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Scléaróis iolrach, próitéin, saillte, agus progesterone

ag Ray Móin PhD ar 13/02/10 ag 13:39

ag Raymond Móin, PhD

Táimid faoi réir i gcónaí chun ualaí antaigineach. Tá an cheist tábhachtach a dhéanamh lenár gcumas chun teorainn a chur le freagra inflammatory ar na hualaí.

I MS [scléaróis iolrach], is léir go bhfuil an próiseas inflammatory féin millteach, agus go bhfuil estrogen ina fhachtóir mór predisposing. Idirghníomhú aigéid shailleacha neamhsháithithe, agus éagothroime aiste bia de aimínaigéid go dlúth le hyperestrogenism agus hypothyroidism a thabhairt ar aird na galair autoimmune degenerative.

Is Laghdú ar an idirghabhálaithe de athlasadh níos fearr ná cur le gníomhaire amháin antiinflammatory mar cortisol. Cé drugaí immunosuppressive, lena n-áirítear an "aigéid sailleacha riachtanach," ná a mhaolú comharthaí inflammatory go sealadach, tá siad cur dócha leis an paiteolaíochta bunúsacha.

Daoine le MS Tá méadú tagtha ar hainsealach tháirgeadh cortisol. Cruthaíonn sé seo saobhadh de chomhshamhlú próitéine, cosúil le próitéin easnamh cothaitheach. Serotonin iomarcach agus estrogen a chur faoi deara léiriú réasúnta neamhrialaithe cortisol. Is féidir le fáinne fí de idirghabhálaithe inflammatory agus éagothroime aimínaigéad mar thoradh air.

Storm, Lupus, tá migraine, sos míostraithe, diaibéiteas, agus ag dul in aois gnéithe éagsúla meitibileach tábhachtach i bpáirt le MS.

Tá teiripí Coitianta illogical, agus is dócha a chur faoi deara dul chun cinn galar.

Ard-chaighdeán próitéin, thyroid, pregnenolone agus progesterone claonadh a cheartú an paiteolaíochta bunúsacha. Is iad seo antiinflammatory, ach nach bhfuil siad immunosuppressive nó catabolic.

Airde ard agus aeráide Mostly a bhaineann le minicíocht íseal de MS.

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Scléaróis iolrach (MS), cosúil le galair autoimmune eile difear, mná níos minice ná fir (thart ar 2-1), tá a theacht i rith na bliana atáirgthe (go háirithe tar éis 30 bliain d'aois, nuair a bhíonn estrogen an-ard), go bhfuil níos measa go minic premenstrually , agus tá mhaolú uaireanta le toirchis (Drew agus Chavez, 2000), nuair a bhíonn progesterone an-ard. Mná le cóimheas ard estrogen le progesterone a shuífear go bhfuil an loit inchinn is gníomhaí (Bansil, et al., 1999). Chuid is mó de na idirghabhálaithe de athlasadh go bhfuil baint acu MS-crann cealla, ocsaíd nítreach (NO), serotonin, prolactin, peroxidation lipid, aigéid sailleacha saor in aisce, agus prostaglandins isoprostanes, agus an cytokines éagsúla (IL, TNF)-atá bainteach go dlúth le éastraigin gníomhartha, agus in ainmhithe, is féidir galair autoimmune a thabhairt maidir le cóireáil le estrogen (Ahmed agus Talal).

Tá an cumann láidir MS le estrogen thoradh ar illogical, ach i gcrích tóir agus dea-fhógartha leighis go bhfuil estrogen cosanta i gcoinne MS, agus cuid acu a éilítear go bhfuil estrogen éifeachtaí teiripeacha tairbheach. Tá sé seo ar bhealach aisteach smaointeoireachta a choibhéis i an smaoineamh sin, ós rud é go bhfuil mná i bhfad níos mó seans ann ná fir a fhorbairt galar Alzheimer, is estrogen cosanta i gcoinne é; nó go, toisc go bhfuil mná cnámha níos leochaileach ná mar a dhéanann fir, agus a n-caillteanas cnámh go comhleanúnach tharlaíonn le linn na hamanna a nochtadh is mó a estrogen, cosc ​​estrogen oistéapóróis.

Sa timpeallacht seo leighis, cumainn dlúth idir estrogen agus galair degenerative a admháil, ach tá siad tugtha ar mhalairt brí le tuiscint coiteann ag rá go bhfuil an cumann toisc nach bhfuil go leor estrogen. Dó an sorn tú de bharr nach bhfuil sé te go leor.

Mar a bheadh ​​Dave Barry rá, nach bhfuil mé ag déanamh seo suas. Le déanaí tá earraí maith le fios poiblíocht a chosnaíonn estrogen ar an inchinn (fiú amháin in aghaidh stróc!) Toisc go méadaíonn sé serotonin agus NÍL [ocsaíd nítreach]. Tá rud éigin nach mór taitneamhach esthetically nuair earráidí móra an oiread sin atá dírithe isteach airteagal amháin. Ocsaíd nitric agus serotonin bhfuil an dá néarthocsaineacha (Joseph, et al, 1991. Skaper, et al, 1996;. Parkinson, et al, 1997;. Santiago, et al, 1998.. Barger, et al, 2000), mar atá thoradh ar riospráid mitochondrial shochtadh. NÍL Tá ról mór i peroxidation lipid agus demyelination. Tá sé suimiúil a fheiceáil serotonin agus NÍL a bhaineann go hoscailte le estrogen, a bhfuil a thocsaineacht curtha i bhfolach go cúramach ó radharc an phobail mitochondrial.

Tá teoiricí éagsúla faoi chúis MS, teoiricí d'aois faoi ghéinte agus víris, agus teoiricí níos nuaí thart ar baictéir, easnaimh vitimín, easnaimh ola, poisons, agus imoibrithe le vacsaíní (go háirithe le haghaidh heipitíteas B agus fliú). Is í an teoiric amháin gur tréigeadh an teoiric 19ú haois síciatrach faoi "pairilis thug le," cé go bhfuil duine éigin ag caint ó am go chéile go fóill faoi na cúiseanna mhothúchánach na scléaróis iolrach; an téarma "hysteria baineann" tagtha isteach "neamhord chomhshó."

