protexid paper 1

8/11/2019 Protexid Paper 1

1/6

J. Pineal Res. 2006; 41:195200 2006 The AuthorJournal comilation 2006 !lac"#ell $un"s%aar&

'oi:10.1111().1600*0+9,.2006.00-59.Journal o/ Pineal Research

Re%ression o/ %astroesoha%eal reu &isease smtoms usin%&ietar sulementation #ith melatonin 3itamins an& aminoaci&s:comarison #ith omeraole

Astract: The re3alence o/ %astroesoha%eal reu &isease 78R' is Ricar&o &e oua Pereiraincreasin%. 78R' is a chronic &isease an& its treatment is rolematic. 'eto. &e armacia*t ma resent #ith 3arious smtoms inclu&in% hearturn re%ur%itation Para?a= A3 &as !araunas= -51(@amus&sha%ia cou%hin% hoarseness or chest ain. The aim o/ this stu& #as to s are the Irst*line choice in oth reu>ntro&uction

esoha%itis an& nonerosi3e reu &isease B8R'. PP>s7astroesoha%eal reu &isease 78R' is the reu o/ e ecti3elff inhiit the &uration an& etent o/ %astric aci&%astric contents into the esoha%us an&(or a&)acent or%ans secretion an& ro3i&e more comlete remission o/ the#ith or #ithout tissue &ama%e L1M. The most rominent smtoms o/ hearturn than others /orms o/ aci&*sures*smtom is hearturn #ith or #ithout re%ur%itation o/ sant thera L+ M. No#e3er the resonse to PP>s in%astric contents into the mouth. 78R' is a common atients #ith B8R' is less e cacious #hen comare& #ithfficon&ition #ith an estimate& 44G o/ the a&ult oulation atients #ith erosi3e 78R' L2 9M.in n !rail Cansoraole omeraole esomeraole an& raera*there is no national stu& &one #ith a&eFuate an& seciIc ole ha3e otentiall serious a&3erse si&e e ects.ff Thestatistical analsis L-M. aolish aci& ro&uction so comletel that serum %astrin

7astroesoha%eal reu &isease can e su&i3i&e& into le3els rise. >n ro&ents enterochroma n*li"e cell tumors an&ffi

se3eral %rous: a nonerosi3e 78R' B8R'; erosi3e carcinoi& tumors ha3e &e3eloe&. >t is not "no#n #hether78R'; c !arrettOs esoha%us #ith 78R'*relate& com* these &ru%s are carcino%enic in humans a similarlications. B8R' has een &eIne& as the resence o/ mechanism L10 11M. $oreo3er acterial o3er%ro#th matical smtoms o/ 78R' cause& intra*esoha%eal &e3elo in the stomach in the asence o/ aci&. !acterialaci& in the asence o/ 3isile esoha%eal mucosal in)ur L2M. metaolism o/ &ietar nitrites ma then lea& to the>t is estimate& that u to +0G o/ atients #ith tical ro&uction o/ B*nitroso comoun&s that are carcino%enic78R' smtoms in the estern Nemishere ha3e normal L10 12M. This ris" is not limite& to chronic omeraoleen&osco L4M. treatment; it can theoreticall occur #ith an e ecti3e lon%*ff

Aci&*suressant &ru%s re&ominate in the treatment o/ term antaci& re%imen. $oreo3er omeraole aears to78R'. Proton um inhiitors PP>s such as omera* a ectff ctochrome P450. Althou%h initial stu&ies su%%este&ole esomeraole the *enantiomer o/ omeraole lan* an inhiitor e ectff more recent stu&ies in&icate thatsoraole an& raeraole are #i&el use& /or the omeraole ma in&uce the ctochrome P450 1A su/amiltreatment o/ 78R' an& the are also use& in maintenance that is associate& #ith acti3ation o/ certain chemical

195


2/6

Pereira

rocarcino%ens such as olcclic aromatic h&rocaronsmtom se3erit

L10M.To romote the re%ression o/ the i3otal smtoms o/ Patients recor&e& the se3erit o/ 78R' smtoms in a

