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.

A specific notation for contrast medium and dehydrated ethanol injection into the vein of Marshall during mitral isthmus ablation-A case report.

BACKGROUND: Ablation of the vein of Marshall (VOM) by dehydrated ethanol (DE) is an important method for completely blocking the mitral isthmus (MI). Before DE ablation of the VOM, Marshall angiography should be performed so that the contrast medium is inevitably exposed to DE. METHOD: We present a case of DE ablation of the VOM. When iodixanol was exposed to DE, some floccule embolized the lumen of the over-the-wire (OTW) balloon dilatation catheter and led to the impossibility of DE ablation. Then, we performed in vitro experiments: iodixanol, not iomeprol, produced many stable white floccules when it encountered DE. CONCLUSION: Iodixanol is not an appropriate contrast for DE ablation of the VOM. However, if there is no other alternative contrast, the following methods might be used to address the problem: ⑴ diluted iodixanol (iodixanol:normal saline 1:1) could be used for VOM ablation; or ⑵ the lumen of the OTW could be flushed by NS after VOM angiography, and then DE injection could be performed.

A multiple-metabolites model to predict preliminary renal injury induced by iodixanol based on UHPLC/Q-Orbitrap-MS and 1H-NMR.

BACKGROUND & AIMS: There are some problems, such as unclear pathological mechanism, delayed diagnosis, and inaccurate therapeutic target of Contrast-induced acute kidney injury (CI-AKI). It is significantly important to find biomarkers and therapeutic targets that can indicate renal injury in the early stage of CI-AKI. This study aims to establish a multiple-metabolites model to predict preliminary renal injury induced by iodixanol and explore its pathogenesis. METHODS: Both UHPLC/Q-Orbitrap-MS and 1H-NMR methods were applied for urine metabolomics studies on two independent cohorts who suffered from a preliminary renal injury caused by iodixanol, and the multivariate statistical analysis and random forest (RF) algorithm were used to process the related date. RESULTS: In the discovery cohort (n = 169), 6 metabolic markers (leucine, indole, 5-hydroxy-L-tryptophan, N-acetylvaline, hydroxyhexanoycarnine, and kynurenic acid) were obtained by the cross-validation between the RF and liquid chromatography-mass spectrometry (LC-MS). Secondly, the 6 differential metabolites were confirmed by comparison of standard substance and structural identification of 1H-NMR. Subsequently, the multiple-metabolites model composed of the 6 biomarkers was validated in a validation cohort (n = 165). CONCLUSIONS: The concentrations of leucine, indole, N-acetylvaline, 5-hydroxy-L-tryptophan, hydroxyhexanoycarnitine and kynurenic acid in urine were proven to be positively correlated with the degree of renal injury induced by iodixanol. The multiple-metabolites model based on these 6 biomarkers has a good predictive ability to predict early renal injury caused by iodixanol, provides treatment direction for injury intervention and a reference for reducing the incidence of clinical CI-AKI further.

Off-label intrathecal use of gadobutrol: safety study and comparison of administration protocols.

PURPOSE: Magnetic resonance imaging (MRI) contrast agents have been used off-label for diagnosis of cerebrospinal fluid (CSF) leaks and lately also for assessment of the glymphatic system and meningeal lymphatic drainage. The purpose of this study was to further evaluate the short- and long-term safety profile of intrathecal MRI contrast agents. METHODS: In this prospective study, we compared the safety profile of different administration protocols of intrathecal gadobutrol (GadovistTM; 1.0 mmol/ml). Gadobutrol was administered intrathecal in a dose of 0.5 mmol, with or without iodixanol (VisipaqueTM 270 mg I/ml; 3 ml). In addition, a subgroup was given intrathecal gadobutrol in a dose of 0.25 mmol. Adverse events were assessed at 1 to 3 days, 4 weeks, and after 12 months. RESULTS: Among the 149 patients, no serious adverse events were seen in patients without history of prior adverse events. The combination of gadobutrol with iodixanol did not increase the occurrence of non-serious adverse events after days 1-3. Intrathecal gadobutrol in a dose of 0.25 mmol caused less severity of nausea, as compared with the dose of 0.5 mmol. The clinical diagnosis was the major determinant for occurrence of non-serious adverse events after intrathecal gadobutrol. CONCLUSION: This prospective study showed that intrathecal administration of gadobutrol in a dose of 0.5 mmol is safe. Non-serious adverse events were to a lesser degree affected by the administration protocols, though preliminary data are given that side effects of intrathecal gadobutrol are dose-dependent.

