Excretion Rate Research Articles

Does sedation with AQUI-S® mitigate transport stress and post transport mortality in ballan wrasse (Labrus bergyltae)?

Ballan wrasse (Labrus bergylta) are commonly used as cleaner fish in salmon farms as a biological treatment to mitigate sea lice infestation. Improved welfare for cleaner fish both during production of these fish and when in sea-cages with salmon is crucial for the industry's development. A common operational procedure in ballan wrasse production is transporting juveniles from one land-based farm to another for further on-growing. Episodes of increased mortality have been reported after such transportations. In this study, the relationship between transport stress and post-transport mortality at the on-growing facility was examined. It was also investigated if light sedation with AQUI-S® can mitigate stress during transport. Stress was quantified by measuring cortisol release rate to the tank water during transport. This was investigated in 10 commercial live carrier truck transports (6 without AQUI-S® sedation and 4 with sedation during loading and transport). The total time of transport varied between 12 and 21 h. In general, mortality was significantly higher (1.0 ± 0.6% day-1) the first five days post-transport compared to 15-20 days post transport (0.5% day-1). There was also a strong relationship between fish weight at transport and post-transport mortality, where higher mean weight at transport reduced mortality. In contrast to what was expected, AQUI-S® treatment during transport procedures increased cortisol excretion rate, suggesting a stimulating effect of AQUI-S® on the stress axis in ballan wrasse. Considering these results, the value of using AQUI-S® to reduce stress during transport of juvenile ballan wrasse might be questioned. However, there was no relationship between cortisol release rate during transport and post-transport mortality. Furthermore, this study emphasizes that water cortisol measurements can be used as a none-invasive tool for monitoring stress and can be integrated into the welfare evaluation during commercial fish transports.

Bioaugmentation in Leachate Treatment: Enhancing Ammonia Nitrogen Elimination in US Landfills

Purpose: This research seeks to assess the quantitative effects of implementing bioaugmentation solutions within existing landfill leachate management systems. The study involves the analysis of different sites to gauge the influence on leachate composition, considering various industry management practices such as lagoons, tanks, sewer discharge, or off-site trucking. The primary objective is to examine changes in microbial communities within the leachate, specifically focusing on their impact on ammonia nitrogen elimination rates. The ultimate goal is to achieve lower levels of ammonia nitrogen before the discharge of leachate to publicly owned treatment works (POTW).Methodology: The research employs a comprehensive methodology that involves the examination of diverse landfill sites utilizing various industry management practices for leachate treatment. The analysis includes assessing leachate composition and the study evaluates effectiveness of bioaugmentation in enhancing ammonia elimination rates, considering different leachate treatment approaches and operating conditions. This involves a systematic comparison of outcomes across sites and management practices.Findings: The findings of this study indicate that bioaugmentation is an effective strategy for accelerating ammonia elimination rates in landfill leachate. The analysis reveals notable improvements in microbial communities, leading to reduced levels of ammonia nitrogen in the leachate prior to its discharge to POTW. The study highlights the versatility of bioaugmentation across different industry management practices, showcasing its potential benefits under varying operating conditions and treatment setups.Unique contributor to theory, policy and practice: Based on the study's outcomes, it is recommended that landfill operators and leachate management practitioners consider implementing bioaugmentation solutions to expedite ammonia elimination rates. The findings suggest that bioaugmentation is a cost-effective and fast-to-deploy solution that requires negligible capital expenditure. This approach has the potential to generate significant savings, especially in the face of a more stringent regulatory environment. The recommendations emphasize the adaptability and efficiency of bioaugmentation across a broad range of operating conditions within existing landfill leachate management infrastructure.

Study on the degradation of triethylamine wastewater by catalytic ozone-biological coupled system of Ce-Fe@ZSM-5

Triethylamine (TEA) is an organic amine, due to the development of the pesticide industry, TEA wastewater volumes of yearly increasing, the poor biochemical performance and high toxicity. Therefore, we report a novel ozone catalyst as biological treatment technology by compounding Ce-Fe@ZSM-5 molecular sieve and domesticated activated sludge to construct a catalytic ozone-biodegradation coupling system. The low efficiency of ozone utilization was addressed by optimizing the stability and activity strength of the catalyst with a large specific surface area. The degradant rate of TEA reached 89.5 % versus 82 % of biological treatment and the elimination rate of TOC reached 71.5 %, which is 7.5 % increase the biological treatment of TEA. In order to efficiently degrade TEA and other organic amine compounds, the degradation pathway and mechanism of TEA were investigated. This research offered a theoretical foundation and prospective application for degradation of TEA.

