The binding of [³H]opioid ligands to homogenates prepared from the spinal cords of rat and other species has been studied. Similar numbers of sites were seen in all areas of the cord when measured in a rostrocaudal direction. There was found to be approximately 2 x higher density of sites in the dorsal half of the cord compared with the ventral half. Binding studies suggested a similar relative distribution of mu, delta and kappa sites in all areas of the cord. The results are discussed in relation to the reported distribution of opioid peptides. In the above study the kappa binding site was defined as the binding of [³H] unselective opioids in the presence of cold ligands to suppress binding to mu- and delta-sites. Competitive binding assays, however, suggested this site did not have the properties of a single homogeneous group. Approximately 50% of the apparent kappa binding was consistent with a classical kappa site. Saturated binding assays afforded Bmax values which suggested lower 'true' kappa site numbers than previously supposed, values which were confirmed using the kappa peptide' [³H]Dynorphin A-(1-9), and the kappa selective [³H]U-69593. Heterogeneity was also seen in other central nervous system tissues. The heterogeneous nature of the kappa site may be due to different sites, due to interactions at a non-opioid site or may represent different conformations of the same site. The second possibility was discounted since observed binding followed the cellular distribution of the plasma marker Na+/K+-ATPase was stereoselective for levorphanol over dextrorphan, and fully displaceable by naloxone. The third possibility was investigated by studying the role of Na+ and MG2+ ions, which are reported to affect receptor conformation in binding assays employing brain tissues. None of the results obtained suggested that conformational changes were responsible for the observed effects, although the experiments were not exhaustive.

No description available.

En este artículo, se realizó un análisis de infiltración de agua en la presa de tierra Coltani ubicada en el departamento de Tacna, Perú. Primero, se realizó un análisis de infiltración mediante el programa Slide el cual permite evaluar flujos de agua por medio de la hipótesis flujo permanente, de manera bidimensional y con un suelo isotrópico. Luego, se estudió la infiltración del agua subterránea de la presa Coltani tanto en su condición inicial como en su condición con muro pantalla. En esta última, se consideró como referencia el caudal de infiltración máximo permisible para proponer las alternativas en relación a su ubicación. Se consideró un diámetro de 1.5 metros y una profundidad de 30 metros con posibles ubicaciones al inicio, centro y final de la presa. Finalmente, se obtuvieron diversos resultados de caudales de salida en el primer estrato del suelo demostrando el impacto generado por las diversas ubicaciones de los pilotes secantes como muro impermeable. Se obtuvo como principal resultado, la ubicación ideal de los pilotes secantes al final de la presa Coltani con un valor de infiltración del agua subterránea de 0.00276 m3/s en el estrato inicial, verificándose en relación al caudal de infiltración máximo permisible (Qfmp). / In this article, a water seepage analysis was performed in the Coltani earth dam located in the department of Tacna, Peru. First, a seepage analysis was carried out using the Slide program, which allows to evaluate water flows through the permanent flow hypothesis, in a two-dimensional way and with an isotropic soil. Subsequently, the seepage of the underground water from the Coltani dam was studied, both in its initial condition and in its condition as a barrier wall. The maximum allowable seepage flow was considered as a reference to propose the alternatives in relation to its location. A diameter of 1.5 meters and a depth of 30 meters were considered with possible locations at the beginning, center and end of the dam. Finally, various outflow results were obtained in the first soil stratum, demonstrating the impact generated by the various locations of the secant piles as an impermeable wall. The main result was the ideal location of the secant piles at the end of the Coltani dam with a groundwater seepage value of 0.00276 m3/s in the initial stratum, verified in relation to the maximum allowable seepage flow (Qfmp). / Trabajo de investigación

