Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2013-04-18T19:50:07Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AvaliacaoAudiometricaPacientes.pdf: 5250268 bytes, checksum: a28385f4a2649f6226a3b1bb08578125 (MD5) / Approved for entry into archive by Ana Rosa Silva(arosa@ufpa.br) on 2013-04-19T15:13:19Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AvaliacaoAudiometricaPacientes.pdf: 5250268 bytes, checksum: a28385f4a2649f6226a3b1bb08578125 (MD5) / Made available in DSpace on 2013-04-19T15:13:19Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AvaliacaoAudiometricaPacientes.pdf: 5250268 bytes, checksum: a28385f4a2649f6226a3b1bb08578125 (MD5) Previous issue date: 2007 / Este estudo mostra a avaliação audiométrica, composta de audiometria tonal limiar e imitanciometria, em pacientes tratados de meningite por Cryptococcus gattii. Trata-se de um estudo tipo relato de casos. Foram avaliados seis pacientes com infecção comprovada do sistema nervoso central pelo Cryptococcus gattii, internados no Hospital Universitário João de Barros Barreto, entre janeiro de 2000 a novembro de 2007, para tratamento antifúngico. A idade dos pacientes analisados variou entre 12 e 37 anos. Três eram homens e três mulheres. Todos procedentes de municípios vizinhos, não sendo ninguém da capital Belém. As principais manifestações clínicas foram cefaléia e vômitos, presentes nas histórias de todos os pacientes, seguidas de febre e rigidez de nuca, cada uma delas ausentes em apenas um paciente, não coincidentes. O tempo de doença até o diagnóstico variou de 3 a 8 semanas. Dos três homens avaliados, dois apresentaram perda auditiva. Num deles a perda foi moderada e unilateral e no outro foi assimétrica e bilateral. Das três mulheres, apenas uma apresentou alteração auditiva. Nessa paciente houve apenas um rebaixamento leve numa freqüência isolada, de 4.000 Hz. Descreve-se achados audiométricos em relato de casos de pacientes tratados de meningite por Cryptococcus gattii. / This study shows the audiometric evaluation, composed by tonal audiometry and imitanciometry, in patients treated for Cryptococcus gattii meningitis. It was analyzed six patients with proven Cryptococcus gattii central nervous system infection, interned in the Hospital Universitário João de Barros Barreto, Belém, PA, Brazil, between January of 2000 and November of 2007, for antifungal treatment. The age of the analyzed patients ranged from 12 to 37 years-old. Three were men and three women. All of them originating from neighboring cities, nobody from the capital, Belém. The most common clinical findings were headache and vomiting, present in all the patients; fever and nuchal rigidity, each one absent in only one patient, not coincidents. The time of illness until the diagnosis varied from 3 to 8 weeks. Of the three evaluated men, hearing loss was presenting in two. In one of them deafness was moderate and unilateral and in the other it was bilateral and not symmetrical. Of the three women, only one presented hearing impairment. In this patient, occurred just a mild alteration in an isolated frequency, of 4.000 Hz. It is described audiometric findings in a relate of cases of patients treated for meningeal neurocryptococcosis due to Cryptococcus gattii.

A identificação histopatológica dos agentes fúngicos é um método excelente de diagnóstico, devido ao fato de que as estruturas são facilmente identificadas por meio das técnicas histoquímicas. Até o momento, não dispõem-se de métodos aceitáveis para quantificação da atividade da infecção. Esta investigação protocola um método de estimativa para atividade biológica da criptococose através da determinação dos índice de brotamentos e carminofílico do Cryptococcus. Objetivos: Descrever os aspectos histopatológicos da criptococose através das técnicas histoquímicas básicas e especiais da micologia. Métodos: Foram avaliados 33 pacientes com diagnóstico histopatológico prévio da criptococose. Resultados: Houve predominância do sexo masculino. A idade variou entre 10 a 81 anos, com média de 45,6 anos. A criptococose é doença definidora dos casos de Aids, sendo considerado seu principal fator predisponente, seguido de transplantes. O trato respiratório é o mais envolvido. O microrganismos tem tropismo para o sistema nervoso central e apresenta disseminação para outros órgãos. Resultados falso-negativos é reflexo da deficiência de material capsular. A mortalidade foi de 36%, sendo o maior índice obervado até os 3 primeiros meses após o diagnóstico. A criptococose apresenta-se sob duas formas, reativa e paucireativa. Na infecção reativa, os organismos foram menos abundantes e predominantemente intracelulares aos histiócitos e às células gigantes. Na