Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

Pipersentan: A De Novo Synthetic Endothelin Receptor Antagonist that Inhibits Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension.

Background: Although major advances have been made in the pathogenesis and management of pulmonary arterial hypertension (PAH), the endothelin system is still considered to play a vital role in the pathology of PAH due to its vasoconstrictive action. Endothelin receptor antagonists (ERAs), either as monotherapy or in combination with other drugs, have attracted much attention in the treatment of this lethal disease, and research is continuing. Methods: A novel ERA, pipersentan 5-(1,3-Benzodioxol-5-yl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-N-(2-methoxyethylsulfamoyl)pyrimidin-4-amine, was recently synthesized and the physicochemical characterizations and the pharmacology both in vitro and in vivo were studied. Results: This orally administered ERA can both competitively and selectively inhibit the binding of endothelin-1 (ET-1) to its receptors with good physicochemical characteristics. Pipersentan efficaciously antagonized the effects of ET-1 on pulmonary artery smooth muscle cell proliferation, migration and calcium mobilization and effectively improved right ventricular hypertrophy and pulmonary arterial pressure in both monocrotaline- and hypoxia-induced pulmonary hypertension (PH) rat models. Conclusions: This profile identifies pipersentan as a new agent for treating ET-1 system activation-related PH.

Central endothelin ETB receptor activation reduces blood pressure and catecholaminergic activity in the olfactory bulb of deoxycorticosterone acetate-salt hypertensive rats.

Endothelins regulate catecholaminergic activity in the olfactory bulb (OB) in normotensive and hypertensive animals. Administration of an endothelin ETA receptor antagonist decreases blood pressure in deoxycorticosterone acetate-salt (DOCA-salt) rats along with a reduction in tyrosine hydroxylase (TH) activity and expression. In the present work, we sought to establish the role of brain endothelin ETB receptor on blood pressure regulation and its relationship with the catecholaminergic system within the OB of DOCA-Salt rats. Sprague-Dawley male rats were divided into control and DOCA-Salt groups. Blood pressure, heart rate and TH activity as well as neuronal nitric oxide synthase (nNOS) expression were assessed following IRL-1620 (selective endothelin ETB receptor agonist) applied to be brain. IRL-1620 significantly reduced systolic, diastolic, and mean arterial pressure in DOCA-Salt hypertensive rats. It also decreased TH activity, TH total and phosphorylated forms expression as well as its mRNA in the OB of hypertensive animals. The expression of phospho-Ser1417-nNOS, which reflects nNOS activation, was significantly decreased in the of OB of DOCA-salt rats, but it was enhanced by IRL-1620. These findings suggest that DOCA-Salt hypertension depends on endogenous central endothelin ETA receptor activity, rather than on ETB, and that low endothelin ETB stimulation is essential for blood pressure elevation in this animal model. The effect of endothelin ETA receptor antagonism may also result from endothelin ETB receptor overstimulation. The present study shows that endothelin receptors are involved in the regulation of TH in the OB and that such changes are likely implicated in the hemodynamic control and sympathetic outflow.

Effect of cold stress on ovarian & uterine microcirculation in rats and the role of endothelin system.

BACKGROUND: Cold, an environmental factor, induces many reproductive diseases. It is known that endothelin (ET) is a potent vasoconstrictor, and cold stress can increase the expression of ET and its receptors. The cold stress rat model was developed to examine two parameters: (1) the effects of cold stress on ovarian and uterine morphology, function, and microvascular circulation and (2) possible mechanisms of ET and its receptors involved in cold stress-induced menstruation disorders. METHODS: The rat cold stress model was prepared with an ice water bath. The estrous cycle was observed by methylene blue and hematoxylin and eosin (H&E) staining. Serum estradiol 2 (E2), testosterone (T), progesterone (P) were detected by radioimmunoassay. Hemorheology indices were measured. The real-time blood flow of auricle and uterine surfaces was measured. Expressions of CD34 and α-SMA in ovarian and uterine tissues were detected by immunohistochemistry. ET-1 contents in serum were tested, and expressions of ET-receptor types A and B (ET-AR and ET-BR) in ovarian tissues were detected via Western blotting. RESULTS: Cold stress extended the estrous cycle, thereby causing reproductive hormone disorder, imbalance of local endothelin/nitric oxide expression, and microcirculation disturbance. Cold-stress led to up-regulation of ET-AR expression and protein and down-regulation of ET-BR expression in rats. CONCLUSIONS: This study suggests that the reason for cold stress-induced dysfunction in reproductive organs may be closely related to the imbalance of ET-1 and its receptor expressions, leading to microvascular circulation disorders in local tissues.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

Lipopolysaccharides (LPS) Induced Angiogenesis During Chicken Embryogenesis is Abolished by Combined ETA/ETB Receptor Blockade.

