A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

Biomarkers Of Oxidative Stress In Patients With Chronic Respiratory Insuficiency (cresi) During Long Term Oxigen Therapy (ltot) [biomarcadores De Estresse Oxidativo Em Fumantes Crônicos E Em Portadores De Insuficiência Respiratória Crônica (iresc) Durante Oxigenoterapia Domiciliar Prolongada (odp)]

Sumary Objective: The aim of this study was to evaluate several biomarkers of oxidative stress in patients with Chronic Respiratory Insuficiency (CResI) at three moments: before, after 7 and 270 days of Long Term Oxigen Therapy (LTOT).Methods: The blood catalase (CAT), and glutathione reductase (GR), the Hemoglobin (Hb), lactate and Uric Acid concentration (AU) in total blood were measured. The total sulphydrils (TSH) and Protein carbonyls concentration were measured in plasma in these patients, using spectrophotometric techniques. The blood oxygen saturation (SpO2) was evaluated using a pulse oxymeter.Results: When compared Chronic Smokers (CS) with CResI group and both with Nonsmokers group (NS) observed that CResI group presented an increase in oxidative stress level, represented for decrease of three biomarkers: CAT, GR and TSH. After 7 days of LTOT the SpO2, CAT and GR activity and AU concentration were increased (P<0,05). On the other hand, the decrease on GST concentration was manteined in this period (P<0,05). The pacients submitted of 7 to 270 of LTOT showed a significant decrease on GR activity (P<0.05).Conclusion: These results showed that the major level of oxidative stress in patients with CResI happened probably as consequence of chronic hypoxemia and the LTOT was not able to block the clinic evolution of disease. © Copyright Moreira Jr. Editora.719295302Molfino, N.A., Genetics of COPD (2004) Chest., 125 (5), pp. 1929-1940Barnes, P.J., Mediators of chronic obstructive pulmonary disease (2004) Pharmacol Rev., 56 (4), pp. 515-548Antczak, A., Kharitonov, S.A., Montuschi, P., Inflammatory response to sputum induction measured by exhaled markers (2005) Respiration., 72, pp. 594-599Rahman, I., Antioxidant therapies in COPD (2006) Int J Chron Obstruct Pulmon Dis., 1 (1), pp. 15-29Louhelainen, N., Myllärniemi, M., Rahman, I., Kinnula, V.L., Airway biomarkers of the oxidant burden in asthma and chronic obstructive pulmonary disease: Current and future perspectives (2008) Int J Chron Obstruct Pulmon Dis., 3 (4), pp. 585-603Rahman, I., Macnee, W., Role of transcription factors in inflammatory lung diseases (1998) Thorax., 53, pp. 601-612Pryor, W.A., Dooley, M.D., Church, D.F., The mechanisms of inactivation of human alpha-1-proteinase inhibitor by gas phase cigarrette smoke (1986) Free. Radic. Biol. Med., 2, pp. 161-168Epstein, H.E., Mechanisms of disease (1985) New. England. J. Med., 312, pp. 159-163Sussman, M.S., Bulkley, G.B., Oxygen-derived free radicals in reperfusion Injury (1990) Meth. Enzimol., 186, pp. 711-723Cañas, P.E., The role of xanthine oxidase and the effects of antioxidants in ischemia reperfusion cell injury (1999) Acta. Physiol. Pharmacol., 49 (1), pp. 13-20Demiryurek, A.T., Wadsworth, R.M., Superoxide in pulmonary circulation (1999) Pharmacol. Ther., 84 (3), pp. 355-365Stuart-Harris, C., Flenley, D.C., Bishop, J.M., Longterm domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating bronchitis and emphysema (1981) Lancet., 1, pp. 681-686Zièlinski, J., Indications for long term oxygen therapy: A reappraisal (1999) Monaldi. Arch. Chest. Dis., 54 (2), pp. 178-182Boyum, A., Separation of leukocytes from blood and bone marrow (1968) Scand J.Clin.Lab. Invest., 21 (97), p. 77Drabkin, D.L., Spectrophotometric studies-XIV. The crystalographic and optical properties of the hemoglobin in man in comparison with those in other species (1946) J. Biol. Chem., 164, p. 703Smith, I.K., Vierheller, T.L., Thorne, C.A., Assay of glutathione reductase in crude tissue homogenates using 5,5 ditiobis (2-nitrobenzoic acid) (1988) Anal. Biochem., 175, pp. 408-413Aebi, H., Catalase (1984) Meth. Enzymol., 105, pp. 121-126Hu, M.L., Measurement of protein thiol groups and glutathione in plasma (1994) Meth. Enzymol., 233, pp. 381-383Levine, R.L., Garland, D., Oliver, C.N., Amici, A., Climent, I., Determination of carbonyl content in oxidatively modified proteins (1990) Meth. Enzymol., 49, pp. 465-479Rosa, G.J.R., (1994) Desenvolvimento de Aplicativo Para A Análise de Perfil Na Experimentação Zootécnica, , Dissertação (Mestrado). Faculdade de Medicina Veterinária e Zootecnia-UNESP, BotucatuVerbeke, G., Molenberghs, G., (1997) Linear Mixed Models in Practice: A SAS-Oriented Approach, 306. , NY: SpringerLittell, R.C., Milliken, G.A., Stroup, W.W., Wolfinger, R.D., (1996) SAS System for Mixed Models, p. 633. , Cary, NC: SAS Institute IncRahman, I., Van Schadewijk, A.A., Crowther, A.J., Mac-Nee, W., 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lung of patients with chronic obstructive pulmonary disease (2002) Am. J. Respir. Crit. Care. Med., 166 (4), pp. 490-495Taylor, J.C., Madison, R.A., Kosinska, D., Is antioxidant deficiency related to chronic obstructive pulmonary disease? (1986) Am. Rev. Respir. Dis., 134, pp. 285-289Rahman, I., Adcock, I.M., Oxidative stress and redox regulation of lung inflammation in COPD (2006) Eur Respir J., 28, pp. 219-242Continuos or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease, a clinical trial (1980) Annintern Med., 93, pp. 391-398. , Nocturnal Oxygen Therapy Trial GroupGórecka, D., Gorzelak, K., Sliwinski, P., Effect of long term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia (1997) Thorax., 52, pp. 674-679Pinamonti, S., Leis, M., Barbieri, A., Detection of xanthine oxidase activity products by EPR and HPLC in bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease (1998) Free. Radic. Biol. Med., 25, pp. 771-779Brown, R.K., Wyatt, H., Price, J.F., Kelly, F.J., Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress (1996) Eur. Respir. J., 9, pp. 334-339Repine, J.E., Bast, A., Lankhorst, I., Oxidative stress in chronic obstructive pulmonary disease (1997) Am. J. Respir. Crit. Care. Med., 156, pp. 341-357. , and the oxidative stress study groupSalvi, S.S., Barnes, P.J., Chronic obstructive pulmonary disease in non-smokers (2009) Lancet, 374, pp. 733-743MacNee, W., Tuder, R.M., New paradigms in the pathogenesis of chronic obstructive pulmonary disease i (2009) Proc Am Thorac Soc, 6, pp. 527-531Barnes, P.J., Triple inhalers for obstructive airways disease: Will they be useful? (2011) Expert Rev Respir Med, 5, pp. 297-300Pelagrino, N.R.G., Godoy, I., Doença pulmonar obstrutiva crônica (2001) Revista Brasileira de Medicina., 58 (1), pp. 81-8

Mechanisms involved in the rat peritoneal leukocyte migration induced by a Kunitz-type inhibitor isolated from dimorphandra mollis seeds

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICODMTI-II is a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds that causes rat inflammatory edema by mechanisms involving activation of mast cells and sensory C-fibers. The present study aimed to further explore the inflammatory mechanisms involved in DMTI-II-induced inflammation, focusing to the leukocyte migration in vivo. Male Wistar rats (250-280 g) were injected with DMTI-II (1-100 mu g/cavity), and at 4-24 h thereafter the leukocyte counts in peritoneal lavage were evaluated. DMTI-II caused dose- and time-dependent accumulation of neutrophils and eosinophils. The peritoneal neutrophil influx initiated at 4 h, achieving maximal responses at 16 h after DMTI-II injection (16- and 22-fold increase, respectively). The DMTI-II-induced eosinophil recruitment was observed as early as 4 h achieving the maximal responses at 16 h (12- and 17-fold increase, respectively). The mononuclear cell number increased at 4 h and 16 h (1.5-fold and 1.6-increase, respectively). Prior treatments with dexamethasone, the cyclooxygenase (COX) inhibitors indomethacin and celecoxib, as well as the PAF receptor antagonist PCA4248 largely reduced the