infecção paucireativa, há um grande número de leveduras, que proliferam-se extracelularmente e estão associadas a destruição do tecido afetado. Ambos infecções, reativas e paucireativas mostraram grande variação no índice de brotamento. O índice carminofílico foi menor nas infecção reativas, quando comparados a infecção paucireativa. Discussão: A coloração de Hematoxilina-Eosina é usada para visualizar as alterações estruturais das lesões, bem como da reação tecidual. A coloração da prata é a mais utilizada para identificação dos organismos fúngicos como o Cryptococcus. A coloração de Mucicarmim de Mayer detecta a cápsula mucopolissacarídica circundante corada na cor magenta. A coloração de FM oferece diagnóstico diferencial nos casos inconclusivos à coloração de Mucicarmim de Mayer. A quantificação de IB e IC é uma escala útil na interpretação da resposta inflamatória do hospedeiro e atividade biológica da criptococose. / The histopathologic identification from the fungal agents that's a method excellent of diagnostic, due the fact of what the structures são easily identified for histochemical techniques. So far, there is no methods you accepted about to measurement of biologic activity. This investigation aponta to an method of estimate of the activity biologic of cryptococcal infection by determination of the Budding Index and Carminophilic Index of the Cryptococcus. Objectives: Describes the histologic features of cryptococcosis by basic and special histochemical techniques of mycology. Methods: Have been evaluated 33 patients with previous cryptococcosis histopathologic diagnostic. Results: There is an predominance of the males. The age of the patients ranged from 10 to 81 years with a median value 45,4 years. The HIV infection was the main risk factor for disease, followg of transplants. The respiratory tract is the most frequently involved among the organ systems organs. The false-negative latex test are due to capsular deficiency. The moratlity rate was 36%, The high rate of 50% was observed between of 1 to 3 months. The cryptococcal infections is divided into two major histologic categories, reactive and paucireactive, based upon the host reaction. In reactive infection, the organisms were lessa abundant and were predominantly intracellular within histiocytes and giant cells. In paucireactive infection, thre is large numbers of yeats in the lesions, cryptococci proliferate extracellarly within the involved tissues, associated histologically with mucoid degeneration of the surrounding tissue. Both reactice and paucireactive infections showed great variation in Budding Index. The Carminophilic Inded was lower in the reactive infections, when compared with the paucireactive infection. In this Carminophilic Index presented higher measurements.. Discussion: The Hematoxilin-Eosin stain is used to look for strucutural changes of the infectd lesion, as well tissues reactions. The Gomori’s methenamine-silver stain is the more commonly used in identificatifying these organisms. The mucicarmine stain detecting the surrounding mucopolisacharides capsule of the magenta color. The Fontana-Masson staining offers differential diagnostic. The determination of IB and IC is an scale that relied, because it provides an interpretation of the host response and biological activity of the cryptoccosis.

A identificação histopatológica dos agentes fúngicos é um método excelente de diagnóstico, devido ao fato de que as estruturas são facilmente identificadas por meio das técnicas histoquímicas. Até o momento, não dispõem-se de métodos aceitáveis para quantificação da atividade da infecção. Esta investigação protocola um método de estimativa para atividade biológica da criptococose através da determinação dos índice de brotamentos e carminofílico do Cryptococcus. Objetivos: Descrever os aspectos histopatológicos da criptococose através das técnicas histoquímicas básicas e especiais da micologia. Métodos: Foram avaliados 33 pacientes com diagnóstico histopatológico prévio da criptococose. Resultados: Houve predominância do sexo masculino. A idade variou entre 10 a 81 anos, com média de 45,6 anos. A criptococose é doença definidora dos casos de Aids, sendo considerado seu principal fator predisponente, seguido de transplantes. O trato respiratório é o mais envolvido. O microrganismos tem tropismo para o sistema nervoso central e apresenta disseminação para outros órgãos. Resultados falso-negativos é reflexo da deficiência de material capsular. A mortalidade foi de 36%, sendo o maior índice obervado até os 3 primeiros meses após o diagnóstico. A criptococose apresenta-se sob duas formas, reativa e paucireativa. Na infecção reativa, os organismos foram menos