Spatiotemporal Visualization of Paraquat Distribution, Toxicokinetics, and Its Detoxification in Zebrafish Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging.

Paraquat is a highly toxic quaternary ammonium herbicide. It can damage the functions of multiple organs and cause irreversible pulmonary fibrosis in the human body. However, the toxicological mechanism of paraquat is not yet fully understood, and due to the lack of specific antidotes, the clinical treatment of paraquat intoxication is still a great medical challenge. In-depth research on its toxicity mechanism, toxicokinetics, and effective antidotes is urgently demanded. A new molecular imaging technique, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), can simultaneously achieve quantitative and spatial analysis and offer an alternative, distinct, and useful technique for paraquat intoxication and consequent detoxication. Here, we visualized the spatial-temporal distribution and conducted toxicokinetic research on paraquat in zebrafish by using stable isotope-labeled internal-standard-aided MALDI-MSI for the first time. The results indicated that paraquat had a fast absorption rate and was widely distributed in different organs, such as the brain, gills, kidneys, and liver in zebrafish. Its half-life was long, and the elimination rate was slow. Paraquat reached its peak at 30 min and was mainly distributed in kidneys and intestines and then showed a tendency of declining first but mildly rising later at 6 h, accompanied by a wide distribution in kidneys and intestines again. It suggested that entero-systemic recirculation might lead to the observed secondary peaks, and perhaps it extended the residence time of paraquat in the body. In addition, we validated the potential detoxification effect of sodium salicylate as a potential antidote for paraquat from both the dimensions of distribution and quantification. In conclusion, MALDI-MSI conveniently provided the distinct and quantitative spatial-temporal distribution information on paraquat in the whole body of zebrafish; it will promote the understanding of its toxicokinetic characteristics and provide more valuable information for clinical treatment.

First-in-human study of CPL207280, a novel G-protein-coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration.

To assess the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of CPL207280, a new G-protein-coupled receptor 40 agonist developed to treat type 2 diabetes (T2D). The phase 1 study in healthy volunteers (White, age 18-55 years, body mass index 18.5-29.9 kg/m2 ) was performed after single (24 subjects, 5-480 mg) and multiple (32 subjects, 60-480 mg) once-daily administration of CPL207280. The effect of food intake and interaction with metformin were evaluated in additional cohort (12 subjects, 120 mg). The primary objective was the safety and tolerability of CPL207280. Secondary objectives included PK and pharmacodynamic (PD) characteristics (glucose, insulin, C-peptide, proinsulin, glucagon levels) observed during the 14-day treatment period. No deaths or serious adverse events (AEs) were reported. All reported AEs were classified as unrelated to the study product. No clinically significant differences in safety parameters were observed between cohorts and no food or metformin effect on safety parameters was identified. The ascending dose of CPL207280 caused an increase in the PK parameters maximum observed plasma concentration (Cmax ) or area under the plasma concentration-time curve up to 24 h. However, dose-normalized Cmax decreased with ascending dose. There was no relationship between the CPL207280 dose or prandial state and terminal elimination half-life and terminal elimination rate constant. No clear relationship between CPL207280 dose and PD area under the effect curve values was observed. CPL207280 was found to be safe and well tolerated by healthy volunteers (with a low risk of hepatotoxicity) for up to 14 days of administration. The PK profile of CPL207280 supports single-daily administration and justifies further development of this therapy for patients with T2D.

Optimizing the Antimicrobial Activity of Sodium Hypochlorite (NaClO) over Exposure Time for the Control of Salmonella spp. In Vitro.

