Levels Of Microparticles Research Articles

Loss of Renal Peritubular Capillaries in Hypertensive Patients Is Detectable by Urinary Endothelial Microparticle Levels.

Hypertension, an important cause of chronic kidney disease, is characterized by peritubular capillary (PTC) loss. Circulating levels of endothelial microparticles (EMPs) reflect systemic endothelial injury. We hypothesized that systemic and urinary PTC-EMPs levels would reflect renal microvascular injury in hypertensive patients. We prospectively measured by flow cytometry renal vein, inferior vena cava, and urinary levels of EMPs in essential (n=14) and renovascular (RVH; n=24) hypertensive patients and compared them with peripheral blood and urinary levels in healthy volunteers (n=14). PTC-EMPs were identified as urinary exosomes positive for the PTC marker plasmalemmal-vesicle-associated protein. In 7 RVH patients, PTC and fibrosis were also quantified in renal biopsy, and in 18 RVH patients, PTC-EMPs were measured again 3 months after continued medical therapy with or without stenting (n=9 each). Renal vein and systemic PTC-EMPs levels were not different among the groups, whereas their urinary levels were elevated in both RVH and essential hypertension versus healthy volunteers (56.8%±12.7% and 62.8%±10.7% versus 34.0%±17.8%; both P≤0.001). Urinary PTC-EMPs levels correlated directly with blood pressure and inversely with estimated glomerular filtration rate. Furthermore, in RVH, urinary PTC-EMPs levels correlated directly with stenotic kidney hypoxia, histological PTC count, and fibrosis and inversely with cortical perfusion. Three months after treatment, the change in urinary PTC-EMPs levels correlated inversely with a change in renal function ( r=-0.582; P=0.011). Therefore, urinary PTC-EMPs levels are increased in hypertensive patients and may reflect renal microcirculation injury, whereas systemic PTC-EMPs levels are unchanged. Urinary PTC-EMPs may be useful as novel biomarkers of intrarenal capillary loss.

Acute effects of haemodialysis on circulating microparticles.

BackgroundMicroparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD).MethodsBlood was sampled from 20 consecutive HD patients before and 1 h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers.ResultsConcentrations of platelet (CD41+) (P = 0.039), endothelial (CD62E+) (P = 0.004) and monocyte-derived MPs (CD14+) (P < 0.001) significantly increased during HD. Similarly, endothelial- (P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activation markers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE+ MPs (P = 0.032) as well as TF+ platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers.ConclusionDialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

Changes of microparticle levels before and after daunorubicin-based chemotherapy in patients with acute leukemia

Objective To observe the serum levels of endothelial microparticles (EMP) and tissue factor-bearing microparticles (TF+ MP) in patients with acute leukemia before and after daunorubicin-based chemotherapy. Methods From July 2012 to February 2013, 15 patients with newly diagnosed acute leukemia in Peking Union Medical College Hospital received DA (daunorubicin + cytarabine) regimen or VDCLP (vincristine + daunorubicin + cyclophosphamide + L-asparaginase + prednisone) regimen chemotherapy. There were 8 males and 7 females, and the median age of patients was 44 years old. Eleven patients were acute myeloid leukemia (M0 1 case, M1 1 case, M2 9 cases), and 4 were acute lymphocytic leukemia. The peripheral blood samples were taken before induction chemotherapy and after 3 days of daunorubicin. Levels of EMP and TF+ MP were assessed using flow cytometry. Results The serum EMP and TF+ MP levels were significantly higher after 3-day daunorubicin infusions than those before induction chemotherapy (28.94/μl vs. 10.74/μl, P = 0.001; 64.24/μl vs. 43.80/μl, P = 0.02). Conclusion Daunorubicin-based chemotherapy may cause increased numbers of EMP and TF+ MP in patients with acute leukemia. Key words: Leukemia, acute; Antineoplastic combined chemotherapy protocols; Daunorubicin; Endothelial particles; Tissue factor-bearing microparticles

