Maximum Concentration Research Articles

Characteristics of surface microlayer film under different freshwater environments: physical, chemical, and biological properties

The surface microlayer film (SMF) has been observed worldwide in water environments and its environmental behavior plays a vital role in the migration and transformation of water pollutants. However, there has been little description and explanation of their characteristics in freshwater environments. Here, we investigate the characteristics of SMF under different freshwater trophic status. The results demonstrated that under sufficient nutrition, the interior characteristics of the SMF are densely arranged Fe3O4 skeletal structures, and the enrichment concentration of Fe3+ on the SMF reached 4.66μg/mL, the dominant bacteria is Zoogloea. Under the constraint of nitrogen, the interior characteristics of the SMF is a tightly spherical encapsulated organic matter, the maximum enrichment concentration of Fe3+ on the SMF was only 0.75μg/mL, Limnobacter and Acidocella are the dominant bacteria in the carbon and nitrogen constraint. Under iron constraint, the interior of the SMF is an entangled organic organism, and the coverage rate of the SMF was only 31.41%, which decreased by 20.55% and 8.58%, compared with carbon and nitrogen constraint respectively, and the main microbial species is Cloacibacterium. These results reveal a strong correlation between water nutrient types and the formation of SMF, and established a connection between water pollution and SMF characteristics, provided a new approach for predicting water types using water surface microlayers, and have important implications for managing freshwater ecosystems.

A lab-scale frugal solar bioreactor design for cleaner production of bioproducts from thermophilic bacteria in outdoor conditions

Our study introduces an economical solar-powered bioreactor design for producing a model bioproduct, elucidated as a variant of poly-gamma-glutamic acid, using a thermophilic Bacillus licheniformis in a sterile-compromised growth environment. This frugal solar bioreactor (SB) setup repurposes an out-of-service jacketed stirred tank reactor with a working volume of 5 L and incorporates solar photovoltaic (PV) modules and a solar thermal unit to supply the necessary electrical load (1680 Wh) and heat for carrying out 24-hour batch fermentation at 50 °C. By repurposing the condemned equipments, the cost of SB fabrication was brought down by 59 %. In a batch mode of operation, the solar bioreactor yielded a maximum biopolymer concentration of 19.8 ± 0.9 g/L, which was 14.5 % less than the biopolymer titre obtained from a commercial bioreactor under similar production conditions. The molecular weight (MW) of the biopolymer was found to be dependent on the temperature of fermentation with a maximum MW of 865.7 kDa achieved at 50 °C. It is envisaged that the proposed solar bioreactor design can be used for the effective production of thermophilic bacterial products suited for various low-cost applications.

Biological characterization of marine algae and its potent in vitro antioxidant, antimicrobial and larvicidal activity: a focus on Ulva lactuca Linnaeus 1753: 1163.

This study evaluated the biological characteristics of seaweeds Turbinaria ornata, Ulva lactuca, and Gracilaria crassa. Among the seaweeds tested, ethyl acetate extract of Ulva lactuca exhibited the highest antibacterialactivity against Salmonella enterica, Staphylococcus aureus, and Pseudomonas aeruginosa. The phytochemical analysis of ULME and ULEA showed the presence of most of the tested phytochemicals, whereas only amino acids, tannins, glycosides, and carbohydrates were detected by ULHE. The DPPH scavenging property of U. lactuca exerted the maximum antioxidant property of 62.54% (ULME), 75.64% (ULEA), and 39.55% (ULHE), whereas the alpha amylase inhibitory property (µg/mL) of ULME, ULEA, and ULHE was, respectively, 80.99, 51.15, and 49.23. ULME, ULEA, and ULHE exhibited the greatest alpha-glucosidase inhibition, with IC50 values (g/mL) of 116.12, 45.59, and 170.10 correspondingly. ULEA also showed potent mosquito-larvicidal effects against Aedes aegypti larvae with the maximum lethal concentration values with LC50 and LC90 values (mg/mL) being 11.55 and 65.97, respectively. FTIR analysis of ULME, ULHE, and ULEA were found to have various functional groups, including alkanes, carboxylic acids, alkenes, alkynes, aldehydes, amides and alkanes, ketones, and aromatics, while HPLC revealed a strong peak at 4.760 retention time. In conclusion, Ulva lactuca, particularly its ethyl acetate extract, demonstrates significant antibacterial, antioxidant, and enzyme-inhibitory properties, highlighting its therapeutic and biotechnological potential. Its diverse phytochemicals and effective mosquito-larvicidal activity further support its broad application prospects.

