Plasma Values Research Articles

Can Obesity Affect Alpha-Tocopherol Plasma Values Mediated by Leptin? A Mediation Analysis in a Population-Based Study

Can Obesity Affect Alpha-Tocopherol Plasma Values Mediated by Leptin? A Mediation Analysis in a Population-Based Study

Effect of Combined Exercises on Glucose Homeostasis and Plasma Levels of Sirtuin 1 and FOXO1 in Obese Elderly Men

Introduction: Aging and obesity have common symptoms, including glucose and lipid metabolism changes. Activation of sirtuin 1 and FOXO1 (Forkhead Box Protein O1) can positively affect metabolic disorders associated with aging and obesity. This research aimed to investigate 16 weeks of combined exercise on the plasma levels of sirtuin 1, FOXO1, and glucose homeostasis in obese elderly. Methods: 40 obese elderly men with an average age of 61.90 ± 2.84 were selected and randomly divided into two experimental and control groups. The participants trained three days a week (each session 90 minutes) for 16 weeks. 48 hours before and after exercise, anthropometric characteristics and plasma values of sirtuin 1, FOXO1, fasting blood sugar, insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and HOMA-B (Homeostasis Model Assessment of β-Cell) were taken from the samples and measured by ELISA method. Data analysis was done using SPSS 16 software, independent and dependent t-tests at a significance level of P˂ 0.05. Results: Levels of fasting blood sugar (P=0.04), and insulin (P=0.008) in the experimental group decreased significantly compared to the control group, while the serum levels of sirtuin1 (P=0.0001) and FOXO1 (P=0.0001) had a significant increase. Correlated t results in the experimental group showed a significant decrease in insulin, HOMA-IR, and HOMA-B (P = 0.001) and a significant increase in the serum levels of sirtuin1 (P = 0.0001) and FOXO1 (P = 0.0001) (P ˂ 0.05). Conclusion: Based on the results of this study, it seems that 16 weeks of combined training has a favorable effect on improving glucose homeostasis, increasing sirtuin 1 and FOXO1 levels in elderly obese men.

HGG-48. THE BLOOD-BASED TELOMERIC DNA C-CIRCLE ASSAY CAN DETECT ALTERNATIVE LENGTHENING OF TELOMERES (ALT) IN PEDIATRIC HIGH-GRADE GLIOMAS

Abstract BACKGROUND High-grade gliomas (HGG) comprise ~10% of pediatric brain tumors; 40% of pediatric HGG use the alternative lengthening of telomeres (ALT) mechanism to maintain replicative immortality. ALT cancers share a unique biology providing potential therapeutic targets. Extrachromosomal telomere DNA repeats, termed C-circles, can be detected by a unique PCR assay, providing a sensitive and specific biomarker for ALT cancers. C-circles have been detected in ALT tumors and serum of ALT patients. We have adapted the C-circle assay (CCA) to provide a sensitive and specific assay with cfDNA in patient plasma. Here we determined if cfDNA in plasma can be used to detect patients with ALT-positive HGG. METHODS Frozen plasma samples were collected in Streck tubes at time of surgery prior to resection from patients with HGG. DNA was extracted and quantified. Isothermal rolling C-circle amplification and real-time telomere PCR was performed followed by analysis. The C-circle positive neuroblastoma cell line, CHLA-90, and C-circle negative neuroblastoma cell line, CHLA-20, served as the positive and negative controls respectively. CCA values in plasma of 2 and above indicate positivity for C-circles. RESULTS Plasma samples were analyzed by CCA from three pediatric patients whose brain tumors were previously biopsied and identified as ATRX mutation positive. ATRX mutation indicates ALT however, not all ALT cancers have ATRX mutations. All plasma samples were above the 2.0 cutoff at 3.37, 3.13, and 4.59 and thus classified as C-circle positive. CONCLUSIONS This preliminary cohort shows that the CCA has potential for identifying ALT pediatric brain tumors using cfDNA from plasma. As novel therapies effective against ALT HGG are developed, the plasma CCA may allow accelerated initiation of neoadjuvant therapy to shrink tumor prior to surgical resection and lessen or prevent the need for tumor biopsy. Expansion of the initial test cohort is underway. Supported by NCI UO1 CA63988.

Effect of Food, Crushing of Tablets, and Antacid Coadministration on Maribavir Pharmacokinetics in Healthy Adult Participants: Results From 2 Phase 1, Open-Label, Randomized, Crossover Studies.

