Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Lee, Sang Bae | Kim, Yu-Sik | Kim, Jung Hye | Park, Kahui | Nam, Ji Sun | Kang, Shinae | Park, Jong Suk | Shin, Sehyun | Ahn, Chul Woo

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: Hemorheologic alterations have been suggested to play a role in the pathogenesis of diabetic microvascular complications. We measured various hemorheologic parameters and assessed their possible role as a diagnostic tool for diabetic nephropathy (DN). METHODS: 248 subjects with type 2 diabetes and 222 subjects with prediabetes were included in this study. Hemorheologic parameters, including erythrocyte sedimentation rate (ESR), elongation index at 3 Pa (EI) were measured using microfluidic hemorheometer. Various metabolic parameters were measured from fasting blood samples. The subjects were stratified into three groups according to classification of DN by urinary albumin to creatinine …ratio (ACR) and four groups by estimated glomerular filtration rate (GFR), than analyzed. RESULTS: Significant differences were observed in metabolic and hemorheologic parameters according to progression of DN. Among them, (Fibrinogen×ESR)/ EI differed in all three groups of urinary ACR. In multiple regression analysis, (Fibrinogen×ESR)/ EI was an independent predictor of urine ACR after adjusted with confounding factors (ß  = 0.010, p  <  0.001). (Fibrinogen×ESR)/ EI also showed significant difference no or minimal CKD stage, moderate CKD and severe CKD classified by GFR. This parameter showed area under curve (AUC) of the receiver operating characteristic (ROC) curve of 0.762, and moderate sensitivity and specificity to predict prevalence of microalbuminuria. CONCLUSIONS: (Fibrinogen×ESR)/ EI is a sensitive parameter for screening diabetic nephropathy. Show more

Keywords: Diabetic nephropathy, RBC deformability, hemorheology, elongation index

DOI: 10.3233/CH-180434

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Leitão Guerra, Ricardo Luz | Bastos, Mateus Abdalla | Salles, Cristina

Article Type: Letter

DOI: 10.3233/CH-180462

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-2, 2018

Authors: Adams, Rachel A. | Potter, Stephen | Bérubé, Kelly | Higgins, Timothy | Jones, Tim | Evans, Shelley-Ann

Article Type: Research Article

Abstract: BACKGROUND: Exposure to air pollution is associated with cardiovascular disease, including increased morbidity and mortality rates. OBJECTIVE: The aim of this investigation was to assess the effect, in rats, of intratracheal instillation of particulate air pollution on biomarkers of leucocyte activation and vascular endothelial damage. METHODS: Air pollution particles (PM10) were instilled into rats, and blood samples were taken three days and six weeks post instillation. Plasma neutrophil elastase and VonWillebrand factor were measured by ELISA. RESULTS: Plasma neutrophil elastase increased from 175±44 ng/ml at baseline to 288±26 ng/ml 3 days post instillation (p … = 0.038). vWF increased from 0.160±0.015 IU/ml at baseline to 0.224±0.015 IU/ml at 3 days post and 0.208±0.01 IU/ml at 6 weeks post (p  = 0.006, ANOVA). sICAM-1 increased from 17.75±0.70 ng/ml at baseline to 19.03±0.33 ng/ml at 3 days post and 21.72±1.16 ng/ml at 6 weeks post (p  = 0.009, ANOVA). CONCLUSION: Instillation caused prolonged systemic inflammation, activation of blood leucocytes and damage to the vascular endothelium. Show more

Keywords: Particles, cardiovascular disease, inflammation, endothelial damage and leucocyte

DOI: 10.3233/CH-180377

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Astapenko, David | Dostalova, Vlasta | Dostalova jr, Vlasta | Kraus, Jaroslav | Radochova, Vera | Dostal, Pavel | Ticha, Alena | Hyspler, Radomir | Lehmann, Christian | Cerny, Vladimir

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: The endothelial glycocalyx (EG) is fragile and sensitive to damage such as exposure to hypernatremia. Our aim was to describe the influence of hypernatremia on the EG in sublingual and brain microcirculation in rabbits. METHODS: Hypernatremia was induced by intravenous administration of 10% NaCl solution. The sublingual and brain microcirculation were evaluated by the Side-stream Dark Field imaging before (T1) and 20 minutes after infusion of 10% saline (T2). Damage to the EG was quantified by automated analysis of Perfused Boundary Region (PBR) indicating the amount of penetration of red blood cells into the EG. …Syndecan-1 levels were also measured. RESULTS: Hypernatremia was reached in all 20 animals, the PBR values of the sublingual area raised from 1,98 (0,3) to 2,17 (0,18) μ m (p  = 0,05). The levels of syndecan-1 (1,23 (0,36); 1,31 (0,33) ng/l, p  = 0,3) did not mirror PBR changes. CONCLUSIONS: Hypernatremia increased the PBR within the sublingual microcirculation in our animal model, probably due to compression of the EG related to temporary intravascular hypervolemia and changes of the EG charge in RBC instead of direct damaging effect on EG, which has been excluded by rather unchanged levels of syndecan-1. Show more

