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Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1 ). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s -1 . Erythrocyte rigidity index (T k ) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in T k in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased T k and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Devis Ozcelik reports financial support was provided by Istanbul University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant ( p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.

Blood is a highly complex fluid with rheological properties that have a significant impact on various flow phenomena. In particular, it exhibits a non-Newtonian elongational viscosity that is comparable to polymer solutions. In this study, we investigate the effect of three different anticoagulants, namely EDTA (ethylene diamine tetraacetic acid), heparin, and citrate, on the elongational properties of both human and swine blood. We observe a unique two stage thinning process and a strong dependency of the characteristic relaxation time on the chosen anticoagulant, with the longest relaxation time and thus the highest elongational viscosity being found for the case of citrate. Our findings for the latter are consistent with the physiological values obtained from a dripping droplet of human blood without any anticoagulant. Furthermore, our study resolves the discrepancy found in the literature regarding the reported range of characteristic relaxation times, confirming that the elongational viscosity must be taken into account for a full rheological characterization of blood. These results have important implications for understanding blood flow in various physiological, pathological and technological conditions.

Background: Mechanistic studies suggest that proprotein convertase subtilisin/kexin type 9 inhibitors can modulate inflammation., Methods: Double-blind, placebo-controlled trial randomized 41 ASCVD subjects with type 2 diabetes with microalbuminuria and LDL-C level >70 mg/dL on maximum tolerated statin therapy received subcutaneous evolocumab 420 mg every 4 weeks or matching placebo. The primary outcomes were change in circulating immune cell transcriptional response, lipoproteins and blood viscosity at 2 weeks and 12 weeks. Safety was assessed in all subjects who received at least one dose of assigned treatment and analyses were conducted in the intention-to-treat population., Results: All 41 randomized subjects completed the 2-week visit. Six subjects did not receive study medication consistently after the 2-week visit due to COVID-19 pandemic suspension of research activities. The groups were well-matched with respect to age, comorbidities, baseline LDL-C, white blood cell counts, and markers of systemic inflammation. Evolocumab reduced LDL-C by -68.8% (p < 0.0001) and -52.8% (p < 0.0001) at 2 and 12 weeks, respectively. There were no differences in blood viscosity at baseline nor at 2 and 12 weeks. RNA-seq was performed on peripheral blood mononuclear cells with and without TLR4 stimulation ("Stress" transcriptomics). "Stress" transcriptomics unmasked immune cell phenotypic differences between evolocumab and placebo groups at 2 and 12 weeks., Conclusions: This trial is the first to demonstrate that PCSK9 mAB with evolocumab can modulate circulating immune cell properties and highlights the importance of "stress" profiling of circulating immune cells that more clearly define immune contributions to ASCVD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Rosenson reports research funding to his institution from Amgen, Arrowhead, Eli Lilly, Merck, Novartis, Novo Nordisk, and Regeneron, consulting fees from Amgen, Arrowhead, Avilar Therapeutics, CRISPER Therapeutics, Eli Lilly, Lipigon, Novartis, Precision BioSciences, Regeneron, UltraGenix, and Verve Therapeutics, royalties from Wolters Kluwer (UpToDate), and stock holdings in MediMergent, LLC. Provisional patents: PCT/US2019/026364, PCT/US2020/63104926, PCT/US2021/63248837. Dr. Goonewardena reports provisional patents PCT/US2019/026364, PCT/US2020/63104926. The other authors have no relevant disclosures., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of low-dose aspirin combined with vitamin E on the incidence of intrauterine growth restriction and hemorheological indexes of pregnant women in patients with gestational hypertension., Method: 134 elderly patients with chronic urticaria treated in our hospital from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation and control groups. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7 ± 2.75) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3 ± 3.17) years. No significant difference was observed between the two groups ( P > 0.05)., Results: The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. There were significant differences in the above results ( P < 0.05). The number of patients with preterm birth in the observation group was less than that in the control group, but there was no significant difference in the results ( P > 0.05). The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter in the control and observation groups increased significantly after treatment ( P < 0.05). Compared with the control group, the head circumference, abdominal circumference, biparietal diameter, and femoral diameter in the observation group increased more after treatment, and the results were statistically poor ( P < 0.05). The systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment. The results were statistically different ( P < 0.05). The plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different ( P < 0.05). The control and observation groups' fetal systolic/diastolic pressure and pulsatile index decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically poor ( P < 0.05)., Conclusion: Low-dose aspirin combined with vitamin E is effective in treating intrauterine growth restriction in patients with gestational hypertension. It can effectively control the blood pressure and blood flow of patients and newborns and improve pregnancy outcomes without increasing the incidence of adverse reactions. It is worthy of clinical promotion., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Tengfei Shan et al.)

Purpose: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied., Methods: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography., Results: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001)., Conclusion: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammation and oxidative stress play a key role in the pathophysiology of sickle cell disease (SCD). However, the potential influence of different sickle genotypes, or hydroxyurea (HU) treatment, on these factors remains poorly documented. The present study compared several plasma markers of inflammation and oxidative stress, as well as microvascular function, between patients with sickle SC disease (HbSC, n = 19) and patients with sickle cell anemia (HbSS) under hydroxyurea (HU) treatment (n = 16), or not (n = 13). Hemorheological parameters and levels of inflammatory (IL-6, IL-8, IFN-γ, MCP-1, MIP-1β, TNF-α) and oxidative stress (AOPP, MDA, MPO) markers were determined. Peripheral microcirculatory cutaneous blood flow and immediate microvascular response to local heat were evaluated using laser Doppler flowmetry. Oxidative stress and inflammation were lower in HbSC patients and HbSS patients under HU therapy compared to HbSS patients not treated with HU. Blood viscosity was higher in HbSC than in HbSS patients treated with or not with HU. Vasodilation response of the cutaneous microcirculation to heat stress was higher in HbSS patients receiving HU treatment. Our results clearly established that both sickle cell genotype and HU treatment modulate inflammation and oxidative stress., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti-factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site., (© 2020, The American College of Clinical Pharmacology.)

