Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. Includes bibliographical references.

Thesis (PH. D.)--Michigan State College of Agriculture and Applied Science, 1933. / Description based on print version record. Bibliography: p. 22.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 103-112).

Thesis (MScAgric)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: Internal breakdown (internal browning - IB and gel breakdown - GB), over maturity and immaturity are the main factors adversely affecting the quality of exported South African plums. Maturity problems occur when plums are strip harvested, i.e., all the fruit in a block or orchard are harvested once, when the majority of the fruit are at optimum maturity. This results in both ovennature and immature fruit being harvested and contributes to a high percentage of fruit being rejected for export. In general, internal browning occurs when plums are exported under a single 10\,,, temperature regime and gel breakdown occurs when plums are exported under a dual temperature regime. However, GB can also occur at harvest in fruit that are very ripe and may occur at single low temperatures, where it would be masked by lB. While it is known that some cultivars, like 'Angeleno', can withstand a single temperature regime, others cannot. To the best of our knowledge, the reason for this difference is not understood. Many factors affect the quality of plums, including light incidence in the canopy, mineral nutrition and harvest maturity. Plums that were grown on high density training systems such as 'a V- or spindle system yielded consistently high quality fruit with low incidences of gel breakdown. This was in contrast to earlier findings where low-density training systems produced high levels of GB, especially in the lower part of the tree canopy. Branches that were shaded with 80% shade netting yielded fruit with high levels of GB, indicating that the main effect of improved canopy structure on quality was improved light management. A postharvest boron application on 'Songold' plums prior to storage had no effect on the incidence of intemal breakdown in the fruit, but did damage the cuticle, resulting in severe shrivel. However, internal conductivity and firmness measurements indicated that there was some effect of the boron on cell membranes. A more thorough investigation of pre- and postharvest application of boron is recommended in order to determine whether there could be a positive effect of boron in improving fruit quality in plums. Four cultivars of plums ('Pioneer', 'Sapphire', "Songold ' and 'Angeleno') were harvested throughout, and extending beyond, the commercial harvesting period. In all cultivars, the drop in firmness between harvests was not as great as expected and the later harvested fruit were of a similar, if not superior, quality as compared to the earlier harvested fruit. Later harvested plums tended to have higher TSS and better colour development. Contrary to what was expected, later harvested fruit did not have more internal disorders than earlier harvested fruit. This indicates the importance of harvesting at optimum maturity. 'Angeleno' plums had no internal disorders, even after five weeks of cold storage at a single low temperature. 'Pioneer' and 'Sapphire' plums were classified as climacteric and 'Songold' and 'Angeleno' were classified as suppressed climacteric based on ethylene production. The climacteric plums respired and produced ethylene at a higher rate than the suppressed climacteric plums. Climacteric plums ripened faster during shelf life than suppressed climacteric plums. Furthermore, while climacteric plums did not need a cold storage period prior to ripening, suppressed climacteric plums needed a cold storage period in order to ripen normally. The longer the cold storage period prior to transfer to higher temperatures, the faster the plums ripened and the higher the ethylene production at the higher temperature. The suppressed climacteric genotype could possibly be incorporated into plum breeding programs in order to extend the storage period and shelflife of new plum cultivars. The long storage times required to ship plums from South Africa to the export markets has necessitated research on postharvest physiology and quality of this fruit. The use of the climacteric and suppressed climacteric system to classify fruit is expected to assist in