rats. It was established that under the conditions of poisoning, there is also a substantial increase (P &lt; 0.05) in the content of the examined heavy metals in the blood, liver, and kidneys. In animals poisoned with heavy metals, a decrease in the pool of free amino acids in the kidneys is observed. In particular, the content of aspartic acid, valine, glycine, tyrosine, and cystine (more than 1.5 times) in the kidneys of such rats decreases; alanine, leucine, serine, taurine, threonine, phenylalanine (more than 2.0 times), lysine – 3.4-4.9 times. Therewith, an increase in the level of isoleucine and methionine by 1.3-1.5 times, ornithine – by 1.8-2.1 times, and glutamic acid – by 4.4-5.3 times in rats of the experimental group compared to intact ones was identified. The results of the study can be helpful in the professional activities of doctors of veterinary medicine, toxicologists, biologists, and environmentalists and used to control the quality of livestock products, conduct toxicological studies, and analyse environmental objects

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.

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.

Evaluation of the impact of hot environmental conditions on physical activity among soccer players.

The aim of the study was to evaluate the effect of a hot environment on several physiological variables of soccer players and suggest feasible solutions to it. The study is of prospective design, considering 66 participants comprising professional soccer players. All the participants completed the Physical Activity Readiness Questionnaire (PARQ). The participants were assigned to 3 different groups. Each group was assigned 22 participants. They were made to play in three different chambers, maintained at cool, moderate and hot temperatures. Players were made to play and various variables were determined to assess the effect of hot temperature on them. Several variables were determined including absolute and relative oxygen uptake, heart rate, minute ventilation, the blood concentration of lactate and time to get exhausted. All the variables of players who played in hot temperatures have revealed higher heart rate, ventilation and increased lactate concentration. Players in a hot environment ran out faster. The study was concluded due to the players' dehydration and physiological deteriorated factors in a hot environment, leading to poor performances and also affecting the players' health in the long run. Further, the study suggested improving the environment around the game venues.

Differential biochemical-inflammatory patterns in the astrocyte-neuron axis of the hippocampus and frontal cortex in Wistar rats with metabolic syndrome induced by high fat or carbohydrate diets

Metabolic syndrome (MetS) is a public health problem and a risk of developing cardiometabolic and neurodegenerative diseases. The biochemical-inflammatory impairment in brain areas related to learning and memory has not been differentiated between MetS models. We aimed to compare the effect of the MetS generated by consuming high-fat (HFD) or -carbohydrate diets (HCD) on the hippocampus and frontal cortex, related to astrocyte-neuron metabolism and neuroinflammation origin. Sixty male Wistar rats were separated into three groups: 1) control group, 2) HCD group, and 3) HFD group. After 3 months, we evaluated zoometry, a serum bioclinical profile, and in the hippocampus and frontal cortex, we performed biochemical assays (concentration of lactate, glutamate, fatty acids, and ASAT, ALAT, and LDH activity), immunoreactivity tests (GFAP, COX2, CD36, and BDNF), and immunoassays (TNF-α, IL-1β, IL-6, and PGE2). The bioclinical parameters showed that both diets induce MetS. At the brain level, it is noteworthy that the HCD group had an increase in lactate and glutamate concentration, reactive astrogliosis, immunoreactive COX2 neurons in the CA1 subfield hippocampus and frontal cortex, and high levels of PGE2, TNF-α, IL-1β, and IL-6, and low BDNF immunoreactivity. Meanwhile, the HFD is highlighted by increased fatty acid levels and CD36 expression in the hippocampus and frontal cortex, strong reactive astrogliosis and COX2 immunoreactivity, and the greatest inflammation with the lowest BDNF immunoreactivity. In conclusion, MetS induction by an HFD or HCD generates different biochemical, cellular, and inflammatory patterns in the hippocampus and frontal cortex.