Ethnopharmacological Relevance: Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed., Materials and Methods: The "compound-target-cell-disease" network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model., Results: Through the "compound-target-cell-disease" network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3'-O-gallate, torachrysone-8-O-beta-D-(6'-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB., Conclusions: This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Panacis majoris Rhizoma, which is a member of herbal medicine, is known for many years to remove blood stasis, promote blood circulation, and enrich the blood. The active ingredients of this plant are mainly attributed to saponins., Aim of the Study: The total saponins from Panacis majoris Rhizoma (TSPJ), and the degradation products of TSPJ (DTSPJ), were designed in this study to compare the protective effects on myocardial ischemia-reperfusion injury, and the aim of this approach is to discover more effective agents for the treatment of ischemic heart diseases. We analyzed the main constituents of TSPJ and DTSPJ, aiming to make clear which saponins played important roles in this protective effect, and also investigated the possible mechanisms., Materials and Methods: DTSPJ was prepared by the method of alkaline hydrolysis. High performance liquid chromatography (HPLC) were used to analyze the main chemical constituents of TSPJ and DTSPJ, which were isolated by chromatographic techniques and identified by comparison with the Nuclear Magnetic Resonance (NMR) data in reported literature. Male Wistar rats were randomized to sham-operated group, ischemia-reperfusion group, three TSPJ (50, 100 and 200 mg/kg) groups, three DTSPJ (50, 100 and 200 mg/kg) groups, and isosorbide dinitrate tablet (5.0 mg/kg) group. The rats in all groups were intragastrically administrated once per day for three successive days. The establishment of the model of myocardial ischemia-reperfusion injury was used the following method: firstly, the left coronary artery of experimental rat was ligated for 30 min and then reperfused for 120 min. Then the myocardial infarct size, hemorheological and biochemical parameters, whole blood viscosity, plasma viscosity, platelet adhesion rate, platelet aggregation and histopathology changes were assessed., Results: Five C 3 ,C 28 -bidesmosidic oleanane-type saponins and ginsenoside Rd were the main constituents of TSPJ, and their total content in TSPJ was 79.2 %. The main constituents of DTSPJ were five C 3 -monodesmosidic oleanane-type saponins and ginsenoside Rd, and their total content in DTSPJ was 72.6 %. The HPLC analysis revealed that the five C 3 ,C 28 -bidesmosidic oleanane-type saponins in TSPJ were completely turned into five C 3 -monodesmosidic oleanane-type saponins in DTSPJ through the method of alkaline hydrolysis, but ginsenoside Rd remained unchanged. Both TSPJ and DTSPJ could significantly reduced myocardial infarct size, and improved heart function, and lowered the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase isoenzymes (CK-MB), and malonyldialdehyde (MDA) content, as well as the levels of whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation; on the contrary, both the level of glutathione peroxidase (GSH-Px) and the activity of superoxide dismutase (SOD) were notablely increased. The results of histopathological examination further supported the cardioprotective effects of TSPJ and DTSPJ., Conclusion: Both TSPJ and DTSPJ can guard cardiomyocytes against myocardial ischemia-reperfusion injury. The underlying mechanisms may be closely related to its enhancing anti-oxidative properties, modifying blood viscosity, and inhibiting platelet aggregation and platelet adhesion. As a whole, the protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ. The results display the prospect of DTSPJ as a drug candidate for treating ischemic heart disease., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

c-Jun N-terminal kinases (JNKs) are involved in the myocardial and aortic remodeling, increased arterial tone, and arterial blood pressure elevation associated with hypertension. The aim of the present study was to investigate the antihypertensive effect of a new JNK inhibitor, 1H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), on spontaneously hypertensive rats (SHRs). Experiments were performed using normotensive Wistar-Kyoto (WKY) rats and SHRs. Experimental groups of SHRs received IQ-1S intragastrically for 6 weeks in daily doses of 5 and 50 mg/kg; experimental groups of WKY rats received 50 mg/kg IQ-1S according to the same regimen. The IQ-1S administration regimen induced decreases in systolic blood pressure, mean arterial blood pressure, total peripheral resistance, blood viscosity, hematocrit, myocardial cell cross-sectional area, and aortic wall thickness in SHRs vs untreated SHRs. There were no significant differences in systolic blood pressure values between the control and experimental groups of WKY rats during the treatment period. A concentration-dependent decrease in the tone of carotid arterial rings isolated from SHRs was observed after JNK inhibitor application in vitro. Application of the JNK inhibitor diminished endothelin-1 secretion by human umbilical vein endothelial cells in vitro. The main mechanisms of the antihypertensive effect of IQ-1S included the attenuation of blood viscosity due to decreased hematocrit, a vasodilatory effect on arterial smooth muscle cells, and a decrease in endothelin-1 production by endothelial cells.

Purpose: We aimed to illustrate the benefits of using warmed glue for viscosity reduction via the triaxial microballoon system for the treatment of various vascular disorders., Methods: Seven patients who underwent 10 treatment sessions for hemoptysis, type II endoleak, post-pancreatic surgical bleeding, spontaneous retroperitoneal bleeding, or ovarian tumor bleeding were evaluated based on technical and clinical outcomes. In the procedure, the triaxial system, consisting of a 4.5-Fr guiding catheter, a 2.8-Fr microballoon catheter, and a 1.9-Fr no-taper microcatheter, was advanced into the target lesion. Glue (33% n-butyl cyanoacrylate mixed with Lipiodol) warmed to 40°C was injected under balloon occlusion., Results: The common hepatic, right bronchial, intercostals, internal mammary, costocervical, lateral thoracic, superior thoracic, thoracoacromial, inferior thyroid, iliolumbar, lumbar, internal pudendal arteries, and branch of the inferior mesenteric artery were successfully embolized; 100% technical success and 100% clinical success were obtained after each session., Conclusion: Our modified balloon-occluded glue embolization may lead to better handling with more distal glue penetration capability.

Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studieson the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro. Compared with the model group in vivo, astragalin could shorten the coagulation time and significantly increase the number of platelets. Meanwhile, astragalin could significantly reduce the effectual time of PT and APTT and increase the content of FIB. The contents of 6-keto-PGF 1 α and eNOS significantly decreased. Astragalin could increase whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and packedcell volume (PCV). All of the above revealed that astragalin had good procoagulant effects by promoting the intrinsic and extrinsic coagulation system., Competing Interests: The authors declare that they have no conflict of interest.

Background: Severe bacterial infections initiate inadequate inflammation that leads to disseminated intravascular coagulation and death., Objectives: To evaluate the influence of bacterial infection on blood viscosity and red blood cells (RBCs) morphology, and the ability of Calotropis procera proteins (CpLP) to prevent the patho-hemorheology in infected animals., Methods: Rheology of blood, atomic force microscopy measurements on specific blood elements and blood count were performed to examine changes in blood viscosity, RBCs morphology, platelets activation, and RBCs indices., Findings: Infected mice hold their blood rheological behaviour as compared to that of the control group. However, they presented hyperactivated platelets, RBCs at different stages of eryptosis, and variation on RBCs indices. CpLP administration in healthy animals altered blood behaviour from pseudoplastic to Bingham-like fluid. Such effect disappeared over time and by inhibiting its proteases. No alterations were observed in RBCs morphology or platelets. Treatment of infected animals with CpLP prevented the changes in RBCs indices and morphology., Main Conclusions: The inflammatory process triggered by bacterial infection induced pathological changes in RBCs and platelets activation. Treatment of infected animals with CpLP prevented the emergence of RBCs abnormal morphology and this may have implications in the protective effect of CpLP, avoiding animal death.

It is known that oxidative stress is related to disease in humans and dogs. Many traditional Chinese medicines have been reported to have anti-oxidative effects, but there are no reports that they have anti-oxidative effects in dogs. In this study, we examined the anti-oxidative effects of Juzen-taiho-to, a traditional Chinese medicine, in dogs. Five healthy female beagle dogs (38-41 months of age weighing 8.6-10.7 kg) were orally administered Juzen-taiho-to at 450 mg/kg with food for 28 days. Blood samples were taken from all five dogs on days 0, 7, 14, 21, and 28. Using the blood samples, improvement of the antioxidant level as assessed by the biological antioxidant potential (BAP), reduced oxidative stress level as assessed by derivatives of reactive oxygen metabolites (d-ROMs), and improvement of blood fluidity were examined. Regarding the antioxidant level and blood fluidity, no significant difference was observed, but the oxidative stress level on days 14, 21, and 28 was significantly lower than that on day 0. Thus, Juzen-taiho-to may have anti-oxidative effects in dogs by reducing oxidative stress and be useful for oxidative stress-related diseases in dogs.