Gach ceann de na teoiricí is mó a bhfuil fíricí a roinnt go bhfuil an chuma chun tacaíocht a thabhairt dó, ach má fhaillíonn sé cuntas a thabhairt ar fhíorais go leor eile. Tá ag gach duine aontaíonn go bhfuil an córas imdhíonachta a bhaineann MS ar bhealach éigin, ach sin i ndáiríre nuair a thosaíonn an fhadhb, mar gheall ar an smaoineamh go bhfuil athlasadh chuid intreach de díolúine. Más "Is athlasadh is gá agus go maith," ansin bíonn sé ina fhadhb a shainiú go díreach ina bhfuil an teorainn idir le frithghníomhú cuí agus próiseas degenerative. Is féidir éidéime, riospráid cheallach laghdaithe, cailleadh feidhmeanna gnáth, fiobróis ina chéimeanna éagsúla, gach comhpháirt de athlasadh a fheiceáil i solas maith, mar chuid de "frithghníomh imdhíonachta cosanta." Nuair a dtagann díobháil fíochán a dheisiú, "mór" é a fheiceáil mar tairbhiúil, fiú amháin má eascraíonn sé leis an ghlóthach a scar i bhfeidhm de fíochán feidhme, toisc go bhfuil an chomparáid idir toradh shamhlaithe is measa is féidir, agus a ghnóthú neamhfhoirfe, seachas i gcomparáid leis an bpróiseas athlastacha leis an bhféidearthacht go d'fhéadfadh a bheith díobhálach d'fhéadfadh a bheith déanta ghníomhaire aon dochar ar chor ar bith.

Ba é an léiriú is simplí ar conas a bhaineann leis an athlasadh orgánach acmhainní dturgnamh inar athraíodh glúcóis fola, fad is a bhí faoi lé ainmhí le ceimiceáin a bheidh éagsúil ó mildly irritating a d'fhéadfadh a deadly. Nuair a bhí an t-ainmhí siúcra fola an-íseal, d'fhéadfadh an greannach mildest a bheith deadly, ach nuair a bhí coinnithe a glúcóis fola an-ard, a bhí fiú an antaiginí deadly amháin mildly irritating. Éagsúla an tiúchan sóidiam fola a bhí cosúil leis, ach níos laige, éifeachtaí.

Tá claonadh ann athlasadh a fheiceáil ní hamháin mar ghnáthchuid de díolúine, ach é a fheiceáil mar comhréireach leis an nádúr an antigen, ach amháin nuair a bheidh an córas imdhíonachta a primed chun é trí theagmháil roimhe sin, agus sa chás sin beidh an orgánach ceachtar ní freagairt ar chor ar bith (mar tá sé díolmhaithe), nó beidh sé i bhfad níos mó a imoibríonn go foirtil ná mar a bhí sé ar an chéad nochtadh, mar tá sé ailléirgeacha. Ach, i ndáiríre, is féidir leis an tiúchan ach ní bhíonn ach glúcóis agus sóidiam san fhuil (agus de thyroid, agus substaintí eile go leor nach bhfuil a mheastar a bheith mar chuid den chóras imdhíonachta) difríocht a dhéanamh ollmhór i méid na imoibriú "imdhíoneolaíoch" .

Sa riocht ró-íogair a tháirgtear trí hypoglycemia, roinnt rudaí a tharlóidh a chuireann le freagra maladaptive inflammatory áibhéalacha.

Adrenaline méaduithe i hypoglycemia, agus, má theipeann ar an adrenaline glycogen a thiontú i glúcóis, beidh sé ar fáil breosla ionadúil ag aigéid shailleacha saor in aisce fuascailliú ó cealla saille.

Má tá an aigéid sailleacha liberated neamhsháithithe, beidh siad faoi deara serotonin a secreted, agus beidh an dá serotonin agus an aigéid sailleacha neamhsháithithe riospráid mitochondrial bhaint de, go mór leis an hypoglycemia. Beidh siad ag spreagadh an scaoileadh cytokines, activating ar éagsúlacht na próisis imdhíoneolaíoch agus inflammatory, agus beidh siad faoi deara soithigh fola a bheith leaky, ag cruthú agus ag tosú éidéime na céimeanna chéad fiobróis. Beidh an dá adrenaline agus serotonin spreagadh a scaoileadh cortisol, a eagraíonn sé aimínaigéid ó fíocháin, mar shampla na matáin chnámharlaigh mór. Go bhfuil na matáin cuid mhór de na cistéin agus tryptophan, a, i measc éifeachtaí eile, faoi chois an thyroid. An tryptophan méadú, go háirithe i láthair aigéid sailleacha saor in aisce, is dócha a thiontú serotonin breise, ó scaoileadh aigéid sailleacha tryptophan ó albaimin, ag méadú a theacht isteach san inchinn. Aigéid shailleacha saor in aisce agus serotonin níos mó a laghdú éifeachtacht meitibileach (as ar aghaidh insulin, mar shampla) agus stát inflammatory a chur chun cinn.

Tá saillte i sruth na fola-rochtain éasca ar an inchinn, agus an aigéid sailleacha neamhsháithithe saor in aisce a tháirgeadh éidéime inchinn (Chan, et al., 1983, 1988). Nuair a éidéime inchinn de bharr sceitheadh ​​soithíoch, is féidir próitéiní atá eisiata de ghnáth isteach. An inchinn malartuithe spreagadh, excited agus fatigued glutamine do tryptophan, dlús a glacadh ó na fola.

Nuair a fíochán gortaithe nó béim, antasubstaintí atá déanta mar fhreagra ar na comhpháirteanna athraithe na fíocháin. Dá bhrí sin, d'fhéadfadh muid glaoch a bruise nó sprain ar riocht autoimmune, ach níl aon tástálacha tráchtála do brúite-shin antasubstaintí. Dealraíonn sé infhaighteacht na tástálacha le haghaidh antasubstaintí ar leith a bheith ar an fachtóir riachtanach i rangú riocht mar autoimmune, mar atá i "thyroiditis autoimmune." Ar an drochuair, tá an mbealach seo a bhaineann le húsáid teanga neadaithe i gcultúr atá lán de smaointe neamhréadúil na cúisíochta, agus na mílte de na daoine a thógáil a ngairmeacha beatha ar an cuardach a dhéanamh ar an "genes mutated atá freagrach as an galar," agus do na drugaí a cheartú an locht.

Go luath sa staidéar ar imdhíoneolaíocht, bhí an fócas ar antasubstaintí. Fiú amháin níos luaithe, bhí athlasadh conceptualized i dtéarmaí an "humors," agus smaointe prescientific eile. Chomh luath agus a scléaróis iolrach / bhí rangaithe mar pairilis thug le galar autoimmune, smaointe primitive faoi nádúr an chórais imdhíonachta, idirghníomhú le smaointe primitive faoi nádúr an inchinn agus struchtúr na cealla, a chumasc ina na teoiricí éagsúla de ghalar cad é an Is é.

