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Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: A gynecologic oncology group study allergy home purchase deltasone 5 mg without a prescription. Quality of life in women with vulvar cancer submitted to surgical treatment: A comparative study. A comparative study of radical vulvectomy and modified radical vulvectomy for the treatment of invasive squamous cell carcinoma of the vulva. Urinary incontinence after radical vulvectomy treated with Macroplastique implantation. Transurethral polydimethylsiloxane implantation: A valid option for the treatment of stress urinary incontinence due to intrinsic sphincter deficiency without urethral hypermobility. Tunneled modified lotus petal flap for surgical reconstruction of severe introital stenosis after radical vulvectomy. Flap reconstruction following gynaecological tumour resection for advanced and recurrent disease-A 12 year experience. Anatomic study of the superficial perineal neurovascular pedicle: Implications in vulvoperineal flap design. Sexual, psychological, and relational functioning in women after surgical treatment for vulvar malignancy: A literature review. Sexual function and somatopsychic reactions after local excision of vulvar intra-epithelial neoplasia. Sexuality issues in gynaecological oncology patients: Post treatment symptoms and therapeutic options. Lymphedema after gynecological cancer treatment: Prevalence, correlates, and supportive care needs. A comparison of quality of life between vulvar cancer patients after sentinel lymph node procedure only and inguinofemoral lymphadenectomy. Moreover, non-proliferative entities marked by increased pigmentation may occur, the most frequent being benign melanosis (1,2). Because of overlapping clinical and histological features between malignant and benign processes, pigmented vulvar lesions are often challenging. In this chapter, we summarize the distinguishing clinical characteristics of vulvar melanotic macules. These noninvasive imaging techniques may aid in the diagnosis of pigmented vulvar lesions. Vulvar melanotic macules, also called melanosis, are the most frequent type of pigmented macule of the vulva. Clinically, vulvar melanosis presents as single or, more commonly, multiple asymmetric macules or patches with variable shades of tan to black color, irregular and poorly demarcated borders, and variable sizes. In a recent study, vulvar melanosis occurred more frequently on the labia majora as compared to melanoma, which is most commonly found on the labia minora (5). The reticular-like pattern is similar to the pigment network observed in acquired-type nevi on skin. It does not show a typical honeycomb polygonal disposition, but a rather ovoid or round-shaped honeycomb. Histopathologically, it is correlated with the presence of melanin in the epidermal basal cells, with the lines of the network resulting from the projection of the pigmented rete ridges to the skin surface. The epidermis is hyperacanthotic, with thick, hyperpigmented epidermal crests with bridging of their base. The globular-like pattern shows aggregated round to oval structures, tan to dark brown in color, similar to globules of melanocytic lesions. On histopathologic examination, the lesions show variable distribution of the melanin pigment along the epidermal basal layer and several melanophages in the dermis, with no increase in the number of melanocytes. Dendritic cells are a possible finding in the epithelium of more than a third of cases. They are small in size and mainly confined in the basal layer of the epithelium around the dermal papillae, rendering possible, in the majority of cases, a differential diagnosis with malignant melanocytes that are preferentially located in the suprabasal layer (pagetoid scattering). The ring-like pattern is characterized by multiple round to ovoid structures, with regular hyperpigmented, well-defined borders arranged in a grape-like manner in some areas. The parallel pattern is composed of linear and curved streaks, lines, or globules running parallel to the skin surface. The predominant dermoscopic patterns of vulvar nevi are the globular and homogeneous patterns (5). These can be difficult to distinguish from the globular-like and the homogeneous patterns of vulvar melanosis. The globular pattern is defined by the presence of aggregated roundish to oval structures, tan to dark brown in color, corresponding histopathologically to dermal nests of melanocytes. The homogeneous pattern is characterized by the presence of homogeneous pigmentation in the absence of other dermoscopic structures. The lesion was showing more than one dermoscopic structure, color variegation from brown to gray and white color, and the presence of dotted vessels. Early stages of vulvar melanoma can be in differential diagnosis with benign melanotic macules. However, a recent study highlighted that in vulvar melanomas, a dermoscopic combination of blue, gray, or white color plus structureless zones is highly predictive of melanoma (19). Therefore, it is important to look for the presence of dendrites that characterize the melanocytes. However, hyper-reflective dendritic cells can also correspond to Langerhans cells, which are a frequent finding in inflamed and even normal mucosa. In melanoses, roundish, large, medium-reflective cells correspond to melanophages. When melanophages are present, they are usually numerous and can be distinguished from an initial spread of melanocytes towards the chorion because they are less reflective and are associated with edged papillae and a normal epithelium, which are not found in the case of invasive melanoma. Dermoscopy shows gray, white, and brown colors with structureless areas in the melanoma and a brown ring-like pattern in the melanosis. Reflectance confocal microscopy shows hyper-reflective polymorphic melanocytes in the upper part of the epithelium of the melanoma and hyper-reflective keratinocytes and dendritic cells corresponding to Langerhans cells around the chorion papillae at the basal layer of the epithelium of the melanosis. Moreover, the presence of a homogeneous hyper-reflective rim around the papillae is usually not found in melanoma and favors the diagnosis of melanosis. Vulvar nevi, melanosis, and melanoma: An epidemiologic, clinical, and histopathologic review. Dermoscopy of pigmented lesions of the vulva: A retrospective morphological study. Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation. Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: Case report. Reflectance confocal microscopy for the diagnosis of vulvar melanoma and melanosis: Preliminary results. Noninvasive assessment of benign pigmented genital lesions using reflectance confocal microscopy.