[ES] La sectorización de las redes ha demostrado ser una metodología estratégica en la reducción de los volúmenes incontrolados fugados, considerado uno de los principales problemas a los que tienen que enfrentarse diariamente los gestores de los sistemas de distribución de agua. Su principal objetivo es facilitar la monitorización de las redes, dividiéndolas en subsistemas, sobre los que se puede realizar un mejor y más fácil control de las anomalías en el consumo y presión. Uno de los inconvenientes que presenta esta técnica recae en su diseño. No existe una solución única, sino que atiende a diversos criterios para realizarlo. De manera generalizada, este diseño se basa en la experiencia del propio diseñador, siguiendo criterios puramente prácticos y con procesos manuales de prueba y error, cuyo grado de dificultad está vinculado al tamaño y complejidad de la propia red. Esta tesis plantea una metodología sistemática para el diseño de la sectorización de una red de distribución de agua, según criterios energéticos, con el fin de facilitar la delimitación de cada uno de los sectores de la red. Como resultado, se obtiene una organización de la red en sectores buscando una optimización energética de la misma, de tal modo que posteriores técnicas de mejora, como es el caso de la gestión de presiones, se vean favorecidas. La sectorización ha resultado ser una técnica eficaz en la búsqueda de fugas. Sin embargo, como supone una pérdida de capacidad hidráulica y una merma en la calidad del agua, esta tesis se cuestiona el planteamiento de una técnica no intrusiva alternativa que logre los mismos resultados. Así, se propone el desarrollo de una metodología que localice las fugas centrada en la interdependencia de todos los elementos y en el empleo de sensores de caudal y presión. El trabajo pone de manifiesto que es posible sectorizar la red de tal manera que se consigan mayores beneficios para la misma. Ahora bien, también es posible el empleo de otras técnicas que no requieran el cierre de tuberías pero que desprendan soluciones similares. El empleo de una técnica u otra dependerá de cada caso, de los objetivos establecidos y de la política de trabajo de cada gestor. / [CA] La sectorització de les xarxes ha demostrat ser una metodologia estratègica en la reducció dels volums incontrolats perduts, considerat un dels principals problemes als quals han d'enfrontar-se diàriament els gestors dels sistemes de distribució d'aigua. El seu principal objectiu és facilitar la monitorització de les xarxes, dividint-les en subsistemes, sobre els quals es pot realitzar un millor i més fàcil control de les anomalies en el consum i pressió. Un dels inconvenients que presenta aquesta tècnica recau en el seu disseny. No existeix una solució única, sinó que atén diversos criteris per a realitzar-ho. De manera generalitzada, aquest disseny es basa en l'experiència del propi dissenyador, seguint criteris purament pràctics i amb processos manuals de prova i error, el grau de dificultat del qual està vinculat a la grandària i complexitat de la pròpia xarxa. Aquesta tesi planteja una metodologia sistemàtica per al disseny de la sectorització d'una xarxa de distribució d'aigua, segons criteris energètics, amb la finalitat de facilitar la delimitació de cadascun dels sectors de la xarxa. Com a resultat, s'obté una organització de la xarxa en sectors buscant una optimització energètica d'aquesta, de tal manera que posteriors tècniques de millora, com és el cas de la gestió de pressions, es vegen afavorides. La sectorització ha resultat ser una tècnica eficaç en la cerca de fuites d'aigua. No obstant això, com suposa una pèrdua de capacitat hidràulica i una disminució en la qualitat de l'aigua, aquesta tesi es qüestiona el plantejament d'una tècnica no intrusiva alternativa que aconseguisca els mateixos resultats. Així, es proposa el desenvolupament d'una metodologia que localitze les fuites d'aigua centrada en la interdependència de tots els elements i en l'ús