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Pattern Baldness In 3 Generatiins Of Addams Family

Puberty Hen

I 5.12 Pattern baldness is a sex-influenced trait. This trait is seen in three generations of the Adams family (a) John Adams (1735-1826), the second president of the United States, was father to (b) John Quincy Adams (1767-1848), who was father to (c) Charles Francis Adams (1807-1886). Pattern baldness results from an autosomal gene that is thought to be dominant in males and recessive in females. (Part (a) National Museum of American Art, Washington, D.C. Art Resource, NY (b) National Portrait Gallery, Washington, D.C. Art Resource, N.Y. (c) Bettmann Corbis.) An example of a sex-influenced characteristic in humans is pattern baldness, in which hair is lost prematurely from the front and the top of the head ( FIGURE 5.12). Pattern baldness is an autosomal character believed to be dominant in males and recessive in females, just like beards in goats. Contrary to a popular misconception, a man does not inherit pattern baldness from his mother's side of the family (which would be the...

Another Sex Influenced Trait Male Pattern Baldness

A more dramatic example of a sex-influenced trait is male pattern baldness. Because mostly men are affected, one might guess that it is a sex-linked trait. A classic case of male pattern baldness appears in President Adams's family. The second U.S. president, John Adams, and his son John Quincy Adams, the sixth president, as well as the latter's son and grandson, all had male pattern baldness. If this trait was on the X chromosome, as figure 3.2 shows, a father could not pass the trait onto his sons, meaning they must have received the trait from their mothers. However, it would be quite a coincidence if all four of the mothers of the individuals listed above were carriers of male pattern baldness. Actually, male pattern baldness is also a sex-influenced trait. The difference in the appearance of the trait is due to the hormonal differences between men and women. Thus in men the trait behaves as a dominant trait, while in women it behaves as a recessive trait.

Hair Follicles And Hair

Each hair follicle represents an invagination of the epidermis in which a hair is formed Hair follicles and hairs are present over almost the entire body they are absent only from the sides and palmar surfaces of the hands, sides and plantar surfaces of the feet, the lips, and the region around the urogenital orifices. Hair distribution is influenced to a considerable degree by sex hormones these include, in the male, the thick, pigmented facial hairs that begin to grow at puberty and the pubic and axillary hair that develops at puberty in both genders. In the male, the hairline tends to recede with age, and in both genders, the scalp hair thins with age because of reduced secretion of estrogen and estrogenlike hormones. The hair follicle is responsible for the production and growth of a hair. Coloration of the hair is due to the content and type of melanin (see page 409) that the hair contains. The follicle varies in histologic appearance, depending on whether it is in a growing or a...

Plate 43 Hair Follicle And Nail

Hairs are composed of keratinized cells that develop from hair follicles. Hairs are present over almost the entire body, being conspicuously absent only from the sides and palmar surfaces of the hands, from the sides and plantar surfaces of the feet, from the lips, and from the skin around the urogenital orifices. Coloration of the hair is due to the content and type of melanin that it contains. The follicle varies in appearance, depending on whether it is in a growing or a resting phase the growing follicle is the more elaborate. The skin appendages (adnexa), especially hair follicles and sweat glands, are particularly important in healing of skin wounds. They serve as the source of new epithelial cells when there is extensive loss of epidermis, as in deep abrasions and second-degree burns. The growing end of a hair follicle consists of an expanded bulb of epithelial cells that is invaginated by a papilla (HP) of connective tissue. The epithelial cells surrounding the papilla at the...

Dihydrotestosterone Metabolism

Dihydrotestosterone is metabolized rapidly in peripheral tissues. Different enzymes can use DHT as a substrate (Fig. 2.3). It can undergo reduction of the 3-ketone group to form either 5a-androstane-3a,17 -diol (also referred to as 3a-androstanediol or 3a-diol) via the enzyme 3a-HSD or 5a-androstane-3 ,17 -diol (3 -an-drostanediol or 3 -diol) via the enzyme 3 -HSD. These reactions are reversible. In vivo, the back-conversion of 3a-diol to DHT is greater than 50 .108 The former metabolite (3a-diol) is considered to have some androgenic activity.109 SRD5A AKR1C -DIHYDROTESTOSTERONE 5a-ANDROSTANE-3a,17B-DIOL Dihydrotestosterone (DHT)

Alopecia

A RCT of scalp massage using thyme, rosemary, lavender and cedarwood essential oils in 86 patients with alopecia areata found a significant improvement in hair growth after 7 months (Hay et al 1998). Although the efficacy of lavender as a stand-alone treatment was not clarified with this trial, it is known that the herb has some antibacterial and antifungal activity that may play a role. In a single case study, topical application of lavender, together with other essential oils, was reported to assist in treating scalp eczema (De Valois 2004).

Effect Does Not Equal Effect

The severity of the disease and dose. These nonstochastic effects occur mainly in radiation therapy. In interventional radiology and neuroradiology such as cardiovascular stenting or percutaneous treatment of complex arteriovenous malformations in the CNS, nonstochastic effects such as radiation-induced erythema, ulcerations, or hair loss have been reported anecdotally in patients undergoing complex procedures exposed to prolonged fluoro-scopy, for example. Obviously this also poses a serious threat to the physicians involved. Radiation-induced lens injury has been reported in interventional radiology.

Integumentary form and function

Teeth Herbivore Carnivore Adaptation

The dermis is mainly a supportive layer for the epidermis and binds it to underlying tissues. Blood vessels in the dermis pass near the basal layer of the epidermis and provide the cells of the avascular epidermis with nutrients. The dermis also contains muscle fibers, associated with hair follicles, and nervous tissue that provides assessment of the environment. A subcutaneous layer lies below the dermis and is a site of adipose (fat) deposition, which serves as both insulation and energy storage. Mammals have a number of skin glands that are found in no other vertebrate. Mammals have two types of coiled, tubular sweat glands, apocrine (or sudoriferous) and eccrine. Apocrine sweat glands are usually associated with a hair follicle, and secrete the odorous component of sweat. Eccrine sweat glands secrete sweat onto the surface of the skin to remove heat through evaporative cooling. Most mammals have both these glands in the foot pads. They are more widely distributed on a few mammals,...

Adjuvant Therapy For The Individual Patient

Adjuvant therapies now available and currently being investigated have been described in this chapter. For the individual patient assessed in the clinic, a decision must be made by the multidisciplinary team as to whether the patient is fit to receive any of these therapies. All treatments administered are likely to induce some toxic reaction, and these must be weighed against the benefits likely to be achieved. The different regimes with different drugs have their own individual side-effect profiles. These have been detailed in this text and in Chapter 17 when the drugs have been discussed in the metastatic colorectal setting. The risks of infection and thrombophlebitis associated with prolonged venous access, and the likelihood of inducing neutropenic incidents, as well as risks of other physical harm, must be assessed by the physician and presented to the patient. Patients would also have their own views as to which side effects are acceptable to them. Some may find the alopecia...

Complications Of Radiosurgery

It is true that there are almost no immediate complications of radiosurgery, but complications do occur. Such problems include small patches of alopecia for tumors adjacent to the scalp, brain edema, radiation necrosis, neurological deficits, and failure to achieve the intended goal. The risk of complications is a function of the tissue volume being treated, the dose delivered, the location, and prior radiation treatments.

Established Hidradenitis Suppurativa Fig 44ae

Inflammation Apocrine Glands

Histological changes in established HS. a Chronic folliculitis - dense lymphocytic infiltrate around hair follicle. b (i) Acute and chronic inflammatory cells around apocrine glands - low power. (ii) Acute and chronic inflammatory cells around apocrine glands - high power. c Pus in follicle. d Sinus tract formation. e Scarring around hair follicle Fig. 4.4 a-e. Histological changes in established HS. a Chronic folliculitis - dense lymphocytic infiltrate around hair follicle. b (i) Acute and chronic inflammatory cells around apocrine glands - low power. (ii) Acute and chronic inflammatory cells around apocrine glands - high power. c Pus in follicle. d Sinus tract formation. e Scarring around hair follicle

Dissecting Folliculitis of the Scalp

Clinically, dissecting folliculitis of the scalp is characterized by peri-follicular pustules, nodules, abscesses and sinus that progressively evolve into scarring alopecia. The clinical picture is often complicated by a keloid tendency 4, 9, 15, 23 . The course of the disease is chronic and relapsing. Squamous cell carcinoma may arise in chronic relapsing lesions and has a recognized metastasizing potential. Death from metastatic carcinoma has been described in one patient 9 .

Clinical Experience Etretinate and Acitretin for HS

Sion 3 months after stopping etretinate 37 . Scheman 38 treated a 41-year-old man, who presented with severe nodulocystic facial acne and HS on the inguinal folds, with acitretin (0.6 mg kg per day). After 2 months, the patient's HS was completely controlled, and his very severe acne improved to only a few inflamed nondraining facial cysts. With a dosage of acitretin of 0.9 mg kg per day the patient was completely free of inflammatory lesions on his face and groin. After 4 months on this dosage, however, alopecia and unacceptable joint pain developed. After 1 month off acitretin, the patient's side-effects resolved. Treatment was resumed back at a dose of 0.6 mg kg per day, with results similar to those when the patient was previously on this dosage. After 5 months of therapy, improvement continued to be satisfactory 38 .

