scholarly journals Intraplatelet serotonin and plasma 5-hydroxyindoles in health and disease

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 505-509 ◽  
Author(s):  
RD Shuttleworth ◽  
JR O'Brien

Abstract Using a fluorometric test sensitive to serotonin (5-HT) and to other 5- hydroxyindoles (5-HIs) it was shown that platelets take up 5-HT and that the added 5-HT and the inherent test-positive material in platelet lysate can be directly measured. However, platelets do not take up 5- hydroxyindole acetic acid or the 5-HIs from the plasma. Thus, 5-HT and the other 5-HIs can be distinguished. Various methods of liberating intraplatelets 5-HT were investigated. Several anticoagulants, temperatures, and speeds of centrifugation were employed, with no effect on the results. It was found that in healthy donors, with increasing age, there was a decrease in intraplatelet 5-HT and an increase in plasma 5-HIs. The quantities of these substances were inversely related. In acute myocardial infarction, the 5-HT was normal taking age into account, but the plasma 5-HIs were increased. In postoperative patients, the platelet 5-HT was low and the plasma 5-HIs were normal. In patients with chest pain but no myocardial infarction, both platelet 5-HT and plasma 5-HIs were normal. The relevance of these findings to 5-HT metabolism and the evidence for in vivo activation of platelets is discussed.

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 505-509 ◽  
Author(s):  
RD Shuttleworth ◽  
JR O'Brien

Using a fluorometric test sensitive to serotonin (5-HT) and to other 5- hydroxyindoles (5-HIs) it was shown that platelets take up 5-HT and that the added 5-HT and the inherent test-positive material in platelet lysate can be directly measured. However, platelets do not take up 5- hydroxyindole acetic acid or the 5-HIs from the plasma. Thus, 5-HT and the other 5-HIs can be distinguished. Various methods of liberating intraplatelets 5-HT were investigated. Several anticoagulants, temperatures, and speeds of centrifugation were employed, with no effect on the results. It was found that in healthy donors, with increasing age, there was a decrease in intraplatelet 5-HT and an increase in plasma 5-HIs. The quantities of these substances were inversely related. In acute myocardial infarction, the 5-HT was normal taking age into account, but the plasma 5-HIs were increased. In postoperative patients, the platelet 5-HT was low and the plasma 5-HIs were normal. In patients with chest pain but no myocardial infarction, both platelet 5-HT and plasma 5-HIs were normal. The relevance of these findings to 5-HT metabolism and the evidence for in vivo activation of platelets is discussed.


2020 ◽  
Author(s):  
Hang Xiang ◽  
Tianyuan Xiang ◽  
Hongxia Zhang ◽  
Ann Xu ◽  
Matthew John Horwedel ◽  
...  

Abstract BackgroundHuman adipose derived mesenchymal stem cells (ASCs) are ideal candidates for the treatment of acute myocardial infarction (AMI), due to their favorable availability and regenerative potential. However, in vivo studies showed that ASCs are not resilient at the infarcted area, for a shortage of blood and oxygen supply. Material and methodsTo solve the problem of living in the hypoxic environment, we accommodated ASCs within the hypoxic condition. To enhance the capillary system, we combined the hypoxic pretreated ASCs (HP-ASCs) with cord blood mononuclear cells (CBMNCs), which have a great potential for neovascularization. We hypothesized that this combination system would improve the transplantation efficiency. ResultsIn vitro study showed that HP-ASCs had a wide range of paracrine function, with the incretion growth factors and their receptors, which would support the cell survivals. In addition, HP-ASCs also gained potentials in hypoxic adaptation (increased expression of HO-1 and SDF-1), as well as homing and immigrating abilities (CXCR4, ICAM-1 and ICAM-2). In vivo studies showed that, 30 days after transplantation in AMI rats, the HP-ASCs group had a better improvement in cardiac function; reduction of the infarct size; and decrease of ASCs death than the other groups (HP-ASCs > HP-ASCs + CBMNCs ≧ CBMNCs > PBS) (p<0.05). However, the combined group of HP-ASCs and CBMNCs had more significant angiogenesis than the other groups (HP-ASCs + CBMNCs > CBMNCs > HP-ASCs > PBS) (p <0.05).ConclusionsHP-ASCs alone had a greater potential in improving cardiac function in AMI rats. However, the combination of HP-ASCs and CBMNCs had a better result in angiogenesis.


