Search

Iodixanol is an iso-osmolar non-ionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)-approved iso-osmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low-osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. These contrast agents are used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability, and efficacy of iodixanol are reviewed, specifically evaluating the use of CCTA and coronary angiography, including outcome studies, randomized trials, and comparisons to other contrast agents.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages and presents a novel, efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses, from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. The best practices and rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls, and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwhile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of these multivalent soft-matter nanorods. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Yang Zhao,1 Hua Wang,2 Zhengjun Wu,1 Yunxiang Zhu,1 Jingsong Wang1 1Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jingsong Wang, Department of Pharmacy, Guangyuan Central Hospital, Guangyuan, Sichuan, People’s Republic of China, Email wjs5515@163.comBackground: Adverse reactions induced by isoosmolar contrast medium (iodixanol) are mostly mild, with rashes and headaches being the most common. Although anaphylactic shock has been reported, no related incidents have been documented on cerebral angiography.Objective: This article reports a serious case of anaphylactic shock possibly induced by iodixanol and provides an overview of the case report.Case Summary: A 65-year-old female with persistent headaches for nearly six months and CTA examination revealed multiple intracranial aneurysms. After two treatments, she returned to the hospital for aneurysm of reexamination a month ago. Following a preoperative assessment, cerebral angiography was performed. Three minutes after the procedure, the patient experienced dizziness, increased heart rate, followed by hypotension (BP 90/43 mm Hg), a sudden drop-in heart rate (HR 68 bpm), and a drop in SpO2 to 92%. Intravenous dexamethasone for anti-allergic were administered immediately, along with therapy through oxygen-inhalation. However, the patient then developed limb convulsions, unresponsiveness, and was urgently given diazepam for sedation and sputum aspiration to maintain airway patency. Blood pressure decrease to 53/29 mm Hg, and SpO2 readings were unavailable. Intravenous dopamine to elevates blood pressure, and assists breathing by intubating in the endotracheal. After 3 minutes, as the blood pressure remained undetectable, intermittent intravenous epinephrine 1mg was administered to raise the blood pressure, gradually restoring it to 126/90 mm Hg, and SpO2 increased to 95%. The patient was diagnosed with iodixanol-induced anaphylactic shock and urgently transferred to the NICU for monitoring and treatment. The patient died despite immediate treatment.Conclusion: A 65-year-old female developed serious anaphylactic shock during cerebral angiography after receiving iodixanol. Although iodixanol is considered one of the safest iodinated contrast mediums (ICM), clinicians should be aware of its the potential for serious hypersensitivity reactions that can lead to fatal and life-threatening events.Keywords: iodixanol, cerebral angiography, hypersensitivity reaction, anaphylactic shock

Objective: This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection. Methods: A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method. Results: 126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories--calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines--as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08-2.15), 1.70 (95% CI: 1.68-1.73), 3.85 (95% confidence interval [CI]: 3.75-2.30), 2.30 (95% CI: 2.26-2.35), and 1.95 (95% CI: 1.89-2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%-3%), calcium gluconate (0.19%-0.52%), adrenergic/dopaminergic agents (2.20%-3.37%), glucocorticoids (3.13%-3.76%), and antihistamines (1.05%-1.32%). Conclusion: This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with =7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs. [ABSTRACT FROM AUTHOR]

Objective:This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection.Methods:A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method.Results:126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories—calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines—as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08–2.15), 1.70 (95% CI: 1.68–1.73), 3.85 (95% confidence interval [CI]: 3.75–2.30), 2.30 (95% CI: 2.26–2.35), and 1.95 (95% CI: 1.89–2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%–3%), calcium gluconate (0.19%–0.52%), adrenergic/dopaminergic agents (2.20%–3.37%), glucocorticoids (3.13%–3.76%), and antihistamines (1.05%–1.32%).Conclusion:This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

This study was conducted to evaluate the effect of the comparative study of contrast media for gastrography of the mynah bird. This study was conducted on 12 adult male mynah birds. Using different contrast agents, all the birds were studied five times, with a minimum of two days of the time interval between each study. Radiographic tests were performed 1, 5, 15, 30, 60, and 90 minutes after ingesting the contrast agent via using a gavage tract; imaging was performed at a time interval of 30 minutes and continued until the time when the contrast agent reached the cloaca and was excreted. There was a statistically significant difference between the results of digestive system studies using Iodixanol, Iohexol, and barium sulfate in terms of mean scores of the contrast agent’s ability to fill different parts of the gastrointestinal tract, clarity of observations, and observing details of the gastrointestinal tract at all times of radiography (p < 0.05). Iodixanol is less nephrotoxic and is a better contrast agent, however, we do not recommend using Iodixanol and Iohexol diluted by water at a ratio of 1:1.

