Nutrição e Inflamação, Maio, 2013

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Nutrição e Inflamação, Maio, 2013

  1. 1. Pedro Carrera Bastos, 2013NUTRIÇÃO E INFLAMAÇÃO
  2. 2. PLASMALEUCÓCITOSPLAQUETASERITRÓCITOS
  3. 3. MacrophagesMonocytesInnateMain functionPhagocytosisExocytosis,CytotoxicityModulationAntibodyproductionAdaptiveBasophilsEosinophilsT CytotoxicT lymphocytesB lymphocytesT Helper(Th1, Th2)NeutrophilsGranulocytesNK lymphocytesFigure 10.1 Cellular components of the immune system and their main functions.Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases, 2013
  4. 4. MacrophagesMonocytesInnateMain functionPhagocytosisExocytosis,CytotoxicityModulationAntibodyproductionAdaptiveBasophilsEosinophilsT CytotoxicT lymphocytesB lymphocytesT Helper(Th1, Th2)NeutrophilsGranulocytesNK lymphocytesFigure 10.1 Cellular components of the immune system and their main functions.Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases, 2013
  5. 5. Inflammationandeccentricexercise•77Figure 1 Exercise-induced muscle damage and subsequent muscle inflammation and regeneration process(PMN, polymorphonuclear leucocyte; Mb, myoglobin; CK, creatine kinase; ROS, reactive oxygen species)PMNsatellite cellsregeneratedmuscle fibresRecovery• proliferation of satellite cells• acquisition of protective effectAfter exercise• leukocyte infiltration• inflammationDuring exercisemechanical damage to muscletissuemonocytesmacrophagesgrowthfactorscytokinesphagocytosiscytokineschemoattractantsprimingdamagedmuscle fibresROSenzymesmuscle tissuefragmentsCKCKMbMbmuscle tissuefragmentsphagocytosisadhesion moleculesendothelial cellsblood circulationExercise 24 hours after exercise 1 day to 2 weeks after exerciseInflammationandeccentricexercise•77Figure 1 Exercise-induced muscle damage and subsequent muscle inflammation and regeneration process(PMN, polymorphonuclear leucocyte; Mb, myoglobin; CK, creatine kinase; ROS, reactive oxygen species)PMNsatellite cellsregeneratedmuscle fibresRecovery• proliferation of satellite cells• acquisition of protective effectAfter exercise• leukocyte infiltration• inflammationDuring exercisemechanical damage to muscletissuemonocytesmacrophagesgrowthfactorscytokinesphagocytosiscytokineschemoattractantsprimingdamagedmuscle fibresROSenzymesmuscle tissuefragmentsCKCKMbMbmuscle tissuefragmentsphagocytosisadhesion moleculesendothelial cellsblood circulationExercise 24 hours after exercise 1 day to 2 weeks after exercisePeake J, Nosaka K, Suzuki K. Exerc Immunol Rev. 2005;11:64-85
  6. 6. acsainhaoppanacosiR(CtiointhfoananFIGURE 2. Diagrammatic representation of the movement of leukocytesthrough the endothelium and the subsequent generation of inflammatorymediators.  Calder PC. Am J Clin Nutr 2006;83(suppl):1505S–19S)
  7. 7. INFLAMAÇÃO AGUDADelves PJ, Roitt, IM. N Engl J Med. 2000 Jul 6;343(1):37-49.Calor Vermelhidão Inchaço DorPerda defunção
  8. 8. acsainhaoppanacosiR(CtiointhfoananFIGURE 2. Diagrammatic representation of the movement of leukocytesthrough the endothelium and the subsequent generation of inflammatorymediators.  Calder PC. Am J Clin Nutr 2006;83(suppl):1505S–19S)
  9. 9. The Chemistry of Food – and of Bodies 11Aqueous (polar) environmentoutside cellPhospholipidmolecule Intrinsic protein(e.g. sugar carrier,hormone receptor)CholesterolmoleculesNon-polar(hydrophobic)regionwithinmembraneAqueous (polar) environmentinside cellFigure 1.5 Structure of biological membranes in mammalian cells. Cell membranesand intracellular membranes such as the endoplasmic reticulum are composed of bilayers of phos-pholipid molecules with their polar head-groups facing the aqueous environment on either side andtheir non-polar ‘tails’ facing inwards, forming a hydrophobic center to the membrane. The membranealso contains intrinsic proteins such as hormone receptors, ion channels, and sugar transporters, andmolecules of cholesterol which reduce the ‘fluidity’ of the membrane. Modern views of cell mem-brane structure emphasize that there are domains, known as ‘rafts,’ in which functional proteinsco-locate, enabling interactions between them. These lipid rafts are characterized by high concentra-Frayn KN. Metabolic Regulation. Blackwell Pub; 2010:384.
  10. 10. De Caterina R. N Engl J Med 2011AINES ÁCIDO ARAQUIDÓNICO
  11. 11. De Caterina R. N Engl J Med 2011Coxibs ÁCIDO ARAQUIDÓNICO
  12. 12. Nonsteroidal Anti-Inflammatory Drugs 241FCHCO2HCH3BrSFSO2CH3 Bulky groupingCOX-1 inhibitorFlurbiprofenCOX-2 inhibitorDuP697Intracellular membraneNSAID binding spaceCOX-1 COX-2“Side pocket”Figure 18.2. Serhan CN, Ward PA, Gilroy DW, editors. Fundamentals of Inflammation. Cambridge Univ Pr; 2010: 234-243.AINESCoxibs
  13. 13. Inflammationandeccentricexercise•77Figure 1 Exercise-induced muscle damage and subsequent muscle inflammation and regeneration process(PMN, polymorphonuclear leucocyte; Mb, myoglobin; CK, creatine kinase; ROS, reactive oxygen species)PMNsatellite cellsregeneratedmuscle fibresRecovery• proliferation of satellite cells• acquisition of protective effectAfter exercise• leukocyte infiltration• inflammationDuring exercisemechanical damage to muscletissuemonocytesmacrophagesgrowthfactorscytokinesphagocytosiscytokineschemoattractantsprimingdamagedmuscle fibresROSenzymesmuscle tissuefragmentsCKCKMbMbmuscle tissuefragmentsphagocytosisadhesion moleculesendothelial cellsblood circulationExercise 24 hours after exercise 1 day to 2 weeks after exerciseInflammationandeccentricexercise•77Figure 1 Exercise-induced muscle damage and subsequent muscle inflammation and regeneration process(PMN, polymorphonuclear leucocyte; Mb, myoglobin; CK, creatine kinase; ROS, reactive oxygen species)PMNsatellite cellsregeneratedmuscle fibresRecovery• proliferation of satellite cells• acquisition of protective effectAfter exercise• leukocyte infiltration• inflammationDuring exercisemechanical damage to muscletissuemonocytesmacrophagesgrowthfactorscytokinesphagocytosiscytokineschemoattractantsprimingdamagedmuscle fibresROSenzymesmuscle tissuefragmentsCKCKMbMbmuscle tissuefragmentsphagocytosisadhesion moleculesendothelial cellsblood circulationExercise 24 hours after exercise 1 day to 2 weeks after exercisePeake J, Nosaka K, Suzuki K. Exerc Immunol Rev. 2005;11:64-85
  14. 14. fibers, as previously mentioned.These cells have also been usedgenetic disease (such as Duch-enne muscular dystrophy [DMD]),skeletal muscle is limited and veryoften, fibrotic tissue forms, delay-Figure 1. Generalized scheme of myogenic differentiation. Other markers are used by different investigators. (Adapted from Deasyet al., 2001, Blood Cells Mol Dis, 27, 924–933)MODULATING SKELETAL MUSCLE REPAIR BY MUSCLE DERIVED STEM CELLS AND ANTIFIBROTIC AGENTS 83Mio D – factor de transcrição responsávelpela activação das células satélite esubsequente proliferação dos mioblastosGharaibeh B, et al. Birth Defects Res C Embryo Today. 2012 Mar;96(1):82-94.
  15. 15. 52 • Exercise-induced muscle damage and inflammation-60-50-40-30-20-10010-24 0 24 48 72 96 120 144 168Changeinforce-generatingcapacity(%)Time (hours after exercise)Mild damageModerate damageSevere damageFigure 2. Recovery of the force-generating capacity of subjects that have performed heavyresistance exercise or maximal eccentric exercise (subjects from several studies are com-bined: (230,248-251), as well as unpublished data). The subjects are organized so thatthose who recover their force-generating capacity within 48 hours are represented as mildPaulsen G, Mikkelsen UR, Raastad T, Peake JM. Exerc Immunol Rev. 2012;18:42-97
  16. 16. ü 14 atletasü Corrida de 36 Kmü Indometacina (100 mg) vs Placeboü  Ingestão: durante 4 dias antes da corrida até à data daúltima biópsiaRESULTADOS:J Appl Physiol 103: 425–431, 2007
  17. 17. 39CélulasSatéliteJ Appl Physiol 103: 425–431, 2007
  18. 18. 40J Appl Physiol 107: 1600–1611, 2009200 contrações excêntricasNSAID numa perna (antes, durante e até 4,5 h depois) e a outra como controloCélulassatélite
  19. 19. protein accretion seen in eccentric protocols. Other studies,however, seem to refute whether a reversal of the sizeprinciple actually does occur. An extensive review of theliterature by Chalmers (26) concluded that the preponder-ance of evidence does not support selective recruitment ofgenerally less compared with those performed concentri-cally. This paradox was demonstrated by Grabiner et al. (55),who found that the maximum EMG of the vastus lateralisduring eccentric knee extension was only 84 6 41% of thatobtained concentrically. Hence, although the potential toTABLE 1. Summary of human studies investigating the effect of NSAID consumption on satellite cell activity.*Study Subjects NSAID/dosage ResultsBondesen et al. (16) Rodents SC-560/3 mgÁkg21Ád21SC-236 /6 mgÁkg21Ád21Significant blunting of satellite cellactivity in NSAID comparedwith placeboBondesen et al. (17) Rodents SC-236 /6 mgÁkg21Ád21Significant blunting of satellite cellactivity in NSAID compared withplaceboMackey et al. (91) Humans Indomethacin/100 mg Significant blunting of satellite cellactivity in NSAID compared withplaceboMikkelsen et al. (100) Humans Indomethacin/45 mg Significant blunting of satellite cellactivity in NSAID compared withplaceboPaulsen et al. (117) Humans Celcoxib/400 mg No significant differences in satellitecell activity between groups*NSAIDs = nonsteroidal anti-inflammatory drugs.Exercise-Induced Muscle DamageSchoenfeld BJ. J Strength Cond Res. 2012 May;26(5):1441-53.
  20. 20. Am J Physiol Cell Physiol 287: C475–C483, 2004Inibidor deCOX-2Lesão induzida pelo frio
  21. 21. Inibidor da COX-2
  22. 22. ACETAM IBUPROF PLACEBOJ. Clin. Endocrinol. Metab. 2001 86: 5067-5070
  23. 23. Lesão c/ contracçõesexcêntricas em Coelhos2xdiaDurante 6 dias
  24. 24. 48 Am J Physiol Regul Integr Comp Physiol 296: R1132–R1139, 2009.
