No description available.

Submitted by Raquel Vergara Gondran (raquelvergara38@yahoo.com.br) on 2016-05-05T18:44:25Z No. of bitstreams: 1 fernanda arnhoud pagnussatt - inibio do crescimento de espcies do complexo fusarium.pdf: 1615887 bytes, checksum: daa606d7216768f4d2df2f8137006ec3 (MD5) / Approved for entry into archive by cleuza maria medina dos santos (cleuzamai@yahoo.com.br) on 2016-05-05T20:35:57Z (GMT) No. of bitstreams: 1 fernanda arnhoud pagnussatt - inibio do crescimento de espcies do complexo fusarium.pdf: 1615887 bytes, checksum: daa606d7216768f4d2df2f8137006ec3 (MD5) / Made available in DSpace on 2016-05-05T20:35:57Z (GMT). No. of bitstreams: 1 fernanda arnhoud pagnussatt - inibio do crescimento de espcies do complexo fusarium.pdf: 1615887 bytes, checksum: daa606d7216768f4d2df2f8137006ec3 (MD5) Previous issue date: 2013 / Fusarium é um gênero de fungo comumente encontrado em grãos e alimentos a base de cereais e reconhecido produtor de uma ampla gama de micotoxinas. A necessidade de aumentar a segurança alimentar norteia a busca por substâncias naturais como alternativa ao uso de fungicidas químicos. Compostos fenólicos têm demonstrado propriedades antifúngicas e antimicotoxigênicas e a incorporação dessas substâncias em sistemas carreadores, tais como lipossomos, pode preservar ou mesmo potencializar este efeito. Em função disso, o objetivo do trabalho foi estudar a atividade antifúngica de compostos fenólicos extraídos de Spirulina sp. LEB-18 na forma livre e encapsulada visando aplicá-los para diminuir o impacto da contaminação micotoxicológica em grãos por espécies filogenéticas do complexo Fusarium graminearum (Fg). Primeiramente, algumas rotas metabólicas foram avaliadas através da determinação de compostos estruturais (glicosamina e ergosterol) e da atividade de enzimas do metabolismo primário de 12 isolados de Fg em presença do extrato fenólico. A concentração necessária para inibir 50% o crescimento micelial (IC50) foi obtida em valores correspondentes entre 3 a 8% (v/v) de extrato fenólico e a glicosamina foi o indicativo de inibição que melhor representou o efeito inibidor sobre o crescimento fúngico. Padrões de ácidos fenólicos foram testados e comparados ao extrato fenólico de Spirulina, sendo observado que o ácido gálico foi o que apresentou maior efeito inibidor, porém inferior ao extrato fenólico de Spirulina. A incorporação do extrato fenólico em lipossomos alterou a dinâmica das regiões polares e apolares da fosfatidilcolina da membrana lipídica, influenciando a região fosfato do lipídio e aumentando a fluidez dos metilenos presentes na cauda apolar da membrana. Este efeito está relacionado com a inibição superior a 90% no crescimento de isolados do complexo Fg em presença de lipossomos contendo 8% de extrato fenólico (v/v). A produção de glicosamina foi reduzida de 11,5 mg g-1 para 6,1 mg g-1 no meio com lipossomo puro e extrato fenólico incorporado ao lipossomo, respectivamente, e aumentou em 15 vezes e 6 vezes a inibição da produção das micotoxinas NIV e 15AcDON. Ficou demonstrado que a técnica de encapsulamento garantiu a manutenção das propriedades de compostos bioativos, com atividade antifúngica e antimicotoxigênica superior ao extrato fenólico livre. / Fusarium is a fungal strain commonly found in grains and foods from cereals and a recognized mycotoxin producer. The need to increase food safety leads the search for biologically active natural substances as an alternative to the sinthetic fungicides. Phenolic compounds have demonstrated antifungal and antimicotoxigenic properties and the incorporation of these substances in carrier systems such as liposomes, may can preserve or even enhance this effect. As a result, this work aimed to study the antifungal activity of phenolic compounds extracted from Spirulina