de sensors de cabal i pressió. El treball posa de manifest que és possible sectoritzar la xarxa de tal manera que s'aconseguisquen majors beneficis per a aquesta. Ara bé, també és possible l'ús d'altres tècniques que no requerisquen el tancament de canonades però que desprenguen solucions similars. L'ús d'una tècnica o una altra dependrà de cada cas, dels objectius establits i de la política de treball de cada gestor. / [EN] The sectorization of networks has proven to be a strategic methodology in the reduction of uncontrolled leakage volumes, considered one of the main problems that water distribution system managers must face on a daily basis. Its main objective is to facilitate the monitoring of the networks, dividing them into subsystems, on which a better and easier control of anomalies in consumption and pressure can be performed. One of the drawbacks of this technique lies in its design. There is no single solution, but it is based on different criteria. In general, this design is based on the designer's own experience, following purely practical criteria and with manual trial and error processes, whose degree of difficulty is linked to the size and complexity of the network itself. This thesis proposes a systematic methodology for the design of the sectorization of a water distribution network, according to energy criteria, in order to facilitate the delimitation of each of the sectors of the network. As a result, an organization of the network in sectors is obtained, looking for an energetic optimization of the same, in such a way that later improvement techniques, such as pressure management, are favoured. Sectorization has proven to be an effective technique in the search for leaks. However, as it implies a loss of hydraulic capacity and a decrease in water quality, this thesis questions the approach of an alternative non-intrusive technique that achieves the same results. Thus, it is proposed the development of a methodology to locate the leaks focused on the interdependence of all the elements and the use of flow and pressure sensors. The present work shows that it is possible to sectorize the network in such a way as to achieve greater benefits for the network. However, it is also possible to use other techniques that do not require pipe closure but provide similar solutions. The use of one technique or another will depend on each case, on the established objectives and on the working policy of each manager. / Salguero Barceló, FJ. (2021). La sectorización basada en criterios energéticos como herramienta para la gestión hídrica de redes de distribución de agua [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/178235 / TESIS

It was generally accepted that dopamine receptors D1 (D1R)- and D2 (D2R)-expressing neurons are homogeneously and randomly distributed throughout the striatum. However, in reporter transgenic mice, the specific subregions of the caudal lateral striatum have been reported: the D1R-poor zone, in which D2R-expressing neurons are predominant, and the D2R-poor zone, in which D1R-expressing neurons are predominant. The present study demonstrated the presence of these distinct subregions not only in rodents but also in marmosets using endogenous dopamine receptors. We also showed that direct pathway medium spiny neurons in these distinct subregions preferentially project to parvalbumin-positive GABAergic neurons in the dorsal part of the substantia nigra pars lateralis. / 博士(理学) / Doctor of Philosophy in Science / 同志社大学 / Doshisha University

Post-traumatic stress disorder (PTSD) is a psychiatric condition caused by exposure to a traumatic event. Veterans are at especially high risk of PTSD. In Canada, in a survey conducted in 2016, 16% of Regular Force Veterans released during 1998-2015 reported having PTSD, which is at least two times higher than the estimated prevalence rate in the general population. Individuals with PTSD experience a range of debilitating symptoms, such as the intrusion of unwanted and distressing memories, persistent flashbacks, hypervigilance and nightmares. The neuropathophysiological mechanisms underlying symptoms of PTSD are not well understood, which remains a significant