Compression Socks Reduce Running-Induced Intestinal Damage.

ABSTRACT: Zadow, EK, Edwards, KH, Kitic, CM, Fell, JW, Adams, MJ, Singh, I, Kundur, A, Johnstone, ANB, Crilly, J, Bulmer, AC, Halson, SL, and, and Wu, SSX. Compression socks reduce running-induced intestinal damage. J Strength Cond Res 36(9): 2461-2464, 2022-Exercise is associated with a reduction in splanchnic blood flow that leads to the disruption of intestinal epithelium integrity, contributing to exercise-induced gastrointestinal syndrome. Strategies that promote intestinal blood flow during exercise may reduce intestinal damage, which may be advantageous for subsequent recovery and performance. This study aimed to explore if exercise-associated intestinal damage was influenced by wearing compression garments, which may improve central blood flow. Subjects were randomly allocated to wear compression socks ( n = 23) or no compression socks (control, n = 23) during a marathon race. Blood samples were collected 24 hours before and immediately after marathon and analyzed for intestinal fatty acid-binding protein (I-FABP) concentration as a marker of intestinal damage. The magnitude of increase in postmarathon plasma I-FABP concentration was significantly greater in control group (107%; 95% confidence interval [CI], 72-428%) when compared with runners wearing compression socks (38%; 95% CI, 20-120%; p = 0.046; d = 0.59). Wearing compression socks during a marathon run reduced exercise-associated intestinal damage. Compression socks may prove an effective strategy to minimize the intestinal damage component of exercise-induced gastrointestinal syndrome.

Deep vein thrombosis in a well-trained masters cyclist, is popliteal vein entrapment syndrome to blame?

Whilst athletes are the epitome of health, venous thromboembolisms (VTE) including deep vein thrombosis and pulmonary embolism have been demonstrated to occur in well-trained athletes. VTE is frequently misdiagnosed and poorly treated within this population, often resulting in career or life-threatening ramifications. Furthermore, VTE risk rises with increasing age (> 40 years), potentially affecting masters athletes. A 44-year-old well-trained male cyclist volunteered to participate in a research project investigating the influence of exercise on haemostasis in well-trained athletes. The cyclist presented with elevated D-Dimer levels both pre- (2251 ng/mL) and post-exercise (2653 ng/mL). The cyclist reported constant mild-pain in the left mid-calf region, with a cold tingling sensation in their left foot. Diagnosis of DVT was confirmed via a DVT squeeze test and Doppler ultrasound, with the clot located in the left popliteal vein. During the research project, the cyclist was exposed to numerous thrombogenic risk factors including travel, dehydration, prolonged sitting and exercise. The DVT in the popliteal vein may have resulted from repetitive movements associated with cycling. Additionally, hypertrophy of the gastrocnemius muscle may have impinged the vein. When diagnosing DVT within a cycling population, PVES should not be overlooked as a contributing factor.

Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation.

The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC50: IC50 (95% CI) 32.9 (19.9-54.3)/219 (144-246) µmol/l). U266B1 cells were more resistant to CAP than THP-1 and U937. Metabolic activity was significantly inhibited by CAP in U937 compared to U266B1 cells (IC50: 197 versus 431 µmol/l, respectively, p < 0.008). Transient receptor potential vanilloid-1 (TRPV1) and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (p < 0.001). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with CAP in U937 cells. CAP inhibits the metabolic activity of malignant hematological cells through non-TRPV1-dependent mechanisms.

Association of von Willebrand factor blood levels with exercise hypertension.

PURPOSE: A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. METHODS: Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥ 170 mmHg/men and ≥ 160 mmHg/women). Rest, exercise and post-exercise blood samples were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). RESULTS: HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240-2,615, vs. 1,129 mU/mL, 95 % CI 871-1,386; p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p < 0.05 for all). Rest vWf predicted exercise brachial systolic BP (ß = 0.220, p = 0.043; adjusted R (2) = 0.451, p < 0.001) independent of age, sex, body mass index, triglycerides, rest brachial systolic BP and aortic stiffness. CONCLUSIONS: Increased rest blood levels of vWf are independently associated with moderate intensity exercise systolic BP. These findings implicate abnormalities in haemostasis as a possible factor contributing to HRE at moderate intensity.

Tissue factor pathway inhibitor: then and now.

Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner, helping to control thrombin generation and ultimately fibrin formation. The importance of TFPI is demonstrated in models of hemophilia where lower levels of FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a bleeding phenotype. There are two major isoforms in vivo; TFPIα contains three Kunitz-type inhibitory domains (designated K1, K2, and K3), is secreted by endothelial cells and requires protein S to enhance its anticoagulant activity. In contrast, TFPIß contains only the K1 and K2 domains, but it is attached to the endothelial surface via a glycosylphosphatidylinositol anchor. This review will initially provide a brief history of the major discoveries related to TFPI, and then discuss new insights into the physiology of TFPI, including updates on its association with protein S and FV, as well as the current understanding of its association with disease.

Thrombosis in systemic lupus erythematosus: role of impaired fibrinolysis.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can affect any part of the body, including the skin, liver, kidneys, and blood. Thrombosis is a frequent manifestation in SLE, contributing significantly to patient morbidity and mortality, although the precise mechanism(s) of how this occurs remains unclear. Fibrinolysis is the physiologic process of thrombus digestion and provides an important balance to hemostasis. This process is triggered upon vessel injury with the release of tissue-type plasminogen activator (t-PA) from endothelial cells. The central component of the fibrinolytic pathway is plasminogen, a zymogen that is converted to plasmin by t-PA. Plasminogen/plasmin is absorbed into the developing thrombus and digests fibrinogen and fibrin within the hemostatic plug to prevent excessive clot formation. Abnormalities of the fibrinolytic pathway are associated either with the development of thrombosis (impaired fibrinolysis) or, to a lesser extent, bleeding (excessive fibrinolysis). Indeed, impaired fibrinolysis has been reported in patients with SLE and may contribute to both the development of hypercoagulability and an increased risk of thrombosis. Here we discuss the role of impaired fibrinolysis and its contribution to hypercoagulability and thrombosis in SLE.

Effect of whole-body mild-cold exposure on arterial stiffness and central haemodynamics: a randomised, cross-over trial in healthy men and women.

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent predictors of cardiovascular risk and mortality, but little is known about the effect of air temperature changes on these variables. Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness (aortic and brachial PWV), and on central haemodynamics [including augmented pressure (AP), AIx], and aortic reservoir components [including reservoir and excess pressures (P ex)]. Sixteen healthy volunteers (10 men, age 43 ± 19 years; mean ± SD) were randomised to be studied under conditions of 12 °C (mild-cold) and 21 °C (control) on separate days. Supine resting measures were taken at baseline (ambient temperature) and after 10, 30, and 60 min exposure to each experimental condition in a climate chamber. There was no significant change in brachial blood pressure between mild-cold and control conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval (CI) 0.36-4.36; p = 0.01] and AIx (+6 %, 95 % CI 1.24-10.1; p = 0.02) increased, and time to maximum P ex (a component of reservoir function related to timing of peak aortic in-flow) decreased (-7 ms, 95 % CI -15.4 to 2.03; p = 0.01) compared to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI -0.47 to 0.55; p = 0.87) or brachial PWV (+0.36 m/s; -0.41 to 1.12; p = 0.35) between conditions. We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness.

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections. An imbalance between the components of the PNS might contribute to pathogenesis and the further development of certain diseases. In this review, we have explored the "thread" (hardwiring) of the connections between the immune system (e.g., primary/secondary/tertiary lymphoid tissues/organs) and PNS (e.g., sensory, sympathetic, parasympathetic, and enteric nervous systems (ENS)) in health and disease in vitro and in vivo. Neuroimmune cell units provide an anatomical and physiological basis for bidirectional crosstalk between the PNS and the immune system in peripheral tissues, including lymphoid tissues and organs. These neuroimmune interactions/modulation studies might greatly contribute to a better understanding of the mechanisms through which the PNS possibly affects cellular and humoral-mediated immune responses or vice versa in health and diseases. Physical, chemical, pharmacological, and other manipulations of these neuroimmune interactions should bring about the development of practical therapeutic applications for certain neurological, neuroimmunological, infectious, inflammatory, and immunological disorders/diseases.

Optimized flow cytometric detection of transient receptor potential vanilloid-1 (TRPV1) in human hematological malignancies.

The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers, including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and presents an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients' peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients including B-cell non-Hodgkin's lymphoma (B-NHL), MM, and others and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM = 2, B-NHL = 2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical samples and show that TRPV1 is increased in a subset of patients with hematological malignancies.

Estradiol-Responsive miR-365a-3p Interacts with Tissue Factor 3'UTR to Modulate Tissue Factor-Initiated Thrombin Generation.

