bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-enhanced ultrasound versus conventional ultrasound in the diagnosis of polypoid lesion of gallbladder: A multi-center study of dynamic microvascularization
Authors: Zheng Shu-Guang , Xu Hui-Xiong , Liu Lin-Na , Lu Ming-De , Xie Xiao-Yan , Wang Wen-Ping , Hu Bing , Yan Kun , Ding Hong , Tang Shao-Shan , Qian Lin-Xue , Luo Bao-Ming
Published: December 2019

OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of polypoid lesions of gallbladder (PLGs). METHODS: CEUS was performed to 116 patients (mean age, 49.6 years; range, 21–80 years) with PLGs from 8 university hospitals. 9 cases of biliary sludge were proven by surgery and the remaining 107 cases were confirmed by histopathological examination. The confidence level, diagnostic performance, inter-observer agreement of two independent readers with different experience was assessed. The readers were blind to the imaging and clinical results of the patients. RESULTS: There were significant differences between benign and malignant PLGs in patient age, gender, lesion size, echogenicity, stalk, time-to-peak, vascularity on CEUS, enhancement pattern, and wall destruction. The confidence levels increased significantly and the interobserver agreement increased from 0.425 to 0.601 after CEUS. The sensitivity increased from 22.2 to 77.8% after CEUS in the staff radiologist, and from 22.2 to 66.7% in the resident radiologist. The correctly characterized lesions were 64.7% before versus 87.1% after CEUS (P = 0.125) for the staff radiologist, and 57.8% versus 70.7% for the resident radiologist (P = 0.007). No significance was found in the subgroup of lesions ≤1.0 cm before and after CEUS for the two radiologists. CONCLUSIONS: CEUS using convex multifrequency probes could detect the dynamic microvascularization of PLGs greater than 1.0 cm and facilitate the differentiation between benign and malignant tumors.
Parametric imaging with contrast-enhanced ultrasound: Usefulness for characterization of dynamic effects of microvascularization for hepatocellular carcinoma and focal nodular hyperplasia
Authors: Zheng Shu-Guang , Xu Hui-Xiong , Liu Lin-Na , Wang Yan , Zhang Yi-Feng , Guo Le-Hang , Liu Chang , Xu Jun-Mei , Sun Li-Ping , Wu Jian
Published: December 2019

OBJECTIVE: To evaluate whether parametric imaging with contrast-enhanced ultrasound (CEUS) is equal to experienced radiologists after review of CEUS in differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH). METHODS: An image processing software was used to quantitatively analyze the CEUS clips of 30 HCCs (mean diameter, 3.4 ± 0.9 cm; range, 1.8–5.0 cm) and 30 FNHs (mean diameter, 3.0 ± 1.1 cm; range, 1.1–5.0 cm). Low mechanical index contrast specific imaging modes and contrast agent of SonoVue® were applied for CEUS. Fourteen HCCs were pathologically diagnosed and 16 were clinically diagnosed, whereas all the FNHs were confirmed by pathological examination. Quantitative parameters of HCC and FNH were compared. The diagnostic performance between parametric imaging and two experienced readers was compared using the receiver operating characteristic (ROC) curve analysis. RESULTS: On parametric imaging, the rise time, time to peak and mean transit time for HCC and FNH were 16.7 ± 11.1 s vs. 21.9 ± 9.0 s (P = 0.052), 29.9 ± 14.1 s vs. 33.2 ± 11.1 s (P = 0.322), 115.0 ± 90.9 s vs. 271.5 ± 147.6 s (P < 0.001), respectively. The ROC analysis showed that, for the differentiation between HCC and FNH, the cut-off point for mTT was 107.93 s with the Az value of 0.817 (95% CI: 0.703–0.931), and the Az value was 0.834 (95%CI: 0.728–0.941) for two experienced readers (P = 0.417 compared with mTT). The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were 96.7%, 66.7%, 81.7%, 74.4%, and 95.2%, respectively, for parametric imaging, and 86.7%, 76.7%, 81.7%, 78.8%, and 85.2%, respectively, for two experienced readers (all P > 0.05 compared with parametric imaging). CONCLUSION: Parametric imaging with CEUS is helpful for characterization the typical dynamic effects of microvascularization of HCC and FHH and is equal to experienced readers in the differential diagnosis between HCC and FNH.
Measurement of RBC agglutination with microscopic cell image analysis in a microchannel chip
Authors: Cho Chi Hyun , Kim Ju Yeon , Nyeck Agnes E. , Lim Chae Seung , Hur Dae Sung , Chung Chanil , Chang Jun Keun , An Seong Soo A. , Shin Sehyun
Published: December 2019

Since Landsteiner's discovery of ABO blood groups, RBC agglutination has been one of the most important immunohematologic techniques for ABO and RhD blood groupings. The conventional RBC agglutination grading system for RhD blood typings relies on macroscopic reading, followed by the assignment of a grade ranging from (-) to (4+) to the degree of red blood cells clumping. However, with the new scoring method introduced in this report, microscopically captured cell images of agglutinated RBCs, placed in a microchannel chip, are used for analysis. Indeed, the cell images' pixel number first allows the differentiation of agglutinated and non-agglutinated red blood cells. Finally, the ratio of agglutinated RBCs per total RBC counts (CRAT) from 90 captured images is then calculated. During the trial, it was observed that the agglutinated group's CRAT was significantly higher (3.77−0.003) than that of the normal control (0). Based on these facts, it was established that the microchannel method was more suitable for the discrimination between agglutinated RBCs and non-agglutinated RhD negative, and thus more reliable for the grading of RBCs agglutination than the conventional method.
Plasma hyaluronan and hemorheology in patients with septic shock: A clinical and experimental study
Authors: Sallisalmi Marko , Tenhunen Jyrki , Kultti Anne , Tammi Markku , Pettilä Ville
Published: December 2019