barrier to developing effective treatments. Hallmark PTSD symptoms such as hyperarousal and sleep disturbances may be related to dysregulation of noradrenaline (NA), a neurotransmitter produced in the locus coeruleus (LC) known to modulate cognition, arousal and sleep. This thesis examines the possible associations between dysregulation in rapid-eye-movement (REM) sleep and dysfunction in NA-containing neurons in the LC among veterans with PTSD. Twenty-two operationally deployed veterans with a history of PTSD were recruited through the Royal Ottawa Mental Health Centre in Ontario, Canada. A novel, non-invasive neuroimaging method, neuromelanin-sensitive magnetic resonance imaging (NM-MRI), was used to detect a by-product of NA called neuromelanin (NM) in the LC of each participant. Then a contrast-to-noise ratio (CNR) was calculated to obtain a marker of the NA function. The LC was segmented into three subdivisions to assess whether the association between NM and REM sleep may differ across regions of the LC. As hypothesized, we observed different associations between NM and REM sleep across regions of the LC. After controlling for antidepressant usage, there was (i) a moderate, negative, significant correlation between the percentage of REM sleep and rostral LCCNR, r(19) = -.476, p = .029, (ii) a weak positive non-significant correlation between the percentage of REM sleep and caudal LCCNR, r(19) = .33, p = .145, and (iii) no significant correlation between REM sleep percentage and LCCNR in the middle LC, r(19) = -.04, p = .876. This thesis is the first study to show that NM and REM sleep may be related in veterans with PTSD and that this relationship may vary across subdivisions of the LC. These results improve understanding of REM sleep among individuals with PTSD. The results may stimulate the investigation of novel pharmacotherapy focused on sleep disturbances in PTSD, the development of personalized treatments for PTSD, and the search for clinical biomarkers of PTSD based on brain function. The current study also made methodological contributions that may be applicable beyond the research on PTSD to the field of REM sleep and the NA system. Specifically, the current study showed the suitability of the NM-MRI method for examining the connections between NM and REM sleep, and it showed that segmenting the LC can lead to a more nuanced understanding of its role in the human body.

No description available.

Les anomalies du tube neural (ATN) sont des malformations congénitales parmi les plus fréquentes chez l’humain en touchant 1-2 nouveau-nés par 1000 naissances. Elles résultent d’un défaut de fermeture du tube neural pendant l’embryogenèse. Les formes les plus courantes d'ATN chez l'homme sont l'anencéphalie et le spina-bifida. Leur étiologie est complexe impliquant à la fois des facteurs environnementaux et des facteurs génétiques. Un dérèglement dans la signalisation Wnt, incluant la signalisation canonique Wnt/β-caténine et non-canonique de la polarité planaire cellulaire (PCP), peut causer respectivement le cancer ou les anomalies du tube neural (ATN). Les deux voies semblent s’antagoniser mutuellement. Dans cette étude, nous investiguons les rôles de Lrp6 et deANKRD6, entant qu’interrupteurs moléculaires entre les deux voies de signalisation Wnt, et CELSR1, en tant que membre de la PCP, chez la souris mutante Skax26m1Jus, générée par l’agent mutagène N-Ethyl-N-Nitrosuera, et dans une cohorte de patients humains ATN. Pour Lrp6, nous avons démontré que Skax26m1Jus représente un allèle hypermorphe de Lrp6 avec une augmentation de l’activité de la signalisation Wnt/canonique et une diminution de l’activité JNK induite par la voie PCP. Nous avons également montré que Lrp6Skax26m1Jus interagit génétiquement avec un mutant PCP (Vangl2Lp) où les doubles hétérozygotes ont montré une fréquence élevée d’ATN et des défauts dans la polarité des cellules ciliées de la cochlée. Particulièrement, notre étude démontre l'association des nouvelles et rares mutations faux-sens dans LRP6 avec les ATN humaines. Nous montrons que trois mutations de LRP6 causent une activité canonique réduite et non-canonique élevée. Pour ANKRD6, nous avons