A Novel Coacervate Embolic Agent for Tumor Chemoembolization.

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents.

Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression.

Iodinated non-ionic contrast medium does not inhibit Escherichia coli growth in ex vivo inoculated canine urine.

OBJECTIVE: To investigate the effect of iohexol on standardized quantitative urine culture results in dogs. The authors hypothesized that the presence of iohexol in inoculated urine samples would result in lower bacterial concentrations (CFU/mL) and, therefore, decrease culture sensitivity. SAMPLE: Urine samples were aseptically collected during cystoscopy from a single client-owned dog untreated with antimicrobials. PROCEDURES: An experimental controlled study. The urine sample was divided into 38 aliquots (0.5 mL each) that were used as negative controls or inoculated with an equal amount of Escherichia coli (105 CFU/mL). Different volumes (0.1 and 0.5 mL) of contrast or saline were added to the aliquots and quantitative culture results were compared. Two different incubation times between the preparation of aliquots and culture were evaluated (15 minutes and 24 hours). RESULTS: All aliquots from samples inoculated with E. coli (positive controls and iohexol-group) had the same reported quantitative result (104 CFU/mL). No growth was reported for the negative controls. Iohexol did not show any anti-E. coli properties in canine urine cultures for dilutions up to 1:2 contrast:urine and concentrations up to 120 mgI/mL. No difference was reported when iohexol was incubated with inoculated urine for 15 minutes or 24 hours. CLINICAL RELEVANCE: Based on the experimental in vitro conditions described, administration of iohexol before the collection of urine during urologic procedures does not negatively impact the isolation and growth of E. coli.

The effect of contrast agents on the anticoagulant properties of oral factor Xa inhibitors.

BACKGROUND: Contrast agents may affect the anticoagulant properties of novel oral anticoagulants. PURPOSE: To evaluate the effect of iohexol as a contrast agent on the anticoagulant activity of oral factor Xa inhibitors. MATERIAL AND METHODS: The study included 65 individuals who underwent contrast computed tomography(CT). Group 1 comprised 20 patients using rivaroxaban, Group 2, 20 patients using apixaban, and Group 3, 20 patients using edoxaban. Group 4 was the control group of five healthy volunteers. Iohexol (60 mL) was used as a contrast agent. Blood samples of 2 mL were withdrawn into two tubes at 4 h after the drug dose and 1 h after the contrast CT (CT was performed 3 h after the drug was taken) from all the patients, and for the control group, at any time before and 1 h after contrast CT. The anticoagulant properties of rivaroxaban, apixaban, and edoxaban were evaluated using anti-factor Xa levels. RESULTS: The anti-factor Xa level was increased after using the contrast agent in the rivaroxaban group (0.66 ± 0.32 U/mL vs. 0.67 ± 0.32 U/mL; P = 0.01) and the edoxaban group (0.74 ± 0.35 U/mL vs. 0.76 ± 0.36 U/mL; P = 0.006). No significant difference was observed in the apixaban group (0.66 ± 0.33 U/mL vs. 0.66 ± 0.32 U/mL; P = 0.21) and control group (0.02 ± 0.01 U/mL vs. 0.03 ± 0.01 U/mL; P = 0.33). CONCLUSION: The anticoagulant properties of rivaroxaban and edoxaban tended to increase significantly, but there was no statistically significant difference in the anticoagulant properties of apixaban after the administration of contrast agent. To determine whether the small laboratory difference has a clinical effect, there is a need for larger clinical trials (NCT04611386).

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

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

Baseline risk markers and visit-to-visit variability in relation to kidney outcomes - A post-hoc analysis of the PERL study.