78R'(B8R' hearturn or aci& re%ur%itation a /ormu* &ail &iar. e3erit #as %ra&e& on a I3e*oint scale /romlation #ith melatonin 3itamins an& aminoaci&s #hich has none 0 mil& 1 mo&erate 2 se3ere - an& 3er se3ereno si%niIcant si&e e ects #as &e3eloe&. This /ormulationff 4 /or each o/ the /ollo#in% smtoms: &a*time heart*is ase& on in/ormation accumulate& our research urn ni%ht*time hearturn &a*time re%ur%itation an&

%rou L1-19M an& those otaine& /rom scientiIc literature ni%ht*time re%ur%itation.ase& on the /act that melatonin has inhiitor actions on Dther uer 7> smtoms o/ elchin% eructation earl%astric aci& secretion L20 21M an& on the iosnthesis o/ satiet the sensation o/ Illin% u Fuic"l loatin% /eelin%nitric oi&e L21 22M. As the sulement contains natural li"e > ha3e a lot o/ %as in m ell nausea an& 3omitin%comoun&s /oun& in /oo&s this /ormula resents /e#er #ere also recor&e& on the I3e*oint scale as elaine&si&e e ectsff than me&ications currentl use& in clinical ao3e.me&icine. mtom se3erit #as score& accor&in% to the /ollo#in%

scale: 0 no smtoms; 1 mil& smtoms are resentoccasionall an& atients can continue #ith &ail acti3ities;

$aterials an& metho&s 2 mo&erate smtoms are resent most o/ the time utatients can er/orm &ail acti3ities; - se3ere smtoms

TT analsis #hich

8clusion criteriainclu&e& also atients #ho &i& not comlete the stu&. The

Patients #ith heatitis li3er cirrhosis or other serious &emo%rahic an& clinical characteristics o/ the t#o %rousconcomitant illnesses #ere eclu&e& /rom this stu&. A an& ! #ere comare& @hi*sFuare test or isherOs

196


3/6

$elatonin 3itamins an& aminoaci&s /or 78R'

eact test. The results o/ treatment #ere comare& @hi* Tale 2. Nealin% rates o/ atients in the t#o treatment %roussFuare test. P K 0.05 #as consi&ere& statisticall si%niI*

7rou A 7rou !cant. 2

n S 1+6 n S 1+5 P*3alue 3 *test

PP analsis G 1+6(1+6 100 115(1+- 66.5 0.001 +0.+66Results >TT analsis G 1+6(1+6 100 115(1+5 65.+ 0.001 +2.+5Patients

A total o/ -51 atients #ith hearturn entere& the sur3eil*lance ro%ram et#een Januar 2001 an& 'ecemer 2005. Tale -. A&3erse e3ents &urin% the treatments use& in the current$ean a%e at enrollment #as 44 r #ith a ran%e /rom 1 to reort

r; 59.2G #ere #omen. The numer o/ atients7rou A n S 1+6 7rou ! n S 1+5

recruite& er ear increase& o3er the course o/ the stu&as the ractice %re#; the me&ian ear o/ enrollment #as 'iarrhea 0 0 + 4200-. Nea&ache 0 0 2 1.1

>n terms o/ %eo%rahical area the su)ects are /rom 19 Nertension 0 0 - 1.+omnolence 159 90.- 4 2.-

&i erentff cities an& to#ns /rom I3e !railian states: 19+atients 56.12G are /rom aoH Paulo 14 42.1+G /rom The 3alue are %i3en as n G.$inas 7erais three 0.5G /rom Parana= t#o 0.5+G/rom 8s?rito= anto an& one 0.29G /rom 'istritoe&eral. ome o/ them are searate& one another aout

#ere si%niIcant &i erencesff in era&ication rates et#een

o/ 2500 "m. >n terms o/ social class: +4 atients 21.09G the t#o %rous. The &emo%rahic an& clinical character*are rich 1+2 49G are /rom mi&&le class an& 105 29.91Gistics o/ the -51 su)ects in the t#o %rous are sho#n in

are oor. >n terms o/ e&ucation: 124 -5.-2G ha3eTale 1.

uni3ersit &e%ree L/rom these 1+ 4.4G are uni3ersitA/ter Inishin% the 40 &as o/ treatment total re%ression

ro/essors an& scientists an& t#o 0.56G are hsiciansMo/ the smtoms mar"e&l imro3e& #as oser3e& in

209 59.54G ha3e hi%h school 1+ 4.4G ha3e incomlete100G o/ the su)ects o/ the %rou A. The reorte& relie/ o/

hi%h school an& one 0.-G is illiterate.the smtoms a/ter + &as ta"in% the sulementation.

