Homemade Skin Care Recipes

Rejuvenating Skin Care Recipes

The Naturally Skinsational eBook shares the simple secrets that will teach you how to use the potent rejuvenating properties of common all natural ingredients to effectively rejuvenate your skin. Consider all the benefits of making your own skin treatments using all natural recipes: Gives your aging skin effective anti-aging treatments and defense against damage using the science of herbal lore to proactively address the symptoms of aging skin including fine lines, wrinkles, age spots and sagging skin. Provides your skin with all-natural rejuvenating properties of herbs that best combat degeneration by stimulating healing, collagen production, and offer powerful antioxidant protection against further signs of aging, skin damage and deterioration. Nourishes your skin with powerful natural antioxidants and nutrients that stimulate cell regeneration. Saves you ridiculous amounts of money on store bought skin treatments. Uses common ingredients found right in your own kitchen. Quick and easy skin care recipes that use ingredients with proven natural anti-aging attributes. Gives you piece of mind that your skin treatments are made with quality fresh ingredients. Provides a deep sense of satisfaction that your homemade skin care products have maximized the potency of natural ingredients. Continue reading...

Rejuvenating Skin Care Recipes Summary


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Diseases Of Botulinum And Tetanus Neurotoxins

Human botulism manifests itself in a number of different forms, depending on the mode of entry of the toxin into the circulation. Three naturally occurring types of botulism exist foodborne, wound, and intestinal. The latter occurs predominantly in infants and only rarely in adults. Inhalation botulism is an additional, man-made form of the disease that can occur when aerosols of the toxin are absorbed through the mucosal surfaces. Of the seven botulinum serotypes, outbreaks of human botulism are almost exclusively limited to serotypes A, B, E, and F. Types A, B, and E predominate.1 Enviromental factors determine the C. botulinum serotype associated with foodborne disease. C. botulinum type E is abundant in the sediments of aquatic environments of Europe and North America, based on the fact that type E toxin is almost exclusively associated with foodborne outbreaks involving contaminated fish and other aquatic foods. Serotypes A and B predominate in outbreaks involving meat products...

Structure Of Botulinum Neurotoxin Serotype A Light Chain

The three-dimensional structure of BoNT A wild-type LC (BoNT A-LC PDB accession code 1E1H) has been solved at 1.8 A resolution by Selgeke, Balhorn, and Rupp,13 and an inactive double mutant (E224Q Y366F) BoNT A-LC form was recently reported at 2.2 A resolution in the apo (PDB accession code 1XTF) and substrate-bound (PDB accession code 1XTG) forms by Axel Brunger's group.14 The wild-type BoNT A-LC and apo double-mutant structures are similar to the structure of the serotype A holotoxin (LCs and HCs intact as expressed by C. botulinum bacteria) solved by Stevens' lab in 1998 (Figure 2.1).1

Clostridium botulinum

Clostridium botulinum is the cause of botulism and is due to intoxication with a group of similar clostridial neurotoxins (types A to G) that predominantly affect the peripheral neuro-muscular junction and autonomic synapses.102 Although classically associated with food-borne, wound, and infantile presentations, an inhalational form in the setting of bioterror-ism has been discussed.102 All forms lead to similar neurologic presentations.

How does diabetes affect your skin

Your skin is your body's first line of defence against invasion by germs and the development of infections. Unfortunately, people with diabetes are at increased risk A small minority of people with diabetes may have skin problems caused by damage to the small blood vessels. When this occurs, it results in reddening and thinning of the skin over the lower shinbones - a condition known as necrobiosis lipoidica. Unfortunately, there is no effective treatment. Other skin-related problems that are statistically more likely to occur in people with diabetes include fungal infections, a depigmentation of the skin called vitiligo, and loss of hair on the head, known scientifically as alopecia.

Botox Injection A Nonsurgical Method for Reducing Facial Wrinkles

Botulinum toxin (Botox) is a medication with the unique property of relaxing muscles after direct injection into the muscle. This medication is a purified protein produced by Clostridium botulinum, the bacterium that causes botulism. Botulism occurs in humans when they are exposed to large doses of botulinum toxin, usually by ingesting food that has been contaminated with the bacterium. The disease can be fatal if large amounts of the toxin are ingested because the toxin causes paralysis of all muscles, including those required for breathing. Extremely small doses of botulinum toxin are effective at safely paralyzing the muscles into which it is injected (without producing any systemic effect because it does not reach other parts of the body). The paralysis produced by Botox injection is temporary (3-6 month duration). At the nerve ending between motor nerve cells and skeletal muscle cells, molecules of the neurotransmitter acetylcholine are released from the nerve cell and migrate to...

Clinical Use Of Botulinum Neurotoxins

As noted, botulinum neurotoxins are the most potent acute lethal toxins known, with lethal doses occurring at 10-9 g kg of body weight.52 Despite this lethality, the same toxins, and in particular serotype A, have found increasing use in recent years to treat diseases and conditions involving neuromuscular or autonomic neuronal transmission. This transformation of a widely feared neurotoxin into a widely accepted clinical agent has been underpinned by a strong base of basic research. Demonstrations of both the safety and therapeutic effectiveness of botulinum neurotoxin clinical preparations have driven ever-growing medical uses of these materials. In recent years, botulinum neurotoxins have been demonstrated to exert direct beneficial effects in a range of clinical conditions including a number of chronic pain syndromes. It is of interest to note that Kerner, who first described botulism as a medical The clinical use of botulinum neurotoxin to effect a chemical denervation in a...

Possible Proteolytic Mechanisms Of Botulinum Neurotoxins

FIGURE 2.9 Proposed reaction mechanism for synaptobrevin proteolysis by botulinum neurotoxin. Dotted lines represent noncovalent and hydrogen bonding interactions. Relevant interatomic distances are labeled in the reactants and products. An alternative mechanism involves Tyr372 stabilizing the transition state oxyanion in conjunction with Arg369 instead of donating a hydrogen to the leaving group. (From Hanson, M.A. and Stevens, R.C., in Scientific and Therapeutic Aspects of Botulinum Toxin, Brin, M.F., Jankovic, J., and Hallett, M., Eds., Lippincott Williams & Wilkins, Philadelphia, 2002. With permission.) FIGURE 2.9 Proposed reaction mechanism for synaptobrevin proteolysis by botulinum neurotoxin. Dotted lines represent noncovalent and hydrogen bonding interactions. Relevant interatomic distances are labeled in the reactants and products. An alternative mechanism involves Tyr372 stabilizing the transition state oxyanion in conjunction with Arg369 instead of donating a hydrogen to...

