Submitted by Alessandra Portugal (alessandradf@ioc.fiocruz.br) on 2013-09-17T15:45:54Z No. of bitstreams: 1 Tese Biologia Parasitaria Michele Costa da Silva.pdf: 12475456 bytes, checksum: 609ce8de504a83a73a1066ce6c810c6c (MD5) / Made available in DSpace on 2013-09-17T15:45:54Z (GMT). No. of bitstreams: 1 Tese Biologia Parasitaria Michele Costa da Silva.pdf: 12475456 bytes, checksum: 609ce8de504a83a73a1066ce6c810c6c (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / O munícipio de Sumidouro é localizado na região serrana do estado do Rio de Janeiro, onde a infecção por Schistosoma mansoni tem sido descrita em humanos e em roedores silvestres. A população humana vem sendo submetida a sucessivos programas de controle desde a década de 1950. Vários estudos indicam que o rato d’água (Nectomys squamipes) é um reservatório natural de S. mansoni, a sua presença em localidades endêmicas, pode prejudicar os programas de controle da esquistossomose. Em condições de laboratório, vermes adultos de S. mansoni apresentam plasticidade fenotípica induzida por modificações no microambiente do parasita, principalmente durante a primeira passagem em condições de laboratório. Em nosso estudo, avaliamos o efeito do praziquantel (PZQ) no isolado R, isolado de N. squamipes naturalmente infectados, provenientes de Sumidouro, utilizando parâmetros parasitológicos e morfológicos. Os parâmetros parasitológicos (ovos eliminados nas fezes, a redução de vermes adultos e o oograma) foram utilizados para avaliar os efeitos do PZQ no isolado R de S. mansoni. Utilizamos também, um isolado de laboratório (isolado BH) como controle. Camundongos infectados com 50 cercárias foram tratados por via oral com PZQ nas seguintes dosagens: 62,5mg/kg (grupo 1), 125mg/kg (grupo 2), 250mg/kg (grupo 3) e 500mg/kg (grupo 4). Cada dose foi dividida em 3 dias (49, 50 e 51 dias pós-infecção). Os dados foram analisados usando o teste estatístico ANOVA. Nos experimentos com o isolado R, não foram observados ovos nas fezes com as doses 250mg/kg e 500mg/kg (p<0,05), enquanto a excreção em BH chegou à zero com todas as doses. A redução da carga parasitária foi significativamente maior (p<0,05) nas duas concentrações maiores testadas de PZQ, independente do isolado. Com 62,5mg/kg, a porcentagem de ovos imaturos variou de 17% (isolado R) à 38% (isolado BH). Na dosagem de 125mg/kg, a porcentagem de ovos imaturos variou de 20% (isolado R) à 16% (isolado BH). Com 250mg/kg, a contagem de ovos imaturos caiu significativamente à 1% (isolado R) e à 4% (isolado BH). Com 500mg/kg, não foram encontrados ovos imaturos no isolado R, enquanto que em BH o valor era de 8%. Nenhuma dosagem afetou, significativamente (p>0,05), a porcentagem de ovos maduros, independente do isolado. Todos os grupos tratados apresentaram um grande aumento na quantidade de ovos mortos, com diferenças significativas (p<0,001) de 62% e 64% nos grupos 3 e 4, respectivamente (isolado R). A porcentagem de ovos mortos subiu de 34% (grupo 1) para 58% (grupo 3) no isolado BH. Embora o grupo 4 tenha mostrado um pequeno aumento na porcentagem de ovos mortos (46%), foi significativamente maior (p<0,001) comparado com os 8% do controle. Os helmintos machos do isolado R (grupos 3 e 4) apresentaram diminuição dos tubérculos. Dos espécimes fêmeas analisados do isolado R, 44% (grupo 3) não apresentaram ovo. O isolado BH, também apresentou diminuição de tubérculos nos helmintos machos (grupos 3 e 4). Os lobos testiculares dos vermes dos grupos tratados apresentaram área e comprimento menor em relação aos helmintos recuperados de camundongos não tratados. Os nossos dados demonstram que o isolado silvestre testado é susceptível ao PZQ. / Sumidouro municipality is a mountain region of the Rio de Janeiro state, where natural schistosomiasis mansoni has been described in both human and water rat population. The human population has been submitted to successive control programs since around 1955. A number of studies suggest that water rat (Nectomys squamipes) is one natural reservoir of Schistosoma mansoni, which may implicate as a confounding factor for control programs of schistosomiasis. Under laboratory conditions, S. mansoni adult worms present phenotypic plasticity induced by modifications in the parasite's microenvironment, mainly during the first passage under laboratory conditions. In our study the effects