[Biomarkers of oxidative stress and inflammation in contrast-associated acute kidney injury].

BACKGROUND: Iodinated contrast-induced acute kidney injury (CI-AKI) is a common cause of renal failure, especially in patients with risk factors. This study analyses different renal biomarkers in patients undergoing computed tomography scans with iodinated contrast to identify the molecular and cellular mechanisms involved in the pathogenesis of CI-AKI. METHODOLOGY: Prospective study that included patients with high risk of renal disease who received iodinated contrast (iohexol) for the computed tomography scans. Functional biomarkers (creatinine and cystatin C), inflammatory and oxidative stress markers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-8 [IL-8], superoxide dismutase [SOD], F2-isoprostanes, and cardiotrophin-1), and cell cycle biomarkers (Nephrocheck®) were analysed before the iodinated contrast and 4, 12, 24, and 48 hours post-contrast, in relation to the incidence of IC-AKI. RESULTS: IC-AKI was observed in 30.6% of the 62 study participants and in 57.1% of the patients with diabetes and renal dysfunction. Factors associated with IC-AKI were a higher mean age (74.4 vs 64.9 years), pre-existing renal dysfunction (60 vs 16.7%), and higher adjusted mean volume of iohexol (42.9 vs 32.1%). As for non-functional biomarkers. No differences were found between patients with and without CI-AKI. The use of iodinated contrast was associated with a decrease in SOD antioxidant activity at 4 hours and an increase in IL-8 at 12 hours post-administration of the iodinated contrast. CONCLUSIONS: Administration of iohexol in computed tomography scans in patients with high risk of renal disease results in an elevated percentage of CI-AKI, attributable to ischemia/reperfusion injury and/or direct toxicity of the iodinated contrast.

GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques.

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.

Monitoring iohexol and its transformation products as evidence of reclaimed water irrigation input to contiguous waterbodies.

Irrigation with reclaimed water alleviates water supply shortages, but excess application often results in impairment of contiguous waterbodies. This project investigated the potential use of iohexol, an iodinated contrast media used in medical imaging, together with its bio- and phototransformation products as unique reconnaissance markers of reclaimed water irrigation intrusion at three golf courses within the state of Florida. Inter-facility iohexol concentrations measured in reclaimed waters ranged over ~2 orders of magnitude while observed intra-facility seasonal differences were ≤1 order of magnitude. A ~50 % reduction in iohexol was observed post-disinfection for reclaimed water facilities utilizing UV light while none was observed with use of chlorine. Iohexol biotransformation products were observed to decline or shift to lower molecular weight compounds when exposed to UV light but not during disinfection using chlorine. Iohexol biotransformation products were observed in most of the samples but were more prevalent in samples collected during the dry season. Much fewer iohexol phototransformation products were observed in chlorinated reclaimed water, and they were only observed in UV light irradiated reclaimed water when the pre-disinfectant iohexol concentration was ≥5000 ng/L or from solar exposure of reclaimed water spiked with 10 µM of iohexol. For the Hillsborough golf course overlaying an aquifer, the groundwater did not contain iohexol or phototransformation products but did contain biotransformation products. It is not known if these biotransformation products are from active or historical intrusion. The additional presence of sucralose in the aquifer suggests that intrusion has occurred within the past 3 years. This study demonstrates three crucial points in attempting to utilize iohexol to denote reclaimed water intrusion from irrigation overapplication: (1) interpretable results are obtained when iohexol concentrations in the reclaimed water employed for irrigation are ≥1000 ng/L, with higher concentrations in the range of ≥5000 ng/L better able to meet analytical sensitivity requirements after further dilution or degradation in the environment; (2) it is beneficial to assess iohexol transformation products in tandem with iohexol monitoring to account for environmental transformations of iohexol during storage and transport to the receiving water of concern; and (3) inclusion of monitoring for sucralose, an artificial sweetener ubiquitous in wastewater sources that is comparatively stable in the environment, can aid in interpretating whether reclaimed water intrusion based on identification of iohexol and transformation products in the receiving water is attributable to historic or ongoing irrigation overapplications.

Skin Test Reactivity Patterns in Patients Allergic to Iodinated Contrast Media: A Refined View.

