[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.

Improved reductive transformation of iopromide by magnetite containing reduced graphene oxide nanosacks as electron shuttles.

The novel application of magnetite containing reduced graphene oxide nanosacks (MrGO-N) as electron shuttles to improve the reductive degradation of pharmaceutical pollutant, iopromide (IOP), was evaluated. The MrGO-N were synthesized by ultrasonicated nebulization process, and their physicochemical characterization was performed by potentiometric titrations, zeta potential, high resolution transmission electron microscopy (HR-TEM), X-ray diffraction, as well as by Raman and Fourier transform infrared spectroscopies. Results demonstrated the thermal reduction of precursor graphene oxide sheets, the removal of different oxygenated groups, and the successful assembly of magnetite nanoparticles (MNP) in the graphene sacks. Also, reduction experiments revealed 72 % of IOP removal efficiency and up to 2.5-fold faster degradation of this pollutant performed with MrGO-N as redox catalysts in batch assays and with sulfide as electron donor. Chemical transformation pathway of IOP provides evidence of complete dehalogenation and further transformation of aromatic ring substituents. Greater redox-mediating ability of MrGO-N was observed, which was reflected in the catalytic activity of these nanomaterials during the reductive degradation of IOP. Transformation byproducts with simpler chemical structure were identified, which could lead to complete degradation by conventional methodologies in a complementary treatment process. Redox-mediating activity of MrGO-N could potentially be applied in wastewater treatment systems in order to facilitate the biodegradation of priority contaminants.

Novel application of magnetic nano-carbon composite as redox mediator in the reductive biodegradation of iopromide in anaerobic continuous systems.

The redox-mediating capacity of magnetic reduced graphene oxide nanosacks (MNS) to promote the reductive biodegradation of the halogenated pollutant, iopromide (IOP), was tested. Experiments were performed using glucose as electron donor in an upflow anaerobic sludge blanket (UASB) reactor under methanogenic conditions. Higher removal efficiency of IOP in the UASB reactor supplied with MNS as redox mediator was observed as compared with the control reactor lacking MNS. Results showed 82% of IOP removal efficiency under steady state conditions in the UASB reactor enriched with MNS, while the reactor control showed IOP removal efficiency of 51%. The precise microbial transformation pathway of IOP was elucidated by high-performance liquid chromatography coupled to mass spectroscopy (HPLC-MS) analysis. Biotransformation by-products with lower molecular weight than IOP molecule were identified in the reactor supplied with MNS, which were not detected in the reactor control, indicating the contribution of these magnetic nano-carbon composites in the redox conversion of this halogenated pollutant. Reductive reactions of IOP favored by MNS led to complete dehalogenation of the benzene ring and partial rupture of side chains of this pollutant, which is the first step towards its complete biodegradation. Possible reductive mechanisms that took place in the biodegradation of IOP were stated. Finally, the novel and successful application of magnetic graphene composites in a continuous bioreactor to enhance the microbial transformation of IOP was demonstrated.

Lack of impact of iodinated contrast media on kidney cell-cycle arrest biomarkers in critically ill patients.

BACKGROUND: Iodinated contrast media may contribute to acute kidney injury. However, several recent works suggest that this toxicity is minimal in the clinical setting. Recently, urinary G1 cell-cycle arrest proteins tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin like growth factor binding protein 7 (IGFBP-7) were identified as highly sensitive and specific biomarkers for early detection of kidney aggression. The impact of contrast administration on those biomarkers has not been specifically evaluated but could provide clues about the toxicity of contrast media. This study aimed at measuring changes in TIMP-2 and IGFBP-7 urinary concentrations before and after a contrast-enhanced computed tomography in critically ill patients. METHODS: 77 patients were included in a prospective observational cohort study. Urinary [TIMP -2]·[IGFBP-7] was measured before, 6 and 24 h after contrast infusion. Urine output and serum creatinine were followed 3 days. RESULTS: Median [TIMP-2]·[IGFBP-7] was 0.06 [interquartile range 0.04;0.26], 0.07 [0.03;0.34] and 0.10 [0.04;0.37] (ng/mL)2/1000 respectively before, 6 and 24 h after contrast infusion. Individual changes from baseline were - 0.01 [- 0.11;0.11] and 0.00 [- 0.10;0.09] (ng/ml)2/1000 at 6 and 24 h. These changes were not higher among the patients increasing their Kidney Disease Improving Global Outcome (KDIGO) classification within 3 days after contrast infusion (n = 14 [18%] based on creatinine criterion only, n = 42 [55%] based on creatinine and urine output). CONCLUSIONS: Changes in [TIMP-2]·[IGFBP-7] urinary concentration after contrast-enhanced computed tomography were insignificant, suggesting minimal kidney aggression by modern iodinated contrast media.

