Whole Blood Viscosity Research Articles

Comparative studies of the anti-thrombotic effects of saffron and HongHua based on network pharmacology

Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology.
 Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua.
 Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT.
 Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua.
 Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network model

Whole blood viscosity predicts nondipping circadian pattern in essential hypertension.

Aim: We aimed to investigate the association between whole blood viscosity (WBV) and nondipping pattern in patients with essential hypertension. Materials & methods: A total of consecutive 530 patients who had been evaluated by ambulatory blood pressure monitoring were included. WBV was estimated by using hematocritand plasma total protein levels for both WBV in low shear rate(0.5 s-1) and WBV in high shear rate(208 s-1) according to the de Simone's formula. Results: In the multivariate analysis, low shear rate and high shear rate of WBV were associated independently with nondipping pattern in patients with essential hypertension. Conclusion: As a simple, inexpensive andnoninvasive tool, WBV seems to be a significant predictor of nondipping hypertension.

Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease.

Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β‐globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale flow in whole blood samples from 53 individuals with no hemoglobinopathies (HbAA, N = 10), hemoglobin SC disease (HbSC, N = 14), or homozygous SCD (HbSS, N = 29) with mean WBV of 4.50 cP, 4.08 cP, and 3.73 cP, respectively. We found that WBV correlated with RBC count and hematocrit in subjects with HbSC or HbSS. There was a significant inverse association between WBV and RBC adhesion under both normoxic and physiologically hypoxic (SpO2 of 83%) tests, in which lower WBV associated with higher RBC adhesion to LN in subjects with HbSS. Low WBV has been found by others to associate with endothelial activation. Altered WBV and abnormal RBC adhesion may synergistically contribute to the endothelial damage and cumulative pathophysiology of SCD. These findings suggest that WBV and RBC adhesion may serve as clinically relevant biomarkers and endpoints in assessing emerging targeted and curative therapies in SCD.

Performance evaluation of the ZL 6000i cone-plate rotational viscometer

Elevated whole blood viscosity (WBV) is associated with increasing blood flow resistance in the microcirculation and is used to predict the occurrence and outcome of cardiovascular diseases. We evaluated the analytical performance of the ZL 6000i (Zonci Technology, Beijing, China), new fully automated cone-plate rotational type viscometer. We collected blood samples from 287 adults to establish a reference range. We evaluated total precision for 20 days using quality control (QC) samples and within-run precision was evaluated by performing 50 consecutive measurements of blood samples. Aliquots of blood samples were stored at room temperature and 5°C to assess the effect of storage time and temperature on viscosity measurement. The reference ranges and median values of WBV were significantly higher in males than in females due to difference in hematocrit level. The coefficients of variation (CVs) for precision using QC and human blood samples were < 7.5% at all shear rates. WBV of the samples stored at room temperature for up to 6 h, and at 5°C for samples stored up to 2 days was not different from the control. In this study, the ZL 6000i viscometer yields reproducible WBV data and is clinically useful for monitoring viscosity.

The association between thrombotic and inflammatory biomarkers and lower-extremity peripheral artery disease.