BACKGROUND: Two-dimensional (2D) classifications of iodinated contrast media (ICM) are insufficient to explain the observed skin test (ST) reactivity patterns in patients with drug hypersensitivity reactions (DHRs) to ICM. OBJECTIVE: To refine the current view on allergic DHRs to ICM by analyzing ST reactivity patterns in patients with previous reactions to ICM. METHODS: Patients with a history of DHR to ICM and positive STs, who presented at the University Hospital of Montpellier between 2004 and 2022, were included in the study. The relative difference between every two ICM products was measured by Manhattan distance and odds ratios were computed for all pairs of products in the immediate reaction (IR) and non-immediate reaction (NIR) ST groups. RESULTS: A total of 181 patients were included in the study. Odds ratio analysis identified significant associations between classical cross-reactive ICM, such as iohexol-ioversol, iohexol-iomeprol, iomeprol-ioversol, and iohexol-iodixanol in the IR ST group and iohexol-ioversol, iopromide-iohexol, and iomeprol-ioversol in the NIR ST group. We also identified uncommon associations, such as ioxitalamate-amidotrizoate in the IR ST group and amidotrizoate-iopamidol and amidotrizoate-ioxitalamate in the NIR ST group. The results were reflected by the Manhattan distance, which suggested the existence of clusters containing the same classically associated ICM as well as uncommon associations, which we hypothesize to be related to similarities in the 3D structure of the respective ICM. CONCLUSIONS: Current chemical (2D) classifications cannot explain all observed ST reactivity patterns. Whether the 3D structure can be integrated into the current classifications to interpret the observed ST reactivity patterns and predict tolerance to alternative ICM requires further research.

Graphene-based nanomaterials for adsorption of iodinated X-ray contrast media from contaminated water: A comparative study.

Iodinated X-ray contrast media (ICM) was frequently detected in the aqueous environment. In this work, the applicability of three graphene-based nanomaterials (graphene nanosheets (GNS), graphene oxide (GO), and reduced graphene oxide (rGO)) for the adsorptive removal of the six ICMs including iohexol, iopamidol, iomeprol, iopromide, iodixanol and ioversol from aqueous solution was firstly evaluated by batch adsorption method. Among the three graphene-based nanomaterials, the GNS displayed the best adsorption performances for the adsorption of the six ICMs. The maximum uptakes of the six ICMs by the GNS (161.5 mg g-1 for iohexol, 267.2 mg g-1 for iodixanol, 197.7 mg g-1 for iopromide, 197.0 mg g-1 for iopamidol, 109.6 mg g-1 for iomeprol, and 168.2 mg g-1 for ioversol) can rapidly achieved within 10 min and indicate no dependence on pH in the range of 4-9. The results obtained from the calculations of isotherms, kinetics and thermodynamic supported the occurrence of a chemisorption of the GNS for the six ICMs. The π-π interactions between benzene ring of the ICMs and the sp2-hybridized two-dimensional sheet of GNS were deemed the predominant adsorption mechanism.

Hypersensitivity Reactions Induced by Iodinated Contrast Media in Radiological Diagnosis: A Disproportionality Analysis Based on the FAERS Database.

PURPOSE: This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis. RESULTS: In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased. CONCLUSION: The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

A physiological model for iohexol plasma clearance supporting diagnostics of kidney function.

BACKGROUND: There are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol. METHODS: A mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period. RESULTS: The mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately. CONCLUSIONS: The physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.

Low-iodine-dose computed tomography coupled with an artificial intelligence-based contrast-boosting technique in children: a retrospective study on comparison with conventional-iodine-dose computed tomography.

