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Salvia miltiorrhiza Bunge is a Traditional Chinese Medicine used for the treatment of diseases related to the heart and liver. Owing to the abundance of salvianolic acids and tanshinones, S. miltiorrhiza exhibits various pharmacological activities, such as stimulating blood circulation, eliminating blood stasis, relieving menorrhea and pain, and improving polydipsia. Neocryptotanshinone (NCTS) is one of the tanshinones isolated from S. miltiorrhiza and exhibits anti‐inflammatory, hypoglycemic, and preventive effects against cardiovascular diseases; however, its pharmacokinetic properties have not been reported to date. Therefore, a simple and reliable LC–MS/MS method was developed to determine absorption, distribution, and excretion of NCTS in rat physiological samples. We demonstrated that NCTS had high oral absolute bioavailability of 85.96% ± 25.32%, and it was rapidly distributed in both the heart and brain, and the fecal excretion of NCTS was the highest. This study provides a theoretical basis for further development of NCTS as a potential clinical candidate. [ABSTRACT FROM AUTHOR]

This article discusses the hemodynamics and urinary excretion of kidney injury biomarkers in pediatric kidney transplantation. The study aimed to investigate the relationship between perioperative hemodynamic values and the excretion of acute kidney injury biomarkers in pediatric kidney transplantation with a large donor-acceptor size mismatch. The results suggest that an increased cardiac output (CO) is required to limit postreperfusion donor kidney injury, but excessive therapy to reach a supraphysiological CO, such as high central venous pressure (CVP) and vasopressor infusion rates, may be associated with early donor kidney injury. Further research is needed to determine the clinical consequences of hemodynamic therapy and the most sensitive biomarkers for detecting early donor kidney injury in pediatric kidney transplantation. [Extracted from the article]

Objective: This study aimed to determine the effects of different energy loads on the gut microbiota composition and the rates of energy and nutrient excretion via feces and urine. Method s : A randomized crossover dietary intervention study was conducted with three dietary conditions: overfeeding (OF), control (CON), and underfeeding (UF). Ten healthy men were subjected to each condition for 8 days (4 days and 3 nights in nonlaboratory and laboratory settings each). The effects of dietary conditions on energy excretion rates via feces and urine were assessed using a bomb calorimeter. Results: Short‐term energy loads dynamically altered the gut microbiota at the α‐diversity (Shannon index), phylum, and genus levels (p < 0.05). Energy excretion rates via urine and urine plus feces decreased under OF more than under CON (urine −0.7%; p < 0.001, urine plus feces −1.9%; p = 0.049) and UF (urine −1.0%; p < 0.001, urine plus feces −2.1%; p = 0.031). However, energy excretion rates via feces did not differ between conditions. Conclusions: Although short‐term overfeeding dynamically altered the gut microbiota composition, the energy excretion rate via feces was unaffected. Energy excretion rates via urine and urine plus feces were lower under OF than under CON and UF conditions. [ABSTRACT FROM AUTHOR]

Swear words are impolite words or words that make other people offended or get angry. Every region has its' own particular swear words, especially in Indramayu. The swear words used by the Javanese people of Indramayu have various types and functions. Therefore, this study describes the types and functions of Indramayu Javanese swear words in the novel Aib dan Nasib by Minanto. The result reported nine types of swear words in the novel Aib and Nasib by Minanto. They are 1) excretion in the word of tahi; 2) death in the word of mampus; 3) body function term in the word of kontol, memek, endas, kuping; 4) religious term in the word of dedemit, setan; 5) mother in law in the word of telembuk, lonte, perung, jalang; 6) sex term in the word of ngentot, rabenan; 7) animal term in the word of kirik, ketek; 8) imbecilic term in the word of dungu, goblok, koplok, cecunguk, campleng; 9) general term in the word of, sinting, lancang, bangsat. Meanwhile, the functions of those swear words in the novel Aib dan Nasib by Minanto are: to create attention; to discredit; to provoke; to create interpersonal identification; and to provide catharsis. [ABSTRACT FROM AUTHOR]

(R)-Benzylsuccinate is generated in anaerobic toluene degradation by the radical addition of toluene to fumarate and further degraded to benzoyl-CoA by a β-oxidation pathway. Using metabolic modules for benzoate transport and activation to benzoyl-CoA and the enzymes of benzylsuccinate β-oxidation, we established an artificial pathway for benzylsuccinate production in Escherichia coli, which is based on its degradation pathway running in reverse. Benzoate is supplied to the medium but needs to be converted to benzoyl-CoA by an uptake transporter and a benzoate-CoA ligase or CoA-transferase. In contrast, the second substrate succinate is endogenously produced from glucose under anaerobic conditions, and the constructed pathway includes a succinyl-CoA:benzylsuccinate CoA-transferase that activates it to the CoA-thioester. We present first evidence for the feasibility of this pathway and explore product yields under different growth conditions. Compared to aerobic cultures, the product yield increased more than 1000-fold in anaerobic glucose-fermenting cultures and showed further improvement under fumarate-respiring conditions. An important bottleneck to overcome appears to be product excretion, based on much higher recorded intracellular concentrations of benzylsuccinate, compared to those excreted. While no export system is known for benzylsuccinate, we observed an increased product yield after adding an unspecific mechanosensitive channel to the constructed pathway. [ABSTRACT FROM AUTHOR]

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3–5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 μmol/l for low-risk (LR) and 65 μmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 μmol/l and 69.7 μmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p =.014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p =.001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL. [ABSTRACT FROM AUTHOR]

