Growth Differentiation Factor 15 and Matrix Metalloproteinase 3 in Plasma as Biomarkers for Neuropathy and Nephropathy in Type 1 Diabetes.

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy.

Systemic biomarkers of microvascular alterations in type 1 diabetes associated neuropathy and nephropathy - A prospective long-term follow-up study.

Introduction: This study aimed to investigate circulating biomarkers associated with the risk of developing diabetic peripheral neuropathy (DPN) and nephropathy in type 1 diabetes (T1D).

Materials And Methods: Patients with childhood-onset T1D (n = 49, age 38.3 ± 3.

Platelet adhesion in type 2 diabetes: impact of plasma albumin and mean platelet volume.

Background: Altered mean platelet volume (MPV) and plasma albumin has been reported in type 2 diabetes (T2D). MPV is suggested to predict cardiovascular risk but there is a lack of evidence for associations between MPV and platelet adhesion. Plasma albumin and magnesium are other factors reported to influence thrombotic risk.

Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy.

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.

Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro.

Cigarette smoking is a leading cause of cardiovascular disease. The cardiovascular effects of smoking are probably multifactorial, including effects on platelets. Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent.

In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation.

Background: Although several studies show that there is an increased risk of bleeding events during antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs), few studies show direct effects in vitro of SSRIs on hemostasis.

Methods: This study was undertaken to investigate the effects on platelet adhesion and plasma coagulation (APTT and PT) of two common SSRIs, citalopram and sertraline, the selective noradrenaline reuptake inhibitor reboxetine, and the serotonin and noradrenaline reuptake inhibitor venlafaxine.

Results: None of the compounds affected plasma coagulation significantly but all compounds except for venlafaxine inhibited platelet adhesion by approximately 50% or more at the highest concentration (100 μg/l, p < 0.

Nanomolar concentrations of adrenaline induce platelet adhesion in vitro.

Adrenaline is a platelet activator having a resting plasma concentration of <1 nmol/l that increases to a few nmol/l during stress. However, most in vitro assays only detect effects of adrenaline in micromolar concentrations. This makes it difficult to estimate the relevance of in vitro data for the in vivo situation.

Enhanced platelet adhesion in essential thrombocythemia after in vitro activation.

Objective: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by elevated platelet counts and increased risk of thrombosis. Ex vivo data suggest increased platelet reactivity in agreement with the increased thrombosis risk, while in vitro tests often detect decreased platelet activity. The present study aimed to investigate adhesion of ET-platelets in vitro, which is an aspect of platelet function that has been addressed in only a few studies on ET patients.

Characterization of static adhesion of human platelets in plasma to protein surfaces in microplates.

Platelet adhesion is a complex and important event for prevention of blood loss after vessel injury. This study investigated fundamental adhesive mechanisms occurring in an in-vitro assay developed for the measurement of static adhesion of human platelets in plasma. The aim was to gain methodological knowledge that could be used for interpretations of results from other studies using this specific assay.

Similar inhibition of platelet adhesion, P-selectin expression and plasma coagulation by ioversol, iodixanol and ioxaglate.

Contrast media (CM) are reported to possess both prothrombotic and anticoagulant properties. The mechanisms are not clearly understood, and early reports are contradictory. To study the effects of CM on haemostasis, we analysed the ex vivo effects of ioversol and iodixanol on platelet adhesion and P-selectin expression, and the in vitro effects of ioversol, iodixanol and ioxaglate on platelet adhesion, P-selectin expression and plasma coagulation.

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study.

Background: Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays.

In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation.

1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis.

Weak relationship between ionized and total magnesium in serum of patients requiring magnesium status.

Measurement and monitoring of magnesium (Mg) are important to prevent the development of serious and potentially fatal complications in critically ill patients. Although ion-selective electrodes are available and earlier reports suggest that free ionized magnesium (iMg2+) is the most useful test to estimate Mg status, most clinical laboratories still only measure total Mg. To compare the relationship among iMg2+, total Mg, and albumin in serum, samples were collected from 48 consecutive patients admitted to an intensive care unit or a primary health center.

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates.

Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males.

Aim: To observe if the total amount of platelet P-selectin (tP-selectin) in patients with inflammatory bowel disease (IBD) was related to disease entity or activity, 5-aminosalicylic acid (5-ASA) medication or gender.

Methods: tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls.

Results: Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication.

Measurement of adhesion of human platelets in plasma to protein surfaces in microplates.

Introduction: Platelet adhesion is an initial, crucial and complex event for inhibiting blood loss upon vascular injury. Activation and adhesion of platelets also play a fundamental role in the development of thrombosis. A combination of exposed extracellular matrix proteins in the vascular wall and release of activating compounds from the participating cells activate the platelets.

Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in platelets.

We examined the interplay between adenosine and the nitric oxide (NO)-containing oxatriazole derivative GEA 3175 in human platelets. The importance of cyclic guanosine 3'5'-monophosphate (cGMP)-inhibited phosphodiesterases (PDEs) was elucidated by treating the platelets with adenosine combined with either GEA 3175 or the PDE3-inhibitor milrinone. The drug combinations provoked similar cyclic adenosine 3'5'-monophosphate (cAMP) responses.

CTC-11 (Teijin).

Teijin and Chemo-Sero are codeveloping CTC-111 as a treatment for disseminated intravascular coagulation (DIC) due to protein C deficiency. The drug was launched for the treatment of protein C deficiency in Japan on January 31, 2001 and as of October 2001 was awaiting approval for the treatment of DIC, also in Japan [426762]. CTC-111 was evaluated in a multicenter pharmacokinetic trial in venous thrombosis patients with inherited protein C deficiency.

Comparison of plasma levels of cytokines and in vitro generation of reactive oxygen species after nicotine infusion in nicotine users with normal and impaired renal function.

Several in vitro and animal studies suggest effects of nicotine on the immune system, but little evidence exists regarding the in vivo immunomodulation of nicotine in humans. The increased use of nicotine replacement therapy to aid smoking cessation claims further understanding of how nicotine affects blood leukocytes. This is of particular importance when nicotine therapy is used in diseases associated with alterations of the immune system, such as chronic renal failure.

Divalent cations and the protein surface co-ordinate the intensity of human platelet adhesion and P-selectin surface expression.

At sites of blood vessel injury, platelets adhere to exposed vessel components, such as collagen, or immobilized fibrinogen derived from plasma or activated platelets. The divalent cations Mg(2+) and Ca(2+) are essential for platelet adhesion and activation, but Mg(2+) can also inhibit platelet activation. The present study evaluates, by an enzymatic method, the effects of various divalent cations on the adhesion of isolated human platelets to collagen, fibrinogen, albumin or plastic in vitro.

Pexelizumab Alexion.

Alexion and Procter & Gamble (P&G) are developing pexelizumab (h5G1.1-SC), a short-acting, recombinant complement C5 inhibitor for the potential treatment of complications of cardiovascular surgery, such as complement activation during cardiopulmonary bypass (CPB) procedures, for which it has completed phase II trials [275707]. By November 2001, the companies were also conducting two phase II trials for the treatment of acute myocardial infarction (MI) and by March 2002, patient accrual in the first of these MI trials (COMPLY) had been completed [429171], [443067].

Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease.

Objective And Design: P-selectin, a membrane glycoprotein which is expressed on activated platelets and endothelial cells, plays a crucial role in the inflammatory response. The main action is adhesion of leukocytes, facilitation of diapedesis and induction of cytokine production from monocytes (MCP-1 and IL-8), mediated via RANTES released from activated platelets. An abnormal platelet activity has been reported in patients with ulcerative colitis (UC) and Crohn's disease (CD), jointly referred to as inflammatory bowel disease (IBD), which could have an aggravating influence on the inflammatory response.

Nitric oxide donors and angiotensin-converting enzyme inhibitors act in concert to inhibit human angiotensin-converting enzyme activity and platelet aggregation in vitro.

This study investigates the effects of exogenous and endogenous nitric oxide (NO) on human circulating and endothelial angiotensin-converting enzyme activity and platelet aggregation. The NO donor S-nitroso-N-acetylpenicillamine (10(-8)-10(-6) M) significantly and dose-dependently inhibited serum angiotensin-converting enzyme activity. The concomitant addition of S-nitroso-N-acetylpenicillamine to angiotensin-converting enzyme inhibitor-treated (captopril or enalaprilat) serum, further reduced angiotensin-converting enzyme activity.

Acute effects of nicotine infusion on platelets in nicotine users with normal and impaired renal function.

The role of platelets in cardiovascular disease associated with smoking is becoming more established, but the effects of nicotine on platelets are unclear. Nicotine therapy is used for smoking cessation in both health and disease. Consequently, the effects of nicotine on platelets are of particular significance in disorders such as renal disease, which is associated with defective platelet function, increased cardiovascular morbidity, and altered nicotine metabolism.

Platelets enhance neutrophil locomotion: evidence for a role of P-selectin.

It has been suggested that the accumulation of platelets at sites of vascular damage and inflammation regulates the function of leukocytes. In this study, we investigated the effects of platelets on the transmigration of neutrophil granulocytes through microporous membranes. We demonstrate that platelets markedly enhance both the random and the chemotactic migration of neutrophils.