Differences Between Upper and Lower Limbs in Venous Endothelial Reactivity in Humans

1994 ◽  
Vol 9 (1_suppl) ◽  
pp. 10-14
Author(s):  
O. Bailliart ◽  
L. Boudaoud ◽  
Ph. Bonnin ◽  
C. Bal Dit Sollier ◽  
J. Roussi ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Cell Activity ◽  
Lower Limbs ◽  
Cell Recovery ◽  
Significant Difference ◽  
Cell Release ◽  
The Right ◽  
Pai 1

Objective: To determine the variability of endothelial reactivity to venostasis in the upper and lower limbs of healthy subjects. Participants: Ten healthy volunteers were investigated twice, at an interval of 1-week. Main outcome measures: Plasma concentrations of substances released from endothelial cells were determined in each limb after 10 min of venostasis in a sequential manner. Tissue plasminogen activator (tPA), plasminogen activator inhibiting factor (PAI-1), thrombin–antithrombin complexes (TAT) and D-dimers (D-Di) were used as indicators of the thrombotic process and its reactions; angiotensin converting enzyme (ACE) and endothelin-1 (ET1) were related to endothelial cell activity involved in vascular tone regulation. Results: No difference was observed in endothelial cell recovery following venostasis after an interval of 1 week. A significant difference in endothelial cell release was found between the upper and lower limbs and between the right and left legs. Conclusions: Excellent reproducibility of measurements was observed. In keeping with the higher frequency of venous thrombosis in the lower limbs, the left leg seemed to be less reactive after venostasis, and the endothelium was more reactive in the upper than in the lower limbs.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

Immunoreactivity of Tissue Plasminogen Activator and of Its Inhibitor Complexes

1989 ◽  
Vol 61 (03) ◽  
pp. 409-414 ◽  
Author(s):  
M Rånby ◽  
G Nguyen ◽  
P Y Scarabin ◽  
M Samama
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Degradation Products ◽  
Gel Filtration ◽  
Free Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Samples ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Pai 1

SummaryAn enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 8l% for free tPA and tPA in complex with PAI-1, PAI-2, α2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about l00%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasffi, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.

Analysing CYP2D6*4 Allele frequency in Patients with Schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S101-S102
Author(s):  
V. Djordjevic ◽  
T. Jevtovic Stoimenov
Keyword(s):  
Allele Frequency ◽  
Plasma Concentrations ◽  
Clinical Severity ◽  
Genotype Distribution ◽  
Healthy Individuals ◽  
Wild Type ◽  
Specific Pcr ◽  
Significant Difference ◽  
Schizophrenic Patients ◽  
The Right

IntroductionSchizophrenia is treated with antipsychotics and other psychotropic medications, many of which are substrates for the highly polymorphic CYP2D6 enzyme. The most frequent variant allele is CYP2D6*4- leading cause of poor metabolism (PM) phenotype. PM causes the reduction of therapeutic response, increase the risk of adverse drug reactions and increase the plasma concentration of both drug and its metabolites above the levels of toxicity.The AimAnalysing CYP2D6*4 allele frequency among schizophrenic patients for further individualisation and rationalisation of therapy.Patients and methodsResearch was conducted on 38 schizophrenic patients and 110 healthy individuals. CYP2D6*4 allele was detected with allele specific PCR.ResultsBoth wild type allele carriers are 55% of the schizophrenic patients, 45% are wild type/*4heterozygous, and *4/*4 homozygous are not identified. There is a statistically significant difference in the genotype distribution (P < 0.05) between schizophrenic patients and healthy individuals. Significantly higher *4 allele frequency (37%) comparing to healthy individuals (P < 0.0001) indicates the necessary caution in administration of CYP2D6 substrates. A lower frequency of PMs in schizophrenic patients than in healthy individuals could be explained with CYP2D6 neuroactive substrate metabolism. Forty-five percent of the schizophrenic patients are intermediate metabolisers carrying the higher risk of adverse response to CYP2D6 substrates comparing to wild type homozygous. As none of the analyzed patients was PM, exceeded plasma concentrations of medications above toxic levels are not expected when administrating the right dosage.ConclusionAltered CYP2D6 metabolism may contribute to the vulnerability, clinical severity and treatment outcome of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The plasminogen activator inhibitor-1 (PAI-1) promoter haplotype is related to PAI-1 plasma concentrations in lean individuals

2005 ◽  
Vol 181 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Maartje Verschuur ◽  
Annemarie Jellema ◽  
Else M. Bladbjerg ◽  
Edith J. M. Feskens ◽  
Ronald P. Mensink ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Promoter Haplotype

scholarly journals Muscle strength and inflammatory response to the training load in rowers

