Pax1/Foxa2- 1 of the primary genetic reasons why we balding men- are balding

[eldarlmario]

On Calcitirol:

http://www.medscape.com/viewarticle/776915_3

Thus, VD inhibits the polarization of Th0 cells to either Th1 or -2 cells(inhibits both TH1 and Th2 production) and simultaneously facilitates the converison of naive Th0 cells to Tregs ones, which protect the organism from autoimmune diseases(promotes t cell differentiation to Regulatory t cells instead) (vide supra). Therefore, it is not surprising that Cantorna et al. have found the number of TGF-? transcripts multiplied upon treating mice with D3 simultaneously with blockade of experimentally induced encephalomyelitis.[112] Evidently, the ratio of differentiation of naive T0 cells to Th1 or Treg cells has tremendous clinical significance[113 - 117] since, as discussed above, the formers induce autoimmune disease, while the latter (Treg cells) exert their tolerogenic action by reducing the production of IL-2, as discussed above. Also, the transcription factor Foxp3 and the above mentioned CTL-4 are involved in this process since the inactivation of the latter factor abolishes the tolerogenic action of Tregs, downregulation of the MHC class II complexes and costimulatory ligands as B1, B2 and CD40.[87,88,113 - 117] Interestingly, one of the latter groups found the IL-4, -5, -13 and IFN-? levels decreased during allergic inflammation upon VD treatment.(Calcitirol treatment decreased il-4(the 'master' cytokine in charge of differentiating other cytokines in the TH2 type . Not to be confused with GATA3- who is the master regulator)[113]

As for the regulatory, that is, tolerogenic T cells, it is important that the 'immunomodulant'[118] VDR favors the differentiation to 'tolerogenic' Tregs, more precisely to CD4+ CD25+ Fox3+ cells producing mainly IL-10, TGF-? but less NF-?B and AP-1 than other T cells.[93,119] Infact, VD also upregulates the expression of CTLA-4 and Foxp3 more exactly CD4+ CD25+ Fox3+ cells.[80] Finally, it is probably worth mentioning that VDR shifts the balance of Th1 versus -2 cells toward the latter(that was the common consensus reached by other studies too). This fact is amply proven by the clinical findings discussed in the second part of the review and some experimental data (vide infra). Nevertheless, this phenomenon does not seem to be quite evident, since VDR inhibits the activity of both the Th1 and -2 cells as discussed below.(This study found that consensus to be contrary) It might probably be explained by the radical reduction of Th1-type cells (vide infra), which under physiological conditions tonically inhibit the Th2 cells, that is, the altered balance might be due to desinhition of Th2 cells.

[eldarlmario]

The sum of these events might result in the enhancement of certain Th2 cell functions, that is, an enhanced propensity toward asthma, allergy, eczema and related disorders at least under experimental conditions,[131] but as discussed in the next part of this review, under clinical conditions VD rather suppresses the atopic disorders.(Calcitirol suppresses TH2-mediated immune responses instead of promoting it. Taken in context- this means it suppresses the majority of immune responses in AGA)

According to several early studies in human T lymphocytes, VD inhibits the production of IgM and IgE(pro-inflammatory Immunogoblin B cells in the blood that mediates allergy responses) by the B cells,[132 - 134] though VD upregulates the GATA-3[135] one of the main transcription factors of Th2 cells. It is tempting to use these experimental findings for interpretation of clinical findings but these studies have not been either repeated or confirmed during the last 20 years.

Further immune effects of calcitriol include suppression of T lymphocyte proliferation in humans,[129] presumably by inhibition of IL-2 production, inhibition of B-cell proliferation and antibody production by them in humans and animals,[40,134 - 136] and inhibition of chemokine-mediated migration and homing (into the lymph nodes) of naive and effector CD4+ T cells and macrophages due to blocking upregulation of E selectin ligands.[136 - 138]

A final earlier neglected point is inhibition by VD Th17 cells and IL-17 production. IL-17 as a newly described cytokine was isolated from TCR-C4-CD8- mouse thymocytes by Kennedy et al.[139] still in 1996, but its physiological and pathological significance has been recognized only a decade later. The IL-17-producing CD4+ cells are termed Th17 cells and are considered pathogenic.[140 - 144] Discussed above, Th17 cells are cytotoxic like the Th1 cells but this lineage is not identical to previously known lineages.[140,141,144] The mature Th17 cells are not suppressed by either Th1 or Th2 cytokines and they are independent of the transcription factors of the former T cells.[140] The development of these Th17 cells is inhibited by both IFN-? and IL-4.[140] In one study, the Th1 pathway antagonized the Th17 one[135] but this work has not yet been confirmed. In mice, Treg cells inhibit Th17 cell responses by IL-10.[145] Thus, Th1 and -17 represent different lineages, but their physiological functions are similar and both are antagonized by Treg cells.[140] That is, Treg cells might be physiological antagonists of both subsets of cytotoxic T cells.

