Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-25Bitstream added on 2014-06-13T19:56:56Z : No. of bitstreams: 1 mazoti_ma_me_botfm.pdf: 303335 bytes, checksum: 4f4fd9740f381b988fb0ea70236c2a7c (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução. Cirurgia gera no paciente uma resposta inflamatória conhecida como stress. Não está esclarecido o papel dos anestésicos voláteis e venosos na modulação do perfil de citocinas inflamatórias em pacientes saudáveis submetidos a cirurgias eletivas pouco invasivas. Assim, o objetivo deste trabalho foi estudar o perfil das citocinas IL-1 , IL- 6, IL-8, IL-10, IL-12 e TNF- frente à anestesia inalatória com isoflurano e intravenosa com propofol, em pacientes saudáveis submetidos a cirurgias eletivas pouco invasivas. Métodos. Quarenta pacientes ASA I, submetidos à cirurgia de otorrinolaringologia, foram alocados ao acaso para receber anestesia com isoflurano 1 CAM (concentração alveolar mínima) (n = 20) ou com propofol 2 a 4 μg mL-1 (n = 20). Também foram administrados fentanil 5 mg kg-1 e brometo de rocurônio 0,6 mg kg-1 a todos os pacientes. Foram coletados 10 mL de sangue venoso de cada paciente em cada um dos seguintes momentos: antes do início da cirurgia e anestesia (M1), 2 h após o início da cirurgia (M2) e no dia posterior ao ato anestésico-cirúrgico (M3). As concentrações plasmáticas das interleucinas IL-1β, IL-6, IL-8, IL-10 e IL-12 e do fator de necrose tumoral TNF-α foram mensuradas em cada amostra pela técnica de citometria de fluxo, utilizando o método Cytometric Bead Array (CBA). Amostras de sangue venoso de quinze voluntários não submetidos a stress também foram coletadas como controle, dosando nessas amostras as mesmas citocinas. Resultados. A comparação das concentrações plasmáticas de citocinas entre os grupos de anestésicos (M1) e o grupo de voluntários mostrou aumento de IL-8 nos grupos propofol e isoflurano. Os pacientes dos grupos isoflurano e propofol apresentaram baixas concentrações plasmáticas das citocinas pró-inflamatórias IL-1 , IL-12 e TNF- e da anti-inflamatória... / Introduction. A surgery causes in the patient an inflammatory response known as stress. The role of volatile and venous anesthetics on the modulation of inflammatory cytokine profile in healthy patients subjected to minimally invasive elective surgeries is not elucidated. Thus, the aim of this paper was to study the profile of cytokines IL-1 , IL-6, IL-8, IL-10, IL-12 and TNF- under inhalation anesthesia with isoflurane and intravenous anesthesia with propofol in healthy patients subjected to minimally invasive elective surgeries. Methods. Forty ASA-I patients, subjected to otorhinolaryngology surgery, were randomly allocated to receive anesthesia with isoflurane 1 MAC (minimum alveolar concentration) (n = 20) or propofol 2 to 4 μg mL-1 (n = 20). Fentanyl 5 mg kg-1 and rocuronium bromide 0.6 mg kg-1 were also administered to all patients. Venous blood (10 mL) was collected from each patient at each of the following times: before the beginning of surgery and anesthesia (T1), 2 h after the beginning of surgery (T2), and on the day after the anesthetic-surgical procedure (T3). Plasma concentrations of interleukins IL-1β, IL-6, IL-8, IL-10 and IL-12 and tumor necrosis factor (TNF-α) were measured in each sample through flow cytometry technique by using the method Cytometric Bead Array (CBA). Venous blood samples from fifteen volunteers not subjected to stress were also collected as control, and the same cytokines were measured. Results. Plasma concentrations of IL-8 increased in Propofol and Isoflurane groups (T1), compared to the group of volunteers. Patients of Isoflurane and Propofol groups had low plasma concentrations of proinflammatory cytokines IL-1 , IL-12 and TNF- and anti-inflammatory cytokine IL-10 throughout the study period. On the other hand, plasma concentration of IL-6 significantly increased at T2 and T3 in the group of patients... (Complete abstract click electronic access below)

Despite being integral to the practice of surgery, the mechanisms by which general anesthetics mediate their effects remain unknown. For this reason, it is difficult to predict adverse side-effects and to determine how treatment should be modified for specific patient populations. Recent clinical studies have reported post-operative neuropsychological and behavioral abnormalities in children and protracted periods of post-operative cognitive decline in elderly patients. Definitively linking these post-operative consequences to the agents used to induce anesthesia has been difficult, due to a lack of proper clinical controls and an abundance of confounding health factors. Animal studies, have repeatedly shown that general anesthetics can be neurotoxic and lead to lasting impairments in learning and memory acquisition in both the very young and old. However, the scope and causes of these post-exposure impairments and the reasons why age seems to measurably affect outcomes remain unclear. Here we employ multi-neuronal fluorescence imaging in the nematode Caenorhabditis elegans to measure changes in neuronal activity and connectivity across the animal’s nervous system, following exposure to the volatile anesthetic isoflurane during neurodevelopment and senescence. Employing transgenic expression of the fluorescent calcium indicator GCaMP6s, we measure neuronal activity of specific command interneurons as well as across the majority of the nervous system with single cell resolution. Isoflurane exposure during developing, results changes in the transition rate between neuronal activity states and an overall increase in excitatory connectivity. Importantly these effects are dependent on cellular stress pathways involved mTOR and daf-16 but not on apoptotic cell death (medatied by ced-3). Measuring neuronal activity across the animals lifespan, we identify substantial age-related alterations to neural activity, connectivity and functional organization of the system. These include a progressive loss of system-wide organization and a corresponding shift in individual neuron activity toward higher frequencies. We also observe a specific loss of anti-correlative (i.e. inhibitory) signaling between neurons, resulting in an overall shift in the excitatory/inhibitory balance of the system. In support of this, we find that application of the GABAA agonist muscimol diminishes certain aspects of nervous system decline in aged animals. We further identify genes that either hasten or delay the progression toward senescent neural activity patterns, including the presynaptic voltage-gated Ca2+ channel UNC-2/CaV2, and also CED-4, a key mediator of the conserved cell-death pathway. Finally, imaging post-exposure consequences of isoflurane during senescence reveals long term effects on neuronal signaling that involved a decrease in excitatory connectivity, the opposite of what is observed during development. We conclude that anesthetic exposure during development cause permanent alteration in neuronal activity and signaling which involves cellular stress pathways but that these effects are distinct from long-term effect of anesthetic exposure we observe in age animals. Our studies also begin to define the changes in neuronal dynamics with age and demonstrate the importance of excitatory/inhibitory balance in this processes. Through comprehensive multi-neuronal imaging in C. elegans, we are able to measure the progressive breakdown of neuronal activity and system dynamics with age and isoflurane exposure and begin to identify the cellular processes and changes in synaptic signaling that contribute to these declines. Moreover, we leverage this platform to gain insight into the age-dependency of isoflurane-induced insult to neural systems.