  25. 25. ü 24 adultos masculinosü RCT com Placeboü 10-14 series de 10 rep excéntricas RMDIMINUIÇÃO (24h): Fractional synthesis rateSem efeitos na dor comparado com placeboAm J Physiol Endocrinol Metab 2002; 282: E551–E556
  26. 26. 50Am J Physiol Endocrinol Metab 2002; 282: E551–E556Fractional Synthesis Rate
  27. 27. Basic & Clinical Pharmacology & Toxicology 2007; 102: 10–14
  28. 28. 52INFLAMAÇÃO AGUDAINFLAMAÇÃO CRÓNICAREGENERAÇÃOAhn KS, Aggarwal BB. Ann N Y Acad Sci. 2005 Nov;1056:218-33Serhan CN. Annu. Rev. Immunol. 2007. 25:101–37Roubenoff R. Nutr Rev. 2007 Dec;65(12 Pt 2):S208-12Tidball JG, Villalta SA. Am J Physiol Regul Integr Comp Physiol 2010; 298: R1173–R1187Lesão e Dor CrónicaCatabolismo muscular e ósseoSíndrome de Morte SúbitaDoenças Metabólicase Neurodegenativas
  29. 29. Chen LC, Ashcroft DM. Pharmacoepidemiol Drug Saf. 2007 Jul;16(7):762-72
  30. 30. 54INFLAMAÇÃO AGUDAINFLAMAÇÃO CRÓNICAREGENERAÇÃOAhn KS, Aggarwal BB. Ann N Y Acad Sci. 2005 Nov;1056:218-33Serhan CN. Annu. Rev. Immunol. 2007. 25:101–37Roubenoff R. Nutr Rev. 2007 Dec;65(12 Pt 2):S208-12Tidball JG, Villalta SA. Am J Physiol Regul Integr Comp Physiol 2010; 298: R1173–R1187AA  Lesão e Dor CrónicaCatabolismo muscular e ósseoSíndrome de Morte SúbitaDoenças Metabólicase Neurodegenativas
  31. 31. 55GORDURAS
  32. 32. 56ACILGLICERÓIS PODEM TER:1 ácido gordo (acil):monoacilglicerol ou monoglicéridos2 ácidos gordos (acil): díacilglicerolou diglicéridos3 ácidos gordos (acil): Triacilglicerolou TriglicéridosErasmus U. Fats that heal, fats that kill. Alive Books 1993
  33. 33. 57Erasmus U. Fats that heal, fats that kill. Alive Books 1993HidrofóbicaApolarHidrofílicoPolarÓmega(Metil)Carboxil
  34. 34. 58ü Cadeia curta: 4-6 carbonosü Cadeia média: 8-12 carbonosü Cadeia longa: 14-20 carbonosü Cadeia muito longa: 22+ carbonosH H H H H H H H H H H OI I I I I I I I I I I IIH-C-C-C-C-C-C-C-C-C-C-C-C-OHI I I I I I I I I I I IH H H H H H H H H H H H112Grupo CarboxilOmega(Grupo Metil)Mataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.
  35. 35. 59CADA ÁTOMO DE CARBONO TEM 4 UNIÕESH H H H H H H H H H H OI I I I I I I I I I I IIH-C-C-C-C-C-C-C-C-C-C-C-C-OHI I I I I I I I I I I IH H H H H H H H H H H HGrupo CarboxilÓmega(Grupo Metil)Mataix J. Nutrición y Alimentación Humana – Tomo I: Nutrientes y Alimentos. Ergon, 2002.
  36. 36. 60Erasmus U. Fats that heal, fats that kill. Alive Books 1993
  37. 37. 61AG MONOINSATURADOSH H H H H H H H H H H H H H H H H OI I I I I I I I I I I I I I I I I IIH-C-C-C-C-C-C-C-C-C=C-C-C-C-C-C-C-C-C -OHI I I I I I I I I I I I I I IH H H H H H H H H H H H H H HÁcido Oleico = 18:1n-91 união duplaLongitude: 18 carbonos9 carbonos a partir do ómegaÓmega(Metil)CarboxilCordain, 2006
  38. 38. 62Erasmus U. Fats that heal, fats that kill. Alive Books 1993
  39. 39. 63Erasmus U. Fats that heal, fats that kill. Alive Books 1993
  40. 40. 64AG POLINSATURADOS N-6H H H H H H H H H H H H H H H H H OI I I I I I I I I I I I I I I I I IIH-C-C-C-C-C-C=C-C-C=C-C-C-C-C-C-C-C-C -OHI I I I I I I I I I I I IH H H H H H H H H H H H HÁcido Linoleico = 18:2n-6Ómega(metil)CarboxilCordain, 2006
  41. 41. 65H H H H H H H H H H H H H H H H H OI I I I I I I I I I I I I I I I I IIH-C-C-C=C-C-C=C-C-C=C-C-C-C-C-C-C-C-C -OHI I I I I I I I I I IH H H H H H H H H H HÁcido α Linolénico = 18:3n-3Ómega(metil)CarboxilCordain, 2006AG POLINSATURADOS N-3
  42. 42. 66CitosolFluidoExtracelular
  43. 43. De Caterina R. N Engl J Med 2011
  44. 44. Ácido Eicosapentaenóico(EPA)20:5 n-3Lipooxigenases CiclooxigenasesÁcido Araquidónico20:4 n-6LTA4LTB4LTC4LTD4LTE412-HETETXA2PGE2PGF2αPGD2PGI2TXA3PGE3PGF3 αPGD3PGI3LTA5LTB5LTC5LTD5LTE5Bastos P. An Nutr Esp Func 2007; 7(36): 17-24
  45. 45. EPA/DHA E AACalder PC. Am J Clin Nutr 2006;83(suppl):1505S–19S.
  46. 46.  Calder PC. Am J Clin Nutr 2006;83(suppl):1505S–19S)DHA  
  47. 47.  Calder PC. Am J Clin Nutr 2006;83(suppl):1505S–19S)DHA  
  48. 48. Gilroy DW. 2010RESOLUÇÃO DA INFLAMAÇÃO
  49. 49. Serhan CN, Chiang N. Rheum Dis Clin N Am 30 (2004) 69–95
  50. 50. Serhan CN, Chiang N. Rheum Dis Clin N Am 30 (2004) 69–95
  51. 51. 1578 SerhanAJP October 2010, Vol. 177, No. 4Serhan CN. Am J Pathol. 2010 Oct;177(4):1576-91!Lipoxinas!RESOLUÇÃO DA INFLAMAÇÃO
  52. 52. Serhan CN, Chiang N. British Journal of Pharmacology (2008) 153, S200–S215.
  53. 53. Serhan CN, Chiang N. British Journal of Pharmacology (2008) 153, S200–S215.
  54. 54. Serhan, CN. Annu. Rev. Immunol. 2007. 25:101–37
  55. 55. DOSES BAIXAS DE ASPIRINAChiang N et al. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial.PNAS 2004. 101; 42
  56. 56. De Caterina R. N Engl J Med 2011
  57. 57. Barnes PJ, Karin M. N Engl J Med. 1997 Apr 10;336(15):1066-71.
  58. 58. LXA4 INIBE TRANSLOCAÇÃO NFK-B!Kure I, et al. J Pharmacol Exp Ther. 2010 Feb;332(2):541-8
  59. 59. LXA4 INIBE PRODUÇÃO TNF-ALFA!Kure I, et al. J Pharmacol Exp Ther. 2010 Feb;332(2):541-8
  60. 60. LXA4 RESOLVE INFLAMAÇÃO SINOVIAL!Fiore et al. Prostaglandins, Leukotrienes and Essential Fatty Acids 73 (2005) 189–196
  61. 61. EPA & DHACalder PC. Biochimie. 2009 Feb 3. [Epub ahead of print]
  62. 62. 91EPA E DHA DIMINUEMü IL1-ßü IL6ü TNF-α  Calder PC. Braz J Med Biol Res 36(4) 2003
  63. 63. A meta-analysis of the analgesic effects of omega-3 polyunsaturatedfatty acid supplementation for inflammatory joint painRobert J. Goldberg a,c, Joel Katz a,b,c,d,*aDepartment of Psychology, York University, Toronto, ON, CanadabSchool of Kinesiology and Health Science, York University, Toronto, ON, CanadacDepartment of Anesthesia and Pain Management, Toronto General Hospital and Mount Sinai Hospital, CanadadDepartment of Anesthesia, University of Toronto, CanadaReceived 1 September 2006; received in revised form 23 December 2006; accepted 22 January 2007AbstractBetween 40% and 60% of Americans use complementary and alternative medicine to manage medical conditions, prevent disease,and promote health and well-being. Omega-3 polyunsaturated fatty acids (x-3 PUFAs) have been used to treat joint pain associatedwith several inflammatory conditions. We conducted a meta-analysis of 17 randomized, controlled trials assessing the pain relievingwww.elsevier.com/locate/painPain 129 (2007) 210–223
  64. 64. showed significant improvements. Improvements inmorning stiffness and NSAID consumption were noted,stiffness, and SMD: À0.65; 95% CI: À1.40 to 0.09,p = 0.09 for NSAID consumption). Significant effectsGeusens 1994 19 1.58(0.57) 20 1.75(2.68) 32.18 -0.08 [-0.71, 0.54]Remans 2004 26 38.00(7.00) 29 38.00(18.00) 45.33 0.00 [-0.53, 0.53]Total (95% CI) 62 61 100.00 -0.14 [-0.49, 0.22]Test for heterogeneity: Chi² = 1.14, df = 2 (P = 0.56), I² = 0%Test for overall effect: Z = 0.76 (P = 0.45)-4 -2 0 2 4Favours Omega-3 PUFA Favours PlaceboReview: Omega-3 polyunsaturated fatty acids for painComparison: 02 Omega-3 polyunsaturated fatty acids versus placebo for joint pain: supplementation for 3-4 monthsOutcome: 03 Morning Stiffness (minutes)Study Omega-3 PUFA Placebo SMD (random) Weight SMD (random)or sub-category N Mean (SD) N Mean (SD) 95% CI % 95% CIKremer 1985 23 56.00(48.00) 21 131.00(142.00) 13.78 -0.71 [-1.32, -0.10]Cleland 1988 23 25.00(30.00) 23 38.00(45.00) 14.63 -0.33 [-0.92, 0.25]vanderTempel 1989 14 15.00(18.70) 14 50.00(48.64) 9.83 -0.92 [-1.71, -0.14]Kremer 1990 17 39.10(75.30) 12 26.30(32.70) 10.68 0.20 [-0.54, 0.94]Tulleken 1990 13 45.00(35.70) 14 75.00(52.68) 9.98 -0.64 [-1.42, 0.14]Nielson 1992 27 78.75(41.25) 24 120.00(60.00) 14.91 -0.80 [-1.37, -0.22]Remans 2004 26 76.00(70.00) 29 71.00(40.00) 16.31 0.09 [-0.44, 0.62]Berbert 2005 13 21.00(49.00) 13 46.00(47.00) 9.88 -0.50 [-1.29, 0.28]Total (95% CI) 156 150 100.00 -0.43 [-0.72, -0.15]Test for heterogeneity: Chi² = 10.77, df = 7 (P = 0.15), I² = 35.0%Test for overall effect: Z = 2.95 (P = 0.003)-4 -2 0 2 4Favours Omega-3 PUFA Favours PlaceboReview: Omega-3 polyunsaturated fatty acids for painComparison: 02 Omega-3 polyunsaturated fatty acids versus placebo for joint pain: supplementation for 3-4 monthsOutcome: 04 Number of Painful / Tender JointsStudy Omega-3 PUFA Placebo SMD (random) Weight SMD (random)or sub-category N Mean (SD) N Mean (SD) 95% CI % 95% CIKremer 1985 23 6.40(5.60) 21 9.00(8.30) 10.40 -0.36 [-0.96, 0.23]Cleland 1988 23 9.50(7.50) 23 12.00(10.25) 10.98 -0.27 [-0.85, 0.31]vanderTempel 1989 14 29.00(26.19) 14 42.00(33.67) 6.58 -0.42 [-1.17, 0.33]Kremer 1990 17 3.00(5.15) 12 6.20(4.15) 6.40 -0.65 [-1.41, 0.11]Tulleken 1990 13 14.50(12.69) 14 16.50(8.78) 6.47 -0.18 [-0.94, 0.58]Nielson 1992 27 8.00(3.00) 24 11.00(5.00) 11.44 -0.73 [-1.30, -0.16]Geusens 1994 19 15.00(8.72) 20 19.00(13.42) 9.25 -0.34 [-0.98, 0.29]Adam 2003 30 33.60(18.07) 30 36.00(21.91) 14.44 -0.12 [-0.62, 0.39]Remans 2004 26 10.70(4.10) 29 9.70(5.10) 13.14 0.21 [-0.32, 0.74]Sundrarjun 2004 23 9.13(6.62) 23 12.30(10.31) 10.90 -0.36 [-0.94, 0.22]Total (95% CI) 215 210 100.00 -0.29 [-0.48, -0.10]Test for heterogeneity: Chi² = 7.35, df = 9 (P = 0.60), I² = 0%Test for overall effect: Z = 2.97 (P = 0.003)-4 -2 0 2 4Favours Omega-3 PUFA Favours placeboFig. 3. Analysis of data used in overall result assessment from studies providing 3–4 month supplementation of x-3 PUFAs. Conducted usingCochrane Review Manager 4.2.8. software. SD, standard deviation; SMD, standardized mean difference; CI, confidence interval.www.elsevier.com/locate/painPain 129 (2007) 210–223