[eldarlmario]

btw a trivial:

This seems to fit the theory of those who preach that AGA is atually a condition induced by bacteria on the scalp:

http://en.wikipedia.org/wiki/Cathelicidin

[eldarlmario]

Now as for VD, IL-17 enhances the expression of cathelicidin in human keratinocytes but only in the presence of this vitamin. Otherwise according to some very recent studies, VD also inhibits the Th17-mediated immune functions.[86,155,156] Chang et al. found that in mice, VD inhibited the expression of IL-17 at the level of translation, more precisely via enhanced expression of C/EBP homologous proteins known to inhibit the process of translation and ameliorated experimental encephalomyelitis.[155] VD also inhibits experimental autoimune uveitis by suppressing TH17 polarization.[156] In another study made on stimulated peripheral blood mononuclear cells taken from patients in the early stage of rheumatoid arthritis, VD inhibited the expression of IL-17A, IFN-? and IL-4.[157] VD combined with vitamin A blocked the expression of IL-17 and -23 in both naive and in human CD4+ memory cells.[158] The physiological significance of these findings is proven by the study of Bruce et al. who found that in VDR knockout mice, the number of Th17 cells was higher and the experimentally induced bowel disease was aggravated.[159](in summary- Cacitirol suppresses Th17-mediated autoimmune responses too)

[eldarlmario]

Epidemiological & Genetic Data

Acccording to some recent studies and meta-analyses, serum VD level is reduced in asthma patients and in other diseases accompanied with reduced FEV1, for example, according to the meta-analysis of Paul et al., in the USA 61% of young asthmatics have VD deficiency.[183] Nevertheless, they concluded that "VD supplementation as a preventive or secondary treatment is advisable and must await results of ongoing trials...".[183] Recently, Morales et al. reported that higher maternal circulating VD concentrations were associated with a lower risk of respiratory tract infection in childhood but not with less wheezing and asthma.[184] Thus, the etiological role of VD is not fully proven. However, two groups noted recently that low serum VD level in asthma was associated with impaired lung function, FEV1, airway hyperresponsiveness and reduced therapeutic efficacy of inhaled corticosteroids.[185,186] Wjst et al. came to the conclusion that in spite of the significant influence of external factors such as dietary intake and exposure to sunshine, the serum 25-OH-D3 (calcitriol) level seems to be a heritable trait in families with asthma.[45] Their conclusion was confirmed by several other groups.[28,187] Thus, VD hypovitaminosis is really an etiological factor in asthma, which is, however, also dependent on genetic disposition. Therefore, VD supplementation is apparently at the threshold of becoming a standard component of asthma prevention and its secondary/adjunct treatment as put forward by Majak et al..[185] Nevertheless, the situation is complicated by several further confounding factors:

Low VD serum level is associated with increased airway smooth muscle mass, which is not secondary to asthmatic inflammation, nevertheless it may aggravate the eventually coexisting asthma;[188,189]

Solar exposure in the vicinity of the equator might be beneficial for increasing the synthesis of VD but the same climate per se favors to allergic sensitization;[190,191]

VD as an overall immunosuppressant agent might be favorable in asthma treatment but the shift of the Th1/2 balance toward the latter could facilitate the development of asthma;

Both too low and too high VD levels have been found to enhance sensitization to aeroallergens;[191]

Finally, an unexplained finding that in the brochoalvelar lavage, but not in the serum, the level of VD binding protein is particularly high in severe therapy-resistant asthma.[192]

If VD is really linked to the genesis of asthma, the eventual polymorphism of the VDR gene is expected to be associated with the prevalence of asthma. In most related studies, the polymorphism of the VDR gene was examined by restriction enzymes (Bsml, Apal, TaqI and so on).[193] In some studies, the polymorphism of genes coding for the enzymes involved in the synthesis of VD[8,194] has been observed. Certain variants identified by restriction length polymorphism of VDR showed statistically significant but modest correlation with the prevalence of asthma.[195 - 199] Wjst et al. found a single-base variation in the VDR gene upon comparing asthmatic and their unaffected siblings.[198] Thus, they concluded that VDR exerts protective action against asthma. As mentioned above, the genetic polymorphism of VD binding protein in the plasma has been linked to airway diseases.[200] Others detected gene variants expressed in human activated NKT cells or CD8+ lymphocytes.[197] Finally, in a recent study by Bener et al., they found that more than a third of the asthmatic children had positive familial history of asthma and/or VD deficiency.[201] Truly in an earlier work[202] the VDR gene was found associated with asthma. Probably in this earlier work the technique used was not sophisticated enough. (In summary- Vitamin D deficiency could be the pathological cause of asthma AND AGA because we ARE having 'asthma of the balding scalp. Rememeber- CRTH2 inhibitors are originally designed for asthma and the 'allergen' in AGA is sadly- our hair follicles.'