Fish is a nutritionally rich product; however, it is easily contaminated by pathogenic microorganisms, such as Salmonella spp. Therefore, this study aimed to identify the best concentration of sodium hypochlorite (NaClO), exposure time, and water temperature that allow the most effective antimicrobial effect on the viable population of Salmonella spp. Thus, Salmonella Enteritidis ATCC 13076 and Salmonella Schwarzengrund were exposed to different time frames, ranging from 5 min to 38.5 min, temperatures between 5 and 38.5 °C, and NaClO concentrations ranging from 0.36 to 6.36 ppm, through a central composite rotational design experiment (CCRD). The results demonstrated that the ATCC strain exhibited a quadratic response to sodium hypochlorite when combined with exposure time, indicating that initial contact would already be sufficient for the compound's action to inhibit the growth of the mentioned bacteria. However, for S. Schwarzengrund (isolated directly from fish cultivated in aquaculture), both NaClO concentration and exposure time significantly influenced inactivation, following a linear pattern. This suggests that increasing the exposure time of NaClO could be an alternative to enhance Salmonella elimination rates in fish slaughterhouses. Thus, the analysis indicates that the Salmonella spp. strains used in in vitro experiments were sensitive to concentrations equal to or greater than the recommended ones, requiring a longer exposure time combined with the recommended NaClO concentration in the case of isolates from aquaculture.

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF 2-(4-ETHOXYPHENYL SULPHONAMIDO) PENTANE-DIAMIDE, A NOVEL ANTITUMOR AND ANTIANGIOGENIC AGENT, IN RAT SERUM AND APPLICATION OF THE METHOD IN DETERMINATION OF PHARMACOKINETIC PARAMETERS

Objective: The present study focuses on the development and validation of a bioanalytical method for the quantification of 2-(4-ethoxyphenyl sulphamido) pentane-diamide, a candidate antitumor and antiangiogenic agent, in rat serum. The developed method was subsequently applied to determine the pharmacokinetic parameters of the compound. Methods: To quantify the compound and determine its pharmacokinetic properties in rats, a liquid chromatography-mass spectrometry (LC-MS) bioanalytical method has been developed and the pharmacokinetic parameters were computed by compartmental model analysis. Results: A linear relationship was detected within the concentration range of 10 to 5000 ng/ml prepared by adding standard solutions of the test compound to the pooled serum of 10 SD rats, which exhibits high levels of precision, accuracy, and reproducibility. An appreciable recovery in the range of 97.20±0.63 to 93.22±1.48 percent was determined, with no noticeable impact from the matrix. The pharmacokinetic parameters, namely oral absorption rate constant (Ka) (5.054±0.238 1/h), elimination rate constant (KE) (2.585±0.357 h), volume of distribution (V) (8.173±0.333 L/kg), and bioavailability of (73.2%), were determined by the utilization of PK-solver software. Conclusion: We developed a simple yet precise and validated LC-MS method to analyze the drug candidate in rat serum. Simple protein precipitation and extraction were cost-effective. This bioanalytical approach was successful due to its good linearity, high recoveries, no matrix influence, and matrix stability. PK solver derived I. V. and oral pharmacokinetics parameters from the best-fit one-compartment model. Because of its high oral absorption, biological half-life, and bioavailability, the compound is suitable for oral administration.

Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis

Background/ObjectivePrevious studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. MethodsOne hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. ResultsFifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. ConclusionsSM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in the plasma, urine, and feces of fattening male donkeys following single oral administration.

Florfenicol (FF) is a commonly used antibacterial agent in animals. We investigated the pharmacokinetics of FF and its metabolite florfenicol amine (FFA) in donkeys. Donkeys were administered FF (30 mg/kg bodyweight, p.o.). Pharmacokinetic parameters were calculated using a non-compartmental model. The FF (FFA) pharmacokinetics parameters were characterized by along elimination half-life (t1/2 kz) of 5.92 h (15.95 h), plasma peak concentration (Cmax) of 0.13 μg/mL (0.08 μg/mL), and the time taken to reach Cmax (Tmax) of 0.68 h (0.72 h). The area under plasma concentration-time curve and mean residence time of FF (FFA) in plasma were 1.31 μg·mL-1·h (0.47 μg·mL-1·h) and 10.37 h (18.40 h), respectively. The t1/2 kz of FF and FFA in urine was 21.93 and 40.26 h, and the maximum excretion rate was 10.56 and 4.03 μg/h reached at 25.60 and 32.20 h, respectively. The respective values in feces were 0.02 and 0.01 μg·h-1 reached at 33.40 h. The amount of FF and FFA recovered in feces was 0.52 and 0.22 μg, respectively. In conclusion, FF (FFA) is rapidly absorbed and slowly eliminated after a single oral administration to donkeys. Compared to FF, FFA was more slowly eliminated. FF (FFA) is mostly excreted through urine.

