Maximum Concentration Research Articles

A rare case of Anti-Jk3 Alloimmunization

Abstract Introduction/Objective The Kidd blood group system was discovered in 1951 and consists of two antithetical antigens, Jka and Jkb, in addition to a third high-incidence antigen, Jk3. Jk null, also known as Jk(a-b-), is an extremely rare blood group in which all Kidd antigens are absent. Jk is a urea transporter found in the renal medulla, and Jk-deficient individuals are unable to concentrate urine to its maximum concentration. If these individuals are exposed to the Jk antigen via transfusion or pregnancy, they are able to produce antibodies against the Jk3 antigen with a high incidence. Jk3 is expressed in over 99.9% of the blood donor pool, which has severe clinical implications and complicates transfusion. Methods/Case Report CASE PRESENTATION: A 68-year-old male was admitted to the Stanford Medical Center with chronic right midshaft tibia osteomyelitis and a sinus drainage tract for a right tibial diaphysectomy. His test for antibodies was positive. Plasma from the patient is reactive with all tested cells except auto control, AHG in PEG, and solid phase. Phenotyping yielded negative results for Jka and Jkb, suggesting that the antibody is Jk3. Anti-Jk3 was eliminated by adsorption and rendered nonreactive. Results (if a Case Study enter NA) NA Conclusion Anti-Jk3 should be suspected in a previously pregnant or transfused patient during antibody screening and identification if it demonstrates the pattern of an antibody reacting to all cells in the panel, i.e., reacting to a high- frequency antigen with negative autocontrol. Awareness on the part of blood bank personnel regarding the variability of the blood group phenotype and the capricious nature of Kidd antibodies may aid in the improved management of these patients. It is recommended that patients with rare antibodies carry an antibody ID card indicating the rare antibody they have to prevent further exposure. A patient may be advised to undergo an autologous transfusion. Fortunately, the patient’s procedures were uncomplicated, so a blood transfusion was unnecessary. Awareness on the part of blood bank staff regarding the variability of the blood group phenotype and the unpredictability of Anti-Jk3 may aid in improving patient care. To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.Jk3 antigen blood donors are underrepresented in the general donor pool. It is recommended to develop a systematic recruitment for Jk3 antigen donors.

Novel Fimasartan Fluidized Solid Dispersion and Its Tablet: Preparation, Crystallinity, Solubility, Dissolution, and Pharmacokinetics in Beagle Dogs.

Fimasartan, an angiotensin II receptor antagonist, exhibits low bioavailability due to its poor solubility; consequently, using solubilization technologies is essential to improve its bioavailability. In this study, novel fimasartan fluidized solid dispersion (FFSD) was developed using a fluid bed granulator to enhance the drug solubility andoral bioavailability. An appropriate FFSD was prepared in 50% ethanol using a fluid bed granulator, and its drug dissolution, morphology, and crystallinity were evaluated in comparison to the powdered drug. Moreover, the dissolution in various pH conditions and pharmacokinetics of the FFSD tablet in beagle dogs were investigated compared to the commercial fimasartan tablet. Among the hydrophilic polymers tested, hydroxypropyl methylcellulose (HPMC)showed the highest solubility. The FFSD, composed of fimasartan, HPMC, and microcrystalline cellulose at the weight ratio of 20:10:25, gave a granular aggregation of several particles with a smooth surface. The drug in this FFSD existed as an amorphous state, leading to a greatly increased drug dissolution. The FFSD tablet was prepared by compressing a mixture of FFSD, mannitol, croscarmellose sodium, and magnesium stearate at the weight ratio of 55:40:5:1. The FFSD tablet gave significantly higher drug dissolution, plasma concentrations, maximum plasma concentration (Cmax) andarea under the whole blood concentration-time curve (AUC) values than did the commercial fimasartan tablet. In the beagle dogs, the FFSD tablet (140.39±27.40ng·h/ml) had about a 1.7-fold higher AUC than the commercial fimasartan tablet (80.58±22.18 ng·h/ml), indicating an enhancement in thebioavailability. This novel FFSD tablet could be a potential oral pharmaceutical product with the improved oral bioavailability of fimasartan.

