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Sklerożi multipla, proteini, xaħmijiet, u progesterone

minn Ray Pit PhD fuq 13/02/10 fil 13:39

minn Raymond Pit, PhD

Aħna dejjem suġġetti għal piżijiet antiġeniċi. Il-kwistjoni importanti għandha x'taqsam mal-kapaċità tagħna li jillimita l-rispons infjammatorju li dawn il-piżijiet.

Fl-SM [sklerożi multipla], huwa ċar li l-proċess ta 'infjammazzjoni innifsu huwa distruttivi, u li l-estroġenu huwa fattur ewlieni predisposizzjoni. Aċidi grassi mhux saturati, u żbilanċ tad-dieta ta 'aċidi amino jinteraġixxu mill-qrib mal hyperestrogenism u ipotirojdiżmu li jipproduċu l-mard deġenerattiv awtoimmuni.

Tnaqqis ta 'medjaturi ta' infjammazzjoni huwa aħjar minn jkattru aġent anti-infjammatorji wieħed bħal cortisol. Għalkemm mediċini immunosoppressivi, inkluż l-"aċidi grassi essenzjali," ma jittaffew is-sintomi infjammatorji temporanjament, huma probabbilment jikkontribwixxu għall-patoloġija sottostanti.

Persuni SM kronikament żieda fil-produzzjoni ta 'cortisol. Dan joħloq distorsjoni tal-assimilazzjoni ta 'proteina, li jixbħu defiċjenza ta' proteina ta 'nutriment. Serotonin eċċessiv u l-estroġenu jikkawżaw produzzjoni relattivament mhux ikkontrollat ​​ta 'cortisol. Ċirku vizzjuż ta 'medjaturi infjammatorji u żbilanċ aċidu amminiku jista' jirriżulta.

Dipressjoni, lupus,, emigranja menopawsa, dijabete, u x-xjuħija għandhom diversi karatteristiċi metaboliċi importanti komuni ma 'Stati Membri.

Terapiji popolari huma illoġika, u x'aktarx jikkawżaw progressjoni tal-marda.

Kwalità għolja proteina, tirojde, pregnenolone u progesterone tendenza li jikkoreġu l-patoloġija sottostanti. Dawn huma anti-infjammatorji, iżda mhumiex immunosoppressiva jew catabolic.

Altitudni għolja u l-klima xemxija huma assoċjati ma 'inċidenza baxxa ta' SM.

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Isklerożi multipla (MS), bħal mard awtoimmuni oħra, jaffettwa lin-nisa aktar spiss mill-irġiel (madwar 2 sa 1), għandha bidu tagħha matul is-snin riproduttivi (speċjalment wara l-età ta '30, meta estroġenu hija għolja ħafna), spiss tittellef premenstrually , u xi kultant mtaffija minn tqala (Drew u Chávez, 2000), meta proġesteron huwa għoli ħafna. Nisa bi proporzjon għoli ta 'estroġenu li proġesteron nstabu li għandhom l-leżjonijiet fil-moħħ l-aktar attivi Bansil, et al., 1999). Ħafna mill-medjaturi tal-infjammazzjoni li huma involuti fl-MS-arblu ċelluli, ossidu nitriku (NO), l-serotonina, prolactin, l peroxidation lipidi, aċidi grassi ħielsa, prostaglandini u isoprostanes, u l-ċitokini varji (IL, TNF)-huma assoċjati mill-qrib ma ' azzjonijiet estroġenu fuq, u fl-annimali, mard awtoimmuni jistgħu jiġu miġjuba minn kura b'estroġenu (Ahmed u Talal).

L-assoċjazzjoni qawwija ta 'MS ma estroġenu wassal għal illoġika, iżda popolari u sew ppubbliċizzati konklużjoni mediku li estroġenu hu protettiv kontra SM, u xi wħud qalu li l-estroġenu għandha effetti terapewtiċi ta' benefiċċju. Dan il-mod stramb ta 'ħsieb għandha l-ekwivalenti tiegħu fl-idea li, peress li n-nisa huma ħafna aktar probabbli mill-irġiel li jiżviluppaw marda ta' Alzheimer, estroġenu hu protettiv kontriha, jew li, peress li n-nisa jkollhom l-għadam iktar fraġli mill-irġiel tagħmel, u telf tagħhom għadam progressiva iseħħ matul iż-żminijiet ta 'espożizzjoni akbar tagħhom għall-estroġenu, estroġenu jipprevjeni osteoporożi.

F'dan l-ambjent mediku, assoċjazzjonijiet mill-qrib bejn l-estroġenu u mard deġenerattiv huma rikonoxxuti, iżda dawn jingħataw kuntrarju tifsira li s-sens komun billi qal li l-assoċjazzjoni iseħħ minħabba li ma hemmx estroġenu biżżejjed. Il-fuklar ħruq inti għaliex mhuwiex sħun biżżejjed.

Bħala Dave Barry ngħid, jien ma tagħmel dan up. Riċentement artikoli ukoll ppubbliċizzati ssuġġerew li l-estroġenu jipproteġi l-moħħ (puplesija anki kontra!) Minħabba li żżid serotonin u NO [nitric oxide]. Hemm xi ħaġa kważi esthetically pjaċir meta l-iżbalji tant kbar huma kkonċentrati fi f'artikolu wieħed. Nitric oxide u serotonin huma t-tnejn newrotossiċi (Joseph, et al, 1991;. Skaper, et al, 1996;. Ta 'Parkinson, et al, 1997;. Santiago, et al, 1998;.. Barger, et al, 2000), kif riżultat ta 'respirazzjoni mitokondrijali soppressjoni. LE għandu rwol ewlieni fil peroxidation lipidi u demajlinazzjoni. Huwa interessanti li wieħed jara serotonin u NO miftuħ assoċjati ma 'l-estroġenu, li mitokondrijali tossiċità tfasslet b'reqqa f'għajnejn il-pubbliku.

Hemm teoriji diversi dwar il-kawża tal-Istati Membri, teoriji qodma dwar ġeni u vajrusijiet, u t-teoriji ġodda dwar batterji, nuqqasijiet vitamina, nuqqasijiet taż-żejt, veleni, u reazzjonijiet fil-tilqim (speċjalment għall-epatite B u l-influwenza). It-teorija biss li ġiet abbandunata huwa l-teorija seklu 19 psikjatriku dwar "paraliżi hysterical," għalkemm kultant xi ħadd ma għadu jitkellmu dwar kawżi emozzjonali ta 'sklerożi multipla; it-terminu "isteriżmu femminili" evolviet "disturb konverżjoni."