The effect of food composition, tablet crushing, and antacid coadministration on maribavir pharmacokinetics was assessed in 2 Phase 1 studies in healthy adults. In the first, a single maribavir 400-mg dose was administered under fasting conditions, with a low-fat/low-calorie or a high-fat/high-calorie meal. In the second, a single maribavir 100-mg dose was administered under fasting conditions, as a crushed tablet, or as a whole tablet alone or with an antacid. The 90% confidence intervals of the geometric mean ratios were within 80%-125% for area under the concentration-time curve (AUC), but not for maximum plasma concentration (Cmax) for low-fat/low-calorie and high-fat/high-calorie meals versus fasting or for whole tablet with antacid versus whole tablet alone. The 90% confidence intervals of the geometric mean ratios for AUC and Cmax were within 80%-125% for crushed versus whole tablet. Maribavir median time to Cmax value in plasma under fed conditions was delayed versus fasting conditions, but there was no statistical difference for crushed versus whole tablet or with versus without antacid. As the antiviral efficacy of maribavir is driven by AUC but not Cmax, findings suggest that maribavir can be administered with food or antacids or as a crushed tablet.

Validation of the method for determining lincomycin levels and calculating lincomycin levels in broiler chicken plasma using high-performance liquid chromatography.

Antibiotic residues that come from food of animal origin, such as broiler chicken, have a variety of consequences on human health and increase the likelihood of antibiotic resistance. Lincomycin residue investigations in broiler chicken especially in plasma broiler chicken should be undertaken utilizing the validation method analysis. The purpose of this study is to determine the high-performance liquid chromatography (HPLC) as a validation method for calculating the residual concentration of lincomycin in broiler chicken blood plasma and compare it with the minimum Inhibitor Concentration (MIC) and Maximum Residue Limits (MRLs) standards for lincomycin. Thirty-five-day-old broiler chickens cobb 700 were weighed and randomly allocated to and separated into control (placebo) and six treatment groups of varying doses and duration. The treatment group's suggested dosage of lincomycin was 50, 100, or 150 mg/kg/day given to 18-day-old chicken, along with drinking water for a week (A group) and 2 weeks (P group). Lincomycin levels in blood plasma were validated using HPLC. The residual lincomycin concentrations 24 hours and 1 week after injection were compared to the lincomycin MIC and the Indonesian National Standard of MRL. The validation of linscomycin reveals a linear value in blood plasma with an R2 of 0.9983. Precision and accuracy levels indicate promising results for detecting lincomycin. The retention duration for 100 µg/ml lincomycin was 10.0-10.5 minutes. Lincomycin had LOD and LOQ values of 13.98 and 4.86 µg/ml, respectively. After 1 week of dosing at 50 and 100 mg/kg dosages, lincomycin residue detection was 0.00, which was below the MRL criterion of <0.1 ppm. The study found that the residual concentration of 150 mg/kg dosages for a week and 100/150 mg/kg doses for 2 weeks above the lincomycin MIC limits against Mycoplasma synoviae, Staphylococcus aureus, and Salmonella enteritidis. Lincomycin detection by HPLC in chicken blood plasma showed promising results in terms of linearity, accuracy, precision, specificity, and sensitivity. Lincomycin administration for 1 week at doses of 50 and 100 mg/kg resulted in the lowest residual concentration below the lincomycin MIC and MRL standards.

#233 Marine n-3 polyunsaturated fatty acids and cardiovascular events in patients with end-stage renal disease receiving hemodialysis