1,25(OH) 2 D 3 has already been reported to function in some diseases. However, its role in hyperlipidemia (HLP) remains unknown. This study aims to investigate the effect of 1,25(OH) 2 D 3 on HLP rats. Rat models were established by high-fat diet feeding, perfusion of different doses of 1,25-(OH) 2 D 3 and injection of TGF-β1 siRNA. Whole blood viscosity, plasma viscosity, hematocrit, and erythrocyte aggregation index were detected, together with levels of biochemical indexes, 6-keto-PGF1α, and TXB2 in serum. Levels of oxidative stress indexes and inflammatory factors in serum and liver tissues were determined. TGF-β1 and Smad3 expression in serum, liver tissues, and aorta was detected. 1,25(OH) 2 D 3 lowered HLP-induced rise of whole blood viscosity, red blood cell aggregation index, plasma viscosity, and hematocrit, TC, TG, LDL-C, apoB, ALT, AST, TXB2, MDA, IL-1β, TNF-α, and increased HLP-induced decrease of HDL-C, apoAI, 6-keto-PGF1α, SOD, GSH-Px, CAT, and T-AOC. TGF-β1 and Smad3 expression in serum, liver tissue, and aorta of 1,25(OH) 2 D 3 -treated rats reduced. High 1,25(OH) 2 D 3 dose and inhibited TGF-β/Smad signaling pathway alleviated lipid metabolism, liver function, and atherosclerotic injury in HLP rats. Our study found that 1,25(OH) 2 D 3 improves blood lipid metabolism, liver function, and atherosclerosis injury by constraining the TGF-β/Smad signaling pathway in rats with HLP.

This study is to investigate pharmacokinetics (PK) and hemorheology (HR) of exogenous phosphocreatine (PCr), a cardio-protective agent, and its active metabolite creatine (Cr), with particular focus on the PK and PD comparison between PCr and Cr. A specific ion-pair reversed-phase HPLC-UV assay was used to simultaneously measure PCr, Cr and ATP concentrations in plasma and red blood cells (RBC) samples of rabbits. PK and HR parameters were calculated based on concentration-time (C-T) curves and effect-time (E-T) curves, respectively, obtained after i.v. dosing. Meanwhile the apparent pharmacological activity ratio (R app ) and real pharmacological activity ratio (R real ) of Cr to PCr were calculated. The PCr disappeared from plasma rapidly and in a biphasic manner; plasma PCr was converted to Cr fast and largely with the elimination rate limited metabolite disposition in vivo (K m  < K). The i.v. administration of PCr led to a markedly elevated and long-lasting ATP level in RBC. After i.v. administration of preformed Cr, plasma Cr displayed similar elimination kinetics behaviors to that of Cr generated metabolically after i.v. PCr. The Cr could also raise ATP level in RBC, but to less extent than PCr. Approximately 43% of PCr-derived ATP came from Cr-derived ATP in RBC. PCr could significantly reduce whole blood viscosity and RBC osmotic fragility and Cr could do so, but weakly with estimated R app of 0.53-0.68 and R real of 0.38-0.48. PCr also inhibited platelet aggregation significantly, as opposed to Cr. The PCr-caused improvement of HR is related to the rise in ATP level in RBC. Cr is likely to partially mediate HR effect of PCr., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Clinical guidelines indicate that hematocrit should be monitored during testosterone replacement therapy (TTh), with action taken if a level of 0.54 is exceeded., Aim: To consider the extent of changes in hematocrit and putative effects on viscosity, blood flow, and mortality rates after TTh., Methods: We focused on literature describing benefits and possible pitfalls of TTh, including increased hematocrit. We used data from the BLAST RCT to determine change in hematocrit after 30 weeks of TTh and describe a clinical case showing the need for monitoring. We consider the validity of the current hematocrit cutoff value at which TTh may be modified. Ways in which hematocrit alters blood flow in the micro- and macro-vasculature are also considered., Main Outcome Measures: The following measures were assessed: (i) change in hematocrit, (ii) corresponding actions taken in clinical practice, and (iii) possible blood flow changes following change in hematocrit., Results: Analysis of data from the BLAST RCT showed a significant increase in mean hematocrit of 0.01, the increase greater in men with lower baseline values. Although 0 of 61 men given TTh breached the suggested cutoff of 0.54 after 30 weeks, a clinical case demonstrates the need to monitor hematocrit. An association between hematocrit and morbidity and mortality appears likely but not proven and may be evident only in patient subgroups. The consequences of an increased hematocrit may be mediated by alterations in blood viscosity, oxygen delivery, and flow. Their relative impact may vary in different vascular beds., Conclusions: TTh can effect an increased hematocrit via poorly understood mechanisms and may have harmful effects on blood flow that differ in patient subgroups. At present, there appears no scientific basis for using a hematocrit of 0.54 to modify TTh; other values may be more appropriate in particular patient groups. König CS, Balabani S, Hackett GI, et al. Testosterone Therapy: An Assessment of the Clinical Consequences of Changes in Hematocrit and Blood Flow Characteristics. Sex Med Rev 2019;7:650-660., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Introduction : The genomic landscape of Waldenström macroglobulinemia (WM) is characterized by recurrent MYD88 ( MYD88 L265P ) and CXCR4 mutations ( CXCR4 MUT ), detected in 90% and 30% of cases, respectively. The role of CXCR4 MUT in clinical features and outcomes to therapy in WM patients is evolving. Areas covered : We performed a systematic review aimed at evaluating the prevalence of CXCR4 MUT in WM patients, and at assessing differences in clinical features and outcomes to therapy between WM patients with and without CXCR4 MUT . Seventeen studies were included in our analysis. The pooled prevalence of CXCR4 MUT in WM patients was 31%; 34% in MYD88 L265P and 5% in MYD88 WT patients. CXCR4 MUT were associated with higher serum IgM levels and higher risk of hyperviscosity than CXCR4 WT patients. Very good partial response (VGPR) and progression-free survival (PFS) rates to ibrutinib, with and without rituximab, appeared lower in CXCR4 MUT than in CXCR4 WT patients. Response and PFS rates were not affected by CXCR4 MUT status on patients treated with proteasome inhibitors. Expert opinion : Our systematic review shows that WM patients with CXCR4 MUT have specific clinical features and have lower response and PFS rates to BTK inhibitors. Our findings support standardization of CXCR4 testing and development of CXCR4-directed therapy.

