Harmful effect of repetitive intravenous iodinated contrast media administration on the long-term renal function of patients with early gastric cancer.

This retrospective study investigated whether repetitive exposure to intravenous iodinated contrast media (ICM) affects long-term renal function in patients who undergo curative surgery for early gastric cancer (EGC) collected from the Korean Health Insurance and Review Assessment (HIRA) database. Patients diagnosed with gastric cancer between January 2010 and December 2013 underwent regular computed tomography (CT) scans to monitor for extragastric recurrence. Patients who already had chronic kidney disease (CKD) before cancer diagnosis or had undergone chemotherapy or repeated surgery were excluded. A nested case-control study design was chosen to analyze the effect of repetitive ICM exposure to long-term renal function by comparing patients who developed CKD 2 years after cancer diagnosis and patients who did not. Among 59,971 patients collected according to inclusion and exclusion criteria, 1021 were diagnosed with CKD 2 years after cancer diagnosis. Using 1:5 matching after adjusting for age, sex and date of cancer diagnosis, 5097 control patients were matched to 1021 CKD patients. Conditional logistic regression showed that the number of CTs taken using ICM slightly increased the odds of CKD (odds ratio, 1.080; 95% confidence interval (CI): 1.059, 1.100; P < 0.0001). Thus, the administration of ICM might contribute to chronic renal function impairment.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

CHRONIC EFFECTS OF CADMIUM CHLORIDE ON RAT EMBRYOGENESIS.

The purpose of this study was to analyze the effects of cadmium toxicity on rat embryogenesis when exposed to other heavy metal citrates. Despite the variety of scientific publications discussing the influence of cadmium on mammalian postnatal development, the effect of this metal on embryogenesis has not yet been sufficiently studied. In this experimental study, cadmium chloride was administered to experimental pregnant female Wistar rats at a daily dose of 1.0 mg/kg. Rats were allocated at random into groups receiving either cadmium chloride alone or additional zinc citrate, cerium citrate, or nanocomposite (based on iodine, sulfur, and selenium citrate). The control group received distilled water at an equivalent volume. In each group, operational intervention occurred at the 13th and 20th day of gestation to assess numbers of live fetuses, corpora lutea, pre-implantation losses, post-implantation losses, and total implantation losses. When cadmium chloride alone was administered, a pronounced embryotoxic effect was observed, manifested as a significant decrease in the number of live fetuses. Experimental groups which received cadmium chloride with zinc citrate, cerium citrate, or nanocomposite had an increased number of live fetuses and corpora lutea, as well as a decreased number of implantation losses, compared to the group which only received cadmium chloride. Each combination of cerium, zinc, and selenium nanocomposite citrates demonstrated a compensatory effect on all measures of embryogenesis impacted by cadmium embryotoxicity. Thus, administration of the citrates of cerium, zinc, and selenium nanocomposite reduces cadmium embryotoxicity and its accumulation in the body.

Contrast-enhanced mammography-guided biopsy: technical feasibility and first outcomes.

OBJECTIVES: To evaluate the feasibility of contrast-enhanced mammography (CEM)-guided biopsy at Hospital del Mar, a Spanish university hospital. METHODS: We retrospectively reviewed all consecutive women with a suspicious enhancing finding eligible for CEM-guided biopsy, who were prospectively enrolled in a pre-marketing clinical validation and feasibility study (October 2019 to September 2021). CEM-guided biopsy is a stereotactic-based procedure that, by using intravenous iodinated contrast media administration and dual-energy acquisition, provides localisation of enhancing lesions. All the biopsies were performed using a vacuum-assisted device. We collected procedural characteristics (patient position and type of approach), and histopathological results. Feasibility endpoints included success (visualisation of the enhancing lesion, post-procedural biopsy changes and clip placement), procedural time, number of scout acquisitions and complications. RESULTS: A total of 66 suspicious enhancing lesions (18.0% foci, 44.0% mass, 38.0% non-mass enhancement; median size 8.5 mm) in 64 patients (median age 59 years, mostly minimal [48.4%] or mild [32.8%] background parenchymal enhancement) were referred for CEM-guided biopsy in the study period. The success rate was 63/66 (95.4%). Amongst successful procedures, patients were most frequently seated (52/63, 82.5%) and the preferred approach was horizontal (48/63, 76.2%). Median total time per procedure was 15 min. Median number of acquisitions needed before targeting was 2 (range 1-4). Complications consisted of hematoma (17/63, 27%) and vasovagal reaction (2/63, 3.2%). At histology, the malignancy rate was 25/63 (39.7%). CONCLUSION: In this first patient series, CEM-guided breast biopsy was feasible, with success and complication rates similar to those previously reported for magnetic resonance guidance. KEY POINTS: • CEM may be used to guide biopsy of enhancing lesions through a stereotactic-based procedure combined with intravenous iodinated contrast media administration and dual-energy acquisition. • In this first patient series (n = 64), the success rate of CEM-guided biopsy was above 95%, the only complications were hematoma (22.2%) and vasovagal reaction (3.2%), and median total time per procedure was 15 min. • CEM-guided biopsy is feasible and could potentially be a widely available biopsy technique for enhancing-only lesions.