BACKGROUND: High estradiol (E2) levels are linked to an increased risk of venous thromboembolism; however, the underlying molecular mechanism(s) remain poorly understood. We previously identified an E2-responsive microRNA (miR), miR-494-3p, that downregulates protein S expression, and posited additional coagulation factors, such as tissue factor, may be regulated in a similar manner via miRs. OBJECTIVES: To evaluate the coagulation capacity of cohorts with high physiological E2, and to further characterize novel E2-responsive miR and miR regulation on tissue factor in E2-related hypercoagulability. METHODS: Ceveron Alpha thrombin generation assay (TGA) was used to assess plasma coagulation profile of three cohorts. The effect of physiological levels of E2, 10 nM, on miR expression in HuH-7 cells was compared using NanoString nCounter and validated with independent assays. The effect of tissue factor-interacting miR was confirmed by dual-luciferase reporter assays, immunoblotting, flow cytometry, biochemistry assays, and TGA. RESULTS: Plasma samples from pregnant women and women on the contraceptive pill were confirmed to be hypercoagulable (compared with sex-matched controls). At equivalent and high physiological levels of E2, miR-365a-3p displayed concordant E2 downregulation in two independent miR quantification platforms, and tissue factor protein was upregulated by E2 treatment. Direct interaction between miR-365a-3p and F3-3'UTR was confirmed and overexpression of miR-365a-3p led to a decrease of (1) tissue factor mRNA transcripts, (2) protein levels, (3) activity, and (4) tissue factor-initiated thrombin generation. CONCLUSION: miR-365a-3p is a novel tissue factor regulator. High E2 concentrations induce a hypercoagulable state via a miR network specific for coagulation factors.

Shedding of soluble glycoprotein VI is neither affected by animal-derived antibeta-2-glycoprotein 1 antibodies nor IgG fractions from patients with systemic lupus erythematosus.

: Antibeta-2-glycoprotein 1 (antiß2GP1) antibodies are associated with increased risk of thrombosis in patients with systemic lupus erythematosus (SLE). The specific effect(s) of antiß2GP1 antibodies on platelets are unclear. Platelet activation in response to antiplatelet antibodies has been shown to induce shedding of the ectodomain of the platelet collagen receptor, glycoprotein VI (GPVI), releasing soluble GPVI (sGPVI). The aim of this study was to therefore determine whether antiß2GP1 antibodies, and/or purified IgG fractions, from patients with SLE shed sGPVI from platelets. We determined sGPVI levels in platelet poor plasma from SLE patients with/without antiß2GP1 antibodies (n = 37), as well as in platelet-rich plasma from healthy donors treated with either SLE-derived IgG fractions containing antiß2GP1, animal-derived antiß2GP1, or isotype control antibodies. Levels of sGPVI were higher in three SLE-derived platelet poor plasma with antiß2GP1 antibodies (103.52 ±â€Š12.32 ng/ml) compared with those without (28.11 ±â€Š12.73 ng/ml). Neither SLE-derived IgG fractions containing antiß2GP1 antibodies, nor animal-derived antiß2GP1 antibodies induced significant shedding of sGPVI from healthy donor platelets compared with isotype controls. These results suggest that antiß2GP1 antibodies do not affect shedding of sGPVI, and therefore collagen-mediated platelet signalling pathways. The shedding activity in SLE patients may be due to factors other than antiß2GP1 antibodies, for example, metalloproteinases.

Acute effect of a high-carbohydrate low-fat meal on platelet aggregation.

Conflicting information is available regarding patient preparation with respect to the fasting and feeding states prior to blood collection in order to conduct platelet aggregation tests. Some literature suggests avoidance of only high-fat foods and allowance of non-fat foods and clear liquids; others suggest a fast of 8-10 hours. We conducted a study in 16 healthy subjects aged 44.0 +/- 12.7 (mean +/- SD) years to investigate and compare the effects of fasting and a high-carbohydrate low-fat meal on measures of platelet aggregation. Blood samples collected after an overnight fast of 10-12 hours and those collected at 40 and 120 minute postprandially (post-high-carbohydrate low-fat meal; 1900 kJ energy; 69, 16 and 15% of energy from carbohydrate, protein and fat, respectively), were tested for platelet aggregation in response to adenosine diphosphate. There was a significant reduction in maximum aggregation and area under the aggregation curve from fasting to 120 minute post meal (overall p < 0.001). Serum triglyceride concentrations did not change significantly from fasting to postprandial state (p = 0.53). Although there was a significant association between serum insulin, plasma glucose and measures of platelet aggregation, correcting for the effects of these metabolic parameters did not alter the results, providing evidence that other, currently unknown, factors associated with food consumption affect postprandial platelet aggregation. We propose that protocols for control of pre-analytical variables in platelet aggregation studies should make a fasting sample mandatory rather than "preferable" unless the objective of the study is to measure acute effects in response to a medication or food.

