Discussion in 'Hair Loss and Alopecia Published Studies' started by squeegee, Jan 8, 2011.
I have the answer. It's somewhere between :dunno: and :dunno:
Diseases like Diabetes have reported lower circulation of progenitor cells...this is maybe why insuline resistance or cardiovascular diseases have a relation with male pattern baldness... DHT maybe has to do with something also...Something that accelerate apotosis (cell death). I bet Hairloss start with a thyroid problem.. which control your metabolism state... then your hormones goes imbalance.. you body slow down producing Pregnenolone ..the mother of all hormones... from cholesterol.. then you body go pro-dht ( inflammation. free radicals...) and problems start and never stop. That's the thing about male pattern baldness.. it is a cascade of lot of things... this is why the cure doesn't exist yet..... arghhhhhhhhhhh
Interesting reading: Effect of 5 -Dihydrotestosterone and
Testosterone on Apoptosis in Human
Dermal Papilla Cells
http://www.crcberlin.com/fileadmin/date ... iarska.pdf
CHRONIC INFLAMMATION, HAIR LOSS, AND WHAT YOU CAN DO ABOUT IT
Chronic systemic inflammation has been found to at the root of many serious disorders, such as cardiovascular disease, asthma, arthritis, cancer, diabetes, depression and androgenetic alopecia. These â€œage relatedâ€ disorders are accompanied by a pathological increase of inflammatory cytokines. Lowering pro-inflammatory cytokines, such as tumor necrosis factor â€“alpha, interleukin â€“ 6, interleukin 1(B) and/or interleukin B4, could help prevent and treat many age related diseases. After several published studies, which showed that inflammation is present in androgenetic alopecia, male pattern baldness Research reported these important findings to readers, particularly stressing the need to address inflammation in any hair loss treatment approach, including our recommended protocol. Excessive levels of cytokines can be systemically and topically countered by an appropriate regimen of drugs, nutrients, dietary changes, and/or hormones. For example, fish oil has been shown to effectively lower these levels, as does DHEA, Nettle extract, GLA, and some antioxidants (vitamin E and N-acetyl cysteine). Meanwhile certain herbal extracts patented by Asian companies, Emu oil, copper peptides and ketoconazole can be used to topically partially inhibit cytokine formation. Following is an extensive analysis (in laymanâ€™s terms) that makes the connection between inflammation, and the â€œprogrammed cell deathâ€ of the hair follicle, a process known as â€œapoptosisâ€. It is partially based upon input from Waseda, a Japanese researcher who has been researching inflammation and androgenetic hair loss for many years. He has been able to initiate extensive hair regrowth after being a â€œslick baldâ€ Norwood 5 for many years using an aggressive combination of therapies specifically designed to counter inflammation and an apoptosis factors.
TOWARDS A COMPREHENSIVE TREATMENT OF male pattern baldness
First we must recognize that hair loss is the consequence of hair cell apoptosis, or programmed cell death. Apoptosis is the final result of what is termed the caspase activation cascade. Essentially DHT, superoxide, and other free radicals damage the cellâ€™s mitochondria, and the damaged mitochondria in turn vomits cytochrome C, which activates the caspase 9 cascade. TGF-beta and alpha activate caspase 9 around hair follicles. The activated caspase 9 propagates downstream into caspase 3. Activation of caspase 3 is thought to be a direct cause of cell apoptosis (programmed cell death) in general. What then causes a caspase activation cascade and how can one intervene in the context of hair loss?
Protein Kinase C (PKC) as an executor of apoptosis PKC isozymes are involved in the final execution of hair cell apoptosis in relation to caspase 3. What are good inhibitors of PKC? Cycloporin (dangerous), Grape Seed Extract, Resveratrol (as in red wine), Vitamin E, and N-Acetyl Cysteine. Topically, Grape Seed Extract (a patented treatment for hair loss), and Perilla Leaf Extract.
