Influence of nimodipine combined with ulinastatin on neurological function and inflammatory reaction in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group. RESULTS: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05). CONCLUSION: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.

Acute Beetroot Juice Ingestion Does Not Alter Renal Hemodynamics during Normoxia and Mild Hypercapnia in Healthy Young Adults.

Arterial hypercapnia reduces renal perfusion. Beetroot juice (BRJ) increases nitric oxide bioavailability and may improve renal blood flow. We tested the hypothesis that acute consumption of BRJ attenuates both decreases in blood velocity and increases in vascular resistance in the renal and segmental arteries during acute hypercapnia. In fourteen healthy young adults, blood velocity and vascular resistance were measured with Doppler ultrasound in the renal and segmental arteries during five minutes of breathing a carbon dioxide gas mixture (CO2) before and three hours after consuming 500 mL of BRJ. There was no difference between pre- and post-BRJ consumption in the increase in the partial pressure of end-tidal CO2 during CO2 breathing (pre: +4 ± 1 mmHg; post: +4 ± 2 mmHg, p = 0.4281). Segmental artery blood velocity decreased during CO2 breathing in both pre- (by -1.8 ± 1.9 cm/s, p = 0.0193) and post-BRJ (by -2.1 ± 1.9 cm/s, p = 0.0079), but there were no differences between pre- and post-consumption (p = 0.7633). Segmental artery vascular resistance increased from room air baseline during CO2 at pre-BRJ consumption (by 0.4 ± 0.4 mmHg/cm/s, p = 0.0153) but not post-BRJ (p = 0.1336), with no differences between pre- and post-consumption (p = 0.7407). These findings indicate that BRJ consumption does not attenuate reductions in renal perfusion during acute mild hypercapnia in healthy young adults.

Pilot assessment of omega-3 fatty acids and potassium thiocyanate in sickle cell anemia patients with conditional peak systolic cerebral artery blood velocity.

OBJECTIVE: The purpose of this pilot study was to explore the effect of omega-3 fatty acids and potassium thiocyanate on conditional peak systolic cerebral artery blood velocity in children with sickle cell anemia (SCA). METHODS: Transcranial doppler ultrasonography (TCD) was done on 232 SCA children, and 21 found with conditional peak systolic blood velocity (PSV) of 200-249 cm/s in internal carotid, middle or anterior cerebral arteries. These were randomized to receive omega-3 fatty acids and potassium thiocyanate with standard treatment of SCA (test group, N = 14), or standard treatment only (control group, N = 7). After 3 months of treatment, PSV was measured again. RESULTS: Right middle cerebral artery PSV was significantly reduced in the test relative to the control groups (p = 0.04). PSV returned to normal in 79% of the test versus 43% of the control group; and increased to abnormal in one member of the control group, but none of the test group. CONCLUSIONS: The pilot data suggest that in SCA, omega-3 fatty acids and potassium thiocyanate might reduce conditional blood velocity to normal, or prevent progression to abnormal values. A larger, randomized, clinical trial is required to further address the current gap in management of conditional TCD blood velocity.

Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers.

The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.

Salviae miltiorrhizae radix and puerariae lobatae radix herbal formula improves circulation, vascularization and gait function in a peripheral arterial disease rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: DG is a herbal formula, containing the root of Salvia miltiorrhiza Bunge (Danshen) and the root of Pueraria lobate (Willd.) Ohwi (Gegen), has a history of usage in China for cardiovascular protection and anti-atherosclerosis. AIM OF THE STUDY: The present study aims to determine the beneficial effect of DG on the hind-limb ischemia rat model which mimics peripheral arterial disease (PAD) and its vasodilative effect on isolated femoral artery. MATERIALS AND METHODS: The vasodilatory effects were assessed by contractile responses to DG in the isolated femoral artery and its underlying mechanisms were evaluated by the involvement of endothelium, potassium channel and calcium channel. For hind-limb ischemia study, treatment outcomes were assessed by evaluating hind-limb blood flow, functional limb recovery, muscle histology and angiogenesis. RESULTS: Our results demonstrated positive dose-dependent vasodilatory response to DG via an endothelium-independent mechanism that involved inwardly rectifying K+ channels and Ca2+ channels. We also demonstrated significant improvement in blood perfusion and micro-vessel density in the ischemic limb and positive effects in functional limb recovery. CONCLUSION: In conclusion, our study supported the potential use of DG as a novel treatment for symptomatic PAD.

