Potential analgesic effect of Foshousan oil-loaded chitosan-alginate nanoparticles on the treatment of migraine.

Background: Migraine is a common neurovascular disorder with typical throbbing and unilateral headaches, causing a considerable healthcare burden on the global economy. This research aims to prepare chitosan-alginate (CS-AL) nanoparticles (NPs) containing Foshousan oil (FSSO) and investigate its potential therapeutic effects on the treatment of migraine. Methods: FSSO-loaded CS-AL NPs were prepared by using the single emulsion solvent evaporation method. Lipopolysaccharide (LPS)-stimulated BV-2 cells and nitroglycerin (NTG)-induced migraine mice were further used to explore anti-migraine activities and potential mechanisms of this botanical drug. Results: FSSO-loaded CS-AL NPs (212.1 ± 5.2 nm, 45.1 ± 6.2 mV) had a well-defined spherical shape with prolonged drug release and good storage within 4 weeks. FSSO and FSSO-loaded CS-AL NPs (5, 10, and 15 µg/mL) showed anti-inflammatory activities in LPS-treated BV-2 cells via reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO), but elevating interleukin-10 (IL-10) expressions. Moreover, FSSO-loaded CS-AL NPs (52 and 104 mg/kg) raised pain thresholds against the hot stimulus and decreased acetic acid-induced writhing frequency and foot-licking duration in NTG-induced migraine mice. Compared with the model group, calcitonin gene-related peptide (CGRP) and NO levels were downregulated, but 5-hydroxytryptamine (5-HT) and endothelin (ET) levels were upregulated along with rebalanced ET/NO ratio, and vasomotor dysfunction was alleviated by promoting cerebral blood flow (CBF) in the FSSO-loaded CS-AL NPs (104 mg/kg) group. Conclusion: FSSO-loaded CS-AL NPs could attenuate migraine via inhibiting neuroinflammation in LPS-stimulated BV-2 cells and regulating vasoactive substances in NTG-induced migraine mice. These findings suggest that the FSS formula may be exploited as new phytotherapy for treating migraine.

Potential mechanisms of acupuncture in enhancing cerebral perfusion of ischemic stroke.

Ischemic stroke is the predominant cause of long-term disability and death worldwide. It is attributable to the sudden interruption of regional cerebral blood flow, resulting in brain cell death and neurological impairment. Acupuncture is a widely used adjuvant treatment for ischemic stroke in China and shows promising efficacy in clinical practice. This review mainly focused on the evidence to illustrate several possible mechanisms of acupuncture therapy on cerebral perfusion in ischemic stroke. Studies have shown that acupuncture is probably effective in the enhancement of cerebral perfusion after ischemic stroke. It promotes the improvement of hemodynamics, the release of vasoactive substances, the formation of new blood vessels, as well as the restitution of microcirculation. Multiple factors may contribute to the variability in acupuncture's therapeutic effects, including the acupoint selection, stimulation frequency and intensity, and retaining needle time. Acupuncture has the potential to become a non-pharmacological adjuvant approach to enhance cerebral perfusion in ischemic stroke. Future studies are required to gain our insight into acupuncture as well as accelerate its clinical translation.

Effect of Physical Training on Nitric Oxide Levels in Patients with Arterial Hypertension: An Integrative Review

Abstract The regular practice of physical exercise as a non-pharmacological treatment of arterial hypertension (AH) has been encouraged due to causing a series of physiological responses in the cardiovascular system, such as the production of vasoactive substances, including nitric oxide (NO). NO is a relaxation factor released by the endothelium, and the decrease in its bioavailability is related to coronary and arterial diseases, such as AH. This study aimed to perform an integrative literature review to elucidate the effect of physical training on NO levels in patients with AH and to establish a relationship between these levels and blood pressure (BP) control. A literature review was was performed by searching PubMed / MEDLINE, Lilacs, Scielo, Cinahl and Embase databases. The search string used was ("arterial hypertension" OR hypertension) AND (exercise OR "physical exercise" OR "aerobic exercise" OR "exercise training" or "physical activity") AND ("nitric oxide"). We included fully available controlled and uncontrolled clinical trials published in English and Portuguese languages in the last 10 years. The review consisted of 16 articles, of which 13 reported an increase in NO production after the physical training intervention, and three studies found no change. In addition, 15 studies observed a reduction in BP after the intervention. In conclusion, regular practice of physical exercises, advocating moderate intensity, can improve NO bioavailability in pre-hypertensive and hypertensive individuals, which seems to be one of the mechanisms responsible for BP reduction.