Kull wieħed mill-teoriji prinċipali għandha ftit fatti li jidhru li jappoġġjaw, iżda jittraskura milli kont għal fatti oħra ħafna. Kulħadd jaqbel li s-sistema immunitarja tkun involuta fl-MS b'xi mod, iżda li verament fejn il-problema tibda, minħabba l-idea li l-infjammazzjoni hija parti intrinsika ta 'immunità. Jekk "infjammazzjoni huwa meħtieġ u tajjeb," imbagħad isir problema li wieħed jiddefinixxi eżatt fejn il-konfini huwa bejn reazzjoni xierqa u proċess deġenerattiv. Edema, respirazzjoni ċellulari mnaqqsa, telf ta 'funzjonijiet normali, fibrożi fi gradi varji tagħha, kull komponent ta' infjammazzjoni tista 'tidher f'dawl tajjeb, bħala parti minn "reazzjoni immunitarja difensiva." Meta korriment tessut twassal għat-tiswija, huwa "għandu" jitqies bħala ta 'benefiċċju, anke jekk din twassal għall-formazzjoni ta' ċikatriċi fil-post ta 'tessut funzjonali, minħabba li l-paragun huwa bejn riżultat immaġinarji agħar possibbli, u ta' rkupru imperfetta, aktar milli jqabbel l-proċess ta 'infjammazzjoni bil-possibbiltà li potenzjalment jagħmlu l-ħsara aġent jista 'jkollhom isir l-ebda ħsara fil-livelli kollha.

L-illustrazzjoni sempliċi ta 'kif infjammazzjoni tirrigwarda-riżorsi tal-organiżmu kien esperiment li glucose fid-demm ġie varjat, filwaqt li annimal ġie espost għall-kimiċi li varja minn ħafif irritanti għall potenzjalment fatali. Meta l-annimal kellu zokkor fid-demm baxx ħafna, l-irritanti mildest jista 'jkun fatali, imma meta glucose fid-demm tiegħu kienet miżmuma għolja ħafna, anke l-antiġeni fatali kienu biss kemmxejn irritanti. Tvarja l-konċentrazzjoni tas-sodju fid-demm kienu simili, iżda aktar dgħajfa, l-effetti.

Hemm tendenza biex tara infjammazzjoni mhux biss bħala parti normali tal-immunità, iżda li jarawha bħala proporzjonali għall-natura ta 'l-antiġen, ħlief meta s-sistema immunitarja tkun ġiet ipprajmata għaliha permezz ta' kuntatt ta 'qabel, f'liema każ l-organiżmu se jew ma jirreaġixxix kollha (peress li tkun saret immunitarja), jew se jirreaġixxu aktar vjolenti milli għamlet fuq l-ewwel espożizzjoni, peress li tkun saret allerġika. Iżda, fir-realtà, il-konċentrazzjoni sempliċi ta 'glukosju u sodju fid-demm (u tat-tirojde, u sustanzi oħra ħafna li mhumiex meqjusa bħala parti mis-sistema immunitarja) tista' tagħmel differenza enormi fil-grad ta '"immunoloġika" reazzjoni .

Fil-kondizzjoni eċċessivament sensittivi prodotta minn ipogliċemja, diversi affarijiet jiġri li jikkontribwixxu għar-rispons infjammatorju maladaptive esaġerat.

Adrenalina żidiet fil ipogliċemija, u, jekk l-adrenalina jonqos milli jikkonvertu glycogen fi glukożju, se jipprovdi fjuwil alternattiv minn aċidi grassi liberi jillibera minn ċelluli tax-xaħam.

Jekk l-aċidi grassi mhux saturati liberat huma, dawn ser jikkawżaw serotonin li għadda, u kemm serotonin u l-aċidi grassi mhux saturati se jrażżnu respirazzjoni mitokondrijali, taggrava l-ipogliċemija. Huma se jistimulaw ir-rilaxx ta 'ċitokini, attivazzjoni ta' varjetà ta 'proċessi immunoloġiċi u infjammatorju, u dawn ser jikkawżaw vini li jsiru leaky, il-ħolqien edema u jibdew l-ewwel stadji ta' fibrożi. Kemm adrenalina u serotonina se jistimulaw ir-rilaxx ta 'cortisol, li jimmobilizza aċidi amino minn tessuti bħall-muskoli skeletriċi kbar. Dawk il-muskoli fihom ammont kbir ta 'cysteine ​​u triptofan, li, fost effetti oħra, soppressjoni-tirojde. Il-triptofan żdied, speċjalment fil-preżenza ta 'aċidi grassi liberi, x'aktarx li jiġu kkonvertiti serotonin addizzjonali, peress aċidi grassi rilaxx triptofan minn albumina, jiżdied dan jidħol fis-moħħ. Aċidi xaħmija ħielsa u inibituri akbar jnaqqsu l-effiċjenza metabolika (li jwassal għal reżistenza għall-insulina, per eżempju) u jippromwovu stat infjammatorji.

Xaħmijiet fid-demm u l-fluss jkollhom aċċess faċli għall-moħħ, u l-aċidi grassi mhux saturati ħielsa jipproduċu edima moħħ (Chan, et al., 1983, 1988). Meta edema moħħ huwa kkawżat minn tnixxija vaskulari, proteini li huma normalment esklużi jista 'jidħol. Il stimulata, eċċitati u mħaddma moħħ iskambji glutamina għal triptofan, l-aċċellerazzjoni adozzjoni tagħha mid-demm.

Meta tessut korra jew enfasizzat, l-antikorpi huma ffurmati bi tweġiba għall-komponenti mibdula ta 'dak tessut. Għalhekk, nistgħu sejħa titbenġel jew sprain kundizzjoni awtoimmuni, iżda m'hemm l-ebda testijiet kummerċjali għall imbenġla-qasba tas-sieq antikorpi. Id-disponibbiltà ta 'testijiet għal antikorpi speċifiċi jidher li huwa l-fattur essenzjali klassifikazzjoni ta' kondizzjoni awtoimmuni, bħal fil-"thyroiditis awtoimmuni." Sfortunatament, dan il-mod ta 'użu tal-lingwa huwa nested fil-kultura li hija sħiħa ta' ideat mhux realistiku ta 'kawżalità, u eluf ta 'nies jibnu karrieri tagħhom fuq it-tfittxija għall-"ġeni mutazzjoni li huma responsabbli għall-marda," u minflok il-mediċini li se tikkoreġi d-difett.

Kmieni fl-istudju tal-immunoloġija, l-enfasi kien fuq antikorpi. Anki qabel, infjammazzjoni kienu kunċettwalizzat f'termini tal-"humors," u l-ideat prescientific oħra. Hekk kif sklerożi multipla / paraliżi hysterical kienet ikklassifikata bħala marda awtoimmuni, ideat primitive dwar in-natura tas-sistema immuni, li jinteraġixxi ma 'ideat primitive dwar in-natura tal-moħħ u l-istruttura ta' ċelluli, imħallat fil-teoriji varji ta 'dak il-marda huwa.

