Measurement Of Lactate Levels Research Articles

Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Quantitative analysis of intestinal perfusion with indocyanine green (ICG) and methylene blue (MB) using a single clinically approved fluorescence imaging system: a demonstration in a porcine model.

Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB. Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25mg/kg-0.50mg/kg MB was administered after 10min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2mg/kg) after 60min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG. Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = -0.7709; p = < 0.001; r = -0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values. Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

A Prospective Study of Lactate Levels in Uncomplicated Spontaneous and Induced Labor.

Maternal pushing can yield lactate levels that are above the normal range for nonpregnant individuals. Many hospitals require lactate levels as part of sepsis bundles, and this can confuse the clinicians when measured during labor. The objective of this study was to observe lactate levels in uncomplicated labor. This was a prospective study of patients presenting to Labor and Delivery in early labor. Patients met inclusion criteria if they presented at 37 weeks' gestation or greater and were either 3 to 4 cm dilated, in early labor with rupture of membranes less than 12 hours, or were being induced for oligohydramnios or postdates gestation. A baseline maternal lactate level was collected at enrollment. Further levels were collected at complete cervical dilation and every 30 minutes during the second stage of labor up to 3 hours or until delivery. From January 7, 2021, through December 30, 2021, a total of 148 screened patients met the inclusion criteria and 38 were enrolled. Eight (21%) patients withdrew after baseline lactate level was drawn. Twenty-three (61%) patients had a level drawn at complete dilation. Of the 12 (32%) patients with a lactate level drawn at complete and after 30 minutes of pushing, the mean change in lactate level was 2.0 ± 1.8 mmol/L or 0.07 ± 0.06 mmol/L/min (p < 0.01). This change is more pronounced in the second stage of labor for patients with chorioamnionitis (2.6 mmol/L), although this difference is not statistically significant (p = 0.41). Lactate levels increase significantly once a patient reaches complete cervical dilation within 30 minutes of pushing. This increase is more pronounced, although significantly, in patients with chorioamnionitis. As sepsis is one of the leading causes of maternal morbidity and mortality, this pilot study is relevant for providers to see the natural course of lactate levels in labor. · The change in lactate level during normal labor is unknown.. · We measured lactate levels in uncomplicated labor.. · Lactate levels can be elevated in uncomplicated labor..

Measurement of cerebrospinal fluid lactate levels in pediatric patients with suspected ventriculoperitoneal shunt infection: A retrospective cohort study

IntroductionVentriculoperitoneal shunt (VPS) infection is a severe complication. Early diagnosis could help to decrease morbidity and treatment costs. Lactate has been used for the diagnosis of other central nervous system infections. The aim of this study is to determine the usefulness of lactate for the diagnosis of VPS infection. MethodologyRetrospective cohort study. Lactate was measured in patients who consulted with VPS dysfunction between May 2019 and May 2022. Mean were compared according to culture results. A Receiver Operating Characteristic (ROC) curve was performed to determine the appropriate cut-off point. ResultLactate has a high negative predictive value but a low positive predictive value for the diagnosis of ventriculitis.

Measurement Of Umbilical Venous Lactate Levels For Predicting Poor Neonatal Outcomes

Objectives: To determine the utility of umbilical venous lactate measurements for predicting poor neonatal outcomes. Method: This observational study was conducted at Kahuta Research Laboratories (KRL) hospital, Islamabad from May 2019 to October 2019. Singleton pregnancies with no known fetal congenital anomalies and gestational age greater than 28 weeks were included. Descriptive statistics were used to analyse the characteristics of study subjects and also composite neonatal outcomes. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Result: Umbilical venous lactate levels were found to be highest in instrumental deliveries (48.7%) and lowest in those delivered by elective cesarean section (25.7%). Low APGAR score, need for initial resuscitation &amp; neonatal intensive care unit admission, mechanical ventilation and neonatal morbidity were all associated with significantly higher lactate levels. Based on the maximal yield index, the optimal cut-off point for predicting neonatal morbidity was 46.5mg/dl (area under the receiver operating characteristics curve was 0.8). Based on this optimal cut-off point, it has a sensitivity of 62%, specificity of 92%, PPV 51% and NPV 94% for neonatal morbidity. Conclusion: Umbilical venous lactate measurement is a good predictor of poor neonatal outcome especially in situations when umbilical arterial blood cannot be taken due to technical difficulty. Mode of delivery has a strong association with fetal hypoxia and raised umbilical lactate levels. Keywords: lactate, neonatal outcomes, labour ward.