BACKGROUND/AIMS: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. METHODS: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. RESULTS: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. CONCLUSION: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.

Effect of oxygen glucose deprivation-reperfusion in astrocytes overexpressing endothelin-1 on the proliferation of neural stem/progenitor cells / 器官移植

Objective To investigate the effect of oxygen glucose deprivation-reperfusion (OGD-R) in astrocytes overexpressing endothelin (ET)-1 on the proliferation of neural stem/progenitor cells (NSPCs). Methods OGD-R models of negative control astrocytes (C6-Mock) and astrocytes over-expressing ET-1 (C6-ET-1) were constructed. Transwell co-culture system of astrocytes and NSPCs was established. Morphologic observation and identification of the astrocytes and primary NSPCs were performed. The cells were divided into four groups: C6-Mock+NSPCs, OGD-R+C6-Mock+NSPCs, C6-ET-1+NSPCs and OGD-R+C6-ET-1+NSPCs groups and co-cultured for 0, 24, 48 and 72 h respectively. The diameter of neurosphere was measured in each group. Results In the C6-Mock and C6-ET-1 cells, type Ⅰ astrocytes in fibrous morphology were observed. Glial fibrillary acidic protein (GFAP) was expressed in the cytoplasm of these two types of cells. Primary NSPCs were positive for nestin staining. After co-culture for 48 and 72 h, the neurosphere diameter in the OGD-R+C6-Mock+NSPCs group was significantly greater than that in the C6-Mock+NSPCs group. The neurosphere diameter in the OGD-R+C6-ET-1+NSPCs group was considerably greater than that in the C6-ET-1+NSPCs group. The neurosphere diameter in the OGD-R+C6-ET-1+NSPCs group was significantly greater compared with that in the OGD-R+C6-Mock+NSPCs group (all P<0.05). Conclusions OGD-R astrocytes can promote the proliferation of NSPCs. ET-1 over-expression further accelerates the proliferation of NSPCs.

Correlation between the degree of coronary artery stenosis and endothelial dysfunction in patients with coronary heart disease and subclinical hypothyroidism / 西安交通大学学报(医学版)

Objective To study the correlation between coronary artery stenosis and endothelial dysfunction in patients with coronary heart disease and subclinical hypothyroidism.Methods According to the results of coronary angiography and thyroid function,the patients were divided into coronary heart disease with subclinical hypothyroidism (group A,n=71),coronary heart disease without subclinical hypothyroidism (group B,n=73), and normal coronary angiography (control group,n=59).The degree of coronary artery stenosis was evaluated by Gensini integral method.Fasting blood was taken to measure nitric oxide (NO),high sensitivity C reactive protein (hs-CRP),and endothelin (ET)to evaluate endothelial dysfunction.Results TC,TG,LDL-c,FT3,TSH,hs-CRP,ET and Gensini score were higher in Group A than in Group B and control group (P＜0.05).The level of NO in Group A and Group B were lower than that in control group (P＜0 .0 5).Multivariate Logistic regression analysis showed that age,TSH,ET and NO were independent risk factors for coronary heart disease.ET and NO levels in patients with coronary heart disease combined with subclinical hypothyroidism were correlated with Gensini scores (r=0.431,r=-0.383,P＜0.001).Conclusion Subclinical hypothyroidism may cause endothelial dysfunction in patients with coronary heart disease,which may increase cardiovascular risk in these patients.