sp. LEB-18 in free and encapsulated form in order be applied in the reduction of the impact of micotoxin contamination in grains by Fusarium graminearum (Fg). First, the possibility affected metabolic pathways potentially affected were evaluated by determining structural compounds (glucosamine and ergosterol) and the enzymatic activity corresponding to primary metabolism of Fg 12 isolates in the presence of phenolic extract. The half inhibition concentration of fungal growth (IC50) was obtained in phenolic extracts concentrations between 3-8% (v/v) and glucosamine was the inhibition indicative which best represented the inhibitory effect on fungal growth. Phenolic acids standards were tested comparatively to Spirulina phenolic extract, and among them, being gallic acid showed the greatest inhibitory effect. However, this effect was lower than the Spirulina phenolic extract. The phenolic extract incorporation in lipossomes change the dynamics of the lipid membrandes of phosphatidylcholine polar and nonpolar regions, influencing the lipid phosphate region and increasing the fluidity of methylenes present in apolar hydrophobic acyl chains. This effect is related to the Fg growth inhibition of the complex isolates, wich was greater than 90% in the presence of liposomes containing 8% phenol extract (v/v). The production of glucosamine was reduced from 11.5 mg. g-1 to 6.1 mg. g-1 in the medium with pure liposome and phenolic extract incorporated into the liposome, respectively and increased by 15 and 6 times the inhibition of the mycotoxins NIV and 15AcDON. This showed that encapsulation technique ensured the maintenance of bioactive compounds with antifungal activity and antimicotoxigenic properties above the free phenolic extract.

Made available in DSpace on 2018-06-27T18:56:32Z (GMT). No. of bitstreams: 3 Maura Zubiaurre dos Santos.pdf: 1338832 bytes, checksum: 234dfe007337129aa96815091aad7c42 (MD5) Maura Zubiaurre dos Santos.pdf.txt: 74878 bytes, checksum: fe3a8ab94635867f402fde8650d28b72 (MD5) Maura Zubiaurre dos Santos.pdf.jpg: 3071 bytes, checksum: 63c016cce951cddaa53f7b933b5a025c (MD5) Previous issue date: 2010-03-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the present work, several compounds derived from monosacharide D-Glucosamine were synthetized. These compounds were used successfully against gram-positive and gram-negative microorganisms. In the synthesis of compounds, classical methods in organic chemistry were used.The products were readily prepared from D-Glucosamine in few easy steps. In the first step, we have obtained he imine derivatives 2a or 2b. The resultant imines were protected in the OH groups at C1, C3, C4 and C6 positions with acetyl group. Selective desprotection of C2 aminogroup and coupling with cmnamic acid fford compound 5. All compounds were tested as antimicrobial agents against gram-positive and gram-negative microorganisms. Best results were obtained when compound 2b was used. / No presente trabalho, foram sintetizados vários compostos derivados da D-Glucosamina. Estes compostos foram usados com sucesso contra microorganismos grampositivos e gram-negativos. Na síntese dos compostos, foram utilizados métodos clássicos em química orgânica. Os produtos foram facilmente preparados a partir da D-glucosamina em poucas etapas. Na primeira etapa, foram obtidas as iminas derivadas 2a ou 2b. As iminas resultantes foram protegidas nos grupamentos OH ligados nas posições C1, C3, C4 e C6, por grupos acetila. Desproteção seletiva do grupamento amino ligado na posição C2, e posterior acoplamento com ácido cinâmico, forneceu o composto 5. Todos os compostos foram testados como agentes antimicrobiannos contra microorganismos gram-positivos e gram-negativos. Os melhores resultados foram obtidos quando o composto 2b foi utilizado.