Response of oxidative stress and neurotoxicity biomarkers in rainbow trout (Oncorhynchus mykiss) after exposure to six-metal mixtures

ABSTRACT The activity of liver catalase and brain acetylcholinesterase was assessed in rainbow trout (Oncorhynchus mykiss) after 7- and 14-day exposure to a six-metal mixture at the maximum permissible concentrations accepted for inland waters in the EU (2013/39/EU; 2008/105/EC) (Zn − 0.1, Ni − 0.034, Cu − 0.01, Cr − 0.01, Cd − 0.0015 and Pb − 0.014 mg L−1) and to the same six-metal mixtures with tenfold reduced concentration of Cu and Cr ions. A statistically significant increase of up to 26% of catalase and 52% of acetylcholinesterase activity was observed in rainbow trout after 7 days of exposure to the six-metal mixture at the maximum permissible concentrations in comparison to a control group. After 14-day treatment, neither CAT nor AChE showed significant response to all tested metal mixtures. The six-metal mixture with the tenfold reduced concentration of Cr increased brain AChE activity in O. mykiss after 7 days of exposure (35%). Enhancement of catalase activity caused by the mixture of the six metals at the maximum permissible concentrations and the increased acetylcholinesterase activity in response to the same metal mixture and mixture with tenfold reduced Cr concentration after 7 days of exposure indicates the induction of oxidative stress and disturbance of cholinergic system homeostasis respectively.

Biosynthesis of pterostilbene in Escherichia coli from resveratrol on macroporous adsorption resin using a two-step substrate addition strategy.

Pterostilbene (PST), a 3',5'-O-methylated derivative of resveratrol (RSV), is a potent natural antioxidant produced by some plants in trace amounts as defense compound. It exhibits various health-promoting activities, such as anticancer, antiviral, and antimicrobial effects. Large-scale biosynthesis of PST is crucial due to the challenges associated with extracting it from plants. This study aims to develop an efficient method for PST production using an engineered Escherichia coli strain by feeding RSV as a precursor. We introduced a two-step substrate addition strategy combined with immobilized RSV (IMRSV) on macroporous adsorption resin (MAR) to enhance PST production. Five MARs were selected for RSV immobilization, and the substrate addition strategy and fermentation parameters for PST synthesis were optimized. A maximum PST concentration of 403 ± 9 mg/L was achieved, representing a 239% increase over the control, which in a one-step addition of free RSV. The PST titer reached 395 ± 24 mg/L in a 3-L bioreactor. In conclusion, the combination of a two-step substrate addition system and IMRSV is a promising approach for the economical and industrial-scale production of PST.

Surfactant-Assisted Wet Granulation-Based Matrix Tablets without Exceptional Additives: Prolonging Systemic Exposure of Model BCS Class II Ketoprofen.

The present studywas aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1-5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (Cmax) of 5.72µg /ml ± 0.30 h, time to Cmax (Tmax) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml-1 till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained Cmax of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC0-∞) of MT2 (78.65 ± 7.64 µg.h.ml-1) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml-1 of MT16. With decreased Cmax, increased AUC0-∞, delayed Tmax and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the in-vitro sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation.

Pharmacokinetic interaction between single and multiple doses of darunavir, in combination with cobicistat or ritonavir, and single-dose dabigatran etexilate in healthy adults