Clinical effect of fasudil in heart failure induced by chronic pneumocardial disease and the influence in serum level of NO and ET-1 / 药物评价研究

Objective To investigate the clinical effect of fasudil in heart failure induced by chronic pneumocardial disease and the influence in serum level of NO and ET-1.Methods 100 cases of patients with heart failure induced by chronic pneumocardial disease in our hospital from September 2013 to September 2016 were selected and divided into observation group and control group,50 cases in each group.Patients in the control group were treated with conventional therapy,and in the observation group were treated with fasudil based on the conventional therapy.Compared the clinical effect,blood oxygen partial pressure (PaO2),CO2 partial pressure (PaCO2),tricuspid regurgitation speed,fight ventricular outflow tract inside diameter(RVOT),left ventricular ejection fraction (LVEF) and serum biochemical indexes (NO and ET-1) levels.Results After treatment,the total effective rate of the observation group was significantly higher than control group (P ＜ 0.05).PaO2,LVEF,serum level of NO of the two groups were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 significantly lower than before treatment (P ＜ 0.05),and the PaO2,LVEF,serum level of NO of observation group were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 of observation group were significantly lower than control group (P ＜ 0.05).Conclusion Fasudil had remarkable clinical effect in heart failure induced by chronic pneumocardial disease,and improve the patient's clinical symptoms,adjust the serum level of NO and ET-1.

Neurobiology of opioid withdrawal: Role of the endothelin system.

Morphine and oxycodone are potent opioid analgesics most commonly used for the management of moderate to severe acute and chronic pain. Their clinical utility is limited by undesired side effects like analgesic tolerance, dependence, and withdrawal. We have previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate opioid analgesia and eliminate analgesic tolerance. Mechanistically, G proteins and regulatory proteins such as ß-arrestins have shown to play an important role in mediating opioid tolerance, dependence, and withdrawal. Recently, the involvement of central ET mechanisms in opioid withdrawal was investigated. ETA receptor antagonist was shown to block majority of the signs and symptoms associated with opioid withdrawal. This review focuses on ET as one of the potential novel strategies to manage the challenge of opioid withdrawal. An overview of additional players in this process (G proteins and ß-arrestin2), and the possible therapeutic implications of these findings are presented.

Antiallodynic effect through spinal endothelin-B receptor antagonism in rat models of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a very complicated chronic pain disorder that has been classified into two types (I and II). Endothelin (ET) receptors are involved in pain conditions at the spinal level. We investigated the role of spinal ET receptors in CRPS. Chronic post-ischemia pain (CPIP) was induced in male Sprague-Dawley rats as a model for CRPS-I by placing a tourniquet (O-ring) at the ankle joint for 3h, and removing it to allow reperfusion. Ligation of L5 and L6 spinal nerves to induce neuropathic pain was performed as a model for CRPS-II. After O-ring application and spinal nerve ligation, the paw withdrawal threshold was significantly decreased at injured sites. Intrathecal administration of the selective ET-B receptor antagonist BQ 788 dose-dependently increased the withdrawal threshold in both CRPS-I and CRPS-II. In contrast, ET-A receptor antagonist BQ 123 did not affect the withdrawal threshold in either CRPS type. The ET-1 levels of plasma and spinal cord increased in both CRPS types. Intrathecal BQ 788 decreased the spinal ET-1 level. These results suggest that ET-1 is involved in the development of mechanical allodynia in CRPS. Furthermore, the ET-B receptor appears to be involved in spinal cord-related CRPS.

Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-ß1/IL-2/COX-2/endothelin ET(B) receptor cascade.

Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-ß1, TGF-ß1). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-ß1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats.

Effect of leonurine hydrochloride on endothelin and the endothelin receptor-mediated signal pathway in medically-induced incomplete abortion in rats.

OBJECTIVE: Endothelin (ET) is involved in uterine contractions. Our previous study showed that leonurine hydrochloride (LH) inhibits abnormal bleeding caused by incomplete abortion through an increase in uterine contractions in rats. The present study was conducted to show that LH treatment regulates the ET-mediated signal pathway in abortion in rats. STUDY DESIGN: Early pregnancies in rats had incomplete abortions induced using mifepristone in combination with misoprostol. After the abortions, the rats were treated with LH orally for 7 days and surgery was performed. The sinistro-uterus was dissected for measurement of ET and nitric oxide (NO); the dextro-uterus was stored at -80°C for ET receptor (ETA and ETB) analysis. Myometrial cells from the dextro-uterus were cultured for measurement of phospholipase C (PLC) activity, intra-cellular Ca(2+) concentration ([Ca(2+)]i), and protein kinase C (PKC) activity. RESULTS: In in vivo experiments, LH treatment elevated the ET level and ET/NO ratio in rats with induced abortions and up-regulated ETA mRNA expression (P<0.01 vs. the model group), but there was no change in ETB mRNA. LH significantly increased the [Ca(2+)]i, PLC activity, and relative production of PKC protein in myometrial cells. CONCLUSION: LH increased uterine contractions in rats with incomplete abortions by modulating the ET receptor-mediated signal pathway.

