endothelin-1 and Syndrome

To evaluate the efficacy and safety of Tongxinluo Capsule (, TXL) for patients with cardiac syndrome X (CSX).. Randomized controlled trials (RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction (AMI), angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph (ECG) improvement, and serum endothelin-1 (ET-1) level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses.. Twelve RCTs (696 patients) were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio (RR): 1.46, 95% confidence interval (CI) (1.25, 1.71), P<0.01], and improving ECG [RR: 1.45, 95% CI (1.21, 1.74), P<0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR: 0.20, 95% CI (0.02, 1.61), P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number:-1.63, 95% CI (-2.29,-0.96), P<0.01]. No serious adverse events were reported.. TXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.

Topics: Capsules; Cardiovascular Diseases; Drugs, Chinese Herbal; Electrocardiography; Endothelin-1; Humans; Middle Aged; Outcome Assessment, Health Care; Publication Bias; Syndrome

Age-associated structural and functional remodeling of the arterial wall produces a productive environment for the initiation and progression of hypertension and atherosclerosis. Chronic aging stress induces low-grade proinflammatory signaling and causes cellular proinflammation in arterial walls, which triggers the structural phenotypic shifts characterized by endothelial dysfunction, diffuse intimal-medial thickening, and arterial stiffening. Microscopically, aged arteries exhibit an increase in arterial cell senescence, proliferation, invasion, matrix deposition, elastin fragmentation, calcification, and amyloidosis. These characteristic cellular and matrix alterations not only develop with aging but can also be induced in young animals under experimental proinflammatory stimulation. Interestingly, these changes can also be attenuated in old animals by reducing low-grade inflammatory signaling. Thus, mitigating age-associated proinflammation and arterial phenotype shifts is a potential approach to retard arterial aging and prevent the epidemic of hypertension and atherosclerosis in the elderly.

Topics: Aging; Animals; Arteries; Atherosclerosis; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Humans; Hypertension; Inflammation; Phenotype; Renin-Angiotensin System; Sympathetic Nervous System; Syndrome; Vascular Stiffness

Several therapies commonly used for the treatment of acute heart failure syndromes (AHFS) present some well-known limitations and have been associated with an early increase in the risk of death. There is, therefore, an unmet need for new pharmacologic agents for the early management of AHFS that may improve both short- and long-term outcomes.. To review the recent evidence on emerging pharmacologic therapies in AHFS.. A systematic search of peer-reviewed publications was performed on MEDLINE, EMBASE and Clinical Trials.gov from January 1990 to August 2007. The results of unpublished or ongoing trials were obtained from presentations at national and international meetings and pharmaceutical industry releases. Bibliographies from these references were also reviewed, as were additional articles identified by content experts.. Cumulative data from large studies and randomised trials suggest that therapies with innovative mechanisms of action may safely and effectively reduce pulmonary congestion or improve cardiac performance in AHFS patients.. Some investigational agents for the management of AHFS are able to improve haemodynamics and/or clinical status. In spite of these promising findings, no new agent has demonstrated a clear benefit in terms of long-term clinical outcomes compared to placebo or conventional therapies.

Topics: Adenosine; Cardiovascular Agents; Endothelin-1; Etiocholanolone; Heart Failure; Hemodynamics; Humans; Hydrazones; Natriuretic Peptide, Brain; Perhexiline; Pyridazines; Randomized Controlled Trials as Topic; Simendan; Sodium-Potassium-Exchanging ATPase; Syndrome; Vasodilator Agents

Vasospasm can have many different causes and can occur in a variety of diseases as well as in otherwise healthy subjects. We distinguish between primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a spasm to stimuli like cold or emotional stress. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, migraine and silent myocardial ischemia. The ocular vasospastic syndrome is clearly associated, among other manifestations, with glaucomatous optic neuropathy and non arteritic anterior ischemic optic neuropathy. The ocular vasospasm leads to a compromised autoregulation, and therefore sensitizes the eye to intraocular pressure or to a decrease in blood pressure. A variation in ocular perfusion may lead to an increase in free oxygen radicals and in glutamate. This may finally induce apoptosis cascade in retinal ganglion cells. Valuable diagnostic tools are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists are discussed.