ObjectiveDarunavir (DRV) is a P-glycoprotein (P-gp) inhibitor. Dabigatran etexilate, prodrug of the anticoagulant dabigatran, is a P-gp probe substrate. This study evaluated the effect of single and multiple doses of DRV, coadministered with cobicistat (COBI) or ritonavir (rtv), on the pharmacokinetics (PK) of single-dose dabigatran etexilate.MethodsThis was an open-label, fixed-sequence, single-center, 2-panel, phase 1 study in which healthy adult participants were equally divided over 2 panels. In panel 1, participants received single and multiple doses of DRV/COBI 800/150 mg coadministered with single-dose dabigatran etexilate 150 mg. In panel 2, participants received single and multiple doses of DRV 800 mg + rtv 100 mg coadministered with single-dose dabigatran etexilate 150 mg. Key PK parameters evaluated were maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to infinity (AUCinf) for free and total dabigatran.ResultsOverall, 28 participants were enrolled and treated (n = 14 per panel). Dabigatran Cmax and AUCinf increased 2.64-fold after a single dose of DRV/COBI and 1.99- and 1.88-fold, respectively, after multiple doses of DRV/COBI. Dabigatran Cmax and AUCinf increased 1.64- and 1.72-fold, respectively, after a single dose of DRV + rtv and 1.22- and 1.18-fold, respectively, after multiple doses of DRV + rtv. In both panels, the most commonly reported adverse events were diarrhea and headache.ConclusionFindings of increased dabigatran exposure with DRV/COBI or DRV + rtv coadministration indicate an inhibitory effect of single-dose boosted DRV on P-gp, and a mixed inhibitory/inductive effect of multiple doses of boosted DRV on P-gp.Trial registrationClinicalTrials.gov, NCT04208061. Registered December 19, 2019

Intranasal nanocrystals of tadalafil: in vitro characterisation and in vivo pharmacokinetic study

Tadalafil (TDA) is a class II drug of the biopharmaceuticals classification system (BCS), with limited aqueous solubility and high permeability. This study aims to improve the bioavailability of poorly soluble tadalafil by developing intranasal nanocrystals (NCs) of TDA. TDANCs that were stabilised by polyvinyl alcohol (PVA) had the lowest size and the best solubility. F11 had a 196 nm in size with PDI and zeta potential of 0.21 and -11.20, respectively, which shows 5.5 and 1.6-fold higher in solubility (9.37 ± 0.36 μg/mL) and dissolution (50.11 ± 1.69%) than pure tadalafil, respectively. An in vivo animal study demonstrated that the maximum plasma concentration (Cmax) and total area under the curve (AUC0∞) achieved in the TDANCs group were 352.77 ± 35.17 ng/mL and 3377 ± 558 ng.h/mL, respectively, and were significantly higher than the pure TDA group after intranasal administration. In conclusion, TDANCs were successfully prepared by the sonoprecipitation technique, with significant enhancement in in vitro and in vivo properties. Therefore, intranasal administration of TDA nanocrystals was a good model for the treatment of erectile dysfunction.

Contamination profile and hazards of neonicotinoid insecticides in honey from apiaries in Beijing, China.

The residues of neonicotinoid insecticides in honey have raised global concern for their adverse effects on non-target organisms. However, information on the presence of neonicotinoids in raw honey in China is limited. Our study investigated the distribution profiles of neonicotinoids in raw honey samples collected from apiaries in plain and mountainous areas surrounding Beijing City. At least one of four neonicotinoids, imidacloprid, thiamethoxam, acetamiprid, or clothianidin, was found in 46.9% of samples. Neonicotinoids in multi-floral honey in plain areas exhibited higher concentrations and prevalence than in uni-floral honey collected from mountainous areas. These results indicated that neonicotinoid residues in honey were linked to the agricultural ecosystems influenced by geographies, particularly the intensity of agriculture and nectariferous plant types. The dietary risks to adult and children health from neonicotinoid exposure were deemed de minimis, while risks to honeybees at the maximum concentration level require much attention through refined, higher-tier assessments and possible mitigation measures for the use of these products.

Drug-Drug Interaction Between Dihydroartemisinin-Piperaquine and Sulfadoxine-Pyrimethamine During Malaria Chemoprevention in Pregnant Women.