Valoración fisiológica y manejo de pacientes post-COVID con pruebas funcionales cardiopulmonares y de imagen normales

ObjectiveContributing to elucidate the pathophysiology of dyspnoea and exertion intolerance in post-COVID syndrome patients with normal cardiopulmonary imaging and functional tests at rest, while determining their fitness and level of endurance in order to individualize working parameters for physical rehabilitation. Material and methodsAfter an anamnesis and clinical examination at rest, 27 subjects (50±11.9 years) (14 women) with post-COVID syndrome of more than 6 months of evolution performed a continuous maximal-incremental graded cardiopulmonary exercise test (CPET) with breath-by-breath gas-exchange monitoring and continuous ECG registration, on an electromagnetically braked cycle ergometer. The values obtained were compared with those of reference, gender or controls, using the Chi-square, t-Student or ANOVA test. ResultsThe clinical examination at rest and the CPET were clinically normal and without adverse events. Reasons for stopping exercise were leg discomfort. It is only worth noting a BMI=29.9±5.8kg/m2 and a basal lactate concentration of 2.1±0.7mmol/L. The physiological assessment of endurance showed the following results relative to predicted VO2máx: 1)peakVO2=80.5±18.6%; 2)VO2 at ventilatory threshold1 (VO2VT1): 46.0±12.9%; 3)VO2VT2: 57.2±16.4%; 4)working time in acidosis: 5.6±3,0minutes; and 5)maximum lactate concentration: 5.1±2.2mmol/L. ConclusionsThe CPET identified limited aerobic metabolism and early increase in glycolytic metabolism as causes of dyspnoea and exercise intolerance, determined fitness for physical rehabilitation, and individualized it based on the level of endurance.

Macrocyclic anti-inflammatory diterpenes from the South China Sea soft coral Sinularia erecta and their isolation by combined column chromatography

Eleven new macrocyclic casbane-type diterpenes, namely sinueracasbanones E–O (1–11), have been isolated from the South China Sea soft coral Sinularia erecta using combined column chromatography. The structures of new compounds were elucidated by extensive spectroscopic data analysis, the modified Mosher's method, X-ray diffraction analysis and quantum mechanical calculation methods. In bioassay, compounds 2, 5, 10 and 11 displayed interesting anti-inflammatory activities by the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α protein release with half maximal inhibitory concentration (IC50) values of 15.6, 7.1, 13.7 and 6.6 µM, respectively.

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD. The main purpose of this study was to identify CBD clinical pharmacokinetic properties through meta-analysis. In particular, we sought to derive valid, interpretable independent variables and interpret their pharmacokinetic parameter correlations in relation to the large inter-individual and inter-study variability in CBD pharmacokinetics. For this study, CBD-related clinical trial reports were extensively screened and intercomparisons were performed between internal data sets through systematic classification and extraction of pharmacokinetic parameter values. The candidate independent variables associated with interpretation of CBD pharmacokinetic diversity established and explored in this study were as follows: diet, tetrahydrocannabinol (THC) combination, sample matrix type, liver and renal function, exposure route, dosage form, CBD exposure dose, cannabis smoking frequency, multiple exposure. The results of this study showed that CBD pharmacokinetics were influenced (increased plasma exposure by approximately 2-5 times) by diet immediately before or during CBD exposure, and that THC was not expected to have an antagonistic effect on the CBD absorption. The influence of changes in liver function would be significant in CBD pharmacokinetic diversity. Due to decreased liver function, the plasma exposure of CBD increased 2.57-5.15 times compared to healthy adults, and the half-life and clearance showed a 2.58-fold increase and a 5.15-fold decrease, respectively. CBD can be rapidly absorbed into the body (time to reach maximum concentration within 3.18h) by oral, transdermal, and inhalation exposures, and lipid emulsification and nanoformulation of CBD will greatly improve CBD bioavailability (up to approximately 2 times). The pharmacokinetics of CBD generally follow linear kinetic characteristics. The importance of this study is that it suggests key factors that should be considered in terms of pharmacokinetics in further clinical trials and formulations of CBD in the future.