identifié quatre nouvelles et rares mutations faux-sens chez 0,8% des patients ATN et deux chez 1,3% des contrôles. Notamment, seulement deux, des six mutations validées (p.Pro548Leu et p.Arg632His) ont démontré un effet significatif sur l’activité de ANKRD6 selon un mode hypomorphique. Pour CELSR1, nous avons identifié une mutation non-sens dans l'exon 1 qui supprime la majeure partie de la protéine et une délétionde 12 pb. Cette perte de nucléotides ne change pas le cadre de lecture et élimine un motif putatif de phosphorylation par la PKC " SSR ". Nous avons également détecté un total de 13 nouveaux et rares variants faux-sens qui avaient été prédits comme étant pathogènes in silico. Nos données confirment le rôle inhibiteur de Lrp6 dans la signalisation PCP pendant la neurulation et indiquent aussi que les mutations faux-sens identifiées chez LRP6 et ANKRD6 pourraient affecter un équilibre réciproque et un antagonisme très sensible à un dosage précis entre les deux voies Wnt. Ces variants peuvent aussi agir comme facteurs prédisposants aux ATN. En outre, nos résultats impliquent aussi CELSR1 comme un facteur de risque pour les anomalies du tube neural ou l’agénésie caudale. Nos résultats fournissent des preuves supplémentaires que la voie de signalisation PCP a un rôle pathogène dans ces malformations congénitales et un outil important pour mieux comprendre leurs mécanismes moléculaires. / Neural tube defects (NTDs) are among the most common congenital malformations in humans affecting 1–2 infants per 1000 births. NTDs are caused by failure of the neural tube to close during embryogenesis. The most common forms of NTDs in humans are anencephaly and spina bifida. Their etiology is complex implicating environmental and genetic factors. Wnt signaling has been classified as canonical Wnt/ β-catenin dependent or non-canonical planar cell polarity (PCP) pathway. Misregulation of either pathway is linked mainly to cancer or neural tube defects (NTDs) respectively. Both pathwaysseem to antagonize each other. In this study, we investigate the role of Lrp6andANKRD6 as molecular switches between both Wnt pathways as well as CELSR1 as PCP member, in a novel ENU mouse mutant of Lrp6 (Skax26m1Jus) and in human NTDs. For Lrp6, we demonstrate that Skax26m1Jus represents a hypermorphic allele of Lrp6 with increased Wnt canonical and abolished PCP-induced JNK activities. We also show that Lrp6Skax26m1Jusgenetically interacts with a PCP mutant (Vangl2Lp) where double heterozygotes showed an increased frequency of NTDs and defects in cochlear hair cells’ polarity. Importantly, our study also demonstrates the association of rare and novel missense mutations in LRP6 that is an inhibitor rather than an activator of the PCP pathway with human NTDs. We show that three LRP6 mutations in NTDs led to a reduced Wnt canonical activity and enhanced PCP signaling. For ANKRD6: We identified four rare missense mutations in 0.8% of the NTD patients and 2 rare missense mutations in 1.3% of the controls. Notably, when all 6 mutations were validated, only two mutations identified in NTD patients, p.Pro548Leu, p.Arg632His, significantly altered DIVERSIN activity in Wnt signaling assays in a hypomorphic fashion. For CELSR1: We identified one nonsense mutation in exon 1 of CELSR1 that truncates the majority of the protein in one NTD patient and one in-frame 12 bp deletion that removes a putative PKC phosphorylation“SSR” motif in one caudal agenesis patient. We also detected a total of 13 novel missense variants in 12 patients (11 NTDs and 1 caudal agenesis) that were predicted to be pathogenic in silico. Our data confirm an inhibitory role of Lrp6 in PCP signaling in neurulation and indicate that rare missense mutations in LRP6 and ANKRD6 could affect a balanced reciprocal and a highly dosage sensitive antagonism between both Wnt pathways in neurulation and act as predisposing factors to NTDs in a subset of patients. Also, our findings implicate CELSR1 as a risk factor for NTDs or caudal agenesis. Our findings provide additional evidence for a pathogenic role of PCP signaling in thesemalformations and an important tool for better understanding their molecular mechanisms.