In áit a bheith ag féachaint ar damáiste nerve imdhíoneolaíoch mar an chúis na gnéithe eile de scléaróis iolrach, Sílim go bhfuil sé tábhachtach chun breathnú ar roinnt de na gnéithe ginearálta an riocht, mar comhthéacsanna ina bhfuil a léirmhíniú ar na himeachtaí i nerves.

Tá sé ar eolas ar feadh i bhfad go bhfuil claonadh minicíocht na Ballstáit a mhéadú le achar ón meánchiorcal. Minicíocht íseal i climates tirim grianmhar, agus ag airde ard. Dhá tionchair aiste bia soiléir a shuífear: muiceoil a ithe, agus feoil chapaill.

Ní dhéanann daoine a bhfuil a n-MS rialáil teocht an choirp go han-mhaith. Tá a sheoladh nerve mall, agus i ndaoine gnáth, tá seoladh níos tapúla ag teochtaí níos airde, ach i daoine le MS Is é an seoladh níos moille ag an teocht gnáth-F céimeanna 98.6 ná ag teochtaí níos ísle. Tá teocht subnormal bainteach freisin le sean-aoise, agus leis an flashes te de sos míostraithe.

Tá metabolism Brain de glúcóis an-íseal i scléaróis iolrach, agus i mo bharúlacha féin, is é an ráta meitibileach ginearálta subnormal. Mar sin féin, ar chúis éigin daoine go bhfuil an hypometabolism ba chúis leis an loit, seachas vice versa.

Tá Ainmhithe go bhfuil easpa an aigéid sailleacha neamhsháithithe ar ráta níos airde meitibileach agus cumas glúcóis a úsáid, a athrú sé le CO2 níos éasca, tá friotaíocht níos mó le tocsainí (Harris, et al, 1990; fiú cobra venom:.. Morganroth, et al, 1989), lena n-áirítear endotoxin (Li, et al., 1990)-chosc iomarcach soithíoch sceitheadh-agus chun damáiste imdhíoneolaíocha (Takahashi, et al., 1992), agus chun tráma, agus tá a n-freagra neuromuscular luathú cé go bhfuil matáin bpreabfaidh tapa níos lú go héasca fatigued (Ayre agus Hulber, 1996).

I daoine le MS, is é an fhuil níos slaodach, agus pláitíní an claonadh a bhíonn le clump le chéile níos éasca. Is é an leibhéal cortisol níos airde ná gnáth, agus tá a n-adrenal cortex pituitary-spreagthach hormone níos deacra a bhaint de. Is é seo an coinníoll go bhfuil le feiceáil freisin i dúlagar agus seanaois. In ainneoin an cortisol hainsealach ardaithe, daoine le MS bhfuil de ghnáth hypoglycemia. Tá siad le fáil ó am go chéile go bhfuil sóidiam fola íseal, hyponatremia, ach tá sé seo deacair a chinneadh nuair a bhíonn ábhar uisce na fola ar athraitheach. Tá a prolactin dócha go mbeidh ard, agus is féidir é seo mar thoradh ar estrogen ard, serotonin ard, íseal sóidiam, nó thyroid íseal. Is féidir uisce óil i bhfad ró-mhéadú prolactin, agus is féidir iatán myelin an nerves 'damáiste a dhéanamh; bíonn serotonin i bhfad an iomarca a chur faoi deara ól iomarcach. Is féidir le suaitheadh ​​den ábhar glúcóis fola, sóidiam, agus uisce isteach struchtúr myelin an inchinn ar. Disturbs estrogen Ard na fola osmotically, ag déanamh a choimeád sé an iomarca uisce i ndáil leis an solutes, agus seo a bhaineann le go leor de estrogen ar éifeachtaí; toisc gur féidir athruithe osmotic simplí damáiste a dhéanamh ar na struchtúir myelin, is cosúil gur cheart an mheicníocht seo a fhiosrú go maith sula bhfuil sé Glactar leis go bhfuil na himeachtaí imdhíoneolaíocha bunscoile.

Tá cealla crann, a chur chun cinn trí scaoileadh substaintí athlasadh, mar shampla histamine agus serotonin (agus a chur ar soithigh fola leaky), níos mó go leor san inchinn i scléaróis iolrach ná i brains gnáth. Ós rud é serotonin clumping pláitíní scaoileadh, agus freisin toisc go bhfuil níos mó ná serotonin arna moladh ag gnéithe sin go leor eile de MS, antagonists serotonin (ondansetron agus ketanserin, mar shampla) a bheith in úsáid teiripeach le rath.

Estrogen is cúis le cealla crann a scaoileadh a n-idirghabhálaithe inflammatory, agus é a pláitíní faoi deara go comhiomlán, scaoileadh lena serotonin. Ós rud é go bhfuil ceannas estrogen a bhaineann go dlúth le láithreacht na loit inchinn gníomhach, a bheadh ​​cosúil go léir antiestrogen teiripe i MS. Progesterone counteracts éastraigin le héifeachtaí ar an dá cealla agus pláitíní crann.

Aspirin cosaint i gcoinne éagsúla próisis inflammatory, ach tá sé an chuid is mó clú ar an chosc ar na prostaglandins. Cé go bhfuil aspairín a úsáidtear go minic chun faoiseamh a pian i MS, agus tá eile inhibitor na sintéise prostaglandin, indomethacin, baineadh úsáid as teiripeach i MS, go mbeadh sé cuí imscrúdú a dhéanamh níos mó go cúramach aspirin ról is féidir a chosc nó fhaoiseamh MS.

Tá easnamh próitéine simplí éifeachtaí iontas go leor. Lowers sé teocht an choirp, agus shochtadh an thyroid, ach méadaíonn sé athlasadh agus an claonadh fola a clot. Ós rud é a cheangal ar an inchinn agus croí agus na scamhóga soláthar leanúnach de aimínaigéid riachtanach má tá siad ag feidhmiú chun leanúint ar aghaidh, in éagmais próitéin aiste bia, ní mór cortisol a thabhairt ar aird leanúnach a shlógadh aimínaigéid ó na fíocháin expendable, atá den chuid is mó ar na matáin chnámharlaigh. Tá na matáin tiúchan ard de tryptophan agus cistéin, a choisceann an thyroid. Cistéin is excitoxic, agus tryptophan is é an réamhtheachtaí do serotonin. Is dócha, a láithreacht i, agus strus-spreagtha scaoileadh as, na matáin ar cheann de na meicníochtaí sin a laghdú le linn gníomhaíochta meitibileach cineálacha áirithe strus.