Study on the Protective Effect of Bilobalide on Ischemical Reperfusion Injury in Rats Undergoing Liver Transplantation / 中国药房

OBJECTIVE:To observe the effect of Bilobalide on ischemical reperfusion injury in orthotopic liver transplantation model rats and to discuss its protective effect on ischemical reperfusion injury of rats undergoing liver transplantation.METHODS:The model of orthotopic liver transplantation was established by in rats by setting up the bridge between portal vein and left renal vein and building blood bypass by inlaying of canal in the inferior vena,after modeling,the rats were treated with Bilobalide,then levels of NO(active medium of blood vessel)and ET1 before ischemia and at 10 min,30min and 2h after reperfusion were determined by nitratase reduction method;serum levels of ALT,AST,ALP,LDH enzymology,ATP and MDA in the liver tissues were determined as well.The hepatic tissue sample was taken at 2h and fixed with formalin to be made into specimen for observation of the ultrastructure of liver cells and hepatic lobules under electron microscope.RESULTS:After being treated by Bilobalide,serum NO level was elevated and the pathological elevated levels of ALT,AST and LDH were brought down,the microcirculation in ischemical reperfusion injury rats was improved and the extent of damage in the ultrastructure of liver cells was lessened in rats.CONCLUSION:Bypass of portal vein and inferior vena cava prior liver transplantation is helpful for the prevention of ischemical reperfusion injury of liver.The balance of NO/ET1 is possibly a factor influencing the blood flow in the microcirculation of transplanted liver.Bilobalide was proved to be of protective effect on ischemical reperfusion injury in rats.

Human Cytomegalovirus Infection and Endothelial Function Disorder in Patients with Nonspecific Low Back Pain / 中国康复理论与实践

@# ObjectiveTo study the relationship between Human Cytomegalovirus (HCMV) infection and endothelial function disorder and its possible role in nonspecific low back pain (NLBP).MethodsHCMV-DNA, -IgM, -IgG, HE stain, endothelin (ET) were detected in 50 patients with NLBP and 36 healthy people without NLBP(non-NLBP group).ResultsThe positive rate of HCMV-DNA,-IgM,-IgG, HE stain were higher in NLBP group than that in non-NLBP group(P<0.05), as well as the levels of ET(P<0.05).ConclusionHCMV infection may relate with NLBP, and ET may play an important role in it.

Effect of Yiqihuoxue Recipe on Left Ventricular Remodeling after Acute Myocardial Infarction / 中国康复理论与实践

@#ObjectiveTo observe the effect of Yiqihuoxue recipe on left ventricular remodeling after acute myocardial infarction (AMI).Methods40 patients with AMI were randomly divided into treatment group and control group with 20 cases in each group and received Yiqihuoxue recipe or fasinopril respectively for 6 months. Changes of clinical symptoms, the level of plasma angiotensin Ⅱ(ATⅡ), aldosterone (ALD), endothelin (ET) and echocardiographical indexes: left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), ejection fraction (EF), left ventricular mass index (LvmassI), wall motion index (WMI), wall thick (WT), E/A were assessed before discharge, and in the end of 3rd and 6th month after AMI.ResultsClinical symptoms of patients of treatment group improved significantly (P<0.01). EF and E/A of all patients in two groups increased (P<0.01 or P<0.05), LvmassI and WT reduced (P<0.05), but there were no significantly differences between two groups in LVEDVI, LVESVI, EF, LvmassI, WMI, E/A and WT(P>0.05). The level of plasma ET decreased in treatment group (P<0.05), the level of plasma ATⅡ and ALD of control group decreased more than that of treatment group (P<0.05).ConclusionYiqihuoxue recipe can significantly improve clinical symptoms, cardic function, and left ventricular remodeling, showing a better clinical efficacy.

