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Thermosensitive liposome-based drug delivery systems (DDS) are powerful tools for site-specific delivery of chemotherapeutics, especially when combined with regional hyperthermia. The objective of this work was to develop a novel thermosensitive liposomal DDS loaded with lomustine, a chemotherapeutic compound, and iohexol, a contrast medium for visualization by CT. Thermosensitive compound liposomes (TSCLs) composed of DPPC were prepared by reverse-phase evaporation and investigated for encapsulation efficiency, temperature-sensitivity, release kinetics, and In Vivo pharmacokinetics. The size and zeta-potential of TSCLs ranged from 250 to 300 nm and −15 to −30 mV, respectively. At 41 °C, TSCLs were shown to release over 90% of iohexol and lomustine within 4 h. The in vitro release profiles of iohexol and lomustine at 41 °C conformed to first-order kinetics and Weibullmodel, respectively. Phase-transition did not occur after incorporation of cholesterol and soybean phospholipids. In Vivo evaluation performed with C6 glioma model rats proved the prolonged half-lives and improved bioavailability by liposomal encapsulation for both compounds under mild local hyperthermia. The TSCLs used in this study may offer a clinically promising mean of increasing efficacy and controlling toxicity.

Background Vascular spasm is well known to occur in the arterial system. Central venous spasm during pacemaker implantation is uncommon with only a few cases reported from time to time. Sometimes, the venous spasms may not respond to nitroglycerine injections which requires a change of access site and undue discomfort for the patient. Case presentation A 72-year-old female patient with no prior comorbidities presented to us with recurrent dizziness on exertion and at rest. The electrocardiogram showed complete heart block, likely to be of sclerodegenerative etiology as the patient did not have any ischemic symptoms, also the electrocardiogram and echocardiogram did not show any evidence of ischemia. As part of the hospital protocol, a venogram was performed by giving intravenous diluted contrast (iohexol) through the left brachial vein, which showed good-sized axillary and subclavian veins. We attempted to cannulate the left axillary vein with a 16G needle using Seldinger technique, but the axillary vein could not be cannulated despite multiple attempts. We gave incremental boluses of intravenous nitroglycerine, despite that the left axillary vein could not be cannulated. Repeat intravenous contrast injection showed severe spasm of axillary and subclavian veins. Finally, the axillary vein was cannulated from the right side using anatomical landmarks and a pacemaker was implanted. Conclusions Venous spasm during device implantation although uncommon, it should be anticipated in patients with difficult cannulation to prevent inadvertent complications like pneumothorax and arterial injuries. Mild venous spasm may relieve with time but severe venous spasm may require a change of access site

PURPOSE OF REVIEW Acute kidney injury (AKI) is common and associated with high patient mortality, and accelerated progression to chronic kidney disease. Our ability to diagnose and stratify patients with AKI is paramount for translational progress. Unfortunately, currently available methods have major pitfalls. Serum creatinine is an insensitive functional biomarker of AKI, slow to register the event and influenced by multiple variables. Cystatin C, a proposed alternative, requires long laboratory processing and also lacks specificity. Other techniques are either very cumbersome (inuline, iohexol) or involve administration of radioactive products, and are therefore, not applicable on a large scale. RECENT FINDINGS The development of two optical measurement techniques utilizing novel minimally invasive techniques to quantify kidney function, independent of serum or urinary measurements is advancing. Utilization of both one and two compartmental models, as well as continuous monitoring, are being developed. SUMMARY The clinical utility of rapid GFR measurements in AKI patients remains unknown as these disruptive technologies have not been tested in studies exploring clinical outcomes. However, these approaches have the potential to improve our understanding of AKI and clinical care. This overdue technology has the potential to individualize patient care and foster therapeutic success in AKI.

Tucatinib is a potent tyrosine kinase inhibitor selective for human epidermal growth factor receptor 2 (HER2) approved by the US Food and Drug Administration for the treatment of HER2‐positive metastatic breast cancer and in development for other HER2‐positive solid tumors. Modest, reversible serum creatinine (SCr) elevations have been observed in tucatinib clinical trials. SCr is conveyed by the renal drug transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) and 2‐K (MATE2‐K) and can increase in the presence of inhibitors of these transporters. In vitro, tucatinib inhibited OCT2‐, MATE1‐, and MATE2‐K‐mediated transport of metformin, with IC50 values of 14.7, 0.340, and 0.135 µM, respectively. Tucatinib also inhibited OCT2‐ and MATE1‐mediated transport of creatinine, with IC50 values of 0.107 and 0.0855 µM, respectively. A phase 1 study with metformin administered orally in the absence and presence of tucatinib was conducted in 18 healthy subjects. Renal function was assessed by measuring glomerular filtration rate (GFR; based on iohexol plasma clearance) and endogenous markers (SCr, cystatin C‐based estimated glomerular filtration rate [eGFR]) with and without tucatinib. Metformin exposure increased (1.4‐fold) and renal clearance decreased (29.99‐17.64 L/h) with tucatinib, with no effect on metformin maximum concentration. Creatinine clearance transiently decreased 23% with tucatinib. GFR and eGFR, which are unaffected by OCT2 and/or MATE1/2‐K transport, were unchanged with tucatinib. These data demonstrate that tucatinib inhibits OCT2‐ and MATE1/2‐K‐mediated tubular secretion of creatinine, which may manifest as mild SCr elevations that are not indicative of renal impairment.