Nuair a iompar clainne ainmhithe a bhaint de próitéin, ní mór na n-ainmhithe nuabheirthe leibhéil thar ard serotonin, agus na heinsímí atá freagrach as sin níos mó ná an claonadh a choimeád ar bun os cionn serotonin fiú nuair atá siad tar éis fás agus tá próitéin leordhóthanach. Tá sé seo ar aon dul leis an éifeacht na estrogen bhreis go luath sa saol, a chruthaíonn an claonadh a fhorbairt chíche nó ailse próstatach i ndaoine fásta. Bheadh ​​sé suimiúil a thabhairt faoi staidéar a dhéanamh ar an taithí gestational, m.sh., fad na tréimhse iompair agus meáchan breithe, de na daoine a fhorbairt níos déanaí MS.

Cé nach bhfuil daoine i dtíortha thuaidh de ghnáth próitéin-starved, an bhfuil siad claonadh a fháil ar chuid mhór dá próitéine ón meats muscle. I gcultúr traidisiúnta, bhí gach cuid de na hainmhithe bia a itheann-cearc troigh, cinn, agus necks, ainmhithe 'chluasa agus eyeballs, etc-agus mar sin an t-iarmhéid aimínaigéad a bhí fabhrach a chothabháil ráta ard meitibileach agus a chosc struis.

Is é an tuairim go bhfuil scléaróis iolrach a bhaineann leis an tomhaltas muiceola agus feoil chapaill, ach ní mairteoil, uaineoil, nó gabhar, an-suimiúil, ós rud é go bhfuil an saille de na hainmhithe go bunúsach ar nós na saillte na n-ábhar plandaí a itheann siad, rud a chiallaíonn go bhfuil sé Tá an-ard i aigéid linoleic agus linolenic. Tá rumen na mbó, caorach, gabhar agus baictéir a thiontú an saillte polyunsaturated i saill sháithithe níos mó. Bac saillte neamhsháithithe na heinsímí go n-othar díolama próitéine, agus MS a thuairisciú go bhfuil droch-dhíleá ar fheoil (Gupta, et al., 1977).

Is iad na saillte polyunsaturated iontu féin tocsaineach don mitochondria, agus faoi chois ocsaídiú glúcóis, agus an fheidhm thyroid bac ar a bhfuil an éifeacht chéanna suppressive ar an gcumas chun glúcóis oxidize, ach tá siad ag iompú freisin, enzymically, isteach sa prostaglandins, agus neamh-enzymically, ag peroxidation lipid spontáineach, sa isoprostanes tocsaineach. An isoprostanes, agus roinnt de na prostaglandins, atá ardaithe sna fíocháin inchinn agus eile do dhaoine faoi MS.

Is peroxidation lipid an-ard i scléaróis iolrach. Is ocsaíd nitric (a bhfuil a sintéis a chur chun cinn ag estrogen i gcodanna chuid is mó de na hinchinne) a radacach saor in aisce go CCF peroxidation.

Peroxidation lipid milleann roghnach, go nádúrtha, an saillte polyunsaturated éagobhsaí. I Atherosclerosis, go bhfuil an plaiceanna soitheach fola ramhar is beag neamhsháithithe. Tá sé seo toisc go bhfuil siad peroxidized sin go tapa, ach tá a n-cóimheas ard sáithithe a saillte neamhsháithithe a úsáid chun a mhaíomh go bhfuil an olaí polyunsaturated "cosanta chroí." Hargóintí den chineál céanna a dhéantar go minic i MS, cé nach bhfuil roinnt staidéir tacú leis an smaoineamh go bhfuil easpa aon cheann de na saillte neamhsháithithe. Ós rud é go peroxidation lipid an-ard, go mbeadh sé réasúnach glacadh leis go raibh raidhse de saillte polyunsaturated á peroxidized trí imoibrithe le catalaíoch, mar shampla iarann ​​(SM Levine, 1997) agus ocsaíd nítreach agus peroxynitrile.

Creidim go bhféadfadh gné thábhachtach de na éadulaingt le haghaidh teasa mar sin is minic a thuairiscítear i daoine le MS a bheith an claonadh hyperthermia i gcoibhneas le scaoileadh méideanna níos mó de aigéid shailleacha saor in aisce isteach i sruth fola. Mná, mar gheall ar estrogen ar éifeachtaí, de ghnáth ag leibhéal i bhfad níos airde de aigéid shailleacha saor in aisce san fhuil ná mar a dhéanann fir. Estrogen méaduithe a scaoileadh saor ó aigéad sailleach saille stóráil, agus na saillte neamhsháithithe synergize leis an dá estrogen agus prolactin, ag méadú a n-éifeachtaí.

Rialachán teocht i gceist dealraimh roinnt cealla nerve go teocht an-chiall go cruinn, agus athrú a gcuid gníomhaíochta dá réir sin. Uisce a bhfuil toilleadh teasa thar cuimse ard, rud a chiallaíonn go dtógann sé le méid réasúnta mór teasa a athrú teochta. Tá an "teas imeacht" á gcaitheamh ag athruithe struchtúrtha san uisce. Próitéiní an saghas céanna de chastacht struchtúrtha mar uisce, agus le chéile is féidir leo a dhéanamh transducers teocht éifeachtach, "teirmiméadair." (Substaintí eile claonadh a bhíonn le dul faoi athruithe móra struchtúrtha ach amháin de réir mar a leá nó vaporize. An cáiliúil "criostail leachtacha" Tá cúpla ar leith céimeanna struchtúrtha, ach chíteaplasma Is cosúil le criostail leachtacha an-subtle.) an "cealla teirmeastat" ag freagairt iarbhír go pointe de struchtúr inmheánach, gan an teocht sa teibí. Mar sin, beidh rudaí a athrú ar a struchtúr inmheánach a mhodhnú a n-teocht "gléas-phointe."

Cúiseanna estrogen méadaithe ainmhí níos ísle a theocht, agus is dócha a dhéanann sé seo ag méadú an "teocht struchtúrtha" de na cealla teirmeastat, "leá" a struchtúr inmheánach. Progesterone deara an t-ainmhí a mhéadú a theocht, agus a dhéanann sé cosúil seo trí mhéadú ar an struchtúr / laghdú ar an teocht struchtúrtha de na cealla teirmeastat. Má chuir tú oighir ar an teirmeastat, faigheann an seomra te.

