Browsing by Author "Pillay, Karen."

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An audiological and genetic profile of hearing of learners suspected of familial hearing loss attending schools for the deaf in KwaZulu-Natal.
(2017) Pillay, Karen.; Joseph, Lavanithum.; Aldous, Arnolg Clifford.
This study focused on genetic familial hearing loss, concentrating on learners attending schools for the Deaf in Kwazulu Natal .The study sought to identify the audiological profile characteristics of suspected genetic familial hearing loss in the learners and their family members with hearing loss. Currently there is a scarcity of research in the area of genetics and hearing loss in South Africa. The study aimed at providing both an audiological and genetic profile of familial hearing loss of learners with a history of hearing loss in the family. A quantitative multicase study research design was chosen. Participants were identified based on a positive family history of hearing loss in learner records and the referral from the school Audiologists. An audiological assessment and family pedigree was conducted on affected learners and their families who volunteered to participate in the research. The study sample consisted of 40 learners from 25 families with 70 affected participants who underwent audiological assessments and a family pedigree analysis, of which 31 were male and 39 were female. The pedigree analysis of the 25 families also presented 417 individuals who were reported to have normal hearing and 20 individuals with a reported hearing loss that were unable to undergo audiological testing in the study. The study identified an autosomal dominant inheritance present in 32% (8) of families an autosomal recessive inheritance in 56% (14) and a presumed co-incidental familial hearing loss in 12% (3) of families. The audiological and genetic profile of families within the study, revealed significant differences between the profile of autosomal dominant and autosomal recessive hearing loss. The autosomal recessive group revealed a profile of hearing loss that was predominately congenital, prelingual, sensorineural, severe to profound in severity and flat in configuration. The autosomal dominant inheritance revealed a profile that was both prelingual and postlingual in onset with a moderate to severe sensorineural hearing loss and a sloping configuration. The results of the study are supported by other studies with regard to the description and auditory profile differences of autosomal recessive and autosomal dominant hearing loss. An understanding of the audiometric profiles of genetic familial hearing loss, will be useful to health professionals when assessing and managing these families with a history of hearing loss. It is believed that a standard method of profiling genetic familial hearing loss and the use of a family pedigree analysis, would be beneficial to professionals who encounter families with hearing loss. The role of the multidisciplinary team which includes Audiologists, geneticists and genetic counsellors in the family with a familial hearing loss are invaluable. This study provided data on the current incidence of genetic familial hearing loss at schools for the deaf in the province of KwaZulu-Natal. It is expected that with the advancement of research in the area of genetic familial hearing loss, an increase in professionals in the field of genetics such as geneticists and genetic counsellors will be available.
Bio-guided isolation of biologically active compounds from seeds of selected South African medicinal plants.
(2016) Perumal, Amanda.; Govender, Patrick.; Naidoo, Sershen.; Pillay, Karen.
Abstract available in PDF file.
Membrane permeability of HIV-1 protease inhibitors.
(2014) Ramlucken, Uraisha.; Govender, Patrick.; Pillay, Karen.