Reliability of a point of care testing blood gas analyzer for measurement of lactate levels in cerebrospinal fluid

Analysis of cerebrospinal fluid (CSF), including lactate, is key for diagnosis of acute meningitis. Since blood gas analyzers (BGA) enable rapid and safe blood-lactate measurements, we evaluated the reliability of RAPIDPoint 500 BGA to provide a fast and accurate measure of CSF lactate. In this study, CSF lactate levels were measured by a reference assay and on RAPIDPoint 500 BGA. Comparability was evaluated through difference analysis, using Bland Altman test, and linear regression analysis, using the Passing Bablok test. Agreement rate according to CSF lactate (≥3.5 and <3.5 mmol/L) was calculated using kappa (κ) statistic. Population study included 98 CSF samples. Concerning difference analysis, according to Bland-Altman test, bias was 0.13 mmol/L (CI 95%: −0.26 to 0.52 mmol/L. In regression analysis, according to Passing-Bablok equation a systematic difference between both assays was found. In concordance analysis, the interrate realibility was very high (κ: 0.964). According to our resuls, although a systematic difference was detected when lactate levels were measured on RAPIDPoint 500 BGA, the results from Bland-Altman test and the high agreement rate support that this POCT analyzer could be useful for a early and safe detection of patients with high probability of increased CSF lactate level.

Application of graphene oxide nanosheet lactate biosensors in continuous assessment of athlete fitness

This study presents a groundbreaking approach in sports science, introducing a novel graphene oxide (GO) nanosheet-based lactate biosensor designed for the non-invasive, continuous assessment of athlete fitness. Traditional lactate monitoring techniques, typically invasive and offering only intermittent data, are significantly outperformed by this innovative method. Our biosensor uniquely combines lactate oxidase (LOx) with GO nanosheets to measure lactate levels in sweat with unprecedented accuracy and real-time response. Notably, this sensor exhibits exceptional sensitivity and a wide dynamic range, effectively capturing the complete spectrum of physiological lactate variations, from resting states to peak exertion levels. The practical implications of this research are vast, offering a revolutionary tool for enhancing athlete performance monitoring and tailoring training regimens. This biosensor stands as a testament to the potential of nanotechnology in transforming sports science, providing a non-invasive, efficient solution for precise lactate threshold measurement and opening new horizons in personalized athletic training and health monitoring.

Predictive role of lactate in dogs with acute pancreatitis advanced to systemic inflammatory response syndrome.

Acute pancreatitis (AP) can develop into life-threatening conditions such as systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome. Thirty-nine of 54 client-owned dogs admitted to the Referral Animal Medical Center and diagnosed with AP within 24 hr of onset were retrospectively reviewed to assess early predictors of progression from AP to SIRS. The patients were divided into SIRS (SIRS occurring after AP) and non-SIRS (AP occurring but no SIRS) groups. The population and mean values of laboratory variables within 24 hr of admission were assessed and compared between both groups. There were significantly more dogs with abnormal lactate levels in the SIRS group (80.00%) than non-SIRS group (11.10%). Other parameters did not differ significantly. Mean lactate level values were significantly higher at 3.64 ± 1.75 mmol in the SIRS group compared to 1.68 ± 0.52 mmol in the non-SIRS group. The increased energy required by activated immune cells may lead to metabolic changes characterized by anaerobic glycolysis and increased lactate production. This study's results suggest blood lactate monitoring in the early stages of progression from AP to SIRS in small animal clinical practice. Measuring lactate levels at the early stages of pancreatitis could lead to rapid therapeutic intervention for SIRS and ultimately reduce mortality.