Clinical Manifestations

NME is the hallmark finding in glucagonoma syndrome. It is characterized by a polymorphous eruption that most commonly presents as scaly, erythematous papules and plaques with superficial erosions. The lesions typically are in a perioral distribution on the face (Fig. 9), but also involve the perineum, lower abdomen, thighs, buttocks, and less commonly the distal extremities. NME has been reported to be the presenting complaint in approximately two-thirds of patients with this tumor, but there are only rare cases of glucagonoma without NME ever occurring. Stomatitis, glossitis, dystrophic nails, and alopecia can also be seen. The eruption is frequently misdiagnosed as seborrheic dermatitis or intertrigo and can also resemble pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, or psoriasis.

Identification of a Second HS Locus to Chromosome

Of the nuclear receptor superfamily of transcription factors 34, 56, 62 . Oestrogen is known to exert an effect on reproductive activity but is also involved in the circulatory system, bone reabsorption and immune system. Oestrogens have significant effects on the skin and administration of oestrogen has been correlated with proliferation of basal cells in the epidermis and increased production of collagen 44, 55 . The increased oestrogen concentration affects secondary sexual characteristics in both males and females as large doses of oestrogen can increase or reduce the size of sebaceous glands and also apocrine sweat glands 44, 55 . An abnormality in the sizes of these glands has not been reported in HS but one report has demonstrated that the hair follicles in HS patients were larger than normal 28 . Oestrogen is involved in the production of pubic hair and both receptors are expressed in the hair follicle, and therefore may also exert an influence on the size of the hair...

Surgical Pathology Specimens Laboratory Protocols

Punch Biopsy Alopecia

Punch biopsy for alopecia punch biopsies are taken to establish the cause of alopecia and are embedded in the usual manner. In some centres, depending on the experience of the dermatopathologist, the punch biopsy may be bisected, with one half embedded and sectioned in the usual vertical fashion and the other half sectioned transversely. This is thought to give a better view of the hair follicle structures and assist in the diagnosis of alopecia (Figure 37.3). Figure 37.3. Vertical and horizontal sections of a punch biopsy for the diagnosis of alopecia.

Care Of Captive Bat Populations

It is important to keep a systematic record of the health condition of every bat in a captive colony. Individuals should be weighed regularly to assess for weight loss, which may be a sign of illness, as well as hyperphagia, though it is important to remember that hibernating bats will gain weight in preparation for hibernation. Other clinical signs to assess include diarrhea, vomiting, loss of pigmentation and or dryness of the skin, hair loss, and lethargy. Several of the books listed in the Recommended Resources section of this chapter have helpful information on diagnosing common medical conditions.

Scalp and Facial Hair Patterning

Hair directional slope is secondary to the plane of stretch exerted on the skin by the growth of underlying tissues during the period of down-growth of the hair follicles at around 10-12 weeks gestation. The posterior parietal hair whorl is interpreted as the focal point from which the growth stretch is exerted by the dome-like out-growth of the brain during the time of hair follicle development. Malformations that antedate hair follicle development, such as encephalocele, produce aberrations in scalp patterning. Eighty-five percent of patients with primary microcephaly have altered scalp hair patterning, indicating an early onset of abnormal brain development. Aberrant scalp patterning is also found frequently in association with established syndromes including Down syndrome. Thus, aberrant scalp hair patterning may be utilized as an indicator of altered size and or shape of the brain prior to 12 weeks gestation. Early anomalies in development of the eye and of the face can...

Early Lesions Fig 43ad

What Vomeronasal Lesion

Follicular hyperkeratosis with plugging and dilatation of the hair follicle is seen as an early event in HS. The follicular epithelium may proliferate or may be destroyed. Inflammation is frequently not apparent in early lesions but peri-folliculitis will ensue and the inflammatory infiltrate embraces neutrophils, lymphocytes and histiocytes. Early lesions may show acute inflammation involving the apocrine gland and duct but this is not always apparent and would appear to be a rare primary event 7 . In a study of 36 patients apocrinitis was present in only 5 11 . Fig. 4.3 a-d. Early lesions in hidradenitis suppurativa. a Acute HS - lower power. b Follicular plugging. c Folliculitis - dense collection of neutrophils around hair follicle. d Acute folliculitis in HS Fig. 4.3 a-d. Early lesions in hidradenitis suppurativa. a Acute HS - lower power. b Follicular plugging. c Folliculitis - dense collection of neutrophils around hair follicle. d Acute folliculitis in HS

And the Pilosebaceous Unit

Pilosebaceous Unit

The sebaceous glands are an integral part of the pilosebaceous unit and are found over the entire body surface with the exception of the palms and soles. The gland itself is made up of several lobules, which are separated by vascular connective tissue. These lobules all empty into a short duct which then empties into the upper part of a hair follicle at the level of the infun-dibulum. More than one sebaceous duct may drain into the upper part of the hair follicle. The hair follicle, the hair, the sebaceous gland and arrectores pilorum muscle and (in certain regions) the apocrine glands make up the pilo-sebaceous unit (Fig. 4.2). Apocrine glands are found predominantly in the axillary and anogenital regions, although they are also found in the ear canal (ceruminal glands) and eyelids (Moll's glands). They are derived from epidermis and develop as an outgrowth of follicular epithelium. They represent compound sweat glands with a secretory coil that extends deep through the dermis into...

Trigonocephaly And Angels Kisses

Forming the outer side of each naris (nostril). albinism Deficiency or absence of pigment in the hair, skin, and or eyes. alopecia Absence, loss, or deficiency of hair may be patchy or total transient tragion Superior margin of the tragus of the ear. trichoglyphics Pattern of hair follicles.

Gender Effects on Phenotype

Example, a gene for hair growth pattern has two alleles, one that produces hair all over the head and another that causes pattern baldness (fig. 24.13). The baldness allele is dominant in males but recessive in females, which is why more men than women are bald. A heterozygous male is bald, but a heterozygous female is not. A bald woman would have two mutant alleles.

IL1 Receptors in the Skin

Mation, such as inflammatory bowel diseases, alopecia areata, psoriasis, lichen sclerosus or lupus erythematosus, IL1RN*2 homozygosity increases the severity of the inflammation, suggesting that persons with this allele have a more prolonged and more severe proinflammatory immune response than do persons with other IL-1RA genotypes 73 . Interestingly, the frequency of the two-repeat allele of IL-1RN is increased among patients with acne conglobata but not among those with HS. In addition, IL1RN*2 homozygosity was detected only amongst patients with severe acne conglobata, suggesting that allele 2 of the IL-1RN gene may contribute to the development of acne conglo-bata but not HS 38 .

Benign Prostatic Hyperplasia

What Does Prostatic Hypertrophy Mean

Benign prostatic hyperplasia is a common disease of aged males. It is associated with low urinary tract syndrome and can result in serious complications including renal failure. The main pathophysiological factors, and consequently, therapeutic targets, are sex hormones and sympathetic activity. Testosterone, dihydrotestosterone, and estradiol play crucial roles, and their effects are influenced by several genetic factors. Nevertheless, testosterone and dihydrotestosterone (DHT) seem to be of major importance. Both steroids are recognized by the intracellular androgen receptor, but the activation of this transcription factor via DHT is stronger by a factor of 10 in comparison to testosterone. The production of DHT from testosterone is mediated by the enzyme 5-alpha reductase. Inhibiting this catalytic activity pharmacologically is one of the major therapeutical approaches currently used in the treatment of BPH. The levels of testosterone slightly increase due to the inhibition of...

Gnrh Enters Blood Vessels In

Round And Ovarian Ligaments

The hormone testosterone (tes-tos'te-ron) is the most abundant androgen. It is secreted and transported in the blood, loosely attached to plasma proteins. Like other steroid hormones, testosterone combines with receptor molecules usually in the nuclei of its target cells (see chapter 13, p. 507). However, in many target cells, such as those in the prostate gland, seminal vesicles, and male external accessory organs, testosterone is first converted to another androgen called dihydrotestosterone, which stimulates the cells of these organs. Androgen molecules that do not reach receptors in target cells are usually changed by the liver into forms that can be excreted in bile or urine.

Trichoglyphics Introduction and Embryology

The patterning of hair follicles is called trichoglyphics. The hair shaft directional slope is secondary to the plane of the stretch exerted on the skin when the hair follicles are forming. During the first two months of gestation, the embryo is completely hairless. Then the primary hair, called lanugo, starts to grow. The origin of the hair directional patterning is the original sloping angulation of the hair follicle. The hair follicles start to push downward into the underlying mesenchyme at 10-12 weeks of gestation (Fig. 12.9). On the scalp, the angle of the hair shaft reflects the prior plane of growth of the skin (e.g., the plane of growth present at the time when the follicle was forming). The plane of growth of the scalp skin is usually determined by the growth of the underlying brain. The posterior parietal hair whorl is considered to be the focal point from which the growth stretch is exerted by the dome-like outgrowth of the brain during the time of hair follicle...