Qualitative and Quantitative Assessment of Abdominal and Pelvic CT Image Quality Using Iopromide With Different Concentrations of Iodine (300 and 370 mg I/mL).

OBJECTIVE: The purpose of this study was to analyze the quality of MDCT images obtained using iopromide with two different concentrations of iodine (300 and 370 mg I/mL) in daily clinical settings. SUBJECTS AND METHODS: Patients from 38 hospitals in China undergoing abdominal or pelvic CT with iopromide were prospectively recruited. MDCT was performed using iopromide with an iodine concentration of 300 or 370 mg I/mL. CT quality image was graded as excellent, good, adequate, and poor. Objective indicators were the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Outcomes were compared according to organ studied, tumor type (benign vs malignant), saline usage, and type of MDCT (16-MDCT vs 64-MDCT). RESULTS: A total of 4506 patients (63.7% men) with a mean (± SD) age of 56.3 ± 14.1 years and mean body mass index (weight in kilograms divided by the square of height in meters) of 23.2 ± 3.3 were included. Iopromide with 300 mg I/mL was used for 3042 patients (67.5%), and 370 mg I/mL was used for 1464 patients (32.2%). A total of 1847 scans (41.0%) had excellent image quality, 2454 (54.5%) had good quality, 176 (3.9%) had adequate quality, and 29 (0.6%) had poor quality. No differences were noted between CT scans that did or did not use saline, 16-MDCT versus 64-MDCT scans, and 300 versus 370 mg I/mL iopromide. Variations in the CNR and SNR were noted between the two iodine concentrations with respect to other parameters examined. CONCLUSION: Iopromide with both concentrations of iodine provided acceptable image quality, though according to CNR and SNR, one or the other may provide better quality in different situations.

Subjective and objective image differences in pediatric computed tomography cardiac angiography using lower iodine concentration.

BACKGROUND: Several recent studies showed the optimal contrast enhancement with a low-concentration and iso-osmolar contrast media in both adult and pediatric patients. However, low contrast media concentrations are not routinely used due to concerns of suboptimal enhancement of cardiac structures and small vessels. OBJECTIVE: To evaluate the feasibility of using iso-osmolar contrast media containing a low iodine dose for CT cardiac angiography at 80 kilovolts (kVp) in neonates and infants. MATERIALS AND METHODS: The iodixanol 270 group consisted of 79 CT scans and the iopromide 370 group of 62 CT scans in patients ≤1 year old. Objective measurement of the contrast enhancement was analyzed and contrast-to-noise ratios of the ascending aorta and left ventricle were calculated. Regarding subjective measurement, a four-point scale system was devised to evaluate degrees of contrast enhancement, image noise, motion artifact and overall image quality of each image set. Reader performance for correctly differentiating iodixanol 270 and iopromide 370 by visual assessment was evaluated. RESULTS: Group objective and subjective measurements were nonsignificantly different. Overall sensitivity, specificity and diagnostic accuracy for correctly differentiating iodixanol 270 and iopromide 370 by visual assessment were 42.8%, 59%, and 50%, respectively. CONCLUSION: The application of iodixanol 270 achieved optimal enhancement for performing pediatric cardiac CT angiography at 80 kVp in neonates and infants. Objective measurements of contrast enhancement and subjective image quality assessments were not statistically different in the iodixanol 270 and iopromide 370 groups.

Is there any role of epithelial to mesenchymal transition in the pathogenesis of contrast nephropathy?