Pjuttost milli jaraw immunoloġiku ħsara fin-nervituri bħala l-kawża tal-karatteristiċi oħra ta 'sklerożi multipla, naħseb li huwa importanti li wieħed iħares lejn uħud mill-karatteristiċi ġenerali tal-kundizzjoni, kif kuntesti li fih tinterpreta l-avvenimenti fil-nervituri.

Ġie magħruf għal żmien twil li l-inċidenza ta 'MS għandha tendenza li żżid mad-distanza mill-ekwatur. Inċidenza huwa baxx fi klimi niexef xemxija, u f'altitudni għolja. Żewġ influwenzi dieta ċari nstabu: majjal ikel, u laħam taż-żiemel.

Persuni SM ma jirregolawx temperatura tal-ġisem tagħhom tajjeb ħafna. Konduzzjoni tan-nervituri tagħhom huwa bil-mod, u fin-nies normali, konduttività hu aktar mgħaġġel f'temperaturi ogħla, iżda fin-nies ma 'MS-konduzzjoni hija aktar baxxa fit-temperatura normali ta' gradi F 98.6 minn f'temperaturi aktar baxxi. Temperatura subnormal hija wkoll assoċjata ma 'xjuħija, u mal-fwawar tal-menopawsa.

Metaboliżmu Moħħ tal-glukożju huwa baxx ħafna fi sklerożi multipla, u osservazzjonijiet tiegħi, ir-rata metabolika ġenerali hija subnormal. Madankollu, xi raġuni nies li l-hypometabolism hija kkawżata mill-leżjonijiet, aktar milli viċi versa.

Annimali li m'għandhomx l-aċidi grassi mhux saturati għandhom rata metabolika għolja u abbiltà li persuna tuża glukosju, li jikkonverti lill-CO2 aktar faċilment, għandhom reżistenza ikbar għall tossini (Harris, et al, 1990, anke Cobra velenu.. Morganroth, et al, 1989), inklużi endotoxin (Li, et al., 1990)-prevenzjoni eċċessiva vaskulari tnixxija-u għall-ħsara immunoloġiċi (Takahashi, et al., 1992), u trawma, u r-rispons newromuskolari tagħhom hija mgħaġġla filwaqt muskoli twitch fast huma inqas faċilment mħaddma (Ayre u Hulber, 1996).

Fil-nies ma 'MS, l-demm huwa aktar viskuża, u l-plejtlits għandhom tendenza li miċ flimkien aktar faċilment. Livell cortisol tagħhom huwa ogħla min-normal, u pitwitarja adrenali-kortiċi li jistimula tagħhom ormon huwa aktar diffiċli biex jeqred. Din hija kundizzjoni li jintlemaħ ukoll fl-dipressjoni u l-età qodma. Minkejja l-cortisol kronikament elevati, persuni bi SM tipikament ikollhom ipogliċemija. Huma kultant misjuba li jkollhom tad-demm baxxa tas-sodju, iponatremja, iżda dan huwa diffiċli biex jiddeterminaw meta kontenut ta 'ilma-demm huwa varjabbli. Prolactin tagħhom x'aktarx li jkunu għoljin, u dan jista 'jirriżulta minn estroġenu għolja, ta' serotonin għolja, baxxa tas-sodju, jew tat-tirojde baxxa. Ilma tax-xorb wisq jista 'jżid prolactin, u jistgħu jagħmlu ħsara lill-kompartimenti myelin-nervituri "; serotonin wisq tendenza li tikkawża xorb eċċessiv. Disturbi ta 'glucose fid-demm, sodju, u kontenut ta' ilma jistgħu jfixklu l-istruttura myelin tal-moħħ. Estroġenu Għoli tiddisturba-demm osmotically, li jagħmilha żżomm l-ilma wisq fir-rigward ta-sustanzi maħlula, u dan jirrelata għal ħafna mill-effetti estroġenu fuq; peress varjazzjonijiet osmotika sempliċi jistgħu jagħmlu ħsara lill-istrutturi myelin, jidher li dan il-mekkaniżmu għandu jkun investigat sewwa qabel ma jkun jassumi li l-avvenimenti immunoloġiċi huma primarja.

Ċelluli mast, li jippromwovu infjammazzjoni billi toħroġ sustanzi bħal istamina u serotonin (u jagħmlu vini leaky), huma aktar numerużi fil-moħħ l-isklerożi multipla milli imħuħ normali. Peress plejtlets serotonin rilaxxi tagħqid, u wkoll minħabba eċċess ta 'serotonin huwa ssuġġerit mill-karatteristiċi tant oħrajn ta' MS, antagonisti ta 'serotonin (ondansetron u ketanserin, per eżempju) ġew użati terapewtiku ta' suċċess.

Estroġenu tikkawża ċelluli mast li jirrilaxxa medjaturi infjammatorji tagħhom, u tikkawża plejtlits għal aggregat, jirrilaxxa serotonin tagħhom. Peress dominanza estroġenu huwa strettament marbut mal-preżenza ta 'leżjonijiet fil-moħħ attivi, antiestrogen terapija jidher ovvju fl-MS. Proġesteron jikkumbatti l-effetti estroġenu dwar kemm ċelluli mast u plejtlets.

Aspirina jipproteġi kontra varjetà ta 'proċessi infjammatorji, iżda huwa aktar famużi għall-inibizzjoni ta' prostaglandini. Filwaqt aspirina hija spiss użata biex ittaffi l-uġigħ fl-SM, u inibitur ta 'sintesi ta' prostaglandin, indomethacin, ġiet użata b'mod terapewtiku fl-MS, jidher xieraq li tinvestiga aktar bir-reqqa r-rwol possibbli aspirina fil-prevenzjoni jew iserrħu SM.

Id-defiċjenza ta 'proteina sempliċi għandu effetti sorprendenti ħafna. Hija tbaxxi temperatura tal-ġisem, u trażżan l-tirojde, iżda dan iżid infjammazzjoni u t-tendenza ta 'demm biex jagħqad. Peress li l-moħħ u qalb u pulmuni jeħtieġu provvista kontinwa ta 'aċidi amino essenzjali jekk iridu jkomplu funzjonament, fin-nuqqas ta' proteini fid-dieta, cortisol għandu jiġi prodott kontinwament biex timmobilizza aċidi amino mit-tessuti paletti, li huma prinċipalment l-muskoli skeletriċi. Dawn il-muskoli jkollhom konċentrazzjoni għolja ta 'triptofan u cysteine, li jrażżnu l-tirojde. Cysteine ​​huwa excitoxic, u triptofan hija l-prekursur għall serotonin. Preżumibbilment, il-preżenza tagħhom fi, u l-istress indotta rilaxx minn, il-muskoli huwa wieħed mill-mekkaniżmi li jnaqqsu l-attività metabolika matul ċerti tipi ta 'stress.