Systematic studies on the kinetic process of 20(S)-protopanaxadiol in rats and dogs: absorption, distribution, metabolism and excretion.

Ginseng has been regarded as a precious medicinal herb with miraculous effects in Eastern culture. The primary chemical constituents of ginseng are saponins, and the physiological activities of ginsenosides determine their edible and medicinal value. The aim of this study is to comprehensively and systematically investigate the kinetic processes of 20(S)-protopanaxadiol (PPD) in rats and dogs, in order to promote the rational combination of ginseng as a drug and dietary ingredient. PPD was administered, and drug concentration in different biological samples were detected by liquid chromatography tandem mass spectrometry (LC/MS/MS) and radioactive tracer methods. Pharmacokinetic parameters such as absorption, bioavailability, tissue distribution, plasma protein binding rate, excretion rate, and cumulative excretion were calculated, along with inference of major metabolites. This study systematically investigated the absorption, distribution, metabolism, excretion (ADME) of PPD in rats and dogs for the first time. The bioavailabilities of PPD were relatively low, with oral absorption nearly complete, and the majority underwent first-pass metabolism. PPD had a high plasma protein binding rate and was relatively evenly distributed in the body. Following oral administration, PPD underwent extensive metabolism, potentially involving one structural transformation and three hydroxylation reactions. The metabolites were primarily excreted through feces and urine, indicating the presence of enterohepatic circulation. The pharmacokinetic processes of PPD following intravenous administration aligned well with a three-compartment model. In contrast, after gastric administration, it fitted better with a two-compartment model, conforming to linear pharmacokinetics and proportional elimination. There were evident interspecies differences between rats and dogs regarding PPD, but individual variations of this drug were minimal within the same species. This study systematically studied the kinetic process of PPD in rats and also investigated the kinetic characteristics of PPD in dogs for the first time. These findings lay the foundation for further research on the dietary nutrition and pharmacological effects of PPD.

Impact of lactoferrin supplementation on cotrimoxazole pharmacokinetics: A preliminary clinical investigation.

Cotrimoxazole, a commonly prescribed antibiotic, has substantial resistance, especially in Indonesia, with its uropathogenic resistance reaching 67% in 2017. Although cotrimoxazole has been suggested to be co-administered with lactoferrin to enhance its antibacterial effectiveness and this practice has been widely adopted since the Covid-19 pandemic, the impact of lactoferrin on the pharmacokinetics of cotrimoxazole remains relatively unknown. This study aims to conduct a preliminary clinical investigation into the impact of lactoferrin supplementation on the pharmacokinetics of cotrimoxazole, focusing on the elimination rate and excretion of unchanged drug in urine. This study employed a blinded, cross-over, single-dose pharmacokinetics investigation, which included five healthy volunteers as participants. In the initial period, the first group received cotrimoxazole (80 mg trimethoprim and 400 mg sulfamethoxazole) along with a lactoferrin-containing supplement, while the second group only received cotrimoxazole. Subsequently, after a washout period, the conditions were reversed. Urine sampling was conducted at intervals from 0 to 24 hours post-medication, and drug levels in the urine were determined using high-performance liquid chromatography. The population-based pharmacokinetic analysis revealed that the optimal model was the one-compartment model with first-order elimination and proportional residual error. The findings show that the administration of lactoferrin-containing supplements did not significantly influence the covariate model and, therefore, did not alter the pharmacokinetics parameter of cotrimoxazole in urine with a single administration, implying that lactoferrin did not cause drug interaction problems when given simultaneously.

Direct observation of β-alkynyl eliminations from unstrained propargylic alkoxide Cu(i) complexes by C-C bond cleavage.