Tá cill ar struchtúr inmheánach atá coibhéiseach lena bhfonnmhaireacht chun seirbhísí a oibriú. Tuirse Léiríonn sé beagán "leáite" staid na cille, ina bhfuil struchtúr a bheith arna gcaitheamh chomh maith leis na cúlchistí fuinneamh ceimiceach. Turgnaimh gur léirigh an éifeacht a bhí an-soiléir, ach bhí siad neamhaird toisc nach raibh siad oiriúnach daoine smaoineamh stereotyped na cille. Le teirmiméadar an-íogair, is féidir a thomhas an teas a tháirgeadh le nerve nuair a spreagadh. Ní haon ionadh é sin. Ach tá sé iontas go, nuair a bhíonn an nerve ais ó na spreagadh, súnn sé teas ón timpeallacht, an teocht a ísliú go háitiúil. Gur sháraigh fiú roinnt daoine gcoincheap de "eantrópachta," ach is féidir a léiriú go héasca go bhfuil athruithe ag athrú an bhfoirm ar roinnt ábhair a n-saintoilleadh teasa, mar nuair a banda rubair sínte (fhaigheann sé te), nó conarthaí (faigheann sé with).

An excitants, estrogen agus cortisol, mall an seoladh de nerves, toisc go bhfuil siad faoi deara a struchtúr inmheánach a scaipeadh. Cruthaíonn siad ar "réamh-fatigued" stát sa chill.

I turgnaimh le hearts coinín, léirigh Szent-Gyorgyi go estrogen laghdaigh an croí ar ullmhacht a bheith ag obair, agus go progesterone méadú a bhfonnmhaireacht chun seirbhísí a oibriú, agus dúirt sé go raibh sé seo ag "déanmhas fhoirgneamh." Dúirt sé go bhfuil, le haghaidh drugaí a tugadh nó spreagadh eile, tá cealla freagra tréith, ag éirí níos ceachtar ngníomh nó níos mó bac, ach léirigh sé go bhfuil, taobh amuigh den tiúchan gnáth nó raon déine an spreagadh, tá cill freagra droim ar ais go minic.

Más é seo leis an staid sa nerves i MS, míníonn sé an iompar aisteach, a laghdaíonn an téamh nerve a fheidhme. Is é an impleacht go struchtúr inmheánach Ní mór (agus fuinneamh) a chur ar ais chuig an nerves. Sa turgnamh go bhfuil mé cur síos i nuachtlitreacha roimhe seo, ag méadú sóidiam, ATP, dé-ocsaíd charbóin, agus progesterone, agus méadú ar an cóimheas idir maignéisiam go cailciam, a shuífear a mhéadú fuinnimh agus struchtúr cheallacha. Is é an hormone thyroid deireadh thiar freagrach as cothabháil cealla 'fuinnimh agus struchtúr, agus freagrúlacht, ach má tá sé méadú tobann gan ligean ar fad ar na fachtóirí eile a choigeartú, beidh sé ardú teochta freisin go tobann. Ní mór é a ghlacadh ar feadh i bhfad, ach go léir ar na fachtóirí a bheith i láthair ag an am céanna.

Serotonin, melatonin, estrogen, agus saillte polyunsaturated claonadh ar fad go dtí teocht an comhlacht níos ísle. Ó tharla go bhfuil estrogen agus na saillte neamhsháithithe excitants cheallacha, cuidíonn an laghdú iarbhír i teocht an choirp a fhritháireamh a n-éifeachtaí excitatory.

An dá solas geal agus airde ard claonadh a laghdú serotonin ar éifeachtaí. Laghdaíonn an dé-ocsaíd charbóin fíochán a coinníodh ag airde ard ar an minicíocht galair go leor, agus a d'fhéadfadh difear a scléaróis iolrach mar a bhfuil galar croí agus ailse. Tá sé ar eolas go bhfuil dé-ocsaíd charbóin i gceist i rialachán myelin an dá ábhar uisce féin. Hyperventilation, le cúis le caillteanas de dhé-ocsaíd charbóin Press, idir histamine agus serotonin, ag déanamh níos mó slaodach fola, agus a dhéanamh níos tréscaoilteach soithigh fola, agus is cúis leo constrict.

Má tá daoine le MS fhorbair sé trí idirghníomhaíochtaí estrogen iomarcach, serotonin, saillte neamhsháithithe, iarann, agus uisce, agus thyroid easnamhach, agus pregnenolone easnamhach a tháirgtear in na cealla myelin-foirmithe (oligodendrocytes), tá a lán rudaí is féidir a dhéanamh chun stop a dhul chun cinn, agus, b'fhéidir, chun é a aisiompú.

Ós rud é go mbeidh méadú tobann i teocht scaoileadh méideanna níos mó de na saillte pro-inflammatory, ba chóir rudaí a athrú de réir a chéile. Is salann méadaithe thermogenic, ach tá níos mó maignéisiam cosanta i gcoinne hyperthermia, maignéisiam sin méadú (folcthaí salainn Epsom, mar shampla, caife, torthaí, glasraí agus roinnt Feoil) a bheadh ​​ina chuidiú. Maignéisiam atá caillte go tapa ó chealla i hypothyroidism. Siúcra, nuair ag gabháil saillte agus mianraí, mar atá i bainne, tá gá le cortisol níos ísle, agus a choimeád ar bun gníomhaíocht thyroid. Beidh próitéiní Chothrom, amhail cáis, prátaí, uibheacha, agus mairteoil-nó-uan brat (as ábhar geilitín agus mianraí, go háirithe) cosc ​​a chur ar an bhreis tryptophan go shochtadh an thyroid agus tá sé d'fhéadfadh a bheith ina tocsain nerve. Saill, saill sháithithe, a úsáidtear go rialta, laghdú ar na héifeachtaí tocsaineacha láithreach antimetabolic na saillte stóráil neamhsháithithe, ach a thógann sé tamall fada a athrú ar an iarmhéid saillte stóráil.

Ós rud é go lowers aspirin teocht is é sin, antiinflammatory, i roinnt cásanna antiestrogenic, agus is antioxidant cumhachtach, is dócha go mbeadh sé comharthaí a mhaolú agus dul chun cinn MS chosc, de réir mar a dhéanann sé i galair degenerative eile. Ós rud é go gcomhshuimeofar pláitíní dócha go mbeidh baint acu leis an Díríonn na athlasadh, d'fhéadfadh aspirin cabhrú chun cosc ​​a chur ar an foirmiú na réimsí nua damáiste.

Cé go bhfuil an glucocorticoids úsáideach le haghaidh a gcuid gníomhartha antiinflammatory, tá cortisol ar eolas a chur chun cinn an marú na cealla inchinn ag excitotoxicity. Ós rud é go laghdaíonn éastraigin GABA, agus an dá estrogen agus serotonin a ghníomhachtú an tharchuradóirí aigéad excitatory aimín, is é an Chomh maith glucocorticoids sintéiseach leis an mbreis cortisol a bhí ann cheana ar dóigh dóibh díobháil codanna den inchinn i dteannta leis na réimsí inflamed.