Biosensor for Rapid Measurement of Lactate in Exhaled Breath Condensate

Lactate concentration plays an important role in disease diagnostics. Higher lactate concentrations are associated with sepsis and septic shock [2], trauma [3], tissue hypoxia due to acute lung injury [4], and respiratory diseases [5]. Lactate level is also widely used in monitoring athletes’ training and fitness as long-term exhausting exercise leads to a rapid increase in lactate level and result in muscle weakening and fatigue [6]. Compared with the traditional blood sample media which is invasive and capillary blood monitoring is not suitable for routine clinical use, the exhaled breath condensate (EBC) is simple and non-invasive method with no potential for adverse effects for lactate analysis.In this presentation, a point-of-care electrochemical biosensor is introduced for the EBC lactate analysis. This disposable and low-cost sensor is aimed to be inserted in an EBC collection device developed by our team that enables real-time monitoring and rapid measurements of EBC lactate level. The sensor measurement is done directly after EBC sample collection, that minimizes the risk of sample degradation and is cheaper than the traditional laboratory techniques such as fluorometry or mass spectrometry.The sensor is modified with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), Prussian blue (PB) and lactate oxidase (LOD) enzyme. Lactate concentration is measured from amperometric current response generated by the redox reactions on sensor surface. The enzyme gel formulation is optimized based on rotating disk electrode (RDE) experiments and kinetics analysis, investigating the effect of LOD concentration and gel thickness, and was then applied to disposable sensors.Finally, human EBC analysis is conducted on healthy subjects at rest and after 30 min of intense aerobic cycling exercise. Sensor’s results in real EBC lactate measurements demonstrate a good correlation with fluorometry and mass spectrometry calibrations and exhibit high stability and sensitivity in both short-term and long-term use. Mass production of the sensor is done by robotic gel dispensing using a Biodot aspirate dispensing machine.Note: This presentation is based on the corresponding author's recent publication ‘Rapid Measurement of Lactate in the Exhaled Breath Condensate: Biosensor Optimization and In-Human Proof of Concept’ in ACS Sensors (doi.10.1021/acssensors.2c01739) [1]

EARLY BLOOD LACTATE AS A BIOMARKER FOR CARDIOVASCULAR COLLAPSE IN EXPERIMENTAL SEPSIS.

Cecal ligation and puncture (CLP) is the gold standard model for studying septic shock, which is characterized by hypotension and hyporeactivity to vasoconstrictors. However, approximately 30% of CLP animals do not exhibit cardiovascular changes, requiring more replicates because of the high variability of the model. Therefore, biomarkers enabling the early prediction of cardiovascular collapse in sepsis would greatly benefit sepsis nonclinical studies, refining experimental models and improving clinical translation. Thus, this study aimed to test whether the early increase in lactate levels could predict hypotension and hyporesponsiveness to vasoconstrictors in a rat model of sepsis. Male and female Wistar rats were subjected to CLP or sham procedure. Tail blood lactate was measured 6, 12, and 24 h after surgery. Then, inflammatory, biochemical, and hemodynamic parameters were evaluated. Rats subjected to CLP developed hypotension, hyporesponsiveness to vasoconstrictors, an intense inflammatory process, and increased plasma markers of organ dysfunction. By using receiver operating characteristics curve analysis, we have established that a lactate value of 2.45 mmol/L can accurately discriminate between a rat exhibiting a normal vasoconstrictive response and a vasoplegic rat with 84% accuracy (area under the curve: 0.84; confidence interval [CI]: 0.67-1.00). The sensitivity, which is the ability to identify a diseased rat (true positive), was 75% (CI: 41-95), and the true negative rate was 81% (CI: 57-93). Therefore, early measurement of lactate levels in sepsis could serve as a valuable biomarker for distinguishing vasoplegic rats from those exhibiting normal vasoconstrictive responses.

