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Recently, solution-based surface-enhanced Raman scattering (SERS) detection technique has been widely recognized due to its cost-effectiveness, simplicity, and ease of use. However, solution-based SERS is limited for practical applications mainly because of the weak adsorption affinity of the target biomolecules to the surface of plasmonic nanoparticles. Herein, we developed a highly sensitive solution-based SERS sensing platform based on mercaptopropionic acid (MPA)-capped silver-coated gold nanostars (SGNS@MPA), which allows efficient enrichment on the nanostars surface for improved detection of an analyte: creatinine, a potential biomarker of chronic kidney disease (CKD). The SGNS@MPA exhibited high enrichment ability towards creatinine molecules in alkaline medium (pH-9) through multiple hydrogen bonding interaction, which causes aggregation of the nanoparticles and enhances the SERS signal of creatinine. The detection limit for creatinine was achieved at 0.1 nM, with a limit of detection (LOD) value of 14.6 pM. As a proof-of-concept demonstration, we conducted the first quantitative detection of creatinine in noninvasive human fluids, such as saliva and sweat, under separation-free conditions. We achieved a detection limit of up to 1 nM for both saliva and sweat, with LOD values as low as 0.136 nM for saliva and 0.266 nM for sweat. Overall, our molecular enrichment strategy offers a new way to improve the solution-based SERS detection technique for real-world practical applications in point-of-care settings and low-resource settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25-24 mM), low detection limit (0.17 mM), and high sensitivity (306 μA mM -1 cm -2 ). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine.

3D printing technologies are an attractive for fabricating electrochemical sensors due to their ease of operation, freedom of design, fast prototyping, low waste, and low cost. We report the fabrication of a simple 3D-printed electrochemical sensing device for non-enzymatic detection of creatinine, an important indicator of renal function. To create the 3D-printed electrodes (3DE), carbon black/polylactic acid (CB/PLA) composite filament was used. The 3DE was activated using 0.5 M NaOH via amperometry prior to use to improve electrochemical performance. To give selectivity for creatinine, the activated 3DE was modified with a copper oxide nanoparticle-ionic liquid/reduced graphene oxide (CuO-IL/rGO) composite. The modified 3DE was characterized using microscopy and electrochemistry. Cyclic voltammetry and amperometry were used to evaluate sensor performance. The modified 3DE provided electrocatalytic activity towards creatinine without enzymes. Under optimal conditions, the modified 3DE directly coupled with a portable smartphone potentiostat exhibited the linear detection range of 0.5-35.0 mM, and the limit of detection was 37.3 μM, which is sufficient for detecting creatinine in human urine samples. Furthermore, the other physiological compounds present in human urine were not detected on the modified 3DE. Therefore, the modified 3DE could be a tool for effective creatinine screening in the urine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gold nanoclusters (AuNCs) are an intensely pursued class of fluorophores with excellent biocompatibility, high water solubility, and ease of further conjugation. However, their low quantum yield limits their applications, such as ultra-sensitive chemical or molecular sensing. To address this problem, various strategies have been adopted for augmenting their fluorescence intensity. Herein, we report a facile and scalable approach for the fluorescence enhancement of bovine serum albumin (BSA) capped AuNCs (BSA-AuNCs) using periodic, close-packed polystyrene colloidal photonic crystals (CPCs). The slow photon effect at the bandgap edges is utilized for the increased light-matter interactions and thereby enhancing the fluorescence intensity of the BSA-AuNCs. Compared to the planar polystyrene control sample, the CPC film yielded a 14-fold enhancement in fluorescence intensity. Further, we demonstrated the as-prepared BSA-AuNCs-CPC as a solid-state platform for the highly sensitive and selective fluorescence turn-off detection of creatinine at nanomolar level., (© 2022 Wiley-VCH GmbH.)

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients ( n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Although various inhibitors have been employed to react with phenylacetaldehyde to form adducts and thus interrupt the formation of 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP), high concentrations of PhIP remain in the final system. It remains unknown whether other critical aldehyde or ketone intermediates are involved in the generation of PhIP, and scavenging these reactive carbonyls simultaneously may achieve higher inhibitory efficiency of PhIP. In this study, reactive carbonyls in a glucose/creatinine/phenylalanine model system were first identified by gas chromatography-mass spectrometry (GC-MS), and then the single and synergistic effects of nonprecursor amino acids (cysteine, methionine, proline, histidine, arginine, and leucine) on scavenging reactive carbonyls were investigated to find out promising combination partners. The obtained results showed that the concentrations of benzaldehyde and phenylacetaldehyde in the glucose/creatinine/phenylalanine model system reached 0.49 ± 0.01 and 6.22 ± 0.21 μg/mL, respectively. Heating these carbonyl compounds in the presence of creatinine resulted in the quantity of PhIP produced increasing linearly with the added quantity of benzaldehyde ( r = 0.9733, P = 0.0002) and phenylacetaldehyde ( r = 0.9746, P = 0.0002), indicating that both compounds are key intermediates for PhIP generation. Among the investigated amino acids, histidine produced the maximum inhibition of PhIP formation (78-99%) in the benzaldehyde/creatinine model system, and proline produced the maximum inhibition of PhIP formation (13-97%) in the phenylacetaldehyde/creatinine model system, where both compounds decreased PhIP formation in a dose-dependent manner. Histidine in combination with proline enhanced the inhibitory effect against PhIP formation at a low addition level, where the highest inhibitory efficiency was obtained using a 1:3 mass ratio of histidine to proline (2 mg/mL in total), reducing PhIP formation by 96%. These findings suggest that histidine-proline combinations can scavenge benzaldehyde and phenylacetaldehyde simultaneously, enhancing the suppression of PhIP formation.

Creatinine level in biological fluids is a clinically relevant parameter to monitor vital functions and it is well assessed that measuring creatinine levels in the human body can be of great utility to evaluate renal, muscular, or thyroid dysfunctions. The accurate detection of creatinine levels may have a critical role in providing information on health status and represents a tool for the early diagnosis of severe pathologies. Among different methods for creatinine detection that have been introduced and that are evolving with increasing speed, fluorescence-based and colorimetric sensors represent one of the best alternatives, thanks to their affordability, sensitivity and easy readability. In this work, we demonstrate that the fluorescein-Au 3+ complex provides a rapid, selective, and sensitive tool for the quantification of creatinine concentrations in ranges typical of sweat and urine. UV-visible absorption, diffuse reflectance spectroscopy, steady state and time resolved fluorescence spectroscopy were used to shed light on the molecular mechanisms involved in the changes of optical properties, which underlie the multiplexed sensor analytical reply. Interestingly, sensing can be performed in solution or on solid nylon support accessing different physiological concentrations from micromolar to millimolar range. As a proof-of-concept, the nylon-based platform was used to demonstrate its effectiveness in creatinine detection on a solid and flexible substrate, showing its analytical colorimetric properties as an easy and disposable creatinine point-of-care test., (© 2022 IOP Publishing Ltd.)