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10355
Author(s):  
Tomasz Podgórski ◽  
Alicja Nowak ◽  
Katarzyna Domaszewska ◽  
Jacek Mączyński ◽  
Magdalena Jabłońska ◽  
...  
Keyword(s):  
Muscle Metabolism ◽  
Creatine Kinase Activity ◽  
Lower Limbs ◽  
Total Testosterone ◽  
Blood Biochemical ◽  
Global Force ◽  
Significant Difference ◽  
Muscle Groups ◽  
Torque Values ◽  
The Right

Background Regular exercise leads to changes in muscle metabolism. The consequence of this is the adaptation to higher training loads.The aim of this study was to evaluate biomechanical and biochemical parameters describing the functions of skeletal muscles in periods when changes in training forms were introduced. Methods Seventeen male sweep-oar rowers, members of the Polish national rowing team, participated. The study was carried out at the beginning and at the end of the preparatory period. In the first and second examination measurements of torques of selected muscle groups and blood biochemical analysis were performed. Results There was observed a statistically significant decrease in the relative global force of the right lower limb between both terms of examination. A statistically significant increase in maximum torque was found for torso flexors. In the case of muscles responsible for torso rotation, a statistically significant decrease in the torque values of right torso rotators was observed. A significant difference was found with respect to creatine kinase activity, total testosterone concentration, total testosterone to cortisol ratio and total phenolics concentration (p < 0.05). Conclusion The study shows that the rowers’ training should be more focused on building the strength of lower limbs to prevent the overload of lumbar spine and that the amount of force developed may be significantly affected by the antioxidant potential of rowers.

Abstract 267: A Single Dose of Reconstituted High Density Lipoprotein Reduces Expression of Tissue-Factor In Human Carotid Atherosclerotic Plaques

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hosaam H Nasr ◽  
Ian M Loftus ◽  
Saiqa Sayed ◽  
Alun Jones ◽  
Evelyn Torsney ◽  
...  
Keyword(s):  
Single Dose ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Clinical Event ◽  
Tissue Type ◽  
Transcriptional Level ◽  
Rt Pcr ◽  
Significant Difference ◽  
Plaque Stabilisation ◽  
Pai 1

Background: Multiple infusions of HDLs have been shown to mediate approximately 4% reduction in plaque volume. This may relate to removal of intra-plaque lipid, but the precise mechanism is unknown. To test the hypothesis that HDLs may influence plaque stabilisation through modulating transcription, we examined the effects of a single dose of rHDL on expression of thrombomodulatory genes in carotid plaques. Materials and Methods: Forty patients undergoing carotid endarterectomy (CEA) were stratified to three groups: early symptomatics ( n =12, stroke/transient ischemic attack (TIA) 1month before CEA)late symptomatics ( n =14, stroke/TIA > 1month before CEA); and asymptomatics ( n =12). RNA was isolated from plaques following CEA, and expression of the thrombomodulatory genes, tissue factor (TF); tissue factor pathway inhibitor (TFPI); thrombomodulin (TM); tissue type plasminogen activator (tPA); urokinase plasminogen activator (uPA); plasminogen activator inhibitor-1 (PAI-1), measured using QRT-RT-PCR. Nine patients with early symptomatic carotid disease, undergoing CEA, were then randomised to infusion of reconstituted HDL (rHDL) 80mg/kg Apo A-I ( n =4) or a similar volume of phosphate buffered saline ( n =5). Plaque specimens were collected 24 hrs later and RNA isolated for QRT-RT- PCR measurement of thrombomodulatory gene expression. Results: A significant difference in TF, TM, tPA and PAI-1 genes were observed in the 3 patient groups (see Table 1 ). In the rHDL group, a single dose of rHDL reduced the expression of TF (0.71 (0.65–0.75) vs 0.98 (0.81–1.14), P=0.05). No significant difference was observed in other thrombomodulatory factors between the 2 groups. Conclusions: Plaque stabilisation, which occurs within one month of a clinical event may be facilitated, at the transcriptional level, following rHDL infusion. We hope to report a larger double blind placebo controlled trial which will determine the full effects of rHDLs on plaque stability. Table 1

Fibrate-modulated Expression of Fibrinogen, Plasminogen Activator Inhibitor-1 and Apolipoprotein A-I in Cultured Cynomolgus Monkey Hepatocytes

1998 ◽  
Vol 80 (12) ◽  
pp. 942-948 ◽  
Author(s):  
M. Kockx ◽  
H. M. G. Princen ◽  
T. Kooistra
Keyword(s):  
Plasminogen Activator ◽  
Cynomolgus Monkey ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Peroxisome Proliferator ◽  
Plasminogen Activator Inhibitor 1 ◽  
Apolipoprotein A ◽  
Activator Inhibitor ◽  
Pai 1