Submitted by MARCIA ROVADOSCHI (marciar@unifra.br) on 2018-08-14T19:20:28Z No. of bitstreams: 2 Dissertacao_MauraZibiaurreDosSantos.pdf: 1335791 bytes, checksum: 7c6832365c99c38917af3d9b5b44e517 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-08-14T19:20:28Z (GMT). No. of bitstreams: 2 Dissertacao_MauraZibiaurreDosSantos.pdf: 1335791 bytes, checksum: 7c6832365c99c38917af3d9b5b44e517 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2010-03-26 / In the present work, several compounds derived from monosacharide D-Glucosamine were synthetized. These compounds were used successfully against gram-positive and gram-negative microorganisms. In the synthesis of compounds, classical methods in organic chemistry were used. All steps of synthesis are shown in the Scheme below. The products were readily prepared from D-Glucosamine in few easy steps. In the first step, we have obtained he imine derivatives 2a or 2b. The resultant imines were protected in the OH groups at C1, C3, C4 and C6 positions with acetyl group. Selective desprotection of C2 aminogroup and coupling with cmnamic acid fford compound 5. All compounds were tested as antimicrobial agents against gram-positive and gram-negative microorganisms. Best results were obtained when compound 2b was used. / No presente trabalho, foram sintetizados vários compostos derivados da D-Glucosamina. Estes compostos foram usados com sucesso contra microorganismos grampositivos e gram-negativos. Na síntese dos compostos, foram utilizados métodos clássicos em química orgânica. Todas as etapas da síntese estão resumidas no esquema abaixo. Os produtos foram facilmente preparados a partir da D-glucosamina em poucas etapas. Na primeira etapa, foram obtidas as iminas derivadas 2a ou 2b. As iminas resultantes foram protegidas nos grupamentos OH ligados nas posições C1, C3, C4 e C6, por grupos acetila. Desproteção seletiva do grupamento amino ligado na posição C2, e posterior acoplamento com ácido cinâmico, forneceu o composto 5. Todos os compostos foram testados como agentes antimicrobiannos contra microorganismos gram-positivos e gram-negativos. Os melhores resultados foram obtidos quando o composto 2b foi utilizado.

O objetivo do presente estudo é o de comparar funcionalmente ehistologicamente o efeito terapêutico da glicosamina em relação a diacereína no modelo experimental de artrose em ratos. Trinta ratos Wistar foram submetidos a meniscectomia medial do joelho direito. Dez animais receberam 50mg/kg/dia de diacereína a partir do 3o até o 7o mês de pósoperatório (PO), dez animais receberam 40mg/kg/dia de glicosamina e dez animais não receberam nenhuma medicação. Todos foram sacrificados no 7o mês PO. Foram medidos os ângulos de extensão máxima de cada joelho. A análise histológica com hematoxilina-eosina e alcian blue foi feita de cada um dos côndilos tibiais e femorais. Todos os joelhos operados apresentaram amplitude de extensão do joelho mais limitada que o lado contra-lateral (p=0,001), porém os que receberam diacereína apresentavam menor rigidez (p=0,005). Histologicamente, o modelo experimental levou a uma artrose de leve a moderada estatisticamente diferente do joelho contra-lateral não operado (p=0,001). Já os joelhos dos ratos que fizeram uso das medicações não apresentaram diferenças significativas (p=0,3) entre aqueles que tomaram glicosamina e os que fizeram uso da diacereína. As diferenças entre os joelhos operados medicados e não medicados também não foram estaticamente diferentes. Conclusões: O uso terapêutico da diacereína e glicosamina diminuiu a rigidez articular e retardou a progressão da artrose. A diacereína atuou melhor na mobilidade articular do que a glicosamina, porém não houve diferença estatística entre as duas drogas no controle da degeneração articular / The purpose of this study is to compare, based on a functional and histological analysis, the therapeutic effects of glucosamine as compared to diacerhein in an experimental model of arthritis in rats. Thirty Wistar rats were submitted to a medial meniscectomy of the right knee. Ten animals received 50 mg/kg/day of diacerhein from the third through seventh postoperative (PO) months, ten animals received 