abundantes e predominantemente intracelulares aos histiócitos e às células gigantes. Na infecção paucireativa, há um grande número de leveduras, que proliferam-se extracelularmente e estão associadas a destruição do tecido afetado. Ambos infecções, reativas e paucireativas mostraram grande variação no índice de brotamento. O índice carminofílico foi menor nas infecção reativas, quando comparados a infecção paucireativa. Discussão: A coloração de Hematoxilina-Eosina é usada para visualizar as alterações estruturais das lesões, bem como da reação tecidual. A coloração da prata é a mais utilizada para identificação dos organismos fúngicos como o Cryptococcus. A coloração de Mucicarmim de Mayer detecta a cápsula mucopolissacarídica circundante corada na cor magenta. A coloração de FM oferece diagnóstico diferencial nos casos inconclusivos à coloração de Mucicarmim de Mayer. A quantificação de IB e IC é uma escala útil na interpretação da resposta inflamatória do hospedeiro e atividade biológica da criptococose. / The histopathologic identification from the fungal agents that's a method excellent of diagnostic, due the fact of what the structures são easily identified for histochemical techniques. So far, there is no methods you accepted about to measurement of biologic activity. This investigation aponta to an method of estimate of the activity biologic of cryptococcal infection by determination of the Budding Index and Carminophilic Index of the Cryptococcus. Objectives: Describes the histologic features of cryptococcosis by basic and special histochemical techniques of mycology. Methods: Have been evaluated 33 patients with previous cryptococcosis histopathologic diagnostic. Results: There is an predominance of the males. The age of the patients ranged from 10 to 81 years with a median value 45,4 years. The HIV infection was the main risk factor for disease, followg of transplants. The respiratory tract is the most frequently involved among the organ systems organs. The false-negative latex test are due to capsular deficiency. The moratlity rate was 36%, The high rate of 50% was observed between of 1 to 3 months. The cryptococcal infections is divided into two major histologic categories, reactive and paucireactive, based upon the host reaction. In reactive infection, the organisms were lessa abundant and were predominantly intracellular within histiocytes and giant cells. In paucireactive infection, thre is large numbers of yeats in the lesions, cryptococci proliferate extracellarly within the involved tissues, associated histologically with mucoid degeneration of the surrounding tissue. Both reactice and paucireactive infections showed great variation in Budding Index. The Carminophilic Inded was lower in the reactive infections, when compared with the paucireactive infection. In this Carminophilic Index presented higher measurements.. Discussion: The Hematoxilin-Eosin stain is used to look for strucutural changes of the infectd lesion, as well tissues reactions. The Gomori’s methenamine-silver stain is the more commonly used in identificatifying these organisms. The mucicarmine stain detecting the surrounding mucopolisacharides capsule of the magenta color. The Fontana-Masson staining offers differential diagnostic. The determination of IB and IC is an scale that relied, because it provides an interpretation of the host response and biological activity of the cryptoccosis.

A identificação histopatológica dos agentes fúngicos é um método excelente de diagnóstico, devido ao fato de que as estruturas são facilmente identificadas por meio das técnicas histoquímicas. Até o momento, não dispõem-se de métodos aceitáveis para quantificação da atividade da infecção. Esta investigação protocola um método de estimativa para atividade biológica da criptococose através da determinação dos índice de brotamentos e carminofílico do Cryptococcus. Objetivos: Descrever os aspectos histopatológicos da criptococose através das técnicas histoquímicas básicas e especiais da micologia. Métodos: Foram avaliados 33 pacientes com diagnóstico histopatológico prévio da criptococose. Resultados: Houve predominância do sexo masculino. A idade variou entre 10 a 81 anos, com média de 45,6 anos. A criptococose é doença definidora dos casos de Aids, sendo considerado seu principal fator predisponente, seguido de transplantes. O trato respiratório é o mais envolvido. O microrganismos tem tropismo para o sistema nervoso central e apresenta disseminação para outros órgãos. Resultados falso-negativos é reflexo da deficiência de material capsular. A mortalidade foi de 36%, sendo o maior índice obervado até os 3 primeiros meses após o diagnóstico. A criptococose apresenta-se