Tumor Necrosis Factor Alpha (TNF-a) as a promotor of PKC and hair cell apoptosis. TNF-a induces the PKC isozymes and causes cell death through this induction. This pathway is known to be a major cause of hair loss. TNF-a is a quick acting proinflammatory cytokine, and TNF-a is over secreted in cases of rapid hair loss. How can TNF-a be safely inhibited? Ginkgo Biloba Extract, Stinging Nettle Extract, Green Tea Extract, and essential fatty acids found in fish, Emu, Borage, and Perilla oils. Topically, Perilla leaf extract may be useful.
TGF-Family as the bridge between DHT and the activation of the caspase cascade. In recent studies researchers have found DHT promotes TGF, and TGF causes activation of the caspase cascade and thus, hair cell death, which clinically manifests as male and female pattern baldness. What inhibits TGH safely, as opposed to the dangerous anti-cancer compounds? Proteolytic Enzymes such as a bromelain, and the anti-oxidant Curcumin are TGF inhibitors. Shiseido, a Japanese cosmetic company found that Amacha, a sugar alternative found in the orient has TGF inhibition properties. Dr. Sawayaâ€™s latest study about finasteride suggests that the best hair loss prevention would involve the blocking of caspase activation, especially caspase 3. Caspase 3 is the direct cause of programmed hair cell death (apoptosis) that originates â€œupstreamâ€. The first triggers may be DHT damage or oxidative (free radical) stress on the mitochondria, TGF induction from DHT, TNF-A induction from allergic inflammation, or PKC upregulation by caspase activation. Here we can summarize the rationale behind the treatments of various pro-inflammatory mechanisms.
DHT inhibition- Finasteride, Saw Palmetto, Rivoflavin, Green Tea Extract, Copper, Peptides, and Topical Bayberry Extract.
PKC down regulation - Grape Seed Extract, Resveratrol, Vitamin E, Soy Isoflavones.
TNF-a down regulation- Curcumin, Ginkgo Biloba Extract, Stinging Nettle Extract, Green Tea Extract, Fish Oil, Borage Oil, Perilla Oil, and Topical Perilla leaf extract.
TGF down regulation- Curcumin, and topical Amacha.
Taking into account the inhibition of hair apoptosis factors, it is apparent that treatment can be taken to a new level. Again, Waseda himself is experiencing regrowth in all areas of his scalp after being a slick bald â€œNorwood 5â€ for many years.
Thyroid hormone effects on mitochondrial energetics.
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ME Harper, EL Seifert
Thyroid hormones are the major endocrine regulators of metabolic rate, and their hypermetabolic effects are widely recognized. The cellular mechanisms underlying these metabolic effects have been the subject of much research. Thyroid hormone status has a profound impact on mitochondria, the organelles responsible for the majority of cellular adenosine triphosphate (ATP) production. However, mechanisms are not well understood. We review the effects of thyroid hormones on mitochondrial energetics and principally oxidative phosphorylation. Genomic and nongenomic mechanisms have been studied. Through the former, thyroid hormones stimulate mitochondriogenesis and thereby augment cellular oxidative capacity. Thyroid hormones induce substantial modifications in mitochondrial inner membrane protein and lipid compositions. Results are consistent with the idea that thyroid hormones activate the uncoupling of oxidative phosphorylation through various mechanisms involving inner membrane proteins and lipids. Increased uncoupling appears to be responsible for some of the hypermetabolic effects of thyroid hormones. ATP synthesis and turnover reactions are also affected. There appear to be complex relationships between mitochondrial proton leak mechanisms, reactive oxygen species production, and thyroid status. As the majority of studies have focused on the effects of thyroid status on rat liver preparations, there is still a need to address fundamental questions regarding thyroid hormone effects in other tissues and species.
Thyroid hormone action in mitochondria.
Wrutniak-Cabello C, Casas F, Cabello G.
