BackgroundChronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS).MethodsWe have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography).ResultsGene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression.ConclusionThese findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

Pyrometallurgical and hydrometallurgical technologies for recovery of metals from low grade ores require high energy and capital costs. Use of microorganisms in leaching of mineral ores is gaining importance due to the implementation of stricter environmental rules. Microbes convert metal compounds into their water soluble forms and are biocatalysts of leaching processes. This study was performed to isolate and characterize iron solubilizing fungi from low grade iron ore for bioleaching process. Soil samples from iron mine area were used for isolation of iron solubilizing fungi and two fungal species (NTS-1 and NTS-2) were obtained from enrichment culture method. Bioleaching experiments were carried out in batch culture to determine the iron solubilising efficiencies of the isolates. Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) was used to determine the solubilized iron concentration and strain NTS-2 exhibited 40% higher iron solubilization than strain NTS-1. The strain was subjected to 18S-ITS sequence of rRNA studies and the phylogenetic analyses justify a taxonomic position for the strain as a member of Penicillium verruculosum. The isolated strain could be used in solubilizing iron from low grade ores as an efficient, economical and eco-friendly alternative to conventional operations.

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Pyrometallurgical and hydrometallurgical technologies for recovery of metals from low grade ores require high energy and capital costs. Use of microorganisms in leaching of mineral ores is gaining importance due to the implementation of stricter environmental rules. Microbes convert metal compounds into their water soluble forms and are biocatalysts of leaching processes. This study was performed to isolate and characterize iron solubilizing fungi from low grade iron ore for bioleaching process. Soil samples from iron mine area were used for isolation of iron solubilizing fungi and two fungal species (NTS-1 and NTS-2) were obtained from enrichment culture method. Bioleaching experiments were carried out in batch culture to determine the iron solubilising efficiencies of the isolates. Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) was used to determine the solubilized iron concentration and strain NTS-2 exhibited 40% higher iron solubilization than strain NTS-1. The strain was subjected to 18S-ITS sequence of rRNA studies and the phylogenetic analyses justify a taxonomic position for the strain as a member of Penicillium verruculosum. The isolated strain could be used in solubilizing iron from low grade ores as an efficient, economical and eco-friendly alternative to conventional operations.