• Our study showed that a wider safe dosage for iodixanol administration in patients undergoing elective PCI and showed every incremental 100 mL of iodixanol increased the risk of AKI by 16%. • Efforts to limit iodixanol volume in patients undergoing elective PCI did not statistically affect the incidence of AKI, and concerns may be diminished in these populations. • The necessity of minimizing contrast volume is still emphasized, as AKI can occur even when the threshold is not exceeded and increased risk of AKI with incremental iodixanol volume. [ABSTRACT FROM AUTHOR]

To study the effect of non-ionic contrast media on anticoagulated and non-anticoagulated human whole blood samples, calorimetric measurements were performed. The anticoagulated plasma showed the greatest fall in the total ΔH after Iodixanol treatment. The plasma-free erythrocytes revealed a pronounced shift in the Tmax and a decrease in the ΔH of hemoglobin and transferrin. The total ΔH of Iodixanol treatment showed the highest decline, while Iomeprol and Iobitridol had fewer adverse effects. Similarly, the non-anticoagulated samples revealed a decrease both in the Tmax and the ΔH of albumin and immunoglobulin-specific transitions. The total ΔH showed that Iodixanol had more influence on the serum. The serum-free erythrocyte samples resulted in a significant drop in the Tmax of erythrocyte and transferrin (~5–6 °C). The ΔH of deconvolved hemoglobin and transferrin decreased considerably; however, the ΔH of albumin increased. Surprisingly, compared to Iomeprol and Iobitridol treatments, the total ΔH of Iodixanol was less pronounced in the non-anticoagulated erythrocyte samples. In sum, each non-ionic contrast medium affected the thermal stability of anticoagulated and non-anticoagulated erythrocyte proteins. Interestingly, Iodixanol treatment caused more significant effects. These findings suggest that conformational changes in blood components can occur, which can potentially lead to the increased prevalence of cardiovascular dysfunctions and blood clotting. [ABSTRACT FROM AUTHOR]

Lin Qiu, Qihao Cui, Xuepeng Gong, Haiyun Zhou Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Haiyun Zhou, Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email haiyunzhou426@126.comBackground: Iodixanol-induced anaphylactic reaction is a well-known adverse event of contrast agents, which are generally well-tolerated and reversible. Serious and fatal reactions such as anaphylactic shock after computed tomography (CT) enhancement have been described. However, there is no data on these events in the literature.Objective: This report describes a case of a serious anaphylactic reaction, possibly related to iodixanol and provides an overview of case reports.Case Summary: A 47-year-old women who experienced persistent abdominal pain for more than one month, was proposed of hiatal hernia with CT images taken two weeks previously and was admitted to the gastrointestinal surgery department. The patient underwent contrast-enhanced abdominal CT for the evaluation of multiple intraperitoneal hemodynamic features. A few minutes after abdominal enhanced CT scan, the patient was pale, sweating, had muscle tension and trembling, even coma and profound hypotension with 90/43 mm Hg. Immediately she was supported with oxygen inhalation, was treated with adrenaline subcutaneously, dexamethasone intravenously, and rapid intravenous drip of compound sodium chloride. Ten minutes later, the patient was in respiratory and cardiac arrest and the pupils were dilated. CPR and intermittant static push of 1 mg adrenaline were immediately carried. After endotracheal intubation, the patient’s spontaneous heart rate and pupils recovered, and her blood pressure recovered to 105/53 mm Hg. It was suggested that the patient was suffering from iodixanol-induced anaphylactic shock and nephropathy, and she was transferred to the intensive care unit. Despite immediate treatment, the patient died.Conclusion: A 47-year-old female patient with no history of allergies developed severe fatal anaphylactic shock after receiving iodixanol. Although contrast agents induced anaphylactoid/anaphylactic reactions do not often occur, clinicians should be conscious of the potentially serious anaphylactic reaction, which could lead to a life-threatening or fatal event.Keywords: radiocontrast media, iodixanol, anaphylaxis, shock, nephropathy