Lower-extremity peripheral artery disease (LEAD) is associated with increased rates of mortality and morbidity. The aim of this study was to evaluate the associations among inflammatory and thrombotic markers and lower-extremity peripheral disease. A total of 280 patients were enrolled in this study. Of these patients, 152 patients had LEAD on peripheral angiography that was performed because of suspected lower-extremity peripheral disease based on history, physical examination, and non-invasive tests. The control group consisted of 128 patients without LEAD on peripheral angiography. Patients with LEAD were classified according to trans-atlantic inter-society consensus (TASC) II classification. Subsequently, patients in TASC A to B were defined as having mild to moderate peripheral artery disease, and those in TASC C to D were defined as having advanced peripheral artery disease. Thrombotic and inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the high-sensitivity C (hs-C) reactive protein level, the monocyte-to-high-density lipoprotein-cholesterol ratio, the fibrinogen to albumin ratio (FAR), and whole-blood viscosity at high shear rate (HSR) and low shear rate (LSR), were evaluated in this population. The NLR, the monocyte-to-high-density lipoprotein-cholesterol ratio, the FAR, and whole-blood viscosity, both at a LSR and a HSR, were significantly higher in patients with lower-extremity peripheral disease compared with patients without lower-extremity peripheral disease. We determined that lower-extremity peripheral disease severity was correlated with the NLR, monocyte-to-high-density lipoprotein-cholesterol ratio, FAR, whole-blood viscosity at LSR, and whole-blood viscosity at HSR (r = 0.719, P = .004; r = 0.25, P = .008; r = 0.691, P = .002; r = 0.546, P < .001; and r = 0.448, P = .001, respectively). However hs-C reactive protein levels were similar between patients with or without LEAD (2.47 ± 1.32 1.61 ± 0.91 P = .685). In addition, there was no correlation between the severity of LEAD and hs-C reactive levels. In this study, we determined that the levels of inflammatory and thrombotic biomarkers are elevated in peripheral artery disease, and these levels predict disease severity.

Viscosity Measurement of Whole Blood with Parallel Plate Rheometers

There are many factors that affect the increase or decrease of viscosity of the whole blood. Because of this, measuring the viscosity of whole blood is difficult to correlate with specific etiologies, so it tends to disregard the information on blood viscosity. This study is to find out the characteristics of the method of measuring the viscosity of whole blood using the parallel plate method, which is officially registered as a medical device with the approval of the Korea Food and Drug Administration (KFDA), and to apply it to the measurement of whole blood viscosity. The accuracy of the parallel plate measurement is verified by comparing with the measurement results using the commercially available scanning capillary method. In addition, statistically meaningful results are obtained between the viscosity and some components of the whole blood. It is expected that the research will be carried out to understand the correlation between the viscosity of whole blood and specific components of blood and to identify the prognostic signs of etiology in certain diseases, especially in cardiovascular and cerebral vessels diseases.

The Relationship between Blood Viscosity and Acute Arterial Occlusion

Abstract Background: Blood viscosity is a strong predictor of cardiovascular events. However, the relationship between blood viscosity and acute arterial occlusion (AAO) has not been studied adequately so far. Objectives: The aim of the present study was to assess the relationship between whole blood viscosity (WBV) and AAO. Material and methods: The study included 93 patients who were diagnosed with AAO between January 2017 and September 2019, and 90 age- and sex-matched healthy controls. WBV was assessed using a validated calculation formula derived from hematocrit and total plasma protein levels, both as a low (LSR) and a high (HSR) shear rate. Results: There were no significant differences between the two groups in regards to the baseline characteristics, with the exception of smoking and LDL cholesterol levels. Subjects with AAO presented significantly higher WBV values both at LSR (32.2 ± 5.0 vs. 26.6 ± 5.0, p &lt;0.001) and HSR (6.2 ± 0.3 vs. 5.7 ± 0.3, p &lt;0.001). The ROC analysis revealed a cut-off value of 27.4 for WBV at LSR (sensitivity 66%, specificity 64%, AUC = 0.770, p &lt;0.001) and a cut-off value of 5.29 in case of HSR (sensitivity 69%, specificity 74%, AUC = 0.801, p &lt;0.001) for predicting AAO. Multivariate analysis, both LSR (OR 3.33, 95% CI: 1.20–9.43, p = 0.006) and HSR (p = 0.020, OR: 1.70, 95% CI: 1.020–1.123) were independent predictors of AAO. Conclusions: This study demonstrated that WBV levels at both HSR and LSR are significantly higher in the AAO group than in the control subjects, indicating that an increased WBV may be associated with the development of AAO.

Recanalization of Embolized Endovascular Intracranial Aneurysms and Changes in the Blood Viscosity: A Pilot Study.