Modified Sanpiantang in Treatment of Migraine： A Review / 中国实验方剂学杂志

Migraine is a common neurovascular disorder manifested by recurrent severe headaches on one or both sides， occasionally accompanied by nausea， vomiting， photophobia， and phonophobia. It has the characteristics of recurrent attacks and family inheritance. Traditional Chinese medicine （TCM） believes that migraine belongs to the category of "head wind"， which is mostly caused by external wind and is related to the internal stirring of liver wind. Sanpiantang comes from the Record of Syndorme Differentiation·Headache （Bianzhenglu·Toutongmen） created by the physician CHEN Shiduo of the Qing Dynasty. It is composed of Chuanxiong Rhizoma， Angelicae Dahuricae Radix， Pruni Semen， Cyperi Rhizoma， Bupleuri Radix， White Mustard Seed， and Glycyrrhizae Radix et Rhizoma， with the functions of moving Qi to release pain， activating blood and resolving stasis， which is commonly used for the treatment of migraine in clinic. Current clinical studies on the application of Sanpiantang to the treatment of migraine mostly used modified Sanpiantang， either alone or in combination with western medicine/acupuncture. The results of these clinical trials showed that Sanpiantang could significantly lower migraine score， pain visual analog scale and endothelin level， reduce the frequency of painkiller use， and remarkably alleviate migraine symptoms， with few side effects. The animal experiments focused on exploring the mechanism of action of modified Sanpiantang from different anatomical levels of migraine， which mainly included reducing nitric oxide （NO） and nitric oxide synthase （NOS）， reduceing the release of neurotransmitters such as 5 -hydroxyline (5-HT) and neurotipides (NPY)， suppressing neuronal excitation， and blocking the transmission of nociceptive pathways， thereby promoting cerebral blood flow， regulating neurotransmitters and preventing migraine. Based on the pathogenesis of migraine， this paper systematically reviewed the latest progress in clinical application and experimental research of modified Sanpiantang， and summarized its mechanism of action of preventing and treating migraine， which provided new ideas for clinical treatment of migraine.

Secondary Metabolites of Plants as Modulators of Endothelium Functions.

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

Effects of Active Components of Naoxintong Capsule on the Proliferation of HUVEC and Its JAK/STAT Signal Pathway，Vasoactive Substances ，Adhesion Molecules and Inflammatory Factors / 中国药房

OBJECTIVE：To study the effects of the main active components of Naoxintong capsule （NXTC）on the proliferation of human umbilical vein endothelial cell（HUVEC） and its key protein JAK/STAT signal pathway ， vasoactive substances ，adhesion molecules and inflammatory factors so as to clarify the m echanism of NXTC for promoting blood circulation and removing blood stasis. METHODS ：The effects of different concentration of 12 active components [caffeic acid（1.56-200 μmol/L），ferulic acid （1.56-200 μmol/L），senkyunolide H （3.125-200 μmol/L），n-butylidenephthalide（3.125-200 μmol/L），ligustilide（1.56-200 μmol/L），cryptotanshinone（0.625-80 μmol/L），tanshinol sodium （1.56-200 μmol/L），paeoniflorin （1.56-200 μmol/L），formononetin（1.56-200 μmol/L），salvianolic acid B （1.56-200 μmol/L），catechin（1.56-200 μmol/L）and astragaloside Ⅳ（1.56-200 μmol/L）] on the proliferation of HUVECs were evaluated by CCK- 8 assay. The effects of above active components（3 dose groups ，setting up 0 μmol/L blank control group，hereinafter）on mRNA expression of key proteins JAK 2， STAT3，Akt，ERK in JAK/STAT signal pathway were measured by RT-PCR. The effects of each active component on the expression of PAI- 1，VCAM-1，ICAM-1，VEGF and NF-κB p65 were detected by ELISA. RESULTS ：Ferulic acid （6.25，25-200 μg/mL），senkyunolide H （6.25-200 μmol/L），ligustilide（200 μmol/L），cryptotanshinone（10-80 μmol/L），paeoniflorin（1.56， 6.25，12.5 μmol/L），salvianolic acid B （1.56-12.5 μmol/L，200 μmol/L）and catechin （25 μmol/L）could significantly inhibit the proliferation of HUVECs ；caffeic acid （1.56，12.5 μmol/L），ligustilide（50 μmol/L），trashinol sodium （6.25 μmol/L）and paeoniflorin（1.56，100，200 μmol/L）could significantly promote the proliferation of HUVECs （P＜0.05 or P＜0.01）. Compared with blank control group ，mRNA expression of JAK 2，STAT3 and Akt were decreased significantly in some dose groups of ferulic acid，formononetin，salvianolic acid B and astragaloside Ⅳ（P＜0.05 or P＜0.01）；the expression of PAI- 1 were significantly decreased in some dose groups of caffeic acid ，ferulic acid and n-butylphthalide；the expression of ICAM- 1 and VCAM- 1 were decreased significantly in some dose groups of caffeic acid ，ferulic acid ，n-butenylphthalide，cryptotanshinone，formononetin and catechin；the expression of NF-κB p65 were decreased significantly in some dose groups of ferulic acid ，n-butenylphthalide， formononetin，salvianolic acid B and astragaloside Ⅳ；the expression of VEGF were increased significantly in some dose groups of caffeic acid and catechin （P＜0.05 or P＜0.01）. CONCLUSIONS ：The active components of Naoxintong capsule may play the role of promoting blood circulation and removing blood stasis by inhibiting the expression of JAK/STAT signal pathway key protein mRNA and PAI- 1，ICAM-1，VCAM-1，NF-κB p65 in HUVEC ，and promoting the expression of VEGF.