Structure Of Botulinum Neurotoxin 150kDa Holotoxin Light Chainheavy Chain Complex

In the past few years, 21 botulinum neurotoxin (BoNT) protein structures and 8 tetanus neurotoxin (TeNT) structures have been deposited in the publicly accessible Protein Data Bank (PDB Table 2.1). This represents structural information on serotypes A (BoNT A) and B (BoNT B) holotoxins (secreted forms of the neurotoxin with light chains (LC) in complex with heavy chains) LC structures of BoNT A, B, E, and TeNT and TeNT binding domain (C fragment). Given this wealth of structural information, it is exciting to see the insights gained regarding the toxins' structures and functions, but interestingly, more questions than answers appear to have emerged with regards to toxin cell recognition, toxin translocation, and soluble N-ethyl-male-imide-sensitive fusion (NSF) protein attachment receptor (SNARE) proteolysis.

Skin Problems

Some skin problems are caused by diseases or irritations that affect the skin only such as ringworm, diaper rash, or warts. Other skin problems are signs of diseases that affect the whole body such as the rash of measles or the sore, dry patches of pellagra (malnutrition). Certain kinds of sores or skin conditions may be signs of serious diseases like tuberculosis, syphilis, or leprosy. This chapter deals only with the more common skin problems in rural areas. However, there are hundreds of diseases of the skin. Some look so much alike that they are hard to tell apart yet their causes and the specific treatments they require may be quite different.

Structuring life around disease when it gets better I will

One of the most common 'coping mechanisms' displayed by people with skin problems is a desire to treat and get rid of the condition rather than getting on with living with it. Behaviours such as taking up new sports, applying for a promotion or even getting married are postponed in the hope that the condition will be cured, enabling them to lead more enjoyable lives. Here follows a section taken from a counselling session with a 22-year-old Asian woman who had recently been diagnosed with vitiligo.

How is skin disease different from other conditions

As with any illness, a skin disease brings on a variety of life changes and challenges that we may not be prepared to deal with. However, unlike conditions which do not change the way people look, skin problems raise a whole new set of challenges because of their visibility. The visibility of certain conditions may attract attention in social situations, thus making the individual feel that they can't keep their condition private or personal. Furthermore, owing to a lack of health education and awareness in dermatology, some people associate skin disease with contagion or lack of hygiene. This ignorance regarding skin conditions means that a skin disease patient may find that some people react negatively towards them or treat them differently because of the way that they look. In many cases the physical changes that may result from skin disease can have a negative effect on body image. Body image is our perception of the way that others see us, and therefore any sudden changes to the...


It is possible that many of the images that arise from TV adverts are drawn from society at large and can be seen as a kind of barometer of cultural values and beliefs. For instance, media advertising of beauty aids may accentuate the distinction between normal and different people as they often promote the idea that attractive people have better prospects for their professional and social lives. A skin care cream may show a handsome model using the cream to get rid of their spots before they go out and have a great time, mixing successfully with members of the opposite sex, now that they have smooth, clear skin. If you fall for the message that your skin condition prevents you from achieving social and professional success you may be encouraged to 'put your life on hold' until your skin condition clears up. It is important that you don't take this attitude as your skin condition should NOT put you off doing the things that you want to. There are many different aspects to a person and...

Other Modes of Altering Virulence and Pathogenicity

In addition to their own genetic material, many classes of microparasites either contain or are capable of acquiring transferable genetic elements in the form of plasmids, transposons, or bacteriophages. Bacterial virulence factors that are encoded by plasmids include the heat-stable and heat-labile enterotoxins of Escherichia coli, the toxins of Shigella and enteroinvasive E. coli, and the neurotoxin of tetanus. Phage-encoded bacterial virulence determinants include diphtheria toxin, botulinum neurotoxin, and the Shiga-like toxins of enterohemorrhagic E. coli. These transferable genetic elements also provide a means for the spread of resistance to antibacterial drugs, an increasing problem in all regions of the world.27

Neurotoxigenic Clostridia 121 Discovery of Neurotoxins

FIGURE 1.1 Electron micrograph of sporulating C. botulinum terminal spores are clearly visible. (B. Dowsett, Health Protection Agency. With permission.) FIGURE 1.1 Electron micrograph of sporulating C. botulinum terminal spores are clearly visible. (B. Dowsett, Health Protection Agency. With permission.) modes of action of the tetanus and botulinum neurotoxins are described in Chapters 2 and 3. The organisms that produce tetanus and botulinum neurotoxins belong to the genus Clostridium Gram-positive (sometimes Gram-variable), anaerobic, spore-forming bacilli (rods) that may be straight or slightly curved, measuring 0.5 to 2.0 im wide and 1.6 to 22 im long.1,11 The observed variations may reflect differences in culture type, strain, growth medium, and physiological status.10,11 One striking feature of the cellular morphology of the clostridia is the spore, which being wider than the cell, causes a swelling and the characteristic spindle shape from which the name Clostridium derives...

Botulism see also Food poisoning

Botulism is produced by the neurotoxin from the anaerobic Gram-positive bacillus, Clostridium botulinum, which blocks acetylcholine release at peripheral nerve endings. The use of botulinum toxin in hemifacial spasm and related disorders is an interesting and valuable clinical application of this otherwise undesirable toxin.

Vaccine Candidate Selection and Expression

The high sequence and structural homology between TeNT and BoNT led scientists at USAMRIID to take a similar approach for BoNT recombinant vaccines. Several overlapping domains of the DNA sequence encoding the heavy chain of BoNT A were isolated by PCR from the C. botulinum NCTC2916 strain. Expression and purification from Escherichia coli indicated that the most promising vaccine candidate encompassed the approximately 50-kDa domain from the C-terminus of the heavy chain (Hc), crude extracts of which were able to protect mice against BoNT challenge.53 54 This suggested that the domain chosen was folding correctly, thus allowing the correct formation of protective epitopes.