International Society on Thrombosis and Haemostasis core curriculum project: Core competencies in laboratory thrombosis and hemostasis.

BACKGROUND: Laboratory analyses of blood samples are essential for diagnostics and therapy monitoring of patients with bleeding and thromboembolic diseases. Following publication of the core curriculum for clinical thrombosis and hemostasis, the International Society on Thrombosis and Haemostasis (ISTH) recognized that thrombosis and hemostasis laboratory specialists require distinct competencies that differ from medical doctors working clinically with patients. To address this gap the ISTH formed a working group of international hemostasis and thrombosis laboratory specialists to develop an evidence-based core curriculum for laboratory specialists. OBJECTIVE: This research sought consensus from the international community on core competencies required for laboratory specialists in thrombosis and hemostasis. METHODS: A draft list of 64 competencies was developed and an online stakeholder survey was circulated electronically to 15 302 ISTH members and contacts in the wider international community. The results were analyzed and used to develop the final approved core curriculum. RESULTS: Three hundred and thirty responses contained meaningful data, with broad international representation of specialists. No draft competencies were excluded, and 58 were rated as "does" or "shows how." The Leik measure of consensus for most competences was "moderate" (n = 30) or "fair" (n = 32). CONCLUSIONS: The development of an international core curriculum for laboratory specialists provides a foundation for the development and enhancement of education and quality management of the laboratory. Although there is no formal designation for laboratory specialists, international governing bodies and regulatory organizations are encouraged to consider the diagnostic core curriculum for development and accreditation of more standardized educational programs and formal assessment across jurisdictions.

Further insight into the heparin-releasable and glycosylphosphatidylinositol-lipid--anchored forms of tissue factor pathway inhibitor.

The release of tissue factor pathway inhibitor (TFPI) from human umbilical vein endothelial cells (HUVECs) was investigated using heparin and phospholipase C. The experiment included incubating HUVECs with 0, 1, or 10 U/mL heparin diluted in Dulbecco Modified Eagle's Medium plus 5% fetal calf serum for 1 or 24 hours. A statistically significant increase in TFPI activity levels was seen at 1 hour, but not at 24 hours. A 20-fold increase in the release of TFPI after phospholipase C treatment of HUVECs was demonstrated, confirming that it is glycosylphosphatidylinositol-lipid (GPI) anchored. Sequential treatment of HUVECs with phospholipase C and heparin was performed, and a trend was observed where GPI-anchored TFPI levels were increased after 1 hour of pretreatment with heparin but were decreased after 24 hours. Serum is a requirement for the heparin-dependent release of TFPI from HUVECs. Heparin pretreatment of HUVECs may affect levels of GPI anchored TFPI in a time and dose-dependent manner.

Further Investigations of the Effects of Anti-ß2GP1 Antibodies on Collagen-Induced Platelet Aggregation.

Anti-beta-2-glycoprotein 1 (anti-ß2GP1) antibodies are associated with increased thrombotic risk in patients with autoimmune disease. There is conflicting evidence on the effects of anti-ß2GP1 antibodies on platelets, with both enhanced and inhibited aggregation previously reported. However, previous studies did not include isotype antibodies to ensure the observed effects were due to anti-ß2GP1 antibodies. The aims of this study were to (1) investigate the effects of anti-ß2GP1 antibodies on collagen-induced platelet aggregation in parallel with negative control (buffer normal saline) and isotype control antibodies and (2) determine the lupus anticoagulant (LA) activity of anti-ß2GP1 antibodies used. Three animal-derived anti-human-ß2GP1 antibodies (1.25, 2.5, and 5 µg/mL) incubated with healthy platelet-rich plasma were activated by collagen (2.5 µg/mL). Each anti-ß2GP1 antibody demonstrated the inhibition of aggregation compared to negative control, but not to isotype control. No anti-ß2GP1 antibody demonstrated LA activity, suggesting they were probably nonpathological. This study highlights both negative and isotype control markers are important to validate the effects of anti-ß2GP1 antibodies. Assays to measure anti-domain I-ß2GP1 antibodies are recommended to be used in conjunction with functional measures to further investigate the effects of anti-ß2GP1 antibodies.

Crossmatching Maternal and Fetal Blood in Sheep.

