Endothelial glycocalyx degradation and disease severity in Plasmodium vivax and Plasmodium knowlesi malaria

Degradation of the endothelial glycocalyx is associated with mortality in adult falciparum malaria. However, its role in the pathogenesis of non-falciparum malaria is unknown. In Malaysian patients with knowlesi (n = 200) and vivax (n = 61) malaria, and in healthy controls (n = 50), we measured glycocalyx breakdown products plasma syndecan-1 and urinary glycosaminoglycans, and evaluated correlations with biomarkers of disease severity. Urinary glycosaminoglycans were increased in patients with knowlesi and vivax malaria compared to healthy controls, and in knowlesi malaria were highest in those with severe disease. In knowlesi malaria, plasma syndecan-1 was also highest in those with severe disease, and correlated with markers of endothelial activation (angiopoietin-2, osteoprotegerin, ICAM-1), asymmetric dimethylarginine (ADMA) and impaired microvascular reactivity. Syndecan-1 also correlated with endothelial activation (ICAM-1, angiopoietin-2) and ADMA in vivax malaria. In knowlesi malaria increased syndecan-1 was associated with acute kidney injury, after controlling for age and parasitemia. In knowlesi malaria, the difference in median syndecan-1 between severe and non-severe disease was more marked in females than males. Endothelial glycocalyx degradation is increased in knowlesi and vivax malaria, and associated with disease severity and acute kidney injury in knowlesi malaria. Agents that inhibit glycocalyx breakdown may represent adjunctive therapeutics for severe non-falciparum malaria.

Hyaluronan as a predictive biomarker in recurrent renal stone formers

Recurrence of renal calculi after treatments such as extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and surgeries, remains high. A viable diagnostic biomarker is needed to alert the patient and the clinician to monitor for stone recurrences. This study concentrates on idiopathic stone-formers (SF) and 6 groups of subjects were recruited with Active-SF (pre- and post- treatments), Non-SF (with and without infection) for comparisons. Urine and blood samples were collected from the patients (with inclusion and exclusion criteria) from the hospital clinic and processed at the laboratory with ELISA and biochemical methods (electrophoresis and HPLC). 120 samples were collected amongst the 3 groups. The following demographics were obtained: Age-range (32 – 63 years old); Male: Female ratio (58: 42); Mean urinary pH 6.33 ± 0.23 (though in each group there are differential mean pH) and urinalysis done for all samples to verify the integrity of the samples. The first biomarker studied was the excretion of urinary glycosaminoglycans (GAGs). Chondroitin sulphate A/C (CS), dermatan sulphate (DS), heparin sulphate (HS) and hyaluronan (HA) were extracted and quantified. Active SF (prior treatment) had 70% positive indicator for GAGs and those SF (post treatment) had over 90% compared to the Normals. Other biomarkers (not reported here) under investigations are cytokines including NAG and MIP-1α. This study combines majority of the biomarkers in our study under a case-control investigation to suggest a potential and sensitive marker for recurrent SFs. Hyaluronan is one such candidate biomarker. Keywords: Biomarkers; Glycosaminoglycans; Hyaluronan; Recurrence; Urolithiasis

Structural analysis of urinary glycosaminoglycans from healthy human subjects

Urinary glycosaminoglycans (GAGs) can reflect the health condition of a human being, and the GAGs composition can be directly related to various diseases. In order to effectively utilize such information, a detailed understanding of urinary GAGs in healthy individuals can provide insight into the levels and structures of human urinary GAGs. In this study, urinary GAGs were collected and purified from healthy males and females of adults and young adults. The total creatinine-normalized urinary GAG content, molecular weight distribution and disaccharide compositions were determined. Using capillary zone electrophoresis (CZE)–mass spectrometry (MS) and CZE–MS/MS relying on negative electron transfer dissociation, the major components of healthy human urinary GAGs were determined. The structures of 10 GAG oligosaccharides representing the majority of human urinary GAGs were determined.