  65. 65. ÓMEGA-3 E INFLAMAÇÃOü  17 meta-análises deRCTs testando osefeitos de Ómega-3 naARü  3-4 meses: redução dador articular, minutosde rigidez matinal,número dearticulações com dore menor uso de AINESGoldberg RJ, Katz J. Pain 129 (2007)
  66. 66. tTable 2. Comparison of fish oil with adalimumab (Values are thestandardised mean difference*)Tender or swollenjoint count PainFish oil - 0.29† - 0.26†Adalimumab(Humira)- 0.52 to - 0.69‡ - 0.27‡*Hedges’ g was used to calculate the standardised mean difference, which isthe difference between means divided by the pooled standard deviation.†Goldberg and Katz(4).‡Calculated from data in FDA(67).. James et al.ProceedingsoftheNutritionSocietyThe 3rd International Immunonutrition Workshop was held at Platja D’Aro, Girona, Spain on 21–24 October3rd International Immunonutrition WorkshopSession 3: Fatty acids and the immune systemFish oil and rheumatoid arthritis: past, present and futureMichael James*, Susanna Proudman and Les ClelandRheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, AustraliaMeta- and mega-analysis of randomised controlled trials indicate reduction in tender jointcounts and decreased use of non-steroidal anti-inflammatory drugs with fish-oil supplemen-tation in long-standing rheumatoid arthritis (RA). Since non-steroidal anti-inflammatory drugsconfer cardiovascular risk and there is increased cardiovascular mortality in RA, an additionalbenefit of fish oil in RA may be reduced cardiovascular risk via direct mechanisms anddecreased non-steroidal anti-inflammatory drug use. Potential mechanisms for anti-inflammatoryeffects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), andprovision of substrates for synthesis of lipid suppressors of inflammation (resolvins). Futurestudies need progress in clinical trial design and need to shift from long-standing disease toexamination of recent-onset RA. We are addressing these issues in a current randomised con-trolled trial of fish oil in recent-onset RA, where the aim is to intervene before joint damage hasoccurred. Unlike previous studies, the trial occurs on a background of drug regimens deter-mined by an algorithm that is responsive to disease activity and drug intolerance. This allowsdrug use to be an outcome measure whereas in previous trial designs, clinical need to alter druguse was a ‘problem’. Despite evidence for efficacy and plausible biological mechanisms, thelimited clinical use of fish oil indicates there are barriers to its use. These probably include thepharmaceutical dominance of RA therapies and the perception that fish oil has relativelymodest effects. However, when collateral benefits of fish oil are included within efficacy, theargument for its adjunctive use in RA is strong.Rheumatoid arthritis: Fish oil: Pain: Non-steroidal anti-inflammatory drugsEfficacy: different outcome measures and the evidenceThe main reason that patients with rheumatoid arthritis(RA) seek medical treatment is for alleviation of pain anddiscomfort. Meta- and mega-analysis of ten double-blind,placebo-controlled trials showed that fish oil supplying2.9– >6 g long-chain n-3 fatty acids daily for 3 monthswas associated with decreased number of tender joints andduration of morning stiffness in patients with RA of 10–11years’ duration(1,2). It was concluded that there was littledifference in the magnitude of effect between 2.9 and7.1 g/d long-chain n-3 fats(3).Another symptomatic outcome measure is overall painexperience, which is measured most commonly in clinicaltrials by use of a visual linear analogue scale or categoricalscales. A meta-analysis of fish oil trials that measuredinflammatory joint pain, mainly with RA patients, reporteda beneficial effect of fish oil on patient-reported joint painintensity, number of painful or tender joints, duration ofmorning stiffness and non-steroidal anti-inflammatorydrug (NSAID) use(4). However, another meta-analysis thatexamined the effect of fish oil on pain scores in RAreported that ‘There were no significant effects in twelvestudies’(5). However, this latter meta-analysis did not takeAbbreviations: AA, arachidonic acid; COX, cyclooxygenase; DMARD, disease-modifying anti-rheumatic drugs; LOX, lipoxygenase; LTB, leukotriene B;NSAID, non-steroidal anti-inflammatory drugs; RA, rheumatoid arthritis; RCT, randomised controlled trials.*Corresponding author: Dr Michael James, fax 61-8-82224139, email michael.james@health.sa.gov.auProceedings of the Nutrition Society (2010), 69, 316–323 doi:10.1017/S0029665110001564g The Authors 2010 First published online 28 May 2010
  67. 67. Table 4. Clinical indices of disease activity at baseline and 3 years. Data are mean ± SD unless stated otherwise.No Fish Oil Fish OilBaseline, 3 Years, Baseline, 3 Years,n = 13 n = 13 n = 18 n = 18mHAQ 7.1 ± 4.2 3.3 ± 3.2* 6.6 ± 3.2 1.2 ± 1.7*#Tender joint count 28 8.8 ± 3.6 3.5 ± 3.9* 6.4 ± 6.2 0.7 ± 1.1*#Swollen joint count 28 6.9 ± 4.7 0.3 ± 0.6* 5.4 ± 5.5 0.9 ± 1.8*ESR, mm/h, mean (range) 36.5 (4–80) 21.5 (8–46)* 43.1 (1–91) 8.5 (2–34)*#CRP, mg/l, mean (range) 17.2 (4–34) 6.6 (3–15)* 30.8 (1–140) 4.0 (0.3–19)*DAS28 5.7 ± 0.9 3.3 ± 1.0* 5.0 ± 1.5 2.1 ± 0.9*#NSAID Use, %† 86 54 89 22Remission Rates at 3 years, %†† — 31 — 72* Significantly different from baseline (p < 0.01, except for ESR in No fish oil group, where p < 0.05).# Significantly different at 3 years by comparison with the No fish oil group (p < 0.05). † NSAID use at 3 yearsdefined as any use of NSAID for rescue analgesia within 3rd year of the study. †† Remission rate at 3 years isbased on DAS28 < 2.6 according to EULAR criteria. DAS: Disease Activity Score; mHAQ: modified HealthAssessment Questionnaire.J Rheumatol 2006;33:1973–9
  68. 68. ty acid analyses provide a sound basis for examininghemical effects of antiinflammatory doses of fish oilthin the context of structured chemotherapy. Thecompliant users constituted the upper quartile forchange in EPA in plasma phospholipids. It is acknowlthat this measure may be influenced by individual diffein efficiency of incorporation of ingested n-3 fatty acidphospholipids. Notwithstanding, the defining value ofFigure 1. A. Arachidonic acid (AA) as a proportion of AA plus competitor n-3 fatty acids (AA+EPA+DPA+DHA)(mean ± SEM) at 3 years in platelets and peripheral blood mononuclear cells (PBMC). B. Eicosanoid formation inwhole-blood assay at 3 years (mean ± SEM). TXB2 measured in serum (formed through platelet COX-1). PGE2 meas-ured in supernatants after 24 h incubation of anticoagulated blood with LPS (formed through COX-2). *p < 0.01,unpaired t test.Table 3. Lipid cardiovascular risk factors in plasma and erythrocytes from fasting blood samples. RBC Omega-3 Index (EPA+DHA) is an independent index that correlates inversely with CV risk19. Data represent mean ±SD.No Fish Oil Fish OilBaseline, 3 Years, Baseline, 3 Years,n = 11 n = 13 n = 10 n = 18Total triglycerides 1.4 ± 0.7 1.4 ± 0.5 1.6 ± 0.5 0.6 ± 0.2*#Total cholesterol 5.4 ± 0.6 5.3 ± 0.9 5.6 ± 1.5 5.3 ± 0.8HDL 1.2 ± 0.5 1.4 ± 0.4 1.6 ± 0.5 1.9 ± 0.4*#LDL 3.6 ± 0.7 3.3 ± 1.0 3.4 ± 1.2 3.1 ± 0.9Total cholesterol/HDL 4.5 ± 2.4 3.5 ± 1.5 3.6 ± 0.8 3.0 ± 0.8*#RBC omega-3 index — 5.06 ± 0.8 — 13.8 ± 1.8#(EPA+DHA)* Significantly different from baseline (p < 0.01, paired t test); # significantly different at 3 years compared withthe No fish oil group (p < 0.05, t test).J Rheumatol 2006;33:1973–9
  69. 69. ÍNDICE Ω3: % EPA & DHA NA MEMBRANADOS ERITRÓCITOS.8%  Risco Baixo4-8%  Risco Intermédio< 4%  Risco AltoHarris WS. Am J Clin Nutr. 2008 Jun;87(6):1997S-2002S
  70. 70. ACTIVIDADE LIMITADAACTIVIDADLIMITADABETA-OXIDAÇÃO
  71. 71. VEGANS TÊM NÍVEIS BAIXOS DE AA E DHAFokkema et al. Polyunsaturated fatty acid status of Dutch vegans and omnivores. Prostaglandins, Leukotrienes and Essential FattyAcids (2000)
  72. 72. 9 vegans saudáveis suplementados com:ü A: 2.01 g ALA (4 ml óleo de linhaça)ü B: 1.17 g GLA (6 ml óleo borragem)ü A+B
  73. 73. Blasbalg TL, et al. Am J Clin Nutr. 2011FIGURE 4. Regression analysis for the availability of linoleic acid (LA)between 1909 and 1999. The linear relation [LA percentage of energy(en%) = 2115.4221 + 0.0617 · x] was significant at P , 0.000001 withFIGURsupply frindicatedline, and nline. 190data areESSENTIAL FATTY ACID INTAKE IN T
  74. 74. Blasbalg TL, et al. Am J Clin Nutr. 2011lipids (37), presumabdietary intakes of LAaccount for the potenHowever, because LAeffects may be nonlinA randomized trial twith high LA (6.7% ofFIGURE 8. Omega-3 tissue highly unsaturated fatty acid (HUFA)predictions over the 20th century. Solid arrows indicate the percentage ofTABLE 12Sources of docosahexaenoFood categoryPoultryShellfishEggsFinfishBeefGameTotal1NA, not applicable.