Topics: Apoptosis; Calcium Channel Blockers; Diagnosis, Differential; Endothelin-1; Excitatory Amino Acid Antagonists; Eye; Eye Diseases; Free Radicals; Glutamic Acid; Humans; Optic Nerve Diseases; Syndrome; Vascular Diseases

Essential hypertension probably results from combinations of small genetic variations that are partly normal variations and may not be appreciably harmful individually. Strategies to identify genes contributing to hypertension are discussed in this review. Gene targeting approaches, especially gene titration, have been used in these studies of hypertension. Gene titration experiments vary the expression of a chosen gene product by generating animals having different numbers of copies of the gene coding for the product. Gene titration is powerful for analyzing quantitative variations seen in common polygenic disorders, such as kidney diseases, diabetes mellitus, and atherosclerosis, as well as hypertension, because it allows tests of causation by determining the effects on a phenotype by changes in expression of the altered gene and because it matches normal quantitative variations more closely than is possible with classic transgenic mice. The use of zero-copy (gene "knockout") animals generated by gene disruption for studies of qualitative gene effects is also discussed. These various gene targeting experiments help identify genes regulating BP, promote a better understanding of the pathophysiology of the condition, and help identify potential targets for therapies.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Endothelin-1; Gene Targeting; Humans; Hyperaldosteronism; Hypertension; Mice; Mice, Knockout; Models, Genetic; Mutation; Nitric Oxide Synthase; Receptor, Bradykinin B2; Receptors, Bradykinin; Renin-Angiotensin System; Syndrome

We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects.. Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after L-arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, L-arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, L-arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, L-arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release.. Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous L-arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.

Topics: Angina Pectoris; Arginine; Blood Pressure; Coronary Angiography; Cyclic GMP; Endothelin-1; Endothelium, Vascular; Female; Forearm; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged; Nitric Oxide; Regional Blood Flow; Syndrome

Type 2 diabetes and metabolic syndrome are major cardiovascular risk factors in postmenopausal women, but the role of vasoconstrictive endothelin-1 (ET-1) in these conditions is not known. We studied the levels of ET-1 and the effect of postmenopausal hormonal therapy on ET-1 levels in postmenopausal women.. We compared plasma levels of ET-1 in 22 postmenopausal type 2 diabetic women and 14 postmenopausal women with metabolic syndrome with plasma levels in 10 healthy postmenopausal control women. The basal values for ET-1 were measured for all groups. These women were then randomised to receive in a double-dummy, crossover trial: either oral continuous oestradiol (2.0 mg) + norethisterone acetate (1.0 mg) per day or continuous transdermal oestrogen-only (50 mg/day) for 3 months. Between the active therapy there were 3-month wash-out periods. ET-1-values were measured again at the end of each treatment period.. The type 2 diabetic women had significantly (p < 0.003) elevated ET-1 levels (4.8+/-1.0 pg/ml) whereas those with metabolic syndrome (4.4+/-1.7 pg/ml]) had non-significantly (NS) elevated ET-1 levels compared to controls (3.6+/-0.3 pg/ml). Both oral and transdermal hormone replacement therapy (HRT) failed to affect plasma ET-1 except in 14 hypertensive women from the diabetes and metabolic syndrome groups who were on angiotensin convertase enzyme (ACE) inhibitors. These women's ET-1 levels before oral HRT (4.6+/-1.1 pg/ml) fell to 4.1+/-0.9 pg/ml (p < 0.05).. Type 2 diabetes in postmenopausal women is associated with elevated ET-1 levels. Oestrogen replacement therapy does not affect the levels of ET-1 in postmenopausal women with type 2 diabetes or metabolic syndrome.