Measurement of sweat lactate levels in exercise and non-exercise activities using capillary electrophoresis system with contactless conductivity detection and cyclodextrin-modified buffer

This study presents the analysis of lactate in sweat using capillary electrophoresis with contactless conductivity detection. Two cyclodextrin (CD) compounds, carboxymethyl-β-cyclodextrin sodium salt (CM-β-CD) and heptakis (2,3,6-tri-O-benzoyl)-β-cyclodextrin (TRIME-β-CD), were evaluated as buffer modifiers for the separation of chloride, nitrate, sulfate, oxalate, maleate, acetate, lactate, and phosphate anions. The concentrations of these modifiers were tested at 0.05, 0.1, and 0.5 mM for eight anions separation. The buffer was 40.0 mM MES/L-His (pH 6.0) with 0.05 mM CTAB, resulting in anodic separation. Due to separation efficiency in resolving lactate and phosphate peaks, TRIME-β-CD at a concentration of 0.1 mM was selected as the suitable buffer additive for sweat lactate analysis. The calibration of the developed method, using maleate as an internal standard, resulted in the linear ranges of 0.1–5.0 mM, r2 of 0.9999, and an instrumental LOD of 0.042 mM. The intra-day and inter-day precisions of the relative migration time (RMT) were 0.3–0.4% and 3–4% RSD, respectively. Lactate levels in sweat samples from the same group of volunteers were measured after two distinct activities: exercise (after running) and non-exercise (after sauna). For non-exercise activities, lactate concentrations ranged from 15 ± 1 mM to 36 ± 2 mM. While, after exercise, the concentrations were between 26 ± 1 mM and 136 ± 1 mM. Further evaluation of the stability of sweat storage for monitoring lactate contents, it was found that the changes in lactate levels were insignificant when stored for up to 24 weeks at 4 °C. This was confirmed by paired t-tests (t-stat ragnes from -0.59 to 2.49; t-critical = 2.57, P = 0.05). The measured lactate concentrations from volunteers were significantly higher, approximately 2–6 times, in exercise activities compared to non-exercise activities. This substantial difference in lactate secretion indicates a clear distinction in the factors that stimulate sweat lactate production. To evaluate the intensity of exercise based on lactate levels in sweat, a proposed cut-off level of 36.0 mM, with a decision limit of 40.0 mM, can be proposed.