Effect of electrical stimulation on local microvessel regeneration and expression of plasma endothelin-1 and nitric oxide in a rat model of myofascial trigger points / 中国组织工程研究

BACKGROUND: Plenty of evidences have revealed that electrical stimulation (ES) can promote local tissue vascular regeneration and regulate the expression of vasoactive substances, but it is unclear whether ES may promote local revascularization and change blood flow state in myofascial trigger points (MTrPs) or not. OBJECTIVE: To investigate the effect of ES on microvascular regeneration and plasma endothelin-1 and nitric oxide levels in MTrPs. METHODS: Fifty-four Sprague-Dawley rats were randomly divided into blank control, model and ES groups, with 18 rats in each group. And each group was equally subdivided into three subgroups (before, 7 and 15 days after intervention). In the model and ES groups, the rat model of MTrPs was established using combat and eccentric motion. Once the MTrPs model was made, the ES group was given ES intervention (depth: 2 mm, voltage: 6 V, frequency: 20 Hz, pulse width: 160 ms) at MTrPs, 30 minutes per day, for 15 days. Six rats from each group were executed at 7 and 15 days of intervention. Paraffin sections were manufactured for hematoxylin-eosin and immunohistochemical staining after the local tissues of MTrPs were dissected and separated. Subsequently, pathological changes were observed under light microscope. Microvessel density was counted and analyzed. The levels of plasma endothelin-1 and nitric oxide were detected by ELISA. The study protocol was approved by the Experimental Animal Ethics Committee of the Nanfang Hospital of Southern Medical University in China. RESULTS AND CONCLUSION: The changes of brittleness and insect-likes erosion in local MTrps tissues were observed under the light microscope in the model and ES groups. The micro-vessel density in MTrps increased and the tissue structure of MTrps gradually returned to be normal after ES intervention. The microvessel density in the model and ES groups was lower than that in the blank control group before intervention, but the microvessel density in the ES group was significantly higher than that in the other two groups at 7 and 15 days of intervention (both P 0.05). The levels of plasma endothelin-1 and nitric oxide were higher in the model and ES groups than the blank control group before intervention. After 15 days of intervention, the levels of plasma endothelin-1 in the ES group were decreased (P 0.05). These results reveal that ES intervention can promote the regeneration of microvessels and regulate the expression of vasoactive substances in MTrPs tissue, improve ischemia and hypoxia state of MTrPs and contribute greatly to local tissue repair.

A Review of the Actions of Endogenous and Exogenous Vasoactive Substances during the Estrous Cycle and Pregnancy in Rats.

Vascular endothelium plays a key role in regulating cardiovascular homeostasis by controlling the vascular tone. Variations in sex hormones during the reproductive cycle of females affect the homeostasis of the cardiovascular system. Also, the evidence shows that estrogens show a cardioprotective effect. On this basis, this study describes some vascular responses induced by vasoactive substances during the estrous cycle in rats. We obtained the information available on this topic from the online databases that included scientific articles published in the Web of Science, PubMed, and Scielo. Many investigations have evaluated the vasoactive response of substances such as acetylcholine and norepinephrine during the estrous cycle. In this review, we specifically described the vascular response to vasoactive substances in rats during the estrous cycle, pregnancy, and in ovariectomized rats. In addition, we discussed the existence of different signaling pathways that modulate vascular function. The knowledge of these effects is relevant for the optimization and development of new treatments for some vascular pathologies.

Randomized double-blind clinical studies of ularitide and other vasoactive substances in acute decompensated heart failure: a systematic review and meta-analysis.

AIMS: Acute decompensated heart failure (ADHF) has a poor prognosis and limited treatment options. No direct comparisons between ularitide-a synthetic natriuretic peptide being evaluated in ADHF-and other vasoactive substances are available. The aim of this meta-analysis was to determine haemodynamic effect sizes from randomized double-blind trials in ADHF. METHODS AND RESULTS: Eligible studies enrolled patients with ADHF requiring hospitalization and haemodynamic monitoring. Patients received 24-48 h of infusion with a vasoactive substance or comparator. Primary outcome measure was pulmonary artery wedge pressure (PAWP). Treatment effects were quantified as changes from baseline using mean differences between study drug and comparator. Results were analysed using random-effects (primary analysis) and fixed-effects meta-analyses. Twelve randomized, double-blind studies were identified with data after 3, 6, and 24 h of treatment (n = 622, 644, and 644, respectively). At 6 h, significant PAWP benefits for ularitide over placebo were seen (Hedges' g effect size, -0.979; P < 0.0001). On meta-analysis, treatment difference between ularitide and pooled other agents was statistically significant (-0.501; P = 0.0303). Effect sizes were numerically higher with ularitide than other treatments at 3 and 24 h. After 6 h, a significant difference in effect size between ularitide and all other treatments was observed for right atrial pressure (Hedges' g, -0.797 for ularitide and -0.304 for other treatments; P = 0.0274). CONCLUSIONS: After 6 h, ularitide demonstrated high effect sizes for PAWP and right atrial pressure. Improvements in these parameters were greater with ularitide vs. pooled data for other vasoactive drugs.