1993 ◽  
Vol 39 (6) ◽  
pp. 972-979 ◽  
Author(s):  
C Larue ◽  
C Calzolari ◽  
J P Bertinchant ◽  
F Leclercq ◽  
R Grolleau ◽  
...  

Abstract The screening by immunoenzymometric assay (IEMA) of 784 monoclonal antibody (MAb) combinations resulted in the selection of an optimal pair of MAbs for measuring human cardiac troponin I (TnI). Using a one-step IEMA described here, we were able to detect TnI within the range of 0.2-20 micrograms/L in 30 min at room temperature. No cross-reactivity was observed with the skeletal isoforms of troponin up to a concentration of 500 micrograms/L. This assay was used to measure cardiac TnI in the plasma of 43 patients with acute myocardial infarction (AMI). TnI was detected relatively early after the onset of chest pain (4.3 +/- 2.1 h, mean +/- SD); the peak occurred after 12.2 +/- 4.6 h in a population that had undergone fibrinolysis. TnI disappearance was generally observed between 5 and 9 days after the onset of chest pain. No cardiac TnI could be detected in 145 healthy donors or in a control group of 6 patients (with skeletal damage or rhabdomyolysis). This assay allows a specific diagnosis of AMI in its early acute phase, with a high diagnostic specificity and sensitivity.


1987 ◽  
Author(s):  
R Fears

Selective fibrinolysis may be achieved physiologically by the binding of both endogenous plasminogen activator (t-PA) and plasminogen to fibrin. It has been suggested that t-PA may also exhibit fibrin-selectivity when used at therapeutic doses for acute myocardial infarction whereas the other principal thrombo-lytics, urokinase (UK) and streptokinase (SK).plasminogen, are not bound. However, in the present kinetic studies it was found that plasminogen activation by SK.lys-plasminogen was enhanced by soluble fibrin (the effect mainly on Km), the affinity of binding to fibrin was similar to t-PA (dissociation constant approx. 100 nM) and the reaction mechanism appeared similar (Rapid Equilibrium Ordered Bireactant). When evaluating the in vivo significance of fibrin-enhancement, variation in the form of the substrate (i.e., glu1- or lys77-forms) and the contribution of heparin must also be considered. Both t-PA and UK activities were potentiated by heparin (the effect mainly on Km) but in the presence of fibrin the effect of heparin on t-PA was attenuated; SK.plasminogen enzymatic activity was unaffected by heparin. Thus, in the presence of heparin, in vivo, there may be an exacerbation of the systemic action of t-PA. As differences in fibrin binding and enhancement between t-PA and intact SK.plasminogen - the activator that is produced from APSAC (Eminase) - are relative rather than absolute, therapeutic activity will be influenced more by the dosage regimen and the clearance rate.


2020 ◽  
Author(s):  
Hang Xiang ◽  
Tianyuan Xiang ◽  
Hongxia Zhang ◽  
Ann Xu ◽  
Matthew John Horwedel ◽  
...  