of praziquantel (PZQ) were evaluated on the isolate (R) first isolated from naturally-infected N. squamipes from Sumidouro by parasitological and morphological parameters. The therapeutic effects of PZQ against a S. mansoni isolate derived from N. squamipes (isolate R) and a susceptible isolate (BH) were analyzed in Swiss mice by fecal egg counting, adult worm load and oogram pattern. Infected mice were orally administrated with 62.5mg/kg; 125mg/kg 250mg/kg and 500mg/kg, each dose divided over 3 days (49, 50 and 51 days after infection). The data were analyzed using one-way analysis of variance (ANOVA). In regard to isolate R, no fecal eggs were observed with 250mg/kg and 500mg/kg (p < 0.05), whereas BH excretion reached zero with all doses. Mean worm burden reduction was significantly (p < 0.05) higher at the two highest concentrations tested of PZQ, regardless of isolate. At 62.5mg/kg, the percentage of immature eggs varied from 17% (isolate R) to 38% (BH isolate). At 125mg/kg, the percentage of immature eggs varied from 20% (isolate R) to 16% (isolate BH). At 250mg/kg, immature eggs dropped significantly to 1% (isolate R) and 4% (isolate BH). At 500mg/kg, no immature eggs were found in isolate R, whereas in BH was 8%. No dosage significantly (p > 0.05) affected the percentage of mature eggs, regardless of isolate. There was a large increase in the percentages of dead eggs in all treated groups with significant (p < 0.001) increases of 62% and 64% in groups 3 and 4, respectively (isolate R). The percentage of dead eggs rose from 34% (group 1) to 58% (group 3) in isolate BH. Although group 4 showed lowest increase in the percentage of dead eggs (46%), it was significantly higher (p < 0.001) compared to the 8% in the control. Male worms from isolate R (groups 3 and 4) showed decrease of the tubercles. In female worms from isolate R, 44% (group 3) showed no egg. The isolate BH also showed decrease of the tubercles in male worms (groups 3 and 4). In general, morphometric values of reproductive system (testicular lobes) specimens grown in treated mice were lower than those of control mice. Our findings indicate that the wild isolate from N. squamipes is susceptible to PZQ.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:21:19Z (GMT) No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) / Made available in DSpace on 2017-06-07T19:21:19Z (GMT). No. of bitstreams: 1 IzadoraDeSouza_DISSERT.pdf: 2477888 bytes, checksum: 7568590836d5bc820ccba775908ac117 (MD5) Previous issue date: 2015-07-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Cristais l?quidos (CL) possuem um arranjo molecular bastante estruturado que combina propriedades dos estados l?quido e s?lido, bem como o fluxo dos l?quidos e a ordena??o da estrutura cristalina dos s?lidos. Foram testadas t?cnicas de alta e baixa energia para produzir CL, utilizando oleato de s?dio, fosfatidilcolina de soja, ?leo de soja, N-metilpirrolidona (NMP) e ?gua. As intera??es entre NMP e oleato de s?dio da formula??o foram investigadas. CL obtidos por t?cnica de alta energia foram caracterizados por microscopia de luz polarizada (MLP), reologia e tamanho de part?cula. MLP exibiu estruturas que sugerem presen?a de CL lamelares. Na reologia, as amostras apresentaram viscosidade newtoniana limitante nas curvas de fluxo e uma diminui??o no grau de estrutura??o nos testes oscilat?rios, quando a concentra??o de NMP diminu?a. Uma nova t?cnica para obter sistemas lip?dicos de libera??o de f?rmacos foi desenvolvida a partir da dilui??o de CL produzidos por baixa energia. CL foram produzidos por agita??o magn?tica e, posteriormente, foram dilu?dos com ?gua e solu??o aquosa de NMP 10%, a 25 ? C e 70 ?C, em que foram avaliados tamanho de got?cula e incorpora??o de praziquantel (PRZ). Os sistemas dilu?dos com ?gua apresentaram menor faixa de tamanho (165,22 ? 381,26 nm) e maior faixa de incorpora??o de PRZ (40,96 ? 