Stat3Mediated Transduction of IL6 Signaling Is Essential for Tissue Repair

STATs (signal transducers and activators of transcription) are cytoplasmic molecules that transduce signals from a variety of growth factors, cytokines, and hormones. Once activated by tyrosine phosphorylation, they dimerize and translocate to the nucleus, where they bind to specific DNA elements and thus activate target gene expression (67). Stat-3 is activated by IL-6 signaling and is thus a likely candidate for a role in wound repair. Since Stat-3 null mice die during embryogenesis (68), Sano et al. (69) used a Cre-lox approach to knock out Stat-3 in keratinocytes. Consistent with a low level of IL-6 expression in normal skin, they saw no effect on skin morphogenesis. However, following full-thickness excisional wounding, the healing process was severely compromised, with dramatically reduced reepithelialization (Fig. 2), showing clear similarities to the reepithelialization phenotype of the IL-6 knockout mice. The overall effect on repair was less dramatic than in the IL-6 null...

Prospects for the Future

In the future, continued advances in molecular biology will undoubtedly lead to additional novel therapies to accelerate wound repair. Studies of the molecular biology of aging are yielding new insights into aging in vivo in skin and other tissues. Initial experiments utilized cells aged in culture (by serial passage) and demonstrated that somatic cells, such as dermal fibroblasts, have a finite ability to undergo cell division. This process was termed replicative or cellular senescence and provided the foundation for advances in the cell biology of aging (95). Although a causal relationship between cellular senescence and organismic aging in vivo has not been established, recent data indicate that senescent cells could negatively impact aging skin and subsequent wound healing in the aged. Dimri et al. (96) have shown that there is an increase in the number of cells that express SA-P-galactosidase, a marker of senescence, in both the dermis and epidermis of aged human skin....

Structure And Physiological Functions Of The Skin

Dermal fibroblasts also produce matrix metalloproteinases (MMPs) that provide for a dynamic turnover of extracellular matrix proteins and also are important in wound healing (Pilcher et al., 1999). These MMPs include collagenase-1 (MMP-1), stromelysin-1 (MMP-3), and gelatinase B (MMP-9). A balance between synthesis and enzymatic degradation of extracellular matrix proteins is required for homeostasis in the dermis. In aging skin, the synthesis of matrix proteins slows, while expression of MMPs is increased (West, 1994). These biochemical changes in the dermis can result in the sagging and wrinkles commonly observed in aged skin. Chronic exposure to sunlight can further exacerbate these biochemical changes in the dermis (Wlaschek et al., 2001).

Cutaneous Absorption And Deposition Of Dietary And Topically Applied Retinol And Retinyl Esters

While vitamin A is required for development and maintenance of healthy skin, humans, as well as other animals, are incapable of de novo synthesis of compounds with vitamin A activity. These compounds must, therefore, be obtained exogenously. For the skin, compounds with vitamin A activity

Microbial Pathogens

This organism is sometimes called the fish botulism organism. Under suitable conditions, the organism will grow and produce a toxin. The toxin is extremely lethal and may cause death if ingested. The toxin is heat sensitive and will normally be destroyed by proper cooking. The organism can grow in improperly processed canned fish, in vacuum-packaged products, and in some smoked products.

Vitiligo White Areas of the Skin

In some persons, certain areas of the skin lose their natural color (pigment). Then white patches appear. These are most common on the hands, feet, face, and upper body. This loss of normal skin color called vitiligo is not an illness. It can be compared to white hair in older people. No treatment helps or is needed, but the white skin should be protected from sunburn with clothing or an ointment of zinc oxide. Also, special coloring creams can help make the spots less noticeable.

Temporal summation in secondary hyperalgesic areas

The facilitation of temporal summation to either laser or electrical stimuli in secondary hyperalgesic areas seems controversial and depends on the stimulus modality and configuration 31, 40, 50, 51 . In the human topical capsaicin model, the summation of both electrical and radiant heat stimuli were facilitated in the secondary hyperalgesic area compared with normal skin 40 . Pedersen et al. 51 used the controlled-heat injury model for the induction of hyperalgesia and found no facilitation of temporal summation to painful electrical stimuli in the hyperalgesic areas. It is unclear if capsaicin and controlled-heat injury initiate different forms of central sensitization with different characteristics, which may result in different effects on temporal summation. Furthermore, it is not known if different stimulus modalities used to evoke temporal summation are of importance to explain the mechanisms of hyperalgesia and temporal summation. Therefore, Yucel et al. 31 performed a...

Endopeptidase Fragments For Pain Relief

The analgesic properties of the botulinum neurotoxins described above strongly support the view that if clostridial endopeptidases could be selectively targeted to peripheral nociceptive afferents in preference to other neurons, transmission of pain responses could be specifically and potently inhibited. The key to achieving selectively targeted clostridial endopeptidase-based analgesics is the identification of a suitable ligand able to specifically target nociceptive afferents and, following binding, to internalize with the clostridial endopeptidase. It has been reported that galactose-containing carbohydrates are selectively present on nociceptive afferents in the central and peripheral nervous systems relative to other neurons.59 60 Lectins from Erythrina species have been identified to bind such galactose-containing carbohydrates and the lectin from Erythrina cristagalli was selected to test the hypothesis that clostridial endopeptidases could be selectively retargeted to...

Clinical Features

Most tropical ulcers develop at exposed sites on the limbs, possibly areas subject to trauma such as a scratch or insect bite, and are therefore commonest on the lower legs and on the unshod foot. They may also occur on the arms. The ulcer goes through an evolutionary phase starting with a preulcerative papule on apparently healthy skin. This is an area of hyperpigmentation and swelling which may rarely blister (Fig. 62.1). A characteristic is its rapid breakdown to form an ulcer with an indurated edge. The sudden appearance of the ulcer from an area of discomfort on an exposed site together with subsequent pain and the regular punched out appearance are very typical (Fig. 62.2). The floor of the ulcer is covered by a foul-smelling, grayish, purulent slough. Pain is common and there may be fever and constitutional symptoms. There is usually no regional lymph node swelling. If the lesion is treated promptly with careful dressing, the spread is limited to a lesion, 2-4 cm in diameter,...

Use of High Throughput Microarray Membranes for cDNA Analysis of Cutaneous Wound Repair

Because of the ability to store large data sets and compare different experiments, it is possible not only to compare hypertropic scar with normal scar or to normal skin, as we have previously reported, but also to compare the data from those arrays to other data sets such as acute wounds. This allows a

Health Hazards In Semiperishable Subsistence

(1) Characteristics of botulism contamination. Food poisoning types of other than Clostridium botulinum are rarely found in canned foods. Clostridium botulinum has been the cause of many deaths from consumption of home-canned foods. Since commercial heat processes are regulated by FDA and USDA, the problem is very rare in commercially canned foods. In addition to its deadly toxin, Clostridium botulinum normally produces gas from most sugars (and thus swells the container) or digests the low-acid canned food. Therefore, the person opening the container has some indication of its presence. When an odor is produced, it is putrefactive, not fecal or sour, but sickening.