Preventive effects of total coumarin and essential oil of Angelicae Dahuricae Radix on migraine rats and their mechanisms / 吉林大学学报(医学版)

Objective: To observe the preventive effects of combined application of total coumarin and essential oil of Angelicae Dahuricae Radix on the migraine rats induced by nitroglycerin, and to explore their mechanisms. Methods: A total of 56 Wistar rats were randomly divided into normal control group (saline 0. 1 mL · 10 g 1), migraine model group (saline 0. 1 mL · 10 g 1), total coumarin of Angelicae Dahuricae Radix group (100 mg · kg-1), essential oil of Angelicae Dahuricae Radix group (100 mg · kg-1), and low dose (25 mg · kg-1), middle dose (50 mg · kg-1) and high dose (100 mg · kg-1) of total coumarin and essential oil composition of Angelicae Dahuricae Radix groups (composition groups) (n=8). After continuously intragastric adminstration for 7 d, the rats were injected subcutaneously with nitroglycerin (10 mg · kg-1) for establishing the migraine models. The behavior of the rats were observed, the levels of nitric oxide (NO) in serum and brain tissue of rats, the levels of calcitonin gene related peptide (CGRP) and endothelin (ET) in plasma of the rats in various groups were detected. Results: Compared with normal control group, the frequencies of head shaking, the face shoting times of posterior legs and the scratching times of anterior limbs of the rats in migraine model group were increased (P<0. 05 or P<0. 01), and the levels of NO in serum and brain tissue of the rats were increased (P< 0. 01). Compared with migraine model group, the frequencies of head shaking, the face shoting times of posterior legs and scratching times of anterior limbs of the rats in total coumarin group, essential oil group, and composition groups were decreased (P<0. 05 or P<0. 01), and the levels of NO in serum and brain tissue of the rats were decreased (P<0. 05 or P<0. 01). Compared with migraine model group, the levels of CGRP and ET in plasma of the rats in essential oil group, total coumarin group and middle and high doses of composition groups were decreased (P<0. 05). Conclusion: The composition of two active ingredients of Angelicae Dahuricae Radix, total coumarin and essential oil, has preventive effects in the migraine rats induced by nitroglycerin, and their mechanisms may be related to regulation of the levels and function of vasoactive substances.

[Effects of astragalus polysaccharide on cardiac dysfunction in rabbits with severe scald injury].

