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Alopecia areata is the most prevalent autoimmune disorder which causes non-scarring hair loss. It may increase the anxiety of patients and increase their chances of developing psychological and psychiatric disorders. There are two proposed theories for the pathogenesis of alopecia areata.The most evidence-based hypothesis is an autoimmune reaction caused by collapse of hair follicle immune privilege, Immune privilege collapse is assumed to be either a primary event that triggers antigen presentation in a disturbed hair follicle environment, or an event that occurs as a result of dysregulation of central immune system that involves the follicles.Several gene loci have been identified with alopecia areata. The key immune effectors in the pathogenesis include autoreactive effector T cells, natural-killer group 2, member (NKG2D) + CD8+cytotoxic T cells, natural killer (NK) cells, Janus kinase, signal transducers and activators of transcription (JAK/STAT) pathway, MHC-I chain-related gene A (MICA), interferon‐γ (IFN‐γ) and interleukin-15 (IL-15). Alopecia areata has no accepted cure and has an unpredictable response to treatment. The recognition of the exact pathogenic mechanisms of alopecia areata is necessary to identify the potential therapeutic targets. Key words: alopecia areata, pathogenesis, immune privilege.

Alopecia areata is a common cause of nonscarring alopecia, with patchy, confluent or diffuse patterns, involving mainly the scalp and other hairy areas of the body. It's considered a therapeutic challenge due to prognosis, unpredictable course and variable efficacy of available therapies. Several studies have evaluated the efficacy of cryotherapy in the treatment of alopecia areata with varying success rates.Superficial cryotherapy using liquid nitrogen mainly was used in several studies for treating alopecia areata with various subtypes including mild, moderate and recalcitrant alopecia areata, and alopecia totalis with variable rates of therapeutically accepted terminal hair regrowth. Its main mechanisms of efficacy in alopecia areata are vascular changes and immunomodulation. Superficial cryotherapy was effective and safe in treating alopecia areata of the eyebrows. It was nearly as effective as topical steroids and topical PUVA therapy, and was combined with topical immunotherapy and topical steroid with increased efficacy. It's well-tolerated, convenient and simple office-based procedure, especially in children who are susceptible to side effects of other conventional therapeutic options.The reported side effects of superficial cryotherapy included vesiculation, erosion, crust formation, transient pigmentary alteration and partial leukotrichia, however they were transient. Key words: alopecia, cryotherapy, liquid nitrogen

Objective To investigate the effects of in vitro myo-inositol (Myo-Ins) supplementation of cryopreserved human semen on the cryo-survival rate (CSR). Methods Semen samples were obtained from 41 infertile men. Following routine semen analysis, each sample was divided into two equal aliquots (0.5 mL each). One aliquot was treated with 1 mg of Myo-Ins dissolved in 10 µL of sperm preparation medium. The second aliquot was treated with 10 µL of the same medium (control). Both aliquots were incubated for 20 minutes prior to freezing to slow the freezing process. The frozen samples were examined for post-thaw percentages of total motility (TM), progressive motility (PM), and the CSR, defined as the percentage of post-thaw TM divided by the percentage of pre-freeze TM and multiplied in 100. The results were expressed as median and interquartile range (25th and 75th percentiles). Results The pre-freeze TM (50% [30%-50%]) and PM (35% [20%-35%]) were significantly higher than the post-thaw TM and PM in the Myo-Ins group (15% [10%-35%] and 10% [5%-20%]; p