Antiandrogenic Progestins

Other progestins with antiandrogen properties 11, 14 (antagonists at the AR levels) include chlormadinone acetate (CMA), drospirenone and dienogest. They may be used either in combination with EE 5, 8, 16 as a contraceptive OC (similarly the combination of CPA 2mg + 30 g EE) or as antiandrogenic progestin alone (CMA for instance) according to countries where the drugs have been approved. In fact no evaluation of the effects of these progestins exists in women with hirsutism, severe acne or chronic alopecia.

Psychosocial Factors Involved In Hair Cosmetics

Hair is midway between nature and culture 1 . Haircare attitudes are different from one society to another regardless of economic differences, and from one person to another within societies e.g., hair loss is not equally perceived by everybody in all societies in the same manner 2-5 . Some people are seriously psychologically affected and ready to spend a fortune in order to cope with the problem, whereas others just do not care at all. In the former group, styling is of high significance as is the selection of cosmetic agents.

Measure of Quality of Life Quantitative Approach

A quantitative approach for measuring QoL in HS was performed 2 . Questionnaires widely used in other skin diseases such as the Dermatology Life Quality Index (DLQI) questionnaire, Skindex and VQ-Dermato 1, 4, 5 were chosen. This approach allows a direct comparison of the results with those from previous studies on other skin diseases. We will discuss two studies, one already published and our unpublished data 2 . In both studies, in addition to this questionnaire, basic demographic data and aspects of the history of HS were collected 114 patients participated in the first one 2 and 61 in the second. In the study of der Werth and Jemec 2 the recorded mean DLQI score was 8.9, higher than scores found in several other dermatological conditions such as alopecia, acne, psoriasis, Hailey-Hailey disease, vascular anomalies of face, and atopic dermatitis. In our center (unpublished data) using two other skin-disease-specific QoL questionnaires (Skindex and VQ-Dermato) 1, 5 , the scores...

Testimony on the Anabolic Steroid Control Act of 2004

The perils of anabolic steroid use are well known. In Olympic sport, the most notable, systematic state-supported program of doping with anabolic steroids was conducted by the East Germans from 1974 until the Berlin Wall fell. One of the anabolic substances developed by the East Germans as part of their doping program was androstenedione. In the body, androstenedione metabolizes into the anabolic steroid, testosterone. The documented side effects of the East German steroid program, particularly for women athletes, were tragic. These side effects include damage to the liver and reproductive system, susceptibility to cancers, and permanent masculinization of women. It is also well known that men who abuse steroids and steroid precursors risk serious health consequences including gynecomastia, baldness, shrunken testicles, infertility and susceptibility to aggressive behavior or rage. For adolescents who use steroids the side effects can include all of the above, as well as a strong...

Sexual differentiation

Into 5a-dihydrotestosterone, which binds to androgen receptors with a higher affinity than does testosterone. The formation of 5a-dihydrotestosterone from testosterone within reproductive tissues can enhance the process of virulization of the male genitalia. The differential expression of the androgen receptor or of factors regulating the downstream effect of the androgen receptor on gene expression or protein-protein interactions could likewise modulate the degree of masculinization. A familial reductase deficiency common in the Dominican Republic (Imperato-McGinley, 1979) results in the severely limited levels of 5a-dihydrotestosterone and in incomplete masculinization. It is reasonable to assume that the process of masculinization admits to degrees, even at the more rudimentary level of the reproductive tract and genitalia. Such variation is evident in cases of testicular feminization (or androgen insensitivity) or congenital adrenal hyperplasia, in which varying levels of androgen...

Hormone Receptor Status Of Breast Cancers

Breast cancer is diagnosed at a level of about 100,000-120,000 new cases per year in the United States, and 40,000 die each year from this most common cause of cancer in women. For some time breast cancers have been classified on the basis of receptor measurements from biopsy specimens. Thus, in general, these cancers fall into three categories estrogen receptor (ER) positive and progesterone receptor (PR) positive ER positive and PR negative and ER negative and PR negative. These measurements show that in those cancers with normal levels of ER and PR the cells should be responsive to the growth-stimulating effects of estrogen. Furthermore, the positive expression of PR indicates that the ER is functional in that PR is a pheno-typic product of ER action. Such tumors are more amenable to treatment and therapy with antiestrogens and other maneuvers. The progression of tumor status from hormone dependent to hormone independent (ER-, PR-) is a bad sign, and a hormone-independent tumor is...

Acne acne vulgaris OMIM 604324

Three etiological factors are known sebum excretion from sebaceous glands, infection, and hair follicle duct obstruction (most sebaceous glands empty into the hair follicle duct). The main determinant of sebum excretion rate is hormonal, principally androgens. Therapies rely on targeting each of the etiological factors reducing sebum excretion (retinoids, estrogens), infection (antibiotics) and duct obstruction (keratolytics).

Mucocutaneous Manifestations

The mucocutaneous manifestations of CS are the most common, yet the most difficult to recognize, with an estimated penetrance of 99 by the end of the third decade (17). The characteristic skin lesions of CS are trichilemmomas and papillomatous papules (25). Trichilemmomas are hamartomas of the infundibulum of the hair follicle and are characteristically found at or near the hairline while papillomatous papules are condyloma-like lesions occurring frequently on the face, hands, feet, or oral mucosa. It is not uncommon to see papillomatous papules proliferate at pressure points particularly on the palmar and plantar surfaces. Additional cutaneous manifestations include acral keratoses, small punctate lesions commonly seen on the palmar surface of the hands, which are often associated with a central depression or pit. Lipomas are a feature, but are seen more commonly in BRRS (14). Patients appear predisposed to excessive scarring, even cheloid formation, at the site of traumatic or...

Radiation Oncology Nurse

Radiation therapy provides an important role in the management of HGG. Nursing care provided by the radiation oncology nurse begins at the initial consult visit and continues into the early post-radiation phase. Patients and families must be educated regarding treatment schedules and expected effects and side effects. Options available to patients include conventional regional radiation, whole brain radiation, stereotactic radiosurgery such as gamma knife or photon beam, brachytherapy, and hyperthermia (31). It is often difficult to assess if symptoms are being caused by the radiation therapy itself, tumor growth, or other concurrent therapies. Acute symptoms occur within the first few weeks to months and are usually self-limiting. These include nausea but rarely vomiting, anorexia, impaired taste, fatigue, increased seizures, increased neurologic deficits, skin changes, hair loss, and impaired wound healing. Some patients whose radiation fields lie near the ear can experience hearing...

Plate 40 Eccrine And Apocrine Sweat Glands

Sweat glands are of two types apocrine and eccrine. Apocrine glands have a limited distribution in the human, they are found in the axilla, anogenital region, and mammary areola. Apocrine sweat glands are large tubular structures that are sometimes branched. They empty into the upper portion of the hair follicle and produce a product that becomes odoriferous after being secreted. The product of the apocrine sweat gland is important in other mammals, serving as a sex attractant and a marker of territory. Apocrine glands develop at puberty under the influence of sex hormones. They respond to nerve stimulation but not to elevated ambient temperature. In addition to the apocrine glands that are obviously sweat glands, two other types of glands, namely, the ceruminous glands of the external ear and the glands of Moll in the eyelids, are also classified as apocrine glands. This section of adult skin shows both apocrine and eccrine sweat glands. The apocrine sweat glands (aSG) are easily...

Hormonal Carcinogenesis

A second, and arguably relevant, concept related to human studies of hormonal carcinogen-esis has gradually emerged from studies of the epidemiology of prostate cancer.20 A series of prospective studies of circulating testosterone (T) and dihydrotestosterone (DHT) did not show the same consistent relationship of higher serum androgen levels and prostate cancer risk.21 In their meta-analysis, Eaton et al.21 concluded the following

And Antiandrogen Therapies

Additional hormonal treatment of hyperan-drogenism includes (1) inhibition of the conversion of testosterone (T) into its active metabolite dihydrotestosterone (DHT) through 5a-reductase inhibition (2) suppression of ovarian androgen production with oral contraceptives (OC) (3) elevation of sex-hormone-binding globulin (SHBG) levels through oestrogens, either natural oestradiol, (E2, as oestrogen therapy) or ethinyloestradiol (EE, with OC), with a further decrease in plasma free androgen levels (Table 16.1). CPA is a progestin with several antiandrogenic activities binding to AR, inhibition of androgen metabolism and antigonadotropic activity. CPA has been used extensively in Europe for 30 years in the treatment of hirsutism. It can be given according to various regimens (usually 50 mg daily on days 1-20 of each menstrual cycle, but other regimens are possible with CPA of 50 or 100 mg) together with natural E2 or with an OC pill. Good results may be obtained in hirsutism and also in...