The su)ects #ere &i3i&e& in t#o %rous: it #as allo#e&These results in&icate that 78R' can e re%resse& #ith

to 1+6 atients use the sulement containin% melatoninmelatonin 3itamins an& aminoaci&s o/ the /ormulation

aminoaci&s an& 3itamins &escrie& in this aer &urin%resente& in this aer. @omlete& Fuestionnaires aout

40 &as #ithout usin% an other me&ication e3en antac*the a&3erse e3ents an& comliance #ere otaine& /rom all

i&s %rou A an& /or comarison the other hal/ n Sthe -51 atients. A total o/ 159 atients 90.-G o/ %rou A

1+5 3olunteers use& omeraole %rou !. o thererelate& somnolence an& slee imro3ement.

Tale 1. !aseline characteristics o/ atients enrolle& in the current A total o/ 115 atients o/ %rou ! 65.+G reorte& relie/stu& o/ the smtoms mar"e&l imro3e& a/ter 9 &as o/

treatment /our atients 2.-G reorte& artial relie/7rou A 7rou ! sli%htl imro3e& an& the remain&er continue& to /eeln S 1+6 n S 1+5 all smtoms &escrie& 40 &as e/ore startin% the treat*

7en&er $( 61(115 0(95 ment. T#o atients 1.1G o/ %rou ! #ith&re# /rom theA%e r .'. 4-.6 1-.- 44.26 15.2 stu& ecause o/ ersistent hea&ache cause& omeraole.mo"in% +5 42.6G 50.-G >n terms o/ re%ression o/ all smtoms there #as a

Alcohol ause 4.5G 10 5.+G statiscall si%niIcant &i erenceff et#een %rous A an& !:Pre3ious me&ication -2 1.2G 19 10.G the acti3e healin% rate #as 100G 1+6(1+6 in %rou A/or reu &isease

su)ects #ho use& sulementation o/ melatonin amino*

i%. 1. Photo%rahs o/ the /ace o/ a atient o/ the %rou A #ith an esoha%eal ulcer o/ 6 cm #ho use& the &ietar sulementation #ithmelatonin 3itamins an& aminoaci&s in /our &i erent time erio&s: A $arch 2002: e/ore the ulcer aeare& atient #ei%he& 0 "%; !ffDctoer 12 200-: &urin% the erio& o/ the ulcer atient #ei%he& 40 "%; @ Bo3emer 14 200-: a/ter -2 &as o/ treatment atient #ei%he&+0 "%; ' Jul 2 2004: a/ter 9 months o/ treatment. The atient no# has o& #ei%h as o/ $arch 2002 0 "%.

19+


4/6

Pereira

A

!

i%. 2. 8n&osco recor&s er/orme& on atient o/ the %rou A in: A Jul 200-: sho#in% the ulcer in&icate& an arro#; ! Jul 2004:sho#in% that the ulcer #as racticall &isaeare& a/ter 9 months o/ treatment.

aci&s an& 3itamins an& 65.+G 115(1+5 in %rou ! Patients o/ %rou ! relate& more si&e e ects than those o/ffsu)ects #ho too" omeraole P K 0.05 see Tale 2. %rou A. Dnl somnolence #as reorte& /or sulementa*

Althou%h one atient o/ %rou A 0.56G has anconi tion o/ melatonin 3itamins an& aminoaci&s &urin% then&rome La &isor&er in #hich the roimal renal tuules treatment see Tale -.o/ the "i&ne &o not roerl reasor electroltes an& A/ter the #or" comlete 60 su)ects -4.-G o/ %rou !nutrients aminoaci&s 3itamins minerals electroltes an& #ho reorte& ersistence o/ the smtoms use& theicaronate ut instea& Qsill them in the urineM L2426M; sulement /or 40 &as. A/ter this erio& all atientsshe #as resumal heale& o/ 78R' ecause melatonin 100G o/ this su%rou reorte& that all smtomsattenuates anconi n&rome L2+M. &isaeare&.