Microfluidic Sensor for Phagocytosis Quantification from Whole Blood Samples

Immune system activates in response to pathogenic infections in human bodies. One of the critical processes of the inflammatory pathway is the killing of pathogens/ microbes by specific white blood cells, called as Phagocytes. Neutrophils represent majority of phagocytes and recognize the immunoglobulin (IgG) bound bacteria with subsequent binding, internalization and finally killing. Quantifying the efficacy of the phagocytosis process will enable the personalized monitoring of patients’ immune response. This is critical for diagnostics of high-risk patients with infectious diseases in particular sepsis. Sepsis is a global health concern with major clinical diagnostics bottlenecks impacting the patients’ outcomes. In United States, more than a million patients are diagnosed with severe sepsis, out of which more than 30% die. Identifying high risk septic patients is critical to save their lives. To address this unmet need, here, we have developed a microfluidic biosensor to quantify the phagocytic activity of neutrophils using blood samples collected from hospital patients.The biosensor is composed of impedance spectroscopy based electronic sensor with integrated magnetic module. The microfluidic impedance sensor is built by fabricating co-planar gold microelectrodes on glass substrate and bonding it with PDMS based microfluidic channel. The impedance spectroscopy will generate the voltage pulses as each blood cell will flow through the sensing zone over microelectrodes. The sensing zone is coupled with the quadrupole magnetic configuration which allows generating high concentrated magnetic field lines at the start and end of the sensing zone. Further, to mimic the pathogens, IgG coated magnetic particles of similar size were used. As the blood cells will pass through the sensing zone, the magnetic particles internalized by neutrophils will experience a speed differential by magnetic modulation. The resulting electrical pulses will produce signature differences in its profile when a neutrophil with internalized magnetic particles will flow compared to non-phagocytes. We obtained multivariate data from each pulse which included pulse amplitude, width, rise/ fall times of the pulses. Further we developed a machine learning model based on artificial neural network (ANN) and fed each pulse data to classify a phagocytosis event.We collected 17 patient samples from Robert Wood Johnson Medical Hospital and ran on our microfluidic sensor. These samples were equally divided into control (with no phagocytosis) and positive (with phagocytosis) cells. Tens of thousands of blood cells from each sample were ran through our biosensor and collected data was fed to ANN model for classification. Contingency tables and receiver operating curves (ROC) were developed. ANN model was able to predict phagocytosis samples with 88% accuracy and AUC of 0.92. Similarly, lactate level measurements (provided by the hospital) were used to classify high-risk and low-risk patients (threshold of 2mm/L was used). Employing collected electronic data, our ANN model was also able to classify the patients to the appropriate risk groups with 88% accuracy and AUC of 0.85.In conclusion, we have developed microfabricated microfluidic biosensor with impedance spectroscopy and magnetic modulation. Sensor validation was done using real patient samples from the hospital. This sensor can be utilized for diagnostics applications for infectious diseases in different healthcare settings.Reference: C. Norton, U. Hassan, “Bioelectronic Sensor with Magnetic Modulation to Quantify Phagocytic Activity of Blood Cells Employing Machine Learning,” ACS Sensors, 7, 7, 1936–1945, 2022.

일주일간의 입원 기간 동안 운동 기반 심장재활이 급성 심근경색 환자의 젖산 수치에 미치는 영향

Purpose: Few studies have been conducted to examine changes in lactate levels associated with the severity of myocardial infarction during cardiac rehabilitation. Thus, this study aimed to investigate the effects of exercise-based cardiac rehabilitation on lactate levels in patients with acute myocardial infarction. Methods: A total of eight patients (7 males and 1 female, aged 64.1 ± 12.8 years) who were diagnosed with acute myocardial infarction and participated in an inpatient cardiac rehabilitation program were included in this study. Lactate levels were measured using Lactate Plus (Nova Biomedical, Rodermark, Germany), which can measure lactate levels from 0.3 to 25.0 mmol/L. Exercise intensity during the inpatient cardiac rehabilitation period was set at 40%-60% of peak oxygen uptake (peak VO2), and cardiopulmonary exercise testing and lactate level measurements were conducted before and after exercise. Normally distributed data were analyzed using paired t-tests, and non-normally distributed data were analyzed using the Wilcoxon signed-rank test. Results: VO2peak and metabolic equivalents significantly increased, and minute ventilation per unit carbon dioxide production showed a decreasing trend but not a significant decrease (p=.014, p=.02). During the one-week inpatient rehabilitation period, lactate levels at rest before exercise on the first and last days of rehabilitation significantly decreased (p=.036). Lactate levels significantly increased immediately after exercise (p=.014), while lactate levels before exercise showed a decreasing trend in all eight patients. Conclusion: In patients with acute myocardial infarction, lactate levels increased immediately after exercise-based cardiac rehabilitation, while lactate levels at rest decreased during the one-week rehabilitation period as aerobic capacity improved.

Effect of lactate levels on extubation time in coronary artery bypass grafting surgery.

