TY - GEN A1 - Jung, Ernst Michael A1 - Stroszczynski, Christian A1 - Jung, Friedrich T1 - Contrast enhanced ultrasonography (CEUS) to detect abdominal microcirculatory disorders in severe cases of COVID-19 infection: First experience T2 - Clinical Hemorheology and Microcirculation N2 - In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow. KW - Corona virus KW - contrast enhanced ultrasound sonography (CEUS) KW - COVID-19 KW - liver KW - kidney Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209003 U6 - https://doi.org/10.3233/CH-209003 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 4 SP - 353 EP - 361 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Stroszczynski, Christian A1 - Jung, Friedrich T1 - Contrast enhanced ultrasound (CEUS) to assess pleural pulmonal changes in severe Covid 19 infection: First results T2 - Clinical Hemorheology and Microcirculation N2 - AIM: Use of contrast enhanced ultrasound (CEUS) in severe cases of COVID-19 infection to assess pulmonary changes near the pleura. MATERIAL AND METHODS: Bedside examinations by an experienced intensive care unit examiner using a multi-frequency probe (C1-6 MHz) with B-mode and CEUS to assess pleural-near changes in severe cases of COVID-19 infection with respiratory failure. CEUS with bolus delivery via a central venous catheter of 2.4 ml Sulphur hexafluoride microbubbles from the arterial phase (10–15 s) to the late phase of 5 min. Digital storage of cine sequences of the lung sound with abdomen for independent assessment with the subsequently performed contrast-enhanced dual-source CT. RESULTS: In 11 intubated and ventilated patients (arithmetic mean 62 years, 48 to 78 years, 3 women) with confirmed severe COVID-19 infections, a peripherally accentuated consolidation with irregular hyperemia was found in the CEUS and also in the CT examination. Of the 5 cases with pulmonary arterial embolisms, signs of right ventricular failure were found. In all cases, using CEUS low perfused areas of the pleura with adjacent hyperemia could be detected, while, with CT segmental contrast medium, gaps with subpleural compressions were found. Interstitial changes near the pleura led to B-lines and to ground glass opacities in the CT. Near the diaphragm a delayed arterial contrast of the liver was observed. In addition, in 2 cases partial atelectasis, in 3 cases marginal pleural effusions were found. CONCLUSION: CEUS opens up new possibilities for bedside monitoring of pleural reactive inflammatory or peripheral thrombus embolism in severe cases of COVID-19 infection. KW - COVID-19 infection KW - lung- Contrast-enhanced ultrasound (CEUS) KW - pleural affection KW - peripheral embolic consolidation Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209005 U6 - https://doi.org/10.3233/CH-209005 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 1 SP - 19 EP - 26 ER - TY - GEN A1 - Peschel, G. A1 - Jung, Ernst Michael A1 - Fisser, C. A1 - Putz, F. J. A1 - Wertheimer, T. A1 - Sinner, B. A1 - Lunz, D. A1 - Jung, Friedrich A1 - Müller, M. T1 - Interstitial lung opacities in patients with severe COVID-19 pneumonia by bedside high-resolution ultrasound in association to CO2 retention T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). OBJECTIVE: This single centre cross-section study aimed to grade the severity of pneumonia by bed-side lung ultrasound (LUS). METHODS: A scoring system discriminates 5 levels of lung opacities: A-lines (0 points),≥3 B-line (1 point), coalescent B-lines (2 points), marked pleural disruptions (3 points), consolidations (4 points). LUS (convex 1–5 MHz probe) was performed at 6 defined regions for each hemithorax either in supine or prone position. A lung aeration score (LAS, maximum 4 points) was allocated for each patient by calculating the arithmetic mean of the examined lung areas. Score levels were correlated with ventilation parameters and laboratory markers. RESULTS: LAS of 20 patients with ARDS reached from 2.58 to 3.83 and was highest in the lateral right lobe (Mean 3.67). Ferritin levels (Mean 1885μg/l; r = 0.467; p = 0.051) showed moderate correlation in spearman roh calculation. PaCO2 level (Mean 46.75 mmHg; r = 0.632; p = 0.005) correlated significantly with LAS, while duration of ventilation, Horovitz index, CRP, LDH and IL-6 did not. CONCUSIONS: The proposed LAS describes severity of lung opacities in COVID-19 patients and correlates with CO2 retention in patients with ARDS. Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch200925 U6 - https://doi.org/10.3233/CH-200925 VL - 77 IS - 4 SP - 355 EP - 365 ER - TY - GEN A1 - Wiesinger, Isabel A1 - Jung, Friedrich A1 - Jung, Ernst Michael T1 - Contrast-enhanced ultrasound (CEUS) and perfusion imaging using VueBox® T2 - Clinical Hemorheology and Microcirculation N2 - The external perfusion software (VueBox™) for contrast-enhanced ultrasound (CEUS), enables the quantitative analysis of micro-vascularization within non-cystic lesions in terms of characterization and detection. This review summarizes our work about parathyroid gland, thyroid gland, liver, prostate and other tissues as well as original studies in the use of parametric perfusion imaging. Useful perfusion parameters are introduced. Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch201040 U6 - https://doi.org/10.3233/CH-201040 VL - 78 IS - 1 ER - TY - GEN A1 - Werner, Jens Martin A1 - Zidek, Martin A1 - Kammerer, Sylvia A1 - Platz Batista da Silva, Natascha A1 - Jung, Friedrich A1 - Schlitt, Hans Jürgen A1 - Hornung, Matthias A1 - Jung, Ernst Michael T1 - Intraoperative contrast-enhanced ultrasound can have a crucial role in surgical decision-making during hepato-pancreatico-biliary surgery –Analysis of impact and input T2 - Clinical Hemorheology and Microcirculation N2 - OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the out-come after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4–5 ml Sulphur hexafluoride microbubbles using a 6–9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%). The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required. Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases. KW - Surgical decision-making KW - hepato-pancreatico-biliary surgery KW - CEUS KW - elastography Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch201031 U6 - https://doi.org/10.3233/CH-201031 VL - 78 IS - 1 SP - 1 EP - 14 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Steinbrecht, Susanne A1 - Jung, Conrad H. G. A1 - Westphal, Sophia A1 - Klöpzig, Stefanie A1 - Waldeck, Peter A1 - Küpper, Jan-Heiner A1 - Storsberg, J. A1 - Jung, Friedrich T1 - Arthrospira platensis accelerates the formation of an endothelial cell monolayer and protects against endothelial cell detachment after bacterial contamination T2 - Clinical Hemorheology and Microcirculation N2 - Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field. KW - Arthrospira platensis KW - endothelial cells KW - xCELLigence system Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch201096 U6 - https://doi.org/10.3233/CH-201096 SN - 1386-0291 VL - 78 IS - 2 SP - 151 EP - 161 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Kammerer, Sarah A1 - Brandenstein, M. A1 - Putz, F. J. A1 - Stroszczynski, Christian A1 - Jung, Friedrich T1 - High resolution flow (HR Flow) and Glazing Flow in cases of hepatic flow changes: Comparison to color-coded doppler sonography (CCDS) T2 - Clinical Hemorheology and Microcirculation N2 - AIM: To evaluate the possibilities of flow detection using high resolution flow (HR Flow) and Glazing Flow technique in patients with liver parenchymal changes and flow changes in comparison to color-coded Doppler sonography (CCDS). MATERIAL AND METHODS: All examinations were performed using a multi frequency matrix convex probe with high resolution technique (SC6-1U/Resona7, Mindray, Shenzhen, China) by one experienced examiner to evaluate the venous, portal venous and arterial liver flow with digital documentation of the dynamic flow parameters like peak systolic flow, end-diastolic flow and resistance index. For liver parenchymal stiffness changes shear wave elastography was performed with at least 10 measurements. By two independent readers an elevation was performed to evaluate the image quality and the degree of flow artefacts, from 0 = not available to 5 points with excellent image quality without flow artefacts. RESULTS: All 40 patients (24 men, 16 women, age 27–83 years, mean 56±5 years) showed morphology changes from B-Mode of the liver parenchyma to inhomogeneous tissue with higher stiffness evaluated by the shear wave elastography (1.45 m/s up to 2.79 m/s±1.79 m/s, considering F1 up to F4 fibrosis) and in 15 cases histopathologically proven liver cirrhosis. In 9 cases after non-acute thrombosis flow reduction of the portal vein was the reason for the diameter less than 5 mm. Flow parameters for the venous flow were between 8 cm/s up to 29 cm/s, mean 14±4 cm/s, for the hepatic portal vein 5 cm/s up to 57 cm/s, mean 17±5 cm/s, for the hepatic artery systolic flow between 50 cm/s up to 127±33 cm/s, end-diastolic flow from 22 cm/s up to 47±8 cm/s. Resistance index for the hepatic artery was between 0.41 up to 0.73, mean 0.67±0.25. The image quality for CCDS over all cases was evaluated for CCDS between 1 up to 4. The mean quality was 2.5±0.5, for HR Flow in combination with Glazing Flow 3±0.5, with significant differences for the 2 readers (P < 0.01). CONCLUSION: Combination of HR Flow with Glazing Flow could be helpful to evaluate morphological und hemodynamic changes of liver arterial flow, portal venous and venous flow. Reduction of flow artefacts in combination with a higher image quality could be helpful for optimizing the digital measurements also for follow up examinations. KW - Liver vascular imaging KW - high resolution flow (HR) KW - Glazing Flow KW - imaging quality KW - artefact reduction Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219102 U6 - https://doi.org/10.3233/CH-219102 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 3 EP - 17 ER - TY - GEN A1 - Diesch, S. T. A1 - Jung, Friedrich A1 - Prantl, Lukas A1 - Jung, Ernst Michael T1 - Surface imaging of breast implants using modern high-frequency ultrasound technology in comparison to high-end sonography with power analyses for B-scan optimization T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-219204 SN - 1875-8622 SN - 1386-0291 VL - 80 IS - 4 SP - 487 EP - 495 ER - TY - GEN A1 - Jung, Friedrich A1 - Lamby, Philipp A1 - Prantl, Lukas A1 - Wiggermann, P. A1 - Jung, Ernst Michael A1 - Krüger-Genge, Anne A1 - Franke, Ralf-Peter T1 - Post-mortem distribution of Iodinated Contrast Media (ICM) (iodixanol versus iopromide) in the porcine kidney after multiple bolus injections in vivo into the supra-renal aorta T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-229102 SN - 1875-8622 VL - 85(2023) IS - 3 SP - 289 EP - 295 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Jung, Friedrich A1 - Stroszczynski, Christian A1 - Wiesinger, Isabel T1 - Dynamic endoluminal contrast enhanced ultrasound (CEUS) for display of drainages in inflammatory abdominal fluid collections T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-211370 SN - 1875-8622 SN - 1386-0291 VL - 80 IS - 2 SP - 49 EP - 59 ER - TY - GEN A1 - Jung, C. G. H. A1 - Nghinaunye, Theopolina A1 - Waldeck, Peter A1 - Braune, Steffen A1 - Petrick, Ingolf A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Decarbonization of Arthrospira platensis production by using atmospheric CO2 as an exclusive carbon source: proof of principle T2 - International Journal of Environmental Science and Technology N2 - There is an urgent need to develop technologies for removing CO2 from the atmosphere to combat climate change. Microalgae and cyanobacteria, such as Arthrospira platensis (AP), have shown promise due to their high photoautotrophic biomass production. Conventional AP culture media are supplemented with high concentrations of NaHCO3 since AP utilizes as a carbon source. These culture conditions result in significant amounts of CO2 escaping into the atmosphere, instead of being sequestered during cultivation. Here, we investigated whether ambient air (0.042% CO2) can be used for growing AP in a culture medium lacking a fossil-based carbon source. AP was cultured in 2 L glass bioreactors containing: (1) Zarrouk medium with 16.8 g/L NaHCO3 and aeration with 0.236 vvm air with 2% CO2 (“NaHCO3/CO2-based”) to compensate carbon loss due to CO2 outgassing, and (2) Zarrouk medium without NaHCO3 and a gas flow with ambient air (0.926 vvm) as the only carbon source (“air-based”). The air-based production resulted in the biofixation of 3.78 gCO2/L during the linear growth phase. With NaHCO3/CO2-based production, a comparable amount of 3.42 gCO2/L was obtained while 659.12 g of CO2 was released into the atmosphere. Total protein, phycocyanin, chlorophyll-a, and carotenoids were present in similar or increased amounts in AP produced by the air-based method. We concluded that cultivation of AP with Zarrouk medium lacking NaHCO3 but using ambient air with atmospheric CO2 as the only carbon source is possible