Prolongation of the gastric residence time of caffeine after administration in fed state: Comparison of effervescent granules with an extended release tablet.

The aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, tmax tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state.

The Effect of Cooling Fluid Composition on Ablation Size in Hepatic Laser Ablation: A Comparative Study in an Ex Vivo Bovine Setting.

PURPOSE: Hyperthermic ablation is a minimally invasive mode of tumour therapy which serves as a viable alternative to surgical intervention. However, one of the major drawbacks, besides the heat sink effect and the risk of damaging adjacent organs, is limited ablation size. The use of a cooling fluid during ablation has been shown to increase the ablation volume and decrease the carbonisation rate. The aim of this study was to investigate whether the composition of the cooling fluid has an effect on ablation size and carbonisation rate during hepatic laser ablation in an ex vivo bovine setting. METHOD: In this study bovine hepatic tissue was ablated in an ex vivo setting using an internally cooled laser applicator. A total of 45 tissue samples were assigned to three groups: 0.9% saline infusion (n = 15), distilled water infusion (n = 15) and a 50%/50% mixture of 0.9% saline and distilled water (n = 15). Ablation was conducted using a 1064 nm Nd:YAG laser at a wattage of 25 W and time interval of 10 min. The ablation volume and carbonisation rate were then measured and recorded through postprocedural MRI. One-way ANOVA and post-hoc testing were performed to assess the effect of the cooling fluid composition on the ablation volumes. RESULTS: We found that using a mixture of saline and distilled water as a cooling fluid during hyperthermic ablation resulted in a larger ablation volume (mean ± SD: 22.64 ± 0.99 cm3) when compared to saline infusion (21.08 ± 1.11 cm3) or distilled water infusion (20.92 ± 0.92 cm3). This difference was highly significant (p < 0.001). There was no significant difference in ablation size between the saline group and the distilled water group. The highest carbonisation rate occurred in the saline group (12/15), followed by the mixed infusion group (3/15) and the distilled water group (1/15). CONCLUSIONS: The results of this study suggest that cooling fluid composition during hepatic laser ablation affects ablation volume in an ex vivo bovine setting. There was no statistically significant difference when comparing ablation volumes during saline infusion and distilled water infusion, but the carbonisation rate was significantly higher when using saline. The combination of saline and distilled water in a 50%/50% mixture as cooling fluid appears to be an auspicious alternative, as ablation volumes created with it are larger when compared to saline and distilled water alone, while carbonisation rate remains low. This might improve patient outcome as well as patient eligibility for hyperthermic ablation.

Identification of early predictors for infected necrosis in acute pancreatitis.

BACKGROUND: In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet. METHODS: This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection. We conducted a retrospective analysis from the hospital information and reimbursement data system and screened 705 patients hospitalized with diagnosis of acute pancreatitis who underwent contrast-enhanced computed tomography and additional diagnostic puncture or drainage of necrotic collections. Both clinical and laboratory parameters were analyzed for an association with a microbiologically confirmed infected pancreatic necrosis. A prediction model was developed using a logistic regression analysis with stepwise inclusion of significant variables. The model quality was tested by receiver operating characteristics analysis and compared to single parameters and APACHE II score. RESULTS: We identified a total of 89 patients with necrotizing pancreatitis, diagnosed by computed tomography, who additionally received biopsy or drainage. Out of these, 59 individuals had an infected necrosis. Eleven parameters showed a significant association with an infection including C-reactive protein, albumin, creatinine, and alcoholic etiology, which were independent variables in a predictive model. This model showed an area under the curve of 0.819, a sensitivity of 0.692 (95%-CI [0.547-0.809]), and a specificity of 0.840 (95%-CI [0.631-0.947]), outperforming single laboratory markers and APACHE II score. Even in cases of missing values predictability was reliable. CONCLUSION: A model consisting of a few single blood parameters and etiology of pancreatitis might help for differentiation between infected and non-infected pancreatic necrosis and assist medical therapy in acute necrotizing pancreatitis.

Epidemiological Factors Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Dual Center Case-Control Study.