Keywords: Hypernatremia, endothelial glycocalyx, sublingual microcirculation, syndecan

DOI: 10.3233/CH-189907

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Kauffmann, Philipp | Troeltzsch, Markus | Brockmeyer, Phillipp | Bohnenberger, Hanibal | Manzke, Marietta | Martin, Canis | Gaayathiri, Suntharalingam | Schliephake, Henning | Prantl, Lukas | Aung, Thiha

Article Type: Research Article

Abstract: INTRODUCTION: The oral squamous cell carcinoma (OSCC) is a leading cause of death in human malignancies. The aim of this study is to integrate the CAM Assay as a reliable and good working in vivo model for the evaluation of OSCC tumor samples and its growth into the clinical work flow. MATERIAL AND METHODS: Fresh human Tumor samples (OSCCs) 1×1 cm in size were cut into 350–450μ m thick slices by a Vibratome and put on the prepared CAM model. After growth of the tumor tissue on the CAM, we started with topical induction of proinflammatory cytokines (TNFα …) and growth factors (TGFβ ). After further growth of the tumor on the assay, we explanted the tumor tissue and first performed microscopic and then immunohistochemical examinations. E-cadherin and vimentin were used as Epithelial-to-mesenchymal transition (EMT) -makers and the histologic preparations were evaluated histomorphometrically. The results were correlated with clinical parameters of the patients. RESULTS: Under TNFα , the small tumors (T1 / T2) show higher E-cadherin expression than larger tumors (T3 / T4). The vimentin expression under TNFα behaved in the opposite direction, at T1 / T2 the expression decreased in T3 / T4 increased. Furthermore, an increased E-cadherin expression in N0 and diminished E-cadherin expression in N1 / N2b patients could be detected depending on the N-stage of the patients. Vimentin, on the other hand, was reduced in the N0 group and expressed more frequently in the N1 / N2b group. TGFβ induction also led to increased expression of vimentin in the T3 / T4 tumors and N1 / N2b stages. CONCLUSION: By integrating a CAM assay into the clinical workflow, tumors with preserved tumor architecture can be cultured and subjected to histological and molecular biology studies. Effects on biological behavior are recognizable and demonstrable in this model. The key markers E-cadherin and vimentin alone are not sufficient to represent the complexity of the EMT in this model. Further molecular biology and signaling pathway analyzes are necessary. Show more

DOI: 10.3233/CH-189315

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-8, 2018

Authors: Rieger, Juliane | Hopperdietzel, Carsten | Kaessmeyer, Sabine | Slosarek, Ilka | Diecke, Sebastian | Richardson, Ken | Plendl, Johanna

Article Type: Research Article

Abstract: BACKGROUND: Human and equine patients are known to frequently develop vascular complications, particularly thrombosis both in veins and arteries as well as in the microvasculature. OBJECTIVE: The aim of the present study was to investigate and compare the angiogenic response of human and equine endothelial cells to lesions in an in vitro scratch assay. METHODS: Endothelial cells from human umbilical vein (HUVEC), abdominal aorta (HAAEC) and dermal microvasculature (HDMEC) as well as equine carotid artery (EACEC) and jugular vein (EVJEC) were cultured and an elongated defect was created (scratch or “wound”). Cultures were monitored over …a period of 90 hours in a life cell imaging microscope. RESULTS: In the human endothelial cell cultures, there was a uniform and continuous migration of the cells from the scratch fringe into the denuded area, which was closed after 17 (HUVEC), 15 (HAAEC) and 26 (HDMEC) hours. In the equine endothelial cell cultures, a complete closure of the induced defect occurred after 17 (EVJEC) and 35 (EACEC) hours. CONCLUSIONS: In the equine arterial cells, the delay in closure of the denuded area seems to be the results of a disoriented and uncoordinated migration of endothelial tip cells resulting in slow re-endothelialization. Show more

Keywords: Equine, horse, human, endothelial cells, life cell imaging, scratch assay, wound healing, angiogenesis, cell migration, collective cell migration

DOI: 10.3233/CH-189316

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-15, 2018

Authors: Probst, Ute | Sieron, Dominik | Bruenn, Karin | Fuhrmann, Irene | Verloh, Niklas | Stroszczynski, Christian | Jung, Ernst-Michael | Wiggermann, Philipp | Haimerl, Michael