Topics: Administration, Cutaneous; Administration, Oral; Biomarkers; Body Constitution; Body Mass Index; Cholesterol, HDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Endothelin-1; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hyperlipidemias; Hypertension; Middle Aged; Norethindrone; Norethindrone Acetate; Postmenopause; Reference Values; Syndrome; Triglycerides

To demonstrate the presence of endothelin-1 (ET-1), atrial natriuretic peptide (ANP) in peritoneal fluid of women and their effects on pathogenesis of pelvic venous congestion syndrome after sterilization (PVCSS).. This randomized controlled study determined the concentrations of ET-1 and ANP in both peritoneal fluid and plasma, counts of macrophage in peritoneal fluid and volumes of peritoneal fluid in 21 cases of PVCSS. 12 normal women after sterilization and 11 normal women as control in early follicular phase by radioimmunoassay.. concentrations of ET-1, ratio of ET-1/ANP and counts of macrophage in peritoneal fluid with PVCSS were lower than those in control (P < 0.005, P < 0.001, P < 0.001) and all had significant negative correlation with scores quantifying the severity of PVCSS (P < 0.05), but volumes of peritoneal fluid in PVCSS were larger than that in control (P < 0.001); counts of macrophage in peritoneal fluid had significant positive correlation with the concentrations of ET-1 of peritoneal fluid in all the three groups (P < 0.05); plasma concentrations of ET-1 and ANP didn't show any significant differences among the three groups (P > 0.05).. ET-1 was present in peritoneal fluid of normal women. Lower concentrations of ET-1 and (or) lower ratio of ET-1/ANP in peritoneal fluid contributed to the pathogenesis of PVCSS.

Topics: Adult; Ascitic Fluid; Atrial Natriuretic Factor; Endothelin-1; Female; Humans; Pelvic Pain; Pelvis; Sterilization, Tubal; Syndrome

Hypertension occurred in 50% obstructive sleep apnea-hypopnea syndrome (OSAHS) patients meanwhile OSAHS occurred in 30% hypertension patients. The present study aimed to explore the molecular mechanism of GATA2-EDN1-AGT induced hypertension in the development of obstructive sleep apnea-hypopnea syndrome. OSAHS patients (56 cases: 36 cases of male, 20 cases of female, 42~60 years old) were divided into two groups (case group: patients with hypertension monitored by 24 h ambulatory blood pressure and polysomnography; control group: patients without hypertension). Wistar rats were used to establish the OSAHS model (narrow pharyngeal cavity). PaO2 and PaCO2 of patients and rats were measured by an automatic blood gas analyzer. The profile of total protein in the OSAHS group and normal group was evaluated. Protein-protein-interaction (PPI) was carried out to show all matter proteins related. The levels of EDN-1, AGTII and atrial natriuretic peptide (ANP) in blood samples of patients and rats were analyzed by enzyme-linked immunosorbent assay (ELISA). The expression of GATA2, EDN1, endothelin-converting enzyme 1 (ECE-1) and AGTⅡ was measured. The results showed that SaO2 and AHI were positively associated with systolic pressure (P<0.05) in OSAHS patients. There was no correlation among other indexes (P>0.05). It was also observed that GATA2 had a strong relationship with AGTⅡ and EDN1. The results of ELISA presented that the levels of EDN1, AGTⅡ and ANP in the OSAHS group of human and animal models were significantly increased (P<0.05). The results of immunochemistry showed that the expression of GATA2 and AGTⅡ in the vascular of OSAHS group was upregulated manifestly (P<0.05). It was concluded that OSAHS can induce AHI, which increases hypertension via the GATA2-EDN1-AGT Ⅱ axis.