neutrophil and eosinophil accumulation. The selective lypoxygenase inhibitor AA861, the tachykinin NK(1) antagonist SR-140333 and the nitric oxide inhibitor L-NAME reduced only the eosinophil number. The eotaxin levels were significantly higher in DMTI-II-injected rats compared with control animals. In conclusion, DMTI-II causes an early migration of eosinophils and neutrophils by mechanisms involving COX-2- and lipoxygenase-derived metabolites, PAF, substance P and NO. The capacity of DMTI-II to recruit eosinophils at early times is likely to reflect the allergen properties of proteinase inhibitors belonging to Kunitz family533323329FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ – CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOsem informaçãosem informaçã

Enhancement Of The Pulmonary Allergic Granulocyte Recruitment In Rats Exposed To Dmti-ii, A Kunitz-type Inhibitor Isolated From Dimorphandra Mollis Seeds

DMTI-II (23-kDa trypsin inhibitor purified from Dimorphandra mollis seeds) promotes acute inflammation accompanied by an early infiltration of eosinophils, a critical cell type involved in allergic diseases. We have evaluated here the capacity of DMTI-II to enhance the allergic pulmonary inflammation, looking over time to the leukocyte trafficking from bone marrow to peripheral blood, and their recruitment into the allergic airways. Male Wistar rats were sensitized and challenged with ovalbumin (OVA). At 2 to 16 h prior to OVA challenge, animals were exposed to DMTI-II (10 μg). Bronchoalveolar lavage fluid (BAL), circulating blood and bone marrow were examined at 24 h post-OVA challenge. Challenge with OVA significantly increased the influx of total inflammatory cells, neutrophils and eosinophils in BAL and lung tissue. Pre-exposure to DMTI-II potentiated total inflammatory cell and neutrophil recruitment (p &lt; 0.05). Neutropoiesis and neutrophilia accompanied pulmonary cell influx. Pre-exposure to DMTI-II also significantly increased eosinophil recruitment to BAL, an effect starting at 4 h, remaining markedly elevated at 16 h (p &lt; 0.05). Eosinopoiesis and eosinophilia (seen within 2 to 4 h) were also observed. Exposure to DMTI-II alone increased the IL-4 levels, and further increased the IL-4 levels in OVA-challenged rats. The levels of IgE, LTB 4 and eotaxin in OVA-challenged rats were greater compared with non-sensitized rats, but DMTI-II exposure failed to further enhance such levels. In summary, our study shows that DMTI-II itself presents granulocytopoietic activity, and enhances allergen-induced neutrophil and eosinophil mobilization from bone marrow to lung tissues that is accompanied by enhanced IL-4 production. © 2011 Elsevier B.V. All rights reserved.116740747Hiemstra, P.S., Novel roles protease inhibitors in infection and inflammation (2002) Biochem Soc Trans, 30, pp. 116-120Richardson, M., Seed storage proteins: The enzyme inhibitors (1991) Methods in Plant Biochemistry, 1, p. 5. , New York: Academic PressValueva, T.A., Mosolov, V.V., Proteins inhibitors of proteinases in seeds: 1. Classification, distribution, structure and properties (1999) Russ J Plant Physiol, 46, pp. 307-321Heath, R.L., McDonald, G., Christeller, J.T., Lee, M., Bateman, K., West, J., Van Heeswijck, R., Anderson, M.A., Proteinase inhibitors from Nicotiana alata enhance plant resistance to insect pests (1997) Journal of Insect Physiology, 43 (9), pp. 833-842. , DOI 10.1016/S0022-1910(97)00026-7, PII S0022191097000267Jongsma, M.A., Bolter, C., The adaptation of insects to plant protease inhibitors (1997) Journal of Insect Physiology, 43 (10), pp. 885-895. , DOI 10.1016/S0022-1910(97)00040-1, PII S0022191097000401Shewry, P.R., Lucas, J.A., Plant proteins that confer resistance to pest and pathogens (1997) Adv Bot Res, 26, pp. 135-192Schuler, T.H., Poppy, G.M., Kerry, B.R., Denholm, I., Insect resistant transgenic plants (1998) Trends Biotechnol, 16, pp. 168-175DeClerck, Y.A., Imren, S., Proteases inhibitors: Role and potential