43,44 mg/mL) quando comparadas com as dilu?das com a solu??o de NMP. N?o houve contribui??o da solu??o de NMP para a forma??o de got?culas menores e para a maior incorpora??o de PRZ. Houve um aumento na solubilidade do PRZ em sistemas dilu?dos com ?gua, aumentando a fra??o sol?vel de f?rmaco em at? 200 vezes quando comparada ? sua solubilidade em ?gua. Testes utilizando Espalhamento de raios-X a baixo ?ngulo e MLP comprovaram a transi??o da mesofase lamelar para sistemas com micelas vermiformes, confirmando o sucesso da nova t?cnica em obter sistemas lip?dicos de libera??o de f?rmacos atrav?s da dilui??o de CL. / Liquid crystalline mesophase (LC) have an organized molecular arrangement and combining properties of liquid and solid state as the flow of liquids and the ordered and crystalline structure of solids. High- and low energy techniques were used to produce LC. N-methylpyrrolidone (NMP) and sodium oleate interactions with the system were investigated. LC fabricated by high-energy method were characterized by polarizing light microscopy (PLM), rheology and droplet size. PLM showed structures that indicated lamellar phases. Surface tension no important difference between the samples was observed. Rheology showed a zero shear viscosity in flow curves with a shear-thinning behavior in oscillatory tests, which with increasing of NMP, there was a decrease in degree of structure. Novel method to obtain lipid based drug delivery system (LBDDS) were developed through LC dilution and drug-loading was tested. LC fabricated with low-energy method was diluted with water and NMP 10% aqueous solution, at 25 ?C and 70 ?C, which droplet size and drug loading were evaluated. The systems diluted with water showed lower range size (165.22 nm- 381.26 nm) and higher drug-loading (40.96 mg/mL - 43.44 mg/mL) when compared with systems diluted by NMP solution. NMP aqueous solution did not contribute to form smaller particle size and higher praziquantel-loading. An increment in the apparent solubility of Praziquantel was achieved from incorporation in dilution of LC with water, increasing the soluble drug fraction approximately 200-fold when compared with water solubility. Small angle X-ray scattering (SAXS) measurements and PLM comproved the transition from lamellar mesophase to worm-like micelle systems confirming the success of new techinique for obtain LBDDS from LC dilution.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T21:45:30Z No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-07T19:30:54Z (GMT) No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) / Made available in DSpace on 2017-06-07T19:30:54Z (GMT). No. of bitstreams: 1 JairoSoteroNogueiraDeSouza_DISSERT.pdf: 2124011 bytes, checksum: 0d7ba6395004ada41813188b5d73116b (MD5) Previous issue date: 2016-11-28 / A utiliza??o de ciclodextrinas para aumentar a solubilidade de f?rmacos em solu??o aquosa tem sido bastante estudada. No presente estudo, o mecanismo de intera??o do praziquantel (PZQ) com a beta-ciclodextrina e com a hidroxipropil-beta-ciclodextrina na presen?a dos co-solventes trietanolamina (TEA) e a N-metilpirrolidona (NMP) foi realizado com o objetivo do aumento da solubilidade do praziquantel. Atrav?s dos diagramas de solubilidade e dos diagramas de Job?s Plot foi poss?vel observar a forma??o de complexos sol?veis com estequiometria 1:1. A presen?a dos co-solventes TEA e NMP diminuiu a estabilidade e solubilidade dos complexos formados, no entanto atrav?s dos estudos de modelagem molecular foi mostrado que este efeito pode facilitar a sa?da do f?rmaco da cavidade e, consequentemente, beneficiar a absor??o do f?rmaco. Os resultados mostraram-se elucidativos e bastantes promissores na obten??o futura de complexos que possam ser utilizados para melhor biodisponibilidade do praziquantel. / The use of cyclodextrin (CD) to enhace the praziquantel (PZQ) water solubility has been widely studied in the literature. In this present paper, the interaction has not yet studied between the PZQ and both the beta-cyclodextrin (?-CD) and hydroxyl-propyl-cyclodextrin (HP-?-CD) or its association with the solvents triethanolamine (TEA) and N-methyl-pyrrolidone (NMP) was carefully conducted with the purpose to enhance the water solubility of the PZQ. The solubility diagrams and job?s plot diagrams showed that water soluble complexes were formed with 1:1 stoichiometry. The association of the complexes with the TEA and NMP diminished considerably the complex stability and its solubility. However, throught the molecular modeling study it was showed that this effect may be beneficial for the output of the drug from the CD cavity, and consequently to benefit the drug absorption. The results showed up adequately enlightening to propose that these systems can be investigated to enhance the PZQ bioavailability.