We investigated the incidence of ex vivo incompatibility between ovine maternal RBC and fetal plasma. Time-mated singleton pregnant ewes (n = 8) underwent cesarean delivery of the fetus; at the time of delivery, paired maternal and fetal blood samples were collected and subsequently separated for storage as packed RBC and fresh frozen plasma. Gel column crossmatching was performed 3 to 4 wk later. All fetus-dam crossmatches were considered major crossmatches, combining fetal (recipient) plasma with dam (donor) RBC. The plasma of 8 fetuses was cross-matched with RBC from 5 dams; all autologous controls were negative, and all but one crossmatch (1 of 40, 2.5%) were considered compatible. In addition, the plasma of 3 dams was crossmatched with RBC from 5 dams; all autologous controls were negative; however, significant incompatibility was noted. In total, 4 of 13 (30.8%) dam-dam crossmatches were considered incompatible. The results of this initial study suggest that when a single animal receives multiple blood-product transfusions, the risk of an immunologic transfusion reaction can be reduced by ensuring that the blood products are obtained from a single donor, performing a crossmatch prior to transfusion, and the use of synthetic products to increase the oxygen carrying capacity of fetal blood.

Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden.

Polymorphisms within the tissue factor pathway inhibitor (TFPI) gene may determine TFPI expression and increase the risk of venous thromboembolism (VTE) in predisposed individuals. We tested this hypothesis by comparing TFPI activity and the frequency of common TFPI polymorphisms, -33T->C, -399C->T and -287T->C, in patients with antiphospholipid syndrome (APS) (n = 24) or factor V Leiden (n = 44) who had a history of VTE (n = 26), compared with those without VTE (n = 42) and also with normal control individuals (n = 56). TFPI activity was measured using a modified amidolytic assay and genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. We found that only APS patients with a history of venous thrombosis had TFPI activity levels significantly different from control individuals (1.77 +/- 0.60 vs 0.77 +/- 0.19 U/ml; P = 0.0001), and this was associated with inheritance of the TFPI -33C allele (1.70 +/- 0.72 U/ml for TC/CC genotypes vs 0.97 +/- 0.56 U/ml for TT; P = 0.01). Multivariate analysis of APS and factor V Leiden patients revealed that the greatest independent contributor to VTE was TFPI activity (adjusted odds ratio = 16.84; 95% confidence interval = 2.47-114.36, P = 0.004), while inheritance of either the TFPI -33C or -399T alleles each increased the odds of VTE by nearly 13 times (95% confidence interval = 2.39-69.91, P = 0.003; and 95% confidence interval = 2.25-71.23, P = 0.004, respectively). These results indicate that the TFPI -33T->C and -399C->T polymorphisms are significantly associated with venous thrombosis in the presence of other risk factors, especially APS, and may be clinically relevant in patients who are prone to hypercoagulability.

Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke.

The present study aimed to determine whether four previously described polymorphisms found within the tissue factor pathway inhibitor (TFPI) gene are associated with free plasma TFPI levels or with TFPI activity as well as the risk of ischaemic stroke in stroke patients and control individuals. We conducted a case-control study of 162 first-ever ischaemic stroke cases and 170 randomly selected community control individuals. The TFPI genotype was determined for the T-287C, C-399T, Intron 7 C-33T, and Val264Met (G874A) polymorphisms. Free plasma TFPI and TFPI activity were measured during the first 7 days and 3-6 months after the acute stroke event. Free plasma TFPI levels were significantly lowered 3-6 months after stroke compared with levels observed in the patient group during the acute phase of the stroke (mean, 16.3 versus 22.46 ng/ml; P = 0.046) and among the control group (mean, 16.3 versus 22.79 ng/ml; P < 0.0001). Conversely, TFPI activity was significantly up-regulated during the acute phase (mean, 1.30 versus 1.11 U/ml; P = 0.0051) and remained elevated 3-6 months later (mean, 1.28 versus 1.11 U/ml; P = 0.03). The TFPI gene polymorphisms studied were not significantly associated with TFPI levels or activity, nor with the risk of ischaemic stroke. In conclusion, the TFPI activity and concentration in plasma varied significantly after an ischaemic stroke; however, these variations were not found to be due to the presence of any of the genetic mutations analysed in this study. Our results are consistent with the emerging model suggesting the lipoprotein-bound portion of TFPI has a significant influence on coagulation and diseases of haemostasis.

TRPV1 Channels in Immune Cells and Hematological Malignancies.

Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation. In contrast, TRPV1 (and other TRP channels) appears to be required for T-cell receptor activation by mitogens. Additionally, studies in cell lines derived from hematological and other malignancies suggest altered expression/function of TRPV1 might serve as a target for novel cytotoxic therapies.