understanding the different physiological responses of the cultivars and assist in developing handling protocols. Preharvest factors, particularly light and nutrition, also playa role in postharvest quality. / AFRIKAANSE OPSOMMING: Interne verval (interne verbruining en gelverval), oorrypheid en onryp vrugte, is die hoof faktore wat die uitvoer van Suid Afrikaanse pruime negatief beïnvloed. Rypheidsprobleme ontstaan wanneer pruime gestroop-oes word, met ander woorde, al die vrugte in 'n blok of boord word geoes wanneer die meerderheid vrugte optimum rypheid bereik het. As gevolg hiervan word 'n groot persentasie vrugte vir uitvoer afgekeur, omdat hulle te ryp of nie ryp genoeg is nie. Oor die algemeen vind interne verbruining plaas wanneer vrugte onder 'n enkel lae temperatuur uitgevoer word en gelvervel vind plaas wanneer vrugte onder 'n dubbele temperatuur regime vervoer word. Gel verval kan egter in baie ryp vrugte by oes voorkom en mag by enkel lae temperature voorkom .waar dit deur interne verbruining gemaskeer sal word. Kultivars soos 'Angeleno' kan onder enkel lae temperatuur uitgevoer word sonder interne probleme, terwyl ander pruimkultivars me so uitgevoer kan word nie. So ver ons weet, word die rede hiervoor nie goed verstaan nie. Daar is baie faktore wat die kwaliteit van pruime beïnvloed, onder meer lighuishouding, minerale voeding en die rypheid waarby die pruime geoes word. Pruime wat in hoë-digtheid sisteme soos 'n V- of "spindle" groei het goeie kwaliteit vrugte met 'n lae persentasie gelverval gelewer. Dit is in teenstelling met vroeër bevindinge, waar vrugte van lae digtheid boorde hoë persentasies geverval gelewer het, veral in die onderste gedeeltes van die boom. Takke wat met 80% skadunet bedek is het hoër persentasies gelverval as die kontrole gelewer, wat aandui dat die hoof effek van die verbeterde boom struktuur op kwaliteit, verbeterde lighuishouding was. 'n Na-oes aanwending van boor op 'Songold' pruime het geen effek op die voorkoms van gelverval gehad nie, maar het die kutikula beskadig en tot hoë persentasies verrimpeling gelei. Fermheid en inteme weerstand lesings het egter getoon dat daar wel 'n effek van die boor op die selmembrane en selwande was. 'n Meer omvattende ondersoek van voor- en na-oes aanwending van boor word aanbeveel om vas te stelof daar wel 'n positiewe effek van boor in die verbetering van pruim kwaliteit is. Vier pruim kultivars, ('Pioneer', 'Sapphire', 'Songold' en 'Angeleno'), is gedurende, sowel as later as die kommersiële oesperiode geoes. In al die kultivars was die afname in fermheid kleiner as wat verwag is, en vrugte wat later geoes is het dieselfde, en soms beter, kwaliteit as die vrugte wat vroeër geoes is gehad. Pruime wat later geoes is het beter kleur en gewoonlik hoër suikers gehad. In teenstelling met wat verwag is, het pruime wat later geoes is nie meer interne verval gehad as die pruime wat vroeër geoes is nie. Dit dui die belangrikheid van optimale oesrypheid aan. 'Angeleno' het geen interne verval gehad nie, selfs na vyfweke opberging by -0.5°C. 'Pioneer' en 'Sapphire' pruirne is as klimakteries en 'Songold' en 'Angeleno' as onderdrukte klimakteries geklassifiseer, gebaseer op etileen produksie. Die klimakteriese pruime het teen 'n hoër tempo gerespireer en etileen geproduseer as die onderdrukte klimakteriese pruime. Gedurende raklewe het klimakteriese vrugte vinniger as onderdrukte klimakteriese vrugte ryp geword. Verder, terwyl klimakteriese pruime nie opbgerging by 'n lae temperatuur nodig gehad het nie, het onderdrukte klimakteriese vrugte welopberging by 'n lae temperatuur nodig gehad om normaal ryp te word. Hoe langer die koel opbergingsperiode was, hoe vinniger het die pruime ryp geword by raklewe en hoe hoër was hulle etileen produksie. Die onderdrukte klimakteriese genotipe kan moontlik in teelprogramme geïnkorporeer word om kultivars met verlengde opbergings- en raklewe te teel. Die lang vervoer tye wat benodig word om Suid Afrikaanse pruime by die uitvoer markte te kry het dit nodig gemaak om navorsing oor die na-oes fisiologie en kwaliteit van pruime te doen. Die klassifisering van pruime as klimakteries of onderdrukte klimakteries kan ons in staat stelom die verskillende fisiologiese reaksies van die kultivars te verstaan en om hanterings prosedures te ontwikkel. Voor-oes faktore, veral lighuishouding en mineraalvoecling speelook 'n rol in na-oes kwaliteit van pruime.