Abstract Background and Aims Cardiovascular (CV) disease is the leading cause of death in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). The two major marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have cardioprotective effects. This study aimed to investigate the predictive value of plasma n-3 PUFAs on CV events and all-cause mortality in patients with ESRD receiving HD. Method A validated prospective multicenter cohort study of 336 patients with ESRD receiving HD with 5 years of follow-up was conducted. Blood samples were collected at baseline and analyzed for the plasma levels of EPA and DHA expressed as a weight percentage (wt%) of total plasma fatty acids. The primary outcome was CV events defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease (PAD), or cardiovascular mortality. The secondary outcomes were all-cause mortality and each individual component of CV events. The sum of EPA and DHA (EPA+DHA) was used in all analyses and expressed as n-3 PUFAs in wt%. The population was divided into three groups according to n-3 PUFA tertiles. Kaplan-Meier curves and multivariable Cox regressions adjusted for relevant confounders were used to analyze the association between plasma n-3 PUFA levels and study outcomes. Results Median follow-up time was 5.05 years (IQR, 5.02-5.07). Mean age was 65 ± 15 years and plasma n-3 PUFA levels ranged from 2.1 to 16.8 wt%, with a median of 5.7 wt% (IQR, 4.72-6.96 wt%). During follow-up 60% of the cohort died, 17% died of CV disease, and 42% had a CV event. Figure 1 shows the unadjusted associations between the plasma n-3 PUFA tertiles and the risk of CV events. A n-3 PUFA level between 5.06-6.52 wt% was associated with a 36% lower risk of CV events [unadjusted HR 0.64 (95% CI 0.43-0.96)]. Additionally, a n-3 PUFA level above 6.52 wt% was associated with a 34% lower risk of CV events [unadjusted HR 0.66 (95% CI 0.44-0.98)], both in comparison to levels below 5.06 wt%. After adjusting for relevant confounders, as shown in Figure 2, n-3 PUFA levels between 5.06 to 6.52 wt% were associated with a significantly lower risk of CV events [adjusted HR 0.60 (95% CI 0.40-0.92)], PAD [adjusted HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [adjusted HR 0.61 (95% CI 0.42-0.86)], when compared to levels below 5.06 wt%. Conclusion In this study of patients with ESRD receiving HD, a low plasma level of n-3 PUFA was associated with a higher risk of CV events, peripheral artery disease, and all-cause mortality.

Triglyceride Glucose Index: A Potential Indicator in the Evaluation of Graves Ophthalmopathy.

To determine the relationship between Graves ophthalmopathy (GO) and triglyceride glucose index (TGI) and to evaluate the predictive importance of this index in terms of GO activity. This retrospective study included 20 inactive GO patients, 20 active GO patients, and 20 healthy controls. TGI was calculated using fasting plasma triglyceride and fasting plasma glucose levels and values were compared between the groups. The receiver operating characteristics curve was used to calculate the optimal TGI cutoff value and the sensitivity and specificity of this value between active and inactive GO groups. No significant difference was detected between the groups in terms of age and gender (p = 0.561 and p = 0.762, respectively). TGI value was 8.49 (8.41, 8.67) in the control group, 8.76 (8.74, 8.87) in the inactive GO group, and 9.06 (8.87, 9.08) in the active GO group (p < 0.001 for control group vs. inactive GO group; p < 0.001 for control group vs. active GO group; p = 0.001 for inactive GO group vs. active GO group). The optimal receiver operating characteristics cutoff value of TGI between active and inactive GO groups was 8.86 with 85% sensitivity and 75% specificity (area under curve: 0.837, p < 0.001, 95% confidence interval: 0.711-0.964). TGI was higher in both inactive and active GO patients compared with controls. It also appears that TGI may be used as a predictive marker indicating GO activity. This cheap and easily accessible parameter may be beneficial in detecting the disease and monitoring its activity in clinical practice.

Predicting coronary artery severity in patients undergoing coronary computed tomographic angiography: Insights from pan-immune inflammation value and atherogenic index of plasma

Background and aimsCoronary computed tomographic angiography (CCTA) is pivotal in diagnosing coronary artery disease (CAD). We explored the link between CAD severity and two biomarkers, Pan-Immune Inflammation Value (PIV) and Atherogenic Index of Plasma (AIP), in stable CAD patients. Methods and resultsA retrospective observational study of 409 CCTA patients with stable angina pectoris. Logistic regression identified predictors of severe CAD, stratified by CAD-RADS score. Receiver Operating Characteristic (ROC) curves evaluated predictive performance. PIV and AIP were significant predictors of severe CAD (PIV: OR 1.002, 95% CI: 1.000–1.004, p < 0.021; AIP: OR 0.963, 95% CI: 0.934–0.993, p < 0.04). AUC values for predicting severe CAD were 0.563 (p < 0.001) for PIV and 0.625 (p < 0.05) for AIP. Combined with age, AUC improved to 0.662 (p < 0.02). ConclusionsPIV and AIP were associated with severe CAD, with AIP demonstrating superior predictive capability. Incorporating AIP into risk assessment could enhance CAD prediction, offering a cost-effective and accessible method for identifying individuals at high risk of coronary atherosclerosis.