Background: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations., Methods: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa., Findings: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m 2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa., Interpretation: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed., Funding: The GSK Africa Non-Communicable Disease Open Lab., Translations: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests The Ugandan and Malawian study was funded by a project grant from the GSK Africa Non-Communicable Disease Open Lab (project number 8111). CHH received funding from Medical Research Council (MRC) Grant Reference MR/R010161/1. The South African study was jointly funded by the South African MRC, MRC UK (via the Newton Fund), and GSK Africa Non-Communicable Disease Open Lab (via a supporting grant; project number 074). Additional sources of funding for the South African project were obtained from the International Society for Nephrology Clinical Research Program 15–2-015 (Validation of eGFR equations in South Africans; South Africa); the National Health Laboratory Services; and Faculty of Health Sciences Research Incentive Grant (number 0012838434203512110500000000000000004550), University of the Witwatersrand. Funding supported implementation, execution, and completion of the study in Malawi, South Africa, and Uganda., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine sponges, we have investigated the sponge Hemimycale sp. The cytotoxic fraction of the organic extract of the sponge afforded three new compounds, hemimycalins C-E ( 1 - 3 ). Their structural assignments were obtained via analyses of their one- and two-dimensional NMR spectra and HRESI mass spectrometry. Hemimycalin C was found to differ from the reported hydantoin compounds in the configuration of the olefinic moiety at C-5-C-6, while hemimycalins D and E were found to contain an 2-iminoimidazolidin-4-one moiety instead of the hydantoin moiety in previously reported compounds from the sponge. Hemimycalins C-E showed significant antimicrobial activity against Escherichia coli and Candida albicans and cytotoxic effects against colorectal carcinoma (HCT 116) and the triple-negative breast cancer (MDA-MB-231) cells.

Mixed matrix membranes (MMMs) of cellulose acetate/poly(vinylpyrrolidone) (CA/PVP) infused with acid functionalized multiwall carbon nanotubes (f-MWCNTs) were fabricated by an immersion phase separation technique for hemodialysis application. Membranes were characterized using FTIR, water uptake, contact angle, TGA, DMA and SEM analysis. The FTIR was used to confirm the bonding interaction between CA/PVP membrane matrix and f-MWCNTs. Upon addition of f-MWCNTs, TGA thermograms and glass transition temperature indicated improved thermal stability of MMMs. The surface morphological analysis demonstrated revealed uniform distribution of f-MWCNTs and asymmetric membrane structure. The water uptake and contact angle confirmed that hydrophilicity was increased after incorporation of f-MWCNTs. The membranes demonstrated enhancement in water permeate flux, bovine serum albumin (BSA) rejection with the infusion of f-MWCNTs; whereas BSA based anti-fouling analysis using flux recovery ratio test shown up to 8.4% improvement. The urea and creatinine clearance performance of MMMs were evaluated by dialysis experiment. It has been found that f-MWCNTs integrated membranes demonstrated the higher urea and creatinine clearance with increase of 12.6% and 10.5% in comparison to the neat CA/PVP membrane. Thus, the prepared CA/PVP membranes embedded with f-MWCNTs can be employed for wide range of dialysis applications., (Copyright © 2021. Published by Elsevier B.V.)

Objective: This study explored the risk factors influencing the length of hospital stay (LOS) and establish whether the type of anesthesia is independently associated with the LOS in patients after primary unilateral total knee arthroplasty (TKA)., Methods: In this retrospective cohort study, 2309 patients undergoing unilateral TKA were recruited between January 2013 and June 2014 in a tertiary academic medical center in Singapore. Univariate and multivariate linear regression analyses were used to identify the independent risk factors associated with LOS. Besides, subgroup and interaction analyses were performed to evaluate the relationship between the type of anesthesia and LOS., Result: In total, 2309 patients were identified. Out of these, 791 patients underwent general anesthesia, whereas 1518 patients underwent regional anesthesia. Multivariate regression analyses revealed that prolonged LOS was significantly associated with age ≥ 65 years (β = 0.48; 95% CI, 0.09-0.87; P = 0.015), diabetes mellitus (DM) (β = 0.8; 95% CI, 0.33-1.27; P = 0.001), congestive cardiac failure (CCF) (β = 4.1; 95% CI, 2.02-6.17; P < 0.001), perioperative blood transfusion (β = 5.71; 95% CI, 4.86-6.56; P < 0.001), creatinine > 2 mg/dL (β = 4.54; 95% CI, 2.46-6.62; P < 0.001), ASA status (III) (β = 1.72; 95% CI, 0.72-2.71; P = 0.001), general anesthesia (β = 0.78; 95% CI, 0.41-1.66; P < 0.001). The LOS further decreased among participants receiving regional anesthesia at advanced age (age ≥ 65 years) (β = - 1.12; 95% CI, - 1.66 to - 0.58; P < 0.001), patients with BMI ≤ 25 kg/m 2 (β = - 1.92; 95% CI, - 2.73 to - 1.11; P < 0.001) or ≥ 30 kg/m 2 (β = - 0.58; 95% CI, - 1.1 to - 0.06; P = 0.029)., Conclusion: Our findings demonstrated that age ≥ 65 years, DM, CCF, perioperative blood transfusion, creatinine > 2 mg/dL, ASA status (III), general anesthesia are associated with a prolonged LOS after primary TKA. Elderly patients (age ≥ 65 years) and patients with BMI ≤ 25 kg/m 2 or ≥ 30 kg/m 2 receiving regional anesthesia have a further reduced LOS. Therefore, when TKA is performed, priority for regional anesthesia is given to the elderly patients (age ≥ 65 years old) and those with BMI ≤ 25 kg/m 2 or ≥ 30 kg/m 2 ., (© 2021. The Author(s).)

In the current study, a phase inversion scheme was employed to fabricate hydroxyapatite (HA)/polysulfone (PSF)-based asymmetric membranes using a film applicator with water as a solvent and nonsolvent exchanging medium. Fourier Transform Infrared (FTIR) and X-ray diffraction (XRD) spectroscopic studies were conducted to confirm the bonding chemistry and purity of filler. The inherent thick nature of PSF generated sponge-like shape while the instantaneous demixing process produced finger-like pore networks in HA/PSF-based asymmetric membranes as exhibited by scanning electron microscope (SEM) micrographs. The FTIR spectra confirmed noncovalent weak attractions toward the polymer surface. The leaching ratio was evaluated to observe the dispersion behavior of HA filler in membrane composition. Hydrophilicity, pore profile, pure water permeation (PWP) flux, and molecular weight cutoff (MWCO) values of all formulated membranes were also calculated. Antifouling results revealed that HA modified PSF membranes exhibited 43% less adhesion of bovine serum albumin (BSA) together with >86% recovery of flux. Membrane composition showed 74% total resistance, out of which 60% was reversible resistance. Biocompatibility evaluation revealed that the modified membranes exhibited prothrombin time (PT), and thrombin time (TT) comparable with typical blood plasma, whereas proliferation of living cells over membrane surface proved its nontoxic behavior toward biomedical application. The urea and creatinine showed effective adsorption aptitude toward HA loaded PSF membranes., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

The Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline on Chronic Kidney Disease (1) recommends calculating estimated glomerular filtration rate (eGFR) using equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for adults ≥18 years (2) and by the Chronic Kidney Disease in Children (CKiD) for ages <18 years (3). These equations were recommended because they used readily available information, serum/plasma/blood creatinine, plus age, sex, and race for adults, and height for children; and have been validated in large and diverse cohorts of people who had measured glomerular filtration rate (mGFR) as a basis for establishing accuracy., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Reaction mixtures of reactive carbonyls and creatinine were submitted to high temperature and studied to identify the reactive carbonyl(s) responsible for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) formation. MeIQx was produced by reaction of acrolein and creatinine within a wide pH range and with an activation energy of 81.1 ± 1.4 kJ/mol. No additional reactants were required, although methylglyoxal, ammonia, and formaldehyde also participated in the reaction. Nevertheless, these additional reactants were produced in situ from either acrolein or creatinine. A reaction pathway that both explains the formation of MeIQx and is valid for the formation of other heterocyclic aromatic amines (HAAs) with the structure of quinoxaline is proposed. Obtained results demonstrate the key role of reactive carbonyls present in foods (the food carbonylome) on HAA formation. Because creatinine is ubiquitous in proteinaceous foods, the control of the food carbonylome seems to be the key point to control HAA formation in foods., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The formation of chitosan dimer and its interaction with urea and creatinine have been investigated at the density functional theory (DFT) level (B3LYP-D3/6-31++G**) to study the transport phenomena in hemodialysis membrane. The interaction energy of chitosan-creatinine and chitosan-urea complexes are in range -4 kcal/mol < interaction energy <-20 kcal/mol which were classified in medium hydrogen bond interaction. The chemical reactivity parameter proved that creatinine was more electrophilic and easier to bind chitosan than urea. The energy gap of HOMO-LUMO of chitosan-creatinine complex was lower than chitosan-urea complex that indicating chitosan-creatinine complex was more reactive and easier to transport electron than chitosan-urea complex. Moreover, the natural bond orbital (NBO) analysis showed a high contribution of hydrogen bond between chitosan-creatinine and chitosan-urea. The chitosan-creatinine interaction has a stronger hydrogen bond than chitosan-urea through the interaction O18-H34....N56 with stabilizing energy = -13 kcal/mol. The quantum theory atom in molecule (QTAIM) also supported NBO data. All data presented that creatinine can make hydrogen bond interaction stronger with chitosan than urea, that indicated creatinine easier to transport in the chitosan membrane than urea during hemodialysis process., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Creatine kinase (CK) enzyme overexpression has been suggested to play a role in the process of tumorigenesis and metastasis. Cyclocreatine (CCR) is a substrate analog of creatine kinase (CK), where its phosphorylated form is a poor phosphate donor in comparison with native bioenergetic molecule, creatine phosphate (Cr-P). The compound CCR has been shown to markedly inhibit the growth of a broad spectrum of cancers, both in vitro and in vivo. Intracellularly, CCR is phosphorylated by CK to yield a synthetic phosphagen [(N-phosphorylcyclocreatine (CCR ~P)], with thermodynamic and kinetic properties distinct from those of creatine phosphate (Cr-P). Distinct inhibition of tumor growth and metastasis has been attributed to CCR accumulation as CCR ~P in tumor cells, especially in those expressing a high level of CK protein, with minimal adverse effects. Unfortunately, the clinical use of CCR against malignancies is quite limited due to its amphoteric nature, which accounts for most of its extremely low membrane permeability, as well as limited oral bioavailability (BA) and poor systemic pharmacokinetics (PK).Our current work describes the encapsulation of CCR , utilizing freeze and thaw vesicles (FTV )-composed mostly of saturated PC, DOPE, and Chol-into stealth™ liposomes , postcoated with 4.5 M% PEG-PE. Following physicochemical characterization, in vitro release and cellular uptake kinetics confirmed efficient delivery of liposomal CCR (CCR-Lip), leading to intracellular accumulation of its CC-P metabolic product. Successful delivery of CCR to cancer cell effectively depleted low energetic cancer cells of ATP significantly mediating myc-induced metabolic changes. CCR-Lip showed significant antimetastatic and anticancer effectiveness against both MCF-7 and PC-3 human carcinoma models (p < 0.05-0.01), with 4- to 6-fold lower IC50 values vs. closest drug control. Such shift in bioenergetics was coupled via AMPK and phospho-p53 to the mitochondrial apoptosis effector Bak , thus inducing a cell-intrinsic mechanism to counteract uncontrolled neoplastic proliferation, in target cancer cells. Our novel liposomal delivery system of the CCR substrate analog demonstrated strong inhibition of malignant cell bioenergetics, leading to significant antineoplastic and proapoptotic actions, against different cancers.

The COVID-19 pandemic has become a major worldwide crisis. Although respiratory symptoms are a key feature of the disease, many people who are hospitalized with COVID-19 also suffer acute kidney injury, a condition that exacerbates patient mortality and may have to be treated through renal replacement therapy. Much of the focus on hospital capacity during the pandemic has centered on the availability of ventilators. However, supplies for dialysis treatment, including dialysate, have also run dangerously low in hospitals at the epicenter of the pandemic. Therefore, there is an urgent need to develop materials that can efficiently and rapidly regenerate dialysate, removing toxins and restoring electrolyte concentrations so that this vital resource remains readily available. In this work, Ti 3 C 2 T x , a two-dimensional transition-metal carbide (MXene) that is known to efficiently adsorb urea, was used to remove creatinine and uric acid from an aqueous solution and dialysate, with a maximum adsorption capacity of 45.7 and 17.0 mg/g, respectively. We systematically analyzed and modeled the adsorption kinetics, isotherms, and thermodynamics, thus determining the rate-limiting step and adsorption mechanism. A fixed-bed column loaded with Ti 3 C 2 T x was designed to further evaluate the adsorption performance under continuous fluid-flow conditions, mirroring conditions of continuous renal replacement therapy modalities. The maximum capacity and 50% breakthrough volume were calculated to further approach the practical application of Ti 3 C 2 T x for removal of uremic toxins. Our findings suggest that Ti 3 C 2 T x has the potential to be used as an efficient sorbent for the regeneration of dialysate, allowing for accelerated dialysate regeneration by removing filtered toxins and leading to more portable dialysis devices.