Association between arginase-containing platelet-derived microparticles and altered plasma arginine metabolism in polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disease associated with insulin resistance and increased risk of cardiovascular diseases. However, a biomarker for potential cardiovascular disease in PCOS patients is not available. Materials and MethodsTwenty-two patients with PCOS and 22 healthy controls were included in the present study and amino acid profiling was performed on fasting plasma samples. Circulating microparticles were characterized by FACS analysis and complemented with enzyme activity assays. ResultsThe ratio of ornithine to arginine was significantly increased in plasma form PCOS patients and was associated with a significant increase in plasma arginase levels and activity. Platelet-derived microparticles were identified to be the main sources of the increased plasma arginase activity. ConclusionsIncreased levels of arginase-bearing platelet-derived microparticles contribute to the alteration of the arginine metabolism in patients with polycystic ovary syndrome. Moreover, ornithine and arginine levels represent early biomarkers of potential cardiovascular disease in PCOS patients.

The relationship between habitual dietary sodium intake and RAAS blockade on circulating microparticle levels in type two diabetes.

Low sodium intake is paradoxically associated with adverse cardiovascular outcomes in individuals with type 2 diabetes mellitus (T2D), possibly from renin-angiotensin-aldosterone system (RAAS) activation, leading to endothelial dysfunction. In the present study, we investigated the associations between habitual sodium intake and RAAS blockade on endothelial function by measuring circulating microparticles (MPs) in individuals with T2D. We conducted a prospective, cross-sectional study in 74 individuals with T2D. Habitual dietary sodium intake was estimated by using the mean of three corrected 24-h urine sodium excretion measurements (24hUNa). MP subtypes in platelet-free plasma were quantitated using flow cytometry. No associations between 24hUNa with levels of endothelial MPs were observed. Instead, a trend toward higher diabetes related CD36+/CD235a+ MP levels was associated with lower 24hUNa (rho = -0.23, P=0.05). When stratified according to tertiles of 24hUNa, platelet-derived CD42b+/CD41+ and CD42+/CD41+/Annexin V+ MPs were higher in the lowest tertile (24hUNa < 157 mmol/24 h) (P=0.02 respectively). Despite RAAS blockade being associated with lower levels of most MP subsets, it was not associated with lower MPs, in the setting of low sodium intake. Lower sodium intake is associated with higher circulating procoagulant MPs, but not with evidence of endothelial dysfunction in individuals with T2D.

Microparticles as autoantigens in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs) and the formation of immune complexes with nuclear antigens. These complexes can drive pathogenesis by depositing in the tissue to incite inflammation or induce cytokine production by cells of the innate immune system. While ANAs can bind to purified nuclear molecules, nuclear autoantigens invivo most likely exist attached to other molecules or embedded in larger structures. Among these structures, microparticles (MPs) are membrane bound vesicles that are released from dead and dying cells by a blebbing process; MPs can also be released during activation of platelets. The presence of MPs in the blood or tissue culture media can be assayed by flow cytometry on the basis of light scattering as well as binding of marker antibodies to identify the cell of origin. As shown by biochemical analyses, MPs contain an ensemble of intracellular components including nuclear, cytoplasmic and membrane molecules. Because of the display of these molecules on the particle surface or in an otherwise accessible form, ANAs, including anti-DNA, can bind to particles. Levels of MPs are increased in the blood of patients with SLE, with flow cytometry demonstrating the presence of IgG-containing particles. In addition to forming immune complexes, MPs can directly stimulate immune responses. Together, these findings suggest an important role of particles in the pathogenesis of SLE and their utility as biomarkers.

A11518 Hemodialysis reduces levels of circulating microparticles in individuals with hypertension