Background: Cirrhosis often is a silent disease Clinical symptoms at presentation may include jaundice of the eyes or skin, pruritus, gastrointestinal bleeding, coagulopathy, increasing abdominal girth, and mental status changes. Pruritus may be the presenting symptom, arising years before any other classic clinical and laboratory markers of hepatic dysfunction. This study examines the clinical, laboratory and histopathological changes in the skins of cirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control skins . Patients and Methods: To evaluate clinical, laboratory and histopathological changes in cirrhotic patients with pruritus, cirrhotic patients without pruritus and corresponding healthy (control). skin biopsies (20 specimens each) using hematoxylin and eosin stain and to study mast cell density using gimesa stain. Results: In the skin biopsy specimens of the cirrhotic patients with pruritus we found several histological changes including: epidermal hyperplasia (acanthosis) ,vascular ectasia(dilated dermal blood vessels), hypertrophied dermal nerve endings, mixed inflammatory cellular infilterate and lymphocytic vasculopathy (swelling of the endothelial cell lining of the blood vessels without fibrinoid necrosis, leucocytoclasia or extravasation of red blood cells). Evaluation of mast cell count in Gimesa stained skin sections revealed an increased numbers of these cells in the group of cirrhotic patients with pruritus ( N=5-10). The cells noted in perivascular, perineural and interstitial distribution (between collagen bundles). Conclusions: We report, for the first time, some histopathologial changes in the skins of cirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control skins .

Background:Hepatic pruritus is a very common symptom among different chronic liver diseases, particularly in those related to cholestasis. Its prevalence is variable among liver diseases, ranging from 5% in chronic hepatitis C virus infection to 70% in primary biliary cirrhosis. Its etiopathogenesis remains poorly understood.Nerve growth factor (NGF) is a member of neurotrophins. many studies clearly demonstrate their role in pruritus. Nerve growth factor (NGF) is overexpressed in prurigonodularis and its therapeutic administration is pruritogenic. In atopic dermatitis, NGF is released by keratinocytes, mast cells and fibroblasts and plasma levels of NGF are also elevated and correlate with disease activity.This study examines the hypothesis that expression of NGF protein is altered in cirrhotic patients with pruritus. Patients and Methods: To test our hypothesis, we examined the expression patterns of NGF protein in cirrhotic patients with pruritus, cirrhotic patients without pruritus and corresponding healthy (control). skin biopsies (20 specimens each) were evaluated using immunoperoxidase staining techniques. Results: We found variations between the skins of cirrhotic patients with and without pruritus and healthy skin. In healthy skin, the expression of NGF protein was strong (basal cell keratinocytes), moderate (spinouslayer), and weak or abscent (granular cell layer). In contrast, marked expression of NGF protein was observed in all layers of skin (total NGF epidermis and dermis) incirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control and this was statistically significant. NGF protein expression was strong (basal cell keratinocytes), moderate (spinous layer), and weak or abscent (granular cell layer). The expression of NGF protein was strong in the adnexal structures. Conclusions: We report, for the first time, increased expression of NGF protein in the epidermal keratinocytes of cirrhotic patients with pruritus skin. Our findings suggest possible roles for this protienin pathophysiology of hepatic pruritus. The clinical ramifications of these observations mandate further investigations.

Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.

BACKGROUND/OBJECTIVES Cutaneous warts (CW), or verrucae, are benign proliferation of skin that result from infection with human papilloma viruses. Cellular immune reactivity plays a significant role in wart regression. The aim of this study was to elucidate the cellular immune status of patients with CW through measurements of their serum levels of interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF,) and, identify the possible role of IL-17 and MIF in CW. We assessed serum IL-17 and MIF levels in patients with different forms of CW and compare the results with controls. PATIENT AND METHODS Serum levels of IL-17 and MIF were measured using commercially available ELISA assay kits in 60 patients with CW and 20 healthy controls. RESULTS Serum levels of IL-17 and MIF were significantly lower in patients with CW when compared with the controls (P-value

