Search

Objective: Previous studies have shown that damage occurs to internal genital tract during hysterosalpingography (HSG). The aim was to show that endometrial and tubal epithelium underwent free radical damage during HSG in an animal model. Material and Methods: Forty rats were evaluated in five different groups. Two groups received ionizing radiation (15-20 miliRad three times) only. Two further groups received ionizing radiation in combination with iohexol (1-2 mL). The remaining group served as control. Groups were evaluated after seven and forty-two days. Inflammation and cellular changes were evaluated histopathologically. Cellular activity of antioxidant enzymes was assessed immunohistochemically. Results: Inflammation, and cellular changes were detected at certain rates in all groups (p<0.001). Glutathione reductase, catalase, superoxide dismutase, glutathione S-transferase activities were found to be increased after the HSG (p<0.001). Conclusion: It is obvious that the cell suffers acute and chronic damage during HSG due to both radioactivity and chemicals. Although there is a lot of research done before, there is no definitive method yet to protect against the harmful effects of iodinated contrast agents and ionizing radiation. So, new methods need to be explored to protect cells and tissues from reactive oxygen radical damage caused by HSG. [ABSTRACT FROM AUTHOR]

Copyright of Namık Kemal Tıp Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol.Methods: Carboplatin was administered IV to female mice at 60 mg/kg with or without iohexol at 300 mg/kg. Plasma ultrafiltrate, kidney and bone marrow platinum was quantitated by atomic absorption spectrophotometry. Paclitaxel microsomal and gemcitabine cytosolic metabolism as well as metabolism of CYP and UGT probes was assessed with and without iohexol at 300 µg/mL by LC-MS/MS.Results: In vivo carboplatin exposure was not significantly affected by iohexol co-administration (platinum AUC combination vs alone: plasma ultrafiltrate 1,791 vs 1920 µg/mL min; kidney 8367 vs 9757 µg/g min; bone marrow 12.7 vs 12.7 µg/mg-protein min). Paclitaxel microsomal metabolism was not impacted (combination vs alone: 6-α-OH-paclitaxel 38.3 versus 39.4 ng/mL/60 min; 3-p-OH-paclitaxel 26.2 versus 27.7 ng/mL/60 min). Gemcitabine human cytosolic elimination was not impacted (AUC combination vs gemcitabine alone: dFdU 24.1 versus 23.7 µg/mL/30 min). Iohexol displayed no relevant inhibition of the CYP and UGT enzymes in human liver microsomes.Conclusions: Iohexol is unlikely to affect the clinical pharmacokinetics of carboplatin, paclitaxel, gemcitabine, or other agents used in combination with carboplatin treatment. Measuring GFR with iohexol to better dose carboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions. [ABSTRACT FROM AUTHOR]

• Iohexol as a marker of GFR. • Optimization, matrix effect and stability of iohexol. Determination of glomerular filtration rate (GFR) is considered the best indicator of renal function. Iohexol, a non-ionic contrast agent, is currently considered to be a reference marker since it meets all the requirements of an ideal GFR marker. The aim of our work is to develop and optimize a method for iohexol measurement by HPLC-UV. The results showing the following optimal conditions : a mobile phase with water and 5% of acetonitrile, a C18 analytical column (250 × 4 mm, 5 μm particle size) with a temperature of 40 °C and a flow rate of 1 ml/min. Serum samples are deproteinized by addition of perchloric acid (6%), while urine samples are only diluted. For both matrices, the method is linear (r2 > 0.99) and the recovery is > 98%. For selectivity, no interfering endogenous components at the retention time of iohexol was observed. The results of the matrix effect showed a clinically acceptable variation in most concentration levels except for 100 μg/mL, in urine, where the effect was slightly present. Iohexol stability in urine decreases significantly only after 3 freeze–thaw cycles and after freezing at −80 °C for two months. According to those findings results this method is simple, specific, linear, precise and robust, which allows its application for the direct measurement of the GFR after its analytical validation. [ABSTRACT FROM AUTHOR]

Chronic kidney disease of unknown aetiology (CKDu), which is widespread in the North Central Province (NCP) of Sri Lanka, is not associated with commonly known factors such as diabetes, hypertension, and glomerulonephritis. The pathogenicity of CKDu is not well understood, but people with a low body mass index (BMI) and mineral and nutrient deficiencies are more vulnerable to develop CKDu. To understand this situation, the relationship between BMI and the estimated glomerular filtration rate (eGFR) was investigated in people with CKDu in comparison with unaffected age-matched control groups in disease-endemic areas of the NCP. This community-based cross-sectional study was performed in Medirigiriya in the Polonnaruwa district of Sri Lanka, which has one of the highest densities of patients with CKDu. The data for identifying demographic factors and the relationship between CKDu and BMI were investigated by using a validated survey questionnaire. Findings indicated that the group with the highest number of people affected with CKDu (i.e. eGFR of less than 60 mL/min/1.73 m2) had the lowest BMI compared to those with normal eGFR. The majority affected were male farmers. The severity of the disease was inversely associated with BMI values and had a higher prevalence of smoking and alcohol consumption. In addition, those who consume water from household dug wells had significantly lower eGFR (p < 0.0001). A linear regression analysis revealed a significant positive association between lower eGFR and lower BMI (p < 0.001). We hypothesised that the low BMI in those with CKDu may have increased susceptibility to develop CKDu, in the presence of exposure to multiple nephrotoxins and adverse conditions. [ABSTRACT FROM AUTHOR]

Backgrounds: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time—consuming. Methods: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. Results: The preparation method is easy and cost—effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first—order elimination kinetics and, it has a short half—life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. Conclusions: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications. [ABSTRACT FROM AUTHOR]

Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration. Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 µg/ml in pigeons, 12.97 µg/ml in chickens, 14.24 µg/ml in cockatiels, and 47.81 µg/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 µg/ml in pigeons, 21.59 µg/ml in chickens, 32.03 µg/ml in cockatiels, and 55.96 µg/ml in falcons. Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability. [ABSTRACT FROM AUTHOR]

Over recent years, pigs have been promoted as potential animal model due to their anatomical and physiological similarities with humans. However, information about the contribution of distinct renal elimination processes [glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular secretion, and reabsorption] in pigs is currently limited. Therefore, a cocktail of renal markers, consisting of iohexol (GFR), para-aminohippuric acid (ERPF and net tubular anion secretion), pindolol (net tubular cation secretion), and fluconazole (net tubular reabsorption) was administered intravenously to 7-week-old male conventional pigs. Plasma and urinary concentrations were determined using validated analytical methods. The clearance of iohexol (GFR) was 97.87 ± 16.05 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 226.77 ± 62.45 ml/min/m², whereas the net tubular secretion of PAH was 130.28 ± 52.62 ml/min/m². The net tubular secretion of R-pindolol and S-pindolol was 13.53 ± 12.97 and 18.01 ± 39.23 ml/min/m², respectively. The net tubular reabsorption of fluconazole was 78.32 ± 13.52 ml/min/m². Overall, this cocktail of renal markers was considered to be safe for use in pigs since no adverse effects were observed. Iohexol, PAH and fluconazole were considered suitable renal marker to assess the porcine renal function. Pindolol seems less appropriate due to the high degree of nonrenal clearance in pigs. The values of GFR, ERPF, and anion secretion are within the same range for both human and pig. Regarding the tubular reabsorption of fluconazole, slightly higher values were obtained for pigs. Nevertheless, these results indicate the conventional pig could be an appropriate animal model to study renal drug elimination processes in humans. [ABSTRACT FROM AUTHOR]