  75. 75. DIET AND RED BLOOD CELL n–6 AND n–3 FATTY ACIDSLA diminuiDHA namembranadoseritrócitosLA diminuiEPA namembranadoseritrócitosFriesen RW, Innis SM. Am J Clin Nutr. 2010 Jan;91(1):23-31.N= 105Mulheres(Canadá)Grávidas(com 36semanas degestação)
  76. 76. Original ResearchInvolvement of CYP 2C9 in Mediating theProinflammatory Effects of Linoleic Acid in VascularEndothelial CellsSaraswathi Viswanathan PhD, Bruce D. Hammock PhD, John W. Newman, PhD, Purushothaman Meerarani PhD,Michal Toborek MD, PhD, and Bernhard Hennig PhD, FACNMolecular and Cell Nutrition Laboratory, College of Agriculture (S.V., P.M., B.H.), Department of Surgery (M.T.), University ofKentucky, Lexington, KY, 40546-0215, and Department of Entomology and UC Cancer Center (B.D.H., J.W.N.), University ofCalifornia, Davis, CA, USA.Key words: linoleic acid, CYP 2C9, leukotoxin, leukotoxin diol, oxidative stressObjective: Polyunsaturated fatty acids such as linoleic acid are well known dietary lipids that may beatherogenic by activating vascular endothelial cells. In the liver, fatty acids can be metabolized by cytochromeP450 (CYP) enzymes, but little is known about the role of these enzymes in the vascular endothelium. CYP 2C9is involved in linoleic acid epoxygenation, and the major product of this reaction is leukotoxin (LTX). Weinvestigated the role of CYP-mediated mechanisms of linoleic acid metabolism in endothelial cell activation byexamining the effects of linoleic acid or its oxidized metabolites such as LTX and leukotoxin diol (LTD).Methods: The effect of linoleic acid on CYP 2C9 gene expression was studied by RT-PCR. Oxidative stresswas monitored by measuring DCF fluorescence and intracellular glutathione levels, and electrophoretic mobilityshift assay was carried out to study the activation of oxidative stress sensitive transcription factors. Analysis ofoxidized lipids was carried out by liquid chromatography/mass spectrometry.Results: Linoleic acid treatment for six hours increased the expression of CYP 2C9 in endothelial cells.Linoleic acid-mediated increase in oxidative stress and activation of AP-1 were blocked by sulfaphenazole, aspecific inhibitor of CYP 2C9. The linoleic acid metabolites LTX and LTD increased oxidative stress andactivation of transcription factors only at high concentrations.Conclusion: Our data show that CYP 2C9 plays a key role in linoleic acid-induced oxidative stress andsubsequent proinflammatory events in vascular endothelial cells by possibly causing superoxide generationthrough uncoupling processes.INTRODUCTIONAtherosclerosis is believed to be a chronic inflammatorydisease, and the earliest event of coronary atherosclerosis ischaracterized by endothelial activation and dysfunction [1].Several factors are implicated in the initiation of endothelialdysfunction of which the formation of reactive oxygen speciesis believed to play a critical role during this process [2,3].Endothelial cells are continuously exposed to circulatinglipids (e.g., dietary fatty acids) and to lipids that have accumulatedin sub-endothelial regions. These biologically active lipids play animportant role in the development of atherosclerosis. Polyunsatu-rated fatty acids and/or their metabolites can have potent biolog-ical effects in various cell types by functioning as signaling mol-ecules. Evidence suggests that linoleic acid, a major dietaryunsaturated fatty acid in the American diet, has proinflammatoryand proatherogenic effects by causing endothelial cell activation[4]. Linoleic acid-induced endothelial activation is considered tobe mediated through oxidative stress [4,5]. However, the precisemechanism involved in linoleic acid-induced oxidative stress andAddress reprint requests to: Bernhard Hennig, PhD, RD, FACN, Molecular and Cell Nutrition Laboratory, College of Agriculture, 213 Garrigus Building, University ofKentucky, Lexington, KY 40546-0215. E-mail: bhennig@uky.eduSaraswathi Viswanathan PhD, Bruce D. Hammock PhD, John W. Newman, PhD, Purushothaman Meerarani PhD,Michal Toborek MD, PhD, and Bernhard Hennig PhD, FACNMolecular and Cell Nutrition Laboratory, College of Agriculture (S.V., P.M., B.H.), Department of Surgery (M.T.), University ofKentucky, Lexington, KY, 40546-0215, and Department of Entomology and UC Cancer Center (B.D.H., J.W.N.), University ofCalifornia, Davis, CA, USA.Key words: linoleic acid, CYP 2C9, leukotoxin, leukotoxin diol, oxidative stressObjective: Polyunsaturated fatty acids such as linoleic acid are well known dietary lipids that may beatherogenic by activating vascular endothelial cells. In the liver, fatty acids can be metabolized by cytochromeP450 (CYP) enzymes, but little is known about the role of these enzymes in the vascular endothelium. CYP 2C9is involved in linoleic acid epoxygenation, and the major product of this reaction is leukotoxin (LTX). Weinvestigated the role of CYP-mediated mechanisms of linoleic acid metabolism in endothelial cell activation byexamining the effects of linoleic acid or its oxidized metabolites such as LTX and leukotoxin diol (LTD).Methods: The effect of linoleic acid on CYP 2C9 gene expression was studied by RT-PCR. Oxidative stresswas monitored by measuring DCF fluorescence and intracellular glutathione levels, and electrophoretic mobilityshift assay was carried out to study the activation of oxidative stress sensitive transcription factors. Analysis ofoxidized lipids was carried out by liquid chromatography/mass spectrometry.Results: Linoleic acid treatment for six hours increased the expression of CYP 2C9 in endothelial cells.Linoleic acid-mediated increase in oxidative stress and activation of AP-1 were blocked by sulfaphenazole, aspecific inhibitor of CYP 2C9. The linoleic acid metabolites LTX and LTD increased oxidative stress andactivation of transcription factors only at high concentrations.Conclusion: Our data show that CYP 2C9 plays a key role in linoleic acid-induced oxidative stress andsubsequent proinflammatory events in vascular endothelial cells by possibly causing superoxide generationthrough uncoupling processes.INTRODUCTION in sub-endothelial regions. These biologically active lipids play anJournal of the American College of Nutrition, Vol. 22, No. 6, 502–510 (2003)
  77. 77. fatty acids may beTo examine if theo oxidative stress,Fig. 8. Proposed model for the mechanism of linoleic acid (LA)-mediated endothelial cell activation. LA treatment results in CYP 2C9tabolites. Cells were; upper trace) for 24ed epoxides and diolsy. These metaboliteswithout supplemen-arachidonates werea not shown). Resultsaliquots analyzed byJournal of the American College of Nutrition, Vol. 22, No. 6, 502–510 (2003)
  78. 78. ÓLEOS VEGETAIS RICOS EM ÓMEGA-6DIMINUEM O RISCO DE DCV
  79. 79. Mensink  RP,  Zock  PL,  Kester  AD,  Katan  MB.  Am  J  Clin  Nutr.  2003  May;77(5):1146-­‐55  
  80. 80. non-­‐fatal  myocardial  infarcIon  (MI)  +  CHD  death.  n-6 specific PUFA trials non significantly increased the risk ofnon-fatal MI + CHD death by 13%(risk ratio (RR) 1·13; 95% CI 0·84, 1·53; P=0·427)
  81. 81. EPA & DHA por cada 100g peixeFedacko. n−3 PUFAs—From dietary supplements to medicines. Pathophysiology 14 (2007) 127–132
  82. 82. 117CONCENTRAÇÕES DE MERCÚRIOPeixeConcentraçãoMercúrio(ppm)Peixe-espada 0,97Arenque 0,35Atum 0,12Bacalhau 0,11Salmão 0,01Adaptado: FDA (EUA)
  83. 83. 118
  84. 84. RÁCIO ÓMEGA 6/ÓMEGA 3 DE ALGUNS ALIMENTOSAlimento Rácio ω6/ω3Ovo convencional 19,4Ovo de Creta 1,3Carne (músculo) bovinaalimentada com cereais5,19Carne (músculo) bovinaalimentada a pasto2,2Cordain L et al. European Journal of Clinical Nutrition 2002; 56:181 – 191.Simopoulos AP. J Nutr. 2001 Nov;131(11 Suppl):3065S-73S. Review
  85. 85. ESTIMAÇÃO DA INGESTÃO DE PUFASDURANTE O PALEOLÍTICOÁcidos Gordos(g)Dieta Baseadaem CarneDieta Baseada emPeixe e CarneDieta Baseada emPeixeALA 7,73 - 13,4 8,63 - 17,4 6,57 - 17,0EPA 0,14 - 0,59 0,30 – 2,80 1,41 – 6,61DHA 0,29 – 2,84 0,81 – 8,79 3,93 – 21,7LA 8,60 – 11,2 7,20 – 12,2 5,53 – 9,96AA 1,15 – 2,77 1,15 – 4,61 2,14 – 10,7ALA/LA 0,70 – 1,56 0,93 – 1,75 1,19 – 1,79(EPA+DHA) / AA 0,49 – 1,41 0,78 – 2,58 2,45 – 2,66n-6/n-3 0,79 – 1,59 1,01 – 2,01 1,82 – 2,05Kuipers RS, et al. Br J Nutr. 2010 Dec;104(11):1666-87
  86. 86. Time course relativo à incorporação de EPA e DHAem fosfolipídios de membrana de células mononuclearesIndivíduos saudáveis: 2,1 g EPA + 1,1 g DHA/dia/12 semanas0 4 8 12 2001234Time (weeks)EPAinmononuclearcellPL(%)0 4 8 12 201234Time (weeks)DHAinmononuclearcellPL(%)Eur. J. Clin. Invest. 30, 260-274, 2000Eur. J. Clin. Invest. 30, 260-274, 2000INCORPORAÇÃO DE EPA E DHA NOSFOSFOLÍPIDOS DE CÉLULAS MONONUCLEARES
  87. 87. • DCV• Hipertensão•  SíndromeMetabólica• Sarcopenia• Osteoporose• Depressão• CancroNF-KB E DOENÇAS DA CIVILIZAÇÃOAhn KS, Aggarwal BB. Ann N Y Acad Sci. 2005 Nov;1056:218-33
  88. 88. Informaçãopara oresto doorganismoStraub, R.H. et al., 2010. Journal of Internal Medicine
  89. 89. GASTO ENERGÉTICOStraub, R.H. et al., 2010. Journal of Internal Medicine
  90. 90. ü EM repouso: 1600 kJ•  (381 Kcal/dia)ü Activação: 2000 kJ•  (477,6 Kcal/dia)•  25% da TMRStraub, R.H. et al., 2010. Journal of Internal MedicineSISTEMA IMUNOLÓGICO70%
  91. 91. ORIGINAL ARTICLEMod Rheumatol (2007) 17:470–475 © Japan College of Rheumatology 2007DOI 10.1007/s10165-007-0628-1Anwar Arshad · Rozita Rashid · Kim BenjaminThe effect of disease activity on fat-free mass and resting energyexpenditure in patients with rheumatoid arthritis versus noninflammatoryarthropathies/soft tissue rheumatismReceived: June 11, 2007 / Accepted: July 5, 2007Abstract Rheumatoid arthritis (RA) is a chronic jointdisease of undetermined cause that is associated with sig-nificant disability. Low-grade fever, anemia, and weight lossare recognized extra-articular features associated withincreased disease activity.Weight loss and cachexia are well-established features of RA. The mechanism behind weightloss in RA is not known and may be multifactorial. Reducedenergy intake and hypermetabolism are the major twofactors frequently implicated in the etiology of RA cachexia.One would expect the effect of the above two factors to behighest during increased disease activity and lowest duringremission. The purpose of this study was: (a) to establishwhether in RA patients changes in body composition mirrorchanges in disease activity, (b) to investigate the relationcachexia in RA patients is determined by the frequency andintensity of disease activity (flare) for a given disease dura-tion. Hypermetabolism with increased REE was moreevident during increased disease activity. Hypermetabolismin the face of increased energy intake continued to causeloss of the FFM. Interleukin-6 correlates with increasedREE and erythrocyte sedimentation rate. There was nodirect association between IL-6 level and low FFM. Weconclude that loss of FFM is common in RA, cytokine pro-duction in RA is associated with altered energy metabolism,and preservation of FFM is important in maintaining goodquality of life in patients with RA.Key words Fat-free mass · Nutrition · Resting energy expen-Table 2. Outcome variables in subjects with RA and controlsRA patients Control P valueBMI (w/h2) 22.1 ± 3.2 25.5 ± 3.5 <0.022FM (kg) 25.1 ± 9.7 27.2 ± 11.1 NSFFM (kg) 24.7 ± 9.2 35 ± 12.1 <0.013FFM/H29.9 ± 3.1 12.9 ± 4.1 <0.027REE (kcal/day) (unadjusted) 1409 ± 291 1413 ± 288 NSREE (kcal/day) (adjusted for FFM) 1498 ± 162 1330 ± 206 <0.031Energy intake (kcal/day) 1820 ± 690 1760 ± 620 NSIL-6 (U/ml) 132 ± 15 – –BMI, body mass index; FM, fat mass; FFM, fat-free mass; H, height; REE, resting energy expen-diture; IL, interleukinnear regression model for outcomes of REE with body Table 4. Linear regression model with FFM as the outcom
  92. 92. MembranedepolarizationGlucose Glucose ATPGlycolysisGlucose oxidationK+K+K+Ca2+Ca2+InsulinVoltage-sensitiveCa2+channelATP-sensitiveK+channelInsulinGLUT2++++SecretoryvesiclesGKG6PFigure 6.4 Glucose stimulation of insulin secretion in the pancreatic β-cell. Glucoseenters the cell via the transporter GLUT2 (but see below) and is phosphorylated by glucokinase (GK)Frayn KN. Metabolic Regulation. Blackwell Pub; 2010:384.
  93. 93. IR
  94. 94. GLICEMIA E INSULINEMIALast  AR,  Wilson  SA.  Low-­‐Carbohydrate  Diet.  Am  Fam  Physician  2006;73:1942-­‐8    
  95. 95. IR
  96. 96. Resistência à Insulinaé a primeira alteraçãometabólica daSíndrome MetabólicaLudwig  D.JAMA  2002;287:2414–2423.  