sob duas formas, reativa e paucireativa. Na infecção reativa, os organismos foram menos abundantes e predominantemente intracelulares aos histiócitos e às células gigantes. Na infecção paucireativa, há um grande número de leveduras, que proliferam-se extracelularmente e estão associadas a destruição do tecido afetado. Ambos infecções, reativas e paucireativas mostraram grande variação no índice de brotamento. O índice carminofílico foi menor nas infecção reativas, quando comparados a infecção paucireativa. Discussão: A coloração de Hematoxilina-Eosina é usada para visualizar as alterações estruturais das lesões, bem como da reação tecidual. A coloração da prata é a mais utilizada para identificação dos organismos fúngicos como o Cryptococcus. A coloração de Mucicarmim de Mayer detecta a cápsula mucopolissacarídica circundante corada na cor magenta. A coloração de FM oferece diagnóstico diferencial nos casos inconclusivos à coloração de Mucicarmim de Mayer. A quantificação de IB e IC é uma escala útil na interpretação da resposta inflamatória do hospedeiro e atividade biológica da criptococose. / The histopathologic identification from the fungal agents that's a method excellent of diagnostic, due the fact of what the structures são easily identified for histochemical techniques. So far, there is no methods you accepted about to measurement of biologic activity. This investigation aponta to an method of estimate of the activity biologic of cryptococcal infection by determination of the Budding Index and Carminophilic Index of the Cryptococcus. Objectives: Describes the histologic features of cryptococcosis by basic and special histochemical techniques of mycology. Methods: Have been evaluated 33 patients with previous cryptococcosis histopathologic diagnostic. Results: There is an predominance of the males. The age of the patients ranged from 10 to 81 years with a median value 45,4 years. The HIV infection was the main risk factor for disease, followg of transplants. The respiratory tract is the most frequently involved among the organ systems organs. The false-negative latex test are due to capsular deficiency. The moratlity rate was 36%, The high rate of 50% was observed between of 1 to 3 months. The cryptococcal infections is divided into two major histologic categories, reactive and paucireactive, based upon the host reaction. In reactive infection, the organisms were lessa abundant and were predominantly intracellular within histiocytes and giant cells. In paucireactive infection, thre is large numbers of yeats in the lesions, cryptococci proliferate extracellarly within the involved tissues, associated histologically with mucoid degeneration of the surrounding tissue. Both reactice and paucireactive infections showed great variation in Budding Index. The Carminophilic Inded was lower in the reactive infections, when compared with the paucireactive infection. In this Carminophilic Index presented higher measurements.. Discussion: The Hematoxilin-Eosin stain is used to look for strucutural changes of the infectd lesion, as well tissues reactions. The Gomori’s methenamine-silver stain is the more commonly used in identificatifying these organisms. The mucicarmine stain detecting the surrounding mucopolisacharides capsule of the magenta color. The Fontana-Masson staining offers differential diagnostic. The determination of IB and IC is an scale that relied, because it provides an interpretation of the host response and biological activity of the cryptoccosis.

Adjacent cells communicate through gap junctions (GJs). These GJs are formed by head to head docking of two hemichannels (HCs) from two adjacent cells. HCs are connexin hexamer proteins. Connexin mutation is the most frequent cause of childhood hearing loss. This hearing impairment affects 2 in every 2000 children. Inhibition of the HCs might be the key factor to treat such disorders. A library of amphiphilic kanamycins was synthesized to be tested as HC inhibitors. These compounds showed excellent inhibition activity in comparison with the parent compound (kanamycin A) with less toxicity. A library of monosaccharide esters with varying carbon chain lengths (acetyl (C2) to hexadecyl (C16)) were synthesized, characterized, and tested for bioactivity. Carbohydrate esters showed low toxicity while remaining active against bacteria and fungi. The compound 6-O-tetradecanoyl-D-mannopyranose (MAN014), a mannose ester with a fourteen-carbon chain, showed the greatest antibacterial and antifungal properties. A mode of action study was tested against Staphylococcus aureus (bacteria) and Fusarium graminearum (fungus) and found the compound perturbed the cell membrum.

No description available.

