Increase In Lactate Concentration Research Articles

Sex Differences In Blood Lactate Concentration And Changes In Lifting Velocity During And After Resistance Exercise For Strength Gain And Muscle Hypertrophy.

Strength training variants, such as load, repetition, and set, are manipulated for strength gain and muscle hypertrophy. However, there is little evidence of optimal training variants for women. PURPOSE: To investigate sex differences in blood lactate concentration and changes in lifting velocity during and after resistance exercise for strength gain and muscle hypertrophy, respectively. METHODS: Fourteen subjects (men=8, age 21.1±0.8 years, weight 70.9±7.2 kg, height 170.7±5.4 cm; women=6, age 20.7±1.1 years, weight 58.3±5.0kg, height 159.5±5.5 cm) with significant physical education and resistance training experience participated in this study. Participants performed four sets of parallel squats as part of two protocols, one for strength gain (four repetitions at 85% of 1RM) and one for muscle hypertrophy (10 repetitions at 70% of 1RM) using a cross over design. We measured blood lactate concentration before, during, and after the exercise. We also measured lifting velocity during exercise using a transducer (GymAware). RESULTS: Blood lactate concentration significantly increased after both protocols in both men (strength 1.4±0.7 to 4.1±1.7 mmol/l, p=0.001, hypertrophy 1.6±0.5 to 8.3±2.0 mmol/l, p<0.001) and women (strength 1.3±0.3 to 1.8±0.5 mmol/l,p=0.012, hypertrophy 1.5±0.3 to 4.0±2.0 mmol/l,p=0.269). The protocol for muscle hypertrophy, led to a more significant increase in blood lactate concentration in both men (p=0.001) and women (p=0.040) after exercise than the protocol for strength gain. After both protocols were applied, blood lactate concentration immediately after exercise was significantly higher in men than in women (strength p= 0.008, hypertrophy p=0.005, respectively). Lifting velocity showed a decreasing tendency for both protocols, especially for muscle hypertrophy, in men, but without any significant differences between men and women. CONCLUSIONS: Our results suggest that there are no significant sex differences in blood lactate concentration and lifting velocity during and after the application of the two protocols for strength gain and muscle hypertrophy. However, blood lactate concentration was significantly higher in men than in women.

Metabolomic Reprogramming Detected by 1H-NMR Spectroscopy in Human Thyroid Cancer Tissues.

Thyroid cancer cells demonstrate an increase in oxidative stress and decreased antioxidant action, but the effects of this increased oxidative stress on cell function remain unknown. We aimed to identify changes in the metabolism of thyroid cancer cells caused by oxidative stress, using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Samples of thyroid cancer and healthy thyroid tissue were collected from patients undergoing thyroidectomy and analyzed with 1H-NMR spectroscopy for a wide array of metabolites. We found a significant increase in lactate content in thyroid cancer tissue compared to healthy tissue. Metabolomic analysis demonstrated significant differences between cancer tissue and healthy tissue, including an increase in aromatic amino acids, and an average decrease in citrate in thyroid cancer tissue. We hypothesize that these changes in metabolism may be due to an oxidative stress-related decrease in activity of the Krebs cycle, and a shift towards glycolysis in cancer tissue. Thus, thyroid cancer cells are able to reprogram their metabolic activity to survive in conditions of high oxidative stress and with a compromised antioxidant system. Our findings, for the first time, suggested a connection between oxidative stress and the alteration of the metabolic profile in thyroid tumors.