Reactions involving reactive carbonyls, creatinine, and ammonia-producing compounds were investigated in order to clarify the formation of the heterocyclic aromatic amine (HAA) 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ). Obtained results showed that MeIQ was only produced when 2-butenal (crotonaldehyde) was present. Reaction yields depended on the pH, with a maximum around pH 6.5, and on concentrations of crotonaldehyde and creatinine. Ammonia was also required for MeIQ formation, but ammonia was produced by creatinine decomposition. The amount of MeIQ formed increased with reaction time, temperature, and oxygen content in the reaction atmosphere. Activation energy for MeIQ formation from crotonaldehyde, creatinine, and glutamine was 72.2 ± 0.4 kJ·mol -1 . A reaction pathway that explains MeIQ formation is proposed. Obtained results suggest a main role of reactive carbonyls formed in foods (the food carbonylome) on HAA formation. In addition, they provide scientific basis for the understanding of how HAAs are formed and could be mitigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The development of wearable artificial kidney demands an efficient dialysate recovery, which relies upon the adsorption process. This study proposes a solution to solve the problem of competitive adsorption between the uremic toxins by employing two adsorptive components in a membrane separation process. Dual-layer hollow fiber (DLHF) membranes, which are composed of a polysulfone (PSf)/activated carbon (AC) inner layer and a PSf/poly(methyl methacrylate) (PMMA) outer layer, were prepared for co-adsorptive removal of creatinine and urea from aqueous solution. The DLHF membranes were characterized in terms of morphological, physicochemical, water transport, and creatinine adsorption properties. The membrane was then subjected to an ultrafiltration adsorption study for performance evaluation. The incorporation of AC in membrane, as confirmed by microscopic and surface analyses, has improved the pure water flux up to 25.2 L/(m 2 h). A membrane with optimum AC loading (9 wt %) demonstrated the highest maximum creatinine adsorption capacity (86.2 mg/g) based on the Langmuir adsorption isotherm model. In the ultrafiltration adsorption experiment, the membrane removed creatinine and urea with a combined average percent removal of 29.3%. Moreover, the membrane exhibited creatinine and urea uptake recoveries of 98.8 and 81.2%, respectively. The combined action of PMMA and AC in the PSf DLHF membrane has made the adsorption of multiple uremic toxins possible during dialysate recovery.

Enterosorbents are widely-used materials for human body detoxification, which function by immobilizing and eliminating endogenous and exogenous toxins. Here, activated carbons, obtained from the lignocellulosic raw vegetal materials of indigenous provenance, have been studied. Walnut shell and wood from local species of nuts and apple-trees were carbonized, and further activated at high temperatures with water vapors in a rotary kiln. A second activation was carried out, in a fluidized bed reactor, but for shorter times. The textural properties of the samples were determined from the adsorption isotherms of nitrogen at 77 K, allowing the obtaining of highly mesoporous materials, while the adsorption capacity permitted an essential rise of six to seven times in the maximal adsorption values of the metabolites, which was determined by the reactivation process. A kinetic study of vitamin B 12 and creatinine immobilization was performed, the optimal immobilization time for the apple-tree wood reactivated carbons being 2 times longer than for those originating from walnut shells. An additional investigation was also performed in specific conditions that simulate the real environment of immobilization: the temperature of a febrile human body (at the temperature T = 38 °C) and the characteristic acidity of the urinary tract and stomach (at the pH of 5.68 and 2.53, respectively). The activated carbonic adsorbents studied here, together with the results of the immobilization studies, show that these procedures can conduct a good incorporation of some endogenous metabolic products, such as vitamin B 12 and creatinine, therefore presenting a good opportunity for their use as forthcoming commercial enterosorbents.

Thermal food processing has many beneficial consequences, although it also produces some unintentional undesired effects, such as the formation of potentially mutagenic and carcinogenic substances. Among them, the formation of heterocyclic aromatic amines (HAAs) has been related to the declared carcinogenicity of processed meats. In spite of this importance, HAA formation pathways remain mostly unknown, which avoids the design of targeted procedures to inhibit HAA appearance. The objective of this review is to collect information recently appeared that allow advancing in the understanding of how these compounds are produced. Particularly, the possibility that aminoimidazoazarenes are produced similarly to PhIP is discussed, including their formation by cyclizations and oligomerizations of aldehydes and creatinine under usual cooking conditions. Present data suggest that HAA formation might be related to the pool of carbonyl compounds existing in foods, the food carbonylome, which can be controlled by carbonyl-trapping agents, such as amine and phenolic compounds., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Creatinine, commonly found in muscle tissue, has been demonstrated as an essential precursor of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) in thermally possessed foods. In this current study, formamide and N-methylformamide were identified as the main thermal degradation products of creatinine. The raised production of PhIP and the decreased level of aldol condensation product occurred simultaneously with the increased addition of formamide in the model system of creatinine and phenylacetaldehyde. It was demonstrated that formamide reacted with the aldol condensation product to close the pyridine ring to form PhIP. The radical pathway of PhIP formation was then proposed and verified by density functional theory (DFT) computation and an ion-trap time-of-flight mass spectrometer (IT-TOF-MS). This is the first report of the role of the creatinine thermal degradation product in the pathway of PhIP formation, which could facilitate potential strategies against the inhibition of PhIP formation in thermally processed foods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Kidneys play a crucial role in maintaining metabolic homeostasis in a body. Serum creatinine concentration is a simple test used as an indicator of renal function. One of the known ways of quantifying creatinine concentration is the liquid chromatography-mass spectrometry (LC-MS) method, using an isotopically labeled analog of creatinine as an internal standard. Unfortunately, such isotope-labeled analogs are expensive and their synthesis is complex. Here we demonstrate a facile preparation of deuterated analogues of creatinine, via the H/D exchange of hydrogens located at the α-carbon (α-C) of the N-methylated amino acid part, under basic conditions. The stability of retrieved isotopologues was analyzed under both neutral or acidic conditions, and the results revealed that the introduced deuterons do not undergo back-exchange. In addition, the coelution of deuterated and non-deuterated forms under acidic and neutral conditions was observed. The prepared isotopologues were successfully applied in the quantitative LC-MS analysis of urine samples, and the results demonstrated that the presented strategy is novel and inexpensive, and that the quantification correlates with the commonly used Jaffe test method.

Calix[4]pyrrole phosphonate-cavitands were used as receptors for the design of supramolecular sensors for creatinine and its lipophilic derivative hexylcreatinine. The sensing principle is based on indicator displacement assays of an inherently fluorescent guest dye or a black-hole quencher from the receptor's cavity by means of competition with the creatinine analytes. The systems were thermodynamically and kinetically characterized regarding their 1:1 binding properties by means of nuclear magnetic resonance spectroscopy ( 1 H and 31 P NMR), isothermal titration calorimetry, and optical spectroscopies (UV/vis absorption and fluorescence). For the use of the black-hole indicator dye, the calix[4]pyrrole was modified with a dansyl chromophore as a signaling unit that engages in Förster resonance energy transfer with the indicator dye. The 1:1 binding constants of the indicator dyes are in the range of 10 7 M -1 , while hexylcreatinine showed values around (2-4) × 10 5 M -1 . The competitive displacement of the indicators by hexylcreatinine produced supramolecular fluorescence turn-on sensors that work at micromolar analyte concentrations that are compatible with those observed for healthy as well as sick patients. The limit of detection for one of the systems reached submicromolar ranges (110 nM).

Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π-π interaction. First, Kevlar nanofiber-graphene oxide (K-GO) beads are produced by liquid-liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K-GO interface by π-π interaction and initiated to achieve the composite gel (K-GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K-GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π-π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.