Ethylene-vinyl acetate co-polymers are widely used as cold-flow improving additives in diesel fuels. Although their functionality is undisputed, the mechanisms of action at a molecular level are not fully understood. Theories that EVA acts as both a nucleating agent for small wax crystals and as a crystal growth inhibitor are generally acknowledged, however the understanding of the effect of structure on additive performance is limited. Studies have been carried out using molecular simulation techniques with the aims of improving the understanding of the interactions between EVA and diesel fuels, and assessing the potential of these methods for the analysis of different additive structures and fuel compositions. Firstly, the ability of Monte Carlo simulations to predict the chemical potentials of n-alkanes in organic solvents was studied. This information would be of use in determining the characteristics of different fuel compositions. It was found that the particle insertion method used becomes more efficient as the aspect ratio of the solvent increases relative to that of the solute. Despite the identification of expected linear trends in the chemical potential of n-alkanes, it was not possible to produce high quality quantitative data using this method. The effect of vinyl acetate spacing and solvent environment on the configuration of lone EVA molecules in the liquid phase was studied. Molecular dynamics showed that closely spaced vinyl acetate groups increase the tendency of the molecule to fold at that point, whilst molecules with 2 or 3 ethylene groups in between show resistance to folding. It was shown that n-hexane as a solvent produced more folded configurations than benzene and n-hexadecane respectively. Monte Carlo simulations were also performed but were largely unsuccessful. Finally, molecular dynamics simulations were performed to study the effect of different EVA structures on the spontaneous crystallisation of n-hexadecane, and the interaction of the EVA with the resulting structures at a molecular level. It was shown that different EVAs had varying effects on the crystallisation, with trends attributed to the spacing of the vinyl acetate groups and the length and position of extended aliphatic sections of the EVA molecules. One molecule, with evenly spaced side-groups and no extended aliphatic sections was shown to fully prevent the formation of any crystalline structure within the time of the simulation where all other EVA molecules allowed some degree of wax formation to occur.

Cyanide is produced throughout a plant's life cycle alongside the hormone ethylene by oxidation of 1-aminocyclopropane-1-carboxylic acid. Production increases during certain developmental stages such as seed germination, seedling elongation, fruit ripening and senescence. Abiotic stresses increase ethylene production giving rise to `stress cyanide'. Cyanide also comes from metabolism of cyanogenic compounds. Cyanide is however, a toxic chemical which readily binds to metallo-enzymes inhibiting primary metabolic processes. Plants have mechanisms to maintain cyanide homeostasis such as the β-cyanoalanine pathway whereby cysteine reacts with cyanide forming β--cyanoalanine, mediated by β-cyanoalanine synthase and cysteine synthase. A dual nitrilase 4 enzyme then converts the β-cyanoalanine into asparagine or aspartate and ammonium. Studies have suggested that the physiological function of the pathway is not restricted to detoxification and assimilation of excess cyanide. The overall research goal was to investigate the role of the pathway in plant tolerance to water deficit and exogenous cyanide exposure in Arabidopsis thaliana. The first objective was to investigate responsiveness of the pathway to duration and intensity of water deficit and cyanide exposure. The second was to investigate the contribution of enzymes associated with the pathway to cyanide metabolism. The questions addressed were whether there is enzymatic redundancy in enzymes associated with the first step of cyanide detoxification and whether there is pathway redundancy between the β-cyanoalanine and an alternative sulfurtransferase pathway. A. thaliana Col-0 and three SALK-line mutants with a T-DNA insertion for the genesAtCysA1, AtCysC1 and AtNIT4 were grown and exposed to water stress. Physiological and biochemical measurements were taken. The results showed a transient increase in cyanide concentration and β-cyanoalanine synthase activity on exposure to stress. The response pattern was similar regardless of intensity or duration of stress. Knocking out AtCysA1 or AtCysC1 did not impair the ability of plants to metabolize cyanide and tolerate stress i.e the enzymes were functionally redundant. The AtNIT4 mutant however, was impaired in cyanide metabolism and exhibited a sensitive phenotype under both stresses, suggesting that the cyanoalanine pathway is the sole pathway in cyanide detoxification. The results show that the pathway may be an important tool in improvement of plant tolerance to abiotic stress.