Initiation Of Dopamine Agonist Therapy

Dopaminergic medications have similar side effect profiles nausea, sleepiness, confusion, orthostatic hypotension, and hallucinations among others (Table 2). Besides these problems, lower extremity edema, hair loss, and weight gain have also been seen with dopamine agonist use. The ergoline-derivatives, bromocriptine, cabergoline, and pergolide, also have a slight risk of erythromelalgia and pulmonary and retroperitoneal fibrosis, which have been reported in 2 to 5 of patients exposed to these agents (1). With all dopaminergic agents, it is possible that excessive daytime sleepiness, unexpected sleep episodes, and reduced impulse control leading to behaviors such as pathological gambling could occur in a small percentage of patients (34-39). Therefore, patients should be educated to be vigilant of these potential side effects and notify their physician if they occur. The side effects of these agents are quite similar, but vary from patient to patient, so it is important for a patient...

Solutions To Exercises Lesson

Papillae prevent the dermis and epidermis from sliding on each other. Other structures found in the dermis include blood vessels, lymph vessels, nerve endings, hair follicles, and glands. (para 3-3b) 11. A hair follicle is formed by the extension of the skin (dermis and epidermis) deeper into the surface of the body. At the base of the hair follicle is the hair root. The hair shaft grows out from the root. The hair shaft is made of cells from the outermost layers of the epidermis. (paras 3-5a, b) 13. Sebaceous glands produce an oily substance. Its function is to lubricate the skin and hairs and to keep them flexible. The sebaceous glands are usually found as a part of the walls of hair follicles. (para 3-6b)

Androgen Action And Metabolism Of T

T is metabolized to dihydrotestosterone (DHT) and to estradiol (E2) in tissues that have 5 -reductase activity and or aromatase activity. DHT is a very potent androgen at the tissue level. It contributes most of the androgenic effects in genital tissues, accessory sex organs, and hair follicles. Five-alpha-reductase activity also is present in some areas of the brain and in bone (Russell et al., 1994). Aromatase activity is primarily present in adipose tissue, so most of the circulating estradiol and estrone in males comes from peripheral conversion of T and andro-stenedione (Simpson et al., 1997). T production rates in young adult males range between 4 and 10 mg 24 hours with an average of 6.6 mg 24 hours (Vermeulen, 1976). In men over age 65, the mean production rate decreases to approximately 4 mg 24 hours. Plasma levels of T reflect an age-related decrease in both secretion and the metabolic clearance rate.

Biological Functions of Shps

The phenotypes of me me and mev mev mice differ only in severity, with me me mice succumbing to abnormalities earlier (2-3 weeks) than mev mev (9-12 weeks) 93-98 . For this reason, we use me to refer generically to Shp1-deficient mice. The me phenotype derives its name from patchy hair loss, which gives the mice a motheaten appearance. The hair loss, in turn, results from sterile dermal abscesses consisting of neu-trophils. Inflammation also is prominent elsewhere, including the joints, liver, and lungs. The latter leads to the early demise of me mice, due to severe interstitial pneumonitis caused by

Wayne D Tilley Grant Buchanan Gerhard A Coetzee

The androgen-signaling axis is the principal regulator of the development, function, and growth of the prostate gland and plays a vital role in prostate cancer predisposition and progression. The major components of this axis include the biosynthesis and transport of testosterone to target tissues, where it is converted to the more active metabolite 5a-dihydrotestosterone (DHT) maturation of the androgen receptor (AR) to a ligand-binding-competent form nuclear import and the subsequent transcriptional regulation of AR target genes. The AR, which is the pivotal component of androgen signaling, is a member of the superfamily of nuclear transcription factors that regulate a diverse range of cellular functions by providing a direct link between signaling molecules and gene transcription.1-3 The AR is unique among nuclear receptors (NRs) in that a strong constitutive transactivation function involving at least three overlapping regions of the N-terminal domain (NTD) is responsible for...

Importance Of Androgens In The Carcinogenesis Of Prostate Cancer

The prostate is an androgen-dependent organ. Testosterone and androgen precursors freely diffuse into prostate cells. Through a coordinated network of enzymes, they can be rapidly and irreversibly converted to their reduced and more potent metabolic form, dihydrotestosterone (DHT). Both DHT and, to a lesser extent, testosterone bind to and induce the conformational change and activation of the androgen receptor (AR). The activated androgen-receptor complex then binds to the androgen response element (ARE) of androgen-responsive genes and initiates or inhibits their transcription.69-72 After fulfilling their role in transcriptional regulation, DHT and testosterone are oxidized to biologically inactive derivatives by another set of enzymes. The intracellular steady-state active androgen level, which is balanced by the availability of testosterone and dehydroepiandrosterone (DHEA), the formation of DHT, and the degradation of DHT and other androgens, is thought to be an important...

Androgen Receptor CAG Repeat

Receptor dimerization and phosphorylation, nuclear transport, DNA binding, recruitment of components of the transcription machinery (TM) and other cofactor molecules (such as the p160 coactivators), and ultimately activation of androgen-regulated gene pathways. SHBG, sex hormone-binding globulin DHT, dihydrotestosterone CBP, cyclic adenosine monophosphate response element binding protein.

Plate 41 Sweat And Sebaceous Glands

Sebaceous glands develop from the epithelial cells of the hair follicle and discharge their secretion into the follicle, from where it reaches the skin surface. The sebaceous secretion is rich in lipid, and this is reflected in the cells of the sebaceous gland. A section of a sebaceous gland and its related hair follicle is shown in this figure. At this level, the hair follicle consists of the external root sheath (RS) sur rounding the hair shaft. The sebaceous gland (Seb) appears as a cluster of cells, most of which display a washed-out or finely reticulated cytoplasm. This is because these cells contain numerous lipid droplets and the lipid is lost by dissolution in fat solvents during the routine preparation of the H&E-stained paraffin section. The opening of the sebaceous gland through the external root sheath (eRS) and into the hair follicle is shown in the lower right. hair follicle. The sebaceous secretion includes the entire cell, and therefore, cells need to be replaced...

Legal Attempts To Regulate Biotechnology And Assign Ownership

How has patent law managed to be seen under western law as neutral and somehow removed from cultural or ethical considerations Historically the subject matter of patents, inventions, have been associated with science as positive, objective and progressive. Clearly this has coloured the view that patent law is merely the body of apolitical technical rules to which Recital 23 refers. The question of patenting genetic information, particularly that of humans, has brought ethical concerns into the debate, but salient matters have still to be resolved. For instance, while Article 53(a) of the European Patent Convention states that patents are not to be granted for inventions, the publication of which would be contrary to ordre public or morality, the European Patent Office traditionally decides issues under this section in a utilitarian risk benefit balancing act, an approach which is explicitly endorsed in Recital 21. In practice, cases involving genetic modification tend to be decided...

Nuclear Receptor Ligands

Consideration of the diverse stereospecific structures of the known ligands for NRs reflects the diversity and size of the superfamily (Figs. 3.8-3.10). As discussed previously, the ligand-binding function of NRs evidently evolved in very small steps, yielding a large family of proteins capable of discriminating minor differences in chemical structures. The majority of known ligands are lipophilic, polycyclic planar compounds containing a variable number of ring structures, side chains, and alcohol, car-boxylate, or ketone functional groups. Many of the receptors (including the class I receptors, VDR, LXR, EcR, FXR, PXR, and CAR) recognize unique metabolites of the mevalonate pathway that share a three- or four-ring cholesterol-like structure. The natural sterol moieties are recognized with high affinity by the classical steroid receptors, with dissociation constants in the low to high nanomolar range, making these receptors exquisitely sensitive to changes in steroid levels. The...

Allergic Reactions And Other Toxicities

One of the most common acute side effects of germ cell tumor treatment is alopecia. The principal agents that cause alopecia are etoposide, ifosfamide, and paclitaxel only WHO grade I hair loss is associated with cisplatin, vinblastine, and bleomycin, as single agents. With combination chemotherapy, used predominantly for treating this disease, the majority of patients will suffer significant alopecia.1315,50

Quasidrugs In The Future

Generally, topically applied quasidrugs are intended to mollify unwanted aspects of the skin and have a mild action on the human body, whereas medical drugs are intended to treat specific diseases. Therefore, hair-growth products with a mild action on male-pattern baldness, which is not a disease 2 , are quasidrugs. On the other hand, products intended for alopecia areata, which is a disease, are regarded as drugs. The natural aging of skin, like wrinkling, is not a disease, for example. We should also keep in mind that ''high efficacy'' should not always involve ''strong action.'' There will be many pseudo-drugs or cosmeceutical products with mild actions showing good efficacy.

