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.

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.

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.

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.

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.

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.

Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. MATERIAL AND METHODS: In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. RESULTS: In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. DISCUSSION: Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.

Structure-Based Drug Design for Targeting IRE1: An in Silico Approach for Treatment of Cancer.

BACKGROUND: Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a key role in cancer progression. The aggregation of incorrectly folded proteins in the ER generates ER stress, which in turn activates the UPR as an adaptive mechanism to fix ER proteostasis. Inositol-requiring enzyme 1 (IRE1) is the most evolutionary conserved ER stress sensor, which plays a pro-tumoral role in various cancers. Targeting its' active sites is one of the most practical approaches for the treatment of cancers. OBJECTIVE: In this study, we aimed to use the structure of 4µ8C as a template to produce newly designed compounds as IRE1 inhibitors. METHODS: Various functional groups were added to the 4µ8C, and their binding affinity to the target sites was assessed by conducting a covalent molecular docking study. The potential of the designed compound for further in vitro and in vivo studies was evaluated using ADMET analysis. RESULTS: Based on the obtained results, the addition of hydroxyl groups to 4µ8C enhanced the binding affinity of the designed compound to the target efficiently. Compound 17, which was constructed by the addition of one hydroxyl group to the structure of 4µ8C, can construct a strong covalent bond with Lys907. The outcomes of ADMET analysis indicated that compound 17 could be considered a drug-like molecule. CONCLUSION: Our results revealed that designed compound 17 could inhibit IRE1 activity. Therefore, this designed compound is a remarkable inhibitor of IRE1 and introduces a promising therapeutic strategy for cancer treatment.

Low Dose Iodinated Contrast Material and Radiation for Virtual Monochromatic Imaging in Craniocervical Dual-Layer Spectral Detector Computed Tomography Angiography: A Prospective and Randomized Study.

RATIONALE AND OBJECTIVES: To investigate the feasibility of virtual monochromatic imaging (VMI) of dual-layer spectral detector computed tomography (SDCT) to reduce iodinated contrast material (CM) and radiation dose in craniocervical computed tomography angiography (CTA). MATERIALS AND METHODS: A total of 280 consecutively selected patients performed craniocervical CTA with SDCT were prospectively selected and randomly divided into four groups (A, DoseRight index (DRI) 31, iopromide 370mgI/mL, volume 0.8 mL/kg; B, DRI 26, iopromide 370mgI/mL, volume 0.4 mL/kg; C, DRI 26, ioversol 320mgI/mL, volume 0.4 mL/kg; D, DRI 26, iohexol 300mgI/mL, volume 0.4 mL/kg). 50-70 kiloelectron volts (keV) VMIs in group B were reconstructed and compared to group A to select the optimal keV. Then, the optimal keV in groups B, C and D was reconstructed and compared. Objective image quality, including vascular attenuation, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), was evaluated. Subjective image quality was assessed using a 5-point Likert scale. In addition, the effective dose (ED), iodine load and iodine delivery rate (IDR) were compared between groups A and D. RESULTS: 55 keV VMI was the optimal VMI in group B. The objective and subjective image quality of 55 keV VMI in group B were equal to or better than those of the CI in group A. The SNR, CNR and subjective image quality in group D were similar to those in group B (P > 0.05). The ED, iodine load and IDR of group D were reduced by 44%, 59% and 19%, respectively, when compared to those of group A. CONCLUSION: Low dose iodinated CM and radiation for 55 keV VMI in craniocervical CTA using SDCT could still provide equivalent or better image quality than the conventional scanning protocol.

Design, synthesis, and structure-activity relationship of novel RIPK2 inhibitors.