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The electron-withdrawing effect of the resulting Schiff base labilizes the other bonds on the bound carbon allergy forecast yonkers ny purchase deltasone pills in toronto, thus serving as the basis of the catalytic roles of pyridoxal and pyridoxamine. That coenzyme plays critical roles in several aspects of metabolism, giving the vitamin importance in such diverse areas as growth, cognitive development, depression, immune function, fatigue, and steroid hormone activity. Vitamin B6 is fairly widespread in foods of both plant and animal origin; therefore, problems of primary deficiency are not prevalent. Still, vitamin B6 status can be antagonized by alcohol and other factors that displace the coenzyme from its various enzymes to increase the rate of its metabolic degradation. A genomic analysis of 256 representative organisms of the human gut microbiota found half capable of de novo synthesis of the vitamin. Those findings suggested that hindgut microbial synthesis may produce as much as 2. The term pyridoxine (Pn) is used Vitamin B6 Chapter 14 353 86% of the daily human need for vitamin B6, a finding consistent with the fact that primary deficiency of the vitamin is rarely observed. Colonocyte uptake of the vitamin has been demonstrated;3 however, it is likely that a large portion of the microbially produced vitamin is taken up by nonsynthesizing microbes such that noncoprophagous animals derive little benefit from this source of the vitamin. In contrast, ruminants benefit from their rumen microflora, which produces vitamin B6 in adequate amounts to meet their needs proximal to where it is absorbed. However, appreciable amounts of the vitamin in some foods are not biologically available. The determinants of the bioavailability of vitamin B6 in a food include as follows: l Distribution in Foods Vitamin B6 is widely distributed in foods, occurring in greatest concentrations in meats, whole grain products (especially wheat), vegetables, and nuts (Table 14. In the cereal grains, vitamin B6 is concentrated primarily in the germ and aleuronic layer. Thus, the refining of grains in the production of flours, which removes much of these fractions, results in substantial reductions in vitamin B6 content. The chemical forms of vitamin B6 tend to vary among foods of plant and animal origin; plant tissues contain mostly Pn (the free alcohol form), whereas animal tissues contain mostly Pal and Pm. A large portion of the vitamin B6 in many foods is phosphorylated or bound to proteins via the -amino groups of lysyl residues or the sulfhydryl groups of cysteinyl residues. The vitamin is also found in glycosylated forms such as 5-O-(-dglucopyranosyl) Pn. Vitamin B6 glycosides are found in varying amounts in different foods but little, if at all, in animal products. In addition, the presence of Pn glycosides has been found to reduce the utilization of coingested free Pn. Peptide adducts-Vitamin B6 can condense with peptide lysyl and/or cysteinyl residues during food processing, cooking, or digestion; such products are less well utilized than the free vitamin. The reductive binding of Pal and Pal 5-phosphate to e-amino groups of lysyl residues in proteins or peptides produces adducts that are not only biologically unavailable but that also have vitamin B6-antagonist activity. Stability Vitamin B6 in foods is stable under acidic conditions but unstable under neutral and alkaline conditions, particularly when exposed to heat or light. Because it is particularly stable, pyridoxine hydrochloride is used for food fortification and in multivitamin supplements. Vitamin B6 is poorly available from the bran fraction of the grain; therefore, the bioavailability of the vitamin from whole wheat bread is less than that of Pn-fortified white bread. Diffusion Linked to Phosphorylation the vitamers Pn, Pal, Pm as well as some Pn glycosides can be absorbed by passive diffusion throughout the gut. Intact Pn glycosides taken up by diffusion are later converted to Pn by cytosolic -glucosidase and then oxidized to PalP. Uptake by Facilitated Transport There is also evidence for carrier-mediated absorption of the vitamin. Most (>90%) of the circulating vitamin is PalP derived from the hepatic turnover of flavoenzymes. The circulating vitamin is tightly bound to albumin and other plasma proteins via Schiff base linkages. In erythrocytes, it forms a Schiff base with hemoglobin by binding to the amino group of the N-terminal valine residue of the hemoglobin -chain. This binding, twice as strong as that to albumin, drives uptake of the vitamin by erythrocytes. Erythrocyte vitamin B6 levels are particularly high in infants but decline to adult levels by about 5 years of age. In humans and other animals, plasma PalP concentrations decline during pregnancy, as a result of a shift in the distribution of the vitamer in favor of erythrocytes over plasma, as neither the absorption, excretion, or hepatic uptake of the vitamin is affected. Renal failure has been found to reduce the plasma PalP level;9 whereas, submaximal exercise has been shown to increase it. Schiff bases are condensation products of aldehydes and ketones with primary amines; they are stable if there is at least one aryl group on either the N or the C that is linked. The vitamin also forms a Schiff base with the amino acid substrates of the enzymes for which it functions as a coenzyme; this occurs by the bonding of the amino nitrogen of PalP and the -C of the substrate. Its preferential uptake by tissues suggests roles of phosphatases in the cellular retention of the vitamin. After being taken into the cell, the vitamin is phosphorylated by Pal kinase to yield the predominant tissue form, PalP. Small quantities of vitamin B6 are stored, mainly as PalP, but also as Pm phosphate. Because the nonphosphorylated vitamers cross membranes more readily than their phosphorylated analogues, phosphorylation appears to be an important means of retaining the vitamin intracellularly. Protein binding is thought to protect PalP from hydrolysis while providing storage of the vitamin. Moderate exercise has been found to increase plasma PalP concentrations substantially. This appears to be related to the increased need for gluconeogenesis, which results in the release of PalP from glycogen phosphorylase. The rapidity of this response suggests either that the vitamer rapidly undergoes hydrolysis, discharge from the muscle, and then rephosphorylation in the liver, or that it is released intact through interstitial fluid. Erythrocyte Pal kinase activity in African-Americans has been reported to be about half that of white Americans, although lymphocytes, granulocytes, and fibroblasts show no such differences. This may indicate reduced erythrocyte retention of vitamin B6, which depends on the phosphorylation. Pyridoxal kinase also binds the antianxiety drug benzodiazepine,12 suggesting that the mode of drug action may involve enhancement of neuronal -aminobutyrate levels. Alkaline phosphatases-Phosphorylated forms of the vitamin can be dephosphorylated by membrane-bound alkaline phosphatases in many tissues. Pyridoxamine phosphate oxidase-This enzyme catalyzes the limiting step in vitamin B6 metabolism. Pyridoxal-5-phosphate synthase13-This enzyme catalyzes the oxidation of PnP and PalP to PalP. In the rat, urinary excretion of 4-pyridoxic acid increases with age in parallel with increases in the hepatic activities of Pal oxidase and Pal dehydrogenase. However, 4-pyridoxic acid is not detectable in the urine of vitamin B6-deficient subjects, making it useful in the clinical assessment of vitamin B6 status. This is formed by the reaction of an amino group of urea with a hydroxyl group of the hemiacetal form of the aldehyde at position 4 of Pal. For example, humans given 100 mg of Pal excrete about 60 mg 4-pyridoxic acid and 2 mg Pal over the next 24 h. Although no explanation has been offered for the correlation, it is of interest that excretion of relatively low amounts (<0.