and the study goes on and on and on(9 pages long)

So please ready the study yourself and i will just post the conclusion of this study:

Five-year View
It can be hoped that the public health significance of undiagnosed VD hyopvitaminosis(suggesting that pathology of AGA could be due to a lack of Cacitirol-activated Cacitirol Receptor levels on the balding scalp) will be finally recognized first by the medical community then by society in general(It might be- Multiple ethinc groups living north of the Equator has a lack of vitamin D levels in their body- not to mention that Vitamin D was only originally classed as a vitamin(the name of it already tells us so) before being reclassed as a critical nuclear hormone that has diverse fucntions in the human body- particularly Calcium homeostasis and the Immune system. Coupled with the fact that the Pax1 gene is in charge of sclerotome planning of the spine and skull, and is also expressed on the adult human scalp- there remains the possibility that variants in the region of the Pax1/foxa2 locus is influencing VDR's function(atually it is indeed doing so by altering VDR's 'binding site'- as indicated by the Scoliosis study)- localized to the balding scalp and skull) Hopefully more and more lay people will understand that VD deficiency is a risk factor of many diseases affecting broad segments of society just as the lack of vitamin C, certain minerals, unhealthy nutrition and so on are detrimental. In an ideal scenario, complaint-free people will be regularly screened not only for hypertension, diabetes and various types of cancer but also for VD hypovitaminosis. Epidemiologists might provide more data on that which factors of living conditions and eating habits contribute to VD hypovitaminosis, which has already reached epidemic proportions.

[eldarlmario]

Guys remember i said i was certain i wasnt really imagining things about this chronic and annoying weird inner ear problem i have. Remember I said i had 1)chronic tinnitus, 2)had a nerve'twisted' in my head whenever i adjust my jaw or moved my neck, 3)inner ear pain:

and i suspect this gene has got to do with it

H6 family homeobox 2 <====Inner ear and vestibular function (altered gene by the Pax1/Foxa2 AGA/Scoliosis haplotype variant)

and i've got a slightly-curved spine diagnosed by my school medical team during my elementary school days.

look what i just found today:

http://immortalhair.forumandco...oulders-are-misaigned

"My left shoulder is higher then my right one(Idiopathic Scoliosis) and it could be the reason maybe why I had this ringing in my right ear(Tinnitus) for 2 years. I did a free chiropractic consultation."

I thought they were BSing me just to say that for me to come in and make some coin, but I look in the mirror and its pretty noticable, had a family member comment on it the same day and I didnt even tell them about the consultation.

Anyone here have any experience with one?



"1)chronic tinnitus, 2)had a nerve'twisted' in my head whenever i adjust my jaw or moved my neck, 3)inner ear pain"

http://www.youtube.com/watch?v=xoml9njNExI

[eldarlmario]

The position of the Atlas influences the entire body

In a chain-reaction process, a misalignment of the Atlas may cause asymmetries of the entire skeleton, such as one shoulder being higher than the other with pain in the scapula, scoliosis, tilted pelvis with consequent danger of herniated discs (discopathy), pain in the back, hips, knees and even feet.

As long as postural defects exist, permanent muscular tension develop which, as well as being painful, can cause other vertebrae in the column to become blocked (subluxations).

The resulting subluxations may create persistent compression on certain nerve roots. More and more frequently doctors use cortisone against those irritations, which is indeed a useful medicament, but which causes severe, well noted side effects in the long term.

Compression of certain nerves (leads to pins and needles) in arms and legs, while the pressure put on other nerves leads to malfunctions in the corresponding organs. This gives rise to a series of disturbances, even in apparently unrelated areas of the body.

Enlarged, hardened muscles as a result of constant tension compress lymphatic structures as well as the arteries and veins which run between these muscles. This leads to decreased blood flow and a build-up of metabolic waste products in the tissue. This condition causes a vicious circle, making the muscles even more rigid.

Certainly, there are other factors to be taken into account which can affect a symmetrical, upright posture of the body. However, misalignment of the Atlas can be absolutely decisive. Experience has shown that in many cases - after a simple correction of the Atlas - the skeleton consequently takes on a more correct and natural shape.

If one shoulder is higher than the other or the pelvis is tilted, complaints are inevitable, sooner or later.

everything is true. that's what i have been complaining about the lymph nodes below my jawline and under my ears for a longtime.

[eldarlmario]

Atlas Verterba:

[eldarlmario]

https://en.wikipedia.org/wiki/Vertebral_artery

[eldarlmario]

The topmost area with the veins coloured in yellow is where im having my lifelong-chronic discomfort that began during puberty Guess where 1 of the blood arteries lead to? Yes- the temples