OBJECTIVE To evaluate the effect of slice thickness on CT perfusion analysis of the pancreas in healthy dogs. ANIMALS 12 healthy Beagles. PROCEDURES After precontrast CT scans, CT perfusion scans of the pancreatic body were performed every second for 30 seconds by sequential CT scanning after injection of contrast medium (iohexol; 300 mg of 1/kg) at a rate of 3 mL/s. Each dog underwent CT perfusion scans twice in a crossover-design study with 2 different slice thicknesses (2.4 and 4.8 mm). Computed tomographic pancreatic perfusion variables, including blood flow, blood volume determined with the maximum slope model, times to the start of enhancement and peak enhancement, permeability, and blood volume determined by Patlak plot analysis, were measured independently by 2 reviewers. The CT perfusion variables were compared between slice thicknesses. Interoperator reproducibility was determined by ICC calculation. RESULTS Interoperator reproducibility of CT perfusion variable measurements was excellent on 2.4-mm (mean ± SD ICC, 0.81 ± 0.17) and 4.8-mm (0.90 ± 0.07) slice thicknesses, except for time to peak pancreatic enhancement on 2.4-mm-thick slices, which had moderate reproducibility (intraclass correlation coefficient, 0.473). There was no significant difference in measurements of blood flow, blood volume by either method, times to the start and peak of pancreatic enhancement, or permeability between slice thicknesses. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that a thin slice thickness of 2.4 mm can be used for assessment of pancreatic perfusion variables in healthy dogs.

Background Proton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti‐inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation. Hypothesis/Objectives To evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone. Animals Six healthy adult colony beagle dogs. Methods Gastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3‐period design. In the first 7‐day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7 days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey‐Kramer post hoc tests (P

Backgrounds Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time—consuming. Methods In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. Results The preparation method is easy and cost—effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first—order elimination kinetics and, it has a short half—life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. Conclusions This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Contrast-induced nephropathy (CIN), a complication caused by using contrast medium during diagnostic and interventional procedures, occurs frequently and lacks effective treatment. AdipoRon, the agonist of adiponectin receptors, has been shown to benefit many organs including the kidney. This study aimed to investigate the role of AdipoRon in treating CIN. CIN model was established via infusing iopromide (1.8 g/kg) in Sprague–Dawley (SD) rats; NRK52E cells were treated with iopromide (5–50 μM). Renal function, renal histopathology, levels of lactate dehydrogenase (LDH) release, cell vitality, oxidative stress and inflammatory markers were measured to evaluate the protective effects of AdipoRon. The level of pAMPK/AMPK was determined by western blot. AdipoRon (50 mg/kg) significantly reversed serum creatinine, blood urea nitrogen, creatinine clearance and urinary kidney injury molecule-1 levels induced by iopromide in SD rats. Besides, it decreased the renal injury score and apoptosis of renal cells. AdipoRon also reversed the changes of antioxidant markers, pro-oxidant and inflammatory markers induced by iopromide. Moreover, the in vitro studies showed that AdipoRon decreased LDH release and increased cell vitality in NRK52E cells treated with iopromide. Then, we demonstrated that the protection of AdipoRon was accompanied by augmented AMPK phosphorylation. Both in vivo and in vitro studies demonstrated that compound c, an AMPK inhibitor, reversed the AdipoRon-mediated improvement in the CIN model. Our data indicate that AdipoRon protects against the CIN by suppressing oxidative stress and inflammation via activating the AMPK pathway, showing that AdipoRon might be a potential candidate for the prevention and therapy of CIN.

To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) in treating traumatic mesenteric injuries with active bleeding, to report the outcome in a case series, and to compare the results with the existing data. All consecutive patients with active mesenteric bleeding due to blunt abdominal trauma referred to a level-one Trauma Center and treated by TAE were included; the related demographic and medical data were retrospectively reported. A literature review was conducted; all reported cases were collected and analysed together with our case series. A univariate analysis of risk factors for TAE failure, bowel necrosis, complication and length of stay was performed. Four consecutive patients were included. Technical success was 100%. One patient developed colon ischemia after the procedure and underwent surgical treatment; another presented transient mild renal failure and late respiratory failure. No 30-day mortality was reported. These results are consistent with those reported in literature. The analysis of our cases together with case collected from literature resulted in a case series of 25 patients. Univariate analysis showed colon as site of bleeding as a significant risk factor for bowel necrosis and older age as a significant risk factor for longer length of stay. TAE failure was not significantly associated neither with a higher complication rate nor with a higher length of stay. TAE is a safe and effective procedure to control mesenteric bleeding, thus should be considered, in selected cases and in appropriate setting, as an alternative to emergency surgery.