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Biotinidase is the major biotin-binding protein in plasma; it is also present in breast milk allergy symptoms productive cough discount generic deltasone uk, in which its activity is particularly high in colostrum. The proteolytic liberation of biotin from its bound forms is essential for the reutilization of the vitamin, which is accomplished by its reincorporation into another holoenzyme. Mitochondrial biotinyl acetyl-CoA carboxylase may serve as a reservoir to maintain hepatic acetyl-CoA at appropriate levels in the cytosol. This would also provide biotin indirectly to support other biotinyl mitochondrial enzymes under biotin-limiting conditions. It also functions as a regulator of gene expression, as a substrate for the posttranslational modification of proteins by biotinylation. This function is implemented by five biotin-dependent carboxylases and transcarboxylases21 (Table 15. Transcarboxylase has been called the "Mickey Mouse enzyme," as the electron micrograph image of the bacterial enzyme, with its large single subunit and two smaller flanking subunits, resembles the head of the famous rodent. A small fraction is oxidized to biotin d- and l-sulfoxides; however, the ureido ring system is not otherwise degraded. The side chain of a larger portion is metabolized via mitochondrial -oxidation to yield bisnorbiotin and its degradation 19. This is sometime called "biotin holoenzyme synthetase" and, in microorganisms, "biotin protein ligase. The catalytic action of each proceeds by a nonclassic, two-site, ping-pong mechanism, with partial reactions being performed by dissimilar subunits: 1. Carboxyl transfer (at the carboxyl transferase subsite)-involving transfer of the carboxyl group from carboxybiotin to the acceptor substrate. In each enzyme, the carboxylase and carboxyl transfer two subsites appear to be spatially separated. Genetic defects in all of the biotin enzymes have been identified in humans (Table 15. These are rare, affecting infants and children, usually with serious consequences. Biotinidase deficiency occurs at a frequency of 1 in 60,000 live births, with affected individuals having <30% of normal serum biotinidase activity, compromising their ability to release biotin from dietary proteins and recycle it from endogenous biotinylated proteins. They show the neurological and dermatological symptoms of biotin deficiency, with onset in the first year of life (sometimes within weeks). They also experience additional signs including hearing loss and optic atrophy, which has been interpreted as suggestive of other, still-unidentified functions of biotinidase. Defects involving the absence of an apocarboxylase do not respond to supplements of the vitamin. It requires acetyl-CoA and catalyzes the incorporation of bicarbonate into pyruvate to form oxaloacetate, a key step in gluconeogenesis. Proliferating lymphocytes increases their uptake of biotin, as well as their activities of -methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase. Evidence indicates that biotin status affects the regulation of gene expression by affecting cell signaling and histones. Urinary 3-hydroxyisovalerate has, therefore, been proposed as a biomarker of biotin deficiency. Symptomsc: vomiting, lethargy, hypotonia, mental retardation, cramps Changes in energy production, gluconeogenesis, and other pathways. Symptoms: myopathy, neurologic changes Deficiencies of all biotin-containing holocarboxylases; acidosis and aciduria. Symptoms: vomiting, lethargy, hypotonia Deficiencies of all biotin-containing holocarboxylases; acidosis and aciduria. Symptoms: skin rash, alopecia, conjunctivitis, ataxia, developmental anomalies, neurological signs disease. Three histones (H3 and H4 primary targets; H1 to H2A to lesser extents) can be covalently modified by biotinylation at a dozen-specific lysyl residues to affect chromatin structure and stability of repeat regions and transposable elements. While debiotinylation of histones occurs, the mechanism is not clear; it may be catalyzed by an isoform of biotinidase. Reduction of histone biotinylation by biotin-deprivation reduced life span and heat tolerance in Drosophila melanogaster (Camporeale, G. In fact, recommended intakes for biotin have not been established in the United States (Table 15. Biotin deficiency can be induced by antagonists, the most prominent is avidin, a biotin-binding protein found in egg whites. Other Biotin-Containing Proteins It is possible that there may be unidentified biotin-dependent proteins and enzymes. A mass spectrometric screening of human embryonic kidney cells detected more than a hundred biotinylated proteins. Those include heat shock proteins and enzymes involved in glycolysis and protein synthesis. Egg White Injury In the mid-1930s, it was found that biotin supplements prevented the dermatitis and alopecia produced in experimental animals by feeding uncooked egg white. Degree of biotin saturation of biotin-dependent enzymes-This is a useful means of assessing biotin status. It is a homologous tetramer, each 128-amino acid subunit of which binds a molecule of biotin by linking to two to four tryptophan residues and an adjacent lysine in the subunit binding site. The binding of biotin to avidin is the strongest known noncovalent bond in nature39. Avidin is secreted by the oviductal cells of birds, reptiles, and amphibians and, thus, found in the whites of their eggs in which is thought to function as a natural antibiotic, as it is resistant to a broad range of bacterial proteases. It antagonizes biotin by forming with the vitamin a noncovalent complex40 that is also resistant to pancreatic proteases, thus preventing the absorption of biotin. Therefore, although raw egg white is antagonistic to the utilization of biotin, the cooked product is without effect. The consumption of raw or undercooked whole eggs is probably of little consequence to biotin nutrition, as the biotin-binding capacity of avidin in the egg white is roughly comparable to the biotin content of the egg yolk. However, as a tool to produce experimental biotin deficiency, avidin in the form of dried egg white has been useful. Few cases of clinical manifestations of biotin deficiency have been reported in humans. Signs included periorificial dermatitis, ketolactic acidosis, conjunctivitis, alopecia, hypotonia, ataxia, seizures, developmental delays, and increased risk to skin infections. The signs and symptoms included dermatitis, glossitis, anorexia, nausea, depression, hepatic steatosis, and hypercholesterolemia. Two similar biotin-binding proteins have been identified, both of which show considerable sequence homology with avidin at the biotin-binding site: streptavidin from Streptomyces avidinii and an epidermal growth factor homolog in the purple sea urchin Strongylocentrotus purpuratus. Other structural analogs of biotin are also antagonistic to its function: -dehydrobiotin, 5-(2-thienyl)valeric acid, acidomycin, -methylbiotin, and -methyldethiobiotin; several of these are antibiotics. The biotin content of human milk, particularly early in lactation, is often insufficient to meet the demands of infants for which reason it is recommended that nursing mothers take a biotin supplement. That practice substantially increases the biotin contents of their breast milk. The frequency of marginal biotin status (deficiency without clinical manifestation) is not known. Studies with validated biomarkers of biotin status indicate that subclinical biotin deficiency may occur in as many as one-third of pregnancies. That pregnant women experience increased catabolism of the vitamin is indicated by their increased urinary excretion of bisnorbiotin, biotin sulfoxide, and other biotin metabolites. Increased urinary excretion of 3-hydroxyisovaleric acid in late pregnancy has been found to respond to biotin supplementation. It has been suggested that vegetarians may be at risk for deficiency; however, studies have failed to support that hypothesis. This may be due to anticonvulsant drug therapy, known side effects of which are dermatitis and ataxia. About 15% of alcoholics have plasma biotin concentrations <140 pM, a level shown by only 1% of nonalcoholics. That hemodialysis can deplete patients of biotin is suggested by the finding that biotin supplementation reduced the severity of muscle cramps in hemodialysis patients. The major lesions appear to involve impairments in lipid metabolism and energy production. In rats and mice, this is characterized by seborrheic dermatitis and alopecia, a hind limb paralysis that results in kangaroo gait.