Recurrent epileptic seizures following cardiac catheterization with iodixanol: a case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications. CASE PRESENTATION: Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient's EEG was normal. No antiepileptic drugs were administered throughout this process. CONCLUSIONS: CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.

Evaluation of synergic effects of iodixanol and trehalose on cryosurvival of electroejaculated ram semen.

The primary aim of the study was to investigate whether iodixanol and trehalose would have a synergic effect on the cryosurvival of electroejaculated ram semen. Tris-based diluter was used to prepare 9 different extenders by the addition of iodixanol or trehalose alone or varying combinations of these substances. Diluters were prepared as follows: Tris (control), Io5 (5% iodixanol), Tr25 (25 mmol/L trehalose), Tr50 (50 mmol/L trehalose), Tr50 + Io1.25 (50 mmol/L trehalose and 1.25% iodixanol), Tr50 + Io2.5 (50 mmol/L trehalose and 2.5% iodixanol), Tr50 + Io5 (50 mmol/L trehalose and 5% iodixanol), Tr25 + Io5 (25 mmol/L trehalose and 5% iodixanol) and Tr12.5 + Io5 (12.5 mmol/L trehalose and 5% iodixanol). Supplementation of the freezing extender with trehalose or iodixanol alone supported the protection of both morphological and functional integrity of ram spermatozoa and total motility at 1 and 4 hr post-thawing respectively. However, beyond these positive effects, the combination of trehalose (25 mmol/L) and iodixanol (5%) significantly increased post-thaw sperm longevity and motion properties at the end of 4-hr incubation. The results of the study clearly showed that there was positive synergic effect of iodixanol and trehalose on cryosurvival of ram semen.

An open label, prospective, multicenter, non-interventional study of iodixanol 270 mg I/mL for use in individuals undergoing computed tomography angiography in real-world clinical practice.

BACKGROUND: Concern about radiation exposure is leading to an increasing interest in low-concentration contrast medium administration. PURPOSE: To evaluate the image quality and safety profile after administration of iodixanol 270 mg I/mL at 100-kVp tube voltage with iterative reconstruction in subjects undergoing computed tomography angiography (CTA). MATERIAL AND METHODS: Patients who completed CTA examination using iodixanol 270 mg I/mL and 100-kVp tube voltage along with iterative reconstruction for coronary, aortic, head and neck, renal, or pulmonary arteries were included. Image quality was qualitatively and quantitatively evaluated. Incidence of adverse events (AEs) and adverse drug reactions (ADRs) within seven days and radiation dose were also analyzed. RESULTS: A total of 4513 individuals in 42 centers in China were enrolled, among which 4367 were included in efficacy analysis. The mean image quality score was 4.8 ± 0.45 across all arteries (all above 4.6) and 99.7% of the individuals' images were classified as evaluable. The CT attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the regions of interest (ROIs) were 431.79 ± 99.018, 18.29 ± 11.947, and 28.21 ± 19.535 HU, respectively. Of all the participants, 68 (1.5%) and 65 (1.4%) experienced AEs and ADRs, respectively. No serious AEs or AEs leading to discontinuation occurred. The average effective radiation dose was 3.13 ± 2.550 mSv. CONCLUSION: Iodixanol 270 mg I/mL in combination with 100-kVp tube voltage and iterative reconstruction could be safely applied in CTA and yield high-quality and evaluable images with reduced radiation dose.