Mycosis Fungoides And Sezary Syndrome

SS is generally regarded as the leukemic form of epidermotropic cutaneous T-cell lymphoma (MF). Clinically, SS is characterized by erythroderma, palmoplantar keratoderma, partial alopecia, lymphadenopathy, and pruritis. Atypical lymphocytes are seen in the blood and take the form of lymphocytes with grooved, cerebriform nuclei of large (typical Sezary cells,) or small (so-called Lutzner cells) size. Although originally described in 1961 by Tasell and Winkelmann,49 the exact definition of SS is still not uniformly agreed upon. Disagreement revolves around both clinical issues and laboratory issues. Clinically, distinction is made by some authors between classical SS, in which patients develop signs and symptoms over a rapid period of time usually without a prior history of

George V Thomas Charles L Sawyers

Both normal and cancerous prostate cells are dependent on androgens, mainly in the form of testosterone and dihydrotestosterone (DHT), to promote proliferation and inhibit apoptosis.1-3 Androgen mediates its biological actions through the androgen receptor (AR), a ligand-activated transcription factor of the steroid nuclear receptor superfamily (see Color Fig. 18.1 in separate color insert).4-6 Androgen-ablative treatment modalities rely on either surgical or medical castration, the latter usually administered via luteinizing hormone-releasing hormone (LHRH) analogs (termed monotherapy when used singly) and AR antagonists (termed total androgen-ablative therapy when used in combination).7,8 Counter intuitively, AR continues to be expressed even as the cancer progresses from the androgen-dependent (AD) to an androgen-independent (AI) stage. Immuno-histochemical studies have shown the presence of AR in both AD and AI tumors.9,10 A rise in serum prostatic-specific antigen (PSA), an

Significance to humans

Insectivores are secretive, nocturnal, shy, and for most humans fall into neither the cute and cuddly nor the big and scary attention-generating categories. A few individual insectivore species, however, have been singled out for attention. The greater hedgehog tenrec (Setifer setosus), for example, is probably the most recognizable of the insectivores. This creature is easy to keep as a pet and has a large enthusiastic following. Hedgehogs are also important in research on diseases such as foot and mouth disease, yellow fever, and influenza. Old home remedies sometimes called for hedgehog blood, entrails or ashes. Mixed with pitch or resin, the burned hindquarters supposedly helped cure baldness. The hedgehog was used to predict the weather and if buried under a building was thought to bring good luck. The Romans kept hedgehogs as pets during the fourth century B.C. and they remain domesticated to this day. Other uses over the years for this spiny insectivore include consumption of...

Future Lines of Research

Future research using the bat as a model for the study of aging may reveal mechanisms that confer resistance to expected senescent processes observed in other long-lived mammals. Elucidation of the physiological mechanisms that give rise to the exceptional longevity observed in bats may provide insight into the development of novel treatments and therapies of degenerative diseases associated with senescence in humans. Chien and Karsenty (2005) describe the typical manifestation of the aging phenotype in long-lived mammals as development of osteoporosis, reduction in body weight, lean-reduced fat tissue, loss of hair or alopecia, cardiomyopathy, early loss of fertility in females, anemia with extramedullary hematopoiesis, reduction in physical activity, and lack of obvious cause of death. Following is a brief review of potentially heuristic lines of research using the bat as a model for the study of aging.

Prospective Dose Intensity Trials for Breast Cancer

Mg mL, methotrexate 40 mg mL, 5-fluorouracil 600 mg mL) and low dose (cyclophosphamide 300 mg mL, methotrexate 20 mg mL, 5-fluorouracil 300 mg mL). Response rates were higher for the standard-dose cohort (30 vs 11 , p 0.3), but there was no statistical difference in overall survival (15.6 mo vs 12.8 mo, p 0.12). Although the rates of toxicity (vomiting, alopecia, myelosuppression, and conjunctivitis) were higher in the standard-dose cohort, patients in the standard-dose cohort had an improved quality of life. Based on the increased response rate, trend to improved survival, and overall improvement in quality of life, the authors concluded that the rate of disease palliation was improved with higher dose therapy.

Decline In Systems Redundancy With

Many age changes in living organisms can be explained by cumulative effects of cell loss over time. For example, the very common phenomenon of hair graying with age is caused by depletion of hair follicle melanocytes (Commo et al., 2004). Melanocyte density in human epidermis declines gradually with age at a rate approximately 0.8 per year (Gilchrest et al., 1979). Hair graying is a relatively benign phenomenon, but cell loss can also lead to more serious consequences.

The Somatosensory System

A number of different vertebrate receptors perceive pressure, vibration, and texture. These are known as Meissner's corpuscles, Pacinian corpuscles, Merkel's disks, and Ruffini endings. The first two are rapidly adapting, whereas the second two adapt slowly. The act of picking up a stick, for example, is quickly perceived by Meissner's and Pacinian corpuscles, but they quickly adapt and stop sending the signal to the brain. Merkel's disks and Ruffini endings, however, continue to alert the brain to the presence of the stick in the hand. The hair follicle receptor is found in hairy skin, where nerve endings wrap around single hair follicles and transduce signal on deflection of the hair from that follicle.

The Mechanism of FAS Regulation by Progestin

In BC, FAS is specifically regulated via the PR since its induction by R5020 was inhibited by RU 486 but not by flutamide. Androgens such as dihydrotestosterone (DHT) were only active at p,uM concentrations. Therefore, in ERa+ and PR+ BC cell lines, progesterone was the major hormone to regulate FAS expression. Recently, other laboratories showed that mitogens such as the growth factors EGF, FGF-1, and HER-2 neu also induce FAS by stimulating PI-3 kinase and MAP kinase pathways leading to induction of the sterol regulatory element binding protein (SREBP1) transcription factor . This pathway has been documented in two ERa mammary cell lines MCFlOa transfected with ras (32), and H16 transfected with the HER-2 neu oncogene (33). In MCF7 and T47D BC cell lines, the classical pathway following activation of nuclear PRs by progestins was found to be the predominant or even exclusive regulation. Therefore in-vivo, in ERa and PR-positive BCs, FAS is most likely induced by progestins acting...

Mutations of the Androgen Receptor in PCA

In contrast to AR mutations detected in patients with androgen insensitivity syndromes, several structural changes of the AR in PCA lead to gain of function. This was first observed in LNCaP cells, whose mutant AR is efficiently activated by adrenal androgens, anti-androgens, and estrogenic or progestagenic steroids (17). In LNCaP cells, threonine at position 877 is mutated to alanine. The mutation changes the stereochemistry of the binding pocket of the AR. The first two mutations discovered in PCA patients have very similar functional consequences in each of these two ARs, amino acid valine (at positions 715 and 730, respectively) is substituted by methionine (18,19). These ARs are increasingly activated by adrenal androgens, products of dihydrotestosterone (DHT) metabolism, and hydroxyflutamide. Higher AR activity was induced by these hormones, although there were no major changes in AR binding affinity. A more efficient AR activation by adrenal androgens and DHT metabolism may...

The Structure and Properties of Hair

Hair follicles, which in tens of thousands are deeply invaginated in the scalp tissue, are the essential growth structures of hair. At the base of each follicle, the cells proliferate and, as they stream upwards, the complex and intertwined processes of protein synthesis, structural alignment, and keratinization transform the cytoplasm into the tough fibrous material known as hair. Hair is unique in that its structural and growth characteristics are different between races, sexes, individuals of the same race, areas in the same individuals, and even within the same follicle. The development of hair is a dynamic, cyclical process in which duration of the growth cycle depends not only on the body site, but also on such variables as the individual's age, nutritional habits, and hormonal factors. In the scalp, each hair grows steadily (about 1 cm per month) and continuously for 3 to 5 years (anagen phase) growth then stops and is followed by a brief transient stage (catagen) and a 2- to...

Side Effects Of Radiotherapy Acute Reactions

Desquamation and some degree of erythema, which are managed with local ointments. Temporary alopecia within the radiation field is a common sequela. Fatigue may be observed with radiation therapy, but is often a function of several other variables such as age, performance status, underlying medical status, and extent of brain being irradiated.

Pathological Conditions

Basal cell carcinoma basal cell carcinoma is the commonest malignant tumour of the skin, and overall in humans. The vast majority is associated with chronic sun exposure and occur in the head and neck area of fair-skinned people. A few occur at sites of scarring in the skin and a small number of patients with a genetic predisposition develop multiple basal cell carcinomas. These patients often present at an early age. Basal cell carcinomas have a variety of clinical appearances from a nodular lesion to an ulcer or scarred areas and they may also be multifocal. The colour of the tumours can vary. The cell of origin of basal cell carcinoma is thought to be either the basal cell layer of the epidermis or hair follicle. Basal cell carcinomas are locally aggressive tumours, often infiltrating and destroying adjacent tissue. They do not, however, metastasise to other sites. The treatment of choice is surgical removal. The clinician may submit a variety of specimen types to the laboratory...