Objective: To investigate the effects of in vitro Myo- inositol supplementation of cryopreserved human semen on the post-thaw sperm quality. Design: A randomized controlled clinical trial (RCT). Materials and Methods: The study included 41 fresh semen samples obtained from 41 infertile men. Following routine semen analysis and estimation of sperm motion kinetics by CASA, each sample was divided into 2 identical aliquots. One aliquot (Myo- aliquot) was cryopreserved after Myo-inositol supplementation, while the other aliquot was cryopreserved as it is. Semen analysis and sperm motion kinetics were re – estimated and sperm cryosurvival rate was calculated for both aliquots after thawing. Results: Among patients with abnormal semen samples, Myo aliquot showed a highly significant increase in the following parameters in comparison with control aliquot: Percentage of progressive motility (P< 0.00001), percentage of total motility (P=0.00001), cryosurvival rate (P< 0.00001) and PR recovery rate (P< 0.0001). All sperm motion kinetics were also higher in Myo aliquot than control aliquot among this group, but failed to reach a statistical significant difference. Conclusion: in vitro myoinositol supplementation of human sperm prior to cryopreservation resulted in a highly significant increase in cryosurvival rate among abnormal semen samples, and an increase in cryosurvival rate among normozoopermic samples that failed to reach a statistical significant difference. These findings may pave the way to include myoinositol in the manufacture of human sperm cryopreservation media.

Background Coetaneous warts are benign papillomas of the skin of which common warts and plantar warts are the most common types. Up to one third of primary school children have coetaneous warts. Warts are caused by infection with human papillomavirus (HPV) Objective to investigate the serum levels of MIF in patients with coetaneous wartsfrom the outpatient clinic of the Dermatology and Venereology Department, Nag- Hamady general hospital during the period from 1-1-2015 to 1-1- 2016 Results This study included 50 patients with clinical evidence of different types of coetaneous warts and 20 healthy control participants. In this study, there was a statistically significant difference between serum levels of MIF in the patients and controll subject p value= 0.02). The serum levels of MIF were lower in the patients than control subjects Conclusion It is study concluded that there was statistically significant low serum levels of MIF in patients with different types of coetaneous warts compared with healthy participants

Genital warts (GWs) are most prevalent sexually transmitted infections, presenting especially among the sexually active young population of both sexes. Efficient cell-mediated immunity is needed for regression of GWs. To clarify the reactivity of cellular immunity among patients with GWs by means of measurements of their levels of serum interleukin (IL)-21 and IL-33, hence, to identify the possible role of IL-21 and IL-33 in GWs, this study aimed to evaluate serum levels of IL-21 and IL-33 among patients with GWs in comparison with the results of the controls. Levels of serum IL-21 and IL-33 were assayed utilizing commercially enzyme-linked immune-sorbent assay kits in 45 patients with GWs and 45 healthy control subjects. Levels of serum IL-21 and IL-33 were significantly decreased among patients with GWs in comparison with the controls (p < .0001). There was a highly significant positive correlation between IL-21 and IL-33 (r = .73, p < .0001). Low levels of serum IL-21 and IL-33 could have a contributive role in development, persistence, severity, and recurrence of GWs which rely basically on the defectiveness of cell-mediated immunity. This could receive new light on nonconventional strategies for the prospective medical therapies of GWs by means of regulation of IL-21 and IL-33.

Klippel–Trenaunay–Weber syndrome (KTWS) is a rare congenital disorder characterized by asymmetric limb hypertrophy, usually of the lower limbs, as well as vascular anomalies and capillary malformations under the skin, termed as port-wine stain. KTWS is prevalent in all parts of the world. It has a high degree of diversity of the associated malformations. In the present case, vascular/lymphatic malformations were evident by the presence of bilateral port-wine stain and lymphangioma. More interestingly, prominent aberrant veins (truncal varicosities) were found in the anterior chest wall, together with the presence of multiple angiolipomatosis. Bone deformities were more than limb hypertrophy and macrodactyly and extended to spinal deformities in the form of scoliotic changes.