The aim of the presented study was to investigate if distribution of the drug-contrast medium mixture in CT-guided periradicular therapy can predict intervention success. Over a 15-month period, 97 patients admitted to our institution by a pain physician for CT guided periradicular therapy were treated. In 420 CT guided interventions, we measured the relative distribution of the drug mixture in relationship to the neuroforamen. The distribution was correlated to the patient's pain score over time. In addition, dependence of success in treatment with regards to the treating physician was evaluated. Ninety percent of the patients experienced a decrease of pain score under therapy, only 10 % showed no change. On average there was an improvement in pain score from 7.4 (2-10) before therapy to 3.7 (0-9) at the end of therapy. We observed a weak correlation of -0.22 (p 0.028) between distribution of drug mixture to the neuroforamen and reduction of pain score. The therapy outcome displayed a dependency regarding the treating physician (p 0.0084). CT guided periradicular therapy offers good pain reduction in most of the patients. Drug distribution near the affected nerve and treating physician are factors for clinical success. · CT-guided periradicular therapy shows a good or very good improvement in the symptoms in 90 % of the treated patients.. · In addition to technical performance, the treating radiologist is an important parameter determining success.. · The success of CT-guided treatment is only moderately correlated with an absolute distribution of the drug mixture..· Stueckle CA, Talarczyk S, Hackert B et al. CT-guided Interventional Therapy of Back Pain - Predictors of Success in Treatment. Fortschr Röntgenstr 2021; 193: 42 - 48.ZIEL: Die vorliegende Arbeit untersucht, ob über die Verteilung des Medikamenten-Kontrastmittel-Gemisches im Rahmen der CT-gesteuerten periradikulären Therapie eine Aussage über den zu erwartenden Erfolg getroffen werden kann. Über einen Zeitraum von 15 Monaten wurden konsekutiv insgesamt 97 Patienten untersucht, die vom Schmerztherapeuten zur CT-gesteuerten periradikulären Therapie überwiesen worden sind. Insgesamt konnten wir 420 CT-gesteuerte Interventionen einschließen. Wir haben die relative Verteilung des Medikamentengemisches in Korrelation zum Neuroforamen mit dem Schmerzscore des Patienten im Verlauf korreliert. Zudem wurde überprüft, ob es eine Abhängigkeit des Behandlungserfolgs vom behandelnden Arzt gibt. Die Patienten zeigten insgesamt ein sehr gutes Outcome: 90 % der mittels CT-gesteuerter periradikulärer Therapie behandelten Patienten zeigten eine Verbesserung der Schmerzsymptomatik. 10 % zeigten keine Verbesserung durch die CT-gestützte Intervention. Im Durchschnitt verbesserte sich der Schmerzscore von 7,4 (2–10) vor der Intervention auf 3,7 (0–9) am Ende der Therapie. Es zeigte sich eine negative Korrelation von –0,22 (p 0,028) zwischen der Schmerzreduktion und der Nähe des Medikamentengemisches zum Neuroforamen. Zudem zeigten unsere Daten eine Abhängigkeit des Outcomes vom behandelnden Arzt (p 0,0084). Die CT-gesteuerte periradikuläre Therapie führt in den meisten Fällen zu einer guten Schmerzreduktion. Neben einer guten Platzierung des Medikamentengemisches in der Nähe der affektierten Nervenwurzel scheint auch der ausführende Arzt eine Rolle beim Outcome für den Patienten zu spielen. · Die CT-gesteuerte periradikuläre Therapie zeigt bei 90 % der behandelten Patienten eine gute oder sehr gute Besserung der Beschwerdesymptomatik.. · Der behandelnde Radiologe ist neben der technischen Durchführung ein wichtiger, den Erfolg mitbestimmender Parameter.. · Der Erfolg der CT-gesteuerten Behandlung ist nur mäßig mit einer absoluten Verteilung des Medikamentengemisches korreliert..· Stueckle CA, Talarczyk S, Hackert B et al. CT-guided Interventional Therapy of Back Pain – Predictors of Success in Treatment. Fortschr Röntgenstr 2021; 193: 42 – 48.

The aim of our study is to investigate the impact of iodine quantification on image reconstruction when employing a vascular-specific contrast media phantom with varying iodine concentrations. A 30-cm phantom simulating arterial and venous blood vessel diameters was manufactured. Small (9 mm) and medium (12 mm) cylinders contained iodine concentrations from 10 to 100% while large (21 mm) cylinders were in quartiles from 25 to 100% diluted in blood equivalent medium. Each phantom was filled with either iohexol 350 mgI/mL (Group A) or iodixanol 320 mgI/mL (Group B) and then scanned separately. For each group, tube potential (80–140 kVp) and current (50–400 mAs) were changed and all image series were reconstructed with filtered back projection (FBP), hybrid-based iterative reconstruction (HBIR) and model-based iterative reconstruction (MBIR). Mean opacification was measured in all groups. All data were compared employing an independent t test and Pearson’s correlation. Visual grading characteristic (VGC) and Cohens’ kappa analyses were performed. At 80 kVp, mean opacification using HBIR was significantly higher in Group B (2165 ± 1108 HU) than in Group A (2040 ± 1036 HU) (p

OBJECTIVE. The purpose of this study was to perform quantitative and qualitative evaluation of a deep learning image reconstruction (DLIR) algorithm in contrast-enhanced oncologic CT of the abdomen...