Reproductive Biology

Demodex Your Mouth

Females may lay up to 20-25 oval eggs on one hair follicle. Larvae (protonymph) and nymphs (deutonymph), with physical features similar to adults, are swept by sebaceous flow to mouth of follicle. First stage larvae emerge without legs. Larvae in later stages have six legs, as opposed to eight for adults. As immature mites grow, they become tightly packed. When mature, mites leave follicle, mate, and find new follicle in which to lay eggs. Entire life cycle spent on host 14-18 days.

T187m R227q F234l F194l

Several other androgen-signaling genes have been preliminarily studied in the context of prostate cancer risk. Testosterone is synthesized from cholesterol in a series of enzymatic steps involving several of the cytochrome P-450 enzymes.64 The enzyme cytochrome P-450c17 catalyzes two sequential reactions of the biosynthesis of T, in both the gonads and the adrenals. The first step is the conversion of pregnenolone to 17-hydroxypregnenolone (hydroxylase activity), and the second is its subsequent conversion to C19 steroid dehydroepiandrosterone (lyase activity), a steroid with androgenic activity.64 The CYP17 gene on chromosome 10 encodes the P-450c17 enzyme involved in these two sequential reactions in T biosynthesis.65 A T-to-C transition SNP exists in the 5'-UTR of the CYP17 gene (A2 allele).66 While the functional relevance of this polymorphism is in dispute, it has been linked to polycystic ovarian cancer risk in women, male pattern baldness in men,66 various estrogen metabolic...

Control of Androgen Action and Medicinal Applications

In the early 1960s, we found that As can rapidly enhance RNA synthesis in target organs, such as the ventral prostate of rats, suggesting that As act by modulating gene expression in target cell nuclei (2-4). Subsequently, we (5, 6) and Bruchovsky and Wilson (7) showed that, in many target organs, testosterone, the major A produced by testis and circulating in blood, is converted by 5a-reductase to 5a-dihydrotestosterone (5a-DHT). 5a-DHT is the active A that binds to a specific nuclear androgen receptor (AR) (8-12). The 5a-DHT-AR complex, apparently in conjunction with other chromosomal proteins (13), then regulates specific transcription of genes and production of specific proteins that modulate cellular activities and organ functions. Cloning and sequence determination ofthe genes for AR (10, 11) and 5a-reductase (14) have shown that mutations of these genes are responsible for A-insensitivity syndromes, including pseudo-hermaphroditism. are now being utilized as therapies for...

Imatinib Mesylate as a Paradigm for the Development of Molecular Therapeutics

A series of highly elegant PD studies were performed in the original phase I trials of gefitinib. In these, skin was proposed as a surrogate tissue because of ease of access and high EGFR expression. In these studies by Baselga, Albanell, and colleagues, paired skin biopsies were taken pretherapy and on-therapy (day 28) immunohistochemical analysis of EGFR status, EGFR phosphorylation, ERK 1 2 phosphorylation, proliferation marker Ki67, p27KIP1, keratin 1, and phospho-STAT3 expression were performed in paraffin-embedded sections (Albanell et al., 2002 Baselga et al., 2002). Statistically significant inhibition of EGFR activation in the basal layer of interfollicular epidermis and in hair follicle keratinocytes was achieved in all paired skin samples during gefitinib treatment. ERK 1 2 phosphorylation was assayed as a downstream marker of EGFR signaling and showed a significant reduction in expression at day 28, providing proof of concept for target inhibition. In addition, cell...

Testosterone T

Testosterone can act either (a) directly on target cells or (b) indirectly by being converted first to its principal metabolites, dihydrotestosterone (DHT), and estradiol. Although both T and DHT bind to the androgen receptor, the latter does so more strongly and is therefore more potent. Two enzymes convert T to its metabolites 5 alpha-reductase, which converts T to DHT and which is found especially in prostate, skin, and reproductive tissues, and aromatase which converts T to estradiol and is found especially in adipose tissue, liver, and some central nervous system nuclei. Thus, the actions of T are widespread throughout the body.

Human Sult2b1

The hydroxysteroid SULT subfamily also includes the two isoforms of SULT2B1. These enzymes represent two transcriptional products from the SULT2B1 gene that is localized at the same gene locus as the SULT2A1 gene (Her et al., 1998 Otterness et al., 1995a). The SULT2B1 gene was initially identified by screening a human placental expressed sequence tag database with an oligonucleotide encoding a highly conserved amino acid sequence motif RKGxxGDWKNxFT present in the SULTs (Her et al., 1998). This procedure identified two related cDNA sequences that were derived from the same gene but utilized different transcriptional start sites to incorporate different first exons. The cDNAs were termed SULT2B1a and SULT2B1b. SULT2B1b is 365 amino acids in length, whereas SULT2B1a is 350 amino acids in length. The final 344 amino acids of both sequences are identical since they are derived from the same exons. Expression of the SULT2B1 cDNAs in COS-1 cells utilizing the pCR3.1 vector generated both...

Inflammation

The exact cause of the rupture of the follicle is not established, although a lymphocytic inflammatory infiltrate appears to be present in early lesions (see Chap. 4). There is some evidence of infundibular epithelial hyperproliferation as well. In older lesions, sinus tract formation predominates the histopathology. It is speculated that the introduction of follicular material into the dermis as well as secondary colonization of sinus tracts cause flares of HS. These mechanisms suggest that HS can be classified as a folliculitis of unknown origin affecting the deeper end of the hair follicle and not involving the sebaceous glands. The polymicrobial colonization

Sebaceous Glands

Sebaceous glands develop as outgrowths of the external root sheath of the hair follicle, usually producing several glands per follicle (see Fig. 14.14). The oily substance produced in the gland, sebum, is the product of holocrine secretion. The entire cell produces and becomes filled with the fatty product while it simultaneously undergoes programmed cell death (apoptosis) as the product fills the cell. Ultimately, both the secretory product and cell debris are discharged from the gland as sebum into the in-fundibulum of a hair follicle, which with the short duct of the sebaceous gland forms the pilosebaceous canal. New cells are produced by mitosis of the basal cells at the periphery of the gland, and the cells of the gland remain linked to one another by desmosomes. The basal lamina of these cells is continuous with that of the epidermis and the hair follicle. The process of sebum production from the time of basal cell mitosis to the secretion of the sebum takes about 8 days....

Sectioned Sebaceous

Human Skin Showing Sweat Gland 45x

Locate the epidermis, dermis, and subcutaneous layer, a hair follicle, an arrector pili muscle, a sebaceous gland, and a sweat gland. Hair follicle Hair follicle 11. Using low-power magnification, locate a hair follicle that has been sectioned longitudinally through its bulblike base. Also locate a sebaceous gland close to the follicle and find a sweat gland. Observe the detailed structure of these parts with high-power magnification.

Androgen Metabolism

Androgens testosterone and the less potent androgens in women A4-androstenedione (A4A) and dehydroepiandrosterone (DHEA) are synthesized by the adrenals (mostly DHEA and its sulfate - SDHEA) and the ovaries (mostly A4A) and may be subsequently transformed into oestrogens through the aromatization of the molecules. Sex hormone binding globulin (SHBG) synthesized in the liver is the major carrier protein for androgens and oestradiol. Only free androgens, unbound to SHBG, are directly active on target cells. In tissues, androgens are first metabolically transformed into the active form dihydrotestosterone (DHT), which then binds to androgen receptors (AR) 16 . - and or acne or androgenic alopecia Sebaceous glands, but also keratinocytes from the acroinfundibulum and dermal papilla cells, can synthesize androgens de novo from cholesterol or by locally converting weaker androgens (A4A and DHEA) to testosterone and DHT. As in other classic steroidogenic organs, the pilosebaceous unit...

Fox Fordyce Disease

The pathogenesis of acne embraces increased sebum production, follicular hyperkeratosis, colonization with propionibacteria and inflammatory changes. The sebaceous duct hyperkera-tinization is mediated by the production of in-terleukin-1 alpha (IL1-a) and tumour necrosis factor alpha (TNF-a) by keratinocytes and T-lymphocytes. The result is hyperproliferation of keratinocytes, reduced apoptosis and consequent hypergranulosis. As a result the sebaceous follicle becomes blocked with densely packed keratin and so evolves the comedo. Early comedones show a dilated hair follicle associated with infundibular hyperkeratosis. Later due to rupture an acute dermal inflammatory response ensues. This can be complicated by a foreign body granulomatous reaction. In severe cases abscesses frequently present and cysts and sinuses form. Dermal scarring frequently results in these cases. All three diseases, HS, acne conglobata and dissecting folliculitis, represent chronic, recurrent deep-seated...

Figure 1420

A sample of thin skin is shown here to compare with the thick skin in Figure l. In addition to sweat glands, thin skin contains hair follicles (HF) and their associated sebaceous glands (SGI). Each sebaceous gland opens into a hair follicle. Often, as in this tissue sample, the hair follicles and the glands, both sebaceous and sweat, extend beyond the dermis (De) and into the hypodermis. Note the blood vessels (BV) and adipose tissue (AT) in the hypodermis.