Cutaneous aging is a complex biological phenomenon consisting of two components: intrinsic aging and extrinsic aging. Intrinsic aging is also termed true aging which is an inevitable change attributable to the passage of time alone and is manifested primarily by physiologic alterations with subtle but undoubtedly important consequences for both healthy and diseased skin and is largely genetically determined [1]. Extrinsic aging is caused by environmental exposure, primarily to UV light, and more commonly termed photoaging. In sun-exposed areas, photoaging involves changes in cellular biosynthetic activity that lead to gross disorganisation of the dermal matrix [2]. The intrinsic rate of skin aging in any individual can be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible aging of skin, also greatly increases the risk of cutaneous neoplasms. So, the processes of intrinsic and extrinsic aging are superimposed. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin aging to decreasing the genuine morbidity associated with problems of the aging skin. Therefore, a better understanding of both the intrinsic and extrinsic influences on the aging of the skin, as well as distinguishing the retractable aspects of cutaneous aging (primarily hormonal and lifestyle influences) from the irretractable cutaneous aging (primarily intrinsic aging), is very important to solve the problem of aging [2].

Survivin, a member of the inhibitor of apoptosis protein family, has an important role in cell cycle regulation. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone with wide range of biologic effects including stimulation of lipogenesis in sebaceous glands. Their overexpression in some fibrotic disorders suggests a possible implication of both IGF-I and survivin in the pathogenesis of acne and/or acne scars. The current study aimed to assess and correlate serum levels of IGF-I and survivin in patients with active acne vulgaris and postinflammatory acne scars and to evaluate their lesional expressions in comparison to healthy controls. Serum IGF-I and survivin were estimated using commercially available ELISA kits and their tissues expressions were investigated using Western blotting. Our findings suggest that IGF-I and survivin could play potential roles in the pathogenesis of active acne vulgaris and more importantly in postinflammatory acne scars with significant positive correlation coefficient between serum levels of IGF-I and survivin which support IGF-I-/PI3K-/AKT-mediated downregulation of nuclear expression of FoxO transcription factors resulting in enhanced survivin expression.

Involucrin is a structural component of the keratinocyte cornified envelope that is expressed early in the keratinocyte differentiation process. It is a component of the initial envelope scaffolding and considered as a marker for keratinocyte terminal differentiation. The expression pattern of involucrin in human scalp skin and hair follicle cycle stages is not fully explored. This study addresses this issue and tests the hypothesis that “the expression of involucrin undergoes hair follicle cycle-dependent changes”. A total of 50 normal human scalp skin biopsies were examined (healthy females, 51–62 years) using immunofluorescence staining methods and real-time PCR analysis. In each case, 50 hair follicles were analyzed (35, 10 and 5 follicles in anagen, catagen and telogen, respectively). Involucrin was prominently expressed in the human scalp skin and hair follicles, on both gene and protein levels. The protein expression showed hair follicle cycle-associated changes i.e. a very strong expression during early and mature anagen, intermediate to strong expression during catagen and prominent decline in the telogen phase. The expression value of involucrin in both anagen and catagen was statistically significantly higher than that of telogen hair follicles (p

Background: RhoB belongs to the Ras homologous (Rho) subfamily which consists of low molecular weight mass GTP-binding proteins. Rho proteins are regulatory molecules that mediate changes in cell shape, contractility, motility and gene expression. Aim: To test the hypothesis that ‘RhoB protein is expressed in the human skin and its expression undergoes hair follicle cycle dependent changes'. To test this hypothesis, we examined the expression of RhoB in the normal human skin and hair follicles (HFs) using immunohistochemical methods. Methods: A total of 50 normal human scalp skin specimens were obtained from 50 females (age: 53–57 years) undergoing elective cosmetic plastic surgery. The specimens were obtained from both frontal and temporal regions of the scalp. A total of 50 HF, (35 anagen, 10 catagen and 5 telogen) were examined in each case using immunohistologic staining methods. Semiquantitative analysis was done. Results: RhoB protein was strongly expressed in the various elements of the human scalp skin and hair follicles. In the epidermis, a moderate RhoB immunoreactivity was found in all layers except stratum corneum where RhoB protein was completely absent. In sebaceous glands, a strong RhoB immunoreactivity was detected in all sebaceocytes. In the hair follicles, the expression of RhoB protein showed hair follicle cycle stages-associated changes, i.e. strong expression during anagen, but weak and completely absent expressions during catagen and telogen phases, respectively. Semiquantitative analysis revealed statistically significant high expression values (staining intensity, percentage of positive cells and immunoreactivity scores) in the anagen VI hair follicles compared to either cantagen or telogen ones (p < 0.05). Similarly, RhoB protein expression was significantly high in the stratum basale, stratum spinosum and sebaceous glands compared to stratum granulosum (p < 0.05). Conclusions: Here we report, for the first time, the distribution of RhoB protein in the human scalp skin and hair follicles. We also provide the first indication that there are variations in the expression of this protein in the different stages of the hair cycle. Adly M.A, Assaf H.A, Hussein M.R.A. Expression of Ras homologous B protein in the human scalp skin and hair follicles: hair follicle cycle stages-associated changes