Priming exercise increases Wingate cycling peak power output

Purpose: The aim of the present study was to investigate the effect of priming exercise on Wingate performance and fatigue. Methods: Twelve recreationally active young male volunteers participated in the study (age: 25 ± 5 years; weight: 75.0 ± 7.5 kg; height: 177 ± 6 cm; BMI: 24.0 ± 1.7). During a first visit, participants performed a typical test and a supramaximal assessment of on a cycle ergometer, while during the next three visits, the participants performed in a random order a Wingate test (i) with no priming exercise, (ii) after priming exercise followed by a 15-min recovery (Priming15) and (iii) after priming exercise followed by a 30-min recovery (Priming30). Priming exercise lasted 6 min, at work rate corresponding to the gas exchange threshold (GET) plus 70% of the difference between the GET and . Results: The Priming 30 condition exhibited greater peak power output (595 ± 84 W) compared to the control (567 ± 85 W) and the Priming15 condition (569 ± 95 W) (P < .05). Regarding fatigue index, a tendency towards increased resistance to fatigue was observed in the Priming30 condition compared to the control and the Priming15 conditions (P = .072). Pre-Wingate lactate levels were found to be significantly different between the Priming15 (7.18 ± 3.09 mmol/L) and the Priming30 (4.87 ± 2.11 mmol/L) conditions (P < .05). Conclusions: Priming exercise of high intensity followed by a prolonged recovery leads to increased peak power in a subsequent Wingate test. Moreover, our data are consistent with the idea that a priming exercise-induced modest increase in blood lactate concentration at the onset of the following criterion bout is a key factor of performance.

In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring.

The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 hour after oxytocin-induced placental ischemia-hypoxemia. Persistent upregulation of select mitochondrial electron transport chain complex proteins in the anterior cingulate cortex of adolescent male offspring suggested that this sex-specific effect was enduring. Functionally, offspring exposed to oxytocin-induced uterine hypercontractility showed male-specific abnormalities in social behavior with associated region-specific changes in gene expression and functional cortical connectivity. Our findings, therefore, indicate that even transient but severe placental ischemia-hypoxemia could be detrimental to the developing brain and point to a possible mitochondrial link between intrauterine asphyxia and neurodevelopmental disorders.

Effects of dietary Sargassum horneri on resisting hypoxia stress, which changes blood biochemistry, antioxidant status, and hepatic HSP mRNA expressions of juvenile black sea bream Acanthopagrus schlegelii

Aquatic hypoxia is a frequent event and a complex set of physiological and biochemical alterations are employed to cope with this environmental stress in fish. This study aimed at evaluating the protective effects of Sargassum horneri on hypoxia stress in black sea bream Acanthopagrus schlegelii. Four hundred and eighty fingerlings with approximate mean body weight of 12.0 ± 0.1 g were randomly distributed into four experimental groups in triplicate. Each group was stocked with 40 fish and fed with isonitrogenous (42% crude protein) and isolipidic (12% crude lipid) experimental diets containing either 0% (control), 3%, 6%, or 9% S. horneri in the feed. At the end of 8 weeks of experimental feeding, fish were exposed to hypoxia (dissolved oxygen 2.5 mg L−1) conditions for 12 h and subsequent recovery to normoxia (dissolved oxygen 7.2 mg L−1). Fish samples were collected after hypoxia stress at 0, 6, 12 h, and 12 h recovery to normoxia, respectively. Hypoxia stress caused a significant increase in the serum concentrations of cortisol, glucose, and lactate at 6 h after hypoxia, as well as the activities of hepatic superoxide dismutase (SOD) and MDA content at 12 h after hypoxia compared with 0 h after hypoxia. Moreover, the fish exhibited a significantly higher level in the mRNA expressions of hepatic Cu/Zn-SOD, HSP70, and HSP90 at 12 h after hypoxia. However, dietary S. horneri supplementation could significantly improve antioxidant capacity and resistance against hypoxia stress, particularly in the 6% S. horneri group. Therefore, the optimal dietary S. horneri level based on increasing the resistance of hypoxia for juvenile black sea bream in the present study was estimated to be approximately 6% dry diet.

Metagenomic Analyses of Microbial and Carbohydrate-Active Enzymes in the Rumen of Dairy Goats Fed Different Rumen Degradable Starch.