BackgroundThe purpose of our research was to evaluate the relationships between blood viscosity and recanalization of coiled intracranial aneurysms.Material/MethodsThe study included consecutives patients treated endovascularly by a team of experienced neurosurgeons and neuroradiologists due to brain aneurysm. A total of 50 patients (the average age was 57.48 years, SD=13.71) were assigned to 2 groups: group A with recanalization (4 male and 8 female patients) and group B without recanalization (10 male and 28 female patients) were examined. All patients underwent a 6-month follow-up of the whole-blood viscosity test with a Brookfield DV III+pro cone-plate viscometer using the Rheocalc program. Differences between groups were assessed using the Statistica 12 computer program (StatSoft Inc., Tulsa, OK, USA).ResultsStudies have shown no significant difference in the age range between group A and B (P=0.31). In group A, higher viscosity values were found for whole blood [median: 4.14 dyn×sec/cm2 (mPa×sec) quartile range 0.42], compared to group B [median: 3.92 dyn×sec/cm2 (mPa×sec); quartile range 0.40; (P=0.04)]. This difference was significant (P=0.04). Additionally, the level of hematocrit was positively related with recanalization, the higher the hematocrit, the more frequent recanalization. A very strong and statistically significant relationship occurred between the frequency of recanalization and smoking (P<0.001).ConclusionsThe occurrence of higher values of whole blood viscosity which increase turbulent flow through the vessels may be a risk for recanalization of the coiled intracranial aneurysm.

Relationship between apical thrombus formation and blood viscosity in acute anterior myocardial infarction patients.

Aim: This study sought to investigate the predictive value of whole blood viscosity (WBV) to identify high-risk patients who will develop an apical thrombus during the acute phase of anterior transmural infarction. Materials & methods: Consecutive 1726 patients with first acute anterior myocardial infarction were evaluated. WBV was calculated according to the Simone's formula. Results: Patients with an apical thrombus had prolonged pain to balloon time, higher rate of post-PCI thrombolysis in myocardial infarction flow ≤1 and significantly higher mean WBV values at both shear rates than those without an apical thrombus. Conclusion: WBV values at both shear rates were found to be significant and independent predictors for early LV apical thrombus formation complicating a first-ever anterior wall myocardial infarction.

Intraoperative changes in whole-blood viscosity in patients undergoing robot-assisted laparoscopic prostatectomy in the steep Trendelenburg position with pneumoperitoneum: a prospective nonrandomized observational cohort study

BackgroundThe aim of this study was to investigate the effect of the steep Trendelenburg position (STP) with pneumoperitoneum on whole-blood viscosity (WBV) in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). The study also analyzed the associations of clinical patient-specific and time-dependent variables with WBV and recorded postoperative outcomes.MethodsFifty-eight adult male patients (ASA physical status of I or II) undergoing elective RALP were prospectively analyzed in this study. WBV was intraoperatively measured three times: at the beginning of surgery in the supine position without pneumoperitoneum; after 30 min in the STP with pneumoperitoneum; and at the end of surgery in the supine position without pneumoperitoneum. The WBV at a high shear rate (300 s− 1) was recorded as systolic blood viscosity (SBV) and that at a low shear rate (5 s− 1) was recorded as diastolic blood viscosity (DBV). Systolic blood hyperviscosity was defined as > 13.0 cP at 300 s− 1 and diastolic blood hyperviscosity was defined as > 4.1 cP at 5 s− 1.ResultsThe WBV and incidences of systolic and diastolic blood hyperviscosity significantly increased from the supine position without pneumoperitoneum to the STP with pneumoperitoneum. When RALP was performed in the STP with pneumoperitoneum, 12 patients (27.3%) who had normal SBV at the beginning of surgery and 11 patients (26.8%) who had normal DBV at the beginning of surgery developed new systolic and diastolic blood hyperviscosity, respectively. The degree of increase in WBV after positioning with the STP and pneumoperitoneum was higher in the patients with hyperviscosity than in those without hyperviscosity at the beginning of surgery. Higher preoperative body mass index (BMI) and hematocrit level were associated with the development of both systolic and diastolic blood hyperviscosity in the STP with pneumoperitoneum. All patients were postoperatively discharged without fatal complications.ConclusionsChanges in surgical position may influence WBV, and higher preoperative BMI and hematocrit level are independent factors associated with the risk of hyperviscosity during RALP in the STP with pneumoperitoneum.Trial registrationClinical Research Information Service, Republic of Korea, approval number: KCT0003295 on October 25, 2018.