Abstract BackgroundHuman adipose derived mesenchymal stem cells (ASCs) are ideal candidates for the treatment of acute myocardial infarction (AMI), due to their favorable availability and regenerative potential. However, in vivo studies showed that ASCs are not resilient at the infarcted area, for a shortage of blood and oxygen supply. Hypoxic pretreatment was proven to be an effective way to enhance cell survival in ischemic atmosphere. Moreover, co-transplantation of stem cells was another promising strategy to improve cardiac function after transplantation. So, we hypothesized that hypoxic pretreated ASCs combined with proangiogenic cord blood mononuclear cells (CBMNCs) would promote treatment efficacy after co-transplantation.MethodsASCs extracted from male volunteer were preconditioned in hypoxic condition (HP-ASC) for 24h, and total RNA were extracted after that. Gene expressions were compared between HP-ASC and ASC. Then, we transplanted stem cells to female Wistar rats which divided into different groups: (1) HP-ASCs group (n=10, 1x106ASCs); (2) HP-ASCs + CBMNCs group (n=10, 0.5×106 ASCs+0.5×106 CBMNCs); (3) CBMNCs group (n=10, 1×106 ASCs); (4) Control group (n=10, 40μL PBS); (5) Sham group (n=10). Echocardiogram was performed before (0d) and after (30d) after cell transplantation. Hearts were harvested at 30d to analyze the infarct size, myocardium apoptosis, stem cells viability and angiogenesis. ResultsIn vitro study showed that HP-ASCs had a wide range of paracrine function, with the incretion growth factors and their receptors, which would support the cell survivals. In addition, HP-ASCs also gained potentials in hypoxic adaptation (increased expression of HO-1 and SDF-1), as well as homing and immigrating abilities (CXCR4, ICAM-1 and ICAM-2). In vivo studies showed that, 30 days after transplantation in AMI rats, the HP-ASCs group had a better improvement in cardiac function; reduction of the infarct size; and decrease of ASCs death than the other groups (HP-ASCs > HP-ASCs + CBMNCs ≧ CBMNCs > PBS) (p<0.05). However, the combined group of HP-ASCs and CBMNCs had more significant angiogenesis than the other groups (HP-ASCs + CBMNCs > CBMNCs > HP-ASCs > PBS) (p <0.05).ConclusionsHP-ASCs alone had a greater potential in improving cardiac function in AMI rats. However, the combination of HP-ASCs and CBMNCs had a better result in angiogenesis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Watanabe ◽  
H Yoshino ◽  
T Takahashi ◽  
M Usui ◽  
K Akutsu ◽  
...  

Abstract   Both acute aortic dissection (AAD) and acute myocardial infarction (AMI) present with chest pain and are life-threatening diseases that require early diagnosis and treatment for better clinical outcome. However, two critical diseases in the very acute phase are sometimes difficult to differentiate, especially prior to arrival at the hospital for urgent diagnosis and selection of specific treatment. The aim of our study was to clarify the diagnostic markers acquired from the information gathered from medical history taking and physical examination for discriminating AAD from AMI by using data from the Tokyo Cardiovascular Care Unit (CCU) Network database. We examined the clinical features and laboratory data of patients with AAD and AMI who were admitted to the hospital in Tokyo between January 2013 and December 2015 by using the Tokyo CCU Network database. The Tokyo CCU Network consists of &gt;60 hospitals that fulfil certain clinical criteria and receive patients from ambulance units coordinated by the Tokyo Fire Department. Of 15,061 patients diagnosed as having AAD and AMI, 3,195 with chest pain within 2 hours after symptom onset (537 AAD and 2,658 AMI) were examined. The patients with out-of-hospital cardiac arrest were excluded. We compared the clinical data of the patients with chest pain who were diagnosed as having AAD and AMI. The following indicators were more frequent or had higher values among those with AAD: female sex (38% vs. 20%, P&lt;0.001), systolic blood pressures (SBPs) at the time of first contact by the emergency crew (142 mmHg vs. 127 mmHg), back pain in addition to chest pain (54% vs. 5%, P&lt;0.001), history of hypertension (73% vs. 58%, P&lt;0.001), SBP ≥150 mmHg (39% vs. 22%, P&lt;0.001), back pain combined with SBP ≥150 mmHg (23% vs. 0.8%, P&lt;0.001), and back pain with SBP &lt;90 mmHg (4.5% vs. 0.1%, P&lt;0.001). The following data were less frequently observed among those with AAD: diabetes mellitus (7% vs. 28%, P&lt;0.001), dyslipidaemia (17% vs. 42%, P&lt;0.001), and history of smoking (48% vs. 61%, P&lt;0.001). The multivariate regression analysis suggested that back pain with SBP ≥150 mmHg (odds ratio [OR] 47; 95% confidence interval [CI] 28–77; P&lt;0.001), back pain with SBP &lt;90 mmHg (OR 68, 95% CI 16–297, P&lt;0.001), and history of smoking (OR 0.49, 95% CI 0.38–0.63, P&lt;0.001) were the independent markers of AAD. The sensitivity and specificity of back pain with SBPs of ≥150 mmHg and back pain with SBPs &lt;90 mmHg for detecting AAD were 23% and 99%, and 4% and 99%, respectively. In patients with chest pain suspicious of AAD and AMI, “back pain accompanied by chest pain with SBP ≥150 mmHg” or “back pain accompanied by chest pain with SBP &lt;90 mmH” is a reliable diagnostic marker of AAD with high specificity, although the sensitivity was low. The two SBP values with back pain are markers that may be useful for the ambulance crew at their first contact with patients with chest pain. Funding Acknowledgement Type of funding source: None