Objective: To investigate the effects of astragalus polysaccharide (AP) on cardiac dysfunction in rabbits with severe scald injury. Methods: Sixty-four New Zealand white rabbits were divided into pure scald group and AP group according to the random number table, with 32 rabbits in each group. Rabbits in the two groups were all inflicted with 30% total body surface area full-thickness scald on the back. Immediately after injury, rabbits in two groups were intraperitoneally injected with lactated Ringer's solution once for antishock. Rabbits in AP group were intraperitoneally injected with 10 mL AP solution with the dosage of 200 mg/kg 10 min after injury and the following 6 days respectively, once a day. Rabbits in pure scald group were injected with 10 mL normal saline instead. Eight rabbits of each group were respectively selected before injury hour (BIH) 1 and on post injury day(PID) 1, 3, 7, and 14 to collect blood samples from ear marginal vein, and then sacrificed immediately to collect hearts at each time point post injury. The morphology of myocardium was observed after HE staining. The serum content of cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent assay (ELISA). The serum content of aspartate transaminase (AST), creatine kinase (CK), CK isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH) was detected by fully automatic chemistry analyzer. The content of angiotensin Ⅱ (Ang Ⅱ) in serum and myocardium was detected with radioimmunoassay and the content of endothelin 1 (ET-1) in serum and myocardium was detected by ELISA. Another 8 normal rabbits were sacrificed to detect the content of Ang Ⅱ and ET-1 in the myocardium as the value of the two groups of scalded rabbits at BIH 1. The serum content of superoxide dismutase (SOD) and malondialdehyde (MDA) was detected by ELISA. The values of whole blood viscosity (ηb), reductive viscosity of whole blood (ηr), plasma viscosity (ηp), hematocrit (HCT), erythrocyte rigidity index (TK), erythrocyte aggregation index (EAI), and erythrocyte sedimentation rate (ESR) were detected by fully automatic hematology analyzer. Data were processed with analysis of variance of factorial design, independent sample t test, and Dunnett test. Results: (1) Compared with those in pure scald group, the degrees of cardiomyocyte swelling, steatosis, necrosis and rupture of muscle fiber were significantly alleviated in rabbits of AP group on PID 1 and 3. There was no obvious increase in cell size, no breakage of muscle fiber or infiltration of inflammatory cells in myocardial interstitium on PID 7. The myocardial tissue structure and muscle fiber arrangement returned to normal condition on PID 14, with no interstitial fibroblast hyperplasia or excessive extra cellular matrix deposition. (2) Serum content of cTnI, CK, and LDH of rabbits in AP group was significantly lower than that in pure scald group on PID 1, 3, and 7 (with t values from 2.69 to 13.99, P<0.05 or P<0.01), while there was no significant difference between the two groups on PID 14 (with t values from -0.32 to 0.68, P values above 0.05). Serum content of AST and CK-MB of rabbits in AP group was significantly lower than that in pure scald group on PID 1 and 3 (with t values from 2.21 to 12.65, P<0.05 or P<0.01), while there was no significant difference between the two groups on PID 7 and 14 (with t values from 0.03 to 1.67, P values above 0.05). (3) Serum content of Ang Ⅱ of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 14 (with t values from 3.38 to 32.58, P values below 0.01). Serum content of ET-1 of rabbits in AP group was significantly lower than that in pure scald group from PID 3 to 14 (with t values from 3.54 to 11.02, P values below 0.01), while there was no obvious difference on PID 1 (t=0.39, P>0.05). Content of Ang Ⅱ and ET-1 in myocardial tissue of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 7 (with t values from 1.27 to 13.79, P values below 0.01), while there was no obvious difference on PID 14 (with t values respectively 0.07 and 0.81, P values above 0.05). (4) Serum content of SOD of rabbits in AP group was respectively (15.65±2.64), (14.67±0.74), and (8.43±0.56) ng/mL on PID 1, 3, and 7, which was significantly higher than (6.35±0.83), (2.62±0.75), and (2.84±0.41) ng/mL in pure scald group (with t values from -29.79 to -9.10, P values below 0.01); while there was no obvious difference on PID 14 [with (4.02±0.26) ng/mL in pure scald group and (4.11±0.52) ng/mL in AP group, t=-0.01, P>0.05]. Serum content of MDA of rabbits in AP group was respectively (1.31±0.61), (1.72±0.64), and (0.65±0.42) µmol /mL on PID 1, 3, and 7, which was significantly lower than (1.68±0.57), (2.34±0.79), and (1.06±0.32) µmol/mL in pure scald group (with t values from 1.63 to 3.16, P<0.05 or P<0.01), while there was no obvious difference on PID 14 [with (0.31±0.09) µmol/mL in pure scald group and (0.24±0.08) µmol/mL in AP group, t=2.11, P>0.05]. (5) Values of ηb1 and EAI of rabbits in AP group were significantly lower than those in pure scald group from PID 1 to 7 (with t values from 2.718 to 11.170, P<0.05 or P<0.01), while there were no obvious differences on PID 14 (with t values respectively 2.078 and -1.423, P values above 0.05). Values of ηb2 and ηr2 of rabbits in AP group were significantly lower than those in pure scald group on PID 3 and 7 (with t values from 2.178 to 19.205, P<0.05 or P<0.01), while there were no obvious differences on PID 1 and 14 (with t values from -0.730 to 1.320, P values above 0.05 ). Values of ηr1 and ESR of rabbits in AP group were significantly lower than those in pure scald group on PID 3, 7, and 14 (with t values from 3.021 to 8.058, P values below 0.01), while there were no obvious differences on PID 1 (with t values respectively 1.200 and 1.263, P values above 0.05 ). Value of ηp of rabbits in AP group was significantly lower than that in pure scald group on PID 1 (t=2.430, P<0.05), while there were no obvious differences on PID 3, 7, and 14 (with t values from 0.002 to 1.446, P values above 0.05 ). Value of HCT of rabbits in AP group was close to that in pure scald group on PID 1 (t=1.079, P>0.05), and the values were significantly lower than those in pure scald group on PID 3 and 14 (with t values respectively 3.849 and 4.208, P values below 0.01), while the value was significantly higher than that in pure scald group on PID 7 (t=-4.925, P<0.01). Value of TK of rabbits in AP group was lower than that in pure scald group on PID 7 (t=2.847, P<0.05), while there were no obvious differences on PID 1, 3, and 14 (with t values from -1.102 to 0.875, P values above 0.05). Conclusions: AP can alleviate the damage of myocardium of rabbits with severe scald by reducing the production of vasoactive substances Ang Ⅱ and ET-1, decreasing oxidative stress injury by increasing the content of SOD and decreasing the production of MDA, improving blood flow performance and microcirculation perfusion.

Effects of astragalus polysaccharide on cardiac dysfunction in rabbits with severe scald injury / 中华烧伤杂志