Background: Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) and diffusion tensor imaging (DTI) are useful methods for investigating the morphology and function of the kidneys, including revealing unilateral renal damage. Nevertheless, these techniques have not yet been applied for bilateral renal function. The aim of this study was to investigate whether the combination of DTI and BOLD could be used to examine different degrees of contrast-induced acute kidney injury (CI-AKI) in bilateral kidneys compared to standard methods such as serum creatinine (SCr) detection.Methods: Forty-Two New Zealand white rabbits were divided into two groups: the experimental group and the control group. Physiological saline and iodine contrast agent (iohexol, 1.0 g iodine/kg, 1.0 ml/sec) were injected via the right renal artery. DTI and BOLD-MR data were acquired longitudinally at the baseline and 1, 24, 48, and 72 h after high-pressure syringe injection to measure the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative transverse relaxation rate (R2*). After the MR scan at each time point, three rabbits in each group were sacrificed, and changes in SCr and hypoxia-inducible factor-1α (HIF-1α) were analyzed using histopathology and immunochemistry.Results: Twenty-four hours after iohexol administration, the values of ADC and FA decreased significantly (P < 0.05), while R2* values increased (P < 0.05) in the renal cortex (CO), outer medulla (OM) and inner medulla (IM). Besides, significant negative correlations were observed among ADC, FA, and R2* in CO, OM, and IM (all P < 0.001, r = - 0.654-0.828).Conclusions: DTI and BOLD can simultaneously and non-invasively assess different degrees of CI-AKI in bilateral kidneys. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment of kidney function is needed for a variety of clinical indications and for research. The measurement of the serum clearance of iohexol has emerged as a feasible method to reach this objective. We report the analytical validation and clinical application of a new high-performance liquid chromatography (HPLC) – tandem mass spectrometry (MS/MS) assay to quantify iohexol in human serum. Specificity was enhanced due to the use of method specific acceptance limits for relative ion (RI) intensities. Methods: The internal standard ioversol was added to 50 μL serum prior to protein precipitation with methanol. Linear gradient elution was performed on a Waters Oasis® HLB column. Three transitions for both iohexol and ioversol were monitored allowing calculation of RIs. Measurements acquired during method validation were used as a training set to establish stricter acceptance criteria for RIs which were then tested retrospectively on clinical routine measurements (86 measurements) and on mathematically simulated interferences. Results: The method was linear between 5.0 μg/mL (lower limit of quantification [LLOQ]) and 100.3 μg/mL iohexol. Intraday and interday imprecision were ≤2.6% and ≤3.2%, respectively. Bias was −1.6% to 1.5%. All validation criteria were met, including selectivity, recovery, extraction efficiency and matrix effects. Retrospectively acceptance limits for RIs could be narrowed to ±4 relative standard deviations of the corresponding RIs in the training set. The new limits resulted in an enhanced sensitivity for the simulated interferences. Conclusions: Criteria for validation were met and the assay is now used in our clinical routine diagnostics and in research. [ABSTRACT FROM AUTHOR]

Background: Estimating glomerular filtration rate (GFR) is important for clinical management in kidney transplantation recipients (KTR). However, very few studies have evaluated the performance of the new GFR estimating equations (Lund-Malmö Revised–LMR, and Full Age Spectrum–FAS) in KTR. Methods: GFR was estimated (eGFR) using CKD-EPI, MDRD, LMR, and FAS equations and compared to GFR measurement (mGFR) by reference methods (inuline urinary and iohexol plasma clearance) in 395 deceased-donor KTR without corticosteroids. The equations performance was assessed using bias (mean difference of eGFR and mGFR), precision (standard deviation of the difference), accuracy (concordance correlation coefficient—CCC), and agreements (total deviation index—TDI). The area under receiver operating characteristic curves (ROC) and the likelihood ratio for a positive result were calculated. Results: In the total population, the performance of the CKD-EPI, MDRD and FAS equations was significantly lower than the LMR equation regarding the mean [95%CI] difference in bias (-2.0 [-4.0; -1.5] versus 9.0 [7.5; 10.0], 5.0 [3.5; 6.0] and 10.0 [8.5; 11.0] mL/min/1.73m2, P<0.005) and TDI (17.10 [16.41; 17.88], 25.91 [24.66; 27.16], 21.23 [19.48; 23.13] and 25.84 [24.16; 27.57], respectively). Concerning the CCC, all equation had poor agreement (<0.800) without statically difference between them. However, all equations had excellent area under the ROC curve (>0.900), and LMR equation had the best ability to correctly predict KTR with mGFR<45 mL/min/1.73 m2 (positive likelihood ratio: 8.87 [5.79; 13.52]). Conclusion: Among a referral group of subjects KTR, LMR equation had the best mean bias and TDI, but with no significant superiority in other agreement tools. Caveat is required in the use and interpretation of PCr-based equations in this specific population. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is implicated in the pathogenesis of many diseases. Proper management of oxidative stress requires antioxidants from external sources to supplement that of the body. Plants are considered as a major source of antioxidants because of their natural origin and therapeutic benefits. Objectives: This study was aimed at investigating the renoprotective and antioxidant capacity of hydroethanolic extract of Senecio serratuloides (HESS). Materials and Methods: In vitro and ex vivo antioxidant capacity of the extract was investigated. Female Wistar rats were treated with Nw-nitro L-arginine methyl ester (L-NAME) (40 mg/kg) for 4 weeks and then cotreating with L-NAME (20 mg/kg) and extract (HESS150 or HESS300 mg/kg) for 2 weeks and finally with plant extract or normal saline only for 2 weeks making a total of 8 weeks. Twenty-four-hour urine samples were collected during the study, and at the end of the study; blood and kidneys were harvested for biochemical and histological assays. Results: HESS exhibited high antiradical activity against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50values of 0.1 and 0.4 mg/ml, respectively. HESS significantly (P < 0.01) augmented L-NAME-induced decrease in creatinine clearance, glomerular filtration rate, and serum calcium concentration. HESS significantly increased in vivo antioxidant capacity (P < 0.01), decreased malondialdehyde (P < 0.01), and Bax (P < 0.001) concentration. It showed renoprotection and significantly (P < 0.01) prevented collagen deposition in the kidneys. Conclusion: S. serratuloides has renoprotective and free radical-scavenging properties and therefore maybe important in combating oxidative stress-mediated diseases in the kidneys and other parts of the body. [ABSTRACT FROM AUTHOR]

Background: Plasma iohexol clearance (CLiohexol) is a reference technique for glomerular filtration rate (GFR) determination. In routine practice, CLiohexol is calculated using one of several formulas, which have never been evaluated in kidney transplant recipients. We aimed to model iohexol pharmacokinetics in this population, evaluate the predictive performance of three simplified formulas and evaluate whether a Bayesian algorithm improves CLiohexol estimation. Methods: After administration of iohexol, six blood samples were drawn from 151 patients at various time points. The dataset was split into two groups, one to develop the population pharmacokinetic (POPPK) model (n = 103) and the other (n = 48) to estimate the predictive performances of the various GFR estimation methods. GFR reference values (GFRref) in the validation dataset were obtained by non-compartmental pharmacokinetic (PK) analysis. Predictive performances of each method were evaluated in terms of bias (ME), imprecision (root mean square error [RMSE]) and number of predictions out of the ±10% or 15% error interval around the GFRref. Results: A two-compartment model best fitted the data. The Bayesian estimator with samples drawn at 30, 120 and 270 min allowed accurate prediction of GFRref (ME = 0.47%, RMSE = 3.42%), as did the Brøchner-Mortensen (BM) formula (ME = − 0.0425%, RMSE = 3.40%). With both methods, none of the CL estimates were outside the ±15% interval and only 2.4% were outside the ±10% for the BM formula (and none for the Bayesian estimator). In patients with GFR ≤30 mL/min/1.73 m2, the BM formula performed very well, while the Bayesian method could not be evaluated in depth due to too small a number of patients with adequate sampling times. Conclusions: GFR can be estimated with acceptable accuracy in kidney transplant patients using the BM formula, but also using a Bayesian algorithm. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Acute kidney injury is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In this experimental animal study, we evaluated the effects of atrial natriuretic peptide (ANP) on renal function, perfusion, oxygenation and tubular injury during CPB. METHODS Twenty pigs were blindly randomized to continuous infusion of either ANP (50 ng/kg/min) or placebo before, during and after CPB. Renal blood flow as well as cortical and medullary perfusion was measured. Blood was repeatedly sampled from the renal vein. Glomerular filtration rate was measured by infusion clearance of 51Cr-EDTA. RESULTS Glomerular filtration rate was higher (P  < 0.001), whereas renal blood flow or renal oxygen delivery was not affected by ANP during CPB. Renal oxygen consumption did not differ between groups during CPB, whereas renal oxygen extraction was higher in the ANP group (P  = 0.03). Urine flow and sodium excretion were higher in the ANP group during CPB. Blood flow in the renal medulla, but not in the cortex, dropped during CPB, an effect that was not seen in the animals that received ANP. CONCLUSIONS ANP improved renal function during CPB. Despite impaired renal oxygenation, ANP did not cause tubular injury, suggesting a renoprotective effect of ANP during CPB. Also, CPB induced a selectively reduced blood flow in the renal medulla, an effect that was counteracted by ANP. [ABSTRACT FROM AUTHOR]

