Hypercoagulability in patients with haematological neoplasia: no apparent initiation by tissue factor

Patients with haematological malignancies carry increased risk of venous thrombosis (VT). However, the mechanisms that link these malignancies to activated coagulation have not been fully identified. Since anti-haemostatic agents are studied in clinical trials for their potential to prolong survival in cancer patients, a detailed characterisation of haemostatic markers in cancer subtypes is needed. Hence, in this study, we measured the plasma concentrations and mRNA expression in blood mononuclear cells of haemostatic parameters in 93 patients with haematological neoplasias (acute myeloid leukaemia, chronic lymphatic leukaemia, multiple myeloma, and non-Hodgkin's lymphoma) before start and after completion of cancer therapy. At diagnosis we found activation of coagulation and fibrinolysis, especially in patients with acute myeloid leukaemia. This hypercoagulation was not associated with increased levels of tissue factor (TF) or factor VII (fVII) antigen or mRNA, or levels of activated fVII. In conclusion we found a hypercoagulable state in patients with haematological malignancy that did not seem to be initiated by TF.     

Up-regulation of platelet-derived growth factor by peripheral-blood leukocytes during experimental allergic encephalomyelitis

In multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), clinical disease is associated with infiltration of the central nervous system (CNS) by immune cells. Subsequent remission with remyelination has been linked to an increased occurrence of oligodendrocyte progenitor (O2A) cells. Platelet-derived growth factor (PDGF) and fibroblast growth factor-2 (FGF-2) are key growth factors for O2A cells, yet little is known about their relevance in EAE and MS. We analyzed the expression of PDGF, FGF-2, and their receptors by peripheral-blood leukocytes (PBLs) and lymphocyte subsets during MBP-induced EAE. Strong up-regulation of PDGF, but not FGF-2, was observed in PBLs, with the highest expression after the disease maximum. T, NK, and NKT cells expressed PDGF, which is a novel observation because thus far only monocytes/macrophages have been reported to express PDGF. These results extend the idea that growth factors may contribute to improved CNS tissue repair, including PDGF, which is secreted by lesion-homing immune cells. The production of PDGF by lymphocytes may have potential therapeutic value when activating or modulating T-cell responses in demyelinating diseases.     

p11 (S100A10)--an inducible adaptor protein that modulates neuronal functions

p11 (S100A10) is a member of the S100 protein family and forms a heterotetrameric complex with annexin 2. p11 has also been found to interact with a diverse set of proteins that includes several ion channels and the serotonin 5-HT1B receptor. Several factors such as dexamethasone, growth factors, nitric oxide and antidepressant therapies regulate the expression of p11. Furthermore, studies using mutant mouse models, RNA interference and antisense constructs have implicated p11 in several biological processes; in particular, there is evidence that p11 is involved in the pathophysiology underlying nociception and depression-like states.     

Stimulation of tendon repair: mechanical loading,GDFs and platelets. A mini-review

The repair of subcutaneous tendon ruptures can be stimulated by a single application of one of several growth factors [e.g. platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMPs) like growth differentiation factor (GDF)-5, -6, -7] or by a thrombocyte concentrate (PRP). The response to these measures is dependent on the mechanical microenvironment, which is crucial for repair. So far, almost all research has been limited to rodent models, mostly using the rat Achilles tendon. Ruptured human Achilles tendons appear to be mechanically loaded in spite of immobilisation. This suggests that the mechanical microenvironment might be favourable for the clinical use of growth factors or platelets for this indication. New methods to quantitate human Achilles tendon repair have been developed.

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Résumé La réparation de rupture tendineuse sous cutanée peut être améliorée par une simple application d’un ou de plusieurs facteurs de croissance (PDGF, TGF-beta, IGF-1, VEGF, BMPs, GDF like -5, -6, -7) ou par un concentré de plaquettes (PRP). Ce modèle a surtout été utilisé, au niveau du tendon d’Achille des rats. Cette étude nous montre que le micro environnement mécanique peut être amélioré par l’utilisation de facteurs de croissance et de concentrés de plaquettes. De nouvelles méthodes permettant de quantifier l’importance de la réparation du tendon d’Achille humain ont été développées.

     

Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness

We here report a series of derivatives describing the structure-activity relationship around liraglutide, a once-daily human glucagon-like peptide-1 fatty acid derivative, with respect to potency as well as protraction in vivo. The spacer region between the fatty acid and the peptide is mostly important for potency, whereas the fatty acid or fatty acid mimetic is important for both potency and protraction. The length of the fatty acid is the most important parameter for protraction.     

Protein S100B after cardiac surgery: an indicator of long-term anxiety?

OBJECTIVES: The aim of the study was to assess long-term state and trait anxiety in cardiac surgical risk patients. DESIGN: Thirty two patients with serum S100B>0.3 microg/l 48 hours after cardiac surgery with cardiopulmonary bypass were matched according to age, gender, type, date and length of surgery with 35 operated patients without elevated S100B. They completed Spielberger's Anxiety Inventory (STAI). RESULTS: Patients with elevated S100B reported more state anxiety and trait anxiety. S100B was an independent predictor of both state and trait anxiety when controlling for perioperative variables. CONCLUSIONS: Patients with elevated S100B reported more anxiety 3-6 years after cardiac surgery. A postoperative blood sample can identify risk patients and facilitate appropriate follow-up.