Objective@#To investigate the effects of astragalus polysaccharide (AP) on cardiac dysfunction in rabbits with severe scald injury.@*Methods@#Sixty-four New Zealand white rabbits were divided into pure scald group and AP group according to the random number table, with 32 rabbits in each group. Rabbits in the two groups were all inflicted with 30% total body surface area full-thickness scald on the back. Immediately after injury, rabbits in two groups were intraperitoneally injected with lactated Ringer′s solution once for antishock. Rabbits in AP group were intraperitoneally injected with 10 mL AP solution with the dosage of 200 mg/kg 10 min after injury and the following 6 days respectively, once a day. Rabbits in pure scald group were injected with 10 mL normal saline instead. Eight rabbits of each group were respectively selected before injury hour (BIH) 1 and on post injury day(PID) 1, 3, 7, and 14 to collect blood samples from ear marginal vein, and then sacrificed immediately to collect hearts at each time point post injury. The morphology of myocardium was observed after HE staining. The serum content of cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent assay (ELISA). The serum content of aspartate transaminase (AST), creatine kinase (CK), CK isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH) was detected by fully automatic chemistry analyzer. The content of angiotensin Ⅱ (Ang Ⅱ) in serum and myocardium was detected with radioimmunoassay and the content of endothelin 1 (ET-1) in serum and myocardium was detected by ELISA. Another 8 normal rabbits were sacrificed to detect the content of Ang Ⅱ and ET-1 in the myocardium as the value of the two groups of scalded rabbits at BIH 1. The serum content of superoxide dismutase (SOD) and malondialdehyde (MDA) was detected by ELISA. The values of whole blood viscosity (ηb), reductive viscosity of whole blood (ηr), plasma viscosity (ηp), hematocrit (HCT), erythrocyte rigidity index (TK), erythrocyte aggregation index (EAI), and erythrocyte sedimentation rate (ESR) were detected by fully automatic hematology analyzer. Data were processed with analysis of variance of factorial design, independent sample t test, and Dunnett test.@*Results@#(1) Compared with those in pure scald group, the degrees of cardiomyocyte swelling, steatosis, necrosis and rupture of muscle fiber were significantly alleviated in rabbits of AP group on PID 1 and 3. There was no obvious increase in cell size, no breakage of muscle fiber or infiltration of inflammatory cells in myocardial interstitium on PID 7. The myocardial tissue structure and muscle fiber arrangement returned to normal condition on PID 14, with no interstitial fibroblast hyperplasia or excessive extra cellular matrix deposition. (2) Serum content of cTnI, CK, and LDH of rabbits in AP group was significantly lower than that in pure scald group on PID 1, 3, and 7 (with t values from 2.69 to 13.99, P<0.05 or P<0.01), while there was no significant difference between the two groups on PID 14 (with t values from -0.32 to 0.68, P values above 0.05). Serum content of AST and CK-MB of rabbits in AP group was significantly lower than that in pure scald group on PID 1 and 3 (with t values from 2.21 to 12.65, P<0.05 or P<0.01), while there was no significant difference between the two groups on PID 7 and 14 (with t values from 0.03 to 1.67, P values above 0.05). (3) Serum content of Ang Ⅱ of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 14 (with t values from 3.38 to 32.58, P values below 0.01). Serum content of ET-1 of rabbits in AP group was significantly lower than that in pure scald group from PID 3 to 14 (with t values from 3.54 to 11.02, P values below 0.01), while there was no obvious difference on PID 1 (t=0.39, P>0.05). Content of Ang Ⅱ and ET-1 in myocardial tissue of rabbits in AP group was significantly lower than that in pure scald group from PID 1 to 7 (with t values from 1.27 to 13.79, P values below 0.01), while there was no obvious difference on PID 14 (with t values respectively 0.07 and 0.81, P values above 0.05). (4) Serum content of SOD of rabbits in AP group was respectively (15.65±2.64), (14.67±0.74), and (8.43±0.56) ng/mL on PID 1, 3, and 7, which was significantly higher than (6.35±0.83), (2.62±0.75), and (2.84±0.41) ng/mL in pure scald group (with t values from -29.79 to -9.10, P values below 0.01); while there was no obvious difference on PID 14 [with (4.02±0.26) ng/mL in pure scald group and (4.11±0.52) ng/mL in AP group, t=-0.01, P>0.05]. Serum content of MDA of rabbits in AP group was respectively (1.31±0.61), (1.72±0.64), and (0.65±0.42) μmol /mL on PID 1, 3, and 7, which was significantly lower than (1.68±0.57), (2.34±0.79), and (1.06±0.32) μmol/mL in pure scald group (with t values from 1.63 to 3.16, P<0.05 or P<0.01), while there was no obvious difference on PID 14 [with (0.31±0.09) μmol/mL in pure scald group and (0.24±0.08) μmol/mL in AP group, t=2.11, P>0.05]. (5) Values of ηb1 and EAI of rabbits in AP group were significantly lower than those in pure scald group from PID 1 to 7 (with t values from 2.718 to 11.170, P<0.05 or P<0.01), while there were no obvious differences on PID 14 (with t values respectively 2.078 and -1.423, P values above 0.05). Values of ηb2 and ηr2 of rabbits in AP group were significantly lower than those in pure scald group on PID 3 and 7 (with t values from 2.178 to 19.205, P<0.05 or P<0.01), while there were no obvious differences on PID 1 and 14 (with t values from -0.730 to 1.320, P values above 0.05 ). Values of ηr1 and ESR of rabbits in AP group were significantly lower than those in pure scald group on PID 3, 7, and 14 (with t values from 3.021 to 8.058, P values below 0.01), while there were no obvious differences on PID 1 (with t values respectively 1.200 and 1.263, P values above 0.05 ). Value of ηp of rabbits in AP group was significantly lower than that in pure scald group on PID 1 (t=2.430, P<0.05), while there were no obvious differences on PID 3, 7, and 14 (with t values from 0.002 to 1.446, P values above 0.05 ). Value of HCT of rabbits in AP group was close to that in pure scald group on PID 1 (t=1.079, P>0.05), and the values were significantly lower than those in pure scald group on PID 3 and 14 (with t values respectively 3.849 and 4.208, P values below 0.01), while the value was significantly higher than that in pure scald group on PID 7 (t=-4.925, P<0.01). Value of TK of rabbits in AP group was lower than that in pure scald group on PID 7 (t=2.847, P<0.05), while there were no obvious differences on PID 1, 3, and 14 (with t values from -1.102 to 0.875, P values above 0.05).@*Conclusions@#AP can alleviate the damage of myocardium of rabbits with severe scald by reducing the production of vasoactive substances Ang Ⅱ and ET-1, decreasing oxidative stress injury by increasing the content of SOD and decreasing the production of MDA, improving blood flow performance and microcirculation perfusion.