Submitted by LETÍCIA RODRIGUES ALVES null (leticiarodalves@yahoo.com.br) on 2016-08-23T15:29:42Z No. of bitstreams: 1 AlvesLR_DISSERTAÇÃO+CERTIFICADO.pdf: 2471666 bytes, checksum: bbe3b90a7ad821bca3d2ff9e298beb5f (MD5) / Rejected by Ana Paula Grisoto (grisotoana@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo a orientação abaixo: A folha de aprovação deve constar após a ficha catalográfica. A versão submetida por você é considerada a versão final da dissertação/tese, portanto não poderá ocorrer qualquer alteração em seu conteúdo após a aprovação. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2016-08-24T16:10:04Z (GMT) / Submitted by LETÍCIA RODRIGUES ALVES null (leticiarodalves@yahoo.com.br) on 2016-09-05T16:31:58Z No. of bitstreams: 1 Dissertação_LR Alves - atualizada2.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-09-06T12:52:43Z (GMT) No. of bitstreams: 1 alves_l_me_jabo.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) / Made available in DSpace on 2016-09-06T12:52:43Z (GMT). No. of bitstreams: 1 alves_l_me_jabo.pdf: 1845174 bytes, checksum: 6d6d5923f6f594ad941d882c5beadab0 (MD5) Previous issue date: 2016-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A contaminação por metais pesados é um problema mundial e é uma das causas mais severas de estresse abiótico nas plantas, desencadeando perdas na produtividade e risco de contaminação para a saúde humana. A concentração de cádmio aumentou consideravelmente no meio ambiente devido a fatores antropogênicos. As plantas podem absorver o cádmio, levando a alta produção de espécies reativas de oxigênio, o que desencadeia cascatas de oxidação descontroladas, resultando em danos a planta. Com o objetivo de adicionar novas informações nesta área, foi realizada uma discussão sobre a contaminação dos solos agrícolas por metais pesados, os danos causados na homeostase celular, o sistema antioxidante de defesa e o impacto para os consumidores. Além disso, foi feito um estudo sobre a comunicação da raiz para a parte aérea durante uma condição de estresse, interconectando a resposta especifica das espécies reativas de oxigênio e a ação dos hormônios nesta comunicação. Pare este propósito, foi utilizado como ferramenta a enxertia e os mutantes hormonais para investigar a modulação da resposta antioxidante de defesa entre os órgãos. / Heavy metal contamination is a worldwide concern and one of the most severe causes of abiotic stress in plants, triggering losses in crop production and contamination risks to human health. Cadmium concentration have been increased in environment due to several anthropogenic factors. Plants can uptake cadmium, which lead to a high production of reactive oxygen species and trigger an uncontrolled oxidation cascade in cells, resulting in damages to plant. In order to gain new information about this subject, we carried out a deep discussion about heavy metal contamination in agricultural soils, damages in cell homeostasis, antioxidant defense system and the impact to food consumers. Moreover, we studied root-to-shoot communication during stress condition and the specific responses of reactive oxygen species and hormones in this communication. For this propose, we used grafted hormonal mutants as a tool to investigate the modulation of antioxidant stress responses between organs. / FAPESP: 2013/27080-4

Submitted by Natália Baraldi Cunha null (nataliabcunha@gmail.com) on 2016-09-07T13:56:55Z No. of bitstreams: 1 Tese final Natália Baraldi Cunha.pdf: 2266420 bytes, checksum: dcf97228e8c74e2d108a5822a0bca60d (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-09-09T20:21:52Z (GMT) No. of bitstreams: 1 cunha_nb_dr_bot.pdf: 2266420 bytes, checksum: dcf97228e8c74e2d108a5822a0bca60d (MD5) / Made available in DSpace on 2016-09-09T20:21:52Z (GMT). No. of bitstreams: 1 cunha_nb_dr_bot.pdf: 2266420 bytes, checksum: dcf97228e8c74e2d108a5822a0bca60d (MD5) Previous issue date: 2016-07-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introduction: The calcium oxalate is the major metabolic component involved in the formation of renal calculus. Therefore, different pharmacological approaches have been or are being