Salmon oil supplementation in dogs affects the blood flow of testicular arteries.

The administration of fish oils is known to cause changes in several reproductive parameters of domestic animals. The ingestion of polyunsaturated fatty acids (PUFAs) of the omega-3 family, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been described and correlated with changes in the semen quality, testosterone levels and male fertility. Nevertheless, few studies monitored and registered effects after ceasing supplementation. In the present study, we monitored the Doppler velocimetric and ultrasonographic parameters of nine dogs' testis for 90 days (D90) checking the effect of salmon oil supplementation, and monitoring continued for 60 days more, after ceasing supplementation (D150). Ultrasonographic evaluations comprised determining the Doppler velocimetric parameters, testicular and epididymal volume, and testicular echotexture. Peak systolic velocity (PSV) as well as final diastolic velocity (EDV) in the supratesticular arteries (STA), and marginal artery (MA) increased during the period of treatment and kept that level up to D150. There was no difference between the fish-oil supplementation period and the unsupplemented one regarding the testicular and epididymal volume and echogenicity and heterogeneity characteristics. A negative correlation was found between heterogeneity of testis and sperm production (r = -.41, p = .008). Doppler velocimetry indices were affected by the supplementation, leading to an increase in testicular blood flow.

Effects of Beetroot Powder with or without L-Arginine on Postprandial Vascular Endothelial Function: Results of a Randomized Controlled Trial with Abdominally Obese Men.

BACKGROUND: Through effects on nitric oxide bioavailability, vascular endothelial function is improved after the intake of a high amount of nitrate or L-arginine, but decreased after the intake of a high-fat meal. Therefore, we compared the effects of beetroot powder with or without L-arginine on postprandial brachial artery flow-mediated vasodilation (FMD) after consumption of a high-fat mixed-meal. METHODS: Eighteen abdominally obese men completed this randomized, double-blinded, cross-over trial. The study consisted of five test days, each separated by a wash-out period of at least one week. Participants received in random order, a blended meal with a control or nutritional supplement consisting of beetroot powder providing 200 mg nitrate, beetroot with 0.8 g of L-arginine, beetroot with 1.5 g of L-arginine, or 3.0 g of L-arginine. Participants then fasted and 2 h postprandial FMD measurements were performed. RESULTS: No significant differences between meals were observed for postprandial FMD (p = 0.45) levels. However, there was a non-significant trend towards a more beneficial postprandial FMD response with the beetroot-containing meals as compared with meals without beetroot. CONCLUSION: This trial could not provide evidence for beneficial additive effects of a single dose of beetroot powder combined with L-arginine on postprandial endothelial function in abdominally obese men.

Self-Reported Omega-3 Supplement Use Moderates the Association between Age and Exercising Cerebral Blood Flow Velocity in Older Adults.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions, including diet and exercise, to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively normal older adults (n = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed that self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

KEY POINTS: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. ABSTRACT: Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non-communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult-onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PaO2 and SaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

Shexiang Tongxin Dropping Pill Improves Peripheral Microvascular Blood Flow via Cystathionine-γ-Lyase.