BACKGROUND: Baseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP), HbA1c, serum creatinine, and uric acid (UA) are potential risk markers of kidney function decline in type 1 diabetes. METHODS: Post-hoc analysis of a double-blind randomized placebo-controlled clinical trial investigating allopurinol's effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. Furthermore, VVs of SBP, HbA1c, serum creatinine, and UA were calculated using measurements from the run-in period; thereafter assessed by linear regression, with iGFR change as the dependent variable. RESULTS: 404 participants were included in the primary analyses. In the optimized baseline variable model, higher HbA1c, SBP, iGFR, albuminuria, and heart rate, and mineralocorticoid receptor antagonist prescription were associated with greater iGFR decline. Higher VV of SBP was associated with greater iGFR decline (adjusted ß (ml/min/1.73 m2/50 % increase): -0.79, p = 0.01). CONCLUSIONS: We identified several risk markers for faster iGFR decline in a high-risk population with type 1 diabetes. While further research is needed, our results indicate possible new and clinically feasible measures to risk stratify for DKD in type 1 diabetes.

Baicalin Alleviates Contrast-Induced Acute Kidney Injury Through ROS/NLRP3/Caspase-1/GSDMD Pathway-Mediated Proptosis in vitro.

Purpose: To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media. Methods: Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again. Results: After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-1ß, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-1ß, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited. Conclusion: Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway.

Effect of different contrast medium injection protocols for analysis of hepatic computed tomography perfusion in healthy dogs.

OBJECTIVE: To evaluate the hepatic CT perfusion (CTP) for determining the appropriate protocol for the dual-input maximum-slope model in dogs. ANIMALS: 5 healthy dogs. PROCEDURES: Each dog underwent CTP with different contrast medium administration protocols. Combinations of three different injected doses of iohexol (450, 600, and 750 mg/kg) and injection durations (5, 10, and 15 seconds) were used. The CT values at the aorta, portal vein, and hepatic parenchyma were measured to create a time-density curve, and CTP parameters were measured simultaneously on each hepatic lobe using a 320-row multidetector CT scanner. RESULTS: The maximum peak enhancement at the aorta, portal vein, and hepatic parenchyma was greater with the 750-mg/kg dose than with the 450-mg/kg dose. With an injection duration of 15 seconds, the aortic enhancement peak was less, and the arrival time at the aortic enhancement peak was longer compared to that with a 5-second injection duration. The CTP parameters in the caudate process of the caudate lobe and left lateral lobe differed with different injection durations. The CTP parameters in the caudate process of the caudate lobe, left lateral lobe, and right lateral lobe differed with varying injected doses. CLINICAL RELEVANCE: Our study demonstrated that rapid administration of the contrast medium was required for quantitative analysis of hepatic CTP in healthy dogs. The CTP parameters differed with respect to the contrast medium administration protocol, and it was necessary to administer the contrast medium within a fixed duration and at a fixed dose to evaluate CTP correctly.

Zinc Preconditioning Provides Cytoprotection following Iodinated Contrast Media Exposure in In Vitro Models.

Methods: Normal human proximal renal kidney cells (HK-2) were preconditioned with either increasing doses of ZnCl2 or control. Following this preconditioning, cells were exposed to increasing concentrations of Iohexol 300 mg I2/ml for four hours. Key outcome measures included cell survival (MTT colorimetric assay) and ROS generation (H2DCFDA fluorescence assay). Results: Contrast media induced a dose-dependent reduction in survival of HK-2 cells. Compared to control, contrast media at 150, 225, and 300 mg I2/ml resulted in 69.5% (SD 8.8%), 37.3% (SD 4.8%), and 4.8% (SD 6.6%) cell survival, respectively (p < 0.001). Preconditioning with 37.5 µM and 50 µM ZnCl2 increased cell survival by 173% (SD 27.8%) (p < 0.001) and 219% (SD 32.2%) (p < 0.001), respectively, compared to control preconditioning. Zinc preconditioning resulted in a reduction of ROS generation. Zinc pre-conditioning with 37.5 µM µM ZnCl2 reduced ROS generation by 46% (p < 0.001) compared to control pre-conditioning. Conclusions: Zinc preconditioning reduces oxidative stress following exposure to radiographic contrast media which in turn results in increased survival of renal cells. Translation of this in vitro finding in animal models will lay the foundation for future use of zinc preconditioning against contrast induced nephropathy.