According to the 2012 UNAIDS global report, sub-Saharan Africa hosts 69% of the world’s total population living with HIV, South Africa being the most affected with a reported 24% incidence rate. To date, extensive research is being conducted globally, particularly involving anti-HIV treatment that targets the retroviral enzymes: reverse transcriptase, integrase and protease. The discovery of inhibitors to HIV protease which disrupts virion protein assembly has made this enzyme a prime target of anti-retroviral therapies, thus there exists a concerted research initiative to identify compounds with HIV protease inactivation potential. This study employs HIV protease that is isolated and purified from a genetically modified HIV protease overexpressing Escherichia coli strain to monitor the inhibitory capacity of new lead compounds. Optimized growth conditions for HIV protease production displayed that the use of chemically defined media resulted in higher yields of the enzyme. Recent research studies have shown that peptide-based cage and glycosylated compounds displayed HIV protease inhibitor activity in cell free enzymatic reactions that are comparable to commercially available HIV protease inhibitors. However, in contrast it has also been reported that these inhibitors are inactive in whole T-cell assays, when employing HIV infected CD4 cells. It is a well-known fact that potential new chemical entities that do not possess oral bioavailability, in terms of their absorption properties, are not successful candidates within the drug discovery industry. Following this, the current study was designed to determine if inefficient membrane permeability of these promising anti-HIV protease lead compounds could result in their inactivity in whole T-cell assays. Two different methods were considered, a cell-based method using the Madin Darby Canine Kidney strain I (MDCKI) cell line and a non-cell based method, the parallel artificial membrane permeability assay (PAMPA). MDCKI cells have been extensively used to form monolayers that mimic human intestinal membranes whilst the PAMPA utilizes an artificial lipid membrane composition on a filter support. Data from permeability assays using the novel chemically synthesized inhibitors have been compared to commercially available drugs, antipyrine, metoprolol and caffeine, which displayed efficient membrane permeability characteristics, thereby validating the assay. The results indicated that novel cage-derived and glycosylated peptide inhibitors do not possess sufficient passive diffusion properties which may explain their inactivity in whole T-cell assays.
Over-expression of FLO11 encoded mannoprotein in Saccharomyces cerevisiae.
(2015) Govender, Kamini.; Govender, Patrick.; Pillay, Karen.
Abstract available in PDF file.
Silver nanoparticles from biological extracts and their antimicrobial activities.
(2017) Moodley, Jerushka S.; Govender, Patrick.; Pillay, Karen.
The increasing incidence of multi-drug resistant organisms has led to the resurgence in application of Ag-based compounds. Accordingly, increased efforts have been made in the field of nanotechnology to develop silver nanoparticle (AgNP) synthetic strategies that are inexpensive and environmentally friendly without the use of hazardous chemicals. To this end, sunlight irradiation, a relatively new primary source of energy was used instead of heat to drive the synthesis of AgNPs. Biologically-derived capping substrates were independently extracted fromfresh (F) and freeze-dried (FD) leaf samples of the medicinal tree species, Moringa oleifera. Importantly, the extracted substrates advantageously displayed a dual functionality by reducing Ag+ as well as stabilising the resulting AgNPs. Yield analysis indicated a recovery ranging from 0.81 mg and 0.91 mg AgNPs per gram dry mass F and FD leaf tissue, respectively. AgNPs from both sample types were consistent in terms of their spherical shape with average diameters of 9 nm and 11 nm for F and FD samples, respectively. Fourier transform infrared (FTIR) spectroscopic analysis suggested that flavones; terpenoids and polysaccharides predominate and are primarily responsible for the reduction and subsequent capping of AgNPs. Interestingly, bioactivity screening revealed that AgNPs exhibited broad-spectrum antimicrobial activity against both bacterial and fungal strains. The results suggest that AgNPs derived from M. oleifera leaf extracts exhibit potential for application as broad-spectrum antimicrobial agents.
Synthesis and aggregation dynamics of amylin.
(2012) Pillay, Karen.; Govender, Patrick.
Amylin is a 37 amino acid long peptide that aggregates into toxic oligomers and fibrils. Since amylin is secreted by and also acts on pancreatic beta cells, type II diabetes is classified as an amyloidogenic disease. This study focuses on the development of a cost effective chemical synthetic strategy for amylin synthesis as previous studies relied on extremely expensive pseudoproline derivatives. Furthermore, commercially available amylin varies between batches and also contains impurities that could generate anomalies and affect reproducibility of experiments. Secondly, chemically synthesized non-methylated and N-methylated derivatives of amylin were shown to inhibit toxicity of full length amylin. A fluorescentlylabeled chemically synthesized derivative of amylin was used to track cellular localization of amylin via confocal microscopy. Amylin aggregation kinetics was established using a surface plasmon resonance (SPR) biosensor. In addition, nanoparticle tracking analysis (NTA) was used as a novel technique to determine the size of oligomers over real time. This technology indicated that the size range of the toxic species of amylin is between 200-300 nm. Furthermore, it can be suggested that NTA could potentially be developed into a screening tool for inhibitors of amylin-mediated cytotoxicity.