without reducing productivity. These results improve our understanding of how atmospheric CO2 can be reduced by culturing AP. KW - Arthrospira platensis KW - Atmospheric CO2 KW - Biomass production KW - Climate change KW - Carbon capturing KW - Decarbonization Y1 - 2023 UR - https://link.springer.com/article/10.1007/s13762-023-05215-x#citeas U6 - https://doi.org/10.1007/s13762-023-05215-x SN - 1735-2630 ER - TY - GEN A1 - Jung, Conrad H. G. A1 - Waldeck, Peter A1 - Petrick, Ingolf A1 - Akinwunmi, Mosunmol A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Light-induced changes in the morphology and fluorescence of Arthrospira platensis T2 - Clinical Hemorheology and Microcirculation N2 - The cyanobacterium Arthrospira platensis is a well-known source of bioactive substances. Growth and the generation of bioactive ingredients of Arthrospira platensis depend mainly on the quantity of light in a controlled environment. Photoinhibition is a time, nutrient, and light intensity-dependent decrease in photosynthetic efficiency. However, too strong illumination can induce two harmful effects: (1) photoinhibition as a reduction in photosynthetic rate and (2) photooxidation which can have lethal effects on the cells, and which can lead to total loss of the culture. The results of this microscopical study demonstrate, that under the procedures described and very high photon flux den-sities, not only a decrease in the photosynthetic efficiency but beyond, also destruction of Arthrospira platensis can occur. KW - Arthrospira platensis KW - light stress KW - photoinhibition KW - phototoxicity KW - morphology KW - fluorescence Y1 - 2023 UR - https://content.iospress.com/articles/journal-of-cellular-biotechnology/jcb239001 U6 - https://doi.org/10.3233/JCB-239001 SN - 1386-0291 VL - 9 IS - 1 SP - 71 EP - 77 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Jung, Friedrich A1 - Stroszczynski, Christian A1 - Wiesinger, Isabel T1 - Quantification of dynamic contrast-enhanced ultrasound (CEUS) in non-cystic breast lesions using external perfusion software T2 - Scientific Reports N2 - The aim of this present clinical pilot study is the display of typical perfusion results in patients with solid, non-cystic breast lesions. The lesions were characterized using contrast enhanced ultrasound (CEUS) with (i) time intensity curve analyses (TIC) and (ii) parametric color maps. The 24 asymptomatic patients included were genetically tested for having an elevated risk for breast cancer. At a center of early detection of familial ovary and breast cancer, those patients received annual MRI and grey-scale ultrasound. If lesions remained unclear or appeared even suspicious, those patients also received CEUS. CEUS was performed after intravenous application of sulfur hexafluoride microbubbles. Digital DICOM cine loops were continuously stored for one minute in PACS (picture archiving and communication system). Perfusion images and TIC analyses were calculated off-line with external perfusion software (VueBox). The lesion diameter ranged between 7 and 15 mm (mean 11 ± 3 mm). Five hypoechoic irregular lesions were scars, 6 lesions were benign and 12 lesions were highly suspicious for breast cancer with irregular enhancement at the margins and a partial wash out. In those 12 cases, histopathology confirmed breast cancer. All the suspicious lesions were correctly identified visually. For the perfusion analysis only Peak Enhancement (PE) and Area Under the Curve (AUC) added more information for correctly identifying the lesions. Typical for benign lesions is a prolonged contrast agent enhancement with lower PE and prolonged wash out, while scars are characterized typically by a reduced enhancement in the center. No differences (p = 0.428) were found in PE in the center of benign lesions (64.2 ± 28.9 dB), malignant lesions (88.1 ± 93.6 dB) and a scar (40.0 ± 17.0 dB). No significant differences (p = 0.174) were found for PE values at the margin of benign lesions (96.4 ± 144.9 dB), malignant lesions (54.3 ± 86.2 dB) or scar tissue (203.8 ± 218.9 dB). Significant differences (p < 0.001) were found in PE of the surrounding tissue when comparing benign lesions (33.6 ± 25.2 dB) to malignant lesions (15.7 ± 36.3 dB) and scars (277.2 ± 199.9 dB). No differences (p = 0.821) were found in AUC in the center of benign lesions (391.3 ± 213.7), malignant lesions (314.7 ± 643.9) and a scar (213.1 ± 124.5). No differences (p = 0.601) were found in AUC values of the margin of benign lesions (313.3 ± 372.8), malignant lesions (272.6 ± 566.4) or scar tissue (695.0 ± 360.6). Significant differences (p < 0.01) were found in AUC of the surrounding tissue for benign lesions (151.7 ± 127.8), malignant lesions (177.9 ± 1345.6) and scars (1091 ± 693.3). There were no differences in perfusion evaluation for mean transit time (mTT), rise time (RT) and time to peak (TTP) when comparing the center to the margins and the surrounding tissue. The CEUS perfusion parameters PE and AUC allow a very good assessment of the risk of malignant breast lesions and thus a downgrading of BI-RADS 4 lesions. The use of the external perfusion software (VueBox, Bracco, Milan, Italy) did not lead to any further improvement in the diagnosis of suspicious breast lesions and does appears not to have any additional diagnostic value in breast lesions. Y1 - 2021 UR - https://www.nature.com/articles/s41598-021-96137-6 U6 - https://doi.org/10.1038/s41598-021-96137-6 SN - 2045-2322 VL - 11 ER - TY - GEN A1 - Jung, Conrad H. G. A1 - Waldeck, Peter A1 - Petrick, Ingolf A1 - Braune, Steffen A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Bioreactor for the cultivation of Arthrospira platensis under controlled conditions T2 - Journal of Cellular Biotechnology N2 - A vertical flat-type bioreactor consisting of transparent polyethylene (food safe) was constructed, which is characterized by a flexible design and allows the adjustment of a light path of 1 cm – 8.5 cm and a working volume of 1.5 l – 4 l. To characterize the performance of the bioreactor, cultivation experiments were performed with the cyanobacterium Arthrospira platensis (AP). The growth was assessed continuously by monitoring optical density and intermittently by measuring the dry weight of the AP biomass. An on-line measurement technique for estimating biomass production rate in a photosynthetic microalgae culture was developed. The oxygen produced by AP in the culture medium was flushed out sparging using a mixture of air and CO2 (1%). Factors which might influence the AP growth were monitored: pH, temperature, oxygen concentration and the filling level were corrected automatically to compensate evaporation losses. As an example, the huge influence of the light intensity on the AP growth was tested. The increase of the photon flux density of 15 to 1200μmol/(l · d) led to a 22-fold increase of the productivity and a 3.1-fold shorter doubling time. Using an online measurement technique - together with the control of the growth process via a wireless local area network (WLAN) router and virtual private network - allows monitoring the growth of Arthrospira platensis remotely. Y1 - 2021 UR - https://content.iospress.com/articles/journal-of-cellular-biotechnology/jcb210032 U6 - https://doi.org/10.3233/JCB-210032 VL - 7 IS - 1 SP - 35 EP - 40 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Jung, Conrad H. G. A1 - Braune, Steffen A1 - Harb, K. A1 - Westphal, S. A1 - Klöpzig, Stefanie A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers T2 - Clinical Hemorheology and Microcirculation N2 - Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%. Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations. KW - Arthrospira platensis KW - spirulina KW - endothelial cells Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219200 U6 - https://doi.org/10.3233/CH-219200 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 193 EP - 203 ER - TY - GEN A1 - Jung, Friedrich A1 - Jung, Conrad H. G. A1 - Krüger-Genge, Anne A1 - Waldeck, Peter A1 - Küpper, Jan-Heiner T1 - Factors influencing the growth of Spirulina platensis in closed photobioreactors under CO₂ – O₂ conversion T2 - Journal of Cellular Biotechnology N2 - Since there is growing interest throughout the world in photosynthetic microbes as a potential source of food or food supplements, an assessment of factors which influence the biomass obtained in bioreactors, protein contents and constituents is important. This work reviews the autotrophic cultivation conditions of Spirulina platensis especially the dependency on the strain, the composition of the nutrient solution, pH, temperature of the medium, light intensity and color as well as exposure rhythm, the flow rate and composition of the aerating gas mixture and the bubble size, the content of oxygen, CO₂ and HCO₃ in the medium and last but not least from the optical density of the spirulina suspension during growth. KW - spirulina platensis KW - influencing factors KW - temperature KW - light intensity KW - wave length Y1 - 2019 U6 - https://doi.org/10.3233/JCB-199004 SN - 2352-3697 SN - 2352-3689 VL - 5 IS - 2 SP - 125 EP - 134 ER - TY - GEN A1 - Dropco, Ivor A1 - Kaiser, Ulrich A1 - Wagner, Lola A1 - Brunner, Stefan M. A1 - Schlitt, Hans Jürgen A1 - Stroszcynski, Christian A1 - Jung, Friedrich A1 - Yi, Dong A1 - Herr, Wolfgang A1 - Jung, Ernst Michael T1 - Color mapping using ultrasound system-integrated perfusion software for evaluation of focal liver lesions: a possible first step for more independent reading T2 - Journal of Gastrointestinal and Liver Diseases N2 - Aims To assess the value of using integrated parametric ultrasound software for contrast-enhanced ultrasonography (CEUS) of liver tumors. Methods 107 patients with liver tumors were studied. CEUS were performed to detect focal lesions. Parametric images were based on continuous CINE LOOPs, from the early-arterial phase (15 s) to the portal-venous phase (1 min) generated by perfusion software. The evaluations of the parametric images and their dignity for liver lesions were performed independently by an experienced and a less-experienced investigator. Computed tomography, magnetic resonance imaging scans or histological analysis were used as references. Results High parametric image quality were obtained in all patients. Among the patients, 44% lesions were benign, 56% were malignant. The experienced investigator correctly classified 46 of 47 (98%) as benign, and 60 of 60 (100%) as malignant tumors based on the parametric images. The less-experienced investigator correctly classified 39 of 47 (83%) as benign, and 49 of 60 (82%) malignant tumors, acheaving a high statistical accuracy of 98% with this type of diagnostic. Conclusion Parametric imaging for grading the malignant degree of tumor may be a good complement to existing ultrasound techniques and was particularly helpful for improving the assessments of the less-experienced examiner. KW - CEUS KW - parametric imaging KW - dynamic vascularization KW - liver malignancies Y1 - 2023 UR - https://europepmc.org/article/med/38147619 U6 - https://doi.org/10.15403/jgld-4997 SN - 1842-1121 VL - 32 IS - 4 SP - 479 EP - 487 ER - TY - GEN A1 - Nghinaunye, Theopolina A1 - Waldeck, Peter A1 - Jung, C. G. H. A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich A1 - Braune, Steffen T1 - Response of Arthrospira platensis to different temperatures regarding growth and biochemical composition T2 - Clinical Hemorheology and Microcirculation N2 - The growth of cyanobacteria can vary considerably depending on the ambient temperature. Since the optimal growth temperature for Arthrospira platensis (strain SAG21.99) is not yet known, this was investigated in the present study. The study revealed that a process temperature of 30°C seems to be optimal for the Arthrospira strain SAG21.99 cultivation in terms of a maximum biomass productivity. This was also true for the phycocyanin content which was at 30°C significantly higher than at 20 or 40°C. KW - Arthrospira platensis KW - growth KW - temperature KW - bioreactor Y1 - 2023 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch238104 U6 - https://doi.org/10.3233/CH-238104 SN - 1386-0291 SP - 1 EP - 7 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Stroszczynski, Christian A1 - Jung, Friedrich T1 - Advanced multimodal imaging of solid thyroid lesions with artificial intelligence-optimized B-mode, elastography, and contrast-enhanced ultrasonography parametric and with perfusion imaging: Initial results T2 - Clinical Hemorheology and Microcirculation N2 - Goal of the study was the assessment of AI-assisted diagnosis of solid thyroid foci with multimodal modern ultrasound imaging. 