Ionic Iodinated Contrast Media Research Articles

Comparing the toxicity of iodinated X-ray contrast media on eukaryote- and prokaryote-based quantified microarray assays

This study compared the toxicity mechanisms of four X-ray-based iodinated contrast media (ICM) on Escherichia coli (E. coli) and yeast microarray assays, aiming to determine the diverse toxicity mechanisms among different exposed organisms and the relationship between toxicity and their physical and chemical characteristics. The conventional phenotypic endpoint cytotoxicity and the change in reactive oxygen species (ROS) level were employed in conjunction with toxicogenomics to quantify changes in the gene/protein biomarker level in the regulation of different damage/repair pathways. The results showed that molecular toxicity endpoints, named transcriptional effect level index (TELI) and protein effect level index (PELI) for E. coli and yeast, respectively, correlated well with the phenotypic endpoints. Temporal altered gene/protein expression profiles revealed dynamic and complex damage/toxic mechanisms. In particular, compared with E. coli cells, yeast cells exposed to ICM exhibited significantly higher stress intensity and diverse stress types, resulting in stress or damage to the organism. The toxic mechanisms of ICM are concentration/property-dependent and relevant to the cellular structure and defense systems in prokaryotes and eukaryotes. In particular, the toxicity of ionic ICM is higher than that of non-ionic ICM, and eukaryotes are more susceptible than prokaryotes to ICM exposure.

P635 Assessment of sarcopenia and nutritional status in a cohort of patients with Crohn’s disease

Abstract Background Altered body composition may negatively impact on the clinical outcome and quality of life of patients with IBD. Sarcopenia, defined as a progressive loss of skeletal muscle mass and function, is commonly observed in patients with IBD and can be reliably assessed by computed tomography (CT) which allows accurate and reproducibile quantification of both abdominal adipose tissues (subcutaneous and visceral), as well as skeletal muscles. We aimed to assess the prevalence of sarcopenia in Crohn’s disease (CD) patients undergoing contrast-enhanced CT(CECT). We further investigated the associations of sarcopenia with visceral fat parameters, disease severity and surgery Methods 40 CD patients (22F, aged 44±16 yrs; BMI 20.8±3.7) who underwent CECT for clinical assessment were retrospectively enrolled. CECT was performed using a 64-rows multi-detector equipment after i.v. injection of non ionic iodinated contrast media with a tailored scan delay. Demographic and clinical data were collected at the date of abdominal CT. Clinical outcome included the rate of surgery within one year. The skeletal muscle index (SMI) at the level of third lumbar vertebra was used to assess sarcopenia defined as a SMI<38.5cm2/m2 in women and <42cm2/m2 in men (Fig1).Clinical malnutrition was defined by a BMI<18.5 kg/m2, while visceral obesity as a visceral fat area ≥130cm2 Results Mean duration of disease was 117 months ± 84. Most patients 60% had a moderate-severe clinical activity based on Harvey Bradshaw index (HBI) >8, whereas 35% had a mild activity (HBI 5–7) and 5% were in remission (HBI<5). Overall, 17(42.5%) patients were sarcopenic. In detail, 14 out of 22 (63.6%) females and only 3 out of 18 (16.6%) males (p=0.04). The majority (65%) had moderate activity of inflammation with a mean of HBI 9.2 ± 1.6. Malnutrition occurred in 41,2% sarcopenic patients with a mean BMI of 16.5±3.75. A significant correlation was observed between BMI and sarcopenia (r=0.4,p<0.001). A total of 25 (62.5%) patients underwent surgery within one year. Among them, 40% patients were sarcopenic, while 60% non sarcopenic (p=0.7). In the total population the mean of visceral fat was 48,03±58.04 and only 4 patients had a visceral fat area ≥104 cm2. The ratio between visceral fat and subcutaneous fat area (VFA/SFA) was 0,57±0.5. The correlation between SMI and visceral fat was significant (r=0.4,p=0.02),while it was not significant with VFA/SFA (p=0.7). For all IBD patients, univariate analysis revealed that female sex (p=0.002) and low BMI (p=0.003) were significantly associated with sarcopenia Conclusion Approximately 42.5%CD patients were sarcopenic. Female sex and low BMI were significantly associated with sarcopenia but this latter did not correlate with the clinical outcome

Hypersensitivity Reactions to Iodinated Contrast Media: Is it a True Allergy?