Blood viscosity measurements are crucial for the diagnosis and understanding of a range of hematological and cardiovascular diseases. Such measurements are heavily used in monitoring patients during and after surgeries, which necessitates the development of a highly accurate viscometer that uses a minimal amount of blood. In this work, we have designed and implemented a microfluidic device that was used to measure fluid viscosity with a high accuracy using less than 10 μl of blood. The device was further used to construct a blood viscosity model based on temperature, shear rate, and anti-coagulant concentration. The model has an R-squared value of 0.950. Finally, blood protein content was changed to simulate diseased conditions and blood viscosity was measured using the device and estimated using the model constructed in this work. Simulated diseased conditions were clearly detected when comparing estimated viscosity values using the model and the measured values using the device, proving the applicability of the setup in the detection of rheological anomalies and in disease diagnosis.

Environmental noise is a well-recognized health risk and part of the external exposome-the World Health Organization estimates that 1 million healthy life years are lost annually in Western Europe alone due to noise-related complications, including increased incidence of hypertension, heart failure, myocardial infarction, and stroke. Previous data suggest that noise works through two paired pathways in a proposed reaction model for noise exposure. As a nonspecific stressor, chronic low-level noise exposure can cause a disruption of sleep and communication leading to annoyance and subsequent sympathetic and endocrine stress responses leading to increased blood pressure, heart rate, stress hormone levels, and in particular more oxidative stress, being responsible for vascular dysfunction and representing changes of the internal exposome. Chronic stress generates cardiovascular risk factors on its own such as increased blood pressure, blood viscosity, blood glucose, and activation of blood coagulation. To this end, persistent chronic noise exposure increases cardiometabolic diseases, including arterial hypertension, coronary artery disease, arrhythmia, heart failure, diabetes mellitus type 2, and stroke. The present review discusses the mechanisms of the nonauditory noise-induced cardiovascular and metabolic consequences, focusing on mental stress signaling pathways, activation of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system, the association of these activations with inflammation, and the subsequent onset of oxidative stress and vascular dysfunction. © 2019 BioFactors, 45 (4):495-506, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

Ethnopharmacological Relevance: Whitmania pigra Whitman (Whitmania pigra, WP), firstly recorded in the Shennong's Herbal Classic and officially listed in the Chinese Pharmacopoeia, is a well-used cardiovascular protective traditional Chinese medicine derived from leeches. Traditional Chinese physicians prefer to prescribe the dried whole body of leech processed under high temperatures. It has been reported that dried WP remains clinically effective. However, the therapeutic mechanism has yet not be clearly elucidated., Aim of the Study: This study was designed to investigate the protective activity of the extract of WP in a high-molecular-weight dextran-induced blood hyperviscosity rat model, and to explore the role of WP in improving blood hyperviscosity related metabolic disorders and to clarify the possible mechanism of metabolic regulation., Materials and Methods: The hemorheological parameters were measured with an automated blood rheology analyzer. Hematoxylin-eosin staining was used to observe the pathological changes in aortic tissues samples. Further, a liquid chromatography-mass-spectrometry (LC-MS)-based untargeted metabolomics approach was applied to characterize the metabolic alterations., Results: WP has evident attenuating effects on blood hyperviscosity and related metabolic disorders, and the influences are distinct from those of aspirin. The results showed that WP had good effects in reducing blood viscosity and ameliorating histopathological changes in the thoracic aorta in a high molecular weight dextran-induced blood hyperviscosity rat model. The middle dose (2.5 g raw material/kg body weight) of WP exhibited effects equivalent to aspirin (100 mg/kg) on hemorheological and histopathological parameters (P > 0.05). However, when using metabolomics profiling, we found that WP could significantly improve blood hyperviscosity-related metabolic disorders and restore metabolites to normal levels; while aspirin showed little effect. With principal component analysis and orthogonal partial least-squares discriminant analysis, WP regulated many more endogenous metabolites than aspirin. With pathway enrichment analysis, the differential endogenous metabolites were involved in cysteine and methionine metabolism, TCA cycle, arachidonic acid metabolism, etc., highlighting the metabolic reprogramming potential of WP against blood hyperviscosity-induced metabolic disorders., Conclusions: The study suggest that WP has a more potent effect, but a different mechanism, than aspirin in improving either blood hyperviscosity or related metabolic disorders associated with cardio- and cerebrovascular diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aspirin eugenol ester (AEE) is a novel compound that is formed from the esterification of aspirin (acetylsalicylic acid (ASA)) and eugenol. This study aimed to investigate the effects of AEE on blood stasis in rats and to characterize the underlying mechanisms using a plasma metabolomic study. The results indicate that AEE and ASA could modulate whole blood viscosity (WBV), plasma viscosity (PV), blood coagulation parameters, platelet count, platelet aggregation, lactate dehydrogenase (LDH), creatinine (CR) and the levels of thromboxane A2 (TXA 2 ) and 6-keto prostaglandin F1α (6-keto-PGF 1α ). The metabolic profiles of the plasma samples from all groups were clearly separated in the score plots. Nineteen potential metabolites were selected and identified, and disordered levels of these metabolites could be regulated by AEE and ASA. Pathway analysis showed that the mechanism of action of AEE on blood stasis might be principally related to the metabolism of amino acid, fatty acid, energy and glycerophospholipid. The above results indicate that AEE protected the rats against blood stasis, and that this effect might have been caused by the anticoagulation activity of AEE and its abilities to maintain a balance between TXA 2 and PGI 2 , reduce blood viscosity, inhibit platelet aggregation and normalize the plasma metabolic profile.

Background: Microvascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM)., Methods: Randomized, double-blind, double-dummy, crossover trial design that compares treatment with aspirin 81 mg/ticagrelor placebo, aspirin 81 mg/ticagrelor 90 mg twice daily and aspirin placebo/ticagrelor 90 mg twice daily on high-shear (300 s -1 ) and low-shear (5 s -1 ) BV, and laser Doppler flowmetry (LDF) in the dorsum of the feet of participants with T2DM., Results: We randomized 70 (45% female) participants aged (mean ± SD) 72 ± 9 years. The duration of LEAD was 12.3 ± 10.3 years, and 96.9% reported intermittent claudication symptoms. Use of statins was 93% (high-intensity 43%, moderate intensity 49%), renin-angiotensin-aldosterone system inhibitors (75%) and beta-blockers (61%). Treatment with ticagrelor with or without aspirin reduced high-shear BV by 5%, in both cases, while aspirin monotherapy increased high-shear BV by 3.4% (p < 0.0001). Ticagrelor with or without aspirin reduced low-shear BV by 14.2% and 13.9% respectively, while aspirin monotherapy increased low-shear BV by 9.3% (p < 0.0001). The combination of ticagrelor and aspirin increased MBF in the left foot compared to the other two treatments (p = 0.02), but not in the right foot (p = 0.25)., Conclusions: Ticagrelor should be considered in the treatment of microvascular disease in patients with LEAD and T2DM. Trial registration Registration number: NCT02325466, registration date: December 25, 2014.