A low-cost and disposable microcell was constructed with a screen-printed electrode for the non-enzymatic electrochemical determination of creatinine. The working electrode was modified with carbon black and maintained in contact with paper-adsorbed iron (III) ions. A small sample volume of 3 μL was required for the device operation. Then, iron (III) ions were complexed in the presence of creatinine in a chemical step, followed by an electrochemical reduction of non-complexed metallic ions in excess. Cyclic voltammetry and differential-pulse voltammetry experiments were employed for the electrochemical characterizations and analytical performance evaluation of the microcell. The working electrode modification with carbon black provided a significant increase of analytical signal. The sensor presented a linear response for creatinine concentrations ranging from 0.10 to 6.5 mmol L -1 , with a limit of detection of 0.043 mmol L -1 . Experiments for creatinine determination in real samples were successful performed through of standard recovery in urine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Determination of urinary retinol, which is a new promising early biomarker of renal damage typically expressed in the clinical environment as retinol/creatinine ratio, is currently difficult to accomplish. We have developed and validated the new ultra-high-performance liquid chromatography method with UV and mass spectrometry detection for the separation and quantification of retinol and creatinine in human urine in a single run. The separation of these two substances with completely different physicochemical properties was achieved using a column packed with fluorinated stationary phase and acetonitrile and aqueous ammonium formate buffer as the mobile phases. The separation was completed within 4 min. Our new method involves very fast and simple sample preparation requiring small amount of sample matrix and solvents. Deuterium labeled internal standard was used for the more precise quantification. The method was tested with real-life samples using urine collected from patients suffering from breast, colorectal, head, and neck cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study evaluated the possible ameliorative efficacy of selenium nanoparticles (SeNPs) on AlCl 3 -induced hepatorenal injury in rats. Animals were randomly divided into four groups (n = 6): group 1, the control; group 2, received SeNPs (0.4 mg/kg b.wt) for 21 days; group 3, injected with three doses of AlCl 3 intraperitoneally (30 mg/kg/body weight) every 5 days; group 4, received SeNPs for 7 days prior to AlCl 3 and then received SeNPs concurrently with AlCl 3 for the following 14 days. It was observed that AlCl 3 increased the levels of AST, ALT, ALP, LDH, total bilirubin, creatinine, urea, uric acid, and MDA significantly; as well as the reduction in the levels of GSH, SOD, GPx stores in comparison with the control group. These biochemical alterations were accompanied and confirmed by the lesion appeared in histological sections in addition to the increase in the expression of caspase-3 and the decrease of the Bcl-2expression. Treatment with SeNPs ameliorates the hepatorenal dysfunction, replenishes the endogenous antioxidant system, downregulates the expression of caspase-3, and upregulates the expression of Bcl-2. This hepatorenal ameliorative role may be due to the ability of SeNPs to equilibrate the oxidant/antioxidant system besides its ability to attenuate apoptosis process.

We report a novel amperometric flow-injection (FI) analysis of creatinine based on a sensor comprising copper oxide nanoparticles (CuO) coated with a molecularly-imprinted polymer (CuO@MIP) and decorating a carbon-paste electrode (CPE) to form the CuO@MIP/CPE electrode. The CuO@MIP was synthesized by using CuO as the supporting core, creatinine as the template, methacrylic acid (MAA) as monomer, N, N'-(1,2-dihydroxyethylene)bis(acrylamide) (DHEBA) as cross-linker, and 2,2'-azobis (2-methylpropionitrile) (AIBN) as initiator. Morphology and structural characterization reveal that CuO nanoparticle imprinted sites (CuO) synthesized using a precipitation method, exhibits features that are well suited to creatinine detection: high surface area, good analyte diffusion and adsorption characteristics that provide shorter response times, and large numbers of specific cavities for enhanced analyte capacity and sensitivity. Cyclic voltammetric measurements indicate that our sensor provides excellent performance toward electro-oxidation of creatinine. The amperometric FI system was used to quantitatively determine creatinine at the CuO@MIP/CPE sensor, in a phosphate buffer carrier. The imprinted sensor exhibits excellent performance for creatinine oxidation at an applied potential of +0.35 V and flow rate of 0.6 mL.min -1 . The as-prepared sensor exhibits a linear dynamic range for creatinine detection from 0.5 to 200 μM (r 2  = 0.995) with a limit of detection of 0.083 μM (S/N = 3). The system exhibits satisfactorily good precision (%RSD = 1.94%, n = 30) and selectivity toward creatinine. There is only approximately 20% loss from initial response after 2 weeks when stored at 4 o C. We successfully applied the FI detection system to detect creatinine in human urine samples., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Indoor air pollution is an important risk factor for the generation of lung diseases in developing countries. The indigenous population is particularly susceptible to be exposed to the mixture of pollutants from the biomass burning, among them, polycyclic aromatic hydrocarbons (PAHs). The objective of this study was to assess respiratory health and exposure to PAHs in indigenous populations of the Huasteca Potosina in Mexico. The urinary metabolite 1-hydroxypyrene (1-OHP) was evaluated by HPLC with fluorescence detector, the forced expiratory volume in one second (FEV 1 ) and the FEV 1 /FVC ratio (forced vital capacity) by spirometry in the Teenek indigenous adult population of the communities from Tocoy (TOC), Xolol (XOL), and Tanjajnec (TAN). A total of 134 subjects participated in the study: 64 from TOC, 30 from XOL, and 40 from TAN; in all the communities, high percentages of overweight and obesity were presented (from 50 to 73%). The average hours of firewood usage per year were 281.06, 284.6, and 206.6 in TOC, XOL, and TAN, respectively. The average of the three communities of the % FEV 1 post-bronchodilator was 86.1%. There were identified from 4.5 to 6.6% and from 12.5 to 15.5% of spirometric obstructive and restrictive patterns respectively, in all communities. The highest exposure levels reported as median were found in TOC (1.15 μmol/mol of creatinine) followed by TAN (0.94 μmol/mol of creatinine) and XOL (0.65 μmol/mol of creatinine). Considering the magnitude of the indigenous population exposed to pollutants from the biomass burning and the possible effects on respiratory health, it is important to design strategies that mitigate exposure and evaluate the effectiveness through biological monitoring and effects.

Ambient ionization in open environment brings a capability of a coupled mass spectrometry to detect target molecules in situ. However, it is limited to qualitative and semi-quantitative analysis. By coupling of an ambient ionization-based Direct Analysis in Real Time (DART) with high-resolution quadrupole time-of-flight mass spectrometry (QTOF/MS), we observe that, in one-chemical system, the target molecule displays a non-linear response in MS signal vs concentration, accompanying with large variation in MS signal, suggesting two obstacles for quantification to be overcome. Surprisingly, in a two-chemical system, we observe an apparent suppression effect. We prove that, due to this observed suppression effect, a fluctuant response in the MS signal of the stable isotope-labeled analogue can immediately reflect the change in the analyte concentration and ionization efficiency. For example, by taking advantage of this effect, even the analyte of different concentrations despairingly displayed similar signals would be accurately calibrated through the suppression of the internal stable isotope standard. This puts an important foundation on accurate and linear quantitation of analytes in complex matrix using DART-MS assay. Moreover, we for the first time demonstrate an application of in situ calibration of DART-MS for direct and accurate quantification of target molecule (creatinine) in highly complex samples (human urine) without any pre-separation. The quantification is also validated using HPLC-UV analysis (n = 38). At last, we show that stable isotope-labeled-creatinine (m/z 117.0850 amu) can be used for simultaneous in situ calibration of some other urinary metabolites with a mass/charge ratio varying from 120.069 amu to 333.125 amu., (Copyright © 2019. Published by Elsevier B.V.)