Objectives: Individuals with end stage kidney disease (ESKD) and hypertension are at increased risk of cardiovascular complications. Circulating microparticles (MPs) are putative biomarkers of vascular injury and circulating levels of MPs are increased in both hypertension and ESKD. The purpose of this study was to determine the effect of hemodialysis on circulating MPs in individuals with and without hypertension. Methods: 37 individuals with hypertension and 17 normotensive individuals on conventional 3 times weekly hemodialysis were studied (age 61 ± 2 years). Plasma samples from were collected in a non-fasting state immediately before and after hemodialysis at the mid-week hemodialysis session. An FX 800 hemodiafilter (Fresenius Medical Care) was used. Levels of endothelial (CD144 + ), platelet (CD41 + ), leukocyte (CD45 + ) and total (Annexin V + ) microparticles were assessed by flow cytometry. Results: Across all participants, significant reductions were seen in circulating annexin V + ve MPs (3x107vs1.6x107, P < 0.01), platelet MPs (1.8x107vs1.0x107, P < 0.001), leukocyte microparticles (2.4x106vs 1.8x106, P < 0.05), and endothelial MPs (8.4x105vs5.9x105, P < 0.01). There were no differences in pre-dialysis or post-dialysis MP levels (total, endothelial, leukocyte, or platelet) between hypertensive and non-hypertensive individuals and the inter-dialytic increases in MP levels were not significantly different between hypertensive and non-hypertensive individuals. Conclusion: Hemodialysis is associated with reductions in circulating platelet, leukocyte, and endothelial MPs. There may be significant interdialytic variation in MP levels and this should be an important consideration in studying MPs as biomarkers in ESKD. The presence of hypertension does not appear to alter inter-dialytic increases in circulating MPs.

A10228 Endothelial microparticles from vegf inhibitor (vegfi)-treated cancer patients mediates endothelial cell signaling and et-1 production

Objectives: Vascular endothelial growth factor receptor inhibitors (VEGFRi), used as anti-angiogenic drugs to treat cancer, causes hypertension where mechanisms are still not fully elucidated. Microparticles (MPs) are biomarkers of cell damage. MPs also act as biovectors and influence vascular cell signalling and function. We questioned whether plasma levels of endothelial MPs from cancer patients treated with VEGFi are elevated (possibly reflecting underlying vascular injury) and whether these MPs influence endothelial cell signalling. Methods: Plasma MPs were isolated from cancer patients before and after treatment with VEGFRi (sunitinib, pazopanib or sorafenib). Human aortic endothelial cells (HAEC) were stimulated with isolated MPs (10*6 MPs/mL). MPs were characterized by flow cytometry; protein and gene expression by immunoblotting and qPCR; ROS and NO production by lucigenin and immunofluorescence. Results: VEGFRi treatment increased plasma endothelial cells-derived MPs (1.5 fold; p < 0.05 vs before treatment). HAEC exposed to post-treatment MPs increased pre-pro-ET-1 mRNA (9.1 fold; p < 0.01). Post-treatment MPs also increased ROS generation (5 min: 1.2 fold, p < 0.01; 30 min: 1.6 fold, p < 0.01; 60 min: 1.8 fold, p < 0.05) and phosphorylation of the inhibitory site of eNOS (Thr495) in HAEC (1.8 fold; p < 0.05). NO levels in HAEC exposed to MPs were decreased (1.2 fold; p < 0.05), an effect blocked by an ETB antagonist BQ788. Inflammatory marker gene expression was increased only in HAEC exposed to post-treatment MPs (p < 0.01). Conclusion: In conclusion, our data demonstrate that VEGFi treatment causes an increase in circulating MPs and that play a role in endothelial cell signalling and ET-1 production. These molecular processes may contribute to vascular dysfunction and hypertension in VEGFi-treated cancer patients.

Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review.

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

Microparticle miRNAs as Biomarkers of Vascular Function and Inflammation Response to Aerobic Exercise in Obesity?

This study aimed to explore the role of nine microRNAs (miRNAs) in microparticles (MPs) on the efficacy of aerobic exercise in the regulation of inflammation and vascular function in obesity. Sedentary women with normal weight (n = 6, BMI < 25 kg/m2 ) and women with obesity (n = 9, BMI > 30 kg/m2 ) were recruited at F. Hached Hospital (Sousse, Tunisia) and enrolled in an 8-week aerobic program. Vascular function was assessed using laser Doppler flowmetry/iontophoresis, circulating MPs by flow cytometry, miRNAs by real-time polymerase chain reaction, and inflammation by ELISA, before and after exercise. Women with obesity presented with high prevalence of cardiovascular risk factors and a higher circulating MP level compared with healthy subjects. The MP miRNA profile was significantly different in the two groups. Exercise reduced BMI and inflammation in both groups and significantly improved endothelial-dependent response (acetylcholine cutaneous vascular conductance) for healthy subjects, with a trend for women with obesity. Circulating MP level was increased after exercise, and miRNA expression was differentially modulated in both populations. Pearson analysis revealed a correlation between MPs miR-124a and miR150 and adiponectin, TNFα, or IL-6 levels. The relation between MPs and miRNA profile, inflammation, vascular function, and exercise is of particular interest for defining "miRNA biomarker signature" in patients with cardiovascular disease who are potentially susceptible to respond to exercise.

