The effects of dyslipidaemia and cholesterol modulation on erythrocyte susceptibility to malaria parasite infection

Abstract: Background: Malaria disease commences when blood-stage parasites, called merozoites, invade human erythrocytes. Whilst the process of invasion is traditionally seen as being entirely merozoite-driven, emerging data suggests erythrocyte biophysical properties markedly influence invasion. Cholesterol is a major determinant of cell membrane biophysical properties demanding its interrogation as a potential mediator of resistance to merozoite invasion of the erythrocyte. Methods: Biophysical measurements of erythrocyte deformability by flicker spectroscopy were used to assess changes in erythrocyte bending modulus on forced integration of cholesterol and how these artificial changes affect invasion by human Plasmodium falciparum merozoites. To validate these observations in a natural context, either murine Plasmodium berghei or human Plasmodium falciparum merozoites were tested for their ability to invade erythrocytes from a hypercholesterolaemic mouse model or human clinical erythrocyte samples deriving from patients with a range of serum cholesterol concentrations, respectively. Results: Erythrocyte bending modulus (a measure of deformability) was shown to be markedly affected by artificial modulation of cholesterol content and negatively correlated with merozoite invasion efficiency. In an in vitro infection context, however, erythrocytes taken from hypercholesterolaemic mice or from human clinical samples with varying serum cholesterol levels showed little difference in their susceptibility to merozoite invasion. Explaining this, membrane cholesterol levels in both mouse and human hypercholesterolaemia erythrocytes were subsequently found to be no different from matched normal serum controls. Conclusions: Based on these observations, serum cholesterol does not appear to impact on erythrocyte susceptibility to merozoite entry. Indeed, no relationship between serum cholesterol and cholesterol content of the erythrocyte is apparent. This work, nonetheless, suggests that native polymorphisms which do affect membrane lipid composition would be expected to affect parasite entry. This supports investigation of erythrocyte biophysical properties in endemic settings, which may yet identify naturally protective lipid-related polymorphisms

(RESEARCH ARTICLE) EFFECT OF POYMERIC RATIOS OF HPMC K15, SODIUM ALGINATE AND XANTHAN GUM ON THE SWELLING INDEX OF NIMODIPINE SUSTAINED RELEASE RE EASE AND IT’S SIGNIFICANCE

The present study focuses on studying the effect of swelling capacity of Nimodipine Sustained release tablets such that for all formulations it increases as increase the concentration of gum in each formulation. During the study it was observed that drug release decreases with increasing concentration of gum and swelling index. The reason attributed to this fact is formation of thick gel layer by matrices around tablets that delays diffusion and release drug. It was observed that swelling index of matrix tablets containing only one natural polymer was less this may attributed to the lower water uptake and less hydrophilicity. For all the ten formulations there was no occurrence of initial burst release, but the release was constant in a controlled manner for a prolong period of time up to 12hrs. The initial release of drug from these matrices occurs by the drug dissolution in the water penetrated into the matrix. The overall drug release from these matrices is governed by hydration, gel layer formation and drug diffusion into the gel layer and to the dissolution media. Polymer erosion also plays a major role in releasing drug from these matrices.. Swelling index of tablets prepared from NMP5 resulted as better swelling behavior with respect to concentration

Macroeconomic reforms: Risks, flash points and the way forward

This Working Paper examines India's growth and employment generation performance over the last ten years in the context of key indicators such as fiscal and current account balances and inflation and suggests priorities for macroeconomic reforms. An improvement in the central Government's finances is seen as a critical pre-requisite but that this should not be achieved on the back of reducing capital expenditures. The Paper reviews the distorted nature of India's labour markets and recommends legislative and the other steps needed to work around constraints. The need for India to widen its relatively narrow tax base is highlighted in the paper. The Paper also indicates the steps which are required to improve the Public-Private Partnership model and how to enhance the probability of crowding-in private investment into the infrastructure sector. The factors which have inhibited the development of Indian bond markets including the shortcomings in the Government Rupee yield curve are explained in the Paper. The Paper reviews the possibility of capital flight and Rupee exchange rate volatility due to an overvaluation of the Rupee's real exchange rate and assesses the quality of India's foreign exchange reserves. This Paper's review of the Indian economy and corresponding reforms takes the global economic environment into account, particularly anticipated developments in G7 countries

Is the Rupee over-valued?

The paper's objective is to examine whether the Indian Rupee was fairly valued as of end March 2015. First, the movements of the trade weighted real effective exchange rate (REER) of the Rupee are tracked over the last ten years. Next, the underpinnings of the Harrod-Balassa-Samuelson effect, which suggests taking changes in productivity levels into account in arriving at reliable estimates of exchange rates, and associated studies, are assessed. The paper also discusses varying approaches to Behavioural Equilibrium Exchange Rate (BEER) models and uses one to analyse whether the Rupee is fairly valued. The conclusion of the paper that the Rupee is substantially over-valued is based on a comparison of results obtained using differing methodologies

Can asset reconstruction companies (ARCs) be part solution to the Indian debt problem?

The Indian debt overhang issue is one of the major reasons that fresh investments are currently not being made in the scale required to promote higher growth and boost employment. Among banks the public sector banks (PSBs) are burdened with the bulk of net non-performing loans (NNPAs). These NNPAs are concentrated in long gestation projects, for example, in the steel, power and infrastructure sectors and most of the lending was to about 50 major borrowers. This paper details the approaches of other countries when their banking sectors were burdened with unsustainable levels of impaired assets. The paper examines the bad debt situation in India, the circumstances under which Asset Reconstruction Companies were registered and the changing regulatory requirements under which they have been operating in India. Till now, the extent to which ARCs have helped towards resolving the debt problem has been limited. Given that fixed costs in setting up ARCs have already been incurred this paper suggests how ARCs could play a catalytic and more significant role in addressing the debt overhang. The paper does not discuss the causal origins of Indian bad debt in any detail and is not intended to suggest comprehensive remedies to this debt problem

Financial Sector Legislative Reforms Commission (FSLRC) & financial sector regulation in India

The Financial Sector Reforms Commission (FSLRC) which was set up in 2011 by the Ministry of Finance was mandated to study existing legislation and financial sector regulatory practices in India and to propose improvements. The FSLRC submitted its report in 2013 and four of its members recorded dissenting notes. This paper examines the changes in regulation in four G7 countries post the financial sector breakdown of 2008 and suggestions made by the Financial Stability Board with respect to e.g. capital adequacy, shadow banking and accounting. The paper also reviews the current levels of development of the Indian banking, capital markets, pensions and insurance sub-sectors and past episodes of egregious wrongdoing. The last section of the paper examines and comments on the principal FSLRC proposals to further develop India's financial sector, regulate it better and protect consumers. The dissenting notes of four FSLRC members are also covered in this section followed by conclusions