Co-administration of dihydroartemisinin-piperaquine (DP) and sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria in pregnancy (IPTp) may be superior in preventing adverse birth outcomes compared with either therapy alone, but potential drug-drug interactions require investigation. We conducted intensive and sparse pharmacokinetic (PK) studies in a subset of Ugandan women participating in a randomized controlled trial of monthly IPTp with SP vs. DP vs. DP + SP. Intensive PK sampling was performed from day 0 to 23 after dosing at 28 weeks gestation in 87 participants across treatment arms. Sparse sampling was performed on day 28 (trough) after dosing at 20 and 28 gestational weeks in additional 196 participants receiving SP vs. DP + SP. Intensive PK analysis demonstrated that compared with SP alone, co-administration of DP + SP was associated with lower maximal concentrations, the area under the concentration-time curves (AUC), and day 23 concentrations of sulfadoxine (25%, 25%, and 27%) and pyrimethamine (26%, 34%, and 32%) (P < 0.05 for all comparisons). Sparse PK results demonstrated participants co-administered DP + SP had lower trough concentrations after dosing at 20 and 28 gestational weeks for sulfadoxine (6%, P = 0.68 and 31%, P = 0.023, respectively) and pyrimethamine (18%, P = 0.032 and 33%, P < 0.001, respectively) compared with SP alone. Co-administration of DP + SP was associated with a 19% reduction in piperaquine AUC (P = 0.046), but no significant difference in other PK parameters compared with DP alone. In summary, co-administration of DP + SP was associated with significantly reduced SP exposure, with a greater magnitude during the third vs. second trimester. The clinical consequences of this interaction are yet unknown.

Ethanol Production Using Zymomonas mobilis and In Situ Extraction in a Capillary Microreactor

The bacterium Zymomonas mobilis is investigated as a model organism for the cultivation and separation of ethanol as a product by in situ extraction in continuous flow microreactors. The considered microreactor is the Coiled Flow Inverter (CFI), which consists of a capillary coiled onto a support structure. Like other microreactors, the CFI benefits from a high surface-to-volume ratio, which enhances mass and heat transfer. Compared to many other microreactors, the CFI offers the advantage of operating without internal structures, which are often used to ensure good mixing. The simplicity of the design makes the CFI particularly suitable for biochemical applications as cells do not get stuck or damaged by internal structures. Despite this simplicity, good mixing is achieved through flow vortices caused by Taylor and Dean vortices. The reaction system consists of two phases, in which the aqueous phase carries the bacterium and an oleyl alcohol phase is used to extract the ethanol produced. Key parameters for evaluation are bacteria growth and the amount of ethanol produced by the microorganism. The results show the suitability of the CFI for microbial production of valuable compounds. A maximum ethanol concentration of 1.26 g L−1 was achieved for the experiment in the CFI. Overall, the cultivation in the CFI led to faster growth of Z. mobilis, resulting in 25% higher ethanol production than in conducted batch experiments.

Classroom indoor air quality and noise level assessment of different educational institutions in a university area in Bangladesh

Introduction: The classroom environment is crucial for fostering effective learning and safeguarding teacher-student health. This study assessed the Indoor Air Quality (IAQ) and noise levels in classrooms across three institutions: a university, a secondary and higher secondary school (called a school and college), and a primary school. Materials and methods: Various IAQ parameters such as Particulate Matters (PM2.5 and PM10), Carbon monoxide (CO), Carbon dioxide (CO2), Total Volatile Organic Compound (TVOC), and temperature, Relative Humidity (RH), light, and noise levels were measured using calibrated instruments from February to March 2024. Results: The air pollutants and noise levels varied among the institutions. The mean values of PM 2.5 (76.6 µg/m3) and PM (116.7 µg/m3) were highest The mean values of PM 2.5 (76.6 µg/m3) and PM (116.7 µg/m3) were highest in the primary school, while CO (0.82 ppm), light (92.9 lux), temperature (27.6 °C), and noise levels (77.6 dB) peaked in the school and college. University classrooms showed the maximum concentrations of CO2 (804.9 ppm), TVOC (32.9 ppb), and RH (58.6%). In all institutions, PM2.5, PM10, and noise levels exceeded WHO-recommended limits, whereas CO, CO2, RH, and temperature remained within their respective standards. Light levels were below Occupational Safety and Health Administration (OSHA) guidelines. Correlation analysis showed significant positive correlations between PM2.5 PM10, and CO. Hazard Quotient (HQ) values for PM 2.5 and PM10 exceeded 1.0, indicating potential health risks. Variations in pollutants and noise levels among institutions may be due to classroom facilities, student density, ventilation systems, and student activities. Conclusion: Long-term exposure to IAQ pollutants and noise levels could impair cognitive function, respiratory health, and overall well-being of the students and educators. Implementing proper ventilation (e.g., HEPA filters) systems, soundproofing acoustic panels, and continuous IAQ monitoring is recommended for a safer classroom environment.