Microparticle Release During Normal Cesarean Delivery

(Anesth Analg. 2018;126:925–927) Microparticles (MPs) are spherical cytoplasm-free parts of cell membranes released from cells during physiological or pathologic processes; the origin of MPs can be identified based on their membrane proteins. The relationship between coagulability and MP levels surrounding normal delivery has not been characterized. A better understanding of peripartum coagulation may permit better identification of those at risk for postpartum hemorrhage. The authors of this brief report hypothesized that an increase in MP levels in plasma occurs around the time of placental separation and subsides after several hours.

Monomeric C-reactive protein and local inflammatory response in patients with stable coronary artery disease

Aim: Monomeric C-reactive protein (mCRP) may be involved in a local inflammatory response produced by atherosclerotic damage of artery wall tissues. We measured plasma levels of platelet and leukocyte microparticles bearing mCRP in patients with stable coronary artery disease (CAD) and detected tissue deposits of mCRP in autopsy samples of coronary atherosclerotic plaques and intact coronary arteries.

Circulating endothelial cells and microparticles as diagnostic and prognostic biomarkers in small-cell lung cancer

ObjectivesIt has been proposed that circulating endothelial cells (CECs) and microparticles (MPs) may be useful for the assessment of patients with non-small-cell lung cancer (NSCLC). However, little is known about the potential clinical relevance of these biomarkers in small-cell lung cancer (SCLC). Therefore, we investigated the utility of baseline levels of CECs and MPs in SCLC patients. Materials and methodsAn immunomagnetic separation (IMS) technique was used to isolate and quantify CECs in the peripheral blood, while plasma samples were analyzed using flow cytometry for the measurement of circulating MPs. ResultsWe prospectively collected data from 56 patients and 41 healthy individuals. Forty-three patients presented at initial diagnosis and 13 patients presented at relapse. Baseline levels of CECs and MPs were significantly higher in SCLC patients either at initial diagnosis or at relapse than in healthy subjects (p < 0.0002 and p < 0.007, respectively). However, estimated tumor volume (ETV) was significantly correlated with basal MP values (p < 0.0001) but not with pretreatment CECs (p = 0.57). The amount of baseline CECs and MPs was significantly lower in patients with an objective response (OR, n = 23) than in those with progressive disease (PD, n = 15) after treatment (p = 0.016 and 0.05, respectively). With cut-off values of 110 cells/mL for CECs and 1257 events/μL for MPs according to receiver operating characteristics (ROC) analysis, baseline levels of these biomarkers were not significantly correlated with either progression-free survival (PFS) or overall survival (OS). However, patients with 6-month PFS displayed significantly decreased pretreatment CEC counts (p = 0.042), whereas basal MP values significantly increased in 1-year survivors compared with those in non-survivors (p = 0.05). ConclusionOur results suggest that baseline CECs and MPs may be predictive biomarkers of tumor response and long-term survival in SCLC patients.

Activated platelets and leukocyte activations in young patients with β-thalassemia/HbE following bone marrow transplantation

Bone marrow transplantation (BMT) is the only curable option for thalassemia major, β-thalassemia/HbE. However, some patients still have the risk of hypercoagulable complications. We used a whole blood flow cytometric analysis to measure the circulating microparticle (MP) levels, activated platelets, and leukocyte-platelet aggregates in 59 young β-thalassemia/HbE patients compared with 20- and 28-matched healthy and patients receiving regular blood transfusion (RT), respectively. Results from the studies showed that blood samples from BMT group contained a significantly higher numbers of circulating MPs originated from platelets (ann-V+CD41a+), leukocyte (ann-V+CD45+) and endothelial cells (ann-V+CD146+) when compared to samples from healthy subjects and RT patients. In contrast, the percentages of activated/procoagulant platelets (CD62P and CD142 expressing platelets) were decreased in BMT group. In addition, monocytes forming microaggregates were the major population among other leukocyte-platelet complexes. Different patterns of CD11b, CD62P and CD142 expression on platelet-leukocyte microaggregate surface were also found. These data suggest that circulating MPs together with leukocyte-platelet aggregates may be responsible, in part, in pathogenesis of hypercoagulable state in β-thalassemia/HbE patients who undergone BMT.