Meta annimali tqal huma mċaħħda ta 'proteina, l-annimali tat-twelid għandhom livelli għolja b'mod anormali ta' serotonin, u l-enzimi responsabbli għall-dak l-eċċess tendenza li jżommu l-eċċess ta 'serotonin anke meta jkunu mkabbra u jkollhom proteini adegwata. Dan huwa analogu għall-effett ta 'estroġenu żejjed kmieni fil-ħajja, li joħloq tendenza li tiżviluppa sider jew kanċer tal-prostata fi stat adult. Ikun interessanti li jistudja l-esperjenza tat-tqala, eż, it-tul tat-tqala u twelid piż, tal-persuni li aktar tard jiżviluppaw SM.

Għalkemm in-nies fil-pajjiżi tat-Tramuntana ma jkunux normalment proteini jsibux, dawn għandhom tendenza li jiksbu parti kbira ta 'proteina tagħhom mill-laħmijiet muskoli. Fil-kulturi tradizzjonali, kull parti ta 'l-annimali l-ikel kienu jittiekel-tiġieġ saqajn, irjus, u għenuq, widnejn annimali u l-għajnejn, eċċ-u hekk il-bilanċ aċidu amminiku kien favorevoli għaż-żamma rata metabolika għolja u l-prevenzjoni stress.

L-osservazzjoni li sklerożi multipla hija assoċjata mal-konsum tal-majjal u laħam taż-żiemel, iżda mhux ċanga, tal-ħaruf, jew mogħoż, huwa interessanti ħafna, peress li x-xaħam dawk l-annimali huwa essenzjalment bħal xaħmijiet tal-materjali tal-pjanti li jieklu, li jfisser li hija estremament għolja fl-aċidi linolejiku u linolenic. Il-kirxa tal-baqar, nagħaġ, mogħoż u fih batterji li jaqilbu l-xaħmijiet polyunsaturated fis xaħmijiet saturati aktar. Xaħmijiet saturati jimpedixxix l-enzimi li l-pazjenti proteina jiddiġerixxu, u SM ġew irrapportati li għandhom diġestjoni ħażina ta 'laħam (Gupta, et al., 1977).

Il-xaħmijiet polyunsaturated huma fihom infushom tossiċi għall mitochondria, u jrażżnu ossidazzjoni glukosju, u jinibixxu l-funzjoni tat-tirojde, bl-effett soppressiva istess fuq il-ħila li jossidaw glukosju, iżda huma wkoll daru, enzymically, fil-prostaglandini, u mhux enzymically, minn peroxidation lipidi spontanju, fil-isoprostanes tossiċi. Il isoprostanes, u xi wħud mill-prostaglandini, huma għoljin fit-tessuti tal-moħħ u oħrajn ta 'nies ma' Stati Membri.

Peroxidation lipidi hija għolja ħafna fl-isklerożi multipla. Nitric oxide (li sinteżi huwa promoss mill-estroġenu fl-aktar partijiet tal-moħħ) huwa radikali ħielsa li jattiva peroxidation.

Peroxidation lipidi selettiv jeqred, naturalment, il-xaħmijiet polyunsaturated instabbli. Fil aterosklerożi, l-plakek arterja fihom ftit xaħam mhux saturat. Dan huwa minħabba li huma peroxidized tant malajr, iżda proporzjon għoli ta 'saturati li xaħmijiet saturati ġie użat biex jargumentaw li l-żjut polyunsaturated huma "protettiv tal-qalb." Argumenti simili huma spiss magħmula fl-Istati Membri, għalkemm xi studji ma jsostnux l-idea li hemm nuqqas ta 'xi waħda mill-xaħmijiet saturati. Peress peroxidation lipidi hija għolja ħafna, ikun raġonevoli li wieħed jassumi li kien hemm abbundanza ta 'xaħmijiet polyunsaturated qed peroxidized permezz ta' reazzjonijiet ma 'katalisti bħal tal-ħadid (SM Levine, 1997) u ossidu nitriku u peroxynitrile.

Nemmen li aspett importanti ta 'l-intolleranza għall-sħana hekk spiss rrappurtati persuni SM jista' jkun it-tendenza ta ipertermija relattiva li jiġu liberati ammonti akbar ta 'aċidi grassi liberi fil-fluss tad-demm. Nisa, minħabba l-effetti estroġenu, ġeneralment għandhom livelli ferm ogħla ta 'aċidi grassi liberi fid-demm mill-irġiel do. Estroġenu iżid ir-rilaxx ta 'aċidi grassi liberi minn xaħam maħżuna, u l-xaħmijiet saturati synergize ma' kemm estroġenu u prolactin, tiżdied l-effetti tagħhom.

Regolament tat-temperatura apparentement jinvolvi xi ċelloli tan-nervituri li temperatura sens b'mod preċiż ħafna, u jibdlu l-attività tagħhom kif xieraq. Ilma għandu kapaċità sħana tassew għoli, li jfisser li hija tieħu ammont relattivament kbir ta 'sħana għall-bidla tat-temperatura tagħha. Il-"sħana jisparixxu" qed jiġi kkunsmat minn bidliet strutturali fl-ilma. Proteini jkollhom l-istess tip ta 'kumplessità strutturali bħala ilma, u flimkien ikunu jistgħu jagħmlu transducers temperatura effettivi, "termometri." (Sustanzi oħra għandhom tendenza li jgħaddu minn bidliet strutturali kbar biss kif jdub jew vaporizzazzjoni. Il-famuża "kristalli likwidi" għandhom distinta ftit fażijiet strutturali, iżda ċitoplasma huwa bħal kristall likwidu ħafna sottili.) Il-"ċelloli termostat" huma attwalment jirrispondu għal grad ta 'struttura interna, ma t-temperatura fl-astratt. Allura affarijiet li jbiddlu l-istruttura interna tagħhom se timmodifika t-temperatura tagħhom "set-punt."

Estroġenu Żieda jikkawża annimali biex ibaxxu t-temperatura tagħha, u probabbilment ma dan billi jiżdied il-"temperatura strutturali" taċ-ċelloli termostat, "tidwib" istruttura interna tagħhom. Proġesteron tikkawża l-annimali biex tiżdied it-temperatura tiegħu, u apparentement ma dan billi jiżdied l-istruttura / tonqos it-temperatura strutturali taċ-ċelloli termostat. Jekk inti tpoġġi silġ fil-termostat, il-kamra gets sħun.

