Respostas fisio-patológicas e desafio por Aeromonas hydrophila em Pacu alimentado com ração suplementada com 1,3 beta-Glucano

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos da dexmedetomidina sobre a lesão de isquemia e reperfusão renal em ratos: avaliação pela NGAL, histologia e interleucinas

Pós-graduação em Anestesiologia - FMB

Efeito da ingestão aguda de taurina sobre o desempenho físico e metabolismo lipídico de nadadores de elite de Ribeirão Preto

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Risk factors for postoperative delirium in the elderly

Background: Delirium is defined as an acute disorder of attention and cognition. Delirium is common in hospitalized elderly patient and is associated with increased morbidity, length of stay and patient care costs. Although Delirium can develop at any time during hospitalization, it typically presents early in the post-operative period (Post-Operative Delirium, POD) in the surgery context. The molecular mechanism and possible genetics basis of POD onset are not known, as well as all the risk factors are not completely defined. Our hypothesis is that genetic risk factor involving the inflammatory response could have possible effects on the immunoneuroendocrine system. Moreover, our previous data (inflamm-aging) suggest that aging is associated with an increase of inflammatory status, favouring age-related diseases such as neurodegenerative diseases, frailty, depression among other. Some pro-inflammatory or anti-inflammatory cytokines, seem to play a crucial role in increasing the inflammatory status and in the communication and regulation of immunoneuroendocrine system. Objective: this study evaluated the incidence of POD in elderly patients undergoing general surgery, clinical/physical and psychological risk factors of POD insurgency and investigated inflammatory and genetic risk factors. Moreover, this study evaluated the consequence of POD in terms of institutionalization, development of permanent cognitive dysfunction or dementia and mortality Methods: patients aged over 65 admitted for surgery at the Urgency Unit of S.Orsola-Malpighi Hospital were eligible for this case–control study. Risk factors significantly associated with POD in univariate analysis were entered into multivariate analysis to establish those independently associated with POD. Preoperative plasma level of 9 inflammatory markers were measured in 42 control subjects and 43 subjects who developed POD. Functional polymorphisms of IL-1 α , IL-2, IL-6, IL-8, IL-10 and TNF-alpha cytokine genes were determined in 176 control subjects and 27 POD subjects. Results: A total of 351 patients were enrolled in the study. The incidence of POD was 13•2 %. Independent variables associated with POD were: age, co-morbidity, preoperative cognitive impairment, glucose abnormalities. Median length of hospital stay was 21 days for patients with POD versus 8 days for control patients (P < 0•001). The hospital mortality rate was 19 and 8•4 % respectively (P = 0•021) and mortality rate after 1 year was also higher in POD (P= 0.0001). The baseline of IL-6 concentration was higher in POD patients than patients without POD, whereas IL-2 was lower in POD patients compared to patients without POD. In a multivariate analysis only IL-6 remained associated with POD. Moreover IL-6, IL-8 and IL-2 are associated with co-morbidity, intra-hospital mortality, compromised functional status and emergency admission. No significant differences in genotype distribution were found between POD subjects and controls for any SNP analyzed in this study. Conclusion: In this study we found older age, comorbidity, cognitive impairment, glucose abnormalities and baseline of IL-6 as independent risk factors for the development of POD. IL-6 could be proposed as marker of a trait that is associated with an increased risk of delirium; i.e. raised premorbid IL-6 level predict for the development of delirium.

Ruolo della Interleuchina-6 nella colite ulcerosa long-standing: regolazione della p53 ed induzione delle cellule mesenchimali epiteliali