Phosphatidylserine expressing platelet microparticle levels at hospital presentation are decreased in sepsis non-survivors and correlate with thrombocytopenia

BackgroundSepsis induced platelet activation releases platelet microparticles (PMPs). PMPs express phosphatidylserine (PS) and can serve as a scaffold for the prothrombinase complex, thereby promoting coagulation. Studies of PMPs in intensive care unit sepsis patients demonstrate mixed results, while the earliest changes and potential effects of clinical interventions remain understudied. We hypothesized PMPs would be associated with patient outcome and dysfunctional coagulation shortly after emergency department presentation with sepsis. MethodsCohort study of patients from a single center enrolled in a previously published randomized control trial comparing two early resuscitation strategies. Adults presenting to the emergency department (ED) with suspected infection, ≥2 SIRS criteria, and either systolic blood pressure <90 mm Hg or lactate >4 mmol/L were eligible. Triple positive platelet microparticles (PMPs) expressing phosphatidylserine and integrin complexes alphaIIb (CD41) and beta3 (CD61) were quantitated using plasma from the time of enrollment. The primary outcome was in-hospital mortality. Secondary outcomes included platelet count, disseminated intravascular coagulation (DIC), and prothrombin time (PT). Results193 patients were enrolled and 184 had samples available. In-hospital mortality was 21%. 10 (5%) patients developed DIC. Median platelet count was 197 (IQR 135, 280) and PT was 13.2 (IQR 11.9, 16.8). Median triple positive PMP counts were 932 per μL (IQR 381, 1872). PMPs were significantly lower in non-survivors (575 vs 1128, p = 0.02) and non-significantly lower in DIC (387 vs 942, p = 0.17). PMPs demonstrated a positive linear association with platelet count (p < 0.001, R2 = 0.21). After adjusting for platelet count, PMPs were no longer significant predictors of mortality (p = 0.28). We observed no association between PMPs and PT. ConclusionSimilar to patients enrolled later in the intensive care unit, PS-expressing PMPs are lower in emergency department sepsis non-survivors. These changes primarily reflect the degree of thrombocytopenia, and an independent prognostic role was not observed. Future studies should control for platelet count in assessment of PMP prognosis in sepsis.

Prothrombotic mechanisms in patients with congenital p.Cys89Tyr mutation in CD59

BackgroundThrombosis is the prognostic factor with the greatest effect on survival in patients with paroxysmal nocturnal hemoglobinuria (PNH), who lack dozens of membrane surface proteins. We recently described a primary homozygous Cys89Tyr congenital nonfunctioning CD59 in humans with clinical manifestation in infancy, associated with chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy. Here we investigated hypercoagulability mechanisms characterizing the syndrome. MethodsMembrane attack complex (MAC) deposition (anti-SC5b-9) and free hemoglobin (colorimetric assay) were assessed. Platelet activation was identified (anti-CD61, anti-CD62P), and microparticles (MPs) of 0.5–0.9 μm, were characterized (Annexin V, anti-human GlyA, anti-CD15, anti-CD14, anti-CD61). Platelet-monocyte aggregation was assessed with FlowSight. Findings2/7 patients (29%) with homozygosity for Cys89Tyr and 6/12 (50%) with any of four described CD59 mutations had recurrent strokes. In plasma samples from four patients carrying identical mutations, MAC deposition was increased on RBCs (p < 0.0003), neutrophils (p < 0.009), and platelets (p < 0.0003). Free-plasma hemoglobin levels were abnormally high, up to 100 mg/dl. Patients with CD59 mutation had RBC-derived MP levels 9-fold higher than those in healthy controls (p < 0.01), and 2–2.5 fold higher than PNH patients (p < 0.09). Leukocyte-activated platelet aggregation was increased (p < 0.0062). Loss of CD59 was shown in the endothelium of these patients. InterpretationNonfunctioning CD59 is a major risk factor for stroke and hypercoagulability. Uncontrolled hemolysis causes massive MP release and endothelial heme damage. MAC attack on unprotected endothelium and platelet activation and aggregation with leukocytes mediate additional mechanisms leading to vascular occlusion. It is suggested that CD59 loss represents a major arterial prothrombotic factor in PNH and additional diseases.

