The association of plasminogen activator inhibitor-1 level with ischemic stroke (preliminary study)

Surjawan, Yenny; Setiabudy, Rahajuningsih Dharma; Suryaatmadja, Marzuki; Ranakusuma, Teguh

doi:10.13181/mji.v19i3.403

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…16 In one case control study design, it was concluded that, high PAI-1 level was found more frequent in ischemic stroke subjects. 17 Together with the recent observation that the activators of PPARγ a ligand reduces the incidence of stroke in patients with type 2 diabetes, this review supports the concept that rosiglitazone is effective drug against ischemic injury. 18 Of the two FDA-approved thiazolidinediones, pioglitazone is known to cross BBB more efficiently than rosiglitazone, but the affinity of pioglitazone to PPAR is 10 times lower (Kd of 400 nM) than for rosiglitazone (Kd of 40 nM).…”

Section: Rosiglitazone -Neuroprotective Effects In Brain Ischaemia (Ssupporting

confidence: 61%

Repurposing Diabetes Drugs for Neurodegenerative Diseases: Anti-Diabetic Drug Reposition

Parmar¹,

Panchal²

2019

Int. Res. J. Pharm.

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This study was aimed to find drug-repurposing opportunity of anti-diabetic drugs for treatment of neurodegenerative diseases using pharmacovigilance approach. We have retrieved the source data from United States FDA Adverse Event Reporting System for the last 15 years covering duration from 2004 to 2018. Medical dictionary for Regulatory Activities, version 19.1 was used to decode the relevant preferred terms for reported indications and side-effects. We have targeted reposition of anti-diabetic drugs for neurodegenerative disease. A primary target was set to identify anti-diabetic drug, which has therapeutic or prophylactic effect for neurodegenerative disease. Molecular mechanism of drugs and phenotypic characteristic of reported side-effects were compared with 'very common' side-effects of approved drugs for treatment of 'neurodegenerative disease'. Statistical analysis includes quantitative methods to calculate proportional reporting ratio for confirmed signal. Signals calculated with proportional reporting ratio value more than two, were only considered as positive result outcome. Through our systematic review of safety data, we have identified rosiglitazone, insulin (intranasal administration) and exenatide as convincing molecules for them reposition to treat neurodegenerative disease as novel therapeutic indication. Through this study, we have proposed to create a novel opportunity to find anti-diabetic drug that fully convinced for treatment of neurodegenerative disease. In future, well-designed, double-blind randomized controlled trials with large samples are required to conclude the efficacy of proposed reposition for anti-diabetic drugs.

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Section: Rosiglitazone -Neuroprotective Effects In Brain Ischaemia (Ssupporting

confidence: 61%

Repurposing Diabetes Drugs for Neurodegenerative Diseases: Anti-Diabetic Drug Reposition

Parmar¹,

Panchal²

2019

Int. Res. J. Pharm.

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“…The link between PAI-1 and ischaemic stroke has been well studied [35]. Elevated levels of PAI-1 not only positively correlated with the severity of stroke but also greatly increased the failure rate of thrombolytic therapy.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea

et al. 2016

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Obstructive sleep apnoea (OSA) induces thrombophilia and reduces fibrinolysis. Alpha-2-antiplasmin (a-2-AP) and plasminogen activator inhibitor 1 (PAI-1) are major inhibitors of the fibrinolytic system. Increased concentrations of these factors are associated with a higher risk of cardiovascular diseases. The aim of this study was to assess plasma a-2-AP and PAI-1 in patients with OSA and evaluate correlations with the polysomnographic record and selected risk factors of cardiovascular diseases. The study group comprised 45 patients with OSA, and the control group consisted of 19 patients who did not meet the diagnostic criteria of OSA. Plasma a-2-AP and PAI-1 concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). In the study group, the median value of plasma a-2-AP was higher than that of the control group (157.34 vs. 11.89 pg/ml, respectively, P<0.0001). A-2-AP concentration increased proportionally to the severity of OSA. The concentration of a-2-AP was positively correlated with the apnoea-hypopnoea index (AHI), apnoea index (AI), respiratory disturbances time (RDT), and desaturaion index (DI), and negatively correlated with mean and minimal oxygen saturation (SpO2 mean, SpO2 min, respectively). The median value of PAI-1 was higher in the study group than the control group (12.55 vs. 5.40 ng/ml, respectively, P = 0.006) and increased along with OSA severity. PAI-1 concentration was positively correlated with AHI, AI, RDT, DI, and body mass index (BMI) and negatively correlated with SpO2 mean and SpO2 min. Higher plasma concentrations of a-2-AP and PAI-1 in patients with OSA indicated that these patients had increased prothrombotic activity. OSA increases the risk of cardiovascular complications as it enhances prothrombotic activity.

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“…A decrease in the plasma concentration of PAI-1 with increasing age has been described. 10 Therefore, we suspect that the association between levels of PAI-I and the profile “HIV-negative stroke” is due to a residual confounding effect of age.…”

Section: Discussionmentioning

confidence: 99%

HIV is associated with endothelial activation despite ART, in a sub-Saharan African setting

Kamtchum‐Tatuene

Mwandumba

Al-Bayati

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo study the relationship between endothelial dysfunction, HIV infection, and stroke in Malawians.MethodsUsing a cross-sectional design, we measured plasma levels of intercellular adhesion molecule-1 (ICAM-1), plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), and soluble thrombomodulin (sTM) in stroke patients and controls, stratified by HIV status. These biomarkers were measured using ELISA. After dichotomization, each biomarker was used as the dependent variable in a multivariable logistic regression model. Primary independent variables included HIV and stroke status. Adjustment variables were age, sex, hypertension, diabetes mellitus, tobacco and alcohol consumption, personal/family history of stroke, antiretroviral therapy status, and hypercholesterolemia.ResultsSixty-one stroke cases (19 HIV+) and 168 controls (32 HIV+) were enrolled. The median age was 55 years (38.5–65.0) for controls and 52 years (38.0–73.0) for cases (p = 0.38). The median CD4+ T-cell count was 260.1 cells/mm3 (156.3–363.9) and 452 cells/mm3 (378.1–527.4) in HIV-infected cases and controls, respectively. HIV infection was independently associated with high levels of ICAM-1 (OR = 3.6, 95% CI: 1.3–10.6, p = 0.018) in controls but not in stroke cases even after excluding patients with a viral load >1,000 RNA copies/mL (OR = 4.1, 95% CI: 1.3–13.1, p = 0.017). There was no association between the clinical profiles of HIV-positive controls or HIV-positive stroke and high levels of PAI-1, VEGF, and sTM.ConclusionsHIV infection is associated with endothelial activation despite antiretroviral treatment. Our findings underscore the need for larger clinical cohorts to better understand the contribution of this perturbation of the endothelial function to the increasing burden of cardiovascular diseases in sub-Saharan Africa.

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The association of plasminogen activator inhibitor-1 level with ischemic stroke (preliminary study)

Cited by 3 publications

References 26 publications

Repurposing Diabetes Drugs for Neurodegenerative Diseases: Anti-Diabetic Drug Reposition

Repurposing Diabetes Drugs for Neurodegenerative Diseases: Anti-Diabetic Drug Reposition

Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea

HIV is associated with endothelial activation despite ART, in a sub-Saharan African setting

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