A simple and rapid HPLC-MS/MS method was developed and validated for simultaneous measurement of phosphocreatine and its metabolites creatine and creatinine in children's plasma. A 50 μL aliquot of plasma was prepared by protein precipitation with acetonitrile-water (1000 μL, 1:1, v/v) followed by separation on a Hypersil Gold C 18 column (35°C) with gradient mobile phase consisting of 2 mm ammonium acetate aqueous solution (pH 10) and methanol at a flow rate of 0.3 mL/min and analyzed by mass spectrometry in both positive (phosphocreatine) and negative (creatine and creatinine) ion multiple reaction monitoring mode. Good linearity (r > 0.99) was obtained for the three analytes. The intra-day and inter-day values of CV were <5.46% (-13.09% ≤ RE ≤ 2.57%). The average recoveries of the three analytes were 70.9-97.5%. No obvious impact was found for the quantitation of three analytes in normal, hemolyzed and hyperlipemic plasma. In the end, this method was successfully applied to a pharmacokinetic study of phosphocreatine in children (six cases) with viral myocarditis of children after intravenous infusion of 2 g of the test drug. The pharmacokinetc parameters of phosphocreatine/creatine were as follows: t 1/2 0.24/0.83 h, T max 0.49/0.55 h, C max 47.34/59.29 μg/mL, AUC last 17.07/59.63 h μg/mL, AUC inf 17.16/79.01 h μg/mL and MRT 0.29/0.67 h., (© 2019 John Wiley & Sons, Ltd.)

On incidence of kidney failure, the concentration of urea increases and there is need for patients to visit the hospital all through the week for blood purification. However, current hemodialysis has been found to reduce only 66-75% urea in the blood of patients. The main goal of this article is to observe the effect of biocompatible and high mechanical hemodiafiltration in reducing urea and creatinine within the shortest time frame, using two methods of Nano electrospinning fiber (hybrid and coaxial). Hybrid electrospinning was made by zeolite 940-HOA(beta), Fe 3 O 4 , polyacrylonitrile as well as the addition of nettle plant's leaf extract. Dispersing solution and enzymes were added to two different syringes and was used in making hybrid nanofibers by the electrospinning process. Nessler's Reagent adsorption method was used for measuring the concentration of ammonia after urease enzyme activation. Second coaxial filter was made by the core-shell electrospinning system and cellulose acetate phthalate (CAP) as well as polyurethane (PU) were utilized. The data show hybrid hemodiafiltration with enzyme coating, decomposed urea and enzymes were activated for two days after electrospinning. The core-shell filtration can also reduce creatinine. Core-shell CAP-PU nanofiber was previously used for intravaginal drug delivery and PU was used as an artificial renal microfluidic chip. Thus, our study focused on using CAP-PU to reduce creatinine in dialysis patients. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1736-1743, 2019., (© 2019 Wiley Periodicals, Inc.)

Mimicking the structures and functions of biological systems is considered as a promising approach to construct artificial materials, which have great potential in energy, the environment, and health. Here, we demonstrate a conceptually distinct design by synergistically combining a kidney-inspired porous membrane and natural sponge-inspired heterostructured nanoporous particles to fabricate a bioinspired biomolecule cleaning device, achieving highly efficient biomolecule cleaning spanning from small molecules to macromolecules. The bioinspired biomolecule cleaning device is a two-layer microfluidic device that integrates a polyamide porous membrane and heterostructured nanoporous poly(acrylic acid)-poly(styrene divinylbenzene) particles. The former as a filtration membrane isolates the upper sample liquid and the latter fixed onto the bottom of the underlying channel acts as an active sorbent, particularly enhancing the clearance of macromolecules. As a proof-of-concept, we demonstrate that typical molecules, including urea, creatinine, lysozyme, and β2-microglobulin, can be efficiently cleaned from simulant liquid and even whole blood. This study provides a method to fabricate a bioinspired biomolecule cleaning device for highly efficient biomolecule cleaning. We believe that our bioinspired synergistic design may expand to other fields for the fabrication of integrated functional devices, creating opportunities in a wide variety of applications.

Creatine transporter deficiency (CTD) is caused by a defect in the X-linked creatine transporter SLC6A8 gene leading to severe neurologic and physiologic conditions. Cyclocreatine and phosphocyclocreatine supplementation is seen as a potential treatment, but the presence of these compounds within commercially available dietary supplements presents the risk of self-medication. High-performance liquid chromatography-mass spectrometry (HPLC-MS) is an excellent technique to assess composition of complex amino acid mixtures. Herein, we have developed a facile HPLC-MS method using a cyano column in hydrophilic interaction liquid chromatography (HILIC) mode with isocratic elution over 4 min to identify the main components of two commercially available dietary supplements. The relative standard deviation (RSD) for retention time and extracted ion integrated area are <0.3% and 4%, respectively, showing excellent reproducibility. Cyclocreatine and phosphocyclocreatine were not detectable within the dietary supplements, even at ppm levels, demonstrating the power and importance of the developed HPLC-MS method in analyzing complex mixtures.