Effect to Therapy of Sodium-Iodine Symporter Expression by Alpha-Ray Therapeutic Agent via Sodium/Iodine Symporter.

This study confirmed the effect of sodium/iodine symporter (NIS) expression on existing drugs by in vitro and in vivo tests using cultured cell lines. The tumor growth inhibitory effect of sodium astatide ([211At]NaAt) was evaluated by in vitro and in vivo tests using human thyroid cancer cells (K1, K1/NIS and K1/NIS-DOX). NIS expression in cancer cells was controlled using the Tet-On system. [131I]NaI was used as control existing drug. From the results of the in vitro studies, the mechanism of [211At]NaAt uptake into thyroid cancer cells is mediated by NIS, analogous to [131I]NaI, and the cellular uptake rate correlates with the expression level of NIS. [211At]NaAt's ability to inhibit colony formation was more than 10 times that of [131I]NaI per becquerel (Bq), and [211At]NaAt's DNA double-strand breaking (DSB) induction was more than ten times that of [131I]NaI per Bq, and [211At]NaAt was more than three times more cytotoxic than [131I]NaI (at 1000 kBq each). In vivo studies also showed that the tumor growth inhibitory effect of [211At]NaAt depended on NIS expression and was more than six times that of [131I]NaI per Bq.

Zeroing on Gadolinium to Complement Intravascular Ultrasound in Zero-Contrast Percutaneous Coronary Interventions.

BACKGROUND: Many techniques have been developed to minimize the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) through drastic reductions in iodinated contrast volume and the use of intravascular ultrasound (IVUS). While some of the described techniques completely avoid contrast use and rely on transthoracic echocardiography to check for potential pericardial bleeding, this strategy may miss or delay the treatment of potentially life-threatening complications. We hereby propose the use of group II gadolinium (Gd)-based contrast agents, instead of iodinated contrast, to complement IVUS, in order to achieve the goal of zero-contrast percutaneous coronary intervention, without raising the risk of CIN. These agents have been shown to be relatively safe in the setting of advanced CKD, with an overall reported risk of nephrogenic systemic fibrosis of <0.07% and no significant nephrotoxicity. Combining the use of Gd with the "live IVUS technique" in patients with advanced CKD seems to achieve the goal of high-precision PCI, without significantly compromising procedural safety.

Clinical Characteristics of Most Frequent Use of Iodinated Contrast Media for CT.

Given the integral role of CT in patient care, the current global contrast media shortage creates profound and manifold patient care implications. We used a large insurance dataset to highlight examinations (abdominopelvic and chest CT), delivery settings (emergency department and outpatient hospital), and clinical indications (acute abdominopelvic and chest disease and cancer surveillance) for which contrast-enhanced CT is most commonly used. Such information may help inform emerging national guidelines and institutional policies.

Isn't it time to consider oncological status as a new risk factor of iodinated contrast media hypersensitivity?