β-Carbon eliminations of aryl, allylic, and propargylic alkoxides of Rh(i), Pd(ii), and Cu(i) are key elementary reactions in the proposed mechanisms of homogeneously catalysed cross-coupling, group transfer, and annulation. Besides the handful of studies with isolable Rh(i)-alkoxides, β-carbon eliminations of Pd(ii)- and Cu(i)-alkoxides are less definitive. Herein, we provide a comprehensive synthetic, structural, and mechanistic study on the β-alkynyl eliminations of isolable secondary and tertiary propargylic alkoxide Cu(i) complexes, LCuOC(H)(Ph)C[triple bond, length as m-dash]CPh and LCuOC(ArF)2C[triple bond, length as m-dash]CPh (L = N-heterocyclic carbene (NHC), dppf, S-BINAP), to produce monomeric (NHC)CuC[triple bond, length as m-dash]CPh, dimeric [(diphosphine)CuC[triple bond, length as m-dash]CPh]2, and the corresponding carbonyl. Selective β-alkynyl over β-hydrogen elimination was observed for NHC- and diphosphine-supported secondary propargylic alkoxide complexes. The mechanism for the first-order reaction of β-carbon elimination of (IPr*Me)CuOC(ArF)2C[triple bond, length as m-dash]CPh is proposed to occur through an organized four-centred transition state via a Cu-alkyne π complex based on Eyring analysis of variable-temperature reaction rates by UV-vis kinetic analysis to provide ΔH ‡ = 24(1) kcal mol-1, ΔS ‡ = -8(3) e.u., and ΔG ‡ (25 °C) = 27 kcal mol-1 over a temperature range of 60-100 °C. Additional quantitative UV-vis kinetic studies conclude that the electronic and steric properties of the NHC ligands engendered a marginal effect on the elimination rate, requiring 2-3 h at 100 °C for completion, whereas complete β-alkynyl eliminations of diphosphine-supported propargylic alkoxides were observed in 1-2 h at 25 °C.

Efficacy and safety of catheter ablation for atrial fibrillation in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Catheter ablation (CA) effectively treats atrial fibrillation (AF) in heart failure (HF) with reduced ejection fraction (HFrEF), improving clinical outcomes. However, its benefits for AF patients with heart failure with preserved ejection fraction (HFpEF) are still unclear. We systematically searched PubMed, Embase, Web of Science, the Cochrane Library, and Scopus for studies investigating outcomes of CA in AF patients with HFpEF. Efficacy indicators included freedom from AF and antiarrhythmic drugs (AAD) free AF elimination. Safety indicators comprised total complications, HF admission, all-cause admission, and all-cause mortality. Sixteen studies with 20,796 patients included in our research. The comprehensive analysis demonstrated that, when comparing CA with medical therapy in HFpEF, no significant differences were observed in terms of HF admissions, all-cause admissions, and all-cause mortality [(OR: 0.42; 95% CI: 0.12-1.51, P = 0.19), (HR: 0.78; 95% CI: 0.48-1.27, P = 0.31), and (OR: 1.10; 95% CI: 0.83-1.44, P = 0.51)], while freedom from AF was significantly higher in CA (OR: 5.88; 95% CI: 2.99-11.54, P < 0.00001). Compared with HFrEF, CA in HFpEF showed similar rates of freedom from AF, AAD-free AF elimination, total complications, and all-cause admission were similar [(OR:0.91; 95% CI: 0.71,1.17, P =0.47), (OR: 0.97; 95% CI: 0.50-1.86, P = 0.93), (OR: 1.27; 95% CI: 0.47-3.41, P = 0.64), (OR: 1.11; 95% CI: 0.72, 1.73; P = 0.63)]. However, CA in HFpEF was associated with lower rates of HF admission and all-cause mortality [(OR: 0.35; 95% CI: 0.20, 0.60; P = 0.0002), (OR: 0.40; 95% CI: 0.18, 0.85; P = 0.02)]. Compared with patients without HF, CA in HFpEF patients exhibited lower rates of AAD-free AF elimination (OR: 0.48; 95% CI: 0.30, 0.75; P = 0.001). However, their rates of freedom from AF and total complications were similar [(OR: 0.70; 95% CI: 0.48, 1.02; P = 0.06), (OR: 0.60; 95% CI: 0.19, 1.90; P = 0.38)]. This meta-analysis conducted provided a comprehensive evaluation of the efficacy and safety of CA in patients with AF and HFpEF. The results suggest that CA may represent a valuable treatment strategy for patients with AF and HFpEF. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier (CRD42024514169).

On the mechanism of carboxylate elimination from carbohydrate monoester-derived radicals.