Synthesis, characterization and evaluation of antibacterial, antidiabetic and toxicological profiles of newly-derived therapeutic agents.
(2016) Gannimani, Ramesh.; Govender, Patrick.; Pillay, Karen.
Abstract available in PDF file.
Yeast encapsulation for bioethanol production.
(2014) Nene, Njabulo Eugene.; Govender, Patrick.; Ramchuran, Santosh.; Pillay, Karen.
The bioethanol production industry is faced with hurdles such as uncovering cheap and abundantly available fermentation substrates, as well as yeast strains possessing high ethanol tolerance properties. Cane molasses is a substrate that sufficiently fits the aforementioned description and this has catapulted its use in bioethanol production. However, the downside to employing cane molasses as a fermentation substrate under laboratory conditions for comparative fermentation studies is nutrient composition variability in different batches. This has prompted the development of a standardised chemically defined molasses medium that facilitates the generation of more consistent and reliable fermentation data. In the first aspect of this study, a chemically defined molasses medium was formulated based on nutrient composition data of 10 different cane molasses batches as provided by the South African Sugar Research Institute (SASRI). The ability of laboratory and industrial Saccharomyces cerevisiae strains to ferment chemically defined molasses medium and industrially-derived cane molasses sourced from the Amatikulu, Felixton and Gledhow South African-based sugar mills was evaluated. The batch fermentation of the chemically defined molasses medium supplemented with yeast extract by BY4743 (laboratory strain), dry yeast (baker’s yeast), Angel and cream yeast (distiller’s yeast) were similar to those attained in batch fermentations of cane molasses in terms of fermentation kinetic profiles (sugar conversion, ethanol titer, yield and productivities). It was also observed irrespective of the fermentation substrate involved that cream yeast produced the highest ethanol output followed by angel yeast, dry yeast and then BY4743. These results seem to suggest that the chemically defined molasses medium containing yeast extract can be employed as a standardised laboratory medium. Increased bioethanol yield is commercially attractive to relevant fermentation-based industries. In this regard, the immobilization of yeast by cell encapsulation has been touted as a tool which may increase the yeast’s tolerance to higher ethanol levels. In this study, a strategy was developed in which the better performing Angel and cream yeast strains were immobilized in calcium alginate, alginate-chitosan, and low melting point agarose capsules. The fermentation efficiency in terms of ethanol production of encapsulated cells versus their free-suspended yeast cell counterparts was evaluated. The reusability of the capsules for more than one fermentation cycle was also investigated. The fermentation of Amatikulu and chemically defined molasses medium containing 10 g/L of yeast extract by Angel yeast encapsulated in low melting point agarose resulted in a 10% increase in bioethanol yields in comparison to their free-suspended Angel yeast counterparts. However, it was also observed that cream yeast fermentations with free-suspended and encapsulated cells generated similar fermentation profiles and bioethanol yields. Only alginate-chitosan and low melting point agarose were used in the investigation of capsule reusability because of their superior stability over calcium alginate capsules. The low melting point agarose capsules remained stable and active for the three consecutive batch fermentations of Amatikulu cane molasses and synthetic CDM-YE molasses. The alginate-chitosan capsules remained active and stable for two cycles of fermentation and only showed signs of breakage during the third fermentation cycle. Fermentations with encapsulated Angel and cream yeast resulted in sustained ethanol outputs for the three fermentation cycles. The data seem to suggest that the cell encapsulation strategy may be beneficial to the bioethanol industry in that lower ethanol tolerant distillers yeast and other yet to be used strains which produce significantly less undesirable by-products such as acetic acid, ethyl aldehyde, n-propanol and methanol can be improved in terms of their bioethanol yield to meet the requirement of industry.