AIM: Contrast medium-induced nephropathy is one of the major complications of intravenous contrast medium use. But its pathogenesis is unclear. Epithelial mesenchymal transition (EMT) is defined as the transformation of the primer epithelial cells to mesenchymal cells. EMT in tubular cells might cause tubulointerstitial damage. In this study, we investigated whether or not EMT has a role in radiocontrast-induced nephropathy. Radiocontrast medium might be triggering reversible EMT via serum and glucocorticoid-regulated kinase 1 (SGK 1). We investigated the effect of different concentrations of the contrast agent iopromide on human proximal tubule cell (HK-2) culture by measuring the level of SGK1, snail family zinc finger 1 (SNAIL1), connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL1A1). METHODS: We conducted a scratch assay and qPCR. HK-2 cells were cultured in the petri dishes/flasks and starved with serum-free medium. The 40, 20, and 10 mg/mL doses of iopromide were administrated to cells. The scratches were photographed immediately and again at the 20th hour. The levels of gene expression of SGK1, SNAIL1, CTGF, and COL1A1 were measured using the real-time qPCR system at the end of the 24th hour. RESULTS: Iopromide caused the breaking of intercellular connections, the disappearance of the cobblestone appearance of cells, and the migration of cells at the 20th hour in the scratch assay. It also increased the expression of SGK1, SNAIL1, CTGF, and COL1A1 genes. CONCLUSION: Our study concluded that certain important markers of EMT increase in different concentrations of the contrast agent. High osmolality might trigger EMT. The relationship between contrast agent and EMT has not been defined before. Further in vivo and in vitro studies are required.

Iopromide in combination with IFN-γ induces the activation of HMC-1 cells via IL-4 and MCP-1 expression.

In this study, we investigated whether IFN-γ has a role in contrast-medium-induced adverse reactions. Iopromide, a nonionic iodinated contrast agent, slightly induced mast cell proliferation and significantly increased the expression of IL-4 and MCP-1 at low doses. The pretreatment of cells with IFN-γ dramatically increased the expression of iopromide-induced IL-4 and MCP-1. An evaluation of mast cell activator secretion revealed that IFN-γ- or IL-4-pretreated HMC-1 cells released dramatically increased levels of ß-hexosaminidase and histamine when stimulated with iopromide. We also found that the migration of EoL-1 and THP-1 cells was significantly increased in culture conditions with iopromide-stimulated IL-4-pretreated HMC-1 cells. Taken together, our findings suggest that measuring IFN-γ or IL-4 levels in serum would be helpful as a potential biomarker of adverse patient reactions and that blocking IFN-γ or IL-4 may be crucial in preventing the delayed allergy-like reaction induced by contrast medium in patients with various diseases.

Development of a capillary electrophoretic method for determination of plasma clearance of iohexol in dogs and cats.

Renal function can be monitored by estimation of the glomerular filtration rate (GFR), for example, through measurement of the plasma clearance of a marker that is freely filtrated through the kidney without reabsorption. It has been proposed that iohexol is the most accurate marker for GFR determination in cats and dogs. However, there is a need for a validated capillary electrophoretic method that covers the concentration range for a full curve clearance estimate of iohexol. In the final method, the plasma samples were protein precipitated and the supernatant was analyzed in a background electrolyte containing borate buffer (0.06 m, pH 10.0). The method developed was proved to be linear (concentration range 18- 2900 mg/L) and had a good precision (e.g. 2.3-2.9% at 88 mg/L) and accuracy (e.g. 101-105% at 88 mg/L). Finally, the method was compared with a previously published and validated HPLC-UV method by parallel analysis of clinical plasma samples from dogs and cats administered Omnipaque®. This comparison showed excellent agreement between the two methods and no proportional or systematic error was observed. The proposed method is simple and has a low cost per sample, which makes it applicable for routine analysis.

A new micro-computed tomography-based high-resolution blood-brain barrier imaging technique to study ischemic stroke.

BACKGROUND AND PURPOSE: Micro-computed tomography (mCT) offers high-resolution images, but it suffers from low contrast sensitivity and poor soft tissue contrast. We introduce a new mCT imaging technique with improved sensitivity for the dynamic spatial and temporal characterization of poststroke blood-brain barrier (BBB) dysfunction in small animals in vivo. METHODS: Transient middle cerebral artery occlusion was induced for 1 hour in 10- to 12-week-old C57BL/6 mice (n=35). At 4, 24, and 48 hours after ischemic stroke, serial in vivo mCT imaging was performed 5 minutes after intravenous infusion (n=3) or intracarotid infusion of iopromide (240 µL) for 5 minutes (n=32). After intravenous injection of 2% Evans blue, we performed ex vivo near-infrared fluorescent imaging of parenchymal Evans blue leakage, visual assessment of poststroke parenchymal hematoma, triphenyltetrazolium chloride staining of the brain tissue, and quantitative mapping of stroke-related brain lesions. RESULTS: Infarct-related BBB dysfunction could be demonstrated with intra-arterial but not with intravenous infusion of iopromide. Iopromide leakage across the dysfunctional BBB showed a monophasic (not biphasic) course for 48 hours after ischemic insult in both the parenchymal hematoma (n=5) and the non-parenchymal hematoma (n=24) groups, with relatively severe leakiness and greater hemispheric midline shift in animals with hemorrhage. Parenchymal staining on in vivo mCT overlapped with ex vivo fluorescent staining because of Evans blue. Multivariable analyses showed that midline shift and the amount of iopromide leakage at each of the 3 time points predicted the final infarct size at 48 hours. CONCLUSIONS: The new mCT BBB imaging technique, based on the intra-arterial infusion of clinically available iopromide, allows serial quantitative visualization of poststroke BBB dysfunction in mice, with high resolution and in a sensitive manner.

