Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during plasmodium falciparum invasion of erythrocytes

During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1) an early heparin-blockable interaction which weakly deforms the erythrocyte, 2) EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3) a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4) an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine

Dyslipidaemia in patients with lupus nephritis

Aim: There is little data on the prevalence and severity of dyslipidaemia in Asian patients with lupus nephritis (LN). Whether the dyslipidaemia in LN patients differs from subjects with comparable levels of renal impairment also remains undefined. Methods: Lipid profiles of 100 Chinese patients with quiescent LN (age 46.3 ± 9.3 years, 83% female, maintenance prednisolone dose 5.80 ± 2.43 mg/day) were studied and compared with 100 controls who had non-lupus non-diabetic chronic kidney diseases (CKD), matched for sex, age and renal function. Results: LN patients and CKD controls had similar renal function and proteinuria, while blood pressure was higher in controls. Twenty-five percent of LN patients and 17% of controls were receiving statin treatment. Despite this, 59% of LN patients and 46% CKD controls showed abnormal lipid parameters (P = 0.066). LN patients showed higher levels of total cholesterol (TC) and triglycerides (TG) than controls (5.28 ± 0.12 vs 4.86 ± 0.08 mmol/L, P = 0.004; and 1.62 ± 0.12 vs 1.20 ± 0.07 mmol/L, P = 0.002, respectively). More LN patients had abnormal TC, TG or low-density lipoprotein cholesterol (LDL-C) (54%, 16% and 38%; P = 0.016, = 0.005 and = 0.021, respectively). Hydroxychloroquine (HCQ) treatment was associated with lower TC, LDL-C and HDL-cholesterol. Conclusion: Dyslipidaemia is prevalent in LN patients and is more severe than controls with a similar degree of CKD despite disease quiescence, low steroid dose and low level of proteinuria. Concomitant corticosteroid and renal impairment are likely contributing factors. HCQ treatment is associated with reduced severity of dyslipidaemia in LN patients. Both systemic lupus erythematosus and chronic kidney disease are associated with excess vascular mortality. In this significant cohort of Asian patients with lupus nephritis, Chong et al. show that dyslipidaemia is common, even in inactive lupus nephritis, more common than in controls with a similar degree of chronic kidney disease. © 2011 Asian Pacific Society of Nephrology.link_to_subscribed_fulltex

Conversion between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) may impact on sleep apnea in favor of CAPD

Conference Theme: From Hemodialysis Unit to ICUStudy Objective: To investigate the potential difference in impact on sleep apnea between continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) therapy in end-stage renal disease (ESRD) patients. Patients and Methods: Six patients (2 males, mean age 64.3 6.8 years, 4 had diabetes, 1 had lupus, and 1 had vasculitis as cause of renal failure) underwent standard overnight polysomnography during CAPD and then HD sequentially, or vice versa. The reasons for switching from CAPD to HD were membrane failure in 1, refractory peritonitis in 3, hernia operation in 1, and perforated colon in 1. The mean ( SE) apnea-hypopnea index (AHI), defined as the frequency of apnea and hypopnea per hour of sleep, during HD and CAPD was 34.1 13.0 and 7.9 3.61/hour (P=0.1), respectively. The obstructive apnea index was 13.4 7.1 vs. 7.1 2.6/hour, and the central apnea index was 20.7 13.7 vs. 0.8 0.4/hour during HD and CAPD, respectively. Five patients (83%) had reduction in AHI on switching from HD to CAPD, and this was mainly due to a reduction in the central component of sleep apnea. Conclusion: There is a trend toward reduced severity of sleep apnea associated with renal failure during CAPD compared with HD. A larger larger study cohort is needed to attest this hypothesis. Acknowledgment: Seed Funding Programme for Basic Research, The University of Hong Kong.link_to_subscribed_fulltex