SummaryFibrates are used to lower plasma triglycerides and cholesterol levels in hyperlipidemic patients. In addition, fibrates have been found to alter the plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein A-I (apo A-I). We have investigated the in vitro effects of fibrates on fibrinogen, PAI-1 and apo A-I synthesis and the underlying regulatory mechanisms in primary monkey hepatocytes.We show that fibrates time- and dose-dependently increase fibrinogen and apo A-I expression and decrease PAI-1 expression in cultured cynomolgus monkey hepatocytes, the effects demonstrating different potency for different fibrates. After three consecutive periods of 24 h the most effective fibrate, ciprofibrate (at 1 mmol/l), increased fibrinogen and apo A-I synthesis to 356% and 322% of control levels, respectively. Maximum inhibition of PAI-1 synthesis was about 50% of control levels and was reached by 1 mmol/l gemfibrozil or ciprofibrate after 48 h. A ligand for the retinoid-X-receptor (RXR), 9-cis retinoic acid, and specific activators of the peroxisome proliferator-activated receptor-α (PPARα), Wy14,643 and ETYA, influenced fibrinogen, PAI-1 and apo A-I expression in a similar fashion, suggesting a role for the PPARα/RXRα heterodimer in the regulation of these genes. When comparing the effects of the various compounds on PPARα trans-activation activity as determined in a PPARα-sensitive reporter gene system and the ability of the compounds to affect fibrinogen, PAI-1 and apo A-I antigen production, a good correlation (r = 0.80; p <0.01) between PPARα transactivation and fibrinogen expression was found. Apo A-I expression correlated only weakly with PPARα transactivation activity (r = 0.47; p = 0.24), whereas such a correlation was absent for PAI-1 (r = 0.03; p = 0.95). These results strongly suggest an involvement of PPARα in the regulation of fibrinogen gene expression.

Sex Differences in the Determinants of Fibrinolytic Activity

1998 ◽  
Vol 79 (03) ◽  
pp. 587-590 ◽  
Author(s):  
J. A. Cooper ◽  
D. J. Howarth ◽  
T. W. Meade ◽  
G. J. Miller ◽  
P. K. MacCallum
Keyword(s):  
Plasminogen Activator ◽  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clot Lysis ◽  
Significant Difference ◽  
Main Determinants ◽  
Activator Inhibitor Type ◽  
Pai 1

SummaryImpaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice.Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein.Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only “global” measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.

scholarly journals Evidence that postoperative fibrinolytic shutdown is mediated by plasma factors that stimulate endothelial cell type I plasminogen activator inhibitor biosynthesis

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1758-1764 ◽  
Author(s):  
J Kassis ◽  
J Hirsh ◽  
TJ Podor
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Plasminogen Activator Inhibitor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Postoperative fibrinolytic shutdown has been attributed to an increase in plasma levels of type I plasminogen activator inhibitor (PAI-1) activity and may contribute to postoperative venous thrombosis. The purpose of this study was to determine whether the postoperative increase in PAI-1 is contributed to by a plasma mediator(s) that stimulates PAI-1 synthesis and secretion by vascular endothelium. Plasma samples collected from patients (N = 11) before and after surgery for total hip replacement were (1) assayed for endogenous plasma PAI-1 antigen and activity, and (2) incubated with cultured human umbilical vein endothelial cells (HUVECs) and PAI-1 antigen and activity measured in the conditioned medium (CM). Eighteen hours after surgery, endogenous plasma levels of PAI-1 antigen and activity were increased by 225% (P = .003) and 190% (P = .04), respectively over the preoperative values. In addition, compared with preoperative plasma, postoperative plasma increased HUVEC secretion of PAI-1 antigen and activity by 99% (P = .001) and 66% (P = .002), respectively. This increase in HUVEC PAI-1 secretion reflects an increase in PAI-1 mRNA expression and protein biosynthesis as confirmed by metabolic radiolabeling, immunoprecipitation, and Northern blot analysis. Ultra- filtration experiments indicate that the postoperative plasma mediator(s) that stimulates HUVEC PAI-1 biosynthesis is in a molecular weight (MW) range of approximately 30 to 100 Kd. Heat treatment (56 degrees C; 30 minutes) of postoperative plasma abolished the induction of HUVEC PAI-1 production. Enzyme-linked immunosorbent assay and immunoneutralization experiments indicate that tumor necrosis factor- alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) do not contribute to the postoperative plasma effect on HUVEC PAI-1 synthesis. These observations demonstrate that postoperative patient plasma contains a factor(s) that may stimulate endothelial cell PAI-1 biosynthesis in vivo and thus mediate postoperative fibrinolytic shut- down.

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