An cortisol de bhreis ar dúlagar, a thagann sean-aoise, agus go minic hyperestrogenism síos le húsáid ar fhorlíonadh thyroid, ach pregnenolone bhfuil gníomhaíocht an-dhíreach (i gcoinne serotonin) is féidir go ciúin ar an pituitary, a laghdú ACTH agus cortisol. Progesterone Tá roinnt iarmhairtí den chineál céanna, agus tá sé cosanta i gcoinne cortisol níos mó, agus is fachtóir mór i nerve agus athchóiriú inchinn. Thyroid, progesterone, agus pregnenolone bhfuil baint acu ar fad i bhfoirmiú nua myelin, agus le cosc ​​a chur ar an éidéime go damáiste dó.

Ós rud é thyroid agus progesterone laghdú ar an foirmiú na estrogen i fíochán inflamed, agus spreagann cortisol a fhoirmiú, go mbeadh sé ciallmhar a úsáid thyroid agus progesterone le haghaidh a n-éifeachtaí antiinflammatory láithreach, lena n-áirítear an chosc ar na NÍL foirmiú (Drew agus Chavez, 2000), agus a n-easpa an excitotoxic, estrogen-spreagthach éifeachtaí an glucocorticoids. Cé go bhfuil an glucocorticoids cistéin agus catabolic shaoradh agus tryptophan ó matáin, nach bhfuil thyroid agus progesterone catabolic, agus a chosaint i gcoinne na hiarmhairtí tocsaineach na aimínaigéid.

TAGAIRTÍ

J Neurol Neurosurg Síciatracht 1988 Feabhra; 51 (2) :260-5. Sil-iarann ​​Perivascular agus damáiste soithíoch eile i scléaróis iolrach. Adams CW. "Na cásanna scléaróis iolrach Léirigh sil venous fibrinoid ón dtaobh istigh (7%), haemorrhages déanaí (17%), nochtadh haemorrhages d'aois ag sil haemosiderin (30%), thrombosis (6%) agus veins tiubhaithe (19%). San iomlán, léirigh 41% de na cásanna scléaróis iolrach roinnt fianaise ann damáiste vein. "" Haemosiderin sil-leagan a bhí coitianta sa substantia nigra agus núicléis pigmented eile i ngach cás. Tá sé i gcrích go bhfuil an balla vein cheirbreach i scléaróis iolrach faoi réir damáiste inflammatory ainsealach, a chuireann chun cinn rith fola agus tréscaoilteacht méadaithe, agus is ionann foirm de vasculitis. "

Am J Pathol 1985 Nollaig; 121 (3) :531-51. Hormóin Gnéas, freagairtí imdhíonachta, agus galair autoimmune. Meicníochtaí gníomhaíochta hormone gnéas. Ansar Ahmed S, Penhale WJ, Talal N. Is é "imoibríocht imdhíonachta níos mó ban ná fir i. Sa dá ainmhithe turgnamhacha agus i fear tá preponderance níos mó de na galair autoimmune i baineannaigh, i gcomparáid le fir. Staidéir i múnlaí turgnamhacha curtha ar bun ag go leor go bhfuil an bonn bunúsacha le haghaidh an claonadh gnéis a bhaineann leis na héifeachtaí mharcáilte na hormóin gnéis. Tionchar a imirt ar an gan hormóin Gnéas agus déine na n-idirghabhála imdhíonachta coinníollacha pathologic ag limficítí mhodhnaithe ag gach céim den saol, réamhbhreithe, prepubertal, agus postpubertal. "

J Appl Physiol 1996 Feb;80(2):464-71. Effects of changes in dietary fatty acids on isolated skeletal muscle functions in rats. Ayre KJ, Hulbert AJ The effects of manipulating dietary levels of essential polyunsaturated fatty acids on the function of isolated skeletal muscles in male Wistar rats were examined. Three isoenergetic diets were used: an essential fatty acid-deficient diet (EFAD), a diet high in essential (n-6) fatty acids [High (n-6)], and a diet enriched with essential (n-3) fatty acids [High (n-3)]. After 9 wk, groups of rats on each test diet were fed a stock diet of laboratory chow for a further 6 wk. Muscle function was examined by using a battery of five tests for soleus (slow twitch) and extensor digitorum longus (EDL; fast twitch). Tests included single muscle twitches, sustained tetanic contractions, posttetanic potentiation, sustained high-frequency stimulation, and intermittent low-frequency stimulation. Results for muscles from the High (n-6) and High (n-3) groups were very similar. However, the EFAD diet resulted in significantly lower muscular tensions and reduced response times compared with the High (n-6) and High (n-3) diets. Peak twitch tension in soleus muscles was 16-21% less in the EFAD group than in the High (n-6) and High (n-3) groups, respectively [analysis of variance (ANOVA), P < 0.01). During high-frequency stimulation, EDL muscles from the EFAD rats fatigued 32% more quickly (ANOVA, P < 0.01)]. Also, twitch contraction and half-relaxation times were significantly 5-7% reduced in the EFAD group (ANOVA, P < 0.01). During intermittent low-frequency stimulation, soleus muscles from the EFAD group generated 25-28% less tension than did the other groups (ANOVA, P < 0.01), but in EDL muscles from the EFAD group, endurance was 20% greater than in the High (n-6) group (ANOVA, P < 0.05). After 6 wk on the stock diet, there were no longer any differences between the dietary groups. Manipulation of dietary fatty acids results in significant, but reversible, effects in muscles of rats fed an EFAD diet.

Endocr Res 1999 May;25(2):207-14. Prolactin secretion is increased in patients with multiple sclerosis. Azar ST, Yamout B

Acta Neurol Scand 1999 Feb;99(2):91-4. Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Bansil S, Lee HJ, Jindal S, Holtz CR, Cook SD “Patients with high estradiol and low progesterone levels had a significantly greater number of Gd enhancing lesions than those with low levels of both these hormones. Patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio.”

J Neuroimmunol 1996 Mar;65(1):75-81. Circulating antibodies directed against conjugated fatty acids in sera of patients with multiple sclerosis. Boullerne A, Petry KG, Geffard M “These results suggest that in MS and RA, autoepitopes on cell membranes that are normally hidden from the immune system become immunogenic. This may arise because of previous membrane disruption by oxidative processes.”

J Neurosci Res 2000 Nov 15;62(4):503-9. Dehydroepiandrosterone inhibits microglial nitric oxide production in a stimulus-specific manner. Barger SW, Chavis JA, Drew PD.