Impact of calcium-reinforcement on stability, bioavailability, and bioactivity of quercetin-loaded zein/alginate-pectin nanoparticles.

Cationic calcium ions can crosslink anionic alginate and pectin molecules. It was hypothesized that calcium crosslinking would improve the stability and functionality of biopolymer nanoparticles consisting of zein cores coated by alginate-pectin shells. The effects of calcium ion addition on the structural, physicochemical, and gastrointestinal properties of quercetin-loaded zein/alginate-pectin nanoparticles were therefore investigated. The nanoparticles remained stable to aggregation at calcium ion concentrations of 9 mmol/L or less but aggregated and sedimented at higher concentrations. Calcium ion reinforcement increased the particle dispersion stability even at NaCl concentrations up to 1.4 molL-1. The presence of the calcium ions also reduced quercetin release during the early stages of simulated gastrointestinal digestion but increased its release during the later stages. The relatively high release (56.1%) of quercetin from the calcium-reinforced nanoparticles after digestion resulted in higher intracellular antioxidant activities. The pharmacokinetics of the encapsulated quercetin was measured after its oral administration to rats. The maximal concentration (Cmax) of quercetin in rat plasma for calcium-reinforced nanoparticles was 6.1% higher than non-reinforced nanoparticles; the half-life (t1/2) increased by 17.5%, and the mean retention time (MRT) was 10.0% higher (P < 0.05). These results suggest that calcium ion addition improved the performance and bioavailability of nutraceutical-loaded biopolymer nanoparticles. This might find application in the food and beverage industry. © 2024 Society of Chemical Industry.

Physiological and biomolecular interventions in the bio-decolorization of Methylene blue dye by Salvinia molesta D. Mitch

Methylene blue, a cationic dye as a pollutant is discharged from industrial effluent into aquatic bodies. The dye is biomagnified through the food chain and is detrimental to the sustainability of aquatic flora. Despite of number of physico-chemical techniques of dye removal, the use of aquatic flora for bio-adsorption is encouraged. Thus, we used Salvinia molesta D. Mitch in bio-reduction of methylene blue on concentrations of 0, 10, 20, and 30 mg L−1 through 5 days with biosorption kinetics. The dye removal was concentration-dependent, maximized at 2 days with 30 mg L−1 which altered the relative growth rate (44%) of plants. Biosorption recorded 71% capacity at optimum pH (8.0), 24 h reducing major bond energies of amide, hydroxyl groups, etc. Bioaccumulation of dye changed potassium content (446%) under maximum dye concentration modifying tissues for dye sequestration. Reactive oxygen species were altered on dye reduction by oxidase (33%) with redox homeostasis by enzymes. Plants altered the metabolism with over accumulation of polyamines (51%), abscisic acids (448%), and phosphoenolpyruvate carboxylase (83%) on dye reduction. Thus, this study is rationalized with a sustainable approach where aquatic ecosystems can be decontaminated from dye toxicity with the exercise of bioresources like Salvinia molesta D. Mitch as herein.