There is growing consensus that under physiological conditions, collecting duct H+ secretion is independent of epithelial Na+ channel (ENaC) activity. We have recently shown that the direct ENaC inhibitor benzamil acutely impairs H+ excretion by blocking renal H+-K+-ATPase. However, the question remains whether inhibition of ENaC per se causes alterations in renal H + excretion. To revisit this question, we studied the effect of the antibiotic trimethoprim (TMP), which is well known to cause K + retention by direct ENaC inhibition. The acute effect of TMP (5 µg/g body wt) was assessed in bladder-catheterized mice, allowing real-time measurement of urinary pH, electrolyte, and acid excretion. Dietary K+ depletion was used to increase renal H+-K+-ATPase activity. In addition, the effect of TMP was investigated in vitro using pig gastric H+-K+-ATPase-enriched membrane vesicles. TMP acutely increased natriuresis and decreased kaliuresis, confirming its ENaC-inhibiting property. Under control diet conditions, TMP had no effect on urinary pH or acid excretion. Interestingly, K+ depletion unmasked an acute urine alkalizing effect of TMP. This finding was corroborated by in vitro experiments showing that TMP inhibits H+-K+-ATPase activity, albeit at much higher concentrations than benzamil. In conclusion, under control diet conditions, TMP inhibited ENaC function without changing urinary H+ excretion. This finding further supports the hypothesis that the inhibition of ENaC per se does not impair H+ excretion in the collecting duct. Moreover, TMP-induced urinary alkalization in animals fed a low-K+ diet highlights the importance of renal H+-K+-ATPase-mediated H+ secretion in states of K+ depletion. [ABSTRACT FROM AUTHOR]

Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects of betaine in normotensive and hypertensive rats. Betaine levels were assessed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats (Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis were evaluated. Gene and protein expression of chosen kidney betaine transporters (SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared to normotensive rats, SHRs showed significantly lower concentration of betaine in blood serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p = 0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial blood pressure. The diuretic response was greater in SHRs than in WKYs. There were no significant differences in renal expression of betaine transporters between WKYs and SHRs. Increased renal excretion of betaine contributes to decreased concentration of the protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies evaluating a causal relation between depleted betaine and hypertensive organ damage, including kidney injury. [ABSTRACT FROM AUTHOR]

Aim: Hypernatraemia typically reflects dehydration, yet in rare instances may be caused by salt poisoning. Identifying these rare cases is a difficult challenge. Making the diagnosis of salt poisoning can have severe consequences, such as the removal of the child from its home or even prison sentences for the implicated carer. It is therefore imperative to get the diagnosis right. Guidelines for the assessment of hypernatraemia emphasise the importance of the fractional excretion of sodium to distinguish between dehydration and salt poisoning, but no generally accepted cut‐off value exists. Opinions about the diagnosis of salt poisoning in some cases consequently may differ. Here, we aim to highlight the challenges and stimulate discussion on how to improve the tools for the assessment of hypernatraemia. Methods: Report of a case of unexplained hypernatraemia in which the treating paediatrician raised the suspicion of salt poisoning. Results: Two consulted experts made opposing judgements about the aetiology of the observed hypernatraemia. Conclusion: Clear diagnostic criteria for the diagnosis of salt poisoning are lacking and more data are needed for their establishment. Without this, victims may experience further harm and carers are at risk of devastating, yet potentially erroneous accusations. [ABSTRACT FROM AUTHOR]

Improving the nitrogen (N) utilisation efficiency (NUE) of dairy cows by breeding was considered beneficial for environmental footprints, feeding costs and animal health. Due to the difficult data obtainment of NUE, the cow-individual milk urea (MU) value was suggested as an indicator trait. MU data fulfills the requirements for the breeding value evaluation routine, but studies questioned a stable relationship to NUE. It became evident that a deeper knowledge on the underlying principles of cow-individual N utilisation and -excretion is indispensable before MU can be seriously considered for breeding strategies. In this context four studies were conducted, which focused on the host genome-trait, the host genome-rumen microbiota and the entire host genome-rumen microbiota-trait complex, aiming for a holistic exploration of cow-individual N utilisation and N excretion as a pre-step for future breeding strategies. The results of the studies and their overall interpretation let assume that genomic selection with MU would impact the host genome-rumen microbiota axis (i.e. the holobiont) which subsequently jointly affects MU and NUE- associated phenotypes. [ABSTRACT FROM AUTHOR]

Objectives: Daily uric acid excretion (Eua) is an essential index for patients with gout/hyperuricaemia. We identified alternative indices most correlated with 24-hour uric acid clearance (Cua 24 h) and 24-hour Eua (Eua 24 h) using data from the reference interval of urinary clearance and excretion of urate study. Methods: The subjects were indoor workers aged 20–65 years who met the Clinical and Laboratory Standards Institute Guidelines C28-A3c. Alternative indices using spot urine were urine uric acid creatinine ratio, Cua—creatinine clearance ratio (Cua/Ccr), Eua—CCr ratio (Eua/Ccr), estimated Cua (eCua), and estimated Eua (eEua). eCua and eEua are the values obtained by multiplying Cua/Ccr and Eua/Ccr with the estimated glomerular filtration rate. Results: The final number of subjects analysed was 739. Among the indices using spot urine, eCua and eEua showed the highest correlation with Cua 24 h and Eua 24 h, respectively. Compared with Cua 60 min and Eua 60 min obtained from 60-min urine collection, eCua and eEua showed lower root means squared error, lower bias, and significantly higher accuracy of within 30% and within 15%. Conclusions: The newly proposed eCua and eEua may be appropriate from a practical perspective. [ABSTRACT FROM AUTHOR]