proposed for the treatment of nephrolithiasis by calcium oxalate. Among them, the pyridoxine, a component of vitamin B6, has been suggested as a potential therapeutic agent that can minimize the effects of hyperoxaluria. However, the results are controversial. Objective: To evaluate the effects of pyridoxine (vitamin B6) on the urinary excretion of oxalate and its possible impact on renal disorders caused by nephrocalcinosis induced from an experimental model of hyperoxaluria in rats. Methods: It was used 60 Sprague Dawley male rats and were randomized into four groups: Group 1 [(G1: n = 15) clinical control]; Group 2 [G2: Ethylene glycol (EG) 0.5% + Vitamin D3 (VD3), n = 15], which hyperoxaluria was induced by the administration of EG diluted in water and offered in association with VD3 (Cholecalciferol) at a dose of 0.5 uM; Group 3 [G3: 0.5% EG + VD3 + pyridoxine (VB6); n = 15], which the animals received the same drugs offered to the G2 plus VB6 at a dose of 180mg / kg body weight / day; Group 4 (G4, n = 15) which the animals are supplemented only with the same dose of VB6 in G3. All animals were euthanized after 28 days of intervention and submitted a metabolic study on the urine of 24 hours; histopathological / morphometric analysis of oxidative stress in renal parenchymal and spectroscopic measurement of calcium. Results: Among the urinary parameters evaluated, there was significant reduction in the citrate in G2 compared to the control group- G1 (781.9 and 2414.4mg / L, respectively), while the oxalate was significantly increased in G2 and G3 compared to G1 (7.79, 8.94 and 2.96mg / L, respectively). The urinary calcium was significantly lower in the induced groups (G3: 0.9, G2: 1.5 and G1: 2.25mg / dL). Histomorphometric analysis revealed that only the animals of G2 and G3 developed nephrocalcinosis without, however, no substantially differences from each other in the counting of intratubular crystals were found. Similarly, considering the histopathologic analysis, only the induced animals (G2 and G3) exhibited atrophy, stromal extravasation and inflammatory infiltrate in the renal parenchyma in a similar pattern between the two groups. Regarding to the analysis of oxidative stress, an increase of lipid hydroperoxide levels associated with reduced superoxide dismutase activity and glutathione peroxidase in the G2. In the other groups, the enzyme pattern remained relatively stable compared to the control, except for catalase activity, which activity proved to be increased in all groups. In the other groups, the enzyme pattern remained relatively stable compared to the control (G1), except for the catalase activity, in which activity increased in all groups. As expected, the quantification of calcium in the renal parenchyma was significantly higher in G2 and G3 as compared to groups without induction. Conclusion: Pyridoxine was not able to produce a significant effect in the treatment and / or prevention of urinary disorders, as well as morphological, inflammatory and functional renal tissue in rats with secondary hyperoxaluria obtained from the administration of inducing agents. / Introdução: O oxalato de cálcio (OxCa) é o principal componente metabólico envolvido na formação dos cálculos renais. Por esta razão, diferentes abordagens farmacológicas foram ou estão sendo propostas para o tratamento da nefrolitíase por OxCa. Dentre elas, a piridoxina, um componente da vitamina B6, tem sido sugerida como potencial agente terapêutico capaz de atenuar os efeitos da hiperoxalúria, porém com resultados ainda controversos. Objetivo: Avaliar os efeitos da piridoxina (Vitamina B6) sobre a excreção urinária de oxalato e seu eventual impacto nas alterações renais causadas pela nefrocalcinose induzida a partir de um modelo experimental de hiperoxaluria em ratos. Métodos: Foram utilizados 60 ratos machos da raça Sprague-Dawley, randomicamente distribuídos em quatro grupos: GRUPO 1 (G1: n=15) controle clínico; GRUPO 2 [G2: Etilenoglicol (EG) a 0,5%+vitamina D3 (VD3), n=15] no qual a hiperoxalúria foi induzida a partir da administração de EG diluído em água e ofertado em associação com a VD3 (Colecalciferol) na