BACKGROUND: Total plasma hyaluronan concentration is increased in septic shock. High-molecular-weight hyaluronan has a high intrinsic viscosity. Excessive release of high-molecular-weight hyaluronan in sepsis may induce hyperviscosity. METHODS: Plasma viscosity and the molecular size of plasma hyaluronan were determined in 20 patients with septic shock and in 20 healthy controls. Ex vivo, the effects of 0.4% and 0.047% high-molecular-weight hyaluronan 1560 kDa, 0.9% saline, and 6% hydroxy-ethyl-starch 130 kDa were compared to plasma and whole blood viscosity and red blood cell aggregation at a systemic hematocrit of 0.4, and at a microcirculatory hematocrit of 0.2. RESULTS: Plasma viscosity and total plasma protein content were low in septic shock patients on days one and four of treatment. Hyaluronan concentration was 10-fold higher in sepsis on day 1. Molecular weight of hyaluronan was relatively low, mostly 50–500 kDa, and did not change significantly in sepsis. Ex vivo, 0.4% high-molecular-weight hyaluronan 1560 kDa increased blood viscosity but did not promote red blood cell aggregation. Dilutions of 6% hydroxyl-ethyl-starch 130 kDa and 0.047% high-molecular-weight hyaluronan 1560 kDa had comparable effects on blood viscosity and red blood cell aggregation. CONCLUSIONS: Plasma viscosity of the septic patients remained low for four days despite markedly elevated concentration of relatively small-molecular-weight hyaluronan.
The Nebivolol action on vascular tone is dependent on actin cytoskeleton polymerization and Rho-A activity into ECs and SMCs
Authors: Kadi A. , de Isla N. , Moby V. , Lacolley P. , Labrude P. , Stoltz J.F. , Menu P.
Published: December 2019

Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol in cultured endothelial cells. We studied the effect of Nebivolol (200μM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50μM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in Endothelial Cells (ECs) via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.
Hemorheological profile in primary and secondary Raynaud's phenomenon. Influence of microangiopathy
Authors: Vayá Amparo , Alis Rafael , Romagnoli Marco , Todolí Jose , Calvo Javier , Ricart Jose M.
Published: December 2019

Raynaud's phenomenon (RP) is an episodic peripheral circulatory disorder characterized by local artery spams in subjects exposed to cold or emotional stress. It is not well-established whether RP patients show an altered rheological profile, mostly due to patient classification and clinical severity. We aimed to compare the hemorheological profile in patients with primary and secondary RP with a healthy control group. Eighteen primary RP, 22 secondary RP and 22 healthy controls, were included in the study. RP patients were also divided according to the presence of digital ulcers (7 with, 33 without). Biochemical and hemorheological variables were analyzed, including glucose, triglycerides, total-cholesterol, immunoglobulins, fibrinogen, plasma viscosity, erythrocyte aggregation, erythrocyte deformability and blood viscosity. Age was higher in secondary RP as compared with primary (p = 0.049), while glucose, triglycerides IgA, IgG and plasma viscosity were higher in secondary RP than in healthy subjects (p < 0.05). RP patients with digital ulcers presented higher IgA (p = 0.012), lower erythrocyte aggregation time (p = 0.008) and a trend for higher fibrinogen levels and plasma viscosity (p = 0.064, p = 0.069, respectively). The results of the present study indicate that secondary RP patients show a mild impairment of the rheological profile that aggravates with microangiopathy severity.
Crosstalk between inflammation, iron metabolism and endothelial function in Behçet's disease
Authors: Oliveira Rita , Napoleão Patricia , Banha João , Paixão Eleonora , Bettencourt Andreia , da Silva Berta Martins , Pereira Dina , Barcelos Filipe , Teixeira Ana , Patto José Vaz , Viegas-Crespo Ana Maria , Costa Luciana
Published: December 2019

Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.
Decreased microvascular myogenic response to insulin in severely obese adolescents
Authors: Montero David , Walther Guillaume , Perez-Martin Antonia , Santamaria Cristina , Roche Enrique , Mercier Charles , Vinet Agnès
Published: December 2019