The aim of the study was to assess the effects of orally applied praziquantel on the treatment efficacy against most abundant tapeworms (Atractolytocestus huronensis Anthony, 1958 and Khawia sinensis Hsü, 1935) of common carp (Cyprinus carpio Linnaeus). Naturally infected fish (one-year-old; K1+) were divided into 3 trial groups containing 17 specimens and administered with praziquantel mixed in heat-treated amyloid vehicle (in doses of 50 mg.kg-1 body weight). In 3 groups of control, the fish were administered amyloid vehicle only. Fish were examined by using of gut dissection 2, 4 and 6 days after administration. At 48 hours post-treatment, significantly lower prevalence of both parasites was found. The invasion of A.huronensis was fully eliminated in all fish after 96 hours whereas some specimens of K.sinensis still persisted in the gut of few fish. The full elimination of both parasites was observed 6 days after administration. Our results showed that elimination of K. sinensis takes longer than elimination of A.huronensis. The dose of 50 mg kg-1 of orally applied praziquantel is effectual to control A.huronensis and K sinensis infections in common carp successfully. The effect of oral applied praziquantel on the hematology and biochemical parameters blood of common carp (Cyprinus carpio L.), infected by the tapeworms Atractolytocestus huronensis and Khawia sinensis was the object of analyse. It was the partial goal of the work. The infected fishes were divided to the six groups. The praziquantel was applied stirred in amyloid vehicle in dose 30 mg/kg of quick materiality for two groups and for two to other groups in dose 50mg/kg of quick materiality. Only clean amyloid vehiculum was applied to two control groups. Blood taking and resulting patoanatomic investigation was effected 24 and 96 hours after application of praziquantel. Results of hematology investigation of blood obtained 24 hours after the application point on significant fall (p< 0,01) of the number of erythrocytes, hemoglobin and hematocrit in both groups E1 and E3, which achieved the original surface after 96 hours. The significant upsurge (p<0,05) of the surface serum hepatic enzyme ALT was recorded after 96 hours.

>Magister Scientiae - MSc / Aquaculture is a vast industry all over the world and has increased significantly during the past 30 years. In South Africa, finfish aquaculture farms stretch from Gansbaai to as far as Richards bay with the potential of extending into Mozambique. The future success of this fast growing industry in South Africa strongly relies on the development of the supporting sector such as government legislation, sponsorship, participation of the pharmaceutical industry and research and development in aquatic organism health management. Diplectanum oliveri Williams, 1989, a monogenean gill parasite of both Argyrosomus japonicus (Temminck & Schlegel, 1843) (dusky kob) and A. inodorus Griffiths & Heemstra, 1995 (silver kob) is currently regarded in South Africa as the most persistent ectoparasite associated with the culture of both fish species, causing pathological tissue changes in the areas associated with attachment and feeding which can result in stock losses. The egg production of D. oliveri was used to evaluate and develop a method to quantify monogenean infections on fish, by counting the eggs produced by infra-populations of these parasites over a 24-hour period and to determine the reliability of this method as a non-invasive/non-destructive method to quantify the intensity of an individual infra-population of parasites on a single host. Currently, Diplectanum spp. on dusky kob are being controlled in local mariculture facilities using methods and drugs that are traditionally used for monogeneans (flukes) and are regarded as effective. Most of these drugs are, however, no longer approved for use in food fish and none of them has proven to be very effective in controlling D. oliveri in culture facilities, which can result in subsequent re-infections of epidemic proportion. Currently, there are no anthelmintics registered for aquaculture in South Africa. An registered anthelmintic used in terrestrial animals (sheep, goats, cattle and ostriches) containing praziquantel was tested at various concentrations and exposures against D. oliveri on A. japonicus to determine the efficacy of two different formulations and the potential for "off label" use. The 20 ppm (high) praziquantel concentration treatments eliminated all adult parasites, but caused significant measureable stress and affected the central nervous system of the fish, which resulted in death of all fish in the solution group after 18 hours. The 2 ppm (low) concentrations failed to remove all adult parasites. Although both the 2 hour (short) exposure/high concentration and 24 hour (long) exposure/low concentration of the suspension formulation were effective, but only the short exposure/high concentration eliminated all adult parasites with little change in behaviour by the treated fish.