Protective Effect of Phenolic Compounds Isolated from Mugwort (Artemisia argyi) against Contrast-Induced Apoptosis in Kidney Epithelium Cell Line LLC-PK1.

We investigated whether 14 phenolic compounds isolated from Artemisia argyi could prevent the apoptotic damage caused by iodixanol, an iodinated contrast agent, on LLC-PK1 cells. Iodixanol was used to induce cytotoxicity in LLC-PK1 cells. Apoptotic cell death was observed as the fluorescence intensity emitted by annexin V and Hoechst 33342 stains. Western blotting was used to detect specific proteins. Seven phenolic compounds protected against iodixanol-induced LLC-PK1 cell death in a concentration-dependent manner. Among them, methyl caffeate exerted the strongest protective effect, and co-treatment with 50 and 100 µM methyl caffeate decreased intracellular reactive oxygen species elevated by 25 mg/mL iodixanol. In addition, the treatment of LLC-PK1 cells with iodixanol resulted in an increase in apoptotic cell death, which decreased by co-treatment with methyl caffeate. Iodixanol caused a cytotoxicity-related increase in the phosphorylation of extracellular-signal-regulated kinase, c-Jun N-terminal kinase, and P38; and a similar increase in the expression levels of kidney injury molecule-1 and cleaved caspase-3. However, the up-regulation of these proteins was reversed by co-treatment with methyl caffeate. These findings suggest that phenolic compounds isolated from A. argyi play an important role in protecting kidney epithelium cells against apoptotic damage caused by iodixanol.

Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells.

Preventive effects and corresponding molecular mechanisms of mugwort (Artemisia argyi) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that A. argyi extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases. The flavonoid compounds isolated from A. argyi improved the viability of iodixanol-treated cells against contrast-induced nephrotoxicity. Seven compounds (1, 2, 3, 15, 16, 18, and 19) from 19 flavonoids exerted a significant protective effect. Based on the in silico oral-bioavailability and drug-likeness assessment, which evaluate the drug potential of these compounds, compound 2 (artemetin) showed the highest oral bioavailability (49.55%) and drug-likeness (0.48) values. We further investigated the compound⁻target⁻disease network of compound 2, and proliferator-activated receptor gamma (PPAR-γ) emerged as a predicted key marker for the treatment of contrast-induced nephrotoxicity. Consequently, compound 2 was the preferred candidate, and its protective effect was mediated by inhibiting the contrast-induced inflammatory response through activation of PPAR-γ and inhibition of MAPK phosphorylation and activation of caspases.

Trans-dissemination of exosomes from HIV-1-infected cells fosters both HIV-1 trans-infection in resting CD4+ T lymphocytes and reactivation of the HIV-1 reservoir.

Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4+ T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4+ T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4+ T lymphocytes. Here, we report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4+ T lymphocytes, which appears stronger with mature than immature DCs. Using purified preparations of both HIV-1 and exosomes, we observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4+ T lymphocytes induces efficient trans-infection and HIV-1 expression in target cells. Most relevant, when both mDCs and CD4+ T lymphocytes were isolated from combination anti-retroviral therapy (ART)-treated HIV-1-infected patients, trans-dissemination of exosomes from HIV-1-infected cells led to HIV-1 reactivation from the viral reservoir. In sum, our data suggest a role of exosome trans-dissemination in both HIV-1 spread in the infected host and reactivation of the HIV-1 reservoir.

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.

Layer-by-Layer Sorting of Rhenium Disulfide via High-Density Isopycnic Density Gradient Ultracentrifugation.