Longterm Urologic Management

The use of a chronic indwelling catheter is never desirable because of its complications including epididymitis, urethrocutaneous fistula, traumatic hypospadias, and squamous cell carcinoma. Yet, chronic catheterization remains the most common form of management in patients who are tetraplegic and bedridden. Many female patients, unable to use an external collecting device, are managed with catheter drainage because they fail pharmacologic therapy and or have limited hand function. McGuire followed 35 women managed with either an indwelling catheter or CIC for 2-12 yr following spinal-cord injury and found a significant reduction in the incidence of autonomic dysreflexia, febrile UTIs, pyelonephritic scarring by I VP, and bladder stones in patients managed with intermittent catheterization. This same study showed 92 of women with long-term indwelling catheters eventually had incontinence around the catheter and 54 had urethral erosion, whereas none on CIC had these complications (51)....

Superior Pedicle Vertical Scar Mammaplasty Surgical Technique

Breast Reduction Scarring

In my practice the vertical technique is applied to all reductions and mastopexies regardless of size. I personally do not believe that breast size is a limiting factor rather I believe that the amount of excess skin, the quality of the skin, the relationship of the skin envelope to the breast tissue, and the distance the nipple has to be moved are far more important factors than breast size alone. The best candidates are those with normal skin elasticity and a skin envelope that adheres to the underlying breast tissue and those with moderately large breasts. Less ideal candidates are those with poor-quality skin, a loose envelope where the skin adheres poorly to the underlying breast tissue, and extreme ptosis or breast hypertrophy.

Pathogenic cell adhesion and invasion 431 Adhesion

Because adhesion is a requisite step for any foodborne infection, it stands to reason that preventing bacterial adhesion is a principal way to prevent foodborne infections. A key contributing factor to the prevention of adhesion by foodborne pathogens is the resident competitive microflora in our large intestine. These resident microorganisms are very diverse and most cannot be cultured ex vivo (Hooper and Gordon, 2001). Using traditional culture techniques if possible and, more recently, molecular approaches such as 16S ribosomal RNA gene sequencing, members of the Bacteroides, eubacteria, bifidobacteria, anaerobic Gram-positive cocci, clostridia, lactobacilli, Escherichia, methanogens, fusobacteria, entero-bacteria, Veillonella, staphylococci, Proteus and Pseudomonas, among others, have been identified in the intestine (Bourlioux et al., 2003). The intestinal microflora prevents adhesion by pathogenic organisms by competing with them for limited space and nutrients, as well as by...

Early Toxoid Development and

The first reported use of a botulinum toxoid vaccine in humans was achieved by Velikanov in 1934.23 Research intensified during World War II, and methods for preparing alum-precipitated type A and B toxoids for use in animals and humans were developed by Nigg and coworkers in the United States24,25 and by Rice and coworkers in Canada.26-28 Prevot and Brygoo29 produced type C antitoxin in humans by vaccinating with toxoid prepared from toxin extracted from bacterial cells. A bivalent type AB toxoid was developed and produced at Fort Detrick during World War II.30

Laser Treatment of Tattoos

Q-switched laser treatment of tattoos is moderately painful but usually does not require anesthesia. These extremely short-pulsed lasers produce a sensation similar to that of a rubber band snapping against the skin. The sensation is sharp but very brief, and is painful mainly during the actual treatment. Topical anesthetic creams such as EMLA or Betacaine may be partially helpful but are limited in effect because they numb only the more superficial layers of skin. Unfortunately, it is the deeper layers (in the dermis) where the tattoo ink particles are located. Subsequent laser treatments are progressively less painful because there is less and less ink in the tattoo. In fact, where there is no tattoo ink in the skin, these lasers are virtually painless. This is because tattooed skin contains much more chromophore than does normal skin.

What Are Lasers and How Do They Work

How Medical Lasers Work

For a better understanding of the special advantages of lasers in cosmetic surgery, we need to know what a laser is. How is laser energy produced What are the properties of laser light that distinguish it from conventional light or other energy sources Why are lasers uniquely suited to treat special skin problems of cosmetic concern to patients Is a laser really that special, and why The story of lasers begins over a hundred years ago.

Clinical Testing of rBV AB Pichia pastoris Vaccine

The Phase 1 clinical trial represents the first human experience of the rBV A B (Pichia pastoris) vaccine. The primary objective of the 1 clinical trial is to evaluate the safety, tolerability, and immunogenicity of a two-dose regimen (day 0, day 28) of rBV A B (Pichia pastoris) vaccine at three dosage levels. A secondary objective is to evaluate human neutralizing antibody as a correlate of protective immunity. This will be determined by transfer of sera from the clinical trial volunteers into guinea pigs, and the animals will then be subject to experimental intramuscular challenge with serotype-specific BoNT. This passive transfer model was originally developed for the PBT vaccine as a viable alternative to more conventional Phase 3 clinical testing of botulinum vaccines because the incidence of the disease is extremely low and direct challenge studies in humans are unethical.84 This model requires that human serum containing neutralizing antibodies (measured using a Mouse...

Endocrine Causes of Obesity

Many patients are concerned that they have a metabolic or glandular cause for their obesity. This may be a reflection of the frustration that some of these individuals feel over the difficulties that they have had in battling a weight problem over many years. They may be looking for a medical explanation of why they have not succeeded in their goal of losing weight. Endocrine causes of serious obesity are not common. The three most commonly cited are hypothyroidism, Cushing's syndrome, and hypothalamic obesity. To evaluate the patient for hypothyroidism, questions can be asked about cold intolerance, constipation, irregular menses, fatigue, or depression. The presence of easy bruisability, proximal muscle weakness (difficulty getting out of a chair, trouble getting things out of a high cupboard), a change in appearance, or osteoporosis may be signs of hypercortisolism. The patient can be examined for signs of hypothyroidism including bradycardia, cool dry skin, a firm palpable...