40mg/kg/day of glucosamine and ten animals received no medication at all. All of these animals were sacrificed during the seventh PO month. The maximum angle of each knee extension was measured. A histological analysis was carried out by hematoxilin-eosin and alcian blue staining of each of the tibial and femoral condyles. All the operated knees presented a more limited range of extension than the non-operated knees (p=0.001), however, the animals that received diacerhein presented less stiffness (p=0.005). Histologically, the experimental model caused a light to moderate arthritis statistically different from the other non-operated knee (p=0.001). No significant differences (p=0.3) were detected between the knees of the rats medicated with glucosamine and those that received diacerhein. The operated medicated knees and non-operated knees also showed no statistical differences. Conclusion: The therapeutic use of diacerhein and glucosamine decreased joint stiffness and delayed the progression of the arthritis. The diacerhein had a more positive effect on joint mobility than the glucosamine, even though there was no statistical difference between the two drugs in controlling the degeneration of the joint

M.Tech. (Homoeopathy) / Osteoarthritis (OA) is a musculoskeletal condition affecting the synovial joints of the body, most commonly the knee and hip (Colledge et al., 2010). OA is the most prevalent joint disorder worldwide (Ickinger & Tikly, 2010). The prevalence of OA of the knee in developing countries, including South Africa, is expected to increase due to the increase in obesity and life-expectancy (Woolf & Pfleger, 2003). OA not only impacts negatively on many areas of the patient’s personal life, but it also has a considerable impact on health care systems and cost to the patient (Lapsley et al., 2001; Majani et al., 2005). The two main complaints in patients suffering from OA of the knee are knee pain and decreased daily functionality, such as walking (Samson et al., 2007). The main aim of conventional treatment is pain reduction. This treatment does not prevent progression of the OA, and may have negative side-effects (Day & Graham, 2005). Treatments for OA, such as OsteoEze GoldTM, may provide an effective and safer alternative. The aim of this study is to determine the effect of OsteoEze GoldTM on pain and functional ability in osteoarthritis of the knee using the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale: knee version (Appendix D) and the Short Physical Performance Battery (SPPB) test (Appendix E). This was a 16-week study, conducted at the Homoeopathic Health Centre, Doornfontein campus (DFC), University of Johannesburg (UJ). The study was randomised, double blind placebo controlled, and matched pairs were utilised. Sixty-seven participants, who satisfied the inclusion and exclusion criteria, were recruited, and 48 of the participants completed the study. Participants were recruited by advertisements, placed in and around the UJ Homoeopathy Health Centre (with relevant permission given) and by word of mouth. The participants were split into two groups using matched pairs according to age, gender and severity of symptoms (Appendix H). The participants in group A received the OsteoEze GoldTM capsules, and the participants in group B received the placebo capsules. Each capsule of OsteoEze GoldTM contained 500mg glucosamine sulphate, 267mg of chondroitin sulphate, 50mg of vitamin C and 1mg of manganese. The OsteoEze GoldTM or the placebo capsules were distributed at the initial (week-0) and second (week-8) consultations.

No description available.

Several ligands derived from D-glucosamine, designed for different catalytic reactions havebeen synthesized. The ligands for homogeneous catalysis based on 1,2-glucodiamine wereprepared, and used in reactions of allylic alkylation, hydrogenation and Michael addition.Supported Aqueous Phase Catalyst (SAPC) system was prepared from D-glucosamine anduse with very good results in Suzuki Miyaura cross coupling reactions. Catalyst was alsorecycled. Attempt to prepare ligands grafted on SBA-silica matrix were made as well asligands containing poly(ethylene) glycol moiety.

