17 research outputs found

    NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

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    Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

    Influence Of Lithium On The Neuromuscular Blockade Produced By Atracurium And Cisatracurium. Study On Rat Phrenic Nerve-diaphragm Preparations [influência Do Lítio No Bloqueio Neuromuscular Produzido Pelo Atracúrio E Pelo Cisatracúrio. Estudo Em Preparações Nervo Frênico-diafragma De Rato]

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    BACKGROUND AND OBJECTIVES: Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS: Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL -1); atracurium (20 μg.mL-1), and cisatracurium (3 μg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 μg.mL-1) and cisatracurium (5 μg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS: Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS: Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action. © Sociedade Brasileira de Anestesiologia, 2007.573289300Stahl, S.M., (2002) Psicofarmacologia, Base Neurocientífica e Aplicações Práticas, pp. 93-287. , 2a Ed, Rio de Janeiro, MedsiAbdel-Zaher AO, The myoneural effects of lithium chloride on the nerve-muscle preparations of rats. Role of adenosine triphosphate-sensitive potassium channels. Pharmacol Res, 2000;41:163-178Vizi, E.S., Illes, P., Ronai, A., Effect of lithium on acetylcholine release and synthesis (1972) Neuropharmacology, 11, pp. 521-530Borden, H., Clarke, M.T., Katz, H., The use of pancuronium bromide in patients receiving lithium carbonate (1974) Can Anaesth Soc J, 21, pp. 79-82Hill, G.E., Wong, K.C., Hodges, M.R., Lithium carbonate and neuromuscular blocking agents (1977) Anesthesiology, 46, pp. 122-126Saarnivaara, L., Ertama, P., Interactions between lithium/rubidium and six muscle relaxants. A study on the rat phrenic nerve-hemidiaphragm preparation (1992) Anaesthesist, 41, pp. 760-764Waud, B.E., Farrell, L., Waud, D.R., Lithium and neuromuscular transmission (1982) Anesth Analg, 61, pp. 399-402Bulbring, E., Observation on the isolated phrenic nerve-diaphragm preparation of the rat (1946) Br J Pharmacol, 1, pp. 38-61Amdisen, A., Lithium and drug interactions (1982) Drugs, 24, pp. 133-139Branisteanu, D.D., Volle, R.L., Modification by lithium of transmitter release at the neuromuscular junction of the frog (1975) J Pharmacol Exp Ther, 194, pp. 362-372Havdala, H.S., Borison, R.L., Diamond, B.I., Potential hazards and applications of lithium in anesthesiology (1979) Anesthesiology, 50, pp. 534-537Tardelli MA - Função Neuromuscular: Bloqueio, Antagonismo e Monitorização, em: Yamashita AM, Takaoka F, Auler Junior JOC et al. - Anestesiologia SAESP, 5a Ed, São Paulo, Atheneu, 2001;217-244Kelly, J.S., Antagonism between Na+ and Ca2+ at the neuromuscular junction (1965) Nature, 205, pp. 296-297Kelly, J.S., The antagonism of Ca2+ by Na+ and other monovalent ions at the frog neuromuscular junction (1968) J Exp Physiol, 53, pp. 239-249Tarnopolsky, M.A., Hicks, A., Winegard, K., The effects of lithium on muscle contractile function in humans (1996) Muscle Nerve, 19, pp. 311-318Post, R.L., Merritt, C.R., Kinsolving, C.R., Membrane adenosine triphosphatase as a participant in the active transport of sodium and potassium in the human erythrocyte (1960) J Biol Chem, 235, pp. 1796-1802Wespi, H., Active transport and passive fluxes of K, Na and Li in mammalian non-myelinated nerve fibres (1969) Pfluegers Arch, 306, pp. 262-280Reimherr, F.W., Hodges, M.R., Hill, G.E., Wong, K.C., Prolongation of muscle relaxant effects by lithium carbonate (1977) Am J Psychiatry, 134, pp. 205-206Smith, J.S., Coronado, R., Meissner, G., Single channel measurements of the calcium release channel from skeletal muscle sarcoplasmic reticulum. Activation by Ca2+ and ATP and modulation by Mg2+ (1986) J Gen Physiol, 88, pp. 573-588Rudy, B., Diversity and ubiquity of K channels (1988) Neuroscience, 25, pp. 729-749Nichols, C.G., Lederer, W.J., Adenosine triphosphate-sensitive potassium channels in the cardiovascular system (1991) Am J Physiol, 261, pp. 1675-1686Carmody, J.J., Gage, P.W., Lithium stimulates secretion of acetylcholine in the absence of extracellular calcium (1973) Brain Res, 50, pp. 476-479Crawford, A.C., Lithium ions and the release of transmitter at the frog neuromuscular junction (1975) J Physiol, 246, pp. 109-142Hill, G.E., Wong, K.C., Hodges, M.R., Potentiation of succinylcholine neuromuscular blockade by lithium carbonate (1976) Anesthesiology, 44, pp. 439-442Pestronk, A., Drachman, D.B., Mechanism of action of lithium on acetylcholine receptor metabolism in skeletal muscle (1987) Brain Res, 412, pp. 302-310Dunham, E.T., Glynn, I.M., Adenosine triphosphatase activity and the active movements of alkali metal ions (1961) J Physiol, 156, pp. 274-29