Pharmacokinetic/pharmacodynamic relationships of enrofloxacin against Klebsiella pneumoniae in an in vivo infection model in young chicks

Klebsiella pneumoniae is a serious pathogenic bacterium that poses a significant threat to young poultry and the cause of significant chick mortality and economic loss. We investigated the therapeutic efficacy of enrofloxacin in treating K. pneumoniae infections in chicks and employed an in vivo pharmacokinetic/pharmacodynamic (PK/PD) model. In vivo efficacy was evaluated using six multiple-dose groups (oral administration once a day for three days) and two single-dose groups (oral administration once only). The PK and PD parameters of plasma and lung were analyzed using PK/PD fitting analysis. K. pneumoniae administered intratracheally (108 CFU/mL in 0.4 mL saline) was used to establish a model for pulmonary infection. The plasma protein binding of enrofloxacin was 20.18%. Enrofloxacin displayed T1/2β values of 4.78 ± 0.69 h and 4.78 ± 1.02 h in plasma and lung of infected chicks, respectively. When the dosage in the multiple-dose group was ≥ 20 mg/kg, bactericidal activity was found and complete eradication was not achieved when the dosage was ≤ 40 mg/kg. When TMSW was set at 20%, the calculated dosage and bacterial reduction (E) based on plasma free drug data were 4.03 mg/kg and -1.982 Log10 CFU/mL, respectively. In the calculation of PK/PD parameters for reducing 3 log10 CFU/mL and using Cmax/MIC, AUC72h/MIC and TMSW of free drug in plasma values at 9.479, 379.691 and 44.395%, respectively, the value of AUC72h/MIC based on the concentration of drug in lung was 530.800. According to the fitting correlation R2, the PK/PD fitting results of free drug in plasma were better. The corresponding enrofloxacin dosage for AUC72h/MIC of the plasma free drug concentration was 14.16 mg/kg. The administration regimen corresponding to these dosages was once daily for 3 days. This dosage regimen (14.16 mg/kg) was relatively high compared to the clinically recommended dosage in China (7.5 mg/kg) when treating infections caused by K. pneumoniae with MIC ≥ 0.125 μg/mL, so careful consideration is needed.

Neutrophil-mediated Inflammatory Plasminogen Degradation, Rather Than High Plasminogen-Activator Inhibitor-1, May Underly Failures and Inefficiencies of Intrapleural Fibrinolysis

Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? We obtained infected pleural fluid and circulating plasma from hospitalized adults (n= 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vssurgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05. Pleural fluid elastase activity was more than fourfold higher (P= .02) and plasminogen antigen levels were more than threefold lower (P= .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P= .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. ClinicalTrials.gov; No.: NCT03583931; URL: www. gov.

Quantitative analysis of optical emission spectroscopy for plasma process monitoring

In the field of plasma materials processing, various plasma parameters should be evaluated quantitatively and precisely to control the plasma process adequately, particularly with non-invasive methods, one of which is optical emission spectroscopy (OES) measurement. It has sufficient scientific feasibility to derive the electron density N e, electron temperature T e, and the electron energy distribution function (EEDF) even for various processing plasmas in a state of non-equilibrium. In this review, previous studies are reviewed to measure the N e, T e, and EEDF values of argon plasma with low-electron temperature (T e ≃ 1–10 eV) under not only low-pressure conditions but also atmospheric-pressure discharge using the OES measurement. First, to diagnose low-pressure discharge argon plasmas, we explain the basics and applications of the “collisional radiative model”, which models the population kinetics of the excited states in plasma at the elementary process level in non-equilibrium plasma. Methods for analyzing the plasma parameters are shown from the actual measurement results of emission spectra, including machine learning analysis of the excited-state populations. Next, the research results of the method to measure N e, T e, and EEDF are introduced for the measurement of atmospheric-pressure non-equilibrium plasmas using OES measurement of continuum emission, which also includes methods based on machine learning and data-scientific methods for the analysis of the OES data observed as bremsstrahlung of free electrons scattered against neutral molecules.