50 patients (26–81 years, 54.7±13.1 years) were included in the study. Multimodal ultrasound imaging by means of B-mode with linear probe (4–12 MHz) with option of automated documentation of findings by means of AI, with supplementary Ultra MicroAngiography (UMA) was used. Macrovascularisation was assessed by dynamic contrast ultrasonography (CEUS) with parametric evaluation and perfusion analysis, and microvascularization was assessed by combined strain and shear wave elastography on a novel high-performance ultrasound system (Resona R9/Mindray) by an experienced examiner with independent reading. The evaluation was performed according to TI-RADS III-V. The volume of the thyroid lobes on both sides averaged 39 ml±5 ml (27 to 69 ml). The 13 cases of histologically confirmed thyroid carcinomas (8 papillary, 2 medullary, 2 microfollicular, 1 anaplastic CA) with a mean size of 15 mm±6 mm (9–21 mm) were correctly evaluated by TI-RADS V on the basis of irregular shape, induration > 2.5 m/s or > 30kPA and striking wash-out kinetics. Tumor lymph nodes could only be correctly detected preoperatively in one case of medullary carcinoma according to the surgical findings, based on irregular vascularization with UMA in roundish shape with cortex > 4 mm, transverse diameter up to 11 mm. In 25 cases of inhomogeneous nodular goiter an evaluation with TI-RADS III was performed in 31 cases, in 4 cases with incomplete marginal contour, partial marginal vascularization with UMA and partial wash out with indurations up to 2.5 m/s 30 kPA an evaluation with TI-RADS IV and surgical excision for nodular goiter. In 12 cases regressive nodular changes without relevant malignancy criteria resulted in nodular goiter, with focal changes up to 1.5 cm in diameter, classified as requiring control with TI-RADS III. There were no relevant changes in findings in the controls after 6 months. From the AI tool, the 20/25 goiter nodes were assessed as TI-RADS III, 7/12 adenomas, 5 goiter nodes, and 5 adenomas as TI-RADS IV, 5/13 carcinomas as TI-RADS IV, and 8/13 carcinomas as TI-RADS V. Multimodal ultrasound diagnostics supported by AI has a high diagnostic potential for the evaluation of solid thyroid lesions and standardizes the reporting with digital representative image documentation. CEUS perfusion and modern elastography techniques allow targeted follow-up of TI-RADS III findings. KW - Thyroid lesions KW - multimodal ultrasound KW - artificial intelligence (AI) KW - UMA-elastography KW - contrast enhanced ultrasonography (CEUS) KW - parametric-perfusion analysis Y1 - 2023 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch239102 U6 - https://doi.org/10.3233/CH-239102 SN - 1386-0291 VL - 84 IS - 2 SP - 227 EP - 236 ER - TY - GEN A1 - Martina, Georgieva A1 - Kammerer, Sarah A1 - Prantl, Lukas A1 - Jung, Friedrich A1 - Stroszczynski, Christian A1 - Jung, Ernst Michael T1 - Imaging of breast implant and implant-associated complications: Capsular contracture and intraor extracapsular rupture T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: In recent years, follow-up after breast reconstruction with silicone implants and the detection of complications have been relieved by the possibility of improved diagnostic methods. METHODS: Between January 2015 and December 2019 a total of 40 patients (29–84 years) with silicone implants were included in this retrospective study. The implants were examined clinically and with modern imaging: general ultrasound imaging (US), magnetic resonance imaging (MRI), high resolution computed tomography (CT) and positron emission tomography –computed tomography (PET-CT). If necessary, a histological/cytological sample was taken. The breast implants were assessed by three radiologists specialized in breast imaging. The grade of capsular contracture was classified according to the Baker classification. RESULTS: All 40 women obtained a clinical examination and an US diagnostic to identify early and more common complications such as implant folding and capsular fibrosis. Depending on the clinical examination and ultrasound findings additional MRI (n = 10), CT (n = 9) and/or PET-CT (n = 2) were performed. 16 patients had implants folding proven with US (n = 16), MRI (n = 6) and CT (n = 1). The grade of capsular fibrosis was determined according to the Baker classification. The following results were obtained in our study: 25 breast implants with Baker grade I and eleven breast implants with Baker grade II, both proven with US; one breast implants with Baker grade III and one breast implant with Baker grade IV, proven with US (n = 2), MRI (n = 1) and CT (n = 1). One patient had intracapsular rupture and one patient had extracapsular rupture, both detected on CT and surgically proven. No patient had a silicone accumulation in the lymph nodes. One patient had pathologically enlarged axillary lymph nodes, which were evaluated as inflammatory changes in PET-CT. Long-term complications such as the development of malignant breast tumors could not be observed. CONCLUSION: To detect early complications after breast implant surgery, a regular clinical examination is indispensable. Imaging methods complement each other and if they are used multimodal, it is easier to identify early complications. Modern diagnostic modalities like ultrasound and magnetic resonance imaging expand the spectrum and improve diagnostic safety. KW - Breast implant KW - ultrasound KW - magnetic resonance imaging KW - capsular contracture Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209218 U6 - https://doi.org/10.3233/CH-209218 SN - 1875-8622 SN - 1386-0291 VL - 76 IS - 2 SP - 221 EP - 231 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Wertheimer, T. A1 - Putz, F. J. A1 - Jung, Friedrich A1 - Kammerer, Sarah A1 - Pregler, B. A1 - Luerken, L. A1 - Stroszczynski, Christian A1 - Beyer, L. T1 - Contrast enhanced ultrasound (CEUS) with parametric imaging and time intensity curve analysis (TIC) for evaluation of the success of prostate arterial embolization (PAE) in cases of prostate hyperplasia T2 - Clinical Hemorheology and Microcirculation N2 - AIM: To evaluate the use of dynamic contrast enhanced ultrasound (CEUS) with parametric color-coded imaging and time intensity curve analysis (TIC) for planning and follow-up after prostate arterial embolization (PAE). MATERIAL/METHOD: Before and after selective iliacal embolization by PAE with a follow up of 6 months 18 male patients (43–78 years, mean 63±3.5 years) with histopathological proven benign prostate hyperplasia were examined by one experienced examiner. A multifrequency high resolution probe (1–6 MHz) was used for transabdominal ultrasound and CEUS with bolus injections of 2.4 ml sulphur-hexafluoride microbubbles. Independent evaluation of color-coded parametric imaging before and after PAE by in PACS stored DICOM loops from arterial phase (10–15 s) up to 1min were performed. Criteria for successful treatment were reduction of early arterial enhancement by changes of time to peak (TTP) and area under the curve (AUC) by measurements in 8 regions of interest (ROI) of 5 mm in diameter at the margin and in the center and changes from hyperenhancement in parametric imaging (perfusion evaluation of arterial enhancement over 15 s) from red and yellow to blue and green by partial infarctions. Reference imaging method was the contrast high resolution 3 tesla magnetic resonance tomography (MRI) using 3D vibe sequences before and after PAE and for the follow up after 3 and 6 months. RESULTS: PAE was technically and clinically successful in all 18 patients with less clinical symptoms and reduction of the gland volume. In all cases color-coded CEUS parametric imaging was able to evaluate partial infarction after embolization with changes from red and yellow to green and blue colors in the embolization areas. Relevant changes could be evaluated for TIC-analysis of CEUS with reduced arterial enhancement in the arterial phase and prolonged enhancement of up to 1 min with significant changes (p = 0.0024). The area under the curve (AUC) decreased from 676±255.04 rU (160 rU–1049 rU) before PAE to 370.43±255.19 rU (45 rU–858 rU) after PAE. Time to peak (TTP) did not change significantly (p = 0.6877); TTP before PAE was 25.82±9.04 s (12.3 s–42.5 s) and after PAE 24.43±9.10 s (12–39 s). Prostate volume decreased significantly (p = 0.0045) from 86.93±34.98 ml (30–139 ml) before PAE to 50.57±26.26 ml (19–117 ml) after PAE. There were no major complications and, in most cases (14/18) a volume reduction of the benign prostate hyperplasia occurred. CONCLUSION: Performed by an experienced examiner CEUS with parametric imaging and TIC-analysis is highly useful to further establish prostatic artery embolization (PAE) as a successful minimal invasive treatment of benign prostatic hyperplasia. KW - Contrast enhanced ultrasound (CEUS) KW - parametric imaging KW - time intensity curve analysis (TIC) KW - prostate arterial embolization (PAE) Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209202 U6 - https://doi.org/10.3233/CH-209202 SN - 1875-8622 SN - 1386-0291 VL - 76 IS - 2 SP - 143 EP - 153 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Jung, Friedrich A1 - Hufert, Frank A1 - Jung, Ernst Michael A1 - Küpper, Jan-Heiner A1 - Storsberg, J. T1 - Effects of gut microbial metabolite trimethylamine N-oxide (TMAO) on platelets and endothelial cells T2 - Clinical Hemorheology and Microcirculation N2 - Thrombotic events result from different pathologies and are the underlying causes of severe diseases like stroke or myocardial infarction. Recent basic research now revealed a link between food uptake, food conversion and gut metabolism. Gut microbial production of trimethylamine N-oxide (TMAO) from dietary nutrients like choline, lecithin and L-carnitine was associated with the development of cardiovascular diseases. Within this review we give a systematic overview about the influence of TMAO on blood components like platelets and endothelial cells which both are involved as key players in thrombotic processes. In summary, a mechanistic correlation between the gut microbiome, TMAO and cardiovascular diseases becomes obvious and emphasizes to the significance of the intestinal microbiome. KW - Microbiome KW - trimethylamin-N-oxide KW - platelets KW - endothelial cells KW - atherosclerosis Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209206 U6 - https://doi.org/10.3233/CH-209206 SN - 1875-8622 SN - 1386-0291 VL - 76 IS - 2 SP - 309 EP - 316 ER - TY - GEN A1 - Lamby, Philipp A1 - Minkow, Alexander A1 - Handt, Stefan A1 - Falter, Johannes A1 - Schellenberg, Eva-Lotte A1 - Graf, Stefanie A1 - Hiebl, Bernhard A1 - Haerteis, Silke A1 - Gemeinhardt, Ole A1 - Krüger-Genge, Anne A1 - Klosterhalfen, Bernd A1 - Jung, Ernst Michael A1 - Franke, Ralf-Peter A1 - Momeni, Arash A1 - Prantl, Lukas A1 - Jung, Friedrich T1 - Histological and SEM assessment of blood stasis in kidney blood vessels after repeated intra-arterial application of radiographic contrast media T2 - Life N2 - Background: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. Methods: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n = 8), or Iopromide (n = 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. Results: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p < 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p = 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert’s fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and “box-like” deformations. Conclusions: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide. KW - acute kidney injury KW - nephrotoxicity KW - nephropathy KW - renal pathology KW - iodinated contrast media KW - electron microscopy KW - histopathology Y1 - 2020 UR - https://www.mdpi.com/2075-1729/10/9/167 U6 - https://doi.org/10.3390/life10090167 SN - 2075-1729 VL - 10 IS - 9 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Hösl, Vanessa A1 - Fraunberg, Sarah von A1 - Jung, Friedrich A1 - Prantl, Lukas T1 - Ultrasound elastography for the detection of capsular fibrosis in breast implants: First results T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Capsular contractures around breast implants usually develop leading to pain and aesthetically inadequate results and ultimately often requires the replacement of the implants. Textured silicone implants are the most commonly placed implant, but polyurethane-coated implants are increasingly being used in an attempt to ameliorate the long-term complications associated with implant insertion. AIM: Capsular contracture is traditionally classified using the Baker scale, a subjective classification system based upon clinical findings. Aim of this study was to evaluate the association between pain due capsular contraction, Baker Score and different techniques of US elastography. MATERIAL AND METHODS: Patients were contacted who had undergone an implant replacement due to capsular contracture. Inclusion criterion was the re-implantation of a PU-coated implant. In the third year after changing the implant a follow-up examination was performed in 16 patients with 23 implants. A conventional examination with anamnesis, tactile and visual findings to obtain a Baker score, and ultrasound examinations including shear wave elastography, ARFI and compound elastography were performed. In addition, pain was evaluated using a visual analogue scale (VAS). RESULTS: The pain data showed a significant improvement (before implant exchange: 4.1±2.8 score points) with significance in favor of the current state (1.7±1.0 pain score points; p = 0.002). All patients