BACKGROUND: Low-iodine-dose computed tomography (CT) protocols have emerged to mitigate the risks associated with contrast injection, often resulting in decreased image quality. OBJECTIVE: To evaluate the image quality of low-iodine-dose CT combined with an artificial intelligence (AI)-based contrast-boosting technique in abdominal CT, compared to a standard-iodine-dose protocol in children. MATERIALS AND METHODS: This single-center retrospective study included 35 pediatric patients (mean age 9.2 years, range 1-17 years) who underwent sequential abdominal CT scans-one with a standard-iodine-dose protocol (standard-dose group, Iobitridol 350 mgI/mL) and another with a low-iodine-dose protocol (low-dose group, Iohexol 240 mgI/mL)-within a 4-month interval from January 2022 to July 2022. The low-iodine CT protocol was reconstructed using an AI-based contrast-boosting technique (contrast-boosted group). Quantitative and qualitative parameters were measured in the three groups. For qualitative parameters, interobserver agreement was assessed using the intraclass correlation coefficient, and mean values were employed for subsequent analyses. For quantitative analysis of the three groups, repeated measures one-way analysis of variance with post hoc pairwise analysis was used. For qualitative analysis, the Friedman test followed by post hoc pairwise analysis was used. Paired t-tests were employed to compare radiation dose and iodine uptake between the standard- and low-dose groups. RESULTS: The standard-dose group exhibited higher attenuation, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of organs and vessels compared to the low-dose group (all P-values < 0.05 except for liver SNR, P = 0.12). However, noise levels did not differ between the standard- and low-dose groups (P = 0.86). The contrast-boosted group had increased attenuation, CNR, and SNR of organs and vessels, and reduced noise compared with the low-dose group (all P < 0.05). The contrast-boosted group showed no differences in attenuation, CNR, and SNR of organs and vessels (all P > 0.05), and lower noise (P = 0.002), than the standard-dose group. In qualitative analysis, the contrast-boosted group did not differ regarding vessel enhancement and lesion conspicuity (P > 0.05) but had lower noise (P < 0.05) and higher organ enhancement and artifacts (all P < 0.05) than the standard-dose group. While iodine uptake was significantly reduced in low-iodine-dose CT (P < 0.001), there was no difference in radiation dose between standard- and low-iodine-dose CT (all P > 0.05). CONCLUSION: Low-iodine-dose abdominal CT, combined with an AI-based contrast-boosting technique exhibited comparable organ and vessel enhancement, as well as lesion conspicuity compared to standard-iodine-dose CT in children. Moreover, image noise decreased in the contrast-boosted group, albeit with an increase in artifacts.

Canine preclinical safety evaluation of a multimodal nanoparticle agent (Nanotrast-CF800) for image-guided cancer surgery.

Surgical oncology often requires the use of contrast-enhanced cross-sectional imaging preoperatively to characterize solitary tumours and identify sentinel lymph nodes. Intraoperative optical guidance can effectively aid tissue-sparing tumour excision and locate sentinel lymph nodes. Nanotrast-CF800 (CF800) is a novel dual-modality contrast agent, which co-encapsulates iohexol and indocyanine green (ICG) within a liposomal nanoparticle. It was developed for preoperative and intraoperative imaging of solitary tumours and sentinel lymph node mapping and its efficacy has been demonstrated in preclinical animal models (Zheng et al. 2015). The objective of this study is to evaluate the safety profile of CF800 following intravenous administration in healthy dogs. Six research dogs were randomized into two groups. Group 1 received a low dose (1 mL/kg) and group 2 received a high dose (5 mL/kg). Dogs were placed under general anesthesia and a continuous rate infusion of CF800 was administered based on group allocation. Physiologic parameters including heart rate, respiratory rate, direct arterial blood pressure, cardiac output, and temperature were measured at set time points. Plasma concentrations of iohexol, ICG, and histamine were measured at set time points. Dogs underwent whole body computed tomography scans pre-injection, 2-, and 7-days post-injection (p.i.). Contrast enhancement was measured in select organ systems and great vessels at each time point. There were no significant changes in physiologic parameters following IV infusion of CF800 in all dogs. Plasma iohexol and ICG concentrations peaked at 1 day p.i., while histamine concentrations peaked at 30 minutes p.i. Significant contrast enhancement was noted within the liver, heart, aorta, and caudal vena cava on day 2 p.i., which was significantly different compared to baseline. Prolonged contrast retention within the liver was identified. Intravenous administration of CF800 was safe to use in healthy dogs with no significant systemic adverse effects.

Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations.

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Intra-articular steroids for the treatment of coxarthrosis; a retrospective cohort study comparing three contrast techniques.