Study of mechanism on endothelial dysfunction of spontaneous hypertensive rats / 中国康复理论与实践

@#ObjectiveTo investigate the mechanism on endothelial dysfunction of spontaneous hypertensive rats (SHR).MethodsThe animals were divided into two groups: SHRs (n=8) and Wistar-Kyoto (WKY) rats (n=7) all aged 17 months. Blood pressure was measured by the tail-cuff method. NO3- concentration in serum was assayed by activated cadmium reduction method; endothelin (ET) and cGMP levels were assayed by RIA.ResultsCompared with WKY rats, blood NO3- concentration, ET level and vascular cGMP level of SHRs were all reduced significantly (P<0.01); vascular ET level was only uplifted slightly with no significant difference (P>0.05).ConclusionIt indicates that the vascular endothelial dysfunction in SHR is induced possibly by a diminished synthesis or release of NO, not by changes of ET level.

Effect of scalp point penetration combined with rehabilitation training on endothelin and calcitonin gene-related peptide in plasma of patients with acute cerebral hemorrage / 中国康复理论与实践

@#ObjectiveTo investigate the effect of scalp point penetration combined with rehabilitation training on content of endothelin (ET) and calcitonin gene-related peptide (CGRP) in plasma of patients with acute cerebral hemorrage (ACH).Methods90 ACH patients were randomly divided into the scalp point penetration combined with rehabilitation group (group A), the rehabilitation group (group B) and control group (group C) with 30 cases in each group. The radioimmunoassay was adopted to determinate the content of ET and CGRP in plasma of patients.ResultsAfter treatment, contents of ET and CGRP of all patients were decreased significantly (P<0.01), but group A and group B had a significant difference compared with the group C (P<0.01), and there was also a significant difference between the group A and group B.ConclusionThe scalp point penetration combined with rehabilitation training can regulate the content of ET and CGRP in plasma and make them under a dynamic balance.

Clinical Significance of serum Endothelin-1 and Interleukin-8 in Sepsis / 결핵

BACKGROUND: Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasocon strictor is associated with multiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. METHODS: 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. the APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. RESULTS: The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated wit the creatinine levels in day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. CONCLUSION: ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. these mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.

Effects of compound Stichopus variegatus mucopolysaccharide on the levels of blood nitric oxide and endothelin after angioplasty in rabbits / 中国海洋药物

Objective To investigate the effects of Stichopus variegatus mucopolysaccharide on plasma nitric oxide (NO) and serum endothelin(ET) after angioplasty in rabbits. Methods 50 New Zealand rabbits were randomly divided into four groups: Stichopus group, simvastatin group, model group and normal group. Endothelium of iliac arteries in Stichopus group, simvastatin group and model group were denuded by balloon catheter and the rabbits were fed with 2%cholesterol, 3%lard and 3%yolk mixed forage for six weeks, and then, atherosclerotic stenosis was showed by iliac angiography.When transluminal balloon angioplasty was done, from then on the feeds was changed from high cholesterol to ordinary forage. Stichopus (0.5g?kg -1?d -1) and simvastatin (0.5mg?kg -1?d -1) were given by gastric canal. While NaCl solution (0.9%) was given in model group. All rabbits were fed in separate cages and free drinking. After four weeks since transluminal balloon angioplasty, blood was collected from carotid artery to measure the changes of concentrations of endothelin(ET) and nitric oxide(NO). Examination of pathology by optical and electron microscope were done at same time. Results After four weeks since transluminal angioplasty, the concentration of plasm ET in model group increased significantly compared with the normal group(114.86?24.89 ng?L -1 vs 75.62?9.68 ng?L -1) and serum NO decreased significantly(37.50? 12.79?mol?L -1 vs 106.37?18.01 ?mol?L -1).The concentration of plasm ET in model group was higher than that in the simvastatin groups and Stichopus groups(114.86?24.89 ng?L -1 , 81.08?14.71 ng?L -1 and 83.34?11.41 ng?L -1 ,respectively),and the concentration of serum NO decreased obviously(95.63?8.62 ?mol?L -1,98.80?9.06 ?mol?L -1 and 37.50?12.79 ?mol?L -1,respectively). Conclusion After iliac arterial TA the concentrations of plasm ET were increased and the serum NO were decreased, the endothelial function fell into disorder. The Stichopus variegatus mucopolysaccharide had the effects of improving the endothelial function after angioplasty in rabbits by adjustment of plasm ET and serum NO.