Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Letter from George Cran regarding a Christian mission in India, 1803.

George Cran was the son of a farmer in the parish of Forgue in Aberdeen Shire, Scotland. He became a member of the church at Huntley, Scotland where his devotion to God inspired him to become a Sunday school teacher. He subsequently became a member of the London Missionary Society. In 1801 he was sent to study at the seminary in Gosport, England where he spent two to three years. His desire was to preach Christ to the “heathens”. Messrs. Ringeltaube, Des Granges and Cran were designated to work in India. No ships for the East India Company would grant passage to missionaries due to the open hostility of the government therefore they set sail from Copenhagen on April 20, 1804 and reached Tranquebar on December 5th, 1805. Cran and Des Granges were designated to supervise the churches in Tinnevelly and they were to begin a mission among the northern Circars. This would have meant that they would have to work in two different places which would have separated them by over 500 miles. The society didn’t seem to be aware of the vast hindrances that the missionaries had to face. Cran and Des Granges decided instead to work in Vizagapatam where they were welcomed by many of the European residents. They conducted English services for which they were paid a monthly salary by the governor. They also conducted services for the natives and opened a school for native children. By November of 1806 a mission house had been built and a “charity” school for Eurasian children was opened. Cran and Des Granges were also diligently studying the native language and they began to translate the Bible into Telugu (spoken by the Hindus who live along the lower basins of the Kistna and Godaveri Rivers). In November of 1808 Cran was almost killed by a fever which left him severely weakened. He was only partially recovered, but accepted an invitation by the general who commanded the local district to accompany him on a journey around the province. The journey proved to be too much for Cran and he died on January 6th, 1809. He is buried at Chicacole, India. He is remembered for his successful work at Vizagapatam and his translation of the Bible. The fact that it was 27 years after the arrival of Cran before a single native was converted attests to the fact that this was a very difficult undertaking. The London Missionary Society was formed in 1795 in England by evangelical Anglicans and nonconformists. It is a non-denominational society and now forms part of the Council for World Mission. with information from The Voice of God to the Churches a Sermon on the Death of George Cran, Augustus Des Granges and Jonathan Brain by David Bogue and The History of the London Missionary Society 1795-1895 by Richard Lovett

Letter to J. A. Woodruff from Miller, Miller and Cox, Barristers and Attorneys at Law

Letter to J. A. Woodruff from Miller, Miller and Cox, Barristers and Attorneys at Law stating that they have read the will of Harvey W. Price and it is suggested that Mr. Woodruff submit the money to Harvey Hamilton Price, Aug. 19, 1880.

Letter to the Honourable William Dickson at Wood Lawn, Youngstown, New York from W. Bushby

Letter to the Honourable William Dickson at Wood Lawn, Youngstown, New York from W. Bushby. He says that Mary is probably going to marry Mr. Lyon and he asks if there is any chance that Mr. Dickson could come for the wedding. He says he heard about the death of George Hamilton from John Hamilton (3 ½ pages, handwritten), Sept. 29, 1836.

Una aproximación teórico-práctica para el costeo de cápitas de paquetes de salud

Metodología para la estimación de cápitas de planes de salud. Se propone un método de cuantificación de insumos a emplear, la estimación de costos indirectos asociados a las intervenciones y un método de anualización para los costos fijos que generalmente trascienden en su vida útil al período de duración de una cápita. Finalmente, a través de un ejercicio práctico de estimación de la cápita del Componente de Salud del Programa Oportunidades de México se ilustra la aplicación del desarrollo metodológico expuesto en la parte inicial.

Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1.