Isopycnic density gradient ultracentrifugation (iDGU) has been widely applied to sort nanomaterials by their physical and electronic structure. However, the commonly used density-gradient medium iodixanol has a finite maximum buoyant density that prevents the use of iDGU for high-density nanomaterials. Here, we overcome this limit by adding cesium chloride (CsCl) to iodixanol, thus increasing its maximum buoyant density to the point where the high-density two-dimensional nanomaterial rhenium disulfide (ReS2) can be sorted in a layer-by-layer manner with iDGU. The resulting aqueous ReS2 dispersions show photoluminescence at ∼1.5 eV, which is consistent with its direct bandgap semiconductor electronic structure. Furthermore, photocurrent measurements on thin films formed from solution-processed ReS2 show a spectral response that is consistent with optical absorbance and photoluminescence data. In addition to providing a pathway for effective solution processing of ReS2, this work establishes a general methodology for sorting high-density nanomaterials via iDGU.

One-year results of the ICON (Ionic versus non-ionic Contrast to Obviate worsening Nephropathy after angioplasty in chronic renal failure patients) Study.

BACKGROUND: Long-term clinical outcomes after exposure to non-ionic iso-osmolar contrast medium (IOCM) or ionic low-osmolar CM (LOCM) in patients with chronic kidney disease (CKD) undergoing coronary angiography are unclear. METHODS: The ICON trial was a prospective, double-blinded, multicentre study that randomly assigned 146 patients with CKD undergoing coronary angiography with or without percutaneous coronary intervention to the non-ionic IOCM Iodixanol or the ionic LOCM Ioxaglate. We report the 1-year clinical outcomes. RESULTS: After randomization, baseline and procedural characteristics were well-matched between the two groups. At 1 year, three deaths (4.1%) occurred in the ioxaglate and nine deaths in the iodixanol group (13.6%, P = 0.07). The cardiac death rate at 1 year was 2.7% in the ioxaglate group and 9.1% in the iodixanol group (P = 0.07). There were no significant differences in the rates of myocardial infarction (1.4% vs. 1.5%; P = 1.00) and repeated revascularization (6.8% vs. 9.1%; P = 0.75). CONCLUSIONS: The use of ionic LOCM ioxaglate was associated with a numerically lower mortality at 1 year as compared to iodixanol in patients who underwent cardiac catheterization. Future studies evaluating long-term safety following exposure to different types of CM are warranted.

Protective effect of α-mangostin against iodixanol-induced apoptotic damage in LLC-PK1 cells.

Radiographic contrast media facilitate the visibility of internal body structures, but its use to patients with lowered renal function needs to be careful because of severe side effect in kidney. The present study aims to evaluate potential protective effect and mechanism of Alpha mangostin (α-mangostin) against contrast-induced apoptotic damage in LLC-PK1 cells. As a result, α-mangostin in non-toxic concentrations improved the viability of the iodixanol-treated cells up to 90.42% against contrast-induced damage in LLC-PK1 cells. Iodixanol treatment increased the phosphorylation of p38, ERK and cleavage of caspase-3 in LLC-PK1 cells, which were significantly decreased by co-treatment with α-mangostin (2.5 and 5µM). The protective effect of α-mangostin on contrast-induced apoptotic damage was mediated by the inhibition of MAPKs and caspase activation.

A method for estimating the glomerular filtration rate in conscious monkeys.

To establish a method for estimating the glomerular filtration rate (GFR) in conscious monkeys, the radiographic contrast medium iodixanol and the standard agent inulin were coadministered as tracers to male cynomolgus monkeys (Macaca fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min. An equation based on a single-blood-sample method derived from Jacobsson's formula was prepared using the data from healthy and saline- and gentamicin-treated monkeys by a multisample strategy with iodixanol. The GFR using the equation with iodixanol was in agreement with that from the multisample method with inulin or iodixanol. When the GFR decreased to more than 60% of the basal reference level, serum creatinine concentrations tended to increase, whereas serum blood urea nitrogen concentrations fluctuated. The results suggest that the single-sample-blood method with iodixanol is a practical tool for estimating the monkey GFR in a toxicological research setting therefore minimizing animal sufferings.

Effects of viscosity on power and hand injection of iso-osmolar iodinated contrast media through thin catheters.