BACKGROUND To explore the protective effects of Shexiang Tongxin Dropping Pill (STP) in improving peripheral microvascular dysfunction in mice and to explore the involved mechanism. MATERIAL AND METHODS A peripheral microvascular dysfunction model was established by combined myocardial infarction (MI) and lipopolysaccharide (LPS) injection in mice. Then, the mice were randomized into a model group (n=10) or an STP group (n=10), which were treated with normal saline and STP, respectively. The cremaster muscle microvascular blood flow velocity and numbers of leukocytes adherent to the venular wall were evaluated before and after drug intervention. We assessed the expression of adhesion molecule CD11b and related transcript factor FOXO1 in leukocytes, cystathionine-γ-lyase (CSE) mRNA expression in the cremaster muscle, and mitochondrial DNA copy numbers. RESULTS Compared with those of control mice, the cremaster microvascular blood flow velocity, cremaster CSE expression, and mitochondrial DNA copy number in mice from the model group were significantly lower and leukocyte adhesion and CD11b and FOXO1 expression were significantly higher. Intervention with STP could significantly increase the cremaster microvascular flow velocity (0.480±0.010 mm/s vs. 0.075±0.005 mm/s), mRNA expression of cremaster CSE, and mitochondrial DNA copy number, but it inhibited leukocyte adhesion and decreased leukocyte CD11b and FOXO1 expression. CONCLUSIONS STP significantly improved peripheral microcirculation, in which increased CSE expression might be the underlying mechanism.

Assessment of real-time and quantitative changes in renal hemodynamics in healthy overweight males: Contrast-enhanced ultrasonography vs para-aminohippuric acid clearance.

OBJECTIVE: To determine the ability of renal contrast-enhanced ultrasonography (CEUS) to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide (GLP)-1 receptor agonist exenatide and nitric oxide [NO]-synthase inhibitor L-NG -monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans. METHODS: In this prespecified exploratory analysis of a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27 years; BMI 26-31 kg/m2 ) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences. Renal cortical microvascular blood flow was compared with simultaneously measured effective renal plasma flow in humans, derived from para-aminohippuric acid-clearance methodology. RESULTS: On Day-A, effective renal plasma flow increased by 68 [26-197] mL/min/1.73 m2 during exenatide vs placebo infusion (+17%; P = .015). In parallel, exenatide increased renal cortical microvascular blood flow, from 2.42 × 10-4 [6.54 × 10-5 -4.66 × 10-4 ] AU to 4.65 × 10-4 [2.96 × 10-4 -7.74 × 10-4 ] AU (+92%; P = .027). On Day-B, effective renal plasma flow and renal cortical microvascular blood flow were reduced by l-NMMA, with no significant effect of concomitant exenatide on renal hemodynamic-indices assessed by either technique. Effective renal plasma flow correlated with renal cortical microvascular blood flow on Day-A (r = .533; P = .027); no correlation was found on Day-B. CONCLUSIONS: Contrast-enhanced ultrasonography can detect acute drug-induced changes human renal hemodynamics. CEUS-assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal-to-high range. Renal CEUS cannot replace effective renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion.

"Beet" the cold: beetroot juice supplementation improves peripheral blood flow, endothelial function, and anti-inflammatory status in individuals with Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterized by recurrent transient peripheral vasospasm and lower nitric oxide (NO) bioavailability in the cold. We investigated the effect of nitrate-rich beetroot juice (BJ) supplementation on 1) NO-mediated vasodilation, 2) cutaneous vascular conductance (CVC) and skin temperature (Tsk) following local cooling, and 3) systemic anti-inflammatory status. Following baseline testing, 23 individuals with RP attended four times, in a double-blind, randomized crossover design, following acute and chronic (14 days) BJ and nitrate-depleted beetroot juice (NDBJ) supplementation. Peripheral Tsk and CVC were measured during and after mild hand and foot cooling, and during transdermal delivery of acetylcholine and sodium nitroprusside. Markers of anti-inflammatory status were also measured. Plasma nitrite concentration ([nitrite]) was increased in the BJ conditions (P < 0.001). Compared with the baseline visit, thumb CVC was greater following chronic-BJ (Δ2.0 flux/mmHg, P = 0.02) and chronic-NDBJ (Δ1.45 flux/mmHg, P = 0.01) supplementation; however, no changes in Tsk were observed (P > 0.05). Plasma [interleukin-10] was greater, pan endothelin and systolic and diastolic blood pressure (BP) were reduced, and forearm endothelial function was improved, by both BJ and NDBJ supplementation (P < 0.05). Acute and chronic BJ and NDBJ supplementation improved anti-inflammatory status, endothelial function and blood pressure (BP). CVC following cooling increased post chronic-BJ and chronic-NDBJ supplementation, but no effect on Tsk was observed. The key findings are that beetroot supplementation improves thumb blood flow, improves endothelial function and anti-inflammatory status, and reduces BP in people with Raynaud's.NEW & NOTEWORTHY This is the first study to examine the effect of dietary nitrate supplementation in individuals with Raynaud's phenomenon. The principal novel findings from this study were that both beetroot juice and nitrate-depleted beetroot juice 1) increased blood flow in the thumb following a cold challenge; 2) enhanced endothelium-dependent and -independent vasodilation in the forearm; 3) reduced systolic and diastolic blood pressure, and pan-endothelin concentration; and 4) improved inflammatory status in comparison to baseline.