A rapid, single-point method for colorimetric creatinine determination has been developed as an alternative for a well-established Jaffé assay, which lacks analytical specificity. 3,5-dinitrobenzoic acid was employed in an alkaline environment as a chromophore instead of picric acid. Apart from the spectrophotometer, a simple optoelectronic detector was applied as an alternative detection method. The conditions of the reaction were optimized to provide satisfactory analytical parameters. The linear ranges of the proposed assays were 40-4000 and 10-300 µmol L -1 of creatinine for conventional spectrophotometry and a PEDD detector, respectively. A broad spectrum of potential interferents was examined. The presence of compounds such as glucose, urea or uric acid was the source of a significantly smaller bias in the examined method than in the case of the Jaffé method variants. The presented method was validated with the use of 10 human urine samples with the creatinine level determined by the recommended method. Two-tail paired Student's t-tests with 9 degrees of freedom at the 95% confidence level showed the agreement between the proposed and the reference methods., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The importance of knowing creatinine levels in the human body is related to the possible association with renal, muscular and thyroid dysfunction. Thus, the accurate detection of creatinine may indirectly provide information surrounding those functional processes, therefore contributing to the management of the health status of the individual and early diagnosis of acute diseases. The questions at this point are: to what extent is creatinine information clinically relevant?; and do modern creatinine (bio)sensing strategies fulfil the real needs of healthcare applications? The present review addresses these questions by means of a deep analysis of the creatinine sensors reported in the literature over the last five years. There is a wide range of techniques for detecting creatinine, most of them based on optical readouts (20 of the 33 papers collected in this review). However, the use of electrochemical techniques (13 of the 33 papers) is recently emerging in alignment with the search for a definitive and trustworthy creatinine detection at the point-of-care level. In this sense, biosensors (7 of the 33 papers) are being established as the most promising alternative over the years. While creatinine levels in the blood seem to provide better information about patient status, none of the reported sensors display adequate selectivity in such a complex matrix. In contrast, the analysis of other types of biological samples (e.g., saliva and urine) seems to be more viable in terms of simplicity, cross-selectivity and (bio)fouling, besides the fact that its extraction does not disturb individual's well-being. Consequently, simple tests may likely be used for the initial check of the individual in routine analysis, and then, more accurate blood detection of creatinine could be necessary to provide a more genuine diagnosis and/or support the corresponding decision-making by the physician. Herein, we provide a critical discussion of the advantages of current methods of (bio)sensing of creatinine, as well as an overview of the drawbacks that impede their definitive point-of-care establishment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A new disposable microfluidic electrochemical paper-based device (ePAD) consisting of two spot sensors in the same working electrode for the simultaneous determination of uric acid and creatinine was developed. The spot 1 surface was modified with graphene quantum dots for direct uric acid oxidation and spot 2 surface modified with graphene quantum dots, creatininase and a ruthenium electrochemical mediator for creatinine oxidation. The ePAD was employed to construct an electrochemical sensor (based on square wave voltammetry analysis) for the simultaneous determination of uric acid and creatinine in the 0.010-3.0 µmol L -1 range. The device showed excellent analytical performance with a very low simultaneous detection limit of 8.4 nmol L -1 to uric acid and 3.7 nmol L -1 to creatinine and high selectivity. The ePAD was applied to the rapid and successful determination of those clinical biomarkers in human urine samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The polysaccharide, inulin, is considered the clinical gold standard for measuring glomerular filtration rate (GFR), an assessment of kidney filtering capacity and renal function, and therefore, is a prognostic indicator of chronic kidney disease (CKD). The classic method of measuring GFR is laborious, tedious and invasive. Therefore, estimated GFR (eGFR) has become the favoured measurement, but unfortunately suffers in its accuracy. Here, we describe the development of a near infrared dye-labeled inulin, Cy7.5-inulin conjugate, for use as an optical probe to accurately and non-invasively measure GFR in patients by transcutaneous pulse dye densitometer (TPDD). We have characterized the modifications made to inulin and the dye-polysaccharide conjugate by a number of analytical techniques and demonstrated that it is stable under experimental in vivo conditions. To this end, the probe has been successfully used in a pig model to accurately measure GFR non-invasively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hemodialysis is one of the earliest artificial kidney systems, which removes uremic toxins through using a semipermeable porous membrane. Current report focuses on designation of metal organic framework (MOF) based zirconium@cotton fabric composite and its application in kidney dialysis. UiO-66-(COOH) 2 as MOF material was directly grown within cotton fabric. Fabric was firstly reacted with benzene tetra carboxylic acid forming ester and then Zr was interacted with the free carboxylic groups in the formed ester to produce UiO-66-(COOH) 2 @cotton fabric composite. The obtained composite was characterized by using electron microscope, X-ray diffraction, infrared spectroscopy and colorimetric data. After modification with MOF, fabric was acquired yellowish color. The prepared composite was used in potential kidney application through studying the removal of creatinine from mimic blood. The maximum adsorption capacity of creatinine was 113.6 and 192.3-212.8 mg/g for pristine fabric and UiO-66-(COOH) 2 @fabric composite, respectively. From adsorption data, creatinine adsorption onto composite was followed to pseudo-second order kinetic model and Langmuir isotherm profile. After three regeneration cycles, the applied composite still achieved substantial adsorption capacity by removing of 82% from creatinine. UiO-66-(COOH) 2 @cotton could be considered as successful adsorbent capable of removing creatinine from blood with good reusability, which can be applied in kidney dialysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Renal dynamic contrast-enhanced (DCE) MRI provides information on renal perfusion and filtration. However, clinical implementation is hampered by challenges in postprocessing as a result of misalignment of the kidneys due to respiration. We propose to perform automated image registration using the fat-only images derived from a modified Dixon reconstruction of a dual-echo acquisition because these provide consistent contrast over the dynamic series., Methods: DCE data of 10 hypertensive patients was used. Dual-echo images were acquired at 1.5 T with temporal resolution of 3.9 s during contrast agent injection. Dixon fat, water, and in-phase and opposed-phase (OP) images were reconstructed. Postprocessing was automated. Registration was performed both to fat images and OP images for comparison. Perfusion and filtration values were extracted from a two-compartment model fit., Results: Automatic registration to fat images performed better than automatic registration to OP images with visible contrast enhancement. Median vertical misalignment of the kidneys was 14 mm prior to registration, compared to 3 mm and 5 mm with registration to fat images and OP images, respectively (P = 0.03). Mean perfusion values and MR-based glomerular filtration rates (GFR) were 233 ± 64 mL/100 mL/min and 60 ± 36 mL/minute, respectively, based on fat-registered images. MR-based GFR correlated with creatinine-based GFR (P = 0.04) for fat-registered images. For unregistered and OP-registered images, this correlation was not significant., Conclusion: Absence of contrast changes on Dixon fat images improves registration in renal DCE MRI and enables automated postprocessing, resulting in a more accurate estimation of GFR. Magn Reson Med 80:66-76, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Nutritional status could affect arsenic metabolism and toxicity in the general population chronically exposed to low levels of inorganic arsenic. In this study, we examined the association of serum folate and cobalamin with urinary concentrations of dimethylarsinic acid (DMA), the most abundant metabolite of inorganic arsenic measured in urine, in children and adults who participated in the 2003-2006 US National Health and Nutrition Examination Surveys. A total of 1161 children (aged 6-19 years) and 1938 adults (aged 20-85 years) were analyzed for the association using multivariate general linear models, adjusting for potential confounders. We observed a positive association between serum levels of folate and cobalamin and creatinine-corrected urinary concentrations of DMA in both children and adults. Furthermore, serum levels of folate and cobalamin were inversely associated with homocysteine (Hcy). These results suggest that dietary intake of folate and cobalamin may exhibit protective functions against arsenic toxicity by increasing arsenic metabolism to the less toxic metabolite DMA and decreasing serum levels of Hcy.

