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    2002 CLINICAL EXP RHEUMAT REMUS

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    6 views5 pages

    2002 Clinical Exp Rheumat Remus

    Uploaded by

    Gaby Morales

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    © All Rights Reserved
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    Genotoxicity assess using micronuclei assay in rheumatoid arthritis patients ec co Barragan! FJ, Aceves-Avila? F. Alcaraz-Lopez! F. Fuentes: Ramiver! J. Michel Diaz! 0. Torres: Bugavin? A. Ventura-A gui G6. Zusiga-Gonziter Depart of Bcwnasogs ad he ‘Deparment of Magen Cro MA Mesto. an he Und de Iveco Tnleredes Coin Degeert SC, Gratton Mest, Coun Rams Benne, MD, MS, Hem Depunomenr of Rhonmtelogs Cent Mt Navin Cen del Ios tw Meir del Sogn Sal ad Doe tor Unidad de hve o Baler Giaalaara, Mestso: erin Dare cise ecves Ais MBAS. Fa ‘Meese Lopes. MD. Pee Pontes uinr: MD. Resch Aseate acefina Michel Diaz MD. Rese ‘Asie: Ota Pores gone MD. Resear Asante: Ao Noman Al IMD, Resear scovites Gilera Acecite ©. Supported bs Fane Fen abe Invention gm Ni PP OARS of the Drtina Mesa lel Seq Soci Prone bess convespendenre Dr Cesar Rams Res. Coton No, 2202, Proidencia, Guia, Sa asrndgser ern ad Receive om Mart 19,204; weep in revived fourm Ok aber 2, 20 Fexrr nents RorwaNnoLony 2002, Key words: Micronuelei rts, methtexate, stoid EE ANSTRACE Objectives: This cmd imvestigared uhether: (i) remmatoid aabitie (RA) Durients have more micromicler (MN) thant heal ecm: (i) merlvnvesate (ATTN) treated RA paicats uve mare MW sas tote ne sing APEX el it) Jin eid supplementation decvedse the munber of MA in APEX seated Methods: A assays were performed in onal mucosa sweeps of SD coms five MIX tweated RA pvients. 10 sevamive RA paints not reveiing MTX sind 39 healthy controls MIX termed FA parients were then roxdemy placed in a enmsser designs receive foc iid supine tation, and MA asa were repeated afer 6 w0oks Results: Phe ATXRA patients haa! « sean age of 46% 10 ye cn «inet Aiseane devation ef 129 908: 800% vere women. The AEX dase range was A715 mghevek aad she mes deve fio of se was 16% FA raonts de re how ABIX RA gromp, dhe mewn age sat 1814 90s the oean eisease davies twas EB 9 y0n, and AP rere women AP Baseline, the snes nf MA were Seca igher in RA panini as camped wid controle (RATE 2.1 48 HOH ON). No diferrnce in AU land mose-nsers of MIX. lie cil sq lennon slid nor decrease the MN Inner inthe MIX rete RA ports, Conclusions: Genotoritiy, as asses ‘ed by the A assay: ie increased in RA pariems. These resulgs suggest tha ge Inononchy te awectaned with RA sill dud nt wth MIX ase. lie acd sq ‘pemenanion Fd effect nthe man her of MB Intro Several ties fave estimated the tisk ‘of malignancy fn sseunatud slits {RAY pation I seems hat the esti tion of site-specific eancers in RA is skewed compre tthe geet pops Iation: the incidence of lympho ad blader cancer ie increased, while the incidence of eancerof the digestive or fans is decressed (1,2). Germane to ny examination of RA. sd maligna the cancer ioting potential of RA therapies nd tw eco 4 PANE The influence a RA hy Heol Bepes mental studies and human cohorts have sHuws a redied sk of eolxeetal, Lag cal feast exer iv association with the use of nensereial st inf ory dys (NSAIDs). contrast her of eis Inve Fad an increase risk of waignancy in RA pont oa fe with lisease-msifying ante tvatic dass (DMARDs), For instance vaathiojrine and eyclophesphamie Ihave been repented to increase the risk of Iymphoproiptiratise miignancies in patiens (3-5), Methotexate may also be associated wth hemopecte tvalipnancies, alhugh the literature Consist predominantly enee reports Ina eae contol sty, Willams eto 6) fon that RA paints Peake: init of Tynpiiomaa shoved a en! to ‘wan inereased prior methotexale oF azalhingvine vse compa with mate fa RA contestant fenkemit ar yop There ave tv aan pres in acer taining the influence of specie DMARDs om cager induction. ‘The frst isthe han latency peed betwen epee to given DMARD al the development of malignancy. The wher Fe that RA ps From ene DMARD to sneer