Whole blood viscosity is an independent early predictor for metabolic syndrome and its components in men: A prospective cohort study in Northern Chinese population.

The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men.

Alteration of hemostatic and hemorheological parameters in Nigerian patients with type 2 diabetes mellitus: Does age play a role?

Background: Diabetes mellitus has been associated with coagulation abnormalities characterized by decreased levels of antithrombin, protein C, increased concentrations of fibrinogen and von Willebrand factor, and alteration of hemorheological indices, which have been linked to the increased hyperviscosity state. The aim of this study was to determine the effect of age on hemostatic and hemorheological parameters in patients with type 2 diabetes mellitus. Materials and Methods: Eighty-four patients of 168 participants, aged 30–69 years, were recruited from the Metabolic Clinic of the University of Maiduguri Teaching Hospital, Borno State between January and December 2018, whereas the remaining 84, age- and sex-matched nondiabetic subjects resident in Maiduguri served as controls. Samples for platelet indices, fibrinogen concentration, hematocrit, relative plasma viscosity (RPV), whole blood viscosity (WBV), protein C, antithrombin, and d-dimer were analyzed using standard techniques. Results: The values of platelet indices, prothrombin time (PT), activated partial thromboplastin time (aPTT), protein C, antithrombin, d-dimer, fibrinogen, hematocrit, and RPV in diabetic patients with respect to different age groups showed no significance (P > 0.05). However, significantly lower levels of protein C, antithrombin and hematocrit, and significantly higher values of d-dimer, fibrinogen, and WBV were observed in patients with diabetes irrespective of the age compared to that of nondiabetic subjects (P < 0.05). Conclusion: Age had no influence on the values of platelet count, platelet indices, PT, aPTT, protein C, antithrombin III, d-dimer, fibrinogen, hematocrit, RPV, and WBV in patients with diabetes. However, patients with type 2 diabetes mellitus could be prone to thrombosis and increased fibrinolytic activity irrespective of their age.

Clinical Efficacy of Tonic Traditional Chinese Medicine Injection on Acute Cerebral Infarction: A Bayesian Network Meta-Analysis.

Western medicine (WM) has certain limitations in terms of treating acute cerebral infarction (ACI), while tonic traditional Chinese medicine injections (TCMIs) have been shown to have obvious clinical effects as an adjunct to WM for ACI. However, most randomized controlled trials (RCTs) to date have not performed direct comparisons of efficacy among tonic TCMIs. This study designed a Bayesian network meta-analysis (NMA) to explore the therapeutic effect of tonic TCMIs on ACI. A comprehensive search of RCTs of TCMIs combined with WM for ACI was conducted using electronic databases for studies dated from the start date of each database until February 2020. Stata 13.0 and ADDIS 1.16.7 software were used to plot and analyze the data. Sixty-six RCTs with a total of 5,989 patients involving 7 kinds of tonic TCMIs were included. Among TCMIs, Shenfu injection (SFI) + WM ranked first in terms of improving clinical efficacy and the activities of daily living (ADLs) rating and reducing interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. While Ciwujia injection (CI) + WM was the best choice for reducing neurological impairment and the high-cut viscosity of whole blood (HCV). Shenmai injection (SI) + WM had the greatest effects in terms of decreasing the levels of low-cut viscosity of whole blood (LCV), fibrinogen (FIB), and plasma viscosity (PV). Based on the cluster analysis of the clinical efficacy and the neurological impairment, CI + WM and Shenqifuzheng (SQI) + WM were the best options for treating ACI. With respect to adverse drug reactions (ADRs), 35 RCTs did not monitor ADRs during treatment. In conclusion, tonic TCMIs could assist WM in benefiting patients with ACI. However, due to the limitations of the current study, strict monitoring of ADRs and data from high-quality RCTs will be required in future to verify the advantage of TCMIs.