The objective of this study was to investigate the effects of different dietary rumen degradable starch (RDS) on the diversity of carbohydrate-active enzymes (CAZymes) and Kyoto Encyclopedia of Genes and Genomes Orthology functional categories to explore carbohydrate degradation in dairy goats. Eighteen dairy goats (second lactation, 45.8 ± 1.54 kg) were divided in three groups fed low RDS (LRDS), medium RDS (MRDS), and high RDS (HRDS) diets. The results showed that, HRDS treatment group significantly decreased the ruminal pH (P < 0.05), and increased the propionate proportion (P < 0.05), fumarate and succinate concentrations (P < 0.05), trended to increase lactate concentration (P = 0.50) compared with LRDS group. The relative abundance of acetogens, such as family Clostridiaceae and Ruminococcaceae, genera Clostridium and Blautia were higher in HRDS than LRDS feeding goats. The GH9 family (responsible for cellulose degradation) genes were lower in HRDS than MRDS diet samples, and mainly produced by Prevotellaceae, Ruminococcaceae, and Bacteroidaceae. Amylose (EC3.2.1.3) genes under HRDS treatment were more abundant than under LRDS treatment. However, the abundance of GH13_9 and CBM48 (responsible for starch degradation) were reduced in HRDS group indicating the decreased binding activity from catalytic modules to starch. This study revealed that HRDS-fed dairy goats had decreased CAZymes, which encode enzymes degrade cellulose and starch in the dairy goats.

Anaerobic Threshold Determination in Cycle Ergometer From Rating of Perceived Exertion.

Santos, GAd, Numata-Filho, ES, Rosa, TdS, Passos Neves, RV, Simões, HG, and Moreira, SR. Anaerobic threshold determination in cycle ergometer from rating of perceived exertion. J Strength Cond Res 36(5): 1277-1281, 2022-The objective of the study was to investigate the validity of the rating of perceived exertion threshold (TRPE) for anaerobic threshold (AT) estimation during an incremental test (IT) on a cycle ergometer. Nineteen physically active and healthy men performed an IT on a cycle ergometer. The intensity corresponding to the AT was considered as the point immediately before the abrupt increase in blood lactate concentration ([La]) in the IT. TRPE was determined in the last intensity corresponding to perceptual response previous the 15 arbitrary units (AU) in the 15-point RPE scale. The heart rate (HR), [La], and RPE were obtained at the end of each stage of the IT. There was no significant difference between workload obtained from the AT (150 [120-150] watts) and TRPE (150 [120-150] watts) (p > 0.05). In addition, there were no differences between HR (AT, 139.5 ± 12.7 b·min-1 vs. TRPE, 141.9 ± 14.6 b·min-1, p > 0.05) and [La] (AT, 3.1 [2.8-3.2] mM vs. TRPE, 3.1 [2.9-3.7] mM, p > 0.05). There was a strong correlation between the intensities in AT and TRPE during the IT (r = 0.88). A substantial reliability (intraclass correlation coefficient = 0.84 [0.64-0.94 confidence interval 95%]) was evidenced, as well as a substantial agreement between the AT and TRPE intensities (Pc = 0.84), as confirmed by the Bland-Altman plot (-4.7 [-34.2/24.7]). TRPE was a predictor of the AT (β = 1.146, R = 0.770, SEE = 15.070, p < 0.01). It can be concluded that TRPE is valid for AT estimation during an IT on a cycle ergometer.

Evaluation of subcutaneously administered electrolyte solutions in experimentally dehydrated inland bearded dragons (Pogona vitticeps).