While there have been numerous studies of living kidney donors, most have been retrospective without suitable controls and have yielded conflicting results. To clarify this we studied 205 living donor candidates and 203 controls having no medical conditions precluding donation. Before and at six months, one, two, three, six, and nine years after donation we measured iohexol glomerular filtration rate, clinic blood pressure, urine protein excretion and metabolic parameters reported to be affected by kidney function. We measured 24 hour ambulatory blood pressure at three, six, and nine years and at six and nine years blood pressure after treadmill exercise, carotid-femoral pulse wave velocity and arterial elasticity. Between six months and nine years, the mean (95% confidence interval) change in glomerular filtration rate was significantly different among 133 donors 0·02 (-0·16−0·20) mL/min/1·73m2/year versus -1·26 (-1·52−-1·00) mL/min/1·73m2/year in 113 healthy controls. Blood pressure, urine protein, urine albumin, glucose, hemoglobin A1c, insulin, and lipoproteins were not different in controls versus donors; but parathyroid hormone, homocysteine and uric acid remained higher at nine years. At six and nine years carotid-femoral pulse wave velocity was not different, but the mean small artery elasticity was significantly lower in 141 donors 6·1 mL/mmHg x100, versus 113 controls 7·1 mL/mmHg x100, and 6·1 mL/mmHg x100 in 137 donors versus 7·6 mL/mmHg x100 in 112 controls at six and nine years, respectively [significant adjusted difference of 1·1 mL/mmHg x100]. Thus, donors remain healthy with stable kidney function for the first nine years, but differences in metabolic and vascular parameters could be harbingers of adverse outcomes requiring future interventions.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m(2) of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m(2) in the allopurinol group and 67.3 ml per minute per 1.73 m(2) in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m(2) (95% confidence interval [CI], −1.9 to 1.9; P= 0.99). The mean decrease in the iohexol-based GFR was −3.0 ml per minute per 1.73 m(2) per year with allopurinol and −2.5 ml per minute per 1.73 m(2) per year with placebo (between-group difference, −0.6 ml per minute per 1.73 m(2) per year; 95% CI, −1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.)

In acute ischemic stroke (AIS) patients, eligibility for endovascular intervention is commonly determined through computed tomography perfusion (CTP) analysis by quantifying ischemic tissue using perfusion parameter thresholds. However, thresholds are not uniform across all analysis methods due to dependencies on patient demographics and computational algorithms. This study aimed to investigate optimal perfusion thresholds for quantifying infarct and penumbra volumes using two post-processing CTP algorithms: Vitrea Bayesian and singular value decomposition plus (SVD+). We utilized 107 AIS patients (67 non-intervention patients and 40 successful reperfusion of thrombolysis in cerebral infarction (2b/3) patients). Infarct volumes were predicted for both post-processing algorithms through contralateral hemisphere comparisons using absolute time-to-peak (TTP) and relative regional cerebral blood volume (rCBV) thresholds ranging from +2.8 seconds to +9.3 seconds and –0.23 to –0.56 respectively. Optimal thresholds were determined by minimizing differences between predicted CTP and 24-hour fluid-attenuation inversion recovery magnetic resonance imaging infarct. Optimal thresholds were tested on 60 validation patients (30 intervention and 30 non-intervention) and compared using RAPID CTP software. Among the 67 non-intervention and 40 intervention patients, the following optimal thresholds were determined: intervention Bayesian: TTP = +4.8 seconds, rCBV = –0.29; intervention SVD+: TTP = +5.8 seconds, rCBV = –0.29; non-intervention Bayesian: TTP = +5.3 seconds, rCBV = –0.32; non-intervention SVD+: TTP = +6.3 seconds, rCBV = –0.26. When comparing SVD+ and Bayesian post-processing algorithms, optimal thresholds for TTP were significantly different for intervention and non-intervention patients. rCBV optimal thresholds were equal for intervention patients and significantly different for non-intervention patients. Comparison with commercially utilized software indicated similar performance.

The burden of coronary artery atherosclerosis in patients with atrial fibrillation (AF) is unknown. We aimed to assess the coronary artery calcium (CAC) in AF patients. We retrospectively analyzed 324 consecutive patients with AF who had CT angiogram before AF ablation and their cardiovascular risk were prospectively collected. Mean age of the cohort was 66 years and 71% were male. The previous history of coronary artery disease (CAD) was present in 19% (n = 63) and CAC was positive in all. In patients without known CAD (n = 261), CAC was present in 70% (n = 182) with a comparable prevalence between men and women, which raised the prevalence of coronary atherosclerosis to 76% (n = 245) for the entire cohort. The median CAC score was 170 (range 1 to 6,157) and largely in multivessel distribution in patients without known CAD. Presence of CAC increased with an increasing number of cardiovascular risk factors. Nevertheless, CAC was present in 58% (n = 40) of patients without conventional cardiovascular risk factors. If CAC score >100 was considered as CAD equivalent as 10-year risk of incident atherosclerotic cardiovascular diseases is >7.5% it would have resulted in higher CAD prevalence of 52% and significant reclassification of CHA2DS2-VASc score in 41% of patients without known CAD. In conclusion, coronary calcium is highly prevalent in AF patients, including those without cardiovascular risk factors. Advanced CAC can potentially shift CHA2DS2-VASc score in many AF patients. Our findings suggest that characterizing CAC in AF may be clinically valuable in thromboembolic risk stratification and management of preventive cardiac therapies.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 μg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

