Increased endothelin-1 plasma levels in patients with multiple sclerosis.

OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients. MATERIALS AND METHODS: A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects. RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease. CONCLUSIONS: The plasma ET-1 level is markedly and significantly increased in patients with MS. Neither the cause of such an increase nor the pathogenetic role is known.     

Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases

Tissue Factor Pathway Inhibitor (TFPI) prevents further participation of Tissue Factor (TF) in the coagulation process by forming a stable quaternary complex of TF-FVIIa-FXa-TFPI. Recently, plasma TFPI level were found to be elevated in patients with malignant disease outside the brain. Therefore the aim of this study was to investigate the TFPI plasma level in patients with primary brain tumors and intracerebral metastases. From May 2000 to December 2001 the total tissue factor pathway inhibitor antigen (TFPI) was preoperatively determined in blood samples of 225 patients with primary or metastatic brain tumors. Tumor histology classified as benign (WHO grade I and II) and malignant (WHO grade III and IV, intracerebral metastases) was correlated to plasma TFPI-levels. Plasma TFPI was significantly higher in patients with malignant tumors including intracerebral metastasis compared to benign tumors (80.1 +/- 34.31 versus 64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To exclude the influence of primary systemic neoplasms with secondary brain metastasis on plasma TFPI-level a subgroup of patients with primary brain tumors (meningioma, astrocytoma, oligodendroglioma and glioblastoma) was separated. In this group TFPI-level was also significantly elevated in patients with malignant (n = 66) (78.6 +/- 29.9) compared to benign brain tumors (n = 127) (64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To the authors' knowledge this is the first study describing the correlation of increased plasma TFPI and malignancy in patient with brain tumors. Further studies are needed to clarify the pathogenic mechanism and the clinical relevance of this phenomenon.     

Serum levels of calcification inhibitors in patients with intracerebral hemorrhage

The vascular calcification regulators and inflammatory markers including fetuin-A, osteopontin (OPN), and matrix Gla protein (MGP) may play an important role in the development of intracerebral hemorrhages (ICHs). So far, the relationship between these parameters and ICH has not been studied. Therefore, this study was designed to elucidate whether fetuin-A, MGP, and OPN are involved in the pathophysiology of ICH. The ICH group consisted of 27 consecutive patients with spontaneous ICH evaluated in the neurology intensive care unit within the first 24 hours from the onset of the stroke. The serum OPN levels were significantly increased in patients with ICH compared to the controls. On the other hand, the serum MGP and fetuin-A levels were significantly decreased in the patients with ICH in comparison to the controls. In the patients with ICH, the serum MGP levels of the nonsurvivors were statistically significantly lower than the MGP levels of the survivors. In conclusion, the change in serum fetuin-A, MGP, and OPN levels after ICH indicates that these parameters play a role in the pathophysiological processes leading to an ICH. Measurement of the serum MGP levels may also be of value to estimate mortality.     

Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis

In order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 +/- 0.4 pg/ml, range 1.1-2.8 vs. 1.5 +/- 0.2 pg/ml, range 0.9-2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.     

Increased plasma endothelin-1 in acute ischemic stroke.

BACKGROUND AND PURPOSE: Endothelins are a recently discovered group of most powerful vasoconstrictor peptides. Endothelin-1 is produced by endothelial cells, and endothelin-3 is derived from neuronal tissue. Theoretically, endothelin-mediated vasoconstriction may enhance ischemic neuronal damage. This study aimed to measure plasma levels of both endothelins in patients with acute nonhemorrhagic cerebral infarction. SUMMARY OF REPORT: Plasma levels of endothelin-1 and endothelin-3 were measured by radioimmunoassay in 16 consecutive patients within the first 72 hours after the onset of nonhemorrhagic cerebral infarct, as diagnosed clinically and by computed tomography. There was a marked (fourfold) elevation in plasma endothelin-1 levels in the patients (median, 11.7 pg/ml; 25th and 75th centiles, 5.4 and 13.2 pg/ml) compared with those in a control group of 13 age-matched subjects (median, 2.56 pg/ml; 25th and 75th centiles, 2.4 and 3.0 pg/ml; p less than 0.0001). The first 24 hours after stroke onset were associated with higher endothelin-1 levels, and there was a trend to elevated levels with more severe neurological deficits. In all patients and controls endothelin-3 levels were below 0.5 pg/ml. CONCLUSIONS: Ischemic stroke is associated with acute and marked increases in plasma levels of endothelin-1. This may reflect enhanced production by damaged endothelial cells within the infarcted tissue. Local leakage of endothelin-1 may induce severe and prolonged constriction of collateral vessels and may therefore have a deleterious role in the pathogenesis and final outcome of cerebral infarction.     

Mortality prediction by serum melatonin levels of patients with spontaneous intracerebral hemorrhage

Neurological Sciences - In one study, higher serum melatonin levels have been reported at diagnosis of spontaneous intracerebral hemorrhage (ICH) in non-surviving than in surviving patients. Now,...     