    Influence Of Muscle Mass And Bone Mass On The Mobility Of Elderly Women: An Observational Study

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    Background: The purpose of this study was to investigate the influence of muscle mass and bone mineral density on markers of mobility in dwelling elderly women. Methods. This cross-sectional study included 99 elderly women, who were 65 years old or above, in Campinas-SP, Brazil. To collect data, we used sociodemographic data, the body mass index (BMI), health status, comorbidities, use of medications, mobility tests (TUG and gait speed) and examinations of the body composition (densitometry with dual-emission X-ray absorptiometry "DXA"). In order to examine the relationship between muscle and bone mass with mobility (gait speed and TUG), we applied the Spearman correlation coefficient.Also was applied the analysis of covariance (ANCOVA) adjusted for age and comorbidities. To identify the factors associated with mobility, we used the univariate and multivariate logistic regression analysis. The level of significance for statistical tests was P < 0.05. Results: The correlation between sarcopenia and bone mineral density with mobility tests showed a significant relationship only between sarcopenia and TUG (r = 0.277, P = 0.006) in Spearman correlation coefficient. The result of the correlation analysis (ANCOVA) showed that sarcopenia was associated with gait speed (r2 = 0.0636, P = 0.0018) and TUG (r2 = 0.0898, P = 0.0027). The results of the multivariate analysis showed that age (P = 0.034, OR = 1.081) was associated with worse performance on gait speed. By highlighting the TUG test, the results of the multivariate analysis showed that the age (P = 0.004, OR = 1.111) and BMI in overweight (P = 0.011, OR = 7.83) and obese (P < 0.001, OR = 7.84) women were associated with lower performance of the functionality of the lower limbs. Conclusion: The findings with regard to mobility tests which were analyzed in this study indicate the association of variables related to the aging process that contribute to the decline in physical performance, for example, age, BMI and sarcopenia. © 2014 Falsarella et al.; licensee BioMed Central Ltd.141Shin, H., Panton, L.B., Button, G.R., Ilich, J.Z., Relationship of physical performance with body composition and bone mineral density in individuals over 60 years of age: A systematic review (2011) J Aging Res, 23, pp. 1-14Thomas, E., Croft, P.R., Dziedzic, K.S., Hand problems in community-dwelling older adults: Onset and effect on global physical function over a 3-year period (2009) Rheumatology (Oxford), 48, pp. 183-187. , 19141575Hootman, J.M., Helmick, C.G., Projections of US prevalence of arthritis and associated activity limitations (2006) Arthritis Rheum, 54, pp. 226-229. , 10.1002/art.21562 16385518Brooks, P.M., Impact of osteoarthritis on