UMR DiffÃ©renciation Cellulaire et Croissance (INRA, UniversitÃ© Montpellier II, ENSAM), UnitÃ© d'Endocrinologie Cellulaire, INRA, 2 Place Viala, 34060 Montpellier Cedex 1, France.
Triiodothyronine (T3) is considered a major regulator of mitochondrial activity. In this review, we show evidence of the existence of a direct T3 mitochondrial pathway, and try to clarify the respective importance of the nuclear and mitochondrial pathways for organelle activity. Numerous studies have reported short-term and delayed T3 stimulation of mitochondrial oxygen consumption. Convincing data indicate that an early influence occurs through an extra-nuclear mechanism insensitive to inhibitors of protein synthesis. Although it has been shown that diiodothyronines could actually be T3 mediators of this short-term influence, the detection of specific T3-binding sites, probably corresponding to a 28 kDa c-Erb Aalpha1 protein of the inner membrane, also supports a direct T3 influence. The more delayed influence of thyroid hormone upon mitochondrial respiration probably results from mechanisms elicited at the nuclear level, including changes in phospholipid turnover and stimulation of uncoupling protein expression, leading to an increased inner membrane proton leak. However, the involvement of a direct mitochondrial T3 pathway leading to a rapid stimulation of mitochondrial protein synthesis has to be considered. Both pathways are obviously involved in the T3 stimulation of mitochondrial genome transcription. First, a 43 kDa c-Erb Aalpha1 protein located in the mitochondrial matrix (p43), acting as a potent T3-dependent transcription factor of the mitochondrial genome, induces early stimulation of organelle transcription. In addition, T3 increases mitochondrial TFA expression, a mitochondrial transcription factor encoded by a nuclear gene. Similarly, the stimulation of mitochondriogenesis by thyroid hormone probably involves both pathways. In particular, the c-erb Aalpha gene simultaneously encodes a nuclear and a mitochondrial T3 receptor (p43), thus ensuring coordination of the expression of the mitochondrial genome and of nuclear genes encoding mitochondrial proteins. Recent studies concerning the physiological importance of the direct mitochondrial T3 pathway involving p43 led to the conclusion that it is not only involved in the regulation of fuel metabolism, but also in the regulation of cell differentiation. As the processes leading to or resulting from differentiation are energy-consuming, p43 coordination of metabolism and differentiation could be of significant importance in the regulation of development.
Tagawa N, Tamanaka J, Fujinami A, et al.
Clin Chem. 2000 Apr; 46(4):523-8.
BACKGROUND: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to have protective effects against cardiovascular disease, cancer, immune-modulated diseases, and aging. We examined serum concentrations of DHEA, DHEA-S, and pregnenolone sulfate (PREG-S) in patients with thyroid dysfunction. METHODS: Steroids extracted with methanol from serum sample were separated into an unconjugated fraction (DHEA) and a monosulfate fraction (DHEA-S and PREG-S), using a solid-phase extraction and an ion-exchange column. After separation of unconjugated steroids by HPLC, the DHEA concentration was measured by enzyme immunoassay. The monosulfate fraction was treated with arylsulfatase, and the freed steroids were separated by HPLC. The DHEA and PREG fractions were determined by gas chromatography-mass spectrometry, and the concentrations were converted into those of DHEA-S and PREG-S. RESULTS: Serum concentrations of DHEA, DHEA-S, and PREG-S were all significantly lower in patients with hypothyroidism (n = 24) than in age- and sex-matched healthy controls (n = 43). By contrast, in patients with hyperthyroidism (n = 22), serum DHEA-S and PREG-S concentrations were significantly higher, but the serum DHEA concentration was within the reference interval. Serum concentrations of these three steroids correlated with serum concentrations of thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentration of steroids. CONCLUSIONS: Serum concentrations of DHEA, DHEA-S, and PREG-S were decreased in hypothyroidism, whereas serum DHEA-S and PREG-S concentrations were increased but DHEA was normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids, and DHEA sulfotransferase might be increased in hyperthyroidism
It makes sense. But it could be completely insanely nonsensical. Maybe we should run it by some "experts"? I'll see if I can get a response from Dr. Y on it. Someone else try Dr. P. Another try....I'd better not mention his name. I think he sued one of these sites or something. Think- meds...in the back seat/window of a car..very hot outside... :shock: Or how about that alopecia research site....wonder if they respond to inquiries.