L’infiammazione cronica è un fattore di rischio di insorgenza del cancro, e la citochina infiammatoria IL-6 gioca un ruolo importante nella tumorigenesi. In questo studio abbiamo dimostrato che L’IL-6 down-regola l'espressione e l'attività di p53. In linee cellulari umane, IL-6 stimola la trascrizione dell’rRNA mediante espressione della proteina c-myc a livello post-trascrizionale in un meccanismo p38MAPK-dipendente. L'up-regolazione della biogenesi ribosomiale riduce l'espressione di p53 attraverso l'attivazione della via della proteina ribosomale-MDM2. La down-regolazione di p53 produce l’acquisizione di modifiche fenotipiche e funzionali caratteristiche della epitelio mesenchimale di transizione, un processo associato a trasformazione maligna e progressione tumorale. I nostri dati mostrano che questi cambiamenti avvengono anche nelle cellule epiteliali del colon di pazienti affetti da colite ulcerosa, un esempio rappresentativo di una infiammazione cronica soggetta a trasformazione neoplastica, che scompaiono dopo trattamento con farmaci antinfiammatori. Questi risultati svelano un nuovo effetto oncogenico indotto dall’IL-6 che può contribuire notevolmente ad aumentare il rischio di sviluppare il cancro non solo in pazienti con infiammazioni croniche, ma anche in quei pazienti con condizioni patologiche caratterizzate da elevato livello di IL-6 nel plasma, quali l'obesità e e il diabete mellito di tipo 2.

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 microg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses).

The inhibition of bone resorption in rats treated with (-)-menthol is due to its metabolites

(-)-Menthol, a monoterpene from Mentha species (Lamiaceae), has been shown to inhibit bone resorption in vivo by an unknown mechanism. In the present study, plasma and urine profiling in rats determined by GC/MS demonstrate that (-)-menthol is extensively metabolized, mainly by hydroxylation and carboxylation, and excreted in the urine, in part as glucuronides. In plasma, very low concentrations of (-)-menthol metabolites were detected after a single dose of (-)-menthol, whereas after repeated treatment, several times higher concentrations and long residence times were measured. In contrast, the elimination of unchanged (-)-menthol was increased by repeated treatment. (-)-Menthol, at concentrations found in plasma, did not inhibit bone resorption in cultured mouse calvaria (skull). However, the neutral metabolites of (-)-menthol, extracted from urine of rats fed with (-)-menthol, inhibited bone resorption in vitro, the concentrations being at plasma level or higher. These results suggest that not (-)-menthol itself, but one or several of its neutral metabolites inhibit the bone resorbing cells in vivo.

Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study

INTRODUCTION: Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions-vasoconstriction and shivering-which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34 degrees C without producing significant sedation or respiratory depression. METHODS: Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 mug/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 mug/ml). Volunteers were cooled with 4 degrees C cold Ringer lactate infused over a central venous catheter (rate asymptotically equal to 2.4 degrees C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale. RESULTS: Control shivering threshold was 35.5 degrees C +/- 0.2 degrees C. Skin warming reduced the shivering threshold to 34.9 degrees C +/- 0.5 degrees C (p = 0.01). Meperidine reduced the shivering threshold to 34.2 degrees C +/- 0.3 degrees C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days. CONCLUSION: A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C via an additive interaction and produced only very mild sedation and no respiratory toxicity.

Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men

Melatonin has previously been suggested to affect hemostatic function but studies on the issue are scant. We hypothesized that, in humans, oral administration of melatonin is associated with decreased plasma levels of procoagulant hemostatic measures compared with placebo medication and that plasma melatonin concentration shows an inverse association with procoagulant measures. Forty-six healthy men (mean age 25 +/- 4 yr) were randomized, single-blinded, to either 3 mg of oral melatonin (n = 25) or placebo medication (n = 21). One hour thereafter, levels of melatonin, fibrinogen, and D-dimer as well as activities of coagulation factor VII (FVII:C) and VIII (FVIII:C) were measured in plasma. Multivariate analysis of covariance and regression analysis controlled for age, body mass index, mean arterial blood pressure, heart rate, and norepinephrine plasma level. Subjects on melatonin had significantly lower mean levels of FVIII:C (81%, 95% CI 71-92 versus 103%, 95% CI 90-119; P = 0.018) and of fibrinogen (1.92 g/L, 95% CI 1.76-2.08 versus 2.26 g/L, 95% CI 2.09-2.43; P = 0.007) than those on placebo explaining 14 and 17% of the respective variance. In all subjects, increased plasma melatonin concentration independently predicted lower levels of FVIII:C (P = 0.037) and fibrinogen (P = 0.022) explaining 9 and 11% of the respective variance. Melatonin medication and plasma concentration were not significantly associated with FVII:C and D-dimer levels. A single dose of oral melatonin was associated with lower plasma levels of procoagulant factors 60 min later. There might be a dose-response relationship between the plasma concentration of melatonin and coagulation activity.