The NOD1/2 (nucleotide-binding oligomerization domain-containing protein 1/2) signaling pathways are involved in innate immune control and host defense. NOD dysfunction can result in a variety of autoimmune disorders. NOD-induced generation of inflammatory cytokines is mediated by receptor-interacting protein kinase 2 (RIPK2), which has been considered as a promising therapeutic target. Herein, we disclose the design, synthesis, and SAR study of a series of RIPK2 inhibitors. The lead compound 17 displayed a high affinity for RIPK2 (Kd = 5.9 nM) and was capable of inhibiting RIPK2 kinase function in an ADP-Glo assay. In vitro DMPK studies showed that compound 17 had good metabolic stability and no CYP inhibition. Compound 17 effectively suppressed inflammatory cytokine production in both cells and animal model.

Degradation of iopromide during the UV-LED/chlorine reaction: Effect of wavelength, radical contribution, transformation products, and toxicity.

Three different UV-LED wavelengths (265, 310, and 365 nm) were used in the UV-LED/chlorine reaction to investigate the degradation mechanism of iopromide (IPM) at different wavelengths, a representative iodinated contrast media compound. The degradation rate (k'IPM) increased from pH 6-8 at 265 nm, but, decreased as the pH increased up to 9 at 310 nm and 365 nm. Radical scavenging experiments showed that reactive chlorine species (RCS) are the dominant radical species at all wavelengths, but a higher contribution of OH• was observed at lower pH and longer wavelengths. The contribution of RCS decreased but the contribution of OH• increased as the wavelength increased. Among RCS, the largest contribution was found to be ClO•. Total nine transformation products (TPs) were identified by LC-QTOF-MS during the UV-LED/chlorine reaction at 265 nm. Based on the identified TPs and their time profiles, we proposed a degradation pathway of IPM during UV-LED/chlorine reaction. The Microtox test using V. fischeri showed that no significant increase in toxicity was observed at all wavelengths. The synergistic effect of UV-LED and chlorine was greater at a higher wavelength by the electrical efficiency per order (EEO) calculation.

Iopromide and Iodixanol in the Development of Postoperative Contrast Nephropathy in Patients with Renal Insufficiency: A Meta-Analysis.

In order to compare the effects of iopromide and isoxazole on postoperative contrast-induced nephropathy in patients with renal insufficiency, the paper searches for randomized controlled trials and retrospective cohort studies comparing the effects of iopromide and iodixanol on renal function in patients with renal insufficiency after surgery. The data are extracted from eligible studies. We tried to assess the incidence of contrast-agent nephropathy, preoperative and postoperative serum creatinine indicators, and mortality. This paper includes 8 studies with a total of 1243 patients. The incidence of contrast-induced nephropathy in the iopromide group is higher than that in the iodixanol group, and there is no significant difference between the two groups in postoperative mortality and preoperative serum creatinine expression. Sensitivity analysis and funnel chart show that our research is robust and has low publication bias. Our research shows that in patients with renal insufficiency, the incidence of contrast-medium nephropathy in the iopromide group is higher than that in the iodixanol group. Iodixanol is safer and has less effect on patients' serum creatinine levels.

Risk of Hypersensitivity Reactions to Iopromide in Children and Elderly: An Analysis of 132,850 Patients From 4 Observational Studies and Pharmacovigilance Covering >288 Million Administrations.

PURPOSE: The aim of this study was to analyze the risk of hypersensitivity reactions (HSRs) to iopromide in children and elderly patients in comparison to adults. MATERIALS AND METHODS: Four observational studies were pooled and analyzed (analysis I). In addition, spontaneous reports from 1985 to 2020 from the pharmacovigilance database were evaluated (analysis II). All patients received iopromide for angiographic procedures or contrast-enhanced computed tomography in various indications. In analysis I, a nested case-control analysis, including a multivariable logistic regression model, based on pooled observational study data, was performed. Cases were defined as patients with a typical and unequivocal HSR; controls were patients without any recorded reaction. In analysis II, all spontaneous reports on HSRs after iopromide administration recorded in the pharmacovigilance database were descriptively analyzed. Exposure estimates on the size of the exposed age groups were derived from sales data and data from market research. The primary target variable was the risk of HSR to iopromide in children (<18 years) and elderly patients (≥65 years) compared with adults (≥18 to <65 years). RESULTS: In analysis I, a total of 132,850 patients were included (2978 children, 43,209 elderly, and 86,663 adults). Hypersensitivity reactions were significantly less frequent in children (0.47%) and elderly (0.38%) compared with adults (0.74%). The adjusted odds ratio (vs adults) for children was 0.58 (95% confidence interval, 0.34-0.98; P < 0.043), and that for the elderly was 0.51 (95% confidence interval, 0.43-0.61; P < 0.001), indicating a lower risk for both subpopulations as compared with adults. In analysis II, of the overall >288 million iopromide administrations, 5.87, 114.18, and 167.97 million administrations were administered to children, elderly, and adults, respectively. The reporting rate for HSRs in children (0.0114%) and elderly (0.0071%) was significantly lower as compared with adults (0.0143%) (P < 0.0001). CONCLUSIONS: Hypersensitivity reactions to iopromide were significantly less frequent in children and elderly compared with adults.