To evaluate thyroid, arytenoid, and cricoid cartilage invasion on computed tomography (CT) imaging in patients undergoing total laryngectomy for both primary and recurrent laryngeal carcinoma. Secondary endpoint was to compare laryngeal cartilage invasion between primary and recurrent tumours. Pre-treatment CT of 40 patients who had undergone total laryngectomy was retrospectively evaluated and compared with histology. Focal erosions of thyroid cartilage were accounted for neoplastic invasion of the inner cortex. Full-thickness thyroid cartilage invasion was defined as a tumour-like tissue replacing thyroid cartilage or extended in extra-laryngeal soft tissues. Sclerosis and erosion of arytenoid and cricoid cartilages were assessed as signs of neoplastic invasion. CT erosion showed perfect agreement for thyroid inner cortex and cricoid cartilage invasion and almost perfect agreement (87%) for arytenoid cartilage invasion. For tumours in contact with thyroid cartilages, the absence of CT erosion underestimated inner cortex infiltration. CT showed perfect agreement in predicting full-thickness thyroid cartilage invasion only in the case of extra-laryngeal neoplastic extension. Arytenoid sclerosis showed poor correlation with neoplastic invasion. For primary tumours, CT demonstrated good (inner cortex 75%; full-thickness 85%), substantial (67.5%), and perfect (100%) accuracy in thyroid, arytenoid, and cricoid cartilage invasion, respectively. No CT differences were observed between primary and recurrent laryngeal tumours. Tumour-like tissue extension in the extra-laryngeal soft tissues was accurate in predicting thyroid cartilage full-thickness invasion. Erosions of arytenoid, cricoid, and thyroid cartilages’ inner cortex on CT were highly indicative of neoplastic infiltration. No CT difference in cartilage infiltration between primary and recurrent tumours was observed.

Objective To determine whether the addition of bupivacaine or contrast medium to methylene blue dye would affect dye distribution following ultrasound (US)-guided transversus abdominis plane (TAP) injections. Study design Prospective, randomized, blinded cadaveric study. Animals A total of 29 fresh Beagle dog cadavers. Methods Each hemiabdomen (n = 58) was randomized into one of three groups: group M, 1% methylene blue; group MB, 50:50 mixture of 1% methylene blue and 0.5% bupivacaine; group MC, 25:75 mixture of 1% methylene blue and contrast agent (iohexol). TAP injections (0.5 mL kg–1) were performed bilaterally by a trained individual followed by dissection of the abdominal walls. Craniocaudal and dorsoventral spread along tissue planes was measured. Staining of branches of the thoracic and lumbar spinal nerves was considered successful when dye on the nerve was >10 mm. One-way anova with post hoc Tukey test was used to compare craniocaudal and dorsoventral spread and Kruskal–Wallis test to compare incidence of nerve staining among groups. Results TAP injections were successful in 52 out of 58 hemiabdomens. Dorsoventral spread was greater for group M (60 ± 10 mm) compared with MC (49 ± 9 mm; p = 0.01) but not MB (52 ± 9 mm; p = 0.09). No difference was found in craniocaudal spread or number of nerves stained among groups. Conclusion and clinical relevance The significant difference found in spread of tissue staining between methylene blue alone and methylene blue mixed with contrast in the TAP blocks should be kept in mind when interpreting dye-based cadaveric regional anesthesia studies.

The goal of this study is to provide quantitative data on the ideal volume for intramuscular (IM) injections into the semimembranosus muscle of guinea pigs weighing between 320 to 410 grams. This evaluation comprised 2 experiments. The first was to assess dispersion leakage of intramuscularly injected iohexol, a radiocontrast agent commonly used in Computed Tomography (CT), based on analysis of in vivo imaging. The second used varying volumes of intramuscularly injected sodium chloride (0.9% NaCl) to assess pain and pathology associated with IM injection. Hartley guinea pigs were injected IM with varying volumes of either iohexol or sodium chloride (150, 300, 500, 1000 and 1500 μL). In the iohexol experiment, results suggest IM volumes of 150 and 300 μL remain within the target muscle. In the experiment using sodium chloride, pain and pathology did not increase as IM volume increased. The pathology noted was related to needle tract through the musculature rather than the volume size of the injectate. The results did not reveal a correlation between volume of IM 0.9% NaCl and pain levels. We conclude that volume size correlates more with precision and accuracy of delivery into the intended muscle tissue. Regarding tissue distribution, our findings also suggest that the optimal capacity for IM injection in the semimembranosus muscle should be less than 500 μL.

Recently developed coronary angiography with intraprocedural 320-row computed tomography can be performed in a catheterization laboratory (XACT) by injecting contrast medium from a place close to the coronary arteries, thereby requiring a minimal amount of contrast medium. However, its clinical application has not yet been established. This study aimed to evaluate the diagnostic accuracy of XACT angiography with a minimal volume of contrast medium in patients with suspected coronary artery disease (CAD). A total of 167 coronary segments were analyzed in 14 patients (9 males, median age 70 years) with suspected CAD by XACT angiography with 7.5 ml of contrast medium and invasive coronary angiography (ICA) with standard techniques. The segmental-based diagnostic accuracy of XACT angiography in detecting stenosis of ≥ 50% and ≥ 75% and visualized by ICA was good (sensitivity: 74% and 62%, specificity: 99% and 99%, positive predictive value: 93% and 80%, and negative predictive value: 97% and 97%, respectively). These results suggest that XACT angiography with a very low amount of contrast medium may have strong clinical utility for screening coronary arteries in patients with renal dysfunction or undergoing clinical procedures such as pacemaker implantation.