By means of flowmotion analysis, it is mainly accepted that, in normal conditions, insulin specifically increases the activity of microvascular smooth muscle. The objective of this study was to compare this effect in severely obese and normal-weight adolescents. Laser Doppler measurements were used to assess cutaneous blood flux (CBF) and flowmotion in response to transdermal iontophoresis of insulin in 20 severely obese adolescents (SOA) aged 12–17 years (BMI = 33.34 ± 1.07 kg/m2), and 16 normal-weight adolescents (BMI = 18.85 ± 0.50 kg/m2). Fasting insulin levels were higher in SOA than in normal-weight adolescents (6.25 ± 1.03 vs. 3.11 ± 0.28 μU/ml, P = 0.007). Net insulin-induced increase of CBF did not significantly differ between SOA and normal-weight adolescents (422.41 ± 146.09 vs. 232.36 ± 80.98 %, P = 0.265). A significant impairment of myogenic flowmotion was detected in SOA compared to normal-weight adolescents in response to insulin delivery (5.91 ± 0.35 vs. 8.12 ± 0.63 %, P = 0.003). Severely obese adolescents exhibit decreased myogenic activity in response to insulin, which may be an early step in the development of insulin resistance.
Effects of exercise training and Mediterranean diet on vascular risk reduction in post-menopausal women
Authors: Alkhatib Ahmad , Klonizakis Markos
Published: December 2019

This study tested the potential risk-reduction benefits of Mediterranean Diet (MD) and regular exercise training on microvascular activity and cardiorespiratory capacity in postmenopausal women. Fifteen sedentary postmenopausal participants (age = 54.6 ± 3.6) were randomised into either exercise training or exercise combined with following MD for eight-weeks, and were assessed for their cardiorespiratory capacity, and upper- and lower-limb endothelial cutaneous vascular conductance (CVC) test using Laser Doppler Fluximetry (LDF), coupled with measuring endothelium-dependent Acetylcholine Chloride (Ach) and -dependent Sodium Nitropurruside (SNP) vasodilators. Exercise training improved cardiorespiratory capacity as indicated by ventilatory threshold (11.5 ± 2.1 vs. 14.0 ± 3.0 ml·kg−1·min−1, p < 0.05) and improved the microcirculatory perfusion results of CVC for both vasodilators Ach (p < 0.001, d = 0.65) and SNP (p = 0.003, d = 0.53) in the lower-limb and ACh (p = 0.01, d = 0.41) and SNP (p = 0.03, d = 0.48) in the upper-limb, all (p < 0.05). However, combining exercise with MD showed a stronger improvement in Ach (p = 0.02, d = 0.36) of the lower limb, than in exercise alone group. The results suggest that regular moderate exercise improves microcirculatory vascular function and increases exercise tolerance, both are responsible for reducing cardiovascular risk in postmenopausal women. However, combining MD with exercise suggests additional microvascular vasodialiatory improvement, suggesting an effective strategy for further cardiovascular risk-reduction in this high-risk group.
Leukocyte-endothelial interactions within the ocular microcirculation in inflammation and infection
Authors: Al-Banna N.A. , Toguri J.T. , Kelly M.E.M. , Lehmann Ch.
Published: December 2019

Leukocyte-endothelial interactions within the microvasculature represent a hallmark of inflammation regardless of whether the inflammation results from non-infectious or infectious triggers. In this review, we highlight features of leukocyte recruitment in ocular disease and postulate mechanisms by which the infiltrating cells may lead to the progression of the ocular inflammatory response, including cytokine and chemokine production, T cell or non-T cell responses. Additionally, ex-vivo and in vivo methods used to study the general features of the immune response are discussed, with a specific focus on intravital imaging, which allows real-time non-invasive examination of leukocyte-endothelial interactions in the ocular microvasculature. At the present time there are still significant gaps in our understanding of the process of leukocyte recruitment in vivo in different microvascular beds. Further studies using non-invasive imaging approaches, such as intravital microscopy, provide an opportunity to study dynamic tissue-specific leukocyte-endothelial interactions in vivo and identify novel targets for early intervention in the inflammatory process. This knowledge is essential to the rational use of therapeutics to resolve inflammation in ocular disease.
Influence of a silicon (Si14)-based coating substrate for biomaterials on fibroblast growth and human C5a
Authors: Hiebl B. , Hopperdietzel C. , Hünigen H. , Jung F. , Scharnagl N.
Published: December 2019

Despite considerable efforts in biomaterial development there is still a lack on substrates for cardiovascular tissue engineering approaches which allow the establishment of a tight a functional endothelial layer on their surface to provide hemocompatibility. The study aimed to test the biocompatibility of a silicon (Si14)-based coating substrate (Supershine Medicare, Permanon) which was designed to resist temperatures from −40°C up to 300°C and which allows the use of established heat-inducing sterilization techniques respectively. By X-ray photoelectron spectroscopy it could be validated that this substrate is able to establish a 40–50 nm thick layer of silica, oxygen and carbon without including any further elements from the substrate on an exemplary selection of materials (silicone, soda-lime-silica glass, stainless steel). Analysis of the LDH-release, the cell activity/proliferation (MTS assay) and the cell phenotype after growing 3T3 cells with extracts of the coated materials did not indicate any signs of cytotoxicity. Additionally by measuring the C5a release after exposure of the coated materials with human serum it could be demonstrated, that the coating had no impact on the activation of the complement system. These results generally suggest the tested substrate as a promising candidate for the coating of materials which are aimed to be used in cardiovascular tissue engineering approaches.
Erythrocyte aggregation and metabolic syndrome
Authors: Gyawali Prajwal , Richards Ross S. , Hughes Diane L. , Tinley Paul
Published: December 2019