Japanese yellowtail Seriola quinqueradiata has been commercially farmed in Japan since the 1940s. In comparison, sea-cage farming of yellowtail kingfish Seriola lalandi in Australia is still developing, with commercial production commencing in 1998. In Australia, S. lalandi is parasitised by Zeuxapta seriolae and Benedenia seriolae. In Japan, S. quinqueradiata is parasitised by Heteraxine heterocerca and B. seriolae. These monogeneans affect industries in both countries and management of these parasites is required to prevent impacts on fish health and commercial losses. I investigated efficacy (% reduction of mean parasite abundance) for orally administered praziquantel, fenbendzole and oxfendazole against Z. seriolae and B. seriolae on S. lalandi and the efficacy of orally administered praziquantel and febantel against H. heterocerca and B. seriolae on S. quinqueradiata. Medications were administered to fish by surface coating feed pellets or via direct intubation of the stomach. Seriola lalandi administered fenbendazole and oxfendazole by surface coating of feed had lower abundance of the gill parasite Z. seriolae. Seriola quinqueradiata intubated with febantel had lower abundance of the gill parasite H. heterocerca. Neither fenbendazole nor oxfendazole administered to S. lalandi in Australia, nor febantel administered to S. quinqueradiata in Japan resulted in a lower abundance of the skin parasite B. seriolae. Praziquantel was first administered to S. lalandi by surface coating of feed. Fish rejected medicated feed, suggesting praziquantel affected its palatability. Fish treated with feed medicated with praziquantel had fewer Z. seriolae and B. seriolae than untreated fish. Praziquantel administered to S. lalandi by intubation allowed a more accurate dose to be tested without differential feeding or reduced palatability obstructing results, and resulted in fewer Z. seriolae (99.5-100 % reduction) and B. seriolae (91 – 97.7 % reduction). Intubated praziquantel also led to fewer recruitment life stages of Z. seriolae and B. seriolae, even at low doses, but did not completely eliminate them from S. lalandi. Praziquantel administered to S. lalandi alone and combined with cimetidine had high efficacy (>99%) against Z. seriolae. In comparison, praziquantel administered alone resulted in fewer B. seriolae (68.3 – 69.7 % reduction) than the same doses of praziquantel combined with cimetidine (36.9 – 40.9 % reduction). A 90.4 -100% reduction in H. heterocerca was achieved when praziquantel was administered by intubation to S. quinqueradiata in Japan but there was only a 22-77.8 % reduction in B. seriolae. The dose of PZQ (150 mg kg⁻¹ body weight day⁻¹ for 3 days) on the label of a commercially available product used to treat B. seriolae in Japanese aquaculture resulted in a 50.9% reduction against B. seriolae, but completely eliminated H. heterocerca. In trials against Z. seriolae and B. seriolae on S. lalandi in South Australia, I also screened 27 other anthelmintics and antiparasitics from the chemical groups: amprolium derivatives, benzimidazoles, benzyl ureas, diphosphate salts, imidazothiazoles, macrocyclic lactones, nitromidazoles, organophosphates, piperazines, salicylanilides, substituted phenols and tetrahydropyrimidines. Of these, only the benzimidazole, albendazole, was effective against Z. seriolae and none appeared to have an effect against B. seriolae. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1459172 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2010

Japanese yellowtail Seriola quinqueradiata has been commercially farmed in Japan since the 1940s. In comparison, sea-cage farming of yellowtail kingfish Seriola lalandi in Australia is still developing, with commercial production commencing in 1998. In Australia, S. lalandi is parasitised by Zeuxapta seriolae and Benedenia seriolae. In Japan, S. quinqueradiata is parasitised by Heteraxine heterocerca and B. seriolae. These monogeneans affect industries in both countries and management of these parasites is required to prevent impacts on fish health and commercial losses. I investigated efficacy (% reduction of mean parasite abundance) for orally administered praziquantel, fenbendzole and oxfendazole against Z. seriolae and B. seriolae on S. lalandi and the efficacy of orally administered praziquantel and febantel against H. heterocerca and B. seriolae on S. quinqueradiata. Medications were administered to fish by surface coating feed pellets or via direct intubation of the stomach. Seriola lalandi administered fenbendazole