Istruttura interna A ċelluli huwa ekwivalenti għal-rieda tagħha li taħdem. Għeja jirrappreżenta ftit "imdewweb" l-istat taċ-ċellola, li fiha struttura jidher li jkunu ġew ikkunsmati flimkien mal-riservi ta 'enerġija kimika. Esperimenti wrew li dan l-effett kienu ċari ħafna, iżda dawn kienu injorati għax ma tajbin idea sterjotipati tan-nies taċ-ċellola. B'termometru sensittivi ħafna, huwa possibbli li jitkejjel il-sħana prodotta permezz ta 'nerv meta stimulata. Li mhux sorprendenti. Imma huwa sorprendenti li, meta l-nerv qed tirkupra mill-istimulazzjoni, li jassorbi s-sħana mill-ambjent tagħha, tnaqqis it-temperatura lokalment. Li anke miksura konċepiment xi nies taċ-"entropy," iżda jista 'faċilment jiġi muri li jibdel il-forma ta' xi materjali bidliet tas-sħana kapaċità tagħhom, bħal meta lastiku huwa miġbud (jiġrilha sħun), jew kuntratti (jiġrilha jkessaħ).

Il excitants, estroġenu u cortisol, bil-mod il-konduzzjoni ta 'nervituri, minħabba li jikkawżaw l-istruttura interna tagħha li tkun moħlija. Dawn joħolqu "pre-mħaddma" l-istat fiċ-ċellola.

Esperimenti bil-qlub tal-fenek, Szent-Gyorgyi wera li l-estroġenu naqas rieda tal-qalb biex jaħdmu, u li proġesteron żieda hija lesta taħdem, u hu qal li għamel dan billi "istruttura tal-bini." Huwa ppreċiżat li, għal droga partikolari jew stimolu ieħor, ċelluli jkollhom rispons karatteristika, issir jew aktar attivat jew aktar impeduta, imma huwa wera li, barra l-konċentrazzjoni normali jew firxa intensità tal-istimolu, rispons ċellola hija spiss maqluba.

Jekk dan hija s-sitwazzjoni fil-nervituri fl-MS, hija tispjega l-imġieba stramba, fejn tisħin-nerv inaqqas funzjoni tiegħu. L-implikazzjoni hija li l-istruttura interna (u l-enerġija) trid tiġi restawrata għal-nervituri. Esperimenti li jien deskritti fil-bulettini ta 'qabel, tiżdied sodju, ATP, dijossidu tal-karbonju, u progesterone, u tiżdied il-proporzjon ta' manjesju għall-kalċju, instabu li tiżdied l-enerġija ċellulari u l-istruttura. L-ormon tat-tirojde hija finalment responsabbli għaż-żamma ta 'enerġija ċelloli' u l-istruttura, u r-rispons, imma jekk tiżdied f'daqqa waħda mingħajr ma jippermettu l-fatturi l-oħra biex jaġġustaw, se jgħolli t-temperatura wisq f'daqqa. M'hemmx għalfejn jieħdu żmien twil, iżda l-fatturi kollha għandhom ikunu preżenti fl-istess ħin.

, Serotonin melatonin, oestrogen, u xaħmijiet polyunsaturated kollha tendenza li temperatura tal-ġisem aktar baxxi. Peress estroġenu u l-xaħmijiet saturati huma excitants ċellulari, it-tnaqqis attwali fit-temperatura tal-ġisem tgħin billi tpatti għall-effetti stimulant tagħhom.

Kemm dawl qawwi u altitudni għolja għandhom tendenza li jnaqqsu l-effetti ta 'serotonin fuq. Il-dijossidu tal-karbonju tessut miżmuma f'altitudni għolja jnaqqas l-inċidenza ta 'ħafna mard, u sklerożi multipla jistgħu jiġu affettwati bħala mard tal-qalb u l-kanċer huma. Huwa magħruf li dijossidu karboniku huwa involut fir-regolament myelin ta 'kontenut tagħha ilma stess. Iperventilazzjoni, billi jikkawżaw telf ta 'dijossidu tal-karbonju, jerħi kemm istamina u ta' serotonin, li aktar demm viskuża, filwaqt li jagħmlu vini aktar permeabbli, u li jikkawżawhom li constrict.

Jekk in-nies ma 'Stati Membri żviluppaw dan permezz tal-interazzjonijiet ta' estroġenu eċċessiv, ta 'serotonin, xaħmijiet saturati, ħadid, u ilma, u tat-tirojde defiċjenti, u pregnenolone defiċjenti prodotti fiċ-ċelloli myelin li jiffurmaw (oligodendrocytes), hemm ħafna affarijiet li jista' jsir biex tieqaf il-progress tagħha, u possibilment biex ireġġgħu lura lilha.

Peress li żieda f'daqqa fit-temperatura se jitfa 'ammonti miżjuda ta' l-xaħmijiet pro-infjammatorji, l-affarijiet għandu jinbidel gradwalment. Melħ Żieda hija thermogenic, iżda manjesju akbar huwa protettivi kontra ipertermja, manjesju hekk miżjud (banjijiet Epsom melħ, per eżempju, kafè, frott, xi ħxejjex u laħmijiet) ikun utli. Manjesju huwa malajr mitluf minn ċelloli fil ipotirojdiżmu. Zokkor, meta jkun akkumpanjat minn xaħmijiet u minerali, bħal fil-ħalib, hija meħtieġa biex cortisol aktar baxxi, u biex isostnu l-attività tat-tirojde. Proteini bbilanċjati, bħall-ġobon, patata, bajd, u ċ-ċanga jew tal-ħaruf-brodu-(għall-kontenut ġelatina u minerali b'mod partikolari) se jipprevjenu l-eċċess triptofan li trażżan l-tirojde u huwa potenzjalment tossin nerv. Xaħmijiet saturati, użati regolarment, jitnaqqsu l-effetti immedjati antimetabolic tossiċi tal-xaħmijiet saturati maħżuna, iżda tieħu żmien twil biex tbiddel il-bilanċ ta 'xaħmijiet maħżuna.

Peress aspirina jbaxxi t-temperatura, hija anti-infjammatorji, f'xi sitwazzjonijiet antiestrogenic, u huwa b'saħħtu antiossidant, huwa probabbli li se jittaffew is-sintomi u jipprevjenu progressjoni ta 'SM, kif jagħmel fir mard deġenerattiv oħra. Peress aggregazzjoni tal-plejtlets huwa probabbli li jkunu involuti fil-jiffoka ta 'infjammazzjoni, aspirina jista' jgħin biex jipprevjeni l-formazzjoni ta 'oqsma ġodda ta' ħsara.

While the glucocorticoids are useful for their antiinflammatory actions, cortisol is known to promote the killing of brain cells by excitotoxicity. Since estrogen decreases GABA, and both estrogen and serotonin activate the excitatory amino acid transmitters, the addition of synthetic glucocorticoids to the pre-existing cortisol excess is likely to damage parts of the brain in addition to the inflamed areas.

The excess cortisol of depression, old age, and hyperestrogenism often comes down with use of a thyroid supplement, but pregnenolone has a very direct action (in opposition to serotonin) that can quiet the pituitary, reducing ACTH and cortisol. Progesterone has some similar effects, and is protective against excess cortisol, and is a major factor in nerve and brain restoration. Thyroid, progesterone, and pregnenolone are all involved in the formation of new myelin, and in the prevention of the edema that damages it.