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There it is re-esterified and stored in droplets (some that are membrane-bound and appear to be derived from lysosomes and other allergy list purchase generic deltasone on line, larger ones not associated with membranes). These are the only types of hepatocytes that contain retinyl ester hydrolase activities. Almost all (about 95%) of hepatic vitamin A occurs as long-chain retinyl esters, the predominant one being retinyl palmitate. Kinetic studies of vitamin A turnover indicate the presence, in both liver and extrahepatic tissues, of two effective pools. The parenchymal cell is the predominant cell type of the liver, comprising more than 90% of organ volume. Chylomicron remnants are recognized by high-affinity receptors for their apo E moiety. Are also called pericytes, fat-storing cells, interstitial cells, lipocytes, Ito cells, or vitamin A-storing cells. The metabolism of vitamin A by hepatic cytosolic retinal dehydrogenase increases with increasing hepatic retinyl ester stores. Vitamin A is mobilized as retinol from the liver by hydrolysis of hepatic retinyl esters. The retinyl ester hydrolase involved in this process remains poorly characterized; it shows extreme variation between individuals. These are composed of an eight-stranded, antiparallel -sheet that is folded inward to form a hydrogen-bonded, -barrel that comprises the ligand-binding domain the entrance of which is flanked by a single loop scaffold. Within this domain, a single molecule of all-trans-retinol is completely encapsulated, being stabilized by hydrophobic interactions of the -ionone ring and the isoprenoid chain with the amino acids lining the interior of the barrel structure. Retinol oxidation also produces some retinoic acid most of which in the plasma is bound to albumen. In the rat, hepatic retinyl ester hydrolase activities can vary by 50-fold among individuals and by 60-fold among different sections of the same liver. This effect may explain the apparently impaired hepatic vitamin A mobilization by animals fed very high levels of vitamin E. Retinol-binding proteins isolated from several species (rat, chick, dog, rabbit, cow, monkey, human) have similar sizes and binding properties. Thus, low-serum retinol levels in malnourished individuals may not be strictly indicative of a dietary vitamin A deficiency. Turnover studies have indicated that some retinol recirculates to the liver, perhaps via transfer to lipoproteins. Studies with the rat have shown that the mobilization of vitamin A from adipocytes also differs from that process in other cells. In extrahepatic tissues, this process appears to be regulated by all-trans-retinoic acid. Indeed, retinol has been shown to move spontaneously between the layers of artificial phospholipid bilayers. The intracellular vitamin A-binding proteins appear to be important in the cellular uptake and the intracellular and transcellular transport of vitamin A metabolites. In the liver, their concentrations increase with increasing retinyl ester contents, suggesting that they may function in the transport of retinol from parenchymal cells into the stellate cells, which store retinyl esters. One is a strongly hydrophobic binding pocket; the other is a surface site that interacts with retinol via its polar head group. The protein shows higher affinities for all-trans-retinol and 11-cis-retinal than for other retinoids. Retinol Recycling and Homeostasis the majority of retinol that leaves the plasma appears to be recycled, as plasma turnover rates have been found to exceed utilization rates by more than an order of magnitude. It is estimated that some 50% of plasma turnover in the rat is to the kidneys, 20% to the liver, and 30% to other tissues. These parameters are quite different in the neonatal rat, indicating much faster turnover (turnover number 144) and much shorter transit time (0. In contrast, plasma levels of all-trans-retinoic acid and 4-oxo-retinoic acid respond to the level of ingested vitamin A. This process appears to involve nonenzymatic reactions of retinal and is accelerated in some retinal disorders. Studies in animal models suggest that this retinol is drawn preferentially from recently consumed vitamin A, rather than from hepatic stores. For this reason, vitamin A supplementation of mothers in vitamin A-deficient areas is regarded as a prudent public health strategy. A meta-analysis of randomized controlled trials showed that such measures have reduced infant mortality by 23% in children under 5 years of age in populations at risk to vitamin A deficiency. Plasma levels of carotenoids, in contrast, do not appear to be regulated but reflect intake of carotenoid-rich foods. Careful studies have revealed, however, cyclic changes of up to nearly 30% in the plasma -carotene concentrations during the menstrual cycles of women. Whether these fluctuations are physiologically meaningful or whether they relate to fluctuations in plasma lipids is not clear. Vitamin A in the Eye Retinol is taken up by the retinal pigment epithelium in preference to uptake by nonocular tissues. These systems show marked specificities for saturated fatty acids, in particular, palmitic acid; thus, the most abundant product is retinyl palmitate. However, because only a small amount of retinol appears to undergo phosphorylation in vivo, the physiological significance of this pathway is not clear. These cytosolic and microsomal activities are found in many tissues, the greatest being in the testis. This activity has been identified in several tissues including the retinal pigment epithelium, liver, mammary gland, and kidney. That 9-cis-retinol can be converted to 9-cis-retinoic acid is evidenced by the finding of a 9-cisretinol dehydrogenase. The enzyme in both humans and mice is inhibited by 13-cis-retinoic acid at levels similar to those 71. About 30% of the amount excreted in the bile is reabsorbed and recycled in an enterohepatic circulation back to the liver, and retinyl -glucuronide has been found to be produced in many extrahepatic tissues where it can support growth and tissue differentiation. Male rats fed retinoic acid instead of retinol become aspermatogenic and experience testicular atrophy. Because retinoic acid is the active ligand for the nuclear retinoid receptors, it is very likely that this metabolism is tightly regulated. Several retinoic acid isomers have been identified in the plasma of various species;75 the number having physiological significance is presently unclear. Interconversion of the most common all-trans and various cis vitamers occurs in the eye and is a key aspect of the visual function of vitamin A. In addition to all-trans-, 13-cis-, and 9-cis-retinoic acid, this number includes the 9,13-dicis-, 4-hydroxy-, 4-oxo-, 18-hydroxy-, 3,4-dihydroxy-, and 5,6-epoxy isomers, as well as such derivatives as retinotaurine. That enzyme also catalyzes the isomerization of 11-cis-retinol to the all-trans form. The conversion of all-trans-retinoic acid to 9-cis-retinoic acid has also been demonstrated. While retinol, retinyl esters, and retinal can be oxidized to retinoic acid, retinoic acid cannot be converted metabolically to any of the reduced vitamers. It may be directly conjugated by glucuronidation in the intestine, liver, and possibly other tissues to retinyl -glucuronide.
