Submitted by Inácio Mateus Assane null (inaciomateusassane@gmail.com) on 2018-03-13T16:40:15Z No. of bitstreams: 1 Versão Final da Dissertação_Inácio Mateus Assane.pdf: 2500612 bytes, checksum: e7b1dcaa29bfec4105b34a055b4a403d (MD5) / Approved for entry into archive by Neli Silvia Pereira null (nelisps@fcav.unesp.br) on 2018-03-16T17:46:12Z (GMT) No. of bitstreams: 1 assane_im_me_jabo.pdf: 2500612 bytes, checksum: e7b1dcaa29bfec4105b34a055b4a403d (MD5) / Made available in DSpace on 2018-03-16T17:46:12Z (GMT). No. of bitstreams: 1 assane_im_me_jabo.pdf: 2500612 bytes, checksum: e7b1dcaa29bfec4105b34a055b4a403d (MD5) Previous issue date: 2018-02-28 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Os surtos de bacterioses na piscicultura são imprevisíveis, por essa razão é necessário dispor de opções terapêuticas eficazes para reduzir a morbidade e mortalidade. Para que a terapia seja eficaz, a escolha do antimicrobiano deve se basear nas informações farmacocinéticas do fármaco no hospedeiro, nas condições de produção e na sensibilidade do patógeno. No Brasil, atualmente só dois antimicrobianos são legalizados para uso na aquicultura, a oxitetraciclina (OTC) e o florfenicol (FFC), os quais muitas vezes são ineficazes. Destes, somente o FFC é autorizado para tratar bacterioses em tilápia-do-Nilo, a espécie mais produzida no país. Este cenário nos levou a investigar a atividade antimicrobiana do tianfenicol (TAF) contra as principais bactérias patogênicas de peixes cultivados no Brasil. Foi determinada a concentração inibitória mínima (CIM) e a concentração bactericida mínima (CBM) do TAF para 49 cepas isoladas de surtos de bacteriose ocorridos no período 2011 a 2017 em três estados. Adicionalmente, avaliou-se a atividade antimicrobiana do TAF (G1: 10 mg/kg), do FFC (G2: 10 mg/kg) e da combinação do TAF com o FFC (G3: TAF+FFC: 5 + 2,5 mg/kg e G4: 2,5 + 1,25 mg/kg) no tratamento de aeromonose em tilápia-do-Nilo experimentalmente infectadas com Aeromonas hydrophila. Como resultado do estudo in vitro, mais da metade das cepas testadas foram sensíveis ao TAF, sendo que os gêneros Aeromonas, Lactococcus e Vibrio foram os mais sensíveis. No estudo in vivo, o TAF foi eficaz no tratamento da aeromonose em tilápia-do-Nilo, tanto isolado como combinado. Os grupos G1, G2, G3, G4 e o controle apresentaram uma taxa de sobrevivência de 88,33 ± 11,55%; 70 ± 10%; 73,33 ± 11,55%; 85,93 ± 5,13% e 3,33 ± 5,77%, respectivamente, sendo todos diferentes do controle (p < 0,001). Os resultados do estudo sugerem que o TAF pode ser uma boa opção de tratamento de aeromonose, lactococose e vibriose em peixes. Além disso, a combinação do TAF com o FFC apresentou um efeito sinérgico, mostrando que é possível reduzir a quantidade de antimicrobiano e obter o mesmo efeito terapêutico. / Outbreaks of bacterial diseases in fish farm are unpredictable; therefore, it is necessary to have effective therapeutic options to reduce the morbidity and mortality. For effective therapy, the anticipated pharmacokinetics and antibacterial activity of the antimicrobial in the target fish species under the given conditions must be considered before decide which antimicrobial to use. In Brazil, only two antimicrobials are approved for use in aquaculture, oxytetracycline (OTC) and florfenicol (FFC), which are often innefective. Moreover, only FFC is approved for use to treat bacterial diseases in Nile tilapia, the main specie in Brazil. This scenario led us to investigate the antibacterial activity o thiamphenicol (TAP) against the main bacteria infecting fishes in Brazil. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of TAP were determined for 49 strains isolated from diseases outbreaks registered during 2011 – 2017 in three States. Additionally the antibacterial activity of TAP (10 mg kg-1), FFC (10 mg kg-1) and TAF combined with FFC (G3: TAF+FFC: 5 + 2.5 mg kg-1 e G4: 2.5 + 1.25 mg kg-1) against Aeromonas hydrophila in Nile tilapia aeromoniosi models were evaluated. More than half of the tested strains were in vitro sensitive to TAP, being TAP highly potent against Aeromonas, Lactococcus, and Vibrio. The in vivo therapy with TAP alone and combined with FFC was effective to treat aeromoniosis in Nile tilapia. Groups G1, G2, G3, G4 and control had survival rate of 88.33 ± 11.55%; 70 ± 10%; 73.33 ± 11.55%; 85.93 ± 5.13% e 3.33 ± 5.77%, respectively, all being different from the control (p < 0,001). These findings suggest the potential of TAP as a treatment option for aeromoniosis, lactococcosis and vibriosis. The combination of TAF and FFC has a synergy effect, showing that it is possible to reduce the amount of antimicrobial while maintaining the therapeutic effectiveness. / 190049/2015-4

In zwei Kälberbeständen wurde die therapeutische Wirksamkeit des Breitband-Antibiotikums Florfenicol mit und ohne zusätzliche Kombination des nichtsteroidalen Antiphlogistikums Flunixin-Meglumin bei der Behandlung von bovinen Respirationskrankheiten getestet. Anhand von bakteriologischen und serologischen Untersuchungsbefunden werden die jahreszeitlichen sowie altersabhängigen Beziehungen zwischen der Tiergesundheit, dem Nachweis bakterieller Infektionserreger, C-reaktivem Protein, Anti-Lipid A-Antikörpern und dem Gehalt an Endotoxin aufgezeigt. Florfenicol erwies sich aufgrund seines mikrobiologischen Profils sowie seiner Wirksamkeit für die Behandlung der Enzootischen Bronchopneumonie als gut geeignet. Flunixin-Meglumin stellt hinsichtlich seiner analgetischen, antipyretischen und antiphlogistischen Eigenschaften eine sinnvolle und sichere Ergänzung zur antibiotischen Therapie bei bovinen Respirationserkrankungen dar.