Antibacterial mechanisms

The most common assumption is that it is the alcohol in wine that kills bacteria. After all, alcohol has long been used as an antiseptic and is an effective disinfectant for wounds or healthy skin. The most common alcohol used as an antiseptic is isopropyl alcohol, or isopropanol (chemical structure CH3-CH 2 CH2OH). Isopropanol replaced ethanol as an antiseptic because it has similar properties but is much cheaper to produce. High concentrations of alcohol are required to kill bacteria, and 70 isopropanol has been found to be the most active concentration against Staphylococci and other bacteria (Harrington and Walker 1903). Ethanol, or ethyl alcohol (CH3-CH2OH), is the alcohol found in wine, beer and spirits. Like isopropanol, it is strongly antibacterial at high concentrations, but its efficacy wanes as the percentage decreases (Block 2001). We found that ethanol 40 was almost instantaneously lethal against Staphylococci and enteric bacteria, but ethanol 10 had almost no effect on...

In the Hands of a Young Surgeon Which Pattern Should be Used in Reduction Mammaplasty

My personal algorithm in scar selection is summarized in Fig. 15.1. I choose vertical scar mammaplasty in all patients under 30 years old. These patients usually have good skin quality, and skin retraction is expected. In very large breasts (more than 1000 g), secondary revision of the vertical scar is more likely to be necessary (see Chap. 14).

Lichen Sclerosus Et Atrophicus

Lichen sclerosus et atrophicus (LSA) may be found in males and females of all ages (1,2), but is typically a problem in older women appearing in the vulvar keyhole distribution (3,4). While it is generally assumed that LSA is an acquired disease, there are no longitudinal studies demonstrating its origin in normal skin, so that the possibility of congenital predisposition cannot be ruled out. Because the disease is occasionally found in premenarchal girls, an argument for congenital origin or genetic control may have some weight.

Snaremediated Vesicle Fusion As A Therapeutic Agent

None of the clostridial neurotoxins is known to kill neurons in vivo their extreme toxicity arises from the effect of the blockade of neuronal activity on whole animal physiology. Clinical experience with BoNTs indicates that neurotransmission can be inhibited for extended periods, the exact duration of which varies among sero-types, but can be several weeks or even months, and that the cells ultimately recover functionality. This is a highly desirable attribute of botulinum neurotoxin-based therapies, and one that would be desirable to retain in retargeted LHN endopeptidase based agents. It is also worth noting that clinical use of BoNT C has been reported,34 with no obvious adverse effects indicative of cytotoxic activity, again supporting the view that in vivo the neurotoxins are noncytotoxic. These in vitro data are all supportive of the concept of retargeting LHN to a cell of interest and achieving inhibition of stimulated secretion from the target cell. The next stage in the...

Aspects of Epidermal Regeneration

Blasts established from normal skin or from hypertrophic scar tissue to the growth factor. However, simplified in vitro cell culture systems inherently lack other components that may influence the responses of cells in vivo. For example, study of the response of pure cultures of fibroblasts to a scrape injury (as a model of an incision wound) does not include the contribution of paracrine growth factors and cytokines that may be secreted by epidermal keratinocytes or inflammatory cells. Although constraints exist, both in vitro and in vivo model systems provide important information about aspects of skin wound healing.

Toxin Uptake Toxicity And Clinical Disease Manifestation

BoNTs represent a group of protein toxins produced under anaerobic conditions in protein-rich habitats by Clostridium botulinum, C. barati, and C. butyricum.1-4 TeNT, which is produced by C. tetani and causes different symptoms in humans, shares many features with the BoNTs such as sequence, structure, and function.5 Thus, the classification of the CNTs has more of a historical than a scientific background, and TeNT may be considered another BoNT. The BoNTs are classified on the basis of their serological properties. There are seven types denominated A through G plus TeNT.

Electrophysiological methods to assess hyperalgesia

Repetitive punctuate stimulation with a von Frey hair within the area with hyperalgesia is illustrated. The device stimulates with a fixed time period in contact with the skin and with a fixed frequency. The thickness of the von Frey hair can be changed. After hyperalgesia has been induced, robust punctuate pain is induced with this repetitive paradigm, compared to normal skin. The temporal summation mechanism is facilitated for punctuate and mechanical impact stimuli within the secondary hyperalgesic area 31 . If the von Frey hair is replaced by a thinner filament, tactile allodynia can be assessed. Repetitive tactile stimulation causes pain after hyperalgesia has developed in contrast to normal skin. VAS, visual analog scale. Repetitive punctuate stimulation with a von Frey hair within the area with hyperalgesia is illustrated. The device stimulates with a fixed time period in contact with the skin and with a fixed frequency. The thickness of the von Frey hair can be changed. After...

Trisomy 21 Down Syndrome

Overfolding upper helix, and small or absent earlobes. Hypoplastic teeth are common. Hand findings include short metacarpals and fingers, clinodactyly (60 ), simian crease (45 ), and characteristic prints. They exhibit a wide gap between the first and second toes. Cardiac abnormalities are present in 49 , with endocardial cushion defects, ventricular septal defects (VSDs), patent ductus arteriosus (PDA), and atrial septal defects (ASDs). Cutaneous manifestations include dry skin, cutis marmorata, fine, soft sparse hair, and straight pubic hair. Occasionally, patients have seizures, strabismus, and low-set ears. Patients are at higher risk for duodenal atresia, atlantoaxial instability, leukemia, and thyroid disease.

Treatment And Nursing Care

Diet and activity should be adjusted to the clinical condition of the patient. The extremely ill patient will not want ambulation and may have nausea and vomiting so severe as to require supplements with 10 percent glucose solution. After gradually increasing ambulation, the patient may return to normal activity when he is asymptomatic and the liver tenderness has subsided. There is no specific medical treatment for viral hepatitis. Good general care is required. Pay attention to good oral hygiene, skin care, and elimination. Encourage fluids by mouth if nausea is not a problem. It may be necessary to entice the patient to eat. He may resist eating at first but eventually he will recover his appetite. When the appetite has returned to normal, a diet high in calories, proteins, and moderate carbohydrates is usually ordered. Fats may or may not be limited and vitamins may be given. For the patient with fulminant hepatitis, the common complications are hepatic coma, renal failure, and...