Background: Warfarin is evidence-based therapy for the prevention of cardioembolic stroke, but has not been studied for its effects on whole blood viscosity (WBV). This study investigated the effect of warfarin versus aspirin on WBV in patients presenting with non-valvular atrial fibrillation (NVAF) and acute cardioembolic stroke., Methods: We enrolled patients with acute cerebral infarction, aged 56-90 years who had NVAF, CHADS 2 score ≥ 2, presenting with mild-to-moderate stroke (National Institute of Health Stroke Scale (NIHSS) score < 20 and modified Rankin Scale (2mRS) score < 4) in a single center. The patients were alternately assigned to warfarin or aspirin groups. Post-treatment WBV was assessed after international normalized ratio (INR) reached target range [2, 3] for patients in the warfarin group, and 5 days after baseline in the aspirin group., Results: Total 67 patients were included, and 56 completed this study (33 warfarin and 23 aspirin). Compared to baseline values, warfarin reduced post-treatment BV at all shear rates. The BV reductions greater than 1 cP measured at shear rates of 300, 150, 5, and 1 s - 1 were independently and significantly associated with warfarin treatment compared to aspirin after adjusting for age, sex, CHA 2 DS 2 -VASc scores, and baseline hematocrit., Conclusions: Warfarin confers greater reductions in BV than aspirin in patients with acute cardioembolic stroke. BV could be a useful method to estimate thrombotic risk in patients receiving warfarin., Trial Registration: KCT0001291 , Date of Registration: 2014-12-01.

Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard., Objective: This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers., Methods and Results: Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at t max  = 4 h in WBV at shear rates of 0.512 s -1 (p < 0.005), WBV at shear rates of 5.26 s -1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time., Conclusions: Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Objective: To provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection (GD) as one adjuvant therapy for treating angina pectoris (AP) and to evaluate the relevant randomized controlled trials (RCTs) with meta-analysis., Methods: RCTs concerning AP treated by GD were searched in China Biology Medicine Disc (SinoMed), PubMed, the China National Knowledge Infrastructure Database (CNKI), the Chinese Scientifific Journals Database (VIP), Wanfang Database, Embase, and the Cochrane Library, from inception to February, 2017. The Cochrane Risk Assessment Tool was adopted to assess the methodological quality of the RCTs. The Review Manager 5.3 software was utilized to conduct the meta-analysis., Results: A total of 41 RCTs involving 4,462 patients were included in the meta-analysis. The results indicated that the combined use of GD and Western medicine (WM) against AP was associated with a higher total effective rate [risk ratio (RR)=1.25, 95% confifidence interval (CI): 1.21-1.29, P<0.01], total effective rate of electrocardiogram (RR=1.29, 95% CI: 1.21-1.36, P<0.01). Additional, GD combined with WM could decrease the level of plasma viscosity [mean difference (MD)=-0.56, 95% CI:-0,81 to-0.30, P<0.01], fifibrinogen [MD=-1.02, 95% CI:-1.50 to-0.54, P<0.01], whole blood low shear viscosity [MD=-2.27, 95% CI:-3.04 to-1.49, P<0.01], and whole blood high shear viscosity (MD=-0.90, 95% CI: 1.37 to-0.44, P<0.01)., Conclusions: Comparing with receiving WM only, the combine use of GD and WM was associated with a better curative effect for patients with AP. Nevertheless, limited by the methodological quality of included RCTs more large-sample, multi-center RCTs were needed to confifirm our fifindings and provide further evidence for the clinical utility of GD.

Sickle cell disease (SCD) is an inherited blood disorder associated with severe anemia, vessel occlusion, poor oxygen transport and organ failure. The presence of stiff and often sickle-shaped red blood cells is the hallmark of SCD and is believed to contribute to impaired blood rheology and organ damage. Most existing measurement techniques of blood and red blood cell physical properties require sample contact and/or large sample volume, which is problematic for pediatric patients. Acoustic levitation allows rheological measurements in a single drop of blood, simultaneously eliminating the need for both contact containment and manipulation of samples. The technique shows that the shape oscillation of blood drops is able to assess blood viscosity in normal and SCD blood and demonstrates an abnormally increased viscosity in SCD when compared with normal controls. Furthermore, the technique is sensitive enough to detect viscosity changes induced by hydroxyurea treatment, and their dependence on the total fetal hemoglobin content of the sample. Thus this technique may hold promise as a monitoring tool for assessing changes in blood rheology in sickle cell and other hematological diseases.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO., (Copyright © 2018. Published by Elsevier Inc.)

Background: Lower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity. We hypothesize that the adenosine enhancing properties of ticagrelor will reduce low-shear blood viscosity and improve microcirculatory flow in the dorsum of the feet of patients with type 2 diabetes. Ticagrelor is a P2Y12 receptor antagonist with evidence of cardiovascular event reduction in patients with acute coronary syndromes and those with a previous myocardial infarction. In a large multicenter trial of patients with symptomatic LEAD and a history of limb revascularization, ticagrelor was no more effective than clopidogrel in reducing cardiovascular disease events; however, this trial was not designed to investigate microvascular complications of diabetes., Design: Hema-kinesis will evaluate whether ticagrelor monotherapy or ticagrelor combined with aspirin as compared with aspirin monotherapy can reduce blood viscosity-dependent blood flow in the feet of type 2 diabetes patients with LEAD. Eligible study participants will be randomized into a three-arm double-dummy crossover trial design. All subjects will have baseline blood viscosity measurements and determinations of microvascular flow using laser Doppler flowmetry. If the results of Hema-kinesis are positive, ticagrelor should be considered as treatment to reduce microvascular complications of LEAD in patients with type 2 diabetes.

Background: Many pathological mechanisms are involved in the development of arterial hypertension; disturbance of the rheological properties of blood and microvascular rarefaction are among those mechanisms., Objective: The effect of p-tyrosol (Tyr) on hemorheological parameters and microvascularization in the cerebral cortex of spontaneously hypertensive rats (SHRs) at the stage of blood pressure rising (5-11 weeks) was studied., Methods: Blood viscosity (BV), plasma viscosity (PV), hematocrit, erythrocyte aggregation and deformability, the oxygen transport capacity index (OTCI), and the capillary network in the cerebral cortex after the course of treatment of Tyr (50 mg/kg daily i.g. for 6 weeks) were studied. Control normotensive Wistar-Kyoto (WKY) rats and control SHRs received an equivalent amount of 1% starch mucilage., Results: In comparison with WKY rats, disturbances of rheological blood parameters and a decrease in OTCI were revealed in control SHRs at the 11 weeks of life. By the end of the experiment, brain microvascular rarefaction was observed in the control SHRs (the average density of the capillary bed was reduced due to a decrease in the number of capillaries with a diameter of 3-7 μm). In SHRs rats treated with Tyr, BV and PV, the indices of erythrocyte aggregation were lower, and OTCI was higher in comparison with control SHRs. The density of the capillary network and the number of capillaries of 3-7 μm in the cerebral cortex of SHRs rats receiving Tyr were significantly higher than the corresponding values in control SHRs., Conclusion: When Tyr is administered to young SHRs during the development of hypertension, it limits the development of hyperviscosity syndrome, improves the oxygen transport capacity and eliminates microvascular rarefaction in the cerebral cortex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective : To perform a preliminary study on the quality evaluation of compound Danshen preparations based on the xCELLigence Real-Time Cell-based Assay (RTCA) system and make a pharmacodynamics verification. Methods : The compound Danshen was discussed as a methodological example, and the bioactivity of the compound Danshen preparations were evaluated by real-time cell electronic analysis technology. Meanwhile, an in vivo experiment on an acute blood stasis rat model was performed in order to verify this novel evaluation through the curative effect of dissipating blood stasis. Results : We determined the cell index (CI) and IC50 of the compound Danshen preparations and produced time/dose-dependent cell response profiles (TCRPs). The quality of the three kinds of compound Danshen preparations was evaluated through the RTCA data. The trend of CI and TCRPs reflected the effect of drugs on the cell (promoting or inhibiting), and it was verified that the results correlated with the biological activity of the drugs using a pharmacodynamics experiment. Conclusion : The RTCA system can be used to evaluate the quality of compound Danshen Preparations, and it can provide a new idea and new method for quantitatively characterizing the biological activity of traditional Chinese medicines (TCMs).

