Mechanical characterisation of commercial artificial skin models.

Understanding of the mechanical properties of skin is crucial in evaluating the performance of skin-interfacing medical devices. Artificial skin models (ASMs) have rapidly gained attention as they are able to overcome the challenges in ethically sourcing consistent and representative ex vivo animal or human tissue models. Although some ASMs have become commercialised, a thorough understanding of the mechanical properties of the skin models is crucial to ensure that they are suitable for the purpose of the study.

Influence of Surface Texturing on the Dry Tribological Properties of Polymers in Medical Devices.

There is a constant need to improve patient comfort and product performance associated with the use of medical devices. Efforts to optimise the tribological characteristics of medical devices usually involve modifying existing devices without compromising their main design features and functionality. This article constitutes a state-of-the-art review of the influence of dry friction on polymeric components used in medical devices, including those having microscale surface features.

Heparins: A Shift of Paradigm.

Heparins inhibit the thrombin forming capacity of plasma, i. e., the endogenous thrombin potential (ETP), by their anti-thrombin (aIIa) activity, the anti-factor Xa (aXa) activity is of minimal importance.

Separation of blood microsamples by exploiting sedimentation at the microscale.

Microsample analysis is highly beneficial in blood-based testing where cutting-edge bioanalytical technologies enable the analysis of volumes down to a few tens of microliters. Despite the availability of analytical methods, the difficulty in obtaining high-quality and standardized microsamples at the point of collection remains a major limitation of the process. Here, we detail and model a blood separation principle which exploits discrete viscosity differences caused by blood particle sedimentation in a laminar flow.

The surface tells it all: relationship between volume and surface fraction of liquid dispersions.

The properties of liquid dispersions, such as foams or emulsions, depend strongly on the volume fraction ϕ of the continuous phase. Concentrating on the example of foams, we show experimentally and theoretically that ϕ may be related to the fraction ϕ of the surface at a wall which is wetted by the continuous phase - given an expression for the interfacial energy or osmotic pressure of the bulk system. Since the surface fraction ϕ can be readily determined from optical measurement and since there are good general approximations available for interfacial energy and osmotic pressure we thus arrive at an advantageous method of estimating ϕ.

Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs).

Objectives: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines.

Background: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes.

Water vapour and heat combine to elicit biting and biting persistence in tsetse.

Background: Tsetse flies are obligatory blood feeders, accessing capillaries by piercing the skin of their hosts with the haustellum to suck blood. However, this behaviour presents a considerable risk as landing flies are exposed to predators as well as the host's own defense reactions such as tail flicking. Achieving a successful blood meal within the shortest time span is therefore at a premium in tsetse, so feeding until replete normally lasts less than a minute.

Effect of CYP2C19*2 and *17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications.

The present study was performed to compare the influence of cytochrome P459 2C19 (CYP2C19) *2 and *17 genetic variants on the platelet response to clopidogrel and prasugrel maintenance therapy and to assess the relation between platelet reactivity and bleeding complications. A total of 730 patients were included (517 patients treated with clopidogrel 150 mg/day and 213 discharged with prasugrel 10 mg). Platelet reactivity was assessed at 1 month with the platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP).

CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome.

Objectives: The present study was designed to assess the effect of genetic variants on chronic biological response to prasugrel and bleeding complications.

Background: CYP2C19*2 loss-of-function allele and CYP2C19*17 gain-of-function allele have been linked with response to clopidogrel, but preliminary data did not show any significant influence of these alleles on prasugrel effect.

Methods: A total of 213 patients undergoing successful coronary stenting for acute coronary syndrome and discharged with prasugrel 10 mg daily were included.

Platelet reactivity in diabetic patients undergoing coronary stenting for acute coronary syndrome treated with clopidogrel loading dose followed by prasugrel maintenance therapy.

Background: Diabetes has been identified as a risk factor for impaired clopidogrel response, and these patients might have greater benefit with new P2Y12 blockers such as prasugrel. The present study was designed to assess response to thienopyridine in diabetic patients undergoing PCI for ACS.

Methods And Results: 107 diabetic patients undergoing PCI for ACS were included and treated by clopidogrel 600 mg loading dose and switched to prasugrel 10mg daily after PCI.

An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development.