Heat shock proteins (HSPs) are molecular chaperones involved in protein folding, assembly and transport, and which play critical roles in the regulation of cell growth, survival and differentiation. We set out to test the hypothesis that HSP27 protein is expressed in the human testes and its expression varies with the state of spermatogenesis. HSP27 expression was examined in 30 human testicular biopsy specimens (normal spermatogenesis, maturation arrest and Sertoli cell only syndrome, 10 cases each) using immunofluorescent methods. The biopsies were obtained from patients undergoing investigations for infertility. The seminiferous epithelium of the human testes showing normal spermatogenesis had a cell type-specific expression of HSP27. HSP27 expression was strong in the cytoplasm of the Sertoli cells, spermatogonia, and Leydig cells. Alternatively, the expression was moderate in the spermatocytes, weak in the spermatids and absent in the spermatozoa. In testes showing maturation arrest, HSP27 expression was strong in the Sertoli cells, weak in the spermatogonia, and spermatocytes. It was absent in the spermatids and Leydig cells. In Sertoli cell only syndrome, HSP27 expression was strong in the Sertoli cells and absent in the Leydig cells. We report for the first time the expression patterns of HSP27 in the human testes and show differential expression during normal spermatogenesis, indicating a possible role in this process. The altered expression of this protein in testes showing abnormal spermatogenesis may be related to the pathogenesis of male infertility.

Background Glial cell line–derived neurotrophic factor (GDNF) and a related family member, neurturin (NTN), and their cognate receptors (GFRα-1 and GFRα-2, for GDNF and NTN, respectively) are distal members of the transforming growth factor-β superfamily. They are involved in the control of murine hair follicle (HF) cycling. This study tests the hypothesis that GDNF and NTN, and their cognate receptors, are expressed in the human HF and their expression varies in the different stages of the HF cycle. Methods The expression pattern of these proteins was examined in human HF by immunofluorescence, immunoalkalinephosphatase staining methods, and reverse transcription-polymerase chain reaction (GDNF). The functional effects (GDNF and NTN) were examined in organ culture of the microdissected HFs. Results GDNF, NTN, GFRα-1, GFRα-2, and c-Ret proteins were weakly expressed in catagen and telogen HFs. In contrast, they were strongly expressed in the epithelial and mesenchymal compartments of the anagen HF. GDNF gene was transcribed, both in the human scalp skin and in the isolated anagen HFs (reverse transcription-polymerase chain reaction). In HF organ culture, GDNF (but not NTN) increased the number of the proliferating HF keratinocytes (Ki 67 + cells). GDNF partially protected HFs from transforming growth factor-β2–induced premature catagen transition. Limitations None. Conclusions GDNF, NTN, GFRα-1, GFRα-2, and c-Ret proteins are differentially expressed in the different stages of HF cycle. GFRα-mediated signaling involves c-Ret and may play a role in human HF biology.