Antihypertensive Effect of Pomegranate Polyphenols in Spontaneously Hypertensive Rats / 中国药师

Objective: To observe the anti-hypertensive effect of pomegranate polyphenols in spontaneously hypertensive rats ( SHR) and explore the underlying mechanism. Methods:Totally 40 male SHR rats at the age of 12 weeks were randomly divided into five groups:SHR control group, pomegranate polyphenols groups respectively at the dose of 120 mg·kg-1 , 240 mg·kg-1 and 480 mg ·kg-1 , and captopril group at the dose of 15 mg·kg-1 . The age-matched Wistar-Kyoto ( WKY) rats were randomly divided into two groups:WKY control group and pomegranate polyphenols group at the dose of 480 mg·kg-1 . All the rats were given corresponding drug or water by intragastric administration for four weeks. The systolic blood pressure ( SBP) and diastolic blood pressure ( DBP) were measured weekly. After the 4-week administration, the rats were fasted 12 hours and anaesthetized with 25% urethane solution. The blood samples were collected from abdominal aorta. The serum concentrations of angiotensin II ( Ang II) and endothelin ( ET) were de-termined by euzymelinked immunosorbent assay. The concentration of nitric oxide ( NO) in serum was determined by nitrate reduction test. Results:Pomegranate polyphenols could significantly lower the SBP and DBP, decrease the serum concentrations of Ang II and ET, and increase the serum concentration of NO(P<0.05 or P<0.01). In addition, pomegranate polyphenols had no effects on blood pressure and vasoactive substances in WKY rats. Conclusion: Pomegranate polyphenols has anti-hypertensive effect in SHR rats. The mechanism may be related to regulating the expression of vasoactive substances, such as Ang II, ET and NO.

Hemodynamics and vasoactive substance levels during renal congestion that occurs in the anhepatic phase of liver transplantation.

AIM: To explore hemodynamics and vasoactive substance levels during renal vein congestion that occurs in the anhepatic phase of liver transplantation. METHODS: New Zealand rabbits received ligation of the hepatic pedicle, supra-hepatic vena cava and infra-hepatic vena cava [anhepatic phase group (APH); n = 8], the renal veins (RVL; n = 8), renal veins and hepatic pedicle [with the inferior vena cava left open) (RVHP; n = 8)], or a sham operation (SOP; n = 8). Hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) and the levels of serum bradykinin (BK) and angiotensin II (ANGII) were measured at baseline (0 min), and 10 min, 20 min, 30 min, and 45 min after the surgery. Correlation analyses were performed to evaluate the associations between hemodynamic parameters and levels of vasoactive substances. RESULTS: All experimental groups (APH, RVL, and RVHP) showed significant decreases in hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) compared to baseline levels, as well as compared to the SOP controls (P < 0.05 for all). In contrast, BK levels were significantly increased compared to baseline in the APH, RVL, and RVHP groups at all time points measured (P < 0.05 for all), whereas no change was observed in the SOP controls. There were no significant differences among the experimental groups for any measure at any time point. Further analyses revealed that systolic, diastolic, and mean arterial blood pressures were all negatively correlated with BK levels, and positively correlated with ANGII levels in the APH, RVL, and RVHP groups (P < 0.05 for all). CONCLUSION: In the anhepatic phase of orthotopic liver transplantation, renal vein congestion significantly impacts hemodynamic parameters, which correlate with serum BK and ANGII levels.

Complications of cirrhosis. A 50 years flashback.

In patients with cirrhosis and portal hypertension, it is largely the frequency and severity of complications relating to the diseased liver, degree of portal hypertension and hemodynamic derangement that determine the prognosis. It can be considered as a multiple organ failure that apart from the liver involves the heart, lungs, kidneys, the immune systems and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. With the progression of the disease development of portal hypertension leads to formation of esophageal varices and ascites. The circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.

Involvement of vasoactive substances in hemodynamics disturbances in cirrhosis.

Cirrhosis is a pathological entity characterized by the association of hepatocyte necrosis, fibrosis and regenerative nodules; hemodynamic and neurohormonal metabolic factors intervening in its development mechanisms, resulting in hepatic stellate cell activation and transformation and development of liver fibrosis. Cytokines are key modulators of liver cell fibroblast transformation. Prostaglandins play an important role in the control of vascular tone and in thrombosis; Angiotensin II stimulates fibroblast proliferation by AT-1 receptors. Thrombin influences cellular remodeling in the liver and cardiovascular cirrhotic patients. Oxidative stress is involved in the development of liver cirrhosis by primary and secondary biological irreversible effects. Complex etiology involving vasoactive substances, oxidative stress in the pathogenesis of liver cirrhosis, require further studies to elucidate the mechanisms involved in hemodynamic disturbances associated with this disorder.

Reduced skin reactivity to vasoconstrictor and vasodilator substances in atopic eczema.