suffered from less or no pain three years after exchange of the implant. Pain values and elastography (ARFI values) correlated well (r = 0,873), with increasing Baker score the ARFI values increased. US elastography evaluations can locally determine tissue density but correlate only to a limited extent with the test findings according to Baker. US elastography values of mammary gland tissue without implant did not differ from mammary gland tissue around implants. CONCLUSION: Preoperative Baker scores prior to exchange and the current Baker scores at the follow-up showed significantly lower score points three years after exchange of the implants. Ultrasound elastography seems to be an objective classification of capsular fibrosis. These first results motivate to initiate a prospective multicenter investigation. KW - Capsular fibrosis KW - ultrasound examinations KW - elastography KW - ARFI KW - Baker score Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch200875 U6 - https://doi.org/10.3233/CH-200875 SN - 1386-0291 VL - 77(2021) IS - 3 SP - 247 EP - 257 ER - TY - GEN A1 - Gerk, U. A1 - Franke, Ralf-Peter A1 - Jung, Ernst Michael A1 - Scheller, B. A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - Imaging of coronary arteries using ionic versus non-ionic radiographic contrast media: Intraindividual comparison study T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 U6 - https://doi.org/10.3233/CH-199217 SN - 1875-8622 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Moran, Valentina Ocañaa A1 - Engel, Martin A1 - Krüger-Genge, Anne A1 - Stroszczynski, Christian A1 - Jung, Friedrich T1 - Modified contrast-enhanced ultrasonography with the new high-resolution examination technique of high frame rate contrast-enhanced ultrasound (HiFR-CEUS) for characterization of liver lesions: First results T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-221449 SN - 1875-8622 SP - 1 EP - 16 ER - TY - GEN A1 - Jung, Conrad H. G. A1 - Waldeck, Peter A1 - Sykora, Shadi A1 - Braune, Steffen A1 - Petrick, Ingolf A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Influence of Different Light-Emitting Diode Colors on Growth and Phycobiliprotein Generation of Arthrospira platensis T2 - Life Y1 - 2022 U6 - https://doi.org/10.3390/life12060895 SN - 2075-1729 VL - 12 IS - 6 ER - TY - GEN A1 - Jung, Friedrich A1 - Braune, Steffen A1 - Jung, Conrad H. G. A1 - Krüger-Genge, Anne A1 - Waldeck, Peter A1 - Petrick, Ingolf A1 - Küpper, Jan-Heiner T1 - Lipophilic and Hydrophilic Compounds from Arthrospira platensis and Its Effects on Tissue and Blood Cells—An Overview T2 - Life Y1 - 2022 U6 - https://doi.org/10.3390/life12101497 SN - 2075-1729 VL - 12 IS - 10 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Jung, Friedrich A1 - Verloh, Niklas A1 - Haimerl, Michael A1 - Lürken, Lukas A1 - Jage, Simon A1 - Stroszczynski, Christian A1 - Scharf, Gregor T1 - High resolution flow with glazing flow for optimized flow detection in transjugular intrahepatic portosystemic stent shunt (TIPS): First results T2 - Clinical hemorheology and microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-221427 SN - 1875-8622 SN - 1386-0291 VL - 82 IS - 3 SP - 231 EP - 238 ER - TY - GEN A1 - Brandenstein, M. A1 - Wiesinger, Isabel A1 - Jung, Friedrich A1 - Stroszczynski, Christian A1 - Jung, Ernst Michael T1 - High-performance sonographical multimodal imaging of non cystic thyroid lesions: Chances of the preoperative diagnostics in relation to histopathology T2 - Clinical Hemorheology and Microcirculation N2 - AIM: To improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance ultrasound techniques: optimized B-mode morphology, elastography, Color-Coded Doppler-Sonography (CCDS) and contrast enhanced ultrasound (CEUS) MATERIALS AND METHODS: In 33 cases solid, non-cystic thyroid lesions were rated as TIRADS 3 and up from conventional B-mode examinations. Additional high resolution Power Doppler including HR- and Glazing-Flow as optimized macrovascularization techniques, shear wave elastography and CEUS were performed on these patients by one experienced examiner. For CEUS a bolus of 1–2.4 ml Sulfurhexafluorid microbubbles (SonoVue®, Bracco, Milan, Italy) was injected into a cubital vein and then the distribution kinetics of the contrast agent were documented from the early arterial phase (10 to 15 seconds after injection) to the late venous phase (5 minutes after injection). Postoperative histopathology was the diagnostic gold standard as it provides the most reliable proof. RESULTS: 33 patients (13 males, 20 females; age 29 –77 years; mean 55 years; SD 13 years) were included in this study. 28 of them had benign regressive thyroid nodules, 3 had adenomas and 4 were diagnosed with carcinomas (3 were histologically identified as papillary thyroid carcinomas, one as a medullary thyroid carcinoma). The volume of the thyroid gland ranged from 6.6 to 401.3 cm2 (mean 72.6±92.0 cm2). The adenoma diameters ranged from 9 to 40 mm (mean 22±16 mm) and the carcinoma diameters ranged from 19 to 33 mm (mean 26±6 mm). The 3 adenomas had different echogenicities: One was completely echofree, one was hypoechoic and one isoechoic. The 4 carcinomas however were equally characterized as hypoechoic and echofree. Two of three adenomas and all of the carcinomas showed an incomplete or diffuse margin. Micro-calcifications were found in one adenoma and in every carcinoma. However, no micro-calcifications were observed in cases of benign regressive nodules. Performing shear-wave elastography the adenomas showed lower values than the carcinomas: The tissue velocity of the adenomas ranged from 2.86 m/s to 3.85 m/s (mean 3.32±0.5 m/s) and in carcinomas from 3.89 m/s to 5.66 m/s (mean 4.18±0.3 m/s). Marginal hypervascularization was detected in two adenomas after applying CCDS. One adenoma was hypovascularized. The four carcinomas showed an irregular extreme hypervascularization along their margins as well as an irregular central normo- or hypervascularization in CCDS. The additional HR-Flow helped reducing artefacts. In CEUS the dynamic capillary microvascularization of all carcinomas was very irregular with early enhancement and followed by partial or complete wash-out. In CEUS two adenomas had no wash-out and the other one showed a partial wash-out. CONCLUSION: Using modern multimodal imaging offers new possibilities for the differentiation between benign and malignant thyroid lesions. It is a very important diagnostic tool in addition to the B-Mode TIRADS classification and eases the decision between TIRADS 3, 4 and 5. However, additional multicenter studies are required for more detailed evaluations. KW - Solid thyroid lesions KW - high-resolution ultrasound KW - HR-flow KW - elastography KW - CEUS KW - histopathology Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219101 U6 - https://doi.org/10.3233/CH-219101 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 27 EP - 38 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Dinkel, J. A1 - Verloh, Niklas A1 - Brandenstein, M. A1 - Stroszczynski, Christian A1 - Jung, Friedrich A1 - Rennert, J. T1 - Wireless point-of-care ultrasound: First experiences with a new generation handheld device T2 - Clinical Hemorheology and Microcirculation N2 - AIM: To evaluate the diagnostic reliability of a new generation wireless point-of care ultrasound device for abdominal and thoracic findings. MATERIAL AND METHODS: 40 patients (16 females, 24 males 19 –80 years, on average 56.1 years) were scanned by an experienced examiner using the new wireless Vscan Air device for abdominal and thoracic findings. The probe frequencies were 2–5 MHz (convex probe) and 3–12 MHz for the linear probe. As a reference standard, all patients were also examined using high-end ultrasound (LOGIQ E9/10). Results were interpreted independently by two examiners in consensus, also with regard to the image quality (0–4, from not assessable = 0, to excellent 4). RESULTS: In all 40 patients (100%) examination with conventional high-end ultrasound and the Vscan Air ultrasound device was feasible. Sensitivity, specificity, positive and negative predictive value for the diagnosis of abdominal and thoracic findings were 63.3%, 100%, 100%, and 40%, respectively. Most main diagnostic findings were detected using the mobile device compared to the high-end ultrasound. Limitations were found regarding characterization and classification of hepatic and renal tumorous lesions. Image quality revealed mostly minor diagnostic limitations for the mobile device, mean 2.9 (SD –0.300) and was excellent or with only minor diagnostic limitations for conventional high-end ultrasound, mean 3.25 (SD –0.438). CONCLUSION: Due to its easy application and its high diagnostic reliability, point-of-care ultrasound systems of the latest generation represent a valuable imaging method for the primary assessment of abdominal and thoracic findings, especially in patients on intensive care units or in emergency situations. KW - Point-of-care ultrasound KW - Vscan Air KW - high-end ultrasound Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch211197 U6 - https://doi.org/10.3233/CH-211197 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 3 SP - 463 EP - 474 ER - TY - GEN A1 - Jung, Conrad H. G. A1 - Braune, Steffen A1 - Waldeck, Peter A1 - Küpper, Jan-Heiner A1 - Petrick, Ingolf A1 - Jung, Friedrich T1 - Morphology and Growth of Arthrospira platensis during Cultivation in a Flat-Type Bioreactor T2 - Life N2 - Arthrospira platensis (AP) is a cyanobacterium with a high economic value and is nowadays one of the most important industrially cultivated microalgae. Knowledge of its growth is essential for the understanding of its physiology and yield. The growth of AP biomass occurs through two mechanisms: (1) propagation by fragmentation of trichomes, and (2) the trichomes are extended by binary fission until they reach their mature status. These phases are visualized by live cell light and laser scanning microscopy, demonstrating the different phases of AP growth. KW - Arthrospira platensis KW - Spirulina KW - life cycle KW - morphology KW - fragmentation KW - fission Y1 - 2021 UR - https://www.mdpi.com/2075-1729/11/6/536/htm U6 - https://doi.org/10.3390/life11060536 SN - 2075-1729 VL - 11 IS - 6 ER - TY - GEN A1 - Luderer, V. A1 - Jung, Friedrich A1 - Brandenstein, M. A1 - Stroszczynski, Christian A1 - Jung, Ernst Michael T1 - First assessment of flow phenomena of acute and chronic thrombosis in the jugular veins using new ultrasound vector-flow imaging T2 - Clinical Hemorheology and Microcirculation N2 - AIM: First assessment of flow changes in the jugular veins using high resolution ultrasound vector flow. MATERIAL UND METHODS: 15 patients (8 males, 7 females) with an age range of 35 to 82 years (mean age 58.53±12.26 years) were examined by an experienced examiner using high power ultrasound equipment (Resona R9, Mindray) with probe technology (Mindray L9-3U Linear Array transducer, 2.5 to 9.0 MHz). This group was compared with five healthy subjects (mean age 35.4±13.79 years) as a reference. To assess flow changes, the color-coded duplex sonography and the novel vector flow technique were used. The evaluation was performed of vector morphology changes, turbulence, and wall resistance measurements. RESULTS: There were changes after acute and chronic thrombosis in 9 cases, and venous compression in 7 cases. Turbulence was measurable from 0.01 % to 64.44 %, the average turbulence was 19.73±22.06 % . Wall resistance measurement showed values from 0.01 Pa to 3.14 Pa, depending on the age of the thrombosis or compression. The reference veins showed turbulence of 0.94±1.5 % and a mean wall resistance of 0.05±0.05 Pa. There are statistically significant differences between normal and thrombotic or compressed veins in terms of maximum wall stress (p = 0.006) and mean degree of turbulence (p = 0.012), while the difference in mean wall stress is not statistically significant (p = 0.058). CONCLUSION: Despite still existing technical limitations, the combination of V-flow and wall stress measurements in jugular vein changes suggests a high diagnostic potential. KW - Thrombosis KW - vector-flow-imaging KW - high resolution ultrasound KW - color-coded duplex sonography Y1 - 2024 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch238117 U6 - https://doi.org/10.3233/CH-238117 SN - 1386-0291 VL - 86 IS - 1-2 SP - 133 EP - 142 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Jung, Friedrich A1 - Dong, Yi A1 - Kaiser, Ulrich T1 - Initial description of the novel handheld wireless ultrasound device TE Air with Doppler and Color Duplex imaging T2 - Clinical Hemorheology and Microcirculation N2 - OBJECTIVE: To test and initially describe a new handheld wireless ultrasound technique (TE Air) for clinical use. METHODS: In this pilot study, the new ultrasound device TE Air from Mindray was used to examine the hepatic and renal vessels of healthy volunteers for first impressions. The probe has a sector transducer with a frequency range of 1.8–4.5 MHz. The B-mode and color-coded doppler sonography (CCDS) scanning methods were used. A