Calorie Restriction Protects against Contrast-Induced Nephropathy via SIRT1/GPX4 Activation.

Calorie restriction (CR) extends lifespan and increases resistance to multiple forms of stress, including renal ischemia-reperfusion (I/R) injury. However, whether CR has protective effects on contrast-induced nephropathy (CIN) remains to be determined. In this study, we evaluated the therapeutic effects of CR on CIN and investigated the potential mechanisms. CIN was induced by the intravenous injection of iodinated contrast medium (CM) iopromide (1.8 g/kg) into Sprague Dawley rats with normal food intake or 40% reduced food intake, 4 weeks prior to iopromide administration. We found that CR was protective of CIN, assessed by renal structure and function. CM increased apoptosis, reactive oxygen species (ROS), and inflammation in the renal outer medulla, which were decreased by CR. The silent information regulator 1 (SIRT1) participated in the protective effect of CR on CIN, by upregulating glutathione peroxidase 4 (GPX4), a regulator of ferroptosis, because this protective effect was reversed by EX527, a specific SIRT1 antagonist. Our study showed that CR protected CIN via SIRT1/GPX4 activation. CR may be used to mitigate CIN.

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney Cells via Activating a ROS-dependent Cellular Stress Pathway.

BACKGROUND/AIM: The use of iodinated contrast media may impair renal function. However, no report has addressed the nephrotoxicity of high doses of iodinated contrast media in normal kidney cells and its associated molecular mechanisms. MATERIALS AND METHODS: Cell proliferation was assessed using the MTT assay. Cell death was evaluated through examining the morphological changes and TUNEL assay. Autophagy was detected through acridine orange staining and lysotracker staining. Reactive oxygen species production and AKT kinase activity were examined. RESULTS: Iopromide induced cell death and triggered apoptosis and autophagy in HEK 293 cells. Cell viability was significantly restored in the presence of a pan-caspase inhibitor or a ROS scavenger, N-acetyl-L-cysteine. AKT kinase activity was found to be reduced in iopromide-treated HEK 293 cells. CONCLUSION: High concentrations of iopromide induce cell damage, apoptosis, and autophagy through down-regulating AKT and ROS-activated cellular stress pathways in HEK 293 cells.

[Iopromide-Induced Encephalopathy: A Case Report and Literature Review].

A 42-year-old male was admitted for paroxysmal syncope for 10 + months, chest tightness for 20 + days and chest pain for 10 + days. The patient was diagnosed with hypertrophic cardiomyopathy. The patient did not have a history of hypertension or diabetes. Coronary angiography and left ventricular cardiac catheterization were done in order to examine the coronary artery and the pressure gradient of the left ventricular outflow tract. The cardiac catheterization was performed via a right radial artery approach and a total of 200 mL of 370 mg I/mL iopromide was injected. The patient developed contrast-induced encephalopathy following the cardiac catheterization procedure, displaying severe headache, cortical blindness and neuropsychiatric symptom as the main clinical manifestations. The patient was then given symptomatic and supportive treatment, including decreasing intracranial pressure, analgesics and sedatives, and the patient recovered.