In the last decade, research has shown that most diseases are associated with organelle dysfunction in which metabolites play a crucial role or indicate specific processes. Peroxisomes are cellular organelles attracting an increasing amount of attention and are now recognized as essential players in physiological conditions and diseases. However, a limited amount of research focuses on isolating the organelles and studying their properties and the diseases resulting from organelle dysfunction. All methods for isolating peroxisomes are based on fresh tissue samples. To the best of our knowledge, this is the first work in which peroxisomes have been isolated from frozen rat liver. In our work, we isolated peroxisomes from frozen rat liver at −80 °C and evaluated the separation success and degree of purification of isolated peroxisomes by measuring the relative specific activity, purification fold, and percentage yield (Y%) of organelle marker enzymes in the isolated fractions. The percentage of protein distribution and density was also estimated. Our results showed that the purified peroxisome fraction (F3-peroxisome) had significantly higher relative specific activity, as well as the highest purification fold and percentage yield of catalase compared with the enzyme markers of other organelles in the postnuclear supernatant (PNS), postmitochondrial supernatant (PMS), and light mitochondria–peroxisome (LM-P) fractions. In addition, the percentage of protein distribution was significantly lower in the F3-peroxisome fraction compared with PNS, PMS, and LM-P fractions while the percentage of protein distribution and density of the F3-peroxisome fraction after iodixanol centrifugation were significantly higher than those of the F1 and F2 fractions. The present work demonstrates the possibility of isolating peroxisomes from frozen liver samples efficiently, which could pave the way for further research in the future on other subcellular organelles from frozen samples. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In recent years, three-dimensional (3D) cell culture has been attracting attention as a cell culture model that mimics an environment closer to that of a living organism. It is known that there is a close relationship between cell nuclear shape and cellular function, which highlights the importance of cell nucleus shape analysis in the 3D culture. On the other hand, it is difficult to observe the cell nuclei inside the 3D culture models because the penetration depth of the laser light under a microscope is limited. In this study, we adopted an aqueous iodixanol solution to the 3D osteocytic spheroids derived from mouse osteoblast precursor cells to make the spheroids transparent for 3D quantitative analysis. With a custom-made image analysis pipeline in Python, we found that the aspect ratio of the cell nuclei near the surface of the spheroid was significantly greater than that at the center, suggesting that the nuclei on the surface were deformed more than those at the center. The results also quantitatively showed that the orientation of nuclei in the center of the spheroid was randomly distributed, whereas those on the surface of the spheroid were oriented parallel to the surface of the spheroid. Our 3D quantitative method with an optical clearing technique will contribute to the 3D culture models including various organoid models to elucidate the nuclear deformation during the development of the organs. Insight box Although 3D cell culture has been a powerful tool in the fields of fundamental biology and tissue engineering, it raises the demand for quantification techniques for cell nuclear morphology in the 3D culture model. In this study, we attempted to optically clear a 3D osteocytic spheroid model using iodixanol solution for the nuclear observation inside the spheroid. Moreover, using a custom-made image analysis pipeline in Python, we successfully quantified the nuclear morphology regarding aspect ratio and orientation. Our quantitative method with the optical clearing technique will contribute to the 3D culture models such as various organoid models to elucidate the nuclear deformation during the development of the organs. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the effect of the comparative study of contrast media for gastrography of the mynah bird. This study was conducted on 12 adult male mynah birds. Using different contrast agents, all the birds were studied five times, with a minimum of two days of the time interval between each study. Radiographic tests were performed 1, 5, 15, 30, 60, and 90 minutes after ingesting the contrast agent via using a gavage tract; imaging was performed at a time interval of 30 minutes and continued until the time when the contrast agent reached the cloaca and was excreted. There was a statistically significant difference between the results of digestive system studies using Iodixanol, Iohexol, and barium sulfate in terms of mean scores of the contrast agent’s ability to fill different parts of the gastrointestinal tract, clarity of observations, and observing details of the gastrointestinal tract at all times of radiography (p < 0.05). Iodixanol is less nephrotoxic and is a better contrast agent, however, we do not recommend using Iodixanol and Iohexol diluted by water at a ratio of 1:1. [ABSTRACT FROM AUTHOR]

Iodixanol is an iso-osmolar non-ionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)-approved iso-osmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low-osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. These contrast agents are used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability, and efficacy of iodixanol are reviewed, specifically evaluating the use of CCTA and coronary angiography, including outcome studies, randomized trials, and comparisons to other contrast agents.

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. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to compare the frequency and entity, in computed tomography (CT) urography, of streak artefacts on the urinary tract generated by two contrast agents with a different iodine concentration and osmolarity. Methods: Computed tomography scans including an excretory renal phase, performed on adult subjects in the period May–July 2020, were retrospectively evaluated in consensus by three expert radiologists, to detect any streak artefacts located in the urinary tract. Patients were administered either 1.6 mL/kg of Iodixanol 320 mgI/mL or 1.3 mL/kg of Iomeprol 400 mgI/mL. Results: In total, 144 CT scans were analysed, subdivided into two groups administered either Iodixanol (71/144 (49.3%) patients) or Iomeprol (73/144 (50.7%) patients). In 41% cases, no beam hardening artefacts were found; among these, 12/59 (20.3%) patients had received Iodixanol and 47/59 (79.7%) Iomeprol. In the Iodixanol group, the mean contrast density on the renal pelvis was 2565.6 HU and streak artefacts occurred in 59/71 cases (83.1%); in 33/59 (55.9%) cases, the artefacts were marked, and in 26/59 (44.1%) minimal. In the Iomeprol group, the mean contrast density on the renal pelvis was 1666 HU and streak artefacts occurred in 26/73 cases (35.6%); in 7/26 (27%) cases, the artefacts were marked and in 19/26 (73%) minimal. Conclusion: The study data demonstrate a significant difference in the attenuation values of iodine urine in the excretory system between the Iodixanol and Iomeprol group. Iodixanol induced a higher frequency and burden of artefacts, compared to Iomeprol. [ABSTRACT FROM AUTHOR]