dose de 0,5 μM; GRUPO 3 [G3: EG 0,5%+VD3+Piridoxina(VB6); n=15] onde os animais receberam as mesmas drogas ofertadas ao G2 acrescido da VB6 na dose de 180mg/kg peso/dia; GRUPO 4 (G4, n=15) animais suplementados apenas com a VB6 na mesma dose do G3. Todos os animais foram eutanasiados após 28 dias de intervenção e submetidos a estudo metabólico na urina de 24 horas; análise histopatológica/morfométrica, análise do estresse oxidativo no parênquima renal, bem como dosagem espectroscópica do cálcio. Resultados: Dentre os parâmetros urinários avaliados, observou-se significativa redução do citrato no G2 em relação ao controle (781,9, e 2414,4mg/L, respectivamente), enquanto que o oxalato mostrou-se significativamente aumentado nos G2 e G3 quando comparado ao G1 (7,79; 8,94 e 2,96mg/L, respectivamente). O cálcio urinário foi significativamente menor nos grupos induzidos (G3:0,9, G2:1,5 e G1: 2,25mg/dL). A análise histomorfométrica revelou que apenas os animais dos G2 e G3 desenvolveram nefrocalcinose sem, no entanto, apresentar diferença significativa entre si na contagem dos cristais intratubulares. Da mesma forma, considerando-se a análise histopatológica, apenas os animais induzidos (G2 e G3) exibiram atrofia, extravasamento estromal e infiltrado inflamatório no parênquima renal, em um padrão bastante semelhante entre os dois grupos. Com relação à análise do estresse oxidativo, houve aumento dos níveis do hidroperoxido de lipídeo associado à redução da atividade da superoxido dismutase e glutationa peroxidase no G2. Nos demais grupos, o padrão enzimático manteve-se relativamente estável em relação ao controle, com exceção da atividade da catalase, cuja atividade revelou-se aumentada em todos os grupos estudados. Como esperado, a quantificação do cálcio no parênquima renal foi significativamente maior em G2 e G3 quando comparado aos grupos sem indução. Conclusão: A piridoxina não foi capaz de produzir um efeito significativo no tratamento e/ou na prevenção das alterações urinárias, bem como morfológicas, inflamatórias e funcionais do parênquima renal de ratos com hiperoxalúria secundária obtida a partir da administração de agentes indutores.

Submitted by Isabela Bertanholi Leme da Silva null (isabela.b.leme@hotmail.com) on 2018-03-29T15:26:51Z No. of bitstreams: 1 TESE - Isabela Leme 2018.pdf: 1338053 bytes, checksum: f2792f34c6235d3f7f6e619cc21a2246 (MD5) / Rejected by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: problema 1: para substituição do arquivo submetido, conforme solicitado por e-mail. Assim que tiver efetuado essa correção submeta o arquivo, em PDF, novamente. 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No. of bitstreams: 1 silva_ibl_dr_bot_int.pdf: 1148926 bytes, checksum: d627f33c13d713fb2ae92530fb8ecde7 (MD5) Previous issue date: 2018-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: Embora a LTU seja conhecida pela humanidade desde a antiguidade, o real mecanismo envolvido na formação do cálculo renal ainda não foi completamente esclarecido. Trata-se de um processo complexo, envolvendo uma doença multifatorial resultante de interações entre fatores ambientais, predisposição genética e distúrbios metabólicos. Alterações nos fatores dietéticos têm sido propostas para prevenir ou minimizar o risco da litíase recorrente. Dentre estes fatores, o cranberry tem sido sugerido como potencial agente terapêutico capaz de atenuar os efeitos da hiperoxalúria, porém com resultados ainda controversos. Objetivo: Avaliar as eventuais repercussões metabólicas e histológicas decorrentes da suplementação oral da dieta com cranberry, sobre as alterações morfológicas e urinárias secundárias à hiperoxalúria provocada por agentes indutores, em um modelo experimental em ratos. Métodos: Foram utilizados 40 ratos machos da raça Sprague-Dawley, randomicamente distribuídos em quatro grupos: GRUPO 1 (G1: n=7) controle clínico; GRUPO 2 [G2: Etileno glicol (EG) a 0,5%+vitamina D3 (VD3), n=11] no qual a hiperoxalúria foi induzida a partir da administração de EG diluído em água e ofertado em associação com a VD3 (Colecalciferol) na dose de 0,5 μM; GRUPO 3 [G3: EG 0,5%+VD3+Cranberry); n=11] no