high-end device from the same company (Resona 9, Mindray) was used as a reference. The results were evaluated using an image rating scale ranging from 0 to 5, with 0 indicating not assessable and 5 indicating without limitations. RESULTS: Altogether, 61 participants (n = 34 female [55.7%], n = 27 male [44.3%]), age range 18–83 years, mean age 37.9±16.5 years) could be adequately studied using TE AIR and the high-end device. With one exception, the image quality score for TE Air never fell below 3 and had a mean/median scored of 4.97/5.00 for the B-mode, 4.92/5.00 for the color flow (CF) mode, and 4.89/5.00 for the pulse wave (PW) mode of the hepatic vein, 4.90/5.00 for the portal vein, 4.11/4.00 for the hepatic artery, and 4.57/5.00 for the renal segmental artery. A significant difference in the assessment of flow measurement of the hepatic artery and renal segmental arteries was found between TE AIR and the high-end device. CONCLUSIONS: TE Air represents a new dimension in point-of-care ultrasound via wireless handheld devices. Especially, its flow measurement ability offers a relevant advantage over other available handheld models. TE Air provides a formally sufficient image quality in terms of diagnostic significance. KW - Mindray KW - handheld ultrasound KW - TE Air KW - ultrasound KW - point-of-care ultrasound Y1 - 2024 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch238100 U6 - https://doi.org/10.3233/CH-238100 SN - 1386-0291 VL - 86 IS - 1-2 SP - 89 EP - 97 ER - TY - GEN A1 - Jung, Ernst Michael A1 - Dong, Yi A1 - Jung, Friedrich T1 - Current aspects of multimodal ultrasound liver diagnostics using contrast-enhanced ultrasonography (CEUS), fat evaluation, fibrosis assessment, and perfusion analysis – An update T2 - Clinical Hemorheology and Microcirculation N2 - Current ultrasound multifrequency probes allow both improved detail resolution and depth of penetration when examining the liver. Also, new developments in vascular diagnostics, elastography with fibrosis assessment, evaluation of possible steatosis, and parametric and time intensity curve (TIC) analysis of dynamic microvascularization of the liver with contrast-enhanced ultrasound sonography (CEUS) complement ultrasound-guided diagnostics. State-of-the-art high-resolution technology includes a high frame rate (HiFR) mode for CEUS, fast shear wave measurements with the sound touch quantify (STQ) mode, artifact-free flow detection using HR flow and glazing flow in combination with a special flow-adapted imaging (Ultra Micro Angiography, UMA) and additionally different assessments of possible fatty liver (UltraSound ATtenuation Imaging Technology, USAT). In 50 cases with focal liver lesions, a multimodal liver diagnosis was performed with a still new high-performance ultrasound system as part of the clarification of questions from the university liver consultation and tumor outpatient clinic. KW - Contrast enhanced ultrasonography (CEUS) KW - fibrosis KW - perfusion analysis KW - liver cancer Y1 - 2023 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch239100 U6 - https://doi.org/10.3233/CH-239100 SN - 1386-0291 VL - 83 IS - 2 SP - 181 EP - 193 ER - TY - GEN A1 - Haileka, Vanessa A1 - George, Sandra A1 - Steinbrecht, Susanne A1 - Jung, Friedrich A1 - Reinehr, R. A1 - Küpper, Jan-Heiner T1 - Colon cancer cells cultured under hyperosmotic conditions as in vitro model to investigate dehydration effects on cancer drug susceptibility T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 U6 - https://doi.org/10.3233/CH-199210 SN - 1875-8622 VL - 73 IS - 1 SP - 169 EP - 176 ER - TY - GEN A1 - Gehmert, Sangaa A1 - Lehoczky, Gyözöc A1 - Loibl, Markus A1 - Jung, Friedrich A1 - Prantl, Lukas A1 - Gehmert, Sebastian T1 - Interaction between extracellular cancer matrix and stromal breast cells T2 - Clinical Hemorheology and Microcirculation N2 - Stromal-epithelial interactions are fundamental for normal organ development and there is a multitude of evidence that the different components of the microenvironment are also necessary for the maintenance and promotion of the “tumor organ”. Deregulated tumor associated extracellular matrix (tECM) is a hallmark of cancer, causing an alteration in the amount and composition of the different components (i.e. proteins, proteoglycans, glycoproteins and polysaccharids) of the ECM. As epithelial-stromal interactions are reciprocal, it is possible that tECM itself is able to initiate tumor development. We therefore established a mouse model to examine the influence of tECM of murine breast cancer on developing breast tissue in mice. KW - Breast cancer KW - extracellular matrix KW - microenvironment KW - epithelial-stromal interaction Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch199234 U6 - https://doi.org/10.3233/CH-199234 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 1 SP - 45 EP - 52 ER - TY - GEN A1 - Jung, Friedrich A1 - Krüger-Genge, Anne A1 - Franke, Ralf-Peter A1 - Hufert, Frank A1 - Küpper, Jan-Heiner T1 - COVID-19 and the endothelium T2 - Clinical Hemorheology and Microcirculation N2 - There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. Recent studies showed that this can lead to microcirculatory impairments and in consequence to functional disorders of all inner organs. The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions. KW - COVID-19 KW - endocytosis KW - endothelial cell dysfunction KW - endotheliitis Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209007 U6 - https://doi.org/10.3233/CH-209007 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 1 SP - 7 EP - 11 ER - TY - GEN A1 - Jung, Friedrich A1 - Krieger, Volker A1 - Hufert, Frank A1 - Küpper, Jan-Heiner T1 - Herd immunity or suppression strategy to combat COVID-19 T2 - Clinical Hemorheology and Microcirculation N2 - Some months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Some states, such as the Netherlands, Germany, Great Britain, Sweden and the USA initially focused on keeping the restrictions for economy and society as low as possible. The responsible authorities were of the opinion - and still are e.g. in Sweden - that it is sufficient enough to protect particularly vulnerable persons such as the elderly or people with pre-existing conditions. The idea behind this is that as soon as 60 to 70 percent of the population is infected with a pathogen, a so-called “herd immunity” has developed. However, the increasing numbers of deaths and modelling studies showed the expected overload of the hospitals. Therefore, most countries decided for a temporary lockdown with the exception of Sweden. Based on the number of the total population, three times more people died from COVID-19 in Sweden (2679 deaths per 10 million inhabitants) compared to Germany (6848 deaths per 80 million inhabitants). The comparison Sweden versus Taiwan is even worse because 1072 times more people died in Sweden based on the number of the population (6 deaths per 24 million inhabitants). KW - COVID-19 KW - strategy KW - Sweden KW - Taiwan KW - Germany Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209006 U6 - https://doi.org/10.3233/CH-209006 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 1 SP - 13 EP - 17 ER - TY - GEN A1 - Lau, S. A1 - Rangarajan, R. A1 - Krüger-Genge, Anne A1 - Braune, Steffen A1 - Küpper, Jan-Heiner A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Age-related morphology and function of human arterial endothelial cells T2 - Clinical Hemorheology and Microcirculation N2 - Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies. In our approach, HAEC from 16 donors of varying age (16–63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status. No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p = 0.0374) and the membrane integrity marginally impaired (p = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors. According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly. KW - Cardiovascular implants KW - arterial endothelial cells KW - aging KW - senescence KW - donor variability Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch199238 U6 - https://doi.org/10.3233/CH-199238 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 1 SP - 93 EP - 107 ER - TY - GEN A1 - Mrowietz, Christof A1 - Sievers, H. A1 - Pindur, Gerhard A1 - Hiebl, Bernhard A1 - Jung, Friedrich T1 - Cutaneous microcirculation in patients with peripheral arterial occlusive disease: Comparison of capillary blood circulation in the nail fold of finger and toe T2 - Clinical Hemorheology and Microcirculation N2 - In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area –was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries. KW - Microcirculation KW - peripheral arterial occlusive disease KW - capillary microscopy Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209220 U6 - https://doi.org/10.3233/CH-209220 SN - 1875-8622 SN - 1386-0291 VL - 76 IS - 2 SP - 279 EP - 285 ER - TY - GEN A1 - Schulz, Christian A1 - Krüger-Genge, Anne A1 - Lendlein, Andreas A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture T2 - International Journal of Molecular Science N2 - The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used. KW - human venous endothelial cells KW - adherent KW - non-adherent KW - viability KW - mediator release Y1 - 2021 UR - https://www.mdpi.com/1422-0067/22/3/1493 U6 - https://doi.org/10.3390/ijms22031493 VL - 22 IS - 3 ER - TY - GEN A1 - Braune, Steffen A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effect of Prostanoids on Human Platelet Function: An Overview T2 - International Journal of Molecular Science N2 - Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors. Y1 - 2020 UR - https://www.mdpi.com/1422-0067/21/23/9020 U6 - https://doi.org/10.3390/ijms21239020 VL - 21 IS - 23 ER - TY - GEN A1 - Taghizadeh, Mahmoudreza A1 - Mehdi, Kargarfard A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Mahmood, Naderi T1 - Long-term aerobic exercise training in type two diabetic patients alters the expression of miRNA-223 and its corresponding target, the P2RY12 receptor, attenuating platelet function T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12. OBJECTIVE: The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients. METHODS: Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period. RESULTS: There was a significant improvement in body weight, BMI, VO2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P <  0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P <  0.001) group. Platelets’ miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P <  0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention. CONCLUSIONS: It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function. KW - Exercise training KW - diabetes KW - microRNA-223 KW - P2RY12 receptor KW - Insulin resistance KW - platelet Y1 - 2022 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch211209 U6 - https://doi.org/10.3233/CH-211209 SN - 1875-8622 SN - 1386-0291 VL - 80 IS - 2 SP - 107 EP - 116 ER - TY - GEN A1 - Braune, Steffen A1 - Krüger-Genge, Anne A1 - Köhler, S. A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effects of Arthrospira platensis-derived substances on blood cells T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-229103 SN - 1875-8622 VL - 85(2023) IS - 3 SP - 315 EP - 321 ER - TY - GEN A1 - Tartivel, Lucile A1 - Blocki, Anna M. A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Behl, Marc A1 - Lendlein, Andreas T1 - An Inverse Shape-Memory Hydrogel Scaffold Switching Upon Cooling in a Tissue-Tolerated Temperature Range T2 - Advanced materials interfaces Y1 - 2022 U6 - https://doi.org/10.1002/admi.202101588 SN - 2196-7350 VL - 9 IS - 6 ER - TY - GEN A1 - Shafiee, Neda A1 - Kordi, Negin A1 - Gadruni, Keivan A1 - SalehFard, Ziba A1 - Jung, Friedrich A1 - Heidari, Naser T1 - Cardiac rehabilitation in coronary artery bypass grafting patients: Effect of eight weeks of moderate-intensity continuous training versus high-intensity interval training T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Physical training in patients with heart failure can affect hemodynamic, cardiac and angiogenesis parameters. OBJECTIVE: The aim of the present study was to investigate the effects of traditional moderate-intensity rehabilitation training and interval training on some angiogenesis factors in coronary artery bypass graft (CABG) patients. METHODS: Thirty CABG patients (mean age±SD, 55±3 years) were randomly assigned to one of three groups: high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) or the control group. After the initial assessments, eligible patients in the experimental groups (HIIT and MICT) performed exercise training for 8 weeks, while the control group did not. Angiogenesis and angiostatic indices, including pro-adrenomedullin (pro-ADM), basic fibroblast growth factor (bFGF), and endostatin, were then measured. RESULTS: The results showed no significant difference between pro-ADM in the HIIT and MICT groups (P = 0.99), but a significant difference was found between MICT and the control group and between HIIT and the control group (P = 0.001). There is also no significant difference between the bFGF