OBJECTIVE. The purpose of this study is to determine the degree of the relationship between perfusion CT (PCT) parameters and iodine concentration metrics derived from triple-bolus dual-energy CT (DECT) and to compare the radiation dose delivered. SUBJECTS AND METHODS. This single-center prospective study was conducted from October 2015 to September 2017. Twenty-three consenting adults (15 men and eight women; mean [± SD] age, 56 ± 13 years [range, 25-78 years]) with renal cell carcinomas underwent consecutive PCT and triple-bolus DECT examinations. Triple-bolus DECT consisted of synchronous corticomedullary, nephrographic, and delayed phase scans acquired using a dual-source DECT scanner. Two readers independently analyzed blood flow, blood volume, and permeability, as measured by PCT, and iodine density and iodine ratio, as measured by triple-bolus DECT. Size-specific dose estimates were calculated for both groups. RESULTS. Interreader agreement was good for permeability (intraclass correlation coefficient [ICC] =.812) and blood flow (ICC = 0.849) and excellent for blood volume (ICC = 0.956), iodine density (ICC = 0.961), and iodine ratio (ICC = 0.956). Very strong positive correlations were found between blood volume and iodine density (p < 0.001) and between blood volume and iodine ratio (p < 0.001). Strong positive correlations were found between blood flow and iodine density (p < 0.001) and between blood flow and iodine ratio (p < 0.001). The correlations between permeability and iodine density (p = 0.01) and between permeability and iodine ratio (p = 0.02) were moderate. The mean size-specific dose estimate of triple-bolus DECT was approximately 15 times lower than that of PCT (p < 0.001). CONCLUSION. Quantitative iodine metrics derived from triple-bolus DECT showed significant correlation with CT parameters in renal cell carcinoma, with a significantly lower radiation dose.

To test the technical reproducibility of acquisition and scanners of CT image-based radiomics model for early recurrent hepatocellular carcinoma (HCC). We included primary HCC patient undergone curative therapies, using early recurrence as endpoint. Four datasets were constructed: 109 images from hospital #1 for training (set 1: 1-mm image slice thickness), 47 images from hospital #1 for internal validation (sets 2 and 3: 1-mm and 10-mm image slice thicknesses, respectively), and 47 images from hospital #2 for external validation (set 4: vastly different from training dataset). A radiomics model was constructed. Radiomics technical reproducibility was measured by overfitting and calibration deviation in external validation dataset. The influence of slice thickness on reproducibility was evaluated in two internal validation datasets. Compared with set 1, the model in set 2 indicated favorable prediction efficiency (the area under the curve 0.79 vs. 0.80, P = 0.47) and good calibration (unreliability statistic U: P = 0.33). However, in set 4, significant overfitting (0.63 vs. 0.80, P

The amount of intra-abdominal fat on CT correlates positively with the severity of acute pancreatitis (AP). The objective of the study was to evaluate a fat-modified CT severity index (FMCTSI) and compare its performance with MCTSI. For this retrospective study, 99 patients with AP who underwent contrast-enhanced CT between 3 and 7 days after pain onset were divided into a training cohort (n = 75) and a validation cohort (n = 24). MCTSI was calculated. The total adipose tissue (TAT), visceral adipose tissue (VAT), and total to visceral fat ratio (TVFR) were computed using semi-automatic software. These parameters were given a score of 1–3. FMCTSI was calculated by adding the fat score to MCTSI. Concordance for diagnosing the severity of AP was assessed. Areas under receiver operating characteristic curves (AUC) for predicting clinical outcomes were compared between FMCTSI and MCTSI. The diagnostic performance of the FMCTSI in the validation cohort was also evaluated. In the training cohort, our proposed FMCTSI performed better than MCTSI for all the outcome parameters. The highest concordance for the severity of AP was achieved for VAT-MCTSI. For all outcome parameters, the highest AUC was seen for TVFR-MCTSI. In the validation cohort, the FMCTSI achieved diagnostic performance similar to the training cohort with the highest AUC for TVFR-MCTSI. FMCTSI is a better CT index than MCTSI for predicting the severity and clinical outcomes of AP. Among the various FMCTSI parameters, TVFR-MCTSI is the best performer.

Rationale & Objectives Estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of β2-microglobulin (B2M) and β-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China. Study Design Diagnostic test study. Setting & Participants 1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers. Tests Compared Index tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 − P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys. Outcomes Accuracy was significantly better for eGFRavg (1 − P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 − P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories. Limitations Study population may not be generalizable to clinical settings other than large urban medical centers in China. Conclusions A panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications., Graphical abstract

The recent iohexol shortage has precipitated disruptions in a pharmaceutical supply chain critical to radiologic imaging and has impacted global availability of iodinated contrast media (ICM). The shortage has created a national crisis in radiology departments, curtailing their ability to provide health care to patients who need contrast-enhanced examinations. Radiology departments are familiar with crisis management after more than 2 years of clinical and operational disruptions associated with the COVID-19 pandemic. The iohexol and subsequent ICM shortage has short-term (weeks), midterm (months), and long-term (years) implications. The purpose of this report is to provide strategies for dealing with the shortage in the near term and to discuss long-term issues and potential solutions to supply chain problems impacting radiology departments.

Aims Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples. Methods The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P-15-P-30) with a P-20 acceptance threshold of 80%. Results For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P-15 = 92.0%) and AUCs (n = 25; P-20 = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P-20 = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P-20 = 68.8%), but was considered acceptable given its P-30 of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P-20 = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations. Conclusion The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trend monitoring and immunosuppressant therapeutic drug monitoring in kidney transplant recipients.