Sex differences in amino acid composition in a rodent model of ARPKD, the PCK rat

Polycystic Kidney Disease (PKD) is a severe, genetically inherited disease that leads to renal failure. Like several other chronic kidney diseases, male sex is a risk factor for accelerated PKD. Rat models of both Autosomal Recessive and Dominant forms of PKD (PCK and Han:SPRD rats, respectively) exhibit sex differences in disease progression. Previous studies have found that amino acids (AAs) and peptides are predominant constituents of cystic fluid. We hypothesized that AA homeostasis in male and female cystic fluid would demonstrate sexual dimorphism, and these differences may provide essential information about the progression of cystogenesis. We quantified the AAs in cystic fluid, plasma, and urine in PCK and control Sprague Dawley (SD) rats (only plasma and urine for SD rats). Of the 42 AAs that were measured, only asparagine, serine, aspartic acid, glutamic acid, beta-alanine, cystathionine, and leucine were NOT significantly different between SD and PCK plasma values. Interestingly, only 18 AAs were significantly different in urine of PCK rats compared to SD rats. In SD rats, between sexes, 26 AAs were significantly different in plasma and 5 were significantly different in urine. Among PCK rats, 13 AAs in plasma, 9 AAs in urine, and 4 AAs in cystic fluid were significantly different between sexes. The 4 AAs that differed between male and female cystic fluid were 1-methylhistidine, 3-methylhistidine, ethanolamine, and taurine. Moreover, taurine was the most abundant AA in cystic fluid. Taurine concentrations in both plasma (165 ± 9 vs. 128 ± 4 μM, N=6, p=0.003) and cystic fluid (7508 ± 469 vs. 4557 ± 788 μM, N=6, p=0.01) were significantly different between sexes in the PCK rats (male vs. female, respectively). Urine values for the PCK rats (9705 ± 1863 vs. 7570 ± 1631 μM, N=6) were not significantly different in males and females; however, the average urinary taurine excretion in PCK rats was nearly 4-fold greater than SD rats (8637 ± 1223 vs. 2219 ± 465 μM, N=12, p&lt;0.0001). There were no significant differences in taurine concentrations between SD male and female rat plasma (202 ± 17 vs. 194 ± 7.0 μM, N=6) or urine (2044 ± 614 vs. 2395 ± 752 μM, N=6). Western blot of the taurine transporter, TauT, detected bands at 50 and 75 kDa, and both bands were significantly reduced by ~50% in PCK kidneys compared to SD kidneys. Lastly, immunolabeling in PCK kidney sections demonstrated that TauT is present at the apical membrane of cyst epithelia. These results point to a potential role for AAs, and specifically for taurine in cystogenesis, which likely varies by sex in diseased, but not healthy kidneys. R00 HL153686, BX004024, R01 DK126720, R01 DK129227. This is the full abstract presented at the American Physiology Summit 2024 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.

Rheological and gelling properties of atmospheric pressure cold plasma treated finger millet (Eleusine coracana) starch

Interest in exploring alternative starch sources like finger millet is rising due to wide starch applications. However, native starch often lacks desired qualities, including rheological properties. Modification is thus necessary for specific end uses. Plasma treatment as a greener and sustainable method for starch modification was therefore, studied for its ability to impact rheological properties of finger millet starch (FMS). Considerable changes in the rheological properties on FMS was noted, a significant decrease and increase (p < 0.05) in the peak viscosity (from 3.35 to 0.553 Pa.s) and paste clarity respectively was observed, indicating occurrence of depolymerization. However, intermediate plasma-treated samples (200 V) observed a decrease in paste clarity attributed to aggregate formation and cross-linking. Cross-linking was also confirmed by findings of frequency sweep where a continuous decrease in G’ values of plasma treated FMS gel was interrupted by sudden increase. Despite depolymerization causing alteration of rheological behaviour such as decrease in shear thinning properties, gel strength observed a contradictory increase. This was attributed to incorporation of functional group and absence of shear responsible for network formation giving higher gel strength to FMS gels. This is elaborated in detail in the study. The study thus concluded that cold plasma significantly impacted all the rheological properties of the FMS and hence can prove to be beneficial for modification of starch rheological parameters.

Diagnostic and prognostic value of plasma miR-106a-5p levels in patients with acute heart failure

BackgroundIt is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients.MethodsProspectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve.ResultsPlasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level < 0.655 could assist in AHF diagnosis. Plasma miR-106a-5p levels were markedly lower in poor-prognosis AHF patients than in good-prognosis patients. Plasma miR-106a-5p level < 0.544 could assist in predicting poor prognosis in AHF patients.ConclusionPlasma miR-106a-5p is downregulated in AHF patients and could assist in diagnosis and poor prognosis prediction of AHF.

