Induction of retinopathy by fibrillar oxalate assemblies

AbstractThe formation of metabolite fibrillar assemblies represents a paradigm shift in the study of human metabolic disorders. Yet, direct clinical relevance has been attributed only to metabolite crystals. A notable example for metabolite crystallization is calcium oxalate crystals observed in various diseases, including primary hyperoxaluria. We unexpectedly observed retinal damage among young hyperoxaluria patients in the absence of crystals. Exploring the possible formation of alternative supramolecular organizations and their biological role, here we show that oxalate can form ordered fibrils with no associated calcium. These fibrils inflict intense retinal cytotoxicity in cultured cells. A rat model injected with oxalate fibrils recaptures patterns of retinal dysfunction observed in patients. Antibodies purified from hyperoxaluria patient sera recognize oxalate fibrils regardless of the presence of calcium. These findings highlight a new molecular basis for oxalate-associated disease, and to our knowledge provide the first direct clinical indication for the pathogenic role of metabolite fibrillar assemblies.

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Mechanism of action of β2-glycoprotein I-dependent lupus anticoagulants

Lupus ◽

10.1177/096120339800700206 ◽

1998 ◽

Vol 7 (2_suppl) ◽

pp. 23-28 ◽

Cited By ~ 15

Author(s):

J Amout ◽

J Vermylen

Keyword(s):

Mechanism Of Action ◽

Molecular Basis ◽

Current Knowledge ◽

Indirect Evidence ◽

Integrated Model ◽

Anticardiolipin Antibodies ◽

Pathogenic Role ◽

Lupus Anticoagulants ◽

Glycoprotein I

There is accumulating evidence showing that lupus anticoagulants (LA) are more strongly associated with thrombosis than anticardiolipin antibodies. In addition, indirect evidence has been presented indicating that β2GPI-dependent LA are more strongly associated with thrombosis than prothrombin-dependent LA. From this, one may assume that anti-β2GPl antibodies with LA activity are more pathogenic than anti-β2GPI antibodies without LA activity. Therefore, it is of the utmost importance to understand the molecular basis on which some anti-β2GPI antibodies behave as LA. In this presentation, the current knowledge on the interaction of β2GPI with phospholipids and with anti-β2GPI antibodies is reviewed and an integrated model for the anti-β2GPI - dependent LA activity is proposed with implications for a pathogenic role of these particular antibodies.

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Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

Therapieforum Transplant ◽

10.1055/a-0711-9047 ◽

2016 ◽

Vol 04 (01) ◽

pp. 4-10

Keyword(s):

Lower Incidence ◽

Paradigm Shift ◽

Mtor Inhibitor ◽

De Novo ◽

Expert Panel ◽

Risk Of Infection ◽

Cmv Infection ◽

Expert Meeting ◽

Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

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The pathogenic role of surfactant protein B in formation of bronchopulmonary pathology in children

SOVREMENNAYA PEDIATRIYA ◽

10.15574/sp.2017.84.66 ◽

2017 ◽

pp. 66-71

Author(s):

O. Yablon ◽

◽

N. Zaichko ◽

O. Mazulov ◽

Z.I. Rossokha ◽

...

Keyword(s):

Surfactant Protein ◽

Pathogenic Role ◽

Surfactant Protein B ◽

Protein B

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E-Projects Challenges in India – Role of Human Resource Management and Technology

International Journal of Emerging Research in Management and Technology ◽

10.23956/ijermt.v6i8.149 ◽

2018 ◽

Vol 6 (8) ◽

pp. 263

Author(s):

Ramnik Kaur

Keyword(s):

Developing Countries ◽

Public Administration ◽

Paradigm Shift ◽

Successful Implementation ◽

The Public ◽

Government Services ◽

The Past ◽

The Government ◽

Traditional Approaches

E-governance is a paradigm shift over the traditional approaches in Public Administration which means rendering of government services and information to the public by using electronic means. In the past decades, service quality and responsiveness of the government towards the citizens were least important but with the approach of E-Government the government activities are now well dealt. This paper withdraws experiences from various studies from different countries and projects facing similar challenges which need to be consigned for the successful implementation of e-governance projects. Developing countries like India face poverty and illiteracy as a major obstacle in any form of development which makes it difficult for its government to provide e-services to its people conveniently and fast. It also suggests few suggestions to cope up with the challenges faced while implementing e-projects in India.

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