Prostaglandins (PG) are known to induce pain perception indirectly by sensitizing nociceptors. Accordingly, the analgesic action of nonsteroidal anti-inflammatory drugs (NSAIDs) results from inhibition of cyclooxygenases and blockade of PG biosynthesis. Cyclopentenone PGs, 15-d-PGJ(2), PGA(2), and PGA(1), formed by dehydration of their respective parent PGs, PGD(2), PGE(2), and PGE(1), possess a highly reactive alpha,beta-unsaturated carbonyl group that has been proposed to gate the irritant transient receptor potential A1 (TRPA1) channel. Here, by using TRPA1 wild-type (TRPA1(+/+)) or deficient (TRPA1(-/-)) mice, we show that cyclopentenone PGs produce pain by direct stimulation of nociceptors via TRPA1 activation. Cyclopentenone PGs caused a robust calcium response in dorsal root ganglion (DRG) neurons of TRPA1(+/+), but not of TRPA1(-/-) mice, and a calcium-dependent release of sensory neuropeptides from the rat dorsal spinal cord. Intraplantar injection of cyclopentenone PGs stimulated c-fos expression in spinal neurons of the dorsal horn and evoked an instantaneous, robust, and transient nociceptive response in TRPA1(+/+) but not in TRPA1(-/-) mice. The classical proalgesic PG, PGE(2), caused a slight calcium response in DRG neurons, increased c-fos expression in spinal neurons, and induced a delayed and sustained nociceptive response in both TRPA1(+/+) and TRPA1(-/-) mice. These results expand the mechanism of NSAID analgesia from blockade of indirect nociceptor sensitization by classical PGs to inhibition of direct TRPA1-dependent nociceptor activation by cyclopentenone PGs. Thus, TRPA1 antagonism may contribute to suppress pain evoked by PG metabolites without the adverse effects of inhibiting cyclooxygenases.

Implementação de um protótipo de uma aplicação multimídia sobre a Ilha Rei George, Antártica

Esta dissertação aborda a implementação de um protótipo de aplicação multimídia referente à Ilha Rei George (61º 50’ S, 57º 30’ W e 62º 15’ S, 59º 00' W), Antártica. Nessa ilha o Brasil mantém sua única estação polar, onde realiza parte das pesquisas do Programa Antártico Brasileiro (PROANTAR). O presente trabalho visa reduzir a carência por materiais didáticos em língua portuguesa sobre as regiões polares e aborda aspectos gerais da biota, geografia física (geologia, climatologia e oceanografia) e geografia humana (história de ocupação, turismo, pesquisa e impactos gerados pela presença humana). O público alvo são pessoas com nível de instrução de ensino médio incompleto ou níveis mais avançados. O conteúdo é apresentado de forma a cativar a atenção do usuário, sem exageros estéticos. A fim de obter material para subsidiar o projeto, foram realizados registros por meio de fotografias, gravações em vídeo e entrevistas durante os trabalhos de campo na ilha, realizados no verão de 2004. Além dos registros em campo, são apresentados materiais didáticos tais como textos, ilustrações e animações em 3D. Parte do material gerado está disponível para utilização posterior em outros projetos O ambiente de desenvolvimento utilizado para a aplicação foi o Macromedia Director, para Apple Macintosh. O produto do projeto é um protótipo que pode ser distribuído em mídia removível, CD-ROM (Compact Disk Read Only Memory) ou DVD-ROM (Digital Versatile Disc Read Only Memory) e é encontrado como um encarte no final desta dissertação. A informação compilada e reunida na aplicação permite ao público acesso a dados atualizados sobre o ambiente antártico de forma simples, didática e interativa. O trabalho esclarece as relações entre a Antártica e o mundo, principalmente no que faz referência à ilha Rei George, buscando a valorização das regiões polares.

Predictors of first-year survival in patients with advanced COPD treated using long-term oxygen therapy