Abamectin (ABM) is a widely utilized potent anthelmintic and insecticidal agent. In this study, we investigated the protective effects of caffeic acid phenethyl ester (CAPE) and betaine (BET) against ABM-induced hepatotoxicity and nephrotoxicity in rats. Forty rats were divided into five groups, receiving either oral saline solution (normal control), oral ABM at a dose of 2 mg/kg BW (1/5 LD50), CAPE (10 μmol/kg BW intraperitoneally) followed by ABM, or BET supplementation at a dose of 250 mg/kg BW followed by ABM administration, while group V rats received a combination of i.p. CAPE and oral BET in the same doses before receiving ABM. Biochemical analysis showed that ABM administration significantly (p < 0.05) increased serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, and cholesterol, as well as serum creatinine and urea. Compared to the control group, ABM-intoxicated rats had significantly (p < 0.05) higher tissue concentrations of nitric oxide and malondialdehyde, as well as lower tissue glutathione concentration, total antioxidant capacity, and antioxidant enzymatic activity (glutathione peroxidase, superoxide dismutase, and catalase). Histopathological examination of hepatic and renal tissues of ABM-intoxicated rats showed acute inflammatory and necrotic changes. Pretreatment with CAPE and/or BET reversed the biochemical and histopathological alterations of ABM on the liver and kidneys. Therefore, CAPE and BET (alone or in combination) could be promising protective agents against ABM-induced hepatotoxicity and nephrotoxicity. Future studies should confirm our findings and evaluate the other molecular effects are involved in the combination chemoprotection of CAPE and BET.

In order to define the normal composition of canine amniotic fluid and to detect differences between surviving and non-surviving newborn puppies, the present study determined the uric acid, glucose, lactate and creatinine concentrations and the lactate to creatinine ratio in amniotic fluids collected during elective Caesarean section from small-sized purebred bitches. The possible relationship between newborn survival and the studied parameters, as well as the effects of maternal parity, fetal gender and Apgar score were assessed. The study enrolled 27 small-sized purebred bitches submitted to elective Caesarean section at term. After opening the fetal membranes, amniotic fluid samples were collected aseptically from the amniotic sac of each fetus. The data obtained from 74 amniotic fluid samples collected from 27 bitches showed that amniotic glucose concentration was lower (P < 0.05) in non-surviving than in surviving puppies. Within the normal, surviving puppies, amniotic glucose concentration was higher (P < 0.05) in male than in female newborns, and the lactate/creatinine ratio was significantly higher in multiparous than in primiparous bitches (P < 0.05). These preliminary results demonstrate the relevance of amniotic glucose, but not of uric acid, lactate, creatinine and the lactate to creatinine ratio for detecting puppies at risk of death immediately after birth.

Organic chloramines can interfere with the measurement of effective combined chlorine in chlorinated water and are potential intermediate products of highly toxic disinfection by-products (DBPs). In order to know more about the degradation and transformation of organic chloramines, a typical organic chloramine precursor creatinine was selected for investigation and a corresponding individual organic chloramine chlorocreatinine was prepared in this study. The preparation condition of chlorocreatinine by chlorination was established as chlorine/creatinine = 1 M/M, reaction time = 2 h and pH = 7.0. Then the degradation kinetics of chlorocreatinine during further chlorination was studied, and a second-order rate constant of 1.16 (±0.14) M -1 s -1 was obtained at pH 7.0. Solution pH significantly influenced the degradation rate, and the elementary rate constants of chlorocreatinine with HOCl+H + , HOCl, OCl - and chlorocreatinine - with OCl - were calculated as 2.43 (±1.55) × 10 4  M -2  s -1 , 1.05 (±0.09) M -1 s -1 , 2.86 (±0.30) M -1 s -1 and 3.09 (±0.24) M -1 s -1 , respectively. Besides, it was found that chlorocreatinine could be further converted into several C-DBPs (chloroform and trichloroacetone) and N-DBPs (dichloroacetonitrile (DCAN) and trichloronitromethane (TCNM)) during chlorination. The total yield of DBPs increased obviously with increasing pH, especially for TCNM. In addition, the presence of humic acid in creatinine solution could increase the formation of DCAN obviously during chlorination. Based on the UPLC-Q-TOF-MS analysis, the conversion pathways of chlorocreatinine were proposed. Several kinds of intermediate products were also identified as organic chloramines and some of them could even exist stably during the further chlorination., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Creatinine was found to not only act as a precursor of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) formation but also inhibit PhIP formation in a creatinine/phenylalanine model system. The dual mechanistic effects of creatinine on PhIP formation were then investigated in a model system. Adducts of creatinine-PhIP were detected by quadrupole-time-of-flight mass spectrometry and were found to be a likely explanation for the substantial decrease in the yield of PhIP when excess creatinine was supplied. Structures of probable adducts were predicted in molecular docking studies, which showed that hydrogen bonds were formed between creatinine and PhIP in 1:1 and 2:1 ratios. Furthermore, the active sites during creatinine-PhIP adduct formation (the primary amino groups [N 2 -] and sp 2 nitrogen atoms [N 3 ] of creatinine and PhIP) match the active sites of PhIP metabolism and adducts of PhIP/lipid-derived reactive carbonyls. This verifies that creatinine inhibits PhIP production via the formation of adducts with hydrogen bonds at the N 2 and N 3 sites., Practical Application: This study enhances the understanding of how creatinine affects PhIP formation, reveals a new PhIP inhibition mechanism, and will be useful for developing technology to control PhIP formation during food processing., (© 2018 Institute of Food Technologists®.)

Phenolics can act as either promoters or inhibitors in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation. In an attempt to clarify the structure-activity relationship (SAR) of phenolics for this reaction, the formation of PhIP in mixtures of phenylalanine, creatinine, 13-hydroperoxide of linoleic acid (LOOH) or 4-oxo-2-nonenal, and a wide array of phenolics was studied in the presence and in the absence of oxygen. The obtained results suggested that those phenolics having a high carbonyl scavenging ability inhibited the formation of PhIP. On the other hand, those phenolics that mainly acted as free radical scavengers and, therefore, were easily converted into quinones promoted the formation of PhIP. Phenolics of the first type were m-diphenols and 1,3,5-triphenols. Phenolics of the second type were o- and p-diphenols. Other phenolics, like 1,2,3- and 1,2,4-triphenols, exhibited a behavior either as carbonyl scavengers or as free radical scavengers depending on ring substitutions. Among the studied derivatives, the presence of a carboxylic or a methoxyl group at certain positions inhibited their behavior as carbonyl scavengers and, therefore, promoted the formation of PhIP. A procedure to classify phenolics as either carbonyl or free radical scavengers is proposed.

The effect of reducing sugars on formation of PhIP in fried pork was investigated, and the underlying mechanisms were revealed by studying the reaction pathways between α-dicarbonyl compounds (α-DCs) and PhIP. The addition of reducing sugars (such as glucose) greatly reduced the amount of PhIP in fried pork from 15.5 ng/g to less than 1.0 ng/g. The amount of PhIP decreased significantly with an increasing level of added α-DCs in model systems. Similarly, the addition of methylglyoxal (MGO) decreased significantly the levels of phenylalanine (Phe) and creatinine (Crn) but increased significantly the level of phenylacetaldehyde (PEA). 2-Amino-1-methyl-5-(2-oxopropylidene)-imidazol-4-one and N-(1-methyl-4-oxoimidazolidin-2-ylidene) amino propionic acids were identified in MGO/Crn and MGO/Crn/Phe model systems and fried pork with glucose. These results revealed that the degradation products of reducing sugars-α-DCs-play an important role in inhibiting formation of PhIP by reacting with key precursors of PhIP and itself.