Intra- and interspecific social challenges modulate the levels of an androgen precursor in a seasonally territorial tropical damselfish.

Studies on different vertebrate groups have provided evidence that androgen levels in males increase after competitive social interactions during the breeding season, as postulated by the Challenge Hypothesis. However, social modulation of androgen levels may vary with latitude and may differ between species holding seasonal versus year-round territories. Here, we tested the Challenge Hypothesis on a seasonal tropical damselfish, Abudefduf sexfasciatus, where males temporarily defend territory and eggs against both intra- and interspecific individuals. Carrying out simulated territorial intrusions (STIs) in the laboratory, we document for the first time a consistent increase in the plasma level of the androgen precursor 11-ketoandrostenedione (11KA) in fish confronted to either intra- or interspecific challenges. Collecting samples in the field also revealed higher 11KA levels in fish facing frequent territorial interactions than in non-territorial individuals. Levels of 11-ketotestosterone (11KT) were high in territorial males in the field, but were not incremented after simulated territorial intrusions in the laboratory. Plasma levels of cortisol and testosterone were not affected by challenges but were different in wild and captive specimens. Although the endocrine responses to STIs did not differ between intra- and interspecific challenges, agonistic displays expressed by resident fish were more intense towards intraspecific intruders. Taken together, our study emphasizes the need to incorporate androgen precursor concentrations to advance our understanding on the physiology of territorial interactions.

Evaluación del comportamiento mecánico, estructural y frente a la corrosión, de una nueva armadura de acero inoxidable dúplex bajo en níquel