and oxfendazole by surface coating of feed had lower abundance of the gill parasite Z. seriolae. Seriola quinqueradiata intubated with febantel had lower abundance of the gill parasite H. heterocerca. Neither fenbendazole nor oxfendazole administered to S. lalandi in Australia, nor febantel administered to S. quinqueradiata in Japan resulted in a lower abundance of the skin parasite B. seriolae. Praziquantel was first administered to S. lalandi by surface coating of feed. Fish rejected medicated feed, suggesting praziquantel affected its palatability. Fish treated with feed medicated with praziquantel had fewer Z. seriolae and B. seriolae than untreated fish. Praziquantel administered to S. lalandi by intubation allowed a more accurate dose to be tested without differential feeding or reduced palatability obstructing results, and resulted in fewer Z. seriolae (99.5-100 % reduction) and B. seriolae (91 – 97.7 % reduction). Intubated praziquantel also led to fewer recruitment life stages of Z. seriolae and B. seriolae, even at low doses, but did not completely eliminate them from S. lalandi. Praziquantel administered to S. lalandi alone and combined with cimetidine had high efficacy (>99%) against Z. seriolae. In comparison, praziquantel administered alone resulted in fewer B. seriolae (68.3 – 69.7 % reduction) than the same doses of praziquantel combined with cimetidine (36.9 – 40.9 % reduction). A 90.4 -100% reduction in H. heterocerca was achieved when praziquantel was administered by intubation to S. quinqueradiata in Japan but there was only a 22-77.8 % reduction in B. seriolae. The dose of PZQ (150 mg kg⁻¹ body weight day⁻¹ for 3 days) on the label of a commercially available product used to treat B. seriolae in Japanese aquaculture resulted in a 50.9% reduction against B. seriolae, but completely eliminated H. heterocerca. In trials against Z. seriolae and B. seriolae on S. lalandi in South Australia, I also screened 27 other anthelmintics and antiparasitics from the chemical groups: amprolium derivatives, benzimidazoles, benzyl ureas, diphosphate salts, imidazothiazoles, macrocyclic lactones, nitromidazoles, organophosphates, piperazines, salicylanilides, substituted phenols and tetrahydropyrimidines. Of these, only the benzimidazole, albendazole, was effective against Z. seriolae and none appeared to have an effect against B. seriolae. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1459172 / Thesis (Ph.D.) -- University of Adelaide, School of Earth and Environmental Sciences, 2010

Human schistosomiasis popularly known as bilharzias in many regions of Africa is a freshwater snail-transmitted disease caused by parasitic flatworms known as schistosomes. The growth and development of schistosomes typically requires developmental stages in multiple hosts and transmission stages in freshwater. These life cycle environments present a plethora of stressors. Certain gene families including heat shock proteins (HSPs/Hsps) and universal stress proteins (USPs) help schistosomes to respond to unfavourable conditions. The availability of genomes sequences information for Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium provide unique research resources to apply bioinformatics analysis of its associated USPs to predict regulatory features from sequence analysis. The objectives of the research were to (i) Infer the biochemical and environmental regulation of universal stress proteins of Schistosoma species; (ii) Identify biological function relevant protein sequence and structure features for prioritized universal stress proteins from Schistosoma species; (iii) Determine the distinctive structural features of a predicted regulator of Schistosoma adenylate cyclase activity that has possible influence on the functioning of universal stress proteins. The findings revealed that (i) schistosomes USPs are hydrophilic and very reactive in the water environment or in aqueous phase, which seems adaptive with their immediate environment and developmental stages; (ii) The functions of Smp_076400 and Sjp_0058490 (Q86DW2) are regulated by conserved binding site residues and metallic ions ligands (Ca2+, Mg2+ and Zn2+), particularly Ca2+ predicted to bind to both USPs; (iii) The S. mansoni life cycle and stress resistance pathway protein (Smp_059340.1) is regulated by Ser53, Thr188, Gly210 and Asp207 residues. The overall scope has highlighted the role of bioinformatics in predicting exploitable regulatory features of schistosome universal stress proteins and biological pathways that might lead to identification of putative functional biomarkers of common environmental diseases. The findings of this research can be applicable to other areas of environmental health and environmental genomics. / Environmental Sciences / (D. Litt et Phil. (Environmental Sciences)