刺五加注射液对大鼠脑出血病理变化和血管内皮素-1的影响

目的探讨不同剂量刺五加(AS)注射液对大鼠脑出血(ICH)病理变化、血浆血管内皮素-1(ET-1)水平的影响。方法采用胶原酶注入法建立大鼠ICH模型,干湿重法测定各组脑组织含水量、电镜观察脑组织病理变化、放免法检测血浆ET-1的水平。结果AS注射液可明显减轻ICH后脑水肿,阻断神经细胞和神经胶质细胞的凋亡,降低血浆ET-1水平。血浆ET-1水平与其脑组织含水量之间呈正的直线相关关系。结论AS注射液能明显减轻ICH后脑水肿并阻断脑细胞凋亡。ET-1通过促进ICH后脑水肿的形成而参与了ICH后的损伤机制,AS注射液通过降低血浆ET-1水平而发挥抗损伤作用是其治疗ICH的作用机制之一。     

Brain herniations in patients with intracerebral hemorrhage

Objectives – To study the types, frequency and clinical correlates of brain herniations in patients with intracerebral hemorrhage (ICH). Methods – In 24 patients with ICH (putaminal 22 and thalamic 2) features of raised intracranial pressure (ICP), such as hyperventilation, extensor rigidity, pupillary asymmetry and pyramidal signs on the non‐hemiplegic side, were recorded. Depth of coma was assessed by using the Glasgow Coma Scale (GCS) and severity of stroke by using the Canadian Neurological Scale (CNS). On MRI, evidence of herniation, horizontal and vertical shifts and the edema–hematoma complex were measured and compared with that of 15 matched controls. The clinical signs of herniation correlated with radiological parameters. Results – The mean age of the patients was 57.7 years, six of them were women. Cerebral herniations were present in 11 (46%) patients. Subfalcian herniation (in six) was the commonest followed by uncal (in three). Combination of subfalcian and uncal herniations was present in one and subfalcian, uncal and tonsillar herniations in another. Herniations had significant correlation with the GCS, pupillary abnormalities, cortical atrophy, hematoma size and the edema–hematoma complex. One‐month mortality was related to the GCS score, pupillary abnormalities and the edema–hematoma complex. Horizontal shift was related to the GCS score. Conclusion – In patients with ganglionic ICH, subfalcian herniation was the commonest. Herniation was associated with increased mortality. Horizontal shift correlated with clinical features of raised ICP and outcome.     

高血压脑出血应激性高血糖患者miR-223 HMGB1水平对预后的判断价值

目的研究高血压脑出血(HIH)应激性高血糖患者miR-223、血清高迁移率族蛋白B1(HMGB1)水平对预后的判断价值。方法选取郑州大学附属郑州中心医院2017-03—2019-03收治的125例HIH患者,根据血糖水平分为正常血糖组和高血糖组,收集患者一般资料,比较空腹血脂、血糖水平、神经功能(NIHSS)评分;实时荧光定量PCR(qRT-PCR)法测定血清miR-223水平;酶联免疫吸附法(ELISA)测定血清HMGB1水平;受试者工作特征曲线(ROC)评估miR-223、HMGB1水平对患者预后的判断价值;Logistic回归分析影响预后的因素。结果与HIH正常血糖组相比,HIH高血糖组血糖水平、LDL-C水平、NIHSS评分、miR-223水平、HMGB1水平显著升高(P<0.05);与预后良好组相比,预后不良组患者血清miR-223、HMGB1水平显著升高(P<0.05);根据ROC曲线图可得知,miR-223、HMGB1判断HIH应激性高血糖患者不良预后曲线下面积分别为0.84(95%CI0.721~0.921)、0.81(95%CI0.687~0.899),截断值分别为1.67、4.77 ng/mL;Logistic回归分析表明LDL-C水平、NIHSS评分、miR-223水平、HMGB1水平是影响HIH应激性高血糖患者不良预后的独立危险因素。结论miR-223、HMGB1在HIH应激性高血糖患者血清中水平升高,具有一定的预后判断价值,是影响此类患者不良预后的独立危险因素。     

微创血肿清除术对脑出血患者血浆细胞间黏附分子-1的影响

目的探讨高血压性脑出血微创术对清除血肿后脑水肿患者血浆细胞间黏附分子-1（ICAM-1）的影响。方法113例脑出血患者随机分为内科治疗组60例、微创术血肿抽吸引流组53例;采用酶联免疫法（ELISA）测定脑出血后治疗前、治疗后第3天、第7天和第14天血浆ICAM。1含量。结果微创组和内科治疗组血清ICAM-1含量均升高;两组治疗后第3、7天的含量与治疗前（发病24h内）比较,差异有统计学意义（P〈0．05）;两组治疗后不同时间点血清ICAM-1含量比较,差异有统计学意义（P〈0．05）。结论微创术能降低血清ICAM-1水平。     

Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia

Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia.The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively.Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6 months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder.The concentration of Trx1 in the patients with first episode of psychosis was 1.5 ± 1.0 ng/ml and 0.8 ± 0.6 ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5 ± 0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p < 0.016 and p < 0.001, respectively).Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.     

自发性脑出血的再出血随访分析

对首次脑出血存活者出院后进行２８－８８个月的随访，结果显示，在随访期２７．７％的存活者，经历了一次或次再出血。在正常血压病人出血部位被认为是血管淀粉样变的好部位。     

Injury of fornix in patients with intracerebral hemorrhage

ABSTRACT Objectives: Many diffusion tensor tractography (DTT) studies have reported on fornix injury in various diseases. However, there has been no DTT study on fornix injury by intracerebral hemorrhage (ICH). We attempted to investigate fornix body injury in patients with ICH, using DTT. Methods: We identified 58 consecutive stroke patients using the following criteria: (1) first-ever stroke, (2) age: 45-65 years, (3) hemorrhage confined within the corona radiata and basal ganglion level, (4) an available DTT scan performed during the early stage of ICH (1-5 weeks after onset). Among 58 consecutive patients, we identified six patients who showed disruption at the fornix body.Results: Following ICH, 10.7% of patients revealed complete disruption of the fornix body on DTT. Results from DTT of the fornix showed disruption in anterior and posterior portions of the fornix body in three patients, in the anterior portion of the fornix body in two patient, and in the posterior portion of the fornix body in one patient. Conclusions: We report on six patients who showed complete disruption of the fornix body following ICH. It is our belief that the fornix of patients with ICH could be evaluated using DTT.