In current practice, fast-track protocols are gaining importance in patients undergoing cardiac surgery. For this purpose, besides different application techniques, biomarkers are frequently examined in the peri-operative period. We aimed to examine whether serum lactate levels at different peri-operative intervals had an effect on the extubation time. The patients were analysed in two groups according to the extubation time (early < 6 hours, and late extubation > 6 hours). Individual characteristics, co-existing diseases, blood transfusion, inotropic support, intra-aortic balloon pump, cardiopulmonary bypass time, aortic cross-clamp time, and the serial measurements of serum lactate levels were recorded. Correlations of serial measurements of lactate levels and the peri-operative variables with extubation times were analysed. No significant differences were observed between the groups in terms of co-existing diseases and individual characteristics. However, cardiopulmonary bypass, aortic cross-clamp times and all lactate levels after aortic cross-clamping were found to be significantly different (p = 0.001). A statistically significant correlation was found between the cut-off value of 1.7 for serum lactate levels after aortic-cross clamping (L2); 1.9 for levels after aortic cross-clamp removal (L3); 2.2 for levels after cardiopumonary bypass (L4); 2.1 for levels after intensive care admission (L5); 1.7 for levels after first postoperative hour in the intensive care unit (L6), and 1.8 for the difference between pre-operative levels (L0) and the peak level of lactate in the peri-operative period (ΔL) in predicting extubation time (p < 0.01). We concluded that cardiopulmonary bypass and aortic cross-clamp times, and intra-operative serum lactate levels were important in predicting early extubation after isolated coronary artery bypass graft surgery.

Air-Bubble-Insensitive Microfluidic Lactate Biosensor for Continuous Monitoring of Lactate in Sweat.

This study aimed to develop a lactate sensor with a microchannel that overcomes the issue of air bubbles interfering with the measurement of lactate levels in sweat and to evaluate its potential for continuous monitoring of lactate in sweat. To achieve continuous monitoring of lactate, a microchannel was used to supply and drain sweat from the electrodes of the lactate sensor. A lactate sensor was then developed with a microchannel that has an area specifically designed to trap air bubbles and prevent them from contacting the electrode. The sensor was evaluated by a person while exercising to test its effectiveness in monitoring lactate in sweat and its correlation with blood lactate levels. Furthermore, the lactate sensor with a microchannel in this study can be worn on the body for a long time and is expected to be used for the continuous monitoring of lactate in sweat. The developed lactate sensor with a microchannel effectively prevented air bubbles from interfering with the measurement of lactate levels in sweat. The sensor showed a concentration correlation ranging from 1 to 50 mM and demonstrated a correlation between lactate in sweat and blood. Additionally, the lactate sensor with a microchannel in this study can be worn on the body for an extended period and is expected to be useful for the continuous monitoring of lactate in sweat, particularly in the fields of medicine and sports.

Monocarboxylate transporter 1 in the liver modulates high-fat diet-induced obesity and hepatic steatosis in mice

BackgroundThe monocarboxylate transporter 1 (MCT1) is a member of the MCT family and is implicated in the transport of lactate and a few other monocarboxylates across the cell membrane. How hepatic MCT1 regulates the metabolic functions of the body is currently unknown. MethodsThe functions of hepatic MCT1 on metabolism were analyzed using a mouse model with liver-specific deletion of Slc16a1 that encodes MCT1. Obesity and hepatosteatosis of the mice were induced by high-fat diet (HFD). The function of MCT1 on lactate transport was analyzed by measuring lactate level in hepatocytes and mouse liver. Degradation and polyubiquitination of PPARα protein were investigated by biochemical methods. ResultsHepatic deletion of Slc16a1 aggravated high-fat diet (HFD)-induced obesity in female mice, but not in male mice. However, the increased adiposity in Slc16a1-deleted mice was not associated with obvious reductions in metabolic rate and activity. The lactate level of the liver was significantly increased by Slc16a1 deletion in the female mice under HFD condition, suggesting that MCT1 mainly mediated the efflux of lactate in hepatocytes. Deficiency of MCT1 in the liver aggravated HFD-induced hepatic steatosis in both female and male mice. Mechanistically, deletion of Slc16a1 was associated with reduced expressions of genes involved in fatty acid oxidation (FAO) in the liver. The degradation rate and polyubiquitination of PPARα protein were enhanced by Slc16a1 deletion. Blocking the MCT1 function elevated the interaction of PPARα with an E3 ubiquitin ligase HUWE1. ConclusionsOur findings suggested that the enhanced polyubiquitination and degradation of PPARα upon Slc16a1 deletion likely contributes to the reduced expression of FAO-related genes and aggravation of HFD-induced hepatic steatosis.