individuals and society: How much disability? Social consequences and health economic implications (2002) Curr Opin Rheumatol, 14, pp. 573-577. , 10.1097/00002281-200209000-00017 12192258Dunlop, D.D., Semanik, P., Song, J., Manheim, L.M., Shih, V., Chang, R.W., Risk factors for functional decline in older adults with arthritis (2005) Arthritis Rheum, 52, pp. 1274-1282. , 10.1002/art.20968 15818691Song, J., Chang, R.W., Dunlop, D.D., Population impact of arthritis on disability in older adults (2006) Arthritis Rheum, 55, pp. 248-255. , 10.1002/art.21842 16583415Estrada, M., Kleppinger, A., Judge, J.O., Walsh, S.J., Kuchel, G.A., Functional impact of relative versus absolute sarcopenia in healthy older women (2007) J Am Geriatr Soc, 55, pp. 1712-1719. , 10.1111/j.1532-5415.2007.01436.x 17979895Frisoli, A.J., Chaves, P.H., Ingham, S.J., Fried, L.P., Severe osteopenia and osteoporosis, sarcopenia, and frailty status in community-dwelling older women: Results from the Women's Health and Aging Study (WHAS) II (2010) Bone, 48, pp. 952-957. , 21195216Lang, T., Streeper, T., Cawthon, P., Baldwin, K., Taaffe, D.R., Harris, T.B., Sarcopenia: Etiology, clinical consequences, intervention, and assessment (2010) Osteoporos Int, 21, pp. 543-559. , 10.1007/s00198-009-1059-y 19779761Baumgartner, R.N., Koehler, K.M., Gallagher, D., Romero, L., Heymsfield, S.B., Ross, R.R., Garry, P.J., Lindeman, R.D., Epidemiology of sarcopenia among the elderly in New Mexico (1998) Am J Epidemiol, 147, pp. 755-763. , 10.1093/oxfordjournals.aje.a009520 9554417Gomez-Ambrosi, J., Rodriguez, A., Catalan, V., Fruhbeck, G., The bone-adipose axis in obesity and weight loss (2008) Obes Surg, 18, pp. 1134-1143. , 10.1007/s11695-008-9548-1 18563500Karinkanta, S., Heinonen, A., Sievanen, H., Uusi-Rasi, K., Fogelholm, M., Kannus, P., Maintenance of exercise-induced benefits in physical functioning and bone among elderly women (2009) Osteoporos Int, 20, pp. 665-674. , 10.1007/s00198-008-0703-2 18696173Reid, K.F., Naumova, E.M., Carabello, R.J., Phillips, E.M., Fielding, R.A., Lower extremity muscle mass predicts functional performance in mobility-limited elders (2008) J Nutr Health Aging, 12, pp. 493-498. , 10.1007/BF02982711 18615232Cruz-Jentoft, A.J., Baeyens, J.P., Bauer, J.M., Boirie, Y., Cederholm, T., Landi, F., Martin, F.C., Zamboni, M., Sarcopenia: European consensus on definition and diagnosis: Report of the European working group on sarcopenia in older people (2010) Age Ageing, 39, pp. 412-423. , 10.1093/ageing/afq034 20392703Global database on body mass index BMI Classification, , http://www.apps.who.int/bmi/index.jsp?introPage=intro-3.htmlFried, L.P., Tangen, C.M., Walston, J., Newman, A.B., Hirsch, C., Gottdiener, J., Seeman, T., McBurnie, M.A., Frailty in older adults: Evidence for a phenotype (2001) J Gerontol A Biol Sci Med Sci, 56, pp. 146-156. , 