La durabilidad de las estructuras de hormigón armado no es ilimitada, en especial en determinados ambientes. El ingreso de agentes agresivos en el hormigón, fundamentalmente dióxido de carbono e iones cloruros, rebasando el espesor del recubrimiento y alcanzando las armaduras, reducen el alto pH del hormigón hasta alcanzar un umbral crítico, por debajo del cual, el acero queda despasivado. Posteriormente, si existe el suficiente aporte de humedad y oxígeno, el acero se corroe, lo que supone drásticas reducciones de la vida de servicio de estas estructuras y su inevitable reparación. La utilización de armaduras de acero inoxidable es una alternativa que está recibiendo cada vez más consideración. Su resistencia a la corrosión en los ambientes más agresivos, incluso con ataque de cloruros, lo convierte en el material idóneo para prolongar de forma muy considerable la vida útil de la estructura. En este trabajo se ha evaluado el comportamiento mecánico y estructural, y de resistencia a la corrosión, de un nuevo acero inoxidable dúplex de bajo contenido en níquel, el EN 1.4482 (AISI 2001), y se ha comparado con el inoxidable austenítico más utilizado, el EN 1.4301 (AISI 304), con el dúplex EN 1.4362 (AISI 2304) y con el tradicional acero al carbono B-500-SD. El estudio mecánico y estructural se ha realizado en tres niveles diferentes: a nivel de barra, estudiando las propiedades mecánicas y de ductilidad de los cuatro aceros citados; a nivel de sección, estudiando su comportamiento a flexión con diferentes cuantías de armado por medio de los diagramas momento-curvatura; y a nivel de pieza, ensayando una serie de vigas armadas con diferentes aceros y cuantías, y comprobando su comportamiento a desplazamiento y resistencia por medio de los diagramas carga-desplazamiento. El estudio de resistencia a la corrosión se ha realizado embebiendo barras corrugadas, de los tres aceros inoxidables mencionados, en probetas de mortero contaminadas con diferentes cantidades de cloruros, y realizando mediciones electroquímicas durante un periodo de al menos un año. Se han preparado probetas de mortero para dos comparativas diferentes. La primera, manteniendo las probetas en un desecador con el 95 % de humedad relativa durante todo el periodo de mediciones. La segunda, sumergiendo parcialmente las probetas en una solución tampón para carbonatar el mortero. Los resultados de los ensayos mecánicos han demostrado dos aspectos diferentes. Uno, que las armaduras de acero inoxidable tienen un comportamiento muy similar a las de acero al carbono en lo referente a las resistencias alcanzadas, en el límite elástico y en rotura, pero distinto en cuanto al módulo de deformación longitudinal, cuyo valor es claramente inferior al del acero al carbono, por lo que su utilización en las estructuras de hormigón necesita tener en cuenta ese dato en los análisis lineales de cálculo. El segundo aspecto es que las armaduras de acero inoxidable laminadas en caliente presentan una ductilidad muy superior a las de acero al carbono, por lo que ofrecen una mayor seguridad frente a su rotura o al colapso de la estructura, lo que se debe tener en cuenta en el análisis de cálculo plástico. En cambio, las armaduras de acero inoxidable laminadas en frío sólo cumplen con los límites mínimos de ductilidad establecidos en la instrucción EHE-08 para los aceros soldables, y no para los aceros con características especiales de ductilidad. El estudio a nivel de sección refleja la paradoja de obtener secciones menos dúctiles con las armaduras de acero inoxidable laminadas en caliente que con las armaduras de acero al carbono. Para subsanarlo, se definen los conceptos de curvatura última de rotura y ductilidad de la sección en rotura, que tienen en cuenta las altas deformaciones alcanzadas por las armaduras de acero inoxidable. Los resultados a nivel de pieza permiten identificar el comportamiento estructural del hormigón armado con barras corrugadas de acero inoxidable y compararlo con el de las estructuras de hormigón armado convencionales, verificando los resultados experimentales con los teóricos obtenidos con la formulación recogida en la instrucción EHE- 08. Los ensayos de resistencia a la corrosión por cloruros demuestran, durante el primer año y medio de vida de las probetas, un comportamiento muy similar entre el nuevo acero inoxidable dúplex bajo en níquel y el austenítico y el dúplex utilizados para la comparación, incluso para las probetas carbonatadas. Por último, se añade una comparativa económica, realizada sobre dos edificaciones tipo, para cuantificar el sobrecoste que supone la utilización de armaduras de acero inoxidable respecto a las de acero al carbono. El alto coste inicial de las armaduras de acero inoxidable se ve compensado en el coste final de la estructura de muy diferentes formas, principalmente dependiendo del grado de acero elegido y de si se emplean en el total de la estructura o solamente en los elementos más expuestos. The durability of the concrete structures is limited, especially in certain environments. The attack of aggressive agents in the concrete, mainly carbon dioxide and chloride ions, penetrating the thickness of concrete cover and reaching the reinforcements, reduce the high pH of concrete to the point of reaching a critical threshold, under which, the steel despasivates. Therefore, if there is enough humidity and oxygen, the steel corroes, causing drastic reductions in the service life of these structures and its inevitable repair. Despite the high initial cost compared to carbon steel, the usage of stainless steel reinforcements is an alternative with a major consideration nowadays. Its resistance to corrosion in the most aggressive atmospheres, including chlorides attack, makes the stainless steel a suitable material to extend considerably its lifetime. In this study, it’s been evaluated the mechanical and structural behaviour, and the corrosion resistance, of a new low-nickel duplex stainless steel EN 1.4482 (AISI 2001), and it has been compared with the most widely used austenitic type EN 1.4301 (AISI 304), with duplex steel EN 1.4362 (AISI 2304) and with the traditional carbon steel B-500-SD. The mechanical and structural study has been carried out in three different levels: bar level, studying mechanical properties and ductility of the four steels; section level, studying its behaviour when blending with different amounts of reinforcement through the moment-curvature diagrams; and structural element level, testing a series of reinforced beams with different steels and amounts, and checking its sag and resistance through the load-deflection diagrams. The corrosion resistance study was performed by embedding ribbed bars, using the three stainless steel listed, on mortar specimens contaminated with different amounts of chlorides, and taking electrochemical measurements over a period of at least one year. Mortar specimens have been prepared for two different comparisons. The first, keeping the specimens at 95% of relative humidity during the measurement period. The second, immersing the specimens partially in a carbonate buffer solution. The results of those tests have proved two different aspects. Firstly, that stainless steel reinforcements show a very similar behaviour to carbon steel, according to the reached levels of mechanical resistance, yield stress and steel strength, but a different behaviour in Young’s modulus, which value is clearly lower than the carbon steel. Therefore, when using in concrete structures it is need to consider on that point the existing calculus of linear analysis. The second aspect is that stainless steel reinforcement manufactured by hot-rolling process show a very higher ductility than carbon steel, offering a better security on cracks or structure collapse, which it has to be taken into account on plastic calculus analysis. However, the stainless steel reinfor9 cement cold-rolled bars only meet the minimum thresholds of ductility established by EHE-08 for welded steel, and not for steels with special ductility. The results at the section level reflect the paradox of getting less ductile sections with hot rolled stainless steel reinforcement than with carbon steel reinforcements. To overcome that, the concepts of last break curvature and break ductility section have been defined, which take into account the high deformation value achieved by stainless steel reinforcements. The results at the structural element level allow to identify the structural behaviour of reinforced concrete with stainless steel reinforcements and compared with that of conventional steel reinforcement, contrasting the experimental with the theoretical results obtained from the formulation contained in the instruction EHE-08. Tests on resistance of chloride corrosion show during the first year and a half of specimens life, a similar behaviour between the new low nickel duplex stainless steel and austenitic and duplex used for comparison, even for carbonated specimens. Finally, it has been included an economic comparison on two differents building types, to quantify the additional cost involved on the use of stainless steel reinforcement compared to that of carbon steel. The high initial cost of stainless steel reinforcements is offset in the final cost of the structure in many different ways, mainly depending on the chosen steel grade and whether the reinforcement is used in the total structure or only in risky structural elements.