OBJECTIVE: The present study aimed to identify epidemiological factors associated with the development of intraductal papillary mucinous neoplasms (IPMN) of the pancreas comparing patients after IPMN resection with population-based controls. METHODS: Preoperative data of 811 patients undergoing pancreatic resection for IPMN were matched in a 1:1 ratio with a random sample of volunteers from the Study of Health in Pomerania, which showed no pancreatic cyst greater than 2 mm in magnetic resonance cholangiopancreaticography. RESULTS: A total of 811 controls with a mean age of 61.9 years (standard deviation, 8.4 years) were matched to cases with a mean age of 66.1 years (standard deviation, 9.3 years). A previous history of pancreatitis, endocrine pancreatic insufficiency was significantly more frequent in IPMN patients compared with controls (P = 0.001). Moreover, adjusted data revealed that urogenital cancer (P = 0.034), colorectal cancer (P = 0.021), as well as first-degree family history of colorectal cancer (P = 0.001) were significantly more frequent in IPMN patients. CONCLUSIONS: A history of urogenital and colorectal cancer often coincides with IPMN, which have an indication for surgery and are associated with preoperative episodes of pancreatitis and with endocrine insufficiency. Prospective studies are needed to investigate the role of these factors in IPMN development.

Association between thyroid function and assessment of hepatic fat and iron contents by magnetic resonance imaging.

The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

Diagnostic performance and image quality of low-tube voltage and low-contrast medium dose protocol with hybrid iterative reconstruction for hepatic dynamic CT.

OBJECTIVE: To evaluate the diagnostic performance and image quality of the low-tube voltage and low-contrast medium dose protocol for hepatic dynamic CT. METHODS: This retrospective study was conducted between January and May 2018. All patients underwent hepatic dynamic CT using one of the two protocols: tube voltage, 80 kVp and contrast dose, 370   mgI/kg with hybrid iterative reconstruction or tube voltage, 120 kVp and contrast dose, 600  mgI/kg with filtered back projection. Two radiologists independently scored lesion conspicuity and image quality. Another radiologist measured the CT numbers of abdominal organs, muscles, and hepatocellular carcinoma (HCC) in each phase. Lesion detectability, HCC diagnostic ability, and image quality of the arterial phase were compared between the two protocols using the non-inferiority test. CT numbers and HCC-to-liver contrast were compared between the protocols using the Mann-Whitney U test. RESULTS: 424 patients (70.5 ± 10.1 years) were evaluated. The 80-kVp protocol showed non-inferiority in lesion detectability and diagnostic ability for HCC (sensitivity, 85.7-89.3%; specificity, 96.3-98.6%) compared with the 120-kVp protocol (sensitivity, 91.0-93.3%; specificity, 93.6-97.3%) (p < 0.001-0.038). The ratio of fair image quality in the 80-kVp protocol also showed non-inferiority compared with that in the 120-kVp protocol in assessments by both readers (p < 0.001). HCC-to-liver contrast showed no significant differences for all phases (p = 0.309-0.705) between the two protocols. CONCLUSION: The 80-kVp protocol with hybrid iterative reconstruction for hepatic dynamic CT can decrease iodine doses while maintaining diagnostic performance and image quality compared with the 120-kVp protocol. ADVANCES IN KNOWLEDGE: The 80- and 120-kVp protocols showed equivalent hepatic lesion detectability, diagnostic ability for HCC, image quality, and HCC-to-liver contrast.The 80-kVp protocol showed a 38.3% reduction in iodine dose compared with the 120-kVp protocol.

Hepatic steatosis and hepatic iron overload modify the association of iron markers with glucose metabolism disorders and metabolic syndrome.

BACKGROUND: Iron status has been linked with impaired glucose metabolism (IGM), type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MetS), but the role of hepatic steatosis or iron overload on these associations remains uncertain. METHODS: We analysed data from 2310 participants without known T2DM of the population-based Study of Health in Pomerania (SHIP-TREND, Germany) through logistic regression models. We tested additive and multiplicative interactions between ferritin and hepatic steatosis or iron overload. RESULTS: Serum ferritin was positively associated with IGM (OR per 100 µg/L: 1.11 [1.01, 1.23]), T2DM (OR per 100 µg/L: 1.20 [1.06, 1.36]) and MetS (OR per 100 µg/L: 1.11 [1.02, 1.20]) in the total population as well as in participants without hepatic iron overload. However, the synergistic effect of higher ferritin concentrations and hepatic iron overload showed stronger associations with IGM and T2DM. Similarly, while ferritin was positively associated with T2DM and MetS even in the absence of hepatic steatosis, the synergistic effect of higher ferritin concentrations and hepatic steatosis showed stronger associations with IGM, T2DM and MetS. Transferrin was associated with isolated impaired glucose tolerance but not with T2DM and MetS. CONCLUSIONS: Our study suggests that ferritin may be associated with glucose metabolism disorders and MetS even in people without hepatic steatosis or iron overload. However, in individuals with higher ferritin concentrations, the presence of hepatic steatosis may indicate stronger risk for glucose metabolism disorders and MetS, while the presence of hepatic iron overload may indicate stronger risk only for glucose metabolism disorders.

