An investigation into the ferric leaching of chalcopyrite : a sub-process in the bioleaching of chalcopyrite

Bibliography: leaves 70-79.The current focus of research in the UCT Minerals Bioprocessing Research Unit is to develop an understanding of the chalcopyrite bioleaching sub-processes. This thesis forms part of the greater study on bioleaching, investigating the ferric leaching subprocess. The objective of this thesis was two-folds. Firstly, a detailed literature review was undertaken to develop a better understanding of the ferric leaching of chalcopyrite and the cause of passivation during chalcopyrite leaching. Secondly, leach experiments on pyrite were used to establish the applicability and reproducibility of measuring the rate of ferric leaching at a constant redox potential, using the methodology developed by Kametani and Aoki (1985). Following this, chalcopyrite ferric leach experiments were conducted to obtain the redox potential range where chalcopyrite leaching occurs. The rate of chalcopyrite leaching in a sulfate media decreases with time due to the formation of a passivating layer. This has been described by many researchers as parabolic kinetics (Dutrizac, 1982; Beckstead et al., 1976; Munoz et al., 1979 and Dutrizac and Mac Donald, 1974). The nature of the passivating layer is still under considerable debate. Current theories of passivation include either the formation of jarosite, ferric hyroxy sulfate, sulfur or iron deficient polysulfide like covellite (Klauber et al. , 2001 , Parker et al., 1981 , Munoz et al, 1976, Warren et al., 1985 and Parker et al., 1981). Recent research has suggested that different passivating layers are formed during the various stages of chalcopyrite leaching. These include a ferric hydroxy sulfate layer followed by jarosite over extended period of time (Klauber etal., 2001 and Parker et al., 2001 ). Current investigations are underway to establish whether semiconductor properties of the mineral affects the type of passivating layer formed. To date, most of the work has been performed at temperatures higher than those at which chalcopyrite bioleaching occurs and with varying pH and redox potentials. There has been little consideration of the potential difference between the suspended particles surface and the solution. This problem can be overcome by conducting experiments at a constant solution redox potential. Kametani and Aoki (1985) first presented a method of maintaining a constant redox potential by using potassium permanganate as an oxidant to continuously re-oxidise ferrous-iron to ferric-iron. This method was then adopted by our research group to determine the initial rates of chalcopyrite leaching. Preliminary rates of chalcopyrite leaching were presented in the thesis by Furamera (2000). Further work was required to firmly establish the rates of chalcopyrite leaching and the optimal redox potential range within which chalcopyrite leach occurs. This involved optimising the redox potential control system to obtain better redox potential control during the chalcopyrite leach experiment

Screening of Lactobacillus plantarum isolated from fermented idli batter for probiotic properties

Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host. The objective of this study was to screen eight potential probiotic Lactobacillus plantarum strains from fermented idli batter using in vitro assays such as bile tolerance, acid tolerance, transit tolerance in the upper human gastrointestinal tract, auto-aggregation, co-aggregation, hydrophobicity, susceptibility to various antibiotics, bile salt hydrolase assay, cholesterol assimilation and hemolysis. The isolates were able to tolerate up to 0.3% of bile for 4 to 6 h and pH 2.5, 3.5, 4.5, 6.5, 7.5 and 8.5. The isolates were able to resist growth against gastric and intestinal fluid. The auto-aggregation of the different L. plantarum strains ranged from 65 to 80% in all the isolates. The co-aggregation with pathogens like Listeria monocytogenes (MTCC 657) and Escherichia coli (MTCC 728) ranged from 51 to 64%, however, low levels of co-aggregation were observed in L. plantarum (MTCC 6161) and L. rhamnosus (MTCC 1408) ranging from 32 to 46% and hydrophobicity from 49 to 77%. The isolates showed resistance towards antibiotics like gentamycin, ciprofloxacin, nalidixic acid and norfloxacin. All the isolates showed bile salt hydrolase activity with cholesterol lowering capacity, the highest being 73% by L. plantarum JJ 18. The isolates possessed â-galactosidase activity exhibiting 322 to 1000 MU of enzyme activity. No isolates showed hemolysis activity. Thus, the different L. plantarum isolates exhibited probiotic potential which would attribute beneficial effect to mankind.Key words: Lactobacillus plantarum, probiotics, cholesterol, β-galactosidase