10.1093/gerona/56.3.M146Ries, J.D., Echternach, J.L., Nof, L., Gagnon, B.M., Test-retest reliability and minimal detectable change scores for the timed up & go test, the six-minute walk test, and gait speed in people with Alzheimer disease (2009) Phys Ther, 89, pp. 569-579. , 10.2522/ptj.20080258 19389792Lucki, K., Bach, M., Banzer, W., Vogt, L., Walker use affects timed up and go and gait speed measures (2009) J Am Geriatr Soc, 57, pp. 1963-1965. , 10.1111/j.1532-5415.2009.02475.x 19807815Hayes, K., Johnson, M., Measures of adult general performance tests. The berg balance scale, dynamic gait index (DGI), gait speed, physical performance test (PPT), timed chair stand test, timed up and go, and tinetti performance-oriented mobility assessment (POMA) (2003) Arthritis & Rheuma, 49, pp. 28-42. , 10.1002/art.11411Kanis, J.A., Diagnosis of osteoporosis and assessment of fracture risk (2002) Lancet, 359, pp. 1929-1936. , 10.1016/S0140-6736(02)08761-5 12057569Broadwin, J., Goodman-Gruen, D., Slymen, D., Ability of fat and fat-free mass percentages to predict functional disability in older men and women (2001) J Am Geriatr Soc, 49, pp. 1641-1645. , 10.1111/j.1532-5415.2001.49273.x 11843997Woo, J., Leung, J., Kwok, T., BMI, body composition, and physical functioning in older adults (2007) Obesity, 15, pp. 1886-1894. , 10.1038/oby.2007.223 17636108Aleman, M.H., Lee, S.Y., Javed, F., Thornton, J., Heymsfield, S.B., Pierson, R.N., Pi Sunyer, F.X., Gallagher, D., Elderly Mexicans have less muscle and greater total and truncal fat compared to African-Americans and Caucasians with the same BMI (2009) J Nutr Health Aging, 13, pp. 919-923. , 10.1007/s12603-009-0252-1 19924354Kim, M.J., Yabushita, N., Kim, M.K., Matsuo, T., Okuno, J., Tanaka, K., Alternative items for identifying hierarchical levels of physical disability by using physical performance tests in women aged 75 years and older (2010) Geriatr Gerontol Int, 10, pp. 302-310. , 10.1111/j.1447-0594.2010.00614.x 20345433Öztürk, A., Yümin, E.T., Sertel, M., Yümin, M., The relationship between physical, functional capacity and quality of life (QoL) among elderly people with a chronic disease (2011) Arch Gerontol Geriatr, 53, pp. 278-283. , 10.1016/j.archger.2010.12.011 21215469Escalante, A., Lichtenstein, M.J., Hazuda, H.P., Walking velocity in aged persons: Its association with lower extremity joint range of motion (2001) Arthritis Rheum, 45, pp. 287-294. , 10.1002/1529-0131(200106)45:33.0.CO;2-1 11409671Bohannon, R.W., Brennan, P.J., Pescatello, L.S., Marschke, L., Hasson, S., Murphy, M., Adiposity of elderly women and its relationship with self-reported and observed physical performance (2005) J Geriatr Phys Ther, 28, pp. 10-13. , 16236222Sharkey, J.R., Branch, L.G., Gender difference in physical performance, body composition and dietary intake in homebound elders (2004) J Women Aging, 16 (3-4), pp. 71-9