SUMMARY: Background. The literature describes several risk factors for hypersensitivity (HS) reactions to iodinated contrast media (ICM). Objective. To analyze the characteristics of patients experiencing HS reactions to ICM with a focus on oncological status. Methods. All patients (n = 80) with suspected HS to ICM who underwent an allergy evaluation in a Belgian University Hospital over a 5-year period were retrospectively included. Results. Overall, forty patients (50%) had a history of neoplasia, and this group was characterized by less atopy (p less than 0.004). No significant difference was observed between oncological and non-oncological patients in terms of gender, age, cardiovascular diseases, medical treatment, and number of previous exposures or reactions to ICM. Conclusions. A high proportion of oncological patients was observed in our population with HS to ICM. They did not have other known risk factors, and they were less atopic. Larger multicentric studies should explore cancer as a potential new risk factor.

Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond.

The present review deals with the functional roles of iodine and its metabolism. The main biological function of iodine concerns its role in the biosynthesis of thyroid hormones (THs) by the thyroid gland. In addition, however, further biological roles of iodine have emerged. Precisely, due to its significant action as scavenger of reactive oxygen species (ROS), iodine is thought to represent one of the oldest antioxidants in living organisms. Moreover, iodine oxidation to hypoiodite (IO-) has been shown to possess strong bactericidal as well as antiviral and antifungal activity. Finally, and importantly, iodine has been demonstrated to exert antineoplastic effects in human cancer cell lines. Thus, iodine, through the action of different tissue-specific peroxidases, may serve different evolutionarily conserved physiological functions that, beyond TH biosynthesis, encompass antioxidant activity and defense against pathogens and cancer progression.

Feasibility and safety of automated CO2 angiography in peripheral arterial interventions.

ABSTRACT: Carbon dioxide (CO2) gas is an established alternative to iodine contrast during angiography in patients with risk of postcontrast acute kidney injury and in those with history of iodine contrast allergy. Different CO2 delivery systems during angiography are reported in literature, with automated delivery system being the latest. The aim of this study is to evaluate the safety, efficacy, and learning curve of an automated CO2 injection system with controlled pressures in peripheral arterial interventions and also to study the patients' tolerance to the system.From January 2018 to October 2019 peripheral arterial interventions were performed in 40 patients (median age-78 years, interquartile range: 69-84 years) using an automated CO2 injection system with customized protocols, with conventional iodine contrast agent used only as a bailout option. The pain and tolerance during the CO2 angiography were evaluated with a visual analog scale at the end of each procedure. The amount of CO2, iodine contrast used, and radiation dose area product for the interventions were also systematically recorded for all procedures. These values were statistically compared in 2 groups, viz first 20 patients where a learning curve was expected vs the rest 20 patients.All procedures were successfully completed without complications. All patients tolerated the CO2 angiography with a median total pain score of 3 (interquartile range: 3-4), with no statistical difference between the groups (P = .529). The 2 groups were statistically comparable in terms of comorbidities and the type of procedures performed (P = .807). The amount of iodine contrast agent used (24.60 ±â€Š6.44 ml vs 32.70 ±â€Š8.70 ml, P = .006) and the radiation dose area product associated were significantly lower in the second group (2160.74 ±â€Š1181.52 µGym2 vs 1531.62 ±â€Š536.47 µGym2, P = .043).Automated CO2 angiography is technically feasible and safe for peripheral arterial interventions and is well tolerated by the patients. With the interventionalist becoming familiar with the technique, better diagnostic accuracy could be obtained using lower volumes of conventional iodine contrast agents and reduction of the radiation dose involved.

Quantitative distribution of iodinated contrast media in body computed tomography: data from a large reference cohort.