BACKGROUND: It can be challenging to achieve adequate vessel opacification during percutaneous coronary interventions when using thin catheters, hand injection, and iso-osmolar contrast media (CM) such as iodixanol (Visipaque™). PURPOSE: To explore these limitations and the possibility to overcome them with iosimenol, a novel CM. MATERIAL AND METHODS: Three X-ray contrast media with different concentrations were used in this study. A series of in vitro experiments established the relationship between injection pressure and flow rate in angiography catheters under various conditions. The experiments were conducted with power and hand injections and included a double-blind evaluation of user perception. RESULTS: By using hand injection, it was generally not possible to reach a maximum injection pressure exceeding 50 psi. The time within which volunteers were able to complete the injections, the area under the pressure-time curve (AUC), and assessment of ease of injection all were in favor of iosimenol compared with iodixanol, especially when using the 4F thin catheter. Within the pressure ranges tested, the power injections demonstrated that the amount of iodine delivered at a fixed pressure was strongly related to viscosity but unrelated to iodine concentration. CONCLUSION: There are substantial limitations to the amount of iodine that can be delivered through thin catheters by hand injection when iso-osmolar CM with high viscosity is used. The only viable solution, besides increasing the injection pressure, is to use a CM with lower viscosity, since the cost of increasing the concentration, in terms of increased viscosity and consequent reduction in flow, is too high. Iosimenol, an iso-osmolar CM with lower viscosity than iodixanol might therefore be a better alternative when thinner catheters are preferred, especially when the radial artery is used as the access site.

Acute generalized exanthematous pustulosis induced by iodixanol (Visipaque): a serious reaction to a commonly used drug.

Acute generalized exanthematous pustulosis (AGEP) is an acute sterile pustular eruption most commonly induced by medications. Although antibiotics are the most commonly accused drugs in AGEP, non-antibiotic agents may also cause this disease. We present a case of AGEP following use of iodixanol for coronary angiography in a 61-year-old woman. Given the wide use of this substance in cardiology, clinicians should be aware of this potential complication.

Differential activation of signaling pathways by low-osmolar and iso-osmolar radiocontrast agents in human renal tubular cells.

Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical problem accounting for 12% of all hospital-acquired cases of acute kidney injury (AKI). The pathophysiology of AKI due to RCM is not well understood, but direct toxic effects on renal cells have been postulated as contributing to CIN. It is believed that iso-osmolar RCM (IOCM) are less nephrotoxic than low-osmolar RCM (LOCM) but clinical data have been controversial. We have investigated the intracellular signaling pathways that may be affected by the LOCM iomeprol (IOM) and the IOCM iodixanol (IOD). Both IOM and IOD caused a dramatic decrease in phosphorylation of the kinase Akt at Ser473 and Thr308 in human renal tubular (HK-2) cells, with IOM having a greater effect; IOM also caused a greater decrease in cell viability. IOM also had a greater effect on phosphorylation of p38 MAP kinases, JNKs, and NF-kB (Ser276), and caused a marked decrease in the phosphorylation of forkhead box O3a (FOXO3a) and signal transducer and activator of transcription 3 (STAT3). However, IOD caused a greater decrease in the phosphorylation of mTOR (Ser2448) and phospho-ERK 1/2 while both RCM caused a similar decrease in the phosphorylation of phospho-p70S6 kinase (Ser371). In vivo studies showed that both IOM and IOD caused a significant decrease in both pAkt (Ser473) and pERK 1/2 in rat kidneys. Our study gives an insight into the possible mechanism of toxicity of RCM via their action on intracellular signaling pathways and may help in developing pharmacological interventions for their side-effects.

Hemodialysis clearance of iosimenol, a novel iso-osmolar radiographic contrast medium.