Topics: Angiotensinogen; Animals; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Endothelin-1; Female; GATA2 Transcription Factor; Hypertension; Male; Rats; Rats, Wistar; Sleep Apnea, Obstructive; Syndrome

Currently there is no consensus on the optimal management of small-for-size syndrome following liver transplantation. Here we describe a technique to alleviate portal hypertension and improve the hepatocyte reperfusion in small-for-size liver transplantation in a Lewis rat model.. The rats underwent trans-portal vein intra-hepatic portosystemic shunt using a self-developed porous conical tube (TPIPSS: Fig. 1) on small-for-size liver transplants (SFS) with right lobe graft. The treatment effect was evaluated by comparing hemodynamic parameters, morphological changes, serum parameters, ET-1 and eNOS expression, hepatocyte proliferation and apoptosis, CYP3A2 levels, postoperative complications, and survival between the two groups with SFS liver transplants.. Porous conical prosthesis prolonged the filling time of small-for-size grafts. Moreover, grafts with TPIPSS showed a lower portal vein pressure, improved microcirculatory flow, alleviated histological changes, decreased ET-1 and increased eNOS expressions, and significantly less damage to liver function comparing to grafts without TPIPSS. Mean survival and overall 30-day survival were significantly higher in the TPIPSS group.. These results demonstrate that porous conical tube as trans-portal vein intra-hepatic portosystemic shunt device is an effective way to alleviate portal vein hypertension and improve hepatocyte reperfusion after small-for-size liver transplantation.

Topics: Animals; Apoptosis; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Cell Proliferation; Cytochrome P-450 CYP3A; Endothelin-1; Hemodynamics; Liver Circulation; Liver Transplantation; Male; Nitric Oxide Synthase Type III; Organ Size; Porosity; Portal Vein; Postoperative Complications; Prosthesis Design; Rats, Inbred Lew; Syndrome; Vena Cava, Inferior

The endothelin receptor type A (EDNRA) signaling pathway is essential for the establishment of mandibular identity during development of the first pharyngeal arch. We report four unrelated individuals with the syndrome mandibulofacial dysostosis with alopecia (MFDA) who have de novo missense variants in EDNRA. Three of the four individuals have the same substitution, p.Tyr129Phe. Tyr129 is known to determine the selective affinity of EDNRA for endothelin 1 (EDN1), its major physiological ligand, and the p.Tyr129Phe variant increases the affinity of the receptor for EDN3, its non-preferred ligand, by two orders of magnitude. The fourth individual has a somatic mosaic substitution, p.Glu303Lys, and was previously described as having Johnson-McMillin syndrome. The zygomatic arch of individuals with MFDA resembles that of mice in which EDNRA is ectopically activated in the maxillary prominence, resulting in a maxillary to mandibular transformation, suggesting that the p.Tyr129Phe variant causes an EDNRA gain of function in the developing upper jaw. Our in vitro and in vivo assays suggested complex, context-dependent effects of the EDNRA variants on downstream signaling. Our findings highlight the importance of finely tuned regulation of EDNRA signaling during human craniofacial development and suggest that modification of endothelin receptor-ligand specificity was a key step in the evolution of vertebrate jaws.

Topics: Alopecia; Animals; Base Sequence; Endothelin-1; Exome; Humans; In Situ Hybridization; Mandibulofacial Dysostosis; Molecular Sequence Data; Morpholinos; Mutation, Missense; Pedigree; Real-Time Polymerase Chain Reaction; Receptor, Endothelin A; RNA, Messenger; Sequence Analysis, DNA; Syndrome; Tomography, X-Ray Computed; Zebrafish; Zygoma

Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different.. In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay.. The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (±SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (±1.74), range: (2.37-6.76), whereas in patients without Flammer syndrome they were 1.10 (±0.08), range: 1.00-1.20. Our own normal values are: 1.56 (±0.30), range: (0.90-2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell.. Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow reduction is due to retinal degeneration and how much to the Flammer syndrome? We hypothesise that Flammer syndrome leads to an additional increase of the endothelin-1 level and an additional decrease of ocular blood flow in retinitis pigmentosa patients. Further studies are needed to analyse the causal relationship between retinitis pigmentosa and Flammer syndrome and evaluate potential therapeutic implications.

