High mobility group box 1 as a mediator of endotoxin administration after hemorrhagic shock-primed lung injury

High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 ± 0.05, compared to the control group: 1.02 ± 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 ± 0.08, compared to the control group: 1.07 ± 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 ± 0.08, compared to the control group: 1.05 ± 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

What happens in the first 200 ms of word reading : ERP studies on visual word recognition with top-down and bottom-up approaches /

In this thesis, three main questions were addressed using event-related potentials (ERPs): (1) the timing of lexical semantic access, (2) the influence of "top-down" processes on visual word processing, and (3) the influence of "bottom-up" factors on visual word processing. The timing of lexical semantic access was investigated in two studies using different designs. In Study 1,14 participants completed two tasks: a standard lexical decision (LD) task which required a word/nonword decision to each target stimulus, and a semantically primed version (LS) of it using the same category of words (e.g., animal) within each block following which participants made a category judgment. In Study 2, another 12 participants performed a standard semantic priming task, where target stimulus words (e.g., nurse) could be either semantically related or unrelated to their primes (e.g., doctor, tree) but the order of presentation was randomized. We found evidence in both ERP studies that lexical semantic access might occur early within the first 200 ms (at about 170 ms for Study 1 and at about 160 ms for Study 2). Our results were consistent with more recent ERP and eye-tracking studies and are in contrast with the traditional research focus on the N400 component. "Top-down" processes, such as a person's expectation and strategic decisions, were possible in Study 1 because of the blocked design, but they were not for Study 2 with a randomized design. Comparing results from two studies, we found that visual word processing could be affected by a person's expectation and the effect occurred early at a sensory/perceptual stage: a semantic task effect in the PI component at about 100 ms in the ERP was found in Study 1 , but not in Study 2. Furthermore, we found that such "top-down" influence on visual word processing might be mediated through separate mechanisms depending on whether the stimulus was a word or a nonword. "Bottom-up" factors involve inherent characteristics of particular words, such as bigram frequency (the total frequency of two-letter combinations of a word), word frequency (the frequency of the written form of a word), and neighborhood density (the number of words that can be generated by changing one letter of an original word or nonword). A bigram frequency effect was found when comparing the results from Studies 1 and 2, but it was examined more closely in Study 3. Fourteen participants performed a similar standard lexical decision task but the words and nonwords were selected systematically to provide a greater range in the aforementioned factors. As a result, a total of 18 word conditions were created with 18 nonword conditions matched on neighborhood density and neighborhood frequency. Using multiple regression analyses, we foimd that the PI amplitude was significantly related to bigram frequency for both words and nonwords, consistent with results from Studies 1 and 2. In addition, word frequency and neighborhood frequency were also able to influence the PI amplitude separately for words and for nonwords and there appeared to be a spatial dissociation between the two effects: for words, the word frequency effect in PI was found at the left electrode site; for nonwords, the neighborhood frequency effect in PI was fovind at the right elecfrode site. The implications of otir findings are discussed.

Thoughts upon the conduct of our administration in relation both to Great Britain and France, more especially in reference to the late negotiation, concerning the attack on the Chesapeake

Printed at the Repertory Office

The Bond Girl phenomenon: defining the female protagonists of the James Bond films

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999 C65 F86 2005

Second interim report of the Canadian section and first joint report of the International Waterways Commission (1906)

Report of the Canadian section, dated April 25th, 1906, and report of the joint commission, dated May 3d, 1906, related to regulating the uses of the waters of the Niagara River and the preservation of the Falls.

Alternative Models of Court Administration

Canadian Judicial Council

An ethnolinguistic study of the Yanesha’ (Amuesha) language and speech community in Peru’s Andean Amazon, and the traditional role of Ponapnora, a female rite of passage

Thesis written in co-mentorship with Richard Chase Smith Ph.D, of El Instituto del Bien Comun (IBC) in Peru. The attached file is a pdf created in Word. The pdf file serves to preserve the accuracy of the many linguistic symbols found in the text.

First-principles study of the neutral molecular metal Ni(tmdt)2.

The electronic structure of the molecular solid Ni(tmdt)2, the only well characterized neutral molecular metal to date, has been studied by means of first-principles density functional calculations. It is shown that these calculations correctly describe the metallic vs semiconducting behavior of molecular conductors of this type. The origin of the band overlap leading to the metallic character and the associated Fermi surfaces has been studied.

Analysis of Irish tourism policy’s contribution to urban tourism: Dublin case study

L’objectiu principal del treball és analitzar les polítiques i plans turístics irlandesos nacionals, regionals i locals, i determinar com aquestos influeixen en el turisme urbà a Dublín. L’objectiu secundari és investigar el concepte de turisme urbà i examinar les tendències turístiques actuals i la seva repercussió en la formulació de polítiques

The role of parental investments for cognitive and noncognitive skill formation : evidence for the first 11 years of life. 'El papel de la influencia de los padres en el desarrollo cognitivo y la formación de habilidades cognitivas : evidencias de los primeros 11 años de vida'.

Resumen basado en el de la publicación