Electrodynamic tethers for spacecraft propulsion

Relatively short electrodynamic tethers can use solar power to "push" against a planetary magnetic field to achieve propul sion without expenditure of propellant. The groundwork has been laid for this type of propulsion. Recent important milestones include retrieval of a tether in space (TSS-1, 1992), successful deployment of a 20-km-long tether in space (SEDS-1, 1993), and operation of an electrodynamic tether with tether current driven in both directions (PMG, 1993). The planned Propulsive Small Expendable Deployer System (ProSEDS) experiment will use the flight-proven Small Expendable Deployer System (SEDS) to deploy a 5-km bare copper tether from a Delta II upper stage to achieve -0,4 N drag thrust, thus deorbiting the stage, The experiment will use a predominantly "bare" tether for current collection in lieu of the endmass collector and insulated tether approach used on previous missions, Theory and ground-based plasma chamber testing indicate that the bare tether is a highly efficient current collector. The flight experiment is a precursor to utilization of the technology on the International Space tation (JSS) for reboost and the electrodynamic tether pper stage demonstration misión which will be capable of orbit raising, lowering, and inclination changes—all using electrodynamic thrust. In addition, the use of this type of propulsion may be attractive for future missions to Jupiter.

Expression of lipocalin-type prostaglandin D synthase (β-trace) in human heart and its accumulation in the coronary circulation of angina patients

Lipocalin-type prostaglandin D synthase (L-PGDS) is localized in the central nervous system and male genital organs of various mammals and is secreted as β-trace into the closed compartment of these tissues separated from the systemic circulation. In this study, we found that the mRNA for the human enzyme was expressed most intensely in the heart among various tissues examined. In human autopsy specimens, the enzyme was localized immunocytochemically in myocardial cells, atrial endocardial cells, and a synthetic phenotype of smooth muscle cells in the arteriosclerotic intima, and accumulated in the atherosclerotic plaque of coronary arteries with severe stenosis. In patients with stable angina (75–99% stenosis), the plasma level of L-PGDS was significantly (P < 0.05) higher in the great cardiac vein (0.694 ± 0.054 μg/ml, n = 7) than in the coronary artery (0.545 ± 0.034 μg/ml), as determined by a sandwich enzyme immunoassay. However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis. After a percutaneous transluminal coronary angioplasty was performed to compress the stenotic atherosclerotic plaques, the L-PGDS concentration in the cardiac vein decreased significantly (P < 0.05) to 0.610 ± 0.051 μg/ml at 20 min and reached the arterial level within 1 h. These findings suggest that L-PGDS is present in both endocardium and myocardium of normal subjects and the stenotic site of patients with stable angina and is secreted into the coronary circulation.

Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice.

Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from transgenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight was comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, and 300 days, respectively, after birth. At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and control mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.