19


5/6

$elatonin 3itamins an& aminoaci&s /or 78R'

si&e e ectsff than atients #ho use& omeraole. These'iscussion

results su%%est that 78R' is inhiite& lo# le3els o/Proal the re%ression o/ B8R'(78R' smtoms an& melatonin an& certain 3itamins an& aminoaci&s in thethe relie/ o/ the ain #as ase& on the /ollo#in% /acts: the human. This /ormulation can also e use& /or treatment o/Irst iocomoun& o/ this /ormula is melatonin #hich has slee &isor&ers since 159 su)ects 90.-G o/ %rou Aan inhiitor action on %astric aci& secretion L20 21M an& relate& slee imro3ement.e ectsff on ulcer healin% L21 2--M #hich in3ol3es here*

mia at ulcer mar%in L-4 -5M. V @A$P @aminas aoH Paulo !rail /or theiralle3iate acute ain L-M. This anal%esic e ectff is attriute& critical rea&in%s an& an&ro an& Renato !arieri Dme%aW

to an increase& a3ailailit an&(or e ecti3enessff o/ nora&* Print Xar%inha $7 !rail /or their technical suort.renaline an& serotonin actin% as inhiitor transmitters inthe nociceti3e sstem L-M. Another in%re&ient is /olic aci&

Re/erences#hich rotects a%ainst %astroenterolo%ical cancers L-9M.Proal these iochemicals an& other comonents o/ the 1. $oraes*ilho J @ecconello > 7ama*Ro&ri%ues J et al./ormulation etaine an& methionine in&uce& snthesis o/ !railian consensus on %astroesoha%eal reu &isease: ro**a&enosl*l*methionine A$e L4042M a methl &onor osals /or assessment classiIcation an& mana%ement. Am J#hich has anti*inammator as #ell as anal%esic acti3it 7astroenterol 2002; 9+:24124.#ithout &ama%in% the %astrointestinal mucosa o/ eeri* 2. ass R. 8i&emiolo% an& athohsiolo% o/ smtomaticmental animals L4-M. !eon& that A$e has een use& to %astroesoha%eal reu &isease. Am J 7astroenterol 200-;treat %astric ulcer in animals L44M. 8conomicall these 9:2+.iomolecules are less eensi3e than A$e an& the -. Ba&er &a @osta J Ba&er 7A $otta 7C. Pre3alencecasules coul& e accessile to oorer oulations. o/ hearturn in Pelotas R !rail: oulation*ase& stu&.

ArF 7astroenterol 200-; 40:-1-4.A total o/ 159 atients 90.-G o/ %rou A relate&

4. 7oh EC @han% @ oc" E$ et al. 7astroesoha%ealsomnolence an& slee imro3ement. This /act is elainalereu &isease in Asia. J 7astroenterol Neatol 2000; 15:2-0

&ue to slee*in&ucin% acti3it o/ melatonin L45 46M. o this2-.

/ormulation can also e use& atients #ith slee5. 'er 7. An o3er3ie# o/ roton um inhiitors. 7astroenterol

&isor&ers.Burs 200-; 26:12190.

imilar /ormulations usin% 3itamins an& aminoaci&s #ere 6. Eoo N. An e3i&ence*ase& loo" at harmacothera /orteste& success/ull in nearl 10000 atients #ith &eres* %astroesoha%eal reu. @hirur% 2005; +6:-5--5.sion L4+49M ro3in% that there are no si%niIcant si&e +. Noltmann 7 !ter P $et $ et al. A ran&omie&e ectsff in this /ormulation. &oule*lin& comarati3e stu& o/ stan&ar&*&ose raeraole