Article Type: Research Article

Abstract: PURPOSE: Contrast enhanced magnetic resonance imaging (MRI) is able to assess liver function by characteristic changes of signal intensity (SI). The aim was to evaluate dynamic contrast-enhanced SI-indices of the abdominal aorta, portal vein and liver. METHODS: 72 patients underwent Gd-EOB-DTPA-enhanced MRI and a 13 C-methacetin-based liver breath test (13 C-MBT) for evaluation of liver function. Region-of-interest measurements in the liver, abdominal aorta and portal vein during native, arterial (AP), late arterial (LAP), portal venous (PVP) and hepatobiliary phase (HBP) were applied to analyze SI-indices in T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat-suppression and relative enhancement (RE) …analysis was performed. RESULTS: The liver (p  <  0.001), the portal vein (p  <  0.001) and abdominal aorta (p  = 0.002) showed significant decrease of REs with decreasing liver function. An increasing trend between logarithmic values of 13 C-MBT and REs of hepatic parenchyma (HBP; r  = 0.662, p  <  0.001), portal vein (PVP; r  = 0.532, p  <  0.001) and abdominal aorta (PVP; r  = 0.421, p  <  0.001) was observed. CONCLUSIONS: RE measurements of the hepatic parenchyma proofed to be a trustable evaluation method for liver function evaluation. In accordance with liver function, changes of REs in the portal vein and abdominal aorta occur. Show more

Keywords: Dynamic contrast enhanced MRI, 13C-methacetin liver function breath test, HCC, liver metastases, hepatic parenchyma, portal vein, abdominal aorta, signal intensity, relative enhancement

DOI: 10.3233/CH-189324

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Zou, Jie | Wang, Weiwei | Kratz, Karl | Xu, Xun | Nie, Yan | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Polycarbonate (PC) substrate is well suited for culturing human mesenchymal stem cells (MSCs) with high proliferation rate, low cell apoptosis rate and negligible cytotoxic effects. However, little is known about the influence of PC on MSC activity including senescence, differentiation and secretion. In this study, the PC cell culture insert was applied for human MSC culture and was compared with polystyrene (PS) and standard tissue culture plate (TCP). The results showed that MSCs were able to adhere on PC surface, exhibiting a spindle-shaped morphology. The size and distribution of focal adhesions of MSCs were similar on PC and TCP. The …senescence level of MSCs on PC was comparable to that on TCP, but was significantly lower than that on PS. MSCs on PC were capable of self-renewal and differentiation into multiple cell lineages, including osteogenic and adipogenic lineages. MSCs cultured on PC secreted a higher level inflammatory cytokines and pro-angiogenic factors including FGF2 and VEGF. Conclusively, PC represents a promising cell culture material for human MSCs. Show more

Keywords: Polycarbonate, human mesenchymal stem cells, differentiation, cytokine secretion, senescence

DOI: 10.3233/CH-189322

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Kammerer, Sarah | Küpper, Jan-Heiner

Article Type: Research Article

Abstract: BACKGROUND: Drug induced liver injury (DILI) is the most frequent cause for failure of new drugs in clinical studies. Thus, toxicity studies are indispensable during drug development. The proliferative human liver cell strain HepaFH3 with promising primary-like cellular properties might be a suitable liver model for such studies, but their cytochrome-P450 (CYP) expression is still in low ranges compared to freshly isolated primary human hepatocytes. OBJECTIVE: We aimed to optimize the induction protocol for CYP1A2 and CYP3A4 in HepaFH3 to obtain a physiologically relevant in vitro liver model. METHODS: CYP1A2 and CYP3A4 …were induced by omeprazole and rifampicin, respectively. Induction of the two CYPs was measured by qRT-PCR, immunofluorescence and by P450 Glo enzyme activity assays. RESULTS: The optimized protocol made the experimental design six days shorter than the original procedure. CYP1A2 mRNA levels were induced 118-fold, CYP3A4 levels 36-fold. This result was also reflected at protein level. Enzymatic activity of CYP1A2 increased 3.7-fold and CYP3A4 activity increased 9.8-fold after induction. CONCLUSIONS: We succeeded in optimizing the induction protocol for HepaFH3 to such an extent that CYP1A2 and CYP3A4 are expressed in sufficient amounts that the cell strain can be used as a physiological relevant human liver model for in vitro toxicology studies. Show more

Keywords: Cytochrome P450, CYP induction, DILI, drug induced liver injury, HepaFH3, liver in vitro model, liver toxicity

DOI: 10.3233/CH-189321

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Zhou, Juan | Yang, Hyewon | Lehmann, Christian

Article Type: Research Article

Abstract: Sepsis is a medical condition caused by dysregulated systemic inflammatory response against infection, resulting in high mortality. Despite intensive research over the last few decades, the results from multiple clinical trials targeting specific inflammatory mediators have been disappointing. In the present study, we investigated the role of G protein-coupled receptor GPR55 modulation on immune response in an experimental sepsis model (endotoxemia). Immune response was evaluated by analyzing leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation using intravital microscopy. In addition, the levels of plasma inflammatory cytokines were measured. The results demonstrated that GPR55 inhibition using antagonists, CID16020046 or O-1918, …significantly reduced leukocyte adherence in intestinal submucosal venules and decreased proinflammatory cytokine TNF-α and IL-6 production. These data suggest that GPR55 inhibition may be a novel therapeutic target for attenuating hyperinflammation during sepsis. Show more

DOI: 10.3233/CH-189320

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2018