BACKGROUND: Iodinated contrast media (CM) have molecular and pharmacokinetic properties likely to make them highly dialyzable. Controlled clinical studies allowing for comparisons of hemodialysis clearance between different test substances and in multiple hemodialysis filters are, however, complex and not always practically feasible. A miniaturized in vitro method was therefore developed to evaluate the dialyzability of a new CM. PURPOSE: To evaluate hemodialysis clearance of iosimenol, a novel iso-osmolar contrast medium (CM), in a select variety of hemodialysis filters and in comparison to commercially available CM. MATERIAL AND METHODS: Three different high-flux and one low-flux membrane were used in miniaturized dialyzers to evaluate the in vitro blood clearance of iosimenol. Commercially available CM (iodixanol and iohexol) served as control substances. In vitro dialysis parameters were then used to predict clinical hemodialysis clearances. Residual ratios of endogenous substances (inorganic phosphate, urea nitrogen, creatinine, total bilirubin, and albumin) were used as proof of reliability of the in vitro dialysis system. RESULTS: Dialyzable small endogenous molecules were readily eliminated in all membranes. The removal ratios of iosimenol were generally similar to that of iodixanol in all membranes except the high-flux polysulfone but were consistently lower than that of iohexol. The blood clearance of iosimenol during clinical hemodialysis was predicted as, on average, approximately 85 mL/min with the high-flux membranes and 47 mL/min with the low-flux membrane. CONCLUSION: The dialyzability of iosimenol was evaluated using a newly developed in vitro dialysis system, and iosimenol was readily cleared from blood with all four tested membranes. And it is suggested that the dialysis parameters can predict clinical hemodialysis clearance of CM.

Comparison of patient comfort between iodixanol and iopamidol in contrast-enhanced computed tomography of the abdomen and pelvis: a randomized trial.

BACKGROUND: Previous clinical studies have shown that iso-osmolar iodixanol (Visipaque®) causes less patient discomfort than low-osmolar contrast media (LOCM) when administered via intra-arterial injection. No data are available comparing these agents for patient discomfort when administered intravenously (i.v.) using power injectors. PURPOSE: To compare the frequency and intensity of patient discomfort between iodixanol and iopamidol (Isovue®) administered i.v. using a power injector in contrast-enhanced computed tomography (CECT) of the abdomen and pelvis. MATERIAL AND METHODS: This was a prospective, randomized, double-blind, multicenter study of iodixanol 320 mg I/mL or iopamidol 370 mg I/mL on patient discomfort. The presence of discomfort (heat, pain, coldness) and intensity was verbally rated by patients on a 0-10 scale and converted into four categories (0, none; 1-3, mild; 4-7, moderate; 8-10, severe). Image quality was evaluated. RESULTS: Of the 299 evaluable patients enrolled at nine centers, 151 received iodixanol and 148 received iopamidol. The average age was 58 years. Iodixanol patients experienced significantly less moderate/severe discomfort (35.1% vs. 67.3%; P < 0.0001) or heat (29.8% vs. 63.9%; P < 0.0001), and severe discomfort (2.6% vs. 16.3%; P = 0.0004) or heat (2.6% vs. 15%; P = 0.0008), but three times more no discomfort (21.2% vs. 7.5%; P = 0.0008) than iopamidol patients. Excellent image quality was in 95.4% of iodixanol vs. 89.9% of iopamidol patients (P = 0.0508). Overall, adverse event (AE) rate excluding patient discomfort was 19.9% in the iodixanol group and 14.9% in the iopamidol group (P = 0.2870), but contrast-related AEs were comparable: 11.3% vs. 10.1% (P = 0.8522). Delayed skin reactions occurred in 2.6% of patients in the iodixanol group and in no patient in the iopamidol group (P = 0.1226). CONCLUSION: Patients receiving iodixanol had significantly lower moderate-to-severe or severe discomfort than patients receiving iopamidol, with heat being the major contributor. Iodixanol use trended towards better image quality but the difference was not statistically significant. No significant differences in incidences of overall or contrast-related AEs or delayed skin reactions were seen between the two groups. These data support that CM osmolality may be a key determinant of patient discomfort.