Polygonum cognatum Meissn, a perennial herbaceous belonging to the Polygonaceae family, is an aromatic plant. High‐performance liquid chromatography/diode array detector method was developed and validated for the phytochemical analysis of the plant. Also, various methods were used to investigate the antioxidant, antimicrobial, and cytotoxic activities of the methanolic extracts. Antioxidant activities were researched by 2,2′‐diphenyl‐1‐picrylhydrazyl and cupric reducing antioxidant capacity methods. Among the tested standard microbial strains, Candida albicans was found to be more sensitive with a 24.60 ± 0.55 mm inhibition zone according to the diffusion tests. In the microdilution tests, the minimum inhibitory concentration and minimum bactericidal/fungicidal concentration values were 4.75 and ≥ 4.75 mg/mL, respectively, for all tested pathogens. Human colon carcinoma cells were used to investigate cytotoxicity by using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide analysis (IC50 = 2891 μg/mL for Plant A, IC50 = 3291 μg/mL for Plant B). Molecular docking and absorption, distribution, metabolism, excretion, and toxicity analysis were used to explain inhibition mechanisms of major phenolic compounds of plants against Tankyrase 1, Tankyrase 2 enzymes, and deoxyribonucleic acid gyrase subunit B and found compatible with experimental results. [ABSTRACT FROM AUTHOR]

Chemical communication is important for many social mammals. Scent-related gene clusters have undergone extraordinary expansion in some species, such as the house mouse (Mus musculus). One such family encodes major urinary proteins (MUPs). MUPs can provide recipients with complex information about the signaller and potentially serve as honest signals of social rank. In this study, we examined the development of overall MUP production in two mouse subspecies in the context of establishing their social hierarchy during the critical period between weaning and 100 days of age. We used fraternal pairs as simple social units, where dominant/subordinate ranks were naturally established between two brothers raised together, to test the hypothesis that dominant males of both taxa excrete higher amounts of MUPs in their urine than subordinates. The results were compared to data on ontogeny of steroid hormone levels gathered in the same individuals during an earlier experiment. Higher MUP levels in dominant males were only corroborated in one subspecies (domesticus), whereas musculus males revealed similar MUP quantities irrespective of rank. These results are consistent with the notion that these closely related taxa adopted different strategies for establishing social hierarchy. [ABSTRACT FROM AUTHOR]

Purpose: Although the 24-hours urinary copper excretion is useful for the diagnosis of Wilson disease (WD), there are practical difficulties in the accurate and timed collection of urine samples. The purpose of this study was to verify if the spot morning urinary Copper/Zinc (Cu/Zn) ratio could be used as a replacement parameter of 24-hours urinary copper excretion in the diagnosis of WD. Methods: A cross-sectional study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from June 2019 to May 2021 on 67 children over three years of age who presented with liver disease. Twenty-seven children who fulfilled the inclusion criteria for WD were categorized into the test group, and the remaining forty children were considered to have non-Wilsonian liver disease and were categorized into the control group. Along with other laboratory investigations, spot morning urinary samples were estimated for the urinary Cu/Zn ratio in all patients and were compared to the 24-hour urinary copper excretion. The diagnostic value of the Cu/Zn ratio was then analyzed. Results: Correlation of spot morning urinary Cu/Zn ratio with 24-hours urinary copper excretion was found to be significant (r=0.60). The area under ROC curve with 95% confidence interval of morning urinary Cu/Zn ratio measured using 24-hours urine sample was 0.84 (standard error, 0.05; p<0.001). Conclusion: Spot morning urinary Cu/Zn ratio seems to be a promising parameter for the replacement of 24-hours urinary copper excretion in the diagnosis of WD. [ABSTRACT FROM AUTHOR]

Background: Thalassemia has a high prevalence and carrier rate of 8-10% in Pakistan, repeated blood transfusions lead to iron deposition in organs. In this Prospective study, we have compared the efficacy of three chelation regimens being used in our country. It has been conducted at PBTS, Fatmid Foundation and Children Hospital Lahore. Methods: 60 thalassemia major patients, were divided into 3 groups according to their mode of chelation. Patients in group I were on oral iron chelator deferiprone, 7 days per week. Thalassemics in group II were on parenteral iron chelator deferoxamine given subcutaneously for 4 days a week, and group III patients were on combination therapy, deferiprone for 5 days & deferoxamine given twice weekly. The assessment of chelation was done by measurement of serum ferritin and 24-hour urinary iron excretion at the start of the study and then after six months of follow-up. To assess the hepatic iron, hepatic MRIs were also performed. Results: Ferritin levels were maximally decreased in group II, followed by group III, with no significant reduction in group I. However, a statistically significant difference in mean urinary iron excretion (increased) was seen in group III. The hepatic iron was very high in all three groups as shown by the hepatic MRI. Conclusion: Combination chelation therapy is the most effective chelation therapy in iron-overloaded patients. It helps to improve compliance and increases urinary iron excretion. Patients on DFX had the lowest degree of hepatic siderosis even though it was considerably higher than the normal population. [ABSTRACT FROM AUTHOR]

Luteolin exhibited antibacterial activity against Escherichia coli and its chemical structure similar to that of ciprofloxacin (CPF) which works by inhibiting DNA gyrase. Filtrate from passion fruit extract containing luteolin and its derivatives could inhibit extended-spectrum ß-lactamase (ESBL)-producing E. coli. Antibacterial compounds that can also inhibit ESBL will be valuable compounds to overcome the problem of resistant bacteria. This study aimed to ensure the potency of luteolin and luteolin derivatives targeting DNA gyrase and ESBL by in silico approach. Docking simulation of ligands L1-L14 was performed using AutoDock Vina, and pharmacokinetics and toxicity (absorption, distribution, metabolism, excretion, and toxicity) profiles were predicted by pKCSM online. The docking result revealed higher binding affinity on DNA gyrase (PDB.1KZN) of 12 luteolin derivatives (energy <-7.6 kcal/mol) compared to CPF and higher affinity (energy <-6.27 kcal/mol) of all compounds than clavulanic acid against ESBL CTX-M-15 (PDB.4HBU). The compounds could be absorbed through the human intestine moderately, which showed low permeability to blood-brain barrier, nontoxic and nonhepatotoxic. The most active luteolin glycoside (L6) is capable to inhibit DNA gyrase and ESBL from E. coli which provided the potential against resistant bacteria and was promoted as lead compounds to be developed further. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the lethal toxicity of chlorpyrifos and its effect on food consumption, oxygen consumption rate, ammonia excretion rate and O: N ratio of P. hypophthalmus fingerlings. The acute bioassay test was performed by adopting the static renewal method. Results showed that the median lethal concentration (LC50) of Chlorpyrifos for 96 h was 0.1060 mg L-1. One-fifth T1 (0.0212 mg L-1) and one-tenth T2 (0.0106 mg L-1) of LC50 values were selected for sublethal studies for 45 days revealed that the food consumption rate, oxygen consumption rate and O: N ratio decreased significantly (p<0.05), while ammonia excretion rate increased significantly (p<0.05) at both the concentrations as compared to control. The results obtained in this study proposed that measurements of food consumption rate, oxygen consumption rate, ammonia excretion and O: N ratio can be useful as a stress indicators of P. hypophthalmus fingerlings. [ABSTRACT FROM AUTHOR]