A computational study of the mechanism of hydrogen atom transfer-induced carboxylate elimination from monoacylated 1,2-diol groups in pyranosides is presented. A comprehensive analysis of the 1,2-migration, elimination and fragmentation pathways reveals that concerted elimination via a 7-membered, hydrogen-bonded transition state is favored. Relative rates of elimination inferred from an intramolecular competition experiment are consistent with the trends obtained from the calculations.

Role of CKD273 in Diabetic Nephropathy: A Systematic Review

Introduction: Diabetic Nephropathy (DN) is a major cause of increased morbidity and mortality in patients with Diabetes Mellitus (DM). The development of novel biomarkers for kidney disease, especially DN, is becoming a focus of medical research. Serum creatinine and urine albumin measurements had been the gold standards for the diagnosis of DN until the advent of newer markers like Cystatin C, Kidney Injury Molecule-1, etc. Currently, there is no non invasive investigation for the prediction of DN. Nevertheless, the field of proteomics is advancing at a rapid pace, such that urinary proteomic biomarkers have found a spot in the diagnosis of DN. The role of the urinary proteomic Chronic Kidney Disease 273 (CKD273) classifier, in particular, has been demonstrated in early prediction. Aim: To highlight the performance of the CKD273 classifier in the early prediction of DN. Materials and Methods: Pubmed and Scopus databases were extensively searched using the keywords diabetes, DM, renal disease or kidney disease, proteomics or peptide, urinary markers or biomarkers. Full-text original articles conducted on humans and written in English, published between 2014 and 2022, specifically prospective and retrospective observational studies, crosssectional studies, Randomised Controlled Trials (RCT), and casecontrol studies investigating the efficacy of the urinary biomarker CKD273 in the prediction of DN were included in the review. The literature search, strictly based on Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, led to the identification of eight relevant studies, which were included in the present review. The quality and Risk of Bias (RoB) of the selected articles were assessed using the Newcastle Ottowa scale (NOS) and Risk Of Bias 2 (ROB2) tool. Results: The selected studies proved the efficacy of the urinary proteomic classifier CKD273 as a cost-effective biomarker in predicting the decline in renal function in both normoalbuminuric diabetics and DN patients. Conclusion: Based on the articles included in the present systematic review, it has been found that CKD273 plays a vital role in the early prediction of renal dysfunction in normoalbuminuric diabetics as well as in the detection of progressing renal disease in DN patients. It has also been found to be cost-effective compared to established markers such as estimated Glomerular Filtration Rate (eGFR), Urine Albumin Excretion Rate (UAER), etc.

Thallium - poisoner’s poison: An overview and review of current knowledge on the toxicological effects and mechanisms

Thallium (Tl) is one of the most toxic metals and its historic use in homicides has led it to be known as “the poisoner’s poison.” This review summarizes the methods for identifying Tl and determining its concentrations in biological samples in recently reported poisoning cases, as well as the toxicokinetics, toxicological effects, toxicity mechanisms, and detoxication methods of Tl. Recent findings regarding Tl neurotoxicological pathways and toxicological effects of Tl during pregnancy are also presented. Confirmation of elevated Tl concentrations in blood, urine, or hair is indispensable for diagnosing Tl poisoning. The kidneys show the highest Tl concentration within 24 h after ingestion, while the brain shows the highest concentration thereafter. Tl has a very slow excretion rate due to its large distribution volume. Following acute exposure, gastrointestinal symptoms are observed at an early stage, and neurological dysfunction is observed later: Tl causes the most severe damage in the central nervous system. Alopecia and Mees’ lines in the nails are observed within 1 month after Tl poisoning. The toxicological mechanism of Tl is considered to be interference of vital potassium-dependent processes with Tl+ because its ionic radius is similar to that of K+, as well as inhibition of enzyme reactions by the binding of Tl to -SH groups, which disturbs vital metabolic processes. Tl toxicity is also related to reactive oxygen species generation and mitochondrial dysfunction. Prussian blue is the most effective antidote, and metallothionein alone or in combination with Prussian blue was recently reported to have cytoprotective effects after Tl exposure. Because Tl poisoning cases are still reported, early determination of Tl in biological samples and treatment with an antidote are essential.

Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Simultaneous determination of methyltestosterone and its metabolite in fish by gas chromatography-mass spectrometry.