Structure Of Tetanus Neurotoxin Light Chain

While crystal structures are available for the catalytic domains of several serotypes of botulinum neurotoxin, only a homology-based model has been available for tetanus neurotoxin catalytic domain (TeNT-LC) until now.16 Recently, the crystal structure of TeNT-LC was determined in Swaminathan's laboratory. Not surprisingly, the model is very similar to other botulinum neurotoxin light chains.32 TeNT-LC forms a dimer in the crystal via a crystallographic two-fold with about 10 (3100 2) of the total surface area buried at the interface. A ribbon representation of the catalytic domain of TeNT-LC along with the active site residues is shown in Figure 2.15. Except for BoNT B-LC, all LC structures determined to date exist as dimers in the crystals.


Foster, Ph.D. gained an M.A. in natural sciences from the University of Cambridge in 1977, followed by a Ph.D. from the University of London in 1980. He spent two years as a postdoctoral fellow at the University of Nottingham before joining SmithKline Beecham (SB) as a principal scientist. He left SB in 1993 to join the newly established Speywood Laboratory Limited (TSL) as a research group leader where he established de novo a research facility and team to undertake studies of the therapeutic potential of botulinum neurotoxin fragments. After three years at TSL, Dr. Foster moved with some of his team to the Centre for Applied Microbiology and Research (CAMR), now the United Kingdom Health Protection Agency (HPA) at Porton Down, to continue the work on neurotoxin fragments. The lead application of this technology, long acting analgesics for the treatment of chronic pain, was licensed to Allergan Inc. in 2000. The work on neurotoxin modification established a proprietary...

Bacterial Toxins

Exotoxins are secreted by bacteria into their environment and are potent and specific in their action upon host tissue. The ability to form exotoxins is usually attributed to certain gram-positive rods such as the clostridia and the corynebacteria. The exotoxin has been found to be a highly antigenic, heat labile, proteinaceous substance that is usually destroyed by proteolytic enzymes. However, the very potent and toxic exotoxin of Clostridium botulinum is the exception is not destroyed by proteolytic enzymes. The toxic properties, but not the antigenic properties, of exotoxins are destroyed by formalin, heat, or prolonged storage. Such treated toxins are called toxoids and find great practical use in immunization programs.


As stated at the beginning of this chapter, a wealth of new botulinum structural information has appeared over the past few years, and we now have a better understanding of how the toxin looks and functions. However, several mysteries still exist and a few new ones have evolved based on the structural and mutagenesis work. In particular, the catalytic mechanism, the reason substrate or product molecules cannot be formed with the toxin in an active state, and the binding of multiple inhibitor chemotypes to the active state remain challenges for structural biologists. The recent discovery of multiple subtypes of the serotype is likely to raise even more questions regarding toxin structure and function. However, the only way to answer these questions is to continue the structural and mechanistic work in the hope that convergence will occur in the near future regarding our understanding of BoNT structure and function.


Botulinum toxin detected in patient's serum and canned-food sample with specific antiserum. Characterized by gradual return of muscle strength in most cases. Botulinum toxin is a zinc metalloprotease that cleaves specific components of synaptic vesicle docking and fusion complexes, thus inhibiting the release of acetylcholine at the neuromuscular junction. The disease in adults is due to ingestion of the toxin rather than to bacterial infection. Botulism is also seen in infants secondary to the ingestion of Clostridium botulinum spores in honey.

Nonsurgical approach

This approach consists of MLD, compression bandaging, exercise therapy and patient education regarding skin care. Why take care of your skin Lymphoedema is an excess of water, large proteins and waste material, which has accumulated in the tissues. This is an ideal environment for bacteria to manifest. In some cases, the lymph nodes may have been removed, therefore, the local immune system may be compromised in the swollen area. All of these factors contribute to the increased risk of developing an AIE (cellulitis). Taking care of your skin, minimises the increased risk of infection, which often accompanies lymphatic disorders. How to take care of your skin

Aneurysm Formation

With repeated cannulation over small areas of a graft, there is a tendency for aneurysm formation (actually a pseudoaneurysm). This is a result of longitudinal splitting of the graft. It is not a problem if there is good skin coverage, but if enlarging rapidly or if inflamed, then early revision should be undertaken to prevent rupture and bleeding. The technique is similar to that used for infection, with the exception that excision of the aneurysmal portion of the graft is not always necessary in the absence of infection.


Regrettably, dystonia is not particularly well recognized by the general population and indeed is often misdiagnosed and misunderstood by the medical profession.24 Thus, it is perhaps surprising that at least 250,000 cases of idiopathic dystonia probably exist in the United States. A recent definitive study in northeast England revealed about 30 people per 100,000 population with the diagnosis.25 Prior to the advent of botulinum toxin, not only was the condition often misdiagnosed, but patients had very limited treatment options if it was correctly diagnosed. The advent of botulinum toxin has not only fundamentally changed the treatment possibilities but had the secondary effect of increasing awareness of the condition, leading to improvements in correct and prompt diagnoses and initiation of appropriate treatment.


The other most prevalent use of botulinum toxin is for the management of spasticity in both adults and children. Spasticity is a very significant cause of disability in people with a variety of neurological disorders, particularly stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. It is also a major problem in children and adults with cerebral palsy. It has been defined 46 as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone) with exaggerated tendon jerks, resulting in hyperexcitability of the stretch reflex, as one component of the upper motor neurone syndrome. Spasticity is one component of the upper motor neurone (UMN) syndrome. It is important to emphasize that UMN syndrome can follow any lesion affecting some or all of the descending motor pathways. It has a number of features, many of which are actually more responsible for the disability and consequent handicap than the spasticity itself. Table 6.3...


The recovery of the skin barrier can be followed in open blisters using noninvasive techniques, such as measuring transepidermal water evaporation and blood circulation (13,14). Water evaporation can be measured with an Evaporimeter EP2. The probe is placed on the wound, and three measurements are usually made from each blister. Evaporation from healthy skin is also measured. Water evaporation is usually

Concluding Remarks

The clinical use of botulinum toxin has been a remarkable story in the 33 years since Scott's publication. The injection is an easy, safe, and effective technique with a very high success rate in an increasing variety of conditions. It is particularly useful and indeed is now the treatment of choice for the management of dystonia and has an increasingly important part to play in the overall management of spasticity. It is also finding a major role in the management of other conditions characterized by muscle spasm and hypersecretion. An increasing range of other indications will be outlined in the next chapter. Botulinum toxin is a remarkable clinical product that has changed the lives of many people with a wide range of neurological disabilities. 2. Scott, A.B., Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery, Ophthalmology, 87, 1044, 1980. 4. Odergren, T. et al., A double-blind, randomised, parallel group study to investigate the dose...