Plasma synthesis and characteristics of nanocomposite coatings based on PVA and chitosan with incorporated nanoparticles for the healing of skin wounds

This study investigated the impact of new composites based on PVA and chitosan on wound healing in mice. Metal or metal oxide nanoparticles were synthesized without reagents by creating an impulse discharge between metal electrodes in a polymer dispersion. Polymer composites and coatings were then prepared using these nanoparticles. The composites were analyzed using various techniques, including UV spectroscopy, X-ray diffraction, scanning and transmittance electron microscopy, and infrared spectroscopy. The maximum concentration of nanoparticles in the composite was 3.5%. The average diameter of the nanoparticles was approximately 50-60 nm. The inclusion of Ag and ZnO nanoparticles accelerated the healing process by approximately 25%.

Effect of solids concentration and operational variables on the performance of a geometrically optimized concentrator hydrocyclone employing a pseudoplastic fluid

The employment of hydrocyclones in thickening operations is an attractive option when compared to centrifuges and filters due to their low operating, maintenance, and acquisition costs. However, the performance of hydrocyclone separation is impaired as the concentration of solids and the viscosity of the suspension increases. Using geometric optimization techniques, the Federal University of Uberlândia developed one concentrator hydrocyclone named HC. When working with diluted and Newtonian slurries, the HC could generate a stream 45 times more concentrated than the one fed into it. In this study, the HC performance was evaluated when operating pseudoplastic fluids containing up to 10% solids by volume. The combination of the underflow diameter and vortex finder length with an adequate supply of pressure energy maintained the thickening potential of the HC even when the rheology of the fluid was changed. For different working suspensions, the HC hydrocyclone achieved a minimum water split to underflow of 5%, a maximum concentration ratio of 7.0, and a maximum efficiency of 49%. The encouraging results obtained by the HC validated the benefits of the geometric optimization, as they point to a significant advance in the thickening operation of non–Newtonian sludges with a flow behavior index greater than 0.5.

Highly effective fluorescence detection of UO22+ ions by an anionic Na/Eu heterometallic metal–organic framework with Lewis basic chelating sites

Uranium is a serious radioactive contaminant that can easily migrate into groundwater and surface water, posing a deadly threat to human health. Despite the development of various materials for detecting uranyl ions in water, rational design and synthesis of new uranium sensors with sensitivity, selectivity, and fast response remain challenging. Herein, we demonstrate a novel strategy for obtaining highly sensitive and selective UO22+ sensors by constructing heterometallic metal–organic framework with both an anionic skeleton and abundant chelating sites. Namely, the first anionic Na/Eu heterometallic metal–organic framework (Na/Eu-MOF) based UO22+ sensor is successfully synthesized by using sodium salt and europium salt as reactants, and abundant ether groups were introduced into its porous structure as chelating Lewis basic sites. Beneficial from the synergistic effect between the anionic skeleton and the chelating sites, Na/Eu-MOF achieved rapid, selective adsorption and fluorescence quenching toward uranyl ion. The detection limits of Na/Eu-MOF in deionized and lake water were determined to be 49.7 nM and 113.0 nM, respectively, which are lower than the maximum concentration of 130.0 nM in drinking water proposed by the United States Environmental Protection Agency, indicating potential environmental applications. The detection capability of Na/Eu-MOF is attributed to the combination system of energy competition and interactions between UO22+ ions and Na/Eu-MOF. This work offers a feasible strategy to construct an anionic heterometallic metal–organic framework with chelating sites for uranyl detection in an aqueous solution.

Comparison of a customized glycemic pellets challenge with the oral sugar test to measure glycemic and insulinemic responses in horses.

Testing for insulin dysregulation (ID) in horses is commonly performed to guide management and therapeutic strategies. To evaluate a newly developed glycemic pellets challenge (GPC) and compare results to those obtained using the low-dose oral sugar test (OST). Twenty-four adult horses with unknown insulin status. A randomized crossover trial was performed. Horses underwent GPC (0.5 g glycemic carbohydrates/kg body weight) and OST (0.15 mL corn syrup/kg body weight) 7 days apart. Feed was withheld before testing and blood samples were collected at T0, T60, T120, and T180 minutes for GPC and at T0, T60, and T90 minutes for OST. Blood glucose concentration was measured using a point-of-care glucometer and insulin by radioimmunoassay. Comparisons were made using nonparametric tests, linear regression, and Bland-Altman agreement analysis. Eighteen horses consumed >85% of the GPC pellets within 10 minutes and had acceptable OST results. Maximum glucose (P = .02) and insulin (P = .007) concentrations were significantly higher for GPC compared with OST. Time to maximum insulin concentration (Tmax[ins]) varied within and between tests and neither Tmax[ins] (P = .28) nor maximum insulin concentration (P = .46) was correlated with the time horses took to consume pellets. The GPC is well tolerated and may offer another diagnostic testing modality for ID. Blood glucose and insulin concentrations increase during GPC and reach higher concentrations than observed with low-dose OST. The Tmax[ins] varied for GPC and OST, emphasizing the importance of identifying the optimal time range for the collection of samples to capture diagnostically relevant changes in insulin concentration.