The goal of this study was to produce a sufficient amount of glutathione in the fermentation medium without the addition of cysteine. This would simplify and reduce the cost of its purification. In addition to reducing the cost of cysteine, it also avoids the inhibition of bacterial growth by cysteine. The gshA, gshB, and cysE genes of Escherichia coli were cloned under the control of the strong T5 promoter of the pQE-80L plasmid and introduced into an E. coli strain knocked out for the genes encoding γ-glutamyltranspeptidase and the GsiABCD glutathione transporter, which are responsible for the recycling of excreted glutathione. The overexpression of the gshA and gshB genes, genes for γ-glutamylcysteine synthetase and glutathione synthetase, and the cysEV95R D96P gene, a gene for serine acetyltransferase with the V95R D96P mutation that makes it insensitive to cysteine, were effective on glutathione production. Na2S2O3 was a good sulfur source for glutathione production, while the addition of Na2SO4 did not affect the glutathione production. With the addition of 50 mM glutamic acid and 75 mM glycine, but without the addition of cysteine, to the simplified SM1 medium, 4.6 mM and 0.56 mM of the reduced and oxidized glutathione, respectively, were accumulated in the extracellular space after 36 h of batch culture. This can eliminate the need to extract glutathione from the bacterial cells for purification.

Ethylene glycol 2-ethylhexyl ether (EGEHE) is a solvent used in a variety of applications.We report disposition and metabolism of EGEHE following a single gavage or dermal administration of 50, 150 or 500 mg/kg [14C]EGEHE in rats and mice and in vitro in rat hepatocytes.EGEHE was cleared rapidly in rat hepatocytes (half-life ∼4 min) with no sex difference.EGEHE was well- and moderately absorbed following oral administration (rats: 80-96%, mice: 91-95%) and dermal application (rats: 25-37%, mice: 22-24%), respectively, and rapidly excreted in urine.[14C]EGEHE-derived radioactivity was distributed to tissues (oral: 2.3-7.2%, dermal: 0.7-2.2%) with liver and kidney containing the highest levels in both species.EGEHE was extensively metabolised with little to no parent detected in urine. The alkoxyacetic acid metabolite, which has previously been shown to mediate toxicities of other shorter-chain ethylene glycol ethers, was not detected.There were no apparent dose, species or sex differences in disposition and metabolism of EGEHE, except that the exhaled volatile compounds were greater in mice (19-20%) compared with rats (

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value

Key Clinical Message: Clinicians should not only consider the presence of metallic foreign bodies within the digestive tract but also contemplate the possibility of nicotine poisoning during the diagnostic process. When clinicians encounter cases of accidental ingestion of some types of heated tobacco, they must consider not only nicotine poisoning but also the possibility of a metallic foreign body within the digestive tract during diagnosis. In children, even sharp or relatively large ingested foreign bodies can spontaneously pass below the esophagus. Considering that this 12‐mm metal piece is small, natural excretion may be considered rather than endoscopic removal. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a very common disorder especially past middle age. It is not a disease in itself, but is an important risk factor for coronary, cerebral, renal and peripheral vascular disease. Present study was aimed to study association between 24 hours urinary sodium & potassium excretion and blood pressure at a tertiary hospital. Material and Methods: Present study was prospective, comparative study, conducted in cases (patients of age between 18 and 75 years, diagnosed with hypertension) & controls (same age and sex, normotensive subjects). Results: We compared 40 cases with 40 age & gender matched controls. There was no statistically significant difference observed in age, gender & BMI (p > 0.05). There was a statistically significant difference noted in serum cholesterol (193 ± 14.768 vs 183.15 ± 13.275, p value 0.0024) & average serum sodium (140.43 ± 4.031 vs 138.28 ± 2.837, p value 0.007) among cases & controls. The mean 24 hour urinary sodium excretion was higher in patients with moderate to severe hypertension (178.689 ± 13.039) when compared to subjects with mild hypertension (163.636 ± 13.002) which was statistically significant. (p value 0.002). There was a significant increase in 24 hour urinary sodium excretion in patients with moderate to severe diastolic hypertension (183.33 ± 15.282) as compared to patients with mild diastolic hypertension (169.28 ± 11.433) (P value 0.002). Conclusion: In hypertensive group, there was significantly elevated 24 hour urinary sodium excretion and Na+/K+ molar ratio whereas there was lower 24 hour urinary potassium excretion.24 hour urinary sodium excretion also correlated with severity of hypertension. [ABSTRACT FROM AUTHOR]

BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague–Dawley/Long–Evans rats after a single oral dose of 100 mg/kg (100 μCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N–Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801. [ABSTRACT FROM AUTHOR]