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This is done every day from an early age allergy symptoms after running generic 20 mg deltasone fast delivery, in the evening before going to bed, or before sexual intercourse (125). Washing from a basin, sponge baths, and bathing in rivers and streams are practiced in other regions of the world lacking running water. In the California study cited previously, usage rose with age from 26% among women younger than 41 years of age to 40% among women older than 48 years of age (56). Baby wipes, premoistened toilet wipes, and feminine wipes are all common choices (Procter & Gamble, unpublished data). In the late 1980s, reports appeared of allergic contact dermatitis to preservatives in some European wipes (140). The preservative in question (methylchloroisothiazolinone) is now highly regulated. Moreover, quantitative sensitization risk assessments have progressed over the last 20 years such that it is now possible to safely formulate consumer products containing such preservatives at levels that are so low that they pose no significant risk of inducing contact sensitization. They fell out of favor as anecdotal reports of inflammatory reactions ensued (141). Clinicians consider deodorant sprays unnecessary and generally recommend against their use (54). However, the sprays continue to appeal to women who have deep-rooted beliefs about the need to avoid odor. Douching Vaginal douching is the insertion of a device into the vagina for flushing liquid into the vaginal vault. A preponderance of evidence links the practice to serious adverse health effects, with limited evidence of benefits. Nevertheless, douching is a strongly held cultural norm and a difficult habit to change among those who practice it (39). Commercial preparations include solutions of vinegar or other acidifying agents. Pre-filled disposable bottles, refillable hanging bags, or refillable expandable bags are employed to irrigate the vagina. Bag-type applicators deliver a significantly greater volume and an eight-fold higher exposure duration than do disposable bottles (143). Douching is also other Genital Hygiene Practices Routine Perineal Cleansing Perineal hygiene is part of routine bodily cleansing. Hand-held showerheads are popular in Western Europe but are less popular in America: in a California study, they were used by a quarter to a third of women (56). Sponge baths and the use of hand-held showerheads become more prevalent with increasing age as expected, when reduced mobility becomes a factor. This appears consistent with the traditional belief system that rigorous bodily cleanliness is essential to health and well-being (112). However, cleansing with harsh soaps, chemicals, and antiseptics may cause vulvar contact dermatitis (137,138). For example, such practices were reported by 68% of patients with persistent vulvar symptoms (139). Douching with a variety of substances (soap and water, shampoos, toothpaste, and commercial antiseptics) is a routine practice among sex workers in developing countries (147,148). Motivating Factors Women who douche do so primarily to feel clean and they consider douching to be a sound advice of the mother, family, or friends; Caucasian American women are more influenced by the media (150). This may be due to traditional belief systems, which maintain that cleanliness contributes to health and that the body should be kept clean inside and out (112). Women also douche to avoid odor and to become clean after menstruation and sexual activity; hence, in both Europe and North America, early onset of douching is more prevalent among those who initiate sexual activity at an earlier age (152,153). Strongly held cultural beliefs and the perceived lack of suitable alternatives make it difficult for women to give up douching (150). Warnings that douching may be harmful are not highly persuasive; women reason that commercial douche preparations would not be widely available if they were unsafe. Caucasian women who douche are somewhat more likely to consider douching as unhealthy and may be more readily influenced by health care providers to give up the practice (154). Potential confounding factors cloud the epidemiologic assessment of the health risks, making it difficult to assess whether douching is a causative factor or simply a more common behavior among the demographic groups that are at risk of such health conditions (Table 36. In laboratory studies, douching preparations were antimicrobial to vaginal organisms (155). Depending on their composition and antimicrobial properties, these preparations caused either a transient washout effect in the vagina or a decrease in the density of vaginal microbes beyond the washout effect (156). Douching is more common during menstruation and after intercourse, a time of instability in some vaginal microbial populations (159,160). In a study of racial and ethnic differences in vaginal flora, douching more than once a month was associated with vaginal colonization by sexually transmitted microbes, although the latter was associated more consistently with race than with behavioral factors (158). Based on the weight of the evidence, the consensus remains that douching is unnecessary for genital hygiene and may have serious adverse consequences on reproductive health. Nevertheless, few professional organizations have explicit policies on the health consequences of douching. This may be due to the difficulty in drawing firm conclusions about causation from cross-sectional epidemiologic studies. Successful intervention strategies may ultimately provide a tool for prospectively assessing the risks and benefits of vaginal douching. Such women are more likely to be overweight and to douche, smoke, and drink alcohol (167). Since 1979, numerous retrospective epidemiological studies have linked perineal talc exposure to ovarian cancer. Some studies among women who use perineal powders suggested that tubal ligation was protective (168,169). Conversely, analysis of a subset of hospital studies showed no relationship to talc use, suggesting that a spurious statistical association may account for population-based data. By contrast, a longterm prospective study of 121,700 nurses found no overall association between perineal talc powder and ovarian cancer (171). The risk of epithelial ovarian cancer among talc users was no higher among women who had not had a tubal ligation. Body mass index may be one such factor, since overweight women are more likely to use perineal powders and are at higher risk of ovarian cancer (172). Uncontrolled socioeconomic variables may also play a role in the observed association. Common methods include shaving, the use of chemical depilatories, wax epilation, electrolysis, and laser hair removal. Rare instances of severe cases progressing to keloid scars have been reported on the legs (173). In the late 1990s, an epidemic of allergic contact dermatitis to colophonium in epilating wax occurred in Europe (174).