We have studied a method for making microbial cells transparent by immersing them in a solution with a high refractive index (RI). When the RI of the solution was matching that of the cells, light scattering was greatly diminished (by a factor of up to about 100) and the cell suspension became transparent, facilitating the spectrophotometric determination of intracellular compounds such as hemoglobin. We investigated the properties of several compounds such as sucrose, glycerol, bovine serum albumin, FicollTM, and iodixanol (OptiprepTM), each with advantages and disadvantages. Particularly good overall properties were found for iodixanol at a concentration of around 36% (w/v) and bovine serum albumin at a concentration of about 30% (w/v). By using this RI-matching principle the production of intracellular compounds can easily be followed in near real-time during fermentation processes. For example, some conditions for producing plant hemoglobin in Escherichia coli were conveniently determined without the need of any cell disintegration or product purification.

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

In the last decade, research has shown that most diseases are associated with organelle dysfunction in which metabolites play a crucial role or indicate specific processes. Peroxisomes are cellular organelles attracting an increasing amount of attention and are now recognized as essential players in physiological conditions and diseases. However, a limited amount of research focuses on isolating the organelles and studying their properties and the diseases resulting from organelle dysfunction. All methods for isolating peroxisomes are based on fresh tissue samples. To the best of our knowledge, this is the first work in which peroxisomes have been isolated from frozen rat liver. In our work, we isolated peroxisomes from frozen rat liver at −80 °C and evaluated the separation success and degree of purification of isolated peroxisomes by measuring the relative specific activity, purification fold, and percentage yield (Y%) of organelle marker enzymes in the isolated fractions. The percentage of protein distribution and density was also estimated. Our results showed that the purified peroxisome fraction (F3-peroxisome) had significantly higher relative specific activity, as well as the highest purification fold and percentage yield of catalase compared with the enzyme markers of other organelles in the postnuclear supernatant (PNS), postmitochondrial supernatant (PMS), and light mitochondria–peroxisome (LM-P) fractions. In addition, the percentage of protein distribution was significantly lower in the F3-peroxisome fraction compared with PNS, PMS, and LM-P fractions while the percentage of protein distribution and density of the F3-peroxisome fraction after iodixanol centrifugation were significantly higher than those of the F1 and F2 fractions. The present work demonstrates the possibility of isolating peroxisomes from frozen liver samples efficiently, which could pave the way for further research in the future on other subcellular organelles from frozen samples.

Sustainable production and use of carbon nanotube (CNT)-enabled materials require efficient assessment of CNT environmental hazards, including the potential for CNT bioaccumulation and biomagnification in environmental receptors. Microbes, as abundant organisms responsible for nutrient cycling in soil and water, are important ecological receptors for studying the effects of CNTs. Quantification of CNT association with microbial cells requires efficient separation of CNT-associated cells from individually dispersed CNTs and CNT agglomerates. Here, we designed, optimized, and demonstrated procedures for separating bacteria (Pseudomonas aeruginosa) from unbound multiwall carbon nanotubes (MWCNTs) and MWCNT agglomerates using sucrose density gradient centrifugation. We demonstrate separation of protozoa (Tetrahymena thermophila) from MWCNTs, bacterial agglomerates, and protozoan fecal pellets by centrifugation in an iodixanol solution. The presence of MWCNTs in the density gradients after centrifugation was determined by quantification of 14C-labeled MWCNTs; the recovery of microbes from the density gradient media was confirmed by optical microscopy. Protozoan intracellular contents of MWCNTs and of bacteria were also unaffected by the designed separation process. The optimized methods contribute to improved efficiency and accuracy in quantifying MWCNT association with bacteria and MWCNT accumulation in protozoan cells, thus supporting improved assessment of CNT bioaccumulation.