Topics: Adult; Biomarkers; Diagnosis, Differential; Endothelin-1; Female; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Reproducibility of Results; Retinitis Pigmentosa; Sensitivity and Specificity; Syndrome

Primary myelofibrosis is one of the chronic myeloproliferative disorders characterized by bone marrow fibrosis associated with extramedullary hematopoiesis and osteosclerosis. Endothelin-1 (ET1) is a potent vasoconstrictor that is also a key mediator of osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation.. We report laboratory, radiographic, bone densitometry, and bone histology data of a patient presenting with newly diagnosed, biopsy-proven myelofibrosis and osteosclerosis. We were able to demonstrate abundant ET1 signaling in the bones of our patient.. We believe that ET1 is responsible for the osteosclerosis that develops with advanced myelofibrosis and suggest that ET1 signaling may play a role in other osteosclerotic settings as well.

Topics: Bone and Bones; Bone Marrow; Endothelin-1; Female; Humans; Middle Aged; Osteosclerosis; Primary Myelofibrosis; Signal Transduction; Syndrome

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Coronary Circulation; Diabetes Mellitus; Endothelin-1; Humans; Hyperalgesia; Hypertension, Pulmonary; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Myocardial Infarction; Pneumonia; Receptors, Tumor Necrosis Factor; Syndrome

To elucidate the role of endothelial dysfunction in formation of cardiorenal syndrome in patients with type 1 diabetes and diabetic nephropathy.. Sixty patients with type 1 diabetes were divided according to severity of nephropathy into the following groups: with normal albuminuria (n=15), microalbuminuria (n=15), proteinuria (n=15), and chronic renal failure (n=15). Control group consisted of 15 healthy subjects of similar age and sex. Methods of investigation included assessment of brachial artery endothelium dependent dilation by duplex scanning during test with reactive hyperemia, measurement of levels of serum markers of endothelial dysfunction (endothelin-1, von-Willebrand factor), and inflammation (C-reactive protein), analysis of parameters of 24-hour blood pressure monitoring and echocardiography data.. More severe diabetic nephropathy was associated with higher prevalence of cardiac pathology. Frequency of ischemic heart disease was 13 (2/15), 33 (5/15) and 53% (8/15), frequency of left ventricular concentric hypertrophy and remodeling - 33 (5/15), 40 (6/15) and 60% (9/15) among patients with microalbuminuria, proteinuria and chronic renal failure, respectively. Abnormalities of 24-hour blood pressure rhythm as well as signs of endothelial dysfunction were more pronounced in patients with more severe nephropathy. Correlation analysis revealed significant relationships between markers of endothelial dysfunction, parameters of renal function, blood pressure level and mass of left ventricular myocardium.. In patients with type 1 diabetes: endothelial dysfunction represents a link integrating processes of progression of nephropathy and development of cardiovascular pathology; close relationship between these processes constitutes a basis of cardiorenal syndrome; active search for cardiac pathology should be initiated on the stage of microalbuminuria.

Topics: Adolescent; Adult; Biomarkers; Brachial Artery; C-Reactive Protein; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Endothelin-1; Endothelium, Vascular; Female; Heart Diseases; Humans; Male; Middle Aged; Prognosis; Syndrome; Ultrasonography, Doppler, Duplex; Vasodilation; von Willebrand Factor