Serum pro-B-type natriuretic peptide levels and cardiac index as adjunctive tools of blunt cardiac injury

BackgroundBlunt cardiac injury (BCI) has a variety of symptoms that may be a potentially life-threatening injury that can lead to death. Depending on the diagnosis of BCI, treatment direction and length of stay may vary. In addition, the utility of other diagnostic tests for cardiac disease as diagnostic tools for BCI remain unclear. The purpose of this study was to investigate the competence of N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac index (C.I) as adjunctive diagnostic tools for BCI.MethodsFrom January 2018 to March 2020, severe trauma patients with sternum fracture who were admitted to the traumatic intensive care unit (TICU) were included this study. Patients with sternum fracture, 18 years of age or older, and with an injury severity score > 16 who required intensive care were included. Invasive measurement for the analysis of the pulse contour for C.I monitoring and intravenous blood sampling for NT pro-BNP measurement were performed. Sampling and 12-lead electrocardiogram were performed at different time points as follows: immediately after TICU admission and at 24 h and 48 h after trauma.ResultsAmong 103; 33 patients with factors that could affect NT pro-BNP were excluded; therefore, 63 patients were included in this study. According to the American Association for the Surgery of Trauma Cardiac Injury Scale, 33 patients were diagnosed with non-BCI, and 30 patients constituted with BCI. The median ages of the patients were 58 (52–69), and 60 (45–69) years in the non-BCI and BCI groups, respectively (p = 0.77). The median NT pro-BNP values were higher in the BCI group on admission, hospital day (HD) 2, and HD 3, however, no statistical difference was observed (125 (49–245) vs. 130 (47–428) pg/mL, p = 0.08, 124 (68–224) vs. 187 (55–519) pg/mL, p = 0.09, and 121(59–225) vs. 133 (56–600) pg/mL, p = 0.17, respectively). On the contrary, significantly lower values were observed in the median C.I measurement on admission and HD 3 in the BCI group (3.2 (2.8–3.5) vs. 2.6 (2.3–3.5) L/min/m2, p < 0.01 and 3.2 (3.1–3.9) vs. 2.9 (2.4–3.2) L/min/m2, p < 0.01, respectively); however, no significant difference was observed on HD 2 (3.4 (3.0–3.7) vs. 2.6 (2.4–3.4) L/min/m2, p = 0.17), Furthermore, The median lactate levels in the BCI group upon admission, HD 2, and HD 3 were significantly higher than those in the non-BCI group (1.8 (1.1–2.6) vs. 3.1 (2.1–4.4) mmol/L, p < 0.01; 1.3 (0.8–2.3) vs. 3.0 (2.2–4.7) mmol/L, p < 0.01; and 1.5 (0.9–1.5) vs. 2.2 (1.3–3.7) mmol/L, p < 0.01, respectively).ConclusionConsecutive values of NT pro-BNP and C.I show no correlation with ECG-based BCI diagnosis. However, lactate level measurement may help in the early recognition of BCI as an adjunctive tool. It should be noted that this is a hypothesis-generating study for BCI diagnosis. Further studies should be conducted in larger populations with a prospective approach.

Phenotypic Profiling of Macrocyclic Lactones on Parasitic Schistosoma Flatworms.