UNLABELLED: Atopic eczema is a common chronic inflammatory disease with itchy skin and altered skin reactions to acetylcholine and nicotinic acid compared to healthy non-atopic individuals. AIM: The aim of this study was to evaluate skin reactivity to 11 vasoactive substances and peptides by skin prick and intradermal tests in 20 patients with atopic eczema and 20 healthy controls. METHODS: Skin reactions, blanching, wheal and flare areas were measured by planimetry, 15 minutes after provocation. RESULTS: Patients with atopic eczema had significantly smaller reactions at certain concentrations of the vasodilators acetylcholine, bradykinin, calcitonin gene-related peptide, substance P and vasoactive intestinal peptide for flare, and of substance P and vasoactive intestinal peptide for wheals, in intradermal testing and/or in skin prick testing. Testing of the vasoconstrictors angiotensin-II, arginine-vasopressin, endothelin-1 and noradrenaline in atopic eczema resulted in significantly smaller reactions at certain concentrations for blanching in intradermal testing and/or skin prick testing. Significantly smaller reactions were seen with arginine-vasopressin for wheals and with arginine-vasopressin and noradrenaline for flares in intradermal testing and/or skin prick testing at certain concentrations. Significantly larger wheals were seen with angiotensin-II and endothelin-1 in intradermal testing and/or skin prick testing at certain concentrations. No significant differences were found for prostaglandin E2. CONCLUSION: These results demonstrate not only a reduced responsiveness to vasodilators but also to vasoconstrictor substances and peptides in patients with atopic eczema, which may be considered a general feature of atopic eczema skin.

Experimental Study of Optimized Compatibility Component of Water Extractives of Liqi Huoxue Medicinals by Uniform Designed Method / 世界科学技术-中医药现代化

This experiment was designed to search and identify the active principle as well as the optimal proportion of water-soluble extractives of traditional Chinese medicine (water-soluble extractives) Liqi Huoxue medicinals com-patibility (Qixue Bingzhi Fang-CWQB) in the prevention and treatment of atherosclerosis (As) by optimal uniform design method. The water-soluble extractives of CWQB were divided into 6 sections (A, B, C, D, E, F) through macroporous resin. The effect intensity and step of every component were compared through its effect on blood fat level, platelet aggregation, inflammatory factors, vascular endothelial growth factor (VEGF) and so on among hyper-lipoidemia rat models. The pharmacological experimental results and statistical analysis showed that CWQB water-soluble extractives of component D (mainly is paeoniflorin, accounted for 49.12%), component E (mainly is total flavonoids, accounted for 30.0%) compatibility had better effects on decreasing blood fat and triglyceride (TG). Com-pared with the model group, there was significant difference (P < 0.01). It also had inhibiting effect on endothelin (ET) and maximum platelet aggregation rate (P < 0.01). The component F (mainly is total acids, accounted for 32.7%) had inhibiting effect on serum IL-6 and IL-8 (P< 0.01). It was concluded that different compatibility of wa-ter-soluble extractives of CWQB can be applied to different targets or steps of the body. The active principle extrac-tives include main component of paeoniflorin, flavonoids and total acids. The best proportion is about 1:1:1.

Effect of atorvastatin on endothelial function and vasoactive substances in essential hypertensive patients without hyperlipemia / 中国综合临床

Objective To investigate the effect of atorvastatin on vascular endothelial cell function and vasoactive substances in essential hypertensive patients without hyperlipemia. Methods Sixty-five essential hypertensive(EH) patients without hyperlipemia were enrolled and randomly divided into atorvastatin group and conventional treatment group(oral taken atorvastatin or placebo once every night in addition of routine antihypertensive drugs).Twenty five healthy subjects were also recruited as control.All cases were followed up for eight weeks.Serum cholesterol,nitric oxide(NO),emdothelin-1(ET-1),vonWillebrand-factor(vWF) levels were determined in each case.Flow-medizted dilation(FMD) was determined by high-resolution ultrasonography before and after eight weeks atorvastatin medication.Results (1)Before treatment,the FMD and NO levels of EH group were significantly lower than those of control group(P＜0.01),while the ET-1 and vWF levels of EH group were significantly higher than those of control group(P＜0.01);(2)In EH patients,the FMD and NO levels significantly increased after treatment and increased even more dramatically in atorvastatin group,when compared to conventional treatment group(Ps＜0.01);(3)In EH patients,the ET-1 and vWF levels significantly decreased after treatment and decreased even more dramatically in atorvastatin group,when compared to conventional treatment group(Ps＜0.01).Conclusion In patients of EH without hyperlipemia,atorvastatin can decrease plasma levels of ET-1,vWF,while increase plasma NO concentration and improve vascular endothelial function.

Progress in pathogenesis of patent ductus arteriosus in preterm infants / 国际儿科学杂志

Patent ductus arteriosus(PDA) is a common condition in the premature infants. It is associated with an increase in mortality and sequelae in these infants. The various factors contributing to an patency of the ductus arteriosus in the preterm infants are involved in: insufficient histological development of ductus arteriosus, failure of remodeling theductus, abnormal sensitivity of the ductus to oxygen and vasoactive substances,and genes.