i%. 1 sho#s hoto%rahs o/ the /ace o/ a atient o/ the an& hi%h*&ose omeraole in %astro*oesoha%eal reu &is*%rou A #ho use& the sulementation #ith melatonin ease. Aliment Pharmacol Ther 2002; 16:4+945.3itamins an& aminoaci&s in /our &i erentff time erio&s. . 7almiche JP Yeri 'ucrotte P et al. 'ecreasin%A/ter -2 &as o/ treatment he ha& reco3ere& -0 "%. >n oesoha%eal aci& eosure in atients #ith 78R': a com*hotos ta"en in Dctoer an& Bo3emer o/ 200- the color arison o/ raeraole an& omeraole. Aliment Pharmacol

o/ his hair #as ello# i%. 1!@. The atient reorte& Ther 2001; 15:1-4-1-50.that his hair ha& chan%e& color /rom lac" to ello# a/ter 9. $iner P Drr ilione J et al. Raeraole in non*the ulcer aeare& he &i& not &e his hair. This is erosi3e %astroesoha%eal reu &isease: a ran&omie& laceo*consistent #ith the oser3ations in rats #here malnutrition controlle& trial. Am J 7astroenterol 2002; 9+:1--21--9.chan%e& hair color to ello# L50M. A/ter treatment the 10. Ealant N Roschlau N8. Princiles o/ $e&ical Pharma*atient reco3ere& the natural color o/ hair i%. 1'. i%. 2 colo% 6th e&n. D/or&


6/6

Pereira

1-. Pereira R. Re%ression o/ an esoha%eal ulcer usin% a &ietar the e cacffi o/ raniti&ine an& omeraole in re&ucin% %astric

sulement containin% melatonin. J Pineal Res 2006; 40:-55 &ama%e. J Pineal Res 2002; --:1+.

-56. --. !an&oa&ha ' 7hosh 7 !an&oa&ha A Reiter

14. Pereira R. Atomic /orce microsco: a no3el harmacolo* RJ. $elatonin rotects a%ainst iroicam*in&uce& %astric

%ical tool. !iochem Pharmacol 2001; 62:9+59-. ulceration. J Pineal Res 2004; -6:19520-.

15. Pereira R. The use o/ calcium loc"ers to stu& iochemical -4. hittle !JR Coe*!elmonte J $onca&a . Re%ulation

eha3iour o/ accharomces cere3isiae cells. $ol @ell !iochem o/ %astric mucosal inte%rit en&o%enous nitric oi&e inter*

2001; 22:1+. actions #ith rostanoi&s an& sensor neuroeti&es in the rat.

16. Pereira R. Dser3ation o/ oi&ati3e stress on east cells. !r J Pharmacol 1990; 99:60+611.$etho& $ol !iol 2004; 242:-15-21. -5. Ta"euchi E . Anal%esic an& anal%esia otentiatin% action o/ !

552:155159. 3itamins. chmer 199; 12:1-6141.20. !roo#s"i T Eonture" P@ Eonture" J et al. >n3ol3e* -9. an% JZ ,iao '. olic aci& olmorhism o/ methl*

ment o/ ccloo%enase @D,*2 ro&ucts in acceleration o/ %rou metaolism %enes an& 'BA methlation in relation toulcer healin% %astrin an& heatocte %ro#th /actor. 7> carcino%enesis. J 7astroenterol 200-; -:2129.

J Phsiol Pharmacol 2000; 51:+51++-. 40. etro# @ A3ila JR. 8 cacffi o/ the &ietar sulement21. Ja#ore" J !roo#s"i T Eonture" J. $elatonin as an *a&enosl*l*methionine. Ann Pharmacol 2001; -5:14141425.

or%anorotector in the stomach an& the ancreas. J Pineal Res 41. Renol&s R'. Xitamin !6. >n: $etho&s in @linical @hem*

2005; -:+--. istr. Pesce AJ Ealan CA e&s. @.X. $os @o. ashin%*

22. @reso 8 $acias $ Poo ' et al. $elatonin inhiits ton '@ 19+; . 5556.

eression o/ the in&ucile BD snthase >> in the li3er an& lun% 42. Rosano T7 hitle RJ. @atecholamines an& serotonin. >n:an& re3ents en&otoemia in lioolsacchari&e*in&uce& Tiet Tetoo" o/ @linical @hemistr. -r& e&. !urtis @A

multile or%an &s/unction sn&rome in rats. A8! J 1999; Ash#oo& 8R e&s. .!. aun&ers @o. Phila&elhia 1999; .