  97. 97. Síndrome Metabólica em Portugal: Prevalênciae Implicações no Risco Cardiovascular- Resultados do Estudo VALSIM [107]MANUELA FIUZA, NUNO CORTEZ-DIAS, SUSANA MARTINS, ADRIANA BELO EM NOME DOS INVESTIGADORES DO ESTUDO VALSIMRev Port Cardiol 2008; 27 (12): 1495-1529ARTIGOS ORIGINAISRESUMOIntrodução: A síndrome metabólica (SM) é umaconstelação de factores de risco de origemmetabólica que se associa a risco aumentado dediabetes mellitus tipo 2 (DM) e doençascardiovasculares (DCV). Têm sido realizadosvários estudos regionais para determinação daprevalência, mas são insuficientes para oconhecimento da realidade nacional ou para acaracterização do risco cardiovascular globalem Portugal.Objectivos: Determinar a prevalência da SM ede cada um dos seus componentes napopulação adulta utente dos Cuidados de SaúdePrimários, em Portugal.Métodos: Estudo analítico transversal nosCuidados de Saúde Primários, envolvendo 719médicos de família, segundo distribuiçãoestratificada e proporcional à densidadepopulacional de cada região de Portugalcontinental e ilhas. Os primeiros dois utentesadultos de cada dia de consulta foramconvidados a participar, independentemente domotivo de consulta. Após consentimentoinformado, foi utilizado um inquérito pararecolha de dados sócio-demográficos, clínicos elaboratoriais. Os diagnósticos prévios de doençaABSTRACTMetabolic Syndrome in Portugal:Prevalence and Implications forCardiovascular Risk - Results from theVALSIM StudyIntroduction: The metabolic syndrome (MS) is aconstellation of risk factors of metabolic originthat is associated with increased risk of type 2diabetes mellitus (DM) and cardiovasculardisease (CVD). Several regional studies havebeen conducted to determine its prevalence,but they are insufficient to determine thesituation nationally or to characterize overallcardiovascular risk in Portugal.Objective: To determine the prevalence of MSand each of its components in adult primaryhealth care users in Portugal.Methods: The VALSIM Study, involving 719general practitioners (GPs), was performed in aprimary care setting, based on stratifieddistribution and proportional to the populationdensity of each region of mainland Portugal andthe islands of Madeira and the Azores. The firsttwo adult patients scheduled for an appointmenton a given day were invited to participate,irrespective of the reason for the consultation.NorteNorthern28,17%(H:26,56%; M:29,61%)(M:26,56%; F:29,61%)28,79%(H:27,89%; M:29,61%)(M:27,89%; F:29,61%)26,05%(H:19,5%; M:32,23%)(M:19,5%; F:32,23%)25,71%(H:24,7%; M:26,62%)(M:24,7%; F:26,62%)29,38%(H:25,84%; M:32,33%)(M:25,84%; F:32,33%)30,99%(H:29,68%; M:32,21%)(M:29,68%; F:32,21%)24,42%(H:21,65%; M:27,1%)(M:21,65%; F:27,1%)CentroCentralAçoresAzoresMadeiraLisboa eVale do TejoLisbon andTagus ValleyAlentejoAlgarvePrevalência inferior à mèdia nacional em mais de 10%Prevalence more than 10% below national averagePrevalência inferior à mèdia nacional em 5 a 10%Prevalence 5 to 10% below national averagePrevalência inferior à mèdia nacional em até 5%Prevalence up to 5% below national averagePrevalência superior à mèdia nacional em até 5%Prevalence up to 5% above national averagePrevalência superior à mèdia nacional em 5a 10%Prevalence 5 to 10% above national averagePrevalência superior à mèdia nacional em mais de 10%Prevalence more than 10% above national averageRev Port CardiolVol. 27 Dezembro 08 / December 08Prevalência GlobalNacional: 27,50%O diagnóstico de SM foi efectuado peloscritérios NCEP-ATP III
  98. 98. T.A. Gheita1 · H.A. Raafat1 · S. Sayed1 · H. El-Fishawy2 · M.M. Nasrallah2 ·E. Abdel-Rasheed31 Rheumatology department, Faculty of medicine, Cairo University, Cairo2 Internal Medicine departments, Faculty of Medicine, Cairo University, Cairo3 Clinical pathology department, National Research Centre, CairoMetabolic syndrome and insulinresistance comorbidity insystemic lupus erythematosusEffect on carotid intima-media thicknessAlthough the prognosis for patients withsystemic lupus erythematosus (SLE) im-proved after the advent of immunosup-pressive treatment [1], arterial vasculardisorders have become increasingly im-mune diseases, [13] including SLE [14, 15],with an increased incidence of CVD [16].Classic risk factors, hypertension anddiabetes mellitus, are more prevalent inSLE, and persistent hypercholesterol-tients gave their informed consent priorto their inclusion in the study.Study populationZ Rheumatol 2012DOI 10.1007/s00393-012-1058-9© Springer-Verlag 2012Originalien
  99. 99. a strong strength of association between psoriasisand metabolic syndrome. Importantly, most studiesalso reported a high overall prevalence of metabolicFig 2. Meta-analysis of the prevalence of metabolic syndrome in the psoriasis patients.Armstrong AW, Harskamp CT, Armstrong EJ.J Am Acad Dermatol. 2013 Jan 26.
  100. 100. ORIGINAL PAPERPsoriasis increased the risk of diabetes: a meta-analysisJuan Cheng • Dayu Kuai • Li Zhang •Xueqin Yang • Bing QiuReceived: 15 April 2011 / Revised: 30 November 2011 / Accepted: 8 December 2011 / Published online: 1 January 2012Ó Springer-Verlag 2011Abstract To evaluate the association between psoriasisand risk of diabetes, pertinent studies were identified bysearching electronic databases and by reviewing the ref-erence lists of retrieved articles. We included observationalstudies that examined the association between psoriasis andrisk of diabetes. Two reviewers independently assessedeligibility and used a standardized form to collect datafrom published studies. The study quality was assessed bythe Newcastle–Ottawa Scale. A total of 22 eligible studiesthat included 3,307,516 participants fulfilled the inclusioncriteria. Compared to individuals without psoriasis,subjects with psoriasis had a 1.42-fold increased risk ofdiabetes (95% CI, 1.40–1.45). Findings from this meta-analysis suggest that individuals with psoriasis may have amodestly increased risk of diabetes.Keywords Diabetes Á Psoriasis Á Meta-analysisIntroductionPsoriasis is a chronic, inflammatory disease characterizedby erythematous scaly patches that affect the scalp, trunk,extensor surfaces of the limbs, and the genital area. Pso-riasis affects about 2 to 3% of the adult population [16, 36]and is associated with decreased quality of life, even inpatients in whom the affected body surface area is rela-tively limited [30].Diabetes is a serious and growing health problem in theUSA, where it affects about 17 million people and playskey role in increasing cardiovascular mortality [11, 15, 23,24]. The association between psoriasis and risk of diabeteshas been examined in numerous epidemiologic studies [1–3, 8–10, 13, 17, 18, 20–22, 25, 26, 28, 29, 31–33, 37, 41]and a markedly increased risk for diabetes has been foundin individuals with psoriasis. The adjusted risk ratios forincident diabetes associated with psoriasis range between1.08 and 3.61. In contrast, a few studies have suggestedthat psoriasis is not associated with an increased risk ofdiabetes. The reasons for this difference are not quite clearbut probably due to poor design, inadequate size, theseverity of psoriasis, and consequent lack of power. So ameta-analysis is valuable in synthesizing the availableevidence [7].We therefore, performed a meta-analysis ofall published data to examine the association betweenpsoriasis and risk of diabetes.MethodsSearch strategyJ. Cheng (&)Department of Dermatology,Beijing 302 Hospital, Beijing, Chinae-mail: chengj_2000@126.comD. KuaiDepartment of Digestion, Lu He Hospital, Beijing, ChinaL. ZhangDepartment of Dermatology,Beijing 307 Hospital, Beijing, ChinaX. YangDepartment of Dermatology,Air Force General Hospital, Beijing, ChinaArch Dermatol Res (2012) 304:119–125DOI 10.1007/s00403-011-1200-6syndrome was significantly more common in psoriaticdiabetesh psoriasisRes (2012) 304:119–125 123
  101. 101. 146
  102. 102. 5–12(Table2).DuringthefirstyearfollowingRAdiag- increased RRs were observed for all outcomes, except<49 years 2124 (28.4) 10 571(28.6) N ⁄ S50–59 years 1898 (25.4) 9548(25.8)60–69 years 1791 (24.0) 8893(24.0)70–93 years 1656 (22.2) 8012(21.6)Yearofstart offollow-upb1995–1997 895 (12.0) 4457(12.0) N ⁄ S1998–2001 2547 (34.1) 12 627(34.1)2002–2006 4027 (53.9) 19 940(53.9)RFstatuscPositive 4981 (66.7) N ⁄ A N ⁄ AMissing 300 (4.0) N ⁄ ANA = not assessed ⁄ applicable. NS = nonsignificant. aInterquartile range. bFollow-up began for the comparator subjects at thesame time as for their matched patient with RA. cRF status was determined at diagnosis; data on RF status were missing for 300patientswithRA.Table 2 Relative risk (RRa) for incident MI and other IHD events in the Swedish Early RA Register study population of 7469 patientswith incident RA and 37 024 matched controls aged 16 and above and diagnosed with RA within 18 months of symptom onsetbetween1995andendof2006Outcomeb<1 yearsinceRAdiagnosis1–4 yearssinceRAdiagnosis5–12 yearssinceRAdiagnosis Entirefollow-upAcuteMI 1.4(0.9,2.1)34 ⁄ 115 1.6 (1.3,2.0)134 ⁄ 388 1.6(1.2,2.2)65 ⁄ 198 1.6 (1.4,1.9)233 ⁄ 701AnyIHDc1.1(0.8,1.5)52 ⁄ 215 1.5 (1.2,1.7)197 ⁄ 650 1.5(1.2,1.9)92 ⁄ 315 1.4 (1.2,1.6)341 ⁄ 1180FatalMI 1.3(0.6,2.7)9 ⁄ 33 1.1 (0.7,1.8)19 ⁄ 92 1.1(0.6,2.3)10 ⁄ 56 1.1 (0.8,1.6)38⁄ 181Coronaryrevascularisation1.5(0.7,3.1)10 ⁄ 32 1.4 (1.0,2.0)46 ⁄ 149 2.0(1.3,3.2)27 ⁄ 75 1.6 (1.2,2.1)83⁄ 256Angina pectoris 0.9(0.5,1.5)16 ⁄ 87 1.3 (1.0,1.8)67 ⁄ 241 1.2(0.8,1.9)29 ⁄ 111 1.2 (1.0,1.5)112 ⁄ 439RR and 95% confidence interval, including number of RA events ⁄ number of comparator events. aCox proportional hazardregression models. All models were adjusted for the matching factors: sex, year of birth, county of residence and marital status.bDefined as the first occurrence of the event following RA diagnosis. cDefined as first of MI, coronary revascularisation or anginapectoris.
  103. 103. 14900,511,522,51 2 3 4 5CRP LDLINFLAMAÇÃO E ECV!Quintis de Riesgo Relativo para todos os Acidentes Cardiovasculares!Ridker PM et al. N Engl J Med 2002;347:1557-65.
  104. 104. cause deterioration of fattyplaque ruptures and complemay also act synergisticallyrisk factors in the pathogeneinflammation is associated wand an adverse lipid profile.CVD occurs more frequentlytory burden such as RA. Thidisease severity is associatedand that treatment with psuch as tumour necrosis freduces the cardiovascular riRA group as well as in the gHoorn study, we were unrelationship between inflammight be due to a type II errostudy CVD risk at different lbe that the cumulative inflathe curve for CRP) over the lin order to show an associaCVD risk in patients with Rwith RA without traditioncorrelation was found betTable 2 Prevalence odds ratios (ORs) for cardiovascular disease usingcontrols as a referenceOR (95% CI) p ValueModel INon-diabetic controls 1.00 (reference)DM2 2.62 (1.29 to 5.32) 0.008RA 2.81 (1.46 to 5.42) 0.002Model IINon-diabetic controls 1.00 (reference)DM2 2.31 (1.13 to 4.72) 0.022RA 3.11 (1.59 to 6.08) 0.001Model IIINon-diabetic controls 1.00 (reference)DM2 2.01 (0.90 to 4.51) 0.090RA 2.70 (1.24 to 5.86) 0.012DM2, diabetes mellitus type 2; RA, rheumatoid arthritis.Model I, crude associations.Model II, corrected for age and gender.Model III, corrected for cardiovascular risk factors (age and gender, systolic bloodpressure, antihypertensive agents, total cholesterol/high-density lipoproteincholesterol (TC/HDL) ratio, lipid-lowering drugs, waist circumference, creatinine andsmoking).Extended reportgroup.bmon June 11, 2011 - Published byard.bmj.comDownloaded from
  105. 105. adjusted fment. Incomparinwith RA aDM relatiary analyfor the adSPSS sofvalues lescant. NoRESULTBaselinpopulatiojects (24.1morbiditytheir hospsentiallyFigure 1. Study design. CARRE´ ϭ Cardiovascular Research andRheumatoid Arthritis; IFG ϭ impaired fasting glucose; DM2 ϭtype 2 diabetes mellitus; RA ϭ rheumatoid arthritis.Arthritis & Rheumatism (Arthritis Care & Research) Vol. 61, No. 11, November 15, 2009, pp 1571–1579!