therapeutic use in human cancer (1994) Eur J Cancer, 30, pp. 2170-2180Hayashi, K., Takehisa, T., Hamato, N., Takano, R., Hara, S., Miyata, T., Kato, H., Inhibition of serine proteases of the blood coagulation system by squash family protease inhibitors (1994) Journal of Biochemistry, 116 (5), pp. 1013-1018Kennedy, A.R., Chemopreventive agents: Protease inhibitors (1998) Pharmacology and Therapeutics, 78 (3), pp. 167-209. , DOI 10.1016/S0163-7258(98)00010-2, PII S0163725898000102Oliva, M.L.V., Andrade, S., Batista, I.F.C., Sampaio, M.U., Juliano, M., Fritz, H., Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds (1999) Immunopharmacology, 45, pp. 145-149Oliva, M.L.V., Souza-Pinto, J.C., Batista, I.F.C., Araujo, M.S., Silveira, V.F., Auerswald, E.A., Mentele, R., Sampaio, C.A.M., Leucaena leucocephala serine proteinase inhibitor: Primary structure and action on blood coagulation, kinin release and rat paw edema (2000) Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology, 1477 (1-2), pp. 64-74. , DOI 10.1016/S0167-4838(99)00285-X, PII S016748389900285XMacedo, M.L.R., De Matos, D.G.G., Machado, O.L.T., Marangoni, S., Novello, J.C., Trypsin inhibitor from Dimorphandra mollis seeds: Purification and properties (2000) Phytochemistry, 54 (6), pp. 553-558. , DOI 10.1016/S0031-9422(00)00155-2, PII S0031942200001552Mello, G.C., Oliva, M.L.V., Sumikawa, J.T., Machado, O.L.T., Marangoni, S., Novello, J.C., Purification and characterization of a new trypsin inhibitor from Dimorphandra mollis seeds (2001) J Prot Chem, 20, pp. 625-632Tokarnia, C.H., Dobereiner, J., Peixoto, P.V., Poisonous plants affecting livestock in Brazil (2002) Toxicon, 40 (12), pp. 1635-1660. , DOI 10.1016/S0041-0101(02)00239-8, PII S0041010102002398Mello, G.C., Desouza, I.A., Marangoni, S., Novello, J.C., Antunes, E., Macedo, M.L.R., Oedematogenic activity induced by Kunitz-type inhibitors from Dimorphandra mollis seeds (2006) Toxicon, 47 (2), pp. 150-155. , DOI 10.1016/j.toxicon.2005.10.003, PII S0041010105003594Mello, G.C., Desouza, I.A., Mariano, N.S., Ferreira, T., Macedo, M.L., Antunes, E., Mechanisms involved in the rat peritoneal leukocyte migration induced by a Kunitz-type inhibitor isolated from Dimorphandra mollis seeds (2009) Toxicon, 53, pp. 323-329Sanjar, S., Aoki, S., Kristersson, A., Smith, D., Morley, J., Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: The effect of anti-asthma drugs (1990) Br J Pharmacol, 99, pp. 679-866Matsumoto, T., Ashida, Y., Tsukuda, R., Pharmacological modulation of immediate and late airway response and leukocyte infiltration in the guinea pig (1994) Journal of Pharmacology and Experimental Therapeutics, 269 (3), pp. 1236-1244Vianna, E.O., Garcia-Leme, J., Allergen-induced airway inflammation in rats. Role of insulin (1995) Am J Resp Crit Care Med, 151, pp. 809-814Feder, L.S., Stelts, D., Chapman, R.W., Manfra, D., Crawley, Y., Jones, H., Minnicozzi, M., Kung, T.T., Role of Nitric Oxide on Eosinophilic Lung Inflammation in Allergic Mice (1997) American Journal of Respiratory Cell and Molecular Biology, 17 (4), pp. 436-442Ferreira, H.H.A., Bevilacqua, E., Gagioti, S.M., De Luca, I.M.S., Zanardo, R.C.O., Teixeira, C.E., Sannomiya, P., De Nucci, G., Nitric oxide modulates eosinophil infiltration in antigen-induced airway inflammation in rats (1998) European Journal of Pharmacology, 358 (3), pp. 253-259. , DOI 10.1016/S0014-2999(98)00575-5, PII S0014299998005755Birk, Y., (2003) Plant Protease Inhibitors: Significance in Nutrition, Plant Protection, Cancer Prevention and Genetic Engineering, p. 170. , Berlin, Heidelberg: Springer-VerlagBreiteneder, H., Radauer, C., A classification of plant food allergens (2004) Journal of Allergy and Clinical Immunology, 113 (5), pp. 821-830. , DOI 10.1016/j.jaci.2004.01.779Tatham, A.S., Shewry, P.R., Allergens to wheat and related cereals (2008) Clin Exp Allergy, 38, pp. 1712-1726Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage (1970) Nature, 227, pp. 680-685Erlanger, B.F., Kokowsky, N., Cohen, W., The