qual os animais receberam as mesmas drogas ofertadas ao G2 acrescido de xarope de cranberry na dose de 800mg/kg peso/dia; GRUPO 4 (G4, n=11) animais suplementados apenas com a cranberry na mesma dose do G3. Foi coletada urina de 24 horas após 28 dias de intervenção para estudo metabólico. Neste dia os animais foram eutanasiados e os rins removidos para análise histopatológica/morfométrica, análise do estresse oxidativo no parênquima renal, bem como dosagem do cálcio no parênquima. Resultados: Dentre os parâmetros urinários avaliados, observou-se significativa redução do citrato em todos os grupos em relação ao controle, enquanto que o oxalato mostrou-se significativamente aumentado nos G2 e G3 quando comparado ao G1 (85,8, 93,6 e 51,7 mg/24h, respectivamente). O cálcio urinário foi significativamente menor nos grupos induzidos (G2: 0,84, G3: 1,07 e G1: 1,76mg/dL). A análise histomorfométrica revelou que apenas os animais dos G2 e G3 desenvolveram nefrolitíase sem, no entanto, apresentar diferença significativa entre si na contagem dos cristais intratubulares. Da mesma forma, considerando-se a análise histopatológica, apenas os animais induzidos (G2 e G3) exibiram atrofia, extravasamento estromal e infiltrado inflamatório no parênquima renal, em um padrão bastante semelhante entre os dois grupos. Com relação a análise do estresse oxidativo, os níveis de hidroperóxido de lipídio mostraram-se aumentados no grupo induzido (G2), quando comparado aos demais grupos. Como esperado, a quantificação do cálcio no parênquima renal foi significativamente maior em G2 e G3 quando comparado aos grupos sem indução. Conclusão: Embora a suplementação alimentar com cranberry tenha apresentado alguns efeitos positivos sobre a análise do estresse oxidativo, tais benefícios não foram suficientemente relevantes para impactar positivamente na redução da deposição dos cristais de OxCa e/ou na prevenção dos danos histológicos ao parênquima renal dos animais submetidos ao modelo de indução de hiperoxalúria. / Introduction: Although the importance of UTL, the actual mechanism involved in kidney stone formation has not yet been fully elucidated. It is a complex process, involving a multifactorial disease resulting from interactions between environmental factors, genetic predisposition and metabolic disorders. Changes in dietary factors have been proposed to prevent or minimize the risk of recurrent lithiasis. Among them, cranberry has been suggested as a potential therapeutic agent that can minimize the hyperoxaluria effects. However, the results are controversial. Objective: Evaluate the possible metabolic and histological repercussions resulting from oral supplementation with cranberry, on the morphological and urinary alterations secondary to hyperoxaluria, in an experimental model in rats. Methods: It was used 40 Sprague Dawley male rats and were randomized into four groups: Group 1 [(G1: n = 7) clinical control]; Group 2 [G2: Ethylene glycol (EG) 0.5% + Vitamin D3 (VD3), n = 11], which hyperoxaluria was induced by the administration of EG diluted in water and offered in association with VD3 (Cholecalciferol) at a dose of 0.5 uM; Group 3 [G3: 0.5% EG + VD3 + cranberry; n = 11], which the animals received the same drugs offered to the G2 plus cranberry at a dose of 800mg / kg body weight / day; Group 4 (G4, n = 11) which the animals are supplemented only with the same dose of cranberry in G3. 24 hours urine was collected after 28 days of intervention for metabolic study. On this day the animals were euthanized and the kidneys removed for histopathological / morphometric analysis; oxidative stress analysis; and measurement of renal parenchymal calcium. Results: Among the urinary parameters evaluated, there was significant reduction in the citrate in all the groups compared to the control group, while the oxalate was significantly increased in G2 and G3 compared to G1 (85.8, 93.6 and 51.7mg/24h, respectively). The urinary calcium was significantly lower in the induced groups (G2: 0.84, G3: 1.07 and G1: 1.76 mg/dL). Histomorphometric analysis revealed that only the animals of G2 and G3 developed nephrolithiasis without, however, no