Classically, hypersensitivity reactions to iodinated contrast media (ICM) have been termed pseudoallergic, allergy-like, or anaphylactoid. The origin of these terms to define ICM hypersensitivity reactions could be in relation to the use of traditional, classic, ionic ICMs. These ionic ICMs have a high osmolality, and the reactions have been considered as secondary to non-specific histamine release. Currently, ionic ICMs have been replaced by non-ionic compounds with low or iso-osmolality, which, although to a lesser extent, can also produce hypersensitivity reactions. In recent years, there has been growing evidence that some of these reactions, especially the more severe, can be triggered by an IgE-dependent mechanism. Also, in recent decades, there has been an increase in non-immediate reactions, especially in the form of maculopapular exanthems occurring up to several days after the administration of ICM. In these non-immediate reactions, the involvement of T lymphocytes has been clearly demonstrated. The finding of positive skin tests and other in vitro studies for ICMs would support a specific immunological mechanism in a percentage of ICM-induced reactions. However, although there is a body of evidence suggesting that ICMs can induce true allergy reactions, the main guidelines for contrast media management, such as those proposed by US (American College of Radiology Manual on Contrast Media) or European (European Society of Urogenital Radiology Guidelines on Contrast Media) societies, continue to consider only immediate reactions and handle them as non-allergic reactions, without any allergy testing. In ICM reactions an allergic evaluation should be mandatory, not only to study the possible mechanisms involved but also to identify the ICM involved in the reaction and to find an alternative one that could be used in future radiological explorations.

Time- and Dose-dependent Cytotoxicities of Ioxitalamate and Indigocarmine in Human Nucleus Pulposus Cells