A enzima Glucosamina-6-fosfato desaminase (GlcN6P desaminase) é envolvida na conversão reversível da D-glucosamina-6-fosfato (GlcN6P) em Fru6P e amônia, como parte do caminho metabólico de aminoaçúcares como fonte de energia celular. A enzima hexamérica (peso mol. 178200) exibe uma cooperatividade homotrópica intensa em direção à GlcN6P a qual é modulada alostericamente pelo ativador N-acetil-D-glucosamina 6-fosfato (GlcNAc6P). A GlcN6P desaminase foi cristalizada no grupo espacial R32, com parâmetros de rede a = b = 125.9 &#197 e c = 223.2 &#197 e um conjunto de dados à 2.1 &#197 de resolução foi coletado usando radiação de luz síncrotron (Horjales et ai., 1992). A procura no banco de dados de seqüências OWL não mostrou homologia significante com qualquer outra família de proteína, desta maneira a determinação da estrutura foi feita pela técnica de substituição isomórfica múltipla (MIR) a partir de dois derivados, um composto de platina, o K2PtCl4 e um complexo de mercúrio, o ácido mersálico. O mapa MIR a 3 &#197 de resolução mostrou contornos claros e utilizando técnicas de nivelamento de solvente (solvent flattening) estendeu-se as fases até 2.5 &#197. A enzima cristaliza-se com dois monômeros na unidade assimétrica. A densidade eletrônica final foi interpretada com o auxílio do programa gráfico \'O\', sendo possível determinar sem ambigüidade 230 dos 266 resíduos de cada monômero; a partir daí foram usados subseqüentes mapas de Fourier diferença para a localização de todos os outros resíduos. O refinamento do modelo foi feito utilizando o programa X-PLOR (Brünger, 1993), usando a rotina simulated annealing, obtendo o fator R final de 17.4% com 348 moléculas de água e quatro íons inorgânicos de fosfato. O enovelamento do monômero tem uma estrutura do tipo &#945/&#946 com uma folha-&#946 pregueada paralela central com sete fitas com topologia 4x, 1x, 1x, -3x, -1x, -1x, envolvida por ambos os lados por oito hélices-&#945 e uma hélice 310 com duas voltas. A sexta fita da folha-&#946 central tem um prolongamento no C-terminal que faz parte de uma segunda folha-&#946 antiparalela de três fitas com topologia 2, -1. O hexâmero tem uma simetria local 32, com dois trímeros empacotados frente-a-frente com uma rotação relativa de 15&#176 em tomo do eixo de ordem 3 e ligados por pontes salinas e algumas interações hidrofóbicas em tomo do eixo não cristalográfico de ordem 2. As moléculas de cada trímero formam um contato não usual de três resíduos Cis 219 próximo ao eixo de ordem três. Os complexos com ativador alostérico (GlcNAc6P) e inibidor competitivo (2-desoxi 2-amino glucitol 6-fosfato) foram co-cristalizados isomorficamente com a estrutura nativa. Os mapas Fourier diferença mostram claramente densidades para os ligantes, definindo sem ambigüidade o sítio ativo e alostérico. O refinamento dos complexos produziu a mesma conformação da proteína nativa, na margem de erro experimental. Os sítios alostéricos (seis) estão localizados na interface adjacente dos monômeros de cada trímero e os sítios ativos (ou catalíticos) no lado externo de cada monômero, no C-terminal da folha-&#946 central. O monômero tem uma topologia com enovelamento similar a um domínio de ligação de NAD, excluindo os segmentos de aminoácidos 1-35, 145-188 e 243-266. As estruturas dos complexos e da nativa estão em um estado alostérico R em concordância com o modelo MWC para um sistema do tipo K (Monod et al, 1965). Um mecanismo alostérico similar ao da GlcN6P desaminase é encontrado na enzima fosfofrutoquinase (Evans, 1981). Um mecanismo catalítico é proposto para a reação de isomerisação-desaminação da enzima GlcN6P desaminase a partir do mecanismo geral para aldose-cetona isomerases. / The enzyme Glucosamine-6-phosphate deaminase (GlcN6P deaminase) is involved in the reversible conversion of D-glucosamine-6-phosphate (GlcN6P) into Fru6P and ammonia. The hexameric enzyme (mol.wt.=178200) exhibits an intense homotropic co-operativity towards GlcN6P which is allosterically modulated by the activator N-acetyl-D-glucosamine 6-phosphate (GlcNAc6P). The GlcN6P deaminase was crystallized in space group R32, with cell parameters a=b= 125.9 &#197 and c = 223.2 &#197 and a native dataset was collected to 2.1 &#197 resolution at a synchrotron source (Horjales et al, 1992). A search of the OWL sequences database has shown no significant homology with any other known protein family. Therefore, the structure determination will have to be achieved through the Multiple Isomorphous Replacement technique from two isomorphous derivatives, a platinum compound K2PtCl4 and a mercury complex, mersalyl acid. The MIR map at 3 &#197 resolution showed