Computed tomographic (CT) peritoneography has been widely used as reference standard to evaluate continuous ambulatory peritoneal dialysis-related complications. However, given the varying CT peritoneography approaches used across different institutions, there is no standard value for non-ionic iodinated contrast media (ICM) concentration. Few studies have currently investigated whether non-ionic iodinated contrast media (non-ionic ICM) affects peritoneal function or residual renal function (RRF). This study aimed to determine whether different non-ionic ICM concentrations affect peritoneum and RRF and attempted to evaluate CT peritoneography images to identify the optimal non-ionic ICM concentrations in animals. To this end, 25 male Sprague-Dawley rats were used to establish uraemic models, after which they were injected with a 40-mL mixture of peritoneal dialysate and iohexol at varying concentrations prior to CT peritoneography. Thereafter, two experienced radiologists blinded to the rat groupings evaluated image quality, peritoneal morphology and thickness were assessed using hematoxylin and eosin and Masson staining, and RRF was evaluated using serum creatinine levels hematoxylin and eosin staining of pathological kidney sections. Briefly, non-ionic ICM had negligible effects on the peritoneum and RRF. Our results suggest that a mixture containing 50 mL (350 mgI/mL) iohexol/2 L peritoneal dialysate can be used as reference in rats. [ABSTRACT FROM AUTHOR]

• Direct photolysis of iohexol had significant dependence of UV wavelength spectral. • Distinctive photogenerated intermediates were observed with different photosensitizers. • Reactive sites and transformation pathways of iohexol were proposed. • Iohexol elimination and DBP yields by UV-LED irradiation followed the order of 255 > 265 > 275 > 285 nm. Iodinated X-ray contrast media (ICM) are ubiquitously present in water sources and challenging to eliminate using conventional processes, posing a significant risk to aquatic ecosystems. Ultraviolet light-emitting diodes (UV-LED) emerge as a promising technology for transforming micropollutants in water, boasting advantages such as diverse wavelengths, elimination of chemical additives, and no induction of microorganisms' resistance to disinfectants. The research reveals that iohexol (IOX) degradation escalates as UV wavelength decreases, attributed to enhanced photon utilization efficiency. Pseudo-first-order rate constants (k obs) were determined as 3.70, 2.60, 1.31 and 0.65 cm2 J−1 at UV-LED wavelengths of 255, 265, 275 and 285 nm, respectively. The optical properties of dissolved organic matter (DOM) and anions undeniably influence the UV-LED photolysis process through photon competition and the generation of reactive substances. The influence of Cl− on IOX degradation was insignificant at UV-LED 255, but it promoted IOX degradation at 265, 275 and 285 nm. IOX degradation was accelerated by ClO 2 −, NO 3 −and HA due to the formation of various reactive species. In the presence of NO 3 −, the k obs of IOX followed the order: 265 > 255 > 275 > 285 nm. Photosensitizers altered the spectral dependence of IOX, and the intermediate photoactivity products were detected using electron spin resonance. The transformation pathways of IOX were determined through density functional theory calculations and experiments. Disinfection by-products (DBPs) yields of IOX during UV-LED irradiation decreased as the wavelength increased: 255 > 265 > 275 > 285 nm. The cytotoxicity index value decreased as the UV-LED wavelength increased from 255 to 285 nm. These findings are crucial for selecting the most efficient wavelength for UV-LED degradation of ICM and will benefit future water purification design. [Display omitted] [ABSTRACT FROM AUTHOR]

• The solubility data was measured by the gravimetric method. • The experimental values were correlated by simplified van't Hoff, modified Apelblat, Jouyban-Acree, CNIBS/R-K equation. • The ternary phase diagram of oiling-out for iohexol at three temperatures were drawn. • Intermolecular interaction forces are emphasized as a key factor in oiling-out. • The molecular mechanism of oiling-out was proposed. The impact of oiling-out on the control of the crystallization purification process during iohexol crystallization is significant. Thus, the solubility of iohexol and its oiling-out behavior in a binary solvent mixture of methanol and n-butanol was investigated in this study. The solubility was determined using the equilibrium method at temperatures ranging from 273.15 K to 303.15 K under atmospheric pressure, revealing that solubility increases with temperature and methanol concentration. Four models were employed to model the solubility data, with the CNIBS/R-K model demonstrating the highest correlation. The van't Hoff equation was utilized to calculate the thermodynamic properties, the result indicating that enthalpy predominates in the dissolution process. Furthermore, ternary phase diagrams were constructed to elucidate the nucleation mechanism of iohexol, identifying nucleation sites and performing kinetic simulations from a molecular perspective. These analyses indicated that lower temperatures are favor the control of oiling-out phenomena. The nucleation of iohexol is characterized by a two-step mechanism, initiating with liquid–liquid separation, followed by nucleation and crystal growth. Solubility parameters, derived using Materials Studio, suggest enhanced interactions between iohexol and methanol, which is also corroborated by the solvation energy data from Gaussian software. This interaction explains the tendency of iohexol to oiling out in mixed solvents. Radial distribution function (RDF) analysis illustrates that methanol-iohexol interactions intensify prior to oiling-out, reach a peak during oiling-out, and diminish after nucleation due to desolvation. The occurrence of oiling-out can lead to challenges such as diminished product quality, reduced yields, and difficulties in reprocessing. Therefore, understanding the mechanism of oiling-out is fundamental to addressing these issues, rendering these insights invaluable for the study of crystallization processes and oiling out phenomena in other small organic molecules. [ABSTRACT FROM AUTHOR]

[Display omitted] • A urea perylene diimide (UPDI) concurrent photocatalysis-persulfate activation system was constructed. • The UPDI system is highly stable with excellent performance over a wide pH range. • The higher content of adsorbed oxygen can produce more reactive oxygen species. • The covalently bonded UPDI helps to reduce the activation energy of peroxymonosulfate (PMS). • The UPDI/PMS/Vis system has proven to be a non-radical-dominated process. The self-assembled perylene diimide (SAPDI) connected by hydrogen bonds is limited by the instability of easy disintegration under alkaline conditions. The covalently linked urea PDI (UPDI) was synthesized under air conditions, and concurrent photocatalysis-persulfate activation (CPPA) system was constructed. A distinct synergistic effect was attained when UPDI/peroxymonosulfate (UPDI/PMS, 0.012 min−1) system was combined with photocatalysis (UPDI/PMS/Vis, 0.115 min−1) to degrade iohexol (IOX). The import of the light field can accelerate the electron migration between the electron donor and the acceptor with more reactive oxygen species (ROS) generation. Evidenced by quenching tests, electron paramagnetic resonance, the dominated reactive species in UPDI/PMS system tended to be holes and 1O 2. The utilization efficiency of ROS is crucial to improve the performance of CPPA. The stability of the UPDI system is superior to that of previously reported SAPDI and its derivatives or heterojunctions. The higher content of adsorbed oxygen can produce more reactive oxygen species (ROS), which is one of the reasons for the stable activity of UPDI in cyclic experiments. An enhancement for PMS activation on covalently bonded UPDI was observed based on density functional theory calculation. This study provides a new perspective for the application of stable and efficient metal-free water treatment technology. [ABSTRACT FROM AUTHOR]