Objective(s): Early diagnosis of cancer using noninvasive imaging techniques has been discussed in several recent studies. The present study aimed to assess the synergistic effects of iodixanol-conjugated polyethylene glycol (PEG)-citrate (anionic linear globular) dendrimer G2 on MCF-7 breast cancer cells and human embryonic kidney 293 (HEK293) cells. Materials and Methods: PEG-citrate dendrimer G2 was synthesized and purified. The product was characterized using atomic force microscopy (AFM), electron energy loss spectroscopy (EELS), dynamic light scattering (DLS). At the next stage, the product was conjugated to iodixanol, purified and lyophilized. The cytotoxic effects of the iodixanol, plain PEG-citrate dendrimer G2, and iodixanol-PEG-citrate dendrimer G2 complex were evaluated using methylthiazole-tetrazolium (MTT) assay on the MCF-7 and HEK293 cells. Inductively coupled plasma mass spectrometry (ICP MS) is a mass spectrometry technique, which applies inductively coupled plasma to ionize samples.Results: According to the obtained results, the uptake of PEG-citrate dendrimer G2 iodixanol increased significantly compared to iodixanol alone (PConclusion: Therefore, it was concluded that the addition of anionic linear globular dendrimer G2 to iodixanol affected the cellular uptake of the drug with no significant toxicity. Recent findings also confirmed that this novel complex could be applied as an effective cancer imaging agent for molecular biology and molecular imaging applications.

Abstract 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.

OBJECTIVE: To compare and analyze the adverse drug reactions (ADR) of domestic and imported iodixanol injection during clinical application, so as to provide data support for clinical rational application. METHODS: All the patients treated with iodixanol injection in the hospital from 2020 to 2021 were analyzed, which were divided into three groups according to the manufacturer of iodixanol injection ( two groups of domestic iodixanol injection and one group of imported iodixanol injection), the general information of patients with ADR, as well as the severity, occurrence time and clinical manifestations of ADR were collected. RESULTS: Totally 29 335 patients treated with iodixanol injection were enrolled, and 116 cases of ADR occurred, with the incidence rate of 0. 40%. There was no statistical significance in difference in the incidence of ADR among the three groups(P>0. 05); there were no statistical significance in differences in the male-female ratio, average age and proportion of basic diseases among the three groups(P>0. 05); there was no statistical significance in differences in the severity, occurrence time and clinical manifestations of ADR(P> 0. 05). CONCLUSIONS: The two kinds of domestic iodixanol injection and imported iodixanol injection had the lower incidence of ADR, and the ADR were non-severe, which is comparable in terms of clinical use safety. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Similarities between results of in vitro and in vivo methods were observed. • In vitro , changes occurred 3 days after radiological contrast media (RCM) exposure. • In vivo , serum creatinine concentration increased 3 days after RCM exposure. • In vitro , EDTA, but not Trometamol, induced changes similar to RCM. [ABSTRACT FROM AUTHOR]

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective(s): Early diagnosis of cancer using noninvasive imaging techniques has been discussed in several recent studies. The present study aimed to assess the synergistic effects of iodixanol-conjugated polyethylene glycol (PEG)-citrate (anionic linear globular) dendrimer G2 on MCF-7 breast cancer cells and human embryonic kidney 293 (HEK293) cells. Materials and Methods: PEG-citrate dendrimer G2 was synthesized and purified. The product was characterized using atomic force microscopy (AFM), electron energy loss spectroscopy (EELS), dynamic light scattering (DLS). At the next stage, the product was conjugated to iodixanol, purified and lyophilized. The cytotoxic effects of the iodixanol, plain PEG-citrate dendrimer G2, and iodixanol-PEG-citrate dendrimer G2 complex were evaluated using methylthiazole-tetrazolium (MTT) assay on the MCF-7 and HEK293 cells. Inductively coupled plasma mass spectrometry (ICP MS) is a mass spectrometry technique, which applies inductively coupled plasma to ionize samples. Results: According to the obtained results, the uptake of PEG-citrate dendrimer G2 iodixanol increased significantly compared to iodixanol alone (P<0.05), indicating the importance of lack of significant in-vitro toxicity. Moreover, in the particle size and higher negative zeta potential confirmed the loading of iodixanol in dendrimer G2. Increase, the loading of iodixanol in dendrimer was confirmed by the chemical shifts in HNMR. Conclusion: Therefore, it was concluded that the addition of anionic linear globular dendrimer G2 to iodixanol affected the cellular uptake of the drug with no significant toxicity. Recent findings also confirmed that this novel complex could be applied as an effective cancer imaging agent for molecular biology and molecular imaging applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Contrast-induced encephalopathy (CIE) is a rare complication of the intravascular application of a contrast agent. CIE can be manifested by headache, cortical blindness, consciousness disorders, seizures, or focal neurological deficit. Neurological symptoms are typically transient with temporary abnormal findings on a brain scan. Urgent neuroimaging is important to obtain the correct diagnosis, especially in cases that require an acute management and treatment. We present a case of CIE after a digital subtraction angiography of the vertebral arteries in the patient with a symptomatic pre-occlusive stenosis of the posterior cerebral artery. [ABSTRACT FROM AUTHOR]