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No. of bitstreams: 2 Dissertaçao - Lara Marques Naves - 2018.pdf: 4245553 bytes, checksum: 32754e93d07b1f96bc7f0b9a2bc618ff (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-02 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Hemodynamic and cardiovascular benefits from the hypertonic saline solution (HS) use in the hypotensive hemorrhage (HH) treatment have been reported for several years. Recent investigations have shown the participation of central nervous system (CNS) regions, such as A1 neuronal clusters (located in the caudal ventrolateral medulla; CVLM), A2 neuronal clusters (located in the nucleus of the solitary tract; NTS) and the Median Preoptic Nucleus (MnPO) on hemodynamic responses induced by sodium chloride overload in normovolemic animals. However, the role of the above structures in cardiovascular recovery and autonomic changes induced by HS solution administration in animals submitted to HH has not yet been evaluated. Thus, the present study evaluated the A1, A2 neuronal clusters and MnPO nucleus involvement in the cardiovascular and autonomic responses promoted by HS solution infusion in hypovolemic animals. For this, wistar rats (280-320 g) were separated into four protocols: I. A2 neuronal cluster lesion (A2 Sham: n = 6; A2 Experimental: n = 6); II. A1 neuronal cluster lesion (A1 Sham: n = 6; A1 Experimental: n = 6); III. A1 and A2 neural clusters concomitant lesions (A1 + A2 Sham: n = 6; A1 + A2 Experimental: n = 6) and IV. Pharmacological inhibition of MnPO (MnPO Sham: n = 6; MnPO Experimental: n = 6). The animals of the first three protocols were anesthetized and subjected to saporin-anti-DβH nanoinjections for neuronal lesion (100 nL, 0.105 ng/nl) in experimental groups and Saporin nanoinjections (100 nL, 0.022 ng/nL) in sham groups for fictitious neuronal lesion, respectively, in the NTS, CVLM or simultaneously in the NTS and CVLM regions. After 20 days of recovery, the animals were anesthetized and instrumented to mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nervous activity (RSNA) recordings. Then, HH was performed by blood withdrawal until MAP reached approximately 60 mmHg. After 20 min of HH, sodium overload (3M NaCl, 1.8 mL/g, 90 seconds of infusion, i.v) was conducted. In another series of experiments, MnPO Sham and MnPO Experimental groups were anesthetized and instrumented for MAP, HR and RSNA recordings. Then, the animals were submitted to HH and HS infusion at the end of the hemorrhage. GABAergic agonist Muscimol (4 mM, 100 nL, MnPO Experimental group) or saline nanoinjections (0.15 M, 100 nL, MnPO Sham group) were performed in the MnPO after 10 min from the start of HH. HH-induced hypotension, bradycardia and renal sympathoinhibition in the animals of the A2 Sham, A1 Sham, A1 + A2 Sham and MnPO Sham groups. In the sham groups, HS infusion after HH reestablished MAP, HR, and did not alter the renal sympathoinhibition generated during hypovolemia. In the A2 Experimental and A1 Experimental groups, the specific lesion of A1 or A2 neurons did not alter the hypotension, bradycardia and renal sympathoinhibition caused during HH. In addition, the A1 or A2 neurons specific lesion did not alter the reestablishment of MAP, HR and the RSNA reduction after HS solution infusion. However, in the animals of the A1 + A2 experimental group, the simultaneous A1 and A2 neurons lesion did not alter the decrease in MAP and HR observed during HH, but abolished renal sympathoinhibition. In addition, simultaneous A1 and A2 neurons lesion abolished MAP restoration and ANSR reduction after HS infusion, while HR restoration was not modified. In the MnPO experimental animals, MnPO nucleus inhibition did not alter the decrease in MAP and HR observed during HH, but abolished renal sympathoinhibition. However, MnPO inhibition abolished the MAP restoration and promoted strong sympathetic activation in the renal bed after HS infusion, while HR restoration was not modified. These results suggest that the A1, A2 neuronal clusters and MnPO nucleus are part of the integration and transmission information circuits about changes in plasma osmolarity, participating in cardiovascular and autonomic recovery induced by sodium chloride overload in animals