The excretion care robot's (ECR) accurate recognition of transfer-assisted actions is crucial during its usage. However, transfer action recognition is a challenging task, especially since the differentiation of actions seriously affects its recognition speed, robustness, and generalization ability. We propose a novel approach for transfer action recognition assisted by a bidirectional long- and short-term memory (Bi-LSTM) network combined with a multi-head attention mechanism. Firstly, we utilize posture sensors to detect human movements and establish a lightweight three-dimensional (3D) model of the lower limbs. In particular, we adopt a discrete extended Kalman filter (DEKF) to improve the accuracy and foresight of pose solving. Then, we construct an action prediction model that incorporates a fused Bi-LSTM with Multi-head attention (MHA Bi-LSTM). The MHA extracts key information related to differentiated movements from different dimensions and assigns varying weights. Utilizing the Bi-LSTM network effectively combines past and future information to enhance the prediction results of differentiated actions. Finally, comparisons were made by three subjects in the proposed method and with two other time series based neural network models. The reliability of the MHA Bi-LSTM method was verified. These experimental results show that the introduced MHA Bi-LSTM model has a higher accuracy in predicting posture sensor-based excretory care actions. Our method provides a promising approach for handling transfer-assisted action individual differentiation in excretion care tasks. [ABSTRACT FROM AUTHOR]

Soluble epoxide hydrolase (sEH) is an important enzyme for metabolic and cardiovascular health. sEH converts FFA epoxides (EpFAs), many of which are regulators of various cellular processes, to biologically less active diols. In human studies, diol (sEH product) to EpFA (sEH substrate) ratios in plasma or serum have been used as indices of sEH activity. We previously showed these ratios profoundly decreased in rats during acute feeding, possibly reflecting decreases in tissue sEH activities. The present study was designed to test which tissue(s) these measurements in the blood represent and if factors other than sEH activity, such as renal excretion or dietary intake of EpFAs and diols, significantly alter plasma EpFAs, diols, and/or their ratios. The results show that postprandial changes in EpFAs and diols and their ratios in plasma were very similar to those observed in the liver but not in other tissues, suggesting that the liver is largely responsible for these changes in plasma levels. EpFAs and diols were excreted into the urine, but their levels were not significantly altered by feeding, suggesting that renal excretion of EpFAs and diols may not play a major role in postprandial changes in circulating EpFAs, diols, or their ratios. Diet intake had significant impacts on circulating EpFA and diol levels but not on diol-to-EpFA (D-to-E) ratios, suggesting that these ratios, reflecting sEH activities, may not be significantly affected by the availability of sEH substrates (i.e., EpFAs). In conclusion, changes in FFA D-to-E ratios in plasma may reflect those in the liver, which may in turn represent sEH activities in the liver, and they may not be significantly affected by renal excretion or the dietary intake of EpFAs and diols. [ABSTRACT FROM AUTHOR]

Purpose: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism. Methods: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein. Results: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid. Conclusion: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension. Methods and Results: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901. Conclusion: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a hazardous mycotoxin that often contaminates animal feed and may potentially induce severe liver damage if ingested. The liver is the primary organ responsible for AFB1 detoxification through enzyme-catalyzed xenobiotic metabolism and bile acid (BA)-associated excretion. In this study, we sought to investigate whether exogenous BA improves hepatic AFB1 detoxification to alleviate AFB1-induced liver injury in broiler chickens. Five-day-old broiler chicks were randomly assigned to three groups. CON and AFB1 received a basal diet; AFB1 + BA received a basal diet with 250 mg/kg BA for 20 days. After a 3-day pre-feed, AFB1 and AFB1 + BA were daily gavaged with 250 μg/kg BW AFB1, while CON received gavage solvent for AFB1 treatment. Dietary BA supplementation protected chickens from AFB1-induced hepatic inflammation and oxidative stress. The hepatic biotransformation of AFB1 to its metabolite AFBO was improved, with accelerated excretion to the gallbladder and cecum. Accordantly, AFB1-induced down-regulation of detoxification genes, including cytochrome P450 enzymes, glutathione S-transferases, and the bile salt export pump, was rescued by BA supplementation. Moreover, liver X receptor α, suppressed by AFB1, was enhanced in BA-treated broiler chickens. These results indicate that dietary BA supplementation improves hepatic AFB1 detoxification and excretion through LXRα-involved regulation of xenobiotic enzymes. [ABSTRACT FROM AUTHOR]

Objectives: Protein Z (PZ) is a γ‐carboxyglutamic acid protein present in plasma that is involved in blood coagulation. Detailed analysis of urinary stones from patients with urolithiasis has revealed that PZ is often found in urinary stones composed of calcium oxalate monohydrate. In this study, we compared blood and urinary PZ concentrations between healthy individuals and patients with urolithiasis. Methods: Plasma and urine were collected from healthy individuals and patients with urolithiasis who provided informed consent. PZ was detected as a urinary stone matrix protein in some of the patients. PZ was quantified by ELISA, creatinine was measured by the enzymatic method, and the total protein concentration was measured by the Bradford method. Results: The plasma PZ level was 2.54 ± 1.02 μg/mL in healthy individuals and that in urolithiasis patients classified by stone history were from 1.16 ± 0.77 to 3.73 ± 1.09 μg/mL, which was not significantly different. The urinary excretion of PZ (PZ/creatinine) was also not different in patients with urolithiasis and in healthy individuals (from 54.1 ± 40.9 to 95.4 ± 69.4 ng/mg vs. 73.3 ± 36.0 ng/mg). A positive correlation was found between the plasma PZ level and creatinine‐corrected urinary PZ concentration (r = 0.46). Conclusions: Both the plasma level and urinary excretion of PZ in urolithiasis patients were not significantly different with normal individuals. PZ detected in urinary stones as a matrix protein is thought to be incorporated into urinary stones regardless of blood and urine levels of PZ. [ABSTRACT FROM AUTHOR]

Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by applying high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). After intragastric administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine were comparatively studied for the first time. The plasma concentration of demethyleneberberine reached its peak within 5 min after intragastric administration in both rats and mice. Furthermore, its bioavailability was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of demethyleneberberine in the urine, feces and bile was 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on demethyleneberberine. [ABSTRACT FROM AUTHOR]

