Hair Loss

Redox signaling is an important component of hair regrowth, hair loss and hair loss treatment.

Ther Umsch. 2002;59:21
Pattern Hair loss in men
Bader U, Trüeb RM.

edited for hair loss hair regrowth blog

Male pattern hair loss occurs in approximately 40% of men at the age of 40 and 50% at 50, respectively. Especially for young men progressive hair loss can be distressing. Therefore, understanding of these patients’ concerns is important for appropriate management. Current understanding mainly focuses on androgen metabolism as it affects hair growth. As a result, hair loss treatment has made considerable progress through the introduction of selective 5 alpha-reductase inhibition with finasteride. In trials in men with AGA, treatment with oral finasteride worked. Options for advanced pattern hair loss not amenable to drug treatment are autologous hair transplantation and hair replacement.

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Singh G. Androgenic alopecia. Indian J Dermatol Venereol Leprol 2002;68:40

The treatment of androgenic alopecia is first minoxidil 2% solution, I ml to be applied topically twice daily. The patient is advised to use nizoral shampoo. In about one third of men, there is significant conversion of miniaturized hairs to terminal hairs. The response is better in younger males having a smaller area of hair loss that too in the early stage of baldness…….

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Genes Dev. 2008 Mar 1;22(5):654-67. Epub 2008 Feb 18.

The longest telomeres: a general signature of adult stem cell compartments.
Flores I,.et al

Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine (such as in hair loss treatment ). However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age.

A history of Redox signaling.

Redox cell signaling is an important process in hair loss and in the action of hair loss treatment agents such as minoxidil. E.g., the fibrosis (scaring) found in baling hair follicels is probably redox signaling mediated.

Lancet. 1977 Nov 12;2(8046):1002-3.

Induction of hair growth in alopecia areata with D.N.C.B.
Happle R, Echternacht K.

43 patients with hair loss due to alopecia areata were treated with dinitrochlorobenzene. A significant difference of hair regrowth between the treated and untreated sides was seen in 33 patients. 21 patients showed regrowth of hair exclusively on the treated side, and in 12 patients hair regrowth was considerably faster and more dense on the treated side.

eurosci. 1992 May;12(5):1896-905.

On the role of nerve growth factor in the development of myelinated nociceptors.
Lewin GR, et al

We have previously demonstrated that administration of antisera against NGF (anti-NGF) can have profound effects on developing primary afferents (Ritter et al., 1991). Chronic administration of anti-NGF to rats beginning on the day of birth results in a severe depletion of cutaneous A delta high-threshold mechanoreceptors (HTMRs) from the sural nerve. Here we have carried out further experiments in order to define the period of time over which this change in the cutaneous afferent population can be produced, and to investigate a possible mechanism for the change. Treatment with anti-NGF from postnatal day (PND) 0-14 resulted in a depletion of cutaneous A delta HTMRs from the sural nerve and also a 20% loss of sensory neurons. However, treatment from PND 2-14 produced an identical deficit of HTMRs without any accompanying cell death. Thus, the depletion of cutaneous A delta HTMRs can be achieved in the absence of cell death induced by anti-NGF treatment. snip.. This critical period, PND 4-11, corresponds to a period of anatomical change in the innervation of the skin, from epidermal innervation to primarily dermal innervation. In every case where anti-NGF treatment reduced the proportion of HTMRs, there was a reciprocal increase in the proportion of sensitive A delta hair follicle (D-hair) afferents. We hypothesize that in the absence of NGF, developing cutaneous A delta HTMRs do not die but innervate novel targets in the dermis and become D-hair afferents instead.

The concept that electronically activated species (free radicals and the like) have a messenger role is called Redox signaling. Redox signaling likely plays a key role in regulating the hair loss and hair regrowth cycle, as well as in mediating pattern balding itself.