1975 ◽  
Author(s):  
J. R. O’Brien ◽  
M. D. Etherington ◽  
S. Jamieson ◽  
J. Sussex

We have previously demonstrated that, relative to controls, patients long after myocardial infarction and patients with atherosclerosis have highly significantly shorter heparin thrombin clotting times (HTCT) using platelet poor plasma; but there was considerable overlap between the two groups.We have now studied 89 patients admitted with acute chest pain. In 54 of these a firm diagnosis of acute myocardial infarction (ac-MI) was made and the HTCT was very short (mean 12.8 sees) and in 48 it was less than 16 sees. In 34 patients, ac-MI was excluded and the diagnosis was usually “angina”; the HTCT was much longer (mean 25.1 sees) and in 32 it was over 16 sees. Thus there was almost no overlap between these two groups. It is suggested that this test should be adopted as a quick and reliable further test to establish a diagnosis of ac-MI (providing other reasons for very short HTCTs can be excluded, e.g. D. I. C., and provinding the patient’s thrombin clotting time is normal).This HTCT measures non-specific heparin neutralizing activity; nevertheless the evidence suggests that it is measuring platelet factor 4 liberated from damaged or “activated” platelets into the plasma. These findings underline the probable important contribution of platelets in ac-MI.


2012 ◽  
Vol 58 (3) ◽  
pp. 559-567 ◽  
Author(s):  
Yvan Devaux ◽  
Mélanie Vausort ◽  
Emeline Goretti ◽  
Petr V Nazarov ◽  
Francisco Azuaje ◽  
...  

Abstract BACKGROUND Rapid and correct diagnosis of acute myocardial infarction (MI) has an important impact on patient treatment and prognosis. We compared the diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) and cardiac enriched microRNAs (miRNAs) in patients with MI. METHODS Circulating concentrations of cardiac-enriched miR-208b and miR-499 were measured by quantitative PCR in a case-control study of 510 MI patients referred for primary mechanical reperfusion and 87 healthy controls. RESULTS miRNA-208b and miR-499 were highly increased in MI patients (&gt;105-fold, P &lt; 0.001) and nearly undetectable in healthy controls. Patients with ST-elevation MI (n= 397) had higher miRNA concentrations than patients with non–ST-elevation MI (n = 113) (P &lt; 0.001). Both miRNAs correlated with peak concentrations of creatine kinase and cTnT (P &lt; 10−9). miRNAs and hs-cTnT were already detectable in the plasma 1 h after onset of chest pain. In patients who presented &lt;3 h after onset of pain, miR-499 was positive in 93% of patients and hs-cTnT in 88% of patients (P= 0.78). Overall, miR-499 and hs-cTnT provided comparable diagnostic value with areas under the ROC curves of 0.97. The reclassification index of miR-499 to a clinical model including several risk factors and hs-cTnT was not significant (P = 0.15). CONCLUSION Circulating miRNAs are powerful markers of acute MI. Their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain.


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