A novel technique for preoperative localization of pulmonary nodules using a mixture of tissue adhesive and iohexol under computed tomography guidance: A 140 patient single-center study.

BACKGROUND: The increase in the incidence of pulmonary nodules has made computed tomography (CT) screening a requirement for diagnosis and treatment. Small pulmonary nodule detection during video-assisted thoracoscopic surgery (VATS) or thoracotomy is frequently challenging; however, accurate and efficient localization of nodules is critical for precise resection. Herein, we introduce and evaluate the feasibility and safety of a novel technique for preoperative pulmonary nodule localization. METHODS: From March 2018 to December 2019, 140 patients with 153 pulmonary nodules measuring <2 cm in diameter were enrolled in this study. Preoperative, CT-guided localization was performed on each nodule with an injected mixture of tissue adhesive and iohexol. Patient and nodule characteristics, localization data, complications, surgical data, and pathological results were analyzed. RESULTS: All 153 nodules in 140 patients were successfully marked preoperatively and detected during surgery (n = 153/153). Mean nodule size was 8.7 ± 2.6 mm, and mean distance from nodule to pleura was 7.9 ± 8.2 mm. The mean procedural time was 8.7 ± 1.0 min. Nine patients (6.4%) underwent two simultaneous nodule localizations and two patients (1.4%) underwent three simultaneous nodule localizations. Pneumothorax (17/140, 12.1%), pain (6/140, 4.3%), and pungent odor (5/140, 3.6%) were the major complications. No patient required further treatment, and no allergic reactions or embolisms were observed. CONCLUSIONS: Preoperative CT-guided nodule localization using a mixture of tissue adhesive and iohexol is an efficient technique for localizing small and impalpable pulmonary lesions, including multiple pulmonary nodules. Our study demonstrates that this novel method is safe and straightforward to implement.

Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes.

The objective of this study was to compare the ratio of renal oxygen availability (RO2) to glomerular filtration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%). The RO2:GFR (ms/mL/min) was calculated as RO2 (T2*, ms) divided by GFR (mL/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR was associated with higher UACR (r = -0.31, P = 0.03), RPF (r = -0.52, P = 0.0009), and fat mass (r = -0.33, P = 0.02). Lower medullary RO2:GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.

Non-ionic CT contrast solutions rapidly alter bovine cartilage and meniscus mechanics.

OBJECTIVE: To evaluate effects of a common CT contrast agent (iohexol) on the mechanical behaviors of cartilage and meniscus. METHODS: Indentation responses of juvenile bovine cartilage and meniscus were monitored following exposure to undiluted contrast agent (100% CA), 50% CA/water, 50% CA/Phosphate Buffered Saline (PBS) or PBS alone, and during re-equilibration in PBS. The normalized peak force (Fpk¯), effective osmotic strain (εosm), and normalized effective contact modulus (Ec¯) were calculated for every cycle, with time constants determined for both exposure and recovery via mono- or biexponential fits to Fpk¯. RESULTS: All cartilage CA groups exhibited long-term increases in Fpk¯ following exposure, although the hyperosmolal 100% CA and 50% CA/PBS groups showed an initial transient decrease. Meniscus presented opposing trends, with decreasing Fpk¯ for all CA groups. Re-equilibration in PBS for 1hr after exposure to 100% CA produced recovery to baseline Fpk¯ in cartilage but not in meniscus, and extended tests indicated that meniscus required ∼2.5 h to recover halfway. Ec¯ increased with CA exposure time for cartilage but decreased for meniscus, suggesting an increased effective stiffness for cartilage and decreased stiffness for meniscus. Long-term changes to εosm in both tissues were consistent with changes in Ec¯. CONCLUSION: Exposure to iohexol solutions affected joint tissues differentially, with increased cartilage stiffness, likely relating to competing hyperosmotic and hypotonic interactions with tissue fixed charges, and decreased meniscus stiffness, likely dominated by hyperosmolarity. These altered tissue mechanics could allow non-physiological deformation during ambulatory weight-bearing, resulting in an increased risk of tissue or cell damage.