Erythrocyte aggregation has been consistently associated with insulin resistance, central obesity and hypertension in the literature. Oxidative stress and chronic inflammation are almost always present in metabolic syndrome (MetS). Prooxidants and adipocytokines generated in MetS alter erythrocyte morphology, decrease erythrocyte deformability and increase whole blood viscosity (WBV). Increased WBV has been attributed to erythrocyte aggregation which in turn is greatly influenced by other rheological parameters, including its membrane surface charge and plasma fibrinogen concentration. The interplay of hemorheological factors, oxidative stress and inflammation has a detrimental effect in MetS due to the gross disturbance in microcirculation. The hemodynamic aspect of MetS needs further research and exploration.
Measuring and optimizing results in multipolar RFA: Techniques and early findings in an experimental setting
Authors: Vahldiek Janis L. , Lehmann Kai S. , Poch Franz , Zurbuchen Urte , Kreis Martin E. , Gemeinhardt Ole , Hamm B. , Niehues Stefan M.
Published: December 2019

Radiofrequency ablation (RFA) has shown to be a reasonable alternative for the treatment of hepatic tumors and metastases although multiple limitations remain. Cooling effects due to larger vessels can prevent complete coverage and may lead to early tumor relapse. This preliminary in vivo pig study combines the use of multipolar RFA with three applicators (six electrodes) and interrupted liver perfusion using Pringle's maneuver to overcome the most serious limitations. Furthermore, immediate detection of incomplete RFA is important to revise ablation. We used contrast enhanced computed tomography (CECT) to evaluate post ablation results in comparison to macroscopic images in healthy pig liver. We found significantly (p = 0.001) larger ablation zones and no affection by larger vessels with interrupted liver perfusion. This allows effective RFA for larger tumors. Immediate postinterventional CECT provided comparable results (r = 0.985) to macroscopic evaluation.
Plasma levels of adhesion molecules ICAM-1 and VCAM-1 in athletes with sickle cell trait with or without α-thalassemia during endurance exercise and recovery
Authors: Monchanin Geraldine , Serpero Laura D. , Connes Philippe , Tripette Julien , Wouassi Dieudonné , Francina Alain , Massarelli Raphael , Gozal David , Thiriet Patrice , Martin Cyril
Published: December 2019

The aim of the study was to examine the effects of endurance exercise on circulating vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without α-thalassemia. Five athletes with SCT, 7 athletes with both SCT and α-thalassemia (SCTAT) and 8 control athletes (CONT) performed an incremental test on cycloergometer followed 72 hours later by a 60-min endurance exercise with a workload set at 70% Ppeak (peak power). We assessed levels of sICAM-1, sVCAM-1 and TNF-α at rest, immediately after endurance exercise and 1, 2, and 24 hours of recovery. Although, CONT and SCTAT groups exhibited similar basal plasma levels of adhesion molecules and TNF-α, SCT group had higher sVCAM-1 basal concentrations. No significant variation in sVCAM-1, sICAM-1 and TNF-α was measured following endurance exercise. Consequently, sVCAM-1 remained elevated in the SCT group after exercise and during the recovery period. In conclusion, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances, but these adhesive processes were not further impaired in response to endurance exercise. In addition, α-thalassemia co existing trait may be protective both at rest and after endurance exercise in SCT subjects.
Improving effect of post-treatment with Panax notoginseng saponins on lipopolysaccharide-induced microcirculatory disturbance in rat mesentery
Authors: Yang Ji-Ying , Sun Kai , Wang Chuan-She , Guo Jun , Xue Xin , Liu Yu-Ying , Zheng Jun , Fan Jing-Yu , Liao Fu-Long , Han Jing-Yan
Published: December 2019

Panax notoginseng saponin (PNS) is the collective of the major effective components of Panax notoginseng. The present study intended to explore the effect of post-treatment of PNS on rat mesentery microcirculatory disturbance induced by lipopolysaccharide (LPS) continuous challenge. By virtue of a microcirculation observation system, the vascular hemodynamics were determined continuously until 60 min of LPS (2 mg/kg/h) infusion through the left femoral vein. After observation, blood was taken for assessment of the expression of CD11b/CD18 in neutrophils and the concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interferon-gamma (INF-γ) in plasma with flow-cytometry. The number of leukocytes adherent to venular wall, the intensity of hydrogen peroxide dependent dihydrorhodamine 123 (DHR) fluorescence in the venular walls and albumin leakage from venules were increased impressively after 20 min of LPS infusion, the RBCs velocity diminished after 30 min, and degranulated mast cells increased remarkably after 60 min. Post-treatment with PNS (5 mg/kg/h) through the left jugular vein from 20 min of LPS exposure resulted in significant reduction in the number of adherent leukocytes, degranulation of mast cell, expression of CD11b and the concentration of IL-6, INF-γ, while had no influence on the intensity of DHR fluorescence and albumin leakage. The results suggested that post-treatment with PNS significantly attenuated microcirculatory disturbance induced by LPS.
Ischaemic postconditioning reduces peroxide formation, cytokine expression and leukocyte activation in reperfusion injury after abdominal aortic surgery in rat model
Authors: Sínay L. , Kürthy M. , Horváth Sz. , Arató E. , Shafiei M. , Lantos J. , Ferencz S. , Bátor A. , Balatonyi B. , Verzár Zs. , Sütő B. , Kollár L. , Wéber Gy. , Rőth E. , Jancsó G.
Published: December 2019

Objective: We studied the protective effects of ischaemic postconditioning (PS) on ischemia–reperfusion injury of the lower extremities in a rat model of abdominal aortic intervention. We aimed to examine the evoked oxidative stress, cytokine expression and leukocyte activation after revascularisation surgery.