Assessment of the public health risk caused by exposure to atmospheric emissions from an aluminum plant

Introduction. Aluminum production is accompanied by emissions of pollutants that can negatively affect the environment and public health. The study aims to determine the impact of atmospheric emissions from an aluminum plant on the health of the population of the city of Novokuznetsk based on a risk assessment. Materials and methods. The volume of maximum permissible emissions of the Novokuznetsk Aluminum Plant was used in the work. Experts calculated the maximum and average concentrations of substances at 40 exposure points. The maximum permissible concentrations of substances were determined in accordance with SanPiN 1.2.3685-21. The authors calculated the carcinogenic risk and the risk of non-carcinogenic effects in accordance with the Guidelines 2.1.10.1920-04. They carried out the classification of risk levels based on methodological recommendations 2.1.10.0156-19. 2.1.10. Results. The authors have selected pollutants were for risk assessment: inorganic dust with a SiO2 content of &lt;20%, sulfur dioxide, benz(a)pyrene, hydrogen fluoride, carbon monoxide, nitrogen dioxide, suspended solids, nitrogen oxide, carbon (soot). The maximum concentrations were 0.1–3.77 MPC for inorganic dust (SiO2&lt;20%), 0.1–2.64 MPC for hydrogen fluoride and 0.05–1.74 MPC for sulfur dioxide; average concentrations were up to 9.16 MPC for benz(a)pyrene. The hazard indices for acute exposure are at an acceptable level; For chronic exposures, they correspond to alarming and high levels, reaching the highest value (13.469) at a point located closer to the sources of emissions. Hazard indices for critical organs and systems in acute exposures are at acceptable or minimum (target) levels, in chronic exposures they correspond to alarming and high-risk levels. The respiratory and immune systems are most affected. The total individual carcinogenic risk ranges from 4×10–7 to 8×10–6, without exceeding the upper limit of the permissible risk. Residents of the Kuznetsk district of the city are most affected by emissions. Limitations. The main limitation in the work carried out was the use of calculated concentrations of pollutants for risk assessment without the use of in-kind indicators. Conclusion. Elevated concentrations of pollutants were detected in the atmospheric air of residential areas adjacent to the territory of the aluminum plant, which determine alarming and high levels of non-carcinogenic risk to public health. Ethics. This study did not require the conclusion of the Ethics Committee.

Assessment of the risk to the health of the population living in the zone influenced by atmospheric emissions from the engineering industry

Introduction. During operation, machine-building enterprises emit pollutants that can negatively affect the health of the population. The study aims to determine the impact of emissions from a machine–building plant, as well as background atmospheric pollution, on the health risk of the population of Novokuznetsk. Materials and methods. The work used data from the volume of maximum permissible emissions of a machine-building plant. The researchers calculated the maximum and average concentrations of pollutants using the "ECOcenter – Standard" program at 36 exposure points selected on the city map. Experts determined the maximum permissible concentrations of pollutants in the atmosphere in accordance with SanPiN 1.2.3685-21. The authors calculated the risks to public health in accordance with the Guidelines R 2.1.10.1920-04. The classification of risk levels was carried out on the basis of MP 2.1.10.0156-19. 2.1.10. Scientists also made a risk assessment considering background atmospheric pollution. Results. Specialists carried out a risk assessment from exposure to nitrogen dioxide, carbon monoxide, sulfur dioxide, carbon (soot), inorganic dust, hexavalent chromium. The maximum and average concentrations of pollutants, as well as the maximum concentrations calculated taking into account background pollution, did not exceed the maximum permissible level. The average concentrations of nitrogen dioxide and hexavalent chromium, taking into account the background, exceeded the hygienic standard. The values of the hazard indices for acute and chronic exposures without taking into account the background, as well as for acute exposures taking into account the background, corresponded to the minimum (target) risk level. The values of the hazard indices for chronic inhalation effects, considering the background, corresponded to the alarming risk level at five points, amounting to 3.084–3.800. With chronic exposure, taking into account the background, an alarming level of risk was revealed for the effect on the respiratory organs (at four points the hazard index was 3.117 to 3.616) and blood (at three points the hazard index was in the range from 3.090 to 3.433). The total individual carcinogenic risk, excluding background, did not exceed the permissible level, ranging from 1.08×10–8 to 2.43×10–7 at different points, taking into account the background, amounted to 1.79×10–4–2.26×10–4, which corresponds to an alarming level. Hexavalent chromium makes the main contribution to the formation of carcinogenic risk. Limitations. Calculated concentrations of pollutants were used to assess the risks. Conclusion. The risks from exposure to atmospheric emissions from the machine-building plant correspond to the minimum (target) level. Background concentrations of toxic substances in chronic inhalation exposures determine an alarming level of non-carcinogenic risk at five points, as well as an alarming level of carcinogenic risk at all points of exposure. Ethics. This study did not require the conclusion of the Ethics Committee.