Daprodustat is an oral small molecule hypoxia‐inducible factor (HIF) prolyl hydroxylase inhibitor (PHI) approved in Japan and the United States for the treatment of anemia associated with chronic kidney disease. This phase 1, nonrandomized, 2‐period, crossover study in 6 healthy men characterized and quantified the metabolites generated after a microtracer IV infusion of 50 μg (125 nCi) [14C]‐daprodustat administered concomitantly with a nonradiolabeled therapeutic dose of a 6‐mg daprodustat tablet, followed by a single oral solution dose of 25 mg (62.5 μCi) [14C]‐daprodustat. High‐performance liquid chromatography (HPLC) coupled with radioactivity detection (TopCount or AMS) and HPLC‐tandem mass spectrometry (HPLC‐MSn) were used for quantitative measurement and structural identification of radioactive metabolites in plasma, urine, feces, and bile. Following oral administration of [14C]‐daprodustat, unchanged daprodustat was the principal circulating drug‐related component, accounting for 40% of plasma radioactivity. Predominant oxidative metabolites M2, M3, M4, and M13 individually represented 6–8% of the plasma radioactivity and together accounted for the majority of radioactivity in urine and feces (53% in both matrices; 12% and 41% of dose, respectively). Unchanged daprodustat was not detected in urine and was only 0.7% of total radioactivity in feces (<0.5% of dose), with the remainder of the dose accounted for by oxidative metabolites. The radio‐metabolic profile of duodenal bile following IV infusion of [14C]‐daprodustat was similar to that observed in feces after oral administration. The data suggested that oral daprodustat was extensively absorbed, cleared exclusively by oxidative metabolism, and eliminated via hepatobiliary (primary) and urinary (secondary) excretion. [ABSTRACT FROM AUTHOR]

New compounds of bis(2,3,4-trimethoxyphenyl)azaalkanes differing in the structure of the central atom were obtained. The anti-ischemic and antiarrhythmic activities of the new compounds were studied. Their absorption, distribution, metabolism, and excretion (ADME) characteristics were analyzed. Replacement of the central N atom by other atoms (O, C, S) had practically no effect on their antiarrhythmic and anti-ischemic properties but improved their calculated oral bioavailability. The promising compound ALM-863 {2,2′-oxybis[N-(2,3,4-trimethoxybenzyl)ethane-1-amine] dihydrochloride} at a dose of 3 mg/kg (i.v.) completely repeated the spectrum of cardiotropic properties of the ALM-802 prototype, was less toxic and surpassed it in terms of calculated pharmacokinetic parameters, and was selected. [ABSTRACT FROM AUTHOR]

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism. [ABSTRACT FROM AUTHOR]

Curcumin (CCM), a culinary spice, is widely consumed for its health benefits for managing oxidative and inflammatory conditions, metabolic syndrome, arthritis, and hyperlipidemia. However, due to its extensive metabolism, the oral bioavailability of CCM is very low. In this study, we developed a rapid, sensitive, and selective assay to examine the hypothesis that piperine improves CCM bioavailability after piperine co‐ingestion. We developed a selective, sensitive, and robust LC–MS/MS method to quantify CCM in human urine. The method was linear over a concentration range 0.625–40 ng/mL with LLOQ and LLOD of 0.625 ng/mL and 0.312 ng/mL, respectively. Healthy volunteers have consumed test meals of CCM as turmeric powder with and without black pepper with 1 week wash out. Urine samples were collected for 24 hours and analyzed for CCM excretion. Black pepper increased CCM half‐life from 2.2 ± 0.79 h (CCM alone) to 4.5 ± 0.80 h (CCM + pepper). The CCM 24‐h urinary excreted amount was higher in individuals consuming CCM + pepper (218.14 ± 94.98 μg) than those who received CCM only (49.45 ± 12.94 μg). This preliminary study indicates that piperine significantly increased CCM oral absorption, reduced systemic clearance, and improved bioavailability. [ABSTRACT FROM AUTHOR]

The utilization of engineered gold nanoparticles (GNPs) in biomedical applications is experiencing rapid growth owing to their reactive nature and remarkable flexibility. However, despite these advantages, concerns persist regarding their in vivo biocompatibility and cytotoxicity. This study aimed to assess the toxicity, biodistribution, and excretion pathways of GNPs functionalized with various antibiotics, namely, ciprofloxacin, levofloxacin, cefotaxime, and ceftriaxone, using a mouse model. Following intravenous administration, the nanostructures induced an increase in serum enzyme levels and histological abnormalities in the liver, indicating potential hepatotoxic effects. Analysis of organ distribution revealed accumulation primarily in the liver and spleen, with concentrations gradually decreasing 168-h post-administration. Fecal excretion was identified as the primary route of elimination, with a smaller portion excreted via urine. Among the different nanostructures evaluated, those functionalized with levofloxacin (LEV-NP) exhibited minimal organ toxicity and a high clearance rate. Additionally, LEV-NP, with a size of approximately 12 nm, demonstrated superior drug particle stability and lower red blood cell hemolytic activity compared to other nanostructures. [ABSTRACT FROM AUTHOR]