To compare the accuracy of biomarkers for identifying acute chest syndrome (ACS) in patients with sickle cell disease presenting to a pediatric emergency department (ED).. We conducted a 13-month-long (2002-2003) cohort study with nested case-control in patients with sickle cell disease presenting to the pediatric ED with vaso-occlusive crises or fever in which we compared levels of secretory phospholipase A2 (sPLA2), endothelin-1, interleukin-6 (IL-6), and peripheral white blood cell count (WBC) in cases that were complicated by ACS and in control subjects with uncomplicated illnesses. For diagnosis, a test was considered to be accurate when the area under its receiver operator characteristic curve (AUC) was >0.70. Laboratory tests with AUC values > or =0.70 were entered into a binary recursive partitioning model for diagnosis.. For the period of study, samples from 72 visits were obtained from 51 patients who presented with vaso-occlusive crises (range: 1-4 visits per patient; 15 were enrolled more than once). ACS complicated 19 of 72 visits (26%, 95% confidence interval: 17%-38%). At an AUC value of 0.79, only the sPLA2 test was accurate for diagnosing ACS. AUC values for peripheral WBC, endothelin-1, and IL-6 were 0.68, 0.51, and 0.52, respectively. Binary recursive partitioning retained only sPLA2 at a cutoff of 13.7 ng/mL to be accurate for diagnosis. This cutoff had a sensitivity of 74% (14 of 19), a specificity of 87% (46 of 53), a positive likelihood ratio of 5.6, and a negative likelihood ratio of 0.18.. Secretory phospholipase A2 but not endothelin-1, IL-6, or WBC is an accurate test for identifying present or incipient ACS in young patients who present to the ED with sickle cell pain crises.

Topics: Acute Disease; Adolescent; Anemia, Sickle Cell; Area Under Curve; Biomarkers; Chest Pain; Child; Endothelin-1; Female; Humans; Interleukin-6; Leukocyte Count; Lung Diseases; Male; Phospholipases A; Phospholipases A2; Sensitivity and Specificity; Syndrome

To compare thirst, drinking behaviour, and endothelin-1 (ET-1) plasma levels between vasospastic and non-vasospastic subjects.. We compared 67 subjects with a primary vasospastic syndrome with 64 age- and sex-matched non-vasospastic control subjects. A detailed medical history was recorded, including a questionnaire containing queries about thirst and drinking behaviour, history of migraine or unspecific headache, history of episodes of low blood pressure, and smoking habits. Body mass index (BMI) was calculated and blood samples were drawn for ET-1 measurements.. Subjects with a vasospastic syndrome reported a reduced desire to drink and a lower estimated quantity of daily fluid intake, more often forgot to drink, more often had both migraine and unspecific headache, more often had episodes of low blood pressure, and had an increased plasma level of ET-1. These features differed statistically significantly between the two groups. There was also a non-significant trend among vasospastic subjects to smoke less and to have a smaller BMI.. A reduced desire to drink is found frequently among vasospastic subjects.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Drinking Behavior; Endothelin-1; Female; Glaucoma; Humans; Male; Middle Aged; Raynaud Disease; Surveys and Questionnaires; Syndrome; Thirst; Vasodilation

1. Experiments were conducted to evaluate the effect of a synthetic inhibitor of nitric oxide (NO) synthase (L-NAME) on pulmonary arterial pressure (PAP) and pulmonary hypertension syndrome (PHS) morbidity in broilers. 2. In Experiment 1, broilers were infused intravenously with L-NAME, and the mean pulmonary arterial pressure (mean PAP) and plasma NO were measured at 0, 1, 2 and 4 h after the start of infusion. The mean PAP increased and plasma NO was reduced at 1 to 2 h in broilers treated with L-NAME. 3. In Experiment 2, 180 Arbor Acres broilers were evenly divided into three groups: a control group (group C), and two groups exposed to low environmental temperatures and fed a 3, 3, 5-triiodothyronine (T3) supplemented diet alone (group A) or also including 100 ppm L-NAME (group B). 4. The PHS morbidity of group A was higher than for group C but lower than for group B. Plasma endothelin-1 was higher in broilers in groups A and B than in group C. Plasma NO was not significantly lower in broilers of group B when compared with those in group A. 5. The right/total ventricular weight ratio (RV/TV) and mean PAP were higher in groups A and B than in group C, and the RV/TV ratio increased one week earlier in group B than in group A. 6. These results suggest that L-NAME increases broiler PAP by inhibiting the endogenous synthesis of NO, leading to pulmonary hypertension, right ventricular hypertrophy and the increased morbidity of PHS in broilers.