use a ceinaton a then crn Hie ers fof thie RA, ths king it ficult ‘austin casa inference he mievontcle (MIN) test is ai rect an sensitive meas of eon Sonal hieakage oF anssoprepation a has received inteased attention as a! seine hoe amacher of expusite (7). This est has een applied tothe biolgics monitoring of fuunaw prpiations expec mlagenie and tatcinogenic spenls. MN are extra nuclear bodies composed of elmo ‘sl Fragments oF hie eomesonnes that were st incomporated ines dagh fer smcled at stasis 48). They rest fhom chiomesene breakage o inet fr fence with the mitotic aypaatus, events ttnght tobe toated fo emeinngenesi UEsfolinted cells fom the inter medine nt steric layers ofthe epithelim Ihave heen widely tse in eytolngy to Aetect- abnormal morphology. Me svalignnt einges. and ence (The feclique wsed in this stay invulees cats iequently site NM examination of epithelial smears to determine the prevalence of cells com taining veronica i has been ihe elect of expos toudilferen xenobioties whieh are capa be of inducing cancer (10) herelone, the MN test in exfoliated cells fon al rcs cn eed tool in siesta asessing the potential ponotusiciy of lero ees ‘sed to Wea henna eiscases, Stal ies vit i experinneta sini have reponted tht NIX may induce MN inva dose dependent manner (11 12), ana ha Folie id supplement Vion veduees the cytogenetic damage induced by NIE C1. Yet Wo the best of four howteulge, MIN inductiot has not ‘ben sae i A patie sing MTX "he aims oF this study were to assess (whether RA patients lave mre MN. than healhy contiols, (hp shether MTX treated RA patents have more MN than those not using: MIPX, ad fe) whether folie ail supplementation de Mate We include consecutive RA patients Follilling the ACR evitoria (14) and secondary care ouptic iHeumatolugy tin Mexico, At isetine all p prospective shenmataligle assexsine Demgraphie ‘ies an comorbid conitions were doc tiered esivg 1 stiucttved suestn read elu review, Patients history of ay ecole disease oF ther diseases (sel ny ables me Titus, hypertension, thywidl diseases, ce.) were ot ici Ties pranps were assemble, "The fis Emp wa conned of $0 consecutive RA patients receiving MTX but ot Folie acid supplementation _eruupy costed of RA ps Trad never used MTX. ow azathioprine, Al patients nersvent an MIN assy a thik Fst visit Goo One (RA RIT) was then randomly place in one of tou stbgaonps. f sibons AURA, MUX/Folie Ack patiomts were given folie acl supplementation (5.mg pa ery for wecks al he BIN sty ‘vas repate a the ero week 6th PTE subgroup B RA-MTX-MEX/Falic Acid) the MN assay was repeate 6 weeks fate, sd then the patients were place on Foci (5 yg po ay Fr 6 ‘wes ad the NIN assay ws repeated X the vu this peti The muanber of micronuel iw RA ps tients was compared with a refereice onto) group fron the Mogens Faburatory of the same hospital. Thi sep consisted a 19 heathy adi fle wh see tk ‘who had ne history of sting oral. hot consumption. ‘Twenty-six (67%) were fet av the aca age ofthis op os 12 12 years (range 21-68 IW sample preparation Al paticnts were asked 1 rinse their mouths with war before the mucus sweeps, A polished slide wa used collect cells from the oral mucosa of the tight al Kel cheeks, then the sa ples were spread dincely in v0 sepa tate slides, The smears were ‘an fse in 80% wyethanol For 8 hea stained ing Oveein a Follows, After innersion in TN ICT at 60°C for 8 Imi, the slides were immersed in COwcein reagent for 20 mi rinse wth dsl! water, Fast Green contrasted for M0 secvnnds ad sins with distil wer, Miter thi procede the nucle vats sine i pink oF orange a the slaps in bie (Fig. 1 The slides were analyzed by one ol 0 experince technicians using a fight rmictesenpe (100 x); the te wore blndes the patie data group assignments, Hach verler comute the rnuntr of mietonuetet in a field of 20H cells per slide (1). "The gid Hines for idenuiyig MIN in oral epithe Til cells was Ise on their moxphole sd location within the cell, as pre ously dseribe (16), Briefly, mor phology eviteiaineladed texture com parable the ai nutes, aed 40 ‘oval shape with alistinet howdy, ave size Tes tha onthe