Summary Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that ‘GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5–18 years), adults (19–60 years) and the elderly (61–81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin–biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) and a related family member, neurturin (NTN), as well as their cognate receptors (GDNF receptors, GFRalpha-1 and GFRalpha-2, respectively) are involved in nervous system development and murine hair cycle control. To date, their expression in human scalp skin is still unknown. MATERIALS AND METHODS: The expression pattern of these proteins was examined in human scalp skin by immunofluorescence and immunoalkaline phosphatase staining methods as well as RT-PCR (GDNF). A total of 50 normal human scalp skin biopsy specimens were examined (healthy females, 53-57 years). RESULTS: The expression of GDNF protein was strong in the epidermis and sebaceous and sweat glands. In the epidermis, GDNF protein expression was seen in all layers except the stratum corneum. It was strong in the basal layer and decreased gradually towards the granular layer. The results of RT-PCR analysis revealed that GDNF protein is synthesised in the epidermis. The expression of NTN, GFRalpha-1, and GFRalpha-2 proteins was strong in the papillary dermis and sebaceous and sweat glands. In the epidermis, NTN protein expression was absent. The expression of GFRalpha-1 and GFRalpha-2 proteins was moderate in the epidermis. The expression of c-Ret protein was consistently strong in the epidermis and sebaceous and sweat glands. These proteins were strongly expressed in both epithelial and mesenchymal compartments of human anagen VI scalp hair follicles. CONCLUSIONS: Our investigation reports, for the first time, the expression patterns of GDNF, NTN, GFRalpha-1, GFRalpha-2, and c-Ret proteins in human scalp skin. The expression of these proteins in the skin suggests their possible roles in skin homeostasis. The clinical ramifications of these observations mandate further investigations. Adly MA, Assaf HA, Hussein MR, Paus R. Analysis of the expression pattern of glial cell line-derived neurotrophic factor, neurturin, their cognate receptors GFRalpha-1 and GFRalpha-2, and a common signal transduction element c-Ret in the human scalp skin.

Background Heat shock protein (HSP) is a molecular chaperone involved in protein folding, assembly, and transport and in the regulation of cell growth and differentiation. HSP27 protein is expressed in murine hair follicle (HF) and in human skin during fetal development. In this investigation we hypothesized that HSP27 protein is expressed in the human scalp skin and its expression in HF changes with the transitions form anagen → catagen → telogen stages. Methods To test this hypothesis, the immunoreactivity of HSP27 protein was examined in human scalp skin by immunofluorescent method. A total of 50 normal human scalp skin biopsy specimens were examined (healthy women, age 53-57 years). In each case, 50 HF were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Results HSP27 protein expression was prominent in human scalp anagen, and weak in both catagen and telogen HFs. Within HF, HSP27 protein immunoreactivity was prominent in the outer root sheath, inner root sheath, precorteocytes, and corteocytes of the hair shaft. In addition, HSP27 protein expression was prominent in the epidermis, sebaceous glands, sweat glands, and arrector pili muscles. Limitations Only some types of heat shock proteins are known to date. Also, our knowledge about the exact molecular mechanisms involved in the interactions among these protein and other molecular chaperones is still incomplete. Conclusions Our investigation reports, for the first time, the expression patterns of HSP27 in human scalp skin and HF. The differential expression of HSP27 during HF cycling suggests its possible roles in human HF biology.

Summary Background CD1d belongs to a family of antigen-presenting molecules structurally related to the classical major histocompatibility complex class I proteins. Objectives To examine the expression pattern of CD1d protein in normal human skin with ageing. Methods Twenty normal human skin biopsy specimens were obtained from 20 healthy individuals. The latter were divided into three age groups: children (5–20 years), adults (21–50 years) and the elderly (51–81 years). The intensity of CD1d protein production was examined in human skin using immunofluorescent and immunoalkalinephosphatase staining methods. Results In the epidermis, CD1d protein production was strong in the skin of the children and declined gradually with age, being moderate in adults and weak in the elderly. As compared with values in children, there was a statistically significant decrease (P