Scientific substantiation of the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area

Introduction. Osimertinib, a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor, is currently the only drug registered for the treatment of metastatic non-small cell lung cancer in patients with a positive T790M mutation status. The production of osimertinib mesylate is planned on the territory of the Russian Federation, which necessitates research to substantiate the hygienic standard for the aerosol content of the substance in the air of the working area. Conducting research to substantiate the maximum permissible concentration of a substance requires significant material and time resources, while using the results of preclinical and clinical studies, mathematical modeling of processes, and risk assessment methodology allows for a comprehensive assessment of the substance, while significantly reducing the time and cost of work. The study aims to scientifically substantiate the maximum permissible concentration of the pharmaceutical substance osimertinib mesylate in the air of the working area using data from toxicological studies and mathematical modeling of the effects of the substance on humans in industrial conditions. Materials and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physico-chemical and toxic properties, pharmacotherapeutic activity of osimertinib. Results. The specialists have conducted hygienic regulation of osimertinib, taking into account data on its toxicity, danger, pharmacotherapeutic activity, side effects, long-term consequences, pharmacokinetic studies and modeling. To substantiate the value of the maximum permissible concentration, the authors used the reference points: an inactive NOEL level of 1 mg/­kg/­day for general toxic effect, established in a 92-day experiment on rats with intragastric administration; the lowest observed level of adverse effects of LOAEL is 0.5 mg/kg/day for general toxic effect, established in a 180-day experiment on dogs with intragastric administration; the level that does not cause adverse effects of NOAEL is 10 mg/kg/day for general toxic effect, established in a 180-day experiment on mice with intragastric administration. Safe concentrations of osimertinib in the air of the work area were evaluated using reference points, including the pharmacological effect and the minimum daily therapeutic dose; toxicokinetic modeling of concentrations of a substance in the human body under production conditions and the level of minimal risk. Limitation. The study is limited to the review of open literature sources describing the toxicological/toxicokinetic characteristics of osimertinib mesylate. Conclusion. The most stringent indicators of safe exposure levels, established on the basis of pharmacological effect and toxicokinetic modeling in dogs, allowed us to recommend 0.005 mg/m3, aerosol, hazard class 1 as the maximum permissible concentration in the air of the working area for osimertinib mesylate. Ethics. This study did not require the conclusion of the Ethics Committee.

Effects of dexamethasone on the EC50 of remifentanil combined with dexmedetomidine achieving analgesia during pancreatic extracorporeal shockwave lithotripsy: a prospective, randomized and controlled study