Introduction Ioxitalamate (Telebrix 300) is an ionic iodinated contrast medium (CM) commonly used for discography or PELD (percutaneous endoscopic lumbar discectomy), though it has side effects such as anaphylactic shock and renal toxicity. Indigocarmine is an organic compound dye with a distinctive blue color that is commonly used during PELD to stain the acidic, degenerated nucleus pulposus. Although ioxitalamate and indigocarmine are widely used in spinal surgery, there have been no reports on their effects on nucleus pulposus (NP) cells. We studied the toxicity of both ioxitalamate and indigocarmine to NP cells. Materials and Methods NP cells were obtained via discectomy from lumbar disc patients and isolated. NP cells were cultured in three-dimensional (3D) alginate beads with 0.001, 0.1, 10, and 100 mg/mL ioxitalamate, 0.00001, 0.001, 0.1 and 10 mg/mL indigocarmine, or a mixture of both for 1, 2, or 3 days. The living cells were analyzed with trypan blue staining. FACS analysis using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining was performed to identify live, apoptotic, and necrotic cells. Results Ioxitalamate, indigocarmine, and their combination induced statistically significant NP cell injury that was both time and dose dependent ( p < 0.05). Also, at the same concentration, ioxitalamate was more cytotoxic than was indigocarmine or the combination ( p < 0.05). All three treatments also showed dose-dependent cytotoxicity according to flow cytometry and immunostaining. Conclusion Ioxitalamate and indigocarmine are toxic to human NP cells in vitro in a time- and dose-dependent manner. We assume that ioxitalamate and indigocarmine may have similar effects in patients undergoing discography and PELD. Thus, we suggest that ioxitalamate and indigocarmine should be used carefully at low concentrations. Disclosure of Interest None declared References Stout A. Discography. Phys Med Rehabil Clin N Am 2010;21(4):859–867 Manchikanti L, Glaser SE, Wolfer L, Derby R, Cohen SP. Systematic review of lumbar discography as a diagnostic test for chronic low back pain. Pain Physician 2009;12(3):541–559 Carragee EJ, Tanner CM, Yang B, Brito JL, Truong T. False-positive findings on lumbar discography. Reliability of subjective concordance assessment during provocative disc injection. Spine 1999;24(23):2542–2547 Laslett M, Oberg B, Aprill CN, McDonald B. Centralization as a predictor of provocation discography results in chronic low back pain, and the influence of disability and distress on diagnostic power. Spine J 2005;5(4):370–380 Kim D, Wadley R. Variability in techniques and patient safety protocols in discography: a national multispecialty survey of International Spine Intervention Society members. J Spinal Disord Tech 2010;23(6):431–438 Carragee EJ, Tanner CM, Khurana S, et al. The rates of false-positive lumbar discography in select patients without low back symptoms. Spine 2000;25(11):1373-1380, discussion 1381 Paul MD, Tsou M. Posterolateral percutaneous endoscopic lumbar discectomy. Oper Tech Orthop 2003;13:207-213 Yeung AT. Selective endoscopic discectomy. In: Kambin P, ed. Arthroscopic and Endoscopic Spinal Surgery. Totowa, NJ: Humana Press; 2005:205–225 Mayer HM, Brock M. Percutaneous endoscopic discectomy: surgical technique and preliminary results compared to microsurgical discectomy. J Neurosurg 1993;78(2):216–225 Yeung AT, Tsou PM. Posterolateral endoscopic excision for lumbar disc herniation: Surgical technique, outcome, and complications in 307 consecutive cases. Spine 2002;27(7):722–731 Lee H, Sowa G, Vo N, et al. Effect of bupivacaine on intervertebral disc cell viability. Spine J 2010;10(2):159–166 Hsu SP, Tsai TJ, Chien CT. Ioxitalamate induces renal tubular apoptosis via activation of renal efferent nerve-mediated adrenergic signaling, renin activity, and reactive oxygen species production in rats. Toxicol Sci 2010;114(1):149–158 Lee HC, Chang JG, Yen HW, Liu IH, Lai WT, Sheu SH. Ionic contrast media induced more apoptosis in diabetic kidney than nonionic contrast media. J Nephrol 2011;24(3):376–380 Belhadjali H, Bouzgarrou L, Youssef M, Njim L, Zili J. DRESS syndrome induced by sodium meglumine ioxitalamate. Allergy 2008;63(6):786–787 Lacour B, Lacroix C, Jungers P, Bailly M. [Effects of intravenous urography using sodium and meglumine ioxitalamate (Telebrix 38) on blood creatinine and urinary excretion of N-acetyl-beta-D-glucosaminidase]. Ann Biol Clin (Paris) 1984;42(6):407–411

Time- and dose-dependent cytotoxicities of ioxitalamate and indigocarmine in human nucleus pulposus cells

Background contextIoxitalamate (Telebrix 300) is an ionic iodinated contrast medium commonly used for discography or percutaneous endoscopic lumbar discectomy (PELD), though it has side effects such as anaphylactic shock and renal toxicity. Indigocarmine is an organic compound dye with a distinctive blue color that is commonly used during PELD to stain the acidic, degenerated nucleus pulposus (NP). Although ioxitalamate and indigocarmine are widely used in spinal surgery, there have been no reports on their effects on NP cells. We studied the toxicities of both ioxitalamate and indigocarmine to NP cells. PurposeTo determine the toxicities of both ioxitalamate and indigocarmine to NP cells in vitro. Study designIn vitro, controlled study of the toxicities of both ioxitalamate and indigocarmine to human NP cells. MethodsNucleus pulposus cells were obtained via discectomy from lumbar disc patients and isolated. Nucleus pulposus cells were cultured in three-dimensional (3D) alginate beads with 0.001, 0.1, 10, and 100 mg/mL ioxitalamate, 0.00001, 0.001, 0.1, and 10 mg/mL indigocarmine, or a mixture of both for 1, 2, or 3 days. The living cells were analyzed with trypan blue staining. Fluorescence Activated Cell Sorting analysis using Annexin V and propidium iodide and 3D alginate bead immunostaining was performed to identify live, apoptotic, and necrotic cells. ResultsIoxitalamate, indigocarmine, and their combination induced statistically significant NP cell injury that was both time- and dose dependent (p<.05). Also, at the same concentration, ioxitalamate was more cytotoxic than was indigocarmine or the combination (p<.05). All three treatments also showed dose-dependent cytotoxicity according to flow cytometry and immunostaining. ConclusionsIoxitalamate and indigocarmine are toxic to human NP cells in vitro in a time- and dose-dependent manner. We assume that ioxitalamate and indigocarmine may have similar effects in patients undergoing discography and PELD. Thus, we suggest that ioxitalamate and indigocarmine should be used carefully at low concentrations.