clear molecular boundaries and solvent flattening techniques (Wang, 1985) were used to extend the phase set to 2.5 &#197. The final electron density map was interpreted with the aid of the graphic program \'O\'. The enzyme crystallizes with a dimmer in the asymmetric unit and 230 out of the total 266 residues of each crystallographically independent monomer could be unambiguously identified in the map. The remaining residues were located after subsequent difference Fourier maps. The refinement was made with program X-PLOR (Brunger, 1993), using the simulated annealing routine, obtained R=17.4 % with 348 water molecules and four inorganic phosphate ions. The monomer fold shows an &#945/&#946 structure with a central 7-stranded &#946-sheet with topology 4x, 1x, 1x, -3x, -1x, -1x, surrounded on both sides by eight &#945-helices and 2-turn 310 -helix. The sixth strand of the central &#946-sheet is common to a second 3-stranded anti-parallel &#946-sheet with topology 2, -1. The hexamer has local 32 symmetry, with two trimmers packed in a face-to-face arrangement with a relative rotation of 15&#176 around the 3-fold axis, and linked together by salt-bridge and some hydrophobic contacts. The molecules of each trimmer have extensive contacts and show an unusual feature of the three Cys219 residues closely clustered around the 3-fold axis. The complexes with allosteric activator (GlcNAc6P) and inhibitor (2-deoxy-2-amino glucitol 6-phosphate) were co-crystallized isomorphously with the native structure. The difference Fourier maps shows clear density for the ligands, unambiguously defining the active and allosteric sites. The complexes refinement produced the same conformation of the native, within experimental error. The allosteric sites are located at the interfaces of adjacent monomers from each trimer and the active sites (or catalytic) lie at the external side of each monomer, at the C-terminal end of the central parallel &#946-sheet. The monomer has a similar folding topology as a typical NAD binding domain, excluding the segments of aminoacids 135, 145-188 and 243-266. The native and complexes structures are at the allosteric state R concerted with MWC model for a K-system (Monod et al, 1965). A similar allosteric mechanism is found in the enzyme phosphofructokinase (Evans, 1981). A catalytic mechanism is proposed for the isomerisation-deamination reaction of the enzyme from general mechanism for aldo-keto isomerases.

<p>Heparan sulfate (HS) is a linear polysaccharide, located on the surface and in the extracellular matrix of most cells, that regulates functions of numerous proteins. HS-protein interaction is mainly mediated by sulfate groups found in N-sulfated (NS) regions of the HS, but may also involve rare HS substituents such as N-unsubstituted glucosamine (GlcNH₂) residues. The location of GlcNH₂ in an HS-epitope recognized by the monoclonal antibody 10E4, that specifically stains the prion lesions in scrapie-infected murine brain, suggests an involvement of GlcNH₂ in prion disease and other amyloid-related disorders. HS in general is strongly associated with amyloidosis, including Alzheimer’s disease (AD). Therefore, the aims of this thesis were to structurally characterize GlcNH₂-containing HS sequences found in native tissues, to further study HS epitopes recognized by 10E4, and to investigate the possible role(s) of GlcNH₂ and other HS structures in binding to amyloid β peptide (Aβ) (core material in AD plaque lesions, also stained by 10E4).</p><p>The GlcNH₂ content (0.7-4% of total disaccharide units) varied between HS from different tissues. Most GlcNH₂ units were found in poorly modified N-acetylated (NA-) or NA/NS-domains, located toward the polysaccharide-protein linkage region.</p><p>Binding of human cerebral cortex HS to Aβ(1–40) monomers requires N-, 2- and 6-O-sulfation of HS, while binding to Aβ fibrils requires N- and 2-O-sulfation only. GlcNH₂ units do not appreciably contribute to interaction with Aβ. Aβ fibril-binding HS domains also bind to fibroblast growth factor 2 (FGF-2), indicating that Aβ (neurotoxic) and FGF-2 (neuroprotective) may compete for common binding sites in HS. However, Aβ had no effect on FGF-2-induced MAPK signaling in NIH 3T3 fibroblasts.</p><p>Continued studies on 10E4-antigenic HS epitope(s) showed that binding of 10E4 to the previously identified antigenic tetrasaccharide, ∆UA-GlcNH₂-GlcA-GlcNAc, requires the nonreducing hexuronic acid (∆UA) to be 4,5 unsaturated (induced by lyase cleavage), and thus is artificial. Further studies are needed to clarify the potential involvement of GlcNH₂ in 10E4-recognition of the native HS epitope(s).</p>