levels in the HIIT and MICT training groups (P = 1.00), but the changes in this factor between the training groups and the control group were significant (P = 0.001). There was a significant difference between the levels of endostatin in all three groups. CONCLUSIONS: Two methods of cardiac rehabilitation (HIIT and MICT) may be useful for the recovery of patients with coronary artery bypass grafting. This improvement manifested itself in changes in angiogenesis and angiostatic indices in this study. However, more extensive studies are needed to investigate the effects of these two types of rehabilitation programs on other indicators of angiogenesis and angiostatic. KW - Training KW - angiogenesis KW - cardiovascular KW - endostatin KW - pro-adrenomedullin Y1 - 2023 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch221605 U6 - https://doi.org/10.3233/CH-221605 SN - 1386-0291 VL - 83 IS - 3 SP - 305 EP - 314 ER - TY - GEN A1 - Mantskava, Maia A1 - Jung, Friedrich A1 - Sanikidze, Tamar A1 - Momtselidze, Nana T1 - Parallel study of the rheological status, vascular changes and intracardiac hemodynamics in heart failure in coronary artery disease T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Ischemic heart disease is a pathological chronic and acute condition, which is provoked by insufficient blood supply or its complete cessation. To reduce the number of patients, all approaches and studies that can positively affect the prevention and treatment of the disease are important. This is very important in monitoring and treating diseases of all systems and organs, especially in diseases of the cardiovascular system. The aim of our work was to elucidate the relationship between the rheological status of blood, vascular changes and intracardiac hemodynamics in heart failure in coronary artery disease patients with different functional classes. OBJECTIVES: The aim of our work was to elucidate the relationship between the rheological status of blood, vascular changes and intracardiac hemodynamics in heart failure in coronary artery disease patients with different functionalclasses. METHODS: We examined 76 men and women patients with coronary artery disease - I–IV functional class (by New York Heart Association Functional Classification NYHA)), mean age - 59.2±4 years. The control group consisted of 20 apparently healthy volunteers (Woman: Man –1:1), whose average age was 52±3 years. Representatives of the control group did not take any medication during the study period and were apparently healthy. The electrocardiogram of the subjects in the control group corresponded to the norm. All subjects underwent clinical and laboratory studies in a standard way: to describe the rheological status of blood, the erythrocyte aggregability index (EAI), erythrocyte deformability index (EDI), and plasma viscosity were determined; to assess vascular changes - resistance index of resistive arteries (RIRA); to study intracardiac hemodynamics, echocardiology was performed according to the recommendations proposed by the American Association of Physicians. RESULTS: Rheological changes are present from the very beginning of the disease and progress along with the severity of the disease. Therefore, it is possible to assess the severity of the disease based on rheological disorders, which can precede the onset of ischemic heart disease. The vascular status resistance index increases in the early stages of the disease, with I functional class - RIRA increased by 46%. The cardiac index, which determines the adequacy of the global perfusion pressure, is the main indicator of hemodynamics and is negatively related to the increase in erythrocyte aggregation, although this indicator turned out to be statistically unreliable. CONCLUSION: The interpretation of our data will allow us to better understand the pathogenesis of heart failure, as well as recommend a list of tests, and methods that were discussed in the article to assess the clinical condition of patients. Continuing research in the same direction, we believe that we will be able to make adjustments to research methods and to the algorithm for drug therapy KW - RBC KW - aggregation KW - deformation KW - viscosity KW - resistance arteries Y1 - 2023 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch231744 U6 - https://doi.org/10.3233/CH-231744 SN - 1386-0291 VL - 84 IS - 2 SP - 185 EP - 192 ER - TY - PAT A1 - Scheibner, Katrin A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - In vitro Arzneimittel aus Prodrugs und deren Verwendung Y1 - 2021 UR - https://www.b-tu.de/enzymtechnologie/publikationen/patente ER - TY - GEN A1 - Biermann, Niklas A1 - Sommerauer, Laura A1 - Diesch, Sophia A1 - Koch, Christoph A1 - Jung, Friedrich A1 - Kehrer, Andreas A1 - Prantl, Lukas A1 - Taeger, Christian D. T1 - The influence of pulsed electromagnetic field therapy (PEMFT) on cutaneous blood flow in healthy volunteers T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: The biophysical interaction induced by low energy pulsed electromagnetic field therapy (PEMFT) on the capillary microcirculation is not well understood. Several studies indicate a significant effect of PEMFT in patients with chronic medical conditions. OBJECTIVE: The aim of this study was to evaluate the influence of PEMFT on skin microcirculation in healthy volunteers. METHODS: 15 healthy participants were included. Nine PEMF treatments were applied over three weeks in an 48-hour interval. The PEMFT system (BEMER) was placed beneath one of the participants’ leg with the contralateral side serving as a control. A forty-minute application period was preceded by a 10-minute resting phase. Measuring was done using two Laser Doppler probes (LEA) placed on each anterior lateral thigh. RESULTS: All outcome parameters including flow, mixed venous oxygen saturation and relative venous hemoglobin showed a significant increase during the experiment when compared to the baseline values of the resting phase in both groups (p < 0.01). Comparing both groups, the measurement values during the experiment did not differ (p > 0.05) except for higher flow values in the control group (P = 0.03). Over time, baseline values of both groups showed no significant difference (p > 0.05). CONCLUSION: We found a significant increase of all measurement parameters during the study compared to the baseline values with no difference between the PEMF and control group. KW - Pulsed electromagnetic field therapy (PEMFT) KW - microcirculation KW - cutaneous blood flow Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209224 U6 - https://doi.org/10.3233/CH-209224 VL - 76 IS - 4 SP - 495 EP - 501 ER - TY - GEN A1 - Greif, G. A1 - Mrowietz, Christof A1 - Wendt, M. A1 - Jung, Friedrich A1 - Hiebl, Bernhard A1 - Meyer-Sievers, H. T1 - Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system T2 - Clinical Hemorheology and Microcirculation N2 - The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs’ 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4–8 min exposure to glass. KW - Pig KW - minipig KW - platelet activation KW - platelet count KW - platelet volume KW - FACS KW - monoclonal antibody KW - CD42 KW - CD61 KW - CD62P KW - CD63 Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219201 U6 - https://doi.org/10.3233/CH-219201 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 149 EP - 155 ER - TY - GEN A1 - Braune, Steffen A1 - Krüger-Genge, Anne A1 - Kammerer, Sarah A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies T2 - Life Y1 - 2021 UR - https://www.mdpi.com/2075-1729/11/2/91 U6 - https://doi.org/10.3390/life11020091 VL - 11 IS - 2 SP - 91 ER - TY - GEN A1 - Schulz, Christian A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone T2 - Clinical Hemorheology and Microcirculation N2 - Cell-based in vitro liver models are an important tool in the development and evaluation of new drugs in pharmacological and toxicological drug assessment. Hepatic microsomal enzyme complexes, consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs), play a decisive role in catalysing phase-1 biotransformation of pharmaceuticals and xenobiotics. For a comprehensive understanding of the phase-1 biotransformation of drugs, the availability of well-characterized substances for the targeted modulation of in vitro liver models is essential. In this study, we investigated diphenyleneiodonium (DPI) for its ability to inhibit phase-1 enzyme activity and further its toxicological profile in an in vitro HepG2 cell model with and without recombinant expression of the most important drug metabolization enzyme CYP3A4. Aim of the study was to identify effective DPI concentrations for CPR/CYP activity modulation and potentially associated dose and time dependent hepatotoxic effects. The cells were treated with DPI doses up to 5,000nM (versus vehicle control) for a maximum of 48 h and subsequently examined for CYP3A4 activity as well as various toxicological relevant parameters such as cell morphology, integrity and viability, intracellular ATP level, and proliferation. Concluding, the experiments revealed a time- and concentration-dependent DPI mediated partial and complete inhibition of CYP3A4 activity in CYP3A4 overexpressing HepG2-cells (HepG2-CYP3A4). Other cell functions, including ATP synthesis and consequently the proliferation were negatively affected in both in vitro cell models. Since neither cell integrity nor cell viability were reduced, the effect of DPI in HepG2 can be assessed as cytostatic rather than cytotoxic. KW - Phase-1 KW - biotransformation KW - CYP KW - cytochrome P450 monooxygenase KW - CYP3A4 KW - diphenyleneiodonium KW - DPI KW - HepG2 KW - HepG2-CYP3A4 KW - hepatocytes KW - NADPH-cytochrome P450 oxidoreductase KW - POR KW - CPR Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219117 U6 - https://doi.org/10.3233/CH-219117 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 231 EP - 243 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Steinbrecht, Susanne A1 - Küpper, Jan-Heiner A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: preliminary in vitro results. T2 - Clinical Hemorheology and Microcirculation Y1 - 2018 U6 - https://doi.org/10.3233/CH-189125 SN - 1875-8622 SN - 1386-0291 VL - 69 IS - 1-2 SP - 267 EP - 276 ER - TY - GEN A1 - Jung, Friedrich A1 - Pietzsch, Jens T1 - Regulation of bone regeneration T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch199101 U6 - https://doi.org/10.3233/CH-199101 SN - 1875-8622 SN - 1386-0291 VL - 73 IS - 3 SP - 379 EP - 380 ER - TY - GEN A1 - Wiggermann, P. A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - Editorial T2 - Selected papers of the 38th Conference of the German Society for Clinical Microcirculation and Hemorheology, 21-23 November 2019, Braunschweig, Germany Y1 - 2019 UR - https://pubmed.ncbi.nlm.nih.gov/31561330/#affiliation-3 U6 - https://doi.org/10.3233/CH-199200 VL - 73 IS - 1 PB - IOS Press ER - TY - GEN A1 - Steinbrecht, Susanne A1 - König, Rosalie A1 - Schmidtke, Kai-Uwe A1 - Herzog, Natalie A1 - Scheibner, Katrin A1 - Krüger-Genge, Anne A1 - Jung, Friedrich A1 - Kammerer, Sarah A1 - Küpper, Jan-Heiner T1 - Metabolic activity testing can underestimate acute drug cytotoxicity as revealed by HepG2 cell clones overexpressing cytochrome P450 2C19 and 3A4 T2 - Toxicology Y1 - 2018 U6 - https://doi.org/10.1016/j.tox.2018.11.008 SN - 0300-483X VL - 412 SP - 37 EP - 47 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner A1 - Lehmann, Christian A1 - Franke, Ralf-Peter T1 - Actin type and distribution in erythrocytes T2 - Journal of Cellular Biotechnology N2 - Erythrocytes transport oxygen from the lungs to the tissues. The excess surface area together with the elasticity of the erythrocyte cell membrane provides the flexibility needed to pass through the microvasculature where the oxygen exchange occurs. Although the architecture of the red cell and its membrane-associated cytoskeletal network is known in general, the factors that control the characteristic shape change during echinocyte formation are poorly understood. In this short report we show that in echinocytes a completely reorganized membrane cytoskeleton with a box-like structure of actin filaments prevailed indicating the importance of the actin cytoskeleton during echinocyte formation. KW - Erythrocytes KW - echinocytes KW - submembraneous cytoskeleton KW - actin Y1 - 2018 UR - https://content.iospress.com/articles/journal-of-cellular-biotechnology/jcb179014 U6 - https://doi.org/10.3233/JCB-179014 SN - 2352-3697 SN - 2352-3689 VL - 3 IS - 2 SP - 81 EP - 83 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Braune, Steffen A1 - Walter, Maria A1 - Kratz, Karl A1 - Küpper, Jan-Heiner A1 - Krengel, M. A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Influence of surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability T2 - Clinical Hemorheology and Microcirculation Y1 - 2018 U6 - https://doi.org/10.3233/CH-189130 SN - 1875-8622 SN - 1386-0291 VL - 69 IS - 1-2 SP - 305 EP - 316 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Köhler, Susanne A1 - Laube, Markus A1 - Haileka, Vanessa A1 - Lemm, Sandy A1 - Majchrzak, Karolina