Topics: Animals; Blood Pressure; Chickens; Dose-Response Relationship, Drug; Endothelin-1; Enzyme Inhibitors; Hypertension, Pulmonary; Incidence; Injections, Intravenous; Morbidity; NG-Nitroarginine Methyl Ester; Nitric Oxide; Poultry Diseases; Pulmonary Artery; Random Allocation; Syndrome; Vascular Resistance; Vasodilation

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.

Topics: Blood Coagulation; Capillaries; Cell Adhesion Molecules; Cytokines; E-Selectin; Endothelin-1; Endothelium, Vascular; Fibrinolysis; Humans; Intercellular Adhesion Molecule-1; Interleukin-2; Neoplasms; Syndrome; Vascular Diseases

We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome.

Topics: Adult; Blood Glucose; Blood Urea Nitrogen; Cholesterol; Diastole; Endothelin-1; Heart Rate; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Lipoproteins; Male; Middle Aged; Obesity; Reference Values; Regression Analysis; Syndrome; Systole

The present study was designed to examine the role of endothelin-1 (ET-1), an endothelium-derived potent long-acting vasoconstrictor peptide, in vascular acrosyndromes with hypersensitivity to cold. Plasma ET-1 concentration was measured, before and after cold test, in 12 subjects with "a frigore" vascular acrosyndromes (9 females and 3 males, age range 17-59 years), of whom 6 were with primary Raynaud's phenomenon and 6 with essential acrocyanosis, and in 6 controls (5 females and 1 male, age range 21-37 years). Cold stimulation was performed by immersion of one hand into a water bath at 13 degrees C for 5 minutes. Blood samples were simultaneously drawn from an antecubital vein in the cooled side and in the contralateral arm at baseline, at the stop of cooling, at 10 and 90 minutes from the beginning of the cold challenge. Mean (+/-SD) baseline ET-1 plasma levels, as measured by radioimmunoassay, were higher in patients with "a frigore" vascular acrosyndromes (4.8 +/- 0.3 pmol/l) than in control subjects (1.9 +/- 0.1 pmol/l, p < 0.001). After hand cooling ET-1 rose in patients with "a frigore" vascular disorders to a peak value of 7.0 +/- 0.4 pmol/l, which was much greater than that observed in healthy subjects (2.7 +/- 0.4 pmol/l, p < 0.001). Absolute increase in ET-1 plasma concentrations from baseline to peak value was significantly higher in patients with "a frigore" vascular acrosyndromes than in normal subjects (2.2 +/- 0.3 vs 0.8 +/- 0.2 pmol/l, p < 0.001), being only in the former group the rise in ET-1 still detected 90 minutes after cold test. Plasma levels of ET-1 in the controlateral arm raised in a similar fashion, but absolute values were lower than in cooled arm. Circulating ET-1 levels in patients with primary Raynaud's phenomenon and essential acrocyanosis showed a similar pattern during the study. Our data demonstrate that in patients with "a frigore" vascular acrosyndromes baseline and cold-stimulated plasma ET-1 concentrations are increased. Further, in these vascular disorders, exaggerated ET-1 response to cold is prolonged. These findings suggest that increased ET-1 may contribute to an imbalance between vasoactive mediators in the cutaneous blood vessels contributing to the abnormal vasoconstriction to cold in these disorders. Alternatively, the increment in ET-1 release may represent a marker for endothelial cell damage in "a frigore" vascular acrosyndromes.

Topics: Adolescent; Adult; Cold Temperature; Endothelin-1; Female; Humans; Male; Middle Aged; Raynaud Disease; Syndrome; Vascular Diseases