To evaluate the effects of 3 electrolyte solutions administered SC to experimentally dehydrated inland bearded dragons (Pogona vitticeps). 9 inland bearded dragons. In a randomized, complete crossover study, experimental dehydration was induced by means of furosemide (10 mg/kg, SC, q 12 h for 4 doses), and then lactated Ringer solution, Plasma-Lyte A, or reptile Ringer solution (RRS; 1:1 mixture of 5% dextrose solution and isotonic crystalloid solution) was administered SC in a single 50-mL/kg dose in 3 treatments sessions separated by a minimum of 14 days. Food and water were withheld during treatment sessions. Plasma biochemical values, PCV, blood total solids and lactate concentrations, and plasma osmolarity were measured prior to (baseline) and 4 and 24 hours after fluid administration. Administration of RRS resulted in severe hyperglycemia (mean ± SD plasma glucose concentration, 420 ± 62 mg/dL), compared with baseline values (190 ± 32 mg/dL), and this hyperglycemia persisted for at least 24 hours. It also resulted in significant reductions in plasma osmolarity and sodium and phosphorus concentrations, which were not observed after administration of the other 2 solutions. Administration of lactated Ringer solution caused no significant increase in blood lactate concentration. The changes in plasma glucose, sodium, and phosphorus concentrations and plasma osmolarity observed after SC administration of a single dose of RRS suggested this type of electrolyte solution should not be used for rehydration of bearded dragons. Rather, lactated Ringer solution or Plasma-Lyte A should be considered instead.

Characterization of Oligofructose-Induced Acute Rumen Lactic Acidosis and the Appearance of Laminitis in Zebu Cattle.

Simple SummaryIn this paper we characterize oligofructose-induced acute rumen lactic acidosis in zebu cattle focusing on alterations of the experimental protocol concerning ruminal condition. Here we describe zebu cattle’s lack of adaptation to the oligofructose induction model for laminitis and we provide methodology of adaptation that allows the higher occurrence of laminitis with a lower degree of ruminal acidosis and better animal welfare. Additionally, we compare the animals that required and did not required supportive treatment, to try to understand which factors are related to susceptibility. The induction model promoted marked reduction in rumen pH, rumen anaerobiosis, carbon dioxide pressure, and an increase in rumen lactate, blood osmolarity, and cortisol concentration. The animals treated had lower values of rumen pH and marked dehydration, evidenced by the increase in globular volume and serum urea. The clinical condition caused by excess oligofructose is more severe than the classical sucrose induction model, but is efficient in producing laminitis.The objective of this study was to characterize oligofructose-induced acute rumen lactic acidosis and its consequences in zebu cattle. We used 29 Nellore heifers which were submitted to experimental induction of laminitis by oligofructose excess. During the induction period, the animals underwent clinical examination, including laminitis diagnosis (hoof pressure testing and locomotion score) and blood and ruminal fluid sampling every six hours (over the initial 24 h) and every 12 h (up to 72 h), after the highest dose. Almost half of the animals (48.1%) required treatment with bicarbonate and saline to correct metabolic acidosis and dehydration. Due to this treatment, the animals were analyzed in treated (n = 13) and non-treated (n = 14) groups. The induction model promoted marked reduction in rumen pH, rumen anaerobiosis, carbon dioxide pressure, and increase in rumen lactate, blood osmolarity, and cortisol concentration. The animals treated had lower values of rumen pH and marked dehydration, evidenced by the increase in globular volume and serum urea. The clinical condition caused by excess oligofructose is severe, with the differential of the appearance of ephemeral fever and respiratory compensation against systemic acidosis, in addition to the frequent appearance of laminitis.

HIF1A activates the transcription of lncRNA RAET1K to modulate hypoxia-induced glycolysis in hepatocellular carcinoma cells via miR-100-5p