First-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of RBD4059, a GalNAc-siRNA drug targeting coagulation factor XI (FXI), in healthy subjects

Abstract Background Patients at risk of thrombosis/thromboembolism, require effective and safe anti-coagulation with high compliance. Inhibiting FXI has emerged as a promising strategy with potential for lower bleeding risk compared to currently approved anti-coagulants. Here we report on the safety, PK and PD effects of the GalNAc-conjugated siRNA RBD4059, specifically targeting and repressing FXI protein synthesis in the liver. Purpose Investigate safety, PK, and PD of first-in-human dosing of RBD4059 in healthy subjects. Methods A randomized, single-blind, placebo-controlled, single ascending dose (SAD) phase I study in healthy subjects (NCT05653037), in cohorts of eight randomized 3:1 to receive escalating doses of RBD4059 (50, 150, and 400 mg) or placebo administered subcutaneously. Results As of January 25, 2024, 24 subjects (with follow-up to week 24) with demographics and baseline clinical characteristics shown in Table 1 were enrolled. RBD4059 was well tolerated (Table 2), all related AEs were grade 1. There was no evidence of any clinically relevant bleeding events. Plasma exposure of RBD4059 tended to increase in proportion to the dose. Maximum concentration in plasma (Cmax) was reached in 2 to 4 h and then declined in line with one-compartment kinetics. The mean plasma half-life (t1/2) ranged from 3.2 to 7.0 h. RBD4059 treatment resulted in dose dependent and sustained reductions in FXI activity and FXI antigen (Figure 1A, B, D). Observed mean maximum percentage change from baseline in FXI activity from the 50 mg, 150 mg, and 400 mg SAD cohorts were 67.5%, 81.0%, and 85.8%, respectively, recovering with a maintained effect observed on D141 (50mg: 50.6% inhibition; 150mg: 68.2% inhibition). The reduction in FXI antigen showed a very similar pattern as the reduction in FXI activity, and reductions were accompanied by a concomitant increase in APTT. (Figure 1C, D). PKPD modelling supports that RBD4059 may be dosed every 3 months or less frequent with a >90% FXI reduction throughout the dosing interval, and will be tested in the upcoming phase 2 study. Conclusion(s) RBD4059 demonstrated favorable safety, predictable PK, and pronounced durable PD effect in the dose range of 50 mg - 400 mg. This first-in-human SAD study supports the further development of RBD4059 as an anticoagulant that can maintain a high level of PD effect with a once every 3 month or less frequent dosing regimen, with potential for enhanced compliance in chronic anti-coagulant therapy.Table 1 & Table 2Figure 1.Panels A-D

Acute hemodynamic effect of oral ketones in patients with acutely decompensated heart failure and low cardiac output syndrome: a prospective randomized study.