Generation of sulfate radicals (SO 4 •−) from sulfite activation has emerged as a promising method for abatement of organic pollutants in the water and wastewater treatment. Co(II) has garnered attention due to its high catalytic activity in the sulfite activation, which is compromised by the slow Co(II)/Co(III) redox cycling. Regarding the regulation of Co(II) electronic structure via the complexation effect, monoethanolamine (MEA), a common chelator, is introduced into the Co(II)/sulfite system. MEA addition results in a significant improvement in iohexol abatement efficiency, increasing from 40% to 92%. The superior iohexol abatement relies on the involvement of SO 4 •−, hydroxyl radicals (HO•) and Co(IV). Hydrogen radical (•H) is unexpectedly detected, acting as a strong reducing agent, contributing to the reduction of Co(III). This enhancement of sulfite activation by MEA is due to the formation of the Co(II)-MEA complex, in which the complexation ratio of Co(II) and MEA is critical. Electrochemical characterization and theoretical calculations demonstrate that the complexation can facilitate the Co(II)/Co(III) redox cycling with the concomitant enhancement of sulfite activation. This work provides a new insight into the Co(II)/sulfite system in the presence of organic ligands. [Display omitted] • An efficient Co(II)-MEA/sulfite system is established for the removal of iohexol. • The complex with MEA improves the electron transfer rate of cobalt species. • SO 4 •−, HO• and Co(IV) are the reactive species for iohexol degradation. • The generation of •H is confirmed, contributing to the reduction of Co(III). [ABSTRACT FROM AUTHOR]

The cooperative mechanism of mixed transition metals (TMs) for heterogeneous peroxymonosulfate (PMS) based water treatment can be considered in the viewpoint of cationic superexchange interaction. Herein, Co-Fe cooperation towards PMS activation was studied by modulating octahedral TMO 6 units in Fe-substituted LaCo 1−x Fe x O 3 perovskites. Certain lattice distortion formed at these reactive centers due to Co-Fe ionic radii mismatch, while LaCo 0.95 Fe 0.05 O 3 /PMS (0.136 min−1) achieved superior performance for iohexol degradation. Cobalt cations are identified as active sites by targeted poison and spectroscopic measurements, which prefer to accept electrons from Fe ions. Experimental and theoretical investigations illustrate that slight Fe-substitution induced lattice distortion leads to Co-O-Fe superexchange interaction, facilitating interfacial electron transfer and cationic valence exchange. And, the tolerance factor of catalysts is also indicated as an indicative descriptor to evaluate structure-dependent performance. Our work attempts to shed light on dual TM interactions for synergistic catalysis towards efficient Fenton-like decontamination. [Display omitted] ● Fe substitution in LaCo 1−x Fe x O 3 modulates the lattice distortion. ● Octahedral CoO 6 units activate PMS obeying d-band center catalysis. ● Fe cations denote electron and reduce the barrier height of LaCo 1−x Fe x O 3 for feasible electron transfer. ● The tolerance factor of LaCo 1−x Fe x O 3 affects the superexchange interaction of Co-O-Fe. [ABSTRACT FROM AUTHOR]

Background Videofluoroscopic swallow study (VFSS) is the gold standard for diagnosis of dysphagia in veterinary medicine but lacks standardized protocols that emulate physiologic feeding practices. Age impacts swallow function in humans but has not been evaluated by VFSS in dogs. Hypothesis/Objectives To develop a protocol with custom kennels designed to allow free‐feeding of 3 optimized formulations of contrast media and diets that address limitations of current VFSS protocols. We hypothesized that dogs evaluated by a free‐feeding VFSS protocol would show differences in objective swallow metrics based on age. Animals Healthy juvenile, adult, and geriatric dogs (n = 24). Methods Prospective, experimental study. Custom kennels were developed to maintain natural feeding behaviors during VFSS. Three food consistencies (thin liquid, pureed food, and dry kibble) were formulated with either iohexol or barium to maximize palatability and voluntary prehension. Dogs were evaluated by 16 swallow metrics and compared across age groups. Results Development of a standardized VFSS protocol resulted in successful collection of swallow data in healthy dogs. No significant differences in swallow metrics were observed among age groups. Substantial variability was observed in healthy dogs when evaluated under these physiologic conditions. Features typically attributed to pathologic states, such as gastric reflux, were seen in healthy dogs. Conclusions and Clinical Importance Development of a VFSS protocol that reflects natural feeding practices may allow emulation of physiology resulting in clinical signs of dysphagia. Age did not result in significant changes in swallow metrics, but additional studies are needed, particularly in light of substantial normal variation.

Background: In cases of coronavirus disease 2019 (COVID-19), favipiravir is commonly included to the therapy regimen. Drug interactions between favipiravir and other COVID-19 therapy drugs are frequently researched. However, no research on possible drug interactions between Favipiravir and radiocontrast agents, which have become almost crucial in diagnostic processes while not being part of the treatment, has been found., Aim: To determine potential medication interactions between Favipiravir and radiocontrast agents., Methods: The study comprised patients who were taking Favipiravir for COVID-19 therapy and underwent a contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) test while taking the medicine. The computerized patient files of the cases included in the study, as well as the pharmacovigilance forms in the designated hospital, were evaluated for this purpose., Results: The study included the evaluation of data from 1046 patients. The study sample's mean age was 47.23 ± 9.48 years. The mean age of cases with drug interactions was statistically significant greater than that of cases with no drug interactions ( P = 0.003). When evaluated with logistic regression analysis, a 1-year raises in age increases the risk of developing drug interactions by 1.63 times ( P = 0.023). There was no statistically significant difference in the occurrence of medication interactions between the sexes ( P = 0.090). Possible medication interactions were discovered in 42 cases (4%)., Conclusion: The findings of this study revealed that the most notable findings as a result of the combined use of contrast agents and favipiravir were increased creatinine and transaminase values, as well as an increase in the frequency of nausea and vomiting. The majority of drug interactions discovered were modest enough that they were not reflected in the clinic. Drug interactions become more common as people get older., Competing Interests: Conflict-of-interest statement: All the authors declared no conflict of interest existing in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Augmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CL iohexol ) to measure glomerular filtration rate (GFR)., Methods: This is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CL iohexol . Critically ill children with normal serum creatinine were included, and CL iohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CL iohexol1 ) and repeated (CL iohexol2 ) after 48-72 h whenever possible. ARC was defined as CL iohexol exceeding normal GFR for age plus two standard deviations., Results: Eighty-five patients were included; 57% were postoperative patients. Median CL iohexol1 was 122 mL/min/1.73 m 2 (IQR 75-152). Forty patients (47%) expressed ARC on CL iohexol1 . Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m 2 and 140 mL/min/1.73 m 2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CL iohexol2 ., Conclusions: Our findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure., Trial Registration: ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

The global shortage of freshwater and inadequate supply of clean water have necessitated the implementation of robust technologies for wastewater purification, and Fenton-like chemistry is a highly-promising approach. However, realizing the rapid Fenton-like chemistry for high-efficiency degradation of organic micropollutants (OMs) remains challenging. Herein, one novel system was constructed by a Co single-atom catalyst activating peroxymonosulfate (PMS), and the optimal system (SA-Co-NBC-0.2/PMS) achieved unprecedented catalytic performance towards a model OM [Iohexol (IOH)], i.e., almost 100% decay ratio in only 10 min (the observed rate constant: 0.444 min -1 ) with high electrophilic species 1 O 2 (singlet oxygen) generation. Theoretical calculations unveiled that Co-N 4 sites preferred to adsorb the terminal-O of PMS (more negative adsorption energy than other O sites: -32.67 kcal/mol), promoting the oxidation of PMS to generate 1 O 2 . Iodine (I)23 (0.1097), I24 (0.1154) and I25 (0.0898) on IOH with higher f - electrophilic values were thus identified as the main attack sites. Furthermore, 16S ribosomal RNA high-throughput sequencing and quantitative structure-activity relationship analysis illustrated the environmentally-benign property of the SA-Co-NBC-0.2 and the tapering ecological risk during IOH degradation process. Significantly, this work comprehensively checked the competence of the SA-Co-NBC-0.2/PMS system for organics abatement in practical wastewater., 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 © 2023 Elsevier Inc. All rights reserved.)