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.

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.

Made available in DSpace on 2022-04-28T19:52:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-07-01 Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The X-ray iodinated contrast medium iohexol is frequently detected in aquatic environments due to its high persistence and the inefficiency of its degradation by conventional wastewater treatments. Hence, the challenge faced in this study is the development of an alternative electrochemical treatment using active anodes. We investigate the oxidation of iohexol (16.42 mg L−1) using different operating conditions, focusing on the role of different mixed metal oxide anodes in the treatment efficiency. The electrocatalytic efficiency of the Ti/RuO2–TiO2 anode prepared using a CO2 laser heating and an ionic liquid is compared with Ti/RuO2–TiO2–IrO2 and Ti/IrO2–Ta2O5 commercial anodes. The hypochlorite ions generated by the anodes are also analyzed. The effect of the electrolyte composition (NaCl, Na2SO4, and NaClO4) and current density (15, 30, and 50 mA cm−2) on the iohexol degradation is also studied. The Ti/RuO2–TiO2 laser-made anode is more efficient than the commercial anodes. After optimizing experimental parameters, this anode removes 95.5% of iohexol in 60 min and displays the highest kinetic rate (0.059 min−1) with the lowest energy consumption per order (0.21 kWh m−3order−1), using NaCl solution as the electrolyte and applying 15 mA cm−2. Additionally, iohexol-intensified groundwater was used to compare the efficiency of anodes. The Ti/RuO2–TiO2 is also more efficient in removing the organic charge from the real water matrix (21.7% TOC) than the commercial anodes. Notably, the iohexol removal achieved is higher than all electrochemical treatments already reported using state-of-the-art non-active anodes in lower electrolysis time. Therefore, data from this study indicate that the electrochemical degradation of iohexol using the Ti/RuO2–TiO2 anode is efficient and has excellent cost-effectiveness; thus, it is a promising approach in the degradation of iohexol from wastewater. Furthermore, the Ti/RuO2–TiO2 active anode is competitive and can be an excellent option for treating effluents contaminated with recalcitrant organic compounds such as iohexol. Electrochemistry and Nanotechnology Laboratory Institute of Technology and Research (ITP) Waste and Effluent Treatment Laboratory Institute of Technology and Research (ITP) Graduate Program in Process Engineering (PEP) Tiradentes University Study of Natural Organic Matter Laboratory Federal University of Sergipe Institute of Chemistry UNESP National Institute of Alternative Technologies for Detection Toxicological Evaluation and Removal of Micropollutants and Radioactive Materials (INCT-DATREM), P.O. Box 355 Institute of Chemistry UNESP National Institute of Alternative Technologies for Detection Toxicological Evaluation and Removal of Micropollutants and Radioactive Materials (INCT-DATREM), P.O. Box 355 CNPq: 142034/2020-7 CNPq: 305438/2018-2 CNPq: 311856/2019-5 CNPq: 315405/2018-0 CNPq: 421147/2016-4 CAPES: 88882.365553/2018–01 CAPES: 88887.486184/2020-00

Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein–RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein–RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems.

Three different UV-LED wavelengths (265, 310, and 365 nm) were used in the UV-LED/chlorine reaction to investigate the degradation mechanism of iopromide (IPM) at different wavelengths, a representative iodinated contrast media compound. The degradation rate (k'

Yeast-derived β-glucans impact immunity, though their effects on gut permeability and inflammation are less understood. Most research has investigated other components of the yeast cell wall, such as the prebiotic mannan- and fructo-oligosaccharides. The objective of this study was to assess the effects of feeding a concentrated yeast product on markers of inflammation (serum amyloid A [SAA] and haptoglobin [Hp]) and oxidative status (malondialdehyde [MDA]), fecal products of fermentation, and gut permeability. Nineteen privately owned domestic Siberian huskies, and one Alaskan husky (9 females: 5 intact, 4 spayed; 11 males: 3 intact, 8 neutered), with an average age of 4.8 ± 2.6 yr and body weight (BW) of 25.6 ± 4.1 kg, were used in this study. Dogs were blocked and randomly allocated to one of two diet groups. Ten dogs received a dry extruded diet. The other 10 received the same diet top dressed with yeast for a daily β-glucan dose of 7 mg/kg BW for 10 wk. Fecal collection, for evaluation of fecal metabolites, and scoring occurred weekly. Gut permeability was assessed using the chromium-labeled ethylenediamine tetra-acetic acid (Cr-EDTA) and iohexol markers prior to the initiation of dietary treatment and after 10 wk of treatment. Blood samples were collected premarker administration and 0.5, 1, 2, 3, 4, 5, and 6 h postadministration. Fasting concentrations of SAA, Hp, and MDA were measured on weeks -1, 2, 4, and 8. Incremental area under the curve (I-AUC) was calculated for serum iohexol and Cr-EDTA concentrations. All data were analyzed using PROC GLIMMIX of SAS with dog as random effect, and week as fixed effect and repeated measure. Dogs receiving treatment tended to have decreased I-AUC of Iohexol (P = 0.10) and Cr-EDTA (P = 0.06) between baseline and cessation of treatment compared to the change over time in I-AUC for control (Ctl) dogs. Treatment dogs had lower Hp concentrations (P ≤ 0.05) than Ctl. There were no differences between treatments for SAA and MDA concentrations (P0.05). Fecal arabinose concentrations were greater in treatment (Trt) dogs (P ≤ 0.05) compared to Ctl, though no other fecal metabolites were affected by treatment. There was no difference in the relative frequency of defecations scored at any fecal score between Trt and Ctl dogs, and mean score did not differ between groups (P0.10). These data suggest that concentrated brewer's yeast may have the potential to reduce gut permeability without impacting inflammatory status and markers of health in adult dogs.This study evaluated the effects of concentrated brewer’s yeast on gut health in dogs. Nineteen Siberian Huskies and one Alaskan husky were blocked and randomly allocated to one of two groups. Treatment dogs received a yeast supplement for 10 wk, while control dogs received no supplement. Dogs were administered two markers to assess intestinal permeability prior to start of treatment and following 10 wk of treatment. Blood samples were collected and analyzed for markers of inflammatory status (serum amyloid A [SAA] and Haptoglobin [Hp]) and oxidative status (serum malondialdehyde [MDA]). Fecal samples were collected weekly to assess fecal score as well as fecal metabolite concentrations. Intestinal permeability was reduced in treatment dogs following treatment, and no change was observed in the control group. Treatment dogs had lower Hp concentrations than control (Ctl), but there were no differences between treatments for SAA and MDA. Fecal arabinose concentrations were significantly greater in the treatment group when compared to control. There were no differences in the relative frequency of defecations scored at any fecal score between treatment and Ctl dogs, nor did mean score differ between the groups. This study suggests that concentrated brewer’s yeast may reduce gut permeability and inflammation without detrimentally impacting markers of health in adult dogs.