OBJECTIVES: Dual-energy computed tomography allows for an accurate and reliable quantification of iodine. However, data on physiological distribution of iodine concentration (IC) is still sparse. This study aims to establish guidance for IC in abdominal organs and important anatomical landmarks using a large cohort of individuals without radiological tumor burden. METHODS: Five hundred seventy-one oncologic, portal venous phase dual-layer spectral detector CT studies of the chest and abdomen without tumor burden at time point of imaging confirmed by > 3-month follow-up were included. ROI were placed in parenchymatous organs (n = 25), lymph nodes (n = 6), and vessels (n = 3) with a minimum of two measurements per landmark. ROI were placed on conventional images and pasted to iodine maps to retrieve absolute IC. Normalization to the abdominal aorta was conducted to obtain iodine perfusion ratios. Bivariate regression analysis, t tests, and ANOVA with Tukey-Kramer post hoc test were used for statistical analysis. RESULTS: Absolute IC showed a broad scatter and varied with body mass index, between different age groups and between the sexes in parenchymatous organs, lymph nodes, and vessels (range 0.0 ± 0.0 mg/ml-6.6 ± 1.3 mg/ml). Unlike absolute IC, iodine perfusion ratios did not show dependency on body mass index; however, significant differences between the sexes and age groups persisted, showing a tendency towards decreased perfusion ratios in elderly patients (e.g., liver 18-44 years/≥ 64 years: 0.50 ± 0.11/0.43 ± 0.10, p ≤ 0.05). CONCLUSIONS: Distribution of IC obtained from a large-scale cohort is provided. As significant differences between sexes and age groups were found, this should be taken into account when obtaining quantitative iodine concentrations and applying iodine thresholds. KEY POINTS: • Absolute iodine concentration showed a broad variation and differed between body mass index, age groups, and between the sexes in parenchymatous organs, lymph nodes, and vessels. • The iodine perfusion ratios did not show dependency on body mass index while significant differences between sexes and age groups persisted. • Provided guidance values may serve as reference when aiming to differentiate healthy and abnormal tissue based on iodine perfusion ratios.

Semiautomatic Segmentation and Radiomics for Dual-Energy CT: A Pilot Study to Differentiate Benign and Malignant Hepatic Lesions.

OBJECTIVE. This study assessed a machine learning-based dual-energy CT (DECT) tumor analysis prototype for semiautomatic segmentation and radiomic analysis of benign and malignant liver lesions seen on contrast-enhanced DECT. MATERIALS AND METHODS. This institutional review board-approved study included 103 adult patients (mean age, 65 ± 15 [SD] years; 53 men, 50 women) with benign (60/103) or malignant (43/103) hepatic lesions on contrast-enhanced dual-source DECT. Most malignant lesions were histologically proven; benign lesions were either stable on follow-up CT or had characteristic benign features on MRI. Low- and high-kilovoltage datasets were deidentified, exported offline, and processed with the DECT tumor analysis for semiautomatic segmentation of the volume and rim of each liver lesion. For each segmentation, contrast enhancement and iodine concentrations as well as radiomic features were derived for different DECT image series. Statistical analyses were performed to determine if DECT tumor analysis and radiomics can differentiate benign from malignant liver lesions. RESULTS. Normalized iodine concentration and mean iodine concentration in the benign and malignant lesions were significantly different (p < 0.0001-0.0084; AUC, 0.695-0.856). Iodine quantification and radiomic features from lesion rims (AUC, ≤ 0.877) had higher accuracy for differentiating liver lesions compared with the values from lesion volumes (AUC, ≤ 0.856). There was no difference in the accuracies of DECT iodine quantification (AUC, 0.91) and radiomics (AUC, 0.90) for characterizing liver lesions. CONCLUSION. DECT radiomics were more accurate than iodine quantification for differentiating solid benign and malignant hepatic lesions.

Incorporating Morpholine and Oxetane into Benzimidazolequinone Antitumor Agents: The Discovery of 1,4,6,9-Tetramethoxyphenazine from Hydrogen Peroxide and Hydroiodic Acid-Mediated Oxidative Cyclizations.

The reactivity of hydrogen peroxide and catalytic hydroiodic acid toward 3,6-dimethoxy-2-(cycloamino)anilines is tunable to give ring-fused benzimidazoles or 1,4,6,9-tetramethoxyphenazine in high yield. Mechanisms via a detected nitroso-intermediate are proposed for oxidative cyclization and the unexpected intermolecular displacement of the oxazine. An aqueous solution of molecular iodine is capable of the same transformations. Oxidative demethylation gave targeted benzimidazolequinones, including without cleavage of the incorporated oxetane.

Advanced CT Techniques for Decreasing Radiation Dose, Reducing Sedation Requirements, and Optimizing Image Quality in Children.