Experimental studies on computed tomographic peritoneography. Peritoneal and residual renal function tolerance to iodinated contrast media injected into the peritoneal cavity.

Computed tomographic (CT) peritoneography has been widely used as reference standard to evaluate continuous ambulatory peritoneal dialysis-related complications. However, given the varying CT peritoneography approaches used across different institutions, there is no standard value for non-ionic iodinated contrast media (ICM) concentration. Few studies have currently investigated whether non-ionic iodinated contrast media (non-ionic ICM) affects peritoneal function or residual renal function (RRF). This study aimed to determine whether different non-ionic ICM concentrations affect peritoneum and RRF and attempted to evaluate CT peritoneography images to identify the optimal non-ionic ICM concentrations in animals. To this end, 25 male Sprague-Dawley rats were used to establish uraemic models, after which they were injected with a 40-mL mixture of peritoneal dialysate and iohexol at varying concentrations prior to CT peritoneography. Thereafter, two experienced radiologists blinded to the rat groupings evaluated image quality, peritoneal morphology and thickness were assessed using hematoxylin and eosin and Masson staining, and RRF was evaluated using serum creatinine levels hematoxylin and eosin staining of pathological kidney sections. Briefly, non-ionic ICM had negligible effects on the peritoneum and RRF. Our results suggest that a mixture containing 50 mL (350 mgI/mL) iohexol/2 L peritoneal dialysate can be used as reference in rats.

Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy.

Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

Balancing act between quantitative and qualitative image quality between nonionic iodinated dimer and monomer at various vessel sizes during computed tomography: a phantom study.

PURPOSE: Investigate the impact of nonionic dimer and monomer on iodine quantification in different vessel sizes when employing a vascular specific phantom and varying iodinated contrast media (ICM) concentrations during computed tomography (CT). MATERIALS AND METHODS: We created a vascular specific phantom (30 cm) to simulate human blood vessel diameters (25 cylinders of different diameters: 10 × 9mm, 10 × 12mm and 5 × 21mm). The phantom was filled with two ICM separately: Group: Iohexol(monomer)350 mg ml-1 and B: Iodixanol(Dimer)320 mg ml-1. Cylinders of same size were filled with increasing ICM concentration(10%-100%) while large cylinders were filled in quartiles(25%-100%). Phantom was scanned with different tube potential (80-140kVp), current (50-400mAs), reconstruction method [filtered back projection (FBP), hybrid-based iterative reconstruction (HBIR) and model-based iterative reconstruction (MBIR)] for each ICM. Chi-square was employed to compare mean opacification, contrast/noise ratio (CNR) and noise. Qualitative analysis was assessed by Visual grading characteristic (VGC) and Cohens-kappa analyses. RESULTS: At 80 and140kVp significant difference in opacification between Group A (2054 ± 1040HU and 1696 ± 1027HU) and B (2169 ± 1105HU and 1568 ± 1034HU) was demonstrated (p < 0.001). However, at 100 and 120kVp no difference was noted (p > 0.05). When comparing image noise, it was higher in Group A compared to B (p < 0.05). CNR was higher in Group B (119.99 ± 126.10HU) than A (107.09 ± 102.56HU) (p < 0.0001). VGC: Group A outperformed B in image opacification in all vessel sizes and ICM concentrations except at medium vessels with concentration group 2(0.4-0.6 mg ml-1). Cohens'-kappa: agreement in opacification between each ICM group and iodine concentration 1(0-0.3 mg ml-1): κ = 0.253 and 0.014 respectively, concentration 2(0.4-0.6 mg ml-1):κ = -0.017 and -0.005 respectively and concentration 3(0.7-1 mg ml-1):κ = 0.031 and 0.115 respectively. CONCLUSION: Nonionic dimer (Iodixanol) surpasses monomer (Iohexol) in quantitative image quality assessment by having lower image noise and higher CNR during CT.