Background The p75 neurotrophin receptor (p75NTR) is a death factor (apoptosis-promoting protein) that belongs to the tumor necrosis factor receptor superfamily of membrane proteins. In the murine hair follicle (HF) model, p75NTR plays a critical role during HF morphogenesis, functioning as a receptor that negatively controls HF development. p75NTR signaling is involved in the control of keratinocyte apoptosis during catagen. To date, knowledge about the expression pattern of p75NTR protein in human scalp skin and HFs is limited. In this investigation we hypothesized that p75NTR protein is expressed in human scalp skin and its expression in HFs fluctuates with the transitions from anagen → catagen → telogen stages. Methods To test this hypothesis, the immunoreactivity of p75NTR protein was examined in human scalp skin by immunofluorescent and immunoalkaline phosphatase methods. A total of 50 normal-appearing human scalp skin biopsy specimens were examined (healthy women age 53-57 years). In each case, 50 HFs were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). Results We found variations in p75NTR protein expression with HF cycling. p75NTR expression was negligible in early, mid, and mature anagen and weak during late anagen. p75NTR expression was moderate during anagen-catagen transition. It was strong in both catagen and telogen HF. Also, p75NTR protein expression was strong in the stratum corneum (epidermis), dermal fibroblasts, blood vessels, nerve endings, adipocytes, and both sebaceous and sweat glands. Limitations Our knowledge about other proteins (prosurvival and pro-apoptotic molecules) interacting with p75 is incomplete. Conclusions Our investigation reports, for the first time, the expression patterns of p75NTR in human scalp skin and HFs. p75NTR protein expression exhibited significant hair cycle-dependent fluctuation, suggesting a possible role in human HF biology.

BACKGROUND Nerve growth factor (NGF) and its high-affinity receptor, tyrosine kinase A (TrkA), are members of the neurotrophin family. NGF-TrkA are involved in murine hair morphogenesis and cycling. To date, their expression in human hair follicle (HF) is unknown. In this investigation, we hypothesize that NGF-TrkA proteins are expressed in the human scalp skin. Moreover, NGF-TrkA expression in HF changes with the transitions from anagen-->>catagen-->>telogen stages. MATERIALS AND METHODS To test our hypothesis and to fill this existing gap in literature, the immunostaining values (semiquantitative evaluation of protein expression: SI, staining intensity; PP, percentage of positive cells; and IR score, immunoreactivity score) of NGF and TrkA proteins were examined in human scalp skin by immunofluorescent and immunoperoxidase staining methods. Fifty normal human scalp skin biopsy specimens were examined (healthy females, 53-57 years). In each case, 50 HFs were analyzed (35, 10, and five follicles in anagen, catagen, and telogen, respectively). RESULTS The IR scores were statistically significantly higher (p < 0.001) in anagen as compared with either catagen or telogen HF (9.61 +/- 0.12 vs. 1.4 +/- 0.10 vs. 0.6 +/- 0.10 for NGF and 3.31 +/- 0.02 vs. 0.5 +/- 0.10 vs. 0.2 +/- 0.10 for TrkA). In the anagen HF, high expression values were seen in the distal region, followed by upper distal, lower distal, and bulb regions for both NGF (10.6 +/- 0.21 vs. 10.3 +/- 0.21 vs. 9.2 +/- 0.40 vs. 8.1 +/- 0.30) and TrkA (3.54 +/- 0.07 vs. 3.45 +/- 0.07 vs. 3.31 +/- 0.06 vs. 3.13 +/- 0.04). Both NGF and TrkA proteins showed prominent expression in the melanocytes (7.6 +/- 0.15 vs. 2.50 +/- 0.07), keratinocytes (10.2 +/- 0.40 vs. 2.71 +/- 0.06), sebaceous glands (10.2 +/- 0.40 vs. 2.72 +/- 0.06), and sweat glands (10.4 +/- 0.40 vs. 2.84 +/- 0.05). CONCLUSIONS Our findings report, for the first time, the expression pattern of NGF and TrkA proteins in human scalp skin and HF. The differential expression of these proteins during HF cycling suggests their possible roles in human HF biology. The clinical ramifications of these observations mandate further investigations.