Background Mass spectrometry (MS) analysis using direct infusion of biological fluids is often problematic due to high salts/buffers. Iodinated contrast media (ICM) are frequently used for diagnostic imaging purposes, sometimes inducing acute kidney injury (AKI) in patients with reduced kidney function. Therefore, detection of ICM in spent hemodialysates is important for AKI patients who require urgent continuous hemodiafiltration (CHDF) because it allows noninvasive assessment of the patient’s treatment. In this study, we used a novel desalination tube before MS to inject the sample directly and detect ICM. Methods Firstly, spent hemodialysates of one patient were injected directly into the electrospray ionization (ESI) source equipped with a quadrupole time-of-flight mass spectrometer (Q-TOF MS) coupled to an online desalination tube for the detection of ICM and other metabolites. Thereafter, spent hemodialysates of two patients were injected directly into the ESI source equipped with a triple quadrupole mass spectrometer (TQ-MS) connected to that online desalination tube to confirm the detection of ICM. Results We detected iohexol (an ICM) from untreated spent hemodialysates of the patient-administered iohexol for computed tomography using Q-TOF MS. Using MRM profile analysis, we have confirmed the detection of ICM in the untreated spent hemodialysates of the patients administered for coronary angiography before starting CHDF. Using the desalination tube, we observed approximately 178 times higher signal intensity and 8 times improved signal-to-noise ratio for ioversol (an ICM) compared to data obtained without the desalination tube. This system was capable of tracking the changes of ioversol in spent hemodialysates of AKI patients by measuring spent hemodialysates. Conclusion The online desalination tube coupled with MS showed the capability of detecting iohexol and ioversol in spent hemodialysates without additional sample preparation or chromatographic separation. This approach also demonstrated the capacity to monitor the ioversol changes in patients’ spent hemodialysates.

Iohexol, the raw material of nonionic X-ray computed tomography (X-CT) contrast medium, is usually injected into the vein before CT angiography diagnosis. It is used for angiography, urography, and lymphography. With the advantages of low contrast density and good tolerance, it is currently one of the most popular contrast media. However, the renal toxicity of iohexol seriously affects its safety use. Therefore, it is of great importance to identify new potential diagnostic biomarkers and therapeutic targets in the process of contrast medium-induced acute kidney injury (CI-AKI) in order to safely use iohexol in clinical practice. In this study, in order to understand the metabolic mechanism of CI-AKI, ultra-high-performance liquid chromatography/quadrupole-Orbitrap-mass spectrometry and

Contrast media has been shown to induce nephropathy (i.e., contrast-induced nephropathy) after various types of radiological examinations. The molecular mechanism of contrast-induced nephropathy has been unclear. In this study, we investigated the mechanism of contrast-induced nephropathy by examining the effects of combined treatment of contrast medium and ionizing radiation on kidney cells in vitro and kidney tissue in vivo. In human renal tubular epithelium cells, immunofluorescence analysis revealed that iohexol increased the numbers of radiation-induced γH2AX nuclear foci. The numbers of γH2AX nuclear foci remained high at 24 h, suggesting that some radiation-induced double-strand breaks remain unrepaired in the presence of iohexol. We established a mouse model of contrast-induced nephropathy, then showed that iohexol and ionizing radiation synergistically reduced renal function and induced double-strand breaks. Importantly, iohexol induced significant macrophage accumulation and oxidative DNA damage in the kidneys of contrast-induced nephropathy model mice in the absence of ionizing radiation; these effects were amplified by ionizing radiation. The results suggest that underlying inflammation and oxidative DNA damage caused by iohexol contribute to the enhancement of radiation-induced double-strand breaks, leading to contrast-induced nephropathy.

Background Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. Methods We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. Results GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 3.2-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. Conclusions We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.