Thesis (Ph.D. (Botany)) -- University of Limpopo, 2023 / The use of medicinal plants as a source of treatment for various ailments including fungal infections is still practised in South Africa and across the globe. Fungal infections especially of Cryptococcus, Candida and Aspergillus species are the main cause of morbidity and mortality worldwide, particularly in developing countries. Traditional medicine is used as a source of remedies worldwide and has contributed extensively towards the development of modern medicine. Twelve selected medicinal plants (Kleinia longiflora DC. Berchemia discolor (Klotzsch) Hemsl., Persea americana Mill., Sansevieria hyacinthoides (L.) Druce, Dichrostachys cinerea (L.) Wright &Arn, Withania somnifera Dunal (Ashgandh), Momordica balsamina L., Lonchocarpus capassa, Pappea capensis, Rhus lancea L. fil, Peltophorum africanum, Maytenus heterophylla (Eckl. & Zeyh.) Robson) were analysed qualitatively for antifungal activities against Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. The plant materials were extracted with solvents of various polarities such as acetone, dichloromethane, methanol, hexane, and water. Methanol extracted the highest amount of crude extracts from all the plant species as compared to other organic solvents. Chemical components of the extracts were analysed using aluminum backed Thin Layer Chromatography (TLC) plates and developed using three different eluent systems: Ethyl acetate: methanol: water [EMW], Chloroform: ethyl acetate: formic acid [CEF] and Benzene: ethanol: ammonia hydroxide [BEA]. CEF was the best eluent solvent system since it separated more compounds from plant extracts. This indicates that the active compounds were relatively non-polar. More chemical compounds were observed in TLC chromatograms separated with CEF, followed by BEA and EMW. All plant extracts had shown different chemical components when separated from the three solvent systems. The bioautography and serial dilution assays were used to determine the biological activity of plant extracts against the tested microorganisms, respectively. All the tested plant extracts revealed some varying degrees of fungal inhibition, with minimum inhibitory concentrations (MIC) values ranging between 0.02 mg/ml and 2.5 mg/ml. The aqueous extracts had shown some activity against the tested microorganisms. Noteworthy, antifungal activity was observed in acetone, DCM, hexane, and methanol root extracts of D. cinerea against the three tested microorganisms with MIC values ranging between 0.02 mg/ml and 0.04 mg/ml. Furthermore, acetone extracts of D. cinerea and P. africanum had excellent activity against three fungal pathogens with MIC values of 0.02 mg/ml and 0.08 mg/ml. Active compounds were observed in dichloromethane extracts of W. somnifera with Rf values of 0.40 and 0.64. In TLC chromatograms separated with BEA, active compounds were observed in acetone, hexane, and methanol leaf extract of P. americana, this indicates that the fungal compounds were relatively non-polar. No active compounds were observed in plant extracts of K. longiflora. Active compounds were visible in all extracts of P. capensis in TLC chromatograms developed in CEF and EMW. The antioxidant present in plants prevents the free radicals from causing various diseases in humans by inhibiting the oxidation of free radicals at the cellular level. The qualitative and quantitative 1,1-diphenyl-2-picrylhydrazyl (DPPH) methods were used to determine the antioxidant activities of plant extracts. The presence of antioxidant compounds was indicated by yellow bands against the purple background on the TLC plates. More antioxidant compounds were observed in acetone and dichloromethane extracts of S. hyacinthoides developed in BEA compared to other plant species tested. Methanol, hexane, and water extracts of L. capassa revealed good antioxidant activity against DPPH by having a high percentage of inhibition compared to other solvents. Noticeably, extracts of P. africanum possess strong antioxidant activity as compared to other plant species. Solvent-solvent fractionation using column chromatography of the acetone extract led to the isolation of six compounds. The biological activity of the isolated compounds of L. capassa was investigated against the tested pathogenic fungi. The isolated compounds revealed some varying degrees of inhibition to the fungal pathogens. The largest quantity was isolated from compound 1 (80 mg), compound 4 (39 mg), compound 3 (27 mg), compounds 2 and 5 (14 mg) and the least was compound 6 (4.8 mg). However only three compounds were successfully identified as Lupeol (compound 1), Friedelin (compound 3) and 6-(γ,γ-Dimethylallyl)-3’,4’-dimethoxy-6”,6”- dimethylpyrano-[2”,3”:7,8]-flavanone (compound 4). Compounds 2, 5 and were not identified due to some impurities. More importantly, the isolated compounds exhibited good antioxidant activity in qualitative and quantitative scavenging assays, which indicates that isolated compounds of L. capassa can scavenge the free radicals causing fungal infections in humans. The results support the traditional use of the selected plants to combat fungal infections and related ailments by the local people and traditional health practitioners in Vhembe District, Limpopo Province. The (3-(4,5-dimethylthiazol) -2,5-diphenyltetrazoliumbromide) (MTT) assay was used to determine the toxic effects of the plant crude extract and isolated compounds. Lupeol and 6-(γ,γ-Dimethylallyl)-3’,4’-dimethoxy-6”,6”-dimethylpyrano-[2”,3”:7,8]- flavanone revealed the same degree of cytotoxicity against the Vero monkey kidney cells. All the compounds were not toxic with an LC50 value of ˃ 0.2 mg/ml. / University of Limpopo and National Research Foundation

M. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology / The present study includes the use of a green synthetic method to prepare copper and silver nanoparticles using chitosan, aqueous extracts of Camellia sinensis, Combretum molle and Melia azedarach linn leaves. This study aims to investigate the influence of capping and precursor concentration on the properties of silver nanoparticles with emphasis on the medicinal plants chosen. The effect of capping agent on the properties of copper nanoparticles is also investigated. The phytochemical properties of plant extracts and the antimicrobial activity of the synthesized particles were also studied; this was achieved by using microdilution bioassay. Decoction method was used to extract secondary metabolites from plant leaves. Preliminary phytochemical screening carried out on the aqueous extracts of the plant leaves showed the presence of tannins, proteins, flavonoids, phenols, and carbohydrates. The total phenolic and flavonoids content of the aqueous extract was determined using spectroscopic methods. The highest phenolic content was found in the aqueous extract of Combretum molle (135 mg/g), and the highest flavonoid content was found in the aqueous extract of Camellia sinensis (0.4 mg/g). Characterization was done by a combination of spectroscopic, microscopy and XRD techniques. Both the size and shape of the synthesized silver nanoparticles were dependent on the identity of the capping molecule, precursor and capping agent concentration as depicted from their TEM and XRD results. Silver nanoparticles were found to be predominantly spherical. The capping agent concentration was also found to influence the degree of agglomeration, with an increase in capping agent concentration giving lesser agglomeration. FTIR spectral analysis showed that silver nanoparticles interact with bioactive compounds found in the plants through the hydroxyl functional group. Other shapes including diamond were observed for the effect of precursor concentration. The XRD micrographs revealed a face-centered cubic geometry and the phase remained the same with an increase in precursor concentration. The synthesized silver nanoparticles were all blue shifted compared to the bulk material. The TEM results revealed that copper nanoparticles with different sizes and shapes were successfully synthesized. All the prepared copper and silver nanoparticles showed satisfactory antifungal and antibacterial activity against Candida albicans, Cryptococcus neoformans, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumonia and Pseudomonas aeruginosa. The capping molecules used in this study also showed some antibacterial and antifungal activity against the selected strains. However nanoparticles performed better than these capping molecules. Both silver and copper nanoparticles were found to be more active against gram-negative bacteria compared to gram-positive bacteria. Amongst all the prepared silver nanoparticles Combretum molle capped nanoparticles were found to be the most active nanoparticles. Also with copper nanoparticles, it was found that Combretum molle capped nanoparticles were the most active nanoparticles. Between the two metal nanoparticles, silver nanoparticles showed high antibacterial and antifungal activity compared to copper nanoparticles. The antioxidant activity of silver nanoparticles was assessed using 2.2-diphenyl-1-picrylhydrazyl. Silver nanoparticles were found to have some antioxidant activity. However, the capping molecules were found to be more active than the synthesized nanoparticles. This observation is attributed to the presence of some bioactive compounds in the plant extracts.

<p>Systemic fungal infections brought about by <em>Cryptococcus</em> species are associated with some of the highest mortality rates of any infectious disease. Alarmingly these pathogens have overtaken tuberculosis as the second greatest killer among Sub-Saharan AIDS patients and are an emerging disease among immunocompetent populations on the Pacific Coast of North America. This clinical threat has been exacerbated by our inability to discover novel compounds that specifically target fungal cellular architecture at the genus level. To confront this challenge, we have made a concerted effort to biologically prospect the vast chemical potential of Actinomycete bacteria isolated from diverse and underexplored niches around the world. A novel phenotypic screen was developed whereby bacterial small molecule producers were co-cultured on agar plates in an intimate setting with evolutionary distant fungal pathogens <em>Candida albicans</em> and <em>Cryptococcus neoformans</em>. Diffusible small molecules released by the organisms created a signaling environment that stimulated profound phenotypic changes both in the Actinomycetes and the pathogens. We were able to discern a unique relationship whereby the growth of <em>C. neoformans</em> was specifically inhibited by Nigerian soil Actinomycete isolate curated as WAC 2288. Further bioactivity guided purification and chemical analysis lead to the identification of ibomycin, a previously undescribed 34 membered macrolactone decorated with seven sugar moieties. A draft genome of WAC 2288 revealed a 140kb gene cluster containing 12 type I PKS modules and downstream capacity to generate rare sugars are responsible for ibomycin biosynthesis. Purification of ibomycin analogs has revealed that the terminal vancosamine on the molecule is dispensable for bioactivity, establishing a chemical antecedent for target identification through affinity chromatography. Throughout these studies the unprecedented anticryptococcal activity of ibomycin is consistently recapitulated. Future work on the molecule may validate ibomycin as an effective antifungal therapy.</p> / Master of Science (MSc)