Recombinant human C1 esterase inhibitor (Conestat alfa) for prophylaxis to prevent attacks in adult and adolescent patients with hereditary angioedema

Introduction: Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is a debilitating and potentially lethal disease. Management includes on-demand treatment of angioedema and their prophylaxis. Plasma derived C1-INH is an established treatment for both on demand and prophylaxis of HAE. Conestat alfa is a recombinant form of human C1-INH (rhC1-INH) produced in transgenic rabbits. It has granted drug\u2019s registration as treatment option for acute HAE attacks in adults and adolescents in Europe, America, and other countries. Long-term prophylaxis with rhC1-INH received recent consideration in clinical trials. Areas covered: This review will critically appraise available information about rhC1-INH (conestat alfa) prophylactic treatment in adult and adolescent patients with congenital C1-INH deficiency. Results from a phase II randomized placebo-controlled trial for prophylaxis of severe HAE evidenced positive treatment outcomes for its application, both twice or once weekly. Expert commentary: Phase II clinical studies suggest that rhC1-INH is a viable option for prophylaxis of HAE. Safety and tolerability data are comparable to other available HAE specific drugs, zeroing the possibility for blood-born viral transmission. Sustainability of modern technologies is granting a practically stable and continuous recombinant production process. With other available options, rhC1-INH facilitates tailoring HAE treatment to patients\u2019 needs

Characterisation of Hybrid Pixel Detectors with capacitive charge division

In order to fully exploit the physics potential of the future high energy e+ e- linear collider, a Vertex Tracker providing high resolution track reconstruction is required. Hybrid pixel sensors are an attractive technology due to their fast read-out capabilities and radiation hardness. A novel pixel detector layout with interleaved cells between the readout nodes has been developed to improve the single point resolution. The results of the characterisation of the first processed prototypes are reported.Comment: 5 pages, 2 figures, presented at LCWS2000, Linear Collider Workshop, October 24-28 2000, Fermi National Accelerator Laboratory, Batavia, Illinois, U.S.A. Proceedings to be published by the American Institute of Physic

Hybrid Pixel Detector Development for the Linear Collider Vertex Tracker

In order to fully exploit the physics potential of the future high energy e+e- linear collider, a Vertex Tracker able to provide particle track extrapolation with very high resolution is needed. Hybrid Si pixel sensors are an attractive technology due to their fast read-out capabilities and radiation hardness. A novel pixel detector layout with interleaved cells has been developed to improve the single point resolution. Results of the characterisation of the first processed prototypes by electrostatic measurements and charge collection studies are discussed.Comment: 5 pages, 1 figure, to appear in the Proceedings of the 9th Int. Workshop on Vertex Detectors, Lake Michigan MI (USA), September~200

A Pixel Vertex Tracker for the TESLA Detector

In order to fully exploit the physics potential of a e+e- linear collider, such as TESLA, a Vertex Tracker providing high resolution track reconstruction is required. Hybrid Silicon pixel sensors are an attractive sensor technology option due to their read-out speed and radiation hardness, favoured in the high rate TESLA environment, but have been so far limited by the achievable single point space resolution. A novel layout of pixel detectors with interleaved cells to improve their spatial resolution is introduced and the results of the characterisation of a first set of test structures are discussed. In this note, a conceptual design of the TESLA Vertex Tracker, based on hybrid pixel sensors is presentedComment: 20 pages, 11 figure

The central role of endothelium in hereditary angioedema due to C1 inhibitor deficiency

An impairment of the endothelial barrier function underlies a wide spectrum of pathological conditions. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) can be considered the \u201cpathophysiological and clinical paradigm\u201d of Paroxysmal Permeability Diseases (PPDs), conditions characterized by recurrent transient primitively functional alteration of the endothelial sieving properties, not due to inflammatory-ischemic-degenerative injury and completely reversible after the acute flare. It is a rare yet probably still underdiagnosed disease which presents with localized, non-pitting swelling of the skin and submucosal tissues of the upper respiratory and gastrointestinal tracts, without significant wheals or pruritus. The present review addresses the pathophysiology of C1-INH-HAE with a focus on the crucial role of the endothelium during contact and kallikrein/kinin system (CAS and KKS) activation, currently available and emerging biomarkers, methods applied to get new insights into the mechanisms underlying the disease (2D, 3D and in vivo systems), new promising investigation techniques (autonomic nervous system analysis, capillaroscopy, flow-mediated dilation method, non-invasive finger plethysmography). Hints are given to the binding of C1-INH to endothelial cells. Finally, crucial issues as the local vs systemic nature of CAS/KKS activation, the episodic nature of attacks vs constant C1-INH deficiency, pros and cons as well as future perspectives of available methodologies are briefly discussed

Transgenic plants expressing immunosuppressive dsRNA improve entomopathogen efficacy against Spodoptera littoralis larvae

Transgenic plants that express double-stranded RNA (dsRNA) targeting vital insect genes have recently emerged as a valuable new tool for pest control. In this study, tobacco plants were transformed to produce dsRNA targeting Sl 102 gene that is involved in the immune response of Spodoptera littoralis larvae, a serious lepidopteran pest of several crops. Experimental larvae reared on transgenic tobacco lines showed (1) a strongly reduced level of Sl 102 transcripts, which was positively associated with food consumption; (2) a substantial impairment of the encapsulation response mediated by hemocytes; and (3) a marked increase in the susceptibility to Xentari™, a Bacillus thuringiensis-based insecticide. Importantly, this approach may allow a reduction in the doses of B. thuringiensis used for field applications and enhance its killing activity on mature larvae. The results obtained thus support the use of immunosuppressive RNAi plants to enhance the performance of microbial insecticides on lepidopteran larvae

Enhancement of Bacillus thuringiensis toxicity by feeding Spodoptera littoralis larvae with bacteria expressing immune suppressive dsRNA

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High resolution pixel detectors for e+e- linear colliders

The physics goals at the future e+e- linear collider require high performance vertexing and impact parameter resolution. Two possible technologies for the vertex detector of an experimental apparatus are outlined in the paper: an evolution of the Hybrid Pixel Sensors already used in high energy physics experiments and a new detector concept based on the monolithic CMOS sensors.Comment: 8 pages, to appear on the Proceedings of the International Workshop on Linear Colliders LCWS99, Sitges (Spain), April 28 - May 5, 199

Hybrid pixel detector development for the Linear collider Vertex Detector

In order to fully exploit the Physics potential of future e+ e- linear collider, a Vertex Detector providing high resolution track reconstruction is required. Hybrid Silicon pixel detectors are an attractive option for the sensor technology due to their read-out speed and radiation hardness but have been so far limited by the achievable single point resolution. A novel layout of hybrid pixel sensor with interleaved cells to improve the spatial resolution has been developed. The characterisation of the first processed prototypes is reported.Comment: 5 pages, 5 figures. Presented at the IEEE Nuclear Science Symposium and Medical Imaging Conference, October 15-20 2000, Lyon, Franc