Orientador: Denise Fecchio / Banca: Maria José Carvalho Carmona / Banca: Angela Maria Victoriano de Campos Sales / Resumo: Introdução. Cirurgia gera no paciente uma resposta inflamatória conhecida como stress. Não está esclarecido o papel dos anestésicos voláteis e venosos na modulação do perfil de citocinas inflamatórias em pacientes saudáveis submetidos a cirurgias eletivas pouco invasivas. Assim, o objetivo deste trabalho foi estudar o perfil das citocinas IL-1 , IL- 6, IL-8, IL-10, IL-12 e TNF- frente à anestesia inalatória com isoflurano e intravenosa com propofol, em pacientes saudáveis submetidos a cirurgias eletivas pouco invasivas. Métodos. Quarenta pacientes ASA I, submetidos à cirurgia de otorrinolaringologia, foram alocados ao acaso para receber anestesia com isoflurano 1 CAM (concentração alveolar mínima) (n = 20) ou com propofol 2 a 4 μg mL-1 (n = 20). Também foram administrados fentanil 5 mg kg-1 e brometo de rocurônio 0,6 mg kg-1 a todos os pacientes. Foram coletados 10 mL de sangue venoso de cada paciente em cada um dos seguintes momentos: antes do início da cirurgia e anestesia (M1), 2 h após o início da cirurgia (M2) e no dia posterior ao ato anestésico-cirúrgico (M3). As concentrações plasmáticas das interleucinas IL-1β, IL-6, IL-8, IL-10 e IL-12 e do fator de necrose tumoral TNF-α foram mensuradas em cada amostra pela técnica de citometria de fluxo, utilizando o método Cytometric Bead Array (CBA). Amostras de sangue venoso de quinze voluntários não submetidos a stress também foram coletadas como controle, dosando nessas amostras as mesmas citocinas. Resultados. A comparação das concentrações plasmáticas de citocinas entre os grupos de anestésicos (M1) e o grupo de voluntários mostrou aumento de IL-8 nos grupos propofol e isoflurano. Os pacientes dos grupos isoflurano e propofol apresentaram baixas concentrações plasmáticas das citocinas pró-inflamatórias IL-1 , IL-12 e TNF- e da anti-inflamatória... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction. A surgery causes in the patient an inflammatory response known as stress. The role of volatile and venous anesthetics on the modulation of inflammatory cytokine profile in healthy patients subjected to minimally invasive elective surgeries is not elucidated. Thus, the aim of this paper was to study the profile of cytokines IL-1 , IL-6, IL-8, IL-10, IL-12 and TNF- under inhalation anesthesia with isoflurane and intravenous anesthesia with propofol in healthy patients subjected to minimally invasive elective surgeries. Methods. Forty ASA-I patients, subjected to otorhinolaryngology surgery, were randomly allocated to receive anesthesia with isoflurane 1 MAC (minimum alveolar concentration) (n = 20) or propofol 2 to 4 μg mL-1 (n = 20). Fentanyl 5 mg kg-1 and rocuronium bromide 0.6 mg kg-1 were also administered to all patients. Venous blood (10 mL) was collected from each patient at each of the following times: before the beginning of surgery and anesthesia (T1), 2 h after the beginning of surgery (T2), and on the day after the anesthetic-surgical procedure (T3). Plasma concentrations of interleukins IL-1β, IL-6, IL-8, IL-10 and IL-12 and tumor necrosis factor (TNF-α) were measured in each sample through flow cytometry technique by using the method Cytometric Bead Array (CBA). Venous blood samples from fifteen volunteers not subjected to stress were also collected as control, and the same cytokines were measured. Results. Plasma concentrations of IL-8 increased in Propofol and Isoflurane groups (T1), compared to the group of volunteers. Patients of Isoflurane and Propofol groups had low plasma concentrations of proinflammatory cytokines IL-1 , IL-12 and TNF- and anti-inflammatory cytokine IL-10 throughout the study period. On the other hand, plasma concentration of IL-6 significantly increased at T2 and T3 in the group of patients... (Complete abstract click electronic access below) / Mestre

Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia–reperfusion injury (IRI)— Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. Methods: Medical data of 105 patients undergoing SPKT between 1998–2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included “IRI- associated posttransplant clinical outcome” as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for “pancreatic IRI” and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. Results: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17–0.84; p = 0.029). Conclusions: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.