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With the help of these drawings I could observe my psychic transformations from day to day" (Jung allergy testing utah deltasone 5 mg discount, 1965, p. Participants were instructed to draw for 20-minute intervals for three days in a row. Perhaps a salient factor included the opportunity to express personal symbols and emotional associations with the whole of experience 131 trauma into the personal mandalas. Other studies are suggesting that mandala drawing may be useful with mild levels of stress as well. Journaling, or expressive writing, is a commonly prescribed therapeutic tool and integrative therapy modality. Many variations of expressive writing techniques are encouraged; however, there is a shortage of research pointing to efficacy of using writing as a trauma treatment tool. Some studies show that using short-term expressive writing can have a positive effect on immune system functioning (Pennebaker & Seagal, 1999). However, some subjects also reported a worsening of mood in the immediate hours after writing. Expressive writing may be therapeutic when combined in later stages of trauma treatment with creation of personal narrative and meaning. As brain functions following trauma treatment tip toward top-down and sideto-side functioning, the powerful addition of words and language expressed through writing may lead to healing and resolution. Recommendations for reading or writing poetry may also foster healing, as clients sort through and find meaning in personal struggle. Use of metaphor, as is often found in poetic expression, may be a particularly powerful method of healing, understanding, and integration. Chapter 7 discussed the importance of the expression of personal narrative and meaning as an integral part of recovery and healing of trauma. Telling the story, whether through writing, storytelling, or other expressive arts, can be an effective method to move past trauma and toward healing. Mindfulness, Visualization, Affirmation the concept of mindfulness has become a prominent motif in psychotherapy and trauma treatment. Two basic tenets of mindfulness include being present in the moment and accepting without judgment the thoughts, emotions, 132 the whole of experience and observations that may arise. Learning to be mindful and aware of the present moment often involves a major shift for many people, particularly in our culture. Our fastpaced, future-oriented, outward-focused society tends not to place value on inward reflection, or on gentle acceptance of personal experience, particularly that which is perceived as unpleasant. Inclusion of mindfulness-based interventions in the treatment of trauma appears to have value (Follette et al. Mindfulness during trauma therapy may help the client maintain a dual focus of awareness. As described by Siegel (2010), dual focus of awareness helps clients to maintain "one focus of awareness on the here and now, another on the there and then" (p. A mindful sense of presence in the moment helps clients to quiet states of hyper-arousal, and may decrease dissociative responses upon reexposure to trauma memory fragments. It also may encourage clients to break from habitual patterns of avoidance and engage more fully in therapy. Visualization is defined as a "technique involving focusing on positive mental images in order to achieve a particular goal" ("Visualization," n. These positive resources can be consciously brought to awareness as part of a dual focus approach. Positive imagery may include visualization of a place of calm and comfort, of a nurturing figure available to soothe, or a of mythic figure of strength and protection. Visualization techniques may also evoke an image of a container to use to safely lock away disturbing thoughts or material. Visualization is often used with future focus on success and desired goals or accomplishment. Visualization can be taught and used by any clients wishing to increase resilience, manage stress, or enhance well-being. In the energy psychology method of Tapping, or Emotional Freedom Technique, dual awareness is held with the distressing thoughts expressed simultaneously with a positive statement of affirmation (Feinstein, 2012). Variations usually include the development of the affirmation statement to include the following: "Even though [fill in the blank with summary words of the distressing situation, thought, or memory]. This is similar to the concept of a positive override to negative thoughts and emotion. Rick Hanson (2009) expands on importance of internalizing the positive in his discussion on the broad negativity bias of memory. Hanson describes typical brain function as having a negative bias toward states of vigilance, of frequent scanning for danger, and of reactive and responsive attendance to unpleasant experiences and memories. According to Hanson, the brain is "like Velcro for negative experiences and Teflon for positive ones" (p. Thus, the use of positive affirmations, including repeatedly calling up positive images and holding these simultaneously with the negative memory, may, over time, create a shift that allows the positive to seep in, ultimately creating new neural and memory pathways. The field of positive psychology focuses on similar concepts including cultivating of thoughts of gratitude. Robert Emmons and colleagues (Emmons & Mishra, 2012) from the University of California 134 the whole of experience at Davis have researched the concept of gratitude. Regarding the positive mental health benefits of incorporating a sense of gratitude, Emmons states, "The evidence strongly supports the supposition that gratitude promotes adaptive coping and personal growth" (p. A creative tool for helping clients to promote adaptive coping includes keeping a daily gratitude journal. A simple concept and technique like positive affirmations, when included as a part of trauma therapy, may help clients shift toward positive, bring healing changes in the brain and a new sense of well-being. Case Example Sarah is a 39-year-old woman coming to counseling to learn skills to cope with chronic state of anxiety. Sarah very much wanted to make this trip and opportunity to be with her husband, but the thought of flying to meet him filled her with nearly intolerable levels of anxiety. At a later session, Sarah recounted how she made it through what she had thought would be unbearable, and how she continues to use tapping when she notices her elevated levels of anxiety. Nutrition, Sleep Hygiene, Exercise With an eye turned toward trauma assessment and treatment, therapists may miss the opportunity for trauma interventions at a basic level. Behavioral health assessments for conditions like depression usually include inquiry of recent activity level, recent weight loss or weight gain, and habits of sleep. Psychoeducation given to clients can provide neurosciencebased rationale for physical interventions aimed to improve nutritional status, improve sleep, and encourage exercise. Nutrition In the rush to discover new methods (usually pharmaceutical) for treatment of mental health conditions, basic and fundamental modalities are often overlooked. Dietary interventions and the access to healthy, nutrient-rich foods may be an intervention both preventative and supportive. Ironically, a shift in dietary habits for many Americans from agrarian, fresh from the local farm to packaged, processed, and convenient has often resulted in less than optimal levels of nutrients available for metabolic functioning. Even as many people seek important information and 136 the whole of experience instructions for better nutritional health and functioning, many sources of nutritional information may provide conflicting information. For example, many adopted the recommendations to remove or decrease high intake of dietary fats and oils. However, such a diet that is low fat or "fat free" and promoted as being healthy and a way to avoid obesity, can actually be dangerous and harmful, particularly for young children. The brain itself is the organ in the body that contains the most fat, being comprised of 60% fat (Chang et al. It is crucial for the best type of dietary fat to be included in the diet to assist in proper brain development, for repair following injury, and for ongoing optimal functioning. Particularly for infants and toddlers with their rapidly developing brain and connection-building neurons, an intake of proper fats is crucial and sets the stage for lifelong optimal mental health functioning. So what are the ideal types of fat necessary for proper brain development and mental health functioning There are four types of fat: trans fats, saturated fats, monounsaturated fats, and polyunsaturated fats.
