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

(REVIEW (RE VIEW ARTICLE) FAST DISSOLVING TABLETS ∶ METHOD AND TECHNOLOGY REVIEW

/2013 In the recent years, many of the pharmaceutical groups are focusing their research work on fast dissolving tablets. Fast dissolving tablets are an innovative drug delivery system in which the consumption of the dosage form without any use of water in taking. So, now-a-days, most of the pharmaceutical companies adopted various technologies to manufacture fast dissolving oral formulation in large scale despite of several limitations as an alternative to traditional over-thecounter medicine forms such as tablets, capsules etc. The main advantage of this technology is the administration to paediatrics and geriatrics patient population where the difficulty of swallowing larger oral dosage forms is eliminated. The basic approach used in development of FDT is the use of Superdisintegrants like Cross linked Carboxymelhylcellulose (Croscarmellose), Primogel, Polyvinylpyrrolidone (Polyplasdone) etc or maximizing pore structure in the formulation. The review describes the various methods and technologies employed in this research area

Maximizing the visual outcome in traumatic cataract cases: The value of a primary posterior capsulotomy and anterior vitrectomy

Objective: The objective was to provide evidence-based care for patients with traumatic cataracts, we assessed whether a posterior capsulotomy and anterior vitrectomy, as part of the primary surgical procedure, could be a positive predictor of final visual outcome. Materials and Methods: This is a prospective randomized control trial. Patients presenting at our hospital between January 2010 and December 2012 having ocular trauma and traumatic cataracts were enrolled, according to the inclusion criteria. We enrolled two groups: Those with and without primary posterior capsulotomy and vitrectomy. Information regarding demographic and ocular trauma were collected using the World Eye Trauma Registry form at the first visit and follow-up, and specific information was collected for both the group who underwent posterior capsulectomies and vitrectomies as a part of the primary procedure, and the control group. Data were analyzed to evaluate the predictive value of primary posterior capsulectomy and anterior vitrectomy. Results: We enrolled 120 cases, 60 in each group, comprising 31 females and 89 males. When all other variables were controlled for, the visual outcome (best corrected visual acuity) differed significantly (P < 0.001) between the groups. Conclusion: Performance of posterior capsulectomy and anterior vitrectomy as part of the primary procedure improves the final visual outcome

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