CT is an invaluable diagnostic tool for pediatric patients; however, concerns have arisen about the potential risks of ionizing radiation associated with diagnostic imaging in young patients, particularly for pediatric populations that may require serial CT examinations. Recent attention has also been focused on the immediate and long-term risks of administration of anesthetic medications to infants and young children who require sedation to undergo imaging examinations. These concerns can be mitigated with use of advanced CT techniques that can decrease scan time and radiation dose while preserving image quality. In this article, current state-of-the-art CT acquisition techniques are reviewed as part of a comprehensive strategy to reduce radiation dose, decrease sedation needs, and optimize image quality in infants and young children. Three imaging strategies are discussed, including (a) dual-energy CT (DECT), (b) imaging with a low tube potential, and (c) rapid scanning. Consolidating multiphase imaging protocols into a single phase with virtual nonenhanced imaging on DECT scanners, as well as use of low tube voltage, can reduce the radiation dose while increasing the conspicuity of contrast material-enhanced structures with a reduced volume of iodinated contrast material and a reduced rate of injection. Rapid scanning techniques with either ultrahigh pitch at dual-source CT or with wide-area detector single-source CT facilitate scanning without the need for sedation in many children. ©RSNA, 2019 See discussion on this article by Szczykutowicz .

The administration of contrast media: is there a risk of acute kidney injury? / Administración de medios de contraste. ¿Existe riesgo de daño renal agudo?

OBJECTIVE: To determine whether the intravenous administration of iodinated contrast material for computed tomography (CT) is associated with an increase in creatinine levels and acute kidney injury. MATERIAL AND METHODS: This retrospective cohort study included all patients who presented at the emergency department between 2010 and 2015 with baseline creatinine measurement (C1) and follow-up creatinine measurement (C2) between 24 and 72hours later. The clinical research ethics committee approved the study. The exclusion criteria were age <18 years, creatinine ≤ 0.4mg/dl or ≥4.0mg/dl, and the administration of contrast media within the previous 6 months. The mean number of patients presenting at the emergency department was 105,435.6 per year. Patients who met the inclusion criteria were classified into three groups: those who underwent contrast-enhanced CT (n=6,642), those who underwent noncontrast CT (n=6,193), and those who did not undergo CT (n=33,802). We used the Acute Kidney Injury Network's (AKIN) and the Contrast-induced Nephropathy Consensus Working Panel's (CIN) criteria. Statistical analyses included bivariate statistics and logistic regression. Stata 15 was used for all statistical analyses. RESULTS: We analyzed 52,411 patients; after data cleansing: 46,637; mean age: 67.95 years; C1: mean 1.16mg/dl (SD: 0.61); C2: 1.14mg/dl (SD: 0.66). With AKIN and CIN criteria: contrast-enhanced CT was not associated with a greater probability of developing nephropathy (odds ratio [OR: 0.90; 95% CI: 0.83-0.99] and [OR 0.89, 95% CI: 0.81-0.98], respectively). The propensity score matching study using both sets of criteria (AKIN+CIN) yielded OR 0.80 [95% CI: 0.77-0.84]. Glomerular filtration rates less than 30ml/min were not associated with increased kidney damage [OR: 0.66, 95% CI: 0.47-0.91]. CONCLUSION: The administration of intravenous contrast material in the patients studied is not associated with increased acute kidney injury.

Impacto de la angiografía coronaria rotacional en la cantidad total de contraste administrado y la exposición a las radiaciones ionizantes en pacientes en los que se realizan procedimientos coronarios invasivos: revisión sistemática y metaanálisis / Impact of rotational coronary angiography in the amount of iodinated contrast and the exposure to ionising radiations in patients undergoing invasive coronary procedures: A systematic review and meta-analysis