Labs Botulinum toxin detected in patient's serum and canned-food sample with specific antiserum. Discussion The disease is characterized by gradual return of muscle strength in most cases. Botulinum toxin is a zinc metalloprotease that cleaves specific components of synaptic vesicle docking and fusion complexes, thus inhibiting the release of acetylcholine at the neuromuscular junction. The disease in adults is due to ingestion of the toxin rather than to the ingestion of Clostridium botulinum spores in honey.


Clostridial neurotoxins that have been rendered innocuous possess several unique functional activities that potentially suit them for transport of foreign cargos across anatomical barriers to a variety of locations in the nervous system. This chapter reviews the varied approaches used to generate nontoxic fragments or engineer other important recombinant derivatives of botulinum (BoNT) and tetanus neuro-toxin (TeNT) in order to exploit the potent neuron targeting and delivery capabil


(1) Clostridium botulinum is responsible for a fatal type of food poisoning, botulism. The disease is an intoxication rather than an infection in that outbreaks occur following ingestion of food in which CI. Botulinum has grown and produced a highly potent exotoxin. Within the anaerobic environment of the foodstuff, the spores germinate to form vegetative bacilli, which in turn, produce toxin. Since the spores of CI. Botulinum will withstand a temperature of 100 C for at least 3 to 5 hours, they present a definite hazard to home canning. Toxin-containing foods may appear spoiled and rancid and cans may be swollen due to gas formation by the organism. In some cases, the foodstuff may appear entirely innocuous. The toxin is destroyed by hearing the food at 100 C for 10 minutes. Outbreaks of botulism are rare in the United States because of the rigid regulation of commercial canning and good preservation. Most cases since 1910 have seen those associated with home preparation of...

A Specimens

(2) In cases of botulism, specimens from the patient are almost of no value, since the disease is an intoxication rather than an infection. Laboratory diagnosis is accomplished by demonstrating Clostridium botulinum toxin in leftover food. The organism may be isolated from the food and identified on the basis of biochemical tests and the demonstration of toxin production.

Tfss Ab

Remodelling of actin cytoskeleton may also be a result of modifying Rho family function (e.g., C. botulinum C3), but similar effects can also be achieved by targeting actin polymerization directly. This again demonstrates the conservation of targets across different delivery systems e.g., SpvB (TTSS), C. botulinum C2 (A-B), C. perfringens iota toxin, and related A-B toxins35 . From a therapeutic view, the C3 family has received the most interest principally due to the fact that the C. botulinum enzyme has been used for many years as a tool for understanding Rho signaling. C3 is not naturally taken up into cells unless applied at very high concentrations this is both a drawback and an opportunity. The downside is that the enzyme must be added to a cell targeting system in order to gain entry to the cell. This has been accomplished by various means including the use of modified diphtheria toxin, Pseudomonas ETA and C. botuli-num C2 toxin (lacking their cognate effector domains) as...

From Toxins

As little as two decades ago, deliberately injecting botulinum toxin into patients would have seemed foolhardy at best and criminal at worst. The increased clinical use of botulinum toxins has expanded the body of knowledge available on the structure and function of these proteins. This knowledge can be applied to topics as varied as therapies based on the endopeptidase activity of the toxins, vaccine development, protection against botulism, and vectors for neuronal drug delivery. Based on recent scientific and clinical information from top international authorities, Treatments from Toxins The Therapeutic Potential of Clostridial Neurotoxins reviews the status of current research and development and identifies significant developments. Drawing on their vast experience in this field, the editors present the basic background of the bacteriology and genetics of the neurotoxigenic Clostridia, a history of the discovery of the neurotoxins, and an overview of tetanus and botulism diseases....

Clinical Picture

Early Distal Subungual Onychomycosis

A type of dermatophytosis which is not very well known is dermatophytic gluteae or epidermatophytosis of the diaper area. It affects children under 3 years of age. The diaper area and adjacent skin are involved, with characteristic annular, erythematous, squamous plaques with a few vesicules with areas of spared healthy skin. This type is caused by E. floccosum and rarely by T rubrum.

Specimen Collection

Obtain biopsies of burned and unburned skin from patients at the time of debridement and eschar excision, prior to grafting. Skin samples are best obtained from the extremities or torso because these areas provide a good dermal layer for manipulation. Normal skin should not be taken from the face or genital area, to avoid cosmetic complications. The specimen obtained from the excised burned skin should include the margin between the burned and unburned skin (or zone of stasis and the normal skin). Unburned control skin specimens can be obtained from an area within 5 mm of the zone of stasis second- and third-degree burn samples are obtained from the area contiguous to the zone of stasis. Small pieces of skin that include the margin between the burned and unburned skin can be removed with a 5- to 6-mm punch biopsy. This biopsy should be deep, extending into the adipose tissue to get a good representative section of the tissue in question. This size of punch biopsy will provide adequate...


This category includes lichen simplex chronicus and epithelial hyperplasia, and in the past was often called leukoplakia or hyperplastic dystrophy. Clinically, this typically presents with complaints of itching and burning, and often follows contact with a topical irritant, although the patient may not recall such an exposure. Any part of the vulva may be affected, and the skin may appear erythematous with fissuring and excoriation. Lichenification, or the accentuation of normal skin markings, which results in thickening and raised white plaques, is also commonly seen. The process may be localized or diffuse and can been seen in all of the reproductive stages. This condition frequently may be associated with long-term use of topical therapies such as antifungals or steroids for other conditions, and may be causally related. A history of atopy, allergies, or eczema is also a likely risk factor.


The answer is c. (Adams, 6 e, p 1208.) Botulism is a disorder of the neuromuscular junction (NMJ). The characteristic findings are decremen-tal response of the muscles to repetitive stimulation of the nerve at a low frequency (2 to 5 Hz) and incremental response to repetitive stimulation at high frequency (20 to 50 Hz). Other disorders of the NMJ, such as myas-thenia gravis and Lambert-Eaton myasthenic syndrome (LEMS), also manifest with decremental response to repetitive stimulation at low frequencies due to depletion of acetylcholine in the synaptic cleft. Higher rates of stimulation lead to increased calcium in the presynaptic terminal, which allows more acetylcholine to be released in presynaptic disorders such as botulism and LEMS, thereby increasing the response of muscle. In myasthenia gravis, which is characterized by loss of acetylcholine receptors postsynap-tically, there is no increase in response at higher rates of stimulation, since there is already a maximal amount...