Vascular effects of caffeine found in BOLD fMRI.

The blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) measures neuronal activation indirectly. Previous studies have found aperiodic, systemic low-frequency oscillations (sLFOs, ~0.1 Hz) in BOLD signals from resting state (RS) fMRI, which reflects the non-neuronal cerebral perfusion information. In this study, we investigated the possibility of extracting vascular information from the sLFOs in RS BOLD fMRI, which could provide complementary information to the neuronal activations. Two features of BOLD signals were exploited. First, time delays between the sLFOs of big blood vessels and brain voxels were calculated to determine cerebral circulation times and blood arrival times. Second, voxel-wise standard deviations (SD) of LFOs were calculated to represent the blood densities. We explored those features on the publicly available Myconnectome data set (a 2-year study of an individual subject (Male)), which contains 45 RS scans acquired after the subject had coffee, and 45 coffee-free RS scans, acquired on different days. Our results showed that shorter time delays and smaller SDs were detected in caffeinated scans. This is consistent with the vasoconstriction effects of caffeine, which leads to increased blood flow velocity. We also compared our results with previous findings on neuronal networks from the same data set. Our finding showed that brain regions with the significant vascular effect of caffeine coincide with those with a significant neuronal effect, indicating close interaction. This study provides methods to assess the physiological information from RS fMRI. Together with the neuronal information, we can study simultaneously the underlying correlations and interactions between vascular and neuronal networks, especially in pharmacological studies.

Roasted Barley Extract (Mugi-cha) Containing Cyclo(d-Phe-l-Pro) Prevents Lowering of the Cutaneous Blood Flow and Skin Temperature under Air Conditioning: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

Roasted barley extract (RBE), also known as mugi-cha, is a well-known healthy non-caffeinated beverage, and its health functionality has been widely reported. Our previous clinical study showed that RBE affects the cutaneous blood flow and skin temperature after cold-water immersion and that cyclo(d-Phe-l-Pro) is responsible for its effect. In this study, we investigated whether cyclo(d-Phe-l-Pro)-containing RBE prevents the decrease in the cutaneous blood flow and skin temperature. Subjects remained in the air-conditioned room while ingesting RBE or a placebo. We measured the cutaneous blood flow and skin temperature. We evaluated the effect of RBE administration by two-way repeated measures analysis of variance. A total of 15 subjects were enrolled. The change in cutaneous blood flow in the RBE and placebo groups was -0.79 ± 0.38 and -2.03 ± 0.35 mL min-1 100 g-1, respectively ( p value of 0.041). The change in the skin temperature in the RBE and placebo groups was -1.85 ± 0.35 and -3.02 ± 0.30 °C, respectively ( p value of <0.001). We also did subclass analysis with cold-feeling subjects. For the seven subjects who had cold sensation, the change in the cutaneous blood flow in the RBE and placebo groups was -0.48 ± 0.58 and -2.56 ± 0.48 mL min-1 100 g-1, respectively ( p value of 0.008). The change in the skin temperature in the RBE and placebo groups was -1.46 ± 0.74 and -2.89 ± 0.39 °C, respectively ( p value of 0.009). Thus, RBE containing cyclo(d-Phe-l-Pro) prevents the decrease in the cutaneous blood flow and skin temperature under air conditioning.