High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4–44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p =.003), and 24-h Na+ excretion was not related with extracellular water volume. In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure. We evaluated sodium intake in 510 subjects by measuring their 24-h sodium excretion to the urine and examined whether sodium intake was related with alterations in cardiovascular function and fluid balance. All participants were without blood pressure lowering medications. Blood pressure was recorded by a device that senses the radial artery pulsations form the wrist. The amount of blood pumped by the heart, the transfer of pressure waves following cardiac contractions and body fluid status were evaluated using bioimpedance, a method recording changes in body electrical resistance. For the analyses, the participants were divided into tertiles according to their 24-h sodium excretions. We also compared results between normotensive and hypertensive subjects. The 24-h sodium excretion in the tertiles corresponded to about 6 g, 9 g and 13 g of salt intake per day, respectively. There were no differences between the tertiles in age, routine laboratory analyses, blood pressure, large arterial stiffness, amount blood pumped by the heart and resistance to blood flow in the arteries. However, there was more extracellular fluid in the highest versus the lowest tertile of sodium excretion. Further statistics indicated that extracellular fluid volume in the body was mainly determined by body size, but it was also moderately influenced by sodium intake. No differences in 24-h sodium excretion and extracellular water volume were found between normotensive and hypertensive participants. In subjects not using blood pressure lowering medications, sodium intake predominantly influences the amount of extracellular fluid without a clear effect on blood pressure. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, it has become increasingly clear that ketone bodies have several functions, such as extending longevity, improving memory, increasing susceptibility to certain cancer therapies, and improving metabolic diseases such as obesity, hypertension, kidney disease, dyslipidemia, and non-alcoholic fatty liver disease. In addition, ketone bodies play a distinctive role in the intestinal epithelium, such as stem cell maintenance, cell proliferation and differentiation, and cancer growth. Through the present study, we found that SLC16a6, mTORC1, and autophagy involve ketone body excretion in the intestinal cells. A better understanding of the ketone body regulatory systems will facilitate the fine-tuning of normal and abnormal intestinal cell adaptation in homeostasis and injury. Ketone bodies serve several functions in the intestinal epithelium, such as stem cell maintenance, cell proliferation and differentiation, and cancer growth. Nevertheless, there is limited understanding of the mechanisms governing the regulation of intestinal ketone body concentration. In this study, we elucidated the factors responsible for ketone body production and excretion using shRNA-mediated or pharmacological inhibition of specific genes or functions in the intestinal cells. We revealed that a fasting-mimicked culture medium, which excluded glucose, pyruvate, and glutamine, augmented ketone body production and excretion in the Caco2 and HT29 colorectal cells. This effect was attenuated by glucose or glutamine supplementation. On the other hand, the inhibition of the mammalian target of rapamycin complex1 (mTORC1) recovered a fraction of the excreted ketone bodies. In addition, the pharmacological or shbeclin1-mediated inhibition of autophagy suppressed ketone body excretion. The knockdown of basigin, a transmembrane protein responsible for targeting monocarboxylate transporters (MCTs), such as MCT1 and MCT4, suppressed lactic acid and pyruvic acid excretion but increased ketone body excretion. Finally, we found that MCT7 (SLC16a6) knockdown suppressed ketone body excretion. Our findings indicate that the mTORC1–autophagy axis and MCT7 are potential targets to regulate ketone body excretion from the intestinal epithelium. [ABSTRACT FROM AUTHOR]

Coincidental with the intensified regulatory and industry focus on the design and conduct of human absorption, metabolism, and excretion (hAME) studies in the past 12 months, we have recently completed our 500th cohort involving radiolabeled test item administration to humans. Here, we build upon a recent industry white paper in this journal1 and share some of our own experiences as a Contract Research Organization based upon collaborations with numerous pharma companies and their differing approaches to design and timing, to add further context to the discussion regarding hAME studies and the pivotal role that drug metabolism and pharmacokinetics plays. In this article, we explore how both changing relationships within the industry and shifting regulatory guidelines are impacting strategies, and compare EU and US pre‐study approval requirements, before evaluating the trends from over 500 studies conducted at our global facilities conducted over more than 30 years. We conclude with a review of how improved technical capabilities and strategies are influencing the design and conduct of hAME studies, before speculating on some of the driving factors which may shape the direction they take in the future. [ABSTRACT FROM AUTHOR]

Solasodine, a steroidal alkaloid, is distributed extensively in Solanaceae plants with multiple biological activities such as neuroprotection, antineoplastic and anticonvulsant activities. However, there is little information about the excretion of intact solasodine in vivo. To investigate its excretion, a reliable LC-MS/MS method for quantitation solasodine in rat urine and feces was established and validated. Sample preparation was carried out by liquid-liquid extraction using MTBE as extractant. Moreover, rat urine was preconditioned with BSA, an anti-adsorptive additive, to prevent the nonspecific binding of solasodine to containers and tubes. The method was validated over the range of 4–2000 ng mL−1. The correlation coefficient (r2) were all above 0.999. The intra- and inter-day precision and accuracy were within 16.9% and between −11.0 and 8.9%, respectively. The recovery of solasodine in urine and feces was in the range of 72.5–80.3 and 75.7–80.2%, respectively. IS-normalized matrix factor ranged from 0.94 to 1.12 with RSD% ≤4.02%. This method was successfully applied to the excretion study of solasodine following oral and intravenous administration. [ABSTRACT FROM AUTHOR]

This study aimed to explore the urinary and biliary excretion of toxic and essential metals in 60 patients diagnosed with liver and biliary diseases and their potential association with hepatic fibrosis. The levels of mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), selenium (Se), manganese (Mn), copper (Cu), and zinc (Zn) in patients' urine and bile samples were determined using inductively coupled plasma-mass spectrometry. To assess hepatic fibrosis, we calculated the Fibrosis-4 (FIB-4) index, a non-invasive measure, using a formula incorporating age, aspartate aminotransferase, alanine aminotransferase, and platelet levels. The median values of biliary (urinary) Hg, Pb, Cd, As, Se, Mn, Cu, and Zn in µg.L-1 were 2.7 (3.6), 1.6 (0.2), 0.126 (1.3), 0.319 (6.3), 14.1 (43.7), 43.4 (4.5), 244.3 (82.9), and 201.6 (692.5), respectively. Biliary levels of Pb, Mn, and Cu were significantly higher than those in urine (p for all <0.001), suggesting that these metals are primarily eliminated through biliary excretion. There was a clear imbalance in the biliary Cu and Zn levels; 33 (~57%) patients had a Cu/Zn ratio >1. FIB-4 index >1.3 was found in 28 patients at risk of liver fibrosis. Analysis of covariance revealed patients with FIB-4 index >1.3 had higher urinary levels of Pb (more than threefold) and Zn (approximately twofold) higher than those with lower FIB-4 scores. Conversely, patients with higher FIB-4 scores had significantly lower biliary levels of Mn (approximately fourfold) and Cu (more than twofold). These findings suggest that imbalances in certain metals may play a pivotal role in the pathophysiology of hepatic fibrosis, warranting further exploration. [ABSTRACT FROM AUTHOR]