Skin Resection

Breast Reduction Immages

If the patient presents a mild hypertrophy and good skin quality, a vertical scar with or without a small compensation in the inframammary fold is recommended. These markings must be made in such a way that the final sutures are without tension of any With these principles (Pitanguy's 3-4 principles) in mind,basically we have three different types of skin markings as well as three different types of final scars (Figs. 10.2.1-10.2.4) (a) classic inverted T, (b) inverted T with a small horizontal scar at the inframammary fold, and (c) vertical scar. All these techniques leave a periareolar and a vertical scar. The appearance of these scars will vary according to each individual patient. I have used the periareolar approach 5 for selected cases (mild hypertrophy with good skin quality and with no ptosis). As the indications for the

Vocal Fold Submucosa

The original forms of solubilized collagen were produced from bovine species and were intended for use in the management of dermal deficiencies 5 . Specifically for cosmetic dermal application, collagen was isolated from animal dermal material, purified, and then processed for injection into humans in the form of a xenograft. These bovine collagen compounds, with and without glutaraldehyde cross-linkages, were developed to be placed in the region of the mid-reticular dermis known to be deficient in aging skin. The collagen graft was designed to replace the natural deficiency with similar tissue. The addition of the specific concentration of glutaraldehyde cross-linkages to the collagen implant was hypothesized to increase host fibroblast invasion and neovascularization of the graft 6 , Multiple reports emphasized ease of placement and the relatively stable results in skin augmentation 7-11 . After clinical trials, collagen compounds received approval of the U.S. Food and Drug...

New Indications

In adults, a RCT of BoNT A in 20 patients with Parkinsonism and drooling showed that after treatment the average secretion of saliva in the BoNT A group was significantly lower than in the placebo group. A dose of 450 U Dysport was split between the parotids and submandibular glands under ultrasound guidance. Compared to baseline and to placebo, drooling was significantly reduced (p 0.005) in the active BoNT A group at 1 week, benefits lasted approximately 1 month, and there was no residual treatment effect at 3 months.19 Previous small open label studies using 10 to 30 U Botox in a total of 25 patients reported treatment effects lasting 6 to 8 weeks20 and 4 to 7 months.21 Botulinum Toxin B Studies of the effects of botulinum toxin B in cervical dystonia reported a higher incidence of autonomic side effects such as dry mouth than with type A toxin. This raised the possibility that type B toxin may be useful for autonomic disorders such as sialorrhea. A small open label study...

The Skin and Aging

Aging causes subtle structural and biochemical changes in the skin independently of environmental factors. The most obvious and characteristic changes, however, are largely the result of many years of sun exposure. How old one looks (especially in the face) is much more a function of how much sun damage he or she has suffered than it is of his or her chronological age. The sun produces a great deal of UV radiation, which is largely responsible for the skin damage. The damage ranges from an acute injury such as sunburn to the chronic structural changes that we associate with aging skin, including splotchy pigmentation (age spots) and wrinkles. Most skin cancers are attributable to UV damage to skin cells' genetic material deoxyribonucleic acid (DNA). Protection from sun exposure is by far the most effective measure anyone can take to prevent aging of the skin as well as potentially serious health problems such as skin cancer. Even artificial sunlight (like that from indoor tanning) is...

The Skin

Oil Gland Drawings

Normal skin is composed of a variety of cell types and extracellular materials. Significant changes in the skin's structure occur with aging. Both intrinsic skin pigments such as those present in birthmarks and exogenous pigments such as those present in tattoos can produce cosmetically objectionable skin lesions. Cosmetic lasers have been developed to treat many types of skin lesions by targeting the specific cellular or subcellular skin component that is responsible for the lesion. differentiation). As the epidermis constantly renews itself, the maturing keratinocytes migrate into more superficial layers of the epidermis. The topmost layer is called the stratum corneum and is the surface that you feel when you touch your skin. The stratum corneum is dry on the outside but also contains oils that make it waterproof. When you take a shower, none of the water gets inside you, but rather it beads up on the surface of the stratum corneum, much like rainwater on a waxed car. This...

Tissue Resection

Years Old Breast Hypertrophy

Patient with mild hypertrophy, good skin quality. c, d Six months after mastopexy. Vertical scar and reduced scar in the submammary fold Fig. 10.6 a, b. Patient with mild hypertrophy, good skin quality. c, d Six months after mastopexy. Vertical scar and reduced scar in the submammary fold


Jankovic J, Brin MF 1991 Therapeutic uses of botulinum toxin. N Engl J Med 324 1186. Lecour H, Ramos H, Almeida B et al 1988 Food-borne botulism a review of 13 outbreaks. Arch Intern Med 148 578. Merson MH, Dowell VR 1973 Epidemiologic, clinical and laboratory aspects of wound botulism. N Engl J Med 289 1005.


The lozenge technique cannot be used for every patient. The best results are attained in young women with juvenile hypertrophy and good skin elasticity. The maximum amount of tissue excised, achieving a good result, is 900 g per breast. The technique is also useful in simple cases of ptosis, with small or medium hypertrophy, and as an adjunct when a prosthesis is used along with correction of ptosis. If the patient fits any of these categories but has loose striated skin, the surgeon should be sure that the patient understands that a good result will occur only in the long term.


Birthmarks are collections of cells or skin structures that are aggregated more densely than they are in normal skin. They are visible because they are composed of increased concentrations of the skin's visible pigments, hemoglobin or melanin. Less common birthmarks are normal in color but abnormal in texture because of increased thickness of the epidermis or dermis.

Diabetic Neuropathy

Patient symptoms can be varied, and include burning dysesthesias and occasional interruption of all stimuli (allodynia), decreased sweating, impaired vasodilation, dry skin, cold extremities, and defective thermal sensation. Patients have normal reflexes and motor strength and significantly reduced sensitivity to the 1 g monofilament and vibratory sensation with the 128-Hz tuning fork.


No established satisfactory treatment exists a promising approach is oral psoralen (photosensitizing drug) followed by exposure to artificial long-wave ultraviolet light (UVA) potent fluorinated steroid topically may be helpful. Generalized vitiligo may be treated by depigmentation of normal skin.

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