Human schistosomiasis popularly known as bilharzias in many regions of Africa is a freshwater snail-transmitted disease caused by parasitic flatworms known as schistosomes. The growth and development of schistosomes typically requires developmental stages in multiple hosts and transmission stages in freshwater. These life cycle environments present a plethora of stressors. Certain gene families including heat shock proteins (HSPs/Hsps) and universal stress proteins (USPs) help schistosomes to respond to unfavourable conditions. The availability of genomes sequences information for Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium provide unique research resources to apply bioinformatics analysis of its associated USPs to predict regulatory features from sequence analysis. The objectives of the research were to (i) Infer the biochemical and environmental regulation of universal stress proteins of Schistosoma species; (ii) Identify biological function relevant protein sequence and structure features for prioritized universal stress proteins from Schistosoma species; (iii) Determine the distinctive structural features of a predicted regulator of Schistosoma adenylate cyclase activity that has possible influence on the functioning of universal stress proteins. The findings revealed that (i) schistosomes USPs are hydrophilic and very reactive in the water environment or in aqueous phase, which seems adaptive with their immediate environment and developmental stages; (ii) The functions of Smp_076400 and Sjp_0058490 (Q86DW2) are regulated by conserved binding site residues and metallic ions ligands (Ca2+, Mg2+ and Zn2+), particularly Ca2+ predicted to bind to both USPs; (iii) The S. mansoni life cycle and stress resistance pathway protein (Smp_059340.1) is regulated by Ser53, Thr188, Gly210 and Asp207 residues. The overall scope has highlighted the role of bioinformatics in predicting exploitable regulatory features of schistosome universal stress proteins and biological pathways that might lead to identification of putative functional biomarkers of common environmental diseases. The findings of this research can be applicable to other areas of environmental health and environmental genomics. / Environmental Sciences / (D. Litt et Phil. (Environmental Sciences)

Submitted by Anderson Silva (avargas@icict.fiocruz.br) on 2012-05-23T17:52:57Z No. of bitstreams: 1 aline_f_galvao_ioc_bp_0012_2010.pdf: 3755366 bytes, checksum: 56aff28b3b15de796039925e6364d082 (MD5) / Made available in DSpace on 2012-05-23T17:52:58Z (GMT). No. of bitstreams: 1 aline_f_galvao_ioc_bp_0012_2010.pdf: 3755366 bytes, checksum: 56aff28b3b15de796039925e6364d082 (MD5) Previous issue date: 2010 / CNPq/Fiocruz - FAPERJ/Fiocruz / Fundação Oswaldo Cruz.Instituto Oswaldo Cruz. Rio de janeiro, RJ, Brasil / A esquistossomose é uma das doenças parasitárias mais prevalentes no mundo, sendo a quimioterapia com praziquantel (PZQ) a principal estratégia adotada para seu controle. No entanto, faltam informações sobre o impacto da quimioterapia com PZQ sobre a infecção por Schistosoma mansoni nas condições enfrentadas pelos programas de controle, e ainda não há prova de princípio sobre o melhor regime de dosagem a ser utilizado. Um ensaio clínico randomizado duplo-cego foi realizado com o objetivo de avaliar o impacto do tratamento em dose única de PZQ 60 mg/kg na infecção por S. mansoni comparado à dose padrão de PZQ 40 mg/kg em adolescentes do município de São Lourenço da Mata. Um inquérito coproscópico preliminar selecionou indivíduos para a triagem e aqueles que se adequaram aos critérios de inclusão/exclusão foram recrutados e tratados com dose única de 40 mg/kg ou 60 mg/kg de PZQ. Inquéritos coproscópicos de acompanhamento foram realizados aos 21, 180 e 360 dias pós-tratamento. A prevalência e a intensidade de infecção foram comparadas nos quatro momentos do estudo nos dois grupos de tratamento utilizando tabelas de contingência (Qui-quadrado ou teste exato de Fisher) e ANOVA. A influência de outras variáveis no estudo foi avaliada através da análise de regressão logística. Um levantamento malacológico foi realizado para verificar a infecção natural da espécie hospedeira local, Biomphalaria straminea. A análise da distribuição espacial da infecção nos dois grupos antes e depois (180 e 