Methods: Anesthetized animals (48 Whistar rats) underwent a 60 min infrarenal aorta cross-clamping. After the ischaemic period, an intermittent 4 times 15 s reperfusion – 15 seconds ischaemic episodes – were applied (ischaemic postconditioning: group PS). Then we started a 120 min reperfusion in the aorta. In untreated group animals underwent a long ischaemia (60 min) and the following reperfusion (group IR). Peripherial blood samples were collected before operation, and in early (5, 10, 15, 30, 60 and 120 min) reperfusion periods. Serum peroxide level, TNF-alpha concentration, myeloperoxidase (MPO) activity and PMA-induced leukocyte ROS production were measured.

Results: In PS group, plasma peroxide level elevation was significantly lower in very early reperfusion (5–30 min) comparing to non-conditioned IR group (10.04±1.9 μM/l vs. 16.91±3.67 μM/l, p<0.05). PS also reduced serum TNF-alpha concentration (167.41±31.26 μg/ml vs. 116.55±12.04 μg/ml, p<0.05), MPO activity (1.759±0.239 μM/ml vs. 1.22±0.126 μM/ml, p<0.05) and leukocyte activation detected by PMA-induced leukocyte ROS production (5.7±0.96 AU/103 cells vs. 4.63±0.69 AU/103 cells).

Conclusions: Ischaemic postconditioning could reduce ROI production after IR in early reperfusion period, thus limiting ROI mediated tissue lesion, cytokine–leukocyte activation and inflammatory responses. PS seems to be an effective tool in vascular surgery to reduce reperfusion injuries after revascularization interventions.
Nitric oxide metabolites (nitrite and nitrate) in young patients with recent acute myocardial infarction
Authors: Caimi Gregorio , Montana Maria , Calandrino Vincenzo , Caruso Marco , Carollo Caterina , Catania Anna , Lo Presti Rosalia
Published: December 2019

Nitric oxide (NO) has a role in the pathophysiology of acute and chronic cardiovascular events. We studied the plasma concentration of NO stable end products (nitrite and nitrate – NOx) in 43 patients aged <46 years, with recent acute myocardial infarction (AMI). The evaluation was effected at the initial stage, after 3 and 12 months. We subdivided the patients into subgroups according to the number of the main cardiovascular risk factors and to the extent of coronary disease. In the whole group the NOx concentration was initially increased and progressively decreased after 3 and 12 months, remaining at both times significantly higher than in control subjects. The patients with more risk factors had a significantly higher NOx concentration. In conclusion, the persisting high NOx concentration in AMI patients is the expression of a prolonged inflammatory condition and is significantly influenced by the simultaneous presence of several cardiovascular risk factors.
Non-neuronal cholinergic system and signal transduction pathways mediated by band 3 in red blood cells
Authors: Carvalho Filomena A. , Almeida José Pedro , Fernandes Isabel O. , Freitas-Santos Teresa , Saldanha Carlota
Published: December 2019

Background: Non-neuronal acetylcholine (ACh) and acetylcholinesterase (AChE) have been recognized in the past. Vascular ACh has been associated by us with the regulation of microcirculatory flow by modulating nitric oxide (NO) intracellular mobilization, metabolism (NOx) and release from erythrocytes, as well as the glycolytic flux. Velnacrine maleate is a well-known AChE inhibitor which plays a competitive role by decreasing NO-mediated erythrocyte responses. A plausible hypothesis to explain the mechanisms underlying those events hinges on the NO translocation among nitrosylated molecules and phosphorylated/dephosphorylated states of band 3 protein, processed by major tyrosine-kinases (PTK: p72syk, p53/56lyn and p59/61hck) and phosphotyrosine-phosphatases (PTP).

Methods: To assess this hypothesis under the influence of AChE effectors (acetylcholine/velnacrine), blood samples from healthy donors were harvested and Western blot analysis was subsequently used to determine the degree of band 3 phosphorylation, in the presence and absence of PTK/PTP inhibitors. NO and nitrites/nitrates were quantified using an amperometric method and the Griess Reaction, respectively, in erythrocyte suspensions. Measurements of erythrocyte metabolites (2,3-bisphosphoglycerate; glyceraldehyde 3-phosphate dehydrogenase; glucose-6-phosphodehydrogenase; lactate), hemoglobin and cyclic nucleotides were conducted afterwards.

Results: Increased levels of phosphorylated-band 3 obtained upon p72syk inhibition suggest p59/61hck and p53/56lyn as secondary involved kinases. As to NO/NOx quantification, in the presence of PTKi we reported higher levels with velnacrine-AChE, as opposed to acetylcholine-AChE. Calpeptin, a PTP inhibitor which triggers full band 3-phosphorylation, led to the opposite NO mobilization, being reinforced by ACh. Oxy-hemoglobin, glyceraldehyde 3-phosphate dehydrogenase and glucose-6-phosphodehydrogenase were found to decrease with ACh, whereas P50, lactate and both cGMP/cAMP happened to increase.