Well I got a response but he won't have a response until they're up and running again in Oct. At least he wasn't kidnapped. :shock:
OBJECTIVE Endothelial progenitor cells (EPCs) are decreased in number and function in type 2 diabetes. Mechanisms by which this dysfunction occurs are largely unknown. We tested the hypothesis that a chronic inflammatory environment leads to insulin signaling defects in EPCs and thereby reduces their survival. Modifying EPCs by a knockdown of nuclear factor-?B (NF-?B) can reverse the insulin signaling defects, improve EPC survival, and decrease neointimal hyperplasia in Zucker fatty rats postangioplasty.
RESEARCH DESIGN AND METHODS EPCs from Zucker fatty insulin-resistant rats were cultured and exposed to tumor necrosis factor-? (TNF-?). Insulin signaling defects and apoptosis were measured in the presence and absence of an NF-?B inhibitor, BAY11. Then, EPCs were modified by a knockdown of NF-?B (RelA) and exposed to TNF-?. For in vivo experiments, Zucker fatty rats were given modified EPCs postâ€“carotid angioplasty. Tracking of EPCs was done at various time points, and neointimal hyperplasia was measured 3 weeks later.
RESULTS Insulin signaling as measured by the phosphorylatedâ€“toâ€“total AKT ratio was reduced by 56% in EPCs exposed to TNF-?. Apoptosis was increased by 71%. These defects were reversed by pretreatment with an NF-?B inhibitor, BAY11. Modified EPCs exposed to TNF-? showed a lesser reduction (RelA 20%) in insulin-stimulated AKT phosphorylation versus a 55% reduction in unmodified EPCs. Apoptosis was 41% decreased for RelA knockdown EPCs. Noeintimal hyperplasia postangioplasty was significantly less in rats receiving modified EPCs than in controls (intima-to-media ratio 0.58 vs. 1.62).
CONCLUSIONS In conclusion, we have shown that insulin signaling and EPC survival is impaired in Zucker fatty insulin resistant rats. For the first time, we have shown that this defect can be significantly ameliorated by a knockdown of NF-?B and that these EPCs given to Zucker fatty rats decrease neointimal hyperplasia postâ€“carotid angioplasty.
I saw in this tread back in early 2011, that people were talking about AC-11 and Samento drops.
Did anyone try Samento drops directly to the scalp? that some were talking about trying?
I used the RepHair shampoo and leave-in spray for some time. It seems the AC-11 has something or more of something than other Cat's Claw extracts.
I wouldn't mind adding it to a custom topical..I'll either be doing that soon or going on RepHair again for awhile.
As good a place as any to post this...
what does it have to do with hair at all? :dunno:
There are a # of posts here and in other hair loss forums on telomeres. I think a bunch on the graying of hair as well.
One tidbit: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361120/
my god... stop picking at all those obscure studies.
proliferation happens by itself, the MAIN PROBLEM is that something INHIBITS SUCH FUNCTION(coughs... PGD2.. coughs...). THERE IS YOUR PROBLEM! IF YOU'RE NOT TARGETING THE MAIN PROBLEM, YOU'RE WASTING TIME
You realize you're doing the same thing IH has done for years? Like him..you too..years from now..will still be claiming to know how to fix the problem...
But what happend to "what does it have to do with hair at all?" :laugh:
we know DHT blocking works and we can kind of assume that PGD2 blocking would work as well.... anything that does "something else" is useless...
seriously, what is lamas scalp serum?? Where do you find these things wow