  106. 106. DISCUSSOur prosppatients wgeneral pocreased CVpatients wvious crosslar risk fadid not exsequently,underestimcating thatRA shoulddiovasculaden in RAwe did nobetween pdue to a laFigure 2. Cardiovascular event–free probability to 3 years among1576PROBABILIDADE DE AUSÊNCIA DE ACIDENTE CARDIOVASCULARAO FIM DE 3 ANOSControlosDT2AR semDiabetes
  107. 107. Biologics:Targets & Therapy 2008:2(4)664Nakase et al 1997; Gilbert et al 2000, 2002). Furthermore, bone damage in vivo (Joosten et al 1999; Kong et al 1999;OsteoclastprecursorOsteoclastTNFTNFTNFTNFBone erosionand bone lossRANKOPGRANKLSecretion+ or =OPG+++OsteoblastFigure 1 Increasing the balance of receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB (RANK) induced by tumor necrosis factoralpha (TNFα).Abbreviations: OPG, osteoprotegerin; +, stimulation; O, inhibition.Biologics: Targets & Therapy 2008:2(4) 663–669!
  108. 108. Arthritis Increases the Risk for Fractures —Results from the Women’s Health InitiativeNICOLE C. WRIGHT, JEFFREY R. LISSE, BRIAN T. WALITT, CHARLES B. EATON, ZHAO CHEN,and the Women’s Health Initiative InvestigatorsABSTRACT. Objective. To examine the relationship between arthritis and fracture.Methods. Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295),osteoarthritis (OA; n = 63,402), and rheumatoid arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and theCox proportional hazards model was used to test the association between arthritis and fracture.Results. After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-report-ed clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted frac-ture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for sev-eral covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical frac-tures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA groupwas HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RAgroup. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11;95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fractureincreased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to thenonarthritis group.Conclusion. The increase in fracture risk confirms the importance of fracture prevention in patientswith RA and OA. (J Rheumatol First Release May 15 2011; doi:10.3899/jrheum.101196)Key Indexing Terms:ARTHRITIS EPIDEMIOLOGY FRACTURE POSTMENOPAUSAL WOMENWith an increasing number of older adults in our society,osteoporosis has become a major public health concern.rates2. Age and bone mineral density (BMD) are the prima
  109. 109. Arthritis Increases the Risk for Fractures —Results from the Women’s Health InitiativeNICOLE C. WRIGHT, JEFFREY R. LISSE, BRIAN T. WALITT, CHARLES B. EATON, ZHAO CHEN,and the Women’s Health Initiative InvestigatorsABSTRACT. Objective. To examine the relationship between arthritis and fracture.Methods. Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295),osteoarthritis (OA; n = 63,402), and rheumatoid arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and theCox proportional hazards model was used to test the association between arthritis and fracture.Results. After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-report-ed clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted frac-ture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for sev-eral covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical frac-tures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA groupwas HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RAgroup. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11;95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fractureincreased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to thenonarthritis group.Conclusion. The increase in fracture risk confirms the importance of fracture prevention in patientswith RA and OA. (J Rheumatol First Release May 15 2011; doi:10.3899/jrheum.101196)Key Indexing Terms:ARTHRITIS EPIDEMIOLOGY FRACTURE POSTMENOPAUSAL WOMENWith an increasing number of older adults in our society, rates2. Age and bone mineral density (BMD) are the prta). The potential for the moderate amount of mis-tion in the OA group would bias the results of thishe null. People experiencing joint pain because of ainjury, or having other soft-tissue conditions such ass or other noninflammatory arthritic conditions, maysification, again biasing the estimates toward the null.Not having site-specific or radiographically confirmcases is another limitation of this study. Fracture risk iably different for persons with OA of the hip comparedsons with knee, hand, or spine OA. The OA-affected arThe Journal of Rheumatology 2011; 38:8; doi:10.3899/jrheumPersonal non-commercial use only. The Journal of Rheumatology Copyright © 2011. All rights reserved.Table 4. The risk of fracture by arthritis group. Data were adjusted for age; race; body mass index; physicalactivity; assignment in the hormone therapy trials, the dietary modification trial, and the calcium and vitamin Dtrial; hospitalizations; falls; smoking; hormone use; parental fracture at > age 40 years; calcium and vitamin Dintake; depression score; years since menopause; diabetic treatments; osteoporosis medication; general healthscore; fracture at > age 55 years; and joint replacements.Location No Arthritis, OA, RA,n = 83,295 n = 63,402 n = 960HR (95% CI) p HR (95% CI) pAny fracture, n = 24,137 Reference 1.09 (1.05, 1.13) < 0.001 1.49 (1.26, 1.75) < 0.001Spine, n = 2559 Reference 1.17 (1.05, 1.29) 0.004 1.93 (1.29, 2.90) 0.001Hip, n = 1698 Reference 1.11 (0.98, 1.25) 0.105 3.03 (2.03, 4.51) < 0.001OA: osteoarthritis; RA: rheumatoid arthritis.
  110. 110. CAUSAS DE INFLAMAÇÃO CRÓNICA
  111. 111. ALGUMAS DOENÇAS AUTO-IMUNESAlopecia Areata Gastrite Auto-ImuneAnemia Aplástica Hepatite Auto-ImuneAnemia Hemolítica auto-imune Lúpus Eritematoso SistêmicoArtrite Reumatóide Miastenia GravisColite Ulcerosa Neutropenia Auto-ImuneDermatite Herpetiforme PsoríaseDoença Celíaca Púrpura Trombocitopênica Auto-ImuneDoença de Behcet Síndrome de SjögrenDoença de Crohn Tiróidite de HashimotoEsclerose Múltipla UveíteEspondilite Anquilosante VitiligoRose N R, Mackay IR. Prospectus: The Road to Autoimmune Disease.In Rose N R, Mackay IR. The auto-immune diseases. Academic Press, 2006, pgs xix-xxv
  112. 112. ResearchSystemic lupus erythematosus (SLE) is achronic autoimmune disease of unclearetiology, with a prevalence as high as 1 in2,500 women (Bernatsky et al. 2007). It ischaracterized by an overactive immune systemthat targets normal tissue in nearly any bodyorgan. The resulting inflammation causesdysfunction and damage; involvement ofmajor organs such as the kidneys can be par-ticularly devastating and even life-threatening(Bernatsky et al. 2007).autoimmunity. Recent data have suggestedthat these exposures may be important triggersof systemic inflammation [for a review, seeU.S. Environmental Protection Agency (EPA)2004] that could have important effects interms of autoimmunity.Our aim in this study was to evaluate thepotential influence of PM air pollution onthe clinical course of SLE. We have focusedon the effects of variations in levels of fineambient PM with median aerodynamic diam-et al. 1982). Subjects in the cohort completedan annual evaluation that consisted of a reviewof symptoms, medications, physical find-ings, and laboratory testing. The data wereused to construct validated measures of diseaseactivity [SLE Disease Activity Index, version2000 (SLEDAI-2K)] (Gladman et al. 2002)and damage [Systemic Lupus InternationalCollaborating Clinics/ACR Damage Index(SLICC/ACR)] (Gladman et al. 2002).The SLEDAI-2K is a “weighted” index thatprovides a measurement of disease activityof the organ systems in SLE over a 10-dayperiod before the annual evaluation. Theindex includes central nervous system features,vascular involvement, kidney disease, musculo-skeletal disease, dermatological features, serosalinvolvement, immune system activity, hema-tological features, and constitutional symp-toms (see Appendix). Theoretically, patientscan score a maximum of 105, but in prac-tice, scores greater than 45 are unusual. In thepresent study, we analyzed data collected onpatients who resided on the island of Montrealfrom January 2000 through September 2007.All subjects consented to be included in theregistry, and studies were conducted underethical approval from the MUHC.We studied associations between PM2.5and the SLEDAI-2K total score. We werealso specifically interested in the presence orabsence of renal tubule cellular casts, whichare a marker for severe kidney inflammationrelated to SLE, and the presence or absenceof antibodies against double-stranded DNAAddress correspondence to A. Smargiassi, InstitutAssociations between Ambient Fine Particulate Levels and Disease Activityin Patients with Systemic Lupus Erythematosus (SLE)Sasha Bernatsky,1,2 Michel Fournier,3 Christian A. Pineau,2 Ann E. Clarke,1,4 Evelyne Vinet,2and Audrey Smargiassi 5,61Division of Clinical Epidemiology and 2Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada; 3Directionde santé publique de l’Agence de la santé et des services sociaux de Montréal, Montreal, Quebec, Canada; 4Division of Clinical Immunologyand Allergy, McGill University Health Centre, Montreal, Quebec, Canada; 5Département de santé environnementale et de santé au travail,Université de Montréal, Montreal, Quebec, Canada; 6Institut national de santé publique du Québec, Montréal, Quebec, CanadaBACKGROUND: Systemic lupus erythematosus (SLE) is a chronic disease of unclear etiology,characterized by an overactive immune system and the production of antibodies that may target nor-mal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly inwomen.OBJECTIVE: Our aim was to evaluate the potential influence of particulate matter (PM) air pollutionon clinical aspects of SLE.METHODS: We studied a clinic cohort of SLE patients living on the island of Montreal, followedannually with a structured clinical assessment. We assessed the association between ambient levels offine PM [median aerodynamic diameter ≤ 2.5 µm (PM2.5)] measured at fixed-site monitoring stationsand SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K),which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renaltubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regres-sion models that we adjusted for daily ambient temperatures and ozone levels.RESULTS: We assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000through 2007 (mean age at time of first visit, 41.2 years). PM2.5 levels were associated with anti-dsDNAand cellular casts. The crude and adjusted odds ratios (reflecting a 10-µg/m3 increase in PM2.5 aver-aged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65]and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28(0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM2.5 levels.CONCLUSIONS: We provide novel data that suggest that short-term variations in air pollution mayinfluence disease activity in established autoimmune rheumatic disease in humans. Our results addweight to concerns that pollution may be an important trigger of inflammation and autoimmunity.KEY WORDS: air pollution, antibodies, disease activity, PM2.5, SLE, SLEDAI-2K, systemic lupuserythematous. Environ Health Perspect 119:45–49 (2011). doi:10.1289/ehp.1002123 [Online22 September 2010]