Conclusion: Changes on human erythrocyte NO(x) mobilization and metabolic fluxes occur under influence of non-neuronal ACh/AChE, in turn dependent on the degree of band 3-phosphorylation. Since these vascular events may potentially change under pathological conditions, coadjuvant drugs could become accessible in the setting of microcirculation disease.
Hemorheological changes after intravenous gammaglobulin administration in patients with neurological disorders
Authors: Kowal Piotr , Zmyślony Anna
Published: December 2019

Hemorheological changes due to intravenous gammaglobulin (IVIg) administration have been considered to influence blood viscosity and this way the blood flow in microcirculation.

The study was carried out in the group of 10 patients with various neurological disorders (seven with polyradiculoneuropathy, two suffering from myasthenia and one with multiple sclerosis). Patients were treated routinely with intravenous gammaglobulin infusion (Sandoglobulin, Sandoz, 24 g a day in the course of 5 days therapy). The following hemorheological factors were estimated: relative blood viscosity, plasma viscosity, red cell deformability and erythrocytes aggregation. For rheological examination the microviscosimeter Low Shear 40 (Contraves) was used. Each patient was examined two times: before treatment initiation and at the end of therapy after five days.

At the comparison of first and last measurements a significant increase of plasma viscosity (p<0.04) was found, whereas erythrocyte deformability was significantly improved (p<0.05). The value of relative blood viscosity at shear rate of 0.1 s−1 was significantly decreased (p<0.05) and statistically unchanged at other studied shear rates.

The results suggest an existence of a protective feedback mechanism in the studied group of patients which has been exemplified by the red cell elasticity improvement.
Influence of hypercholesterolemia on deformability and shape parameters of erythrocytes in hyperglycemic subjects
Authors: Babu N.
Published: December 2019

The main objective of the present work is to study the influence of cholesterol in hyperglycemic subjects on deformability and shape parameters of erythrocytes. The deformability of erythrocytes in blood samples of diabetic patients with normal cholesterol (group A) and diabetes with hyper cholesterol (group B) concentration are determined by optical hemorheometer and are compared with healthy subjects. The deformability is measured by passing laser light through erythrocyte suspension in physiological saline while filtration of erythrocytes through cellulose micro pore membrane. Blood samples of 5% hematocrit were prepared in physiological saline for control subjects and diabetes mellitus with normal and hyper cholesterol subjects for deformability measurements. The shape analysis is carried out by shape descriptors based on projected area, perimeter and form factor, as measured by processing of images of erythrocytes. Deformability was reduced in diabetes with normal cholesterol and much reduced significantly in diabetes with hyper cholesterol comparing to healthy subjects was found. The shape descriptor form factor, as determined by processing of erythrocyte images, increases in diabetes with normal cholesterol and further increases in diabetes with hyper cholesterol compare to healthy subjects and shows a pattern similar to filtration time of erythrocyte suspensions through cellulose membranes. This significant decrease in deformability and increase in shape parameters in diabetes with hyper cholesterol may increase the microcirculatory complications compare to diabetes with normal cholesterol.
Contrast-enhanced ultrasound in liver transplant: First results and potential for complications in the postoperative period
Authors: Clevert D.-A. , Stickel M. , Minaifar N. , Löhe F. , Graeb C. , Jauch K.W. , Reiser M.
Published: December 2019

Purpose: This study compared the efficacy of contrast-enhanced ultrasound (CEUS) using a second generation contrast medium versus CT or MRA in the assessment of vascular and biliary complications in postoperative follow-up of liver transplantation.

Methods and materials: The study group consisted of 36 consecutive liver transplant recipients who underwent post-transplantation CEUS examination after developing ascites and/or unclear liver function tests. Real time CEUS was performed after a bolus injection of SonoVue® (1.6–2.4 ml, Bracco, Imaging Germany) followed by 10 ml of saline solution. Using contrast harmonic imaging (CHI) technique (Logiq 9, GE) with a 2.5–4-MHz transducer, a low mechanical index was chosen to avoid early destruction of the microbubbles (MI 0.1–0.2). In order to confirm the results, the patients underwent contrast-enhanced MRI or CT.

Results: Complications were identified in 16 of 36 patients (44.4%). Five transplants (14%) had hepatic artery thrombosis (n=2) or significant stenosis (n=3). Six transplants (16%) developed portal vein stenosis (n=4) or portal vein thrombosis (n=2). MRI or CT confirmed the findings of the CEUS in all 11 cases. Biliary stricture at the anastomotic site was detected in 5 patients. MR-CP confirmed the findings of all strictures.

Conclusion: Due to advances in contrast-enhanced US, vascular and biliary complications in the postoperative period following liver transplantation can be reliably diagnosed non-invasively on the intensive care unit. CEUS shows vascular as well as biliary complications in the postoperative patient with a high degree of accuracy.
Contrast harmonic imaging ultrasound and perfusion imaging for surveillance after endovascular abdominal aneurysm repair regarding detection and characterization of suspected endoleaks
Authors: Pfister K. , Rennert J. , Uller W. , Schnitzbauer A.A. , Stehr A. , Jung W. , Hofstetter P. , Zorger N. , Kasprzak P.M. , Jung E.M.
Published: December 2019

Objective: Is Contrast Harmonic Imaging (CHI) comparable to computed tomography angiography (CTA) scan in detecting and characterizing suspected endoleaks after endovascular abdominal aneurysm repair in a non-selected group including reintervention procedure and branched endografts in daily practice?