Inhibition of xanthine oxidoreductase protects against contrast-induced renal tubular injury by activating adenosine monophosphate-activated protein kinase.

Reactive oxygen species (ROS) play a pivotal role in the development of contrast-induced nephropathy (CIN). The inhibition of xanthine oxidoreductase is known to reduce levels of ROS. We investigated whether febuxostat could attenuate oxidative stress via the activation of adenosine monophosphate-activated protein kinase (AMPK) against CIN. In a mouse model of CIN, renal impairment and tubular injury substantially increased, whereas febuxostat attenuated renal injury. Plasma and kidney xanthine oxidoreductase levels were decreased by febuxostat. Febuxostat administration was accompanied by the upregulation of AMPK phosphorylation and the inhibition of nicotinamide-adenine dinucleotide phosphate oxidase (Nox)1 and Nox2, followed by the inhibition of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 expressions and the suppression of transcription factor forkhead box O (FoxO)1 and FoxO3a phosphorylation. Cell survival was significantly reduced after iohexol administration and febuxostat ameliorated iohexol-induced cell death in proximal tubular (HK-2) cells. Furthermore, febuxostat enhanced AMPK phosphorylation and inhibited Nox1, Nox2, and HIF-1α expression in iohexol-exposed HK-2 cells. Finally, these processes decrease ROS in both in vivo and in vitro models of CIN. AMPK inhibition using small interfering RNA blunted the antioxidative effects of febuxostat in iohexol-treated HK-2 cells. Febuxostat attenuated CIN by modulating oxidative stress through AMPK-NADPH oxidase-HIF-1α signaling.

Synthesis of Bi2WO6-x nanodots with oxygen vacancies as an all-in-one nanoagent for simultaneous CT/IR imaging and photothermal/photodynamic therapy of tumors.

All-in-one nanoagents with a single-component and all-required functions have attracted increasing attention for the imaging-guided therapy of tumors, but the design and preparation of such nanoagents remain a challenge. Herein, we report the introduction of oxygen vacancies to traditional semiconductors with heavy-metal elements for tuning photoabsorption in the near infrared (NIR) region, by using Bi2WO6 (band-gap: ∼2.7 eV) as a model. Bi2WO6-x nanodots with sizes of ∼3 or ∼8 nm have been prepared by a facile coprecipitation-solvothermal method assisted by citric acid (CA, 0.1-1.5 g) as the reduction agent. CA confers the removal of O atoms from the [Bi2O2]2+ layer during the solvothermal process, resulting in the formation of plenty of oxygen vacancies in the Bi2WO6-x crystal. As a result, NIR photoabsorption of Bi2WO6-x nanodots can be remarkably enhanced with the increase of the CA amount from 0 to 1.0 g. Under irradiation of a single-wavelength (808 nm, 1.0 W cm-2) NIR laser, black Bi2WO6-x-CA1.0 nanodots can not only efficiently produce a sufficient amount of heat with a photothermal conversion efficiency of 45.1% for photothermal therapy, but also generate singlet oxygen (1O2) for photodynamic therapy. Furthermore, due to the presence of heavy-metal (Bi and W) elements, Bi2WO6-x-CA1.0 nanodots have high X-ray attenuation ability for CT imaging. After the Bi2WO6-x-CA1.0 nanodot dispersion is injected into the tumor-bearing mice, the tumor can be imaged by using CT and an IR thermal camera. After irradiation with a single-wavelength (808 nm, 1.0 W cm-2, 10 min) NIR laser, the tumor can be completely suppressed by the synergic photothermal and photodynamic effects of Bi2WO6-x-CA1.0 nanodots, without recurrence and treatment-induced toxicity. Therefore, Bi2WO6-x nanodots have great potential as a novel all-in-one nanoagent for the imaging and phototherapy of tumors.