    Comportamento ingestivo de cordeiros texel e ideal alimentados com casca de soja

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    This experiment was conducted in the laboratory of sheep-raising of the Federal University of Santa Maria aiming to evaluate the ingestive behavior of sheep breeds Texel and Ideal, finished in feedlot with diets containing different levels of soybean hulls in place of sorghum silage. Forty male uncastrated lambs were used, 20 from the Texel breed and 20 from Ideal breed, weaned approximately at 50 days and housed in individual pens were randomly divided into four groups according to the level of inclusion of soybean hulls in the diet: 0 %, 33.5 %, 66.5 % and 100 % of soybean hulls in replacement of sorghum silage. The time spent in feed activities, chewing time and the total time spent per meal decreased linearly, while the period of idleness and feeding efficiency of rumination increased linearly with increasing level of sorghum silage substitution by soybean hulls. Texel lambs remained more time on rumination activities and total chewing, spent more time per meal, spent less time in idleness and showed less rumination efficiency when compared with Ideal lambs when confined in the finishing phase.O presente experimento, conduzido no laboratório de ovinocultura da Universidade Fede- ral de Santa Maria, teve como objetivo avaliar o comportamento ingestivo de cordeiros das raças Texel e Ideal, terminados em confinamento com dietas contendo diferentes teores de casca de soja em substituição da silagem de sorgo. Foram utilizados 40 cordeiros machos não castrados, sendo 20 provenientes da raça Texel e 20 da raça Ideal, desmamados aproximadamente aos 50 dias e confinados em baias individuais, distribuídos aleatoriamente em quatro grupos de acordo com o nível de inclusão de casca de soja na dieta: 0 %, 33,5 %, 66,5 % e 100 % de casca de soja em substituição a silagem de sorgo. O tempo despendido em atividades de alimentação, tempo de mastigação total e o tempo gasto por refeição diminuíram linearmente, enquanto que o período de ócio e a eficiência de alimentação e de ruminação aumentaram linearmente, com o aumento do nível de substituição de silagem de sorgo por casca de soja. Cordeiros da raça Texel permaneceram por mais tempo em atividades de ruminação e de mastigação total, gastaram mais tempo por refei- ção, permaneceram menos tempo em ócio e apresentaram menor eficiência de ruminação quando comparados com cordeiros da raça Ideal, quando confinados em fase de terminação

    Phenobarbital Pharmacological Findings On The Nerve-muscle Basis

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    Phenobarbital and carbamazepine are antiepileptic drugs that act at the nervous central system by different mechanisms of action. In this work we investigated the pharmacological effects of these drugs on mouse phrenic nerve-diaphragm preparations through the myographic technique. Carbamazepine (0.105, 1.05, 2.1 and 4.2 mM, n = 8, 6, 6 and 6, respectively), induced a dose-dependent neuromuscular blockade, under indirect or direct muscle stimulation and the neurotransmission was reestablished after washing. Conversely, phenobarbital caused an unexpected facilitatory effect, under several formulations, such as the acid-extracted commercial tablets (1.05, 2.1 and 4.2 mM, n = 7, 6 and 7, respectively), commercial phenobarbital solution (4.2 mM, n = 7) or its correspondent pure active ingredient (4.2 and 2.1 mM, n = 6 each). Only at a higher concentration the acid-extracted phenobarbital performed a neuromuscular blockade (8.4 mM, n = 10). The different responses between carbamazepine (paralysis) and phenobarbital (facilitatory effect) evidentiated a new effect for phenobarbital until now concealed at the neuromuscular junction and may involve the glutamatergic regulation, since its role as an acetylcholine co-transmitter in motoneurons was already established.282211218Grozdanovic, Z., Baumgarten, H.G., (1999) Histol. Histopathol, 14, pp. 243-256Gorio, A., Hurlbut, W.P., Ceccarelli, B., (1978) J. Cell Biology, 78, pp. 716-733Nikolsky, E.E., Oranska, T.I., Vyskocil, F., (1996) Exp Physiol, 81, pp. 341-348Katz, B., Miledi, R., (1977) Proc. R. Soc. Lond. B. Biol. Sci, 196, pp. 59-72Vyskocil, F., Illés, P., (1978) Physiol. Bohemoslov, 27, pp. 449-455Vyas, S., Bradford, H.F., (1987) Neurosci. Lett, 82, pp. 58-64Waerhaug, O., Ottersen, O.P., (1993) Anat. Embryol. (Berl), 188, pp. 501-513Urazaev, A.Kh., N.V. Naumenko, G.I. Poletayev, E.E. Nikolsky & F. Vyskocil (1998) Mol. Chem. 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    Role of the chemokine receptor CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis

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    Pulmonary fibrosis is characterized by chronic inflammation and excessive collagen deposition. Neutrophils are thought to be involved in the pathogenesis of lung fibrosis. We hypothesized that CXCR2-mediated neutrophil recruitment is essential for the cascade of events leading to bleomycin-incluced pulmonary fibrosis. CXCL1 / KC was detected as early as 6 hours after bleomycin instillation and returned to basal levels after Day 8. Neutrophils were detected in bronchoalveolar lavage and interstitium from 12 hours and peaked at Day 8 after instillation. Treatment with the CXCR2 receptor antagonist, DF2162, reduced airway neutrophil transmigration but led to an increase of neutrophils in lung parenchyma. There was a significant reduction in IL-13, IL-10, CCL5/RANTES, and active transforming growth factor (TGF)-beta(1) levels, but not on IFN-gamma and total TGF-beta(1), and enhanced granulocyte macrophage-colony-stimulating factor production in DF2162-treated animals. Notably, treatment with the CXCR2 antagonist led to an improvement of the lung pathology and reduced Collagen deposition. Using a therapeutic schedule, DF2162 administered from Days 8 to 16 after bleomycin reduced pulmonary fibrosis and levels of active TGF-beta(1) and IL-13. DF2162 treatment reduced bleomycin-incluced expression of von Willebrand Factor, a marker of angiogenesis, in the lung. In vitro, DF2162 reduced the angiogenic activity of IL-8 on human umbilical vein endothelial cells. In conclusion, we show that CXCR2 plays an important role in mediating fibrosis after bleomycin instillation. The compound blocks angiogenesis and the production of pro-angiogenic cytokines, and decreases IL-8-induced endothelial cell activation. An effect on neutrophils does not appear to account for the major effects of the blockade of CXCR2 in the system

    Phosphoinositide 3-kinase plays a critical role in bleomycin-induced pulmonary inflammation and fibrosis in mice

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    PI3K gamma is central in signaling diverse arrays of cellular functions and inflammation. Pulmonary fibrosis is associated with pulmonary inflammation, angiogenesis, and deposition of collagen and is modeled by instillation of bleomycin. The role of PI3K gamma in mediating bleomycin-induced pulmonary inflammation and fibrosis in mice and potential mechanisms involved was investigated here. WT or PI3K gamma KO mice were instilled with bleomycin and leukocyte subtype influx, cytokine and chemokine levels, and angiogenesis and tissue fibrosis evaluated. The activation of lung-derived leukocytes and fibroblasts was evaluated in vitro. The relevance of PI3K gamma for endothelial cell function was evaluated in HUVECs. PI3K gamma KO mice had greater survival and weight recovery and less fibrosis than WT mice after bleomycin instillation. This was associated with decreased production of TGF-beta(1) and CCL2 and increased production of IFN-gamma and IL-10. There was reduced expression of collagen, fibronectin, alpha-SMA, and von Willebrand factor and decreased numbers and activation of leukocytes and phosphorylation of AKT and I kappa B-alpha, PI3K gamma KO mice had a reduced number and area of blood vessels in the lungs. In vitro, treatment of human endothelial cells with the PI3K gamma inhibitor AS605240 decreased proliferation, migration, and formation of capillary-like structures. AS605240 also decreased production of collagen by murine lung-derived fibroblasts. PI3K gamma deficiency confers protection against bleomycin-induced pulmonary injury, angiogenesis, and fibrosis through the modulation of leukocyte, fibroblast, and endothelial cell functions. Inhibitors of PI3K gamma may be beneficial for the treatment of pulmonary fibrosis
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