Methyltestosterone is one of the banned drugs in aquaculture, and it should be monitored in food-producing animals. 17α-Methyl-5β-androstane-3α,17β-diol, as the main metabolite of methyltestosterone in vertebrates, could be used as another marker for controlling the administration of methyltestosterone, due to its high residual concentration and slow elimination rate. In this study, an analytical method based on gas chromatography-mass spectrometry (GC-MS) was developed and validated for the simultaneous determination of methyltestosterone and its main metabolite in fish. After pretreatment by liquid-liquid extraction with n-hexane and solid phase extraction with C18 and NH2 columns, the target analytes in the muscle tissues were extracted and concentrated, and the influence of the sample matrix was eliminated. Then, the prepared samples were separated and detected with GC-MS in the selected ion monitoring (SIM) mode. Methyltestosterone-D3 was chosen as the internal standard for quantitation. After optimization, the limits of detection for methyltestosterone and 17α-methyl-5β-androstane-3α,17β-diol were 20 μg kg-1 and 15 μg kg-1, respectively. The limits of quantitation were both 50 μg kg-1. The calibration curves showed good linearity in the concentration range from 50.0 ng mL-1 to 500.0 ng mL-1. The correlation coefficients of methyltestosterone and 17α-methyl-5β-androstane-3α,17β-diol were more than 0.9990. The recoveries of the analytes in real samples were in the range of 99.7-116.6% with the relative standard deviation of 5.2-8.3%. The established method could meet the demand for simultaneous detection of methyltestosterone and its major metabolite, and it could be used to provide more information on the abuse of methyltestosterone in food-producing animals.

Polylactic acid-based dressing with oxygen generation and enzyme-like activity for accelerating both light-driven biofilm elimination and wound healing.

Photodynamic therapy (PDT) is a widely used therapeutic approach for eradicating bacterial biofilms in infected wound, but its effectiveness is limited by the hypoxic environment within the biofilm. This study aimed to investigate whether the efficiency of photodynamic removing biofilm is improving by providing oxygen (O2), as well as the expression of cytokines involved in infected wound healing. Manganese dioxide (MnO2) nanoparticles with catalase-like activity were grown in situ on graphitic phase carbon nitride (g-C3N4, CN) nanosheets to construct an all-in-one CN-MnO2 nanozyme, which was then incorporated into poly-L-lactic acid (PLLA) to prepare CN-MnO2/PLLA wound dressing by electrospinning. Subsequently, the in vitro antibacterial biofilm ratio and antibacterial ratio of CN-MnO2/PLLA wound dressing were examined by spread plate and crystal violet staining under irradiation with 808nm near-infrared light and 660nm visible light. Meanwhile, the rat skin injury model was established, and hematoxylin and eosin (H&E), Masson's, tumor necrosis factor-α (TNF-α), Arginase 1 (Arg-1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (BFGF) were evaluated in vivo to assess the effect of CN-MnO2/PLLA wound dressing on wound healing. Biofilm density caused by Staphylococcus aureus and Pseudomonas aeruginosa had elimination rates of 83 and 62%, respectively, when treated with CN-MnO2/PLLA dressing. Additionally, the dressing exhibited high antibacterial efficacy against both bacteria, achieving 99 and 98.7% elimination of Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Furthermore, in vivo experiments showed that the CN-MnO2/PLLA wound dressing achieved complete healing of infected wounds on Day 14, with a wound healing rate of >99% by increasing collagen deposition, expression of anti-inflammatory cytokine Arg-1, vascularization cytokine VEGF, and epithelial cell BFGF, and inhibiting the expression of inflammatory cytokine TNF-α. The CN-MnO2/PLLA wound dressing exhibited excellent antibacterial properties in vitro and in vivo. In addition, CN-MnO2/PLLA wound dressing accelerated rapid wound healing through an anti-inflammatory, pro-vascular regeneration and skin tissue remodeling mechanism.

Confirmation of the utility of the CA-125 elimination rate (KELIM) as an indicator of the chemosensitivity in advanced-stage ovarian cancer in a "real-life setting".

The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS). Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/favorable (<1.0/≥1.0). KELIM's prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04-3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76; 95% CI=0.66-0.87), and OS (HR=0.79; 95% CI=0.69-0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.