Relationship between PMP, FN, vWF and Bleeding Degree in Patients with Acute Leukemia

To detect the serum levels of platelet microparticle (PMP), fibronectin (FN), and von Willebrand Factor (vWF) in acute leukemia (AL) patients with thrombocytopenic and to analyze the relationship of the serum levels of PMP, FN and vWF with bleeding degree. One hundred and one newly diagnosed AL patients from May 2014 to May 2017 were enrolled the AL group. According to the WHO standard of bleeding stratification, 101 AL patients were divided into 5 sub groups: 0, 1, 2, 3 and 4 score groups; 52 normal persons subjected to physical examination were enrolled in control group. The PMP level was detected by flow cytometry; the FN and vWF levels were detected by ELISA. The levels of PMP, FN and vWF were compared between the AL group and the control group. The serum levels of PMP, FN and vWF were compared according to bleeding degree group. The relationship of bleeding degree with the serum levels of PMP, FN and vWF was analyzed. The patients with newly diagnosed acute leukemia aged 18 to 60, and accounted for 61.39%. The degree of bleeding was mainly 1 score, which accounted for 38.61%. The serum levels of PMP, vWF and FN AL groups were significantly higher than those in control group (6.06%±4.38% vs 0.89%±0.50%, 205.82±24.89 vs 58.04±13.35 µg/L, 398.29±46.93 vs 311.37±26.02 µg/L)(P<0.001). The serum levels of PMP, FN and vWF were different among 5 subgroup (P<0.01); the level of PMP and FN were the highest in 0 score group and the lowest in 4 score group; the vWF level was the highest in 4 score groups and the lowest in 0 score group. The bleeding degree in the patients with acute leukemia negatively correlated with PMP level, and positively with NF and vWF levels (r=-0.753, r=0.648, r=0.805). According to the relationship of the bleeding degree with serum levels of PMP, FN, vWF in patients, the detection of PMP, vWF and FN levels can help to evaluale the bleeding degree in the patients.

Total Circulating Microparticle Levels After Laparoscopic Surgical Treatment for Endometrioma: A Pilot, Prospective, Randomized Study Comparing Stripping with CO2 Laser Vaporization

To evaluate serial generation of microparticles (MPs) after laparoscopic stripping or CO2 laser vaporization in the surgical treatment of patients with ovarian endometrioma (OE). A prospective, randomized, blinded, pilot study (Canadian Task Force classification I). Tertiary care university hospital from December 2014 to July 2016. Thirty women with unilateral OE undergoing laparoscopic surgery. Patients were randomly selected to undergo either CO2 laser vaporization (L group) or laparoscopic stripping (S group) of OE. Blood samples were collected before surgery and at 2 hours, 24 hours, 1 month, and 3 months after surgery. An MP generation curve after OE surgery was created. MP generation was greater in the S group than in the L group at all time points evaluated. The MP generation curve showed a significantly higher area under the curve after excisional surgery (p <.05). The higher MP levels in the S group suggest an increased inflammation and procoagulant response after this procedure.

Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes

BackgroundLittle is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes.MethodsTen never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of “Blu” brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals.ResultsTwo hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine.ConclusionsThis study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking.Trial registrationClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

Emricasan, a pan-caspase inhibitor, improves survival and portal hypertension in a murine model of common bile-duct ligation.

Emricasan, a pan-caspase inhibitor, improves survival and portal hypertension induced by long-term bile-duct ligation (BDL) in mice Emricasan reduces liver damage, hepatocyte death, and fibrosis, following short-term BDL in mice, and these changes are associated with a decrease in circulating microparticle (MPs) Circulating MPs from BDL-placebo but not from BDL-emiricasan-treated mice activate endothelial cells ex vivo.