Ex vivo porcine model to measure pH dependence of chemical exchange saturation transfer effect of glycosaminoglycan in the intervertebral disc.

PURPOSE: Studies have linked low pH and loss of glycosaminoglycan (GAG) in the intervertebral discs (IVDs) of patients with discogenic back pain. The purpose of this study is to determine whether the chemical exchange saturation transfer (CEST) effect of GAG (gagCEST) is pH dependent and whether it can be used to detect pH changes in IVD specimens. Iopromide, a Food and Drug Administration approved agent for CT/X-Ray, was also evaluated as a pH-sensitive CEST probe to explore the agents' potential to measure IVD pH. METHODS: The pH dependency of the CEST effect of chondroitin sulfate (containing GAG) and Iopromide phantoms was investigated at 7 T. Z-spectra from porcine IVD specimens were acquired before and after manipulating the pH with sodium lactate. Iopromide was injected into the specimens and the calibration curve was used to determine the pH status. RESULTS: Chondroitin sulfate showed a non-linear dependence of gagCEST effect with pH and gagCEST signal differences were detected in the specimens. The CEST effect of Iopromide resulted in a sigmoidal relation with pH and was used to measure pH. CONCLUSION: gagCEST is sensitive to pH and enables investigation of the IVD pH status. Iopromide CEST is independent of the local GAG concentration and has the potential for measuring pH in the IVD.

Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.

PURPOSE: A practical, noninvasive method is needed to measure the extracellular pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have optimized a biomedical imaging method, termed acidoCEST MRI, to provide noninvasive assessments of tumor pHe in preclinical models of mammary carcinoma. METHODS: A CEST-FISP MRI method was optimized to detect the chemical exchange saturation transfer (CEST) of two amide protons of a clinically approved CT contrast agent, iopromide. The ratio of the two CEST effects was used to measure pH. Routes of administration of iopromide were evaluated to ensure sufficient delivery of the agent to the tumor. The optimized acidoCEST MRI method was then used to evaluate the change in tumor pHe following alkalinizing bicarbonate treatment. RESULTS: The acidoCEST MRI protocol measured pH between 6.2 and 7.2 pH units. Greater delivery of iopromide was shown to improve the precision of the measurement of tumor pHe, but the agent did not influence the tumor pHe. AcidoCEST MRI was used to longitudinally monitor the effect of bicarbonate treatment on the pHe of tumors and bladders. CONCLUSION: This study demonstrates that an optimized acidoCEST MRI method is a practical, noninvasive method for assessing changes in tumor acidosis.

Safety and tolerability of iopromide intravascular use: a pooled analysis of three non-interventional studies in 132,012 patients.

BACKGROUND: Determining the safety of contrast agents is challenging. In the absence of large controlled clinical trials, non-interventional (post-marketing surveillance) studies provide an opportunity to clearly investigate the safety profile of contrast agents. PURPOSE: To assess the safety profile of iopromide in contrast-enhanced X-ray in clinical practice, using pooled data from three non-interventional studies. MATERIAL AND METHODS: All studies were international, multicenter, non-interventional studies examining iopromide tolerability in clinical practice. Patients received iopromide (iodine concentrations of 300 mg/mL or 370 mg/mL) via intravenous or intra-arterial administration according to the diagnostic indication and in compliance with the local package insert. RESULTS: In total, 132,012 patients (37 countries, >1600 centers) were included. Overall, 3823 patients (2.49%) reported an adverse drug reaction (ADR) and 1983 patients (1.50%) reported an ADR without tolerance indicators (injection site warmth, feeling hot or injection site pain, of mild intensity only). This is a similar rate to other low osmolar contrast media. In most patients, ADRs were mild (n = 2632; 1.99% of all patients) and did not require any action (n = 2799; 2.12% of all patients). ADRs were more common among women (n = 1680 [2.8%]) than men (n = 1586 [2.2%]) and among younger patients (<18 years: n = 98 [3.2%]) than older patients (18-49 years: n = 1261 [3.5%]; 50-69 years: n = 1224 [2.2%]; ≥70 years: n = 362 [1.5%]). The most common ADRs were injection site warmth/feeling hot, nausea/vomiting, and dysguesia. Forty-five serious ADRs were reported in 19 patients. ADRs were more common in at-risk patients (5.00%) than in the overall population. CONCLUSION: This pooled analysis confirms the well-established good safety profile of iopromide in clinical practice in Asian and European countries and the USA.