Since thyroid and progesterone decrease the formation of estrogen in inflamed tissue, while cortisol stimulates its formation, it would seem wise to use thyroid and progesterone for their immediate antiinflammatory effects, which include the inhibition of NO formation (Drew and Chavez, 2000), and their lack of the excitotoxic, estrogen-stimulating effects of the glucocorticoids. While the glucocorticoids are catabolic and liberate cysteine and tryptophan from muscles, thyroid and progesterone are not catabolic, and protect against the toxic consequences of those amino acids.

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Arch Latinoam Nutr 1980 Dec;30(4):580-9. [Prethrombosis in child malnutrition]. Jimenez R, Jimenez E, Mora LA, Vargas W, Atmetlla F, Carrillo JM

Stroke 1991 Nov;22(11):1448-51. Platelet secretory products may contribute to neuronal injury. Joseph R, Tsering C, Grunfeld S, Welch KM “The view that certain endogenous substances, such as glutamate, may also contribute to neuronal injury is now reasonably well established. Blood platelets are known to contain and secrete a number of substances that have been associated with neuronal dysfunction. Therefore, we hypothesize that a high concentration (approximately several thousand-fold higher than in plasma, in our estimation) of locally released platelet secretory products derived from the causative thrombus may contribute to neuronal injury and promote reactive gliosis.” “We further observed that serotonin, a major platelet product, has neurotoxic properties.”

Zh Nevropatol Psikhiatr Im SS Korsakova 1985;85(2):198-206. [Role of disorders of the hemostatic system in the pathogenesis of multiple sclerosis and ways of correcting them]. [Article in Russian] Karlov VA, Makarov VA, Savina EB, Seleznev AN, Savin AA The changes in the hemostatic system were studied in 77 patients with different patterns of disseminated sclerosis (DS). The studies demonstrated activation of both vasculothrombocytic and coagulation components of hemostasis as well as of fibrinolytic blood properties. The latent course of the disseminated intravascular coagulation was revealed in 20.7% of cases. The role of hemostatic disorders in the pathogenetic mechanisms of DS is discussed. The patients with DS received pathogenetic treatment including drugs eliminating hemostatic disorders, which was beneficial for most patients.

Zh Nevropatol Psikhiatr Im SS Korsakova 1990;90(11):47-50. [Changes in rheological properties of blood in multiple sclerosis and their correction]. [Article in Russian] Karlov VA, Savin AA, Smertina LP, Redchits EG, Seleznev AN, Svetailo LI, Margosiuk NV, Stulin ID As many as 45 patients with multiple sclerosis were examined for rheological blood properties. As compared to controls, the group under examination manifested the rise of plasma viscosity, acceleration of red blood cell aggregation. 26.2% of patients demonstrated an appreciable increase of blood viscosity. It is assumed that these changes contribute to the deterioration of microcirculation and aggravate the demyelinating process. Correction of the rheological properties of the blood by plasmapheresis coupled with other methods of pathogenetic therapy turned out effective.

Brain Res 1997 Jun 20;760(1-2):298-303 Iron deposits in multiple sclerosis and Alzheimer's disease brains. LeVine SM “In summary, the localization of iron deposition in MS and AD brains indicates potential sites where iron could promote oxidative damage in these disease states.”

Circ Shock 1990 Jun;31(2):159-70. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability. Li EJ, Cook JA, Spicer KM, Wise WC, Rokach J, Halushka PV.

FEBS Lett 1978 Nov 1;95(1):181-4. Selective inactivation of the NADH-ubiquinone segment of the respiratory chain of submitochondrial particles by endogenous free fatty acids during hyperthermia. Ludwig P, Bartels M, Schewe T, Rapoport S.

J Pain Symptom Manage 2000 Nov;20(5):388-91. Ondansetron in multiple sclerosis. Macleod AD. “Two young women with chronic nausea and vertigo caused by multiple sclerosis responded to the introduction and maintenance of the 5HT3 receptor antagonist, ondansetron.”

Am J Phys Med Rehabil 1994 Jul-Aug;73(4):283-5. Intracranial venous thrombosis in a patient with multiple sclerosis. A case report and review of contraceptive alternatives in patients with disabilities. Malanga GA, Gangemi E.

Folia Biol (Praha) 1999;45(4):133-41. Essential fatty acids and related molecular and cellular mechanisms in multiple sclerosis: new looks at old concepts. Mayer M.

J Clin Endocrinol Metab 1994 Sep;79(3):848-53. Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function. Michelson D, Stone L, Galliven E, Magiakou MA, Chrousos GP, Sternberg EM, Gold PW “Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression.” “Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis.”

Exp Neurol 1977 Oct;57(1):142-57. Tryptophan availability: relation to elevated brain serotonin in developmentally protein-malnourished rats. Miller M, Leahy JP, Stern WC, Morgane PJ, Resnick O.

Am J Physiol 1989 Oct;257(4 Pt 2):H1192-9. Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet. Morganroth ML, Schoeneich SO, Till GO, Pickett W, Ward PA.

Eur J Haematol 2000 Jul;65(1):82-3. More on the relationship between cystic fibrosis and venous thrombosis. Mori PG, Acquila M, Bicocchi MP, Bottini F, Romano L. Letter

Acta Neurol Scand 1982 Ottubru; 66 (4) :497-504, l-aggregazzjoni tal-plejtlets u sklerożi multipla. Neu IS, Prosiegel M, Pfaffenrath kejl V ta 'aggregazzjoni tal-plejtlets fid-demm twettqu fi 30 pazjent li jbatu minn sklerożi multipla (MS) u 15 individwi b'saħħithom. Meta mqabbel mal-grupp ta 'kontroll, il-pazjenti b'MS urew żieda kemm fil spontanju u indotta (ADP u serotonina) aggregazzjoni tal-plejtlets. Is-sinifikat pathogenetic possibbli ta 'dawn ir-riżultati hija diskussa.

Newroloġija 1975 Awissu; 25 (8) :713-6. Schwann ċelluli u riġenerati myelin periferali fi sklerożi multipla: studju ultrastructural. Ogata J, Feigin Tessut I ta 'plakka sklerożi multipla fl-conjunctivum brachium tal-pons magħrufa li jkun fihom myelin periferali bi studji mikroskopiċi dawl tneħħew mill-blokk paraffin u pproċessata għall-istudji mikroskopiċi elettroni. Iċ-ċelloli relatati mal-myelin periferali fil-pussess tal-karatteristiċi ultrastructural ta 'ċelluli Schwann, mal-membrani kantina u fibri collagen assoċjati. Le kontinwità deher mal-periferali fil-tessuti nervużi ċentrali permezz maturazzjoni selettiva ta 'ċelluli Multipotenzjali reticular primittiv, fenomenu konsistenti mal-fehma li ċ-ċelluli Schwann huma mesenkimali fil-karattru.