Microcirculatory Disorders and Protective Role of Xuebijing in Severe Heat Stroke.

This study was conducted to explore underlying mechanism of microcirculation dysfunction and protectiverole of Xuebijing in heat stroke. Forty rats were divided into: control, vehicle + heat stress (HS), superoxide dismutase (SOD) + HS, and Xuebijing + HS groups. Rats in heat stress groups were subjected to continuous heat stress in infant incubator 1 h after tail vein injection of the tested compound and spinotrapezius preparation. Velocity of blood flow through micro-vessels and vascular diameter were detected in real time. Another 27 rats were divided into: vehicle, SOD, and Xuebijing groups, then further divided into three subgroups each: control, Tcore = 38 °C, Tcore = 41 °C. Rats were sacrificed, and spinotrapezius single-cell suspensions were prepared for detecting SOD and reactive oxygen species (ROS). The results showed that heat stress decreased SOD activity, increased ROS levels, and reduced the blood flow rate. Xuebijing increased SOD activity, decreased ROS levels and exhibited a protective effect in terms of blood flow rate but was less protective than SOD. The survival time in Xuebijing + HS group was longer than that in vehicle group but shorter than that in SOD + HS group. The results suggested Xuebijing could decrease ROS levels and have protective effects in severe heat stroke.

Decreased Cerebral Blood Flow in Mesial Thalamus and Precuneus/PCC during Midazolam Induced Sedation Assessed with ASL.

While some previous work suggests that midazolam-induced light sedation results from the functional disconnection within resting state network, little is known about the underlying alterations of cerebral blood flow (CBF) associated with its effects. A randomized, double-blind, within-subject, cross-over design was adopted, while 12 healthy young volunteers were scanned with arterial spin-labeling (ASL) perfusion MRI both before and after an injection of either saline or midazolam. The contrast of MRI signal before and after midazolam administration revealed the CBF decrease in the bilateral mesial thalamus and precuneus/posterior cingulate cortex (PCC). These effects were confirmed after controlling for any effect of injection as well as head motions. These findings provide new evidences that midazolam-induced light sedation is related to the disruption of cortical functional integration, and have new implications to the neural basis of consciousness.

Effectiveness and Safety of Treatment with Direct Oral Anticoagulant Rivaroxaban in Patients with Slow-Flow Vascular Malformations: A Case Series.

BACKGROUND: Slow-flow vascular malformations (VM) can be associated with localized intravascular coagulopathy (LIC) that is characterized by elevated D-Dimer levels and low fibrinogen and platelets. This can lead to bleeding and clotting tendencies, which can give rise to functional limitations such as pain and swelling and even progress to disseminated intravascular coagulopathy. METHODS AND RESULTS: We conducted a chart review of four patients with evidence of LIC who were started on rivaroxaban. We found an improvement of D-Dimer and/or fibrinogen levels in all four patients. They also had an improvement of pain and functionality. CONCLUSIONS: We report on four patients in whom anticoagulation with a direct oral anticoagulant, rivaroxaban, was effective in controlling signs and symptoms of consumptive coagulopathy with no evidence of bleeding from the use of rivaroxaban.

Roasted Barley Extract Affects Blood Flow in the Rat Tail and Increases Cutaneous Blood Flow and Skin Temperature in Humans.