BackgroundIn addition to their classic genomic effects, glucocorticoids also manifest rapid non genomic effects. We speculate that dexamethasone has the potential prompt onset of analgesic effects. The objective of this study is to investigate the influence of a single preoperative dose of dexamethasone on the half maximal effective concentration (EC50) of remifentanil when combined with dexmedetomidine for pain relief during pancreatic extracorporeal shockwave lithotripsy (P-ESWL).MethodsA total of 60 patients undergoing P-ESWL were enrolled and randomized at 1:1 ratio into the dexamethasone (DXM) group and the placebo group. Before anesthesia induction, patients in DXM group received an intravenous injection of 8 mg dexamethasone, while subjects in placebo group received an equal dose of physiological saline. Monitored anesthesia care (MAC) was performed based on remifentanil in combination with dexmedetomidine. Remifentanil was administered by TCI with an initial target concentration of 2.5 µg/mL for both groups. A positive response was defined as that VAS score > 3 by the patient at any time during the procedure. Subsequent target concentrations were adjusted by Dixon up-down sequential method, where dose modifications were performed by 0.3 ng/mL intervals, based on the response of the previous patient. The EC50 of remifentanil for pain relief during P-ESWL treatment was calculated using Dixon’s up-and-down method. Hemodynamic variables, oxygen saturation and adverse events were also recorded.ResultsDixon up-and-down method revealed that the EC50 of remifentanil was significantly higher in placebo group (2.65 ± 0.28 ng/mL) than in DXM group (2.02 ± 0.23 ng/ml) (P < 0.001). Hemodynamic parameter exhibited a significant decrease in mean arterial pressure (MAP) and heart rate (HR) before and after induction in placebo group; however, data of the two groups were comparable (P>0.05). Less adverse events occurred in DXM group, including the incidence of postoperative nausea and vomiting (PONV) and analgesia requirement with in the first 24 h following the procedure at ward.ConclusionDexamethasone exerted analgesic effects with a rapid onset, and patients received dexamethasone 8 mg preoperative had a lower required EC50 of remifentanil during P-ESWL. It is also associated with reduced PONV in addition to reduced postoperative analgesic consumption in the first postoperative 24 h.Trial registrationRegistered in the Chinese Clinical Trial Registry (ChiCTR2300078171) on 30/11/2023.

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 4.66 μg/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 0.75 μg/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.

Optimization and modelling of bioethanol production by the fermentation of CCN‐51 cocoa mucilage using the sequential simplex method and the modified Gompertz model

AbstractThis work deals with the optimization of bioethanol production through a fermentation process of CCN‐51 cocoa mucilage, based on increased concentrations of the Saccharomyces cerevisiae yeast. Cocoa mucilage, considered biomass waste, was selected for its high productivity and the large volumes generated in the cocoa industrial chain in Ecuador. The optimization of the fermentation process was performed using the sequential simplex method with two variables, and the results were experimentally confirmed by quantifying bioethanol through the microdiffusion method. The best operational conditions corresponded to a temperature of 35°C and a pH of 4. Regarding the concentration of yeast, it was found that the optimal value was 8 g/L, since lower concentrations led to low productivities, while higher concentrations resulted in inadequate functioning of the bioreactor. The best results reached a productivity of 1.35 ± 0.04 g/L · h and a maximum bioethanol concentration of 28.3 ± 0.8 g/L for a processing time of 21 h. The production of bioethanol was modelled using the modified Gompertz equation and simulated in MATLAB®, yielding a bioethanol production rate of 2.42 g/L · h with a correlation coefficient (R2) of 0.95. These results contribute to the knowledge of bioethanol production using cocoa mucilage and seek to add a positive value to this residue, whose management and final disposition have both undesirable environmental and economic effects.

Impact of Interfacial Proton Accumulation on Protonation in a Brownmillerite Oxide

AbstractElectrochemical protonation provides ways to control physical properties and even explore unprecedented phases of solid‐state materials. While how proton accumulation changes materials’ properties is investigated, how protonation of solids can be controlled and promoted remains an enigmatic puzzle. In the work reported here, the influence of electrochemical proton injection duration (tVg) is investigated on the protonation of SrCoO2.5 (SCO) films in electric‐field‐effect transistor structures with gate layers of the proton‐conducting electrolyte Nafion. The proton concentration accumulated in SCO films varies depending on the duration of the proton injection. When protons are injected in a relatively short tVg (≤ 600 s), the hydrogen concentration accumulated in SCO film increases with increasing tVg, reaching the maximum proton concentration of ≈1.9 per formula unit of SCO for the tVg = 600 s case. On the other hand, when tVg is longer than 900 s, the proton concentration decreases with tVg, implying the occurrence of counterreactions that extract protons from protonated SCO and oxidize the channel. These observations indicate that protons accumulated at the Nafion/SCO interface play a role in the protonation of SCO films and that suppressing the interfacial proton accumulation is the key to maximizing the proton concentration accumulated in SCO films.