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.

Iopromide for Contrast-Enhanced Mammography: A Systemic Review and Meta-Analysis of Pertinent Literature.

Background: Contrast-enhanced mammography (CEM) is an emerging breast imaging modality. Clinical data is scarce. Objectives: To summarize clinical evidence on the use of iopromide in CEM for the detection or by systematically analyzing the available literature on efficacy and safety. Design: Systematic review and meta-analysis. Data sources and methods: Iopromide-specific publications reporting its use in CEM were identified by a systematic search within Bayer's Product Literature Information (PLI) database and by levering a recent review publication. The literature search in PLI was performed up to January 2023. The confirmatory-supporting review publication was based on a MEDLINE/EMBASE + full text search for publications issued between September 2003 and January 2019. Relevant literature was selected based on pre-defined criteria by 2 reviewers. The comparison of CEM vs traditional mammography (XRM) was performed on published results of sensitivity and specificity. Differences in diagnostic parameters were assessed within a meta-analysis. Results: Literature search: A total of 31 studies were identified reporting data on 5194 patients. Thereof, 19 studies on efficacy and 3 studies on safety. Efficacy: in 11 studies comparing iopromide CEM vs XRM, sensitivity was up to 43% higher (range 1%-43%) for CEM. Differences in specificity were found to be in a range of -4% to 46% for CEM compared with XRM. The overall gain in sensitivity for CEM vs XRM was 7% (95% CI [4%, 11%]) with no statistically significant loss in specificity in any study assessed. In most studies, accuracy, positive predictive value, and negative predictive value were found to be in favor of CEM. In 2 studies comparing CEM with breast magnetic resonance imaging (bMRI), both imaging modalities performed either equally well or CEM tended to show better results with respect to sensitivity and specificity. Safety: eight cases of iopromide-related adverse drug reactions were reported in 1022 patients (0.8%). Conclusions: Pertinent literature provides evidence for clinical utility of iopromide in CEM for the detection or confirmation of breast cancer. The overall gain in sensitivity for iopromide CEM vs XRM was 7% with no statistically significant loss in specificity.

Hemodynamic effects of intravenous bolus injection of iopromide 370 twice in abdominal contrast-enhanced CT and coronary CTA dual-site sequential examinations.

Little information is available about how intravenous bolus injection of iopromide 370 twice in a short time will affect hemodynamics and whether the changes reach clinically relevant levels. In the present study, 31 healthy adult volunteers received abdominal contrast-enhanced CT and coronary CTA sequential examinations. The same dose and rate of normal saline was injected 30 min in advance as self-control. Hemodynamic data were noninvasively collected at selected time points from 1 min prior to injection to 30 min post-injection. The results showed that after iopromide 370 injection, except for stroke volume, all other indicators changed immediately during the first injection, changed most significantly during the second injection (P < 0.05), and returned to baseline within 10 min. Heart rate and cardiac output exhibited the most pronounced changes, with an increasing rate of 33.5% and 33.8%, respectively. For indicators with a change range of > 15% during the second injection, except for mean arterial pressure and total peripheral resistance, the proportions of subjects for the other indicators between the two groups were statistically different (P < 0.05). In conclusion, intravenous bolus injection of iopromide 370 twice in dual-site sequential examinations induced dose-cumulative and time-dependent hemodynamic effects, which all fluctuated within the normal ranges.

Studying the effect of drug-to-excipient ratio on drug release profile for drug coated balloons.