Tohoku J Exp Med 1999 Dec;189(4):259-65. Elevated plasma level of plasminogen activator inhibitor-1 (PAI-1) in patients with relapsing-remitting multiple sclerosis. Onodera H, Nakashima I, Fujihara K, Nagata T, Itoyama Y “Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and one of the earliest changes in inflammatory focus involves the activation of vascular endothelial cells.” “The level of plasma PAI-1 was significantly higher in active MS cases when compared to stable MS and controls.” “These results suggested that PAI-1 plasma levels are associated with MS disease activity and is a good marker for MS relapse.”

J Mol Med 1997 Mar;75(3):174-86. The role of nitric oxide in multiple sclerosis. Parkinson JF, Mitrovic B, Merrill JE “Elevated nitric oxide bio-synthesis has been associated with nonspecific immune-mediated cellular cytotoxicity and the pathogenesis of chronic, inflammatory autoimmune diseases including rheumatoid arthritis, insulin-dependent diabetes, inflammatory bowel disease, and multiple sclerosis.”

Fed Proc 1987 Jan;46(1):91-6. Role of the clotting system in the pathogenesis of neuroimmunologic disease. Paterson PY, Koh CS, Kwaan HC “Our studies of the clotting system and ensuing fibrinolysis implicate coagulation and cleavage of fibrin within or on the luminal surface of the cerebrovasculature as events initiating the inflammation characterizing EAE.” “We postulate that the critical event precipitating EAE is binding of circulating MBP-reactive immune effector cells to MBP immunodeterminants on the surface of cerebrovascular endothelial cells. Coagulation and ensuing fibrinolysis occur at sites of binding of effector cells to cerebrovascular endothelium. Release of biologically active peptides cleaved from fibrin open the BBB, thereby setting the stage for the cascade of inflammatory events culminating in clinical manifestations of EAE.”

Neurotoxicology 1998 Aug-Oct;19 (4-5):599-603. In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines. Parsons RB, Waring RH, Ramsden DB, Williams AC “Cysteine (CYS) is a non-essential amino acid which elicits excitotoxic properties via the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor.. CYS levels are known to be elevated in association with neurological disease such as Alzheimers Disease (AD) and Parkinsons Disease (PD).” “These results show that toxic responses are cell-type specific for CYS and its metabolites and this may be reflected in the patterns of neurodegeneration observed in such diseases as AD and PD.”

WMJ 1983 Mar-April; 55 (2) :146-50. [Effett ta 'eċċess triptofan dieta fuq il-kompożizzjoni aċidu amminiku ta' collagen ġilda u fuq stadju inizjali tal bijosintesi proteina fil-fwied tal-far]. Pechenova TN, Sushkova VV, Solodova VE, Gulyi Proteina MF defiċjenza u tagħbija tryptophan kontra ċomb isfond tagħha għall-sinteżi kollaġen aċidu solubbli fil-ġilda tal-far. The amino acid composition of the collagen differs from the norm. This is accompanied by changes in the free amino acid pool of blood serum and liver, under tryptophane load the free amino acids pool of the liver increasing twice as high. At the same time protein deficiency increases and tryptophane load decreases the level of tRNA amino acylation with tryptophane in the animal liver. Thus, protein deficiency and tryptophane load against its background cause deep changes in the protein biosynthesis.

Fed Proc 1987 Jan;46(1):91-6. Role of the clotting system in the pathogenesis of neuroimmunologic disease. Paterson PY, Koh CS, Kwaan HC “Our studies of the clotting system and ensuing fibrinolysis implicate coagulation and cleavage of fibrin within or on the luminal surface of the cerebrovasculature as events initiating the inflammation characterizing EAE.” “We postulate that the critical event precipitating EAE is binding of circulating MBP-reactive immune effector cells to MBP immunodeterminants on the surface of cerebrovascular endothelial cells. Coagulation and ensuing fibrinolysis occur at sites of binding of effector cells to cerebrovascular endothelium. Release of biologically active peptides cleaved from fibrin open the BBB, thereby setting the stage for the cascade of inflammatory events culminating in clinical manifestations of EAE.”

Dun Esp Fisiol 1983 Mar; 39 (1) :39-44. Intralipid u ħielsa plażmatika triptofan in vitro. Pena JM, Aulesa C, Vinas O, Bosch J, Farriol M, Schwartz S "Fi sforz biex tinvestiga l-irwol tal-Intralipid emulsjoni lipídic fl-iżvilupp ta 'enċefalopatija metabolika f'pazjent juri livelli għolja ta' tryptophan ħieles, ir-relazzjoni bejn lipídic emulsjoni u triptofan ħieles kienet eżaminata esperimenti in vitro. Iż-żieda ta intralipid għas-serum normali tipproduċi żieda immedjata fil mhux esterifikati aċidi grassi u żieda parallela fl triptofan ħieles. Barra minn hekk, meta serum ma intralipid hu inkubat b '37 gradi C, il-lipases rilaxx ġodda mhux esterifikati aċidi grassi u ż-żidiet ta' tryptophan ħieles proporzjonalment. "" Huwa konkluż li intralipid jikkawża żieda fil-livelli ta 'tryptophan ħieles. Huwa magħruf li in vivo triptofan ħieles jimmodula 5-idrossitriptamina sinteżi u għalhekk jista 'jitqies bħala aġent kawżali possibbli għall enċefalopatija. "

Med Hypotheses 1980 May;6(5):545-557. Fatty acids, fibrinogen and blood flow: a general mechanism for hyperfibrinogenemia and its pathologic consequences. Pickart LR, Thaler MM Plasma fibrinogen is elevated in various stressful states and conditions in which active mobilization of free fatty acids (FFA) occurs. Reduction of plasma FFA by an assortment of hypolipidemic drugs is consistently followed by a decrease in the accompanying hyperfibrinogenemia. A direct link between FFA and fibrinogen has been demonstrated in animals, and in experiments employing incubated liver slices. Based on these clinical and experimental observations, we postulate that hepatic fibrinogen synthesis is stimulated by FFA. Since fibrinogen is a major determinant of whole blood viscosity, erythrocyte aggregation, and sludging of red cells in terminal and pre-terminal blood vessels, we propose that microcirculatory blood flow may be impaired in the presence of chronically elevated plasma FFA levls. Consequently, hypolipidemic drugs may be effective in prevention of circulatory complications associated with FFA-induced hyperfibrinogenemia.