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This accounts for more than half of the vitamin B6 in the body allergy treatment ppt discount 5mg deltasone visa, owing to the abundance of both muscle and glycogen phosphorylase (5% of soluble muscle protein). Xanthurenic acid was discovered unexpectedly by Lepkovsky (University of California), who during the Great Depression sought to elucidate the nature of rat adermin. He wrote of his surprise in finding that the urine voided by his adermin-deficient rats was green, whereas that of his controls were the normal yellow color. In pursuing this observation, he found that urine from deficient animals was normally colored when voided but turned green only on exposure to the rusty dropping pans their limited budget had forced them to use. Thus, he recognized that adermin-deficient rats excreted a metabolite that reacted with Fe3+ to form a green derivative. His message: "The investigator has to do more than sit at his desk, outline experiments and examine data. PalP-dependent enzymes function in the biosynthesis of neurotransmitters: tryptophan decarboxylase and aromatic l-amino acid decarboxylase in the synthesis of serotonin; tyrosine carboxylase in the synthesis of epinephrine and norepinephrine; glutamate decarboxylase serves in regulating turnover of a major source 26. The PalP-dependent aspartate aminotransferase, which can have cysteine aminotransferase activity, may also be involved. The apoenzymes involved in these various steps have widely different affinities for PalP. Therefore, vitamin B6 deprivation affects preferentially those decarboxylases with low affinities for the coenzyme. Accordingly, moderate deficiency of vitamin B6 reduces brain serotonin levels without affecting other neurotransmitters. Animal studies of long-term potentiation, a synaptic model of learning and memory, have revealed that maternal deprivation of the vitamin during gestation and lactation specifically reduces the development of the N-methyl-d-aspartate receptor subtype in the young. Although the metabolic basis is not understood, these effects appear to be related to the loss of dendritic arborization in vitamin B6 deficiency. These lesions are thought to underlie reported effects of impaired learning on the part of the progeny of vitamin B6-deficient animals and humans. These reactions can include additions and cyclizations such that the vitamin can be capable of high antioxidant activity by scavenging up to eight hydroxyl radicals. That vitamin B6 plays a role in normal vascular function is evidenced by the fact that lowvitamin B6 status has been associated with increased risk to coronary artery disease. Deprivation of vitamin B6 has been shown to produce moderate hypertension in the rat. These effects were associated with elevations in plasma levels of epinephrine and norepinephrine, and reduced levels of serotonin in the brain and 5-hydroxytryptophan in nerves. Low-vitamin B6 status can also cause homocysteinemia as a result of diminished conversion to cystathionine due to impaired activities of the PalP-dependent enzyme cystathionine -synthase. Homocysteinemia has been associated with increased risks to occlusive vascular disease, total and cardiovascular disease-related mortality, stroke, and chronic heart failure. Histamine Synthesis PalP functions in the metabolism of the vasodilator and gastric secretagogue histamine as a cofactor for histidine decarboxylase. Hemoglobin Synthesis and Function PalP functions in the synthesis of heme from porphyrin precursors as a cofactor for -aminolevulinic acid synthase. The vitamin also binds to hemoglobin at two sites on the chains (the N-terminal valine and Lys-82 residues) and the N-terminal valine residues of the chains. Binding of Pal or PalP at these sites enhances the O2-binding capacity of the protein and inhibits the physical deformation of sickle cell hemoglobin. Lipid Metabolism Vitamin B6 is required for the biosynthesis of sphingolipids via the PalP-dependent serine palmitoyltransferase and other enzymes in phospholipid synthesis. Diminution in the activities of these enzymes is thought to account for the changes observed in phospholipid contents of linoleic and arachidonic acids in vitamin B6-deficient animals. Antioxidant Function Studies with cell systems have demonstrated antioxidant properties of B6 vitamers. Pn, Pm, and PalP have been shown to reduce the production of superoxide (O2-) and lipid peroxides in response to prooxidative conditions. Dietary intakes of vitamin B6 and plasma levels of PalP have been found to be inversely 37. Folic acid produced an average 25% reduction, and vitamin B12 produced an average 7% reduction (Clarke, R. Animal and human studies have demonstrated effects of vitamin B6 deprivation on both humoral (diminished antibody production) and cell-mediated immune responses (increased lymphocyte proliferation, reduced delayed-type hypersensitivity responses, reduced 40. Suboptimal status of the vitamin has been linked to declining immunologic changes among the elderly (Table 14. Elevated intracellular levels of the vitamin are associated with decreased transcription in responses to glucocorticoid hormones (progesterone, androgens, estrogens). Such diminished responses include hydrocortisone induction of rat liver cytosolic aspartate aminotransferase. This inhibits the ligand binding to the glucocorticoidresponsive element in the regulatory region of the gene. Homocystinuria occurs due to a rare (three cases per million), hereditary deficiency of cystathionine -synthase. The impaired homocysteine catabolism is manifest as elevations in plasma levels of homocysteine, methionine, and cysteine with dislocation of the optic lens,47 osteoporosis and abnormalities of long bone growth, mental retardation, and thromboembolism. Hyperoxaluaria (Type I) is due to a variant hepatic alanine glyoxylate transferase with abnormally low PalP-binding capacity. Such studies have been conducted only in Europe; no information is available for other populations. Blood metabolites-The most common means of assessing long-term vitamin B6 status is the measurement of PalP in plasma. The latter is affected by short-term intake as well as tissue stores of the vitamin. Load tests-Vitamin B6 function can be assessed by measuring concentrations of downstream metabolites in pathways safely perturbed using large oral doses of key upstream metabolites: l Urinary xanthurenic acid after a tryptophan load-Because the affinity of kynureninase for PalP is much lower than those of the PalP-dependent transaminases, vitamin B6 deficiency results in increased production and urinary excretion of xanthurenic acid, which effect is amplified after an oral bolus (2 g) of tryptophan. These results can be affected by gender, estrogens, glucocorticoids, and pregnancy and protein intake, which upregulate tryptophan-2,3-dioxygenase, the rate-limiting enzyme in tryptophan metabolism. Degree of PalP saturation of PalP-dependent enzymes-Vitamin B6 status can be assessed by taking advantage of the in vitro binding of PalP by alanine aminotransferase or aspartic aminotransferase from hemolysates. Stimulation of either of these activities upon the addition of exogenous PalP indicates inadequate vitamin B6 status. Less obvious are the metabolic lesions associated with insufficient activities of the coenzyme PalP. Deprivation of vitamin B6 also impairs glucose tolerance, due to reduced activities of PalP-dependent transaminases and glycogen phosphorylase, although it may not affect fasting glucose levels. In addition, studies with volunteers fed a vitamin B6-free diet or a vitamin B6 antagonist62 have shown elevated urinary xanthurenic acid concentrations63 and increased susceptibility to infection. The lesion is morphologically indistinguishable from that produced by riboflavin deficiency. The lesion is morphologically indistinguishable from that produced by niacin deficiency. After tryptophan loading, vitamin B6-deficient subjects also had elevated urinary concentrations of kynurenine, 3-hydroxykynurenine, kynurenic acid, acetylkynurenine, and quinolinic acid. Low-vitamin B6 status is associated with inflammation as indicated by increased circulating levels of C-reactive protein (Table 14. Low-vitamin B6 status has also been associated with an increase in the ratio of n-6:n-3 polyunsaturated fatty acids in plasma, a feature associated with increased risk of inflammation. Neurological signs include convulsive seizures (epileptic form) that can be fatal. That tissue carnitine levels are depressed in vitamin B6-deficient animals has been cited as evidence of a role of the vitamin in carnitine synthesis.