Pancreatitis severity in mice with impaired CFTR function but pancreatic sufficiency is mediated via ductal and inflammatory cells-Not acinar cells.

Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) are an established risk factor for cystic fibrosis (CF) and chronic pancreatitis. Whereas patients with CF usually develop complete exocrine pancreatic insufficiency, pancreatitis patients with CFTR mutations have mostly preserved exocrine pancreatic function. We therefore used a strain of transgenic mice with significant residual CFTR function (CFTRtm1HGU ) to induce pancreatitis experimentally by serial caerulein injections. Protease activation and necrosis were investigated in isolated acini, disease severity over 24h, pancreatic function by MRI, isolated duct stimulation and faecal chymotrypsin, and leucocyte function by ex vivo lipopolysaccharide (LPS) stimulation. Pancreatic and lung injury were more severe in CFTRtm1HGU but intrapancreatic trypsin and serum enzyme activities higher than in wild-type controls only at 8h, a time interval previously attributed to leucocyte infiltration. CCK-induced trypsin activation and necrosis in acini from CFTRtm1HGU did not differ from controls. Fluid and bicarbonate secretion were greatly impaired, whereas faecal chymotrypsin remained unchanged. LPS stimulation of splenocytes from CFTRtm1HGU resulted in increased INF-γ and IL-6, but decreased IL-10 secretion. CFTR mutations that preserve residual pancreatic function significantly increase the severity of experimental pancreatitis-mostly via impairing duct cell function and a shift towards a pro-inflammatory phenotype, not by rendering acinar cells more susceptible to pathological stimuli.

Optimal target b-value on computed diffusion-weighted magnetic resonance imaging for visualization of pancreatic ductal adenocarcinoma and focal autoimmune pancreatitis.

PURPOSE: To compare computed diffusion-weighted imaging (cDWI) feasibility with that of directly acquired DWI for visualizing pancreatic ductal adenocarcinoma (PDAC) and focal autoimmune pancreatitis (AIP). METHODS: From April 2012 to January 2017, 135 patients with PDAC (n = 111) or focal AIP (n = 24) were retrospectively enrolled. They underwent DWI with b-values of 0, 500, and 1000 s/mm2. From DWI0 and DWI1000, we generated cDWIs with targeted b-values of 1500, 2000, and 3000 s/mm2. The lesions' signal intensities, image quality, signal intensity ratio (SIR) of lesions and pancreatic parenchyma to spinal cord, and lesion-to-pancreatic parenchyma contrast ratio (CR) were compared among the five DWI protocols (DWI500, DWI1000, cDWI1500, cDWI2000, and cDWI3000). SIR was analyzed by receiver operating characteristic (ROC) analyses. RESULTS: DWI500, DWI1000, and cDWI1500 had higher image quality than cDWI2000 and cDWI3000 (P < 0.001). The incidence of clear hyperintense PDAC was highest on cDWI2000, followed by cDWI1500, and cDWI3000 (P < 0.001-0.002), while the incidence of clear hyperintense AIP was higher on DWI1000, cDWI1500, and cDWI2000 than on DWI500 and cDWI3000 (P = 0.001-0.022). SIRs decreased whereas CRs increased as the b-value increased, for both PDAC and AIP. The area under the ROC curve (AUC) of SIRlesion was significantly lower on cDWI1500 than on cDWI2000 and cDWI3000 (P < 0.001). CONCLUSION: cDWI1500 or cDWI2000 generated from b-values of 0 and 1000 s/mm2 were the most effective for visualizing PDAC and focal AIP; however, the SIRlesion AUC was significantly lower on cDWI1500 than on cDWI2000 and cDWI3000.

Clinical Evaluation of Respiratory-triggered 3D MRCP with Navigator Echoes Compared to Breath-hold Acquisition Using Compressed Sensing and/or Parallel Imaging.