J Exp Med 1984 Nov 1;160(5):1532-43. Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent. Bowern N, Ramshaw IA, Clark IA, Doherty PC “Iron is believed to influence both the migration and function of immune effector cells. It can also act as a catalyst in the formation of free radicals, which are highly toxic agents causing tissue damage in sites of inflammation.”

J Neurol Neurosurg Psychiatry 1981 Apr;44(4):340-3. Rheological and fibrinolytic findings in multiple sclerosis. Brunetti A, Ricchieri GL, Patrassi GM, Girolami A, Tavolato B. “The whole blood viscosity was found to be increased in multiple sclerosis.”

J Neurochem 1988 Aibreán; 50 (4) :1185-93. Ionduchtú foirmiú superoxide intracellular radacach ag arachidonic aigéad agus ag aigéid sailleacha polyunsaturated i gcultúir astrocytic bunscoile. Chan PH, Chen SF, Yu AC "PUFAs eile, lena n-áirítear aigéad linoleic, aigéad linolenic, agus aigéad docosahexaenoic, bhí éifeachtúil freisin i spreagadh foirmiú NBF i astrocytes, cé go raibh aigéad phailmíteacha sáithithe agus aigéad stéaracha monai-neamhsháithithe neamhéifeachtach. Tugadh éifeachtaí cosúil leis na PUFAs i bhfoirmiú malondialdehyde i gcealla agus carnadh aigéid lachtaigh sa mheán goir. Léiríonn na sonraí gur ionracas an dá scannán agus meitibileacht cheallacha bhí perturbed ag arachidonic aigéad agus ag PUFAs eile. "

Ann Neurol 1983 Meitheamh; 13 (6) :625-32. Induction of brain edema following intracerebral injection of arachidonic acid. Chan PH, Fishman RA, Caronna J, Schmidley JW, Prioleau G, Lee J “Intracerebral injection of polyunsaturated fatty acids (PUFAs), including linolenic acid (18:3) and arachidonic acid (20:4), caused significant increases in cerebral water and sodium content concomitant with decreases in potassium content and Na+- and K+- dependent adenosine triphosphatase activity. There was gross and microscopic evidence of edema. Saturated fatty acids and monounsaturated fatty acid were not effective in inducing brain edema. The [125I]-bovine serum albumin spaces increased twofold and threefold at 24 hours with 18:3 and 20:4, respectively, indicating vasogenic edema with increased permeability of brain endothelial cells” “These data indicate that arachidonic acid and other PUFAs have the ability to induce vasogenic and cellular brain edema and further support the hypothesis that the degradation of phospholipids and accumulation of PUFAs, particularly arachidonic acid, initiate the development of brain edema in various disease states.”

Med Sci Sports Exerc 1997 Jan;29(1):58-62. Effects of acute physical exercise on central serotonergic systems. Chaouloff F “Works from the 1980's have established that acute running increases brain serotonin (5-hydroxytryptamine: 5-HT) synthesis in two ways. Lipolysis-elicited release of free fatty acids in the blood compartment displaces the binding of the essential amino acid tryptophan to albumin, thereby increasing the concentration of the so-called “free tryptophan” portion, and because exercise increases the ratio of circulating free tryptophan to the sum of the concentrations of the amino acids that compete with tryptophan for uptake at the blood-brain barrier level, tryptophan enters markedly in the brain compartment.” “Indirect indices of 5-HT functions open the possibility that acute exercise-induced increases in 5-HT biosynthesis are associated with (or lead to) increases in 5-HT release.”

Hipitéisí Med 1995 Samhain; 45 (5) :455-8. Melanin, melatonin, melanocyte-spreagthach hormone, agus an claonadh chun demyelination autoimmune: réasúnaíocht do theiripe éadrom i scléaróis iolrach. Constantinescu CS "Tá an hipitéis le chéile anseo bunaithe ar an tuairim go bhfuil friotaíocht a scléaróis iolrach agus encephalomyelitis autoimmune turgnamhach bhaineann leis pigmentation craiceann dorcha. Cé gur féidir seo a signify ról cosanta do melanin i gcoinne fachtóirí comhshaoil ​​a tháirgeadh damáiste ocsaídiúcháin, tá an mheicníocht shamhlaítear anseo go bhfuil claonadh chun demyelination autoimmune Tá tionchar ag fachtóirí hormónach, ie an melatonin neurohormones agus hormone spreagúil melanocyte, a bhfuil éifeachtaí i gcoinne ar fheidhmeanna imdhíonachta agus, an am céanna go bhfuil, ar dheitéarmanaint thábhachtach an duine aonair a tháirgeadh melanin. "

Neurosci Lett 1989 Nov 6;105(3):246-50. Presence of Schwann cells in neurodegenerative lesions of the central nervous system. Dusart I, Isacson O, Nothias F, Gumpel M, Peschanski M Ultrastructural analysis of neurodegenerative CNS lesions produced by an excitotoxic substance revealed that the majority of cells ensheathing axons were not oligodendrocytes. By their morphology and the presence of both a basal lamina and collagen fibers they were identified as Schwann cells. The presence of Schwann cells, whose growth-promoting role in the peripheral nervous system has been largely documented, may account for the development of regenerating growth cones which have been observed in the excitotoxically lesioned central nervous system. Further support for this hypothesis came from the analysis of fetal neural transplants implanted into the lesioned area. Schwann cells ensheathing axons were indeed numerous in the neuron-depleted area surrounding the transplants, where neurite outgrowth of graft origin occurred.

J Neuroimmunol 2000 Nov 1;111(1-2):77-85. Female sex steroids: effects upon microglial cell activation. Drew PD, Chavis JA.

Neurology 1999 Nov 10;53(8):1876-9 Cerebrospinal fluid isoprostane shows oxidative stress in patients with multiple sclerosis. Greco A, Minghetti L, Sette G, Fieschi C, Levi G “The CSF level of the isoprostane 8-epi-prostaglandin (PG)-F2alpha (a reliable marker of oxidative stress in vivo) was three times higher in subjects with definite MS than in a benchmark group of subjects with other neurologic diseases.”

J Intern Med 1989 Oct;226(4):241-4. Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis. Grinsted L, Heltberg A, Hagen C, Djursing H.

Am J Gastroenterol 1977 Dec;68(6):560-5. Multiple sclerosis and malabsorption. Gupta JK, Ingegno AP, Cook AW, Pertschuk LP.