Integumentary System

Pattern Root Hair Development

At week 12, ectodermal cells from the stratum basale grow into the underlying dermis and form the hair follicle. 2. The deepest part of the hair follicle soon becomes club-shaped to form the hair bulb. 5. Other epithelial cells of the hair follicle form the external root sheath, which is continuous with the epidermis. 6. Mesodermal cells of the dermis that surround the invaginating hair follicle form the dermal root sheath and the arrector pili muscle. 1. Alopecia is baldness resulting from an absence or faulty development of the hair follicles. C. Sebaceous glands develop from the epithelial wall of the hair follicle and elaborate sebum into the hair follicles. The tarsal (meibomian) glands of the eyelids do not communicate with hair follicles.

Ure 614

Blood Vessels

The healing of a deep partial-thickness burn depends upon accessory organs of the skin that survive the injury because they are located deep in the dermis. These organs, which include hair follicles, sweat glands, and sebaceous glands, contain epithelial cells. During healing, these cells grow out onto the surface of the dermis, spread over it, and form a new epidermis. In time, the skin usually completely recovers, and scar tissue does not develop unless an infection occurs. The skin's accessory structures also show signs of aging. Slowed melanin production causes hair to become gray or white as the follicle becomes increasingly transparent. Hair growth slows, the hairs thin, and the number of follicles decreases. Males may develop pattern baldness, which is hereditary but not often expressed in females. A diminished blood supply to the nail beds impairs their growth, dulling and hardening them. Sensitivity to pain and pressure diminishes with age as the number of receptors falls. A...

Magea4

Most of the etiologic and epidemiologic associations appear to point to an origin in atypical germ cells. The association of testicular maldescent and the formation of testicular tumors has been known for more than 200 years,84,85 and atypical germ cells have been identified in cryptorchid testicles.22 Similarly, testicular cancer is found more commonly in patients with testicular dysgenesis, infertility, and Kleinfelter's syndrome (with expression of an XXY chromosome). Additional epidemiologic associations include reduced body muscle mass and a lower prevalence of male pattern baldness, which may imply lower circulating testosterone levels, as either a cause or an effect of testicular cancer.86 Although testicular trauma and mumps orchitis have largely been discounted as antecedents of GCTs,87 88 earlier studies suggested that both could have mechanisms of oncogenesis predicated on testicular atrophy and the consequent evolution of atypical germ cells. Similar mechanisms have been...

Porphyrias

Thyroid hormone plays a critical role in regulating metabolism. In hypothyroidism, the basal metabolic rate is decreased due to a lack of thyroid hormone, resulting in bradycardia, cold intolerance, alopecia, and weight gain. Neurologic symptoms are relatively common in hypothyroidism and include paresthesias in up to 80 of patients as well as ataxia, coma, headache, seizure, cerebellar signs, and psychosis (132,133). Cranial nerve involvement has also been reported, with the vestibulocochlear nerve most commonly affected in 15 to 31 of patients with hypothyroidism (132). Involvement of the facial nerve is considered rare. Its mechanism is thought to be a compressive phenomenon. In hypothyroidism, myxedematous infiltration and swelling of the soft tissue are hypothesized to have a compressive effect on the facial nerve through the tight confines of the fallopian canal. Anecdotal reports of facial nerve decompression in hypothyroidism have been described (134), but additional reports...

Polyphenols

Procyanidins, also named condensed tannins, are flavonoids found in, e.g., pine bark (Pycnogenol), grape seeds, and fruits. By direct protein interaction, they were shown to protect collagen and elastin, two dermal matrix proteins, against their degradation 61 . Furthermore, some of these procyanidins exhibit a remarkable effect on follicle hair proliferation 62 thus extending the therapeutic applications of flavonoids to alopecia. Although the flavonoids are not part of our endogenous antioxidant defenses, they display a broad spectrum of properties particularly helpful in preventing UVR-caused deleterious effects in human skin.

Anatomy

Hidradenitis Suppurativa The Head

Tention and subsequent infection and inflammation in the apocrine sweat gland. Follicular abnormalities may be a key factor of HS they are apparent in histological as well as ultrasonographic studies of hair follicles in HS patients (see Chaps. 4, 5). There is also clinical evidence suggesting a relationship between HS and an anatomical anomaly of the pilosebaceous duct in the high prevalence of pilonidal cysts in HS patients. In one series (Faye O, Bastuji-garin S, Poli F, Revuz J. Hidradenitis suppurativa a clinical study of 164 patients manuscript in preparation) 30 of 164 patients are reported to have co-existing pilonidal sinus ducts. HS is clearly a follicular disease located to restricted areas of the body. The pathogenic process in the hair follicle may be elucidated from histology, and appears to be rupture of the deeper parts of the follicle, with spillage of the fol-licular contents into the dermis and subsequent inflammation (see Chap. 4). The exact cause of the rupture is...

RHuIL11

In a review by Smith (17), the safety and tolerability of rHuIL-11 administered sc at the recommended dose of 50 g kg d was compared with placebo in two phase 2 studies. The dataset included 308 patients, ranging from 8 mo to 75 yr of age, who received up to eight sequential 1-28-d courses of oprelvekin. In this group, aside from complications associated with underlying malignancy or cytotoxic chemotherapy, most adverse events were of mild or moderate severity and were reversible after cessation of the growth factor. The incidence and type of adverse events were similar between patients who received oprelvekin and those who received placebo. Edema, dyspnea, tachycardia, conjunctival injection, palpitations, and pleural effusion occurred more frequently in the oprelvekin-treated patients. Adverse events that occurred in 10 of patients and were observed in equal or greater frequency among patients receiving placebo included asthenia, pain, chills, abdominal pain, infection, anorexia,...

Indinavir

Paronychia of the toes or fingers and ingrown toenails are typical side effects of indinavir, occurring in 4 to 9 of patients. Furthermore, approximately 30 of patients receiving indinavir show two or more mucocutaneous changes, such as cutaneous xerosis, cheilitis, hair loss or alopecia, resembling retinoid-like side effects. Indinavir is the only antiretroviral drug that induces retinoid-like effects, as it probably interferes with the retinoid metabolism. There is no relation to sex, age or immune status, but to indinavir plasma levels. In these patients, measurement of the plasma level makes sense, adjusting the dose if necessary.

Finasteride

Two patients were reported in 1999 by Farrell et al. 4 to have a good response to finasteride (5 mg day), a dose five times higher than that used in male alopecia. A 56-year-old man with a 10-year past history of HS reported significant improvement in his symptoms as early as the 4th week of treatment. A 55-year-old postmeno-pausal woman with a history of HS since adolescence and a previous absence of response to CPA received finasteride 5 mg day. After 3 months she reported an improvement of her lesions without any significant adverse effects.

The Integument

Indentify Merocrine Gland

A notable feature of the integument is the presence of hairs (pili, sing. - pilus) located within a tube of epithelial cells called the hair follicle. The shaft of the hair is composed of packed, keratinized cells produced in the proximal end or root. The root is enlarged to form a bulb. Within the bulb is an involution, the hair papilla, through which the cells of the root are nourished. The entire root is enclosed in external and internal root sheaths which are infoldings of the epithelium. The deeper glands shown in Figure 6.1 are sudoriferous or sweat glands. There are two types of sudoriferous glands. Those with ducts which open directly onto the surface of the epidermis are termed merocrine (eccrine) sudoriferous glands. The glands which secrete into the hair follicle are apocrine sudoriferous glands. They can be found in the skin of the axillae (armpits), genital areas, nasal canal, and external ear canal. Examine the models of the integumentary system. Be able to identify the...

Figure 1414

Hair Follicle Outer Root Sheath Tem

Hair follicle and other skin appendages, a. Diagram showing a hair follicle. Note the cell layers that form the hair shaft and the surrounding external and internal root sheaths. The sebaceous gland consists of the secretory portion and a short duct that empties into the in-fundibulum. The arrector pili muscle accompanies the sebaceous gland its contraction assists in gland secretion and discharge into the infundibulum. The apocrine gland also empties into the infundibulum of the hair follicle. Note that eccrine sweat glands are independent structures and are not associated directly with the hair follicle, b. Photomicrograph of H8E-stained section of thin skin from human scalp. The growing end of a hair follicle consists of an expanded hair bulb (HB) of epithelial cells that is invaginated by a papilla of connective tissue. The epithelial cells form the unspecialized matrix surrounding the papilla as the cells leave the matrix, they form cell layers that differentiate into the shaft...

Depilation

In general, laser depilation has been shown to be a useful technique for hirsute patients, apparently using any of several types of available lasers. The absorption of laser light in the hair follicle induces transition to a telogen phase, and apparently shortens subsequent anagen phases of the follicle, consequently resulting in the growth of a shorter and thinner hair shaft 12 .

