Summary
Background
Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP‐10 is involved in atherothrombosis.
Objective
The ...purpose of this study was to examine the relationship between proMMP‐10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke.
Methods
We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non‐tPA‐treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP‐9, proMMP‐10, TIMP‐1, tumor necrosis factor‐α (TNFα), interleukin‐6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP‐10 was assessed in vitro.
Results
Serum proMMP‐10 concentration in ischemic stroke patients, non‐treated or treated with t‐PA, which was higher than age‐matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP‐10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP‐9, however, was only associated with HT and severe edema (all P < 0.05).
Conclusions
Increased serum proMMP‐10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome.
The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have ...been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown.
The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10-null mice (Mmp10(-/-)), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator-induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation-mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in Mmp10(-/-) mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator-treated animals were severely impaired in Mmp10(-/-) mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor-deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect.
A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis.
Objectives: Circulating levels of matrix metalloproteinase (MMP)‐10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP‐10 is associated with the ...severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP‐10 levels with atherosclerotic risk factors and subclinical atherosclerosis. Methods and results: Circulating levels of MMP‐1, ‐9 and ‐10, and markers of inflammation fibrinogen, interleukin‐6, von Willebrand factor, and high‐sensitivity C‐reactive protein (hs‐CRP) were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima‐media thickness (IMT) and the presence of atherosclerotic plaques with the use of B‐mode ultrasound in all subjects. MMP‐10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs‐CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP‐10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP‐1 and ‐9. Subjects in the highest MMP‐10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3–31.4, P = 0.024). In addition, MMP‐10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). Conclusion: Higher serum MMP‐10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP‐10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.
Bar pattern speeds in CALIFA galaxies Aguerri, J A L; Mendez-Abreu, J; Falcon-Barroso, J ...
Astronomy and astrophysics (Berlin),
4/2015, Letnik:
576
Journal Article
Recenzirano
Odprti dostop
The bar pattern speed (Omegab) is defined as the rotational frequency of the bar, and it determines the bar dynamics. Several methods have been proposed for measuring Omegab. This method has been ...applied so far to 17 galaxies, most of them SB0 and SBa types. We have applied the TW method to a new sample of 15 strong and bright barred galaxies, spanning a wide range of morphological types from SB0 to SBbc. Combining our analysis with previous studies, we investigate 32 barred galaxies with their pattern speed measured by the TW method. We measured Omegab using the TW method on the stellar velocity maps provided by the integral-field spectroscopy data from the CALIFA survey. Our results indicate that independent of the Hubble type, bars have been formed and then evolve as fast rotators. This observational result will constrain the scenarios of formation and evolution of bars proposed by numerical simulations.
Patients with cancer present with an elevated risk of thrombosis, which entails high morbidity and mortality. Various predictive scales that incorporate clinical and biological data have been ...developed to identify those at high risk of thrombosis, but, in general, they do not allow for the optimal selection of subjects who are candidates for thromboprophylaxis. Recent studies have demonstrated that the mutation profile has a high impact on the risk of thrombosis; this will facilitate developing new predictive models of thrombosis in patients with cancer.
Los pacientes con cáncer presentan un riesgo elevado de trombosis, que condiciona una elevada morbimortalidad. Se han desarrollado diversas escalas predictivas para la identificación de aquellos con alto riesgo trombótico, incorporando datos clínicos y biológicos, pero, en general, no permiten una selección óptima de los sujetos candidatos para recibir tromboprofilaxis. Estudios recientes demuestran que el perfil mutacional tiene un alto impacto sobre el riesgo trombótico, lo que va a facilitar el desarrollo de nuevos modelos predictivos de trombosis en pacientes con cáncer.
A Fe–20.1Mn–1.23Si–1.72Al–0.5C TWIP steel with ultrafine grain structure was successfully processed through equal channel angular pressing (ECAP) at warm temperature up to four passes following the
B
...C
route. The microstructure evolution was characterized by electron backscattered diffraction to obtain the grain maps, which revealed an obvious reduction in grain size, as well as a decrease in the twin fraction, with increasing number of ECAP passes. The texture evolution during ECAP was analyzed by orientation distribution function. The results show that the annealed material presents brass (
B
) as dominant component. After ECAP, the one pass sample presents
A
1
* and
A
2
* as the strongest components, while the two passes and four passes samples change gradually toward
B
/
B
¯
components. TEM analysis shows that all samples present twins. The twin thickness is reduced with increasing the number of ECAP passes. Nano-twins, as a result of secondary twinning, are also observed in the one and two passes samples. In the four passes sample, the microstructure is extensively refined by the joint action of ultrafine subgrains, grains and twins. The mechanical behavior was studied by tensile samples, and it was found that the yield strength and the ultimate tensile strength are significantly enhanced at increasing number of ECAP passes. Although the ductility and strain hardening capability are reduced with ECAP process, the present TWIP steel shows significant uniform deformation periods with positive work hardening rates.
Summary
Objective
To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off‐label indications.
Background
PCCs are approved for the urgent reversal of ...vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off‐label indications are limited, but they are included in massive bleeding protocols.
Methods
This was a retrospective review of cases treated with four‐factor PCCs (4F‐PCCs) between January 2009 and 2016. Efficacy end‐points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24‐h mortality in bleeding coagulopathy. The safety end‐point is the incidence of thromboembolic events.
Results
A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%).
VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24‐h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%).
Conclusion
4F‐PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.
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