Lipoproteins in plasma are constituted by the least dense chylomicron, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) that can be separated using commercially available medium such as iodixanol. Iodixanol constitutes the self-generated density gradient to fractionate lipoproteins by rapid ultracentrifugation method, replacing time-consuming protocols. Filling the centrifuge tubes is technically easier and faster than layering salt gradients and is reproducible. The separated lipoproteins by this method are closest to the native state with 80 to 100% recovery possible. Low-density lipoprotein is the major carrier of cholesterol in systemic circulation. The plasma isolated LDL is purified to be used as native LDL and for the preparation of oxidized LDL (oxLDL). The oxLDL is characterized for its oxidation, by various methods based on assay of the lipid and protein oxidation products such as TBARS, conjugated diene formation, and by other methods such as agarose gel electrophoresis. Rapid isolation of LDL particles from human plasma is useful for lipid peroxidation studies, characterization of subclass for functional studies and clinical correlation especially in cardiovascular diseases apart from lipidomic, and proteomic studies. OxLDL preparations are done in vitro chiefly based on copper-induced oxidation; glucose and other prooxidants. Which are used for various studies using animal model and in vitro cell models especially to understand macrophage-mediated atheroma formation, vascular endothelial cell dysfunction, cell signaling studies has scope for extensive research in metabolic dysfunction of various cells.  This chapter deals with one of the applications in the in vitro cell models using macrophage (THP-1 cell line) and human retinal pigment epithelial cell (ARPE-19 cell line) to study the oxLDL uptake using fluorescently labeled oxidized LDL (DiI-oxLDL)., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue – the region with the highest oxygen demand in the kidney - of pigs. While the mean pO2-value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney. Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol – in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomography angiography (CCTA) is obtained using peripheral intravenous iodinated contrast agents (ICA) injection. There is continuing attempts to derive coronary physiological information like coronary blood flow (CBF) and/or fractional flow reserve from CCTA images. However, no data is available regarding the effect of peripheral intravenous injection of ICA on CBF. Methods: A series of 4 experiments was performed using healthy mongrel dogs. All dogs underwent anesthesia and open thoracotomy with placement of ultrasound flowmeter to one of the coronary artery to provide real time absolute CBF measurements. Different infusion protocols of Isovue-370 and Visipaque-320 were injected into a peripheral vein. Similar doses of normal saline injection were performed to be used as controls. The effect of iodinated contrast media injection on absolute coronary blood flow was monitored and recorded. Results: Injection of normal saline in the peripheral vein did not produce any significant increase in CBF. Peripheral intravenous injection of ICA resulted in a consistent increase of 40–73% in absolute CBF as recorded 5 minutes post-contrast administration. The contrast effect starts about 30 seconds and peaks at about 2 minutepost-contrast injection then slowly fades away in the following 10–15 min. The increase in the CBF was dose related. There was greater increase in the CBF to 50 ml infusion compared to 25 ml infusion of both Visipaque and Isovue. Conclusions: Peripheral venous administration of iodinated contrast-media in dogs results in a dose related, significant and prolonged increase in CBF.

Iodixanol is a non-ionic iso-osmolar contrast agent, but it is a risk factor for kidney damage and increases morbidity and mortality. In this study, we investigated the effect of 9 sesquiterpenes isolated from mugwort (Artemisia argyi) in contrast agent-induced cytotoxicity in LLC-PK1 cells. Cells were exposed to nine sesquiterpene compounds for 2 h, followed by incubation with iodixanol for 3 h. Cell viability was assessed using the Ez-Cytox assay. The level of reactive oxygen species was measured using 2′,7′-dichlorodihydrofluorescein diacetate staining. Apoptotic cell death was detected using annexin V/PI staining. In addition, immunofluorescence staining and western blotting were performed using antibodies against proteins related to apoptosis, oxidative stress, and MAPK pathways. The most effective 3-epi-iso-seco-tanapartholide (compound 8) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound 8 reversed iodixanol-induced increases in the expression of JNK, ERK, p38, Bax, caspase-3, and caspase-9. It also reversed the iodixanol-induced decrease in Bcl-2 expression. Furthermore, pretreatment with compound 8 caused nuclear translocation of Nrf2 and upregulated HO-1 via the Nrf2 pathway in iodixanol-treated LLC-PK1 cells. Thus, we demonstrated here that compound 8 isolated from A. argyi has the potential to effectively prevent iodixanol-induced kidney epithelial cell death via the caspase-3/MAPK pathways and HO-1 via the Nrf2 pathway.