submitted to HH. / Os benefícios hemodinâmicos e cardiovasculares provenientes do uso de solução salina hipertônica (SH) no tratamento da hemorragia hipotensiva (HH) são relatados há vários anos. Recentes investigações mostraram a participação de regiões do sistema nervoso central (SNC), como os grupamentos neuronais A1 (localizado na região caudoventrolateral do bulbo; CVLM), A2 (localizado no núcleo do tracto solitário; NTS) e do núcleo Pré-óptico mediano (MnPO) nas respostas hemodinâmicas induzidas pela sobrecarga de cloreto de sódio em animais normovolêmicos. Entretanto, o papel das estruturas acima relacionadas na recuperação cardiovascular e nas alterações autonômicas induzidas pela administração de solução SH em animais submetidos à HH ainda não foi avaliado. Assim, o presente estudo buscou avaliar o envolvimento dos grupamentos neuronais A1, A2 e do núcleo MnPO nas respostas cardiovasculares e autonômicas promovidas pela infusão de solução SH em animais hipovolêmicos. Para isto, ratos Wistar (280-320 g) foram separados em quatro protocolos: I. Lesão do grupamento neuronal A2 (Controle A2: n=6; Experimental A2: n=6); II. Lesão do grupamento neuronal A1 (Controle A1: n=6; Experimental A1: n=6); III. Lesões concomitantes dos grupamentos neuronais A1 e A2 (Controle A1 + A2: n=6; Experimental A1 + A2: n=6) e IV. Inibição farmacológica do núcleo MnPO (Controle MnPO: n=6; Experimental MnPO: n=6). Os animais dos três primeiros protocolos foram anestesiados e submetidos a nanoinjeções de saporina-anti-DβH para lesão neuronal (100 nL, 0,105 ng/nL) nos grupos experimentais e Saporina (100 nL, 0,022 ng/nL) nos grupos controles para lesão neuronal fictícia, respectivamente, no NTS, na região CVLM ou conjuntamente no NTS e CVLM. Após 20 dias de recuperação, os animais foram novamente anestesiados e instrumentalizados para registro da pressão arterial média (PAM), frequência cardíaca (FC) e atividade nervosa simpática renal (ANSR). Em seguida, a HH foi realizada através da retirada de sangue até que a PAM atingisse aproximadamente 60 mmHg. Após 20 min de HH foi conduzida a sobrecarga de sódio (NaCl 3M, 1,8 mL/kg, 90 segundos de infusão, i.v). Em outra série de experimentos, os animais dos grupos controle MnPO e Experimental MnPO foram anestesiados e instrumentalizados para registro da PAM, FC, ANSR. Em seguida, foram submetidos à HH e a infusão de solução SH ao final da hemorragia. Nanoinjeções do agonista GABAérgico, muscimol (4 mM, 100 nL, grupo experimental MnPO) ou salina (0,15 M; 100 nL; grupo controle MnPO) foram realizadas no MnPO após 10 min do início da HH. A HH promoveu hipotensão, bradicardia e simpatoinibição no território renal nos animais dos grupos controle A2, controle A1, controle A1 + A2 e controle MnPO. Nos grupos controle, a infusão de solução SH após a HH reestabeleceu a PAM, FC e não alterou a simpatoinibição renal gerada durante a hipovolemia. Nos animais dos grupos experimental A2 e experimental A1, a lesão especifica dos neurônios A1 ou A2 não alterou a hipotensão, bradicardia e simpatoinibição provocados durante a HH. Em adição, a lesão especifica dos neurônios A1 ou A2 não alterou o reestabelecimento da PAM, FC e a queda da ANSR gerada após a infusão de solução SH. Entretanto, nos animais do grupo experimental A1 + A2, a lesão simultânea dos neurônios A1 e A2 não alterou a queda da PAM, da FC observada durante a HH, mas aboliu a simpatoinibição renal. Ademais, a lesão simultânea dos neurônios A1 e A2 aboliu a restauração da PAM e a redução da ANSR após a infusão de solução SH, enquanto a restauração da FC não foi modificada. Nos animais do grupo experimental MnPO, a inibição do MnPO não alterou a queda da PAM e da FC observadas durante a HH, entretanto aboliu a simpatoinibição renal. Porém, a inibição do núcleo MnPO aboliu a restauração da PAM e promoveu forte simpatoexcitação no leito renal após a infusão de solução SH, enquanto a restauração da FC não foi modificada. Esses resultados sugerem que os neurônios dos grupamentos A1, A2 e o núcleo MnPO fazem parte dos circuitos de integração e transmissão de informações a respeito de mudanças na osmolaridade plasmática, participando da recuperação cardiovascular e autonômica induzida pela sobrecarga de cloreto de sódio em animais submetidos à HH.