Blood stasis syndrome (BSS) is one of the most common Chinese medicine patterns in coronary heart disease. Our previous work proved that Xueshuan Xinmaining Tablet (XXT) could treat blood stasis through regulating the expression of F13a1, Car1 and Tbxa2r. In the current study, the effect and mechanism of XXT on BSS was comprehensively and holistically investigated based on a metabolomics approach. Urine and plasma samples of 10 BBS rats treated with XXT (XT), 9 BSS model rats (BM) and 11 normal control (NC) rats were collected and then determined by UPLC-Q/TOP-MS. Multivariate analyses were applied to distinguish differentiate urinary and plasma metabolite patterns between three groups. Results showed that a clear separation of three groups was achieved. XT group was located between BM group and NC group, and showing a tendency of recovering to NC group, which was consistent with the results of hemorheological studies. Some significantly changed metabolites like cortexolone, 3α,21-dihydroxy-5β-pregnane-11,20-dione and 19 S -hete and leukotriene A4, chiefly involved in steroid hormone biosynthesis, arachidonic acid metabolism and lipid metabolism, were found and identified to explain the mechanism. These potential markers and their corresponding pathways will help explain the mechanism of BSS and XXT treatment. This work also proves that metabolomics is effective in traditional Chinese medicinal research., Competing Interests: The authors declare no conflict of interest.

Background: Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function., Objective: We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness., Methods: The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software., Results: Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS)., Conclusions: This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Zhang, Zhiqing, Zhonghai Xiao, Bingnan Deng, Xiaohua Liu, Wei Liu, Hongjing Nie, Xi Li, Zhaoli Chen, Danfeng Yang, and Ruifeng Duan. Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats. High Alt Med Biol 19:69-80, 2018.-This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia + acetazolamide (30 mg·kg -1 ·d -1 ), and five hypoxia + methazolamide groups (5, 10, 30, 90, and 120 mg·kg -1 ·d -1 ). Excessive erythrocytosis was induced through 4 weeks of hypobaric hypoxia (8 hours O 2 10%/16 hours O 2 21%). Rats were then treated for 4 weeks, and their body weight was measured. Hematological, hemorheological, and biochemical parameters were analyzed. Renal hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry. Proteomic analysis of plasma was conducted to determine the most differentially expressed proteins. Methazolamide with doses lower than 30 mg·kg -1 ·d -1 had no significant effects on body weight compared with the hypoxia control group (p > 0.05). Methazolamide dose-dependently reduced the hemoglobin concentration, hematocrit (Hct), and blood viscosity. Hct/blood viscosity, an oxygen delivery index, dose-dependently increased after methazolamide treatment. A methazolamide dose of 10 mg·kg -1 ·d -1 showed similar efficacy to an acetazolamide dose of 30 mg·kg -1 ·d -1 for all the above parameters. Plasma levels of low-density lipoprotein cholesterol, total cholesterol, creatinine, and hemoglobin increased substantially after long-term hypoxia, but decreased after methazolamide treatment. HIF-1α and VEGF both increased substantially after long-term hypoxia and decreased in the kidney after methazolamide treatment. The most differentially expressed protein was haptoglobin, an endogenous protective factor, which was depleted in rats with excessive erythrocytosis and increased substantially after methazolamide treatment. In summary, methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia. It also has beneficial effects on oxygen transport and lipid metabolism, which are encouraging with regard to the development of methazolamide-based chronic mountain sickness therapies.

The purpose of the present work was designed to explore protective cerebrovascular effects of hydroxysafflor yellow A (HSYA), and provide preclinical efficacy and mechanism data for its possible application in patients with cerebral ischemia. The protective effect of HSYA on ischemic stroke was evaluated by infarct sizes and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Cerebrovascular permeability was detected by Evans blue dye leakage in MCAO rats. Cerebral blood flow, as well as blood pressure and heart rate were monitored using flow probes in Beagle dogs. Basilar artery tension isolated from Beagle dogs was evaluated with an MPA 2000 data-acquisition system. Coagulation-related function was also judged, including rabbit platelet aggregation by adenosine diphosphate (ADP) and platelet-aggregating factor (PAF), rabbit blood viscosity by a blood viscometer, and thrombus formation by rat arterial-venous shunts. Results showed that HSYA treatment significantly decreased the infarct sizes, neurological scores and cerebrovascular permeability in rats with MCAO. However, cerebral blood flow, blood pressure and heart rate were not affected by HSYA. In vitro, HSYA had a strong effect on cerebrovascular vasodilatation, and significantly decreased platelet aggregation, blood viscosity, and thrombogenesis. Besides well-known anti-coagulation effects, HSYA protects against ischemic stroke by dilating cerebral vessels and improving cerebrovascular permeability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Poloxamer-188 is a synthetic, organic compound that acts by binding hydrophobic pockets on damaged lipid bilayers in the circulation. P-188 reduces blood viscosity and confers anti-inflammatory and cytoprotective effects. Vepoloxamer (Mast Therapeutics, San Diego, Calif) is a purified version of this compound that has limited side effects. The aim of this study was to investigate drug interactions between vepoloxamer and heparin and tissue plasminogen activator (tPA)., Methods: An experimental rat tail transection model was used to study vepoloxamer's interaction with heparin. Sprague-Dawley rats were divided into saline (1 mL/kg; group 1) or vepoloxamer (25 mg/kg; group 2) treatment groups. The rats were then subjected to saline (n = 6), low-dose heparin (125 μg/kg; n = 6), or high-dose heparin (250 μg/kg; n = 6). After 5 minutes, the distal 2 mm of the tail was transected, and time to clot formation was measured as bleeding time. A rat internal jugular vein thrombosis model was used to assess vepoloxamer's interaction with tPA. Sprague-Dawley rats were divided into saline (1 mL/kg; group 1) or vepoloxamer (25 mg/kg; group 2) treatment groups. After internal jugular vein thrombosis, rats were treated with saline (n = 6), systemic low-dose tPA (0.5 mg/kg; n = 6), or systemic high-dose tPA (1.0 mg/kg; n = 6). Clot lysis was assessed using an ultrasound Doppler probe to detect blood flow. No flow up to 15 minutes was recorded as no lysis., Results: Interaction with heparin: Vepoloxamer by itself, without any heparin, increased tail bleeding time (10.3 vs 7.1 minutes; P = .001). Effects of heparin on tail bleeding time were enhanced by vepoloxamer at low dose (14.2 vs 6.2 minutes; P < .001). At high-dose heparin, vepoloxamer did not prolong bleeding time (17.8 vs 17.0 minutes). Interaction with tPA: No rat exhibited spontaneous clot lysis with either saline or vepoloxamer. The effect of tPA was facilitated by vepoloxamer at low dose, as more rats showed clot lysis (4/6 [66%]) compared with tPA alone, which showed no clot lysis (0/6), although statistical significance was not reached (P = .06). At high-dose tPA, vepoloxamer had no additional effects on clot lysis (5/6 [83% ] vs 4/6 [66%])., Conclusions: Vepoloxamer alone modestly increased bleeding time. Vepoloxamer also increased bleeding time in rats treated with low-dose heparin but not with high-dose heparin. Vepoloxamer potentiated clot lysis in the setting of low-dose tPA., (Copyright © 2016. Published by Elsevier Inc.)