Protective effects of Naoxintong Capsule on rats with blood stasis syndrome

Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of cardiovascular diseases in clinic. The present study was designed to clarify the effects of NXT on haemorheology, blood coagulation, hepatic function, antioxidant capacity and inflammatory responses in a rat model of blood stasis syndrome. Rats were placed in ice-cold water for 5 min during the time interval of two adrenaline injections to induce blood circulation disorders after intragastric administration of 10 consecutive days. Blood was collected from abdominal aorta to determine whole blood viscosity (WBV), plasma viscosity (PV), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malonaldehyde (MDA), alanine transaminase (ALT), aspartate transaminase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), platelet activating factor (PAF). The results showed that NXT could significantly decrease the WBV, PV, FIB and prolong the APTT and PT. Meanwhile, NXT significantly decreased the serum contents of MDA, IL-1β, IL-6, ALT, AST and PAF, while elevating T-AOC and SOD levels. These results indicate that NXT could improve coagulation function, enhance antioxidant capacity and suppress inflammation, which might partly account for its mechanisms of action in preventing and treating cardiovascular diseases.

Deciphering the Active Compounds and Mechanisms of Qixuehe Capsule on Qi Stagnation and Blood Stasis Syndrome: A Network Pharmacology Study.

Background Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown. Methods A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH. Results QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS. Conclusion QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways.

BIOMARKERS OF DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and uncontrolled cutaneous and internal organs fibrosis. Diagnosis of SSc in an early phase can be difficult because of a lack of typical symptoms. The delay in diagnosis and treatment of SSc may lead to uncontrolled progression of the disease, thus identification of possible early indicators of skin and organ involvement to prevent their further damage is necessary. The aim of this study is to review the latest biomarkers of organ involvement in SSc. In patients with lung fibrosis lung-epithelial-derived surfactant protein (SP-D), the glycoprotein Krebs von den Lungen-6 (KL-6), and chemokine ligands 2, 4 and 18 (CCL2, CXCL4, CCL18) are elevated, while in patients with skin fibrosis serum levels of heat shock protein 27 (Hsp27), interleukin 16 (IL-16), and IgG-galactosylation ratio are increased. Adiponectin concentration is inversely correlated with the intensity of cutaneous fibrosis. Skin gene profiling also seems very promising. In patients with heart involvement increased serum levels of brain natriuretic peptide (BNP) are present, as well as raised Midkine and Follistatin-like 3 (FSTL3) proteins, ratios of Cu/Se and ceruloplasmin(CP) /Circulating selenoprotein P(SELENOP) and higher whole blood viscosity level. Elevated calprotectin levels are found in individuals with gastrointestinal involvement. Increased levels of chemerin and ARA autoantibodies are associated with renal involvement, whereas high levels of adhesion molecules are found in patients with scleroderma renal crisis (SRC). Currently there are no biomarkers in use that can specifically identify the early involvement of organs.

Curcumin, as a pleiotropic agent, improves doxorubicin-induced nephrotic syndrome in rats.

Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NS rats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.

Coagulant Effects and Mechanism of Schefflera heptaphylla (L.) Frodin.