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Subjective sensory effects are less quantifiable and more complex that the simple perception of a single physical stimulus: rubbing is the perception of a mechanical stimulus (touch) combined with friction; the sensation of wetness may be a combination of the perception of fluid contact combined with a sensation of cooling through heat transfer and evaporation; itching and burning are subjective pathological sensations allergy medicine cats effective deltasone 5 mg. Nevertheless, the frequencies of such effects in different groups of women also yield useful information on vulvar sensation. A prospective trial of feminine wet wipes and dry toilet tissue conducted in France among groups of pre- and postmenopausal women is instructive. In this study, objective vulvar erythema was either not observed, barely discernible, or slight in both product groups, with no statistical difference in frequencies between them. Reported sensory effects included slight burning, itching, or stinging (in both product groups) and a wet or sticky sensation (reported in the wet wipe product group only). The frequencies of vulvar burning and itching in this study did not differ by menopausal status. Interestingly, the frequency of reports of vulvar wetness was not significantly different between premenopausal and postmenopausal wet wipe users (frequencies of 8% and 10%, respectively), despite a clinically observable and statistically significant increase in skin moisture on the labia majora and perineum of postmenopausal women upon clinical examination. This observation is notable because it suggests that the perception of heightened vulvar wetness may have been attenuated in postmenopausal women. Postmenopausal women significantly preferred wet wipes to dry tissue for comfort (84% of postmenopausal compared to 54% of premenopausal women rated the wet wipes excellent to very good for comfort. Stinging was the only sensory reaction for which reported frequencies differed by menopausal status. Stinging is not an end-point typically associated with dry articles; 2% of premenopausal and 3% of postmenopausal women in the toilet tissue group reported slight stinging. Wet wipe users were more likely to report stinging, and premenopausal users reported a slight stinging sensation significantly more frequently than postmenopausal users (17% vs. This observation suggests that the sensory perception of sting on the vulva may be somewhat muted after menopause. The sensation of sting is of interest because dermatologists use the sting response to topically applied lactic acid as a surrogate marker for skin that is hyper-reactive to wind, temperature, and chemical stimuli (35). In summary, in a study of potential skin irritation and the vulvar sensory effects of wet wipes, the sting response was less frequent in postmenopausal women; moreover, these women did not perceive vulvar skin to be wet with any higher frequency following use of the wet wipes, even though this product led to a clinically discernible rise in vulvar wetness among these women when compared to premenopausal wet wipe users. Consequently, sensations of sting and wetness appear to have been attenuated in postmenopausal women. We speculate that the perceptions of burning and itching on the vulva may be conserved to a greater degree with age because these sensations play a role in signaling pathology. Few systematic studies have been performed on ethnic differences in genital sensory perception. Interestingly, older people were also more likely to claim sensitivity on the genitalia but not on the face and body. The characteristics of the sensations leading to these perceptions of sensitivity were not reported. Perhaps the relatively low sensitivity of the labia minora, vestibule, and vagina to mechanical stimuli in healthy women represents an adaptation to the mechanical forces endured during sexual intercourse and childbirth. Interestingly, evidence also exists that the vulva is relatively insensitive to skin irritation induced by either menses or blood when compared to extragenital sites such as the skin of the upper arm. Sensitivity to punctate mechanical stimuli on the vulva in healthy women decreases with age, although limited data suggest that clitoral sensitivity to mechanical stimuli does not deteriorate as rapidly with age as does the perception of such stimuli at other vulvar sites. Although the sensitivity to mechanical stimuli declines with age both on the vulva and at extragenital sites, the decline in vulvar sensitivity to punctate touch is linked to the level of estrogen stimulation of the vulva: perception declines after menopause, but is restored by systemic or topical estrogen supplementation. Estrogen was not shown to affect perceptions of these stimuli at extragenital sites. One caveat is that conclusions about the postmenopausal decline in vulvar sensitivity to touch are based on applying fine punctate pressure to defined locations. For example, the mechanical properties of vulvar tissue, skin barrier function, and vaginal lubrication are altered after menopause, and postmenopausal women report higher levels of subjective sensations, such as irritation and discomfort, associated with these atrophic vulvar changes (40,41). The subjective sensory VulVar and exTrageniTal clinical sensory percepTion 51 effects reported in clinical trials provide further evidence that estrogen status does not affect all forms of vulvar sensory perception in the same way. In clinical trials of external hygiene products, the frequency of slight vulvar burning and itching in response to physical contact with wet wipes or dry tissue was unaffected by menopausal status, but the stinging response (which, when measured on the face, is often associated with hyper-reactive or "sensitive" skin) appeared to be muted in postmenopausal women. Different sensory pathways in the vulva may be differentially affected by age or estrogen status. Lastly, in contrast to healthy women, women with a pain dysfunction known as provoked vestibulodynia. Although the techniques reviewed herein provide some insights, systematic inquiry into vulvar sensory perception is hindered by the lack of standardized assessment methodologies for this morphologically complex tissue. Foundational work is needed in order to validate the experimental conditions used and to enable comparisons between experiments. Moreover, in the vulva, glabrous and semiglabrous keratinized skin are juxtaposed with areas of nonkeratinized mucosa, tissues that differ in their embryonic derivation and structure (42). Factors such as labial shape and thickness may affect the way the stimuli are applied, and stimulus of the labia may affect sensation at other sites, such as the clitoris or vulvar vestibule. Furthermore, the direction of pressure applied to the vestibular mucosa (tangential vs. The challenge of assessing sensation on closely juxtaposed skin and mucosal sites that vary both anatomically and functionally is not unique to the vulva: orofacial researchers address similar challenges (43), and some of their approaches may be useful to the study of vulvar sensation. Future research will seek to standardize and validate conditions for applying stimuli and measuring responses and to investigate the various anatomical, neurological, and dermatological factors that affect vulvar sensory perception. The cortical sensory representation of genitalia in women and men: A systemic review. Influence of aging on thermal and vibratory thresholds of quantitative sensory testing. Quantitative sensory testing: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Ethnic differences regarding tactile and pain thresholds in the trigeminal region. Ethnic identity predicts experimental pain sensitivity in African Americans and Hispanics. African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures. Ethnic differences in pain, itch and thermal detection in response to topical capsaicin: African Americans display a notably limited hyperalgesia and neurogenic inflammation. Age and race effects on pain sensitivity and modulation among middle aged and older adults. Effect of vulvovaginal estrogen on sensorimotor response of the lower genital tract: A randomized controlled trial. Effects of age, menopause, and comorbidities on neurological function of the female genitalia. Effects of sexual arousal on genital and non-genital sensation: A comparison of women with vulvar vestibulitis syndrome and healthy controls. Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome. The assessment of sensory thresholds on the perineum and breast compared with control body sites.