Background: Red blood cell (RBC) deformability and blood viscosity are essential to ensure optimal microcirculation and may contribute to athletic performance., Objective: To investigate the acute responses of density fractionated young, middle old and old RBC, RBC viscosity (RBCV), plasma viscosity (PV) and hematological changes to two running modes (intensive and moderate)., Methods: 27 young and healthy men of different training status participated in this study and were grouped into three groups in accordance to their VO2peak and conducted an intensive and moderate running test, respectively (crossover design). Pre and Post exercise, RBC were fractionated via percoll density gradient centrifugation. RBC deformability of the entire RBC population and the fractionated RBC was determined. Viscosity, hematocrit and mean cellular volume were determined., Results: Baseline results reveal that high trained subjects possess more young RBC and show increased deformability of un-fractioned RBC and middle aged RBC. Baseline PV, RBCV, hematocrit and mean cellular volume did not differ between groups. Applied running modes did not change RBC deformability of any sub-fractions. Viscosity only increased after intensive running. Hematological changes were observed after both exercises., Conclusions: Acute effects of exercise on RBC are marginal, but chronic differences can be observed in RBC function.

Blood stasis (BS) is a complex syndrome with blood flow retardation or cessation. The Traditional Chinese Medicine, Curcumae rhizome (CR) and Sparganii rhizome (SR), showed promising effects on this disease, and especially effective when used in combination. However, the detailed influence of the TCMs on the BSS disturbed metabolic pathways was still unclear. In this study, a BS model was constructed in SD rat and the TCMs were used individually or in combination to assess the effects. As a result, combination of CR and SR led to the improvement in hemorheology parameters of up to 80% in the BS model. Further analyzing using metabolomics showed several metabolic pathways, including center carbon metabolism, amino acid metabolism, etc., recovered to the normal levels after treatment. Informatively, tyrosine and thymidine exhibited potential importance in the BSS and its treatment process. From these results, the metabolic profiles of BS and the SR-CR treatment were provided, which may helpful for better understanding the BSS mechanism and the development of more effective therapies.

The rheological properties of blood play a significant role in the onset and progression of arterial hypertension. The aim of our work was to evaluate the effect of the angiotensin-converting enzyme inhibitor captopril (20 mg/kg/d), pentoxifylline (PTX; 100 mg/kg/d), and the combination of captopril + PTX (20 + 100 mg/kg/d) on the hemodynamic and hemorheological parameters in spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. In the group of animals that received captopril, the mean arterial pressure (MAP) was significantly lower by 30% due to a decrease in cardiac output of 23% and in total peripheral resistance (TPR) of 26% compared with the control group, whereas blood viscosity did not change significantly. PTX-treated SHRs had significantly lower MAP and TPR (by 19% and 31%, respectively) and blood viscosity (by 4%-6%) and a higher erythrocyte deformability index (by 1.5%-2%) than the control group. In the group of animals that received captopril + PTX, MAP and TPR were significantly lower, by 41% and 46%, than those in the control group, and by 16% and 27% than those in the captopril group. The combination of the angiotensin-converting enzyme inhibitor captopril and the hemorheological agent PTX, affecting various systems that are involved in blood pressure regulation, exhibits synergism and prevents an increase in arterial blood pressure during the development of arterial hypertension in SHRs (ie, from 5 to 11 weeks of life)., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to analyze the changes in coagulation in meningioma patients treated with different injections using the method of acute hypervolemic hemodilution (AHH). One hundred fifty hindbrain membrane meningioma patients were randomly divided into 5 groups, 30 per group. The first group were injected 40ml/time with Danhong after anesthesia induction; the second group were injected with 40ml~60ml/time Kangai and combined with interventional chemotherapy and embolization procedure; the third group of AHH were injected with polygeline 15ml/kg; the fourth group were injected with hydroxyethyl starch (130/0.4) sodium chloride in doses of 15ml/kg; the control group underwent basic treatment for lowering blood pressure and lowering blood fat. The changes of coagulation index were recorded before and after surgery and before and after the injection of different medications. Compared to the control group, for the first group of AHH, after being treated for 10 days and 30 days, the concentrations of bone specific alkaline phosphatase (BALP), bone Gla protein (BGP) and pro-collagen carboxy-terminal propeptide (PICP) were higher than that of the control group, the levels of endotoxin (ET) and C-reactive protein (CRP) were decreased compared to the control group (p less than 0.05); for the second group of AHH, after being treated for 10 days, the index of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg) were not significantly changed, but the related level of vascular endothelial growth factor (VEGF) significantly decreased (p less than 0.05). Comparing the coagulation function index after surgery in the third and fourth groups, there were no significant changes in mean arterial pressure (MAP) level, heart rate (HR) value presented a low decrease, central venous pressure (CVP) level increased and the level of interleukin IL-6 showed a steady state after increasing. Analyzing the levels of interleukin IL-8 and tumor necrosis factor-α (TNF-α) after surgery, it was seen that in the third group they increased and in the fourth group they decreased (p less than 0.05). Danhong injection improved the coagulation function and microcirculation of patients, Kangai injection and interventional chemotherapy and embolization restrained the appearance of tumor angiogenesis, AHH operation with polygeline injection and hydroxyethyl starch (130/0.4) sodium chloride kept blood flow in normal parameters.