Schefflera heptaphylla (L.) Frodin, are commonly used in anti-inflammatory, analgesic, traumatic bleeding and hemostasisas. In this paper, the coagulation effect of the ethanol extract (Set), ethyl acetate phase (Sea) and n-butanol phase (Sbu) was evaluated by prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen content (FIB) assays in vitro. Then, Three main lupanine triterpenes (compounds A–C) were isolated and identified from Sea and Sbu by a bioassay-guided method and their structure were identified as 3α-Hydroxy-lup-20(29)-ene-23, 28-dioic acid, betulinic acid 3-O-sulfate and 3α-Hydroxy-lup-20(29)-ene-23, 28-dioic acid 28-O-(α-l-rhamnopyranosyl(1→4)-O-β-d-glucopyranosyl(1→6))-β-d-glucopyranoside) by spectroscopic data analysis. Among of them, compound B was confirmed to have significant coagulant effect in vitro. Furthermore, the pro-coagulation mechanism of S. heptaphylla extracts and compound B were investigated by measuring whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentetion rate (ESR), pack cell volume (PCV), APTT, PT, TT, and FIB in vivo. Meanwhile, the levels of thromboxane B2 (TXB2), 6-keto prostaglandin F1α (6-keto-PGF1α), endothelial nitric oxide synthase (eNOS) and (endothelin-1) ET-1 were detected. The bleeding time (BT) was tested by tail bleeding method, which proved the traumatic bleeding and hemostasis activities of S. heptaphylla. The pharmacology experiments showed that the Set, Sea, Sbu and compound B has significant pro-coagulation effect. In addition, compound B might be the main constituent of pro-coagulation in S. heptaphylla These results could support the fact that S. heptaphylla could be used traditionally to cure traumatic bleeding, and the pro-coagulation effects were associated with the regulation of vascular endothelium active substance and hemorheology parameters.

Antihyperglycaemic, haemorheological and antioxidant activities of Lychnis chalcedonica L. extract in a streptozotocin-induced rat model of diabetes mellitus.

Background New therapeutic strategies, such as the use of agents to correct rheological disorders, are needed for the prevention and treatment of angiopathy in diabetic patients. The aim of this work was to study the antihyperglycaemic, haemorheologic and antioxidant activities of an extract from the flowering plant Lychnis chalcedonica L. (ELC) and 20-hydroxyecdysone using the streptozotocin-induced model of diabetic rats. Methods The streptozotocin-induced model of diabetes was produced using streptozotocin at a dose of 50 mg/kg (ip). Animals from the experimental groups were treated with ELC (150 mg/kg) or 20-hydroxyecdysone (1.1 mg/kg) intragastrically in 1% aqueous starch mucilage daily, for 14 days; rats of control groups received an equal volume of starch mucilage. The following parameters were measured: glucose concentration (GC) in blood, whole blood viscosity (WBV), conjugated dienes in RBC membranes. Macro- and microrheological indicators (viz. plasma viscosity, haematocrit, RBC aggregation (T1/2) and the RBC elongation index (EI)) were additionally measured in rats that received ELC, and in the control group. Results After treatment with ELC, the GC in rats was 19% lower than that in the control group (14.7 ± 0.9 mM compared to 18.2 ± 1.1 mM). Rats with streptozotocin-induced diabetes have hyperviscosity syndrome, which is characterized by increased WBV, increased RBC aggregation and decreased deformability. ELC treatment reduced WBV at shear rates of 10-90s-1 by 5-8%, and T1/2 and EI in the experimental group were 31% and 5-10% higher compared to the control group. 20-Hydroxyecdysone decreased WBV at shear rates of 10-90s-1 by 3-11%. Finally, ELC and 20-hydroxyecdysone lowered the content of conjugated dienes by 27% and by 26% compared to the control groups. Conclusion In the streptozotocin-induced diabetic rat model, ELC showed measurable antihyperglycaemic activity; ELC and 20-hydroxyecdysone demonstrated similar haemorheological, and antioxidant activities.

Usefulness of the whole blood viscosity to predict stent thrombosis in ST-elevation myocardial infarction.

Aim: This study sought to investigate the predictive value of estimated whole blood viscosity (WBV) for stent thrombosis (ST) in ST-elevation myocardial infarction (STEMI) patients who underwent percutaneous coronary intervention. Materials & methods: A total of 1720 STEMI patients treated with primary percutaneous coronary intervention were followed up for median 36.0 months. WBV was calculated according to the Simone's formula. Results: During follow-up period, 119 patients were diagnosed as 'definite' ST. The rate of ST was significantly higher in the high WBV group. In multivariate analysis, adjusted for other factors, higher WBV significantly increased risk of ST at both shear rates. Conclusion: Being an easily accessible and costless parameter, WBV seems to be an emerging predictor of ST in patients with STEMI.