Background: Extracellular vesicles (EVs) (isolated from blood plasma) are currently being extensively researched, both as biomarkers and for their therapeutic possibilities. One challenging aspect to this research is the efficient isolation of high-purity EVs from blood plasma in quantities sufficient for in vivo experiments. In accordance with this challenge, the aim of this study was to develop an isolation method in which to separate the majority of EVs from major impurities such as lipoprotein particles and the abundant plasma proteins albumin and fibrinogen.Methods: Samples of rat blood were centrifuged to remove cells, platelets, large EVs and protein aggregates without prior filtration. Density gradient ultracentrifugation was performed by loading plasma sample onto 50, 30, and 10% iodixanol layers and then centrifuged at 120,000 ×g for 24 h. Ten fractions (F1-10) were collected from top to bottom. Fractions with the highest EV content were further purified by ultracentrifugation, size exclusion, or bind-elute chromatography. Efficiency and purity were assessed by Western blots. Morphology and size distribution of particles were examined by dynamic light scattering and electron microscopy (EM).Results: The highest band intensities of EV markers Alix, Tsg101 and CD81 were detected by Western blot in F6 of small-scale DGUC (61.5 ± 10.4%; 48.1 ± 5.8%; 41.9 ± 3.8%, respectively) at a density of 1.128–1.174 g/mL, where the presence of vesicles with a mean diameter of 38 ± 2 nm was confirmed by EM and DLS. Only 1.4 ± 0.5% of LDL and chylomicron marker, 3.0 ± 1.3% of HDL marker, and 9.9 ± 0.4% of albumin remained in the EV-rich F6. However, 32.8 ± 1.5% of the total fibrinogen beta was found in this fraction. Second-step purification by UC or SEC did not improve EV separation, while after BEC on HiScreen Capto Core 700 albumin and lipoprotein contamination were below detection limit in EV-rich fractions. However, BEC decreased efficiency of EV isolation, and fibrinogen was still present in EV-rich fractions.Conclusion: This is the first demonstration that DGUC is able to markedly reduce the lipoprotein content of EV isolates while it separates EVs with high efficiency. Moreover, isolation of lipoprotein- and albumin-free EVs from blood plasma can be achieved by DGUC followed by BEC, however, on the expense of reduced EV yield.

MicroRNAs are small gene-regulatory RNAs that are found in various biological fluids, including milk, where they are often contained inside extracellular vesicles (EVs), like exosomes. In a previous study, we reported that commercial dairy cow’s milk microRNAs resisted simulated digestion and were not exclusively associated with canonical exosomes. Here, we report the characterization of a milk EV subset that sediments at lower ultracentrifugation speeds and that contains the bulk of microRNAs. Milk EVs were isolated by differential ultracentrifugation and Iodixanol density gradient (IDG), and analysed for (1) microRNA enrichment by reverse transcription and quantitative polymerase chain reaction (RT-qPCR), and (2) EV-associated proteins by Western blot. Milk EVs were characterized further by dynamic light scattering (DLS), density measurements, fluorescent DiR and RNA labelling, high-sensitivity flow cytometry (HS-FCM), transmission electron microscopy (TEM), proteinase K and RNase A assay, and liquid chromatography tandem-mass spectrometry (LC-MS/MS). We found that the bulk of milk microRNAs (e.g., bta-miR-125b, bta-miR-148a, etc.) sediment at 12,000 g and 35,000 g. Their distribution pattern was different from that of exosome-enriched proteins, but similar to that of several proteins commonly found in milk fat globule membranes (MFGM), including xanthine dehydrogenase (XDH). These low-speed ultracentrifugation pellets contained cytoplasm-enclosing phospholipid bilayered membrane vesicles of a density comprised between 1.11 and 1.14 g/mL in Iodixanol. This milk EV subset of ~100 nm in diameter/~200 nm hydrodynamic size resisted to proteinase K digestion and protected their microRNA content from RNase A digestion. Our results support the existence of a milk EV subset pelleting at low ultracentrifugations speeds, with a protein coating comparable with MFGM, which contains and protects the bulk of milk microRNAs from degradation. This milk EV subset may represent a new EV population of interest, whose content in microRNAs and proteins supports its potential bioactivity.