Resumen Antecedentes: Los procedimientos coronarios invasivos conllevan la administración de contraste y la exposición a radiaciones ionizantes, comportando un incremento de la morbimortalidad. La angiografía coronaria rotacional (ACR) permite adquirir múltiples proyecciones con una inyección de contraste. Hasta la fecha, no hay metaanálisis específicos comparando la ACR y la angiografía coronaria convencional (ACC) en pacientes en los que se realizan procedimientos coronarios invasivos, tanto diagnósticos como diagnósticos y terapéuticos. El objetivo de este metaanálisis es evaluar el impacto de la ACR en la cantidad de contraste, y la radiación ionizante en procedimientos coronarios invasivos. Métodos: Se realizó una búsqueda en las bases de datos PubMed y Ovid para identificar estudios tanto diagnósticos como diagnósticos y terapéuticos que comparasen ACR y ACC. Los estudios fueron evaluados sobre la calidad y los sesgos, y fueron incluidos si contemplaban alguna de las siguientes variables de valoración: volumen de contraste, radiación ionizante medida como producto dosis-área, Kerma-aire o tiempo de fluoroscopia. Resultados: Dieciséis estudios, totalizando 2,327 pacientes, fueron incluidos en el análisis final (1,146 pacientes recibieron ACR y 1,181, ACC), objetivándose diferencias significativas en volumen de contraste (diferencia estándar de medias (intervalo de confianza al 95%) −1.887 (−2.472 a −1.302); p < 0.001), producto dosis-área (−0.726 (−1.034 a −0.418); p < 0.001), Kerma-aire (−0.842 (−1.104 a −0.581); p < 0.001) y tiempo de fluoroscopia (0.263 (−0.496 a −0.030); p = 0.027). Conclusiones: La ACR permite reducir el volumen de contraste y la radiación, evaluada como producto dosis-área, Kerma-aire y tiempo de fluoroscopia en pacientes a los que se les realizan procedimientos coronarios invasivos.

Abstract Background: Invasive coronary procedures involve the administration of iodinated contrast and the exposure to ionising radiations, increasing morbidity and mortality. The rotational coronary angiography (RCA) allows acquiring multiple projections with a unique injection of iodinated contrast. To date, there are no meta-analyses specifically comparing RCA and conventional coronary angiography (CCA) in patients undergoing invasive coronary procedures, whether diagnostic or diagnostic and therapeutic. The aim of this meta-analysis is to assess the impact of RCA on the amount of iodinated contrast and the exposure to ionising radiations during invasive coronary procedures. Methods: A search in PubMed and Ovid databases was conducted to identify studies, including diagnostic and diagnostic and therapeutic studies, comparing RCA and CCA. The manuscripts were evaluated on quality and biases, and were included if they analysed any of the following endpoints: volume of contrast and exposure to ionising radiations measured as dose-area product, and Kerma-air or fluoroscopy time. Results: Sixteen studies, with a total of 2,327 patients, were included in the final analysis (1,146 patients underwent RCA and 1,181 patients underwent CCA), with significant differences being detected in volume of contrast (standard difference in means (95% confidence interval) −1.887 (−2.472 to −1.302); P < .001), dose-area product (−0.726 (−1.034 to −0.418); P < .001), Kerma-air (−0.842 (−1.104 to −0.581); P < .001), and fluoroscopy time (0.263 (−0.496 to −0.030); P = .027). Conclusions: RCA reduces the volume of contrast and the exposure to radiation, evaluated as dose-area product, Kerma-air, and fluoroscopy time, in patients undergoing invasive coronary procedures.

In vitro comparative cytotoxicity study of a novel biocidal iodo-thiocyanate complex.

Novel biocides, which avoid the induction of cross-resistance to antibiotics, are an urgent societal requirement. Here, we compared the cytotoxic and bactericidal effects of a new antimicrobial agent, the iodo-thiocyanate complex (ITC), with those of the common antiseptics, hydrogen peroxide (H2O2), povidone iodine (PVP-I) and Lugol's iodine (Lugol). The antimicrobials were co-incubated for 10 min with HeLa and Escherichia coli cells in the presence and absence of organic matter (Dulbecco's modified Eagle's medium, supplemented with 10% fetal bovine serum). The cytotoxic concentrations of ITC were equivalent to its bactericidal concentrations (7.8 µg ml-1). By contrast, cytotoxic effects of H2O2, PVP-I and Lugol were apparent at concentrations lower than their bactericidal concentrations (250, 250 and 125 µg ml-1, respectively). The cellular effects of ITC were not quenched by organic matter, unlike the other antiseptics. ITC, PVP-I and Lugol had hemolytic effect on horse erythrocytes at high concentrations, while H2O2 showed no hemolysis. ITC, at 30 or 300 µg ml-1, did not cause DNA breakage in HeLa cells as assessed by an in vitro comet assay in the absence of S9 metabolic activation, whereas H2O2 caused extensive single-strand DNA breaks. The pronounced antimicrobial potency of ITC and its favorable cytotoxicity profile suggests that ITC should be considered for antiseptic applications.

