Conventional Hair Loss meets Alternative views: The role of inflammation in the gene expression and activation of sex hormone receptor sites

anthonyspencer54 wrote:Hey Floppy,

I think there are more appropriate forums for you to be on. I believe there is hope for you to solve
your problem, and if not, there are plenty of people out there who are completely fine with a small penis.

SlowMoe wrote:I think old flop might be stalking me.

a

SlowMoe wrote:I think old flop might be stalking me.

You and me both man, make sure no private information is here on this forum.

anthonyspencer54 wrote:Haha, sorry SlowMoe, I jumped on here too quick and responded to a spammer. Lesson learned when their comment is removed, I look stupid.

Anyhow, my thoughts on circulation...

First of all, I don't believe hairloss can really be an issue of general circulation. If this was the case we'd see some type of gradient in thinning, with hair getting progressively thinner from the crown down to the neckline. But we don't see this. Unless there is some type of physical barrier there (I haven't seen any research on the Galea theory that leads me to believe it) I'm unaware of that creates the typical MPB line, there must be an issue with micro-circulation specific to the hair bulb itself, perhaps the result of sex hormone related inflammation and subsequent calcification.

If that is the case, the environment would support bacterial invasion. This could easily play a role in the entire chain of events and augment that inflammation already present in the region. So you might be on something there. For me, the difficulty is establishing the chronology. Which came first?

Sex hormone > High distribution of receptors made more sensitive by various inflammatory factors > localized inflammation > degradation of bulb and surrounding capillaries > low oxygen environment > bacterial invasion > more inflammation and immune attack > hair thinning

or...

bacterial invasion > inflammation and hyper immunity localized to hair bulb > vascular damage > low oxygen > promotes maintenance of infection > chronic inflammation and hair thinning

I'm racking my brain trying to determine what the intended target of the lymphocyte attack is. If not infection, what other reason? Autoimmune attack due to sex hormones? (I would love to know if it is possible because that would have huge effects for aging theories). Or perhaps some type of adverse lipidemia inciting the inflammation and immune deposition?

Any and all of the inflammation would only be added to by any dietary factors, heavy metal toxicity (oxidation and immune evasion for pathogens), poor thyroid function (even less oxygen delivery), poor thyroid function and bacterial toxic products lower insulin sensitivity (also compounded by the inflammatory state of leptin resistance) leading to improper blood glucose maintenance which exacerbates the inflammation and any infection present. I picture a coach trying to draw out a complicated football play on a dry erase board for a bunch of 5 year olds and they all just have a poker face '_'. I feel like a five year old trying to envision all of the the different interaction variables here. This would be a damn statistical mess.

Microvascular Complications of Impaired Glucose Tolerance

J. Robinson Singleton1,
A. Gordon Smith12,
James W. Russell3 and
Eva L. Feldman3

+ Author Affiliations

1Department of Neurology, University of Utah, Salt Lake City, Utah
2Department of Pathology, University of Utah, Salt Lake City, Utah
3Department of Neurology, University of Michigan, Ann Arbor, Michigan

Address correspondence and reprint requests to Eva L. Feldman, Professor and Director, JDRF Center for the Study of Complications in Diabetes, University of Michigan, Department of Neurology, 4414 Kresge III 200 Zina Pitcher Place, Ann Arbor, MI 48109. E-mail: efeldman@umich.edu

Abstract

Impaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both large- and small-vessel vascular complications, independent of a patient’s progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known.

Mechanisms of disease: Pathway-selective insulin resistance and microvascular complications of diabetes.
Groop PH, Forsblom C, Thomas MC.
Source

Helsinki University Central Hospital, Finland. per-henrik.groop@helsinki.fi
Abstract

Resistance to the actions of insulin is strongly associated with the microvascular complications of diabetes. To the extent that insulin resistance leads to hyperglycemia, dyslipidemia and hypertension, this association is not surprising. It is now clear that insulin also has direct actions in the microvasculature that influence the development and progression of microvascular disease. In the healthy state, insulin appears to have only minor effects on vascular function, because of the activation of opposing mediators such as nitric oxide and endothelin-1. Diabetes and obesity, however, are associated with selective insulin resistance in the phosphatidylinositol-3-kinase signaling pathway, which leads to reduced synthesis of nitric oxide, impaired metabolic control and compensatory hyperinsulinemia. By contrast, insulin signaling via extracellular signal-regulated kinase dependent pathways is relatively unaffected in diabetes, tipping the balance of insulin's actions so that they favor abnormal vasoreactivity, angiogenesis, and other pathways implicated in microvascular complications and hypertension. In addition, preferential impairment of nonoxidative glucose metabolism leads to increased intracellular formation of advanced glycation end products, oxidative stress and activation of other pathogenic mediators. Despite a strong temporal association, a causal link between pathway-selective insulin resistance and microvascular damage remains to be established. It is possible that this association reflects a common genotype or phenotype. Nonetheless, insulin resistance remains an important marker of risk and a key target for intervention, because those patients who achieve a greater improvement of insulin sensitivity achieve better microvascular outcomes.

PMID:
16929378
[PubMed - indexed for MEDLINE]

"Insulin resistance is the harbinger of metabolic syndrome. Insulin resistance is when the body cannot use insulin effectively. As a result, blood sugar and fat levels rise. Therein lies the path to morbid obesity, diabetes, stroke, and heart problems. A group of Brazilian researchers have taken a strain of mice normally known to be immune to insulin resistance, and made them insulin resistant (pre-diabetic) by changing their gut bacteria. They then gave the mice antibiotics, and by changing their gut bacteria again, reversed the process, curing them of the disease. Their research shows just how influential the bacteria living in our gut can be on our health."

Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice

Andréa M. Caricilli1, Paty K. Picardi1, Lélia L. de Abreu2, Mirian Ueno1, Patrícia O. Prada1, Eduardo R. Ropelle1, Sandro Massao Hirabara3, Ângela Castoldi4, Pedro Vieira4, Niels O. S. Camara4, Rui Curi3, José B. Carvalheira1, Mário J. A. Saad1*

1 Department of Internal Medicine, State University of Campinas, Campinas, Brazil, 2 Department of Nursing, State University of Campinas, Campinas, Brazil, 3 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, 4 Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
Abstract Top

Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics), the metabolic characteristics, and insulin signaling in TLR2 knockout (KO) mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes, and even other immunological disorders.

SlowMoe wrote:Here's what I'm curious about. 

Floppy posted a study where the circulation theory was debunked by transplanting MPB hairs to other areas of the body where circulation was better, and they continued to die.

What I am wondering, is why there are ZERO clinical studied where the control group simply had their head brushed or massaged for 15 minutes a day. I mean the theory had been out there for a hundred years at least! 

Why hasn't there been ONE study performed on humans where increased blood flow to the head was the only variable. 
Not one!
 
About the "MPB line".... I have noticed that during times of stress, the skin on my scalp is very tight, but ONLY in the MPB areas! On either side of the balding areas, the skin is loose and elastic. When I massage the sides of my head where the scalp muscles are it becomes much looser.

So on my scalp, there is definately a correlation between tightness (and assumed poor bloodflow) and hair loss. 

Also- I noticed that when I first started brushing my hair, my s alp was very sensitive and it hurt alot o brush (inflammation?). A couple weeks into it, no pain at all...