Abstract Background Preliminary studies showed positive inotropic effect of mild ketosis in patients with heart failure with reduced ejection fraction (HFrEF). Purpose To evaluate the acute hemodynamic effect of oral administration of beta-hydroxybutyrate (OHB) in patients with HFrEF and low cardiac output syndrome. Methods Patients with acutely decompensated HFrEF treated with inotropic therapy were randomized (1:1) to enteral bolus of OHB (25g of OHB monoester in 65 ml of solution; H.V.M.N Ketone Ester, H.V.M.N, USA) administered three times with 3-hour intervals or to euvolemic placebo. The serum concentration of OHB, biochemical markers, and invasive hemodynamics (Swan-Ganz catheter with continuous thermodilution) were repeatedly measured before and during 24 hours after administration of OHB. The primary endpoint was the maximum change in cardiac index (CI). Results The study included 20 patients with decompensated HFrEF (age: 57 ± 8 years; left ventricular ejection fraction: 21 ± 4%; non-ischemic cardiomyopathy: 16 [80%], median INTERMACS class: 3 [IQR 2 - 4]), who were treated with milrinone (0.5 ± 0.1 ug/kg/min, n=18) or levosimendan (0.1 ug/kg/min up to 25 mg, n=2). Patients in the OHB group (n = 10) did not differ from the placebo group (n = 10) in baseline clinical, biochemical, hemodynamic or echocardiographic characteristics. Baseline OHB concentration was normal (<0.6 mmol/L) in all patients. Administration of OHB increased serum concentration from 0.3 ± 0.2 mmol/L to a maximum of 2.4 ± 0.7 mmol/L (<0.001). Concentrations of OHB peaked at 1.5 ± 0.5 hours after administration of each OHB drink, and the maximum concentration was achieved at 4.1 ± 2.5 hours (Figure 1). No changes in OHB concentration were observed in the placebo group. In both study groups, there was a significant increase of CI at 3 hours compared to baseline, but the increase was significantly greater in the OHB group (OHB: 3.2 ± 0.6 vs. 2.1 ± 0.4 L/min/m2; placebo: 2.3 ± 0.4 vs. 2.0 ± 0.3 L/min/m2; both p<0.001 compared to baseline; p < 0.001 for OHB vs. placebo at 3 hours). The maximum relative increase of CI was 60 ± 24% in the OHB group (p <0.001) and 18 ± 8% in the placebo group (p< 0.01). The change of CI correlated with the change of OHB concentration in the OHB group (r = 0.58, p<0.001) but not in the placebo group (r = 0.1, p = 0.3). The changes in CI were not related to heart rate or concentration of norepinephrine, which did not change significantly throughout the study in both groups. Conclusion Oral administration of OHB leads to a significant temporary increase in myocardial contractility. This novel therapeutic concept might be a promising adjunction to inotropic support in patients with decompensated HFrEF.

Design, synthesis, QSAR modelling and molecular dynamic simulations of N-tosyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors

Tyrosinase is an enzyme crucial for the progression of melanogenesis. Immoderate production of melanin may be the cause of hyperpigmentation and darkening leading to skin diseases. Tyrosinase is the most researched target for suppressing melanogenesis since it catalyzes the rate-limiting stage of melanin production. Thiosemicarbazones have been reported to possess strong inhibition capability against tyrosinase. We have designed and synthesized eighteen N-tosyl substituted indole-based thiosemicarbazones as competitive tyrosinase inhibitors in the current work. All the compounds exhibited outstanding to good potency with half maximal inhibitory concentration in the range of 6.40 ± 0.21 µM to 61.84 ± 1.47 µM. The compound 5r displayed the top-tier inhibition amongst the entire series with IC50 = 6.40 ± 0.21 µM. Compounds, 5q and 5r exhibited competitive inhibitions in concentration dependent manner with Ki = 3.42 ± 0.03 and 10.25 ± 0.08 µM respectively. The binding mode of 5r was evaluated through in silico molecular dynamics simulations and molecular docking, while ADME assessment studies predicted the drug-like characteristics of the derivatives. The newly synthesized derivatives may serve as a structural guide for designing and developing novel tyrosinase inhibitors.

Exploring In Vitro Antibiofilm Potential and In Vivo Toxicity Assessment of Gold Nanoparticles.

In this study, biogenically synthesized AuNPs were first characterized via UV visible spectroscopy, SEM, XRD, and FTIR followed by toxicity evaluation using mice model. UV-visible spectroscopy of biogenic AuNPs showed peaks at 540-549 nm, while FTIR spectrum showed various functional groups involving O-H, Amide I, Amide II, O-H, C-H groups, and so on. SEM showed the size variation from 30 to 60 nm. Antibacterial potential against pathogenic isolates showed bigger ZOI (31.0 mm) against Pseudomonas aeruginosa AuNPs. Antibiofilm activity showing up to 100% inhibition at 90 µg mL-1 concentration of AuNPs. Toxicity evaluation showed LD50 as 70 mg kg-1. Exposure to AuNPs caused significant changes in the levels of serum AST (p < 0.05) at 100-150 mg kg-1 of AuNPs exposure. Histopathology of male albino mice kidney and liver revealed that mice exposed to maximum concentration of AuNPs showed necrosis, cell distortion, and hepatocytes detachment. Present study showed that biologically synthesized AuNPs possess effective antimicrobial and biofilm inhibitory potential. AuNPs strong bactericidal effect even at lower concentration suggest that NPs could have excellent potential for combating pathogens. In conclusion, nanotechnology may revolutionize human life and medical industry by developing innovative drugs with the potential to treat diseases in shorter and noninvasive time period. Hence, in vitro biosafety and experimental observations followed by in vivo outcomes are crucial in shifting the novel therapeutics into medical practice thus leading further into their future development.