Epileptic encephalopathies comprise a heterogeneous group of severe infantile disorders for which the pathophysiological basis of epilepsy is inaccurately clarified by genotype-phenotype analysis. Because a deficit of GABA neurons has been found in some of these syndromes, notably in patients with X-linked lissencephaly with abnormal genitalia, epilepsy was suggested to result from an imbalance in GABAergic inhibition, and the notion of "interneuronopathy" was proposed. Here, we studied the impact of a polyalanine expansion of aristaless-related homeobox (ARX) gene, a mutation notably found in West and Ohtahara syndromes.

Cell-autonomous and cell-to-cell signalling events in normal and altered neuronal migration.

The cerebral cortex is a complex six-layered structure that contains an important diversity of neurons, and has rich local and extrinsic connectivity. Among the mechanisms governing the cerebral cortex construction, neuronal migration is perhaps the most crucial as it ensures the timely formation of specific and selective neuronal circuits. Here, we review the main extrinsic and extrinsic factors involved in regulating neuronal migration in the cortex and describe some environmental factors interfering with their actions.

A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A.

Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown.

Thrombin-generating capacity in patients with von Willebrand's disease.

Background And Objectives: on Willebrand's disease (VWD) is the most common hereditary bleeding disorder. Its severity can be classified on the basis of von Willebrand factor (VWF) and factor VIII (FVIII) plasma levels and according to the clinical relevance of bleeding episodes. However, patients with very low VWF activity may exhibit a mild bleeding tendency.

Linear diffusion of thrombin and factor Xa along the heparin molecule explains the effects of extended heparin chain lengths.

Question: How does the size of the heparin moiety in the anti-thrombin (AT)-heparin complex influence its anticoagulant properties?

Approach: Of 52 heparin fractions of precise Mr between 2800 and 37,000 we determined the dissociation constant (Kd) of the binding of the enzyme to the AT-heparin complex and the decay constant (kdec) of thrombin and factor Xa at 1 microM of that complex.

Results: The Kd of thrombin or factor Xa is constant when expressed in terms of the concentration of sugar units, i.e.

Thrombin generation, a function test of the haemostatic-thrombotic system.

By the use of a fluorogenic thrombin substrate and continuous calibration of each individual sample, it is now possible to obtain a thrombin generation (TG) curve (or thrombogram) in plasma, with or without platelets, in an easy routine procedure at high throughput and with an acceptable experimental error (<5%). Evidence is growing that the parameters of the thrombogram, and notably the area under the curve (endogenous thrombin potential, ETP), are useful in assessing bleeding- or thrombotic risk and its modification by antithrombotic- or haemostatic treatment. Available data strongly suggest that conditions (congenital, acquired, drug-induced) that increase TG all cause a thrombotic tendency and that conditions that decrease TG prevent thrombosis but, beyond a limit, cause bleeding.

Protocols for optimizing MS/MS parameters with an ion-trap GC-MS instrument.

The product ion spectrum allows us to achieve very selective detection of pesticides and to eliminate the ambiguities caused by more conventional analytical approaches. Owing to the enhanced capabilities of GC/MS/MS for multiresidue pesticides, the development of a GC/MS/MS pesticides library will be useful. The aim of this study was to develop a sensitive and specific analytical method for the identification and quantification of compounds without the need of a time-consuming procedure.

Low molecular weight activated protein C inhibitors as a potential treatment for hemophilic disorders.

The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin.

New approaches for measuring coagulation.

Although specific assays of coagulation factors are essential for diagnostic purposes they only give partial information about an individual's haemostatic state. This can be better assessed by various global tests, and recent developments and evaluations of five such tests are described in this symposium: the PFA-100; waveform analysis; thrombin generation; overall haemostasis potential; thrombelastography. Each test has advantages in various applications, but the thrombin generation test and waveform analysis have been found most useful in haemophilia, whilst the PFA-100 is helpful in von Willebrand's disease.

Fixed dosage of low-molecular-weight heparins causes large individual variation in coagulability, only partly correlated to body weight.

Background: Low-molecular-weight heparins (LMWHs) are routinely given without the control of their effect on coagulation. The endogenous thrombin potential (ETP) is a sensitive detector of the heparin effect.

Question: What is the interindividual variation in TG after a fixed dose of LMWH in normal volunteers, is it explained by variation in weight?

Methods: Subcutaneous (s.