Anticonvulsants

A multicenter, randomized, placebo-controlled, six-week, parallel group study of divalproex sodium was conducted in patients with dementia and agitation who also met criteria for secondary mania (Tariot et al., 2001). This study was designed using an aggressive dosing and titration protocol, in which a target dose of 20 mg kg day was achieved in 10 days. This plan resulted in unacceptable sedation in roughly 25 of the drug-treated group and a relatively high dropout rate, leading to premature discontinuation of the study. The original sample size was 172 nursing home residents, with 100 completers at the time the study was suspended. While there was no significant drug-placebo effect on manic features, there was a significant effect of drug on agitation as measured by the Cohen-Mansfield Agitation Inventory (Cohen-Mansfield, 1986). Sedation occurred in 36 in the drug group versus 20 of the placebo group, and mild thrombocytopenia occurred in 7 of the drug group and none of the...

Skin Assessment

One of the most common organs to study is the skin. It is relatively easy to examine and identify phenotypic variations which can become an important resource for gene-targeting studies. When evaluating the skin and coat, it is important to keep in mind that phenotypes can vary dramatically. Some mutations have no obvious effects, whereas others can dramatically change the appearance of the mice. Problems with the skin and coat can be due to environmental problems, parasites, autoimmune disease, nutritional disorders, or can be secondary to certain treatments or genetic changes.16 Signs to watch for include dryness, scaling, alopecia, wounds, dermatitis, piloerection, matting, and excessive oiliness to the coat. It is important to recognize that mice do a lot of grooming to themselves and each other. Barbering is common and should not be confused with alopecia. Barbering appears to be a normal dominance behavior. It is important to keep in mind that mice can respond differently to...

Figure 1419

Epidermal repair is effected by basal cell proliferation or, in extensive trauma, by hair follicle and sweat gland epithelia. The repair of an incision or laceration of the skin requires stimulated growth of both the dermis and the epidermis. Dermal repair involves (a) removal of damaged collagen fibers in the wound site, primarily through the effort of macrophage activity and (b) proliferation of fibroblasts and subsequent production of new collagen and other extracellular matrix components. Application of sutures reduces the extent of the repair area through maximal closure of a wound, minimizing scar formation. Surgical incisions are typically made along cleavage lines the cut tends to parallel the collagen fibers, thus minimizing the need for excess collagen production and the inherent scarring that may occur. In cases in which the full thickness of the epidermal layer is removed either by trauma or in surgery, the deepest parts of hair follicles and glands that remain as islands...

Androgenization

One of the less sex-specific effects of androgens is that on the skin and its appendages, and in particular their action on the pilosebaceous unit. Hirsutism is the major symptom of hyper-androgenism in women. Other dermatological conditions include acne and the chronic hair loss usually termed androgenic alopecia (AGA). Whereas acne, hirsutism and chronic hair loss may coexist in the same patient, it is not unusual to find only one of these androgenic manifestations 16 .

Keratolytics

HS is a disease of the hair follicle with histological signs of poral occlusion 9-11 . Although there are only a few publications about the use of keratolytics in HS 12, 13 , the follicular occlusion brought about by hyperkeratosis may be a therapeutic target. Therefore, by analogy to acne, this also appears to be a good target for keratolytics. In acne, another disease of the follicle with abnormal keratinization (microcom-edo), the mainstay in classical therapy of early lesions is topical treatment with peeling agents, especially topical retinoids 8, 14, 15 . Here, the rationale is that all acne lesions arise out of a comedo and so it makes sense to treat acne patients with comedolytic agents 8, 14, 15 . Topical comedolytic agents are also recommended for use in maintenance therapy in acne by some authors 8, 14, 15 .

Colony Phenotyping

Observational assessments, summarized in Table 10.1, should include general appearance, posture, and mobility. These features can be monitored with the help of trained animal care and technical staff on a consistent and intense basis. Daily reports should be made and weekly assessments compiled. Specific aspects should be tailored to the individual research plan. For example, aging studies can include hair graying and alopecia, body weights, muscle atrophy, lordokyphosis, dermal thickness, and subcutaneous adipose. For hair regrowth assessment, hair is shaved from a 2-cm-square area at the dorso-ventral back near the base of the tail. Regrowth is defined as the first appearance of hair in each of eight sections, designated by a transparent grid, in the shaved area. Aging ad lib-fed mice have been shown to have an extended hair regrowth time compared to calorically restricted mice.9

Figure 151

A distinct submucosa underlies the lining mucosa except on the inferior surface of the tongue. This layer contains large bands of collagen and elastic fibers that bind the mucosa to the underlying muscle it also contains the many minor salivary glands of the lips, tongue, and cheeks. Occasionally, sebaceous glands not associated with a hair follicle are found in the submucosa just lateral to the corner of the mouth and in the cheeks opposite the molar teeth. They are visible to the eye and are called Fordyce spots. The submucosa contains the larger blood vessels, nerves, and lymphatic vessels that supply the subepithelial neurovascular networks in the lamina propria throughout the oral cavity.

Box 142

Hairs vary in size from long, coarse terminal hairs that may reach a meter or more in length (scalp hair and beard hair in males) to short, fine vellus hairs that may be visible only with the aid of a magnifying lens (vellus hairs of the forehead and anterior surface of the forearm). Terminal hairs are produced by large-diameter, long follicles vellus hairs are produced by relatively small follicles. Terminal hair follicles may spend up to several years in anagen and only a few months in telogen. In the balding individual, large terminal follicles are gradually converted into small vellus follicles after several growth cycles. The ratio of vellus follicles to terminal follicles increases as baldness progresses. The completely bald scalp is not hairless but is populated by vellus follicles that produce fine hairs and remain in telogen for relatively long periods.

Back To Mitochondria

Another example of a mouse model with a defect in genome maintenance especially designed to test the hypothesis that genomic instability is involved in aging is the PolgA proofreading-deficient mouse model. PolgA, the catalytic core of the mitochondrial DNA polymerase gamma (Polg), is a mtDNA polymerase, encoded in the nuclear genome. Hence, proofreading defects in this gene would be expected to lead to increased mutations in the mitochondrial genome. Mutations in both nuclear and mitochondrial DNA have been demonstrated to accumulate with age in a tissue-specific pattern (Arnheim and Cortopassi, 1992 Vijg and Dolle, 2002). Hence, in the PolgA deficient mouse we would expect to see the premature appearance of aging-related phenotypes, which turned out to be correct. Apart from a three- to fivefold increase in mtDNA mutations in brain, heart, and liver, and respiratory chain dysfunction in the heart, a host of premature aging symptoms was observed in this mutant, including...

Skin Color

Remarks For documentation of skin color, a color photograph is useful. The color of tooth enamel, nails, iris, body, and scalp hair, as well as skin, should be recorded. The skin around the nipple, especially after pregnancy, may be darker due to hormonal influences. Genital skin and areas of apocrine sweating are usually darker. Pigment changes can occur in specific diseases, such as Addison disease (a bronze skin color) or albinism (where the skin and hair pigment may be reduced or absent).

Physical Differences

On the average, girls reach puberty 2 years earlier than boys, and in junior high school some boys may feel like shrimps alongside their female classmates. By the time both sexes have completed adolescence, females have substantially more body fat (70 more) than males but are shorter (5 inches), less muscular (40 less), and have less facial hair (Myers, 1995). These differences persist and others develop in young adulthood. For example, pattern baldness often starts showing in adult males in their late teens or early twenties. And with respect to the biology of sexual behavior, young women are more likely to become sexually aroused soon after experiencing orgasm.

Discussion

Physical therapies may be directed against either the secondary prevention of early lesions or the destruction of established lesions. For true primary prevention of early lesions the pathogenic process is insufficiently described to allow a causal therapy, although the use of laser depilation may yet prove to be fruitful in proper studies. The possible effect of PDT on the hair follicle is at present unclear. It is not convincingly proven that the penetration of ALA-PDT is sufficiently deep to allow treatment of established lesions of Hurley category II or III. Nor is it established that ALA-PDT has any effect on sinus tracts. The effects may therefore be more in line with the effects of this treatment in acne vulgaris, where a significant clinical effect has been shown in some studies. ALA-PDT is however associated with considerable post-treatment pain and inflammation in acne patients and this may also limit its use in HS. tizer into the hair follicles. The use of red light is...

Irinotecan

Irinotecan is similarly being developed for adjuvant use, having been shown to be active in metastatic colorectal disease both alone and in combination with 5-FU. It is a topoisomerase I inhibitor. (This enzyme is involved in DNA supercoiling.) The advantage over oxaliplatin is a relative lack of long-term side effects, although short-term side effects include diarrhea, myelo-suppression, and alopecia.

Brain Metastases

More than 100,000 patients are diagnosed with brain metastasis annually. The management of brain metastasis patients remains a challenge for oncologists, radiation oncologists, and neurosurgeons. Traditional therapy of single metastasis has been either resection or whole brain radiation (WBRT), with a boost to the affected region, or combined surgery with whole brain radiation. The surgical resection of solitary metastasis with WBRT has been shown to improve survival compared to WBRT alone 7 . The complications of whole brain fractionated radiation include memory loss, alopecia, dementia, and radiation necrosis.

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