  113. 113. Original ArticleAir pollution and type 1 diabetes in childrenHathout EH, Beeson WL, Ischander M, Rao R and Mace JW. Air pollutionand type 1 diabetes in children.Pediatric Diabetes 2006: 7: 81–87.Background: Over the past decade, there has been a worldwide largelyunexplained increase in the incidence of type 1 diabetes in young chil-dren. This study explores the quantitative role of exposure to specific airpollutants in the development of type 1 diabetes in children.Methods: A total of 402 children were retrospectively studied. Zipcode-related, time-specific birth-to-diagnosis exposure to five ambientair pollutants was obtained for 102 children with type 1 diabetes and300 healthy children receiving care at a single hospital. Pollutionexposure levels were created by summing up zip code-specific pollutiondata and dividing by months of exposure from birth to diagnosis.Analysis employed w2, two-tailed independent sample t-test andunconditional logistic regression.Results: Odds ratio (OR) was significantly high for cumulativeexposure to ambient ozone (O3) and sulfate (SO4) in cases comparedwith controls, OR ¼ 2.89 [95% confidence interval (CI) ¼ 1.80–4.62]and OR ¼ 1.65 (CI ¼ 1.20–2.28), respectively, even after adjustmentfor several potential confounders. Passive smoking was more frequent inchildren with diabetes (30 vs. 10%, p ¼ 0.001). Attending day careand breast feeding in infancy were less frequent in children with diabetes(14 vs. 23%, p ¼ 0.025; 59 vs. 78%, p ¼ 0.001). Family history ofdiabetes, autoimmune disease and drug abuse was more frequent incases (p < 0.01).Conclusion: Cumulative exposure to ozone and sulfate in ambient airmay predispose to the development of type 1 diabetes in children. Earlyinfant formula feeding and passive smoking in the household mayprecipitate or accelerate the onset of type 1 diabetes.Eba H Hathouta,W Lawrence Beesonb,Mariam Ischandera,Ravindra RaoaandJohn W MaceaaDepartment of Pediatrics, Loma LindaUniversity School of Medicine, LomaLinda, CA, USA; and bDepartment ofEpidemiology and Biostatistics, School ofPublic Health Loma Linda University,Loma Linda, CA, USAKey words: air pollution – etiology – typeI diabetesCorresponding author:Eba H. Hathout, MD, FAAP, Director,Pediatric Diabetes Center,Loma Linda University Children’sHospital,11175 Campus Street, CP A1120R,Loma Linda, CA 92354USA.Tel.: þ909 558 4130fax: þ909 558 0408e-mail: ehathout@ahs.llumc.eduSubmitted 3 December 2004. Acceptedfor publication 15 September 2005Type1diabetesmellitusreferstoastateofinsulin-deficienthyperglycemiausuallyattributedtoautoimmunedestruc-tion of b-cells of the pancreas. The etiology is multifactor-genetically susceptible individuals progress to developthedisease(3).Inaddition,therelativelyshort-timecoursefor the reported increase in incidence is unlikely to bePediatric Diabetes 2006: 7: 81–87 # 2006 The Authors. Journal compilation # 2006 Blackwell MunksgaardAll rights reservedPediatric Diabetes
  114. 114. Traffic Air Pollution and Oxidized LDLLotte Jacobs1, Jan Emmerechts2, Marc F. Hoylaerts2, Chantal Mathieu3, Peter H. Hoet1, Benoit Nemery1*,Tim S. Nawrot1,41 Occupational and Environmental Medicine, Unit of Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium, 2 Center for Molecular and Vascular Biology,Katholieke Universiteit Leuven, Leuven, Belgium, 3 Department of Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium, 4 Centre for Environmental Sciences,Hasselt University, Diepenbeek, BelgiumAbstractBackground: Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized thatindividual exposure to particulate matter (PM) derived from fossil fuel would correlate with plasma concentrations ofoxidized low-density lipoprotein (LDL), taken as a marker of atherosclerosis. We tested this hypothesis in patients withdiabetes, who are at high risk for atherosclerosis.Methodology/Principal Findings: In a cross-sectional study of non-smoking adult outpatients with diabetes we assessedindividual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputuminduction and by determining the distance from the patient’s residence to a major road, through geocoding. Theseexposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogenactivator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Eachdoubling in the distance of residence from major roads was associated with a 0.027 mm2decrease (95% confidence interval(CI): 20.048 to 20.0051) in the carbon load of airway macrophages. Independently from other covariates, we found thateach increase of 0.25 mm2[interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of22.9 U/L (95% CI: 25.2 to 20.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residenceto major roads, were associated with plasma von Willebrand factor or PAI-1.Conclusions: The observed positive association, in a susceptible group of the general population, between plasma oxidizedLDL levels and either the carbon load of airway macrophages or the proximity of the subject’s residence to busy roadssuggests a proatherogenic effect of traffic air pollution.Citation: Jacobs L, Emmerechts J, Hoylaerts MF, Mathieu C, Hoet PH, et al. (2011) Traffic Air Pollution and Oxidized LDL. PLoS ONE 6(1): e16200. doi:10.1371/journal.pone.0016200Editor: Sayuri Miyamoto, Instituto de Quı´mica, Universidade de Sa˜o Paulo, BrazilReceived August 21, 2010; Accepted December 15, 2010; Published January 19, 2011Copyright: ß 2011 Jacobs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: The studies of the Flemish Center of Expertise on Environment and Health were commissioned, financed and steered by the Ministry of the FlemishCommunity (Department of Economics, Science and Innovation; Flemish Agency for Care and Health; Department of Environment, Nature and Energy). T Nawrotreceived a grant of the Flemish Fund for Scientific Research (FWO-Vlaanderen, krediet aan navorsers). The center for Molecular and Vascular Biology is supportedby the ‘‘Excellentie financiering KULeuven’’ (EF/05/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation ofthe manuscript.Competing Interests: The authors have declared that no competing interests exist.* E-mail: ben.nemery@med.kuleuven.beIntroductionNumerous epidemiological studies link various adverse healthroads [8]. These epidemiological observations strongly suggest thatlong-term exposure to PM exerts a proatherogenic effect. Studiesin laboratory animals have begun to give experimental plausibilityFigure 1. Traffic related exposure variables and oxidized-LDL. An airway macrophage containing carbosurface of the macrophage occupied by carbon (in mm2), in 50 macrophages per person. The carbon load is giveairway macrophages. Pearson correlation between carbon load of airway macrophages and distance from the rediabetes, who are at high risk for atherosclerosis.Methodology/Principal Findings: In a cross-sectional study of non-smoking adult outpatients with diabetes we assessedindividual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputuminduction and by determining the distance from the patient’s residence to a major road, through geocoding. Theseexposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogenactivator inhibitor 1 (PAI-1). We could assess the carbon load of airway macrophages in 79 subjects (58 percent). Eachdoubling in the distance of residence from major roads was associated with a 0.027 mm2decrease (95% confidence interval(CI): 20.048 to 20.0051) in the carbon load of airway macrophages. Independently from other covariates, we found thateach increase of 0.25 mm2[interquartile range (IQR)] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3to 13.3) in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of22.9 U/L (95% CI: 25.2 to 20.72) in oxidized LDL. Neither the carbon load of macrophages nor the distance from residenceto major roads, were associated with plasma von Willebrand factor or PAI-1.Conclusions: The observed positive association, in a susceptible group of the general population, between plasma oxidizedLDL levels and either the carbon load of airway macrophages or the proximity of the subject’s residence to busy roadssuggests a proatherogenic effect of traffic air pollution.Citation: Jacobs L, Emmerechts J, Hoylaerts MF, Mathieu C, Hoet PH, et al. (2011) Traffic Air Pollution and Oxidized LDL. PLoS ONE 6(1): e16200. doi:10.1371/journal.pone.0016200Editor: Sayuri Miyamoto, Instituto de Quı´mica, Universidade de Sa˜o Paulo, BrazilReceived August 21, 2010; Accepted December 15, 2010; Published January 19, 2011Copyright: ß 2011 Jacobs et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: The studies of the Flemish Center of Expertise on Environment and Health were commissioned, financed and steered by the Ministry of the FlemishCommunity (Department of Economics, Science and Innovation; Flemish Agency for Care and Health; Department of Environment, Nature and Energy). T Nawrotreceived a grant of the Flemish Fund for Scientific Research (FWO-Vlaanderen, krediet aan navorsers). The center for Molecular and Vascular Biology is supportedby the ‘‘Excellentie financiering KULeuven’’ (EF/05/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation ofthe manuscript.Competing Interests: The authors have declared that no competing interests exist.* E-mail: ben.nemery@med.kuleuven.beIntroductionNumerous epidemiological studies link various adverse healthoutcomes with air pollution, especially that caused by particulatematter (PM), which to a considerable extent is caused by traffic[1,2]. One of the important recent discoveries has been thatexposure to PM is not only harmful to the lungs, but also to theheart and blood vessels [3–6]. This is undoubtedly true for short-term increases in PM, which are triggers for acute cardiovascularevents [7], but probably also for long-lasting exposure to urbanPM, which increases the risk of cardiovascular mortality andmorbidity [4,6], possibly by accelerating atherosclerosis [8–10]. Across-sectional study in Los Angeles [9] suggested a role of airpollution in intima-media thickening of the carotid artery and afollow-up study described an association between traffic proximityand the progression of intima-media thickness [10]. In a Germanstudy of more than 4000 subjects a strong relation was foundbetween coronary artery calcification and living close to majorroads [8]. These epidemiological observations strongly suggest thatlong-term exposure to PM exerts a proatherogenic effect. Studiesin laboratory animals have begun to give experimental plausibilityto these epidemiological observations [11,12]. However, so far,only few studies have provided mechanistic evidence for an effectof chronic exposure to traffic air pollution on the development ofatherosclerosis in human subjects.It is well established that persons with diabetes have a higherrisk of developing cardiovascular diseases. A population-basedstudy showed that persons with diabetes, without previousmyocardial infarction, have the same risk of developing myocar-dial infarction as nondiabetic patients with previous myocardialinfarction [13]. The metabolic abnormalities caused by diabetesinduce vascular dysfunction that predispose these patients todeveloping atherosclerosis [14]. There is also evidence thatpersons with diabetes and cardiovascular disease are moresensitive to the effects of PM air pollution [15]. So it is relevant– and also probably easier – to study the effects of air pollution inPLoS ONE | www.plosone.org 1 January 2011 | Volume 6 | Issue 1 | e16200
  115. 115. TABACO!