A1 - Kammerer, Sarah A1 - Schulz, Christian A1 - Storsberg, Joachim A1 - Pietzsch, Jens A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Anti-Cancer Prodrug Cyclophosphamide Exerts Thrombogenic Effects on Human Venous Endothelial Cells Independent of CYP450 Activation—Relevance to Thrombosis T2 - Cells N2 - Cancer patients are at a very high risk of serious thrombotic events, often fatal. The causes discussed include the detachment of thrombogenic particles from tumor cells or the adverse effects of chemotherapeutic agents. Cytostatic agents can either act directly on their targets or, in the case of a prodrug approach, require metabolization for their action. Cyclophosphamide (CPA) is a widely used cytostatic drug that requires prodrug activation by cytochrome P450 enzymes (CYP) in the liver. We hypothesize that CPA could induce thrombosis in one of the following ways: (1) damage to endothelial cells (EC) after intra-endothelial metabolization; or (2) direct damage to EC without prior metabolization. In order to investigate this hypothesis, endothelial cells (HUVEC) were treated with CPA in clinically relevant concentrations for up to 8 days. HUVECs were chosen as a model representing the first place of action after intravenous CPA administration. No expression of CYP2B6, CYP3A4, CYP2C9 and CYP2C19 was found in HUVEC, but a weak expression of CYP2C18 was observed. CPA treatment of HUVEC induced DNA damage and a reduced formation of an EC monolayer and caused an increased release of prostacyclin (PGI2) and thromboxane (TXA) associated with a shift of the PGI2/TXA balance to a prothrombotic state. In an in vivo scenario, such processes would promote the risk of thrombus formation. KW - cancer KW - cyclophosphamide KW - human umbilical vein endothelial cells KW - HUVEC KW - liver KW - cytochrome P450 enzymes (CYP) KW - thrombosis Y1 - 2023 UR - https://www.mdpi.com/2073-4409/12/15/1965 U6 - https://doi.org/10.3390/cells12151965 SN - 2073-4409 VL - 12 IS - 15 ER - TY - GEN A1 - Hiebl, Bernhard A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - 39th conference of the German society for clinical microcirculation and hemorheology (DGKMH) T2 - Clinical Hemorheology and Microcirculation Y1 - 2020 UR - https://europepmc.org/article/med/33074223 U6 - https://doi.org/10.3233/ch-209200 SN - 1875-8622 SN - 1386-0291 VL - 76 IS - 2 SP - 121 EP - 122 ER - TY - GEN A1 - Krüger-Genge, Anne A1 - Blocki, Anna A1 - Franke, Ralf-Peter A1 - Jung, Friedrich T1 - Vascular Endothelial Cell Biology: An Update T2 - International Journal of Molecular Sciences Y1 - 2019 U6 - https://doi.org/10.3390/ijms20184411 SN - 1422-0067 SN - 1661-6596 VL - 20 IS - 18 ER - TY - GEN A1 - Park, J. W. A1 - Matschke, K. A1 - Mrowietz, Christof A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - HELP-(Heparin-induced Extracorporeal LDL Precipitation)-apheresis in heart recipients with cardiac allograft vasculopathy and concomitant hypercholesterolemia: Influence of long-term treatment on the microcirculation T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 U6 - https://doi.org/10.3233/CH-199216 SN - 1875-8622 VL - 73 IS - 1 SP - 19 EP - 27 ER - TY - GEN A1 - Nies, A. A1 - Proft, L. A1 - Nehring, M. E. A1 - Gruber, Cnristian A1 - Sievers, H. A1 - Hünigen, Hana A1 - Rodruigues, A. G. A1 - Gemeinhardt, Ole A1 - Mrowietz, Christof A1 - Jung, Friedrich A1 - Hiebl, Bernhard T1 - Growth-related micromorphological characteristics of the porcine femoral artery T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 U6 - https://doi.org/10.3233/CH-199219 SN - 1875-8622 VL - 73 IS - 1 SP - 195 EP - 201 ER - TY - GEN A1 - Jung, Friedrich A1 - Krüger-Genge, Anne A1 - Waldeck, Peter A1 - Küpper, Jan-Heiner T1 - Spirulina platensis, a super food? T2 - Journal of Cellular Biotechnology N2 - Spirulina platensis, a multicelluar, photosynthetic prokaryote (algae) contains a high amount of proteins, vitamins and minerals superior to many foods as e.g. soybeans. Thus, Spirulina platensis was recognized as nutritious food by the United Nations World Food Conference. Due to the high amount of nutritive ingredients Spirulina has a long history as dietary supplement. In addition, spirulina platensis is also efficiently used as forage with known effects on flesh, egg and plumage color, milk yield and fertility. The versatile utilization of the alga can be explained on the one hand with the nutrient levels and on the other hand with recognized effects as anti-viral, anti-bacterial, anti-oxidant, anti-diabetic, anti-cancer and anti-inflammatory substance. Therefore, this alga is named as “superfood”. Beyond, these algae convert carbon dioxide into organic substances and produce oxygen during their growth in alkaline and saline water thereby not wasting fresh water allowing the production in barren areas. Despite this diverse use of Spirulina platensis due to its beneficial properties, many basic mechanisms on a molecular and cellular level are not well understood and should be explored in future studies. KW - Spirulina KW - health effects KW - dietary supplements KW - liver protection KW - virus infection KW - HIV KW - nutrition KW - animal feeding Y1 - 2019 UR - https://content.iospress.com/articles/journal-of-cellular-biotechnology/jcb189012 U6 - https://doi.org/10.3233/JCB-189012 SN - 2352-3689 SN - 2352-3697 VL - 5 IS - 1 SP - 43 EP - 54 ER - TY - GEN A1 - Lemm, Sandy A1 - Köhler, Susanne A1 - Wodtke, Robert A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner A1 - Pietzsch, Jens A1 - Laube, Markus T1 - Investigation of radiotracer metabolic stability in vitro with CYP-overexpressing hepatoma cell lines T2 - Cells Y1 - 2022 U6 - https://doi.org/10.3390/cells11152447 SN - 2073-4409 VL - 11 IS - 15 ER - TY - GEN A1 - Lemm, Sandy A1 - Köhler, Susanne A1 - Wodtke, Robert A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner A1 - Pietzsch, Jens A1 - Laube, Markus T1 - Enabling insights into the cytochrome P450 isoform specific metabolism of radiotracers by CYP overexpressing hepatoblastoma cell lines T2 - Nuclear Medicine and Biology Y1 - 2022 SN - 1872-9614 IS - 108-109, Supplement  SP - S66 EP - S67 ER - TY - GEN A1 - Greif, G. A1 - Mrowietz, Christof A1 - Meyer-Sievers, H. A1 - Ganter, M. A1 - Jung, Friedrich A1 - Hiebl, Bernhard T1 - Differences in human and sheep platelet adherence, aggregation and activation induced by glass beads in a modified chandler loop-system T2 - Clinical Hemorheology and Microcirculation N2 - In human cardiovascular research, sheep in particular are used as a large animal model in addition to pigs. In these animals, medical products, developed and tested for human medical purposes, are almost exclusively used in interventional studies. Therefore, the extent to which platelets from human and ovine blood differ in terms of adherence, aggregation and activation after a 4- or 8-minutes exposure to glass was investigated. Testing was performed with platelet-rich plasma (PRP) and a modified chandler loop-system, with 4- and 8-minute blood-material exposure times corresponding to 20 and 40 test cycles, respectively, through the entire silicone tube loop of the test system. In sheep and human PRP, contact with the silicone tubing resulted in a decrease in platelet count after 4 minutes and 20 test cycles, respectively. Four more minutes (20 additional test cycles) caused a further decrease of the platelet count only in sheep PRP. When the silicon tube was partly filled with glass beads, these effects were more pronounced and stronger in sheep then in human PRP. The mean platelet volume, which was used as parameter for platelet aggregation, did not change over time in human PRP without glass exposure. With glass exposure in human and sheep PRP the mean platelet volume increased within 40 test cycles, but this increase was stronger in sheep than in human PRP. Regarding activation behavior, the activation markers CD62P and CD63 were detectable only in < 30% (sheep) and < 45% (human) of platelets, whereas after 8 min of glass exposure, the proportion of CD62P+ and CD63+ cells was more increased than before only in sheep. These results indicate that ovine platelets adhere more strongly to glass and show stronger aggregation behavior after glass contact than human platelets, but that ovine and human platelets differ only slightly in activability by glass. KW - Sheep KW - platelet KW - activation KW - platelet volume KW - CD42a KW - CD61 KW - CD62P KW - CD63 Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219104 U6 - https://doi.org/10.3233/CH-219104 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 129 EP - 136 ER - TY - GEN A1 - Küpper, Jan-Heiner A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - 40th conference of the German society for clinical microcirculation and hemorheology (DGKMH) T2 - Clinical Hemorheology and Microcirculation Y1 - 2021 U6 - https://doi.org/10.3233/ch-219100 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 1 EP - 2 ER - TY - PAT A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Arthrospira for use in the treatment of diseases Y1 - 2021 UR - https://www.google.de/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwik1t7QrOL5AhVTO-wKHT97CKAQFnoECAQQAQ&url=https%3A%2F%2Fdata.epo.org%2Fpublication-server%2Frest%2Fv1.0%2Fpublication-dates%2F20220302%2Fpatents%2FEP3960193NWA1%2Fdocument.pdf&usg=AOvVaw20GVY_ywjb2xbS0TwSDArJ ER - TY - GEN A1 - Schulz, Christian A1 - Krüger-Genge, Anne A1 - Jung, Friedrich A1 - Lendlein, Andreas T1 - Aptamer supported in vitro endothelialization of poly(ether imide) films T2 - Clinical Hemorheology and Microcirculation N2 - Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface. However, the establishment of a shear resistant cell monolayer is still challenging. In our study, cyto- and immuno-compatible poly(ether imide) (PEI) films were explored as potential biomaterial for cardiovascular applications. Recently, we reported that the initial adherence of primary human umbilical vein endothelial cells (HUVEC) was delayed on PEI-films and about 9 days were needed to establish a confluent and almost shear resistant HUVEC monolayer. To accelerate the initial adherence of HUVEC, the PEI-film surface was functionalized with an aptamer-cRGD peptide based endothelialization supporting system. With this functionalization the initial adherence as well as the shear resistance of HUVEC on PEI-films was considerable improved compared to the unmodified polymer surface. The in vitro results confirm the general applicability of aptamers for an efficient functionalization of substrate surfaces. KW - aptamer KW - endothelialization KW - physical functionalization KW - poly(ether imide) films KW - shear resistance Y1 - 2020 U6 - https://doi.org/10.3233/CH-190775 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 2 SP - 201 EP - 217 ER - TY - GEN A1 - Jung, Friedrich T1 - COVID-19 T2 - Clinical Hemorheology and Microcirculation N2 - The pandemic of coronavirus disease 2019 (COVID-19), a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family. An epidemic of cases with respiratory infections detected in Wuhan, China, was first reported to the WHO Country Office in China, on December 31, 2019. This new virus seems to be very contagious and has quickly spread globally. The estimate for severe cases was approximated at 5% based on experience from China. However, the World Health Organization’s (WHO) estimate from China for severe and critical cases is near 20% [2]. Older age seems to be the highest risk for death. Mortality data from Oxford COVID-19 Evidence Service (25/3/20) indicates a risk of mortality of 3.6% for people in their 60 s, which increases to 8.0% for people older than 70 and to 14.8% for people over 80 s [3]. In addition, a very recent epidemiological study could show that already a small increase in long-term exposure to fine particular matter leads to a 20-times increase in COVID-19 death rate [4], showing that it is not only age and previous illnesses that predispose, but also the environmental conditions. In addition to respiratory disease, cardiovascular complications are reported to be a key threat in COVID-19 [5, 6]. In a second Editorial, F. Wenzel exposes this pandemic from a historical and socio-political perspective in a very interesting article [7]. In a feature about the European – Asian perspective Jung et al. present the development of COVID-19 in Germany and show a way to predict the time point at which no further new infections will occur using Normalized Case Number Curves (plateau day) [8]. Upon reaching the plateau day during a lockdown phase, a residual time-period of about 2-3 weeks can be utilized to prepare a safe unlocking period. First experiences with abdominal contrast-enhanced ultrasound (CEUS) examinations are presented by the group of E.M. Jung [6]. In the stage of an imminent organ failure with significantly reduced kidney and liver function and microcirculation, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. Y1 - 2020 U6 - https://doi.org/10.3233/CH-209001 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 4 SP - 347 EP - 348 ER - TY - GEN A1 - Lau, S. A1 - Rangarajan, R. A1 - Krüger-Genge, Anne A1 - Braune, Steffen A1 - Kammerer, Sarah A1 - Küpper, Jan-Heiner A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Effects of acrolein in comparison to its prodrug cyclophosphamide on human primary endothelial cells in vitro T2 - Toxicology in Vitro N2 - Cyclophosphamide (CPA) is one of the most successful anticancer prodrugs that becomes effective after biotransformation in the liver resulting in the toxic metabolite acrolein. Cancer is often accompanied by thromboembolic events, which might be a result of dysfunctional endothelial cells due to CPA treatment. Here, the effect of 1 mM CPA or acrolein (10/50/100/500 μM) on human umbilical vein endothelial cells (HUVECs) was analyzed after two days of treatment. The addition of CPA or 10 μM acrolein did not affect HUVECs. However, concentrations of 100 μM and 500 μM acrolein significantly reduced the number of adherent cells by 86 ± 13% and 99 ± 1% and cell viability by 51 ± 29% and 93 ± 8% compared to the control. Moreover, pronounced stress fibers as well as multiple nuclei were observed and von Willebrand factor (vWF) was completely released. Lactate dehydrogenase was 8.5 ± 7.0-fold and 252.9 ± 42.9-fold increased showing a loss of cell membrane integrity. The prostacyclin and thromboxane secretion was significantly increased by the addition of 500 μM acrolein (43.1 ± 17.6-fold and 246.4 ± 106.3-fold) indicating cell activation/pertubation. High doses of acrolein led to HUVEC death and loss of vWF production. This effect might be associated with the increased incidence of thromboembolic events in cancer patients treated with high doses of CPA. KW - Human umbilical venous endothelial cells KW - Acrolein KW - Aneuploidy KW - von Willebrand factor KW - in vitro study Y1 - 2020 U6 - https://doi.org/10.1016/j.tiv.2019.104685 SN - 0887-2333 VL - 62 ER - TY - GEN A1 - Lee, Seahyoung A1 - Ganesan, Ramakrishnan A1 - Krüger-Genge, Anne A1 - Kratz, Karl A1 - Franke, Ralf-Peter A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Substrate-enzyme affinity-based surface modification strategy for endothelial cell-specific binding under shear stress T2 - Clinical Hemorheology and Microcirculation N2 - Establishing an endothelial cell (EC) monolayer on top of the blood contacting surface of grafts is considered to be a promising approach for creating a hemocompatible surface. Here we utilized the high affinity interactions between the EC plasma membrane expressed enzyme called endothelin converting enzyme-1 (ECE-1) and its corresponding substrate big Endothelin-1 (bigET-1) to engineer an EC-specific binding surface. Since enzymatic cleavage of substrates require physical interaction between the enzyme and its corresponding substrate, it was hypothesized that a surface with chemically immobilized synthetic bigET-1 will preferentially attract ECs over other types of cells found in vascular system such as vascular smooth muscle cells (VSMCs). First, the expression of ECE-1 was significantly higher in ECs, and ECs processed synthetic bigET-1 to produce ET-1 in a cell number-dependent manner. Such interaction between ECs and synthetic bigET-1 was also detectible in blood. Next, vinyl-terminated self-assembled monolayers (SAMs) were established, oxidized and activated on a glass substrate as a model to immobilize synthetic bigET-1 via amide bonds. The ECs cultured on the synthetic bigET-1-immobilized surface processed larger amount of synthetic bigET-1 to produce ET-1 compared to VSMCs (102.9±5.13 vs. 9.75±0.74 pg/ml). The number of ECs bound to the synthetic bigET-1-immobilized surface during 1 h of shearing (5dyne/cm2) was approximately 3-fold higher than that of VSMCs (46.25±12.61 vs. 15.25±3.69 cells/100×HPF). EC-specific binding of synthetic bigET-1-immobilized surface over a surface modified with collagen, a common substance for cell adhesion, was also observed. The present study demonstrated that using the substrate-enzyme affinity (SEA) of cell type-specific enzyme and its corresponding substrate can be an effective method to engineer a surface preferentially binds specific type of cells. This novel strategy might open a new route toward rapid endothelialization under dynamic conditions supporting the long-term patency of cardiovascular implants. KW - endothelin converting enzyme-1 KW - big endothelin-1 KW - endothelialization KW - shear resistance Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch190736 U6 - https://doi.org/10.3233/CH-190736 SN - 1875-8622 VL - 75 IS - 1 SP - 85 EP - 98 ER - TY - GEN A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich A1 - Krieger, Volker A1 - Hufert, Frank T1 - A comparison of mortality rates between European and Asian States T2 - Clinical Hemorheology and Microcirculation Y1 - 2020 U6 - https://doi.org/10.3233/CH-209008 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 1 SP - 3 EP - 5 ER - TY - GEN A1 - Jung, Friedrich A1 - Krieger, Volker A1 - Hufert, Frank A1 - Küpper, Jan-Heiner T1 - How we should respond to the Coronavirus SARS-CoV-2 outbreak: A German perspective T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: In the early phase of the COVID-19 pandemic Germany missed to set up efficient containment measures. Consequently, the number of cases increased exponentially until a lockdown was implemented to suppress the spread of SARS-CoV-2. Fortunately, Germany has a high capability for coronavirus lab testing and more than 30,000 ICU beds. These capabilities and the lockdown turned out to be an advantage to combat the pandemic and to prevent a health-system overload. AIM: The aim was to predict the plateau day of SARS-CoV-2 infections or deaths. RESULTS: The effect on the viral spread of the German measures taken and the impact on the peak of new infection cases is shown. By normalizing daily case numbers, the plateau day of the current outbreak in Germany could be calculated to be reached at April 12, 2020 (day 103 of 2020). CONCLUSION: Normalized case number curves are helpful to predict the time point at which no further new infections will occur if the epidemic situation remains stable. Upon reaching the plateau day during a lockdown phase, a residual time-period of about 2-3 weeks can be utilized to prepare a safe unlocking period. As can be learned from Asian countries such as South Korea and Taiwan there must be strict rules to keep the risk of infection low. Those include social distancing, face mask wearing in combination with digital contact tracing and serosurveillance studies. Following those rules, a safe dance around the infection curve allows to keep the population at a reduced infection rate. KW - Corona virus KW - SARS-CoV-2 KW - COVID-19 KW - herd immunity KW - hammer and dance strategy Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209004 U6 - https://doi.org/10.3233/CH-209004 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 4 SP - 363 EP - 372 ER - TY - GEN A1 - Kammerer, Sarah A1 - Nowak, Elisabeth A1 - Mantke, René A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - In vitro simulation of the liver first-pass effect with biotransformation-competent HepG2 cells to study effects of MG-132 on liver and cancer cells T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Liver biotransformation is the major route for drug metabolism in humans, often catalysed by cytochrome P450 (CYP) enzymes. This first-pass effect can lead to hepatotoxicity and influences the bioavailability of drugs. OBJECTIVE: We aimed to establish in vitro culture systems simulating the liver first-pass to study effects of the proteasome inhibitor MG-132 simultaneously on hepatocytes and cancer cells. METHODS: The first-pass effect was simulated by conditioned medium transfer (CMT) from pre-treated HepG2 CYP3A4-overexpressing cells to either pancreatic cancer cell line PANC-1 or primary colon cancer cells, and by indirect co-culture (CC) of liver and cancer cells in a shared medium compartment. Experimental proteasome inhibitor MG-132 was used as test substance as it is detoxified by CYP3A4. RESULTS: Cancer cells showed higher viabilities in the first-pass simulation by CMT and CC formats when compared to monocultures indicating effective detoxification of MG-132 by HepG2 CYP3A4-overexpressing cells. HepG2-CYP3A4 cells showed reduced viabilites after treatment with MG-132. CONCLUSIONS: We successfully established two different culture systems to simulate the liver first-pass effect in vitro. Such systems easily allow to study drug effects simultaneously on liver and on target cancer cells. They are of great value in pre-clinical cancer research, pharmaceutical research and drug development. KW - Liver biotransformation KW - first-pass effect KW - CYP3A4 KW - MG-132 KW - cancer cells KW - in vitro culture systems Y1 - 2024 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch238108 U6 - https://doi.org/10.3233/CH-238108 SN - 1386-0291 VL - 86 IS - 1-2 SP - 159 EP - 168 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe T1 - Morphology and Function of Red Blood Cells in COVID-19 Patients: Current Overview 2023 T2 - Life N2 - In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation. KW - COVID-19 KW - SARS-CoV-2 KW - red blood cell KW - deformation KW - aggregation KW - endothelial cell Y1 - 2024 U6 - https://doi.org/10.3390/life14040460 SN - 2075-1729 VL - 14 IS - 4 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2020 T2 - Clinical Hemorheology and Microcirculation Y1 - 2021 UR - https://europepmc.org/article/med/33720877 U6 - https://doi.org/10.3233/ch-219001 SN - 1875-8622 SN - 1386-0291 VL - 77 IS - 3 SP - 245 EP - 246 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2021 T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-229901 SN - 1875-8622 SN - 1386-0291 VL - 82 IS - 3 SP - 199 EP - 200 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2019 T2 - Clinical Hemorheology and Microcirculation Y1 - 2020 UR - https://europepmc.org/article/med/32568189 U6 - https://doi.org/10.3233/ch-209100 SN - 1875-8622 SN - 1386-0291 VL - 75 IS - 1 SP - 1 EP - 2 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2018 T2 - Clinical Hemorheology and Microcirculation Y1 - 2019 U6 - https://doi.org/10.3233/CH-199008 SN - 1386-0291 VL - 72 IS - 2 SP - 117 EP - 118 ER - TY - GEN A1 - Schulz, Christian A1 - Herzog, Natalie A1 - Kubick, Stefan A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Stable Chinese Hamster Ovary Suspension Cell Lines Harboring Recombinant Human Cytochrome P450 Oxidoreductase and Human Cytochrome P450 Monooxygenases as Platform for In Vitro Biotransformation Studies T2 - Cells N2 - In the liver, phase-1 biotransformation of drugs and other xenobiotics is largely facilitated by enzyme complexes consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs). Generated from human liver-derived cell lines, recombinant in vitro cell systems with overexpression of defined phase-1 enzymes are widely used for pharmacological and toxicological drug assessment and laboratory-scale production of drug-specific reference metabolites. Most, if not all, of these cell lines, however, display some background activity of several CYPs, making it difficult to attribute effects to defined CYPs. The aim of this study was to generate cell lines with stable overexpression of human phase-1 enzymes based on Chinese hamster ovary (CHO) suspension cells. Cells were sequentially modified with cDNAs for human CPR in combination with CYP1A2, CYP2B6, or CYP3A4, using lentiviral gene transfer. In parallel, CYP-overexpressing cell lines without recombinant CPR were generated. Successful recombinant expression was demonstrated by mRNA and protein analyses. Using prototypical CYP-substrates, generated cell lines proved to display specific enzyme activities of each overexpressed CYP while we did not find any endogenous activity of those CYPs in parental CHO cells. Interestingly, cell lines revealed some evidence that the dependence of CYP activity on CPR could vary between CYPs. This needs to be confirmed in further studies. Recombinant expression of CPR was also shown to enhance CYP3A4-independent metabolisation of testosterone to androstenedione in CHO cells. We propose the novel serum-free CHO suspension cell lines with enhanced CPR and/or defined CYP activity as a promising “humanised” in vitro model to study the specific effects of those human CYPs. This could be relevant for toxicology and/or pharmacology studies in the pharmaceutical industry or medicine. KW - Chinese hamster ovary cells KW - CHO-K1 KW - CPR KW - CYP450 KW - cytochrome P450 monooxygenase KW - liver KW - NADPH P450 oxidoreductase KW - phase-1 biotransformation KW - serum-free KW - suspension cells Y1 - 2023 UR - https://www.mdpi.com/2073-4409/12/17/2140#metrics U6 - https://doi.org/10.3390/cells12172140 SN - 2073-4409 VL - 12 IS - 17 ER - TY - GEN A1 - Lau, S. A1 - Gossen, Maike A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Differential sensitivity of assays for determining vein endothelial cell senescence T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-211294 SN - 1875-8622 SN - 1386-0291 VL - 81 IS - 3 SP - 191 EP - 203 ER -