Eine effektive Strategie zur Verhinderung der Ausbreitung von Infektionskrankheiten in der Aquakultur ist die Anwendung geeigneter Präventionsmaßnahmen, insbesondere die Impfung von Fischen. Das effektivste Impfverfahren stellt die individuelle Injektion des Impfstoffes dar. Bei Milliarden von Fischen jährlich ist dies jedoch sehr zeit- und kostenintensiv. Bei Säugetieren gilt Niederfrequenz-Sonophorese (LFS) als eine der fortschrittlichsten Technologien zur transdermalen Verabreichung von Wirkstoffen. So entstand die Idee, bei Fischen die Aufnahme von Wirkstoffen während einer Tauchbadbehandlung mit Hilfe von LFS zu verbessern. Die vorliegende Arbeit zeigt, dass mit einer Beschallungsintensität von etwa 60 mW/cm^2 die Aufnahme eines Bakterienimpfstoffs in das Kiemengewebe von Regenbogenforellen um den Faktor 240 erhöht werden konnte. Bei dieser Intensität traten geringe oder keine Nebenwirkungen auf. Bei höheren Beschallungsintensitäten wurde eine noch höhere Aufnahme des Bakterienimpfstoffes, aber auch schädliche Nebenwirkungen beobachtet. Darüber hinaus zeigte LFS eine durch eine lokale Entzündungsreaktion und Aktivierung von T-Helferzellen in den Kiemen charakterisierte, Adjuvans-ähnliche Wirkung. Ein Impfversuch mit Koi Karpfen und einem inaktivierten Impfstoff gegen das Koi-Herpesvirus zeigte, dass LFS das Potential hat, den mit einer Tauchbadimpfung erzielbaren Immunschutz zu verbessern. LFS konnte auch für die Verabreichung anderer Substanzen wie Antibiotika verwendet und die Aufnahme von Oxytetracyclin um den Faktor fünf erhöht werden. Zusammenfassend lässt sich sagen, dass die Effektivität einer Tauchbadimpfung von Fischen mit LFS durch die gesteigerte Impfstoffaufnahme und dessen Adjuvans-ähnlichen Wirkung verbessert werden kann. Darüber hinaus könnte mithilfe LFS die therapeutische Dosis von Antibiotika bei Badbehandlungen verringert werden. Es erfordert jedoch noch weitere Studien, um diese Technologie aus dem Labor in die Praxis zu übertragen. / In aquaculture, the use of prevention methods, such as vaccination of fish, is an effective strategy to avoid infectious diseases. However, the most effective route of vaccination for fish is the one-by-one intraperitoneal injection, which that is very laborious and expensive to apply for billions of fish every year. Low Frequency Sonophoresis (LFS) has been recognized as one of the most advanced technologies in transdermal delivery of substances in mammals. Thus, it has been suggested to use LFS to enhance the uptake of substances in fish during bath treatments. The present study shows that a low sonication intensity of ca. 60 mW/cm^2 at 37 kHz increased the uptake of a bacterin into the gill tissue of rainbow trout by up to a factor of 240. At this intensity, no or only minimal side effects occurred. At higher sonication intensities, an even higher bacterin uptake but also deleterious side effects were observed. In addition, LFS showed an adjuvant-like effect characterized by a local inflammatory response and T-helper cell activation in the gills. A vaccination trial with koi carp and an inactivated vaccine against the Koi Herpes Virus (KHV) showed that LFS has the potential to enhance the immune protection achieved by immersion vaccination. In addition LFS can also be used for the administration of other substances, such as antibiotics, here we showed that the uptake of Oxytetracycline could be increased by factor five. In summary, the efficacy of the immersion vaccination of fish could be improved by low-frequency ultrasound due, to the increased vaccine uptake along with its adjuvant-like effect. Furthermore, LFS could also reduce the required therapeutic dose of antibiotics in bath treatments, making them more effective, cheaper and environmentally friendly. However, further practical studies will be required to transfer this technology from the lab to the field.