substantially differences from each other in the counting of intratubular crystals were found. Similarly, considering the histopathologic analysis, only the induced animals (G2 and G3) exhibited atrophy, stromal extravasation and inflammatory infiltrate in the renal parenchyma in a similar pattern between the two groups. Regarding to the analysis of oxidative stress, an increase of lipid hydroperoxide levels was found in induced group (G2), while compared with all others. As expected, the quantification of calcium in the renal parenchyma was significantly higher in G2 and G3 as compared to groups without induction. Conclusion: Although dietary supplementation with cranberry had some positive effects on the oxidative stress analysis, these benefits were not sufficiently relevant to reduce the deposition of CaOx crystals and / or the prevention of histological damage to the renal parenchyma in rats with secondary hyperoxaluria obtained from the administration of induced agents. / FAPESP: 2015/1006-1

Orientador: Paulo Roberto Kawano / Resumo: Introduction: The calcium oxalate is the major metabolic component involved in the formation of renal calculus. Therefore, different pharmacological approaches have been or are being proposed for the treatment of nephrolithiasis by calcium oxalate. Among them, the pyridoxine, a component of vitamin B6, has been suggested as a potential therapeutic agent that can minimize the effects of hyperoxaluria. However, the results are controversial. Objective: To evaluate the effects of pyridoxine (vitamin B6) on the urinary excretion of oxalate and its possible impact on renal disorders caused by nephrocalcinosis induced from an experimental model of hyperoxaluria in rats. Methods: It was used 60 Sprague Dawley male rats and were randomized into four groups: Group 1 [(G1: n = 15) clinical control]; Group 2 [G2: Ethylene glycol (EG) 0.5% + Vitamin D3 (VD3), n = 15], which hyperoxaluria was induced by the administration of EG diluted in water and offered in association with VD3 (Cholecalciferol) at a dose of 0.5 uM; Group 3 [G3: 0.5% EG + VD3 + pyridoxine (VB6); n = 15], which the animals received the same drugs offered to the G2 plus VB6 at a dose of 180mg / kg body weight / day; Group 4 (G4, n = 15) which the animals are supplemented only with the same dose of VB6 in G3. All animals were euthanized after 28 days of intervention and submitted a metabolic study on the urine of 24 hours; histopathological / morphometric analysis of oxidative stress in renal parenchymal and spectroscopic... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introdução: O oxalato de cálcio (OxCa) é o principal componente metabólico envolvido na formação dos cálculos renais. Por esta razão, diferentes abordagens farmacológicas foram ou estão sendo propostas para o tratamento da nefrolitíase por OxCa. Dentre elas, a piridoxina, um componente da vitamina B6, tem sido sugerida como potencial agente terapêutico capaz de atenuar os efeitos da hiperoxalúria, porém com resultados ainda controversos. Objetivo: Avaliar os efeitos da piridoxina (Vitamina B6) sobre a excreção urinária de oxalato e seu eventual impacto nas alterações renais causadas pela nefrocalcinose induzida a partir de um modelo experimental de hiperoxaluria em ratos. Métodos: Foram utilizados 60 ratos machos da raça Sprague-Dawley, randomicamente distribuídos em quatro grupos: GRUPO 1 (G1: n=15) controle clínico; GRUPO 2 [G2: Etilenoglicol (EG) a 0,5%+vitamina D3 (VD3), n=15] no qual a hiperoxalúria foi induzida a partir da administração de EG diluído em água e ofertado em associação com a VD3 (Colecalciferol) na dose de 0,5 μM; GRUPO 3 [G3: EG 0,5%+VD3+Piridoxina(VB6); n=15] onde os animais receberam as mesmas drogas ofertadas ao G2 acrescido da VB6 na dose de 180mg/kg peso/dia; GRUPO 4 (G4, n=15) animais suplementados apenas com a VB6 na mesma dose do G3. Todos os animais foram eutanasiados após 28 dias de intervenção e submetidos a estudo metabólico na urina de 24 horas; análise histopatológica/morfométrica, análise do estresse oxidativo no parênquima renal, bem com... (Complete abstract click electronic access below) / Doutor