<p>Hirur&scaron;ka inetrvencija aktivira odgovor organizma na stres, pokreću se neuroendokrine promene u organizmu, &scaron;to rezultira neželjenom hemodinamskom nestabilno&scaron;ću, promenama metabolizma, endokrinog i imunog sistema. Cilj ovog istraživanja je bio da se utvrdi uticaj kaudalnog bloka na nivo perioperativnog stresa i njegova efikasnot u zbrinjavanju intra- i postoperativnog bola. Ovo prospektivno, randomizirano kliničko ispitivanje obuhvatalo je 80 dečaka, uzrasta 2-5godina, kojima su bile indikovane urolo&scaron;ke operacije. Jedna grupa (n = 38) je primila op&scaron;tu anesteziju, a druga (n = 38) op&scaron;tu anesteziju sa kaudalnim blokom. Mereni su intraoperativno hemodinamski parametri u 8 merenja, ukupna potro&scaron;nja svih datih lekova i intenzitet bola u 3 navrata postoperativno. Uzorci krvi uzeti su pre uvoda u anesteziju i nakon buđenja pacijenta, i ispitivan je nivo glukoze, kortizola, leukocita, leukocitarne formule, pH i laktata. Deca koja su primila kaudalni blok imala su, postoperativno, značajno niži nivo glukoze u serumu (p &lt;0,01), koncentracije kortizola (p &lt;0,01), leukocita i neutrofila (p &lt;0,01), laktata i acidoze, a takođe su imali i niže ocene bola u sve tri momenta merenja (p&lt;0,01). Intraoperativno utvrđena je veća hemodinamska stabilnost i manja potro&scaron;nja analgetika perioperativno. Takođe, u toj grupi nije bilo komplikacija. Kombinacija kaudalnog bloka sa op&scaron;tom anestezijom je bezbedna metoda, koja dovodi do manjeg stresa, veće hemodinamske stabilnosti, nižih ocena bola i manje potro&scaron;nje<br />lekova.</p> / <p>Surgery generates a neuroendocrine stress response, resulting in undesirable haemodynamic instability, alterations in metabolic response and malfunctioning of the immune system. The aim of this research was to determine the effectiveness of caudal blocks in intra- and postoperative pain management and in reducing the stress response in children during the same periods. This prospective, randomized clinical trial included 80 patients scheduled for elective urological operations. One group (n = 38) received general anaesthesia and the other (n = 38) received general anaesthesia with a caudal block. Haemodynamic paramethers, drug consumption and pain intensity were measured. Blood samples for serum glucose, cortisol level, leukocytes, pH and lactate level were taken before anaesthesia induction and after awakening the patient. Children who received a caudal block had, postoperativly, significantly lower serum glucose (p &lt; 0.01), cortisol concentrations (p &lt; 0.01), leukocytes (p&lt;0,01), lower lactate level and acidosis,also pain scores were lower at all 3 measurments (p&lt;0,01). Intraoperativly greater haemodynamic stability and lower drug consumption were noticed. Also, there were no side effects or complications identified in that group. The combination of caudal block with general anaesthesia is a safe method that leads to less stress, greater haemodynamic stability, lower pain scores and lower consumption of medication.</p>