  116. 116. ynoviocytes is augmented by IL-1 , IL-17, IL-18 orNF [55]. Furthermore, Th17 cells express CC chemokineceptor (CCR) 6, a receptor for CCL20 [56]. Therefore,smoke exposure appeared to induce AhR activation inin AhR/DRE-dependent reporter gene transgenic mice [6ig. (1). A possible mechanism of cigarette smoke contribution to the induction and development of RA. Cigarette smoke indroinflammatory cytokines and chemokines, including IL-1 , IL-1 , IL-6, IL-8 and CCR20 from synovial fibroblast-like cells (SFC), wpartially mediated by aromatic hydrocarbon receptor (AhR) stimulated with polycyclic aromatic hydrocarbons (PAHs) contained inmoke. IL-1 and IL-6 induce the differentiation and development of Th17. PAHs also accelerate the development of Th17 via AhR. CCcruits Th17 into the synovium, and IL-1 activates Th17 for production of IL-17. IL-17 then induces IL-1, IL-6 and TNF production facrophages. The acute inflammation leads to chronic inflammation under the influence of sex hormones and genetic factors, which leadA.Onozaki K. Etiological and biological aspects of cigarette smoking in rheumatoid arthritis. Inflamm Allergy Drug Targets. 2009 Dec;8(5):364-8"
  117. 117. CLINICAL STUDYSmoking and thyroid disorders – a meta-analysisPeter VestergaardThe Osteoporosis Clinic, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000 Aarhus C, Denmark(Correspondence should be addressed to Peter Vestergaard; Email: p-vest@post4.tele.dk)AbstractBackground: Smoking has been associated with Graves’ disease, but it remains unclear if theassociation is present in other thyroid disorders.Outcome variables: Graves’ disease, Graves’ ophthalmopathy, toxic nodular goitre, non-toxic goitre,post-partum thyroid disease, Hashimoto’s thyroiditis, or hypothyroidism.Material and methods: A search of MEDLINE identified 25 studies on the association between smokingand thyroid diseases.Results: In Graves’ disease eight studies were available showing an odds ratio (OR) of 3.30 (95% con-fidence interval (CI): 2.09–5.22) in current smokers compared with never smokers. In ex-smokersthere was no significant excess risk of Graves’ disease (OR à 1:41; 95% CI: 0.77–2.58). The ORassociated with ever smoking in Graves’ ophthalmopathy (4.40, 95% CI: 2.88–6.73, six studies)was significantly higher than in Graves’ disease (1.90, 95% CI: 1.42–2.55, two-sided P-value, 0:01). Ever smoking was not associated with toxic nodular goitre (OR à 1:27; 95% CI: 0.69–2.33, three studies), while there was an increased risk of non-toxic goitre in smokers if men wereexcluded (OR à 1:29; 95% CI: 1.01–1.65, eight studies). The risk associated with smoking was sig-nificantly lower in men than in women for both Graves’ disease and non-toxic goitre. Hashimoto’sthyroiditis and post-partum thyroid dysfunction were also associated with smoking while the associ-ation with hypothyroidism did not reach statistical significance.Conclusions: Cessation of smoking seems associated with a lower risk of Graves’ disease than currentsmoking. Smoking increases the risk of Graves’ ophthalmopathy beyond the risk associated withGraves’ disease alone. Smoking cessation may lead to a decrease in morbidity from Graves’ disease,especially in women.European Journal of Endocrinology 146 153–161IntroductionPrevious studies have associated smoking with Graves’disease (GD) (1–8) and with Graves’ ophthalmopathy(GO – also termed endocrine ophthalmopathy) (1,4–7, 9–15), whereas the studies on the associationbetween smoking and other forms of thyroid diseaseare limited. As smoking is frequent in some countries(16) even a limited association between smoking andnon-smokers? (3) Are other types of thyroid disorders(toxic nodular goitre (TNG), non-toxic goitre (NTG),autoimmune hypothyroidism (AIH), Hashimoto’s thy-roiditis (HT), and post-partum thyroid dysfunction(PPTD)) linked to smoking?In GD, hyperthyroidism is linked to immunologicalfactors whereas this is not the case in TNG (18). Ifsmoking was linked to GD but not TNG, it wouldsuggest that smoking only modulates immunologicalEuropean Journal of Endocrinology (2002) 146 153–161 ISSN 0804-4643
  118. 118. Introducción. Diversos estudios epidemiológicos demuestranque en la esclerosis múltiple (EM) existe un factor genético de sus-ceptibilidad, así como que los factores ambientales juegan un papelprominente en el desarrollo de la misma. Entre los factores ambien-tales estudiados se encuentra el tabaco. De hecho, varios estudiosestablecen relación entre fumar y EM, pero la mayoría de ellos nohallaron resultados significativos o éstos fueron contradictorios.Objetivo. Evaluar la influencia del hábito tabáquico en el riesgode padecer EM.Material y métodos: Estudio caso-control pareado con 138 pacien-tes diagnosticados de EM según los criterios de McDonald y el mismonúmero de controles del mismo sexo, residentes en el mismo municipioy la misma edad ±2 años. Se recogieron los datos demográficos, statusde fumar, escala de discapacidad de Kurtzke (EDSS) y tipo de EM.Resultados. De los 138 pacientes (93 mujeres, 43 hombres), 110presentaban EM remitente recurrente, 20 EM secundariamente pro-gresiva y 7 EM primariamente progresiva. La mayoría de los pacien-tes resultaron ser fumadores y exfumadores (63%) frente al (41,3%)de los controles. Asimismo, la edad de inicio en el hábito de fumar fuemás precoz en los casos que en los controles.Conclusión. Ser fumador/exfumador implica un 27 % más detant role in their development. Smoking is among the environ-ment factors studied. In fact, several studies have established arelationship between smoking and multiple sclerosis, althoughmost of them did not find significant results or found that thesewere contradictory.Objective. To evaluate the influence of the smoking habit onthe risk of suffering MS.Methods. This was a case-control matched study with 138patients diagnosed of MS according to the McDonald criteria whowere paired with the same number of controls of the same gen-der, residents in the same city and having the same age ±2 years.Demographic data, smoking status (never, always smokers, ex-smokers), Kurtzke disability status scale (EDSS) and type of MSwere collected.Results. Out of a total of 138 MS patients (93 women, 43 men),110 had relapsing-remitting MS, 20 secondary progressive MS and7 primary progressive MS. Most of the patients were smokersand ex-smokers (63%). In the control group, only the 41,3% weresmokers/ex-smokers. Moreover, the age of onset for smoking wasearlier in the case group.OriginalesEstudio de casos y controlessobre la influencia del hábito tabáquicoen la esclerosis múltipleA. Rodríguez Regal1M. del Campo Amigo1J. Paz-Esquete2A. Martínez Feijoo3E. Cebrián1P. Suárez Gil1M. A. Mouriño1Servicios de 1 Neurología, 2 Medicina Preventivay 3 Urgencias del Complejo Hospitalariode Pontevedra (CHOP)Introducción. Diversos estudios epidemiológicos demuestranque en la esclerosis múltiple (EM) existe un factor genético de sus-ceptibilidad, así como que los factores ambientales juegan un papelprominente en el desarrollo de la misma. Entre los factores ambien-tales estudiados se encuentra el tabaco. De hecho, varios estudiosestablecen relación entre fumar y EM, pero la mayoría de ellos nohallaron resultados significativos o éstos fueron contradictorios.Objetivo. Evaluar la influencia del hábito tabáquico en el riesgode padecer EM.Material y métodos: Estudio caso-control pareado con 138 pacien-tes diagnosticados de EM según los criterios de McDonald y el mismonúmero de controles del mismo sexo, residentes en el mismo municipioy la misma edad ±2 años. Se recogieron los datos demográficos, statusde fumar, escala de discapacidad de Kurtzke (EDSS) y tipo de EM.Resultados. De los 138 pacientes (93 mujeres, 43 hombres), 110presentaban EM remitente recurrente, 20 EM secundariamente pro-gresiva y 7 EM primariamente progresiva. La mayoría de los pacien-tes resultaron ser fumadores y exfumadores (63%) frente al (41,3%)de los controles. Asimismo, la edad de inicio en el hábito de fumar fuemás precoz en los casos que en los controles.Conclusión. Ser fumador/exfumador implica un 27 % más deriesgo de desarrollar EM frente a los nunca fumadores. Este riesgo esestadísticamente significativo en mujeres y no en varones, probable-mente debido al bajo número de los mismos en el total de la muestra.Palabras clave:Esclerosis múltiple. Tabaco. Epidemiología. Factor de riesgo. Estudio caso-control.Neurología 2009;24(3):177-180tant role in their developmment factors studied. In frelationship between smomost of them did not findwere contradictory.Objective. To evaluatethe risk of suffering MS.Methods. This was apatients diagnosed of MS awere paired with the sameder, residents in the same cDemographic data, smokinsmokers), Kurtzke disabilitwere collected.Results. Out of a total o110 had relapsing-remitting7 primary progressive MSand ex-smokers (63%). Insmokers/ex-smokers. Moreearlier in the case group.Conclusion. Being a ster risk of developing MSsmoked. This risk is statistimen due to the low numbeKey words:Multiple sclerosis; tobacco; epidemioloINTRODUCCIÓNSer fumador/exfumador implicaun 27% más de riesgo dedesarrollar EM frente a los nuncafumadores.
  119. 119. Cigarette Smoking, Alcohol Consumption, and Risk ofSystemic Lupus Erythematosus: A Case-control Studyin a Japanese PopulationCHIKAKO KIYOHARA, MASAKAZU WASHIO, TAKAHIKO HORIUCHI, TOYOKO ASAMI, SABURO IDE,TATSUYA ATSUMI, GEN KOBASHI, YOSHIFUMI TADA, HIROKI TAKAHASHI, and the Kyushu Sapporo SLE(KYSS) Study GroupABSTRACT. Objective. Cigarette smoking may be associated with increased risk of systemic lupus erythematosus(SLE), whereas the role of alcohol consumption is unknown. We examined the association betweenSLE risk and smoking or drinking.Methods. We investigated the relationship of smoking and drinking compared to SLE risk among 171SLE cases and 492 healthy controls in female Japanese subjects. Unconditional logistic regression wasused to compute OR and 95% CI, with adjustments for several covariates.Results. Compared with nonsmoking, current smoking was significantly associated with increased riskof SLE (OR 3.06, 95% CI 1.86–5.03). The higher the level of exposure to cigarette smoke, the higherthe risk of SLE. Inhalation was also associated with increased SLE risk (OR 3.73, 95% CI 1.46–9.94for moderate inhalation; OR 3.06, 95% CI 1.81–5.15 for deep inhalation). In contrast, light/moderatealcohol consumption had a protective effect on SLE risk (OR 0.38, 95% CI 0.19–0.76). As for beer, therisks for non-beer drinkers and beer drinkers were similar. This also applies to alcoholic beverages otherthan beer.Conclusion. Our results suggest that smoking was positively associated with increased SLE risk where-as light/moderate alcohol consumption was inversely associated with SLE risk, irrespective of the typeof alcoholic beverage. Additional studies are warranted to confirm these findings. (First Release May15 2012; J Rheumatol 2012;39:1363–70; doi:10.3899/jrheum.111609)Key Indexing Terms:ALCOHOL CONSUMPTION EPIDEMIOLOGY JAPAN RISK FACTORSYSTEMIC LUPUS ERYTHEMATOSUS SMOKINGFrom the Department of Preventive Medicine, Graduate School ofMedical Sciences, Kyushu University, Fukuoka; Department ofCommunity Health and Clinical Epidemiology, St. Mary’s College,Kurume; Department of Medicine and Biosystemic Science, GraduateSchool of Medical Sciences, Kyushu University, Fukuoka; RehabilitationCenter, Saga University Hospital, Saga; Department of Medicine II,Hokkaido University Graduate School of Medicine, Sapporo; MolecularBiostatistics Research Team, Research Center for Charged ParticleTherapy, National Institute of Radiological Science, Chiba; Department ofClinical Epidemiology, St. Mary’s College; T. Horiuchi, PhD, AssociateProfessor, Department of Medicine and Biosystemic Science, GraduateSchool of Medical Sciences, Kyushu University; T. Asami, PhD, Professor,Rehabilitation Center, Saga Medical School Hospital; S. Ide, PhD,Professor, Department of Community Health and Clinical Epidemiology,St. Mary’s College; T. Atsumi, PhD, Associate Professor, Department ofMedicine II, Hokkaido University Graduate School of Medicine;G. Kobashi, PhD, Team Leader, Molecular Biostatistics Research Team,Research Center for Charged Particle Therapy, National Institute ofDespite intensive research, the etiology of systemic lupus ery-thematosus (SLE) remains unclear. Many environmentalexposures, including smoking, ultraviolet light, medications,infectious agents, hair dyes, and dietary factors have beenhypothesized to be associated with the development ofSLE1,2,3,4,5, although the strength of the evidence implicatingeach of these factors varies. Studies of twin concordance arecommonly used in epidemiology to estimate the role of genet-ics and the influence of environmental factors on disease sus-ceptibility. Disease concordance is much higher in monozy-gotic twins (24%–57%) than in dizygotic twins (2%–5%),suggesting a genetic component to SLE6,7,8. However, identi-fication of these genetic factors has been slow. The geneticbasis of SLE is very complex, and it is difficult to predict howa Japanese PopulationAKO KIYOHARA, MASAKAZU WASHIO, TAKAHIKO HORIUCHI, TOYOKO ASAMI, SABURO IDE,UYA ATSUMI, GEN KOBASHI, YOSHIFUMI TADA, HIROKI TAKAHASHI, and the Kyushu Sapporo SLE) Study GroupSTRACT. Objective. Cigarette smoking may be associated with increased risk of systemic lupus erythematosus(SLE), whereas the role of alcohol consumption is unknown. We examined the association betweenSLE risk and smoking or drinking.Methods. We investigated the relationship of smoking and drinking compared to SLE risk among 171SLE cases and 492 healthy controls in female Japanese subjects. Unconditional logistic regression wasused to compute OR and 95% CI, with adjustments for several covariates.Results. Compared with nonsmoking, current smoking was significantly associated with increased riskof SLE (OR 3.06, 95% CI 1.86–5.03). The higher the level of exposure to cigarette smoke, the higherthe risk of SLE. Inhalation was also associated with increased SLE risk (OR 3.73, 95% CI 1.46–9.94for moderate inhalation; OR 3.06, 95% CI 1.81–5.15 for deep inhalation). In contrast, light/moderatealcohol consumption had a protective effect on SLE risk (OR 0.38, 95% CI 0.19–0.76). As for beer, therisks for non-beer drinkers and beer drinkers were similar. This also applies to alcoholic beverages otherthan beer.Conclusion. Our results suggest that smoking was positively associated with increased SLE risk where-as light/moderate alcohol consumption was inversely associated with SLE risk, irrespective of the typeof alcoholic beverage. Additional studies are warranted to confirm these findings. (First Release May15 2012; J Rheumatol 2012;39:1363–70; doi:10.3899/jrheum.111609)Key Indexing Terms:ALCOHOL CONSUMPTION EPIDEMIOLOGY JAPAN RISK FACTORSYSTEMIC LUPUS ERYTHEMATOSUS SMOKING

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