PURPOSE: To compare the image quality of three-dimensional magnetic resonance cholangiopancreatography (MRCP) acquired with respiratory triggering against breath-hold 3D MRCP with compressed sensing (CS) and parallel imaging (PI) in a clinical setting. METHODS: This study included 93 patients (45 men, mean age: 69.7 ± 9.3 years), in whom three types of 3D MRCP were performed: 3D breath-hold MRCP with CS and PI reconstruction (BH-CS-MRCP) and PI only reconstruction (BH-PI-MRCP) additionally to 3D respiratory triggered MRCP with navigator echoes (Nav-MRCP). Duct visualization and overall image quality were blindly evaluated on a four-point scale by two independent radiologists. Quantitative analysis was performed by calculating the relative duct-to-periductal contrast (RC) of three main biliary segments. Comparison between the methods was performed using paired t-test. RESULTS: Acquisition time was 23 s for both breath-hold MRCP protocols and 1 min 29 s for Nav-MRCP. Mean grading (Nav/CS/PI) for common bile duct (2.74/2.87/2.94), common hepatic duct (2.82/2.92/3.00), central right hepatic duct (2.75/2.85/2.98), central left hepatic duct (2.75/2.85/2.92) and cystic duct (2.22/2.34/2.42) was higher in BH-CS- and BH-PI-MRCP, whereas Nav-MRCP showed higher grading in the peripheral segments (peripheral right hepatic duct: 2.24/2.01/2.12; peripheral left hepatic duct: 2.23/2.02/2.13). Overall image quality of Nav-MRCP (2.91 ± 0.7) was not different from BH-PI-MRCP (2.92 ± 0.6) (P = 0.163), but higher than BH-CS-MRCP (2.80 ± 0.7) (P = 0.031). Quantitative analysis showed lower RC values for CS- and PI-MRCP than Nav-MRCP (P < 0.001). CONCLUSION: Breath-hold 3D MRCP were feasible using PI and CS. Visualization of the greater ductal system was even superior in breath-hold MRCP than in Nav-MRCP by considerably reducing acquisition time. Both breath-hold methods are suitable for revised MRI protocols notably in patients with irregular respiratory cycle.

Gadoxetate disodium-related event during image acquisition: a prospective multi-institutional study for better MR practice.

PURPOSE: To acknowledge the facts of gadoxetate disodium-related events in Japan and to achieve better MR practice by analyzing large cohort data with various MR parameters. MATERIALS AND METHODS: This prospective multi-institutional study included 1993 patients (1201 men, mean age 66.4 ± 12.8 years), who received dynamic MRI with gadoxetate disodium (gadoxetate group, n = 1646) or extracellular gadolinium-based contrast agents (other-GBCAs group, n = 347) between January and November 2016. Recorded data covered adverse reactions including dyspnea, breath-hold failure during acquisition, respiratory artifacts rated with a four-point scale, and MR parameters. We compared data between the two groups in whole cohort and age-, gender-, and institution-matched subcohort using χ2 test (n = 640). Logistic regression model was used to reveal independent associates of substantial artifacts in arterial phase imaging. RESULTS: Transient dyspnea rarely occurred in gadoxetate or other-GBCAs group (both < 1%). Gadoxetate group (vs other-GBCAs group) showed higher rates of breath-hold failure (whole cohort, 18.2% vs 7.7%, p < 0.001; subcohort, 17.6% vs 6.3%, p < 0.001) and substantial artifacts in arterial phase (7.2% vs 2.2%, p = 0.001; 7.4% vs 1.7%, p = 0.001). With single arterial phase protocol, substantial artifacts under gadoxetate were independently associated with age (odds ratio [OR] = 1.04, p < 0.001), hearing difficulty (OR = 2.92, p = 0.008), breath-hold practice required (OR = 1.61, p = 0.039), and short acquisition time (OR = 0.43, p = 0.005). Multiple arterial phase acquisition did not reduce the incident rate of substantial artifacts. CONCLUSION: Gadoxetate disodium was associated with breath-hold failure and substantial artifacts in arterial phase imaging, but not with dyspnea in Japan. Shorter acquisition time should be used to sustain image quality in gadoxetate disodium-enhanced arterial phase imaging. KEY POINTS: • Gadoxetate disodium administration leads to breath-hold failure and substantial imaging artifacts in arterial phase MRI in Japan. • Contrast agent-induced dyspnea in arterial phase and adverse reactions are rare in Japan, without showing differences between gadoxetate disodium or other extracellular gadolinium-based contrast agents. • Shorter acquisition time significantly reduces gadoxetate-induced imaging artifacts in the arterial phase.

Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study.