Hepatocellular carcinoma (HCC) remains the primary cause of cancer-related death. Metabolic change is the major characteristic of cancer. The present study attempted to investigate the regulatory mechanisms of HCC energy metabolism from the perspective of noncoding RNA regulation of HIF1A and LDHA. The expression of miR-100-5p expression was significantly suppressed in HCC tissue samples and HCC cell lines under 1% O2-induced hypoxia. miR-100-5p overexpression significantly suppressed hypoxia-induced increases in lactate concentration and glucose uptake. Exposure to 1% O2 induced HIF1A protein and reduced miR-100-5p expression, while HIF1A silencing dramatically rescued miR-100-5p expression upon 1% O2 exposure. In addition, 1% O2-induced increases in lactate concentration and glucose uptake were also suppressed by HIF1A silencing. Next, by analyzing available data in TCGA, we found that lncRNA RAET1K was correlated with HIF1A and miR-100-5p.LncRNA RAET1K could downregulate the expression of miR-100-5p by acting as a sponge, while HIF1A bound the lncRNA RAET1K promoter region to activate its transcription. LncRNA RAET1K silencing significantly suppressed HCC cell proliferation and invasion and also suppressed hypoxia-induced increases in lactate concentration and glucose uptake, while miR-100-5p inhibition reversed the effects of lncRNA RAET1K silencing on hypoxia-induced glycolysis in HCC cells. Finally, the expression of HIF1A, lncRNA RAET1K, and LDHA was upregulated in HCC tissue specimens; the expression of miR-100-5p was negatively related to HIF1A, lncRNA RAET1K, and LDHA; and HIF1A, lncRNA RAET1K, and LDHA were positively correlated with each other. In conclusion, the HIF1A/lncRNA RAET1K/miR-100-5p axis modulates hypoxia-induced glycolysis in HCC cells and might affect HCC progression.

Insular and occipital changes in visual snow syndrome: a BOLD fMRI and MRS study.

ObjectiveTo investigate the pathophysiology of visual snow (VS), through a combined functional neuroimaging and magnetic resonance spectroscopy (1H‐MRS) approach.MethodsWe applied a functional MRI block‐design protocol studying the responses to a visual stimulation mimicking VS, in combination with 1H‐MRS over the right lingual gyrus, in 24 patients with VS compared to an equal number of age‐ and gender‐matched healthy controls.ResultsWe found reduced BOLD responses to the visual stimulus with respect to baseline in VS patients compared to controls, in the left (k = 291; P = 0.025; peak MNI coordinate [‐34 12 ‐6]) and right (k = 100; P = 0.003; peak MNI coordinate [44 14 ‐2]) anterior insula. Our spectroscopy analysis revealed a significant increase in lactate concentrations in patients with respect to controls (0.66 ± 0.9 mmol/L vs. 0.07 ± 0.2 mmol/L; P < 0.001) in the right lingual gyrus. In this area, there was a significant negative correlation between lactate concentrations and BOLD responses to visual stimulation (P = 0.004; r = −0.42), which was dependent on belonging to the patient group.InterpretationAs shown by our BOLD analysis, VS is characterized by a difference in bilateral insular responses to a visual stimulus mimicking VS itself, which could be due to disruptions within the salience network. Our results also suggest that patients with VS have a localized disturbance in extrastriate anaerobic metabolism, which may in turn cause a decreased metabolic reserve for the regular processing of visual stimuli.

Erythrocyte profile of circulating blood of Neogobius melanostomus (Pallas, 1814) under conditions of experimental hypothermia.

The influence of hypothermia on erythrocyte profile of thermophile teleost species round goby, Neogobius melanostomus (Pallas, 1814), has been studied. Fish were acclimated to temperature 1-2оС, 15-16оС and 19-20оС (control group) and held at given conditions for 5 days. The number of red blood cell precursors (pronormoblasts, basophilic and polychromatophilic normoblasts) in circulating blood has been estimated. Also, the number of abnormal erythrocytes, i.e. cells with micronuclei, nuclei invaginations, red blood cell shades, dacryocytes and cells undergoing amitosis has been determined on smears. The number of immature erythrocytes increased more than two times (p<0,001) at 1-2оС. The number of low-differentiated precursors, pronormoblasts and early basophilic normoblasts, increased for the most part. The number of abnormal erythrocytes did not change substantially, The changes in cellular blood composition were accompanied with the increase of plasma lactate concentration, indicating hypoxic state of fish. The results of the present work indicate that hematopoietic tissue remains sensitive to controlling factors at hypothermia, such as hypoxia, and may enhance proliferation and differentiation of erythroid cells.

Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats.

Conjugated linoleic acid (CLA) is a dietary supplement that has been shown to improve obesity. However, some authors have associated high doses of CLA supplementation with liver impairment and insulin resistance. The aim of this study was to assess whether the consumption of low doses of CLA maintained the beneficial effects on the main metabolic disturbances associated with metabolic syndrome (MetS) but prevented the occurrence of non-desirable outcomes associated with its consumption. Male Wistar rats, fed standard or cafeteria (CAF) diet for 12 weeks, were supplemented with three different low doses of CLA in the last three weeks. Both biochemical and H1 NMR-based metabolomics profiles were analysed in serum and liver. The consumption of 100 mg/kg CLA, but not doses of 200 and 300 mg/kg, ameliorated the increase in body weight gain as well as the serum concentrations of glucose, insulin, cholesterol, triglyceride, diglyceride, and total phospholipid induced by a CAF diet. In turn, CLA reverted the increase in lactate, alanine, and glucose concentrations in the liver of these animals, but enhanced hepatic cholesterol accumulation without any detrimental effect on liver function. In conclusion, a low dose of CLA corrected the adverse effects associated with MetS without compromising other metabolic parameters.

Relationship Between Sweat and Blood Lactate Levels During Exhaustive Physical Exercise

AbstractIn contrast to the generally accepted view, that sweat lactate is irrelevant to blood, we report on the suitability of sweat lactate for diagnostics. We demonstrate a significant increase in lactate concentration in sweat from the working muscle area simultaneously with the rise of blood lactate content during exhaustive physical exercise. The variation rates of lactate concentration in sweat from working and latent muscle areas correlate positively with blood lactate levels (r&gt;0.8 and r=0.7, respectively), thus offering the prospect of a non‐invasive approach for the monitoring of sportsperson training. Moreover, sweat lactate, being the faster indicator of muscle metabolism, would be even more important for sports medicine than the nowadays‐used blood lactate.

Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration.

The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observed before exercise and was sustained thereafter.

Correlation of red cell distribution width and serum lactate levels in critically ill pediatric patients

Background: Blood lactate concentration has been widely used as a marker of altered tissue perfusion. An increase in lactate concentration to >1.5 mEq/L is associated with a higher mortality rate. Red cell distribution width (RDW) measures variability in red blood cell size. The purpose of this research is to see the correlation between lactate levels and RDW. Patients and Methods: We performed a cross-sectional study to assess the correlation between blood lactate concentration and RDW in critically ill children admitted to the pediatric intensive care unit (PICU) from October 2018 until February 2019. Blood lactate and RDW were taken during the first 24 h of admission. Data were obtained from the medical report. The association between RDW and lactate was determined using Spearman's correlation test. Results: There were forty patients enrolled in this study with a median age of 27 months (ranged from 2 months to 17 years), with an equal proportion of male and female. The median PICU length of stay was 7.5 days, with a mortality rate of 42.5%. The most common underlying disease was pneumonia (35%), followed by sepsis (17.5%) and meningitis (10%). The median lactate level was significantly higher in the nonsurvivor group compared to the survivor group (P = 0.002). The median RDW was also higher in the nonsurvivor group (P = 0.001). There is a moderate correlation between RDW and lactate (r = 0.532, P

Monitoring Lactate Dynamics in Individual Macrophages with a Genetically Encoded Probe.

Lactate, the product of aerobic glycolysis, plays a dual role as fuel and intercellular signal in inflammation, immune evasion, and tumor progression. The production of lactate by macrophages has been associated with their polarization and function. Here we describe imaging protocols to characterize the metabolism of cultured human macrophages using a genetically encoded fluorescent sensor-specific for lactate. By superfusing cultures with increasing lactate concentrations and pharmacological inhibitors, it is possible to estimate the kinetic parameters of monocarboxylate transporter 4 (MCT4) and lactate production. Practical advice is given regarding sensor expression, imaging, and data analysis. The spatiotemporal resolution of this technique is amenable to the study of fast events at the single-cell level in different immune and other cell types.