Veterinary care for rabbits has been growing, and, consequently, the anesthetic and analgesic management of this species must be improved. The aim of the present study was to evaluate the technique of localization of the epidural space with the aid of a peripheral nerve stimulator and epidurographic, comparing two techniques for determining the infused volume in rabbits (Oryctolagus Cuniculus). In a prospective, randomized blinded study, six healthy New Zealand rabbits, adults, and weighing from 2.2 kg to 3.8 kg received two treatments, at 1 week intervals: 0.33 mL/kg (treatment I) or 0.05 mL per centimeter of the spine (treatment II) of ioexol epidurally. In both treatments, a peripheral nerve stimulator (2 Hz, 0.25 mA and 0.1 milliseconds) was used to determine the location of the epidural space. Latero-lateral and ventro-dorsal radiographs were taken after five (T5) and twenty-five minutes (T25) of iohexol administration. The epidural space was correctly accessed in 92% of attempts. Treatment I received a smaller volume of contrast than treatment II, 1.0 ± 0.2 mL versus 2.1 ± 0.1 mL (mean ± standard deviation), respectively (p = 0.007). At T5, the cranial progression of the contrast varied between L4 and L5 in treatment I, and L5 and T10 in treatment II. At T25, no contrast was observed in any rabbit. In conclusion, peripheral nerve stimulator aided in accessing the lumbosacral epidural space, and the administration of 0.05 mL per centimeter of the spine resulted in greater cranial progression of contrast., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: No population pharmacokinetic studies of high‐dose methotrexate (HDMTX) have been conducted in infants with brain tumours, which are a vulnerable population. The aim of this study was to evaluate HDMTX disposition in these children to provide a rational basis for MTX dosing. Methods: Patients received 4 monthly courses of HDMTX (5 g/m2 or 2.5 g/m2 for infants aged ≤31 days) as a 24‐h infusion. Serial samples were analysed for MTX by an enzyme immunoassay method. Pharmacokinetic parameters were estimated using nonlinear mixed effects population modelling. Demographics, concomitant medications and genetic polymorphisms were considered as pharmacokinetic covariates while MTX exposure and patient age were considered as covariates for Grade 3 and 4 toxicities. Results: The population pharmacokinetics of HDMTX were estimated in 178 patients (age range 0.02–4.7 years) in 648 courses. The population clearance and volume were 90 mL/min/m2 and 14.4 L/m2, respectively. Significant covariates on body surface area adjusted MTX clearance included estimated glomerular filtration rate and co‐treatment with dexamethasone or vancomycin. No significant association was observed between MTX toxicity and MTX exposure, patient age, leucovorin dosage or duration. MTX clearance in infants ≤31 days at enrolment was 44% lower than in older infants, but their incidence of toxicity was not higher since they also received a lower MTX dosage. Conclusions: By aggressively following institutional clinical guidelines, HDMTX‐related toxicities were low, and using covariates from the population pharmacokinetic model enabled the calculation of a rational dosage for this patient population for future clinical trials. [ABSTRACT FROM AUTHOR]

Sulfate radicals (SO4·−) are highly efficient for the degradation organic pollutants. SO4·− can be produced by activation of sulfites, yet actual heterogeneous activators exhibit a lower reactivity for activation of sulfite to SO4·− at pH 7.0–8.0. Here we hypothesized that zero-valent copper can activate sulfite under mild conditions. We tested the reaction with iohexol, diatrizoate, atrazine, benzoic acid, and p-chlorobenzoic acid contaminants. Reactive radicals were identified by electron paramagnetic resonance, fluorescence spectrometry, and radical scavenging experiments. Results show up to 90% abatement of contaminants by combining sulfite with zero-valent copper at pH 8.0. Moreover, zero-valent copper maintains a crystalline stability and satisfactory reusability with iohexol abatement efficiency up to 80% after five runs. [ABSTRACT FROM AUTHOR]

Dietary biotin intake does not typically result in blood biotin concentrations that exceed interference thresholds for in vitro diagnostic tests. However, recent trends of high-dose biotin supplements and clinical trials of very high biotin doses for patients with multiple sclerosis have increased concerns about biotin interference with immunoassays. Estimates of the prevalence of high biotin intake vary, and patients may be unaware that they are taking biotin. Since 2016, 92 cases of suspected biotin interference have been reported to the US Food and Drug Administration. Immunoassays at greatest risk from biotin interference include thyroid and reproductive hormones, cardiac, and immunosuppressive drug tests. Several case studies have highlighted the challenge of biotin interference with thyroid hormone assays and the potential misdiagnosis of Graves' disease. Biotin interference should be suspected when immunoassay test results are inconsistent with clinical information; a clinically relevant biotin interference happens when the blood biotin concentration is high and the assay is sensitive to biotin. We propose a best practice workflow for laboratory scientists to evaluate discrepant immunoassay results, comprising: (1) serial dilution; (2) retesting after biotin clearance and/or repeat testing on an alternate platform; and (3) confirmation of the presence of biotin using depletion protocols or direct measurement of biotin concentrations. Efforts to increase awareness and avoid patient misdiagnosis should focus on improving guidance from manufacturers and educating patients, healthcare professionals, and laboratory staff. Best practice guidance for laboratory staff and healthcare professionals would also provide much-needed information on the prevention, detection, and management of biotin interference. • Increased use of high-dose biotin raises concerns about immunoassay interference. • Patients and physicians may be unaware of the presence of biotin in supplements. • Biotin interference thresholds vary by assay and by manufacturer. • Education of patients, physicians, and laboratory staff will increase awareness. • Best practice guidance is needed to prevent, detect, and manage biotin interference. [ABSTRACT FROM AUTHOR]