Adverse delayed reactions to the intravenous injection of non—ionic iodinated contrast media

AbstractAdverse delayed reactions (ADRs) to the intravenous injection of non‐ionic iodinated contrast media (NICM) were first recognised in the mid‐1980s and a growing number of articles in the literature have described such reactions as increasingly common. The aim of this article is to increase the understanding of the risk factors, frequency, signs and symptoms of ADRs amongst healthcare staff especially radiographers, nurses, radiologists and physicians who regularly use contrast media (CM). A literature review of multiple studies assessing ADRs performed from 1990–2010 has revealed various misconceptions, particularly in the frequency of ADRs and the influence of ethnic background most likely due to methodological limitations. Therefore, the use of improved research methods and design has the potential to increase our knowledge in this area. Furthermore, new areas of study such as blood testing as a screening tool can assist in risk assessment and prevention of ADRs.

Iodinated contrast media oxidation by nonthermal plasma: The role of iodine as a tracer

The oxidation of trace pharmaceutical compounds in wastewater desalination streams by nonthermal plasma (NTP) was evaluated. Brines from a two stage-RO pilot plant process as well as two sources of tertiary effluents, ultrafiltrated secondary effluents and membrane biological reactor effluents, were comparatively tested with ultra-pure water. The non-ionic and ionic iodinated contrast media (ICM) compounds, iopromide (IOPr) and diatrizoate (DTZ), respectively, were used as model compounds. The neurostabilizer drug carbamazepine (CBZ) was used for reference purposes. Based on deiodination profiles, two distinct patterns of initial oxidation could be established for the ICM. The time profile of deiodination and transformation paralleled for DTZ, indicating that transformation of the aromatic ring is the main initial pattern of transformation. For IOPr, a considerable lag phase of deiodination was observed, suggesting that oxidation of the alkyl chains rather than ring oxidation is the main pattern of initial transformation. Although transformation rate of IOPr was higher compared to DTZ, the rate and degree of deiodination was higher for DTZ than IOPr. Both ICM displayed a markedly lower susceptibility to NTP oxidation compared to CBZ. However, the kinetics of IOPr transformation seems to be less affected by the water matrixes, compared to DTZ and CBZ. Whereas NTP mediated oxidation of ICM followed first-order kinetics, a better fit to Harris model was found for CBZ. As a result of the NTP oxidation, treated brines and effluents displayed a substantial increase in biodegradability (measured as BOD). To conclude, NTP displayed a high potential for treating reluctant pharmaceuticals active compounds such as ICM, even at the background of relatively high DOC concentrations, as can be found in treated effluents and desalination brines, and with no need for chemical additives.

ＣＴ造影製剤特性が造影効果に及ぼす影響

The various nonionic iodinated contrast media used in contrast computed tomography (CT) studies differ in terms of their composition, characteristics, and iodine concentration (mgI/ml), as well as the volume injected (ml). Compared with ionic iodinated contrast media, nonionic iodinated contrast media are low-osmolar agents, with different agents having different osmotic pressures. Using a custom-made phantom incorporating a semipermeable membrane, the osmotic flow rate (HU/s) could easily be measured based on the observed increase in CT numbers, and the relationship between the osmotic pressure and the osmotic flow rate could be obtained (r(2)=0.84). In addition, taking the effects of patient size into consideration, the levels of contrast enhancement in the abdominal aorta (AA) and inferior vena cava (IVC) were compared among four types of CT contrast medium. The results showed differences in contrast enhancement in the IVC during the equilibrium phase depending on the type of contrast medium used. It was found that the factors responsible for the differences observed in enhancement in the IVC were the osmotic flow rate and the volume of the blood flow pathways in the circulatory system. It is therefore considered that the reproducibility of contrast enhancement is likely to be reduced in the examination of parenchymal organs, in which scanning must be performed during the equilibrium phase, even if the amount of iodine injected per unit body weight (mgI/kg) is maintained at a specified level.