OBJECTIVE: To analyse the prevalence, incidence and clinical relevance of pancreatic cysts detected as incidental finding in a population-based longitudinal study. DESIGN: A total of 1077 participants (521 men, mean age 55.8±12.8 years) of 2333 participants from the population-based Study of Health in Pomerania (SHIP) underwent magnetic resonance cholangiopancreaticography (MRCP) at baseline (2008-2012). MRCP was analysed for pancreatic cysts with a diameter ≥2 mm. 676/1077 subjects received a 5-year follow-up (2014-2016). The prevalence and incidence of pancreatic cysts (weighted for study participation) were assessed in association to age, gender and suspected epidemiological risk factors. Mortality follow-up was performed in 2015 for all SHIP participants (mean follow-up period 5.9 years, range 3.2-7.5 years). RESULTS: At baseline pancreatic cysts had a weighted prevalence of 49.1%, with an average number of 3.9 (95% CI 3.2 to 4.5) cysts per subject in the subgroup harbouring cysts. Cyst size ranged from 2 to 29 mm. Prevalence (p<0.001), number (p=0.001) and maximum size (p<0.001) increased significantly with age. The 5-year follow-up revealed a weighted incidence of 12.9% newly detected pancreatic cysts. 57.1% of the subjects initially harbouring pancreatic cysts showed an increase in number and/or maximum cyst size. Of all subjects undergoing MRCP, no participant died of pancreatic diseases within mortality follow-up. CONCLUSION: The prevalence of pancreatic cysts in the general population is unexpectedly high, and their number and size increase with age. Overall, no pancreatic cancer was observed in this collective during a 5-year follow-up. Nevertheless, prospective follow-up imaging showed minimal progress in more than 50%. Only about 6% of cysts and 2.5% of the study group initially presented with cysts of more than 1 cm and thus might be clinically meaningful.

Pulmonary emphysema is a predictor of pneumothorax after CT-guided transthoracic pulmonary biopsies of pulmonary nodules.

PURPOSE: Pneumothoraces are the most frequently occurring complications of CT-guided percutaneous transthoracic pulmonary biopsies (PTPB). The aim of this study was to evaluate the influence of pre-diagnostic lung emphysema on the incidence and extent of pneumothoraces and to establish a risk stratification for the evaluation of the pre-procedure complication probability. MATERIAL AND METHODS: CT-guided PTPB of 100 pre-selected patients (mean age 67.1±12.8 years) were retrospectively enrolled from a single center database of 235 PTPB performed between 2012-2014. Patients were grouped according to pneumothorax appearance directly after PTPB (group I: without pneumothorax, n = 50; group II: with pneumothorax, n = 50). Group II was further divided according to post-interventional treatment (group IIa: chest tube placement, n = 24; group IIb: conservative therapy, n = 26). For each patient pre-diagnostic percentage of emphysema was quantified using CT density analysis. Emphysema stages were compared between groups using bivariate analyses and multinomial logistic regression analyses. RESULTS: Emphysema percentage was significantly associated with the occurrence of post-interventional pneumothorax (p = 0.006). Adjusted for potential confounders (age, gender, lesion size and length of interventional pathway) the study yielded an OR of 1.07 (p = 0.042). Absolute risk of pneumothorax increased from 43.4% at an emphysema rate of 5% to 73.8% at 25%. No differences could be seen in patients with pneumothorax between percentage of emphysema and mode of therapy (p = 0.721). CONCLUSION: The rate of lung emphysema is proportionally related to the incidence of pneumothorax after CT-guided PTPB and allows pre-interventional risk stratification. There is no association between stage of emphysema and post-interventional requirement of chest tube placement.

Prevalence of Fatty Liver Disease and Hepatic Iron Overload in a Northeastern German Population by Using Quantitative MR Imaging.

Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed. On the basis of previous histopathologic calibration, participants were stratified according to their liver fat and iron content as follows: none (PDFF, ≤5.1%; R2*, ≤41.0 sec-1), mild (PDFF, >5.1%; R2*, >41 sec-1), moderate (PDFF, >14.1%; R2*, >62.5 sec-1), high (PDFF: >28.0%; R2*: >70.1 sec-1). Prevalence of fatty liver diseases and iron overload was calculated (weighted by probability of participation). Clinical associations were identified by using boosting for generalized linear models. Results Median PDFF was 3.9% (range, 0.6%-41.5%). Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants). Median R2* was 34.4 sec-1 (range, 14.0-311.8 sec-1). Iron overload was observed in 17.4% (447 of 2561 participants; mild, 14.7% [376 participants]; moderate, 0.8% [20 participants]; high content, 2.0% [50 participants]). Liver fat content correlated with waist-to-height ratio, alanine transaminase, uric acid, serum triglycerides, and blood pressure. Liver iron content correlated with mean serum corpuscular hemoglobin, male sex, and age. Conclusion In a white German population, the prevalence of fatty liver diseases and liver iron overload is 42.2% (1082 of 2561) and 17.4% (447 of 2561). Whereas liver fat is associated with predictors related to the metabolic syndrome, liver iron content is mainly associated with mean serum corpuscular hemoglobin. © RSNA, 2017 Online supplemental material is available for this article.

Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit ß3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.