Determination of creatinine and estimation of Glomerular Filtration Rate (GFR) rapidly before injection of contrast media provides early detection of high-risk patients for acute kidney failure. Hence, a rapid point-of-care (POC) device (result in 30 s) allowing creatinine measurement and eGFR could be of interest. To validate this method, we considered a population referred for measuring GFR. Iohexol plasma clearance was used to measure GFR. For each subject, enzymatic creatinine was quantified with two different devices: in plasma with the Roche Cobas analyzer and in capillary blood with the Nova Biomedical POC device. Both values of creatinine were used in the CKD-EPI equation for estimated glomerular filtration rate (eGFR). eGFR using POC was compared to eGFR using Cobas and to mGFR by Passing Bablok regression, calculation of bias, precision and accuracy (or concordance) within 30%. Also, we calculated the rate of discrepant staging (eGFR >60 or ≤ 60 when mGFR is actually ≤60 and > 60) with both creatinine methods. 120 subjects (52 ± 13 years, 49% of women) were included. Mean mGFR was 77 ± 27 mL/min/1.73m2 with 29 patients presenting mGFR <60 mL/min/1.73m2. Passing- Bablok regression comparing eGFR obtained with the POC and the Cobas was: eGFR POC = −0.1 (95% CI: −7.4; 3.0) + 1.06 (95% CI: 1.00; 1.15) x eGFR COBAS. Mean bias was 3.7 ± 14.1 mL/min/1.73m2. Concordance within 30% was 82%. Compared to mGFR, Passing-Bablok with POC was: eGFR POC = −11.5 (95% CI: −22.9; −0.7) + 1.15 (95% CI: 1.02; 1.29) x mGFR. Mean bias was 0.1 ± 17.6 mL/min/1.73m2. Accuracy within 30% was 81%. Between eGFR COBAS and mGFR, mean bias was −3.7 ± 12.5 mL/min/1.73m2. Accuracy within 30% was 95%. With POC (and Cobas), 3.3% (0.8%) of patients would have been considered with GFR > 60 mL/min/1.73m2 whereas mGFR it was ≤60 and 10% (9.2%) of them would have been considered with GFR ≤60 mL/min/1.73m2 when mGFR was >60. Creatinine measured with the POC has an acceptable performance when used with the CKD-EPI equation to estimate GFR. Its ability to detect GFR <60 mL/min/1.73m2 is not significantly different from the classical Roche assay. StatSensor Creatinine (Nova Biomedical) can be used for GFR screening before contrast media injection. • eGFR before injection of iodine contrast media provides early detection of high-risk patients for acute kidney injury. • A quick determination of creatinine using POC device facilitates the assessment of kidney function. • eGFR obtained with the POC creatinine method were compared with results of mGFR and routine method for eGFR. • StatSensor Creatinine (Nova Biomedical) can be used for GFR screening before contrast media injection. [ABSTRACT FROM AUTHOR]

The contrast agents have different molarities and ionic structures. The high osmolar contrast agents could increase platelet aggregation but the ionic contrast agents decrease platelet aggregation. However there is insufficient data on whether the antiaggregan effect of P2Y12 inhibitors used during coronary interventions are affected by the contrast agents. This study aimed to evaluate the in vitro effects of different contrast agents on the antiaggregant activity of P2Y12 inhibitors (clopidogrel, ticagrelor and prasugrel). Thirty patients (who underwent percutaneous coronary interventions and were treated with a P2Y12 inhibitor for a minimum of 10 days) and five healthy volunteers were divided into four groups: the clopidogrel (10 patients), ticagrelor (10 patients), prasugrel (10 patients) and control (five volunteers) groups. Antiaggregant activity was measured by using the Verify-Now method and was represented as P2Y12 reaction unit (PRU) values. Three tubes of blood were collected from the participants in the three patient groups and in the control group; as the contrast material, 10% iohexol was added to a second tube, and 10% iodixanol was added to a third tube. PRU values of the control and the contrast tubes were measured at 5 min and at 30 min after the contrast material was added. Iohexol and iodixanol led to a significant decrease in the PRU values in the control group (iohexol: 188.4 ± 39.2 vs 142.4 ± 17.0, p =.04; iodixanol: 188.4 ± 39.2 vs 159.2 ± 33.7, p =.04) and in the clopidogrel group (iohexol: 140.8 ± 50.8 vs 106.3 ± 44.4, p =.04; iodixanol: 140.8 ± 50.8 vs 109.4 ± 47.6, p =.009) but not in the ticagrelor and prasugrel groups. The PRU values were significantly lower in the ticagrelor (23.1 ± 26.2) and prasugrel (23.4 ± 27.5) groups than in the clopidogrel (140.8 ± 50.8) and control (188.4 ± 39.2) groups (p <.01), and the PRU values for the ticagrelor and prasugrel groups were similar for both the 5-min and 30-min time periods (p >.05). The antiaggregant activities of iohexol and iodixanol were observed to be similar at the 5- and 30-minute time points for all of the groups (p >.05). Iohexol and iodixanol had in vitro antiaggregant effects, and their antiaggregant effects were similar. Iohexol and iodixanol increased the clopidogrel antiaggregant activity in vitro, but they did not significantly alter the antiaggregant activities of prasugrel and ticagrelor. • Iohexol and iodixanol have similar antiaggregant activity in in vitro setting. • Iohexol and iodixanol icrease the antiaggregant activity of clopidogrel in in vitro setting. • Iohexol and iodixanol did not change the antiaggregant activity of prasugrel and ticagrelor. • Iohexol antiaggregant activity occurs more rapidly than iodixanol. [ABSTRACT FROM AUTHOR]

Iohexol is commonly used as iodinated contrast agent. A novel two-step synthesis process for iohexol is described. The process involves acylation and hydrolysis using 5-amino-N, N'- bis (2,3-dihydroxypropyl)-2,4,6-triiodol-1,3-phthalamide and acetic anhydride as starting materials to prepare acetyl iodide, followed by alkylating the acetyl iodide with glycidyl condensate to give crude iohexol. The crude iohexol can be purified by recrystallization which uses isopropanol and water to form an azeotrope. The overall yield was 65. 52% and the structure of iohexol were confirmed by NMR and MS. This method is suitable for industrial production with easy operation. [ABSTRACT FROM AUTHOR]

Iodinated X-ray contrast media (ICM) are a group of tri-iodinated aromatic compounds used in medical imaging of soft tissues. They are regarded as emerging contaminants, and widely detected in the effluents of wastewater treatment plants, surface water, and groundwater. In the present study, degradation of iohexol, a typical ICM agent, was systematically investigated in a Co2+ activated peroxymonosulfate (Co2+/PMS) oxidation process at neutral conditions. Experimental data revealed that the apparent rate of iohexol degradation was first-order with respect to the concentrations of both Co2+ and PMS. SO 4 − was found to induce the oxidative degradation of iohexol primarily. Presence of humic acid (HA) significantly inhibited the iohexol degradation, while the influence of Cl− was negligible. A total of 11 intermediates were identified by HPLC-MS/MS and three transformation pathways, i.e., cleavage of side chain, H-abstraction from side chain, and oxidative deiodination, were proposed. The degradation started with the oxidation of the side chains in iohexol molecule and followed by deiodination on the aromatic ring. Following the degradation of iohexol, formation of free iodine and iodinated disinfection byproducts (I-DBPs) was found. When 50 µM was treated with 1 mM PMS and 1 µM Co2+, the yields of iodoform and triiodoacetic acid reached 38.12 and 577.99 µg/L, respectively, in 12 h. In addition, the formation of I-DBPs was prominently enhanced by the presence of HA. Because I-DBPs are highly toxic, this study suggests the potential risks when SO 4 − is applied to degrade ICM compounds. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration rate (GFR) is the most sensitive indicator of initial renal function decline during chronic kidney disease (CKD), but conventional protocols for measuring GFR are labor‐intensive and stressful for the dog. Objectives: To assess the diagnostic potential for detecting CKD with simplified GFR protocols based on iohexol plasma clearance. Animals: Seventeen CKD‐positive and 23 CKD‐negative dogs of different breeds and sex. Methods: Prospective nonrandomized study. Plasma iohexol was measured 5, 15, 60, 90, and 180 minutes after injection. Glomerular filtration rate was calculated using 5 samples (GFR5) or simplified protocols based on 1, 2, or 3 samples. The GFR5 and simplified GFR were compared by Bland‐Altmann and concordance correlation coefficient (CCC) analysis, and diagnostic accuracy for CKD by receiver operating characteristic curves. A gray zone for each protocol was bounded by the fourth quartile of the CKD‐positive population (lower cutoff) and the first quartile of the CKD‐negative population (upper cutoff). Results: All simplified protocols gave reliable GFR measurements, comparable to reference GFR5 (CCC >0.92). Simplified protocols which included the 180‐minutes sampling granted the best GFR measure (CCC: 0.98), with strong diagnostic potential for CKD (area under the receiver operating characteristic curve ± SE: 0.98 ± 0.01). A double cutoff including a zone of CKD uncertainty guaranteed reliable diagnosis outside the gray area and identified borderline dogs inside it. Conclusions: The simplified GFR protocols offer an accurate, hands‐on tool for CKD diagnosis in dogs. The gray zone might help decision‐making in the management of early kidney dysfunction. [ABSTRACT FROM AUTHOR]