Free Radic Res 1997 Apr;26(4):351-62. Toxicity of polyunsaturated fatty acid esters for human monocyte-macrophages: the anomalous behaviour of cholesteryl linolenate. Hardwick SJ, Carpenter KL, Law NS, Van Der Veen C, Marchant CE, Hird R, Mitchinson MJ. “The triglycerides showed a direct relationship between toxicity and increasing unsaturation, which in turn correlated with increasing susceptibility to oxidation.” “Triarachidonin (20:4; omega-6), trieicosapentaenoin (20:5; omega-3) and tridocosahexaenoin (22:6; omega-3) were profoundly and rapidly toxic. There was a similar relationship between toxicity and increasing unsaturation for most of the cholesterol esters, but cholesteryl linolenate was apparently anomalous, being non-toxic in spite of possessing three double bonds and being extensively oxidised.” “The toxicity of triglycerides suggests that polyunsaturated fatty acid peroxidation products are also toxic.”

J Clin Invest 1990 Oct;86(4):1115-23. Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. Harris KP, Lefkowith JB, Klahr S, Schreiner GF.

Mikrobiyol Bul 1989 Oct;23(4):342-7. [Leukotrienes and neurological diseases]. [Article in Turkish] Irkec C, Ercan S, Irkec M “LTC4 levels were found to be elevated in MS and Behcet patient in comparison with controls. Augmentation of LTC4 levels underlines the fact that leukotrienes may be held responsible the pathogenesis of these disorders.”

Lancet 1982 Feb 13;1(8268):380-6. Evidence for subacute fat embolism as the cause of multiple sclerosis. James PB “The neurological features of decompression sickness, which is thought to be due to gas embolism, are similar to those of multiple sclerosis (MS). This similarity suggested the re-examination of a concept, first proposed in 1882, that the demyelination in MS is due to venous thrombosis. Unfortunately, although the plaques of MS are often perivenular, thromboses are not always present. Nevertheless, vascular theories can explain the topography of the lesions in MS.” “There is also evidence in man that fat may lodge in the microcirculation of the nervous system and cause distal perivenous oedema with the loss of myelin from axons.”

J Clin Pathol 1979 Oct;32(10):1025-9. Antithrombin activities in childhood malnutrition. Jimenez RA, Jimenez E, Ingram GI, Mora LA, Atmetlla F, Carrillo JM, Vargas W.

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

Stróc 1991 Samhain; 22 (11) :1448-51. Is féidir táirgí secretory Pláitíní cur le gortú neuronal. Joseph R, C Tsering, Grunfeld S, Welch KM "an tuairim gur féidir substaintí endogenous áirithe, mar shampla monosodium, cur le díobháil neuronal atá réasúnta bunaithe go maith anois. Pláitíní Fola ar eol go bhfuil secrete agus roinnt substaintí ar a bhaineann le dysfunction neuronal. Dá bhrí sin, ní mór dúinn hypothesize gur féidir le tiúchan ard (thart ar roinnt mílte-huaire níos airde ná i plasma, inár meastacháin) de go háitiúil a scaoileadh táirgí secretory pláitíní a dhíorthaítear ó na thrombus cúiseach cur le gortú neuronal agus gliosis imoibríoch a chur chun cinn. "" Táimid faoi deara freisin go Tá serotonin, a táirge mór pláitíní, airíonna néarthocsaineacha. "

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 turraing 1990 Meitheamh; 31 (2) :159-70. Friotaíocht de riachtanach aigéad-easnamhach francaigh sailleacha le endotoxin-spreagtha méaduithe i tréscaoilteacht soithíoch. Li EJ, Cook JA, Spicer KM, Wise leithreas, Rokach J, Halushka PV.

FEBS faoi stiúir 1 Samhain 1978; 95 (1) :181-4. Dhíghníomhú roghnaíoch na mírlíne NADH-ubiquinone an slabhra riospráide de cháithníní submitochondrial ag aigéid sailleacha le linn saor in aisce endogenous hyperthermia. Ludwig P, Bartels M, Schewe T, Rapoport S.

Airí Péine J Bainistigh 2000 Samhain; 20 (5) :388-91. Ondansetron i scléaróis iolrach. MacLeod AD. "D'fhreagair Dhá mná óga a bhfuil nausea ainsealach agus veirtige de bharr scléaróis iolrach a thabhairt isteach agus cothabháil an antagonist receptor 5HT3, ondansetron."

Am J Med Phys Rehabil 1994 Iúil-Lúnasa; 73 (4) :283-5. Thrombosis venous Intracranial i othar a bhfuil scléaróis iolrach. 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 Oct;66(4):497-504, Platelet aggregation and multiple sclerosis. Neu IS, Prosiegel M, Pfaffenrath V Measurements of blood platelet aggregation were carried out in 30 patients suffering from multiple sclerosis (MS) and in 15 healthy individuals. Compared with the control group, the MS patients showed an increase in both spontaneous and induced (ADP and serotonin) platelet aggregation. The possible pathogenetic significance of these results is discussed.

Neurology 1975 Aug;25(8):713-6. Schwann cells and regenerated peripheral myelin in multiple sclerosis: an ultrastructural study. Ogata J, Feigin I Tissue of a multiple sclerosis plaque in the brachium conjunctivum of the pons known to contain peripheral myelin by light microscopic studies were removed from the paraffin block and processed for electron microscopic studies. The cells related to the peripheral myelin possessed the ultrastructural characteristics of Schwann cells, with basement membranes and associated collagen fibers. No continuity was seen with the peripheral within the central nervous tissues by selective maturation of multipotential primitive reticular cells, a phenomenon consistent with the view that Schwann cells are mesenchymal in character.

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-Apr;55(2):146-50. [Effect of tryptophan excess in a diet on amino acid composition of skin collagen and on an initial stage of protein biosynthesis in rat liver]. Pechenova TN, Sushkova VV, Solodova EV, Gulyi MF Protein deficiency and tryptophane load against its background lead to the acid-soluble collagen synthesis in the rat skin. 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.”

Rev Esp Fisiol 1983 Mar;39(1):39-44. Intralipid and free plasmatic tryptophan in vitro. Pena JM, Aulesa C, Vinas O, Bosch J, Farriol M, Schwartz S “In an attempt to investigate the role of the lipidic emulsion Intralipid in the development of metabolic encephalopathy in a patient showing high free tryptophan levels, the relationship between lipidic emulsion and free tryptophan was examined in in vitro experiments. The addition of intralipid to normal serum produces an immediate increase in non-esterified fatty acids and a parallel rise in free tryptophan. Moreover, when serum with intralipid is incubated at 37 degrees C, the lipases release new non-esterified fatty acids and the free tryptophan increases proportionally.” “It is concluded that intralipid causes an increase in free tryptophan levels. It is known that in vivo free tryptophan modulates 5-hydroxytryptamine synthesis and thus may be considered a possible causal agent for encephalopathy.”

Hipitéisí Med 1980 Bealtaine; 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.”