INTRODUCTION: Intra-articular steroid injections (IAS) are a treatment for coxarthrosis. This study examines the efficacy of three fluoroscopy-guided IAS contrast techniques for coxarthrosis: contrast-assisted (Iohexol), air arthrogram-assisted and blind (contrast/air free) and stratifies efficacy based on multiple patient variables. MATERIALS AND METHODS: A cohort of 307 hip IAS was retrospectively analysed over a four-year period. The primary outcome was efficacy of IAS between each technique group, defined by duration of symptomatic relief. The secondary outcome was efficacy based on multiple patient variables. Variables included age, BMI, gender, type of osteoarthritis, grade of osteoarthritis, smoking status, co-morbidity index and duration of pre-injection symptoms. Chi-squared, Pearson, One Way ANOVA and F-tests were used for statistical analysis. RESULTS: Total failure (< 1 week symptomatic relief) was 20% (contrast 20%, air 14%, blind 26%). >3 months of symptomatic relief was experienced by 35%, with the air arthrogram technique containing the largest proportion of IAS achieving > 3months of relief within its own group (contrast 35%, air 38%, blind 28%). Non-smokers experienced a longer duration of symptomatic relief in the air arthrogram group (p = 0.04). Older patients had a longer duration of symptomatic relief with the blind technique (p = < 0.001). There were no significant differences between the three techniques based on the other patient variables. CONCLUSION: Air arthrogram is an effective method of confirming injection placement in hip IAS for coxarthrosis and the use of a contrast agent (e.g., Iohexol) may not be required. Non-contrast techniques may produce longer duration of symptomatic relief in non-smokers and in older patients.

Impact of the reductive deiodination on the sorption of iodinated X-ray contrast media to filter sand and activated carbon.

Iodinated X-ray contrast media (ICM) and their aerobic transformation products (TPs) are widespread in the aquatic environment due to their persistent and mobile character. In a previous lab study, we have shown that the reductive (partial) deiodination of selected triiodobenzene derivatives increases the sorption to aquifer sand and loam soil, since iodine affects the compounds by steric hindrance, repulsive forces, resonance and inductive effects. These results suggest that the (partial) deiodination generally occurring to ICM and aerobic ICM TPs during anoxic/anaerobic bank filtration has a potential to increase their removal by sorption to natural sorbents. To basically assess the sorption potential to technically applied materials for drinking water treatment subsequent to bank filtration, we investigated the sorption of iopromide, diatrizoate and 5-amino-2,4,6-triiodoisophtalic acid and their di, mono and deiodinated structures to used filter sand from a waterworks and different fresh powdered activated carbons in batch tests using Berlin drinking water. The filter material, coated by iron and manganese oxides as well as organic material (including biofilm), preferentially removed monoiodinated derivatives, but diffusion through the organic layer heavily slowed the sorption. Therefore, the removal potential by sorption in rapid sand filters of waterworks for (partially) deiodinated benzene derivatives is suggested to be low. The deiodination of iopromide and diatrizoate significantly increased the sorption affinity to activated carbon and the competitiveness with regard to drinking water DOC. Despite the large atom radius of iodine, no clear correlation was found between the pore characteristics of the activated carbons and the molecular size of the compounds. This study emphasises the importance of anoxic/anaerobic conditions for the removal of persistent and mobile ICM and ICM TPs during drinking water treatment.

A Novel Coacervate Embolic Agent for Tumor Chemoembolization.

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthesized compounds were evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method using MCF-7 and MDA-MB-231 breast cancerous cells, compound 17 had the maximum anticancer activity against both breast cancerous cells, recording the lowest half-maximal inhibitory concentration (IC50) values (56.712 µg/mL for MCF-7 cells and 48.743 µg/mL for MDA-MB-231 cells). The results were confirmed in terms of the intrinsic mechanism of apoptosis, where compound 17 had the highest percentage in the case of both cancer cells and recorded Bax (Bcl-2 associated X)/Bcl-2 (B-cell lymphoma 2) ratio 17.5 and 96.667 for MCF-7 and MDA-MB-231 cells, while compound 19 came after 17 in the ability for induction of apoptosis, where the Bax/Bcl-2 ratio was 15.789 and 44.273 for both cancerous cells, respectively. Also, compound 11 recorded a high Bax/Bcl-2 ratio for both cells. The safety of the synthesized compounds was applied on normal WI-38 cells, showing minimum cytotoxic effect with undetectable IC50. Compounds 17, 11, and 19 recorded a significant increase of p53 upregulated modulator of apoptosis (PUMA) expression levels in the cancerous cells. The DFT method was also used to establish a connection between the experimentally determined values of the present investigated compounds and their predicted quantum chemical parameters. It was concluded that Compounds 17, 11, and 19 had anti-breast cancer potential through the induction of apoptotic Bax/Bcl-2 and PUMA expression levels.

Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD-0.67 ± 0.12; 1/5 MAD-0.59 ± 0.07; 1/10 MAD-0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels.

Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients.

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases.

Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure-activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.

Discovery of a stilbenoid-flavanone hybrid as an antitumor Wnt/ß-catenin signaling pathway inhibitor.

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.