Efficient abatement of an iodinated X-ray contrast media iohexol by an emerging sulfite autoxidation advanced oxidation process is demonstrated, which is based on transition metal ion–catalyzed autoxidation of sulfite to form active oxidizing species. The efficacy of the combination of sulfite and transition metal ions (Ag(I), Mn(II), Co(II), Fe(II), Cu(II), Fe(III), or Ce(III)) was tested for iohexol abatement. Co(II) and Cu(II) are proven to show more pronounced catalytic activity than other metals at pH 8.0. According to the quenching studies, sulfate radical (SO4•−) is identified to be the primary species for oxidation of iohexol. Increasing dosages of metal ion or sulfite and higher pH values are favorable for iohexol abatement. Inhibition of iohexol abatement is observed in the absence of dissolved oxygen, which is vital for the production of SO5•− and subsequent formation of SO4•−. Overall, activation of sulfite to produce reactive radicals with extremely low Co(II) or Cu(II) concentrations (in the range of μg L−1) in circumneutral conditions is confirmed, which offers a potential SO4•−-based advanced oxidation process in treatment of aquatic organic contaminants. [ABSTRACT FROM AUTHOR]

The degradation rates and kinetics of one commonly used iodinated contrast medium, iohexol, were investigated and compared during ultraviolet (UV) photolysis, UV/H 2 O 2 and UV/ S 2 O 8 2 − advanced oxidation processes (AOPs). Results indicate that the iohexol degradation rate increased in the order of UV/H 2 O 2 < UV irradiation < UV/ S 2 O 8 2 − and followed pseudo-first-order kinetics. Increasing persulfate concentration significantly increased iohexol degradation rate, whereas increasing H 2 O 2 concentration caused reverse effect. Radical scavenging test results show that UV photolysis, OH and radicals all contributed to iohexol degradation during UV/ S 2 O 8 2 − , but OH was the main contributor during UV/H 2 O 2 and was consumed by excess H 2 O 2. The kinetic models of iohexol degradation by both AOPs were developed, and the reaction rate constants with OH and were calculated as 5.73 (±0.02) × 108 and 3.91 (±0.01) × 1010 M−1 s−1, respectively. Iohexol degradation rate remained stable at pH 5–9 during UV irradiation and UV/H 2 O 2 , but gradually decreased at pH 5–7 and remained stable at pH 7–9 during UV/ S 2 O 8 2 −. The presence of anions displayed inhibitory effects on iohexol degradation during UV/ S 2 O 8 2 − in the order of Cl − > HCO 3 − ≫ S O 4 2 − . UV/ S 2 O 8 2 − AOP exhibited high degradation efficiency and stability on the basis of UV irradiation, which can be applied as a promising degradation method for iohexol. UV/ S 2 O 8 2 − AOP can effectively mineralize iohexol to CO 2 but promoted the generation of toxic iodoform (CHI 3), and the subsequent chlorination had the potential to reduce the content of disinfection by-products; therefore, further evaluation of possible environmental hazards is warranted. • The degradation efficiency of iohexol increased in the order of UV/H 2 O 2 < UV irradiation < UV/ S 2 O 8 2 − . • The iohexol degradation by UV/H 2 O 2 oxidation was mainly contributed by OH radical without UV photolysis. • The rate constants of iohexol reacting with OH and · S O 4 − were calculated as 5.73 (±0.02) × 108 and 3.91 × 1010 (±0.01) M−1 s−1, respectively. • pH has a negligible impact on iohexol degradation during UV irradiation and slight influence during UV/ and UV/H 2 O 2. • Higher concentrations of chloride and bicarbonate (≥2 mM) inhibited iohexol degradation. [ABSTRACT FROM AUTHOR]

Aims: To provide a model‐based prediction of individual urinary glucose excretion (UGE) effect of ipragliflozin, we constructed a pharmacokinetic/pharmacodynamic (PK/PD) model and a population PK model using pooled data of clinical studies. Methods: A PK/PD model for the change from baseline in UGE for 24 hours (ΔUGE24h) with area under the concentration–time curve from time of dosing to 24 h after administration (AUC24h) of ipragliflozin was described by a maximum effect model. A population PK model was also constructed using rich PK sampling data obtained from 2 clinical pharmacology studies and sparse data from 4 late‐phase studies by the NONMEM $PRIOR subroutine. Finally, we simulated how the PK/PD of ipragliflozin changes in response to dose regime as well as patients' renal function using the developed model. Results: The estimated individual maximum effect were dependent on fasting plasma glucose and renal function, except in patients who had significant UGE before treatment. The PK of ipragliflozin in type 2 diabetes mellitus (T2DM) patients was accurately described by a 2‐compartment model with first order absorption. The population mean oral clearance was 9.47 L/h and was increased in patients with higher glomerular filtration rates and body surface area. Simulation suggested that medians (95% prediction intervals) of AUC24h and ΔUGE24h were 5417 (3229–8775) ng·h/mL and 85 (51–145) g, respectively. The simulation also suggested a 1.17‐fold increase in AUC24h of ipragliflozin and a 0.76‐fold in ΔUGE24h in T2DM patients with moderate renal impairment compared to those with normal renal function. Conclusions: The developed models described the clinical data well, and the simulation suggested mechanism‐based weaker antidiabetic effect in T2DM patients with renal impairment. [ABSTRACT FROM AUTHOR]

Objective: To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance.Design: Interventional prospective multicentric study.Setting: Three French ICUs in tertiary teaching hospitals.Patients: Patients with acute circulatory failure within 12 hours after ICU admission.Interventions: IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours.Measurements and Main Results: Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16-44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30-60 and 60-90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was -18.1 mL/min (limits of agreement, -73.5 to 37.4).Conclusions: We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent. [ABSTRACT FROM AUTHOR]

