12 research outputs found
Pharmacological Aspects of Vipera xantina palestinae Venom
In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integrin inhibitors. Viperistatin, a α1β1selective KTS disintegrin and VP12, a α2β1 selective C-type lectin were discovered. These snake venom proteins represent promising tools for research and development of novel collagen receptor selective drugs. These discoveries are also relevant for future improvement of antivenom therapy towards V.x.p. envenomation
Holography, Unfolding and Higher-Spin Theory
Holographic duality is argued to relate classes of models that have
equivalent unfolded formulation, hence exhibiting different space-time
visualizations for the same theory. This general phenomenon is illustrated by
the higher-spin gauge theory shown to be dual to the theory of 3d
conformal currents of all spins interacting with 3d conformal higher-spin
fields of Chern-Simons type. Generally, the resulting 3d boundary conformal
theory is nonlinear, providing an interacting version of the 3d boundary sigma
model conjectured by Klebanov and Polyakov to be dual to the HS theory
in the large limit. Being a gauge theory it escapes the conditions of the
theorem of Maldacena and Zhiboedov, which force a 3d boundary conformal theory
to be free. Two reductions of particular higher-spin gauge theories where
boundary higher-spin gauge fields decouple from the currents and which have
free boundary duals are identified. Higher-spin holographic duality is also
discussed for the cases of and duality between higher-spin
theories and nonrelativistic quantum mechanics. In the latter case it is shown
in particular that () geometry in the higher-spin setup is dual to
the (inverted) harmonic potential in the quantum-mechanical setup.Comment: 57 pages, V2: Acknowledgements, references, comments, clarifications
and new section on reductions of particular HS theories associated with free
boundary theories are added. Typos corrected, V3. Minor corrections:
clarification in section 9 is added and typos correcte
The neutralization mechanism of vipera palaestinae neurotoxin by a purified factor from homologous serum
In vivo interactions between neurotoxin, cardiotoxin and phospholipases A2 isolated from Malayan cobra (Naja Naja Sputatrix) venom
Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease.
BACKGROUND
Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD.
AIMS
To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review.
METHODS
A comprehensive search was conducted across multiple databases. Two independent authors selected the articles and assessed bias using the Newcastle-Ottawa Scale. Data were pooled for analysis, where comparable outcomes were reported.
RESULTS
Thirty-five studies were identified related to disease progression and 12 for the treatment of AATD. Seven per cent of children were reported to develop liver cirrhosis, with 16.5% of individuals presenting in childhood requiring liver transplantation. Of those surviving to adulthood, 10.5% had liver cirrhosis and 14.7% required transplantation. Liver transplantation was the only effective treatment reported and outcomes compare favourably to other indications, with 5-year survival reported as over 90% in children and over 80% in adults.
DISCUSSION
The clinical course of liver disease in individuals with AATD remains poorly understood, but affects about 10% of those with AATD. More research is required to identify those patients at risk of developing liver disease at an early stage, and to provide alternative treatments to liver transplantation
α1-Antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies
α1-Antitrypsin is the prototypical member of the serine proteinase inhibitor or serpin superfamily of proteins. The family includes α1-antichymotrypsin, C1 inhibitor, antithrombin and neuroserpin, which are all linked by a common molecular structure and the same suicidal mechanism for inhibiting their target enzymes. Point mutations result in an aberrant conformational transition and the formation of polymers that are retained within the cell of synthesis. The intracellular accumulation of polymers of mutant α1-antitrypsin and neuroserpin results in a toxic gain-of-function phenotype associated with cirrhosis and dementia respectively. The lack of important inhibitors results in overactivity of proteolytic cascades and diseases such as COPD (chronic obstructive pulmonary disease) (α1-antitrypsin and α1-antichymotrypsin), thrombosis (antithrombin) and angio-oedema (C1 inhibitor). We have grouped these conditions that share the same underlying disease mechanism together as the serpinopathies. In the present review, the molecular and pathophysiological basis of α1-antitrypsin deficiency and other serpinopathies are considered, and we show how understanding this unusual mechanism of disease has resulted in the development of novel therapeutic strategies