1-:15-+1546. 15+01600.

2-. oc" E$ Talle B Nunt R et al. Reort o/ the Asia* 4-. 7ualano $ tramentinoli 7 !erti . Anti*inammatorPaciIc @onsensus on the mana%ement o/ %astroesoha%eal acti3it o/ *a&enosl*l*methionine: inter/erence #ith the

reu &isease. J 7astroenterol Neatol 2004; 19:-5+-6+. eicosanoi& sstem. Pharmacol Res @ommun 19-; 15:6-696.

24. @olson @R 'e!roe $8. Ei&ne in)ur /rom alternati3e 44. 7ior%i 7 $icheli C e%re 7. 8 ectff o/ *a&enosl*l*me&icines. A&3 @hronic Ei&ne 'is 2005; 12:2612+5. methionine on the %astric ulcer in rats. Ri3 8ur ci $e&

25. 8arle E8 ene3iratne T ha"er J hoac" '. anconiOs armacol 19; 10:-65-6+.n&rome in N>X[ a&ults: reort o/ three cases an& literature 45. @amos C il3a*Junior= P !ruin X$ !ruin P@.

re3ie#. J !one $iner Res 2004; 19:+14+21. $elatonin imro3es slee in asthma. Am J Res @rit @are

26. 7ol&man R' Eoren 7. Amhotericin ! nehrotoicit in $e& 2004; 1+0:94+951.

chi&ren. J Pe&iatr Nematol Dncol 2004; 26:421426. 46. !uscemi B Xan&ermeer ! Pan&a R et al. $elatonin /or

2+. ener 7 ehirli D Ze%en !@ et al. $elatonin attenuates treatment o/ slee &isor&ers. 83i& Re Technol Assess 2004;

i/os/ami&e*in&uce& anconi n&rome in rats. J Pineal Res 10:1+.

2004; -+:1+25. 4+. !)ellan& > Tell 7 Xollset 8 et al. olate Xitamin !12

2. Ci N Nelan&er N. Ner%astrinemia increases roli/eration homocsteine an& the $TNR 6++@ \ T olmorhism in

o/ %astro&uo&enal eithelium &urin% %astric ulcer healin% in aniet an& &eression the Nor&alan& homocsteine stu&.

rats. 'i% 'is ci 1996; 41:404. Arch 7en Pschiat 200-; 60:61626.

29. teer $C. The atho%enesis an& athohsiolo% o/ acute 4. Pennin !JN 7uralni" J$ errucci C et al. Xitamin

ancreatitis. J Phsiol Pharmacol 199; 49:4+59. !12 &eIcienc an& &eression in hsicall &isale& ol&er

-0. !roo#s"i T Eonture" P@ Eonture" J et al. Acceler* #omen: ei&emiolo%ic e3i&ence /rom the #omenOs health an&

ation o/ ulcer healin% cholecsto"inin @@E; role o/ @@E* a%in% stu&. Am J Pschiat 2000; 15+:+15+21.

A recetors somatostatin nitric oi&e an& sensor ner3es. 49. Tiemeier N Xan Tui)i NR No/man A et al. Xitamin !12

Re%ul Pet 1999; 2:19--. olate an& Nomocsteine in &eression: the Rotter&am stu&.

-1. !an&oa&ha ' !is#as E !an&oa&ha < et al. Am J Pschiat 2002; 159:20992101.

$elatonin rotects a%ainst stress*in&uce& %astric lesions 50. aterlan& RA Jirtle RC. 8arl nutrition ei%enetic

sca3en%in% the h&rol ra&ical. J Pineal Res 2000; 29:14-151. chan%es at transosons an& imrinte& %enes an& enhance&

-2. !an&oa&ha ' !an&oa&ha A 'as PE Reiter suscetiilit to a&ult chronic &iseases. Butrition 2004; 20:6-

RJ. $elatonin rotects a%ainst %astric ulceration an& increases 6.

200

protexid paper 1

Documents