One of the most important tools used to evaluate kidney function in the context of chronic kidney disease or other renal function related pathologies is the exploration of glomerular filtration rate (GFR). Iohexol is up to this moment a good candidate molecule for the GFR assessment since it exhibits minimum protein binding rates and minimum extra-renal clearance, being neither secreted nor reabsorbed at the tubular level. This study proposes and evaluates a new LC-MS/MS method for the iohexol determination from capillary blood, prelevated using volumetric absorbative microsampling (VAMS) systems. As an alternative to VAMS, a brand new HemaPEN® device for micro-prelevation was also tested. A new high throughput sample preparation protocol adapted for iohexol quantification from whole blood VAMS samples was developed. The medium term stability study of iohexol in dried whole blood VAMS samples that was conducted showed a good stability of this molecule for up to 12 days. By collecting only 10 μL of blood, iohexol can be analyzed from dried whole blood VAMS samples for concentration ranges between 1 and 250 μg/mL. Due to the analyte stability in VAMS for up to 12 days, this approach might be successfully applied for GFR assessment for clinical cases allowing minimum invasiveness and even delayed analysis. Image 1 • Successful VAMS-based bioanalytical method for iohexol analysis in whole human blood. • Proven medium term stability of iohexol in VAMS samples. • HemaPens as a promising alternative for iohexol analysis using only 2.74 μL of blood. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Iomeprol and iohexol can be effectively degraded by Co(II)-activated PMS. • IO 3 − is the major inorganic iodine released from iomeprol and iohexol. • The possible transformation pathways of iomeprol and iohexol are proposed. • Preferential deiodination order is theoretically predicted. Abstract It has already been known that oxidative degradation of organochlorine (e.g. chlorophenols) is accompanied by de novo formation of new polychlorinated compounds, however, whether the similar scenario can happen during decomposition of iodine-containing pollutants is completely unknown. Here degradation of two iodinated X-ray contrast media (ICM), iomeprol and iohexol, by sulfate radical generated through Co(II)-mediated activation of peroxymonosulfate (PMS) was investigated. The influencing parameters, such as the initial concentrations of PMS and Co(II), the initial solution pH and natural water constituents were examined. The pseudo-first-order rate constant of iomeprol in the PMS/Co(II) system is more than twice of iohexol, with values of 7.7 × 10−2 and 3.5 × 10−2 min−1, respectively, indicating that iomeprol seems more susceptible to radicals attack than iohexol. The bimolecular rate constants for reaction of sulfate radical (SO 4 •−) with ICM were determined to be 1.8 × 1010 M−1 s−1 and 7.9 × 109 M−1 s−1 for iomeprol and iohexol, respectively. The low degrees of mineralization and identification of iodinated intermediates of iomeprol and iohexol indicate that the degradation of iomeprol and iohexol in the Co/PMS system were incomplete. A de novo formation of new polyiodinated compounds would not happen because most of released inorganic iodine were ultimately oxidized to iodate (IO 3 −), rather than the reactive iodinated agents. Based on the identified byproducts and quantum chemical calculation, eight main transformation pathways are proposed for the degradation of iomeprol and iohexol as follows: (a) deiodination; (b) hydrogen abstraction; (c) amide hydrolysis; (d) amino oxidation; (e) hydroxyl substituent; (f) transformed alkyl aromatic amides to aromatic carbamoyl; (g) dehydration; (h) oxidized primary alcohol groups to carboxyl groups. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A kinetic model of iohexol degradation in a Fe2+/PS system was well-established. • The rate constant of iohexol reacting with SO 4 − was calculated as (1.83 ± 0.10) × 109 M−1 s−1. • The kinetic model can well predict the effects of Cl−, radical scavengers and NOM. • The developed model is also applicable to predict the degradation of atrazine. • Low-level Cl− can promote iohexol degradation while high-level Cl− inhibits it. Abstract Iohexol can hardly be removed in conventional wastewater treatment processes due to its non-biodegradable and hydrophilic characteristics. In this study, a kinetic model was established to describe iohexol degradation in Fe (II)-activated persulfate system. The developed model can well predict iohexol degradation and evolution of sulfate radical with various initial iohexol and oxidant (ferrous iron and persulfate) concentrations under various water matrix. The rate constant of iohexol reacting with sulfate radical was calculated as (1.83 ± 0.10) × 109 M−1s−1. The effects of the two most common components in natural water bodies, chloride ion and natural organic matter (NOM) on iohexol degradation, were also studied. Both experimental data and model results showed that the low concentration of chloride ion promoted iohexol degradation while high concentration inhibited it, and NOM slightly inhibited iohexol degradation. Besides, radical quenching tests were employed to identify the main radicals formed in the system and further verified the model accuracy. The model is also capable of predicting the atrazine degradation with the correlation coefficients between the experimental data and predicted results above 0.97, suggesting the applicability of the established model for some other recalcitrant contaminant degradation in the Fe2+/PS system. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration is the most important kidney function. The most accurate glomerular filtration rate (GFR) estimates are based on the clearance of exogenous filtration markers. Of these, iohexol is the only exogenous marker that is included in an external quality assessment (EQA) scheme. The aim of the present study was to evaluate the performance of the European laboratories participating in Equalis' EQA scheme for iohexol. Methods: Weighed amounts of iohexol (Omnipaque) were added to plasma samples and distributed to laboratories participating in the EQA scheme for iohexol. All laboratories performed the assays in a blinded fashion. Results: The number of participating laboratories varied between 27 and 34 during the study period. Iohexol was determined by HPLC in 77% of the laboratories and by UPLC/MS/MS methods in 15% of the laboratories. The mean interlaboratory coefficient of variation was 4.7% for the HPLC methods and 6.4% for the UPLC/MS/MS methods. The mean bias between calculated and measured iohexol values was –1.3 mg/L (95% confidence interval ±0.3) during the first part of the study period and 0.1 mg/L (±0.3) during the later part. Conclusions: The low interlaboratory variation demonstrates that iohexol can be measured reliably by many laboratories and supports the use of iohexol as a GFR marker when there is a need for high quality GFR measurements. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate glomerular filtration rate (GFR) estimation by means of plasma clearance of iohexol (IOX) in domestic rabbits and to assess accuracy of limited-sampling models for GFR estimation. ANIMALS 6 healthy domestic rabbits (Oryctolagus cuniculus). PROCEDURES Each rabbit received IOX (64.7 mg/kg [0.1 mL/kg], IV), and blood samples were collected at predetermined times before and after administration. Plasma IOX concentration was determined by high-performance liquid chromatography. The pharmacokinetics of IOX was determined by a non- compartmental method. For each rabbit, plasma clearance of IOX was determined by dividing the total IOX dose administered by the area under the concentration-time curve indexed to the subject's body weight. The GFR estimated from the plasma IOX concentration at 6 sampling times (referent model) was compared with that estimated from the plasma IOX concentration at 5 (model A), 4 (model B), and 3 (models C, D, and E) sampling times (limited-sampling models). RESULTS Mean ± SD GFR was 4.41 ± 1.10 mL/min/kg for the referent model and did not differ significantly from the GFR estimated by any of the limited-sampling models. The GFR bias magnitude relative to the referent model was smallest for model D in which GFR was estimated from plasma IOX concentrations at 5, 15, and 90 minutes after IOX administration. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that plasma clearance of IOX was a safe, reliable, accurate, and clinically feasible method to estimate GFR in domestic rabbits. Further research is necessary to refine the method. [ABSTRACT FROM AUTHOR]

In order to study the renal function, in terms of glomerular filtration and effective renal plasma flow, in broiler chickens and pigs, an ultra-high performance liquid chromatography–tandem mass spectrometry method for the simultaneous determination of iohexol, p-aminohippuric acid (PAH) and exogenously administered creatinine in plasma was developed and validated. Sample preparation consisted of a deproteinization step using methanol for porcine plasma and an Ostro™ Protein Precipitation & Phospholipid Removal Plate was used for broiler chicken plasma. Chromatographic separation was achieved on a Hypersil Gold aQ column using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phases. The total run time was limited to 10 min. Matrix-matched calibration curves for iohexol and PAH were prepared and good linearity (r ≥ 0.9973; gof ≤ 6.17%) was achieved over the concentration range tested (0.25–90 μg/mL). Limits of quantification were 0.25 μg/mL for iohexol and PAH. Water was used as surrogate matrix for analysis of creatinine in plasma. This surrogate calibration curve showed good linearity over the concentration range tested (0.25–90 μg/mL) (r ≥ 0.9979; gof ≤ 5.66%). For creatinine, the relative lower limit of quantification was 201.03 ± 49.20% and 60.14 ± 7.64% for chicken and porcine plasma, respectively. The results for within-day and between-day precision and accuracy fell within the specified ranges. This straightforward, cost-effective and rapid method, determining iohexol, PAH and creatinine within one single chromatographic run, has been successfully used for the analysis in porcine and broiler chicken plasma samples in order to determine the renal function of these species. • Evaluation of the renal function by analysing iohexol, PAH and exogenously administered creatinine in animal plasma • Straightforward and rapid LC-MS/MS method determining three renal markers within one single chromatographic run • Validation of an LC-MS/MS method for creatinine with ultrapure water as surrogate matrix [ABSTRACT FROM AUTHOR]