A sensitive, rapid, and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the first time to quantify agarotriose (A3) in rat plasma, tissues, urine, and feces. A3 and stachyose (internal standard) were separated by a BEH amide column at 65 °C under the mobile phase of 10 mmol L−1 ammonium acetate-acetonitrile (42:58, v/v) with 350 µL min−1. The acquisition of transitions was carried out in multiple reaction monitoring (MRM) pattern operating with positive ionization at m/z 509.16 ≥ 329.15 for A3 and m/z 689.15 ≥ 527.11 for stachyose. The linearity ranges of A3 were 10 to 5000 nmolL−1 for plasma, 20 to 10000 nmolL−1 for tissues, and 40 to 20000 nmolL−1 for urine and feces. The accuracy and precision ranged from 90.9% to 111.6% and 0.7% to 10.1%, respectively. The stability was between 86.1% and 102.5%. The extraction recovery was consistent and reproducible. The matrix effect ranged from 1.5% to 11.4%. The pharmacokinetic, tissue distribution, and excretion studies were successfully conducted with the validated method. Results showed that A3 could be absorbed by rats, and the absolute bioavailability was 6.7%. Furthermore, it was rapidly distributed in rat tissues and mainly eliminated via feces excretion (67.0%) after oral administration. For intravenous bolus, 85.5% was recovered, and renal excretion was the primary pathway (77.6%) for cumulative recovery. [ABSTRACT FROM AUTHOR]

Novel coronavirus species of public health and veterinary importance have emerged in the first two decades of the twenty-first century, with bats identified as natural hosts for progenitors of many coronaviruses. Targeted wildlife surveillance is needed to identify the factors involved in viral perpetuation within natural host populations, and drivers of interspecies transmission. We monitored a natural colony of Egyptian rousette bats at monthly intervals across two years to identify circulating coronaviruses, and to investigate shedding dynamics and viral maintenance within the colony. Three distinct lineages were detected, with different seasonal temporal excretion dynamics. For two lineages, the highest periods of coronavirus shedding were at the start of the year, when large numbers of bats were found in the colony. Highest peaks for a third lineage were observed towards the middle of the year. Among individual bat-level factors (age, sex, reproductive status, and forearm mass index), only reproductive status showed significant effects on excretion probability, with reproductive adults having lower rates of detection, though factors were highly interdependent. Analysis of recaptured bats suggests that viral clearance may occur within one month. These findings may be implemented in the development of risk reduction strategies for potential zoonotic coronavirus transmission. [ABSTRACT FROM AUTHOR]

The experiment aimed to investigate the effect of different levels of protein on growth performance, metabolic indicators and emission reduction benefits of Australian White growing sheep. Twenty-four Australian White growing sheep with similar growth status and weight (40.03 ± 0.21) kg and in good health were randomly divided into four groups, with six replicates in each group and one sheep in each replicate. The growing sheep in control group were fed with a normal protein level daily diet (12.07%), while the growing sheep in experimental group I were fed with a daily diet with a 1% reduction in standard protein, the growing sheep in experimental group II were fed with a daily diet with a 2% reduction in standard protein, and the growing sheep in experimental group IE were fed with a daily diet with a 4% reduction in standard protein. The pre-test lasted for 10 d, and the formal test lasted for 30 d. The results showed that on 10~20 d, the growing sheep in the experimental group I had the highest average gain. On 30 d, the experimental groups had the greatest reduction in fecal copper and urinary arsenic. The growing sheep in the experimental group II had the greatest reduction in fecal nitrogen, fecal phosphorus, fecal chromium, urinary nitrogen, urinary phosphorus, and urinary copper. The growing sheep in the experimental group IE had the greatest reduction in fecal zinc, fecal cadmium, fecal arsenic and urinary zinc. The study indicates that feeding a daily diet with a 2% reduction in protein content can reduce nitrogen and phosphorus as well as heavy metal emissions without affecting growth indicators and reduce environmental pollution. [ABSTRACT FROM AUTHOR]

The microcirculation is a network of complex vascular structures consisting of arterioles, capillaries, and venules unique to each organ it supports. It is essential for the delivery of oxygen and nutrients to cells and the removal of waste for eventual metabolism and excretion. The microcirculation's anatomical complexity is matched by its numerous physiological functions, which are not limited to its role in the inflammatory response, neurotransmitter functions, and coagulation. With the advancement of technology, we have come to appreciate this unique network and its influences on multiple systems. Its effects on perfusion can now be monitored and visualised to influence decision-making and alter clinical judgement continuously throughout any intervention or management. The need to monitor it independently from the macrocirculation has also been established, as certain disease states can lead to a lack of coherence in the two networks. Although we have learnt much about the microvascular network and its influence on the anaesthesiologist's management of patients, we are yet to determine if closer monitoring of the microvasculature will lead to better patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: ferric carboxymaltose (CF) is an intravenous preparation that helps the rapid correction of anemia with a lower risk of adverse reactions. However, an association has been found between the administration of CF and the development of hypophosphatemia. Case report: we present the clinical case of a 57-year-old patient with a history of iron de-ficiency anemia who, after receiving treatment with CF (Ferinjet®) chronically, develops a clinical of severe muscle weakness. Laboratory tests showed hypophosphatemia, normocalcemia, normal vitamin D level (after correction) and increased renal excretion of phosphorus. After study, the diagnosis of chronic hypophosphatemia secondary to the use of CF is reached. Discussion: CF can cause an increase in FGF-23 which acts at the renal level inducing phosphaturia, which can generate severe hypophosphatemia. This case demonstrates the importance of recognizing and treating this clinical entity in time. [ABSTRACT FROM AUTHOR]