Our studies demonstrate that the death of hair follicles involves distinct patterns of expression of active caspases. Active caspase 8, an initiator of the death receptor pathway, was predominately found in the isthmic and upper lower portion of the shaft. This pattern of expression suggests that the death receptor pathway is activated during hair renewal and is initiated by toxic substances that bind to death receptors, i.e., TNF-alpha. Interestingly, activated caspase 3, a downstream effector caspase, was higher in catagen hair then in other phases of the hair cycle, indicating a role in the terminal stage of the apoptotic pathway. Activated caspase 1 was also found in the hair bulb and hair shaft. .. Previously, the dermal papilla area of the hair follicle was thought to be the main control focus of cell regrowth and inhibition [25]. The findings from this study also suggest an important role of the upper-lower portion, infundibular area of the hair shaft where inner and outer root sheath are abruptly changing and that this area may play a role in the regulation of normal hair apoptosis. ….

Dr Proctor’s coments on Stroke and uric acid

Radiation-induced temporary alopecia after embolization of cerebral aneurysms
Nuria Marti, et al, Dermatology Online Journal 14 (7): 19

Abstract
A 29-year-old woman underwent 2 endovascular procedures for treatment of bilateral carotid-ophthalmic artery aneurysms. After each treatment, transient alopecia occurred over the occipital area and is presumed to be radiation induced.

Figure 1. Hair loss over her occipital area 2 months after initial embolization (A) and hair regrowth 1 year after the second embolization (B) Endovascular procedures have become widely used for the treatment of vascular lesions in the brain or spinal cord and their surrounding tissues. Radiation-induced adverse effects of endovascular procedures are seldom mentioned in the literature. Transient alopecia following a therapeutic embolization is a very rare complication [1, 2, 3, 4].

A 29-year-old woman was diagnosed with aneurysms of both carotid-opthalmic arteries. This patient had severe headache, but she was alert and oriented and without neurologic deficits. Her hair appeared normal.

The patient underwent two courses of embolization of the aneurysms with an interval of 3 months between courses. No neurologic deficits occurred after these procedures. However, hair loss over her occipital area was noted 2 weeks after the initial embolization. Physical examination revealed a 13 x 10 cm square patch of almost total hair loss on the occipital region.

The scalp was normal, exclamation-mark hairs were not visible; results of the pull test were normal. Her bilateral occipital and superficial temporal arteries had good pulses. A cutaneous biopsy was not performed because of the anticoagulant treatment of the patient. The hair regrew but 2 weeks after the second embolization, that was performed 3 months later, she again experienced the appearance of a similar patch of diffuse hair loss on the occipital scalp. The hair regrew 4 months after the occurrence of hair loss without treatment.

This patient underwent several angiographic examinations without side effects but alopecia appeared soon after the 2 courses of embolization. Hair loss due to arterial occlusion was considered unlikely. Radiation-induced hair loss was considered as the main cause for the hair loss in this patient. The estimated radiation exposure dose was more than 3 Gy.

J Exp Med. 1942;75:277

SYNTHESIS OF INOSITOL IN MICE.
Woolley DW.

It has been shown that mice are able to synthesize inositol. This synthesis was not observed when pantothenic acid (reported to stimulate hair regrowth ) was absent from the diet. Cultures from the intestinal tract of animals which exhibited spontaneous cure of alopecia (hair loss ) yielded microorganisms which synthesized much more inositol than did organisms isolated in the same fashion from the tracts of mice that had become hairless. Some observations on the distribution of free and combined inositol have been made and it has been shown that several biological materials contain combined inositol. It has been found that deficiency of inositol can develop even when inositol is present in the diet if pantothenic acid is omitted.

Edited for hair loss blog.

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Dr Proctor treats hair loss

Dr Proctor has one of the earliest organic semiconductors in the Smithsonian Chips collection of early electronic devices.

Interestingly, this is another thread of the same research process that eventually led Dr. Proctor to work on hair loss treatment and hair regrowth.

JAMA. 1976;235:2622-3.

Alopecia in crash dieters., Goette DK, Odom RB.

Nine patients experienced profuse hair loss two of five months after starting a vigourous weight reduction program resulting in weight loss of 11.7 to 24.75 kg. Telogen counts of 25% to 50% were observed. Regrowth of hair occurred within several months. Three patients had experienced hair loss closely following a successful weight reduction program on several occasions. Rigorous caloric restriction with subsequent inadequate energy supply of the hair matrix is thought to be the cause for the precipitation of the telogen effluvium of the crash dieter.

edited for hair loss blog

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