preparation and properties of two new chromogenic substrates of trypsin (1961) Arch Biochem Biophys, 95, pp. 271-278Franco-Penteado, C.F., De Souza, I.A., Camargo, E.A., Teixeira, S.A., Muscara, M.N., De Nucci, G., Antunes, E., Mechanisms involved in the enhancement of allergic airways neutrophil influx by permanent C-fiber degeneration in rats (2005) Journal of Pharmacology and Experimental Therapeutics, 313 (1), pp. 440-448. , DOI 10.1124/jpet.104.078147Mariano, N.S., Mello, G.C., Ferreira, T., Schenka, A., Camargo, E.A., De Nucci, G., Pre-exposure to Staphylococcal enterotoxin A exacerbates the pulmonary allergic eosinophil recruitment in rats (2010) Int Immunopharmacol, 10 (1), pp. 43-448Kucharewicz, I., Bodzenta-Łukaszyk, A., Buczko, W., Experimental asthma in rats (2008) Pharmacol Rep, 60, pp. 783-788Dougherty, R.H., Fahy, J.V., Acute exacerbations of asthma: Epidemiology, biology and the exacerbation-prone phenotype (2009) Clin Exp Allergy, 39, pp. 193-202Wood, L.J., Inman, M.D., Watson, R.M., Foley, R., Denburg, J.A., O'Byrne, P.M., Changes in bone marrow inflammatory cell progenitors after inhaled allergen in asthmatic subjects (1998) American Journal of Respiratory and Critical Care Medicine, 157 (1), pp. 99-105Gauvreau, G.M., Ellis, A.K., Denburg, J.A., Haemopoietic processes in allergic disease: Eosinophil/basophil development (2009) Clin Exp Allergy, 39, pp. 1297-1306Furze, R.C., Rankin, S.M., Neutrophil mobilization and clearance in the bone marrow (2008) Immunology, 125, pp. 281-288Mohle, R., Salemi, P., Moore, M.A.S., Rafii, S., Expression of interleukin-5 by human bone marrow microvascular endothelial cells: Implications for the regulation of eosinophilopoiesis in vivo (1997) British Journal of Haematology, 99 (4), pp. 732-738Hogan, S.P., Rosenberg, H.F., Moqbel, R., Phipps, S., Foster, P.S., Lacy, P., Kay, A.B., Rothenberg, M.E., Eosinophils: Biological properties and role in health and disease (2008) Clinical and Experimental Allergy, 38 (5), pp. 709-750. , DOI 10.1111/j.1365-2222.2008.02958.xPoulsen, L.K., Hummelshoj, L., Triggers of IgE class switching and allergy development (2007) Annals of Medicine, 39 (6), pp. 440-456. , DOI 10.1080/07853890701449354, PII 780467545Lamkhioued, B., Renzi, P.M., Abi-Younes, S., Garcia-Zepada, E.A., Allakhverdi, Z., Ghaffar, O., Rothenberg, M.D., Hamid, Q., Increased Expression of Eotaxin in Bronchoalveolar Lavage and Airways of Asthmatics Contributes to the Chemotaxis of Eosinophils to the Site of Inflammation (1997) Journal of Immunology, 159 (9), pp. 4593-4601Crooks, S.W., Stockley, R.A., Leukotriene B4 (1998) International Journal of Biochemistry and Cell Biology, 30 (2), pp. 173-178. , DOI 10.1016/S1357-2725(97)00123-4, PII S1357272597001234Yamamoto, K., Takanashi, S., Hasegawa, Y., Kanehira, Y., Kaizuka, M., Okumura, K., Eotaxin level in induced sputum is increased in patients with bronchial asthma and in smokers (2003) Respiration, 70 (6), pp. 600-605. , DOI 10.1159/000075205Tateno, H., Nakamura, H., Minematsu, N., Nakajima, T., Takahashi, S., Nakamura, M., Fukunaga, K., Yamaguchi, K., Plasma eotaxin level and severity of asthma treated with corticosteroid (2004) Respiratory Medicine, 98 (8), pp. 782-790. , DOI 10.1016/j.rmed.2004.01.005, PII S095461110400040XLintomen, L., Souza-Filho, L.G., Ferreira, T., Camargo, E.A., Teixeira, S.A., Muscará, M.N., Different mechanisms underlie the effects of acute and long-term inhibition of nitric oxide synthases in antigen-induced pulmonary eosinophil recruitment in BALB/C mice (2009) Pulm Pharmacol Ther, 22, pp. 1-8Hallstrand, T.S., Henderson Jr., W.R., An update on the role of leukotrienes in asthma (2010) Curr Opin Allergy Clin Immunol, 10, pp. 60-66Ackerman, S.J., Bochner, B.S., Mechanisms of Eosinophilia in the Pathogenesis of Hypereosinophilic Disorders (2007) Immunology and Allergy Clinics of North America, 27 (3), pp. 357-375. , DOI 10.1016/j.iac.2007.07.004, PII S0889856107000549, Hypereosinophilic Syndrome