Little evidence-based guidance is available to aid clinicians in determining short-term prognoses in very severe COPD patients. Therefore, the present study was designed to provide a prospective assessment (1) of the mortality rates and (2) whether the baseline measurements may be determinants of 1-year mortality in hypoxemic COPD patients receiving long-term oxygen therapy (LTOT).Seventy-eight clinically stable patients with advanced COPD treated using LTOT were enrolled in a prospective cohort study. Outcome variable: first-year mortality. Baseline measurements: categorical variables: age (<60 or >= 60 years); gender; body mass index (<20 or >= 20 kg/m(2)); fat-free mass (FFM) index (<16 [men] and <15kg/m(2) [women]; baseline dyspnea index (BDI) (<= 3 or >3); and corticosteroid use. Continuous variables: smoking history; lung function; FFM; fat mass; hemoglobin; hematocrit; arterial blood gases; forearm muscle strength; St. George's Respiratory Questionnaire (SGRQ); and comorbidity score. By the end of 1-year of follow-up, 12 patients (15.4%) had died. Kaplan-Meier curves showed that BDI <= 3 was the only variable associated with higher mortality. Cox proportional hazards analysis revealed that tower PaO2 and SPO2, higher PaCO2 and SGRQ scores were associated with reduced survival. In the multivariate analysis, BDI remained predictive of mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.31-0.81), as did PaO2 (HR, 0.49; 95% CI, 0.26-0.95). These data suggest that readily available parameters as dyspnea intensity and hypoxemia severity may be useful in predicting first-year survival rates in advanced COPD patients receiving LTOT (C) 2007 Elsevier Ltd. All rights reserved.

Search for right-handed W bosons in top quark decay

We present a measurement of the fraction f(+) of right-handed W bosons produced in top quark decays, based on a candidate sample of t (t) over bar events in the lepton+jets decay mode. These data correspond to an integrated luminosity of 230 pb(-1), collected by the D0 detector at the Fermilab Tevatron p (p) over bar Collider at root s=1.96 TeV. We use a constrained fit to reconstruct the kinematics of the t (t) over bar and decay products, which allows for the measurement of the leptonic decay angle theta(*) for each event. By comparing the cos theta(*) distribution from the data with those for the expected background and signal for various values of f(+), we find f(+)=0.00 +/- 0.13(stat)+/- 0.07(syst). This measurement is consistent with the standard model prediction of f(+)=3.6 x 10(-4).

Search for anomalous heavy-flavor quark production in association with W bosons

We search for anomalous production of heavy-flavor quark jets in association with W bosons at the Fermilab Tevatron p(p) over bar Collider in final states in which the heavy-flavor quark content is enhanced by requiring at least one tagged jet in an event. Jets are tagged using one algorithm based on semileptonic decays of b/c hadrons, and another on their lifetimes. We compare e+jets (164 pb(-1)) and mu+jets (145 pb(-1)) channels collected with the D0 detector at root s = 1.96 TeV to expectations from the standard model and set upper limits on anomalous production of such events.

Measurement of the W boson helicity in top quark decays at D0

We present a measurement of the fraction f(+) of right-handed W bosons produced in top quark decays, based on a candidate sample of tt events in the l + jets and dilepton decay channels corresponding to an integrated luminosity of 370 pb(-1) collected by the D0 detector at the Fermilab Tevatron pp Collider at root s = 1.96 TeV. We reconstruct the decay angle theta* for each lepton. By comparing the cos theta* distribution from the data with that for the expected background and signal for various values of f(+) (where we assume that the fraction of longitudinally-polarized W bosons has the standard model value of 0.70), we find f(+) = 0.056 +/- 0.080 (stat) +/- 0.057 (syst) (f(+) < 0.23 at 95% C. L.), consistent with the standard model prediction of f(+) = 3.6 X 10(-4).

Search for W ' boson production in the W ' -> t(b)over-bar decay channel

We present a search for the production of a new heavy gauge boson W' that decays to a top quark and a bottom quark. We have analyzed 230 pb(-1) of data collected with the DO detector at the Fermilab Tevatron collider at a center-of-mass energy of 1.96 TeV. No significant excess of events above the standard model expectation is found in any region of the final state invariant mass distribution. We set upper limits on the production cross section of W' bosons times branching ratio to top quarks at the 95% confidence level for several different W, boson masses. We exclude masses between 200 and 610 GeV for a W' boson with standard-model-like couplings, between 200 and 630 GeV for a W, boson with right-handed couplings that is allowed to decay to both leptons and quarks, and between 200 and 670 GeV for a W' boson with right-handed couplings that is only allowed to decay to quarks. (c) 2006 Elsevier B.V. All rights reserved.