Autophagy is activated to protect renal tubular epithelial cells against iodinated contrast media­induced cytotoxicity.

With the steady increase in the use of various contrast­related technologies in recent years, contrast­induced nephropathy has received significant attention from clinicians and researchers. The present study aimed to determine the potential role of autophagy in iodinated contrast media (CM)­induced cell injury and apoptosis in human proximal renal tubular epithelial HK­2 cells. The present study used the iodinated CM iohexol (200 mg iodine/ml) to treat HK­2 cells for 6 h, in order to establish a damaged cell model. The autophagy inhibitor 3­methyladenine (3­MA; 10 mM) was used to inhibit the formation of autophagosomes. Immunofluorescence assay and transmission electron microscopy (TEM) were used to observe the formation of autophagosomes in the cytoplasm. The protein expression levels of microtubule­associated protein 1A/1B­light chain 3 (LC3)­II and autophagy­related protein 7 (Atg7) were detected by western blotting. The cytotoxicity of CM was evaluated by MTT assay and lactate dehydrogenase release, and cell apoptosis was detected by flow cytometry. Increased formation of autophagosomes and autophagic vesicles was observed under TEM in HK­2 cells following iohexol treatment for 6 h. Immunofluorescence assay demonstrated that iohexol increased LC3­II expression in HK­2 cells. Furthermore, the expression levels of LC3­II and Atg7 in HK­2 cells were significantly upregulated by iohexol administration; however, LC3­II and Atg7 expression was decreased by 3­MA treatment. These results provided evidence to suggest that autophagy is activated in response to iohexol­induced cell injury and apoptosis, and may exert a renoprotective role in HK­2 cells.

Pythium Insidiosum Keratitis: Histopathology and Rapid Novel Diagnostic Staining Technique.

PURPOSE: To elucidate the histopathology of Pythium insidiosum keratitis and to describe a novel, simple, and rapid staining technique for identification of oomycete Pythium insidiosum and to differentiate it from fungi. METHODS: This is a laboratory investigation study of 38 nonconsecutive cases (37 ocular samples and 1 colonic biopsy); 14 microbiologically diagnosed as Pythium insidiosum keratitis and 24 as fungal keratitis. Review of clinical, demographic details, microbiological results, and identification of cases that necessitated evisceration was performed. Reevaluation of histopathology slides was done using stains such as hematoxylin-eosin, Gomori methenamine silver (GMS), periodic acid-Schiff (PAS), potassium iodide-sulfuric acid (IKI-H2SO4). Morphology, degree, and nature of inflammation and load, distribution, and staining results of Pythium insidiosum and its comparison with fungi were studied. RESULTS: Delay in zoospore formation, failure of growth, and delay in identification of Pythium were the main cause of evisceration. Corneal pythiosis showed epithelial ulceration, stromal destruction, and varying inflammation; load and distribution of Pythium were inversely proportional to inflammation. The filaments were commonly wide, with admixed narrower structures and uncommonly involved Descemet membrane. The oomycete was not discretely discerned with PAS stain and stained distinctly with GMS stain and IKI-H2SO4 stain (100% sensitive). In comparison, fungal organisms stained well with PAS and GMS stain, but not with IKI-H2SO4 stain (100% specific). CONCLUSIONS: Pythium insidiosum keratitis is perhaps not more devastating than fungal keratitis but late diagnosis, misdiagnosis, and treatment as fungal infection are major heralds. Early diagnosis may markedly improve the patient outcome. IKI-H2SO4 is a cost-effective, simple, sensitive, and specific stain for the diagnosis of oomycete Pythium.