Ultravist Induces the Expression of MCP-1 and VCAM-1 in IL-4-Stimulated HUVECs.

The goal of the present study focused on the adverse reaction of contrast medium (CM) via the induction of inflammatory molecules in human umbilical vein endothelial cells (HUVECs). Ultravist-induced monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) gene expression was markedly increased in interleukin-4 (IL-4)-pretreated HUVECs in a time- and dose-dependent manner and was paralleled by concomitant production of MCP-1 and VCAM-1 proteins. MCP-1 and VCAM-1 gene expression by Ultravist in combination with IL-4 was mediated by the c-Jun N-terminal kinases (JNK1/2) signaling pathway. IL-4-pretreated Ultravist-stimulated HUVECs showed greatly increased migration and adhesion of THP-1 cells. Cell migration was decreased by treatment of CCR2 antagonist, and cell adhesion was also decreased by VCAM-1 blocking antibody. Furthermore, when tested in vivo under similar conditions, MCP-1 protein was significantly increased in Ultravist combined with IL-4-injected mice. Taken together, our findings suggest that MCP-1 blocking may be crucial in preventing the endothelial dysfunction induced by contrast medium in patients with inflammatory disease and atherosclerosis.

The Effects of Iodinated Radiographic Contrast Media on Multidrug-resistant K562/Dox Cells: Mitochondria Impairment and P-glycoprotein Inhibition.

Iodinated radiographic contrast media is used in cancer radiography for cancer diagnosis. The aim of this present study was to examine five iodinated radiographic contrast media (IRCM) (i.e., iohexol, iopamidol, iobitridol, ioxaglate, and iodixanol) in terms of their cytotoxicity, mitochondria membrane potential (ΔΨm), and P-glycoprotein function in multidrug resistant K562/Dox cancer cells and corresponding sensitive cancer cells. The cytotoxicity was determined by colorimetric resazurin reduction assay. The ΔΨm and P-glycoprotein function was measured using a noninvasive functional spectrofluorometry. Rhodamine B, fluorescence probe, was used to estimate ΔΨm. The kinetic of P-glycoprotein-mediated efflux pirarubicin was used to monitor P-glycoprotein function in multidrug resistant (MDR) cancer cells. The results showed that ioxaglate and iodixanol show similar efficacy in MDR cancer cells and for their corresponding sensitive cancer cells. Iopamidol, iohexol, and iobitridol showed higher efficacy in MDR cancer cells than for the corresponding sensitive cancer cells by approximately 2 fold. The results also showed no significant change in the |ΔΨm| values in treated K562 and K562/Dox cancer cells when compared to the non-treated K562 and K562/Dox cancer cells. However, there were notable changes detected for iobitridol and iodixanol at 50 mgI/mL. Similarly, the results showed significant differences in P-glycoprotein function of K562/Dox cancer cells after treatment with IRCM when compared to the non-treated K562/Dox cancer cells, with iohexol and iodixanol being the notable exceptions once again. In this present study, IRCM exhibited cytotoxicity on MDR cancer cells and their corresponding sensitive cancer cells. IRCM also showed potential as an anticancer agent in the future.

Are radio-contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?

In the literature, there have been no studies showing clear results on how radio-contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco-molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio-contrast agents. Cell viability, toxicity and proliferation indices were tested at specific time intervals. The cell viability was quantitatively analysed. It was also visually rechecked under a fluorescence microscope with acridine orange/propidium iodide staining. Simultaneously, cell surface morphology was analysed with an inverted light microscope, while haematoxylin and eosin (H&E) staining methodology was used in the histopathological evaluations. The obtained data were evaluated statistically. Unlike the literature, iopromide or gadoxetic acid did not have any adverse effects on the cell viability, proliferation and toxicity (P < 0.05). Although this study reveals that radio-contrast pharmaceuticals used in the discography, often used in neurosurgical practice, can be safely used, it should be remembered that this study was performed in an in vitro environment.