Water treatment using a magnetic field is an attractive but controversial issue with regard to its effects on human health. This study aimed to investigate the effects of water treatment using a magnetic field on the bone mineral density (BMD), bone mineral content (BMC), bone area (BA), bone resistance (BR), blood gas analysis, blood viscosity, and blood biochemical profile of rats. Forty-eight Wistar rats were divided into 2 groups: control (n = 24) and magnetic water-treated (n = 24). Each of these groups was subdivided into 3 groups to evaluate 3 consumption periods (15, 30, and 45 d). The animals were kept in metabolic cages throughout the experiment. A completely randomized design distributed to a 2 × 3 factorial arrangement was used. No significant difference was found in the water intake, dry matter intake, BA, or femoral head resistance between the groups. However, higher anion gap and lower CHCO 3 were found in the arterial blood of the magnetic water-treated group. There was significant interaction between the water consumption period and the BR, BMD, and BMC. With 15 d of consumption, there was no difference in the BMC and BR. With 30 d of consumption, the BR (midshaft), BMD, and BMC showed increases; the increases were greater with 45 d of consumption. In adulthood, every month of the animal is approximately equivalent to 2.5 human years. The consumption of water treated by magnetic field for 45 d provided an effective way to improve BMD, BMC and BR in rats., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objectives: The effect of course administration of amlodipine on whole blood viscosity and on macro- and microrheological parameters was evaluated., Materials and Methods: SHRs were treated intragastrically with amlodipine at a dose of 10 mg/kg for 6 weeks. After finishing the course, hemodynamic and hemorheological parameters were measured., Results: The antihypertensive treatment with amlodipine resulted in a significant decrease in mean blood pressure by 29% and left ventricular to body weight mass index by 7%. Nevertheless, BV tended to increase. The administration of amlodipine had no effect on PV, plasma fibrinogen concentration, RBC aggregation, and RBC deformability, but hematocrit was higher (by 6%) than it was in control group., Conclusions: These results demonstrate that amlodipine has no positive hemorheological improvements when administered to SHRs., Competing Interests: There are no conflicts of interest.

Background: Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent., Methods: Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks., Results: COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment., Conclusions: Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent., (Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.)

Ethnopharmacological Relevance: Yujin Powder (YJP), an old prescription, is one of the most classical prescription for treating the large intestine dampness-heat syndrome (LIDHS). However, its potential modern pharmacological mechanisms remain unclear., Aim of the Study: The present study was designed to explore the essence of LIDHS and treatment mechanisms of the YJP on the LIDHS., Methods: The rat model of LIDHS was established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment (HTHE), drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of LIDHS. Then the clinical symptoms and signs, blood routine, blood biochemistry, whole blood viscosity (WBV), serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed, respectively., Results: The results showed that the clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of LIDHS, moreover, there were obvious systemic inflammatory response and extensive congestion. And after treatment with YJP in different dosages, the clinical symptoms and signs of the rats with LIDHS were improved; the indexes of blood routine and blood biochemistry and inflammatory cytokines levels tended to be normal; the WBV decreased and histopathological changes of major organs were alleviated or returned to normal. There was an obvious dose-effect relationship, and the high dose of YJP (HD-YJP) had the best treatment effects., Conclusions: These results suggested that in LIDHS, diarrhea was the major clinical manifestation; the large intestine was the main lesion area; mucosa injury, inflammation and congestion of the large intestine with systemic inflammatory response and congestion were the most typical pathological characteristics. Meanwhile, YJP exhibited the comprehensive effects of anti-diarrhea, anti-inflammation, lowering blood lipid, relieving blood stasis, repairing intestinal mucosa and regulation and protection of multiple organs on LIDHS. These findings provided not only important information for understanding the essence of LIDHS but also the theoretical basis for developing new-drugs for treating dampness-heat type of diarrheal diseases., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

The most common form of hypertension in young adults is isolated diastolic hypertension. Diastolic arterial pressure is determined by the total peripheral resistance and depends on both vascular hindrance and blood viscosity. The aim of our work was to study the efficiency of pentoxifylline (PTX) in young spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. The effects of a treatment course with PTX (100 mg/kg/day p.o. for 6 weeks, from 5 to 11 weeks old) on the mean, systolic, and diastolic blood pressure (BP); stroke volume; cardiac output; total peripheral resistance (TPR); whole blood viscosity (BV); plasma viscosity; hematocrit; RBC aggregation and deformability; local cerebral blood flow (lCBF); and microvascularization of the visual cortex were studied in SHRs in comparison with control SHRs and Wistar Kyoto rats. PTX-treated SHRs had significantly lower systolic, diastolic, and mean BP (by 24%, 26%, and 15%, respectively) and BV (by 5-9%) and a higher erythrocyte deformability index (by 1.5-2%), lCBF (by 42%), average diameter of capillaries (by 11%), density of the capillary network (by 23%), and percentage of capillaries with a diameter of 3-7 µm in comparison with control SHRs. In conclusion, PTX exerted positive effects on the hemodynamic, hemorheological, and microcirculatory parameters in SHRs during the development of arterial hypertension.

Objective: This study describes the in vivo pharmacokinetics and metabolism of [14C]labeled XQ-1H in male rats., Methods: XQ-1H is a methanesulfonate of XQ, 10-O-(N,N-dimethylaminoethyl)-ginkgolide B, a derivative of ginkgolide B (GB) with enhanced water solubility. Since it is very difficult to synthesize radiolabeled GB, the results obtained in this study may provide helpful insight to further ADME investigation of GB and its analogue compounds. After an i.v. administration of [14C]XQ-1H to male rats, XQ (the freebase form of XQ-1H) was extensively hydrolyzed, moderately metabolized, and mainly excreted in feces (71.5% of the dose) via the biliary route., Results: The main enzyme mediated metabolic pathways were mono- and di-demthylation. Using the radiolabel form of XQ-1H, the temporal binding of XQ to red blood cells was observed., Conclusion: Binding of XQ to RBCs may lower the blood's viscosity and thus provide symptomatic improvement of ischemic stroke patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Previous research has shown fluid replacement beverages ingested after exercise can affect hydration biomarkers. No specific hydration marker is universally accepted as an ideal rehydration parameter following strenuous exercise. Currently, changes in body mass are used as a parameter during post-exercise hydration. Additional parameters are needed to fully appreciate and better understand rehydration following strenuous exercise. This randomized, double-blind, parallel-arm trial assessed the effect of high-pH water on four biomarkers after exercise-induced dehydration., Methods: One hundred healthy adults (50 M/50 F, 31 ± 6 years of age) were enrolled at a single clinical research center in Camden, NJ and completed this study with no adverse events. All individuals exercised in a warm environment (30 °C, 70% relative humidity) until their weight was reduced by a normally accepted level of 2.0 ± 0.2% due to perspiration, reflecting the effects of exercise in producing mild dehydration. Participants were randomized to rehydrate with an electrolyzed, high-pH (alkaline) water or standard water of equal volume (2% body weight) and assessed for an additional 2-h recovery period following exercise in order to assess any potential variations in measured parameters. The following biomarkers were assessed at baseline and during their recovery period: blood viscosity at high and low shear rates, plasma osmolality, bioimpedance, and body mass, as well as monitoring vital signs. Furthermore, a mixed model analysis was performed for additional validation., Results: After exercise-induced dehydration, consumption of the electrolyzed, high-pH water reduced high-shear viscosity by an average of 6.30% compared to 3.36% with standard purified water ( p  = 0.03). Other measured biomarkers (plasma osmolality, bioimpedance, and body mass change) revealed no significant difference between the two types of water for rehydration. However, a mixed model analysis validated the effect of high-pH water on high-shear viscosity when compared to standard purified water ( p  = 0.0213) after controlling for covariates such as age and baseline values., Conclusions: A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, electrolyte water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.