Objective- To evaluate and compare the radiographic efficacy and safety of a non-ionic dimeric and isotonic iodinated contrast medium, iodixanol (320 mgI/ml) and a non-ionic monomer and hypertonic contrast medium, iohexol (300 mgI/ml) in feline cervical myelography. Design- Experimental study Animals- Five adult healthy cats. Procedures- Iodixanol and iohexol were injected into the cerebellomedullary cistern. Radiographs were obtained immediately, 10, 20, 40 and 60 minutes after injection. The myelograms were scored and analyzed for statistical significance. Results- Diagnostically adequate radiographic examinations were obtained with both agents. Adequate opacity in thoracic and lumbar vertebrae was obtained after 10 and 20 minutes post injection for both contrast agents. After 40 minutes contrast agents were had reached the end of lumbar vertebrae column. No significant differences in scoring for image quality were observed between two contrast mediums (p>0.05). Iodixanol and iohexol radiopacified cervical region immediately after injection. Adequate opacity in thoracic and lumbar vertebrae was obtained after 10 and 20 minutes post injection for both contrast agents. Evaluation of each of the radiographs showed good to excellent opacification. No clinical and neurological abnormalities were found related to the myelographic procedure during one week after injection. Vital signs, CBC and some serum biochemical examinations remain in normal ranges. Conclusion and Clinical Relevance- Iodixanol and iohexol proved to be safe and effective contrast materials for myelographic studies in cats. More mean score of iodixanol suggests that, it is preferable to perform myelography with iodixanol.

Iodixanol is an iso-osmolar non-ionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)-approved iso-osmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low-osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. These contrast agents are used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability, and efficacy of iodixanol are reviewed, specifically evaluating the use of CCTA and coronary angiography, including outcome studies, randomized trials, and comparisons to other contrast agents.

Background: Extracellular vesicles (EVs) (isolated from blood plasma) are currently being extensively researched, both as biomarkers and for their therapeutic possibilities. One challenging aspect to this research is the efficient isolation of high-purity EVs from blood plasma in quantities sufficient for in vivo experiments. In accordance with this challenge, the aim of this study was to develop an isolation method in which to separate the majority of EVs from major impurities such as lipoprotein particles and the abundant plasma proteins albumin and fibrinogen. Methods: Samples of rat blood were centrifuged to remove cells, platelets, large EVs and protein aggregates without prior filtration. Density gradient ultracentrifugation was performed by loading plasma sample onto 50, 30, and 10% iodixanol layers and then centrifuged at 120,000 × g for 24 h. Ten fractions (F1-10) were collected from top to bottom. Fractions with the highest EV content were further purified by ultracentrifugation, size exclusion, or bind-elute chromatography. Efficiency and purity were assessed by Western blots. Morphology and size distribution of particles were examined by dynamic light scattering and electron microscopy (EM). Results: The highest band intensities of EV markers Alix, Tsg101 and CD81 were detected by Western blot in F6 of small-scale DGUC (61.5 ± 10.4%; 48.1 ± 5.8%; 41.9 ± 3.8%, respectively) at a density of 1.128–1.174 g/mL, where the presence of vesicles with a mean diameter of 38 ± 2 nm was confirmed by EM and DLS. Only 1.4 ± 0.5% of LDL and chylomicron marker, 3.0 ± 1.3% of HDL marker, and 9.9 ± 0.4% of albumin remained in the EV-rich F6. However, 32.8 ± 1.5% of the total fibrinogen beta was found in this fraction. Second-step purification by UC or SEC did not improve EV separation, while after BEC on HiScreen Capto Core 700 albumin and lipoprotein contamination were below detection limit in EV-rich fractions. However, BEC decreased efficiency of EV isolation, and fibrinogen was still present in EV-rich fractions. Conclusion: This is the first demonstration that DGUC is able to markedly reduce the lipoprotein content of EV isolates while it separates EVs with high efficiency. Moreover, isolation of lipoprotein- and albumin-free EVs from blood plasma can be achieved by DGUC followed by BEC, however, on the expense of reduced EV yield. [ABSTRACT FROM AUTHOR]

Effects of radiographic contrast media (RCM) application were demonstrated in vitro and in vivo where the injection of RCM into the A. axillaris of patients with coronary artery disease was followed by a significant and RCM-dependent decrease of erythrocyte velocity in downstream skin capillaries. Another study in pigs revealed that the deceleration of erythrocytes coincided with a significant reduction of the oxygen partial pressure in the myocardium—supplied by the left coronary artery—after the administration of RCM into this artery. Further reports showed RCM dependent alterations of erythrocytes like echinocyte formation and exocytosis, sequestration of actin or band 3 and the buckling of endothelial cells coinciding with a formation of interendothelial fenestrations leading to areas devoid of endothelial cells. Key to morphological alterations of erythrocytes is the membrane cytoskeleton, which is linked to the band 3 in the erythrocyte membrane via the junctional complex. Fundamental observations regarding the cell biological and biochemical aspects of the structure and function of the cell membrane and the membrane cytoskeleton of erythrocytes have been reported. This review focuses on recent results gained, e.g., by advanced confocal laser scanning microscopy of different double-stained structural elements of the erythrocyte membrane cytoskeleton.