The Pharmacokinetics of Subcutaneous Eprinomectin in Plasma and Milk in Dry Dairy Cattle.

Parasitic infections in dairy cattle reduce herd immunity, milk production, and conception rates. This leads to higher production costs, compromised animal welfare, and increased interest in extralabel drug use. The extralabel use of anthelmintics poses food safety risks for consumers since appropriate withdrawal intervals in milk have yet to be established. Although topical eprinomectin has no milk withdrawal time, more research is needed to determine the residues present in milk after subcutaneous administration. This study aimed to characterize the pharmacokinetics of injectable eprinomectin in dry dairy cows. We hypothesized that, when given at the labeled dose, eprinomectin residues in dry dairy cattle would be below the FDA milk tolerance at the onset of lactation. Plasma was collected daily from 13 mature dairy cattle for 7 days postadministration, followed by periodic samples for 90 days. After calving, milk was collected daily until 90 days. Eprinomectin concentrations were measured using HPLC-fluorescence detection. The maximum eprinomectin concentration in plasma and milk was approximately 36 ng/mL 43 h after administration and 3 ng/mL at the onset of lactation, respectively. The low eprinomectin levels in milk collected from these lactating dairy cattle suggest that administering eprinomectin at dry-off is unlikely to result in violative residues. However, subcutaneous eprinomectin in lactating dairy cattle would be hard to justify unless there is evidence that the approved topical formulation is clinically ineffective.

Three-Stage Solid-State Fermentation Technology for Distillers’ Grain Feed Protein Based on Different Microorganisms Considering Oxygen Requirements

The shortage of feed protein has plagued the development of the animal husbandry industry in China. In this study, a new three-stage fermentation technology for producing distillers’ grain feed protein was developed by introducing Aspergillus niger, yeast, and lactic acid bacteria. During the aerobic stage, there was a negative correlation between the reducing sugar content in the distillers’ grains and the amount of Aspergillus niger. The maximum reducing sugar concentration (36.89 mg g−1) was obtained when the oxygen supply was 30 mL min−1 and the fermentation time was two days. During the microaerophilic stage, the natural exchange of oxygen achieved optimal true protein enhancement (from 10.8% to 16.4%) among the three oxygen supply modes (natural exchange, forced ventilation, and filling supplement). During the anaerobic stage, lactic acid bacteria were inoculated for feed protein preservation and flavor enhancement. Our results provided insight and practical guidance for the high-value use of distillers’ grains.

Determining the Pharmacokinetic Properties of Two Different Doses of Meloxicam in Barred Owls (Strix varia)

Anthropogenic activities have negatively affected many birds, including owls. The Wildlife Hospital of Louisiana (WHL) has seen a 3.2-fold increase in barred owl (Strix varia) cases over the past eight years (2023, 134; 2015, 42). Because most of these animals present with traumatic injuries, analgesics should be considered in their treatment plan. To date, no study has measured the pharmacokinetics of an analgesic in barred owls. The goals of this study were to determine the harmonic means, times to maximum concentration, and elimination half-lives for single 1 mg/kg and 2 mg/kg intramuscular doses of meloxicam. Twelve barred owls (1 mg/kg, n = 6; 2 mg/kg, n = 6) admitted to the WHL and determined to be clinically normal based on examination and blood work were recruited for this study. Meloxicam was administered intramuscularly, and blood samples were collected intermittently over 12 h to measure plasma concentrations using high-performance liquid chromatography. Both doses had rapid elimination half-lives (1 mg/kg, 0.99 ± 0.1 h; 2 mg/kg, 1.07 ± 0.43 h) and were below the limits of quantification (0.1 µg/mL) by 6–12 h. Based on these results, 1 and 2 mg/kg doses of meloxicam were found to produce plasma concentrations below therapeutic concentrations for less than four hours, making current twice-daily recommended dosing intervals unlikely to provide desired analgesia.

Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects.

Pyruvate kinase (PK) deficiency is a rare, hereditary, hemolytic anemia caused by mutations in the PKLR gene encoding the PK enzyme. Mitapivat (previously designated AG-348) is a first-in-class, oral, allosteric activator of PK. We report results from 5 Phase 1 trials in healthy adults to characterize and compare mitapivat pharmacokinetics across different formulations and analyze food effects on mitapivat bioavailability (Studies 1-5). Pharmacokinetic assessments were peak exposure, total exposure, time to maximum plasma concentration of mitapivat, and relative bioavailability (where appropriate). Plasma total exposure of mitapivat was similar in the fasted and fed (high-fat meal or different soft foods) states after capsule, tablet, and pediatric granule formulations. Although mitapivat administration with food reduced the rate of mitapivat absorption (delay in time to maximum plasma concentration; reduction in maximum concentration) versus dosing under fasted conditions, this was not considered clinically relevant, given the lack of effect on total mitapivat exposure. Consequently, the administration instructions for mitapivat relating to food state that "patients may take mitapivat tablets with or without food." These findings will continue to inform clinical studies and development of mitapivat in adult and pediatric patients with hemolytic anemias and may help inform healthcare professionals on mitapivat dosing/administration recommendations in clinical practice.

Population pharmacokinetic modeling study and discovery of covariates for the antidepressant sertraline, a serotonin selective reuptake inhibitor

The purpose of this study was to discover effective covariates related to explanation of inter-individual pharmacokinetic (PK) variations through population pharmacokinetic (Pop-PK) modeling for sertraline and to provide insight into establishing scientific regimen. The bioequivalence results of sertraline performed on 24 healthy Korean men and the physiological and biochemical parameters derived from each individual were used as data to develop a Pop-PK model of sertraline for Koreans. And the relevant effectiveness of ∗10 allele polymorphisms of CYP2D6 in sertraline PK polymorphisms was further confirmed through a modeling approach. The Pop-PK profiles of sertraline were explained by the basic structure of sequential 2-absorption with 1-compartment, and in terms of inter-individual PK diversity, the volume of distribution could be significantly correlated with estimated glomerular filtration rate (eGFR) and clearance with total protein levels. CYP2D6∗10 allele was not significant in interpreting sertraline PK diversity. As a result of model simulation, the concentration of sertraline in serum significantly increased as total protein and eGFR levels became higher and lower, respectively. The mean serum concentrations of sertraline at steady-state differed by up to 2.12 times from 10.36 to 22.02 ng/mL depending on changes in total protein and eGFR levels, and the fluctuations between the maximum and minimum concentration values ranged from 2.02 to 29.51 to 4.31–63.78 ng/mL. The factor that significantly influenced change in mean serum concentration of sertraline at steady-state was the total protein level, which was interpreted to be closely related to the change in clearance due to the high serum protein binding of sertraline.

Detection of AFB1 by Immunochromatographic Test Strips Based on Double-Probe Signal Amplification with Nanobody and Biotin–Streptavidin System

Aflatoxin B1 (AFB1) is highly toxic and difficult to prevent. It is mainly produced by fungi and exists in plants and animals and is classified by the World Health Organization as a class I carcinogen, posing a serious threat to human and animal health. Therefore, it is important to establish an efficient, sensitive, and on-site detection method for AFB1 to protect human health. The immunochromatographic test strip method is simple, sensitive, and can achieve real-time detection. However, traditional immunochromatographic test strips have low sensitivity due to their relatively weak optical properties. In this study, Nb-G8 was biotinylated using a chemical method. Two sizes of gold nanoflowers (AuNFs) were prepared and combined with biotinylated G8 and streptavidin to form two types of probes. These probes were sprayed on gold standard pads and expanded pads, respectively, to enhance the signals through the high affinity interaction between streptavidin and biotin. Under the optimal experimental conditions, the half maximal inhibitory concentration (IC50) of this method was 5.0 ng/mL and the limit of detection (IC10) was 0.03 ng/mL, which increased the sensitivity of the test strip by four-fold compared with that of the traditional biotinylated nanoantibody immunochromatography test strip and had a wider detection range. In conclusion, the use of a high-affinity amplification signal between biotin and streptavidin is a valuable method for the detection of aflatoxin.