Effect of acetylsalicylic acid intake on platelet derived microvesicles in healthy subjects.

Platelet-derived microvesicles (pMVs) are released from platelets in physiological and pathological conditions and exhibit a wide range of prothrombotic, antithrombotic, proatherogenic, and pro-inflammatory properties. Antiplatelet agents, such as acetylsalicylic acid (ASA), are widely used for the prevention and treatment of vascular diseases, but their impact on pMV release remains poorly understood and contradictory mainly because of discrepancies in the methodology and lack of well-standardized MV assessment protocols. The present study investigated the effects of ASA not only on total pMV release but also on their phenotypes defined using the surface expression of pro-inflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers in healthy subjects. Fifty healthy volunteers were enrolled in the study and received a daily dose of 150 mg ASA for 3 consecutive days. Circulating pMVs were characterized and quantified before and after the intervention period using flow cytometry. Serum levels of thromboxane B2 (TXB2) and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were also investigated to assess ASA compliance. In general, ASA did not effect pMV numbers in healthy subjects despite its effective inhibition of platelet aggregation Moreover, in premenopausal women, we noticed an increase in the number of pMVs. Further studies are needed to assess whether dose modification of ASA or combinations or changes in antiplatelet therapy would reduce pMV formation, especially in patients with cardiovascular risk factors.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

INTRODUCTION: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS). MATERIALS AND METHODS: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs. RESULTS: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed. CONCLUSION: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

Association of platelet-derived microvesicles with high on-treatment platelet reactivity in convalescent ischemic stroke patients treated with acetylsalicylic acid

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while "treatment failure" is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Material and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.

Free thyroxine and TSH interact with secreted protein acidic and rich in cysteine-like 1 in ischemic stroke.

The role of the thyroid gland in ischemic stroke pathology is not well understood. As thyroid hormones modulate the extracellular matrix, we explored the possible link between them and secreted protein acidic and rich in cysteine like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with acute ischemic stroke, serum SC1 levels were much higher compared with 30 control subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were higher in stroke subjects compared to those of controls (p=0.03). In stroke patients, TSH concentration was lower than in the control group (p=0.03). SC1 levels positively correlated with fT4 levels (p=0.02) and negatively with TSH (p=0.03) in stroke patients. Our results confirmed the association between thyroid hormones and SC1 - extracellular matrix protein.

The Impact of Vascular Disease Treatment on Platelet-Derived Microvesicles.

Platelet-derived microvesicles (pMVs) are small, heterogeneous vesicles released from platelet membranes as a result of activation. These microvesicles possess a wide range of properties, including prothrombotic, proatherogenic, proinflammatory, immunomodulatory, and even anticoagulant activity. The elevated release of these microvesicles has been observed in various metabolic, inflammatory, thrombotic, and vascular diseases, including ischemic heart disease, stroke, hypertension, diabetes, and connective tissue disease. Modulation of both pMV generation and the expression of their surface molecules may have beneficial clinical implications and could become a novel therapeutic target. However, mechanisms by which pharmacological agents can modify pMV formation are elusive. The purpose of this review is to discuss the effects of drugs routinely used in primary and secondary prevention of vascular disease on the release of pMV and expression of their surface procoagulant and proinflammatory molecules.

Neurological complications of underwater diving.

The diver's nervous system is extremely sensitive to high ambient pressure, which is the sum of atmospheric and hydrostatic pressure. Neurological complications associated with diving are a difficult diagnostic and therapeutic challenge. They occur in both commercial and recreational diving and are connected with increasing interest in the sport of diving. Hence it is very important to know the possible complications associated with this kind of sport. Complications of the nervous system may result from decompression sickness, pulmonary barotrauma associated with cerebral arterial air embolism (AGE), otic and sinus barotrauma, high pressure neurological syndrome (HPNS) and undesirable effect of gases used for breathing. The purpose of this review is to discuss the range of neurological symptoms that can occur during diving accidents and also the role of patent foramen ovale (PFO) and internal carotid artery (ICA) dissection in pathogenesis of stroke in divers.

[Peripheral nervous system involvement in the course of herpes virus infections]. / Powiklania ze strony obwodowego ukladu nerwowego w przebiegu zakazen wirusami z rodziny Herpesviridae.

The herpes viruses are associated with both central and pe-ripheral nervous system complications. Patients with symptoms suggestive of herpes viruses infections coexisting with peri-phe-ral nervous system manifestations, especially Guillain-Barré syndrome, mononeuropathy, plexopathy and radiculopathy, should be screened for the herpes viruses infections in the differential diagnosis. The purpose of this review is to discuss the etiology, pathogenesis and treatment of the neuropathies in the course of herpes viruses infections.

[Neuropathies in the course of primary hepatotropic virus infections]. / Neuropatie w przebiegu zakazen wirusami pierwotnie hepatotropowymi.

The primary hepatotropic viruses are associated with various extrahepatic manifestations including peripheral nervous system disorders. The pathogenesis of these complications is not clear-cut. Patients with confirmed liver damage coexisting with peripheral nervous system manifestations, especially Guillain-Barré syndrome, mononeuropathy, mononeuropathy multiplex and polyneuropathy should be screened for the viral hepatitis in the differential diagnosis. There are no defined strategies of treatment for these manifestations, so the therapy should be individualized. The purpose of this review is to discuss the etiology, pathogenesis and treatment of the neuropathies in the course of primary hepatotropic viral infections such as hepatitis A, B, C and E viruses.