Hepatic lipid accumulation is associated with multiple metabolic pathway alterations but not dyslipidemia and insulin resistance in central bearded dragons (Pogona vitticeps).

To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons. 48 adult central bearded dragons (Pogona vitticeps). Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson's trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics. Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, β-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid. Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.

Using the fish plasma model to evaluate potential effects of pharmaceuticals in effluent from a large urban wastewater treatment plant

Several pharmaceuticals and personal care products (PPCPs) were evaluated using the fish plasma model (FPM) for juvenile Chinook salmon exposed to effluent from a large urban wastewater treatment plant. The FPM compares fish plasma concentrations to therapeutic values determined in human plasma as an indication of potential adverse effects. We used human Cmax values, which are the maximum plasma concentration for a minimum therapeutic dose. Observed and predicted plasma concentrations from juvenile Chinook salmon exposed to a dilution series of whole wastewater effluent were compared to 1%Cmax values to determine Response Ratios (RR) ([plasma]/1%Cmax) for assessment of possible adverse effects. Several PPCPs were found to approach or exceed an RR of 1, indicating potential effects in fish. We also predicted plasma concentrations from measured water concentrations and determined that several of the values were close to or below the analytical reporting limit (RL) indicating potential plasma concentrations for a large number of PPCPs that were below detection. Additionally, the 1%Cmax was less than the RL for several analytes, which could impede predictions of possible effect concentrations. A comparison of observed and predicted plasma concentrations found that observed values were frequently much higher than values predicted with water concentrations, especially for low log10Dow compounds. The observed versus predicted values using the human volume of distribution (Vd), were generally much closer in agreement. These data appear to support the selection of whole-body concentrations to predict plasma values, which relies more on estimating simple partitioning within the fish instead of uptake via water. Overall, these observations highlight the frequently underestimated predicted plasma concentrations and potential to cause adverse effects in fish. Using measured plasma concentrations or predicted values from whole-body concentrations along with improved prediction models and reductions in analytical detection limits will foster more accurate risk assessments of pharmaceutical exposure for fish.

Abstract 3323: Novel Pan-RAS inhibitor ADT-007: A unique mechanism of antitumor selectivity in pancreatic and colorectal carcinoma models

Abstract Multiple types of RAS mutations activate RAS isoforms, HRAS, NRAS, or KRAS, that drive oncogenic signaling leading to uncontrolled cell proliferation and tumor development. RAS mutations occur de novo in approximately one-third of all human cancers, and are especially prevalent in pancreatic, colorectal, and lung tumors. Where RAS mutations are less frequent in other cancers, such as breast cancer, RAS can be pathologically activated by growth factor receptors that engage numerous downstream effectors. The currently FDA-approved KRAS-targeted drugs are designed to covalently inactivate only G12C KRAS mutants, however, this mutation is only prevalent in lung cancer. The most common mutations in pancreatic ductal adenocarcinoma (PDAC) are KRAS-G12D, KRAS-G12V, and KRAS-G12R. Our novel class of pan-RAS inhibitors, exemplified by ADT-007, addresses the urgent need for pan-RAS inhibitors with antitumor activity in cancers harboring these common mutations. These pan-RAS inhibitors have unique pharmacological properties that allow for selective killing of cancer cells harboring RAS mutations. ADT-007 inhibited growth of an array of carcinoma tumor cell lines in vitro with single digit nM IC50 values regardless of RAS mutant allele, and inhibited RAS activation and MAPK/AKT signaling. Because it is a pan-RAS inhibitor, ADT-007 may not be susceptible to commonly reported mechanisms of resistance to covalent KRAS inhibitors, such as activation of wild type (WT) alleles or secondary RAS mutations. Differentiated normal epithelial or hepatic cells, and tumor cells with WT RAS were insensitive to ADT-007 due to enzymatic detoxification of ADT-007 via glucuronidation, representing a novel mechanism of tumor selectivity. An orally bioavailable prodrug of ADT-007 (ADT-1004) is well tolerated in vivo, and produced sustained concentrations of ADT-007 well above IC50 values in plasma and even higher levels in tumors. Daily oral administration of ADT-1004 significantly inhibited RAS signaling and tumor growth in orthotopic and PDX mouse models of pancreatic cancer. Citation Format: Junwei Wang, Adam B. Keeton, Sindhu Ramesh, Peyton Johnson, Yulia Y. Maxuitenko, Jeremy B. Foote, Chung-Hui Huang, Kristy L. Berry, Khalda Fadlalla, Bandi D. Reddy, Ganji P. Nagaraju, Elmar Nurmemmedov, Ivan Babic, Vadim Gaponenko, Xi Chen, Bassel F. El-Rayes, Donald J. Buchsbaum, Gary A. Piazza. Novel Pan-RAS inhibitor ADT-007: A unique mechanism of antitumor selectivity in pancreatic and colorectal carcinoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3323.