Neurologia 1996 Aug-Sep;11(7):272. [Exacerbation of spasticity induced by serotonin reuptake inhibitors. Letter]. del Real MA, Hernandez A, Vaamonde J, Gudin M

J Neurol Neurosurg Psychiatry 1997 Mar;62(3):282-4. Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor. Rice GP, Lesaux J, Vandervoort P, Macewan L, Ebers GC. “It has been previously shown that ondansetron, a 5-HT3 antagonist, can ameliorate vertigo in patients with acute brainstem disorders. A coincidental benefit was the improvement of cerebellar tremor in some patients with both vertigo and tremor. To further evaluate this effect, a placebo controlled, double blind, crossover study was conducted of a single dose of intravenous ondansetron in 20 patients with cerebellar tremor caused by multiple sclerosis, cerebellar degeneration, or drug toxicity.” “Thirteen of 19 patients were deemed to have improved spiral copying after treatment with ondansetron when compared with baseline performance.”

Neurologia 1993 Oct;8(8):252-5. [Retinal periphlebitis in multiple sclerosis. A prospective study]. Rio J, Colin A, Salvador F, Tintore M, Viguera ML, Montalban J, Codina A “In three cases (12.5%) retinal periphlebitis was observed.” “Given the absence of myelin in the retina, the presence of retinal periphlebitis suggests the existence of a vascular mechanism in the pathogenesis of multiple sclerosis.”

Int J Neurosci 1995 Dec;83(3-4):187-98. Premenstrual exacerbation of symptoms in multiple sclerosis is attenuated by treatment with weak electromagnetic fields. Sandyk R. “The present report concerns two women with chronic progressive stage MS who experienced, coincident with increasing functional disability, regular worsening of their symptoms beginning about a week before menstruation and abating with the onset of menstruation. These symptoms resolved two months after the initiation of treatment with EMFs.”

J Physiol Biochem 1998 Dec;54(4):229-37. The role of nitric oxide in the pathogenesis of multiple sclerosis. Santiago E, Perez-Mediavilla LA, Lopez-Moratalla N “The inducible NOS (iNOS) is associated with the development of a number of autoimmune diseases.” “Induction of the enzyme is effected by proinflammatory cytokines, immunomodulating peptides, and even beta-endorphin through a mechanism involving an increase in cAMP. An excessive production of NO has been implicated in the severe lesions observed in multiple sclerosis (MS).”

J Neurol 1980 Jan;222(3):177-82. Cerebrospinal fluid lipids in demyelinating disease. II. Linoleic acid as an index of impaired blood-CSF barrier. Seidel D, Heipertz R, Weisner B “The linoleic acid content of control CSF (1.6 +/- 0.8 nMol/ml) is considerably lower than the corresponding serum value (2.5–4.1 muMol/ml). Although CSF from MS patients contains a significantly higher linoleic acid concentration than controls the close correlation between CSF linoleic acid and CSF albumin is maintained. The high CSF concentration of cholesterol esters rich in linoleic acid, which are abundant in serum but represent only traces in CNS lipids, points towards an impaired BBB function as the cause of CSF linoleic increase. We are able to show that both albumin and linoleic acid are suitable as “serum markers….”

J Neurol Sci 1987 Feb;77(2-3):147-52. Chronic periphlebitis retinae in multiple sclerosis. A histopathological study. Shaw PJ, Smith NM, Ince PG, Bates D Retinal periphlebitis in multiple sclerosis is of particular interest in relation to our understanding of the pathogenesis of the demyelinating central nervous system plaques. Previous studies have largely been clinical, and there is little detailed histopathological information relating to this condition. We present the first detailed report in the neurological literature on the histological findings in chronic periphlebitis retinae associated with multiple sclerosis. The most significant abnormalities of the affected retinal veins were the presence of thick laminated collagen in the wall, associated with a scanty infiltration of plasma cells.

Am Heart J 2000 Aug;140(2):212-8. Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease. Shechter M, Merz CN, Rude RK, Paul Labrador MJ, Meisel SR, Shah PK, Kaul S.

J Neurochem 1996 Mar;66(3):1157-66. Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway. Skaper SD, Facci L, Romanello S, Leon A. “Neurotoxicity required a prolonged period (12 h) of mast cell incubation, and appeared to depend largely on elaboration of the free radical nitric oxide by astrocytes.” “Myelin basic protein and 17 beta-estradiol had a synergistic action on the induction of mast cell-associated neuronal injury.” “Further, palmitoylethanolamide, which has been reported to reduce mast cell activation by a local autacoid mechanism, decreased neuron loss resulting from mast cell stimulation in the mixed cultures but not that caused by direct cytokine induction of astrocytic nitric oxide synthase.” “These results support the notion that brain mast cells could participate in the pathophysiology of chronic neurodegenerative and inflammatory diseases of the nervous system, and suggest that down-modulation of mast cell activation in such conditions could be of therapeutic benefit.”

International Journal of Microcirculation–Clinical and Experimental, 1996, Vol 16, Iss 5, pp 266-270. Hyperventilation enhances transcapillary diffusion of sodium fluorescein. J Steurer, D Schiesser, C Stey, W Vetter, MV Elzi, JP Barras, UK Franzeck. “Voluntary hyperventilation (HV) provokes hemoconcentration due to a loss of fluid from the intravascular space.” “The exact, mechanism of enhanced transcapillary diffusion of Na fluorescein is not known, The distinct increase in FLI without a significant change in microvascular skin flux suggests an HV-induced increase in capillary pressure or an enhancement in capillary permeability for water and small solutes.”

Kidney Int 1992 May;41(5):1245-53. Essential fatty acid deficiency normalizes function and histology in rat nephrotoxic nephritis. Takahashi K, Kato T, Schreiner GF, Ebert J, Badr KF.

Arthritis Rheum 1981 Aug;24 (8):1054-6. Sex steroid hormones and systemic lupus erythematosus. Talal N.

Clin Rheum Dis 1982 Apr;8(1):23-8. Sex hormones and modulation of immune response in SLE. Talal N.

Ann NY Acad Sci 1986;475:320-8. Hormonal approaches to immunotherapy of autoimmune disease. Talal N, Ahmed SA, Dauphinee M.

Ann Nucl Med 1998 Apr;12(2):89-94. Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S “The severity of cerebral hypometabolism was also related to the number of relapses.” “Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information.”

Fed Proc 1987 Jan;46(1):118-26. Pathway to carrageenan-induced inflammation in the hind limb of the rat. Vinegar R, Truax JF, Selph JL, Johnston PR, Venable AL, McKenzie KK “Antiserotonin agents inhibited the hypoalgesia and part of the edema. These findings and histological observations suggested that dermal mast cells were injured by C. The hyperalgesia and part of the edema were sensitive to arachidonate cyclooxygenase inhibitors (AACOIs). It is speculated that injured mast cells metabolize arachidonic acid and reactive intermediates, not prostaglandins, mediate the NPIR hyperalgesia and part of the edema.” “Arachidonic acid metabolism by neutrophils is speculated to produce the mediators of phagocytic inflammatory (PI) edema and hyperalgesia.”