Macrocyclic lactones are front-line therapies for parasitic roundworm infections; however, there are no comprehensive studies on the activity of this drug class against parasitic flatworms. Ivermectin is well known to be inactive against flatworms. However, the structure-activity relationship of macrocyclic lactones may vary across phyla, and it is entirely possible other members of this drug class do in fact show antiparasitic activity on flatworms. For example, there are several reports hinting at the anti-schistosomal activity of doramectin and moxidectin. To explore this class further, we developed an automated imaging assay combined with measurement of lactate levels from worm media. This assay was applied to the screening of 21 macrocyclic lactones (avermectins, milbemycins, and others such as spinosyns) against adult schistosomes. These in vitro assays identified several macrocyclic lactones (emamectin, milbemycin oxime, and the moxidectin metabolite 23-ketonemadectin) that caused contractile paralysis and lack of lactate production. Several of these were also active against miracidia, which infect the snail intermediate host. Hits prioritized from these in vitro assays were administered to mice harboring patent schistosome infections. However, no reduction in worm burden was observed. Nevertheless, these data show the utility of a multiplexed in vitro screening platform to quantitatively assess drug action and exclude inactive compounds from a chemical series before proceeding to in vivo studies. While the prototypical macrocyclic lactone ivermectin displays minimal activity against adult Schistosoma mansoni, this family of compounds does contain schistocidal compounds which may serve as a starting point for development of new anti-flatworm chemotherapies.

Potential Biomarkers of Mitochondrial Dysfunction Associated with COVID-19 Infection.

Mitochondria play crucial roles in modulating immune responses, and viruses can in turn moderate mitochondrial functioning. Therefore, it is not judicious to assume that clinical outcome experienced in patients with COVID-19 or long COVID may be influenced by mitochondrial dysfunction in this infection. Also, patients who are predisposed to mitochondrial respiratory chain (MRC) disorders may be more susceptible to worsened clinical outcome associated with COVID-19 infection and long COVID. MRC disorders and dysfunction require a multidisciplinary approach for their diagnosis of which blood and urinary metabolite analysis may be utilized, including the measurement of lactate, organic acid and amino acid levels. More recently, hormone-like cytokines including fibroblast growth factor-21 (FGF-21) have also been used to assess possible evidence of MRC dysfunction. In view of their association with MRC dysfunction, assessing evidence of oxidative stress parameters including GSH and coenzyme Q10 (CoQ10) status may also provide useful biomarkers for diagnosis of MRC dysfunction. To date, the most reliable biomarker available for assessing MRC dysfunction is the spectrophotometric determination of MRC enzyme activities in skeletal muscle or tissue from the disease-presenting organ. Moreover, the combined use of these biomarkers in a multiplexed targeted metabolic profiling strategy may further improve the diagnostic yield of the individual tests for assessing evidence of mitochondrial dysfunction in patients pre- and post-COVID-19 infection.

SENSOR ELETROQUÍMICO PARA MONITORAMENTO DE SUOR

ABSTRACT Introduction: Attention is given to developing electrochemical sensors for the rapid and real-time measurement of lactate levels. The synthesis of electrochemical sensors is based on an electrode modified with a nanocomposite. Objective: Analyze an electrochemical sensor's feasibility for sports monitoring sweat in lactate. The Au@CNTs were the main focus of this study. Methods: The Au@CNTs composite was synthesized on the GCE surface and tested under pre-established protocols as a sensor. Results: The shape and structure of the modified electrodes were analyzed using SEM. The results showed that the Au@CNTs nanoparticles in the Au@CNTs nanocomposite were evenly distributed throughout the porous CNTs network. The performance of the developed sensor was measured using cyclic voltammetry and amperometry. The electrochemical biosensor responded linearly to lactate over phosphate buffer solution with a low detection limit and sensitivity. Conclusion: The experiment of this sensor evaluated lactate concentrations in real sweat samples that were exceptionally close to the injection amount, enabling it as an effective biosensor for the detection of lactate in sweat samples. Level of Evidence: Therapeutic Studies - Outcome Investigation.