Roasted barley extract (RBE, "Mugicha") is a traditional Japanese beverage reported to improve blood viscosity and affect food functionality. RBE is suggested to contain 2,5-diketopiperazines, which are the functional component with neuroprotective and immunostimulatory effects that are produced in food through roasting. In this study, we investigated the effects of RBE on blood circulation, both clinically and in rats. At first, we confirmed five 2,5-diketopiperazine derivatives in RBE by LC-MS analysis. Secondarily, we revealed that RBE affects blood flow in the rat tail and compared the efficacy on rat tail blood flow among five 2,5-diketopiperazines in RBE. Especially, cyclo(d-Phe-l-Pro) was the most effective in increasing blood flow in the rat tail. We also researched the mechanism of cyclo(d-Phe-l-Pro) with rat aorta study. As a result, we confirmed that cyclo(d-Phe-l-Pro) has an effect on vasodilatation through the release of nitric oxide in the vascular endothelium. Finally, we also confirmed that RBE affects cutaneous blood flow and increases skin temperature in humans.

Effects of S-1-propenylcysteine, a sulfur compound in aged garlic extract, on blood pressure and peripheral circulation in spontaneously hypertensive rats.

OBJECTIVES: This study was designed to investigate the antihypertensive effect of S-1-propenylcysteine, a characteristic sulfur compound in aged garlic extract, using a hypertensive rat model. METHODS: The blood pressure and tail blood flow of both spontaneously hypertensive rats and control Wistar Kyoto rats were measured by the tail-cuff method and the noncontact laser Doppler method, respectively, at various times after single oral administration of a test compound for 24 h. KEY FINDINGS: Treatment with S-1-propenylcysteine (6.5 mg/kg BW) significantly decreased the systolic blood pressure of spontaneously hypertensive rat approximately 10% at 3 h after administration, and thereafter, the systolic blood pressure gradually returned to the baseline level in 24 h. The effect of S-1-propenylcysteine was dose-dependent and was maximal at the dose of 6.5 mg/kg BW at 3 h. However, the other compounds such as S-allylcysteine and S-allylmercaptocysteine in aged garlic extract were ineffective. In addition, S-1-propenylcysteine had no effect on systolic blood pressure of control Wistar Kyoto rats. Furthermore, S-1-propenylcysteine significantly increased the blood flow at 3 h after administration at the dose of 6.5 mg/kg BW. CONCLUSIONS: S-1-propenylcysteine is a key constituent of aged garlic extract responsible for its antihypertensive effect, and the effect of S-1-propenylcysteine involves the improvement in peripheral circulation.

A systematic characterization of the factors influencing polymerization and dynamic behavior of n-butyl cyanoacrylate.

INTRODUCTION: Brain arteriovenous malformations are abnormal connections between arteries and veins without an intervening capillary bed. Endovascular glue embolization with N-butyl cyanoacrylate (NBCA) is an accepted form of treatment. The reported complication rates vary widely from 2% to 15%, and timing of polymerization appears to play a major role. Additionally, the interaction between NBCA and vessel surface as well as the presence of biological catalysts are poorly understood. METHODS: Polymerization time was measured for mixtures of Lipiodol/NBCA of 50/50, 70/30, and 60/40. The influence of pH, temperature, and the presence of biological catalysts on polymerization time was investigated. Contact angles were measured on polyvinyl alcohol cryogel (PVA-C), silicone, and endothelial surfaces in a submerged aqueous environment to assess physical surface interactions. High speed video analysis of glue injection through a microcatheter was performed to characterize simulated coaxial flow. RESULTS: NBCA polymerization rate increased with pH and temperature. A hydrophilic surface such as PVA-C was better than silicone at mimicking the physical properties of endothelium. Live endothelium provided a catalytic surface that at least doubled the rate of polymerization. Blood products further increased the polymerization rate in the following order (slowest to fastest): plasma, platelets, red blood cells (RBCs), and lysed RBCs. These factors could explain the discrepancy between in vitro and in vivo results reported in the current literature. High speed video analysis of NBCA injection showed dripping to jetting transition with significant wall effect which deviated from previous ideal assumptions. CONCLUSIONS: The determinants of NBCA polymerization rate are multifactorial and dependent mainly on the presence of biological catalysts coupled with flow related wall interaction.