Material/methods: In a prospective study computed tomography angiography (CTA) and contrast-enhanced ultrasound (CEUS) were performed in 30 consecutive patients (26 males, 4 females, mean age: 72 years, range: 38–87) with suspected endoleaks in follow-up (mean 13 months, range: 1–95) after endovascular abdominal aneurysm repair or procedure in dissection or penetrated ulcer of the aorta (25 infrarenal, 5 suprarenal stent grafts, mean aortic diameter 56 mm, range: 27–98). CTA was supposed to be gold standard for determining the presence of endoleaks (multislice CT, collimation 16 × 0.75 mm, 100 ml of iodized contrast agent bolus). Ultrasonography used a multi-frequency probe (1–4 MHz) with the modalities of colour coded Doppler sonography (CCDS), power Doppler (PD) combined with contrast enhancement and the technique of contrast harmonic imaging (CHI) and low mechanical index (MI < 0.2). 2.4 ml of SonoVue® (Bracco, Altana Pharma GmbH, Italy) were administered to each patient intravenously as a bolus injection.

Results: Out of 30 patients, 21 endoleaks were identified in CTA (6 type I or III, 15 type II), 22 in CHI. Thus, sensitivity for CHI was therefore 99%, its specificity 85% (Spearman correlation coefficient (CC) 0.92). In follow-up the localizations of endoleak type I or III exclusively detected by CHI were confirmed as true positive by angiography. Due to its dynamic characteristic CHI seemed to be more helpful in characterization of endoleaks than CTA. In case of a rupture after reintervention a type III endoleak leads to prompt intervention before receiving the result of the CT scan. Altogether, CHI failed to identify 1 combined type I and II endoleak (sensitivity 0.99). Both, CCDS and PD were positive only in 6/30 patients (CC 0.33 and 0.39). Interestingly the application of contrast agent doubles the detection rate of endoleaks (12/30) in CCDS and PD (CC 0.39).

Conclusion: Contrast harmonic imaging (CHI) compared to computed tomography angiography (CTA) accurately depicts endoleaks after endovascular abdominal aneurysm repair and stent-graft procedure in dissected and ulcerated aorta. It seems to be superior in characterization of the type of endoleaks and can be established in order to reduce iodized contrast agent and radiation exposure in follow-up. In contrast to CTA scan CHI can be offered to patients with chronic renal insufficiency and allows a dynamic examination and a perfusion analysis.
Cardiovascular benefits in moderate increases of blood and plasma viscosity surpass those associated with lowering viscosity: Experimental and clinical evidence
Authors: Salazar Vázquez B.Y. , Martini J. , Chávez Negrete A. , Tsai A.G. , Forconi S. , Cabrales P. , Johnson P.C. , Intaglietta M.
Published: December 2019

Decreasing blood viscosity has been proposed since the advent of hemodilution as a means for increasing perfusion in many pathological conditions, and increased plasma viscosity is associated with the presence of pathological conditions. However, experimental studies show that microvascular functions as represented by functional capillary density in conditions of significantly decreased viscosity is impaired, a problem corrected by increasing plasma and blood viscosity. Blood viscosity, primarily dependent on hematocrit (Hct) is a determinant of peripheral vascular resistance, and therefore blood pressure. In the healthy population Hct presents a variability, which is not reflected by the variability of blood pressure. This is due to a regulatory process at the level of the endothelium, whereby the increase of Hct (and therefore blood viscosity) leads to increased shear stress and the production of the vasodilator nitric oxide (NO), a finding supported by experimental studies showing that the acute increase of Hct lowers blood pressure. Studies that in the healthy population show that blood pressure and Hct have a weak positive correlation. However, when the effect of blood viscosity is factored out, blood pressure and Hct are negatively and significantly correlated, indicating that as blood viscosity increases, the circulation dilates. Conversely, lower Hct and blood viscosity conditions lead to a constricted circulation, associated with a condition of decreased NO bioavailability, and therefore a pro-inflammatory condition.
Role of plasma proteins in whole blood viscosity: A brief clinical review
Authors: Kwaan Hau C.
Published: December 2019

Whole blood viscosity is affected by a number of factors, among which plasma proteins are a major component. They exert their effects either directly or through their influence on red cell aggregation. Changes in fibrinogen and in immunoglobulins, under both physiologic and pathologic conditions can increase whole blood viscosity. Blood flow through the microvasculature is impaired when viscosity increases, leading to tissue ischemia and a syndrome complex usually referred to as the hyperviscosity syndrome. Abnormalities of fibrinogen greatly increase its ability to cause red cell aggregation, and is a contributory pathogenic factor in ischemic heart disease and stroke. Immunoglobulins may affect blood viscosity directly, or by increasing the red cell aggregation. Changes are seen in many clinical disorders, ranging from inflammatory diseases to plasma cell dyscrasias. The clinical manifestations may be mild and often unnoticed, or they may be life threatening requiring emergency plasmapheresis. Proper management requires a clear understanding of the underlying pathology. When the symptom complex indicates a high probability of the hyperviscosity syndrome, it should lead to early diagnosis and treatment. Therapeutic approaches should include both removing the abnormal plasma protein and treating the primary cause.
Adenosine transport, erythrocyte deformability and microvascular dysfunction: An unrecognized potential role for dipyridamole therapy
Authors: Bhavsar Jignesh , Rosenson Robert S.
Published: December 2019