360 dias) do tratamento foi realizada pela estimativa de densidade de kernel para a detecção de aglomerados de casos. Ao todo, 123 adolescentes (10-19 anos) de São Lourenço da Mata, PE, com mais de 100 ovos por grama de fezes foram examinados nos quatro momentos do estudo. Embora todos os pacientes estivessem negativos 21 dias após o tratamento, 17,9% e 30,9% estavam positivos após 180 e 360 dias, respectivamente. Tanto a prevalência quanto a intensidade de infecção após o tratamento foram significativamente maiores (P < 0,05) no regime de 40 mg/kg do que no de 60 mg/kg. Os sujeitos do sexo masculino e os que foram tratados com PZQ 40 mg/kg tiveram uma chance significativamente maior de estarem positivos 360 dias pós-tratamento. As taxas de infecção natural mensais de B. straminea variaram de 0 a 2,2%. Os aglomerados de prevalência de infecção aos 180 e aos 360 dias tiveram maior densidade e extensão nos sujeitos tratados com 40 mg/kg do que nos tratados com 60 mg/kg. Recomenda-se a dose de PZQ 60 mg/kg para o tratamento dos portadores da infecção por S. mansoni em áreas endêmicas no Brasil, já que, embora tanto a terapia com dose única de PZQ 40 mg/kg quanto com 60 mg/kg tenham tido um impacto alto e comparável na infecção 21 dias após o tratamento, os sujeitos que receberam a dose maior foram capazes de manter níveis significativamente mais baixos tanto de prevalência quanto de intensidade de infecção por até um ano após o tratamento. Os resultados espaciais confirmam os dados parasitológicos e reforçam a necessidade de que medidas preventivas auxiliares sejam integradas com a quimioterapia para se obter um impacto maior sobre o controle da doença. / Schistosomiasis is one of the most prevalent parasitic diseases in the world, and chemotherapy with praziquantel (PZQ) is the main strategy for its control. However, information about the impact of chemotherapy with PZQ on Schistosoma mansoni infection under conditions faced by control programmes is missing, and there is no proof of principle about the best dosing regimen to be used. A randomized, double- blind clinical trial was conducted to evaluate the impact of treatment with the single dose 60 mg/kg PZQ on S. mansoni infection compared to the standard dose of 40 mg/kg PZQ in adolescents from the municipality of São Lourenço da Mata. A preliminary parasitological survey selected individuals for screening and those who filled the inclusion/exclusion criteria were recruited and treated with either 40 mg/kg or 60 mg/kg single dose PZQ. Follow-up stool surveys were performed at 21, 180 and 360 days post-treatment. Prevalence and intensity of infection were compared between treatment groups in the four assessments using contingency tables analysis and Analysis of Variance, respectively. The influence of other variables in the study was assessed by logistic regression analysis. A snail survey was conducted to verify the natural infection rates of the local intermediate host species, Biomphalaria straminea. Spatial analysis of infection in both groups before and after treatment was performed by estimating the kernel density for the detection of clusters of positive cases. Altogether, 123 adolescents (10-19 years) from São Lourenço da Mata, PE, with more than 100 eggs per gram of feces were examined in the four assessments. Although all patients were negative 21 days after treatment, 17.9% and 30.9% were positive at 180 and 360 days, respectively. Both prevalence and intensity of infection after treatment were significantly higher (P <0.05) in the 40 mg/kg regime than in the 60 mg/kg one. The male subjects and those who were treated with 40 mg/kg had a significantly higher chance of being positive 360 days post-treatment than those treated with 60 mg/kg. The monthly infection rates of B. straminea ranged from 0 to 2.2%. Clusters of positive subjects treated with 40 mg/kg had a higher density and extent than those treated with 60 mg/kg both at 180 and 360 days. It is recommended that the 60 mg/kg PZQ dose should be maintained for treatment of S. mansoni infection in endemic areas in Brazil, as both therapy with 40 mg/kg or 60 mg/kg PZQ single doses had a high and comparable impact on infection 21 days after treatment and subjects who received the higher dose were able to maintain lower levels of both prevalence and intensity of infection for up to one year after treatment. The spatial results confirm the parasitological data and reinforce the need of auxiliary, preventive measures integrated with chemotherapy to achieve a greater impact on disease control.