Il faut prémédiquer les allergiques avant un examen d’imagerie avec produit de contraste : contre

Anaphylactic reactions due to iodinated contrast media (ICM) are rare and they occur more frequently with ionic ICM compared with non-ionic ICM. These reactions are more frequent in asthmatic patients, whereas no study is actually available, which would allow us to determine if this risk is greater in allergic subjects. The efficacy of premedication for the prevention of an anaphylactic reaction before injection of an ICM has not been demonstrated in unselected patients, asthmatic patients or allergic patients. Only the use of non-ionic ICMs reduces the risk of an anaphylactic reaction in asthmatics.

Immediate adverse reactions to intravenous iodinated contrast media in computed tomography

This exploratory-descriptive, non-experimental quantitative research aimed to learn about immediate adverse reactions to intravenous iodinated contrast media in hospitalized patients submitted to computed tomography at a teaching hospital in the South of Brazil. During the study period, all adverse reactions showed mild intensity, at a frequency of 12.5% with ionic iodinated contrast media, and 1% with non-ionic contrast agent. The extravasation of contrast occurred in 2.2% of the injections in a peripheral vein without complications in any of the cases. The results are within the limits cited in international literature and suggest that tomography service professionals should know their own rates of adverse reactions to iodinated contrast agent, as well as the conditions in which they occur, in order to obtain evidence to evaluate the respective care delivery processes.

HELICAL COMPUTED TOMOGRAPHIC ANGIOGRAPHY OF THE NORMAL CANINE PANCREAS

Helical abdominal computed tomography (CT) was performed in nine normal beagle-mix dogs. Following cephalic vein injection of ionic iodinated contrast medium via power injector (rate 5 ml/s) dual-phase CT was performed in all dogs. A delayed scan was performed in five dogs between 5 and 13 min after the contrast medium injection. The median time of appearance of contrast medium in the aorta and gastroduodenal artery was 6.3 and 7 s, post start injection and 12 and 12.2 s in the gastroduodenal and portal vein, resulting in a purely arterial pancreatic time window of 5-6s. Pancreatic veins and parenchyma remained enhanced until the end of the dynamic scan (40s). The pancreatic parenchyma showed heterogeneous arterial and homogenous venous contrast enhancement which was slightly hypoattenuating compared to the liver. Delayed scans provided best delineation of the pancreas from the liver. The common bile duct could be identified ventral and to the right of the portal vein joining the dorsomedial aspect of proximal duodenum. Because of the very short time window and variable onset of pure arterial enhancement careful planning of dual-phase studies with previous dynamic CT is recommended. Dual-phase CT angiography enables assessment of the arterial supply, parenchymal perfusion and venous drainage of the canine pancreas.

DYNAMIC COMPUTED TOMOGRAPHY OF THE NORMAL FELINE HYPOPHYSIS CEREBRI (GLANDULA PITUITARIA)

The purpose of this study was to describe normal feline hypophyseal mensuration and contrast enhancement characteristics using dynamic computed tomography (CT) imaging. An intravenous bolus of an ionic iodinated contrast medium was administered to eight cats using a pressure injector while dynamic CT images were obtained every 5 s for five cats and every 7 s for three cats for a total imaging time of 5 min. Each pituitary was measured at its maximum height and width on the peak contrast medium enhancement image. A hand-drawn region of interest was placed around each hypophysis cerebri and time attenuation curves were generated. The specific enhancement pattern of the hypophysis cerebri for each cat was recorded. The mean width and height of the hypophysis cerebri was 5.2 +/- 0.4 (average +/- SD) mm and 3.1 +/- 0.3 mm, respectively. The mean time to maximum contrast enhancement was 28.6 +/- 14.8 s (range 14-50 s) from the onset of contrast medium injection. Four cats had initial dorsal and peripheral contrast enhancement patterns of the hypophysis cerebri, while four cats had an initial central contrast medium enhancement pattern. The hypophysis cerebri had a homogenous appearance in all cats, 28-50 s after contrast medium injection. The average (+/- SD) clearance half-time was 292 (+/- 87) s. Normal hypophysis cerebri mensuration and contrast medium enhancement characteristics will help in clinical evaluation of the feline hypophysis cerebri.

Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.

Iodinated contrast media (ICM) can induce apoptosis (programmed cell death) in renal, myocardial and endothelial cells. Following intravascular injection, circulating immune cells are exposed to high concentrations of ICM. As neutrophils constitutively undergo apoptosis we hypothesized that ICM may adversely affect neutrophil survival. Our aim was to investigate the effect of ICM on neutrophil apoptosis. Neutrophils were isolated from healthy subjects and cultured in vitro with ionic (diatrizoate and ioxaglate) and non-ionic (iohexol and iotrolan) ICM. The effect of ICM on neutrophil apoptosis in both unstimulated and lipopolysaccharide-stimulated neutrophils was determined by annexin V flow cytometry. The influence of physicochemical properties of the different ICM on apoptosis of neutrophils was also studied. We further investigated the effects of ICM on key intracellular signal pathways, including p38 mitogen-activated protein kinase (MAPK) by Western blotting, and mitochondrial depolarization and caspase activity by flow cytometry. Isoiodine concentrations (20 mg ml(-1)) of ionic (diatrizoate 69.6+/-2.9%; ioxaglate 58.9+/-2.0%) and non-ionic (iohexol 57.3+/-2.9%; iotrolan 57.1+/-2.6%) ICM significantly induced neutrophil apoptosis over control levels (47.7+/-1.4%). The apoptotic effect of ICM was influenced by their chemical structure, with ionic ICM having a more significant (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). Furthermore, ICM reversed the anti-apoptotic effect of lipopolysaccharide (1000 ng ml(-1)) treated neutrophils to control levels (23.0+/-3.5% to 61.2+/-5.3%; n=4; p<0.05). These agents induce apoptosis through a p38 MAPK independent pathway that results in mitochondrial depolarization, and is dependent on caspase activation. As neutrophils play a central role in host response to infection and injury, ICM, through induction of neutrophil apoptosis, could have a significant deleterious effect on host immune defence and resolution of an inflammatory response.

Allergy and contrast media.

. THE allergic origin of severe reactions following the injection of iodinated contrast media (ICM) is disputed. However, three publications argue that immediate hypersensitivity is probably due to IgE mediation (1±3). The description of clinical signs and measurement of mediators (histamine, tryptase) play an important role since cutaneous tests and speci®c IgEs are not validated for ICMs. We report ®ve clinical cases of severe reactions (including one death) occurring after an intra-arterial injection of the same ionic ICM in three patients and two nonionic ICMs in two other patients (Table 1). The clinical symptoms corresponded in each case to the grade III (4) minimum. All the patients had been in contact with the culprit ICM at least once (prior exposure). Treatment with intravenous epinephrine was successful in four cases. One patient died from cardiovascular collapse followed by multiorgan failure 16 h after the injection. Measurement of mediators (histamine and tryptase) was done. After the patients gave informed consent, prick tests and intradermal tests (IDT) were carried out 6 weeks after the incident to identify the culprit ICM. A prick test with pure ICM on the forearm, is positive if 15 min later a wheal appears which is equal to at least half the positive control (using an extract of codeine phosphate at 9%) and larger than the negative control (saline solution). An IDT is done on the patient's back by injecting 0.15 ml of ICM at a concentration ranging from 10 to 10, raising a bleb of about 3 mm. The IDT is positive if 15 min Five cases of severe anaphylactoid reactions.

Ionic iodinated contrast medium and amobarbital sodium mixtures: potential for precipitation.

When a small amount of diatrizoate meglumine, an ionic iodinated contrast medium, is left in a catheter system before injection of amobarbital sodium or when the contrast medium is intentionally mixed with amobarbital sodium, a potentially dangerous situation occurs. The authors showed in vitro that a dense precipitate forms in this situation. This is due to an acid-base reaction between the relatively acidic contrast medium and basic barbiturate and the subsequent formation of insoluble amobarbital.