Reperfusion injury and no-reflow phenomenon are known entities that contribute to persistent impairment in myocardial perfusion and regional myocardial dysfunction following restoration of epicardial coronary blood flow after a myocardial infarction. Following prolonged ischemia, oxidative stress and inflammation-mediated alterations in erythrocyte mechanics and microvascular architecture play a major role in ischemia/reperfusion injury and no-reflow phenomenon. An increase in red cell rigidity is an important rheological aspect of RBCs, which facilitates platelet aggregation with the subendothelium. Dipyridamole inhibits the reuptake of adenosine which causes platelet inhibition and vasodilatation. Dipyridamole improves microvascular function by increasing RBC deformability and reducing blood viscosity. In addition, it has anti-oxidant and anti-inflammatory properties that provide protection to the microvasculature. This review discusses the potential role for dipyridamole therapy in the treatment of microvascular dysfunction.
Blood lactate and pyruvate levels in the perioperative period of liver resection with pringle maneuver
Authors: Pietsch Uta-Carolin , Herrmann Marie-Luise , Uhlmann Dirk , Busch Thilo , Hokema Frank , Kaisers Udo X. , Schaffranietz Lutz
Published: December 2019

Introduction: Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery, portal vein, and bile duct. This study aimed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection. Methods: Twenty-five consecutive patients undergoing elective liver resection were prospectively randomized either to be treated with the Pringle maneuver (Pringle group, n = 14) or without clamping (Controls, n = 11). Blood lactate levels, pyruvate levels, and hepatic vein oxygen saturation were monitored perioperatively. Results: Patients were comparable with respect to resection time, intraoperative blood loss, and duration of surgery. The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls (2.6 ± 0.3 vs 1.8 ± 0.2 mmol/l; p < 0.05). Further, the Pringle maneuver significantly increased hepatic venous lactate (3.3 ± 0.3 vs 1.6 ± 0.3 mmol/l; p < 0.05) and lactate/pyruvate ratio in hepatic venous blood (43 ± 8 vs 21 ± 5; p < 0.05) during surgery. This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group (61 ± 4 vs 73 ± 4%; p < 0.05). Conclusion: Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus. Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection.
Calcitonin gene-related peptide, substance P, nitric oxide and epinephrine modulate bone marrow micro circulation of the rabbit tibia and femur
Authors: Vendégh Zsolt , Melly András , Tóth Balázs , Wolf Konrad , Farkas Tamás , Kádas István , Hamar János
Published: December 2019

Different bones have different blood supplies, which may influence bone healing. Therefore, elucidation of the mechanisms involved in the regulation of bone marrow blood flow in different bones is of high clinical importance. To assess the micro circulation of bone marrow of the femur and tibia simultaneously, flow velocities were continuously measured by a two-channel laser-Doppler flowmeter. The probes were introduced into the femoral and tibial diaphysis, respectively, in the anesthetized rabbit. Changes in micro circulation of the bone marrow were elicited by intra-arterial bolus injections of vasoactive substances: epinephrine (E), calcitonine-gene related peptide (CGRP), substance P (SP), sodium nitroprusside (SNP), E and Ebrantil. Systemic arterial blood pressure was recorded with an electro-manometer. Micro vascular resistance (MVR) and 50% recovery time (50RT) to baseline flow level were calculated from the measured data. Flow velocity in the femur was significantly higher. Epinephrine considerably reduced micro vascular blood flow, which could be significantly warded off by Ebrantil. CGRP and SP did not change MVR. Application of SNP resulted in reduction of flow velocity, but it also decreased MVR. No statistically significant differences were found between reactions of the micro circulation in the two marrows. These results suggest that there are no significant differences between the blood flow response patterns of these two bone marrow sites, thus the regulation patterns of the micro circulation of the two bones are also similar.
Interrelationships between lipid peroxidation and total antioxidant status in sedentary controls and unprofessional athletes
Authors: Caimi Gregorio , Canino Baldassare , Presti Rosalia Lo
Published: December 2019

We examined the thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation, and the total antioxidant status (TAS) in 81 unprofessional athletes subdivided into three subgroups. The first group included 28 subjects who practised endurance sports, the second included 30 subjects who practised mixed sports, the third included 23 subjects who practised power sports. We enrolled also a group of 61 sedentary controls (SC). TBARS were increased and TAS was decreased in the whole group of athletes in comparison with SC; an almost similar behaviour was present also subdividing athletes according to the practised sport. A significant negative correlation between these two parameters emerged in SC but not in the whole group of athletes. Unless for the athletes that practised endurance sports a similar trend was found in athletes that practised mixed and power sports. In conclusion, at rest the symmetrical behaviour between the lipid peroxidation increase and the TAS decrease, observed in sedentary controls, was not evident in unprofessional athletes who practised different sports.