Drug-coated balloons (DCB) have emerged as the alternative procedure for restenosis because of their ability to treat a variety of occlusion types with a uniform dose of anti-proliferative drugs. DCB are balloons coated with antiproliferative drugs encapsulated in a polymer matrix. There are several types of coating matrices used to produce DCB. In this study, the relationship between coating composition and drug release under physiologically relevant conditions was examined to understand how differences in coating composition impacts the drug transfer from the balloon surface to the simulated body fluids. To conduct the experiments, the balloons were coated with different paclitaxel (drug)-to-iopromide (excipient) ratios (3:1, 3:2 and 1:2) using an in-house developed micro-pipetting method. Scanning electron microscopy (SEM) images showed that the 3:1 PTX:IOP ratio produced a more uniform, crystalline microstructure with a thinner coating throughout the balloon surface compared to the other drug-to-excipient ratios. The 1:2 PTX:IOP ratio showed the least crystalline microstructure among the three ratios evaluated in this study. Three different drug elution conditions were tested. The amount of drug released to the medium was quantified by high performance liquid chromatography (HPLC). Our soaking study and submerge & deploy study showed that ∼20% of the drug transferred to the target site under physiological conditions. A track and deploy method was performed using a "mock" artery, to simulate an in vitro environment. Coated balloons were passed through the mock artery to mimic tracking turns the balloon within the arteries during the angioplasty procedures. Seven elution samples were collected at different stages of the procedure. Drug release results suggest that the higher excipient ratio helps to deliver the lipophilic drug to the target site under simulated conditions but causes higher drug loss during the balloon transfer process.

Post-mortem distribution of Iodinated Contrast Media (ICM) (iodixanol versus iopromide) in the porcine kidney after multiple bolus injections in vivo into the supra-renal aorta1.

 Iodinated contrast media (ICM) are widely used for diagnostic and interventional procedures in radiology and cardiology. Ideally, they should not interact with blood cells or vascular wall cells to avoid deteriorations of the blood circulation. However, it is well known that ICM can affect erythrocytes as well as endothelial cells which consequently might perturb especially the microcirculation. In former studies the influence of two ICM (iodixanol versus iopromide) on the vascular system, the development of blood stasis, on changes in renal resistive index (RRI) and vascular diameters, and on the post-mortem distribution of iodine as marker for ICM in the explanted kidneys was examined. The modus of ICM application into the supra-renal aorta followed the regime in interventional cardiology, so that 10 bolus injections were administered at steady intervals (iopromide 4,32 ml / iodixanol 5 ml) accompanied by infusion of 500 ml isotonic NaCl-solution.In the present study, the post-mortem X-ray analysis revealed that there were no differences in iodine content in the regions of the mid-cortex and the medullo-pelvic transition zone of the kidneys after application of both ICM. Remarkable differences, however, were found in the region of the capsule-near cortex, where the application of iopromide led to a significantly lower iodine content in the microcirculation. This is in good agreement with former studies, in which a maldistribution in this area, presumably due to a decrease in arteriolar inflow as a result of stasis/occlusion was shown.

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.

Effects and Mechanism of Salvianolic Acid B on the Injury of Human Renal Tubular Epithelial Cells Induced by Iopromide.

With the increasing application of medical imaging contrast materials, contrast-induced nephropathy (CIN) has become the third major cause of iatrogenic renal insufficiency. CIN is defined as an absolute increase in serum creatinine levels of at least 0.50 mg/dl or an increase >25% of serum creatinine from baseline after exposure to contrast. In this study, the protective effects of salvianolic acid B (Sal B) were detected in human renal tubular epithelial cells (HK-2) exposed to iopromide. The results showed that different concentrations of Sal B counteract the loss of cell viability induced by iopromide, and reduce cell apoptosis, the reactive oxygen species (ROS) levels, and the levels of endoplasmic reticulum stress (ERS)-related and apoptosis-related proteins such as p-IRE-1α, p-eIF-2α/eIF-2α, p-JNK, CHOP, Bax/Bcl-2, and cleaved caspase-3. In addition, Sal B at a concentration of 100 µmol/L inhibited ERS and reduced cell damage to a similar extent as the ERS inhibitor 4-PBA. Importantly, treatment with Sal B could abolish the injury induced by ERS agonist tunicamycin, increasing cell viability and the mitochondrial membrane potential, as well as significantly reducing ROS levels and the expression of Bax/Bcl-2, cleaved-caspase-3, GRP78, p-eIF2α, p-JNK, and CHOP. These results suggested that the protective effect of Sal B against HK-2 cell injury induced by iopromide may be related to the inhibition of ERS.