Clinical implications of inaccurate potassium determination in hemolyzed pediatric blood specimens

BackgroundAnalysis of whole blood specimens is rapid and saves blood, but hemolysis may go undetected and compromise the accuracy of potassium measurement. We aimed to define the frequency and magnitude of error in whole blood potassium measurement. Methods34 months of whole blood and plasma potassium data were extracted from patients aged less than 2 years at the time of sample acquisition. Hemolysis was detected using the plasma “H index.” The magnitude of potassium bias was estimated from the difference between paired whole blood and plasma measurement separated by less than 2 h. Results56,000 of the 105,000 data points were from plasma and 20 % of these had significant hemolysis. Rates of hemolysis (nearing 50 %) were greatest in the neonatal nursery. Of 662 proximal whole blood and plasma paired results, 8 % had elevated whole blood potassium with a normal plasma value and 4 % had a normal whole blood potassium with reduced plasma potassium. The bias between whole blood and plasma potassium ranged from −1.0 to 4.0 mmol/L. ConclusionsThe use of whole blood analysis brings with it significant risk for error in potassium measurement. Better tools to detect hemolysis in these types of specimens are indicated.

Observation of the low electron density and electron temperature in an unmagnetized cascaded arc helium plasma by laser Thomson scattering approach

In this study, the electron density (ne ) and temperature (Te ) in an unmagnetized cascaded arc helium (He) plasma are precisely determined using cutting-edge laser Thomson scattering. In our experimental scope, ne is only 1018 m−3 and Te is less than 0.2 eV, both of which are substantially lower than in linear plasma devices (LPDs). The comparison of ne and Te values in He plasma with those in cascaded arc Ar plasma reveals that these two parameters are likewise significantly lower in He plasma than they are in Ar plasma on average. In comparison to Ar gas, the degree of ionization of He is low due to its high ionization potential, and diffusive loss dominates due to its light weight, both of which result in a lower ne . Meanwhile, these two characteristics render the three-body recombination interaction between electrons and He+ ions in He plasma insignificant, thus the electrons cannot be heated effectively, explaining why Te is lower. This study will provide foundational data and build the groundwork for a thorough knowledge of cascaded arc He plasma in LPDs and plasma windows.

Radiative dynamics of laser-driven Li@C n embedded in quantum plasma

This work considers a guest Lithium atom (Li@C n ) in an endohedral fullerene, embedded in a quantum plasma modeled by the more general exponential cosine screened Coulomb (MGECSC) potential, under the influence of a spherical confinement and laser radiation field. The system is examined in nonrelativistic form and the related wave equation is solved using the tridiagonal matrix method (TMM), thus obtaining the discrete-continuum spectrum and related wave functions. The numerical values of the relevant parameters in this process are physically accessible values. The effects of the plasma, laser field and endohedral cavity on the photoionization cross section (PCS) are analysed in detail. The shielding effect of the plasma medium and the pulsating effect of the laser field modify the effective potential energy of the system, affecting the localizations of the 2s and continuum states, causing various overlapping cases. Considering different values of the endohedral encompassement parameters, which means that different types of fullerenes are taken into account, overlapping cases occur for different spectra and wave functions. Scrutinising these overlappings, the confinement and Cooper resonances of the PCSs are analysed. This analysis provides many details for the radiative dynamics of an artificial system Li@C n . The relevant ranges and critical values of plasma, laser field, and endohedral encapsulation parameters in the formation process of these resonances and PCSs are explained, as well as the cross-section curves, resonance positions, effective photoelectron energy range, and general PCS behavior, which can be important for potential experiments in addition to other theoretical investigations.