i Starisvalcnasis Differences hetween 2 comtinsous vat ned with tite 1 tests Dilferences between 3 or more nats! vaviables were compared iy analysis of variance, ie method tor snltiple ving Se ‘conparisons, Dilferences between pro pontions were compared with the ehi- Saeed test and Fisher's exact est Statistica significance was set ah ¢ 1.05, al the confidence interval a 8G. mercer ver variably wa a sessed sing Pearson's correlation in 25 salomly soleted slices real by 2 technicians whe were blindee uo the ptt data, assignation or previously Heteeted umber DF RIN, The study way appnoved by the Fihies Conmitiee of the Hospital de Especial, esis the demographic teristics of RA ps be There were IPRA patients ak ing MEX anal 30 RA pati seo had hover awed MTX oF aathieynie and seho were on otter sexo fine drags ily chleexguine (73%), Most pa ml clinical chara ris ve aha the BORA pat aes une iti MN Pate dation, mean y+ SD Set Te4 ‘ons Gems, women 81 wasn ein ns RA dao, ea 1581 ea hao Ke Tile Heine ferences inthe mnie of MIN in RA patients al eto Table I Frequency dso of microm umber amon tly ashy nee sig ATX a) were female. The mean age (range between wsees ml nom ars OF MTX. 20-76 yeas) ane mean disease iTable 1M shows the freqveney ast tion Gange 140.19 years) did not lifer Gon of BINT ang the sin. groups between the wo groups. However, the Values af MN were defined as noma MTX proup was slightly less educated when bstween # and 1 SD of the eo and Ted higher propottion of siok- tule (0 40 2), as merely increased fers, coffee drinkers and pedaicine when between 4 a ana high whew lusers. Methotiexate was being used MN were > MN at RA patente were po. inall cawes for mean period of 16 more frequently in the moderate to ‘mons (ange 1-78). mean dose of 7 igh enwge compared. with contol, Img. arange of 7.5-12.5 mp/nk. whether or mo they were sens of IT “The in ono the (p< A100. MN assay was 182, Tule H shows the We observe 0 effect of sacking om differences in MN between both groups the RIN number. Cigarette cons ‘oF RA patents andthe healthy eontols. tw was dociented in 4 patients (1 The BIN fest fiom one RA patient i@ out of 50 in the MTX-RA gronp. and | the mon MTX gronp could wot be oat of 3H the mow MTX RA pron) assessed dt to the poor uality oF the Four ofthese were heavy siokers ae slide. At baseline the mumbor of MN smoked an average of 40 ci was significantly Wigher in the RA iy, and 3 an average of 20 per dy, patients than the controls 1p < 02001, ‘The MN amber in these 4 cases was 996 C1 fordilferences hom 1.210.85 —rero. The other 10 patients sme less for MEX sees, andl 3 (0 4 for tom than 6 cigarettes per day amd the MIN tiseis of MEX). However, no difference yniber sawed! sh dilerences. comm ii the MN number was observed pared with the conta. No significant MN number ana oh dling caffeine constmpion, on five use, methotexate dager daa ion, al RA natn, he elfect of Talc acid soppemen ‘ion om the MN number was assess in 40 oot of 50 MEX tcated RA patie ‘he remaining 1 (205%) paviente were Jost t follow-up, No sipificant die enees were fond betwee the mic MN numer at baseline and after foc seid supplementation (NIN mean 3.8 $2998 3.1428, = 0194, 95% Cl ot Aillrences 1.444 1M), Dieusny Ie scene that the distibtion of site- specific cancers in RA Ts skewed com trae ih the general popltions the fnchlence of Iymptonnts nd der ceer is increaed while the fcience lo cancer of the digestive organs is de creased (J, 2), This cout he explained hy the infinence of the disease ise ul the drug teatment Hat #8 used RA patients. However, there are so problems in ascertaining the influence of specific DMARDs on cancer indo tion. The fst she Kn nen pein hetween expasite to & DMARD ad re development of malignatcy, The secon ig thal RA patient frequently site fom ane DMARD tater, {oF use a combination of DMARD de ing the course ofthe disease ‘The MN test permits the assessment in Show-tenn stiles a the genotoxicity seine with RA air the dives tured to tea i, The detection of MIN i ‘widely sed nea short-term mutagen ity te

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