Pilot Study Assessing Differentiation of Steatosis Hepatis, Hepatic Iron Overload, and Combined Disease Using Two-Point Dixon MRI at 3 T: In Vitro and In Vivo Results of a 2D Decomposition Technique

Dysmetabolic iron overload syndrome (DIOS) is frequently observed, but the underlying mechanism remains unclear. We propose the hypothesis that hyperinsulinemia, a common characteristic of DIOS, may stimulate liver transferrin receptor 1 (TFR1) expression via the PI3K/iron regulatory protein 2 (IRP2) pathway, leading to the occurrence of DIOS. The hepatic iron content, serum iron parameters, and expressions of TFRs and IRPs in the liver were determined in rats with temporary or long-lasting hyperinsulinemia induced by acute or chronic administration of insulin. The effect of insulin on TFR1 expression and its molecular mechanism were determined in HL-7702 cells in vitro. It was found that long-lasting hyperinsulinemia significantly increased TFR1 expression in the liver and induced mild-to-moderate hepatic iron overload, which was accompanied by a normal level of serum iron. Insulin markedly upregulated both protein and mRNA levels of TFR1 in HL-7702 cells. The stability of TFR1 mRNA stability, together with expression of IRPs expression, were both significantly increased by insulin treatment. Insulin-induced TFR1 expression was blocked by IRP2, but not by IRP1 interference, and disappeared when HL-7702 cells were pretreated with LY294002, triciribine hydrate, or rapamycin. In conclusion, the findings of this study indicate that hyperinsulnemia could induce hepatic iron overload by upregulating liver TFR1 via the PI3K/AKT/mTOR/IRP2 pathway, which may be one of the main reasons for the occurrence of DIOS.

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Hemolysis-mediated suppression of hepcidin causes hepatic iron overload in alcoholic liver disease

10.1055/s-0037-1605104 ◽

2017 ◽

Author(s):

V Rausch ◽

I Silva ◽

T Peccerella ◽

S Mueller

Keyword(s):

Liver Disease ◽

Iron Overload ◽

Alcoholic Liver Disease ◽

Hepatic Iron ◽

Hepatic Iron Overload

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Hepatic iron overload in alcoholic liver disease: The role of sinusoidal endothelial cells in iron sensing

10.1055/s-0039-3402118 ◽

2020 ◽

Author(s):

S Wang ◽

T Peccerella ◽

V Rausch ◽

S Mueller

Keyword(s):

Endothelial Cells ◽

Liver Disease ◽

Iron Overload ◽

Alcoholic Liver Disease ◽

Hepatic Iron ◽

Sinusoidal Endothelial Cells ◽

Hepatic Iron Overload

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Creatine Supplementation for Patients with Inflammatory Bowl Diseases: A Scientific Rationale for a Clinical Trial

Nutrients ◽

10.3390/nu13051429 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1429

Author(s):

Theo Wallimann ◽

Caroline H. T. Hall ◽

Sean P. Colgan ◽

Louise E. Glover

Keyword(s):

Ulcerative Colitis ◽

Clinical Trial ◽

Crohn’S Disease ◽

Pilot Study ◽

Crohn's Disease ◽

Single Case ◽

Initial Period ◽

Creatine Supplementation

Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease.

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Free‐breathing mapping of hepatic iron overload in children using 3D multi‐echo UTE cones MRI

Magnetic Resonance in Medicine ◽

10.1002/mrm.28610 ◽

2021 ◽

Vol 85 (5) ◽

pp. 2608-2621 ◽

Cited By ~ 1

Author(s):

Youngwook Kee ◽

Christopher M. Sandino ◽

Ali B. Syed ◽

Joseph Y. Cheng ◽

Ann Shimakawa ◽

...

Keyword(s):

Iron Overload ◽

Free Breathing ◽

Hepatic Iron ◽

Hepatic Iron Overload

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Resizable Ventricular Patch Plasty in the Porcine Left Ventricle a Pilot Study

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0b013e3181cfa8f1 ◽

2010 ◽

Vol 5 (1) ◽

pp. 16-21 ◽

Cited By ~ 1

Author(s):

Willemijn H. F. Huijgen ◽

Paul F. Gründeman ◽

Tycho van der Spoel ◽

Maarten-Jan Cramer ◽

Paul Steendijk ◽

...

Keyword(s):

Pilot Study ◽

Animal Experiments ◽

Ventricular Volume ◽

Left Ventricular ◽

Left Ventricular Aneurysm ◽

Patch Shape ◽

End Diastolic Volume ◽

Patch Plasty

Objective Endoventricular circular patch plasty is a method used to reconstruct the ventricular cavity in patients with (post) ischemic left ventricular aneurysm or global dilatation. However, late redilatation with mitral regurgitation has been reported, in which postoperative apex shape seems to play an important role. We studied the feasibility of ventricular volume downsizing with a variably shaped patch in porcine hearts. Methods In five in vitro and two acute animal experiments, a dyskinetic aneurysm was simulated with a pericardial insert. Reducing patch surface by changing patch shape diminished end-diastolic volume. In vitro, static end-diastolic volume was determined for each patch shape using volumetry and echocardiography. In the acute animal experiments, preliminary observations of patch behavior in live material were made, and pressure/time relationship, dPdTmax, was registered. Results In vitro, bringing the convex patch into a flat plane reduced LV volume from 66 ± 7 mL (aneurysm) to 49 ± 5 mL. Four of 5 patch shapes further reduced volume to a mean of 38 ± 7 mL (P = 0.03). The in vitro echocardiographic measurements correlated with volumetry findings (r = 0.81). In the acute animal experiments, dPdTmax varied with patch shape, independent of volume changes. Conclusions In this pilot study, in vitro shape configuration of the resizable ventricular patch resulted in a calibrated end-diastolic volume reduction. The data of the two in vivo pilot experiments clearly indicate that change in patch configuration in the situation of more or less unchanged end-diastolic volume had impact on cardiac performance. Future studies must substantiate the results of this observation.

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