Study of thermo-regulation as a worsening marker of experimental sepsis in an animal model.

Objective: to analyze variations in body temperature and in plasma nitrate and lactate concentrations in rats submitted to the experimental sepsis model.Method: a total of 40 rats divided equally into five groups. The induction of endotoxemia was performed with intravenous administration of lipopolysaccharide, 0.5 mg/Kg, 1.5 mg/Kg, 3.0 mg/Kg, and 10 mg/Kg, respectively. The control group received 0.5 mL of saline solution. The experiment lasted six hours, with evaluations performed at 0 (baseline data), 2nd, 4th, and 6thhours.Results: The animals that received doses up to 3.0 mg/kg showed a significant increase in body temperature compared to the group with 10 mg/kg, which showed a decrease in these values. The increase in plasma nitrate and lactate concentrations in the groups with lipopolysaccharide was significantly higher than in the group that received the saline solution and was correlated with the increase in body temperature.Conclusion: the variations in body temperature observed in this study showed the dose-dependent effect of lipopolysaccharide and were correlated with the increase in the concentrations of nitrate and plasma lactate biomarkers. The implications of this study are the importance of monitoring body temperature, together with the assessment of these pathophysiological markers, which suggest worsening in the prognosis of sepsis.

Effects of sildenafil citrate on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats.

Sildenafil citrate is a potent and selective inhibitor of phosphodiesterase type-5 used to treat erectile dysfunction. We investigated the effects of sildenafil citrate treatment on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Western blot for monocarboxylate transporter (MCT)1, MCT4, and neuronal nitric oxide synthase (nNOS) were performed. Exhaustive swimming exercise decreased time of exhaustion and increased lactate concentration, however, sildenafil citrate enhanced time of exhaustion and decreased lactate concentration. Exhaustive swimming exercise increased MCT1 and MCT4 expressions in the gastrocnemius muscles and sildenafil citrate further enhanced MCT1 and MCT4 expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise decreased nNOS expression in the gastrocnemius muscles and sildenafil citrate enhanced nNOS expression in the exhaustive swimming exercise rats. The most potent effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through antiperipheral fatigue.

Metabolism plays a central role in the cortical spreading depression: Evidence from a mathematical model

The slow propagating waves of strong depolarization of neural cells characterizing cortical spreading depression, or depolarization, (SD) are known to break cerebral homeostasis and induce significant hemodynamic and electro-metabolic alterations. Mathematical models of cortical spreading depression found in the literature tend to focus on the changes occurring at the electrophysiological level rather than on the ensuing metabolic changes. In this paper, we propose a novel mathematical model which is able to simulate the coupled electrophysiology and metabolism dynamics of SD events, including the swelling of neurons and astrocytes and the concomitant shrinkage of extracellular space. The simulations show that the metabolic coupling leads to spontaneous repetitions of the SD events, which the electrophysiological model alone is not capable to produce. The model predictions, which corroborate experimental findings from the literature, show a strong disruption in metabolism accompanying each wave of spreading depression in the form of a sharp decrease of glucose and oxygen concentrations, with a simultaneous increase in lactate concentration which, in turn, delays the clearing of excess potassium in extracellular space. Our model suggests that the depletion of glucose and oxygen concentration is more pronounced in astrocyte than neuron, in line with the partitioning of the energetic cost of potassium clearing. The model suggests that the repeated SD events are electro-metabolic oscillations that cannot be explained by the electrophysiology alone. The model highlights the crucial role of astrocytes in cleaning the excess potassium flooding extracellular space during a spreading depression event: further, if the ratio of glial/neuron density increases, the frequency of cortical SD events decreases, and the peak potassium concentration in extracellular space is lower than with equal volume fractions.