Early manifestations of Anderson Fabry disease

This thesis examines some early renal and neurological manifestations in Anderson Fabry disease (AFD). First, estimating glomerular filtration rate in AFD using serum creatinine (Cr) based equations was assessed in 106 AFD patients. The Modification in diet in renal disease (MDRD) and the Chronic kidney disease epidemiology collaboration (CKD-EPI) equations had the least bias and were the best methods of estimating glomerular filtration rates in AFD patients with chronic kidney disease (CKD) stage 1 to 3. The monitoring of renal involvement in AFD use methods which assess glomerular function predominantly though there is evidence of renal tubular damage and atrophy on renal biopsy. We investigated possible urine markers of renal tubular dysfunction in AFD and 2 other proteins detectable in urine which have been shown to be markers of renal scarring and inflammation. Urine β-hexosaminidase (β-hex) and Monocyte chemoattractant protein-1 (MCP-1) were elevated in AFD patients compared with control demonstrating evidence of renal tubular involvement and possible renal inflammation. Finally we investigated cardiac autonomic function, cardiac neuroendocrine function, sweat function and symptoms related to neuropathic and autonomic function in an AFD cohort. There was little evidence of sweat dysfunction, cardiac autonomic or cardiac neuroendocrine dysfunction, though there is significant evidence of neuropathic pain and autonomic symptoms

Adaptations of the antioxidant system in erythrocytes of trained adult rats: Impact of intermittent hypobaric-hypoxia at two altitudes

We have investigated the effects of daily exposure to intermittent hypobaric-hypoxia to two simulated altitudes (5700 m and 6300 m) in adult male rats that had been regularly swim trained in normoxia at sea level prior to exposures. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) along with the oxidative stress (OS) indices, malondialdehyde (MDA) and protein carbonyl content were measured in erythrocytes and their membranes. Hemoglobin increased in the trained animals exposed to 5700 m and in untrained rats exposed to 6300 m. Osmotic fragility in terms of hemolysis increased in altitude exposed animals. SOD increased in those exposed to 6300 m, while CAT increased in trained rats exposed to 5700 m and to 6300 m unlike in untrained rats where CAT increased only at 6300 m. GSH-Px showed varying degrees of elevation in all animals exposed to both altitudes. Erythrocyte membranes showed significant elevations in malondialdehyde (MDA) at 6300 m, while elevated protein carbonyls were noticeable at both altitudes in whole cells and membranes. These results suggest a positively associated elevation in protein oxidation with altitude in trained rats. At 5700 m, animals were less stressed, unlike at 6300 m, as seen from the magnitude of elevations in the OS indices and from the responses of the antioxidant enzymes. © 2005 Elsevier Inc. All rights reserved

Update on antiarrhythmic drug pharmacology.

Cardiac arrhythmias constitute a major public health problem. Pharmacological intervention remains mainstay to their clinical management. This, in turn, depends upon systematic drug classification schemes relating their molecular, cellular, and systems effects to clinical indications and therapeutic actions. This approach was first pioneered in the 1960s Vaughan-Williams classification. Subsequent progress in cardiac electrophysiological understanding led to a lag between the fundamental science and its clinical translation, partly addressed by The working group of the European Society of Cardiology (1991), which, however, did not emerge with formal classifications. We here utilize the recent Revised Oxford Classification Scheme to review antiarrhythmic drug pharmacology. We survey drugs and therapeutic targets offered by the more recently characterized ion channels, transporters, receptors, intracellular Ca2+ handling, and cell signaling molecules. These are organized into their strategic roles in cardiac electrophysiological function. Following analysis of the arrhythmic process itself, we consider (a) pharmacological agents directly targeting membrane function, particularly the Na+ and K+ ion channels underlying depolarizing and repolarizing events in the cardiac action potential. (b) We also consider agents that modify autonomic activity that, in turn, affects both the membrane and (c) the Ca2+ homeostatic and excitation-contraction coupling processes linking membrane excitation to contractile activation. Finally, we consider (d) drugs acting on more upstream energetic and structural remodeling processes currently the subject of clinical trials. Such systematic correlations of drug actions and arrhythmic mechanisms at different molecular to systems levels of cardiac function will facilitate current and future antiarrhythmic therapy

Therapeutic Efficacy of Saline and Glucose Saline against Dermally applied Sulphur Mustard Intoxication in Mice

A single dose of saline or glucose-saline (5 mg glucose/kg) offered similar protection to mice against sulphur mustard intoxication, the extent of survival being 83 per cent as against 33 per cent without treatment. All the animals were protected when the treatment was extended by another two consecutive days in the glucose-saline treated group. Both saline and glucose-saline treatments could ameliorate the haemoconcentration as well as normalise pO/sub 2/ and % oxygen saturation. The protection conferred is attributed to the probable replenishment of fluid loss

Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts.

Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc-1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12-16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc-1β-/- (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1-adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc-1β-/- genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino-atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc-1β-/- mice. Moreover, Pgc-1β-/- mice displayed electrocardiographic features consistent with the existence of a pro-arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc-1β-/- mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc-1β-/- systems in widespread cardiac regions

Regulatory actions of 3',5'-cyclic adenosine monophosphate on osteoclast function: possible roles of Epac-mediated signaling.

Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.Medical Research Counci

Optimization of nutritional and non-nutritional factors involved for production of antimicrobial compounds from Lactobacillus pentosus SJ65 using response surface methodology

Bacteriocins from lactic acid bacteria are ribosomal synthesized antibacterial proteins/ peptides having wide range of applications. Lactobacillus pentosus SJ65, isolated from fermented Uttapam batter (used to prepare south Indian pan cake), produces bacteriocin having a broad spectrum of activity against pathogens. Optimization studies are of utmost important to understand the source of utilization and the conditions to enhance the production of metabolites. In the present study, an attempt was made to identify the parameters involved for maximal production of antimicrobial compounds especially bacteriocin from the isolate L. pentosus SJ65. Initially, optimal conditions, such as incubation period, pH, and temperature were evaluated. Initial screening was done using methodology onevariable-at-a-time (OVAT) for various carbon and nitrogen sources. Further evaluation was carried out statistically using Plackett-Burman design and the variables were analyzed using response surface methodology using central composite design. The optimum media using tryptone or soy peptone, yeast extract, glucose, triammonium citrate, MnSO4, dipotassium hydrogen phosphate and tween 80 produced maximum bacteriocin activity

Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1β-/- hearts: effects of age.

What is the central question of this study? Can we experimentally replicate atrial pro-arrhythmic phenotypes associated with important chronic clinical conditions, including physical inactivity, obesity, diabetes mellitus and metabolic syndrome, compromising mitochondrial function, and clarify their electrophysiological basis? What is the main finding and its importance? Electrocardiographic and intracellular cardiomyocyte recording at progressively incremented pacing rates demonstrated age-dependent atrial arrhythmic phenotypes in Langendorff-perfused murine Pgc1β-/- hearts for the first time. We attributed these to compromised action potential conduction and excitation wavefronts, whilst excluding alterations in recovery properties or temporal electrophysiological instabilities, clarifying these pro-arrhythmic changes in chronic metabolic disease. Atrial arrhythmias, most commonly manifesting as atrial fibrillation, represent a major clinical problem. The incidence of atrial fibrillation increases with both age and conditions associated with energetic dysfunction. Atrial arrhythmic phenotypes were compared in young (12-16 week) and aged (>52 week) wild-type (WT) and peroxisome proliferative activated receptor, gamma, coactivator 1 beta (Ppargc1b)-deficient (Pgc1β-/- ) Langendorff-perfused hearts, previously used to model mitochondrial energetic disorder. Electrophysiological explorations were performed using simultaneous whole-heart ECG and intracellular atrial action potential (AP) recordings. Two stimulation protocols were used: an S1S2 protocol, which imposed extrasystolic stimuli at successively decremented intervals following regular pulse trains; and a regular pacing protocol at successively incremented frequencies. Aged Pgc1β-/- hearts showed greater atrial arrhythmogenicity, presenting as atrial tachycardia and ectopic activity. Maximal rates of AP depolarization (dV/dtmax ) were reduced in Pgc1β-/- hearts. Action potential latencies were increased by the Pgc1β-/- genotype, with an added interactive effect of age. In contrast, AP durations to 90% recovery (APD90 ) were shorter in Pgc1β-/- hearts despite similar atrial effective recovery periods amongst the different groups. These findings accompanied paradoxical decreases in the incidence and duration of alternans in the aged and Pgc1β-/- hearts. Limiting slopes of restitution curves of APD90 against diastolic interval were correspondingly reduced interactively by Pgc1β-/- genotype and age. In contrast, reduced AP wavelengths were associated with Pgc1β-/- genotype, both independently and interacting with age, through the basic cycle lengths explored, with the aged Pgc1β-/- hearts showing the shortest wavelengths. These findings thus implicate AP wavelength in possible mechanisms for the atrial arrhythmic changes reported here